Efficacy of modified constraint-induced movement therapy in acute stroke.

BACKGROUND: Modified constraint induced movement therapy (m-CIMT) discourages the use of the unaffected extremity and encourages the active use of the hemiplegic arm in order to restore the motor function. AIM: The aim was to assess the efficacy of m-CIMT on functional recovery of upper extremity (UE) in acute stroke patients, as compared to conventional rehabilitation therapy. DESIGN: This is a prospective comparative study. SETTING: This study included sixty patients with acute stroke recruited from neurology department. METHODS: This study included sixty acute stroke patients. Inclusion criteria were: patients within two weeks from the onset of stroke, persistent hemiparesis leading to impaired upper extremity function, evidence of preserved cognitive function, and a minimum of 10 degrees of active finger extension and 20 degrees of active wrist extension. Exclusion criteria were: intra-cerebral hemorrhage, previous stroke on the same side, presence of neglect or a degree of aphasia impeding understanding of instructions, and conditions that limit the use of the upper limb before the stroke. Patients were assessed by Fugl-Meyer motor assessment (FMA), action research arm test (ARAT) and motor evoked potentials (MEPs), recorded from the abductor pollicis brevis (APB) of the affected hand. The clinical and neurophysiological tests were performed pre and postrehabilitation. The patients were divided into two groups: Conventional rehabilitation program group (CRP) included 30 patients who were given a conventional rehabilitation program for two weeks. CIMT group included 30 patients who were subjected to modified CIMT for two consecutive weeks. Total treatment time was the same in both groups. RESULTS: CRP group showed a non-significant improvement in FMA and ARAT. CIMT group showed a significant improvement in clinical scores on all tests (P<0.05). When comparing both groups using FMA and ARAT tests pre- and post- therapy, a significant difference (P<0.05) was found between both groups with CIMT group showing greater improvement. When comparing MEPs in CRP group, pre and postrehabilitation, a non-significant improvement was found for resting motor threshold (RMT), central motor conduction time (CMCT) and amplitude of MEPs. In contrast, each of the MEP parameters exhibited a significant improvement in CIMT group (P<0.05). CONCLUSION: In contrast to conventional rehabilitation therapy, modified CIMT revealed a significant functional and MEP improvement in acute stroke patients indicating that m-CIMT might be a more efficient treatment strategy. CLINICAL REHABILITATION IMPACT: It is advised to use modified constraint movement therapy in rehabilitation of cerebrovascular stroke during acute stage.

The effect of cytokine gene polymorphisms on pediatric heart allograft outcome.

BACKGROUND: Cytokines play a major role in the inflammatory and immune responses that mediate allograft outcome. Several studies have shown that the production of cytokines varies among individuals and these variations are determined by genetic polymorphisms, most commonly within the regulatory region of the cytokine gene. The aim of this study was to assess the effect of these allelic variations on acute rejection after pediatric heart transplantation. METHODS: We performed cytokine genotyping using polymerase chain reaction-sequence specific primers in 93 pediatric heart transplant recipients and 29 heart donors for the following functional polymorphisms: tumor necrosis factor-alpha (TNF-alpha) (-308), interleukin (IL)-10 (-1082, -819, and -592), TGF-beta1 (codon 10 and 25), IL-6 (-174), and interferon-gamma (INF-gamma) (+874). The distribution of polymorphisms in this population did not differ from published controls. The patients were classified as either non-rejecters (0 or 1 episode) or rejecters (> 1 episode) based on the number of biopsy proven rejection episodes in the first year after transplantation. RESULTS: Forty-two of the 69 TNF-alpha patients (61%) in the low producer group were non-rejecters, while 9 of the 24 (37.5%) with high TNF-alpha were non-rejecters (p = 0.047). In contrast, IL-10 genotype showed the opposite finding. Forty-two of the 66 patients (64%) in the high and intermediate IL-10 group were non-rejecters, while 9 of the 26 (35%) in the low IL-10 group were non-rejecters (p = 0.011). The combination of low TNF-alpha with a high or intermediate IL-10 genotype was associated with the lowest risk of rejection (34/49 or 69% non-rejecters). Neither the distribution of the IL-6, INF-gamma, and TGF-beta1 genotype in recipients nor the donor genotype showed any association with acute rejection. CONCLUSION: Genetic polymorphisms that have been associated with low TNF-alpha and high IL-10 production are associated with a lower number of acute rejection episodes after pediatric heart transplantation.

Transforming growth factor-beta (TGF-beta1) genotype and lung allograft fibrosis.

BACKGROUND: TGF-beta1 is a prosclerotic cytokine implicated in fibrotic processes. Fibrosis of the pulmonary parenchyma and airways is a frequent presentation in lung transplant recipients before and after transplantation. There are two genetic polymorphisms in the DNA sequence encoding the leader sequence of the TGF-beta1 protein, located at codon 10 (either leucine or proline) and at codon 25 (either arginine or proline). The codon 25 arginine allele is associated with higher TGF-beta1 production by cells activated in vitro. We tested the hypothesis that inheritance of alleles of the TGF-beta1 gene conferring higher production of TGF-beta1 may be responsible for over-expression of TGF-beta1 in transplant recipients resulting in lung allograft fibrosis. METHODS: We extracted DNA from leukocytes collected from 91 pulmonary transplants performed at our centre and 96 normal healthy volunteers between May 1990 and September 1995. Part of the first exon was amplified by PCR. Samples were genotyped by using sequence specific oligonucleotide probes. RESULT: The distribution of codon 10 alleles was similar in a normal healthy control group and in lung transplant recipients, regardless of their pretransplant lung pathology. By contrast, there was a significant difference in the frequency of codon 25 alleles between the control and transplant groups. In the normal control group 81% were codon 25 arginine/arginine (A/A) homozygotes, 19% were arginine/proline (A/P) heterozygotes and none were proline/proline (P/P) homozygotes. The distribution of codon 25 alleles was similar in lung transplant recipients who did not have a significant fibrosis in pretransplant pathology, but in transplant recipients who came to transplantation with lung fibrosis 98% (41 of 42 patients) were homozygous for the codon 25 A/A allele (p < .05). After lung transplantation 39 of 91 patients developed lung allograft fibrosis, and of these 92.3% (36 of 39 recipients) were of homozygous codon 25 A/A high TGF-beta1 producer genotype (p < .001). Lung transplant recipients who were homozygous for both codon 10 L/L and codon 25 A/A showed poor survival compared with all other TGF-beta1 genotypes (p < .03). CONCLUSION: Homozygosity for arginine at codon 25 of the leader sequence of TGF-beta1 that correlates with higher TGF-b production in vitro, is associated with fibrotic lung pathology before lung transplantation and with the development of fibrosis in the graft. In combination with the codon 10 leucine allele, homozygosity for the codon 25arginine allele is a marker for poor post-transplant prognosis and recipient survival.

Genotypic variation in the transforming growth factor-beta1 gene: association with transforming growth factor-beta1 production, fibrotic lung disease, and graft fibrosis after lung transplantation.

BACKGROUND: Transforming growth factor (TGF)-beta1 is a profibrogenetic cytokine that has been implicated in the development of fibrosis in transplanted tissues. In this study, we have analyzed the genetic regulation of TGF-beta1 production in lung transplant recipients. METHOD: A polymerase chain reaction-single-stranded conformational polymorphism technique was used to detect polymorphisms in the TGF-beta1 gene from genomic DNA. Polymorphisms were shown to correlate with in vitro TGF-beta1 production by stimulated lymphocytes. A single-specific oligonucleotide probe hybridization method was devised to screen for these polymorphisms in lung transplant groups and controls. RESULTS: We have identified five polymorphisms in the TGF-beta1 gene: two in the promoter region at positions -800 and -509, one at position +72 in a nontranslated region, and two in the signal sequence at positions +869 and +915. The polymorphism at position +915 in the signal sequence, which changes codon 25 (arginine-->proline), is associated with interindividual variation in levels of TGF-beta1 production. Stimulated lymphocytes of homozygous genotype (arginine/arginine) from control individuals produced significantly more TGF-beta1 in vitro (10037+/-745 pg/ml) compared with heterozygous (arginine/proline) individuals (6729+/-883 pg/ml; P<0.02). In patients requiring lung transplantation for a fibrotic lung condition, there was an increase in the frequency of the high-producer TGF-beta1 allele (arginine). This allele was significantly associated with pretransplant fibrotic pathology (P<0.02) (n=45) when compared with controls (n=107) and with pretransplant nonfibrotic pathology (P<0.004) (n=50). This allele was also associated with allograft fibrosis in transbronchial biopsies when compared with controls (P<0.03) and with nonallograft fibrosis (P<0.01). CONCLUSION: The production of TGF-beta1 is under genetic control, and this in turn influences the development of lung fibrosis. Hence, the TGF-beta1 genotype has prognostic significance in transplant recipients.