Amyotrophic lateral sclerosis patient antibodies label Ca2+ channel α1 subunit

Sporadic amyotrophic lateral sclerosis is an idiopathic human degenerative disease of spinal cord and brain motor neurons. Prior studies demonstrated that most patients with amyotrophic lateral sclerosis posses immunoglobulins that bind to purified L-type voltage-gated calcium channels, that titers of anti–voltage-gated calcium channel antibodies correlate with disease progression rates, and that amyotrophic lateral sclerosis patient-derived antibodies (ALS IgG) produce electrophysiological changes in the function of voltage-gated calcium channels. Using Western transfer immunoblots and enzyme-linked immunosorbent assays, the calcium ionophore–forming α₁ subunig of the voltage-gated calcium channel is now identified as the major voltage-gated calcium channel antigen to which ALS IgG binds. Additionally, the binding of an L-type voltage-gated calcium channel α₁ subunit–directed monoclonal antibody, which itself mimics the effects of ALS IgG on skeletal muscle voltage-gated calcium channel currents, is selectively prevented by preaddition of ALS IgG. Voltage-gated calcium channel–binding IgG from patients with Lambert-Eaton myasthenic syndrome appears to be differentiated from ALS IgG by the reactivity of the former to both α₁ and β subunits of the calcium channel. These assays provide further evidence linking amyotrophic lateral sclerosis to an autoimmune process, and suggest one means to differentiate immunoglobulins from patients with amyotrophic lateral sclerosis from those of patients with another autoimmune disease expressing calcium channel antibodies.     

The relationship between diuretics and serum cholesterol in Hypertension Detection and Follow-up Program participants

The effect of diuretics, mainly chlorthalidone, on serum cholesterol was studied in 7,006 of the Hypertension Detection and Follow-up Program (HDFP) hypertensive patients not on antihypertensive medication at baseline. Several investigators have reported that diuretic therapy increases serum cholesterol in treated subjects. However, data from two long-term studies indicated that no increase in cholesterol occurred after two years of diuretic treatment. In the present study, yearly changes in serum cholesterol in hypertensives treated with diuretics were observed. The results were in agreement with those reported from both short-term and long-term studies, in that a significant increase in cholesterol was observed in six months to one year into the study but not from the second to the fifth year of therapy. In fact, the serum cholesterol levels were the same as baseline values after two years of drug treatment and decreased slightly thereafter. In the untreated group, no change or a decrease in serum cholesterol was observed during the course of the study. The possible causes for changes in serum cholesterol concentration such as regression to the mean, change in body weight, baseline cholesterol concentration, and the action mechanism of diuretic drugs are discussed.     

Factor VIII concentrates in HIV-1-positive hemophiliacs--is pure better?

39 human immunodeficiency-virus-1 (HIV-1)-positive hemophiliacs who had been regularly treated with non-virus-inactivated intermediate-purity factor VIII concentrates were divided into two groups. Group A consisted of 21 patients with a CD4/CD8 cell ratio of less than 1.0 and group B of 18 patients with a CD4/CD8 cell ratio of greater than 1.0. All patients of group A were switched to a high-purity virus-inactivated factor VIII concentrate, whereas patients of group B continued to receive the intermediate-purity concentrate. There was no significant difference in the average decline of CD4 cells between the two groups during the observation period. 9 patients of group A and 4 patients of group B developed AIDS. 5 patients of group A but 11 patients of group B remained clinically asymptomatic. We conclude that the 15-fold increase in purity of the factor VIII concentrate had no apparent beneficial effect on the CD4 cell counts in this patient group.     

Arthroscopic subacromial decompression. 1-3 year results]

In 148 patients with impingement lesion type I or type II, we performed an arthroscopic subacromial decompression (ASD). 122 patients ran a follow up one to three years post-operatively. All patients were pre- and postoperatively documented by a 100 point shoulder score. The mean score was 57.9 (+/- 11.5) preoperatively. Postoperatively there was a significant increase to 80.7 (+/- 17.9) (p < 0.05). 15% of the patients with a postoperative score less than 70 points were determined as failures. Patients with a preoperative pain history of more than one year had a significantly worse result (79.1 +/- 8.4) compared to those patients with a preoperative course less than one year (88.8 +/- 11.6) (p < 0.05). Other significant factors were the patient's age, and calcific tendinitis, whereas sex, preoperative range of motion, muscle atrophy, and degeneration of the acromioclavicular joint did not significantly influence the result. Our results after ASD in patients with subacromial pathology without a rupture of the rotator cuff are encouraging. Therefore, ASD seems to be a reasonable alternative to open acromioplasty.     

Ginkgo biloba extract in peripheral arterial diseases. Meta-analysis of controlled clinical studies]

In the first part the statistical methods of meta-analysis are discussed. Meta-analysis is considered as a statistical tool for quantitatively summarizing the results of clinical trials with comparable aims (treatments) and designs. Meta-analysis can be based on the significance probabilities or effect values. The last procedure is preferable as it gives an estimate (and confidence interval) for the global effect of the treatment of interest, if homogeneity of the effects between the trials can be assumed. Such a homogeneity can be often achieved by a suitable standardization of the effect variables within the trials. In the second part the methods of meta-analysis are applied to controlled clinical trials with Ginkgo biloba extract EGb 761 in patients with peripheral arterial disease. Included were 5 placebo-controlled clinical trials with similar design and inclusion criteria. In all studies treatment effect was quantified by the increase of walking distance (measured in standardized treadmill exercise). The effect value of EGb 761 treatment was expressed by the standardized mean difference in walking distance increase between EGb 761 and placebo, standardized by the standard deviation. It could be shown that this effect value is homogeneous in all trials. The global effect size was estimated as 0.75. This means that the mean increase in walking distance achieved by EGb 761 is 0.75 times of the standard deviation higher than that achieved by placebo. This value is highly significant different from zero. So the meta-analysis revealed a highly significant therapeutic effect of EGb 761 for the treatment of peripheral arterial disease.     

Erb:YAG and Hol:YAG laser ablation of meniscus and intervertebral discs.

Erb:YAG and Hol:YAG laser ablation rates of fibrocartilage and nucleus pulposus were measured in vitro simulating clinical conditions. After ablation macroscopic and microscopic appearance of the ablation site was investigated. Hol:YAG and Erb:YAG laser mean ablation rates increased almost linearly with rising energies, showing higher total ablation rates for the Hol:YAG laser due to its higher achievable energy density. At comparable energy densities the Erb:YAG laser appears to be more effective with respect to the corresponding ablation rates. Consequently, the ablational threshold proved to be lower for the Erb:YAG laser. Whereas during Hol:YAG laser ablation, some smoke formation and considerable tissue shrinking occurred, these effects could not be observed during Erb:YAG laser ablation. Consequently macroscopic and microscopic inspection showed some thermal damage after Hol:YAG and only minimal alterations after Erb:YAG laser ablation. Adjacent thermal damage was determined and proved to be lower for the Erb:YAG laser. In our opinion the characteristics of each laser system provide certain advantages for special clinical indications.