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Department of Neurology and Psychiatry, University of Santo Tomas, Manila, Philippines
Received date: April 15, 2016; Accepted date: May 18, 2016; Published date: May 25, 2016
Citation: Gozum MALP, Rosales RL (2016) Botulinum Toxin A Therapy in Early Poststroke Spasticity: Providing a Wider Treatment Avenue. Int J Neurorehabilitation 3:207. doi:10.4172/2376-0281.1000207
Copyright: © 2016 Gozum MALP, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Visit for more related articles at International Journal of Neurorehabilitation
The use of Botulinum toxin type A (BoNT) to address spasticity has been established over the years, and recently considered first line treatment in chronic post stroke patients. With its promising results, BoNT is now being combined with early neurorehabilitation to treat post-stroke spasticity in order to address the various neuromuscular and biomechanical impairments, contracture prevention, dystonia, associated reactions and pain. The beneficial effects of BoNT as an adjunct to early stroke rehabilitation, in contrast to customary physical therapy alone, is the case in point of this review, so as to suggest another complementary treatment avenue in rehabilitation care.
Botulinum toxin; Rehabilitation; Post-stroke; Spasticity; Early care
One of the most evident and disabling sequel of stroke is spasticity, in which more than two thirds of stroke survivors who initially experience post-stroke spasticity (PSS) have residual deficits [1-3]. It is believed that spasticity (i.e., involuntary activation of muscles that is intermittently or continuously seen) [4] consequently causes development of secondary complications such as pain and contractures, and henceforth, impaired functional recovery. It is worth note-taking that the phenomenon of spasticity usually precedes the development of the aforementioned secondary complications [5-7]. It is estimated that around 30% of stroke survivors are affected by significant spasticity [8] and 50% who present to hospital with stroke develop at least one severe contracture [9].
Spastic paresis is a complex condition that may be associated with soft tissue contracture, pain and limitations of day-to-day activities, which therefore, substantially impacts on patients' and caregivers' quality of life [10]. The management of spasticity usually involves interdisciplinary subspecialties [11]. However, rehabilitation approaches are generally varied and are aimed primarily at preventing secondary complications and minimizing aggravating factors instead of focusing on the abnormal muscle activity itself [11]. In current practice, treatment of spasticity is delayed until complications are established. It is possible that once initiation of spasticity management is postponed, musculoskeletal impairments may progress to a degree that they already are almost impossible to eradicate [12].
An upper motor neuron (UMN) lesion produces a state of imbalance between the supra-spinal inhibitory and excitatory inputs, disinhibiting the spinal reflexes. These include proprioceptive (stretch) and nociceptive (flexor withdrawal and extensor) reflexes. Changes in muscle tone is believed to be caused by disruption in the balance from reticulo-spinal and other subcortical descending pathways to the motor and interneuronal circuitry of the spinal cord, and the lack of an intact corticospinal system. Alterations in the descending tonic or phasic excitatory and inhibitory inputs to the spinal motor system and the disturbance in the segmental excitatory-inhibitory control may be observed [13]. Following brain and/or spinal cord injury, the input from higher levels (sensori-motor cortex) may be reduced or completely lost, resulting in insufficient regulation of muscle (stretch reflex) activity. The clinical appearance is a non-physiological flexion or extension of affected limbs. Furthermore, reduced activity in the agonist contributes to shortening and over-activity in a usually less-paretic antagonist muscle. As a result, torque imbalance occurs around joints, which leads to the well-known limb deformities.
Based on meta-analysis derived from well-conducted, randomized controlled clinical trials [14], botulinum toxin type A (BoNT) proved to be safe and efficacious in treating upper and lower limb spasticity. In fact, BoNT has been thought to be a first line treatment in focal/ multifocal spasticity in the post-stroke rehabilitation setting [15].
It is now understood that the overall involvement of antagonist resistance, whether of a reflex nature or not, is the critical factor in movement impairment in spastic paresis [16,17]. Hence, the understanding of the pathophysiology of spasticity and its consequences, if recognized, could result in better goal setting and possibly more favorable patient outcomes.
Our aim here is to show how, incorporating BoNT injection in early neurorehabilitation, provide a wider avenue of available treatment options in improving muscle tone and functional ability of the paretic limb in patients suffering from PSS. The focus problem areas in this present work will be on areas of spasticity-related co-contraction, dystonia, associated reactions, local biomechanical changes, contracture and pain. The case in point, being to perhaps shift a frame of mind from what happens of spasticity, left not adequately addressed, lest the "myth" (Figure 1) of not being able to do anything more, remains.
The term 'spasticity' has been inconsistently defined [18]. Measures used to assess spasticity usually do not correspond to the defined clinical features of spasticity. Exaggeration of stretch reflexes leading to velocity-dependent increase in passive resistance to stretch of muscle or muscle groups is the fundamental feature of spasticity [19]. In the 1980s, focus was placed on spinal reflexes, as spasticity was described as "a motor disorder, characterized by a velocity-dependent increase in tonic stretch reflexes (muscle tone) with exaggerated tendon jerks, resulting from hyper-excitability of the stretch reflex as one component of the UMN syndrome" [20]. In the SPASM consortium in 2005 (European Thematic Network to Develop Standardized Measures of Spasticity), the positive symptoms were combined and spasticity was described as "disordered sensorimotor control, resulting from an upper motor neuron (UMN) lesion, presenting as intermittent or sustained involuntary activation of muscle" [13].
Epidemiology and burden of disease
Reported prevalence of PSS ranges from 4% to 27% during the first 6 weeks after stroke [21-23]. The rate has been reported to be 19% at 3 months, 21.7% to 42.6% at 4 and 6 months, [21-24] and 17% to 38% at 12 months [25,26] post-stroke. In addition to the increased muscle tone of PSS, indirect effects, such as limitations of activities and participation due to physical impairments, have significant impacts on a patient's daily functioning (e.g., personal hygiene, housework, and work place activities) and quality of life [27].
Spasticity and its associated impairments
Spastic co-contraction: Spastic co-contraction refers to inappropriate antagonist recruitment triggered by the volitional command on an agonist in the absence of stretch. Spastic co-contraction primarily results from an abnormal pattern of supra-spinal drive, which can be aggravated by abnormal peripheral reflex reactions, particularly to the degree of stretch tonically imposed on the overactive muscle [16,28]. Although some co-contraction (i.e., simultaneous activity in both agonist and antagonist muscles) is common during normal human movement [29], in the scenario of spastic paresis, it is present to an excessive degree.
Spastic co-contraction directly impedes voluntary movement and hence, may be one of the most disabling types of muscle over activity. As muscle over activity predominates in some muscles in spastic paresis, producing agonist–antagonist imbalance [30,31], intramuscular injection of BoNT has been proposed to restore balance around joints by focally reducing muscle over- activity [14]. In a study by Vinti et al. [32], it has been found that in spastic hemiparesis, stretch may facilitate agonist recruitment and spastic co-contraction. On the other hand, in the non-injected antagonist, co-contraction may be reduced by enhanced reciprocal inhibition from a more relaxed, and therefore stretched, agonist or through decreased recurrent inhibition from the injected muscle [32].
Spastic dystonia: Spastic dystonia is defined as a stretch-sensitive tonic muscle contraction in the absence of phasic stretch of the affected muscles and in the absence of voluntary command to adjacent muscles [32]. Simply put, spastic dystonia implies a relative inability to rest muscle that is responsive to the amount and duration of the tonic stretch enforced on the muscle. It alters resting posture and thus contributes to deformity and impairment in passive function (i.e. tasks involving the paretic limb as a passive object such as washing hand or donning sleeve) [33].
Spastic dystonia is highly responsive to the amount and duration of tonic stretch imposed on the dystonic muscle [30]. Along with soft tissue contracture, spastic dystonia is an important factor in increased resistance to passive movement and deformity. In most cases, tonic stretch maintained for at least several seconds inhibits spastic dystonia and improves the ability to rest the muscle. Muscle lengthening should raise the recruitment threshold of the stretch receptors in the muscles affected and thus reduce the severity of these potentially disabling forms of over-activity (in particular spastic dystonia) [32].
Spastic-associated reactions
Associated reactions are abnormal postural reactions commonly observed in the affected side of hemiplegic patients and most easily seen in the upper limb [34]. Recent studies have demonstrated that associated reactions in the upper limb are purposeless and do not contribute posturally to the realization of voluntary movement [35]. Functionally, they are considered to be the product of effort [36,37] and a reflection of underlying postural instability [38]. Their clinical impact is vast. They have been implicated in preventing the return of selective movement in the hemiparetic limb, increasing the probability of contracture formation and interfering with function [39-41].
Consequently, clinicians have targeted associated reactions in various management strategies and have viewed their improvement as a measure of patient progression [42].
Local biomechanical changes and contractures
In patients with UMN syndrome, spasticity is held responsible for the velocity-dependence of muscle hypertonia. However, it must be reiterated that in patients with UMN syndrome, muscle hypertonia is a complex phenomenon, and that spasticity is just one aspect. Studies conducted on animals show that immobilization of muscles at short lengths reduces number of serial sarcomeres [43] and increased the proportion of connective tissue present in the muscle [44]. These changes that emerge very early during stages of immobilization augment muscle resistance to passive movements and increase the resting discharge of muscle spindles and hence, their sensitivity to stretch [45-47]. It is possible that in patients with UMN syndrome, muscle contracture is formed by similar adaptations. In this subset of patients, muscle contracture contributes significantly to hypertonia [48-50]. Thus, in early PSS of less than three months, an opportunity is there to treat prior to occurrence of local biomechanical changes [51] and perhaps even contracture [52].
Spasticity-related pain
Pain can directly induce spasticity [53]. It has been shown that in healthy subjects, lengthening of a contracted muscle can cause interference of some muscle fibers with the release of nociceptive substances [54]. When a spastic muscle is stretched, the same process is expected to happen. In addition, all the positive and negative features of UMN syndrome, in combination with soft tissue changes, disturb distribution of body weight thus inducing unwarranted stress on joint structures and causing pain [55].
Disturbances in sensory inputs also play a role, including the case of post-stroke central neuropathic pain from parietal, thalamic, and brainstem lesions. All of these factors lead to perceived pain by patients with UMN syndrome. The relationship between pain and spasticity is made stronger by the fact that pain increase spasticity, creating a spasticity-pain-disability cycle [56].
Over the last decades, several non-pharmacologic strategies have been used to address spasticity, including muscle stretching, muscle strengthening, physical modalities, and pain management [57]. These procedures may have neurophysiological and biomechanical effects on the spastic movement disorder. It has been validated in a meta-analysis addressing physical regimens, and how these would influence in the management of upper and lower limb PSS [58]. In the case of early PSS, Table 1 summarizes physical modalities that have been performed (Table 1).
|Rehabilitation Management
|Examples of Modalities
|Muscle Stretching[60]
|Passive stretching
Active stretching
Prolonged positioning
Isotonic stretching
Isokinetic stretching
*Often in combination with other interventions such as orthoses, casting, surgery and spasticity-reducing modalities[61]
|To improve the visco-elastic properties of the muscle-tendon unit, and to reduce the risk of muscle-tendon injury
|Muscle Strengthening [58,62]
|Muscle training
Electrical Stimulation
|To generate increased level of muscle force under specific sets of testing conditions to improve muscle strength
|Physical Modalities [60]
|Shock wave therapy
Ultrasound therapy
Electrical stimulation
|To increase local metabolism, circulation, extensibility of connective tissue and tissue regeneration
|Constraint-induced Movement Therapy (CIMT) [63]
|Forced use and the massed practice of the paretic arm by restricting the unaffected arm. The unaffected arm and hand are prevented from moving with a glove and a special arm rest.
|To improve reaching, grasping, and manipulating objects using the paretic arm and improve bi-manual tasks in many aspects of activities of daily living such as eating, bathing, dressing, and toileting
Table 1: Rehabilitation procedures in the management of early post-stroke spasticity.
Use of BoNT in early spasticity
In the post-stroke rehabilitation setting, BoNT represents a firstline treatment for focal spasticity. Many studies and meta-analyses demonstrated its safety and efficacy in decreasing spastic hypertonia and pain, improving arm posture and basic upper limb activities such as hand hygiene and facilitation of dressing [59-65].
Botulinum toxin A: Grade A recommendation has been given by the 2016 Guidelines Development Subcommittee of the American Academy of Neurology on the use of BoNT for the treatment of adult spasticity [66]. An earlier meta-analysis of 16 clinical studies with BoNT indicated that it decreases muscle tone and increases range of motion safely and effectively [67]. BoNT exhibits dual peripheral effects through chemodenervation of cholinergic transmission in both extrafusal and intrafusal muscle fibres [68]. BoNT-induced changes in muscle spindle proprioceptor inputs through denervation of the intrafusal muscle fibers are particularly essential in modulating loss of presynaptic inhibition in dystonia, and this phenomenon of afferent effects also may be true in the case of spasticity [68]. BoNT injections into the shorter of the two co-contracting muscles around the joint will augment stretching activities. There is also some evidence for modulation of sensori-motor loops at the spinal and supra-spinal level, as assessed by neurophysiological and functional MRI technologies (i.e. before and after BoNT treatment) [69].
Interestingly, there are looming good data that BoNT, as applied in person-centered goal-attainment scaling process, may have a better impact in the individuals with PSS [70].
A minimum of 24 to 72 h requires BoNT to take effect. The peak effect occurs at about 10 days, and clinical improvements usually last for up to 12 weeks [71]. It must be recognized that though BoNT use is limited in multifocal and generalized spasticity, and treatment effects are only temporary [72,73] it does open a therapeutic window for a combined neurorehabilitative approach. The reversibility of BoNT effects may lead to repeated treatment in chronic spasticity, but perhaps may modify the course of spasticity in early post-stroke intervention [74].
Optimally, the best time to administer BoNT may be when spasticity becomes evident and bothersome to the patient, resulting in impairment of functions both actively and passively, disability and associated reactions, or when it induces pain [74]. It was shown by the Upper Limb International Spasticity Study (ULIS)-II that 80% of patients with post-stroke upper limb spasticity treated with BoNT in a real-life clinical setting achieved their treatment goals, that is, pain reduction and return to various functions [75]. Early (less than 3 months after stroke) single-dose BoNT treatment of spasticity has been investigated in three upper limb studies [76-78], aimed at reducing muscle tone, contracture prevention and improving function. With the objectives of hypertonia reduction and improving ambulation, the advantage of early BoNT therapy for lower limb PSS and nonprogressive brain lesions, have likewise been demonstrated [79-81]. A summary data on the specific effects of early BoNT intervention in PSS of upper and lower limbs is presented in Table 2. Undoubted effects on hypertonia can be derived with early use of BoNT for upper and lower limb PSS. While the jury is not yet there in regard to early use of BoNT in PSS to improve active function, clinical trials may have to be designed to include longer (i.e., >6months) observation periods for outcomes, as the nervous system adapts to the new changes in the evolution of spasticity.
|Therapeutic Goals
|Upper Limbs
|Lower Limbs
|Upper Limbs
|Lower Limbs
|Reduce hypertonicity
|-Cousins etal.[77]
-Hesse et al.[78]
-Rosales et al.[79]
|-Verplancke et al.[80]
-Fietzek et al.[81]
-Tao et al.[82]
|Reduce pain
|-Hesse et al.[78]
-Rosales et al.[79]
|Improve disability
|-Hesse et al.[78]
|-Rosales et al.[79]
|Improve functionality
(Motor control)
|-Cousins etal.[77]
-Hesse et al.[78]
|-Tao et al.[82]
|-Hesse et al.[78]
-Rosales et al.
|Prevent contracture
|-Hesse et al.[78]
|-Verplancke etal.[80]
|Sustained effect up to 6 months (Reduction of hypertonicity)
|-Rosales etal. [79]
Table 2: Summary of the Use of Early BoNT (type A) in Spasticity (<3 months from Ictus).
Early use of BoNT may also extend the time window for motor re-learning with physiotherapy by decreasing overactive extrafusal muscle fibers and reducing muscle spindle sensitivity through chemodenervation of intrafusal muscle fibres [51]. In effect, the early BoNT intervention paradigm may potentially modify the natural progress of spasticity, prevent spasticity/dystonia-related complications or even delay re-injection [74].
Upper limb rehabilitation
rTMS/OT, and BoNT: Low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with intensive occupational therapy (OT) have been reported to improve the motor function of the paretic upper limb after stroke [82-84]. This combination was based on the premise that that neural activation is facilitated with concomitant application of the two interventions. At present, the combination of rTMS/OT is safely used in several institutions as a therapeutic tool not only for treatment in non-spastic but also for treatment in spastic upper limb hemiparesis [85,86]. However, the effect of rTMS/OT seems to be affected by the severity of the motor functional impairment of the affected upper limb, and this is largely related to the presence or absence of spasticity. Based on these effects, it could be hypothesized that local injection of BoNT into the spastic muscles before the application of rTMS/OT, may potentially enhance the treatment outcome especially in patients with spasticity and post-stroke upper limb hemiparesis.
In a study by Yamada and cohorts [87], eighty patients with PSS were randomized into either the BoNT plus rTMS/OT group versus the rTMS/ OT only group. A total dose of 240 units BoNT was injected into the spastic muscles before rTMS/OT. It was shown that both groups showed significant improvements in terms of spasticity and motor function. However, the addition of BoNT led to better improvement as assessed by the Fugl-Meyer Assessment score and Modified Ashworth Scale of finger flexor muscles (p<0.05). It was concluded that the triple-element protocol consisting of BoNT, rTMS and intensive OT, is a promising therapeutic program for spastic upper limb hemiparesis following stroke.
Lower limb rehabilitation
Ambulatory rehabilitation and BoNT: The benefits of high intensity ambulatory rehabilitation programs over the customary care following BoNT have been examined by Demetrios et al. [88] for PSS among Australian adults. Following BoNT injections for PSS, participants were divided into 1) high intensity ambulatory programs (greater than or equal to three times weekly of one-hour sessions for a total of approximately ten weeks) or 2) customary care programs (less than or equal to two times weekly of one-hour sessions). Assessorblinded outcomes were completed at baseline (0), 6, 12, and 24 weeks. It was found that both groups had significant improvement in goal attainment and participant satisfaction until 24 weeks; no overall between-groups differences were significantly seen. However, there was a statistical trend (p=0.052) for participants to achieve more upper limb goals in the high intensity therapy group. The authors therefore forwarded that there was a trend for high intensity therapy to be related to greater upper limb goal attainment even if patient-centered outcomes after BoNT injections for PSS were not influenced by the intensity of ambulatory rehabilitation strategies [88]. A further research is required to evaluate such effect and determine which elements of therapy programs enhance post-BoNT outcomes. Interestingly for the lower limb spasticity, a Chinese cohort receiving functional electrical stimulation combined with conventional rehabilitation program (as against the conventional rehabilitation program alone) improved mobility and activities of daily living in early PSS [89]. The latter phenomenon opens a divide on whether BoNT (in combination with rehabilitation) [79-81] may still impact on improved care for this group of patients with lower limb PSS (Table 2).
In today's milieu, where PSS and its residual deficits remain to be one of the most incapacitating conditions, comprehensive rehabilitation is of utmost importance. BoNT therapy, in combination with stroke neurorehabilitation programs, when instituted in the early stages (3 months post-ictus), aims to provide a wider avenue of available therapeutic interventions to improving muscle tone, dystonia, associated reactions, contracture prevention and pain among patients suffering from PSS.
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He's a Robel
The Cubs have signed INF Robel Garcia to a 2019 minor league contract and he has been assigned to AAA Iowa.
The 25-year old switch-hitting Garcia was a member of the Italian National team that was a guest of the Oakland Athletics at Fitch Park in Mesa over the past month. (Ex-Cubs minor leaguers RHP Alessandro Maestri and C-1B Alberto Mineo were also on the squad). Besides working out with the A's minor leaguers, Team Italy participated in a dozen AZ Instructional League games, and that's where the Cubs saw Garcia play before offering him a contract. NOTE: While the Cubs did not field an AZ Instructs team this year, Cubs professional scouts did attend games.
Garcia played for UniPolsai Bologna (Fortitudo B. C. 1953) in 2018. He hit 281/343/490 and was 2nd in the league in triples and 10th in doubles during the regular season, before hitting .400 in the semifinali serie and .357 in the finale serie as he helped lead his club to the Federazione Italiana Serie A1 (the Italian major league) championship.
Signed by the Cleveland Indians out of the Dominican Republic as a 17-year old back in March 2010, Garcia spent four very uneventful seasons in the Indians farm system (hitting a combined 217/326/356 in 274 games) before being released at the end of Minor League Camp in 2014, but he didn't give up, so now he will get another chance with the Cubs.
Garcia probably projects as a AAA or AA utility infielder at this point, but time will tell.
If anyone wants to watch
If anyone wants to watch Garcia hit for the cycle in a recent game for Team Italy, here you go. He bats at 0:28, 0:55, 2:03, and 2:52
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never really considered how that might be cool for people used to seeing those midwest fields as an everyday occurance. in the south-east US you rarely see the vastly massive acerage of farm-against-farm-against-farm-etc...
also, i spent a good amount of time out in corn fields in ames, iowa in my last job. everyone wanted to go work the research fields in hawaii, but we always ended up in iowa.
Sonicwind75 17 hours 16 min ago (view)
Hey, I'm pretty excited about the Field of Dreams game. I grew up on a farm in middle of nowhere Iowa and my brother and I spent a lot of time trying to hit baseballs into a corn field. I'm seriously considering coming back next summer from Texas to go to that game if prices aren't super stupid expensive. Added bonus, I won't have to listen to A-Rod and Mendoza ignorantly discussing corn and no, you don't eat field corn like you would sweet corn.
Dolorous Jon Lester 1 day 5 hours ago (view)
That is truly staggering. Shame on the rest of the Central that we are only one loss behind the pissboys, we should have been buried by now with that kind of stat.
crunch 1 day 13 hours ago (view)
...and strop gives up a hit then walks the bases loaded.
...and he closes it out with a K. neat.
this is the 1st cubs road series win since May 17-19 @WAS.
crunch 1 day 13 hours ago (view)
strop comes in to get the last out, but it has to be some kinda slow-walk back in a game that wasn't a save situation.
homer, hbp, k, k...looks healthy.
crunch 1 day 13 hours ago (view)
welcome back kimbrel.
1st pitch goes about 10 miles outside the park by marte.
crunch 1 day 14 hours ago (view)
one takeaway from this game...a slew of cubs players were fans of Hey Arnold! when they were kids.
crunch 1 day 15 hours ago (view)
woo, a good cubs away game.
crunch 1 day 17 hours ago (view)
heyward / cast / bryant / rizzo / baez / schwarb / caratini / kemp(2nd) / Q
crunch 1 day 18 hours ago (view)
so stoked for the williamsport game.
the increasing amount of off-site games is a bit concerning (middle of nowhere Field of Dreams field, really?), but I love this one. it's played out great so far and giving the kids playing in the LL series some primo seats (hope this continues) is a great touch.


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Forklift Drivers
Posted 16 days ago by Pertemps
|Job Type
|£9.50 - £12.18 per hour
|Manufacturing & Industrial
The company are a growing storage & distribution business based in Sharpness that provide a logistics services to all sectors including retail, automotive, food and drink, there 640,000 Sq Ft of storage and warehousing is the largest in the area therefor they requiring a number of forklift drivers ongoing.
Your job working in a busy warehouse as a Counterbalance Forklift driver you will be responsible for stock rotation, stacking pallets and loads in to loading bays and on to vehicles ensuring all orders are picked and sent out within the allotted time correctly. You will be required to drive the Forklift for long hours using a double handling attachment as well as all other warehouse duties that include; Manual handling, lifting, sweeping, tidying and maintaining health & safety.
To be Successful
A valid in date RTITB or ITSSAR Counterbalance Forklift licence.
Scanning, Picking & Packing experience.
Good Reliability & Timekeeping.
Good communication skills.
Own Transport due to location and shift times.
Pass an unpaid onsite forklift induction.
Days £9.50ph Monday to Friday
Overtime £11.50ph after 37.5 hours worked.
Shifts rotating 0600 - 1400 / 1400 - 2200.
Overtime and Bank Holiday rates.
Full training and site induction provided.
Any candidates to be considered must have experience in a similar role.
Register at Pertemps, Unit 4A, Elmbridge Court, Cheltenham Road East, Gloucester, GL3 1JZ - OPEN 08:00 - 17:00 Monday to Friday
Please CLICK APPLY NOW or call Josh at Pertemps Gloucester 01452 507500.


text:
Business Owners:
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text:
According to the World Health Organization 34.3 million people in the world have the
AIDS virus
The Facts: In 1959 scientist identified the AIDS virus. Only In the mid 80's a
scientist at the National Institutes for Health, with a high profile reputation in cancer
research claimed to have proved the link between HIV and AIDS, although disputed
at the time by a handful of scientist, in their desperation to find a cure, the world
stopped looking for the virus and began trying to find a treatment or vaccine.
Sixteen years later governments and private organizations across the world have
poured billions of dollars in research, treatment and prevention strategies and to
date no one has provided scientific proof of the link between HIV and AIDS.
Amongst other that disagreed with the above claims, a German born molecular
Biologist at the University of California Berkeley wrote a book "Inventing the AIDS
myth" his theory coincided with the above, that Western scientist prematurely
concluded that HIV causes AIDS and when billions of dollars became available to
study the disease, scientist jump on the band wagon and have been heading in the
wrong direction ever since.
Some scientist believe that HIV is not sufficient to cause AIDS and there must be
what they call co-factors. No one has yet found a vaccine and claims of evidence of
the isolation of the virus have been disputed.
The human immunodeficiency virus (HIV) is a frequently mutating retrovirus that
attacks the human immune system and which has been shown to cause acquired
immune deficiency syndrome (AIDS).
HIV was discovered and identified as the agent for AIDS by Luc Montagnier of France
in 1984.
A minority of scientists continues to question the connection between HIV and AIDS
and even the very existence of HIV (see AIDS reappraisal).
HIV causes disease by infecting the CD4+ T cells. These are a subset of leukocytes
(white blood cells) that normally coordinate the immune response to infection. By
using CD4+ T cells to replicate itself, HIV spreads throughout the body and at the
same time depletes the very cells that the body needs to fight the virus. Once a
HIV+ individual's CD4+ T cell count has decreased to a certain threshold, they are
prone to a range of diseases that the body can normally control. These opportunistic
infections are usually the cause of death.
There are several reasons that HIV is so hard to fight. First, the virus is an RNA
virus, using the reverse transcriptase enzyme to convert its RNA into DNA. During
that process there is a large chance of mutation. Therefore, the virus becomes
quickly resistent to therapy. Second, the common notion that HIV is a killer feasting
on T cells is not true. If HIV were a killer virus, it would have died out soon because
there would be too little time for new infections. Now, HIV stays in the body for
years, infecting people through unsafe sex, blood transfusions and breastfeeding of
infants while the patient sometimes doesn't know. HIV can survive even when drugs
eliminate all detectable virons in the blood. It integrates itself into the DNA of the
host cell and can stay there for years, lying dormant, immune to all kinds of therapy
because it is just DNA. When the cell divides and the DNA is copied, the virus is
copied too. After years, the virus can become active again, seize the cell's machinery
and replicate. In recent years, the notion that the CD4+ T cells decrease because of
direct HIV infection has become doubted as well. The HIV coating protein readily
detaches from virus particles. The blood becomes filled with these proteins, which
can stick to the CD4+ T cells, gluing them together. In addition, they are recognized
by the immune system, causing the immune cells to attack their own CD4+ cells. In
summary, HIV is a guerrilla terrorist, keeping low and seeking shelter when
threatened, but always ready to hit where it hurts.
HIV Tests
Several tests exist to detect the presence of HIV, the virus that causes AIDS. They
are used for different purposes:
Some terminology:
• The window of a test is the time period after initial infection during which the
test cannot yet detect the presence of HIV. The shorter the better.
• The specificity of a test is the percentage of HIV positive cases that are
correctly identified as positive by the test.
• The sensitivity of a test is the percentage of HIV negative cases that are
correctly identified as negative by the test. The higher the better.
HIV affects the immune system in broad and devastating ways. Its main target is a
special immune system cell called the CD4+ T lymphocyte. These cells help the body
fight infections of all kinds. When HIV infects these cells, it decreases their numbers
and affects how the cells that are left function.
After an adult is infected with HIV, he or she usually has no obvious symptoms for 5
to 10 years. During this time, however, the virus is slowly attacking the immune
system. When the immune system is weakened enough, it becomes susceptible to
other organisms that the body can usually fight off or keep under control. These
other organisms include bacteria, other viruses, fungi, and parasites.
Many serious health problems occur as a result of the immune system damage
caused by HIV. The most serious is AIDS.
Following are some of the signs and symptoms of HIV infection: · abdominal pain
· altered mental status · chest pain · cough · depression, often with suicidal thoughts
· eye problems, such as blurred vision or floaters · fatigue · fever · headache · night
sweats · rashes · shortness of breath, especially with exertion · sore throat · vomiting
and diarrhea · weight loss in adults or failure to thrive in children
People infected with HIV often have other infections because of their weakened
immune system. These infections may include: · infections with unusual organisms
· recurring or ongoing upper respiratory tract infections, such as colds or tonsillitis, in
children · recurring yeast infections in women
Although practicing safer sex cannot completely protect a person from HIV, it can
lower the risk. Condoms help prevent passing along the virus. Research in
laboratories has shown that a spermicidal called nonoxynol-9 kills or stops the
growth of HIV. However, there are not yet any studies that prove spermicides prevent
HIV infection in humans. Some experts do believe that using spermicide on a
condom or putting it into the vagina can kill some HIV organisms before they can
infect the woman. It is safest to avoid sexual intercourse with people who have HIV
infection or unknown HIV status and those who use IV drugs.
A person should not share needles, syringes, or other drug paraphernalia that could
carry tainted blood or body fluids with anyone. When caring for someone in an
emergency, it is important to wear gloves to protect against HIV in body secretions.
A woman who is pregnant or thinking about getting pregnant, should ask her doctor
to test her for HIV. If a woman has HIV, steps can be taken during pregnancy and
birth to avoid passing it to her baby.
The body produces antibodies to fight off HIV infection. HIV is usually diagnosed by
blood tests called antibody titer tests. The enzyme immunoassay, or EIA, is used as a
screening test. If this test is positive, a HIV Western blot test is done to confirm the
diagnosis. The virus can also be detected by testing for viral proteins and by doing
blood cultures. Other tests may be ordered to help diagnose complications of HIV
infection, such as pneumonia.
Negative tests do not always mean that a person is free of infection. Weeks or
months might pass after exposure to the virus before antibodies can be detected in
the body.
HIV causes many long-term effects, including: · autoimmune disorders, which cause
the body to destroy its own tissues · cancers, such as Kaposi's sarcoma and non-
Hodgkin''s lymphoma · cytomegalovirus infections, which can affect vision
· meningitis caused by cryptococcal organisms · neuropsychiatric disorders, which
change the person's thinking and interaction with others · Pneumocystis carinii
pneumonia · premature death · toxoplasmosis, a respiratory infection · tuberculosis
There are a number of medicines that effectively treat HIV. Over the past few years,
combinations of certain drugs have been very promising in controlling HIV. Some of
them are as follows: · antibiotics, such as trimethoprim-sulfamethoxazole or
pentamidine · antifungal medicines, such as amphotericin B and flucytosine
· antiparastic medicines, such as pyrimethamine · antiviral medicines, such as
zidovudine, lamivudine, nevirapine, and ganciclovir · glucocorticoids, such as
prednisone · protease inhibitors, such as indinavir
People who have HIV infection face significant health problems and stress. Following
are some helpful interventions: · Eat a healthy diet, following the food guide
pyramid. · Get plenty of rest and sleep. · Join support groups. · Take medicines to
deal with emotional symptoms. · Use psychotherapy. · Use relaxation therapy and
other stress management techniques.
Unfortunately, most HIV medicines have many side effects, depending on the drug
being taken. Some more common side effects include: · diarrhea · nausea · rashes
· vomiting
Some less common side effects are as follows: · changes in the brain and behavior
· inflammation of the pancreas · kidney stones
There is no cure for HIV infection at this time. The goal of treatment is to keep the
virus under control with the hope of preventing further immune damage. Currently, a
person must be treated for life.
Someone with HIV infection will have regular visits with the healthcare provider,
along with periodic blood tests. Any new or worsening symptoms should be reported
to the provider.


text:
"I don't like physical activities. When I was a student, I hated PE. I don't trust myself when it comes to anything that requires physical strength.
It became worse when I joined last year's #colormanilablacklightrun and got myself into an ambulance after just a kilometer or two.
But that wasn't enough reason to convince me not to join anymore. I hated running, yes, but I'm so in love with colors I would want to play with it that much.
So this year, I signed up again and got myself ready for the 10-kilometer run. Yes, another try.
This time, I made sure I would have enough sleep. I brought with me an energy drink. And I even had daily squats for weeks. I prepared somehow. And now I can finally say, I'm not that weak. I finished the 10-kilometer run…
This is not something to brag about but it's just something I can say proudly to myself who has for many years believed that she can't do more than that.
Actually, she did because she believed she can.
So joining this year means a lot because for someone who hates defeat, a good comeback is a must.
And this year? I defeated my old self. 😉


text:
Best Of The Web
The New American Puritans
"After I interviewed Nancy Pelosi a few weeks ago, The HuffPost huffed that we were Dreaded Elites because we were eating chocolates and — horror of horrors — the speaker had on some good pumps.
Then this week, lefty Twitter erected a digital guillotine because I had a book party for my friend Carl Hulse, The Times's authority on Capitol Hill for decades, attended by family, journalists, Hill denizens and a smattering of lawmakers, including Pelosi, Chuck Schumer and Susan Collins.
I, the daughter of a D.C. cop, and Carl, the son of an Illinois plumber, were hilariously painted as decadent aristocrats reveling like Marie Antoinette when we should have been knitting like Madame Defarge.
Yo, proletariat: If the Democratic Party is going to be against chocolate, high heels, parties and fun, you've lost me. And I've got some bad news for you about 2020.
Sign Up for The Privacy Project Newsletter
If you're online — and, well, you are — chances are someone is using your information. We'll tell you what you can do about it.
The progressives are the modern Puritans. The Massachusetts Bay Colony is alive and well on the Potomac and Twitter.
They eviscerate their natural allies for not being pure enough while placing all their hopes in a color-inside-the-lines lifelong Republican prosecutor appointed by Ronald Reagan.
The politics of purism makes people stupid. And nasty.
My father stayed up all night the night Truman was elected because he was so excited. I would like to stay up 'til dawn the night a Democrat wins next year because I'm so excited to see the moment when the despicable Donald Trump lumbers into a Marine helicopter and flies away for good."
JJ Editor's Picks
"Bangladesh is sometimes known as the "land of the rivers." It's got hundreds of them — and over the years, they've been getting more and more polluted. But as of early July, every single one of them has a remarkable new level of protection..."
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"When climate change comes for our coffee and our wine, we'll moan about it on Twitter, read about it on our favorite websites, and watch diverting videos on YouTube to fill the icy hole in our hearts. We'll do all this until the websites go dark..."
"Voters who trust their government — and each other — are more supportive of ambitious welfare states than those who do not. Across nations, high levels of social trust correlate with high levels of social spending. The relationship between these..."
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text:
Often times, you may want to apply points for things that can't be graded by Mimir Classroom's autograders. More subjective or preferential coding practices like comments, naming conventions, and more can be measured using manual grading on the Mimir Classroom.
A manual grade works similarly to an additional test case - you set how much the grade is worth and the total score is updated accordingly.
In this example, we have an automated grade worth 5 points and a manual grade worth 20. The total grade for this assignment would be 25 points, and the student above would receive an 18 out of 25.
Late penalties apply to manual grades, so if you're student has a 20% late penalty, and you give them 5 points for their manual grade, their final grade will only be increased by 4 points.
In addition to a manual grade, you can add a "Score Modifier". This is a flat modifier to the students final score which is unaffected by late penalties. This can be useful for dealing with special circumstances.
If you enable manual grading, than submissions must be manually graded and the grades must be released in order for students to see their scores on the "My Grades" page.


text:
I have never met a set of training rules that didn't make me flee, screaming, into he night.
I get the game theory reason to still have XP, I just don't like playing with or devving with it. It especially got ridiculous when 4e was designed to be 10 challenging encounters per level... and yet somehow still used XP even though it was just a marker of encounters and how they were tuned. The most it was really used for was calculating what monsters to use with an XP budget.
With Quick-Reply you can write a post when viewing a topic without loading a new page. You can still use bulletin board code and smileys as you would in a normal post.


text:
Quick Facts
- Current Prices:$609,900 to $850,000
- Closed Prices:$499,000 to $995,000
- Median Sale Price:$619,500
- Average $ per sq ft:$238
- Association Fee Ranges:$183 to $210/mo,$0 to $198
- Type:Attached Home (Condo, Townhouse, Loft, etc.), Single Family Home
- Age:2003 to 2018
- Sq. Ft.:2,101 to 5,109Sq. Ft.
- Bedrooms:3 to 5Bedrooms
- Bathrooms:3 to 6Bathrooms
Neighborhood Amenities
This community has numerous amenities available for residents to enjoy.
Homes for Sale
If you're in the market for a new home, Versailles has a fantastic variety of designs to choose from.
Disclaimer: School attendance zone boundaries are supplied by Maponics and are subject to change. Check with the applicable school district prior to making a decision based on these boundaries.


text:
Beautiful 4 bedroom, 3 bathroom, 3 car garage, 3 way split home, situated on a FANTASTIC CORNER LOT in the desirable GATED COMMUNITY of OAKSTEAD. Walking in you are greeted by a spacious dining room and living room nicely accented by dark laminated floors, archways and sliding doors with yard views. HUGE KITCHEN with AMPLE COUNTER SPACE, WOOD CABINETRY, NATURAL GAS STOVE, STAINLESS STEEL APPLIANCES, EXTRA CABINET STORAGE AND CENTER ISLAND. The large FAMILY room has a WOOD BURNING FIRE PLACE, A BUILT-IN SHELF UNIT AND SLIDING DOORS TO THE YARD CREATING A GREAT FLOW IN AND OUT FOR ENTERTAINMENT. The master bedroom has views of the yard and offers two walk-in closets. The master bathroom has double vanities, a garden tub and a separate walk-in shower. There are two nicely sized bedrooms on the opposite side on the house separated by a full size bathroom. A fourth bedroom perfect for guests is at the end of the house with a full bathroom that has access to the yard. FULLY FENCED back yard large enough for a pool. The house is plumbed ready for an outside kitchen and pool. The community offers a swimming pool, clubhouse with fitness center, basketball, volleyball and tennis courts, also play grounds, walking, bicycle trails and more. Oakstead is zoned for great schools and there is a preschool within the community. Conveniently located near the Tampa Premium Outlets, Wiregrass Mall, Veterans Express Way and I -75.
Oakstead Prcl 06 Unit 1 Prcl 07
Cable Available, Cable Connected, Electricity Available, Electricity Connected, Natural Gas Connected, Public, Sprinkler Recycled
Basketball Court, Clubhouse, Deed Restricted, Fitness, Gated Community, Irrigation-Reclaimed Water, Playground, Pool, Tennis Courts
Corner Lot/Unit, Sidewalk, Street Paved
Ceramic Tile, Laminate, Bamboo, Epoxy
Built in Features, Ceiling Fans(s), Eating Space In Kitchen, Kitchen/Family Room Combo, Living Room/Dining Room Combo, Solid Wood Cabinets, Walk-In Closet(s)
Convection Oven, Dishwasher, Disposal, Dryer, Range, Refrigerator, Washer, Gas Water Heater
Lighting, Rain Gutters, Sidewalk, Sliding Doors, Mature Landscaping
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Listing information last updated on August 21st, 2019 at 11:30am EDT.


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L/ Certified, UNLIMITED MILE Warranty Until 6/29/2022! CARFAX 1-Owner, GREAT MILES 12,466! JUST REPRICED FROM $23,597, $1,800 below Kelley Blue Book! Heated Seats, Sunroof, Satellite Radio, iPod/MP3 Input, CD Player, Dual Zone A/CBUY WITH CONFIDENCE161-Point Inspection and Reconditioning, 24/7 - Roadside Assistance, Balance of new car warranty plus 2 years/unlimited miles, Towing, Lockout Service, Emergency Fuel Service, Trip-Interruption Services. Please see dealer for complete coverage details. 2-Year/20k-Mile Complimentary Scheduled Maintenance (up to 4 Services) from date of purchaseEXCELLENT VALUEWas $23,597. This CT 200h is priced $1,800 below Kelley Blue Book.KEY FEATURES INCLUDEHybrid, Satellite Radio, iPod/MP3 Input, CD Player, Onboard Communications System, Aluminum Wheels, Keyless Start, Dual Zone A/C Rear Spoiler, MP3 Player, Keyless Entry, Remote Trunk Release, Steering Wheel Controls.OPTION PACKAGESTILT & SLIDE MOONROOF one-touch open/close, BACKUP CAMERA MOUNTED IN AUTO-DIMMING REARVIEW Compass, SEAT COMFORT PACKAGE 4-way power front passenger seat and heated front seats, ACCESSORY PACKAGE 2 Rear Bumper Applique, SmartAccess Key Gloves, Wheel Locks (PPO), Cargo Mat, Cargo Net. Lexus Hybrid with Redline exterior and Parchment interior features a 4 Cylinder Engine with 134 HP at 5200 RPM*. Serviced here, Non-Smoker vehicle, 15K Service Completed.EXPERTS CONCLUDEThe repeated cycling between the gasoline engine and the electric motor is so smooth you might not even notice. Same goes for the fuel-saving auto stop-start feature that kills the gasoline engine when the car comes to a full stop, and instantly fires it up when it's time to get moving. -Edmunds.com.This dealership charges a dealer closing fee of $579.00 on a motor vehicle sales contract. It is a charge that is permitted but not required by law (Section 37-2-307). The full cash price charged at any dealership depends on many factors, including all prThis Dealership checks the vehicle recall status prior to making any pre-owned vehicle available for sale. Manufacturers and/or NHTSA may announce additional recalls at any time. To inquire about the recall status of this vehicle, visit: https://vinrcl.safercar.gov/vin/
Welcome to Hendrick Nissan Kansas City, your trusted Nissan dealer in the greater metropolitan Kansas area! Our automotive mission is simple. We strive to meet every customer's automotive needs at our full-service Nissan dealership. From searching and purchasing the right vehicle to servicing repairs, our friendly staff is dedicated to assisting you. That's why we've earned the trust from Nissan owners in the communities of Overland Park, Shawnee, and Olathe!
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*$699 Dealer Administrative Charge is not included in advertised price. "AN ADMINISTRATIVE CHARGE IS NOT AN OFFICIAL FEE AND IS NOT REQUIRED BY LAW BUT MAY BE CHARGED BY A DEALER. THIS ADMINISTRATIVE CHARGE MAY RESULT IN A PROFIT TO DEALER. NO PORTION OF THIS ADMINISTRATIVE CHARGE IS FOR THE DRAFTING, PREPARATION, OR COMPLETION OF DOCUMENTS OR THE PROVIDING OF LEGAL ADVICE. THIS NOTICE IS REQUIRED BY LAW." All prices and offers are before state, city and county tax, tag, title and license fees. Out of state buyers are responsible for all state, county, city taxes and fees, as well as title/registration fees in the state that the vehicle will be registered. All prices and offers include all rebates and incentives which the dealer retains unless otherwise specifically provided. Dealer not responsible for errors and omissions; all offers subject to change without notice, please confirm listings with dealer.
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You most likely have obtained the fresh new flooring and it is included and the protecting plastic has to be thrown out within the dumpster. Once the sheetrock is completed it is possible to install your own brand new flooring or have the carpet layers get the job done for you.
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Please use the form below to contact us. We look forward to working with you and will get back to you as soon as possible. All fields are required


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Service Offered
Christina Wood
5891 Ranger Court -
Norcross, Georgia - 30092 - United States
|Over ten years exposure to the creative industry, including post production, advertising and public relations arenas. Highly organized and able to multitask multiple project deadlines. Superior client relations skills with recommendation letters of support.
|English (Creative Writing) with an emphasis in Business, Bachelor of Arts, Florida State University
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Submitted by Christina Wood on Jan 2, 2013
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5891 Ranger Court -


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The Academic Journal of Trinity Southwest University
Volume V
Number 3
God's representation of reality, the Bible, has been given for the purpose of allowing us to see what mere human observers cannot: the hand of God in the whirlwind.
The Academic Journal of Trinity Southwest University
Volume V
Number 3
Values Download, Hard Copy by Mail
The Defendable Faith is a reader-friendly apologetic source presented in way that is understandable and able to be enjoyed by all. Yet, it has been used as an effective college and seminary textbook. The material is clear, concise, and relevant to anyone seeking to develop and defend a biblical worldview. This is one of the best books available on Christian apologetics, written by an experienced and respected archaeologist and biblical scholar. It is a must-read.
Whereas most books on Revelation are theological in nature, this book is distinctively different. Get ready for a verse-by-verse—and sometimes phrase-by-phrase—walk through the apostle John's Revelation of Jesus Christ that will challenge you to think about what John might have actually seen as the Revelation unfolded and how he interpreted what he saw so that he could explain it to his readers. This book is intended to be used as a study guide. It asks a lot of thought-provoking questions and leaves unanswered questions that can be easily answered from the text of Revelation. Background information is provided where needed to help you understand the more subtle issues and difficult passages. Use this book for your own personal study. Use it as a leader's guide for group study. Just be ready to think—and to think outside the box—as you are led through this fascinating last book of the Bible.
An Ulpan is an Israeli language school. This workbook is based on the Ulpan alphabet learning program and is designed to help you learn the Hebrew alphabet and basic pronunciation. It is intended to be used in conjunction with the 18-hour course taught by the author at Trinity Southwest University in Albuquerque, New Mexico, but can be used in any learning context where the instructor is familiar with the Ulpan methodology. If you already have a basic knowledge of Hebrew, then you can also use this workbook for self-study and review to develop and maintain your proficiency with the Hebrew language.
This guide is designed for married couples and will help you study through God's Word in one year's time. It will also provide a common spiritual reference point for you both.


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Pharmacy Technical Assistant (Laboratory Technician)
- Jobs
- Jean Coutu
- Jean Coutu at 100 Boulevard Brien
- Pharmacy Technical Assistant (Laboratory Technician)
About the Job
Please refer to the English description.
About the Brand
The Jean Coutu Group is at the head of a network of 417 franchised stores with close to 20,000 people in Quebec, New Brunswick and Ontario.
Pleasant service, sincerity and most of all, a friendly smile, make us and our brand stand out. These characteristics also serve as the heart of our constantly growing network. Customer satisfaction starts with happy employees.
Our success starts with you.
Whether you are a student, retired or simply looking for a work environment where employees are at the heart of our success, discover the various employment opportunities offered to you.
Personal Care
Jean Coutu is located at 100 Boulevard Brien, Repentigny Canada in Galeries Rive Nord.


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Published at Saturday, August 24th, 2019 - 9:56 AM. mack Wiring Diagram. By Lisa D. Pounders.
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Richmond VA 23220-4130
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We are a Spirit-filled, Bible-believing church that loves building people up in Christ. Pastors Donnie and Jennifer Sutton Passion Ministries vision is to provide: • ...
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Hopewell VA 23860-4933
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Italys most successful wartime bomber the S.79 saw combat with the Regia Aeronautica in France Yugoslavia Greece North Africa East Africa and in the Mediterranean. Initially developed as a transport the aircraft evolved into a dedicated medium bomber during the Spanish Civil War in 1936. The manufacturer then produced the S.79II torpedobomber which entered service in 1939 which primarily saw service against the Royal Navy in the Mediterranean. Illustrated with 30 full colour profiles
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