In vitro stimulation with mitogen and antigen in patients with monoclonal gammopathy

Summary Peripheral blood lymphocytes from 32 patients with defined paraproteinaemia (16 IgG, 9 IgA and 7 IgM) and from 15 healthy donors were studied for their in vitro response to various stimuli, including unspecific mitogens such asPhytohaemagglutinin (PHA),Pokeweedmitogen (PWM) and Concanavalin A (ConA) as well as specific antigens such as purified Tuberculin, Candida, Varidase, Tetanus Toxoid, Vaccinia antigen and Vaccinia-control antigen.Mitogens and antigens were lyophilized in Microtiter plates. The lymphocytes of all tested patient-groups responded (measured by H3-Thymidin-up-take) significantly lower towards the unspecific mitogens than those of the control group. If the patients' lymphocytes were stimulated by the specific antigens, their in vitro response was significantly diminished to candida and vaccinia. Macroglobulinaemia showed significantly lower response to ConA if compared to myelomas of IgG- and IgA-type. No correlation was found between mitogen and antigen response and the serum concentration of the paraproteins or immunoglobulins. The results show that monoclonal gammopathy and especially macroglobulinaemia are associated with abnormalities of the cellular immunity which correlates with the clinical observation of increased fungal and viral infections.Supported in part by SFB 37 München and Euratom/GSF BIAD I 031-64     

Attenuation of pathological tremors by functional electrical stimulation II: Clinical evaluation

In this study we evaluated a technique for tremor suppression with functional electrical stimulation (FES), the technical details of which were described in the previous paper. Three groups of patients were investigated: those with essential tremor, parkinsonian tremor, and cerebellar tremor associated with multiple sclerosis. In each group, tremor was attenuated by significant amounts (essential tremor: 73%; parkinsonian tremor: 62%; cerebellar tremor: 38%). These attenuations were in good accord with predictions based on the dynamic analyses and filter designs derived in the previous paper. With filters “tuned” to the lower mean tremor frequency encountered in the cerebellar patients, more attenuation was possible in this group as well. We identified some practical limitations in the clinical application of the technique in its present form. The most important was that in daily use, only one antagonist pair of muscles can realistically be controlled. At first sight, this restricts the usefulness of the system to patients with single-joint tremors. However, the concomitant use of mechanical orthoses may broaden the scope of application.     

The Cd40 ligand

For several years, the primary function of CD40 ligand (CD40L) has been believed to be in regulation of contact-dependent, CD40-CD40L-mediated signals between B-and T-cells, which are essential for the regulation of thymus-dependent (TD) humoral immune responses. Recently, a flurry of reports indicate that CD40 is expressed by variety of cell types other than B-cells that include dendritic cells, follicular dendritic cells, monocytes, macrophages, fibroblasts, and endothelial cells. These studies show that CD40-CD40L interactions are important in inflammatory process. For the past few years, through the availability of CD40L-knockout mice, new data have emerged to support the belief that CD40L has many more functions than its role in TD humoral immunity. CD40L-deficient mice have provided significant information towards our understanding of the in vivo role of CD40L. The current picture that emerges indicates that CD40-CD40L interactions mediate many cell-mediated immune responses and T-cell-mediated effector functions that are required for proper functioning of the host defense system. This article focuses on the in vivo role of the CD40L in regulation of cell-mediated effector functions.     

High resolution quantitative EEG analysis

Summary High resolution spectral methods are explored as an alternative to broad band spectral parameters (BBSP) in quantitative EEG analysis. In a previous paper (Valdes et al. 1990b) regression equations (Developmental surfaces) were introduced to characterize the age-frequency distribution of the mean and standard deviation of the log spectral EEG power in a normative sample. These normative surfaces allow the calculation of z transformed spectra for all derivations of the 10/20 system and z maps for each frequency. Clinical material is presented that illustrates how these procedures may pinpoint frequencies of abnormal brain activity and their topographic distribution, avoiding the frequency and spatial smearing that may occur using BBSP. The increased diagnostic accuracy of high resolution spectral methods is demonstrated by means of receiver operator characteristic (ROC) curve analysis. Procedures are introduced to avoid type I error inflation due to the use of more variables in this type of procedure.     

Ultrastructural aspects of bubble formation in human fatal accidents after exposure to compressed air

Summary Electron microscopic investigations were performed on samples of human tissue obtained from subjects following fatal decompression sickness, associated with hyperbaric air-therapy. Intra- and extracellular gas bubbles of varying size were identified throughout the entire body. Each bubble was covered by an osmiophilic non-homogeneous coat of cloudy and flocculent material, native to its specific locality. This envelope measured from 30 to 560 Angstroem-units in thickness. Association of this covering with an electrokinetic zonal activity, detected biophysically by Lee and Hairston (1971) is assumed. We consider this surface coat prevents nitrogen from being eliminated via the blood-lung-barrier.     

Histological and cytological criteria in the diagnosis of malignant melanomas by cryostat sections

Summary Although cryostat sections in general allow a distinction to be made between malignant melanomas and other pigmented lesions in clinically doubtful cases, the differential diagnosis may be difficult. The histological and cytological criteria taken into account can be classified as major, minor, and insufficient. Knowing the diagnostic value of each makes a conventionally established diagnosis safer. Variance analysis does not contribute to the problem but it can nevertheless be shown that the evaluation of six major criteria makes a quick and reliable cryostat section diagnosis possible. If these results are confirmed in a prospective study it would be a decisive step on the way to a quicker and safer cryostat section diagnosis of malignant melanoma, even for the less experienced histopathologist.The results published here were presented in part at the DDG meeting 1980 at Westerland/SyltWe are grateful to Miss Schubert, Institute of Biomathematics of the University of Munich, for the statistical evaluations     

Grasp synthesis for upper-extremity FNS

Functional neuromuscular stimulation (FNS) has been used in upper extremity neuroprostheses to provide grasp and release for quadriplegic individuals. The goal of this project was to determine the electrode/muscle input/output characteristics with the greatest influence on the grasp output. This was evaluated by simulating the grasp synthesis procedure, using a model of the electrode/muscle output as a function of stimulus level and joint angle. The parameters of this model were determined from experimental data from 112 electrodes. The grasp output for 500 different modelled pairs of electrodes were analysed, with each pair consisting of a thumb flexor and a thumb extensor. The simulation results indicate that the most influential electrode input/output characteristics are the output stiffness, defined as the change in force output for a unit change in joint angle at a constant level of stimulation, and the length dependency mean-squared error. Recruitment gain was found to be of secondary influence on the grasp output, and the threshold, force direction and non-linearity of the stimulus level to force relationship were found to have little influence on the grasp output. These results establish criteria for electrode selection and implantation for use in upper extremity FNS.     

Heterogeneity of histamine H2-receptor mediated responses in the rabbit aorta

Distribution and properties of histamine H₂-receptor mediated responses in segments of rabbit aorta was studied with histamine and H₂-receptor stimulating drugs, dimaprit and impromidine. All agonists produced concentration-dependent tonus decreased in precontracted vascular strips, which were antagonised by selective H₂-receptor antagonists, cimetidine and oxmetidine. Activities of the agonists were segment-dependent, and increased caudally along the aorta. A nonspecific smooth muscle relaxant, papaverine had homogeneous activity along the vessel, suggesting receptor specific nature of the observed heterogeneity.