Mean blood flow velocities in posterior cerebral arteries during visual stimulation

Changes of mean blood flow velocities (MBFV) in the posterior cerebral arteries (PCA) recorded during visual stimulation in a group of 51 healthy, right-handed volunteers are presented. There were 27 (52.9%) males and 24 (47.1%) females, aged 20-59 years (mean age: 36.98 years). Measurements were performed with a hand-held 2 MHz transcranial Doppler (TCD) probe through the temporal window, with the subjects' eyes open and closed, and while they were looking at constant and at flashing white light. In half of the subjects, first the right PCA was insonated and then the left PCA, while in the other half the reverse procedure was used. Statistical analysis was done using Wilcoxon's matched-pair signed-rank test. Mean MBFV value in the left PCA was 41.2+/-8.6 cm/s (mean +/- SD) with eyes open, 27.8+/-8.5 cm/s with eyes closed, 42.3+/-9.1 cm/s while looking at constant white light, and 43.0+/-9.6 cm/s while looking at flashing white light. Mean MBFV value in the right PCA was 41.7+/-8.9 cm/s with eyes open, 28.2+/-9.1 cm/s with eyes closed, 42.4+/-8.8 cm/s while looking at constant white light, and 43.4+/-9.2 while looking at flashing white light. Value differences for the left PCA, between eyes open and closed and between looking at constant white light and looking at flashing white light were statistically significant (p<0.001, z= -6.2146, and p<0.001, z= -3.4836, respectively). For the right PCA, a value difference between eyes open and closed, and between looking at constant and flashing white light was statistically significant (p<0.001, z= -6.2146 and p<0.001, z= -3.6928), but there was no significant difference between eyes open and constant white light (p=0.03, z= -2.1693). The results showed that simple visual stimulation had an effect on blood flow velocities in PCA and that it could be measured with TCD.     

Monoclonal antibody analysis of blood T-cell subsets in myasthenia gravis

Analysis of peripheral blood T-cell subsets and B-cells in patients with myasthenia gravis was performed using monoclonal antibodies and antibody against surface immunoglobulins (SIg) in an immunofluorescent technique. We found a modest but significant decrease in percentages of OKT3- and OKT8-positive cells (thought to represent total T-cells and T-suppressor/cytotoxic cells, respectively) in myasthenics as a group. The percentage of OKT3-positive cells was significantly decreased in patients with late-onset disease (>35 years old), while the percentage of OKT8-positive cells was significantly reduced in those with early-onset myasthenia (<35 years old). Both thymectomized and nonthymectomized patients exhibited a decreased percentages of SIg-positive cells in myasthenics and controls. Our results suggest that only modest imbalances of circulating immunoregulatory lymphocytes occur in myasthenia gravis; however, it is conceivable that the small differences observed in this study may reflect pathogenetically important reductions in a functionally distinct lymphocyte subpopulation.     

Neurologic consequence of delaying glatiramer acetate therapy for multiple sclerosis: 8-year data

OBJECTIVE: To assess the long-term effectiveness of continuous glatiramer acetate (GA) therapy in relapsing-remitting multiple sclerosis (RRMS). METHODS: This open-label extension followed a randomized, placebo-controlled, double-blind study of GA of approximately 30 months duration. Patients originally randomized to GA continued on it (group A) and those randomized to placebo switched to GA (group B). RESULTS: Of 251 original patients, 142 (56.6%) remained in the study after 8 years. Annual relapse rate for both groups declined to approximately 0.2 (approximately one relapse every 5 years). However, a significantly larger proportion of patients in group A had stable or improved Expanded Disability Status Scale scores compared with group B (65.3% vs 50.4%, respectively; P = 0.0263), possibly attributable to the delay of GA treatment for approximately 30 months in group B. GA was well tolerated and no drug-related laboratory changes were observed. CONCLUSIONS: These data support early initiation of GA therapy as an efficacious and well-tolerated long-term treatment for RRMS patients.     

Glatiramer acetate (Copaxone): comparison of continuous versus delayed therapy in a six-year organized multiple sclerosis trial

The aim of this study was to assess the long-term safety and efficacy of glatiramer acetate (GA) for patients with multiple sclerosis (MS) who received active treatment versus those on placebo for approximately 30 months (24-35 months) before receiving GA during a six-year organized, prospective open label study. Entry required two relapses in the previous two years and an Expanded Disability Status Scale (EDSS) score of 0-5. Patients (251) were equally randomized to daily subcutaneous GA, 20 mg, or to placebo. After approximately 30 months, 208 patients continued in an open label study: 101 continued on GA and 107 switched from placebo to active drug. Groups were well matched at randomization and entry to the open label study. Patients always on GA showed a steady decline in relapses: a mean of 1.5 per year at entry, a mean of 0.42 over the entire six years (95% CI = 0.34-0.51), a 72% reduction (P = 0.0001). They averaged a relapse every four + years (yearly rate 0.23 in year six) and 26/101 remain relapse free. Patients did less well if on placebo for 30 months, but relapses then declined, and by year six the rates were similar. Of patients always on GA, 69% showed neurological improvement of > or = 1 EDSS steps or remained stable compared with 57% if GA treatment was delayed. Of relapse-free patients always on GA over six years, only three of 26 (11%) were worse by > or = 1 EDSS steps, whereas nine of 21 (43%) in the placebo/active group were worse (P < 0.03). Disability, measured every six months, showed that the group of patients always on GA was relatively stable over the six years, while the group who received placebo for the first two-and-a-half years did significantly less well. Daily injections of GA were well tolerated. This longest ever organized MS treatment trial shows that delaying therapy with GA increases the risk of neurologic disability, reinforcing the rationale for using GA as a first-line treatment early in the course of relapsing-remitting MS.     

Long-term therapy with glatiramer acetate in multiple sclerosis: effect on T-cells

Glatiramer acetate (GA) is an immunotherapeutic drug for multiple sclerosis (MS). Several mechanisms of action have been demonstrated which target and affect T-cells that are specific for myelin antigen epitopes. We measured the in vitro proliferation of GA-responsive T-cells from untreated MS patients and from normal healthy subjects; in addition, we determined the effect of prolonged GA therapy or interferon-beta therapy on the in vitro proliferation of GA-responsive T-cells of MS patients. We found that GA induces the proliferation of T-cells isolated from individuals who have not been previously exposed to GA, and that long-term in vivo therapy of MS patients with GA abrogates the GA-induced proliferative response of T-cells. In GA-treated patients, there is no evidence of generalized immunosuppression; both tetanus toxoid and anti-CD3 induced proliferative responses remain unaffected. We propose that prolonged in vivo exposure to GA may result in the eventual induction of anergy or deletion of a population of GA-responsive cells that may also be T-cells that are pathogenic in MS. This mechanism of action, in addition to other mechanisms that have been demonstrated, suggests that GA has pleiotropic effects on the immune system in MS.     

Effect of monthly intravenous cyclophosphamide in rapidly deteriorating multiple sclerosis patients resistant to conventional therapy

Fourteen consecutive clinically definite relapsing-remitting multiple sclerosis (MS) patients were treated with monthly intravenous cyclophosphomide (CTX) for 6 months. All had experienced severe dinical deterioration during the 12 months prior to treatment with CTX despite treatment with conventional immunomodulating agents and intravenous methylprednisolone. Treatment with CTX led to improvement and neurologic stability within 6 months which was sustained for at least 18 months after the onset of treatment with CTX. Therapy with CTX was well tolerated. CTX may be of benefit in MS patients who experience rapid clinical worsening and are resistant to conventional therapy.     

Antiacetylcholine receptor antibody in neonatal myasthenia gravis

Maternal titers to antiacetylcholine receptor antibody (anti-AChR Ab) were higher in two mothers with myasthenia gravis (MG) who had infants with neonatal MG than the nearly normal values in two mothers with MG who had unaffected infants. In one unaffected infant, another IgG antibody crossed the placenta, but an IgM antibody did not. In neonates there seems to be a correlation between the concentration of anti-AChR Ab and the presence and severity of the neonatal syndrome. The absence of fetal symptoms of MG and the delayed onset or worsening of some cases of neonatal MG may be due to high fetal levels of alpha-fetoprotein and its decline in concentration in infants after birth.     

Intraoperative cell salvage with autologous transfusion in liver transplantation

Liver transplant(LT) is the primary treatment for patients with end-stage liver disease. About 25000 LTs are performed annually in the world. The potential for intraoperative bleeding is quite variable. However, massive bleeding is common and requires blood transfusion. Allogeneic blood transfusion has an immunosuppressive effect and an impact on recipient survival, in addition to the risk of transmission of viral infections and transfusion errors, among others.Techniques to prevent excessive bleeding or to use autologous blood have been proposed to minimize the negative effects of allogeneic blood transfusion.Intraoperative reinfusion of autologous blood is possible through previous selfdonation or blood collected during the operation. However, LT does not normally allow autologous transfusion by prior self-donation. Hence, using autologous blood collected intraoperatively is the most feasible option. The use of intraoperative blood salvage autotransfusion(IBSA) minimizes the perioperative use of allogeneic blood, preventing negative transfusion effects without negatively impacting other clinical outcomes. The use of IBSA in patients with cancer is still a matter of debate due to the theoretical risk of reinfusion of tumor cells. However, studies have demonstrated the safety of IBSA in several surgical procedures, including LT for hepatocellular carcinoma. Considering the literature available to date, we can state that IBSA should be routinely used in LT, both in patients with cancer and in patients with benign diseases.