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Biomedical subjects

A Zimmermann

Publications and source records attributed to A Zimmermann.

At least 271 records · Page 15Linked to original sources
PubMed1991

[Orthotopic liver transplantation at the Island Hospital. Initial experiences 1985-1990].

Between 1985 and 1990 22 orthotopic liver transplantations (OLT) were realized in 19 patients. Active infection and diffuse splanchnic venous thrombosis were the only contra-indications to the intervention. Sixteen patients were transplanted electively; three had to be retransplanted urgently. Three patients had an urgent primary transplant. The incidence of surgical complications related to liver implantation was fair. One patient (5%) developed a late portal vein thrombosis; another patient (5%) had to be retransplanted because of hepatic artery thrombosis. All patients presented one or more major postoperative complications. All, but one, patients had a rejection of the allograft; five of them needed treatment with mono- or polyclonal antilymphocytic sera to reverse the rejection. One patient was retransplanted because of a hyperacute rejection. The six-month survival in this series is 68.5% (13 of 18 patients); one patient died 7 months post-OLT due to a neurological complication of her Wilson disease. Quality of life (from 6 to 64 months post-OLT) is excellent in the 12 long-term survivors. This small experience of the Bernese transplantation program shows that liver transplantation is a safe surgical procedure allowing excellent quality of life in a majority of patients.

Adult↗
PubMed1990

[Transluminal balloon coronary angioplasty. Indications and results].

Thirteen years after its introduction transluminal balloon catheter angioplasty is a widely used technique. Owing to major technological advances and to the experience acquired by surgical teams, the primary success rate now reaches 90 p. 100. Hospital mortality has fallen down to 1 p. 100 and the need for emergency aorto-coronary bypass has been reduced to 4 p. 100 of the cases. However, despite repeated attempts at pharmacological or mechanical prevention, the restenosis rate remains around 30 p. 100. Coronary angioplasty is part of a wider strategy of myocardial reperfusion. Its indications are roughly the same as those of surgery. In patients with one-vessel coronary disease angioplasty is the first choice treatment, except for unprotected restenosis of the common trunk or very proximal lesions of the anterior interventricular artery. In multiple vessel disease the more complex the anatomical situation the more pronounced the left ventricular dysfunction and the greater the need for surgery. The acute phase of myocardial infarction is a legitimate indication for angioplasty, notably when thrombolytic agents are contraindicated or have failed when given intravenously, or in case of recurrence after an initially successful thrombolysis.

Angioplasty, Balloon, Coronary↗
PubMed1990

[The differential diagnostic value of polysomnography].

Polysomnography (PSG) is a standard procedure for investigating sleep functions including behavior. This technique is described. The diagnostic value of PSG is shown by statistical data from the literature and our own patient sample which includes 442 insomniacs. In one out of five patients, insomnia is related to a known somatic factor, i.e. periodic movements in sleep or sleep apnea, which can only be reliably identified by PSG. A more differentiated analysis shows that PSG yields important diagnostic information in 50 to 75% of insomniacs. Three cases are reported, showing that even patients without clinical indications for sleep disturbance can have deficient sleep functions. If they can be specifically addressed, this may be the turning point of the treatment. Therefore, a wide application of PSG is favored.

Adult↗
PubMed1990

Mitochondrial structure and function in CCl4-induced cirrhosis in the rat.

To investigate whether the impairment of mitochondrial function in cirrhosis is due to a reduction in liver cell mass or whether mitochondrial function is altered specifically, we analyzed mitochondrial volume and surface density of mitochondrial membranes in control and cirrhotic rats by stereological means. Cirrhosis was induced by long-term exposure to phenobarbital and CCl4. Hepatocellular and mitochondrial volumes were reduced to a similar extent, by 39% and 40%, respectively, in cirrhotic animals (p less than 0.01). Thus the fraction of hepatocytes occupied by mitochondria did not differ between the two groups. Both total outer (31 +/- 3 vs. 19 +/- 6 m2; p less than 0.01) and inner (87 +/- 24 vs. 45 +/- 12 m2; p less than 0.01) mitochondrial membranes were significantly reduced. Membrane surface was normal per unit of mitochondrial volume, however, suggesting intact mitochondrial structure. Matrix and outer membrane enzyme activities expressed per compartment did not differ between control and cirrhotic animals. Inner membrane, in contrast, had an increased enzyme content per unit area both for cytochrome oxidase (10.3 +/- 2.9 vs. 13.0 +/- 1.6; p less than 0.05) and ATPase (13.7 +/- 1.4 vs. 21.2 +/- 2.9; p less than 0.01). Basal oxygen consumption measured in the perfused liver in situ was significantly reduced in cirrhotic livers (1.6 +/- 0.1 vs. 1.1 +/- 0.4 mumol/min-1/gm-1) but was unchanged when expressed per square meter of inner membrane. Our results demonstrate that impaired mitochondrial function is mainly due to loss of hepatocellular mass. Increased enzyme activity per unit surface area of inner mitochondrial membrane may be important to maintain mitochondrial function of the cirrhotic liver.

Animals↗
PubMed1990

Pharmacokinetics and chronic toxicity of cyclosporine A in genetic hydroxylation-deficient dark Agouti rats.

Since oxidation plays a key role in the metabolism of cyclosporine A (CsA), the pharmacokinetics and the toxicity of CsA was investigated in female dark Agouti rats exhibiting a deficiency for debrisoquine hydroxylation and for dextromethorphan demethylation. When compared with Wistar rats (n = 10), dark Agouti rats (n = 10) had a higher mean clearance (4.8 ml/min per kg vs. 3.3 ml/min per kg) and a lower mean residence time (606 min vs. 1361 min) after intravenous dosing of CsA. The systemic availability of subcutaneous CsA was close to 100%. The steady state CsA concentrations assessed by HPLC in whole blood after subcutaneous dosing of 20 mg/kg per day for 23 days (n = 10) were about 1000 ng/ml in dark Agouti rats. When compared with dark Agouti rats treated with cremophore (n = 10) or not treated at all (n = 12), dark Agouti rats on chronic subcutaneous CsA plus cremophore for 23 days (n = 10) had no difference in kidney histology but had slightly increased liver fatty changes. Rats on CsA and/or cremophore had a decreased uric acid clearance and evidence of hypoaldosteronism. The urinary ratio of debrisoquine/4-hydroxydebrisoquine decreased in rats on CsA, whereas the O-demethylation and N-demethylation of liver obtained from rats on cremophore was impaired. Thus, dark Agouti rats show no difference in the metabolism of CsA and when given CsA for 23 days show drug-induced functional but no relevant structural light microscopic changes in the kidney, and functional and slight structural changes in the liver.

Animals↗
PubMed1990

Primary lipid cardiomyopathy.

In this communication, we describe an isolated, apparently congenital cardiomyopathy (CMP) characterized by the accumulation of stainable lipid in mitochondria of cardiomyocytes. This lesion, which we term primary lipid cardiomyopathy, has not been reported so far. The structural alteration was associated with progressive heart failure, leading to death at the age of 3 years, and with massive hypertrophy of myocardium. Lipid storage in heart muscle cells resulted in an impressive yellow to orange color of the myocardium. We suggest that this type of primary CMP may represent a new member within the group of mitochondrial CMPs. Possible pathogenic mechanisms are discussed.

Cardiomyopathies↗
PubMed1990

Decay-accelerating factor in the cardiomyocytes of normal individuals and patients with myocardial infarction.

The presence of decay-accelerating factor (DAF) was clearly demonstrated on the surface of normal cardiomyocytes. In patients who had died of myocardial infarction (MI) cardiomyocytes displayed different appearances: outside the ischaemically damaged region the myocytes showed no significant variations in DAF expression when compared with controls without MI. Within myocardial zones damaged by ischaemia, however, apparently normal myocytes showed large gaps in surface staining of DAF or formed clusters which were entirely devoid of reactivity with anti-DAF antibodies. The number of DAF-deficient myocytes increased with the extent of necrosis and also with the number of days between onset of MI and death. Even though injury to myocytes is to a large extent related to anoxia and to the presence of free oxygen radicals, the complement system also appears to be involved; DAF may have protective functions against complement-mediated injury. We speculate that phospholipase may be involved in the removal of DAF from the cardiomyocyte surface.

Aged↗
PubMed1990

Severe neonatal asphyxia due to X-linked centronuclear myopathy.

Severe neonatal centronuclear myopathy is inherited as an X-linked condition characterized by primary asphyxia, extreme muscular hypotonia and absent spontaneous movements. We report seven cases from three families to point out the importance of diagnosis with regard to prognosis, outcome and genetic counselling. In hypotonic diseases, analysis of cerebrospinal fluid, electromyography, nerve conduction velocity creatine kinase and a skin biopsy for fibroblast cultures for metabolic investigations are usually carried out. Needle muscle biopsy is an additional valuable investigation to establish diagnosis. In all our patients we found an increased number of centrally located nuclei with perinuclear halos confirming the diagnosis of centronuclear myopathy. The diagnosis of this disorder will become of greater importance as soon as carrier detection and prenatal diagnosis by DNA-technology are routinely available.

Asphyxia Neonatorum↗
PubMed1990

Anaplastic astrocytoma and glioblastoma: pion irradiation with the dynamic conformation technique at the Swiss Institute for Nuclear Research (SIN).

Clinical phase I/II studies have been performed at the Swiss Institute for Nuclear Research (SIN) since February 1982. Fifty-two out of 249 patients accepted for pion treatment by the end of 1986 were treated for malignant glioma with high dose pion irradiation. A substantial influence of their radioresistance was expected from increased radiation quality due to the contribution of high LET particles from pion capture, and by the possibility of target volume shaping and dose distribution related to the dynamic spot-scan conformation technique. The patients' treatment followed a dose escalation program with total doses from 2720-3420 cGy, fraction sizes from 170 to 205 cGy (90% isodose, minimum target dose), and treatment times from 4 to 5 weeks. 12/52 patients received an accelerated treatment with 3280 cGy in 14-22 days. 49/52 patients are eligible: 3 with astrocytoma of clinical aggressive behaviour, 14 with anaplastic astrocytoma (median age 42 years), and 32 patients with glioblastoma (median age 52 years). 8/49 patients had total/subtotal tumour resection, 19 patients a stereotactic biopsy. The patients were divided into three groups according to total dose, and a fourth group which received the accelerated treatment. There was no statistically significant difference in the median survival rate between the four groups, which was 13 months for the non-glioblastoma patients and 9 months for the glioblastoma patients. No radiation necrosis and no demyelination was found in 17 patients (6 recraniotomies, 11 autopsies). In 10/17 patients, clearly identifiable tumour cells were not demonstrated. NMR findings showed the tumour-surrounding oedema mostly stimulated by tumour necrosis and tumour progression. From these findings, further dose escalation programs, together with a shaping of the target volume close to the tumour, are not contraindicated.

Adult↗
PubMed1990

Multiple tumors of the biliary tract.

Multiple synchronous tumors of the extrahepatic biliary tree are not frequently reported. Over a 2-year period, 54 operative procedures were performed for tumors of the extrahepatic biliary tract or periampullary region. In five of these cases, unsuspected tumors were observed. Of these, one patient had multiple benign papillomatosis of the extrahepatic biliary tree. All four of the other patients were found to have unsuspected small carcinomas of the gallbladder in association with mid- or low bile duct cancer. Multiple tumors of the extrahepatic biliary apparatus may occur more frequently than previously thought, and the incidence of unsuspected gallbladder cancer in association with bile duct cancer may be high. These tumors should be suspected and looked for in each instance by intraoperative endoscopy and careful histologic examination of the gallbladder.

Adenocarcinoma↗
PubMed1990

Determination of N-methylhistamine in urine as an indicator of histamine release in immediate allergic reactions.

The use of the urine histamine metabolite, N-methylhistamine (N-MH), as a parameter of histamine release in immediate allergic reactions was investigated. Baseline levels were determined in 34 normal control subjects and 29 atopic patients. Increases of urine N-MH values were measured during histamine infusions and in venom-allergic patients receiving bee-sting challenges. N-MH was determined by a newly developed radioimmunoassay. Baseline levels in control subjects and atopic patients demonstrated no significant differences. With regard to challenge tests, fluctuation of N-MH levels during a 6-hour period was measured. Random 6-hour increases in healthy and atopic subjects ranged from 5% to 41%. Before infusion of histamine (0.25 micrograms/kg/min for 30 minutes), baseline values were 137 +/- 11.4 micrograms N-MH per gram of creatinine and 9 +/- 1.1 micrograms N-MH per hour (n = 9). Levels peaked 1 hour after infusion at 275 +/- 45 micrograms/gm of creatinine and 44 +/- 5.6 micrograms/hr and decreased to resting levels after 2 hours. Metabolization by N-MH accounted for 9.5% +/- 4.9% (range, 2.4% to 18.4%) of infused histamine in the urine of the nine subjects. Bee-sting challenges were performed in 12 patients and three control subjects. Only in three patients experiencing generalized urticaria, nausea, dyspnea, and hypotension were significant increases of urine N-MH levels (138%, 144%, and 238%) observed. All other patients and three normal control subjects demonstrated normal local reactions without increase of N-MH values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

The protein kinase C inhibitor H-7 activates human neutrophils: effect on shape, actin polymerization, fluid pinocytosis and locomotion.

The present study demonstrates new properties of H-7. The protein kinase inhibitor H-7 is a potent activator of several neutrophil functions. Stimulation of initially spherical nonmotile neutrophils elicits vigorous shape changes within a few seconds, increases in cytoskeletal actin, altered F-actin distribution, increased adhesiveness and a relatively small increase in pinocytic activity. H-7 has also chemokinetic activities. Depending on the experimental condition, H-7 may elicit or inhibit neutrophil locomotion. It failed to induce chemotaxis. Thus, the response pattern elicited by H-7 is different from that of other leukocyte activators such as chemotactic peptides, PMA or diacylglycerols. The finding that H-7 can elicit shape changes, actin polymerization and pinocytosis suggests that these events can occur without activation of protein kinase C (PKC). PMA-induced shape changes and stimulation of pinocytosis were not inhibited by H-7.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1990

[Special indications for Helal's serial metatarsal osteotomy].

Authors discuss, presenting case reports, the operative indications of Helal's metatarsal serial osteotomy. In their first case this kind of operation was performed because of metatarsalgia, following traumatic amputation of the hallux. In their second case, in a young female with rheumatoid arthritis, considering the age of the patient and the destruction in the metatarsophalangeal joints too, Helal's metatarsus osteotomies were completed with the resection of the basis of the ground phalanx. In both cases good correction was reached and without any complaints.

Accidents, Traffic↗
PubMed1990

Pion irradiation at Paul Scherrer Institute. Results of dynamic treatment of unresectable soft tissue sarcoma.

Since November 1981, when pion irradiation was introduced for deep seated tumors at the Swiss Institute for Nuclear Research (SIN; now Paul Scherrer Institute, PSI) a dynamic, three-dimensional spot scan application technique has been in use. To exploit this technique a special planning system for optimisation of the dose distribution has been designed. From November 1981 to December 1988 a total of 406 patients have been treated with pions. From April 1983 to October 1987 a total of 35 patients were prospectively treated for unresectable soft tissue sarcomas in a phase I/II-study. In 32/35 patients, tumor sites were retroperitoneal, pelvic or in the groin or thigh. 27 patients received a high, curative total dose of 30 to 36 Gy. After a median follow-up time of 19 months (13 to 68) the actuarial five-year rate of local tumor control for these 27 patients was 64%; the actuarial five-year survival rate of the 20 patients treated without metastases was 58%. Late reactions appeared in 5/27 patients: 2/8 patients with extremity/groin sarcomas (1/2 caused by biopsy) and 3/19 patients with retroperitoneal/pelvic sarcomas (one a skin reaction after Actinomycin-D, one a small bowel reaction after 36 Gy, a dose no longer given). Dynamic spot scan pion irradiation proves to be a successful treatment technique for unresectable sarcomas with a high rate of tumor control and a very low rate of severe late reactions.

Aged↗
PubMed1989

Diacylglycerols and the protein kinase inhibitor H-7 suppress cell polarity and locomotion of Walker 256 carcinosarcoma cells.

We show that diacylglycerols, like phorbol myristate acetate (PMA), suppress cell polarity and locomotor activity of Walker carcinosarcoma cells in a dose-dependent fashion in vitro. OAG and diC8 show significant activity at concentrations above 3 x 10(-5) M. The inhibitory effect on locomotion is due to a reduction in the proportion of locomoting cells rather than gradual lowering of the speed of individual cells. Measurement of protein kinase C (PKC) activity in isolated fractions showed a substantial reduction of the total cellular PKC activity and of the activity in the cytosolic fraction following incubation of cells with 10(-8) M PMA for 30 min. In contrast, the total and relative PKC activity associated with the membrane fraction was increased by PMA. The effect of H-7, an inhibitor of PKC as well as of cAMP-dependent kinase, has been tested. H-7 suppressed cell polarity of "unstimulated" control cells (ID50 = 6.5 microM H-7), colchicine-stimulated cells (ID50 = 92 microM H-7) or cells treated with both PMA and colchicine (ID50 = 15 microM H-7), in a dose-dependent fashion. The locomotor activity of the cells was also suppressed. LTB4 had no clearcut activity in this system. Our findings suggest that diacylglycerols and H-7 are of interest as physiological or pharmacological stop signals for tumor-cell locomotion. Contrary to our expectations, PMA and diacylglycerols vs. H-7 did not produce opposing or antagonistic effects on cell polarity and locomotion. This similarity may be due to down-regulation of PKC by PMA and inhibition of PKC by H-7. However, the mechanisms underlying these novel effects of diacylglycerols and of H-7 on cell polarity and locomotion may be even more complex; they require further studies.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1989

In vivo 31P NMR spectroscopy of energy rich phosphates in the brain of the hyperammonemic rat.

Hyperammonemia is a major contributing factor to the neurological abnormalities observed in hepatic encephalopathy and in congenital defects of ammonia detoxication. In rats variable changes in labile energy rich phosphates in the brain have been observed in hyperammonemia using biochemical methods. Using 31P-NMR spectroscopy however no significant changes of the relative concentrations of the energy rich phosphates alpha, beta and gamma-ATP, phosphocreatine, inorganic phosphate and the pH were found in the fronto parietal cortex of the urease treated hyperammonemic rat. Alterations in the metabolites of these compounds do not appear to be a major pathomechanism of ammonia toxicity in this brain area.

Ammonia↗