Effect of Inspiratory Muscle Training in Patients With
Multiple Sclerosis

Brita Klefbeck, PT, PhD, Jallal Hamrah Nedjad, PT, MSc
ABSTRACT. Klefbeck B, Hamrah Nedjad J. Effect of confirmed through laboratory tests. The disease presents either inspiratory muscle training in patients with multiple sclerosis.
with an exacerbating-remitting pattern, which is characterized Arch Phys Med Rehabil 2003;84:994-9.
by periods of impairment followed by full or partial remissionof symptoms, or with a chronic, progressive pattern. This latter Objective: To evaluate whether inspiratory muscle training
(IMT) improves inspiratory muscle strength, respiratory capac- pattern can be subdivided into progressive from the onset and ity, fatigue, and subjective perception of physical endurance in secondarily progressive, in which there is a steady worsening patients with advanced multiple sclerosis (MS).
of symptoms over time, with ataxia, visual loss, weakness, Design: Randomized controlled trial.
spasticity, fatigue, bladder dysfunction, and so on.4-6 Setting: Outpatient clinic in Sweden.
When a neuromuscular disorder is progressive, symptomatic Participants: Fifteen severely disabled patients with MS,
respiratory muscle weakness is inevitable. The MS plaques are randomized to a training or control group.
often found in the brainstem and upper cervical spinal cord.7 Intervention: Seven patients trained with a Threshold in-
Pathophysiology and clinical features of MS vary in each spiratory muscle trainer, twice every other day, with 3 sets of patient. As a result of the demyelinated plaques, abnormalities 10 loaded inspirations (40%– 60% of patients’ maximal in- of speech and weakness of muscle groups responsible for spiratory pressure [PImax]) over a 10-week period.
speech and/or swallowing are common. In addition, patients Main Outcome Measures: Spirometry, PImax, maximal
with bulbar lesions may have both laryngeal and pharyngeal expiratory pressure (PEmax), clinical assessments, and ques- dysfunction, causing symptoms such as dysphonia, dysphagia, tionnaires on the patients’ fatigue severity and physical endur- and aspiration.7 Severe respiratory muscle weakness can be expected in patients with MS who are severely paraplegic, and Results: After training, the PImax (PϽ.008) and PEmax
the weakness increases as the upper extremities become in- (PϽ.02) increased in the training group. The improvement in creasingly involved.8-10 Respiratory complications are a major PImax after 10 weeks of training was higher than the improve- cause of morbidity and mortality in patients with MS.11 Aspi- ment in the control group (PϽ.01) and was maintained 1 month ration and pneumonia secondary to bulbar weakness and im- after the training period ended. The training affected neither mobility have long been recognized as common events in respiratory function nor the patients’ symptoms.
Conclusions: IMT had a beneficial effect on inspiratory
muscle strength in patients with MS and is recommended as a Inspiratory muscle weakness often occurs in neuromuscular complement to ordinary physical training.
disorders. It is sometimes associated with a chronic increase in Key Words:
Multiple sclerosis; Physical therapy tech- arterial carbon dioxide tension.13 Immobility reduces lung vol- niques; Rehabilitation; Respiration.
ume and can lead to postural hypotension, constipation, urine 2003 by the American Congress of Rehabilitation Medi- retention, osteoporosis, depression, and deconditioning.13 Pa- cine and the American Academy of Physical Medicine and tients with MS show a poor exercise tolerance, with fatigue and dyspnea on exertion, which limits their ability to performactivities of daily living14 (ADLs).
MULTIPLE SCLEROSIS (MS) is a chronic inflammatory
Fatigue is a particular problem in patients with MS. Its disease of the central nervous system (CNS); this disease mechanism and precise etiology remain unresolved,3 because affects mostly young and middle-aged adults and is associated fatigue does not correlate with the degree of neurologic im- with selective destruction of the myelin sheaths. This leads to pairment or disability in these patients.15,16 the formation of large demyelinated plaques dispersed through- Efforts have been made to examine the effect of training of out the CNS, with a predilection for the optic nerves, brain- respiratory muscle strength and endurance by using different stem, spinal cord, and periventricular white matter. In partic- resistive breathing devices. In several studies, a Threshold ular, in cases with progressive disease, severe neurologic inspiratory muscle training (IMT) device has been used in deficit axonal destruction and loss can be profound.1-3 MS is patients with chronic obstructive pulmonary disease (COPD) orasthma to improve inspiratory muscle strength and endur-ance.17-23 The usefulness of the IMT device in patients withneurologic dysfunction has been shown by several research-ers24,25 who have explored the influence of this training method From the Neurotec Department, Division of Physiotherapy, Karolinska Institutet on inspiratory muscle strength and endurance. Few studies (Klefbeck); and Habilitation Center for Adults (Hamrah Nedjad), Stockholm, Swe-den.
have, however, focused on increasing respiratory muscle func- Supported by the Swedish Association of the Neurologically Disabled, Norrbacka- tion in patients with MS to improve respiratory function and/or Eugeniastiflelsen, the Foundation of the Swedish Committee for Rehabilitation, and Handicap & Habilitation, Stockholm County Council.
This study evaluated whether 10 weeks of supervised train- No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the author(s) or upon any ing of inspiratory muscles in patients with MS would affect organization with which the author(s) is/are associated.
their respiratory muscle strength, respiratory capacity, and gen- Reprint requests to Jallal Hamrah Nedjad, Habilitation Center for Adults, eral well-being, as measured by indices such as fatigue and Kemistva¨gen 8, SE-183 79 Ta¨by, Sweden, e-mail: subjective perception of physical endurance, without causing 0003-9993/03/8407-7386$30.00/0doi:10.1016/S0003-9993(03)00133-3 any adverse effects. Furthermore, our aim was to establish Arch Phys Med Rehabil Vol 84, July 2003
whether any effects of training would be evident 1 month after Table 1: Patient Characteristics and Pretraining Respiratory
Function Measures of the Training Group (n؍7) and
Control Group (n؍8)
The patients in this study were recruited from 3 rehabilita- tion outpatient clinics in Stockholm, Sweden. All patients met the criteria of Poser et al4 for the diagnosis of MS, presented with a progressive pattern of MS, and scored between 6.5 and 9.5 on the Expanded Disability Status Scale26 (EDSS). This evaluation scale was used to describe symptoms and to quan- tify neurologic deficits, based on a neurologic examination.
Patients who did not meet the diagnostic criteria, according to EDSS, scored 0.0 to 6.0, were excluded from the study, as were patients with chronic obstructive airways, asthma, emphysema,and cystic fibrosis. Also excluded were patients with heart NOTE. No significant differences were observed between the insufficiency, patients with chronic pain, and patients with another diagnosis or other disorders. Patients who had diffi- Abbreviations: FEV , forced expiratory volume in 1 second; FEV%, forced expiratory volume in percent of FVC; FVC, forced vital capac- culty in understanding instructions and patients who were ity; PEF, peak expiratory flow; VC, vital capacity.
already participating in other projects were likewise excluded.
Altogether, 22 patients with MS expressed interest in the study. The first contact between the examiner (JHN) and thepotential participants was by telephone, for the purpose of Evaluation
assessing their physical and mental status, as determined by the All tests were performed at the beginning and at the end of EDSS, and to inquire about what medications they were tak- a 10-week period and again 1 month after the training ended.
ing—with special emphasis on their history of respiratory Respiratory muscle strength was assessed by measuring max- illness—and about their use of tobacco. We also wanted to imal inspiratory pressure (PImax) and maximal expiratory pres- establish whether the patients had medical problems or histo- sure (PEmax), according to the method of Black and Hyatt,27 by ries that were probably not related to MS. Two patients had had using a handheld mouth pressure meter (Micro MPM).a The other diagnoses, such as stroke; 1 patient had rheumatism and Micro MPM consists of a pressure transducer and electronic chronic airway obstruction; 1 patient had another neurologic calculator with a liquid crystal display screen. The patient, disorder and a probable MS diagnosis; and 2 patients said they while comfortably seated and wearing a nose clip, performed were too busy to participate. These 6 patients were excluded maximal inspiratory and expiratory efforts, starting from near from the study. In all, 16 patients met the inclusion criteria and residual volume and near total lung capacity, into an obstructed were sent a letter assigning them an individual examination flanged mouthpiece with a small air leak to prevent generation date at the clinic. The patients were randomized to a training of high buccal pressures. For measurements to be considered (nϭ8) or a control (nϭ8) group. One patient in the training technically acceptable, no air leaks could be detected around group dropped out after 4 weeks, having failed to cooperate, the mouthpiece, and the patient had to maintain the pressure for and was excluded from data analysis.
least 1 second. All measurements were taken at approximately Data were analyzed for 15 patients (9 women, 6 men) the same time of day to minimize the effect of time of day on between the ages of 37 and 61 years (mean age, 49y). All gave patients’ level of subjective fatigue.28 their informed consent to participate in the study, which was Achievement of PImax and PEmax in clinical laboratory tests approved by the local ethics committee. The training group was requires motivation, practice, and effort. Numerous research- composed of 6 women and 1 man. No patient had acute ers28,29 have shown the effect of learning with repeated mea- respiratory or cardiac failure at the time of the study, and none sures of PImax and PEmax in both able-bodied people and experienced an exacerbation or a relapse during the study. All patients with airway obstructions. Therefore, taking into ac- patients were wheelchair bound, and 3 patients were essentially count the learning of the technique of PImax and PEmax bedridden but were able to sit up for a few hours every day.
measurement, the patients were verbally encouraged to achieve Time since MS was diagnosed ranged from 3 to 35 years maximal strength and coordination so that baseline values (mean Ϯ standard deviation [SD], 17Ϯ7.8y). Patients had could be obtained. The maneuver was repeated at least 3 times disabilities ranging from ataxia to quadriplegia, and the median or until 2 reproducible efforts were obtained (ie, within 5% of EDSS score was 8 (range, 6.5–9.0). Most patients showed each other). An interval of about 1 minute was allowed be- laryngeal and pharyngeal dysfunction, as indicated by the tween the measurements to avoid short-term fatigue of the symptoms of dysphonia, dysphagia, and aspiration. They re- respiratory muscles. The reliability of maximal respiratory quired individual attention from 0 to 24 hours per day. Four pressure has been described by several authors.30,31 The higher patients reported being current or former smokers. EDSS score, of 2 reproducible values was considered in the data analysis.
age, medications, and smoking history did not differ for pa- PImax and PEmax were expressed as absolute values in cmH O tients in the training and the control groups.
and as percentages of the predicted normal value, according to The patients’ characteristics are presented in table 1. Most had undergone therapy with interferon-beta and baclofen and Respiratory function through dynamic spirometry was as- had also received physical therapy (PT)—which included bal- sessed, with the subjects sitting, by use of a handheld spirom- ance, coordination, gait, transfer, and strength training, as well eter (Micro Loop).a Pollard et al33 have shown that the Micro as range of motion therapy—1 to 2 times a week. The duration Loop is reliable. The patients wore a nose clip during the test.
and intensity of PT was the same for all patients.
The method has been previously described.34 The vital capacity Arch Phys Med Rehabil Vol 84, July 2003
(VC), forced vital capacity (FVC), forced expiratory volume in The patients were visited in their homes every other week by 1 second (FEV ), forced expiratory volume in percent (FEV%), the authors to exchange logbooks and to help them with log- and peak expiratory flow (PEF) were measured. The values book entries, as needed. During these visits, changes were were expressed as both an absolute value in liters and a per- made in the inspiratory threshold training load, as indicated by centage of the predicted normal value, according to the Euro- the PImax and RPE scale, and any changes in the patients’ pean Coal Community standards.35 No patient had previous clinical status were noted. Furthermore, patient compliance experience with spirometry. The patients were verbally encour- with the procedures was assessed, and, at each visit, they aged to achieve maximal effort, and the best of 3 trials was performed a complete training session. Patients were assured accepted. The Micro MPM and Micro Loop were calibrated to that personal and telephone contact would be maintained with meet the requirements of the American Thoracic Society36 them weekly during the training program to answer their ques- tions and to provide them with feedback. Patients in the control Patients’ subjective perceptions of fatigue were examined group were contacted repeatedly by telephone, but they were through the Fatigue Severity Scale (FSS), as described by given no specific feedback about the study. Deep-breathing Krupp et al.37 The FSS score is established through answers to exercises were, however, a routine part of their ordinary phys- a questionnaire containing a 9-point test about both mental and physical fatigue. In this study, the FSS was used to detectclinical change in fatigue over time. Each item is scored from Statistics
1 to 7, with 1 indicating strong disagreement and 7 indicating Descriptive nonparametric statistics were used to calculate strong agreement with each statement in the questionnaire. The median and range and to characterize variables. Mean and SD mean score is obtained so that the test result range is 1 to 7.
were used for variables with normal distribution. The Wil- Predicted scores for healthy adults are expressed for this ques- coxon rank-sum test was used to compare the groups, and the tionnaire. A high total score indicates severe fatigue.
Wilcoxon signed-rank test was used to characterize changes Patients were asked to estimate their degree of perceived that took place after training in each group. Finally, the Spear- physical exertion on the Borg 6 –20 Ratings of Perceived man rank-order correlation coefficient was used to highlight the Exertion (RPE) scale38 after they had bathed and dressed in the relation between the FSS and the EDSS. Statistical significance morning. The perceived physical exertion on the RPE scale was defined as P less than .05.
was ranked from 6 (not strenuous at all) to 20 (extremelystrenuous at the physical task or exercise level).
Inspiratory Muscle Training
The specificity and overload principles of exercise training All 15 patients passed the initial series of tests. The baseline were used to train the respiratory muscles, as described in the respiratory muscle function did not differ between the groups, study by Smeltzer et al.39 The specific target of training in our and the PImax and PEmax values were significantly lower than study was to strengthen the inspiratory muscles. The overload predicted normal values. The mean PEmax value was principle was implemented through high-intensity exercise of 54Ϯ31cmH O (48%Ϯ17% of the predicted value), and the short duration twice every other day. A Threshold IMT deviceb mean PImax value was 53Ϯ30cmH O (59%Ϯ25% of the pre- was used for IMT. The valve on this device blocks airflow until dicted value); they are presented with median values and range the patient generates sufficient inspiratory pressure to over- come the resistance provided by the spring-load valve. The The baseline respiratory function values did not differ be- threshold pressure is independent of airflow or breathing fre- tween the groups, and the observed values in all respiratory quency. The pressure settings are adjustable in Ϫ2cmH O parameters were markedly reduced compared with predicted increments (range, Ϫ7 to Ϫ41cmH O). The device has been Training Group
Table 2: Pre- and Posttraining Values of Maximal Inspiratory and
Expiratory Pressures, FSS Scores, and Borg RPE Scale Scores in
Before starting the training, the patients had a 1-week run-in 15 Patients With MS
period to become familiar with the Threshold IMT device.
Each patient was asked to record home practice sessions in a logbook and to do the training at home for 10 minutes twiceevery other day, with at least 4 hours between each training session. Over a 10-week period, this totaled 70 training ses- sions. A complete training session consisted of 3 sets of 10 loaded inspirations, with a 1-minute rest between sets. The initial training load was submaximal, was based on 40% to session, was not to be perceived as more than 17 (very hard) on the Borg 6 –20 RPE scale. Patients were encouraged to inter- rupt the training if they reached 17 before the end of the session. The perceived sense of 17 on the RPE scale was defined as very strenuous. Expiration was unloaded, and each patient was free to choose his/her respiratory rate. The patients were also asked to estimate degrees of perceived physical exertion on the RPE scale after bathing or dressing and to record the degrees in the logbook. Patients were asked to make NOTE. Borg RPE scale score was measured after washing and dress- a note of all their activities during the week that were not Arch Phys Med Rehabil Vol 84, July 2003
(40%– 60% of PImax) over a 10-week period, improved thePImax and PEmax (PϽ.008, PϽ.02, respectively) in the train-ing group. The improvement in PImax was higher than that inthe control group (PϽ.01), and the benefits of the 10 weeks ofsupervised training were still seen 1 month later. Inspiratorymuscle training did not affect respiratory parameters, such asFEV , FVC, VC, PEF, and FEV%, nor were its benefits re- flected in the FSS questionnaires or the patients’ subjectiveperception of physical endurance after bathing and dressing inthe morning. No correlation could be found between EDSS andFSS scores.
Respiratory Muscle Function
Baseline PEmax (48%Ϯ17%) was more affected than was baseline PImax (59%Ϯ25%), and both these values were sig-nificantly lower than predicted normal values. This finding haspreviously been described by Smeltzer et al.8 Paralysis inadvanced MS is disposed toward ascending slowly from the Fig 1. PImax (cmH O), measured by mouth pressure meter, from
baseline to 10 weeks of IMT in 7 patients with MS. Abbreviations:
lower extremities to the upper extremities.8 As a result, the Pat, patients.
muscles primarily affected are the expiratory muscles, fol-lowed by the abdominal and intercostal muscles, and, finally,the inspiratory muscles, including accessory inspiratory mus- normal values. The mean FVC was 2.7Ϯ1.5L, the mean FEV1 cles in patients with quadriplegia and who are bedridden.8 value was 2.3Ϯ1.1L, the mean VC was 2.5Ϯ1.4L, and the In this study, patients showed a restrictive respiratory pat- mean PEF was 292Ϯ152L/s. All are presented with median tern. Their immobility, fatigue, reduced respiratory function, tobacco use, dysphagia, aspiration, and use of medication re- The baseline FSS score did not differ between the training inforced their primary restrictive respiratory patterns. There- group (mean, 5.0Ϯ1.3) and the control group (mean, 4.5Ϯ1.3), fore, sustained treatment that combines physical and respira- but their scores were significantly higher than scores for able- tory muscle training should be initiated early to preserve bodied healthy adults (mean, 2.3Ϯ0.7).37 Baseline subjective respiratory function and to avoid aspiration pneumonia. The perception of physical endurance in the morning after bathing importance of combined physical training and respiratory mus- and dressing, as rated on the RPE scale, did not differ between cle training has been confirmed in several studies of patients the training group (median, 13; range, 9 –16) and the control group (median, 14; range, 9 –17). There was no correlation Previous studies39-41 have shown the effect of respiratory muscle training and/or expiratory muscle training to improverespiratory muscle strength and coughing ability in patients Posttraining
with MS. To our knowledge, no other studies have been pub- Respiratory muscle function, as evaluated by the PImax, lished concerning inspiratory muscle training in patients with improved after 10 weeks for the patients in the training group MS. To obtain an effective cough, a deep inspiration, elastic (PϽ.008) (fig 1), but it remained unchanged in the control recoil, abdominal muscle pressure, and glottis closure are group. PEmax was also improved for patients in the training needed.13 In this study, the patients had paralysis or weakness group (PϽ.02), but did not change in the control group (table in the expiratory muscles, as indicated by the reduced PEmax.
2). The improvement in PImax after 10 weeks was significantly Most of the patients also showed laryngeal and pharyngeal higher than the improvement in the control group (PϽ.01), but dysfunction and, thus, an impaired glottis function and diffi- the improvement in PEmax failed to reach statistical signifi- culty in breathing as deeply as needed to produce an effective cance between the groups. Figure 2 shows the median PImaxpercentage of predicted normal values in both groups overtime. The improvement in PImax percentage of predicted nor-mal values remained unchanged in the training group after 1month, compared with the posttraining values (fig 2).
Respiratory function values remained unchanged in the training group after 10 weeks and did not differ between thegroups.
The mean FSS scores were 4.7Ϯ1.4 in the training group and 5.6Ϯ1.4 in the control group. No significant differences couldbe found between the groups. The score of subjective percep-tion of physical endurance in the morning after bathing anddressing did not change after training compared with baselinescores in both groups. There was no evidence of enhancedactivities during the week that were not related to the patients’ordinary ADLs, as perceived by the patients. No complicationswere reported or observed during the 10 weeks.
Fig 2. PImax percentage (median) of predicted normal values, mea-
sured by mouth pressure meter, from baseline to after training

In this study, specific inspiratory threshold loading training, (10wk) and 4 weeks after training (14wk) in the training group (Tg)
twice every other day, by 3 sets of 10 loaded inspirations and the control group (Cg).
Arch Phys Med Rehabil Vol 84, July 2003
cough. The coughing effectiveness might have been improved such maneuvers, Fiz et al29 recommend that a minimum of 9 by the IMT, just as the PImax and PEmax improved. Interest- technically acceptable maneuvers should be performed. Smelt- ingly, our patients showed a strong coughing reflex, which may zer and Lavietes30 assessed the reliability of PImax and PEmax have been caused by retention in the trachea. Unfortunately, in a group of healthy controls and patients with MS and this reflex may be impaired in the later stages of MS and in concluded that 3 maneuvers were needed to obtain a reproduc- patients who are unconscious. Gosselink et al41 studied the ible value in the former group and more than 3 maneuvers were effect of expiratory muscle training in patients with MS with necessary for patients with MS. Previous studies9,14 have stated approximately the same level of neurologic deficit as in our that performing a respiratory function test can be laborious and study (median EDSS score, 8.5; range, 6.5–9.5), using a resis- stressful for patients with MS and that, in fact, such patients tive respiratory device. They showed improvement in both the show a poor activity tolerance and often complain of fatigue.
PImax and coughing in the training group, which reinforces the Therefore, respiratory function tests should be singly per- fact that effective inspiration is an important part of the ability formed in these patients because of the rapid onset of fatigue.
The patients in our study had a manifest and more severe Physical endurance results in our study were dissimilar to neurologic deficit than did those in the study by Smeltzer.30 those in a study by Klefbeck et al24 of patients with polio, who Our patients performed the maneuvers at least 3 times and showed improvement in the performance of ADLs after in- mentioned fatigue often during or after the test. The patients spiratory muscle endurance training with an IMT device. This were, however, probably highly motivated, because they were difference may be because patients in our study were more self-enrolled in the respiratory training study. This high level of affected by neurologic disorders (with 70% of patients wheel- motivation may be the most apparent explanation for the high chair bound and 30% bedridden) and the appearance of fatigue.
reliability in this study. Variation resulting from daytime fa- The patients with prior polio were also users of part-time tigue was avoided by testing each patient at the same time each assisted ventilation and used the assisted ventilation before and after the training program; also, the designs of the 2 studies The questions remain whether the threshold inspiratory differed. In our study, no patient experienced dyspnea while training load and the training intensity were too low or too high performing this kind of activity, because all patients reached and whether the training period needs to be extended to achieve the level of fatigue before dyspnea set in, an observation also improvement in the level of physical activity and fatigue se- verity. This study’s purpose was to strengthen inspiratory mus- The improvement in inspiratory and enhanced expiratory cles; however, the variables of physical activity and fatigue muscle strength in the training group was apparent after 6 severity might be associated with endurance rather than weeks, and significant changes were found after 10 weeks of strength training of inspiratory muscles. The number of pa- training. The improvements continued after 10 weeks for 4 tients in the training group was small, which can be explained patients who continued the training protocol, but it did not because the number of MS survivors at such a high level of change in the other patients. The other 3 patients in the training disability is not large (approximately 20% of the total MS group continued their IMT periodically after 10 weeks, which patients in the selected region). A multicenter trial would be was not difficult because of its training design (it was short and necessary to obtain a larger number of participants.
did not require much time). The subjective outcome of interestin this study was that the patients in the training group reported CONCLUSION
that after 10 weeks of IMT, deep inspiration was easier to The MS patients in this study, with its randomized, con- perform. They thought that the training was most effective and trolled trial, showed a significant improvement of inspiratory was a good way to resist the symptoms of MS; furthermore, muscle strength after 10 weeks of supervised training. The they were more confident and more motivated to do additional improvements were evident 1 month after the study ended.
activities. All patients in the training group knew that training It would be of interest to do a 1-year follow-up to establish with the IMT device was complementary to other physical whether the positive outcomes are still present. Furthermore, training. Most of the patients were restricted to a wheelchair or the optimal training stimulus needed to elicit a clinical benefit to bed much of the time and were limited in their physical in physical activity and fatigue severity is not known in patients activities because of weakness, an increased body temperature with MS. However, this study should provide a better under- as a result of such activities, and a worsening of the fatigue standing of respiratory muscle weakness and patients’ limited symptom. This has also been reported in previous studies.10,14 capability resulting from severe handicap and fatigue and In this regard, our patients were not able to reach optimal should, therefore, enable therapists to design more effective effects of the physical activities; therefore, additional respira- physical and respiratory muscle training protocols.
tory training could be beneficial for them. To ensure propertraining load and no adverse effects, careful assessment of References
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a. Micro Medical Ltd, 6 Ambley Green, Gillingham Business Park, 23. Eastwood PR, Hillman DR, Finucane KE. Ventilatory responses to inspiratory threshold loading and role of muscle fatigue in task b. Health Scan Products Inc, 908 Pompton Ave, Unit B2, Cedar failure. J Appl Physiol 1994;76:185-95.
Arch Phys Med Rehabil Vol 84, July 2003


20th october, 2008

Verva Announces Results of Successful VVP808-002 Phase 2 Clinical Trial in Type 2 Diabetes and Outcome of Annual General Meeting Melbourne, Australia (06 June 2012). Verva Pharmaceuticals Ltd. (“ Verva ” or the “ Company ”) announced the top-line results of the recently-completed VVP808-002 Phase 2 clinical proof-of- concept study with the Company’s insulin sensitizer VVP808 (m

Ijccm july 07.indd

IJCCM October-December 2003 Vol 7 Issue 4 Indian J Crit Care Med July-September 2007 Vol 11 Issue 3 Review Article TNF-alpha inhibitors: Current indications Rashmi Sharma, Chaman Lal Sharma* Advances in the DNA hybrid technology led to the development of various biologicals that specifi cally target TNF-α. There are currently three anti- TNF-α drugs available- etanercept, infl ix

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