Kinetics of soluble TNF-receptors and soluble adhesion molecules ICAM-1, E-selectin and VCAM-1 under systemic rhTNFα therapy

Cytostatic as well as cytotoxic effects of tumour necrosis factor alpha (TNF-α) therapy have been shown in vitro and in experimental in vivo models. Nevertheless, the mechanism of anti-tumour activity in humans in vivo remains unclear. To determine the role of the vascular lining endothelial cells as important mediators of several immunological interactions, we investigated changes in the levels of the soluble endothelial cell adhesion molecules intercellular adhesion molecule 1, E-selectin and vascular cell adhesion molecule 1 as well as of soluble TNF receptors I and II during systemic therapy with recombinant human rhTNF-α (rhTNF-α). All tests were performed by enzyme-linked immunosorbent assays (ELISAs). The clinical efficacy of the intravenous rhTNF-α therapy was poor. Only one patient with isolated intra-arterial limb perfusion had a delayed, marked, but only temporary necrosis of tumour cells. In contrast, we found a marked, significant and (during therapy) undulating augmented increase in the levels of soluble adhesion molecules as well as of the soluble TNF receptors. Taken together, these data support the hypothesis that a sufficient tumour-specific cellular immunity is required to achieve a clinically apparent efficacy of systemic rhTNF-α therapy in addition to cytokine-dependent inducible activation mechanisms. In this context, the vascular lining endothelial cells might play an important role as mediators of the complex immunological antitumoral activity.     

Quantification of motor deficit in Parkinson's disease with a motor performance test series

Summary It was the purpose of the present study to quantify the expected motor deficit in parkinsonian patients with the computer assisted Motor Performance Test Series (MPS), version 05.87 by Schuhfried (1987) and to examine which of the motor test variables found correlate at a significance level of p<0.01 with items of motor examination recorded at neurological examination and activities of daily living of the Unified Parkinson's Disease Rating Scale (UPDRS), version 3.0.38 patients with idiopathic Parkinson's disease (PD) stages I–IV according to Hoehn and Yahr, aged 41 to 73 years were studied. The study design, i.e. initial rating by the physician followed immediately by testing of motor function with MPS was strictly adhered to in each patient.Physician's rating of rigor and the scores of the semiquantitative tests (finger taps, hand movements and alternating movements) as expression of hypokinesia and the activities of daily living correlated with the 3 factors of the Motor Performance Test Series at a highly significant level independent of disease stage. Tremor is only partly and never significantly reflected in the motor data measured. Stages I–II and II–IV (Hoehn and Yahr) differ significantly in the representative data of the Motor Performance Test Series.The results of the study support the assumption that MPS is a valid instrument for quantitative measurement of the motor deficit in parkinsonian patients, but that only some subtests are pathognomonic.     

The psbA-gene from a red alga resembles those from Cyanobacteria and Cyanelles

Summary Plastid DNA (ptDNA) from the unicellular red alga Cyanidium caldarium was isolated. A 5.8 kb Eco RI, fragment containing the entire psbA-gene was cloned and the nucleotide sequence of the psbA-gene determined. At the carboxyl terminus the encoded protein (D1) contains the seven amino acid-insertion which was found to be typical of the cyanobacteria and the cyanelles of Cyanophora paradoxa. However, the overall sequence homology does not support a direct relationship between the plastids of Cyanidium, cyanelles and the cyanobacteria. As in other photosynthetic organisms the psbA-gene is transcribed as a monocistronic mRNA. The ribosomal RNA operon was located 4 kb upstream of the psbA-gene.     

Primary Immunodeficiency Diseases in Latin America: First Report from Eight Countries Participating in the LAGID

The Latin American Group for Primary Immunodeficiencies, formed in 1993, presently includes 12 countries. One goal was to study the frequency of primary immunodeficiencies in various regions of the American continent and to enhance knowledge about these diseases among primary-care physicians, as well as allergist–immunologists. Important for this purpose was the development of a registry of primary immunodeficiencies using a uniform questionnaire and computerized database. To date, eight countries have collected information on a total of 1428 patients. Predominantly antibody deficiencies were reported in 58% of patients, followed by cellular and antibody immunodeficiencies associated with other abnormalities in 18%, immunodeficiency syndromes associated with granulocyte dysfunction in 8%, phagocytic disorders in 9%, combined cellular and antibody immunodeficiencies in 5%, and complement deficiencies in 2% of patients. The information gathered from this initial analysis of data will serve to expand the patient database to more areas within participating countries and to new countries and to increase collaboration toward better diagnosis and treatment of these diseases.     

Lymphocytic Hypophysitis Presenting as a Pituitary Tumor in a 63-Year-Old Man

This report describes a case of lymphocytic hypophysitis in a 63-year-old man who presented with symptoms of a pituitary mass lesion associated with hypothyroidism and hypogonadism. Postoperative endocrinological testing demonstrated gonadotropic, thyrotropic, and corticotropic hypopituitarism, and the patient was commenced on replacement therapy with hydrocortisone and levothyroxine. Histological examination of the pituitary tissue obtained by transsphenoidal surgery revealed lymphocytic hypophysitis without evidence of a pituitary adenoma. The vast majority of patients with lymphocytic hypophysitis are women particularly during pregnancy and the puerperium. Until recently only four men were reported in the literature. The pathogenesis of lymphocytic hypophysitis is uncertain but autoimmune mechanisms are possibly involved.     

Investigations on neurotoxicity of chemical substances at the workplace

Summary A cross-sectional study was performed in order to investigate the influence of chronic lead-exposure on the peripheral nervous system. We examined 148 male workers of a storage battery manufacturing plant, who had been exposed to lead metal and inorganic lead compounds for 1 to 28 years (mean 11 years). Fifteen workers with non-occupational risks of peripheral neuropathy (former diseases, alcohol abuse, medication) were excluded from the study. The investigation program comprised: case history, physical examination, analyses of blood- and urine-samples and determination of maximal motor, mixed and sensory conduction velocity (NCV) of the ulnar and median nerve of the right forearm. Objectively no worker showed any signs of health effects related to lead exposure. The Biological Monitoring included the determination of (1) Blood-lead level (Pb-B), (2) Free erythrocyte porphyrins (FEP), (3) -Aminolevulinic acid dehydratase (ALA-D) and (4) -Aminolevulinic acid in urine (ALA-U). Further time-weighted-average (TWA)-values of Pb-B were calculated on the basis of several determinations over the period 1975–1981. The following actual (TWA) median values resulted: Pb-B 53 g/dl (54 g/dl), ALA-U 5.6 mg/l (8.4 mg/l), FEP 2.0 mg/l (2.0 mg/l). The Biologischer Arbeitsstoff Toleranz Wert (BAT) of 70 g//dl for Pb-B was exceeded in 15 workers (11%), and of 15 mg/l for ALA-U in 30 cases (23%). In comparison with age-matched controls, the lead workers showed a mild slowing of NCV with mean values between 0.8 and 2.0 m/s. Multiple stepwise regression analyses revealed statistically significant correlations between the four NCV and age as well as Pb-B. There were better correlations by using TWA than actual data of Pb-B. Consideration of the results of the regression analyses, together with an evaluation of the individual neurophysiological status as a function of internal lead exposure, a dose-effect-relationship was found only in the case of Pb-B exceeding 70 g/dl. From our study it is concluded that chronic lead exposure resulting in blood-lead levels of below 70 g/dl is no occupational risk causing a functionally significant slowing of nerve conduction velocities.With Grants from the Deutsche Forschungsgemeinschaft, Bonn (Project no. Va 23/19-1)     

Clinical features and outcome of maintenance hemodialysis patients with COVID-19 from a tertiary nephrology care center in Romania

Background There is limited information about the clinical characteristics, treatment and outcome of maintenance hemodialysis patients with COVID-19. Moreover, regional differences are also conceivable since the extend and severity of outbreaks varied among countries.Methods In this retrospective, observational, single-center study, we analyzed the clinical course and outcomes of 37 maintenance hemodialysis patients (median age 64 years, 51% men) hospitalized with COVID-19 from 24 March to 22 May 2020 as confirmed by real-time PCR.Results The most common symptoms at admission were fatigue (51%), fever (43%), dyspnea (38%) and cough (35%). There were 59% mild/moderate patients and 41% severe/critical patients. Patients in the severe/critical group had a significantly higher atherosclerotic burden since diabetic kidney disease and vascular nephropathies were the most common primary kidney diseases and eighty percent of them had coronary heart disease. Also, Charlson comorbidity score was higher in this group. At admission chest X-ray, 46% had ground-glass abnormalities. Overall, 60% patients received hydroxychloroquine, 22% lopinavir–ritonavir, 11% tocilizumab, 24% systemic glucocorticoids, and 54% received prophylactic anticoagulation. Seven (19%) patients died during hospitalization and 30 were discharged. The main causes of death were cardiovascular (5 patients) and respiratory distress syndrome (2 patients). In Cox regression analysis, lower oxygen saturation, anemia and hypoalbuminemia at admission were associated with increased mortality.Conclusions In conclusion, we observed a high mortality rate among maintenance hemodialysis patients hospitalized for COVID-19. Anemia, lower serum albumin and lower basal oxygen saturation at admission were factors associated with poor prognosis.