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Biomedical subjects

M Fischer

Publications and source records attributed to M Fischer.

At least 19 recordsLinked to original sources

[Local infiltration thrombolysis of arterial occlusions with tissue plasminogen activator].

Only few reports deal with local low dose thrombolysis of peripheral arterial occlusions by the infiltration technique with recombinant human tissue plasminogen activator (rTPA). We report the treatment of 45 cases (38 patients, 13 times women and 32 times men, aged 33 to 86 years). The patients suffered from thrombotic occlusions of the femoropopliteal artery (n = 39), a femoro-popliteal PTFE bypass (n = 3), a femorocrural bypass graft (n = 2) or a popliteal embolus (n = 1). The thrombus was infiltrated with 2.5 mg rTPA/hour attenuated to 30 ml normal saline solution. In the mean 7.1 mg rTPA was given. The rate of recanalisation was 76% during the days the patient stayed in hospital. The rate of recanalisation was higher (88%) in 16 cases suffering from acute arterial occlusion (< 24 hours). Even in those cases with undetectable or absent peripheral arterial runoff, therapeutic success was achieved at 92%.

Adult

The prevalence of factor XII deficiency in 103 orally anticoagulated outpatients suffering from recurrent venous and/or arterial thromboembolism.

One hundred and three patients suffering from recurrent venous thrombosis, recurrent arterial thromboembolism and/or recurrent myocardial infarction and 50 healthy subjects were tested for Hageman factor (FXII) coagulant activity and antigen. Among the 103 patients we identified 15 subjects with FXII deficiency (15%), 3 with protein C deficiency (3%) and 3 with protein S deficiency (3%). Combined FXII and protein C, protein S or antithrombin III deficiency was not observed. The 103 patients were divided into subgroups according to the type of thrombotic complication. Among patients with exclusively recurrent venous thromboembolism 8% (p = 0.153) were deficient in FXII. Among patients suffering from recurrent arterial thromboembolism and/or myocardial infarction, the incidence of FXII deficiency was significantly higher (20%, p less than 0.003). In 67% of the patients with FXII deficiency a positive family history of thrombosis could be established. In contrast, only 32% of all venous and 28% of all arterial thrombosis patients had a positive family history. We believe that reduced levels of FXII should be considered as a risk factor in the development of thromboembolism. Consequently, more attention should be payed to the measurement of FXII when evaluating thromboembolic risk factors especially in cases of recurrent arterial thromboembolism and/or myocardial infarction.

Acenocoumarol

Cytokine production by mature and immature CD4-CD8- T cells. Alpha beta-T cell receptor+ CD4-CD8- T cells produce IL-4.

This study follows our previous investigation describing the production of four cytokines (IL-2, IL-4, IFN-gamma, and TNF-alpha) by subsets of thymocytes defined by the expression of CD3, 4, 8, and 25. Here we investigate in greater detail subpopulations of CD4-CD8- double negative (DN) thymocytes. First we divided immature CD25-CD4-CD8-CD3- (CD25- triple negative) (TN) thymocytes into CD44+ and CD44- subsets. The CD44+ population includes very immature precursor T cells and produced high titers of IL-2, TNF-alpha, and IFN-gamma upon activation with calcium ionophore and phorbol ester. In contrast, the CD44- subset of CD25- TN thymocytes did not produce any of the cytokines studied under similar activation conditions. This observation indicates that the latter subset, which differentiates spontaneously in vitro into CD4+CD8+, already resembles CD4+CD8+ thymocytes (which do not produce any of the tested cytokines). We also subdivided the more mature CD3+ DN thymocytes into TCR-alpha beta- and TCR-gamma delta-bearing subsets. These cells produced cytokines upon activation with solid phase anti-CD3 mAb. gamma delta TCR+ DN thymocytes produced IL-2, IFN-gamma and TNF-alpha, whereas alpha beta TCR+ DN thymocytes produced IL-4, IFN-gamma, and TNF-alpha but not IL-2. We then studied alpha beta TCR+ DN T cells isolated from the spleen and found a similar cytokine production profile. Furthermore, splenic alpha beta TCR+ DN cells showed a TCR V beta gene expression profile reminiscent of alpha beta TCR+ DN thymocytes (predominant use of V beta 8.2). These observations suggest that at least some alpha beta TCR+ DN splenocytes are derived from alpha beta TCR+ DN thymocytes and also raises the possibility that these cells may play a role in the development of Th2 responses through their production of IL-4.

Animals

[The effectiveness of paramunization for the control of feline coryza].

20 cats in a cat home were treated prophylactically and therapeutically with Baypamun HK. The animals were allocated into three groups as described. 7 freshly admitted clinically healthy cats were treated prophylactically on day 1, 2 and 9 with 1 ml Baypamun HK (group I). 7 cats, who already were allocated for one year in the home and were sick of the feline respiratory disease complex were treated as described for group I (group II). 6 further cats, who also showed symptoms of the feline respiratory disease complex and had stayed for one year in the home were treated with physiol.saline solution according to group I (group III). From all cats blood samples were taken at day 1, 3, 10 and 17. The blood samples were checked for antibodies against feline calicivirus (FCV), feline herpesvirus (FHV), panleukopenia virus (PLV), feline peritonitis virus (FIPV) and feline immunodeficiency virus (FIV). Also the occurrence of the feline leukemia virus (FeLV) was evaluated. The cellular immunity was evaluated by means of the lymphocyte transformations test (LTT), nitroblue-tetrazolium reduction test (NBT) and cytochrome C-reduction test (CRT). Mean value and standard deviation was calculated from the results. The significance was determined by the t-test. The animals were examined clinically daily for 20 days for the feline respiratory disease complex. When necessary, the animals were treated by homeopathic and antibiotic products. At the time of admission to the home all cats were or had been treated with an attenuated panleukopenia vaccine. The serologic parameters were not influenced in the cats of group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Adjuvants, Immunologic

Normal development and behaviour of mice lacking the neuronal cell-surface PrP protein.

PrPC is a host protein anchored to the outer surface of neurons and to a lesser extent of lymphocytes and other cells. The transmissible agent (prion) responsible for scrapie is believed to be a modified form of PrPC. Mice homozygous for disrupted PrP genes have been generated. Surprisingly, they develop and behave normally for at least seven months, and no immunological defects are apparent. It is now feasible to determine whether mice devoid of PrPC can propagate prions and are susceptible to scrapie pathogenesis.

Aging

[Functional protein S in 77 patients treated with anticoagulants and in 32 probands with normal coagulation parameters].

We determined functional protein S with a new automated clotting assay, total protein S antigen with the Laurell technique and free protein S antigen with an ELISA test and calculated the ratio of total protein S antigen and prothrombin antigen (Laurell) of plasmas of 77 patients oral anticoagulant therapy and of 32 normals. The correlation of total protein S antigen with protein S activity was found to be r = 0.857. The normal range of the tests was calculated for orally anticoagulated patients and for normals and was compared with the analytical data from 4 orally anticoagulated, congenital protein S deficiency patients. We believe that the automated functional protein S clotting assay is a quick and easily performed test, which now allows even for protein S the use of a functional assay as the first step for the screening of coagulation inhibitor deficiencies.

Arterial Occlusive Diseases

Mechanisms of interhemispheric transfer and patterns of cognitive function in acallosal patients of normal intelligence.

We investigated interhemispheric transfer and cognitive function in two boys with normal intelligence in whom agenesis of the corpus callosum was identified following minor head trauma. In patient 1, magnetic resonance imaging scan showed agenesis of the corpus callosum and absent anterior commissure. Results of visual interhemispheric transfer tasks suggested degradation in transfer of information to the left hemisphere. Results of a tactile interhemispheric transfer task suggested degradation of access to the right hemisphere. In patient 2, magnetic resonance imaging scan showed agenesis of the corpus callosum and enlarged anterior commissure. Results for both visual and tactile interhemispheric transfer tasks were normal. Dichotic listening tests showed a slight left ear advantage in both patients. These results support the hypothesis that hypertrophy of the anterior commissure is an important mechanism of functional compensation in agenesis of the corpus callosum. However, the relative subtlety of deficits in patient 1 and results of dichotic listening tests support use of other mechanisms as well. No consistent pattern of cognitive deficits was observed.

Agenesis of Corpus Callosum

Electron microscopy analysis of mineral fibers in human lung tissue.

In the present study, lung samples from 126 autopsied cases were examined to determine the content of mineral fibers using analytical transmission electron microscopy (ATEM). The cases were divided into four groups (22 lungs of persons exposed to ambient environmental pollution, 32 cases of mesothelioma, 38 cases of primary lung cancer, and 34 asbestosis cases, 13 of these with additional pleural plaques). Fibers were counted, measured, and mineralogically identified using a combination of X-ray microanalysis and electron diffraction of the non-oriented fiber. Concentration of fibrous particles (defined as particles above 1 micron in length with roughly parallel long sides and an aspect ratio of 5:1 and greater) was calculated as fibers 10(6)/g dry lung weight. The concentration of chrysotile was found to be similar throughout the groups except for two cases in the asbestosis group with comparably high numbers of chrysotile. However, a remarkable difference for amphiboles could be observed between the groups. Asbestos bodies were mostly found in the asbestosis group. There was a rather good correlation between numbers of amphibole fibers and asbestos bodies, with an average ratio of 10:1. For comparison purposes between occupationally exposed/non-exposed individuals, a transition was found in the concentration range of 3-10(7) asbestos fibers/g dried lung weight.

Analysis of Variance

Effects of combined renovascular hypertension and diabetes mellitus on myocardial cells, non-vascular interstitium and capillaries: a stereological study on rat hearts.

The effects of combined renovascular hypertension and diabetes mellitus on the rat heart were investigated in order to detect possible synergistic effects of the two conditions. Hypertensive diabetic and hypertensive non-diabetic animals were compared to diabetic and non-diabetic controls. Hypertension was established for 12 weeks by a surgical stenosis of the left renal artery; diabetes mellitus was maintained for 8 weeks by a single intraperitoneal injection of 60 mg/kg streptozotocin. Light microscopic stereology did not reveal significant divergences between diabetic hypertensives and non-diabetic hypertensives. Hypertension induced a focal perivascular and interstitial fibrosis with increased volume densities of non-vascular interstitium and fibrosis (P less than 0.001). Capillary density (QA) was decreased in transverse sections (P less than 0.01) and increased in longitudinal sections (P less than 0.01). This indicates a three-dimensional remodelling of the capillary bed with an increased number of obliquely running capillaries. At least the length density (LV) of capillaries (mm/mm3) tends to be normalized in long-term renovascular hypertension. At the ultrastructural level, a synergism of hypertension and diabetes mellitus was observed: the volume ratio of mitochondria to myofibrils was significantly decreased in hypertensive diabetics, but not in non-diabetic hypertensives or in diabetics. This may enhance the risk of cardiac deterioration. We conclude that the primary target of the synergistic damage in hypertensive diabetic heart muscle disease is the myocardial cell and not the cardiac interstitium.

Animals

Cortisol levels and vigilance in eating disorder patients.

Elevated plasma levels of cortisol, as well as deficits in cognitive processes such as attention, have been observed in patients with eating disorders. The association between plasma cortisol and performance in vigilance task was studied in 17 patients with bulimia nervosa or anorexia nervosa during the acute phase of their eating disorder. In comparison to normal young women, the patients had a significantly lower hit rate in a discrimination task and showed an impaired perceptual sensitivity index. They also displayed significantly longer reaction times to hits, but not to false alarms. Cortisol levels of the patients were significantly higher than those of the normal controls. When patients were divided according to their median cortisol level, the patients with higher levels performed significantly more poorly than did the patients with lower levels. In the total patient sample, cortisol levels showed a significant negative correlation with hit-rate (r = -.54) and a significant positive correlation with reaction time to hits (r = .70). Other clinical characteristics were not related to cognitive performance. These results suggest a possible role of cortisol in the development of attentional deficits in eating disorder patients.

Adult

Ultrasonographic evaluation of Legg-Calve-Perthes disease based on sonoanatomic criteria and the application of new measuring techniques.

This study attempts an ultrasonographic classification of Legg-Calve-Perthes disease according to sonoanatomic and sonometric criteria. Four stages, similar to standard radiological staging, could reproducibly be found in 29 patients with unilateral disease. The stages could be significantly differentiated according to descriptive sonoanatomic criteria and partially newly introduced sonographic measurements, including epiphysis-metaphysis-index and acetabulum-epiphysis-distance. Sonographic evaluation of Perthes hips is a simple and standardised procedure, which can serve to stage and monitor the course of the disease and hence reduce the amount of X-ray exposure and treatment costs.

Child

Comparative analysis of native and cysteine-deficient HIV-1 reverse transcriptase.

To study the subunit structure and the active site of human immunodeficiency virus reverse transcriptase (RT), the enzyme was expressed in E. coli and purified to homogeneity in large quantities. The recombinant enzyme consists of two major polypeptides of 66,000 and 53,000 Da in equimolar amounts and a minor species of 51,000 Da. Amino acid sequence analysis of the recombinant proteins revealed that the amino termini of the two major subunits are identical to that of the virion-derived enzyme. The two cysteinyl residues at positions 38 and 280 in the RT amino acid sequence were replaced by alanine in an attempt to elucidate the role of the sulfhydryl groups in RT enzyme activities, heterodimer formation, and intrasubunit linkage. The results reported here show that the two cysteinyls are dispensable and their absence in the amino acid sequence of the reverse transcriptase does not affect DNA polymerase or ribonuclease H enzyme activities or the formation of heterodimer structures. Furthermore, inhibitors of polymerase activity such as 3-azidothymidine triphosphate, dideoxythymidine triphosphate, and tetrahydroimidazo[4,5,1-JK][1,4]benzodiazepens (1H)-one are equally effective on the mutant containing no cysteinyl residues and the wild-type enzyme.

Base Sequence

Fat elimination in acute renal failure: long-chain vs medium-chain triglycerides.

Elimination and hydrolysis of fat emulsions containing long-chain (LCT; Intralipid) or long- and medium-chain triglycerides (MCT; Lipofundin MCT) were compared in seven patients with acute renal failure (ARF) and six healthy control subjects. In control subjects, clearance of MCT was slightly higher than that of LCT (1.93 +/- 0.34 vs 1.55 +/- 0.3 mL.kg body wt-1.min-1, P less than 0.05). The rise in plasma triglycerides was similar and the release of free fatty acids was higher during MCT (P less than 0.02). In ARF, clearance of both LCT and MCT was equally reduced (0.53 +/- 0.12 vs 0.59 +/- 0.14 mL.kg body wt-1.min-1, P less than 0.01 vs control subjects). Again, the rise in triglycerides was comparable. Free fatty acid release was higher during MCT but lower than in control subjects. Plasma concentrations of glucose and lactate were not affected in control subjects but increased during both LCT and MCT in ARF. Thus elimination of both LCT and MCT is profoundly decreased in ARF. The impaired lipolysis in ARF cannot be circumvented by the use of MCT.

Acute Kidney Injury

Healing and relapse of duodenal ulcer during ranitidine therapy in the elderly. The RUDER Study Group.

A total of 2,109 outpatients with active duodenal ulcer (DU) entered an open, prospective study in order to investigate factors influencing healing and relapse during 2 years of ranitidine therapy (300 mg daily for healing, 150 mg as maintenance treatment). In a retrospective analysis, we evaluated the influence of age. Symptoms related to DU in 1,899 evaluable cases in patients over 65 years of age (n = 185) were identical to those of DU patients younger than 65 years old (n = 1,714). Rapid healing within 2 weeks of ranitidine therapy was less frequent in the elderly (32.5%) than in younger patients (40.7%) though identical healing rates (94.1%) in each group were achieved by continuation of ranitidine therapy for 8 weeks. Cumulative recurrence rates during the 2 years of long-term therapy were lower (17.3%) in old age than in patients under 65 years of age (23.3%). Adverse events were rare in both age groups. We conclude that DU healing during ranitidine is delayed in old age. Additional differences in relapse rates in favor of the elderly suggest that DU disease has a different course in the elderly.

Adult

Endoscopic implantation of collagen (GAX) for the treatment of urinary incontinence.

Sixteen women whose ages ranged from 42 to 73 years (mean 57) and 2 men, aged 76 and 80 years respectively, were treated for urinary stress incontinence with transurethral implantation of submucosal glutaraldehyde cross-linked collagen (GAX); 15 females had had several continence operations previously and 1 female was totally incontinent following low anterior resection of the sigmoid colon for cancer. All but 2 patients received 8 ml GAX in a single operative session under general anaesthesia. Before implantation, patients underwent urodynamic evaluation, cystoscopy, urinary stress test and the two-thirds capacity pad weighing test. Post-operative evaluations were carried out after 3, 6 and 9 months and included urinary flow rate, urine analysis, residual urine determination and the two-thirds pad weighing test. The results were encouraging. After 3 months, 8/18 patients were cured, 7/18 had improved and 3/18 had failed to respond. Nine months post-operatively, 7 patients were still continent, 8 had improved and 3 remained unchanged. One of the improved group had a reinjection 18 months post-operatively and has been continent since then. We feel that GAX collagen injection is a safe and easy method for the treatment of urinary stress incontinence; it has no observable or measurable morbidity.

Adult

Regulation of intestinal lactase in adult hypolactasia.

Relative deficiency of intestinal lactase activity during adulthood, adult hypolactasia, is a common condition worldwide. We studied the regulation of lactase-phlorizin hydrolase in normal and adult hypolactasic subjects by correlating transcript abundance in intestinal biopsies with relative synthetic rates for the protein in cultured intestinal explants. After metabolic labelling studies in six subjects, precursor lactase-phlorizin hydrolase was identified in amounts directly proportional to the enzyme-specific activity suggesting that levels of intestinal lactase are regulated by synthetic rate. Total intestinal RNA was extracted from biopsies of these subjects and three hypolactasic adults who had participated in previous biosynthesis studies. Transcript levels were markedly reduced in deficient subjects who demonstrated diminished lactase-phlorizin hydrolase synthesis. The sequence of 1 kb of 5'-flanking region of the lactase-phlorizin hydrolase gene was determined in two hypolactasic subjects and two controls. No sequence variability was identified to account for differences in mRNA levels or biosynthetic rates between the two groups. A single hypolactasic subject previously characterized as demonstrating delayed posttranslational processing, showed message levels intermediate between other deficients and controls. These results suggest that in the majority of our subjects, pretranslational mechanisms account for the predominate regulatory control of lactase-phlorizin hydrolase expression in the proximal intestine.

Adult