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Gingerol inhibits cisplatin-induced vomiting by down regulating 5-hydroxytryptamine, dopamine and substance P expression in minks.
To investigate the antiemetic effect of gingerol and its multi-targets effective mechanism on 5-hydroxytryptamine (5-HT), dopamine (DA) and substance P (SP). The antiemetic effect of gingerol was investigated on a vomiting model of mink induced by cisplatin (7.5 mg . kg(-1), i.p.) in 6 h observation. The levels of 5-HT, DA and distribution of substance P in the area postrema and ileum were measured by high performance liquid chromatography (HPLC) and immunohistochemistry respectively. The frequency of cisplatin induced retching and vomiting was significantly reduced by pretreatment with gingerol in a dose-dependent manner (P<0.05). Cisplatin produced a significant increase in 5-HT and DA levels in the area postrema and ileum of minks (P<0.05), and this increase was significantly inhibited by gingerol in a dose-dependent manner (P<0.05). Substance P-immunoreactive was mainly situated in the mucosa and submucosa of ileum as well as in the neurons of area postrema, and gingerol markedly suppressed the increase immunoreactivity of substance P induced by cisplatin in a dose-dependent manner (P<0.05). Gingerol has good activity against cisplatin-induced emesis in minks possibly by inhibiting central or peripheral increase of 5-HT, DA and substance P. | {
"pile_set_name": "PubMed Abstracts"
} |
Low-dose spironolactone in the management of resistant hypertension: a surveillance study.
We have conducted an open observational study of the use of spironolactone 25-50 mg in the management of patients with resistant hypertension. This drug was recommended in 133 patients who were already receiving an angiotensin-blocking drug in addition to other therapies. Of these, three defaulted from follow-up and 11 could not tolerate spironolactone. We therefore have outcome data on 119 patients. The addition of spironolactone (median dose 25 mg) was associated with a mean (SD) fall in systolic blood pressure of 21.7 mmHg (24.0; P < 0.001) and diastolic blood pressure of 8.5 mmHg (14.9; P < 0.001). In two patients spironolactone had to be discontinued on account of a rise of serum potassium to above 6.0 mmol/l, whereas overall the mean increase in serum potassium was 0.3 mmol/l. With careful monitoring of plasma electrolytes, spironolactone at a low dose is an effective add-in drug in patients with hypertension resistant to a regime that includes an angiotensin-blocking agent. | {
"pile_set_name": "PubMed Abstracts"
} |
The polyphenol-rich baobab fruit (Adansonia digitata L.) reduces starch digestion and glycemic response in humans.
The baobab fruit (Adansonia digitata L.) is found throughout regions of Africa and is becoming increasingly recognized for its high nutrient and polyphenol content. Polyphenols have been beneficial for their effects on reducing the glycemic response (GR) and for improving various other metabolic parameters. Based on previous research, it was hypothesized that the baobab fruit extract would reduce starch digestion in vitro and would show potential for reducing the GR and for increasing satiety and diet-induced thermogenesis in humans. Six extracts of baobab from 6 different locations in Africa were measured for their antioxidant and polyphenol content using the ferric ion-reducing antioxidant power and the Folin-Ciocalteu methods, respectively. Baobab extract was baked into white bread at different doses to determine the optimal dose for reducing starch breakdown and sugar release from white bread after an in vitro digestion procedure. In vivo, baobab extract was consumed in solution at both a low-dose (18.5 g) and a high-dose (37 g) aqueous drink in 250 mL of water along with white bread, and resulting GR, satiety, and postprandial energy expenditure were measured. All extracts in this study were shown to be good sources of polyphenols. Baobab fruit extract added to white bread at 1.88 % significantly (P < .05) reduced rapidly digestible starch from white bread samples. In vivo, the baobab fruit extract at both low and high doses significantly (P < .05) reduced GR, although there was no significant effect on satiety or on energy expenditure. | {
"pile_set_name": "PubMed Abstracts"
} |
Efficacy of risperidone in reducing positive and negative symptoms in medication-refractory schizophrenia: an open prospective study.
Although risperidone has been shown to be an effective antipsychotic medication in schizophrenia, the clinical studies performed for the Food and Drug Administration's approval process focused on only a mixed group of schizophrenic patients. Most of these studies did not directly address the efficacy of risperidone in chronic nonresponding schizophrenics. To better evaluate whether risperidone has a substantial degree of efficacy in schizophrenic non-responders, we conducted an open prospective study of risperidone in a sample of chronically hospitalized schizophrenic patients. Twenty-five patients who met DSM-III-R criteria for schizophrenia or schizoaffective psychosis, who were chronically hospitalized at a tertiary care state facility, and who had not responded to conventional neuroleptics were evaluated before and during treatment with risperidone by using several standard rating scales and adjunctive assessments. Endpoint analysis showed that 36% (N = 9) of the patients were classified as responders on the basis of at least a 20% decrease in total Brief Psychiatric Rating Scale score at final evaluation. A higher percentage of patients were classified as responders when other rating scale criteria were used. Reductions in psychopathology scores were seen in scales reflecting positive symptoms but not in scores of negative symptoms. High baseline negative symptom scores were correlated with poorer response to risperidone as indicated by the decrease in positive symptom scores. This study offers evidence that risperidone may reduce positive symptoms of schizophrenia for a subgroup of chronically hospitalized schizophrenic patients who have not responded to conventional neuroleptics. The comparative evaluation of the efficacy of risperidone versus that of clozapine in these types of patients requires further study. | {
"pile_set_name": "PubMed Abstracts"
} |
Diffusion and concentration profiles of drugs in gels.
A versatile membraneless method was used to study the diffusion of acetaminophen, ibuprofen, indomethacin, theophylline, and chlorpheniramine in thermoreversible gels. Two independent ways to calculate the diffusion coefficients and to verify Fickian transport are presented; the most sensitive criterion for Fickian transport being an agreement between the concentration profile for the drug in the gel and the free diffusion model. The diffusion of acetaminophen, ibuprofen, and indomethacin was studied at different temperatures in 1% (w/w) agarose gels. The diffusion coefficients for these drugs were found to be essentially the same as in water, and the apparent diffusion activation energies are close to that for self diffusion of water (4.62 kcal/mol), indicating a common mechanism for the diffusion of these drugs in the gel. The diffusivity of chlorpheniramine was also studied in 4% (w/w) agarose gels or with part of the agarose substituted with other polymers (e.g., chitosan and sodium alginate). These two oppositely charged polymers, mixed together, were found to occupy an "equivalent polymer volume" that was three times larger than the same amount of each of the constituents. When chitosan and gelatin-B were mixed into the agarose gel, non-Fickian transport resulted. Such non-Fickian transport was also observed with theophylline diffusing in a mixture of agarose, chitosan, and sodium alginate at a low pH. | {
"pile_set_name": "PubMed Abstracts"
} |
[A pharmacokinetic study of antibiotics in patients with benign prostatic hypertrophy].
Twenty cases intravenously received 1 g of cefotetan before the transurethral prostatectomy. High serum and prostatic concentrations were obtained and half-lives were 298 minutes for serum and 250 minutes for the prostate. The mean value of their creatinine clearance was as low as 46.6 ml/min and it was found to be the reason why the serum half-life time was longer than that reported for normal volunteers. | {
"pile_set_name": "PubMed Abstracts"
} |
Assessing beliefs and attitudes towards antipsychotic medication from a recovery-based perspective: Psychometric properties of a new scale.
Antipsychotic medication non-adherence is a complex and multifaceted problem that may hinder recovery in psychosis-spectrum disorders. Therefore, it warrants an early and comprehensive assessment. Current self-report measures focus entirely on behavioral and attitudinal barriers to adherence, failing to provide insight about key psychosocial drivers such as shame and stigma that may also account for non-adherence. This study's main goals were to develop a brief scale for measuring antipsychotic (non)-adherence and associated intra and interpersonal barriers (Antipsychotic Medication Beliefs and Attitudes Scale - AMBAS), and explore its psychometric properties. One hundred and seventy participants with a psychosis-spectrum disorder were recruited and filled in a battery of self-report measures. Exploratory factor analysis supported a two-factor solution, with one factor tapping the influence of different barriers to medication adherence and other factor encompassing perceived positive effects of medication. The scale presented good reliability and convergent validity as evidenced by significant moderate associations with the Medication Adherence Rating Scale. Although in need for further study, AMBAS seems a valid and reliable measure to assess antipsychotic (non)-adherence and underlying behavioral and psychosocial drivers. With replication, AMBAS might be a useful measure that could be used in different clinical and research settings. | {
"pile_set_name": "PubMed Abstracts"
} |
Serotonin transporter binding and acquired obesity -- an imaging study of monozygotic twin pairs.
Serotonin (5-HT) has been implicated as one factor controlling body weight and feeding behaviour. We studied the association between obesity and 5-HT by investigating the brain serotonin transporter (SERT) binding in 16 monozygotic twin pairs with varying body mass index (BMI) differences. The radioligand [(123)I]nor-beta-CIT was used for single photon emission computed tomography (SPECT) imaging of SERT binding. SERT genotype was also identified for each subject. We hypothesized reduced SERT binding in twins with higher BMI as compared to their leaner co-twins, and increased SERT binding in subjects with LL homozygotes compared to LS heterozygotes and SS homozygotes. In pairwise analyses, twins with higher BMI had higher SERT binding than their leaner co-twins in the hypothalamus/thalamus (specific binding ratios 1.21+/-0.23 vs. 1.12+/-0.16, p=0.04). The difference was striking in women (1.17+/-0.24 vs. 1.04+/-0.16, p=0.01), but not in men (1.26+/-0.22 vs. 1.22+/-0.08, p=0.61). In individuals, no correlation between SERT binding and BMI was evident, and no differences were found in SERT binding between the three SERT genotypes. Our finding suggests an association between acquired obesity and the 5-HT system, particularly in women. However, this association was seen only in twin data, where genetic effects and many shared environmental factors are eliminated. | {
"pile_set_name": "PubMed Abstracts"
} |
Factors affecting the regression of surgically replaced abdominal aortic aneurysms.
After endovascular therapy for abdominal aortic aneurysms, aneurysm sac shrinkage is considered to be the best marker of successful treatment. Such shrinkage, however, is infrequent and the rate of shrinkage is variable because of endoleaks. To investigate the factors that influence such contraction, the aneurysm sac regression after a conventional surgical replacement of the abdominal aortic aneurysm in an inclusion fashion was studied. Abdominal aortic aneurysms that measured 5 cm in diameter or larger were studied in 35 patients who underwent surgical replacement. The aneurysm sac was closed anterior to the prosthesis. Of the 35 cases, 4 aneurysms were inflammatory and 10 had aneurysm wall circumferential calcification of greater than 40%. Computed tomography was performed preoperatively, and at 1 week, and then 3 months postoperatively. The maximum major and minor diameters of the aneurysmal sac decreased significantly from 1 week to 3 months after surgery (major diameter: 49 +/- 12 to 32 +/- 8 mm and minor diameter: 39 +/- 10 to 26 +/- 7 mm). In inflammatory aneurysms, the maximum major and minor diameters were significantly larger at 3 months postoperatively, in comparison to nonspecific aneurysms. Among the 31 patients with nonspecific aneurysms, the maximum major diameter was significantly larger in those with aneurysmal calcification of greater than 40% of its circumference at 3 months postoperatively, in comparison to noncalcified aneurysms. The surgically repaired abdominal aortic aneurysm contraction tends to develop over 3 months, and inflammation, thickening, and calcification of the aneurysm wall are all considered to influence the regression of the aneurysm. | {
"pile_set_name": "PubMed Abstracts"
} |
Arthroscopic surgical treatment of medial epicondylitis.
The study purpose was to evaluate the outcomes of patients who received arthroscopic surgical treatment for medial epicondylitis refractory to conservative treatment. This was a retrospective study of 7 patients who underwent arthroscopic surgical débridement of the common flexor tendon for treatment of medial epicondylitis refractory to conservative treatment. The patients were assessed using the Disabilities of the Arm, Shoulder and Hand score; visual analog scale for pain; and Short Form 36 Health Survey. The mean age at the time of surgery was 50 years (range, 36-67 years). The mean duration of symptoms before surgery was approximately 2 years (range, 8 months to 4 years). The mean follow-up duration was 17 months (range, 6-48 months). The average postoperative scores were 17 points on the Disabilities of the Arm, Shoulder and Hand outcome measure; 2 points on the visual analog scale at rest for 6 subjects (86%) with slight pain and 1 (14%) with moderate pain; and 78 on the Short Form 36 Health Survey. No significant complications were observed when the procedure was performed via arthroscopy. Arthroscopic surgical treatment for medial epicondylitis of the elbow exhibits good outcomes and is safe and effective. | {
"pile_set_name": "PubMed Abstracts"
} |
The influence of technological parameters on the physicochemical properties of blank PLGA nanoparticles.
In this work, PLGA nanoparticles were prepared by an emulsification-diffusion technique. The main objective was to optimize the preparation of formulations by evaluating the influence of the technological parameters on the physicochemical properties of PLGA nanoparticles. The effects of variations in polymer and emulsifier concentrations, and homogenization duration, rate and type on the particle size distribution, surface charge and morphology of nanoparticles were assessed. The smallest nanoparticles (177.53 +/- 2.78 nm) were obtained with a 2% PLGA (w/v) concentration in the organic phase and 3% PVA (w/v) in the aqueous phase and were prepared by an emulsification-diffusion method via ultrasonic homogenization at a power of 80 W applied for 30 s. It was observed that nanoparticles prepared by Ultra Turrax were more spherical but larger. In addition, increasing the PVA concentration in the aqueous phase, increasing the PLGA concentration in the organic phase and increasing the homogenization rate decreased the zeta potential values of PLGA nanoparticles. | {
"pile_set_name": "PubMed Abstracts"
} |
Clinical symptoms in endoscopic reflux esophagitis: evaluation in 8031 adult subjects.
This study aimed to evaluate the correlation between symptoms and endoscopic findings in reflux esophagitis. Subjects, 8031 persons without medication for gastrointestinal disease, were briefly asked about the presence of heartburn, dysphagia, odynophagia, and acid regurgitation by associated medical staff before endoscopy for assessment of esophagitis utilizing the Los Angeles Classification. Endoscopically, 1199 (14.9%) were classified as positive reflux esophagitis, and 2223 (27.7%) had heartburn, 1522 (19.0%) had dysphagia, 493 (6.1%) had odynophagia, and 1466 (18.3%) had acid regurgitation. Multivariate analysis indicated that the symptom most related to esophagitis was heartburn (odds ratio: 2.46), although approximately 40% of subjects with grade C or D did not complain of heartburn. Regarding the other symptoms, less than 30% subjects with severe esophagitis complained of the symptoms and the odds ratio was approximately 1. These results indicate that endoscopic esophagitis was not equivalent to any reflux symptoms from which subjects suffered in their daily lives. | {
"pile_set_name": "PubMed Abstracts"
} |
Spontaneous blastogenesis profiles and IL-2 receptor expression on kidney allograft.
To examine immune activation rate of interstitial and glomeruli infiltrating MNC in different conditions of human renal allograft function deterioration, 33 renal transplant biopsies were performed 1-30 months after transplantations. Forty-one patients observed were on immunosuppressives: Pr, Aza, CsA following renal transplantation from a living-related donor parent. The patients were divided according to their histologic diagnosis into the following groups: 1, 15 pts in acute rejection attack (AR); 2, 10 pts with cyclosporine nephrotoxicity (CsN); 3, 10 pts with chronic vascular rejecting kidney (ChR). A conventional histologic investigation and immunohistochemical analyses of CD3 and CD25 molecules were performed in groups 1-3. Spontaneous blastogenesis (SB) of peripheral lymphocytes was simultaneously determined and compared with the controls (C)-30 healthy people, and with patients with stable renal allograft function (S)-8 pts. The highest IL-2R expression on diffuse or focal dense MNC infiltrates in interstitium was observed during AR, without IL-2R+ MNC in glomeruli. Low to moderate focal interstitial infiltrates in damaged areas of renal parenchyma due to CsN, were IL-2R negative. In ChR, moderate IL-2R expression was observed on interstitial spare mild or focal dense MNC infiltrates with IL-2R expression present on glomeruli infiltrating MNC. Significant increases of SB values were recorded during the first week after transplantation and AR in comparison to C. The highest SB values were in ChR group. Values of SB in CsN and S were on the C and before transplantation levels.(ABSTRACT TRUNCATED AT 250 WORDS) | {
"pile_set_name": "PubMed Abstracts"
} |
Dyslipidaemia among type 2 diabetes mellitus patients in a rural hospital in Erode district, Tamilnadu.
Dyslipldaemia In diabetes mellitus is associated with atherosclerosls and higher risk of coronary vascular disease. The study was conducted to find out the dysllpidaemia pattern in type 2 diabetes mellitus patients (n=257) who visited the diabetic clinic in a rural medical college. The patients' case records were verified. Personal data and lipid profile data were collected. The classification of lipid molety was done by adopting Adult Treatment Panel III (ATP III). The difference between groups were considered as significant at p<0.05. The mean values of total cholesterol 186 mg/dl, low density Ilpoprotein (LDL) 101 mg/dl, triglycerides 173 mg/dl, high density Iipoprotein (HDL) 48 mg/dl. The most common dyslipidaemia observed in this study was hypertriglycerldaemia (56%), low HDL (52.9%), and total cholesterol/HDL ratio of >3.5 (76.7%). There was no significant difference of dyslipidaemia distribution in male and female. The study highlighted the emerging importance of LDL dyslipidaemia in type 2 diabetes mellitus patients and there is urgent need for managing LDL dyslipidaemia. The screening for dyslipidaemia in all diabetes mellitus patient is important in all levels of healthcare settings. Considering the higher prevalence, due emphasis may be paid by healthcare practitioners for educating the patients behaviour on diet and physical activities. | {
"pile_set_name": "PubMed Abstracts"
} |
Oral examination and charting: setting the basis for evidence-based medicine in the oral examination of equids.
The oral examination is performed in equids to assess and monitor oral health status, provide diagnoses, and determine efficacy of treatments. While there is currently insufficient scientific material of adequate quality to enable evidence-based medicine in equine dentistry, this by no means negates the clinician's responsibility to provide oral health care in a scientific and ethical manner. To do so requires that the clinician be knowledgable and skilled in dentistry and general medicine, that each case upholds the principles of scientific method, and that data is gathered and appraised in an objective, precise, consistent, uniform, and reliable manner. | {
"pile_set_name": "PubMed Abstracts"
} |
Protection against toxic redox cycles between benzo(a)pyrene-3,6-quinone and its quinol by 3-methylcholanthrene-inducible formation of the quinol mono- and diglucuronide.
Cytotoxic effects of quinones are thought to be mediated by redox cycles between quinones and quinols whereby reactive oxygen species are generated. The role of glucuronidation in preventing these toxic redox cycles was investigated by using benzo(a)pyrene-3,6-quinone and isolated rat hepatocytes or Reuber hepatoma cells (H4IIE). Inhibition of quinol glucuronidation by salicylamide enhanced quinone-dependent oxygen uptake and cytotoxicity. Conjugation of benzo(a)pyrene-3,6-quinol was shown to proceed via the 6-monoglucuronide to the diglucuronide. Diglucuronide formation was low in hepatocytes from untreated controls and phenobarbital-treated rats. However, it was highly stimulated (26-fold) in hepatocytes from 3-methylcholanthrene-treated rats and was also high in Reuber hepatoma cells. Kinetic analysis with liver microsomes indicated that 3-methylcholanthrene-stimulated glucuronidation was due to an increased Vmax of UDP-glucuronosyltransferase which was enhanced 10- and 40-fold or mono- and diglucuronide formation, respectively. These findings suggest that the investigation of quinol glucuronidation (in particular the formation of benzo(a)pyrene-3,6-quinol diglucuronide) is a most useful probe for the 3-methylcholanthrene-inducible isoenzyme(s) of UDP-glucuronosyltransferase. Moreover, this isoenzyme may be particularly suited to protect against toxic redox cycles between benzo(a)pyrene quinones and quinols. | {
"pile_set_name": "PubMed Abstracts"
} |
Overexpression of cardiotrophin-1 and gp130 during experimental acute Chagasic cardiomyopathy.
Cardiotrophin-1 (CT-1), a cytokine with structural similarities to interleukin-6, has been shown to signal through gp130-dependent pathways. In vitro, CT-1 promotes the survival and induces hypertrophy of neonatal cardiomyocytes. Since acute Chagas' disease involves an inflammatory response followed by chamber dilation, with subsequent compensatory hypertrophy, we hypothesized CT-1 and gp130 may participate in this disease process. Thus, we investigated expression and localization of these moieties during acute Chagasic cardiomyopathy. Lewis rats (n = 6/group) were either inoculated with cell culture-derived T. cruzi trypomastigotes or saline, and sacrificed 15 days later. Hearts were collected for histology, immunohistochemistry (IHC), mRNA, and protein analyses. Histology showed dense myocardial infection with amastigotes and diffuse mononuclear cell infiltrate. Northern blot analysis showed low level expression of CT-1 mRNA in controls, which was markedly elevated in infected animals (2.5-fold; P < 0.001). Similarly, Western blotting showed a twofold elevation of CT-1 protein in infected animals (P < 0.025). Likewise, levels of both gp130 mRNA and protein were low in controls, but were approximately threefold higher in infected animals. IHC showed weak and diffuse staining for CT-1 in control myocardium, while intense staining especially localized to the cytoplasmic region of cardiomyocytes, was found in infected animals. Although gp130 immunoreactivity was observed in both normal and infected myocardium, more intense staining was found in infected animals. Unlike CT-1, gp130 staining was granular, and was present in both the cytoplasm as well as in the perinuclear region. These data suggest that there is substantial overexpression of both CT-1 and gp130 in the heart during acute Chagasic carditis. Their overexpression may provide a mechanism for myocyte protection, and for development of compensatory cardiac hypertrophy following myocardial damage in this form of cardiomyopathy. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of vigabatrin on epilepsy in mentally retarded patients: a 7-month follow-up study.
We studied the antiepileptic potency of vigabatrin (gamma-vinyl GABA, GVG) as an open trial in a group of 36 mentally handicapped patients with drug-resistant epilepsy (30 had seizures of partial onset and 6 had primary generalized [PG] tonic-clonic convulsions). With this treatment, 13 (43%) of the patients with seizures of partial onset and 2 (33%) with PG had more than 50% reduction in seizure frequency. The antiepileptic effect appeared during the first month of therapy and continued throughout the 7-month study. The side effects were mild: tiredness, aggressiveness, and ataxia. Other antiepileptic drugs remained at baseline levels during GVG therapy. GVG did not alter EEG recordings. Our results suggest that GVG is effective for treatment of intractable epilepsy, especially the partial type, in mentally retarded patients. Longer follow-up is needed, however, to determine that the clinical effect is maintained and that no severe side effects appear. | {
"pile_set_name": "PubMed Abstracts"
} |
Human Leukocyte Antigens Influence the Antibody Response to Hepatitis B Vaccine.
Hepatitis B virus (HBV) infection and its sequelae such as cirrhosis and hepatocellular carcinoma has remained a serious public health problem throughout the world. The WHO strategy for effective control of HBV infection and its complications is mass vaccination of neonates and children within the framework of Expanded Programme on Immunization (EPI). Vaccination with hepatitis B surface antigen (HBsAg) induces protective antibody response (anti-HBs ≥ 10 IU/L) in 90-99% of vaccinees. The lack of response to HBsAg has been attributed to a variety of immunological mechanisms, including defect in antigen presentation, defect in HBsAg-specific T and/or B cell repertoires, T-cell suppression, increase in the regulatory T cell count, lack of necessary help of T-cells for production of anti-HBs by B cells, defect in Th1 and/or Th2 cytokine production and selective killing of HBsAg-specific B-cells by human leukocyte antigen (HLA)-restricted cytotoxic T lymphocytes. The HLA complex plays an important role in many of these immunological processes. A variety of HLA class I, II, and III alleles and antigens have been reported to be associated with antibody response to HBsAg vaccination in different ethnic populations. Moreover, some HLA haplotypes were also associated with responsiveness to HBsAg. In this review the association of the HLA specificities with antibody response to hepatitis B (HB) vaccine is discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Detection of Aspergillus DNA by a nested PCR assay is able to improve the diagnosis of invasive aspergillosis in paediatric patients.
Fungal infections are a leading cause of morbidity and mortality in severely immunocompromised patients and have been increasing in incidence in recent years. Invasive aspergillosis (IA) is the most common filamentous fungal infection and is, in adults as well as in children, difficult to diagnose. Several PCR assays to detect Aspergillus DNA have been established, but so far, studies on molecular tools for the diagnosis of IA in children are few. We evaluated the results of a nested PCR assay to detect Aspergillus DNA in clinical samples from paediatric and adolescent patients with suspected IA. Blood and non-blood samples from immunocompromised paediatric and adolescent patients with suspected invasive fungal infection were sent for processing Aspergillus PCR to our laboratory. PCR results from consecutive patients from three university children's hospitals investigated between November 2000 and January 2007 were evaluated. Fungal infections were classified according to the EORTC classification on the grounds of clinical findings, microbiology and radio-imaging results. Two hundred and ninety-one samples from 71 patients were investigated for the presence of Aspergillus DNA by our previously described nested PCR assay. Two, 3 and 34 patients had proven, probable and possible IA, respectively. Sensitivity (calculated from proven and probable patients, n=5) and specificity (calculated from patients without IA, n=32) rates of the PCR assay were 80 and 81 %, respectively. Our nested PCR assay was able to detect Aspergillus DNA in blood, cerebrospinal fluid and bronchoalveolar lavage samples from paediatric and adolescent patients with IA with high sensitivity and specificity rates. | {
"pile_set_name": "PubMed Abstracts"
} |
Characteristics of the interaction of melittin with sarcoplasmic reticulum membranes.
Addition of an amphipathic bee venom peptide, melittin, to sarcoplasmic reticulum (SR) vesicles isolated from rabbit skeletal muscles resulted in a fast (<1 min) blue shift in the fluorescence maximum of the melittin--SR membrane complex. Over the following 45 min the position of the fluorescence maximum did not change, but the fluorescence intensity of the melittin--SR membrane complex decreased by approximately 35% with rate constant 0.14 min-1. Melittin rapidly quenched the isotropic signal in the EPR spectrum of spin-labeled stearic acid added to SR membranes. Further changes in the spectral parameters of the spin probe bound to SR membranes in the presence of melittin indicated an increase of the viscosity of the probe microenvironment (empiric parameter T/eta was decreased by approximately 35% with rate constant 0.11 min-1). The surface potential of SR membranes measured using a pH-sensitive dye, neutral red, decreased after melittin addition from -60 to -30 mV. It was demonstrated with the use of a cross-linking agent, cupric o-phenanthroline, that melittin induced slow aggregation of Ca-ATPase protein in SR membranes; the content of enzyme in the monomeric form decreased with rate constant 0.14 min-1. It is concluded that melittin binds rapidly to SR membranes, inducing slow changes in Ca-ATPase conformation and oligomeric state as well as structural transitions in the lipid bilayer of SR membranes. | {
"pile_set_name": "PubMed Abstracts"
} |
The neurobiology of learning and memory.
The study of memory is a great challenge, perhaps the greatest in biological sciences. Memory involves changes in a tiny fraction of an extremely large pool of elements, a conclusion that makes the task of finding those changes using current technologies formidable. What can be done about this roadblock to neurological investigations of learning? One response that has become particularly productive in recent years is to study learning or learning-like phenomena in relatively simple "model" systems. The idea is to extract basic principles from these models in which molecular and anatomical details can be studied and then to use these in analyzing learning in higher regions of the brain. In this article we discuss current progress and emerging concepts derived from the simple system approach using animal models. | {
"pile_set_name": "PubMed Abstracts"
} |
A comparative study on the medium-long term results of endovascular repair and open surgical repair in the management of ruptured abdominal aortic aneurysms.
Although it is generally acknowledged that patients with ruptured abdominal aortic aneurysm (rAAA) obtain the greatest benefit from endovascular repair (EVAR), convincing evidence on the medium-long term effect is lacking. The aim of this study was to compare and summarize published results of rAAA that underwent EVAR with open surgical repair (OSR). A search of publicly published literature was performed. Based on an inclusion and exclusion criteria, a systematic meta-analysis was undertaken to compare patient characteristics, complications, short term mortality and medium-long term outcomes. A random-effects model was used to pool the data and calculate pooled odds ratios and weighted mean differences. A quantitative method was used to analyze the differences between these two methods. A search of the published literature showed that fourteen English language papers comprising totally 1213 patients with rAAA (435 EVAR and 778 OSR) would be suitable for this study. Furthermore, 13 Chinese studies were included, including 267 patients with rAAA totally, among which 238 patients received operation. The endovascular method was associated with more respiratory diseases before treatment (OR = 1.81, P = 0.01), while there are more patients with hemodynamic instability before treatment in OSR group (OR = 1.53, P = 0.031). Mean blood transfusion was 1328 ml for EVAR and 2809 ml for OSR (weighted mean difference (WMD) 1500 ml, P = 0.014). The endovascular method was associated with a shorter stay in intensive care (WMD 2.34 days, P < 0.001) and a shorter total postoperative stay (WMD 6.27 days, P < 0.001). The pooled post-operative complication rate of respiratory system and visceral ischemia seldom occurred in the EVAR group (OR = 0.48, P < 0.001 and OR = 0.28, P = 0.043, respectively). The pooled 30-day mortality was 25.7% for EVAR and 39.6% for OSR, and the odds ratio was 0.53 (95% confidence interval (CI) 0.41-0.70, P < 0.001). There was not, however, any significant reduction in the medium-long all-cause mortality rate (HR = 1.13, P = 0.381) and re-intervention rate (OR = 2.19, P = 0.243) following EVAR. In EVAR group, nevertheless, incidence of type I endoleak was significantly lower than type II endoleak (OR = 0.33, P = 0.039) at late follow-up period. On the basis of this systematic review, rAAA EVAR results in less blood use for transfusion, shorter operation time, shorter intensive care unit and hospital stays, and lower 30-day mortality. However, in the medium-long term, it is not associated with a reduction in all-cause mortality. | {
"pile_set_name": "PubMed Abstracts"
} |
[Effect of testosterone or progesterone implants on the intensity of experimental infestation with Schistosoma mansoni in the female golden hamster].
When administered in pellet form of 20 mg to castrated Golden female hamsters, testosterone leads to a decrease of the intensity of experimental infestation with Schistosoma mansoni. The same result is obtained when estradiol is used in place of testosterone under the same conditions. On the contrary, no statiscally significant decrease has been observed with progesterone. | {
"pile_set_name": "PubMed Abstracts"
} |
Expression of viral proteins in mammalian cells transformed by avian sarcoma viruses.
The expression of viral proteins in nine lines of hamster and rat cells transformed by avian sarcoma viruses (ASV) was studied by indirect immunofluorescence with monospecific antisera to purified gp85 and p27 of AMV-B and a polyvalent antiserum to all the p proteins of this same virus. The lines of ASV-transformed cells were either low virus producers (VP) or inducible or non-inducible non producers (NP). Cytoplasmic expression of p proteins was observed in all the cell lines except the least inducible NP cell line, and cytoplasmic expression of gp85 in all the cell lines. The degree of expression varied widely with the lines and was not related to the class of permissiveness or inducibility. However, in the inducible NP class, the expression of p proteins and gp85 was higher in the most inducible cell lines. The data also suggest that the expression of the p proteins must be uncoordinate in at least some cell lines and must also be uncoordinate with the expression of gp85. In the VP cell lines and the most inducible NP lines, g85 and some p proteins other than p27 were also expressed on the cell membrane. The membrane expression of gp85 and the p proteins which were expressed appeared to be coordinate and to parallel the degree of cytoplasmic expression. In contrast, no, or a negligible expression of viral proteins was observed on the membrane of the least inducible and the non-inducible cell lines. These results suggest that there may exist translational and/or post-translational controls of the expression of viral proteins in the ASV-transformed mammalian cells and that the permissiveness and the inducibility of the cells may depend on the insertion of viral proteins in the cell membrane. The failure of p27 to insert in the cell membrane could account for the low permissiveness or the non-permissiveness of the cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Bystander effects in tumor-free and tumor-bearing rat brains following irradiation by synchrotron X-rays.
Synchrotron microbeam radiation therapy (MRT) is a radiosurgery concept in the preclinical stage, developed mainly for brain tumor treatment. Experimental studies suggest that with MRT a better therapeutic index can be obtained than with homogenous field radiotherapy, but the underlying cellular mechanisms need further understanding. The aim of this study was to investigate the dynamics of radiation-induced bystander effects (RIBE) in rats after exposing one brain hemisphere to either MRT or homogenous synchrotron radiation (HSR). Healthy and tumor-bearing Wistar rats were exposed to doses of 17.5, 35, 70 or 350 Gy, applied either as MRT or HSR to the right cerebral hemisphere. Rats were euthanized at 4, 8 and 12 hours after irradiation to assess the release of bystander signals. Brains and urinary bladders were dissected, and explants for bystander clonogenic reporter assays were set up. Clonogenic survival showed that RIBE occurred in both the non-irradiated brain hemisphere and in bladder of normal and tumor-bearing rats, while the irradiated hemisphere showed the direct effects of radiation. The RIBE observed in our reporter cells shows that both MRT and HSR yield a demonstrable abscopal effect after high doses of irradiation; presumably as part of a systemic response. | {
"pile_set_name": "PubMed Abstracts"
} |
Visualization of anterior chamber angle dynamics using optical coherence tomography.
To describe the technology of optical coherence tomography (OCT) in imaging the anterior chamber angles and its impact on understanding the pathophysiology of angle-closure glaucoma (ACG). Observational case series. Three subjects with, respectively, impending angle-closure attack, plateau iris syndrome, and phacomorphic glaucoma were recruited. The anterior chamber angle in each patient was imaged with a commercially available OCT unit. The angle configurations were assessed and compared before and after laser peripheral iridotomy (LPI) and argon laser peripheral iridoplasty (ALPI). Visualization of the changes in the anterior chamber angle configurations and normalization of the intraocular pressure (IOP). A patient with impending angle-closure attack precipitated by a topical mydriatic agent was treated with LPI. Optical coherence tomography imaging of the anterior chamber angles was performed before and after the laser procedure. Conversion of anterior iris bowing and angle crowding to iris straightening and angle opening after LPI was demonstrated. Intraocular pressure became normalized with the change in angle configuration. The second patient presented with symptoms of intermittent angle-closure attacks and was initially diagnosed with primary ACG. Despite successful LPI, the angles remained occludable, and the IOP continued to be elevated. Optical coherence tomography was used to review the anterior chamber angle configuration and demonstrated a typical pattern compatible with the diagnosis of plateau iris syndrome. Subsequent ALPI converted the plateau configuration to open angle, with normalization of IOP and disappearance of symptoms. The third patient presented with an acute angle-closure attack and was diagnosed with phacomorphic glaucoma. Argon laser peripheral iridoplasty was performed successfully to open the angle, as evident by the OCT images, and the IOP was brought under control, together with relief of symptoms. The commercially available OCT unit can be practically employed for anterior chamber angle imaging. The different patterns of angle configurations are correlated with the underlying pathophysiology in different forms of ACG. | {
"pile_set_name": "PubMed Abstracts"
} |
Patient doses from fluoroscopically guided cardiac procedures in pediatrics.
Infants and children are a higher risk population for radiation cancer induction compared to adults. Although some values on pediatric patient doses for cardiac procedures have been reported, data to determine reference levels are scarce, especially when compared to those available for adults in diagnostic and therapeutic procedures. The aim of this study is to make a new contribution to the scarce published data in pediatric cardiac procedures and help in the determination of future dose reference levels. This paper presents a set of patient dose values, in terms of air kerma area product (KAP) and entrance surface air kerma (ESAK), measured in a pediatric cardiac catheterization laboratory equipped with a biplane x-ray system with dynamic flat panel detectors. Cardiologists were properly trained in radiation protection. The study includes 137 patients aged between 10 days and 16 years who underwent diagnostic catheterizations or therapeutic procedures. Demographic data and technical details of the procedures were also gathered. The x-ray system was submitted to a quality control programme, including the calibration of the transmission ionization chamber. The age distribution of the patients was 47 for <1 year; 52 for 1-<5 years; 25 for 5-<10 years and 13 for 10-<16 years. Median values of KAP were 1.9, 2.9, 4.5 and 15.4 Gy cm(2) respectively for the four age bands. These KAP values increase by a factor of 8 when moving through the four age bands. The probability of a fatal cancer per fluoroscopically guided cardiac procedure is about 0.07%. Median values of ESAK for the four age bands were 46, 50, 56 and 163 mGy, which lie far below the threshold for deterministic effects on the skin. These dose values are lower than those published in previous papers. | {
"pile_set_name": "PubMed Abstracts"
} |
Foot-and-mouth disease. A review for the practitioner.
Foot-and-mouth disease (FMD) is perhaps the most infectious disease known to human and veterinary medicine. This article is written with the practitioner in mind, concentrating on early recognition, epidemiology, occurrence around the world, and sampling and diagnostic methods. The article stresses that there are numerous FMD viruses, and not all behave in a similar fashion. The practitioner must be acute in his or her herd inspection of animals in which vesicular disease is suspected and knowledgeable as to differential diagnosis. | {
"pile_set_name": "PubMed Abstracts"
} |
High spatial resolution electromyography and video-assisted movement analysis in children with obstetric brachial plexus palsy.
Two tools developed at the Institute for Biomedical Technologies and their use in children with obstetric brachial plexus lesions, a rather complex upper limb movement disorder, have been presented in this article. The authors have given examples of useful patterns correlated to defined clinical situations, such as the reinnervation process in a voluntary muscle, the coactivation of antagonistic muscles, and the ill-defined individual motion pattern in an affected limb. The authors believe these dynamic descriptions combining electrophysiologic and video techniques offer excellent clinical possibilities for the future. Further attempts will be made to adapt them to clinical situations and thus contribute to a more objective and better scientific understanding of upper limb movement. | {
"pile_set_name": "PubMed Abstracts"
} |
Alcohol-related cancers in Mediterranean countries.
In most countries bordering the Mediterranean, alcohol ranks second to tobacco as a risk factor for cancer. It is directly implicated in cancer of the mouth, larynx, hypopharynx and esophagus. For all these cancers a dose-response relationship has been demonstrated as well as a combination with the effect of tobacco, the two effects being multiplicative. Alcohol is also responsible for liver cancer developing on alcoholic cirrhosis. In addition, it has been suggested that alcohol consumption may be related to an increased risk of breast cancer. | {
"pile_set_name": "PubMed Abstracts"
} |
Array-CGH characterization of a prenatally detected de novo 46,X,der(Y)t(X;Y)(p22.3;q11.2) in a male fetus.
We report on an apparently normal 5-month-old boy with a X;Y complex rearrangement identified first on prenatal diagnosis and found on array-CGH to have a 7.6 Mb duplication of Xp22.3 chromosome and a deletion of Yq chromosome, distal to the AZFa locus. Karyotype analysis on amniotic fluid cell cultures revealed a de novo homogenous chromosome marker that we interpreted as an isochromosome Yp. FISH analysis using SRY probe revealed only one signal on the derivative Y chromosome. The final karyotype was interpreted as 46,X,der(Y)t(X;Y)(p22.31;q11.22). Translocation Xp22;Yq11 in male are very rare event and only 4 cases have been published, all showing mental retardation and malformations. Herein we discussed some possible explanation for this apparent phenotypic variability. | {
"pile_set_name": "PubMed Abstracts"
} |
Does Previous Breast Reduction Affect the Outcome of Gender-Affirming Subcutaneous Mastectomy?
Despite the rising popularity of subcutaneous mastectomy (top surgery) in patients born female and identifying as male or nonbinary, there are limited studies on how prior breast surgeries affect subcutaneous mastectomy. This study evaluates if previous breast reduction affected subcutaneous mastectomy in this patient population. The case series consists of 5 patients who, having had prior breast reductions, elected to have subcutaneous mastectomy. The data were collected retrospectively for mastectomy conducted from 2015 to 2016. Demographic data collected included age at surgery, body mass index, smoking status, medical comorbidity, and use of hormone medication. Outcome data included postoperative complications and need for operative revision. Postoperative follow-up was at 1 week and at 1, 3, 6, and 12 months. Patients' ages were between 29 and 46 years with body mass index from 24 to 33 kg/m. They underwent breast reduction approximately 9 to 26 months prior to subcutaneous mastectomy. All 5 patients successfully underwent subcutaneous mastectomy via double incision and free nipple grafts. Blood loss was estimated to be approximately 42 mL. All patients were discharged on the same day of surgery. The last follow-up averaged at 13 months after surgery and no major complication was reported. However, 1 patient required revision of the nipple graft and chest scars. This small case series suggests that subcutaneous mastectomy could be safely performed in transmasculine or nonbinary patients who had previous breast reduction. | {
"pile_set_name": "PubMed Abstracts"
} |
[The Structure of Practices and Tasks of Death Watch Care of Residents in the A National Sanatorium for Hansen’s Disease].
This study aims to clarify the structure of practices and tasks of death watch care in the A National Sanatorium for Sufferers of Hansen’s Disease (shown as A Sanatorium). A semi-structured interview was conducted of four nurses with experience of death watch care. Then, it was analyzed using the qualitative unification methods (KJ methods) individually and comprehensively. According to the results of the comprehensive analysis, nurses tended to feel strongly toward “a necessity of death watch care with a focus on family” through their communication with residents with poor relationships with their families. With this feeling in mind, they were placed everyday in “death watch care, focusing on supporting resident’s lives through daily care” while trying to be conscious of life-support for them. In practice every day, they seemed to be satisfied and encouraged by “tasks of death care are to focus on the resident’s value of life.” However, nurses with little experience of death watch care were full of anxiety and dilemmas emerged when they began death watch care. During this process, it was verified that there was “a gap in consciousness among nurses administering death watch care” and “an uncertainness of policies of institutions that accepted the death watch of residents.” In this way, an method for future death watch care in A Sanatorium was shown. | {
"pile_set_name": "PubMed Abstracts"
} |
Sacrospinous ligaments anterior apical anchoring for needle-guided mesh is a safe option: a cadaveric study.
To evaluate the feasibility and safety of using the sacro-spinous ligament (SSL) as a fixation point for anterior-apical pelvic floor compartment mesh implants. The apical support achieved with the sacro-spinous ligament mesh fixation is considered adequate, as it provides a high and stronger anchoring point. Even though, meshes for anterior pelvic floor reconstruction are traditionally anchored to the arcus tendineous fascia pelvis (ATFP). The authors presumed that fixing the anterior mesh to the sacro-spinous ligament instead of the ATFP is both feasible and safe. The present study evaluated the anatomical aspects and relations of a modified tissue passage with sacro-spinous fixation of the anterior apical mesh arms. In 5 embalmed female cadavers and 1 fresh female cadaver, the apical arms of the anterior needle-guided mesh were placed through the SSLs rather than through the ATFP, using a transgluteal approach. The distances between the mesh arms and the ureters and uterine arteries were measured. The minimal final distance between the mesh arms and the ureters or uterine arteries was 1.5 cm in the embalmed cadavers, but only 5 mm in the fresh cadaver. However, when analyzing the procedure carefully, it was noted that during dissection the ureters and arteries were pushed medially by the surgeon's finger, thus the operative procedure did not entail any real risk of injury to these structures. The introduced surgical needle caused no trauma to any adjacent cadaveric organs. Anterior pelvic floor meshes may be safely anchored to the SSL, thus potentially improving the apical support. | {
"pile_set_name": "PubMed Abstracts"
} |
Ca(2+) currents and voltage responses in Type I and Type II hair cells of the chick embryo semicircular canal.
Type I and Type II hair cells, and Type II hair cells located in different zones of the semicircular canal crista, express different patterns of voltage-dependent K channels, each one specifically shaping the hair cell receptor potential. We report here that, close to hatching, chicken embryo semicircular canal Type I and Type II hair cells express a similar voltage-dependent L-type calcium current (I(Ca)), whose main features are: activation above -60 mV, fast activation kinetics, and scarce inactivation. I(Ca) should be already active at rest in Zone 1 Type II hair cells, whose resting membrane potential was on average slightly less negative than -60 mV. Conversely, I(Ca) would not be active at rest in Type II hair cells from Zone 2 and 3, nor in Type I hair cells, since their resting membrane potential was significantly more negative than -60 mV. However, even small depolarising currents would activate I(Ca) steadily in Zone 2 and 3 Type II hair cells, but not in Type I hair cells because of the robust repolarising action of their specific array of K(+) currents. The implications of the present findings in the afferent discharge are discussed. | {
"pile_set_name": "PubMed Abstracts"
} |
Diagnostic use of mean nuclear area and nuclear DNA content in preoperative breast cancer cytology.
Fine needle aspiration (FNA) cytology of breast lumps is a routine procedure, and the diagnostic accuracy can be 95%. Occasional discrepancies arise, and it would be valuable to have additional parameters for accurate diagnosis. We evaluated nuclear DNA content and mean nuclear area (MNA) using image cytometry in the diagnosis of preoperative breast cancers by FNA in those with a discrepancy between clinical, radiologic and cytologic diagnoses. One hundred eighteen consecutive preoperative FNA samples were evaluated for nuclear DNA and MNA and were compared to cytologic and postoperative histologic diagnoses. Sensitivity, accuracy and positive predictive value of routine cytology were 95%, 90%, 95% as compared to nuclear DNA (66%, 66%, 96%) and MNA (61%, 61%, 97%). Combining these 3 parameters gave a sensitivity of 97%, accuracy of 94% and positive predictive value of 99%. These results demonstrate that nuclear DNA and MNA combined with routine cytology may be useful adjuncts in preoperative breast cancer cytologic diagnosis when discrepancies arise. This may lead to better and more accurate planning of treatment regimens in preoperative breast cancer patients. | {
"pile_set_name": "PubMed Abstracts"
} |
Modulation of HeLa cells spreading by the non-receptor tyrosine kinase ACK-2.
The CDC42 regulated non-receptor tyrosine kinase ACK-2 has been associated with integrin signaling. In this report, the effect of ACK-2 on the modulation of cell spreading and motility was examined. HeLa cells expressing epitope-tagged wild type ACK-2 showed a slower rate of spreading on fibronectin when compared with untransfected cells. An ACK-2 protein lacking its SH3 domain was still capable of modulating HeLa cell spreading suggesting that its tyrosine kinase activity is sufficient to induce the observed phenotype. The ACK-2 effect on the rate of cell spreading did not involve inhibition of integrin-mediated activation of PI-3K signaling, since it did not alter membrane translocation of a GFP-PH-AKT domain (AKT pleckstrin homology domain) used as a reporter for PI-3K products induced by cell adhesion. The ACK-2 effect appears to be upstream from the adapter protein CrkII, since co-expression of CrkII and ACK-2 results in a neutralization of ACK-2 mediated effects on HeLa cell spreading. Similarly, co-expression of p130Cas, which interacts with the adapter protein CrkII, with ACK-2, also results in a partial reversion of the ACK-2 effects on cell spreading. CrkII mediated reversal of the ACK-2 induced phenotype requires the activity of the small GTPase, Rap1. Co-expression of ACK-2 and CrkII with a dominant negative form of Rap1 reverses the neutralization by CrkII suggesting that CrkII mediated activation of Rap1 is required. However, an active form of Rap1 is not sufficient to reverse the ACK-2 phenotype by itself. A role for Rac1 in ACK-2 effects was also established. An activated Rac1 protein neutralized the ACK-2 mediated inhibition of cell spreading. A direct measurement of cell motility by either a modified Boyden chamber or wounding assay demonstrates that ACK-2 overexpression increases the motility of the cells. These results suggest that ACK-2 modulates HeLa cells spreading upstream of pathways regulated by CrkII and that ACK-2 may regulate cell motility by controlling the activation of small GTPases such as Rap1 and Rac1. | {
"pile_set_name": "PubMed Abstracts"
} |
[Experimental study of optical characteristics of homogeneous highly-dispersive biological medium].
Specific features of the process of short laser pulse propagation through a highly-dispersive biological medium are considered. Two models are used for the theoretical description of propagation of optical radiation through a highly-dispersive medium: diffusion approximation and non-stationary axial model. Physical characteristics of the dispersive medium are determined in both models. The obtained theoretical dependences are found to be in qualitative agreement with the results of experimental study. | {
"pile_set_name": "PubMed Abstracts"
} |
Pheochromocytomas: can malignant potential be predicted?
The presence of metastatic lesions is the only acceptable fact to confirm malignant pheochromocytoma. Patients with malignant pheochromocytomas, however, have a very poor survival rate. The aim of our study was to postulate predictive values for malignant pheochromocytomas. We evaluated symptoms, diagnostic modalities, treatment, and long-term follow-up of 86 patients with 85 benign and 10 malignant pheochromocytomas. Parameters from the benign were compared with those of the malignant pheochromocytomas. Preoperative 24-hour urinary dopamine was in the normal range for benign pheochromocytomas but increased in malignant pheochromocytomas (P<0.0001). Vanillylmandelic acid was elevated in both benign and malignant pheochromocytomas but higher in malignant than in benign tumors (P = 0.01). No differences could be shown in urinary epinephrine and norepinephrine samplings. Tumor location was divided into 77 adrenal (81%) and 18 extra-adrenal (19%) sites. Malignant pheochromocytomas were located more often at extra-adrenal sites (P = 0.03). There was no increased incidence of malignancy in patients with familial bilateral pheochromocytomas or multiple endocrine neoplasia. Tumors greater than 80 g in weight corresponded to malignancy (P<0.0001). Dopamine tumor concentration was higher in malignant than in benign pheochromocytomas (P = 0.01). Persistent arterial hypertension occurred in 9 (13%) of 72 benign and 6 (60%) of 10 malignant pheochromocytomas (P = 0.001). The 10-year survival rate was 94% for benign pheochromocytomas. All patients with malignant pheochromocytomas died within this period (P = 0.0001). High preoperative 24-hour urinary dopamine levels, extra-adrenal tumor location, high tumor weight, elevated tumor dopamine concentration, and postoperative persistent arterial hypertension are all factors that increase the likelihood of malignant pheochromocytoma. Patients with these characteristics should have more frequent follow-up evaluations to identify malignancy at earlier states. | {
"pile_set_name": "PubMed Abstracts"
} |
Agonist administration in ovo down-regulates cerebellar GABAA receptors in the chick embryo.
Chick embryos with an undeveloped blood-brain barrier were used to examine the down-regulation of GABAA receptors in vivo. The GABAA receptor agonist isoguvacine (5 mumol) was applied to the vascularized chorioallantoic membrane of 8 day embryos. This treatment was repeated on embryonic days 11, 14, and 17, and the embryos were sacrificed on day 18 (stage 42). Isoguvacine administration reduced the clonazepam-displaceable binding of [3H]flunitrazepam to washed cerebellar membranes by 34.0 +/- 3.0% compared to vehicle-treated controls. Binding reductions of lower magnitude were found in membranes from the cerebrum and optic lobes. Administration of isoguvacine had no significant effect on the wet weights of whole embryos or cerebella, the yield of cerebellar membranes, or the binding of [3H]N-methylscopolamine. The reduction of [3H]flunitrazepam binding to cerebellar membranes was dose-dependent, allowing a half saturation value of 8 microM isoguvacine to be estimated. Scatchard analysis showed that the Bmax for [3H]flunitrazepam binding was reduced by 28.3 +/- 6.7% compared to controls, without a change in the Kd. Embryonic exposure to isoguvacine also caused a reduction of 43.6 +/- 6.0% in the binding of the GABAA receptor channel ligand [35S]t-butylbicyclophosphorothionate to washed cerebellar membranes. Taken together, these results indicate that isoguvacine induces a down-regulation of the receptor subunits in vivo. However, measurements of cerebellar GABAA receptor mRNAs for the alpha 1, beta 2L, beta 2S, beta 4, gamma 1, gamma 2L, and gamma 2S subunits by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed no significant alterations by isoguvacine administration. The data suggest that translational or post-translational mechanisms, rather than those modulating the synthesis or stability of subunit mRNAs, take precedence in establishing GABAA receptor down-regulation. | {
"pile_set_name": "PubMed Abstracts"
} |
Bioluminescence and fluoroscopic imaging of tissue pH and metabolites in experimental brain tumors of cat.
The regional distribution of ATP, glucose, lactate and tissue pH was studied by bioluminescence and fluoroscopic imaging of intact cryostat sections of implantation tumors of cat. In tumors, marked heterogeneity of metabolites and pH was present: in solid parts ATP was similar to normal brain but glucose tended to decrease with an increase in lactate and pH to above normal; in necrobiotic regions ATP declined and pH became acidic. In peritumoral edema, ATP was consistently decreased whereas glucose, lactate and pH increased above normal. Correlation of ATP with water revealed an inverse relationship both in tumor and peritumoral edema but correlation of water with pH was direct in edema and inverse in tumors. The associations and dissociations of lactate, ATP and pH are interpreted in terms of aerobic and anaerobic glycolysis, as well as in respect to the extracellular localization of tumor edema. The findings are of relevance for the interpretation of volume selective NMR spectra and stress the importance of precise volume localization for differentiating between edema and tumor-mediated metabolic alterations. | {
"pile_set_name": "PubMed Abstracts"
} |
New flutes document the earliest musical tradition in southwestern Germany.
Considerable debate surrounds claims for early evidence of music in the archaeological record. Researchers universally accept the existence of complex musical instruments as an indication of fully modern behaviour and advanced symbolic communication but, owing to the scarcity of finds, the archaeological record of the evolution and spread of music remains incomplete. Although arguments have been made for Neanderthal musical traditions and the presence of musical instruments in Middle Palaeolithic assemblages, concrete evidence to support these claims is lacking. Here we report the discovery of bone and ivory flutes from the early Aurignacian period of southwestern Germany. These finds demonstrate the presence of a well-established musical tradition at the time when modern humans colonized Europe, more than 35,000 calendar years ago. Other than the caves of the Swabian Jura, the earliest secure archaeological evidence for music comes from sites in France and Austria and post-date 30,000 years ago. | {
"pile_set_name": "PubMed Abstracts"
} |
Split temporalis muscle flap anatomy, vascularization and clinical applications.
For more than a century, the temporalis muscle has been used for facial reconstructions. More recently, a split temporalis muscle flap elevated on the superficial temporal pedicle has been described, for which the resulting gain of length makes crossing of the midline possible, as well as reconstruction of substance losses exceeding the midline. Fourteen fresh cadaveric dissections were performed to study the different techniques for splitting the temporalis muscle. Dissections with catheterization and injection of radio-opaque contrasting agent in the external carotid artery were then performed to specify the vascularization of the flap split on the superficial temporal pedicle. The duplication of the superficial temporal pedicle grants greater length compared to that of the deep pedicles, 57 mm versus 40 (p = 0.036). The middle temporal artery is capable of ensuring the vascularization, and therefore the viability, of the split flap. From these results, we spoke about the limitations of this study and we have inferred the main indications. | {
"pile_set_name": "PubMed Abstracts"
} |
Phase 2 Study of Radiation Therapy Plus Low-Dose Temozolomide Followed by Temozolomide and Irinotecan for Glioblastoma: NRG Oncology RTOG Trial 0420.
To evaluate the toxicity and efficacy of adjuvant temozolomide (TMZ) and irinotecan (CPT-11) for 12 months after concurrent chemoradiation in patients with newly diagnosed glioblastoma (GBM). Trial RTOG 04-20, a single-arm, multi-institutional phase 2 trial, was designed to determine the efficacy and toxicity of concomitant TMZ and radiation therapy (RT) followed by adjuvant TMZ combined with CPT-11 given for 12 cycles compared with historical controls of adjuvant TMZ alone given for 6 cycles. A total of 170 patients were enrolled, 152 of whom were eligible. Adjuvant CPT-11 combined with TMZ was more toxic than expected. A higher rate of hematologic and gastrointestinal toxicities was more frequently noted with the combination regimen compared with adjuvant TMZ alone. Grade 3/4 hematologic toxicity was 38% compared with 14% reported in the Stupp trial. After an early interim analysis, the adjuvant CPT-11 dose was reduced to 100 mg/m2 on days 1 and 5 for the first cycle. CPT-11 dose escalation proceeded over the first 3 cycles if tolerated. Median overall survival for all eligible patients was 16.9 months compared with 13.7 months of the historical control (P = .03). Post hoc subgroup analysis suggested an improvement in overall survival for patients with Radiation Therapy Oncology Group recursive partitioning analysis class 3, although improvement was limited to 22 patients (14% of eligible patients). Although irinotecan and TMZ for 12 cycles given after chemoradiation for patients with newly diagnosed glioblastoma significantly improved median survival compared with historical control data at the time the study was conducted, the historical control median survival time of 13.7 months does not represent the current benchmark for this patient population. Treatment intensification does prolong overall survival compared with the current standard. | {
"pile_set_name": "PubMed Abstracts"
} |
Mitochondrial DNA analysis on remains of a putative son of Louis XVI, King of France and Marie-Antoinette.
Carl Wilhelm Naundorff was buried in 1845 in Delft as Louis Charles, Duc de Normandie, 'Louis XVII'. However, the son of Louis XVI and Marie-Antoinette-Louis XVII--officially died in the Temple of Paris in 1795. In order to resolve the identity of Naundorff, mitochondrial DNA (mtDNA) D-loop sequences of his remains were compared with the sequences obtained from the hairs of two sisters of Marie-Antoinette, Marie-Antoinette herself, and with the sequences obtained from DNA samples of two living maternal relatives. The mtDNA sequence of a bone sample from Naundorff showed two nucleotide differences from the sequences of the three sisters and four differences from the sequences of living maternal relatives. Based on this evidence it becomes very unlikely that Naundroff is the son of Marie-Antoinette. | {
"pile_set_name": "PubMed Abstracts"
} |
Angina pectoris, myocardial infarction and sudden cardiac death with normal coronary arteries: a clinicopathologic study of 9 patients with progressive systemic sclerosis.
The syndrome of angina pectoris or acute myocardial infarction without obstructive coronary artery disease has been the subject of much interest. We studied nine autopsied patients with progressive systemic sclerosis and evidence of ischemic heart disease but morphologically normal coronary arteries. Three patients had angina pectoris and three others chest pains of unknown etiology, six had ventricular arrhythmias, four had clinically suspected acute myocardial infarction, and eight had sudden cardiac death. At autopsy extensive focal myocardial necrosis was present in seven patients and myocardial scarring in all nine, but all patients had widely patent intramural and extramural coronary arteries. The finding of contraction band myocardial necrosis in seven of the eight patients who experienced sudden death suggests that the myocardial damage was a consequence of reperfusion of focally nonperfused myocardium, and thus due to a myocardial Raynaud's phenomenon. Patients with PSS may provide a model of spasm of intramyocardial vessels causing angina pectoris or myocardial infarction with morphologically normal coronary arteries. | {
"pile_set_name": "PubMed Abstracts"
} |
Drop dialysis: time course of salt and protein exchange.
By drop dialysis with membrane filters of 25 or 50 nm average pore size, salt concentrations are reduced to 15% within 25 min. During this time only 10% of ribonuclease with a Mr 13,500 will diffuse in and through the membrane. However, in the presence of 1 M NaCl about 25% of the enzyme is lost. The difference in the rate of salt removal and enzyme loss is caused by the difference in diffusion constants. Therefore with enzymes of higher molecular weights, less protein will be lost, as is shown with beta-galactose dehydrogenase. This enzyme with Mr 64,000 is lost at a lower rate than ribonuclease. The net charge of a protein apparently does not influence the rate with which it diffuses through the membrane. The time course of salt and protein exchange was studied to provide data for estimating the optimal conditions for the required reduction in salt concentration. To prepare small protein samples for electrophoresis or other analytical methods, which require low salt concentrations or a buffer change, drop dialysis is a fast and effective method with tolerable loss of protein. | {
"pile_set_name": "PubMed Abstracts"
} |
Application of edible coating and acidic washing for extending the storage life of mushrooms (Agaricus bisporus).
Hydrocolloid-based materials have been extensively used to coat fruit and vegetables to prolong shelf-life. The effects of different concentrations of acidic washing (acetic, ascorbic, citric and malic acids) followed by coating with gum arabic (GA), carboxymethyl cellulose and emulsified gum arabic (EGA) were evaluated on the weight loss (WL), firmness and color of mushroom. The WL of the uncoated mushrooms was significantly (p < 0.05) greater than that of the coated ones, and the minimum WL was obtained with EGA coating. The mushrooms washed with malic and ascorbic acids showed minimum and maximum of WL, respectively. Loss in firmness of the EGA-coated mushrooms was by 21% (the minimum of loss), while loss value of the uncoated ones was by 39% (the maximum of loss). Firmness of mushrooms was not influenced by the acid type. Concentration of the acid significantly (p < 0.05) influenced the firmness of mushrooms, and at the lowest concentration of acid (1%), the mushrooms tissue was firmest. The L* value of the mushrooms coated with GA was higher than that of others. A significant (p < 0.05) decrease in L* value and a significant (p < 0.05) increase in a* and b* values occurred in the mushrooms washed with acetic acid. Overall, washing with 1% citric or malic acid followed by coating with EGA resulted in minimum decrease in WL and firmness of the mushrooms. | {
"pile_set_name": "PubMed Abstracts"
} |
Intraoperative colonic irrigation with povidone iodine. An effective method of wound sepsis prevention.
In the ten-year period between 1975 and 1986, 367 patients underwent colonic resection with subsequent anastomosis using intraoperative colonic irrigation with 10 percent povidone iodine. One hundred thirty three patients underwent resection of the right or transverse colon, whereas 233 patients had left hemicolectomy with low anterior anastomosis or reanatomosis. Twenty individuals underwent emergency resection for perforation and temporary end colostomy. Nineteen of these patients returned for definitive reanastomosis as part of a two-stage procedure. The rate of wound infection, and/or intra-abdominal abscess formation was retrospectively reviewed and found to be completely nonexistent in these patients. This study examines the various techniques used to reduce the rate of wound infection after colonic surgery and addresses the concept of intraoperative povidone iodine irrigation. | {
"pile_set_name": "PubMed Abstracts"
} |
Simple and rapid detection of Salmonella strains by direct PCR amplification of the hilA gene.
The suitability of a PCR procedure using a pair of primers targeting the hilA gene was evaluated as a means of detecting Salmonella species. A total of 33 Salmonella strains from 27 serovars and 15 non-Salmonella strains from eight different genera were included. PCR with all the Salmonella strains produced a 784 bp DNA fragment that was absent from all the non-Salmonella strains tested. The detection limit of the PCR was 100 pg with genomic DNA and 3 x 10(4) c.f.u. ml(-1) with serial dilutions of bacterial culture. An enrichment-PCR method was further developed to test the sensitivity of the hilA primers for the detection of Salmonella in faecal samples spiked with different concentrations of Salmonella choleraesuis subsp. choleraesuis serovar Typhimurium. The method described allowed the detection of Salmonella Typhimurium in faecal samples at a concentration of 3 x 10(2) c.f.u. ml(-1). In conclusion, the hilA primers are specific for Salmonella species and the PCR method presented may be suitable for the detection of Salmonella in faeces. | {
"pile_set_name": "PubMed Abstracts"
} |
Fingerprinting G protein-coupled receptor signaling.
Heterotrimeric guanine nucleotide-binding protein (G protein)-coupled receptors (GPCRs) control a wide diversity of cellular responses throughout biology. Each GPCR couples to a distinct array of members of the G protein family to control the specificity and diversity of these responses and ultimately determines the therapeutic efficacy of drugs that target these receptors. In this issue of Science Signaling, Masuho et al. developed an approach to broadly defining these GPCR coupling fingerprints. | {
"pile_set_name": "PubMed Abstracts"
} |
[Management of adolescents in pediatric hospitals. A national survey].
Hospital care of adolescents is a challenge for pediatric teams because of the characteristics and specific problems of this age group. In 1996, a questionnaire was sent to all French public pediatric wards, 300 (i.e., 78%) of which participated. The goal of this survey was to investigate the facts and limitations encountered with hospitalization of patients 12 years and older. Data show that for more than half of the pediatric wards, the adolescent patient admission rate is higher than 10%. The upper age for hospitalization shows a shift towards adulthood, with 73% of the wards admitting adolescents up to 18 years of age. The main reasons for pediatric admission in this age group are somatic complaints, chronic diseases and suicide attempts. Psychosocial problems and psychiatric disorders are perceived as the most difficult to manage. However, a majority of pediatric wards appears to have an environment suitable for multidisciplinary networking. At the time of the survey, 39 wards (16%) had beds specifically destined for adolescents. These wards differed from others by their higher number of suicidal and anorexic inpatients. Our study shows that pediatric wards are in the avant-garde of adolescent hospital care and it brings new data on the various problems encountered in these patients. It stresses the special needs of pediatric teams today in the field of adolescent medicine and calls for the development of specific educational programs. | {
"pile_set_name": "PubMed Abstracts"
} |
Cor triatriatum sinister in a dog.
This report describes the transthoracic and transesophageal echocardiographic features of cor triatriatum sinister in an asymptomatic 6-year-old male French bulldog. Although cor triatriatum sinister represents a well-known and widely described cardiac malformation in humans, its description in the canine population is rare. In this clinical case, non-invasive echocardiographic techniques were helpful in visualizing and characterizing the lesion, allowing a valuable assessment of the malformation, and its hemodynamic consequences. | {
"pile_set_name": "PubMed Abstracts"
} |
A comparison of osmotic dilators, Lamicel and Dilapan, and a prostaglandin E1 analogue, gemeprost, for ripening the cervix before legal abortion.
66 primigravid women were allocated at random to receive either intravaginal application of the prostaglandin El analogue, gemeprost, or intracervical insertion of 1 of 2 osmotic dilators, Lamicel or Dilapan, 3 hours before legal abortion at 7-14 weeks gestation. Insertion of the dilators was not possible in 5 patients. All 3 methods were otherwise equally effective in achieving cervical dilatation and there was no difference in the need for or resistance to further dilatation between the 3 groups. Gemeprost was the most easily administered, and would be the most appropriate for routine preoperative use. | {
"pile_set_name": "PubMed Abstracts"
} |
Operational diagnostic criteria for chronic migraine: expert opinion.
The prevalence, disability, progression, and treatment needs associated with chronic migraine (CM) mandate epidemiological, clinical, and basic research to better understand the clinical course of this disorder and to facilitate development of more effective therapies. Such efforts have been significantly impeded by lack of agreement within the headache specialist community of the most appropriate diagnostic criteria for CM. This paper reviews the pertinent nosological literature and extensive field testing already performed. We recommend that the International Classification of Headache Disorders-3β criteria for CM be modified. We would remove the need for 5 prior migraine attacks and would replace "Headache considered by patient to be onset migraine and relieved by a triptan or an ergotamine derivative" with "criteria A and B for 1.5 probable migraine." The proposed criteria are guided by the aims of accurately characterizing patients with migraine who develop primary chronic daily headache, reflecting the large numbers of patients with CM in clinical practice, and facilitating research into a disorder that is an academic and clinical priority. | {
"pile_set_name": "PubMed Abstracts"
} |
Postnatal undernutrition: effect on antral gastrin levels at a later age.
In rats undernutrition from birth to 14 days of age resulted in retardation of growth and diminution of antral gastrin concentration. When the 14-day-old undernourished rats were nutritionally rehabilitated, they grew at a faster rate, and at 27 days of age their body weight and the weight of various tissues of the gastrointestinal tract including the antrum reached the levels of the well-nourished littermate controls. In spite of this, antral gastrin concentration was found to be about one-half of that of the well-nourished littermates. | {
"pile_set_name": "PubMed Abstracts"
} |
Never mind the spider: late positive potentials to phobic threat at fixation are unaffected by perceptual load.
Research suggests that processing of emotional stimuli may be eliminated if a concurrent task places sufficient demands on attentional resources. To test whether this holds for stimuli with strong emotional significance, pictures of spiders as well as mushrooms were presented at fixation to spider-fearful and non-fearful participants. Concurrently, perceptual load was manipulated in two levels with a peripheral letter discrimination task. Results of event-related potentials showed that, compared with non-fearful participants, spider-fearful participants showed greater late positive potentials (LPP) to spiders than mushrooms, which provides a manipulation check that spiders were emotionally meaningful to spider-fearful participants. Critically, this effect was not affected by level of perceptual load. These findings suggest that strong emotional stimuli at fixation may resist manipulations of perceptual load. | {
"pile_set_name": "PubMed Abstracts"
} |
[Membrane-selective electrodes for drug analysis. Note II].
Seven membrane-selective electrodes with PVC matrix and liquid-membrane for N-butylscopolamine with different electroactive materials are presented. These electrodes have a linear response in the concentration range of 10(-6) - 10(-2) M N-butylscopolamine bromide, with a detection limit between 4.58 x 10(-7)M and 1.09 x 10(-6)M. These electrodes were used with good results for quantitative assay by direct potentiometry and potentiometric titration of N-butylscopolamine bromide from pharmaceutical formulations. Recovery was between 95.50% and 99.20% for N-butylscopolamine bromide of injectable solutions. | {
"pile_set_name": "PubMed Abstracts"
} |
Role of heat shock protein HSP70-2 in spermatogenesis.
The HSP70 heat-shock proteins are molecular chaperones that assist other proteins in their folding, transport and assembly into complexes. Most of these proteins are either constitutively expressed or their expression is induced by heat shock and other stresses. However, two members of the Hsp70 family (HSP70-2 and HSC70T in mice) are regulated developmentally and expressed specifically in spermatogenic cells. The HSP70-2 protein is synthesized during the meiotic phase of spermatogenesis and is abundant in pachytene spermatocytes. The knockout approach was used to determine whether HSP70-2 is a chaperone for proteins involved in meiosis. Male mice lacking HSP70-2 were infertile while females lacking HSP70-2 were fertile. Spermatogenic cell development was arrested in prophase of meiosis I at the G2-M-phase transition and late pachytene spermatocytes were eliminated by apoptosis, resulting in an absence of spermatids. HSP70-2 is required for Cdc2 to form a heterodimer with cyclin B1, suggesting that it is a chaperone necessary for the progression of meiosis in the germ cells of male mice. HSP70-2 is also associated with the synaptonemal complex and desynapsis is disrupted in male mice lacking this protein. Homologues of HSP70-2 are present in the testes of many animals, suggesting that the role of this spermatogenic cell chaperone is conserved across phyla. | {
"pile_set_name": "PubMed Abstracts"
} |
Host and clinical aspects in patients with benign migratory glossitis.
Investigate the association of clinical, cytological and genetic characteristics with benign migratory glossitis (BMG). Sample consisted of 175 patients, 44 with BMG and 131 control patients. Clinical examination and DMFT index were assessed. Cytological evaluation determined cell morphology and morphometry. Genetic evaluation was performed by analysing IL6 polymorphisms by real-time PCR. Univariate and multivariate analyses were performed (p<0.05). There was a higher level of anxiety, DMFT score and a prevalence of fissured tongue in BMG group. A high mean nuclear/cytoplasmic area ratio was observed in patients with BMG. There was predominance of Papanicolaou class II I BMG group. IL6 allele G rs2069843 polymorphism was associated with BMG in the dominant model. In multivariate analysis, DMFT and anxiety scale remained associated with BMG. | {
"pile_set_name": "PubMed Abstracts"
} |
Long-term observation of baboons, rhesus monkeys, and chimpanzees inoculated with HIV and given periodic immunosuppressive treatment.
Baboons, rhesus monkeys, and chimpanzees were injected with the human immunodeficiency virus (HIV) and monitored for up to 4 years. Various immunosuppressive regimens were used during this time in attempts to induce development of the acquired immune deficiency syndrome (AIDS). No infectious virus was recovered or anti-HIV antibodies detected in the baboons and rhesus monkeys. Virus has been recovered from lymphocyte cultures of all five of the chimpanzees at intermittent periods following inoculation. The chimpanzees developed anti-HIV antibodies from 1 to 5 months after virus inoculation and had circulating antibodies that neutralized HIV. All the infected animals were capable of in vitro lymphocyte blastogenic responses to recombinant envelope and core HIV antigens. Despite immunosuppressive therapies and evidence of some immunologic abnormalities, none of the five chimpanzees has yet developed AIDS or a related disorder. | {
"pile_set_name": "PubMed Abstracts"
} |
What information should be given to women invited for mammographic screening for breast cancer?
Mammography is the only proven frontline screening method for breast cancer. Following the demonstration of a reduction in breast cancer mortality with mammography, population mammographic screening services have been instituted, and there has been discussion in the medical literature of how to convey the pros and cons of screening to invited women. Much of the discussion has focused on the negative aspects of screening, such as false-positive and negative screens, overdiagnosis and anxiety. Also, some commentators have advocated rather cumbersome amounts of quantitative information. In this article we review the original evidence on the positive and negative aspects of screening, and show that the latter may have been exaggerated in the past. We suggest a few simple and clear points that should be made to the invited women, summarizing the positive and negative aspects without a mass of confusing statistics. | {
"pile_set_name": "PubMed Abstracts"
} |
Vasculitic neuropathy mimicking Guillain-Barré syndrome.
Vasculitic neuropathy classically manifests as a subacute mononeuritis multiplex or polyneuropathy. Patients with a Guillain-Barré syndrome (GBS)-like presentation are usually not considered to have an underlying vasculitis. We describe 2 patients with rapidly progressive areflexic paralysis that was initially diagnosed as GBS, in whom vasculitic neuropathy was found histologically. | {
"pile_set_name": "PubMed Abstracts"
} |
A general, convergent strategy for the construction of indolizidine alkaloids: total syntheses of (-)-indolizidine 223AB and alkaloid (-)-205B.
N-Toluenesulfonyl aziridines comprise effective second electrophiles in the solvent controlled three-component linchpin union of silyl dithianes for the stereocontrolled convergent elaboration of protected 1,5-amino alcohols. This tactic, in conjunction with a one-flask sequential cyclization, constitutes an effective general strategy for the construction of indolizidine and related alkaloids, illustrated here with the total syntheses of (-)-indolizidine 223AB (1) and alkaloid (-)-205B (2). | {
"pile_set_name": "PubMed Abstracts"
} |
Studies on adsorption of crystal violet dye from aqueous solution onto coniferous pinus bark powder (CPBP).
The present study shows that the coniferous pinus bark powder (CPBP) can be used as a potential adsorbent for the removal of crystal violet (basic dye) from aqueous solutions. Experiments were carried out as a function of contact time, concentration, temperature, pH and dosage. The amount of dye uptake was found to vary with increasing initial solution pH and maximum adsorption was observed at pH 8. The equilibrium was attained in 2h. The amount of dye uptake (mg/g) was found to increase with increase in dye concentration and contact time. The % adsorption was found to decrease with increase in amount of adsorbent. The thermodynamic parameters were also calculated and the positive value of DeltaH degrees indicates the endothermic nature of adsorption. The applicability of the three isotherm's model for the present data follows the order: Langmuir>Temkin>Freundlich. The kinetics of crystal violet on to the adsorbent can be described well by pseudo-second order>Elovich>pseudo-first order equation. | {
"pile_set_name": "PubMed Abstracts"
} |
Blood flow regulation by S-nitrosohemoglobin in the physiological oxygen gradient.
The binding of oxygen to heme irons in hemoglobin promotes the binding of nitric oxide (NO) to cysteinebeta93, forming S-nitrosohemoglobin. Deoxygenation is accompanied by an allosteric transition in S-nitrosohemoglobin [from the R (oxygenated) to the T (deoxygenated) structure] that releases the NO group. S-nitrosohemoglobin contracts blood vessels and decreases cerebral perfusion in the R structure and relaxes vessels to improve blood flow in the T structure. By thus sensing the physiological oxygen gradient in tissues, hemoglobin exploits conformation-associated changes in the position of cysteinebeta93 SNO to bring local blood flow into line with oxygen requirements. | {
"pile_set_name": "PubMed Abstracts"
} |
Ex vivo activated memory T-lymphocytes as adoptive cellular therapy of human renal cell tumour targets with potentiation by cis-diamminedichloroplatinum(II).
To determine if cis-diamminedichloroplatinum(II) (CDDP) enhances, by immunomodulation, ex vivo anti-tumour cytotoxicity of autolymphocyte therapy (ALT) against a chemotherapy-resistant tumour, and if lysis is mediated through T-cells, NK-cells, or both. Human renal cell carcinoma (RCC) target cells were derived from surgical specimens and incubated in complete medium (CM) with CDDP, or in CM alone (control group). ALT-cells were prepared from autologous whole peripheral blood mononuclear cells (PBMC) or NK-cell (CD56)-depleted PBMC obtained before surgery. Tumour cells from each group were labelled with chromium-51(51Cr) and used as targets for ALT-cells and PBMC in a standard (4 h) and delayed (18 h) 51Cr-release assay at varying effector/target ratios (E:T). Tumour cells incubated in CDDP showed enhanced lysis, as measured by the 51Cr-release assay, at all E:T tested. This lysis was significantly greater during the 18 h assay and when ALT-cells were used as the effector cells rather than PBMC. Depletion of CD45RO+ (memory) T-cells from the ALT cell population precluded both the 4 and 18 h tumour cell lysis. Depletion of NK-cells (CD56+) diminished the ex vivo lysis of autologous targets during the 4 but not the 18 h assay. ALT-cells derived from two patients demonstrated ex vivo tumour-specificity against autologous and allogeneic RCC. These data suggest that: (i) ex vivo activated memory T-cells are the principal component demonstrating significant tumour-specific cytotoxicity of ALT-cells against RCC tumour targets; (ii) CDDP may alter the physical properties of tumour cells rendering them susceptible to immune-mediated attack; (iii) the combination of ALT and CDDP may lead to increased therapeutic efficacy in patients with metastatic RCC. | {
"pile_set_name": "PubMed Abstracts"
} |
Emergency pain management: a Canadian Association of Emergency Physicians (CAEP) consensus document.
Pain is the most common presenting complaint heard in Emergency Medicine, yet it is poorly controlled. Evaluation of this pain should be with use of objective pain scales completed by the patient, not relying on physician impression. Treatment modalities available in the Emergency Department, a review of medications and their dosing as well as specifics to pediatric pain management are presented. The final section reviews situation or diagnosis specific pain control: headaches, renal colic, polytrauma victims, abdominal pain, soft tissue injury and acute arthritis. These recommendations are based on a Canadian Association of Emergency Physicians (CAEP) consensus conference held in April 1993. The literature was reviewed extensively and used as the basis for the consensus workshops and discussion. At the writing of the consensus paper, however, no specific ideas were borrowed from any one article. The appended bibliography is suggested reading, selected from the larger literature review. There are to date few controlled multi centre trials in overall pain management that would allow guidelines to be produced. | {
"pile_set_name": "PubMed Abstracts"
} |
Generation of mononucleate cells from post-mitotic myotubes proceeds in the absence of cell cycle progression.
The remarkable regenerative ability of adult urodele amphibians depends in part of the plasticity of differentiated cells at the site of injury. Limb regeneration proceeds by formation of a mesenchymal growth zone or blastema under the wound epidermis at the end of the stump. Previous work has shown that when cultured post-mitotic newt myotubes are introduced into the blastema, they re-enter the cell cycle and undergo conversion to mononucleate cells which divide and contribute to the regenerate [11, 13]. In order to investigate the interdependence of these two aspects of plasticity, we have blocked cell cycle progression of the myotubes either by X-irradiation or by transfection of the CDK4/6 inhibitor p16. In each case, the efficacy of the block was evaluated in culture after activation of S phase re-entry by serum stimulation. The experimental myotubes were implanted into limb blastemas along with a differentially labelled control population of myotubes containing an equivalent number of nuclei. X-irradiated myotubes gave rise to mononucleate cells in the limb blastema, and the progeny were blocked in respect of S phase entry. Comparable results were obtained with the p16-expressing myotubes. We conclude that progression through S or M phase is not required for generation of mononucleate cells and suggest that such cells may arise by budding from the muscle syncytium. | {
"pile_set_name": "PubMed Abstracts"
} |
High-resolution AFM imaging of intact and fractured trabecular bone.
Nanoscale structural analyses of biomineralized materials can frequently help elucidate important structure-function relationships in these complex organic-inorganic composites. Atomic force microscope (AFM) imaging of the exterior surface of trabecular bone reveals a densely woven structure of collagen fibrils, banded with a 67-nm periodicity, and densely packed mineral plates. The mineral plates on the collagen fibrils overlap and exhibit a large range of plate diameters from 30 to 200 nm. On the collagen fibrils, small nodular features, spaced 20-30 nm, run perpendicular to the fibrils. In some cases, these nodules are also seen on filaments extending between collagen fibrils. We hypothesize that these protrusions are noncollagenous proteins such as proteoglycans and may have collapsed into compact structures when the sample was dried. AFM images of pristine fractured surfaces reveal a dense array of mineral plates. In a few isolated locations, short sections of bare collagen fibrils are visible. In other regions, the existence of the underlying collagen fibrils can be inferred from the linear patterns of the mineral plates. Fractured samples, rinsed to remove mineral plates, reveal separated collagen fibrils on the fractured surfaces. These fibrils are often covered with protrusions similar to those observed on the exterior surfaces but are less organized. In addition, as on the exterior surfaces, there are sometimes small filaments extending between neighboring collagen fibrils. These studies provide important insights into the nanostructured architecture of this complex biocomposite. | {
"pile_set_name": "PubMed Abstracts"
} |
Noncompetitive blocking of human GLUT1 hexose transporter by methylxanthines reveals an exofacial regulatory binding site.
Glucose transporter (GLUT)1 has become an attractive target to block glucose uptake in malignant cells since most cancer cells overexpress GLUT1 and are sensitive to glucose deprivation. Methylxanthines are natural compounds that inhibit glucose uptake; however, the mechanism of inhibition remains unknown. Here, we used a combination of binding and glucose transport kinetic assays to analyze in detail the effects of caffeine, pentoxifylline, and theophylline on hexose transport in human erythrocytes. The displacement of previously bound cytochalasin B revealed a direct interaction between the methylxanthines and GLUT1. Methylxanthines behave as noncompetitive blockers (inhibition constant values of 2-3 mM) in exchange and zero-trans efflux assays, whereas mixed inhibition with a notable uncompetitive component is observed in zero-trans influx assays (inhibition constant values of 5-12 mM). These results indicate that methylxanthines do not bind to either exofacial or endofacial d-glucose-binding sites but instead interact at a different site accessible by the external face of the transporter. Additionally, infinite-cis exit assays (Sen-Widdas assays) showed that only pentoxifylline disturbed d-glucose for binding to the exofacial substrate site. Interestingly, coinhibition assays showed that methylxanthines bind to a common site on the transporter. We concluded that there is a methylxanthine regulatory site on the external surface of the transporter, which is close but distinguishable from the d-glucose external site. Therefore, the methylxanthine moiety may become an attractive framework for the design of novel specific noncompetitive facilitative GLUT inhibitors. | {
"pile_set_name": "PubMed Abstracts"
} |
Sialendoscopy in treatment of adult chronic recurrent parotitis without sialolithiasis.
The aim of this prospective study was to evaluate the efficacy of sialendoscopy in the management of adult chronic recurrent parotitis without sialolithiasis. In addition, preliminary results of an initial randomized placebo-controlled trial of single-dose intraductal steroid injection given concurrently with sialendoscopy, are presented. Forty-nine adult patients with chronic recurrent parotitis without sialoliths were included in this study. They underwent sialendoscopy and were randomized to receive either a concurrent intraductal injection of isotonic saline solution or 125 mg of hydrocortisone. Symptom severity was evaluated with visual analogue scale (VAS) and by recording symptom frequency and course with a multiple-choice questionnaire completed preoperatively and at 3, 6, and 12 months after the procedure. The mean VAS score was 5.6 preoperatively and dropped to 2.9 at 3 months, 3.0 at 6 months, and 2.7 at 12 months after the procedure. The VAS score and the frequency of symptoms were significantly lower at 3 (p < 0.001), 6 (p < 0.001) and 12 (p < 0.001) months after the procedure when compared with the preoperative scores indicating that sialendoscopy reduces the symptoms of recurrent parotitis. However, complete permanent resolution of symptoms was rare. Single-dose steroid injection concomitant to sialendoscopy provided no additional benefit, but the current study is not sufficiently powered to determine a clinical difference between the steroid and non-steroid groups. Sialendoscopy appears to reduce the symptoms of chronic recurrent parotitis. While total permanent symptom remission is rare, sialendoscopy can be considered a safe and relatively efficacious treatment method for this patient group. | {
"pile_set_name": "PubMed Abstracts"
} |
The influence of total mesorectal excision on local recurrence and survival in rectal cancer patients: a population-based study in Greater Amsterdam.
To determine retrospectively in a population-based setting, the influence of the introduction of total mesorectal excision (TME) on local recurrence and survival in patients with rectal carcinoma. All rectal carcinomas diagnosed during 1988-1991 (979 patients, conventional surgery with blunt dissection of the rectum) and 1998-2000 (890 patients, TME resection) were selected from the Amsterdam Cancer Registry. For all patients who underwent a macroscopically radical resection in the absence of distant dissemination, information on the occurrence of local recurrent disease and distant metastasis was collected. The cumulative 5-year recurrence rate decreased significantly from 20% for patients diagnosed in 1988-1991 to 11% in 1998-2000. Stage (T-category, nodal status), period of diagnosis (conventional surgery vs. TME resection), radiotherapy, and chemotherapy were independent variables of local recurrence in multivariate analysis. There was a non-significant trend for improved 5-year relative survival for all rectal carcinoma cases from 52% (95% CI 48-55) for patients diagnosed in 1988-1991 to 59% (95% CI 55-63) in 1998-2000. A significant decrease in local recurrence and a trend for improved relative survival were observed. The broad introduction of TME and the shift towards preoperative radiotherapy are the most plausible explanations for these observations. | {
"pile_set_name": "PubMed Abstracts"
} |
Autoimmune retinopathies: a report of 3 cases.
To describe 3 representative cases of autoimmune retinopathy (AIR). Clinical records of patients with a diagnosis of AIR were analyzed for demographic data, clinical findings, ancillary and laboratory tests, and treatment employed. Three female patients diagnosed with AIR had bilateral reduction of electroretinogram amplitudes and elevation of visual field threshold within the central 30 degrees of the visual field that was disproportionately more severe than the clinical findings of retinal degeneration. The diagnoses were cancer-associated retinopathy, non-neoplastic AIR, and hereditary retinal dystrophy with secondary inflammation. Optic nerve involvement was also present in all cases. The patient with non-neoplastic AIR was successfully treated with systemic corticosteroids and immunomodulatory agents. High index of suspicion is essential for an early diagnosis of AIR. Visual function and electrophysiological tests should be included in the initial workup of patients who present with suggestive clinical signs and symptoms of AIR. | {
"pile_set_name": "PubMed Abstracts"
} |
Secretion of glucagon-like peptide-1 (GLP-1) in type 2 diabetes: what is up, what is down?
The incretin hormones gastric inhibitory polypeptide and especially glucagon-like peptide (GLP) have an important physiological function in augmenting postprandial insulin secretion. Since GLP-1 may play a role in the pathophysiology and treatment of type 2 diabetes, assessment of meal-related GLP-1 secretory responses in type 2 diabetic patients vs healthy individuals is of great interest. A common view states that GLP-1 secretion in patients with type 2 diabetes is deficient and that this applies to a lesser degree in individuals with impaired glucose tolerance. Such a deficiency is the rationale for replacing endogenous incretins with GLP-1 receptor agonists or re-normalising active GLP-1 concentrations with dipeptidyl peptidase-4 inhibitors. This review summarises the literature on this topic, including a meta-analysis of published studies on GLP-1 secretion in individuals with and without diabetes after oral glucose and mixed meals. Our analysis does not support the contention of a generalised defect in nutrient-related GLP-1 secretory responses in type 2 diabetes patients. Rather, factors are identified that may determine individual incretin secretory responses and explain some of the variations in published findings of group differences in GLP-1 responses to nutrient intake. | {
"pile_set_name": "PubMed Abstracts"
} |
Influence of surgical resection and post-operative complications on survival following adjuvant treatment for pancreatic cancer in the ESPAC-1 randomized controlled trial.
The influence of type of surgery and occurrence of post-operative complications on survival following adjuvant therapy for pancreatic cancer are uncertain. Cox proportional hazard modelling was used to investigate the influence of type of surgery and the presence of complications on survival in conjunction with clinico-pathological variables in the 550 patients of the ESPAC-1 adjuvant randomized controlled trial. Standard Kausch-Whipple (KW) was performed in 282 (54%) patients, 186 (35%) had a pylorus-preserving (PP) KW, 39 (7%) had a distal pancreatectomy and 21 (4%) had a total pancreatectomy. Post-operative complications were reported in 140 (27%) patients. PP-KW patients survived longer with a median (95% CI) survival of 19.9 (17.3, 23.1) months compared to 14.8 (13.0, 16.7) for KW patients (chi(2)(LR) = 15.1, p < 0.001). KW patients were more likely however to have R1 margins (67 (24%) vs. 29 (16%), chi(2) = 4.59, p = 0.032), poorly differentiated tumours (70 (26%) vs. 19 (10%), chi(2) = 18.65, p < 0.001) and positive lymph nodes (165 (60%) vs. 81 (44%), chi(2) = 11.32, p < 0.001). Post-operative complications did not significantly affect survival. Independent prognostic factors were tumour grade, nodal status and tumour size but not type of surgery or post-operative complications. There was a survival benefit for chemotherapy irrespective of the type of surgery or post-operative complications. The KW and PP-KW procedures did not significantly influence the hazard of death in the presence of tumour staging, demonstrating that ESPAC-1 surgeons showed good judgement in their choice of operation. Post-operative complications did not adversely affect the survival benefit from adjuvant chemotherapy. | {
"pile_set_name": "PubMed Abstracts"
} |
Effect of dust exposure in the cotton felt industry.
Respiratory histories and preshift and postshift spirometry were recorded for 90 cotton felt workers and 54 brick workers. Environmental monitoring included area sampling by vertical elutriator and cyclone and personal sampling for respirable dust by cyclone. The prevalence of mill fever and byssinosis was 31% and 5%, respectively, in the cotton workers. Significant dose-response effects were detected for both elutriator and cyclone dust measurements and change in forced expiratory volume at 1 s over the shift. A dose-response relationship was also found for the brick workers. | {
"pile_set_name": "PubMed Abstracts"
} |
Degradation mechanism of Methyl Orange by electrochemical process on RuO(x)-PdO/Ti electrode.
The electrochemical degradation of Methyl Orange in 0.1 M NaCl solution over RuO(x)-PdO/Ti anode was investigated. Chemical oxygen demand (COD), ion chromatography (IC), Fourier Transform Infrared Spectroscopy (FTIR) and Gas chromatography-mass spectrometry (GC-MS) were employed to detect the intermediates formed during the electrochemical degradation. In the present reaction system, Methyl Orange could be effectively degraded. After 1 h treatment, the discoloration could reach 97.9% with COD removal of 57.6%. The results indicated that in the presence of chloride, the electrolysis was able to oxidise the dye with partial mineralisation of carbon, nitrogen and sulfur into CO(2), NO(-)(3) and SO(2-)(4), respectively. After 8 h electrolysis, 62% of sulfur contained in Methyl Orange was transformed to SO(4)(2-), and 17.6% of nitrogen changed to NO(3)(-). The intermediates during electroprocess were detected to be low molecular weight compounds, chlorinated compounds, derivatives of benzene and long chain alkanes. Based on these data, a possible degradation mechanism of Methyl Orange was proposed. | {
"pile_set_name": "PubMed Abstracts"
} |
[Evaluation of depression in elderly people living in nursing homes: a study involving 35 people].
Depression in the elderly is often inadequately diagnosed and insufficiently treated. Regardless of the nature of the depression, the influence and the impact of the biological, situational, social and psychological factors would be more important in old subjects than in young ones when the disorder occurs. The nursing home, as an institution, is another factor facilitating the appearance of depression. The aim of our survey is to determine the prevalence of depression in old people living in a nursing home and to evaluate the degree of their autonomy. Our study is a transverse, descriptive and analytical survey carried out on 35 old people at a nursing home in Sfax. Forty residents were excluded from this survey for reasons of dementia (25 cases), debility (5 cases), disabling psychiatric pathologies (4 cases), deafness (5 cases) and one resident who refused the interview. The evaluation has been achieved using two scales specific to the geriatric practice: • The scale of depression: GDS (geriatric depression Scale) applied to 30 items. • The scale of autonomy: IADL (Instrumental Activities of Daily Living) applied to 6 items. • The examined population was composed of 35 people aged from 65 to 93 with a sex ratio of 1.05. • 51.4% of the residents were in a state of depression. • Depression was more frequent in: • Female subjects (58.8% of women compared to 44.4% of men) • Subjects aged less than 70 (66% of subjects aged less than 70 versus 40% of older subjects) • 17.1% of the residents were independent, 42.9% were dependent and 40% were heavily dependent. Depression in the elderly is related to several depressice factors particularly for patients living in institution. This situation needs very important adaptive capacities. | {
"pile_set_name": "PubMed Abstracts"
} |
Theta-burst stimulation: remote physiological and local behavioral after-effects.
Theta-burst stimulation (TBS), a novel repetitive transcranial magnetic stimulation (TMS) protocol, is capable of suppressing the amplitude of contralateral motor-evoked potentials (MEP) for several minutes after the end of a conditioning train over the motor cortex. It remains unknown whether TBS leads to effects on motor cortical excitability when applied to contralateral brain sites distant but connected to motor cortex and whether TBS triggers measurable changes in force control. Subjects received bursts (50 Hz) of three subthreshold magnetic stimuli repeated at 5 Hz for 20 s (TBS-300) or 40 s (TBS-600) over the hand area of the left motor cortex (M1(LEFT)). With TBS-300, conditioning of right motor cortex (M1(RIGHT)), right dorsal premotor cortex (PMd(RIGHT)), and a mid-occipital (MO) region also were tested. Corticospinal excitability was probed by evoking MEPs in abductor pollicis brevis (APB) muscle by single suprathreshold stimuli over M1(LEFT) or M1(RIGHT) before and after TBS. Force level control was assessed in an isometric right thumb abduction task. With TBS-600, the time course of physiological and behavioral changes was monitored. TBS over either of the motor cortices reduced the amplitude of MEP in the contralateral APB and increased it in the ipsilateral APB. In contrast, conditioning TBS over PMd(RIGHT) or MO did not modify MEP size. Post-TBS right thumb force level control was impaired, with contralateral M1(LEFT) stimulation only, for a duration of at least 5 min. TBS may induce remote physiological effects and reveals local functional properties of the underlying brain region. | {
"pile_set_name": "PubMed Abstracts"
} |
Diastereoselective room-temperature Pd-catalyzed alpha-arylation and vinylation of arylmandelic acid derivatives.
Palladium-catalyzed alpha-arylation and vinylation of dioxolane (S,S)-I, easily obtained from (S)-mandelic acid, proceeds with high yields and excellent diastereoselectivity at room temperature employing commercially available P(t-Bu)(3).HBF(4) and Pd(OAc)(2) as a catalytic precursor system. This method displays general utility for a large variety of aryl, heteroaryl, and vinyl bromides. | {
"pile_set_name": "PubMed Abstracts"
} |
Ultrasonographic assessment of maternal cardiac function and peripheral circulation during normal gestation in dogs.
The aim of this study was to describe changes in cardiac morphology, systolic function and some peripheral hemodynamic parameters during normal pregnancy in dogs. Twenty healthy bitches, 10 pregnant (PG) and 10 non-pregnant controls (CG), were evaluated every 10 days using echocardiography from day 0 of the estrus cycle to parturition or to day 65 for the PG and CG groups, respectively. Systolic blood pressure (SBP) and uterine artery resistance index (RI) were also assessed. Throughout the study, the shortening fraction and cardiac output increased up to 30% vs. 5% (P<0.01) and 45% vs. 2% (P<0.01) in the PG and CG groups, respectively. In contrast, SBP and RI diminished up to 20% vs. 1% (P<0.01) and 29% vs. 0% (P<0.01) in the PG and CG groups, respectively. In conclusion, a decrease in afterload, an increase in cardiac output and cardiac hypertrophy appear to be the result of the hemodynamic modifications occurring during pregnancy in dogs. | {
"pile_set_name": "PubMed Abstracts"
} |
Follicular wave status at the beginning of the FSH treatment modifies reproductive features in superovulated sheep.
In the current study we investigated whether the developmental status of the two largest follicles (LF1 and LF2) at the time of administration of the first two doses (0 and 12 h) of FSH of a superovulatory treatment influences periovulatory events and embryo yields in sheep. A larger size of LF1 was negatively correlated with embryo recovery (r=-0.608 for 0 h and r=-523 for 12 h, p<0.05), fertilization (r=-0.464 for 12 h, p<0.05) and viability (r=-0.775 for 12 h, p<0.005). Embryo viability rates were also lower when a higher difference between LF1 and LF2 (r=-0.839 for 0 h and r=-0.761 for 12 h, p<0.01) and a smaller size of LF2 (r=0.877 for 0 h and r=0.622 for 12 h, p<0.01) were observed. This indicates the existence of a limit in the follicular size that will be able to give rise a viable embryo. Conversely, a larger size of LF2 at the time of administration of the first two FSH doses was correlated with reduced recovery rates (r=-0.884 for 0 h and r=-0.706 for 12 h, p<0.01), whilst a decreasing size of LF1 and LF2 was correlated with an increased ovulation rate and recovered embryos. The dominance effect appeared to affect the timing of the preovulatory LH surge. Ewes with a higher difference between LF1 and LF2 displayed earlier LH surges (r=-0.420 for 0 h and r=-0.401 for 12 h, p<0.05) which were related to a higher number of non viable embryos (r=-0.777, p<0.05). The fact that superovulatory yields were affected by, both LF1 and LF2 supports the hypothesis of co-dominance effects in sheep. | {
"pile_set_name": "PubMed Abstracts"
} |
Combining proton and silaborane-based superhalogen anions - an effective route to new superacids as verified via systematic DFT calculations.
Based on systematic DFT calculations, silaborane-based superhalogen anions, which obey the Wade-Mingos rule, are shown to be capable of giving rise to superacids via their combination with protons. Compared to previous carborane-based systems, the acidities of the composites here are stronger in both the gas phase and solution phase. Thus, the potential of candidates based on silaborane could be greater than those based on carborane in the search for ultra-strong acidic systems. Within a given group, a higher superhalogen anion vertical electron detachment energy (VDE) generally leads to stronger acidity. This consistency arises from the dominant role of the VDE, as established through the decomposition of the gas-phase acidity into different contributions. Thus, constructing superacids from superhalogens is a rational route whose future should be positive. Besides the VDE, other effects, i.e., the deformation energy (DE) and bond dissociation energy (BDE), could also be crucial, especially in terms of the differences between the acidities of composites belonging to different groups. A comparison between the results in the gas phase and solution phase indicates that complete calculations of both gas-phase ΔGacid and solution-phase pKa values are necessary to obtain an unbiased description of the acidity. The solvation free energies of the participants in the deprotonation process, especially the conjugate acid, are responsible for the discrepancies between gas phase and solution phase behavior. | {
"pile_set_name": "PubMed Abstracts"
} |
A single mutation converts the nucleotide specificity of phenol sulfotransferase from PAP to AMP.
Sulfotransferases (STs) catalyze all the known biological sulfonations, in which a sulfuryl group from a common sulfonate donor such as 3'-phosphoadenosine 5'-phosphosulfate (PAPS) is transferred to a nucleophilic acceptor. In addition to PAPS, phenol sulfotransferase (PST), a member of the ST family, utilizes other nucleotides as substrates with much less catalytic efficiency [Lin, E. S., and Yang, Y. S. (2000) Biochem. Biophys. Res. Commun. 271, 818-822]. Six amino acid residues of PST have been chosen for mutagenesis studies on the basis of a model of PST and its sequence alignment with those of available cytosolic and membrane-anchored STs. Systematic analyses of the mutants reveal that Ser134 is important for the regulation of nucleotide specificity between 3'-phosphoadenosine 5'-phosphate (PAP) and adenosine 5'-monophosphate (AMP). Kinetic studies also indicate that Ser134 plays a key role in nucleotide binding (K(m)) but not in catalysis (kcat). Consequently, the catalytic efficiency (kcat/K(m)) of PST can be altered by 5 orders of magnitude with a mutation of Ser134. Moreover, the change in nucleotide specificity from PAP to AMP can be achieved by mutation of Ser134 to any of the following residues: Glu, Gln, Arg, and His. Roles of Lys44, Arg126, and Arg253, which interact directly with the 5'- and 3'-phosphate of PAP, were also investigated by mutagenesis and kinetic experiments. On the basis of these findings, we suggest that Ser134 is the key residue that enables PST to discriminate PAP from AMP. | {
"pile_set_name": "PubMed Abstracts"
} |
Characterization of atherosclerosis in LDL receptor knockout mice: macrophage accumulation correlates with rapid and sustained expression of aortic MCP-1/JE.
Atherosclerosis and the expression of monocyte chemoattractant protein-1 (MCP-1) were quantified in low density lipoprotein receptor knockout (LDLR KO) mice fed 1.25% cholesterol (study #1) or 0.2% cholesterol (study #2). In study #1 plasma total cholesterols leveled-off at 1800 mg/dl whereas plasma triglycerides remained low. In en face specimens of the aortic root and arch, intimal foam cells plus extracellular lipid particles accumulated and by 8 weeks the fatty streak surface area had rapidly expanded at both sites. In study #2, total cholesterols averaged 400 mg/dl and fatty streaks were 2-3-fold smaller compared to those in study #1. In study #3, LDLR KO mice were fed chow or 1.25% cholesterol, and immunostaining demonstrated a few Mac-2-positive intimal macrophages in mice fed chow, and during the first 10 weeks of hypercholesterolemia the number of intimal macrophages increased continuously. In chow-fed mice (0 weeks) there was little MCP-1 in the aorta. After 2 days of hypercholesterolemia intimal macrophages stained for MCP-1, and during the next 10 weeks recently recruited arterial macrophages also expressed MCP-1. Macrophage accumulation was highly correlated with MCP-1 expression. In study #4, feeding LDLR KO mice 1.25% cholesterol for 6 months produced atherosclerotic plaques at both sites and they contained a fibrous cap of smooth muscle cells, macrophage-foam cells, connective tissue and cholesterol crystals. In summary, LDLR KO mice fed cholesterol develop fatty streaks that transform into fibrous plaques. Hypercholesterolemia rapidly triggers MCP-1 expression in resident intimal macrophages, which is followed by the accumulation of more macrophages that also express MCP-1, suggesting that this chemokine may both initiate and amplify monocyte recruitment to the artery wall during early atherogenesis. | {
"pile_set_name": "PubMed Abstracts"
} |
Refining Early Antitumoral Drug Development.
The failure rate of development of new drugs in oncology is high, with up to 95% of drugs tested in Phase I not reaching the market. Causes behind this high failure rate are discussed here, and solutions to increase the success in the development of antitumor drugs are suggested. | {
"pile_set_name": "PubMed Abstracts"
} |
Patency and Incontinence Rates After Robotic Bladder Neck Reconstruction for Vesicourethral Anastomotic Stenosis and Recalcitrant Bladder Neck Contractures: The Trauma and Urologic Reconstructive Network of Surgeons Experience.
To review a robotic approach to recalcitrant bladder neck obstruction and to assess success and incontinence rates. Patients with a recalcitrant bladder neck contracture or vesicourethral anastomotic stenosis who underwent robotic bladder neck reconstruction (RBNR) were identified. We reviewed patient demographics, medical history, etiology, previous endoscopic management, cystoscopic and symptomatic outcomes, urinary continence, and complications. Stricture success was anatomic and functional based upon atraumatic passage of a 17 Fr flexible cystoscope or uroflowmetry rate >15 ml/s. Incontinence was defined as the use of >1 pad per day or procedures for incontinence. Between 2015 and 2017, 12 patients were identified who met study criteria and underwent RBNR. Etiology of obstruction was endoscopic prostate procedure in 7 and radical prostatectomy in 5. The mean operative time was 216 minutes (range 120-390 minutes), with a mean estimated blood loss of 85 cc (range 5-200 cc). Median length of stay was 1 day (range 1-5 days). Three of 12 patients had recurrence of obstruction for a 75% success rate. Additionally, 82% of patients without preoperative incontinence were continent with a median follow-up of 13.5 months (range 5-30 months). There was 1 Clavien IIIb complication of osteitis pubis and pubovesical fistula that required vesicopubic fistula repair with pubic bone debridement. RBNR is a viable surgical option with high patency rates and favorable continence outcomes. This is in contrast to perineal reconstruction, which has high incontinence rates. If future incontinence procedures are needed, outcomes may be improved given lack of previous perineal dissection. | {
"pile_set_name": "PubMed Abstracts"
} |
Role for sentinel lymph node dissection in the management of large (> or = 5 cm) invasive breast cancer.
Sentinel lymph node dissection (SLND) for small, early-stage breast cancer is well accepted. However, the role of SLND for large primary breast cancer is controversial. We investigated the feasibility and clinical applicability of SLND in patients with large (> or = 5 cm) breast cancers and clinically negative axillae. A prospectively entered database was used to identify all patients who underwent surgical management of histopathologically confirmed primary breast carcinomas > or = 5 cm in diameter between September 1991 and August 2000. Patients who had clinically negative axillae and underwent SLND followed by completion axillary lymph node dissection (ALND) were selected for the study. The positivity rate, accuracy rate, and false-negative rate of SLND were determined. Of the 41 patients selected for the study, 24 had infiltrating ductal carcinoma and 17 had infiltrating lobular carcinoma. Mean tumor size was 7.12 cm (range, 5-23 cm). At least one sentinel lymph node (SLN) was identified in all cases. Thirty patients had tumor-positive SLNs. Axillary metastasis was also identified in one patient who did not have a positive SLN. Thus, SLN status accurately predicted regional nodal status in 98% (40 of 41) of cases. The false-negative rate of SLND was 3% (1 of 31). None of the three patients with SLN micrometastasis, defined as a tumor focus < or = 2 mm, had tumor deposits in nonsentinel axillary lymph nodes. Only SLN macrometastasis (> 2-mm tumor deposit) and primary tumor size > or = 7 cm predicted nonsentinel axillary metastasis with significance on multivariate analysis (P = .008 and P = .046, respectively). SLND is feasible and accurate in patients with large breast cancers and clinically negative axillae. Axillary lymph node dissection can be avoided in nearly one third of patients by focused examination of the SLN. | {
"pile_set_name": "PubMed Abstracts"
} |
Immune response in Mansonella ozzardi infection modulated by IL-6/IL-10 axis in Amazon region of Brazil.
Mansonellosis is an endemic disease in the South and Central America. In Brazil, one of the etiological agents is Mansonella ozzardi. This filarial infection is yet poorly understood, with a controversial morbity, presenting since a oligosymptoms, malaria-like signs or without complaint in humans. The knowledge of the human immune response to microfilariae infection is limited mainly by different evolutionary cycles of the parasite in the host. In addition, the prevalence of this filarial parasite infection is high in several regions of Amazonas State. A cross-sectional study was conducted in an endemic area for microfilariae of M. ozzardi (MF) infection in the Amazonas State, Brazil. Proinflammatory and regulatory cytokines (IL-2, IL-4, IL-6, IL-10, TNF, IFN-gamma, and IL-17A) were measured in cryopreserved serum using the Cytometric Bead Array techniques (CBA) in 54 patients diagnosed with M. ozzardi infection and 55 individuals without the infection were included in the study (Controls). The IL-4, IL-6 and IL-10 level increased in infected patients with MF infection, while IL-17A increased in control only. When we compared controls to patients with high or low parasite load, the increased level of IL-6 and IL-10 were maintained. IL-6 contributes to the proinflammatory activity and IL-10 modulates Th1, Th2 and Th17 immune response. Furthermore, IL-4 was detected as a marker in the MF infection and MF patients with low parasite load, indicating the action of the Th2 cell response. The complex network of cytokines acting during M. ozzardi infection depends on a fine balance to determine a host protective effect or filarial persistence. Therefore, these results suggest that the immune response in MF infection is modulated by IL-6/IL-10 axis. | {
"pile_set_name": "PubMed Abstracts"
} |
An analysis of effect of common domestic fuels on respiratory function.
Pulmonary function studies were carried out in 3318 healthy, nonsmoking asymptomatic housewives to evaluate the role of different cooking fuels in domestic use. The women used four different types of cooking fuels: biomass fuel, liquified petroleum gas (LPG), kerosene used in stoves, and a combination of two or more of these (mixed). Four parameters of ventilatory function (FVC, FEV1, PEFR and MMEF) were evaluated. A positive correlation was observed between all these parameters except PEFR with that of height, but a negative correlation was observed between the age, duration of cooking and exposure index. Mixed fuels and biomass fuels affected FVC values (F = 6.39, p = 0.0003) more adversely. Similar trend was observed for FEV1 also. Users of biomass fuel had the lowest mean value for PEFR. Small airways function represented by MMEF was the lowest in users of kerosene. In users of mixed fuels, there was a decline in FVC, FEV1 and PEFR, as the exposure increased. Thus, it is concluded that, mixed fuel has more deleterious effects on pulmonary function than other fuels. | {
"pile_set_name": "PubMed Abstracts"
} |
Health-related quality of life for adults participating in outpatient substance abuse treatment.
Interest exists in assessing health-related quality of life as one aspect of treatment effectiveness with substance abuse clients. The SF-36 Health Survey is a self-report measure assessing subjective health status along physical and mental health dimensions. Subjects were 252 adults in an outpatient, randomized clinical trial for substance abuse treatment. Subjects reported significantly more impairments in functioning when compared to U.S. population norms, but differences disappeared after three months of treatment. There was little support that quality of life functioning was significantly related to substance use during treatment. Results highlight the importance of using the SF-36 to facilitate treatment planning. | {
"pile_set_name": "PubMed Abstracts"
} |
Correlations of nitrenium ion selectivities with quantitative mutagenicity and carcinogenicity of the corresponding amines.
There is a correlation (r(adj)(2) = 0.5491-0.6338) of quantitative mutagenicity, log m, for a series of heterocyclic (HCAs) and carbocyclic (AAs) aromatic amines in Salmonella typhimurium TA 98 (18 amines) and TA 100 (15 amines) vs log S, the log of the azide/solvent selectivity of the corresponding nitrenium ion. Monocyclic aromatic amines, MAAs, are less mutagenic than other amines of similar log S. Multiple variable linear regression analysis led to a two parameter regression model, significant at the 95% confidence level for both variables, that includes log S and a ring index variable, I(rings), that is 0 for MAAs and 1 for all other amines. These models have r(adj)(2) = 0.8448 for TA 98, and 0.8927 for TA 100. Inclusion of a third variable, Clog P, increases r(adj)(2) to 0.8913 for TA 98 and 0.9011 for TA 100. This model is significant at the 95% confidence level for all variables for TA 98, but only for two of the three variables for TA 100. The confidence level is 80% for Clog P in TA 100. Quantitative carcinogenicity data in mice and rats are more weakly correlated with log S (r(adj)(2) = 0.5357 for 12 amines in mice, r(adj)(2) = 0.4216 for 10 amines in rats). Several two parameter regression models, all containing Clog P and one containing log S, adequately correlate the mouse data. | {
"pile_set_name": "PubMed Abstracts"
} |
Phototransduction: crystal clear.
Vertebrate visual phototransduction represents one of the best-characterized G-protein-coupled receptor-mediated signaling pathways. Structural analyses of rhodopsin, G protein, arrestin and several other phototransduction components have revealed common folds and motifs that are important for function. Static and dynamic information has been acquired through the application of X-ray diffraction, solution and solid-state nuclear magnetic resonance spectroscopy's, electron and atomic force microscopy's, and a host of indirect structural methods. A comprehensive understanding of phototransduction requires further structural work on individual components and their relevant complexes in solution and the native disk membrane. Given the accelerated pace of structure determination, it is anticipated that this will be the first G-protein-coupled pathway for which a complete molecular description is ultimately available. | {
"pile_set_name": "PubMed Abstracts"
} |
Influence of health education regarding correct diet on anthropometric indexes in children.
Obesity is one of the leading public health issues in the world whose significance lies, not only in its prevalence, but also in its consequences i.e. diseases that gradually develop in obese people. The aim of the study was to determine obesity prevalence among school children and the influence of health education on its prevalence. Study included pupils of 19 first grades in 8 primary schools of Osijek-Baranja County, Croatia. Body weight and height, waist and hip circumference were measured. Parameters for assessing obesity: body mass index (BMI, according to Croatian referral values), waist circumference (WC), waist and hip circumference ratio (WHR) and waist circumference and height ratio (WHtR) were measured. In order to determine whether the health education of pupils and their parents influences children's anthropometric indexes, health education regarding correct diet, obesity and its consequences and the need for life style changes in terms of daily physical activity was conducted in four primary schools. Pupils of other four primary schools were measured as a control group. Prevalence of overweight children according to BMI before education was 8.9% (6.5% of overweight and 2.4% of obese children). In intervention group of children, according to BMI, there was no decrease in proportion of obese after the health education was conducted and prevalence was 2% before and after the education. On the second measurement, pupils in control group showed increase in proportion of obese from 2.9% to 3.5%. According to weight circumference and height ratio before education there were 10.2% of obese children. After six months, there was an increase in proportion of obese to 11.3%. According to this index there was an increase in proportion of obese in all groups of pupils regardless of gender and conducted education. This study shows that in school-based obesity programs it is necessary to apply more intense interventions with another type of methodology; program should be conducted continuously during longer period, otherwise this condition will continue to rise. | {
"pile_set_name": "PubMed Abstracts"
} |
Prostaglandin D synthase (beta-trace) in meningeal hemangiopericytoma.
The level of prostaglandin D synthase (PGDS), a major protein constituent of cerebrospinal fluid (CSF), is altered in various brain diseases, including meningitis. However, its role in the brain remains unclear. PGDS is mainly synthesized in the arachnoid cells, the choroid plexus and oligodendrocytes in the central nervous system. Among brain tumors, meningiomas showed intense immunoreactivity to PGDS in the perinuclear region. Thus, PGDS has been considered a specific cell marker of meningioma. In this study, we examined 25 meningeal hemangiopericytomas (HPCs) and found that 16 of the tumors (64%) showed immunoreactivity for PGDS in the perinuclear region. For comparison, 15 meningiomas, 14 soft-tissue HPCs, 1 mesenchymal chondrosarcoma, 3 choroid plexus papillomas, and 7 oligodendrogliomas were also examined. Meningiomas showed positive immunoreactivity for PGDS in 13 cases (80%). Except for one case located at the sacrum, none of the other soft-tissue HPCs showed immunostaining for PGDS. Mesenchymal chondrosarcoma arises in the bones of the skull, and its histological pattern resembles that of HPC; however, it showed no immunoreactivity for PGDS. Neither choroid plexus papillomas nor oligodendrogliomas were immunopositive for PGDS. These findings suggest that meningeal HPCs may have a unique molecular phenotype that is distinct from that of the soft-tissue HPCs. The origin of meningeal HPCs may be more closely related to the arachnoid cells. | {
"pile_set_name": "PubMed Abstracts"
} |
Playing in the "Gutter": Cultivating Creativity in Medical Education and Practice.
In comics, "gutters" are the empty spaces between panels that readers must navigate to weave disjointed visual sequences into coherent narratives. A gutter, however, is more than a blank space--it represents a creative zone for making connections and for constructing meaning from disparate ideas, values, and experiences. Over the course of medical training, learners encounter various "gutters" created by the disconnected subject blocks and learning experiences within the curriculum, the ambiguity and uncertainty of medical practice, and the conflicts and tensions within clinical encounters. Navigating these gutters requires not only medical knowledge and skills but also creativity, defined as the ability to make connections between disparate fragments to create meaningful, new configurations. To cultivate medical students' creative capacity, the authors developed the Integrated Clinical Arts (ICA) program, a required component of the first-year curriculum at the Warren Alpert Medical School of Brown University. ICA workshops are designed to place students in a metaphorical gutter, wherein they can practice making connections between medicine and arts-based disciplines. By playing in the gutter, students have opportunities to broaden their perspectives, gain new insights into both medical practice and themselves, and explore different ways of making meaning. Student feedback on the ICA program highlights an important role for creativity and the arts in medicine: to transform gutters from potential learning barriers into opportunities for discovery, self-reflection, and personal growth. | {
"pile_set_name": "PubMed Abstracts"
} |
Cytogenetic effects on cells derived from patients with myelodysplastic syndromes during treatment with hemopoietic growth factors.
Hemopoietic growth factors are used with increasing frequency in the treatment of patients with myelodysplastic syndromes (MDS). While a response occurs regularly, it has not been unequivocally resolved whether this effect is due to the stimulation of normal hemopoiesis or to induced maturation of the abnormal clone. To determine whether selective responses to colony-stimulating factors of normal versus abnormal clones occurred, cytogenetic analysis was performed on bone marrow cells of MDS patients before and during in vivo treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) or recombinant human erythropoietin (rhEPO). A proliferation of additional clones could be demonstrated by karyotypic analysis in one patient during GM-CSF therapy and in two patients during rhEPO treatment. Two patients, initially with completely normal cytogenetics, developed a mixture of normal and abnormal metaphases during treatment. Two patients, initially with all abnormal metaphases, developed normal metaphases during treatment with GM-CSF. A mosaic of normal and abnormal metaphases was present in six patients. The percentage of abnormal metaphases increased in three patients during GM-CSF treatment, and in one patient during rhEPO therapy. The cytogenetic anomalies in one patient persisted after clinical response to treatment, suggesting that GM-CSF enhanced maturation of the abnormal clone. These data indicate that cytokine therapy in MDS may have diverse effects on hematopoiesis. | {
"pile_set_name": "PubMed Abstracts"
} |
An assessment of statin safety by muscle experts.
The National Lipid Association's (NLA) Muscle Safety Expert Panel was charged with the duty of examining the definitions, causative factors, and management of statin myopathy. The Panel was asked to use its evidence-based findings to form recommendations in response to a series of specific questions posed by the Task Force. The panel was composed of a clinical cardiologist, an exercise physiologist and skeletal muscle expert, and an expert in preventive cardiology who also examined skeletal muscle complications of statin use. | {
"pile_set_name": "PubMed Abstracts"
} |
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