abstract: @entity8 (LTs) belong to a large family of lipid mediators, termed @entity6 , which are derived from @entity11 and released from the cell membrane by phospholipases. LTs are involved in the pathogenesis of inflammatory diseases, such as @entity5 , @entity4 , and peripheral @entity3 . In the present study, we examined whether LTs were implicated in pathomechanism of @entity0 following @entity7 . Using the @entity2 ( @entity2 ) model in @entity1 , we investigated the expression of LT synthases (5-lipoxygenase; 5-LO, Five lipoxygenase activating protein; @entity9 , @entity12 ; @entity12 and @entity13 ; @entity13 ) and receptors ( @entity14 , 2 and @entity10 , 2) mRNAs in the @entity1 spinal cord. Semi-quantitative RT-PCR revealed that 5-LO, @entity9 , @entity13 , @entity14 , and @entity10 mRNAs increased following @entity2 , but not @entity15 mRNAs. Using double labeling analysis of in situ hybridization with immunohistochemistry, we observed that 5-LO, @entity9 , and @entity10 mRNAs were expressed in spinal microglia. @entity12 and @entity13 mRNAs were expressed in both spinal neurons and microglia. @entity14 mRNA was expressed in spinal neurons. The p38 mitogen-activated protein kinase inhibitor, but not MEK inhibitor, reduced the increase in 5-LO in spinal microglia. Continuous intrathecal administration of the 5-LO inhibitor or @entity14 and @entity10 receptor antagonists suppressed mechanical allodynia induced by @entity2 . Our findings suggest that the increase of LT synthesis in spinal microglia produced via p38 MAPK plays a role in the generation of @entity0 .

title: Leukotriene synthases and the receptors induced by @entity7 in the spinal cord contribute to the generation of XXXX .

answer: @entity0


abstract: @entity8 (LTs) belong to a large family of lipid mediators, termed @entity6 , which are derived from @entity11 and released from the cell membrane by phospholipases. LTs are involved in the pathogenesis of inflammatory diseases, such as @entity5 , @entity4 , and peripheral @entity3 . In the present study, we examined whether LTs were implicated in pathomechanism of @entity0 following @entity7 . Using the @entity2 ( @entity2 ) model in @entity1 , we investigated the expression of LT synthases (5-lipoxygenase; 5-LO, Five lipoxygenase activating protein; @entity9 , @entity12 ; @entity12 and @entity13 ; @entity13 ) and receptors ( @entity14 , 2 and @entity10 , 2) mRNAs in the @entity1 spinal cord. Semi-quantitative RT-PCR revealed that 5-LO, @entity9 , @entity13 , @entity14 , and @entity10 mRNAs increased following @entity2 , but not @entity15 mRNAs. Using double labeling analysis of in situ hybridization with immunohistochemistry, we observed that 5-LO, @entity9 , and @entity10 mRNAs were expressed in spinal microglia. @entity12 and @entity13 mRNAs were expressed in both spinal neurons and microglia. @entity14 mRNA was expressed in spinal neurons. The p38 mitogen-activated protein kinase inhibitor, but not MEK inhibitor, reduced the increase in 5-LO in spinal microglia. Continuous intrathecal administration of the 5-LO inhibitor or @entity14 and @entity10 receptor antagonists suppressed mechanical allodynia induced by @entity2 . Our findings suggest that the increase of LT synthesis in spinal microglia produced via p38 MAPK plays a role in the generation of @entity0 .

title: Leukotriene synthases and the receptors induced by XXXX in the spinal cord contribute to the generation of @entity0 .

answer: @entity7


abstract: A survey has been conducted of 222 chemicals evaluated for carcinogenicity in @entity1 and @entity2 by the United States NCI/NTP. The structure of each chemical has been assessed for potential electrophilic (DNA-reactive) sites, its mutagenicity to Salmonella recorded, and the level of its carcinogenicity to rodents tabulated. Correlations among these 3 parameters were then sought. A strong association exists among chemical structure (S/A), mutagenicity to Salmonella (Salm.) and the extent and sites of rodent tumorigenicity among the 222 compounds. Thus, a approximately 90% correlation exists between S/A and Salm. across the 115 carcinogens, the 24 equivocal carcinogens and the 83 non-carcinogens. This indicates the Salmonella assay to be a sensitive method of detecting intrinsic genotoxicity in a chemical. Concordance between S/A and Salm. have therefore been employed as an index of genotoxicity, and use of this index reveals two groups of carcinogens within the database, genotoxic and putatively non-genotoxic. These two broad groups are characterized by different overall carcinogenicity profiles. Thus, 16 tissues were subject to @entity3 only by genotoxins, chief among which were the stomach, Zymbal's glands, lung, subcutaneous tissue and circulatory system. Conclusions of carcinogenicity in these 16 tissues comprised 31% of the individual chemical/tissue reports of carcinogenicity. In contrast, both genotoxins and non-genotoxins were active in the remaining 13 tissues, chief among which was the @entity1 liver which accounted for 24% of all chemical/tissue reports of carcinogenicity. Further, the group of 70 carcinogens reported to be active in both species and/or in 2 or more tissues contained a higher proportion of Salmonella mutagens (70%) than observed for the group of 45 single-species/single-tissue carcinogens (39%). 30% of the 83 non-carcinogens were mutagenic to Salmonella. This confirms earlier observations that a significant proportion of in vitro genotoxins are non-carcinogenic, probably due to their non-absorption or preferential detoxification in vivo. Also, only 30% of the @entity1 liver-specific carcinogens were mutagenic to Salmonella. This is consistent with @entity0 being induced in this tissue (and to a lesser extent in other tissues of the @entity1 and @entity2 ) by mechanisms not dependent upon direct interaction of the test chemical with DNA. Detection of 103 of the 115 carcinogens could be achieved by use of only male @entity2 and female @entity1 .(ABSTRACT TRUNCATED AT 400 WORDS)

title: Chemical structure, Salmonella mutagenicity and extent of carcinogenicity as indicators of genotoxic XXXX among 222 chemicals tested in rodents by the U.S. NCI/NTP.

answer: @entity3


abstract: With the arrival of @entity6 therapy for advanced, metastatic and recurrent @entity5 a quarter of a century ago, came the discovery that approximately one-third of all these @entity3 would show a clinical response. Probably no more than half of this group will survive more than 5 years. Identification of the type of @entity1 who is most likely to respond has proven difficult. Both clinical and histopathological characteristics act only as an unreliable guide. The site of @entity2 and the time for a recurrence to appear are the most constant of these factors. It is hoped that the @entity4 receptor content of the @entity3 will prove to be as valuable as it has been in the case of @entity0 . At the moment this is under investigation with numerous ongoing studies. Type, dosage and mode of administration of @entity6 do not appear to be critical factors in @entity3 response, nor does the type of synthetic agent used. However, @entity8 has been the subject of numerous symposia and is the best researched. It also offers the opportunity of being administered orally and in large doses. All agents are virtually free of toxic effects and cessation on this basis is unusual. For @entity1 with @entity3 that either do not respond to @entity6 , or else have a temporary response, other agents--antiestrogens and cytotoxic--may well prove to be of value either simultaneously or sequentially. These possibilities are under current investigation. The definitive therapy of primary 'nonadvanced' disease is not established and is at this point unproven in any significant published randomized study. Orthodox proven methods of treatment, i.e. surgery and irradiation, must form the initial component in every @entity1 's therapy, whatever the stage of the disease. It is hoped that prospective studies will elucidate the place of @entity7 in an adjunctive primary setting. However, it must be emphasized that such studies must concentrate on 'high-risk' @entity1 . The probability of proof in any group of 'good prognosis' @entity1 --whatever the numbers entered--appears to be very low.

title: Adjunctive and therapeutic progestins in XXXX .

answer: @entity5


abstract: @entity5 is a drug with diverse uses ranging from prevention of @entity4 A illness to the treatment of @entity0 with @entity3 . It is available only in oral formulations from which it is well absorbed and widely distributed, little drug being present in the circulation. Apparent volume of distribution is inversely related to dose over the therapeutic range and accounts in part for a noteworthy logarithmic increase in plasma concentration as a function of dose. Elimination is primarily by renal clearance by both glomerular filtration and tubular secretion. @entity5 accumulates in @entity0 with @entity1 . Hence, doses must be reduced in such @entity0 to avoid @entity2 . Interactions with other drugs appear uncommon. Relationships have been demonstrated between @entity5 therapeutic effects and plasma concentrations in different study cohorts, but not in individual @entity0 . Dose schedules have been suggested for individuals in whom @entity5 kinetics are different from healthy subjects. However, these schedules are controversial in their choice of target concentrations and in being untested as to predictive value.

title: Clinical pharmacokinetics of XXXX .

answer: @entity5


abstract: Contractile force of the myocardium can be increased by different molecular mechanisms, and therefore different energetic consequences may result. The influence of the inotropic substances @entity3 and UDCG-115 on myocardial energetics in isometrically contracting left ventricular @entity0 papillary muscles was investigated by means of highly sensitive antimony bismuth thermopiles. @entity3 increased total heat and initial heat by 147% (p less than 0.01) and 69% (p less than 0.02) when normalized to tension-time integral, respectively. No significant change of both heat terms occurred due to UDCG-115. Initial heat was separated into tension-independent heat (" @entity1 cycling") and @entity2 ("cross-bridge cycling") by means of a new method using @entity4 . Both @entity2 per tension-time integral and tension-independent heat increased significantly, due to @entity3 , from 4.9 +/- 1.17 to 7.6 +/- 2.72 mu cal/g.cm.s (p less than 0.05) and from 0.15 +/- 0.06 to 0.22 +/- 0.04 mcal/g (p less than 0.01). UDCG-115 influenced neither tension-independent heat nor @entity2 per tension-time integral significantly. Thus, the economy of force development was not significantly altered due to UDCG-115 whereas @entity3 significantly increased the energy necessary for activation, i.e. @entity1 cycling, and the energy necessary for force production, i.e. cross-bridge cycling. The basic mechanisms of these energetic changes are discussed.

title: Energetic aspects of inotropic interventions in XXXX myocardium.

answer: @entity0


abstract: Heat inactivation was studied at 45, 50, 55, and 60 degrees for all of the @entity5 hydrolases (PVase), including @entity2 esterase (NTE) and inhibitor-resistant esterase (IRE), in homogenates of hen or @entity0 brain or in preparations of hen brain microsomal membranes. Hen and @entity0 brain homogenates were prepared in buffer (50 mM Tris/0.20 mM @entity1 , pH 8.00, at 25 degrees). Hen brain microsomes were suspended either in buffer or in aqueous @entity3 ( @entity3 , 40%, w/v), or solubilized either in aqueous @entity4 (0.10%, w/v) or in 40% (w/v) @entity3 . Enzyme activities were measured at 37 degrees using @entity5 as substrate. Each enzyme activity in all of the preparations exhibited biphasic heat inactivation kinetics. Apparent rate constants were calculated for the fast (kf) and slow (ks) reactions, along with the relative amounts of activity in each component (Af, As) expressed as percentages of the total activity. For a given preparation and temperature, respective values of kf or ks were similar for PVase, NTE, and IRE, with a mean kf/ks ratio of 52 across all preparations. Af and As were a function of temperature. Mean values of the apparent activation energies (Ea) for all activities and preparations were 44 and 25 kcal/mol for the fast and slow inactivation reactions respectively. These results indicate that all @entity5 hydrolases in hen and @entity0 brain undergo a common heat-induced structural change leading to loss of enzymic activity.

title: Kinetics of heat inactivation of XXXX hydrolases from hen and @entity0 brain.

answer: @entity5


abstract: Heat inactivation was studied at 45, 50, 55, and 60 degrees for all of the @entity5 hydrolases (PVase), including @entity2 esterase (NTE) and inhibitor-resistant esterase (IRE), in homogenates of hen or @entity0 brain or in preparations of hen brain microsomal membranes. Hen and @entity0 brain homogenates were prepared in buffer (50 mM Tris/0.20 mM @entity1 , pH 8.00, at 25 degrees). Hen brain microsomes were suspended either in buffer or in aqueous @entity3 ( @entity3 , 40%, w/v), or solubilized either in aqueous @entity4 (0.10%, w/v) or in 40% (w/v) @entity3 . Enzyme activities were measured at 37 degrees using @entity5 as substrate. Each enzyme activity in all of the preparations exhibited biphasic heat inactivation kinetics. Apparent rate constants were calculated for the fast (kf) and slow (ks) reactions, along with the relative amounts of activity in each component (Af, As) expressed as percentages of the total activity. For a given preparation and temperature, respective values of kf or ks were similar for PVase, NTE, and IRE, with a mean kf/ks ratio of 52 across all preparations. Af and As were a function of temperature. Mean values of the apparent activation energies (Ea) for all activities and preparations were 44 and 25 kcal/mol for the fast and slow inactivation reactions respectively. These results indicate that all @entity5 hydrolases in hen and @entity0 brain undergo a common heat-induced structural change leading to loss of enzymic activity.

title: Kinetics of heat inactivation of @entity5 hydrolases from hen and XXXX brain.

answer: @entity0


abstract: The most important determinant of quality of life in @entity0 with @entity2 is complete @entity3 control, and therefore this should be the ultimate goal of pharmacological therapy. @entity3 freedom, or a reduction in @entity3 frequency, however, should not be sought at all costs, and the situation should never arise where a @entity0 with @entity2 is made to suffer more from the side effects of treatment than from the consequences of the underlying disease. Overtreatment is not uncommon in patients taking antiepileptic drugs, and it may occur in many forms and with a variety of mechanisms. Long-term use (or continuation) of anticonvulsant therapy in situations where it is not indicated (e.g. in @entity0 with @entity3 , or in non-epileptic @entity3 -free @entity0 who underwent brain surgery) constitutes a blatant case of overtreatment. Other forms of overtreatment include the use of unnecessarily fast dose escalation rates, which may expose the @entity0 to potentially serious or severe side effects, or the prescription of unnecessarily high maintenance dosages. The latter occurrence may result from inadequate understanding of dose-response relationships, from misinterpretation of serum drug concentrations (e.g. targeting concentrations within the 'range' in @entity0 who are well controlled at lower concentrations) or, at times, from failure to recognize a paradoxical increase in @entity3 frequency as a manifestation of @entity1 . The most common form of overtreatment, however, involves the unnecessary use of combination therapy (polypharmacy) in @entity0 who could be treated optimally with a single drug. Adverse effects associated with polypharmacy often result from undesirable drug-drug interactions. While pharmacokinetic interactions are somewhat predictable and can be minimized or controlled by monitoring serum drug concentrations and/or dose adjustment, pharmacodynamic interactions leading to enhanced @entity6 (as seen, for example, in some @entity0 given a combination of @entity7 and @entity5 ) can only be identified by careful clinical observation. There is evidence that not all antiepileptic drug combinations are equally adverse, and that the combined use of specific drugs (e.g. @entity7 and @entity4 ) may even exhibit an improved therapeutic index compared with either agent given alone, provided appropriate dose adjustments are made. Although the suggestion has been made that adverse effects are more likely to result from combining anticonvulsants having a similar mode of action, our knowledge of the pharmacology of individual agents is insufficient to allow a reliable prediction of the clinical effects of specific drug combinations.

title: Overtreatment in XXXX : adverse consequences and mechanisms.

answer: @entity2


abstract: The obstetric aspects of 54 pregnancies in 20 @entity0 with @entity9 ( @entity9 ) have been reviewed. Forty live births were delivered vaginally, three of them were preterm. Twelve pregnancies miscarried at between 6 and 14 weeks gestation and two were terminated in the 8th week for @entity2 reasons. Fetal losses in two instances were attributed to cervical @entity4 . One baby died at 4 days of age from a complex @entity3 . No abnormal maternal genital or @entity5 was recorded. @entity1 complicated seven pregnancies. Abdominal striae developed in all @entity0 , the severity of which correlated with @entity8 and the number of pregnancies. All the @entity0 had normal gynaecological histories, none had excessive @entity6 or increased episodes of @entity7 . The eye, blood vessels and other organ systems involved in @entity9 were unaffected by pregnancy. Apart from the increased risk of first trimester miscarriage and the cosmetic deterioration of the abdominal skin, there are few serious complications in pregnancy in @entity0 with @entity9 .

title: The obstetric and gynaecological implications of XXXX .

answer: @entity9


abstract: The @entity18 is a @entity6 characterized by extremely high serum IgE levels; recurrent serious @entity4 , primarily involving the skin and sinopulmonary tract; and chronic @entity12 dating from early infancy. The most common organisms that infect these @entity0 are @entity9 and @entity15 . In addition, they have increased susceptibility to infection with @entity5 , @entity13 , enteric gram-negative rods, herpesviruses, and a variety of fungal organisms. The @entity4 are frequently deep-seated, with @entity8 formation in the case of @entity3 and pneumatocele formation in the case of @entity1 . @entity14 , @entity16 , and visceral abscesses are also seen but less frequently. Associated features of this syndrome are coarse facies, @entity10 , @entity2 , @entity17 , and @entity11 . The immunologic basis of the @entity18 is still speculative. It is believed that the elevated IgE levels reflect a T-cell imbalance characterized by T-cell activation and a deficiency of suppressor T cells to inhibit IgE production. The propensity for recurrent infection may be related to a unique abnormality in the humoral immune system: excessive production of IgE directed to @entity9 and other infectious organisms with a concurrent deficit in their ability to synthesize protective IgG antibody against the same organisms. The fluctuating neutrophil chemotactic abnormality found in these @entity0 may be secondary to the underlying T-cell defect with secretion of chemotactic inhibitor substances from mononuclear cells. Alternatively, the interaction of infectious agents with IgE on the surface of Fc epsilon R-bearing immune effector cells results in the release of inflammatory mediators that impair local host immune response. Activation of the immune system may also contribute to the associated features in this syndrome via the secretion of mediators that regulate connective tissue production and bone mineralization. Further studies will be needed before we completely understand the pathogenesis of @entity18 . Therapy primarily involves use of prophylactic anti-S. aureus antibiotics and the use of intravenous antibiotics, antifungal agents, or antiviral agents during @entity7 . Surgical drainage or resection of @entity4 are frequently indicated. In @entity0 who do not respond to conservative management, there may be a role for intravenous gammaglobulin and/or plasmapheresis.

title: Clinical and immunologic aspects of the XXXX .

answer: @entity18


abstract: The rapid mixing/photocross-linking technique developed in our laboratory has been employed in the study of the mechanism of promoter binding by @entity0 RNA polymerase (RPase). We have previously reported on the quantitation of the one-dimensional diffusion coefficient (D1) for RPase along the DNA template (Singer, P. T., and Wu, C.-W. (1987) J. Biol. Chem. 262, 14178-14189). In this paper, we describe the effect of salt concentration and temperature on the kinetics of promoter search by RPase using plasmid pAR1319 DNA, which contains the A2 early promoter from @entity3 , as template. Over a range of @entity2 concentrations from 25 to 200 mM, the apparent bimolecular rate constant (ka) for the association of RPase with the A2 promoter on this DNA template varied approximately 2-fold, achieving a maximal value between 100 and 125 mM @entity2 . More significantly, the transient distribution of RPase among nonspecific DNA binding sites changed markedly as a function of salt concentration, indicative of gross changes in the average number of base pairs covered by sliding during a nonspecific lifetime. Using the mathematical treatment outlined in our earlier report, the nonspecific dissociation rate constant (koff) was calculated from the binding curves for the nonspecific as well as promoter-containing DNA. The observed variations in ka as a function of monovalent cation concentration ([M+]) were due primarily to changes in koff, as D1 was found to be essentially independent of [M+]. Interestingly, D1 decreased by one-third as the concentration of @entity1 was lowered from 10 to 1 mM. In addition, the dependence of koff (and consequently the nonspecific equilibrium association constant, keq) on [M+] agreed qualitatively with the results of deHaseth et al. (deHaseth, P.L., Lohman, T. M., Burgess, R. R., and Record, M. T., Jr. (1977) Biochemistry 17, 1612-1622), though we consistently measure a weaker Keq. The association rate constant was also measured between 4 and 37 degrees C, and was found to vary approximately 2-fold over that range. An activation energy for the bimolecular association of RPase to the A2 promoter was calculated to be 2.2 +/- 0.4 kcal/mol, while the activation energy for one-dimensional diffusion was 4.7 +/- 0.8 kcal/mol.

title: Kinetics of promoter search by XXXX RNA polymerase. Effects of monovalent and divalent cations and temperature.

answer: @entity0


abstract: The outcome of @entity1 by three species of microsporidia in the genera Endoreticulatus, Nosema, and Vairimorpha, isolated from different populations of @entity2 in Bulgaria, was evaluated in the laboratory. All possible combinations of two species were administered either simultaneously or sequentially to larvae, and mortality, duration of development, and larval weight at 20 days post- @entity0 (simultaneous inoculation) or 23 days post- @entity0 (sequential inoculation) were chosen as the outcome variables. Larvae were also dissected and the presence of each species of microsporidia and the tissues infected were recorded for each treatment. Effects of @entity0 were dependent on both host sex and the type of exposure. Infected larvae were more likely to die than uninfected larvae, but there were no differences in mortality between single and @entity1 . Addition of @entity0 of Nosema or Vairimorpha significantly increased duration of development to the fourth ecdysis; this effect was additive. Addition of Nosema or Vairimorpha to an existing @entity0 had no such effect. When Nosema was administered simultaneously with Endoreticulatus or Vairimorpha, infected larvae weighed more than larvae that had single infections with either pathogen. Nosema was displaced from the silk glands by Vairimorpha and Nosema suppressed octospore formation by Vairimorpha in fat body. The histological evidence combined with the data on larval weight supports the hypothesis that competition occurred in @entity1 .

title: The impact of @entity1 of three species of microsporidia isolated from the XXXX , @entity2 L. (Lepidoptera: Lymantriidae).

answer: @entity2


abstract: The outcome of @entity1 by three species of microsporidia in the genera Endoreticulatus, Nosema, and Vairimorpha, isolated from different populations of @entity2 in Bulgaria, was evaluated in the laboratory. All possible combinations of two species were administered either simultaneously or sequentially to larvae, and mortality, duration of development, and larval weight at 20 days post- @entity0 (simultaneous inoculation) or 23 days post- @entity0 (sequential inoculation) were chosen as the outcome variables. Larvae were also dissected and the presence of each species of microsporidia and the tissues infected were recorded for each treatment. Effects of @entity0 were dependent on both host sex and the type of exposure. Infected larvae were more likely to die than uninfected larvae, but there were no differences in mortality between single and @entity1 . Addition of @entity0 of Nosema or Vairimorpha significantly increased duration of development to the fourth ecdysis; this effect was additive. Addition of Nosema or Vairimorpha to an existing @entity0 had no such effect. When Nosema was administered simultaneously with Endoreticulatus or Vairimorpha, infected larvae weighed more than larvae that had single infections with either pathogen. Nosema was displaced from the silk glands by Vairimorpha and Nosema suppressed octospore formation by Vairimorpha in fat body. The histological evidence combined with the data on larval weight supports the hypothesis that competition occurred in @entity1 .

title: The impact of @entity1 of three species of microsporidia isolated from the @entity2 , XXXX L. (Lepidoptera: Lymantriidae).

answer: @entity2


abstract: The outcome of @entity1 by three species of microsporidia in the genera Endoreticulatus, Nosema, and Vairimorpha, isolated from different populations of @entity2 in Bulgaria, was evaluated in the laboratory. All possible combinations of two species were administered either simultaneously or sequentially to larvae, and mortality, duration of development, and larval weight at 20 days post- @entity0 (simultaneous inoculation) or 23 days post- @entity0 (sequential inoculation) were chosen as the outcome variables. Larvae were also dissected and the presence of each species of microsporidia and the tissues infected were recorded for each treatment. Effects of @entity0 were dependent on both host sex and the type of exposure. Infected larvae were more likely to die than uninfected larvae, but there were no differences in mortality between single and @entity1 . Addition of @entity0 of Nosema or Vairimorpha significantly increased duration of development to the fourth ecdysis; this effect was additive. Addition of Nosema or Vairimorpha to an existing @entity0 had no such effect. When Nosema was administered simultaneously with Endoreticulatus or Vairimorpha, infected larvae weighed more than larvae that had single infections with either pathogen. Nosema was displaced from the silk glands by Vairimorpha and Nosema suppressed octospore formation by Vairimorpha in fat body. The histological evidence combined with the data on larval weight supports the hypothesis that competition occurred in @entity1 .

title: The impact of XXXX of three species of microsporidia isolated from the @entity2 , @entity2 L. (Lepidoptera: Lymantriidae).

answer: @entity1


abstract: The clinical, pathologic, and immunopathologic findings of 14 @entity0 with the @entity2 are presented. The @entity2 occurred in Madrid, Spain, as a consequence of ingestion of an industrial oil sold as olive oil. The syndrome occurred in two phases. In the acute phase @entity0 developed an @entity4 , @entity3 , and exanthem, and some died of @entity9 . Of those who survived, some developed a chronic phase with a neuromyopathic and @entity10 -like illness that had many features of a @entity8 . Histologic examination of lung in the acute phase showed an endovasculitis and features of adult @entity5 . In the chronic phase the skin showed various degrees of sclerodermoid changes and @entity1 . Immunofluorescence with antiprocollagen and antifibronectin antibodies revealed abundant perivascular fluorescence suggestive of @entity7 . Electron microscopy corroborated this by the presence of endothelial swelling and basal lamina reduplication. Similar findings have been described in @entity6 , and this provides an important model for study of connective tissue disease, including @entity10 .

title: Clinical, pathologic, and immunopathologic manifestations of the XXXX . Analysis of fourteen cases.

answer: @entity2


abstract: Peripheral neurons can regenerate after axotomy; in this process, the role of cytoskeletal proteins is important because they contribute to formation and reorganization, growth, transport, stability and plasticity of axons. In the present study, we examined the effects of thyroid hormones (T3) on the expression of major cytoskeletal proteins during sciatic nerve regeneration. At various times after sciatic nerve transection and T3 local administration, segments of operated nerves from T3-treated @entity0 and control @entity0 were examined by Western blotting for the presence of neurofilament, tubulin and @entity1 . Our results revealed that, during the first week after surgery, T3 treatment did not significantly alter the level of NF subunits and tubulin in the different segments of operated nerves compared to control nerves. Two or 4 weeks after operation, the concentration of @entity3 and @entity2 isoforms was clearly increased by T3 treatment. Moreover, under T3-treatment, NF proteins appeared more rapidly in the distal segment of operated nerves. Likewise, the levels of betaIII, and of acetylated and tyrosinated tubulin isotypes, were also up-regulated by T3-treatment during regeneration. However, only the tyrosinated tubulin form appeared earlier in the distal nerve segments. At this stage of regeneration, T3 had no effect on the level of @entity1 expression. In conclusion, thyroid hormone improves and accelerates peripheral nerve regeneration and exerts a positive effect on cytoskeletal protein expression and transport involved in axonal regeneration. These results help us to understand partially the mechanism by which thyroid hormones enhance peripheral nerve regeneration. The stimulating effect of T3 on peripheral nerve regeneration may have considerable therapeutic potential.

title: Thyroid hormones stimulate expression and modification of cytoskeletal protein during XXXX sciatic nerve regeneration.

answer: @entity0


abstract: Recent evidence suggests that various @entity1 respond differently to antiepileptic drugs. It follows that a more precise diagnosis, together with a better understanding of AED mechanisms of action, enables them to be used more specifically, and therefore more effectively. @entity0 characteristics including age of onset, @entity2 frequency, EEG data and the findings of imaging studies, provide diagnostic pointers which enable the physician to reach a syndrome diagnosis and to choose the most appropriate AED for the individual @entity0 . Home videotapes of paroxysmal events are becoming increasingly available and are often of great assistance. Parents should be encouraged to record their @entity0 's attacks. Careful history-taking and correct interpretation of clinical data remain the cornerstones of accurate diagnosis and successful treatment. However, the specificity of antiepileptic drugs is relatively limited and often pharmacotherapy should start using an agent with a broad spectrum of activity appropriate for the primary @entity2 type. It is in fact common that several antiepileptic agents have similar or identical effectiveness for one particular form of @entity1 . Therefore, the eventual side effects and the greater or lesser difficulties in handling the drug play an essential role in the choice of a therapeutic agent. Polypharmacy should be avoided and surgery should be considered early for selected @entity0 , particularly @entity0 , who fail to respond to an appropriate drug trial. Correct diagnosis and the first drug(s) used may have a crucial impact on the evolution of given @entity1 . One major emphasis in the management of @entity1 is on information that should be complete, adapted to the level of understanding, and objective, although given in a positive manner. The understanding and cooperation of @entity0 and their families is clearly decisive for the success of therapy, and this requires a confident relationship between the physician and the @entity0 . Current knowledge, on antiepileptic drugs options in @entity1 , is discussed.

title: Treatment options in XXXX .

answer: @entity1


abstract: Effects of bone marrow transplantation (BMT) on the pathology of the central nervous system were evaluated, at light and electron microscope levels, in the homozygous twitcher @entity2 (twi/twi), an authentic @entity2 @entity3 ( @entity3 , @entity3 ) in @entity0 . In the twitcher @entity2 with BMT examined at ages 44 and 71 days (transplanted at the day 9 to 12), degeneration of oligodendrocytes and myelin was still present. In these @entity2 , oligodendrocytes and macrophages containing typical tubular and crystalloid inclusions of @entity3 were observed in the white matter, in particular that of the cerebellum, brainstem, and spinal cord. However, significant morphologic improvement was observed in the central nervous system of the twitcher with BMT which survived more than 100 days. In the cerebellum, brainstem, and spinal cord of these @entity2 , @entity1 and infiltration of macrophages containing typical @entity3 inclusions were either absent or only rarely observed. Instead, many foamy macrophages, either scattered or clustered around blood vessels, were conspicuous. Many nerve fibers with thin myelin sheaths indicative of remyelination were present in the white matter. @entity3 inclusions were, however, still found in the cytoplasm of apparently remyelinating oligodendrocytes. These results suggest that the foamy macrophages are of donor origin, since they are able to digest degraded myelin components completely, because of a sufficient @entity4 activity, and are contributing to the improvement of the central nervous system pathology in the twitcher @entity2 following BMT, by supplying the deficient enzyme, @entity4 . However, the presence of inclusions in oligodendrocytes in the twitcher with BMT, even after 100 days of age indicates that the basic enzymatic defect involving oligodendrocytes could not be completely corrected with BMT.

title: The twitcher XXXX . Central nervous system pathology after bone marrow transplantation.

answer: @entity2


abstract: Obligately aerobic tubercle bacilli are capable of adapting to survive @entity2 by developing into a nonreplicating or dormant form. Dormant bacilli maintain viability for extended periods. Furthermore, they are resistant to antimycobacterials, and hence, dormancy might play a role in the persistence of @entity1 infection despite prolonged chemotherapy. Previously, we have grown dormant @entity3 BCG in an @entity0 -limited Wayne culture system and subjected the bacilli to proteome analysis. This work revealed the upregulation of the response regulator Rv3133c and three other polypeptides (alpha-crystallin and two "conserved hypothetical" proteins) upon entry into dormancy. Here, we replaced the coding sequence of the response regulator with a @entity4 resistance cassette and demonstrated that the loss-of-function mutant died after @entity0 starvation-induced termination of growth. Thus, the disruption of this dormancy-induced transcription factor resulted in loss of the ability of BCG to adapt to survival of @entity2 . Two-dimensional gel electrophoresis of protein extracts from the gene-disrupted strain showed that the genetic loss of the response regulator caused loss of the induction of the other three dormancy proteins. Thus, the upregulation of these dormancy proteins requires the response regulator. Based on these two functions, dormancy survival and regulation, we named the Rv3133c gene dosR for dormancy survival regulator. Our results provide conclusive evidence that DosR is a key regulator in the @entity0 starvation-induced mycobacterial dormancy response.

title: @entity3 BCG response regulator essential for XXXX dormancy.

answer: @entity2


abstract: Obligately aerobic tubercle bacilli are capable of adapting to survive @entity2 by developing into a nonreplicating or dormant form. Dormant bacilli maintain viability for extended periods. Furthermore, they are resistant to antimycobacterials, and hence, dormancy might play a role in the persistence of @entity1 infection despite prolonged chemotherapy. Previously, we have grown dormant @entity3 BCG in an @entity0 -limited Wayne culture system and subjected the bacilli to proteome analysis. This work revealed the upregulation of the response regulator Rv3133c and three other polypeptides (alpha-crystallin and two "conserved hypothetical" proteins) upon entry into dormancy. Here, we replaced the coding sequence of the response regulator with a @entity4 resistance cassette and demonstrated that the loss-of-function mutant died after @entity0 starvation-induced termination of growth. Thus, the disruption of this dormancy-induced transcription factor resulted in loss of the ability of BCG to adapt to survival of @entity2 . Two-dimensional gel electrophoresis of protein extracts from the gene-disrupted strain showed that the genetic loss of the response regulator caused loss of the induction of the other three dormancy proteins. Thus, the upregulation of these dormancy proteins requires the response regulator. Based on these two functions, dormancy survival and regulation, we named the Rv3133c gene dosR for dormancy survival regulator. Our results provide conclusive evidence that DosR is a key regulator in the @entity0 starvation-induced mycobacterial dormancy response.

title: XXXX BCG response regulator essential for @entity2 dormancy.

answer: @entity3


abstract: BACKGROUND: @entity2 (PCT) is a recently described inflammatory marker that has been shown to increase significantly in @entity0 with severe systemic @entity3 . Reports on the diagnostic and predictive value of @entity1 are limited. METHODS: In order to evaluate the role of PCT in systemic @entity4 , 14 @entity0 (mean age 40 years) with proven or probable @entity1 were investigated. Blood samples were collected on days 1, 3, 5, and 10 after the onset of signs and symptoms of @entity1 (clinical and/or laboratory diagnosis and/or radiographic evidence). PCT measurements were performed using an immunoluminometric assay. RESULTS: In five @entity0 with severe @entity1 and an unfavorable course ( @entity0 group 2), PCT levels were moderately elevated on day 3 (0.5-1.0 ng/ml), whereas they were normal in the @entity0 who recovered ( @entity0 group 1). High PCT levels (>/=1.11 ng/ml) were detected on the 10th day of the course of the illness in @entity0 group 2. A normal or moderate elevation of PCT on day 10 was observed in @entity0 group 1. The difference in mean PCT levels in @entity0 groups 1 and 2 on days 3 and 10 were statistically significant. CONCLUSIONS: PCT levels seem to correlate with the severity and outcome of @entity1 . If this finding can be confirmed in a larger number of @entity0 , it could serve as a prognostic indicator.

title: Could @entity2 be a predictive biological marker in XXXX ?. Study of 14 cases.

answer: @entity1


abstract: BACKGROUND: @entity2 (PCT) is a recently described inflammatory marker that has been shown to increase significantly in @entity0 with severe systemic @entity3 . Reports on the diagnostic and predictive value of @entity1 are limited. METHODS: In order to evaluate the role of PCT in systemic @entity4 , 14 @entity0 (mean age 40 years) with proven or probable @entity1 were investigated. Blood samples were collected on days 1, 3, 5, and 10 after the onset of signs and symptoms of @entity1 (clinical and/or laboratory diagnosis and/or radiographic evidence). PCT measurements were performed using an immunoluminometric assay. RESULTS: In five @entity0 with severe @entity1 and an unfavorable course ( @entity0 group 2), PCT levels were moderately elevated on day 3 (0.5-1.0 ng/ml), whereas they were normal in the @entity0 who recovered ( @entity0 group 1). High PCT levels (>/=1.11 ng/ml) were detected on the 10th day of the course of the illness in @entity0 group 2. A normal or moderate elevation of PCT on day 10 was observed in @entity0 group 1. The difference in mean PCT levels in @entity0 groups 1 and 2 on days 3 and 10 were statistically significant. CONCLUSIONS: PCT levels seem to correlate with the severity and outcome of @entity1 . If this finding can be confirmed in a larger number of @entity0 , it could serve as a prognostic indicator.

title: Could XXXX be a predictive biological marker in @entity1 ?. Study of 14 cases.

answer: @entity2


abstract: Multiple types of insults, such as @entity3 , @entity7 and @entity1 , may alter the central nervous system. Strategies to protect the brain against insults remain a very difficult and challenging problem. Damage to the central nervous system can be modulated via excessive excitatory and reduced inhibitory neurotransmission. In addition, increased @entity10 and @entity6 loading through impaired voltage-sensitive channels, as well as alterations in the acid-base balance can contribute to both excitotoxic and apoptotic cell death. @entity4 treatment has always been related to neuroprotection, since it aims to reduce the duration or totally suppress @entity5 . Although the debate on the capacity of simple @entity5 to induce @entity8 is still ongoing, no doubt persists on the disastrous effects of prolonged episodes of status. The next step would be to prevent @entity4 . Several animal models have been used to study the various aspects of the epileptogenic process. In @entity0 , one of the most compelling examples of a series of epileptogenic events is @entity9 ( @entity9 ). @entity9 is often attributed to @entity5 in childhood resulting in @entity11 . However, the relationship between @entity9 , @entity5 in childhood and @entity2 may not be apparent as initially believed. Furthermore, it is well recognized that in a number of @entity0 there is a delay from a specific insult to the onset of @entity5 . This "latent period" could be an opportunity for effective intervention, provided that the underlying mechanisms are understood and that appropriate means for a beneficial modification of the disease process become available. The present review discusses the various steps of @entity9 and provides illustrations of the various mechanisms implicated in @entity8 . Data from animal models is also presented and illustrated with video sequences. Finally, on the basis of what is known on mechanisms of action of available antiepileptic drugs, some suggestions are put forward. Basic science and research are guided by clinical queries and from ongoing dialogue. The present illustrated review deals with only a small part of the important amount of work related to @entity4 and neuroprotection. As such it is necessarily schematic or even simplistic. The review is designed to inform clinicians about the basic issues related to the subject, thus allowing them to follow the ongoing debate and participate with pertinent questions. (Published with video sequences).

title: XXXX and neuroprotection: an illustrated review.

answer: @entity4


abstract: 1 The frequency and selectivity of individual variations of prostanoid agonist responses in aortic strips from a population of male @entity0 was studied. Three levels of responsiveness to the @entity3 mimetic @entity4 occurred: responders (R), intermediate responders (IR), and non-responders (NR). R could be subdivided into R1 and R2 based on an enhanced potency of @entity5 (PGF2 alpha) in R2. In the total population (n = 92), the phenotype frequency was: R, 69%; IR, 11%; and NR, 20%. In a subgroup of this population in which R1 and R2 phenotypes were determined (n = 63), the phenotype frequency was: R1, 54%; R2, 19%; IR, 6%; and NR, 21%. 2 The four @entity0 aorta phenotypes, R1, R2, IR, and NR, were characterized with respect to the rank orders of prostanoid agonist potency, agonist intrinsic activities, and the effects of the @entity3 receptor antagonist @entity6 . The rank order of prostanoid agonist potency was @entity4 greater than PGF2 alpha greater than @entity2 in R1 and R2, and PGF2 alpha greater than or equal to @entity2 greater than @entity4 in IR and NR. For each prostanoid agonist, the intrinsic activity was highest in R (R1 congruent to R2), intermediate in IR, and lowest in NR. In R1, @entity6 inhibited all prostanoid agonist responses equally. The contractile effects of PGF2 alpha and @entity2 were partially resistant to inhibition by @entity6 in R2. Prostanoid agonist responses were not inhibited by @entity6 in IR. 3 The potency of @entity1 was equivalent in R1, R2, IR, and NR. 4 It is concluded that there are individual variations in the functional expression of @entity3 receptor sensitivity, i.e., prostanoid agonist responses inhibited by @entity6 . Also, there are individual variations in the functional expression of the sensitivity of a non- @entity3 receptor or receptors, i.e., prostanoid agonist responses not inhibited by @entity6 . It has been proposed by others that prostanoid receptors be termed P-receptors and that the prostanoid agonist to which they are most sensitive be indicated by a preceding letter, e.g., TP- for @entity3 receptor and FP- for PGF2 alpha-selective receptor. Accordingly, we proposed a working hypothesis that suggests the four phenotypes could result from the independent regulation of the functional expression of TP- and FP-receptor subtypes with (a) R2 containing both the TP- and FP-receptor subtypes in a fully functional state; (b) R1 containing only the functional TP-receptor; (c) IR containing only the functional FP-receptor; and (d) NR containing only a low efficacy FP-receptor system. 5 The mechanisms underlying the observed individual variations are unknown but could include changes in receptor number or affinity, changes in receptor-effector coupling, changes in a second messenger system, or changes in tissue degradative or uptake processes. Further study is needed to differentiate between these possibilities.

title: Individual variations of prostanoid agonist responses in XXXX aorta: evidence for the independent regulation of prostanoid receptor subtypes.

answer: @entity0


abstract: The use of @entity3 long term after orthotopic liver transplantation has been analyzed in 73 adults with particular reference to the dose of drug used, either alone or in combination with other immunosuppressive agents, and the side effects observed. The first 22 @entity0 were given @entity3 10 mg/kg/day for up to 2 years, but thereafter in these, and in all the other @entity0 , the drug dose was regulated by whole blood trough levels. The proportion of @entity0 maintained on @entity3 alone increased from 11% at 3 months to 54.9% and 55.6% at 3 and 4 years, respectively. The dose of @entity6 used in combination with @entity3 was lower than that used with @entity5 (P less than 0.05) up to 12 months after transplantation, but thereafter no significant difference was found. Acute cellular rejection was seen in 5 @entity0 and in all instances was related to cessation of @entity3 , while 10 @entity0 developed chronic graft rejection manifested by the @entity9 . At 12 months and onward, 54.5-73.3% of @entity0 had normal serum @entity7 levels, and 47.6-80.0% had @entity4 aminotransferase levels in the normal range. @entity3 was discontinued in 12 @entity0 , in 8 cases because of @entity1 or @entity2 . A trend toward rising serum @entity8 levels was seen, and after 4 years on @entity3 none of 12 @entity0 had normal levels, and these exceeded 200 mumol/L in 5. The rise in @entity8 levels was probably in part related to the higher doses used early in the study period. The incidence of @entity2 progressively increased from 15.3% at 3 months to 63.6% at 4 years in @entity0 maintained on @entity3 .

title: An analysis of XXXX efficacy and toxicity after liver transplantation.

answer: @entity3


abstract: Between 1971 and March 1986, 61 @entity0 underwent surgery for @entity5 . Age at operation varied from 3.5 to 76 years (mean 38). The standard approach was a generous transaortic myectomy. One-quarter of the @entity0 underwent concomitant repair of associated lesions. There was one operative and two late deaths, for an actuarial 5 years survival 93% (+/- 8%). Average follow-up is 3 years per @entity0 . Sixty-four percent of these @entity0 are asymptomatic and another 30% were in New York Heart Association class II. Persistent symptoms were usually related to @entity4 . Early @entity3 did not occur, but two @entity0 were paced for complex @entity4 3 and 4 years after surgery. Hemodynamic studies (n = 22), two-dimensional echocardiographic (n = 47), and Doppler assessments (n = 23) demonstrated a left ventricular outflow tract pressure gradient of 70 and 14 mm Hg before and after surgery, respectively, left ventricular diastolic pressure of 18 and 14 mm Hg, percent of @entity0 with @entity2 of 70% and 30%, percent of @entity0 with systolic anterior motion of 100% and 35%, and percent of @entity0 with @entity1 of 9% and 49%. Eight-six percent of the @entity0 catheterized had no resting obstruction. Subaortic myectomy produces symptomatic improvement by reducing the left ventricular outflow tract pressure gradient, @entity2 , and left ventricular end-diastolic pressure, and probably improves longevity.

title: Results of surgery for XXXX .

answer: @entity5


abstract: BACKGROUND: Recent studies have focussed on understanding the fundamental aspects of mineralization, searching for insight into the physical and chemical interactions between the organic and inorganic counterparts in bio-inorganic composites. Structural alterations in organic matrices interacting with minerals during the phase transition from un-calcified to calcified affect the mineral micro-environment, resulting in @entity1 . The present study deals with the fabrication of two novel bio-inorganic composites: collagen-brushite and collagen- @entity6 . The mineral counterparts are grown onto collagen by crystal growth, to produce composites adapted to the ambient environment in bone, at pH 5.8 and pH 7.0. The biophysical and material characteristics provide some interesting insights into calcifying mechanisms. MATERIAL/METHODS: The biophysical parameters were evaluated by Fourier Transform Infra Red (FTIR) spectroscopic studies, Differential Scanning Calorimetry (DSC), and @entity2 ( @entity2 ) studies, with biochemical characterization of demineralized and remineralized samples for @entity0 , @entity5 , @entity4 , and net protein content. RESULTS: The biochemical characterization of demineralized and remineralized samples revealed protein loss on mineralization and indicated the possible role of non-collagenous proteins (osteonectin) in mineralization. The FTIR spectra showed loss of @entity3 peaks, while DSC and @entity2 studies showed closer association of collagen with the mineral counterpart. CONCLUSIONS: In vitro collagen mineralization systems reveal the essential role of non-collagenous proteins (osteonectin) in mineralization. The novel composites have mineral counter parts with a physical similarity to bone, and their use as a substitutive tissue is presently being evaluated in animal models.

title: Preparation and characterization of two new composites: collagen-brushite and collagen XXXX .

answer: @entity6


abstract: BACKGROUND: The objective of this study was to investigate, in a single-blind manner over a period of 12 weeks, the efficacy and tolerability of @entity1 versus @entity3 in the treatment of @entity2 ( @entity2 ). METHOD: @entity0 with a DSM-IV diagnosis of @entity2 and a Yale-Brown Obsessive Compulsive Scale (YBOCS) score >/= 16 were randomly assigned to receive @entity1 , 225 to 350 mg/day (26 @entity0 ), or @entity3 , 150 to 225 mg/day (47 @entity0 ), for 12 weeks, with dosage adjustments according to tolerability and response to treatment. All @entity0 were medication-free from at least 2 months prior to study enrollment. Efficacy measures were the YBOCS and the Clinical Global Impressions scale (CGI), which were completed at baseline and every 4 weeks. We defined responders as @entity0 who had an improvement from baseline in YBOCS score of >/= 35% and a CGI score </= 2. An investigator who was blinded to @entity0 ' current medication administered rating scales independently. Moreover, @entity0 were instructed not to reveal their current treatment to this investigator. RESULTS: Twenty-five @entity0 in the @entity1 group and 40 in the @entity3 group completed the 12-week trial. Responder rates at the end of the 12 weeks were 36% for @entity1 (9/25) versus 50% for @entity3 (20/40) according to the visitwise analysis and 34.6% (9/26) for @entity1 versus 42.6% (20/47) for @entity3 according to the last-observation-carried-forward analysis, with no statistically significant difference between the 2 drugs. Adverse experiences were reported by 61.5% of @entity0 receiving @entity1 (16/26) and by 91.5% of those receiving @entity3 (43/47). CONCLUSION: Our results indicate that @entity1 might be as efficacious as @entity3 in the acute treatment of @entity2 , with fewer side effects.

title: @entity1 versus @entity3 in the treatment of XXXX : a preliminary single-blind, 12-week, controlled study.

answer: @entity2


abstract: BACKGROUND: The objective of this study was to investigate, in a single-blind manner over a period of 12 weeks, the efficacy and tolerability of @entity1 versus @entity3 in the treatment of @entity2 ( @entity2 ). METHOD: @entity0 with a DSM-IV diagnosis of @entity2 and a Yale-Brown Obsessive Compulsive Scale (YBOCS) score >/= 16 were randomly assigned to receive @entity1 , 225 to 350 mg/day (26 @entity0 ), or @entity3 , 150 to 225 mg/day (47 @entity0 ), for 12 weeks, with dosage adjustments according to tolerability and response to treatment. All @entity0 were medication-free from at least 2 months prior to study enrollment. Efficacy measures were the YBOCS and the Clinical Global Impressions scale (CGI), which were completed at baseline and every 4 weeks. We defined responders as @entity0 who had an improvement from baseline in YBOCS score of >/= 35% and a CGI score </= 2. An investigator who was blinded to @entity0 ' current medication administered rating scales independently. Moreover, @entity0 were instructed not to reveal their current treatment to this investigator. RESULTS: Twenty-five @entity0 in the @entity1 group and 40 in the @entity3 group completed the 12-week trial. Responder rates at the end of the 12 weeks were 36% for @entity1 (9/25) versus 50% for @entity3 (20/40) according to the visitwise analysis and 34.6% (9/26) for @entity1 versus 42.6% (20/47) for @entity3 according to the last-observation-carried-forward analysis, with no statistically significant difference between the 2 drugs. Adverse experiences were reported by 61.5% of @entity0 receiving @entity1 (16/26) and by 91.5% of those receiving @entity3 (43/47). CONCLUSION: Our results indicate that @entity1 might be as efficacious as @entity3 in the acute treatment of @entity2 , with fewer side effects.

title: XXXX versus @entity3 in the treatment of @entity2 : a preliminary single-blind, 12-week, controlled study.

answer: @entity1


abstract: BACKGROUND: The objective of this study was to investigate, in a single-blind manner over a period of 12 weeks, the efficacy and tolerability of @entity1 versus @entity3 in the treatment of @entity2 ( @entity2 ). METHOD: @entity0 with a DSM-IV diagnosis of @entity2 and a Yale-Brown Obsessive Compulsive Scale (YBOCS) score >/= 16 were randomly assigned to receive @entity1 , 225 to 350 mg/day (26 @entity0 ), or @entity3 , 150 to 225 mg/day (47 @entity0 ), for 12 weeks, with dosage adjustments according to tolerability and response to treatment. All @entity0 were medication-free from at least 2 months prior to study enrollment. Efficacy measures were the YBOCS and the Clinical Global Impressions scale (CGI), which were completed at baseline and every 4 weeks. We defined responders as @entity0 who had an improvement from baseline in YBOCS score of >/= 35% and a CGI score </= 2. An investigator who was blinded to @entity0 ' current medication administered rating scales independently. Moreover, @entity0 were instructed not to reveal their current treatment to this investigator. RESULTS: Twenty-five @entity0 in the @entity1 group and 40 in the @entity3 group completed the 12-week trial. Responder rates at the end of the 12 weeks were 36% for @entity1 (9/25) versus 50% for @entity3 (20/40) according to the visitwise analysis and 34.6% (9/26) for @entity1 versus 42.6% (20/47) for @entity3 according to the last-observation-carried-forward analysis, with no statistically significant difference between the 2 drugs. Adverse experiences were reported by 61.5% of @entity0 receiving @entity1 (16/26) and by 91.5% of those receiving @entity3 (43/47). CONCLUSION: Our results indicate that @entity1 might be as efficacious as @entity3 in the acute treatment of @entity2 , with fewer side effects.

title: @entity1 versus XXXX in the treatment of @entity2 : a preliminary single-blind, 12-week, controlled study.

answer: @entity3


abstract: BACKGROUND: Approximately 50% of @entity0 diagnosed with major @entity4 will experience a recurrent or chronic @entity3 for which long-term treatment is recommended. Moreover, at least 20% of @entity0 diagnosed with @entity4 do not respond satisfactorily to several traditional antidepressant medication treatment trials. Very little is known about the health care costs of @entity0 with treatment-resistant @entity4 . METHOD: Based on medical claims data (MarketScan Research Database, The MEDSTAT Group, Cambridge, Mass.) from January 1, 1995, to June 30, 2000, a naturalistic, retrospective analysis was conducted to study the characteristics and health care utilization of @entity0 with treatment-resistant @entity4 . All @entity0 having an International Classification of Diseases, Ninth Revision (ICD-9), diagnosis code for @entity2 with specified antidepressant dosing and treatment durations were initially selected. @entity0 were then classified as "treatment resistant" if either they switched from or augmented initial antidepressant medication with other antidepressants at least twice (outpatient treatment-resistant group) or they switched from or augmented their initial antidepressant medication and also had a claim for either a @entity4 -related hospitalization or suicide attempt (hospitalized treatment-resistant group). Those meeting the initial medication and diagnosis selection criteria but not meeting the treatment-resistance criteria constituted the comparison group. Members of the comparison group had comparatively stable antidepressant medication use patterns, consistent with an acceptable response to treatment. @entity0 were followed for a minimum of 9 months. Resource utilization was calculated from index date to last available claims data point and then annualized. RESULTS: Treatment-resistant @entity0 were more likely to be diagnosed with @entity2 or concurrent @entity5 or @entity1 than the comparison group (p <.001). Treatment-resistant @entity0 were at least twice as likely to be hospitalized (general medical and @entity4 related) and had at least 12% more outpatient visits (p <.02). Treatment resistance was also associated with use of 1.4 to 3 times more psychotropic medications (including antidepressants) (p <.001). @entity0 in the hospitalized treatment-resistant group had over 6 times the mean total medical costs of non-treatment-resistant @entity4 @entity0 ( 42,344 vs.  6512) (p <.001) and their total @entity4 -related costs were 19 times greater than those of @entity0 in the comparison group ( 28,001 vs.  1455) (p <.001). CONCLUSION: Treatment-resistant @entity4 is costly and associated with extensive use of @entity4 -related and general medical services. These findings underscore the need for early identification and effective long-term maintenance treatment for treatment-resistant @entity4 .

title: The impact of treatment-resistant XXXX on health care utilization and costs.

answer: @entity4


abstract: BACKGROUND AND PURPOSE: @entity2 following @entity0 treatment is a frequent manifestation of @entity3 . In order to document outcomes from @entity3 treatments, reliable, valid, and practical measurements of UE swelling are necessary. The purpose of this study was to compare geometric methods of determining UE volumes with water displacement methods. SUBJECTS: The @entity2 hand, forearm, and upper arm of 50 @entity1 with UE swelling secondary to @entity3 were measured. METHODS: Upper-extremity volumes were determined by water displacement using arm and hand volumeters. Displaced water was weighed to determine volume. Circumferential girth measurements were taken. Width and depth measurements of the hand were taken with a tension-controlled caliper. Geometric volume formulas for a cylinder, frustum, rectangular solid, and trapezoidal solid were used to calculate volumes of the arm and hand at different measurement intervals. RESULTS: Intraclass correlation coefficients [2,1] for interrater and intrarater reliability of all water and geometric measurements of the arm and hand were.91 to.99 and.92 to.99, respectively. Water displacement correlated with geometric measurements in the arm (r=.97-.98) and in the hand (r=.81-.91). The limits of agreement (LOA) indicated that water and geometric measurements of arm volume differed by 479 to 655 mL. Scatterplots of the LOA data indicated in that geometric volumes were either larger or smaller than water volumes. The smallest standard error of measurement for the arm measurements was for the 6-cm frustum method at 115 mL; for the hand measurements, the smallest standard error of measurement was for the frustum method at 16 mL. DISCUSSION AND CONCLUSION: Volume of an @entity2 UE calculated by geometric formulas correlated strongly with volume determined by water displacement. Although strongly correlated, the measurements obtained by the 2 methods did not agree.

title: Upper-extremity volume measurements in @entity1 with XXXX : a comparison of measurements obtained via water displacement with geometrically determined volume.

answer: @entity3


abstract: BACKGROUND AND PURPOSE: @entity2 following @entity0 treatment is a frequent manifestation of @entity3 . In order to document outcomes from @entity3 treatments, reliable, valid, and practical measurements of UE swelling are necessary. The purpose of this study was to compare geometric methods of determining UE volumes with water displacement methods. SUBJECTS: The @entity2 hand, forearm, and upper arm of 50 @entity1 with UE swelling secondary to @entity3 were measured. METHODS: Upper-extremity volumes were determined by water displacement using arm and hand volumeters. Displaced water was weighed to determine volume. Circumferential girth measurements were taken. Width and depth measurements of the hand were taken with a tension-controlled caliper. Geometric volume formulas for a cylinder, frustum, rectangular solid, and trapezoidal solid were used to calculate volumes of the arm and hand at different measurement intervals. RESULTS: Intraclass correlation coefficients [2,1] for interrater and intrarater reliability of all water and geometric measurements of the arm and hand were.91 to.99 and.92 to.99, respectively. Water displacement correlated with geometric measurements in the arm (r=.97-.98) and in the hand (r=.81-.91). The limits of agreement (LOA) indicated that water and geometric measurements of arm volume differed by 479 to 655 mL. Scatterplots of the LOA data indicated in that geometric volumes were either larger or smaller than water volumes. The smallest standard error of measurement for the arm measurements was for the 6-cm frustum method at 115 mL; for the hand measurements, the smallest standard error of measurement was for the frustum method at 16 mL. DISCUSSION AND CONCLUSION: Volume of an @entity2 UE calculated by geometric formulas correlated strongly with volume determined by water displacement. Although strongly correlated, the measurements obtained by the 2 methods did not agree.

title: Upper-extremity volume measurements in XXXX with @entity3 : a comparison of measurements obtained via water displacement with geometrically determined volume.

answer: @entity1


abstract: @entity1 continuously exposed to @entity4 at 0.04, 0.4, and 4.0 ppm for as long as 27 months were submitted to morphological observation and electronmicroscopic morphometry of the lung. At 4 ppm exposure for 9 months, bronchial epithelium showed typical proliferation, which progressed further at 18 months. At this stage, proliferation of @entity3 and @entity0 extension of interstitial tissue were evident and yielded @entity2 at 27 months. At 0.4 ppm, morphological changes in 18-month specimens were still ambiguous, although a tendency toward epithelial changes, as well as @entity0 of the alveolar wall, was noticed under the electron microscope. Slight but definite alteration of the epithelium became evident after 27 months. At 0.04 ppm there were no remarkable changes throughout the entire exposure period. The morphometry revealed concentration- and duration-dependent increases in arithmetic mean thickness (AMT) of the alveolar wall. At 4 ppm, increase of AMT started as early as 9 months, became significant at 18 months, and showed a slight decrease at 27 months. This decrease was interpreted as a recovery of alveolar epithelium and decreased amount of @entity0 , which in turn led to @entity2 . At 0.4 ppm, a slight increase of AMT started at 18 months and extended significantly in 27 months. A similar but insignificant tendency was found even at 0.04 ppm. The morphological alterations were parallel to the concentration and duration of exposure. These findings suggested that an intensive study should be conducted to confirm whether alterations were due to prolonged exposure and/or due to elevated sensitivity of the aged lung.

title: Effects of long-term nitrogen dioxide exposure on XXXX lung: morphological observations.

answer: @entity1


abstract: The @entity7 ( @entity7 ) allows for the isolation of pure @entity0 crypts from @entity4 tissue. In a previous study we reported on the genetic alterations found in @entity1 crypts using the @entity7 ; however, a direct comparison of the genetic alterations found in @entity1 using either conventional methods (CM) or the @entity7 has not previously been performed. Here, we analyzed the impact of this method on the genetic analysis of @entity4 cells by comparing the observed frequency of genetic alterations in @entity4 isolated using CM or the @entity7 . We used a combination of the @entity7 and the fluorescent polymerase chain reaction assay to accurately assess the incidence of @entity2 ( @entity2 ) at a number of chromosomal loci (17p, 5q, 18q, 1p, 8p, 22q), @entity3 ( @entity3 ), and mutations of @entity0 -related genes ( @entity5 and @entity6 genes) in 48 sporadic @entity1 . In addition, genetic alterations seen in @entity0 (defined as @entity0 with both diploid and aneuploid cell populations) identified by the @entity7 were also examined. The incidence of @entity2 at the chromosomal loci tested was more frequently detected in samples isolated from @entity0 using the @entity7 than in those isolated from the same @entity0 using CM. In contrast, we observed no differences in the frequency of @entity3 or @entity0 -related gene mutation between the two groups. Although there was no difference in the frequency of genetic alterations between @entity0 with evidence of multiploidy, sorting of diploid and aneuploid populations allowed detection of distinct genetic changes. The crypt isolation method thus appears to be useful in that it allows purification of @entity0 cells and the accurate assessment of their genetic alterations. In addition, it may also be of benefit in clarifying the genetic profile of multiploid @entity0 cell populations.

title: Application of the XXXX to the assessment of genetic alterations of @entity1 .

answer: @entity7


abstract: The @entity7 ( @entity7 ) allows for the isolation of pure @entity0 crypts from @entity4 tissue. In a previous study we reported on the genetic alterations found in @entity1 crypts using the @entity7 ; however, a direct comparison of the genetic alterations found in @entity1 using either conventional methods (CM) or the @entity7 has not previously been performed. Here, we analyzed the impact of this method on the genetic analysis of @entity4 cells by comparing the observed frequency of genetic alterations in @entity4 isolated using CM or the @entity7 . We used a combination of the @entity7 and the fluorescent polymerase chain reaction assay to accurately assess the incidence of @entity2 ( @entity2 ) at a number of chromosomal loci (17p, 5q, 18q, 1p, 8p, 22q), @entity3 ( @entity3 ), and mutations of @entity0 -related genes ( @entity5 and @entity6 genes) in 48 sporadic @entity1 . In addition, genetic alterations seen in @entity0 (defined as @entity0 with both diploid and aneuploid cell populations) identified by the @entity7 were also examined. The incidence of @entity2 at the chromosomal loci tested was more frequently detected in samples isolated from @entity0 using the @entity7 than in those isolated from the same @entity0 using CM. In contrast, we observed no differences in the frequency of @entity3 or @entity0 -related gene mutation between the two groups. Although there was no difference in the frequency of genetic alterations between @entity0 with evidence of multiploidy, sorting of diploid and aneuploid populations allowed detection of distinct genetic changes. The crypt isolation method thus appears to be useful in that it allows purification of @entity0 cells and the accurate assessment of their genetic alterations. In addition, it may also be of benefit in clarifying the genetic profile of multiploid @entity0 cell populations.

title: Application of the @entity7 to the assessment of genetic alterations of XXXX .

answer: @entity1


abstract: The pheo/eumelanin ratio of cultured normal @entity0 melanocytes is distinct from the ratio observed for the same cells in vivo where they are in close contact with keratinocytes. To study the possible involvement of keratinocytes in the control of melanogenesis, we compared quantitatively and qualitatively the melanin production in melanocyte mono-cultures, in melanocyte-keratinocyte co-cultures and in pigmented reconstructed epidermis. @entity1 and eumelanin contents were assessed by high-performance liquid chromatography with electrochemical and fluorometric detection of their specific degradation products and revealed striking differences in the presence of keratinocytes. In the absence of keratinocytes (melanocyte mono-cultures), we observed a very limited eumelanin production and a very high @entity1 synthesis. The pheo/eumelanin ratio in mono-cultures could be slightly influenced by changing the composition of the culture medium, however, the very strong imbalance in favor of @entity1 remained unchanged. An induction of eumelanin synthesis accompanied by an important reduction of @entity1 formation was only observed in the presence of keratinocytes. The pheo/eumelanin ratio in melanocyte mono-culture dropped from 1043 down to about 25 in the presence of keratinocytes (co-cultures). The same observations were made when the melanocytes were integrated into a reconstructed @entity0 epidermis. Interestingly, under co-culture conditions resulting in only a partial contact between melanocytes and keratinocytes, the reduction of the pheo/ @entity2 ratio were less pronounced. From these results we conclude that keratinocytes play an important role in the melanin production, affecting the melanogenic pathways.

title: Keratinocytes control the pheo/eumelanin ratio in cultured normal XXXX melanocytes.

answer: @entity0


abstract: We have previously demonstrated that pretreatment of ACI recipients with ultraviolet-irradiated donor-specific blood transfusion (UV-DST) leads to permanent cardiac allograft survival without further host immunosuppression (ACI @entity0 are weak responders to Lewis lymphocytes in mixed-lymphocyte reaction). This study examines the effect of UV-DST and the timing of transfusions on ACI cardiac allograft survival in Lewis recipients with and without the addition of peritransplant @entity1 ( @entity2 ) (20 mg/kg i.m.) given on days 0, +1, and +2 in relation to the time of transplantation. The @entity3 ( @entity3 ) of ACI cardiac allografts in Lewis recipients was significantly increased to 33.6 +/- 5.7 days (P less than 0.001) by @entity2 treatment alone as compared to 6.5 +/- 0.5 days survival in control. When DST was given on day -3 combined with @entity2 , graft survival was increased to 42.0 +/- 9.3 days (P less than 0.01), as compared to 5.8 +/- 1.3 days when DST alone was used. When DST was irradiated with ultraviolet B (UV-DST) and administered on day -3 combined with peritransplant @entity2 , the @entity3 was increased to 68.83 +/- 16.1 days as compared to an @entity3 of 10.0 +/- 1.0 days in controls treated with UV-DST alone. When UV-DST was given on day -7 and combined with peritransplant @entity2 immunosuppression, the results were similar. However, when UV-DST was peritransplant @entity2 course, 4 of 6 recipients maintained their ACI heart allografts indefinitely (greater than 300 days) in contrast to the effect of UV-DST alone ( @entity3 of 13.5 days). Third-party (W/F) UV-irradiated blood transfusions were ineffective in prolonging ACI cardiac allografts in Lewis @entity0 , regardless of whether the transfusions were given alone or in combination with peritransplant immunosuppression with @entity2 . In conclusion, these results demonstrate that UV-DST combined with a brief peritransplant immunosuppression with @entity2 induces prolonged heart allograft survival in a histoincompatible, strong responder host, and that such effect is donor specific. The use of UV-DST combined with peritransplant @entity2 immunosuppression offers a promising approach to achieving organ transplant unresponsiveness, and decreased sensitization to the donor blood elements, which eventually may have important clinical implications.

title: Effect of ultraviolet-B-irradiated donor-specific blood transfusions and peritransplant immunosuppression with XXXX on @entity0 cardiac allograft survival.

answer: @entity1


abstract: We have previously demonstrated that pretreatment of ACI recipients with ultraviolet-irradiated donor-specific blood transfusion (UV-DST) leads to permanent cardiac allograft survival without further host immunosuppression (ACI @entity0 are weak responders to Lewis lymphocytes in mixed-lymphocyte reaction). This study examines the effect of UV-DST and the timing of transfusions on ACI cardiac allograft survival in Lewis recipients with and without the addition of peritransplant @entity1 ( @entity2 ) (20 mg/kg i.m.) given on days 0, +1, and +2 in relation to the time of transplantation. The @entity3 ( @entity3 ) of ACI cardiac allografts in Lewis recipients was significantly increased to 33.6 +/- 5.7 days (P less than 0.001) by @entity2 treatment alone as compared to 6.5 +/- 0.5 days survival in control. When DST was given on day -3 combined with @entity2 , graft survival was increased to 42.0 +/- 9.3 days (P less than 0.01), as compared to 5.8 +/- 1.3 days when DST alone was used. When DST was irradiated with ultraviolet B (UV-DST) and administered on day -3 combined with peritransplant @entity2 , the @entity3 was increased to 68.83 +/- 16.1 days as compared to an @entity3 of 10.0 +/- 1.0 days in controls treated with UV-DST alone. When UV-DST was given on day -7 and combined with peritransplant @entity2 immunosuppression, the results were similar. However, when UV-DST was peritransplant @entity2 course, 4 of 6 recipients maintained their ACI heart allografts indefinitely (greater than 300 days) in contrast to the effect of UV-DST alone ( @entity3 of 13.5 days). Third-party (W/F) UV-irradiated blood transfusions were ineffective in prolonging ACI cardiac allografts in Lewis @entity0 , regardless of whether the transfusions were given alone or in combination with peritransplant immunosuppression with @entity2 . In conclusion, these results demonstrate that UV-DST combined with a brief peritransplant immunosuppression with @entity2 induces prolonged heart allograft survival in a histoincompatible, strong responder host, and that such effect is donor specific. The use of UV-DST combined with peritransplant @entity2 immunosuppression offers a promising approach to achieving organ transplant unresponsiveness, and decreased sensitization to the donor blood elements, which eventually may have important clinical implications.

title: Effect of ultraviolet-B-irradiated donor-specific blood transfusions and peritransplant immunosuppression with @entity1 on XXXX cardiac allograft survival.

answer: @entity0


abstract: BACKGROUND: The aim of our study was to determine the maximum tolerated dose of @entity9 combined with a fixed dose of @entity1 and @entity7 in the treatment of @entity6 ( @entity6 ) and to evaluate in a phase II trial the efficacy of this combination. @entity0 AND METHODS: Sixty-two @entity0 with stage IIIB/IV @entity6 were treated with @entity9 in escalating doses from 40-80 mg/m(2) combined with @entity1 and @entity7 at fixed doses of 1000 mg/m(2) and 25 mg/m(2), respectively. All drugs were given intravenously on day 1 and 8 every 3 weeks. RESULTS: In a phase I trial, carried out on 21 @entity0 , grade 4 @entity10 , as dose-limiting @entity2 , occurred at the dosage level of @entity9 80 mg/m(2). In a phase II trial, with @entity9 administered at 70 mg/m(2), 27 out of 41 (66%) assessable @entity0 responded (10% complete responses and 56% partial responses). Objective response was observed in 13 of 16 @entity0 (81%) with stage IIIB disease and in 14 of 25 (56%) with stage IV disease. The median time to treatment failure was 26 weeks (range 3-72 weeks; 32 weeks and 20 weeks for stages IIIB and IV, respectively) and median survival 62 weeks (range 4-176 weeks; 72 weeks and 56 weeks for stages IIIB and IV, respectively). One-year survival was 64% for all @entity0 (72% for @entity0 with stage IIIB and 52% for those with stage IV). Grade 3 and 4 @entity10 were observed in 11 (27%) and seven (17%) cases, respectively; grade 3 @entity4 was observed in three @entity0 (7%) and grade 3 @entity3 in four @entity0 (10%). The most relevant non-hematological @entity2 was grade 2/3 asthenia, which was observed in 12 @entity0 (29%). Alopecia was almost universal, whereas @entity8 were absent. CONCLUSIONS: The combination of @entity9 , @entity1 and @entity7 is effective and tolerable in the treatment of @entity6 . The high activity and low @entity2 of this regimen warrant randomized studies with @entity5 -containing combinations.

title: Phase I/II study of @entity9 , @entity1 and @entity7 as first-line chemotherapy of XXXX .

answer: @entity6


abstract: BACKGROUND: The aim of our study was to determine the maximum tolerated dose of @entity9 combined with a fixed dose of @entity1 and @entity7 in the treatment of @entity6 ( @entity6 ) and to evaluate in a phase II trial the efficacy of this combination. @entity0 AND METHODS: Sixty-two @entity0 with stage IIIB/IV @entity6 were treated with @entity9 in escalating doses from 40-80 mg/m(2) combined with @entity1 and @entity7 at fixed doses of 1000 mg/m(2) and 25 mg/m(2), respectively. All drugs were given intravenously on day 1 and 8 every 3 weeks. RESULTS: In a phase I trial, carried out on 21 @entity0 , grade 4 @entity10 , as dose-limiting @entity2 , occurred at the dosage level of @entity9 80 mg/m(2). In a phase II trial, with @entity9 administered at 70 mg/m(2), 27 out of 41 (66%) assessable @entity0 responded (10% complete responses and 56% partial responses). Objective response was observed in 13 of 16 @entity0 (81%) with stage IIIB disease and in 14 of 25 (56%) with stage IV disease. The median time to treatment failure was 26 weeks (range 3-72 weeks; 32 weeks and 20 weeks for stages IIIB and IV, respectively) and median survival 62 weeks (range 4-176 weeks; 72 weeks and 56 weeks for stages IIIB and IV, respectively). One-year survival was 64% for all @entity0 (72% for @entity0 with stage IIIB and 52% for those with stage IV). Grade 3 and 4 @entity10 were observed in 11 (27%) and seven (17%) cases, respectively; grade 3 @entity4 was observed in three @entity0 (7%) and grade 3 @entity3 in four @entity0 (10%). The most relevant non-hematological @entity2 was grade 2/3 asthenia, which was observed in 12 @entity0 (29%). Alopecia was almost universal, whereas @entity8 were absent. CONCLUSIONS: The combination of @entity9 , @entity1 and @entity7 is effective and tolerable in the treatment of @entity6 . The high activity and low @entity2 of this regimen warrant randomized studies with @entity5 -containing combinations.

title: Phase I/II study of XXXX , @entity1 and @entity7 as first-line chemotherapy of @entity6 .

answer: @entity9


abstract: BACKGROUND: The aim of our study was to determine the maximum tolerated dose of @entity9 combined with a fixed dose of @entity1 and @entity7 in the treatment of @entity6 ( @entity6 ) and to evaluate in a phase II trial the efficacy of this combination. @entity0 AND METHODS: Sixty-two @entity0 with stage IIIB/IV @entity6 were treated with @entity9 in escalating doses from 40-80 mg/m(2) combined with @entity1 and @entity7 at fixed doses of 1000 mg/m(2) and 25 mg/m(2), respectively. All drugs were given intravenously on day 1 and 8 every 3 weeks. RESULTS: In a phase I trial, carried out on 21 @entity0 , grade 4 @entity10 , as dose-limiting @entity2 , occurred at the dosage level of @entity9 80 mg/m(2). In a phase II trial, with @entity9 administered at 70 mg/m(2), 27 out of 41 (66%) assessable @entity0 responded (10% complete responses and 56% partial responses). Objective response was observed in 13 of 16 @entity0 (81%) with stage IIIB disease and in 14 of 25 (56%) with stage IV disease. The median time to treatment failure was 26 weeks (range 3-72 weeks; 32 weeks and 20 weeks for stages IIIB and IV, respectively) and median survival 62 weeks (range 4-176 weeks; 72 weeks and 56 weeks for stages IIIB and IV, respectively). One-year survival was 64% for all @entity0 (72% for @entity0 with stage IIIB and 52% for those with stage IV). Grade 3 and 4 @entity10 were observed in 11 (27%) and seven (17%) cases, respectively; grade 3 @entity4 was observed in three @entity0 (7%) and grade 3 @entity3 in four @entity0 (10%). The most relevant non-hematological @entity2 was grade 2/3 asthenia, which was observed in 12 @entity0 (29%). Alopecia was almost universal, whereas @entity8 were absent. CONCLUSIONS: The combination of @entity9 , @entity1 and @entity7 is effective and tolerable in the treatment of @entity6 . The high activity and low @entity2 of this regimen warrant randomized studies with @entity5 -containing combinations.

title: Phase I/II study of @entity9 , @entity1 and XXXX as first-line chemotherapy of @entity6 .

answer: @entity7


abstract: BACKGROUND: The aim of our study was to determine the maximum tolerated dose of @entity9 combined with a fixed dose of @entity1 and @entity7 in the treatment of @entity6 ( @entity6 ) and to evaluate in a phase II trial the efficacy of this combination. @entity0 AND METHODS: Sixty-two @entity0 with stage IIIB/IV @entity6 were treated with @entity9 in escalating doses from 40-80 mg/m(2) combined with @entity1 and @entity7 at fixed doses of 1000 mg/m(2) and 25 mg/m(2), respectively. All drugs were given intravenously on day 1 and 8 every 3 weeks. RESULTS: In a phase I trial, carried out on 21 @entity0 , grade 4 @entity10 , as dose-limiting @entity2 , occurred at the dosage level of @entity9 80 mg/m(2). In a phase II trial, with @entity9 administered at 70 mg/m(2), 27 out of 41 (66%) assessable @entity0 responded (10% complete responses and 56% partial responses). Objective response was observed in 13 of 16 @entity0 (81%) with stage IIIB disease and in 14 of 25 (56%) with stage IV disease. The median time to treatment failure was 26 weeks (range 3-72 weeks; 32 weeks and 20 weeks for stages IIIB and IV, respectively) and median survival 62 weeks (range 4-176 weeks; 72 weeks and 56 weeks for stages IIIB and IV, respectively). One-year survival was 64% for all @entity0 (72% for @entity0 with stage IIIB and 52% for those with stage IV). Grade 3 and 4 @entity10 were observed in 11 (27%) and seven (17%) cases, respectively; grade 3 @entity4 was observed in three @entity0 (7%) and grade 3 @entity3 in four @entity0 (10%). The most relevant non-hematological @entity2 was grade 2/3 asthenia, which was observed in 12 @entity0 (29%). Alopecia was almost universal, whereas @entity8 were absent. CONCLUSIONS: The combination of @entity9 , @entity1 and @entity7 is effective and tolerable in the treatment of @entity6 . The high activity and low @entity2 of this regimen warrant randomized studies with @entity5 -containing combinations.

title: Phase I/II study of @entity9 , XXXX and @entity7 as first-line chemotherapy of @entity6 .

answer: @entity1


abstract: BACKGROUND: This pilot study was undertaken to assess the feasibility, @entity3 and response to short-course multiagent chemotherapy followed by high-dose chemotherapy (HDC) in @entity0 with poor prognosis @entity6 . @entity0 AND METHODS: A total of 30 @entity0 entered the study. Chemotherapy consisted of four blocks of multiagent chemotherapy administered sequentially over a short period in a dose-intensive manner. This therapy was followed by HDC which consisted of @entity9 at an AUC8 x 3 days, @entity8 400 mg/m(2) x 3 days and @entity7 60 mg/kg x 2 days. RESULTS: A total of 227 cycles of chemotherapy were administered. The main @entity3 (for blocks 1-4) was haematological. There were two treatment-related @entity4 : one post HDC due to @entity5 and one during surgery. High-dose chemotherapy was administered to 11 @entity0 (10 with @entity1 and only one with a @entity1 ). Twenty-seven @entity0 underwent surgery to the primary. Histological response was assessed in 23 @entity0 . Seven @entity0 (30%) had >90% @entity2 . Eight @entity0 underwent pulmonary metastatectomy. The median survival time for the whole group was 16 months. The 2- and 3-year survival rates were 50% and 21% for those with @entity1 and 19% and 13% for those with @entity1 . CONCLUSIONS: Dose-intensive multiagent chemotherapy though feasible in the group of @entity0 with @entity1 did not significantly improve the treatment outcome compared with conventional relapse therapy. Inferior survival rates in the axial skeletal group are attributed to less intensive treatment and poor @entity1 control.

title: A pilot study of short-course intensive multiagent chemotherapy in metastatic and axial XXXX .

answer: @entity6


abstract: Resting plasma fibrinolytic activity and fibrinolytic activity after stimulation by 10 min of @entity1 (fibrinolytic potential) were estimated in 51 @entity0 before femoropopliteal reconstructive surgery. Twelve @entity0 suffered a graft @entity2 in the first month. Resting plasma fibrinolytic activity was similar in @entity0 with thrombosed grafts and those with functioning grafts. However reduced fibrinolytic potential was found to be a risk factor for graft @entity2 in the month after surgery (P = 0.01). Other risk factors were increasing age (P = 0.007) and the indication for surgery (P = 0.03). Thirty-four @entity0 whose grafts were functioning after 1 month were followed up for a mean of 9 months. A further eight grafts thrombosed. Neither fibrinolytic activity nor fibrinolytic potential were found to be risk factors for late graft @entity2 . Fibrinolytic potential has been shown to be an independent risk factor for early graft @entity2 . Perioperative fibrinolytic stimulation might be a method of improving femoropopliteal graft patency.

title: Defective fibrinolysis: a risk factor in early femoropopliteal graft XXXX .

answer: @entity2


abstract: The incidence of mediastinal node involvement of T1 non-small-cell @entity2 was determined in 262 @entity0 for the period June 1981 to January 1986. All @entity0 underwent mediastinoscopy as part of their evaluation. Thirty-five @entity0 (13%) had clinical primary T1 lesions. There were 17 @entity4 , 10 @entity5 , 6 large-cell @entity3 and 2 @entity3 . Five @entity0 had node involvement at mediastinoscopy: two had large-cell @entity3 and one was a @entity5 . Thoracotomy in the remaining 30 @entity0 revealed 2 with pleural @entity1 , 1 with @entity4 with @entity1 to the subaortic nodal area (not assessed by cervical mediastinoscopy). The other @entity0 underwent resection, for a resectability rate of 90%. Therefore the overall incidence of mediastinal node involvement in this series was 17% (6 of 35) and was found to be highest among @entity0 with large-cell @entity3 (2 of 6), followed by @entity4 (3 of 19) and @entity5 (1 of 10). The larger number of large-cell @entity3 in this series probably accounts for the higher incidence of N2 disease found compared with that of previous studies in the literature. Accordingly, preoperative mediastinal staging is recommended for all T1 large-cell @entity3 and @entity4 and for suspicious lesions of undetermined histology.

title: Incidence of mediastinal node involvement in clinical T1 XXXX .

answer: @entity2


abstract: @entity5 ( @entity5 ) is a chronic, familial, @entity2 that primarily affects American Indians. It is more prevalent in young females and may be evident clinically as a pruritic lower lip @entity3 that typically does not respond to conventional therapy. Other clinical features associated with @entity5 include @entity1 , alopecia of the eyebrows, and formation of @entity4 . The histologic features of @entity5 have been described as nonspecific. We are presenting five cases of @entity5 in which the major clinical manifestation was a pruritic, unsightly lower lip @entity3 . All of our @entity0 were American Indians. Three @entity0 were from the same family. The youngest @entity0 was 10 years old and the oldest was 69 years old. All five cases were characterized histologically by numerous germinal centers within the lamina propria and a dense perivascular plasma cell infiltrate. In four of the five cases, there was a moderate to dense infiltrate of eosinophils. All five @entity0 had been generally unresponsive to conventional therapy. With the exception of the youngest @entity0 , all had had the disease for at least several years. One @entity0 , now deceased, had the lower lip lesion surgically removed for cosmetic reasons. To our knowledge, this is the first report in the dental literature that describes the clinical and histologic features of @entity5 of lower lip.

title: XXXX of the lower lip. Review of the literature and report of five cases.

answer: @entity5


abstract: Wound management following laparotomy for @entity2 and varying degrees of @entity1 remains a challenging and controversial problem. Because maintained peritoneal integrity and primary wound closure offer the best opportunity for survival, an original technique involving bilateral incisions to relax skin and rectus fascia is proposed. This technique permits medial myocutaneous advancement and primary tension-free skin closure of midline laparotomy incisions. Sixty-nine @entity0 with severe @entity2 were treated according from 1980 through 1985. Nine of these @entity0 died of advanced @entity6 soon after referral, and eight more died after prolonged treatment. Fourteen @entity0 had one or more reoperations for complications. Only nine wound failures resulted, including five eviscerations and four wound @entity3 followed by progressive dehiscence. The bilateral relaxing incisions healed secondarily without complication. Survivors developed midline wound @entity4 ; ten of the 52 surviving @entity0 have had these repaired. This method of primary closure is safe when performed in conjunction with rigorous surgical care of intraperitoneal @entity3 and may enhance survival. We recommend the technique to surgeons who treat severe @entity2 and @entity1 of @entity5 .

title: @entity1 in XXXX . Successful management by debridement, myocutaneous advancement, and primary skin closure.

answer: @entity2


abstract: Wound management following laparotomy for @entity2 and varying degrees of @entity1 remains a challenging and controversial problem. Because maintained peritoneal integrity and primary wound closure offer the best opportunity for survival, an original technique involving bilateral incisions to relax skin and rectus fascia is proposed. This technique permits medial myocutaneous advancement and primary tension-free skin closure of midline laparotomy incisions. Sixty-nine @entity0 with severe @entity2 were treated according from 1980 through 1985. Nine of these @entity0 died of advanced @entity6 soon after referral, and eight more died after prolonged treatment. Fourteen @entity0 had one or more reoperations for complications. Only nine wound failures resulted, including five eviscerations and four wound @entity3 followed by progressive dehiscence. The bilateral relaxing incisions healed secondarily without complication. Survivors developed midline wound @entity4 ; ten of the 52 surviving @entity0 have had these repaired. This method of primary closure is safe when performed in conjunction with rigorous surgical care of intraperitoneal @entity3 and may enhance survival. We recommend the technique to surgeons who treat severe @entity2 and @entity1 of @entity5 .

title: XXXX in @entity2 . Successful management by debridement, myocutaneous advancement, and primary skin closure.

answer: @entity1


abstract: Massive deep-frozen bone allografts were implanted in 13 @entity0 after en bloc @entity1 resection. @entity0 were followed up for 14 months to 17 years. Most of the reconstructive procedures included a segmental bone allograft with knee or ankle fusion. Graft infections were the most critical complications in regard to the end results, finally requiring amputation in two cases. There were three stress @entity2 ; two of which were successfully treated without further complication. Graft incorporation was assessed by bone scintimetry in four cases. Isotope uptake by the center of the graft was found to be superior to control bone segments at only 15 years after surgery. Two recovered allograft specimens were available for a microradiographic study. Creeping substitution was a very slow process, initiated at the outer surface of the graft and characterized at 2-3 years after implantation by large, incompletely filled osteons. The present investigation demonstrates that massive bone allografts are very slowly revascularized and are intimately anchored by the host bone. Provided that @entity1 control is effective and graft infection is avoided, reconstructive surgery with massive bone allografts represents a successful alternative to prosthetic implants in young adult with a long life expectancy.

title: Massive bone allografts in large skeletal defects after XXXX surgery: a clinical and microradiographic evaluation.

answer: @entity1


abstract: @entity6 , a Gram-negative obligate anaerobic black-pigmented oral bacterium, belongs to a small group of microorganisms that is closely associated with the @entity5 . Lipopolysaccharide (LPS), an outer membrane component, is one of the main virulence factors of this bacterium. The aim of this study was to examine the effects of Prev. intermedia lipopolysaccharide, extracted by the hot- @entity7 -water method, on differentiation (alkaline phosphatase activity) and mineralisation ( @entity1 incorporation) of fetal @entity0 calvarial cells in vitro and to determine the release of the important osteolytic factors @entity3 , @entity2 ( @entity2 ) and matrix metalloproteinases by these cells after treatment with different concentrations of Prev. intermedia lipopolysaccharide (0.2-25 microg/ml). By gelatin zymography, we also characterized the matrix metalloproteinases released by these osteoblasts. Treatment with Prev. intermedia lipopolysaccharide dose-dependently inhibited bone formation by reducing alkaline phosphatase activity and @entity1 incorporation and induced the release of @entity3 , @entity2 and the latent proforms of @entity8 and @entity4 by fetal @entity0 osteoblasts in organoid culture. These results indicate that the lipopolysaccharide from Prev. intermedia not only participates in periodontal tissue destruction and alveolar bone resorption, but also inhibits bone formation.

title: Effects of lipopolysaccharide extracted from XXXX on bone formation and on the release of osteolytic mediators by fetal @entity0 osteoblasts in vitro.

answer: @entity6