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Biomedical subjects

M Schwarz

Publications and source records attributed to M Schwarz.

At least 343 records · Page 19Linked to original sources

[Septic aneurysm in a free flap].

The indications for free flap transfer are well known, and include infected areas or large defects. In the case presented tissue destruction lead to a septic aneurysm with ischemia of the flap. After resection and new anastomosis the flap did not recover. The mistakes and its consequences are shown.

Adult↗

Retrovirus-induced insertional mutation in Mov13 mice affects collagen I expression in a tissue-specific manner.

In the Mov13 mouse mutant, transcription of the alpha 1 (1) collagen gene is blocked by a retroviral insert in the first intron. We now report that teeth derived from homozygous embryos produce a dentin layer containing normal amounts of collagen 1. In situ hybridization and RNAase protection experiments indicate that the mutant allele is efficiently transcribed in odontoblasts, in contrast to other cell types. Correct splicing of the primary transcript containing the viral sequence results in a functional alpha 1 (1) collagen mRNA. The absence of a mutagenic effect in odontoblasts, as opposed to fibroblasts, suggests that the retroviral insert interferes with tissue-specific transcriptional control of the alpha 1 (1) collagen gene, most likely by inactivating cell-type-specific cis-acting regulatory elements.

Animals↗

Myorelaxant effect after intrathecal injection of antispastic drugs in rats.

The effects of intrathecal (i.th.) injections of antispastic drugs were studied on spontaneous activity in the electromyogram (EMG) in genetically spastic rats and on spinal reflex transmission in anaesthetized normal rats. Baclofen, 0.2-2 nmol, and midazolam, 10-80 nmol, suppressed tonic activity in the EMG recorded from the gastrocnemius muscle in mutant rats, whereas tizanidine, 1-100 nmol, enhanced it. The action of baclofen was antagonized by i.th. co-administration of delta-aminovalerate but not by bicuculline, that of midazolam by systemic pretreatment with Ro 15-1788. The effect of i.th. tizanidine was antagonized by co-administration of prazosin but not by yohimbine. Baclofen, 2 nmol, exerted suppressant effects on Hoffman (H)-reflexes and spinal flexor reflexes in normal animals, midazolam, 80 nmol, only on flexor reflexes. Tizanidine, 100 nmol, failed to suppress H-reflexes and flexor reflexes. The present results demonstrate a myorelaxant effect of i.th. injections of baclofen and midazolam but not of i.th. tizanidine.

Animals↗

Mutations at codon 61 of the Ha-ras proto-oncogene in precancerous liver lesions of the B6C3F1 mouse.

Liver tumors of the B6C3F1 mouse frequently contain mutations at specific sites of codon 61 of the Ha-ras proto-oncogene. To address whether these mutations occur early or late during carcinogenesis, we analyzed mutations in the Ha-ras gene in small precancerous liver lesions of the B6C3F1 mouse. For this purpose, 10-microns frozen liver sections were prepared and stained for glucose-6-phosphatase activity. Using punching cannuli, we then took small tissue samples of approximately 5-30 micrograms from enzyme-deficient liver lesions and from normal parts of the liver. These tissue samples were analyzed for mutations in the Ha-ras gene by in vitro amplification of DNA via the polymerase chain reaction combined with selective oligonucleotide hybridization. By this approach we were able to analyze mutations in the Ha-ras gene within lesions with diameters of less than 0.5 mm. Our results demonstrate that approximately 15% of the glucose-6-phosphatase-negative lesions that occurred 24-28 wk after a single injection of diethylnitrosamine contain either C----A transversions at the first base or A----G transitions and A----T transversions at the second base of codon 61 of the Ha-ras gene. The same types of mutations, although with a somewhat higher frequency (33%), were found in liver tumors taken 68 wk after diethylnitrosamine treatment. These findings demonstrate that Ha-ras mutations can be detected even in very small precancerous liver lesions, suggesting that these mutations may be an early, perhaps even the first, critical event during murine hepatocarcinogenesis.

Animals↗

Arterio-venous malformations in childhood: clinical presentation, results after operative treatment and long-term follow-up.

In a series of 182 arterio-venous malformations (AVM) recently published we found 33 children aged 1 to 16 years. In 28 cases, the admitting condition was hemorrhage. For 31 AVMs total excision was possible. We observed one postoperative death accounting for a mortality of 3%. All children but two were followed-up by personal examination. Two were not able to work due to severe neurological deficits and seven had not been able to get into their intended occupation.

Adolescent↗

Antibiotic single-dose prophylaxis of shunt infections.

Shunt infections after implantation or revision of a shunt for CSF drainage in hydrocephalic patients are serious complications. In view of their frequency, this study investigated the efficacy of prophylactic administration of a single dose of the antibiotic cefazedone in reducing in the post-operative infection rate. Fifty children of up to 14 years of age suffering from hydrocephalus of various etiologies were treated prophylactically and compared with a similar untreated group. The diagnosis of infection was based mainly on microbiological and clinical observations and investigations. Classical infection parameters were also recorded and evaluated, but played only a secondary role in establishing the diagnosis as they can change post-operatively without an infection being present. The infection rates observed were 6% in the group of patients who received antibiotic treatment prophylactically and 14% in the untreated control group.

Adolescent↗

Fine structural features of the cerebral microvasculature in hydrocephalic human infants: correlated clinical observations.

Four of 30 human cerebral cortex biopsies from infants ranging from four days to about ten years treated for hydrocephalus by shunt operations are described paying special attention to the vascular structures. The biopsy specimens were studied in semi-thin and ultrathin sections. Attention is drawn to the role of pinocytotic vesicles found in capillaries and smaller vessels as a possible transcellular route for the hydrocephalic oedema resolution. No intercellular dehiscences or the so called blisters were observed. With the passage of time, the number of membrane bound vesicles increased and arrays of pinocytotic vesicles were discernible both on the abluminal as well as luminal aspect of the capillary wall. Additionally, larger vacuoles containing electron-dense material, apparently undergoing autolysis, were also detected. The basal lamina was of uneven thickness and at places duplicated. Hypertrophic pericytes exhibited remarkable oedamatous changes, increased vesicular or vascular transport, demonstrating pericyte brain-barrier dysfunction. Swelling of the astrocytic end-feet bordering the capillaries was remarkable. These findings indicate that the CSF or oedema fluid is absorbed into the vascular system via a transendothelial pathway.

Cerebral Cortex↗

Heterogeneity of enzyme-altered foci in rat liver.

Enzyme-altered foci (EAF) in liver are assumed to be precursor lesions for tumors in this organ. Results obtained with selected hepatocarcinogens which produce lesions of differing phenotype and growth behavior indicate that not the total number of enzyme-altered cells but rather the proliferation of individual cell clones is of major importance for additional changes leading to malignancy. Analyses including multiple marker enzymes demonstrate a relationship between foci phenotype and proliferation. The inducibility of certain downregulated enzymes in EAF indirectly suggests disturbances in the expression of regulatory genes such as proto-oncogenes. Data on Ha-ras and c-myc proto-oncogene expression in EAF are presented.

Adenosine Triphosphatases↗

Testing for cystic fibrosis using allelic association.

A particular haplotype defined by probes XV2c, KM19, and CS.7 at the D7S23 locus was found on 90% of chromosomes which carry cystic fibrosis (CF), but on only 11% of normal chromosomes in a UK sample of CF carriers. We show how such data can be used to calculate carrier risks for people with and without a family history of CF, and give examples of clinical applications. For parents or sibs of dead CF patients, phase and genotypes can often be assigned with only 1 to 2% error. However, this method is not suitable for prenatal testing where there is no history of CF; for couples with no family history, no fetus can be shown to be at more than 2% risk of being affected.

Adult↗

[Periarthritis calcarea of the finger joints].

Calcium deposits close to finger joints are seen very often and are common in systemic diseases. There are also calcium deposits with no relation to other symptoms and therefore diagnosis is difficult. Between 1984-1988 we have analysed twelve such cases and explained the differential diagnosis and therapy. It seems important that these cases with typical clinical and radiologic findings are self-limiting and restitutio ad integrum is common without any therapy.

Adult↗

Paradoxical convulsant action of a novel non-competitive N-methyl-D-aspartate (NMDA) antagonist, tiletamine.

Intracerebroventricular (i.c.v.) injection of tiletamine, 0.001 mumol, a presumed non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, protected mice from convulsions induced by NMDA and quinolinate, but not from those induced by excitatory amino acids interacting preferentially with non-NMDA receptors. At higher doses, however, tiletamine induced convulsions by itself. Tiletamine-induced convulsions were antagonized by the broad spectrum excitatory amino acid antagonist, gamma-D-glutamylamino-methylsulphonate (gamma-D-GAMS), and were potentiated by the competitive NMDA antagonist, 2-amino-7-phosphonohepatanoate (AP7). Intrathecal (i.t.) injection of tiletamine, 0.01-1.0 mumol, dose-dependently suppressed spinal flexor reflexes. Tiletamine, 0.01 and 0.1 mumol, failed to affect spinal Hoffman- (H-) reflexes, whereas tiletamine, 1.0 mumol, led to a 50% increase of the H-reflex amplitude. It is concluded that the anticonvulsant and reflex suppressant action of tiletamine are due to antagonism of NMDA receptor-mediated excitation. The convulsant effect of tiletamine and its excitatory effect on spinal H-reflexes at higher doses, however, appear to be mediated by non-NMDA receptors.

Animals↗

[Retrospective analysis of results and complications following kidney transplantation in diabetic nephropathy--a challenge for the future].

A retrospective analysis was undertaken of the renal transplantation results in diabetic nephropathy over the past 10 years. Out of 428 kidney transplants in 348 patients, 22 transplants were performed in 20 diabetic patients during the observation period. Patient survival for diabetics after 1, 2, and 3 years in contrast to non-diabetic controls was significantly different (70%, 50.9%, 50.9%, respectively versus 93.9%, 89.5%, 83.3% in the non-diabetic control group) (p less than 0.001). Transplant survival was 55%, 42%, 34.4%, versus 74.7%, 67.4%, 57.6% after 1, 2, and 3 years, respectively (p less than 0.08). During the posttransplant period the incidence of cardiovascular and infectious complications, as well as the rate of amputation was much higher than in the pretransplant phase. Main causes of death were cardiovascular or infectious complications. Improvement of the still poor results in diabetic transplant recipients is certainly a challenge for the future.

Adult↗

Reconsideration of the concept of enhanced static fusimotor drive in rigidity in patients with Parkinson's disease.

The electromyographic responses elicited in the first dorsal interosseus muscle by small muscle stretches or by electrical stimulation of the median nerve were investigated in parkinsonian patients and in age-matched healthy subjects. Stimuli were applied during a steady level of contraction in the intrinsic hand muscle. This ensured comparable levels of excitability in the alpha-motoneurone pool in patients and normals. It was found that the normal short-latency stretch reflex was almost absent in rigid patients, while responses to electrical stimulation of low-threshold nerve fibres were of equal size in both groups. This result suggests that there is a change in fusimotor control of muscle spindles in Parkinson's rigidity without alteration of the central gain of the Ia-transmitted stretch reflex.

Electric Stimulation↗

Delta-aminovaleric acid antagonizes the pharmacological actions of baclofen in the central nervous system.

The action of delta-aminovaleric acid (AVA) on the muscle relaxant properties of baclofen, a GABAB receptor agonist, was investigated in two experimental models: (1) the pathologically increased muscle tone of the gastrocnemius muscle in spastic mutant Han-Wistar rats and (2) the Hoffmann (H)-reflex recorded from plantar foot muscles after electrical stimulation of the tibial nerve in barbiturate (60 mg/kg) anaesthetized rats. In both paradigms coadministration of AVA (500 nmol/5 microliter) antagonized the muscle relaxant action of intrathecally applied baclofen (0.2-2 nmol), but failed to affect the muscle relaxant effects of intrathecally injected muscimol (2-20 nmol). In contrast, coadministration of bicuculline (1 nmol) did block the muscle relaxant action of muscimol, but failed to alter the effects of baclofen. When administered alone, bicuculline (1 nmol), or AVA (500 nmol-2 mumol) were without intrinsic action in both paradigms. In an additional series of experiments we investigated the action of AVA on a supraspinal effect of baclofen. Coadministration of AVA (12.5 nmol/0.5 microliter) in the ventromedial thalamic nucleus antagonized the catalepsy induced by baclofen (ED50 10 pmol/0.5 microliter), as indicated by an increase in ED50 of baclofen by a factor of 4.835 and a parallel shift of the probit-log dosage regression line to the right. The parallel shift seems to be consistent with a competitive mechanism of action of AVA. This study presents evidence that AVA antagonizes central pharmacological actions of baclofen at both spinal and supraspinal sites without affecting the actions of a GABAA agonist, muscimol.

Animals↗