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Biomedical subjects

M Schulz

Publications and source records attributed to M Schulz.

At least 199 records · Page 11Linked to original sources
PubMed1988

[Gallopamil poisoning. Its course and therapy].

About two hours after swallowing 7 g of Gallopamil, a calcium antagonist, with suicidal intent a 32-year-old woman was admitted to hospital in a somnolent state. At that time the systolic blood pressure was about 40 mm Hg, in the presence of a 3 degrees A-V block. Orciprenaline, dopamine and dobutamine, as well as calcium, proved ineffective. Initially massive doses of adrenaline and noradrenaline, and their continued administration over the subsequent 26 hours, succeeded in normalizing the blood pressure and after transitory pacing, terminated, the arrhythmia in the course of 24 hours. About four hours after its intake the plasma gallopamil concentration was 8.4 micrograms/ml, about 100 times the therapeutic range.

Adult↗
PubMed1988

Intrathecal production of HIV antibodies in suspected AIDS encephalopathy.

Thirty-one serum and CSF samples from 21 HIV-antibody-positive patients with neurological deficits were examined to prove or exclude intrathecal production of HIV antibodies. By dilution, sera were adjusted to the IgG concentration of the corresponding CSF samples. Both samples were then serially diluted in log2 steps down to the detection limit and were tested in an anti-HIV ELISA. From the dilution obtained at the cut-off level, a quotient QHIV was derived as an indicator of intrathecal production of HIV antibodies. Six of a total of eight samples with a QHIV value of greater than or equal to 2 were correlated which the clinical diagnosis of AIDS-related dementia complex (ARDC). However, a QHIV less than 1 did not exclude the development of ARDC, as was shown during follow-up in one case. Different methods are compared for the determination of intrathecal production of IgG and anti-HIV. A quotient QHIV greater than or equal to 2 is suggested to be highly indicative of intrathecal production of anti-HIV as well as of the development of ARDC.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Chronic borrelia encephalomyeloradiculitis with severe mental disturbance: immunosuppressive versus antibiotic therapy.

A 57-year-old male was repeatedly admitted to hospital because of complex neurological symptoms, including radicular pain, disturbance of micturition, seizures, and severely impaired mental state. The diagnosis was encephalomyeloradiculitis possibly of viral origin, and treatment with immunosuppressants was initiated. An alternating course with a tendency towards improvement ensued. Two and a half years after the occurrence of the initial symptoms, identification of specific antibodies in the blood and CSF led to the diagnosis of borreliosis with CNS involvement. High-dose therapy with penicillin rapidly reduced the symptoms, beginning with those of radicular pain and followed by an improvement of the mental state. Attention is directed to the wide spectrum of clinical symptoms of chronic borreliosis with CNS involvement. Previous reports that immunosuppression may result in some improvement but with a tendency towards relapse are confirmed. Our encouraging treatment results support those of other reports that penicillin therapy may lead to improvement even at late chronic stages in patients with severe CNS deficits.

Chronic Disease↗
PubMed1988

The pharmacokinetics of flutamide and its major metabolites after a single oral dose and during chronic treatment.

Flutamide is a nonsteroidal antiandrogen used in the treatment of prostatic carcinoma. We have investigated the disposition of flutamide and its two major metabolites in ten urological in-patients without significant liver or renal disease. After oral administration flutamide is absorbed from the gastrointestinal tract with a tmax of about 2 h. Flutamide undergoes extensive first-pass metabolism, and its major metabolites are 2-hydroxyflutamide and the hydrolysis product 3-trifluoromethyl-4-nitroaniline. After the oral administration of a single dose of 250 mg or 500 mg maximum flutamide plasma concentrations of 0.02 and 0.1 micrograms.ml-1 respectively were observed. Maximum plasma concentrations of 2-hydroxyflutamide for the same flutamide doses were 1.3 and 2.4 micrograms.ml-1 (mean of n = 2 or n = 3). Steady-state concentrations of the biologically active metabolite 2-hydroxyflutamide (0.94 +/- 0.23 micrograms.ml-1, mean +/- SD, n = 5) were found at 2-4 days after the administration of 250 mg every 8 h. The area under the plasma concentration time curve for 2-hydroxyflutamide averaged 11.4 (10.6 and 12.1) and 24.3 (21.5-29.4, n = 3) micrograms.ml-1.h for 250 mg and 500 mg flutamide orally. 2-Hydroxyflutamide and 3-trifluoromethyl-4-nitroaniline were eliminated monoexponentially with half-times of 4.3-21.9 and 4.3-17.2 h (n = 5) respectively.

Administration, Oral↗
PubMed1988

Compliance in microcomputer-assisted conventional insulin therapy: computer simulation study results.

Compliance in diabetes self-management is a complex issue. It involves the interdependent daily actions of self-measurement of blood glucose and adherence to a prescribed schedule of daily activities. This impacts strongly on lifestyle because it necessitates precise meal timing as well as control of size and carbohydrate content. We sought to identify how strongly relaxing the lifestyle constraints per se would impact the ability to achieve improved metabolic control. To isolate these effects from those that result from poor measurement compliance, we used a computer simulator called OMNI et al. Furthermore, to standardize the "clinical" therapy, a second microprocessor device called an "Insulin Dosage Computer" was used to adjust insulin doses based on the usual clinical practice of four times a day precibal blood glucose measurements. Ten type 1 diabetic patients were stimulated and each followed for 120 simulated days. In each such subject, the simulation was repeated three times to include three different levels of lifestyle compliance ranging from excellent to poor. In all three protocols, starting from a level of poor control of diabetes, mean blood glucose values were significantly improved without significant differences after 120 days of computer-simulated treatment. Only the standard deviations, expressing the fluctuations of blood glucose and hence its stability, increased with decreasing lifestyle compliance. This computer simulation predicts that consistent self-monitoring of four blood glucose values per day is the cornerstone of diabetic self-control and that the use of these data according to a standardized therapeutic algorithm for insulin adjustment may successfully stabilize even patients with poor lifestyle compliance. Clinical studies must follow.

Blood Glucose↗
PubMed1988

Expression of T cell receptor gamma-chain in murine cytotoxic T cells: analysis of a highly transcribed nonrearranged gene cluster.

The murine T cell receptor gamma-gene family is organized in 4 gene clusters which encode variable, joining and constant gene segments. Because the function of the gamma-gene products is still unclear, there is great interest in functional rearrangements of these genes. We searched for new variable gamma-gene segments in the gamma 4-gene cluster. The mapping and sequencing of a supposed new variable segment of a functionally spliced transcript from a cDNA library of the cytotoxic T cell clone 3F9 was attempted. The results show that the supposed variable segment is a transcribed noncoding germline sequence 5' adjacent to the gamma 4-joining segment. With the gamma 4-constant sequence as a probe, strong signals could be shown in Northern analysis of the original T cell clone 3F9 and in other virus-specific T cell clones. Since all the T cell clones investigated did not show any rearrangement in the gamma 4-gene cluster, the observed high transcriptional activity in this region could be involved functionally or as an intermediate in T cell receptor rearrangement.

Animals↗
PubMed1988

Effects of unfractionated and fractionated heparin on platelet function.

Heparin-induced alterations of platelet function have repeatedly been reported over the last 30 years. The development of low-molecular-weight (LMW) heparin fractions prompted us to compare the effect of unfractionated (UF) heparin and LMW heparin on platelet function. Heparin was applied intravenously to healthy volunteers in a dose of 100 U (antifactor Xa)/kg body weight. Sequential evaluation of platelet function ex vivo confirmed that UF heparin may activate platelets in vivo. Studying the ADP-induced fibrinogen binding to platelets in vivo, we were able to show that the effect of heparin on platelets is antibody- and antithrombin-III-independent. LMW heparin fractions in general exhibit a reduced platelet activating activity although there are differences between the LMW heparin fractions available. The stimulating effect of LMW heparin on platelets disappears below a mean molecular weight of 3,000 daltons.

Blood Platelets↗
PubMed1988

On the sulphoxidation of cimetidine and etintidine by rat and human liver microsomes.

1. Sulphoxidation of cimetidine and etintidine was investigated by in vitro assays with liver microsomes from untreated 5,6-benzoflavone- and phenobarbital-pretreated rats as well as with human liver microsomes. The formation rate of cimetidine sulphoxide and etintidine sulphoxide with liver microsomes of normal or pretreated rats reached to 1.1 and 0.9 nmol/min mg microsomal protein, respectively. 2. Inhibition experiments with carbon monoxide and n-octylamine indicated that this sulphoxidation is catalyzed by cytochrome(s) P-450, whereas flavin-containing monooxygenase and/or non-enzymatic reactions (via peroxides) seems not to be involved: no inhibition was observed by methimazole, N,N-dimethylaniline, preheating or glutathione and EDTA. 3. With human liver microsomes the cytochrome P-450-dependent sulphoxidation accounted for no more than 40% of the total oxidation.

Animals↗
PubMed1988

[Determinations of blood theophylline level in a severe asthma attack in childhood treated with respirator therapy].

The authors describe the course of a severe asthma emergency in a boy aged 13 years. Respirator therapy and bronchial lavage were required. A therapeutically effective serum concentration was initially obtained by an aminophyllin infusion (dose 1.2 mg/kg b.w./h after bolus injection with 6 mg/kg b.w.). In the further course of treatment the theophyllin concentration in serum decreased considerably. The advantage of theophyllin determination for guaranteeing a safe therapy is explained on the base of this case report.

Adolescent↗
PubMed1987

Interactions of the histamine H2-receptor antagonist etintidine with rat liver cytochrome P-450: a comparison with cimetidine.

The two imidazole histamine H2-receptor antagonists etintidine and cimetidine interact with the rat liver microsomal cytochrome P-450. From type II spectral changes follows that the affinity of rat liver microsomal preparations for etintidine is about 5 times as high as for cimetidine when comparing both high and low affinity binding sites. After pretreatment with phenobarbital etintidine inhibited benzphetamine N-demethylation competitively (app. Ki: 4.0 mmol/l). Cimetidine inhibited benzphetamine N-demethylation in the same range. After pretreatment with phenobarbital both drugs inhibited the oxidation of benzo(a)pyrene for which etintidine showed a higher inhibitory potency than cimetidine. However, this oxidation could not be inhibited when microsomes of 5,6-benzoflavone pretreated rats were used. After pretreatment with 5,6-benzoflavone only etintidine but not cimetidine inhibited the O-deethylation of ethoxyresorufin competitively (app. Ki: 0.2 mmol/l). Etintidine and cimetidine were metabolized by rat liver microsomes to their corresponding sulphoxides. In conclusion, etintidine may cause mainly the same drug interactions as cimetidine but seems to be a more potent inhibitor.

Animals↗
PubMed1987

Selective in situ pancreatic perfusion via chronic in vivo celiac artery catheterization.

A new technique to catheterize the celiac artery has been developed. This has opened the possibility for direct in vivo, in situ study of pancreatic endocrine cell function in a conscious experimental animal. The catheter is small, soft and placed without arterial ligation so that celiac artery, hepatic, splenic, and pancreatic blood flows were essentially not compromised. Arterial vessel integrity, absence of inflammation, and thrombosis as well as catheter patency were achieved for periods exceeding eight months. Metabolically and hormonally, the presence of the catheter had no effect on the fasting status. However, we found somewhat lower glucose levels and higher insulin levels in the response to oral glucose challenges after catheterization, but these differences were statistically not significant. Glucose loads of 50 mg/kg (0.75 g) administered directly to the pancreas via the celiac artery produced peak insulin levels similar to peripheral glucose loads some tenfold larger. We suggest that this technique may be useful to selectively study the first-pass pancreatic response to a variety of hormones, drugs or metabolic substrates.

Administration, Oral↗
PubMed1987

Physiological relationships between growth hormone level, glycemia and metabolic control in dogs.

This study was undertaken to explore the physiological relationships between fasting glycemia, antecedent glycemic control and fasting growth hormone levels in pancreatectomized dogs. In contrast to other studies, we used continuous intravenous infusions of insulin in an attempt not only to normalize fasting plasma glycemia but also to eliminate the characteristic fluctuations of diabetes usually encountered in the postprandial and postabsorptive periods. For comparison, a similar group of healthy animals served as normal controls. In the healthy dogs, fasting growth hormone (GH) levels were stable and well within normal limits for this species, demonstrating an overall mean +/- SD of 2.50 +/- 0.46 ng/ml. In the pancreatectomized group as a whole, the fasting GH levels were significantly elevated (4.63 +/- 2.42 ng/ml, P less than 0.01) and significantly (P less than 0.001) more variable than in the controls. Multiple regression and analysis of variance confirmed the expected significant positive correlation between fasting GH and fasting plasma glucose levels, but also elucidated a heretofore unknown direct relationship between fasting GH levels and the preceding instability of glycemic control.

Animals↗
PubMed1987

Peptide uptake by astroglia-rich brain cultures.

Uptake of carnosine has been investigated in astroglia-rich primary cultures derived from brains of newborn mice. It could be demonstrated that carnosine is not degraded by these cells but rapidly taken up in an energy- and sodium-dependent process. Uptake and release of carnosine by these cells were found to be mediated by a saturable, high-affinity transport system with apparent kinetic constants of Km = 50 microM and Vmax = 22.7 nmol X h-1 X mg protein-1. Uptake of carnosine is strongly inhibited by other dipeptides as well as by various oligopeptides, e.g., Leu-enkephalin. However, uptake of the radiolabeled tripeptide D-Ala-L-Ala-L-Ala was not observed. Radiolabeled Leu-enkephalin also did not accumulate intracellularly, even if degradation of the peptide was prevented by use of peptidase inhibitors. These results suggest that uptake of carnosine is catalyzed by a dipeptide-specific transport system with broad substrate specificity. With neuronal cells in primary culture, uptake of carnosine or other peptides was not observed.

Amino Acids↗
PubMed1987

Transcriptional activities of mammalian genomes at sites of recombination with foreign DNA.

The nucleotide sequences of several sites of recombination between adenovirus DNA and hamster, mouse, or human cell DNAs were determined. These sites of recombination had been cloned from adenovirus type 2 (Ad2)- or type 12 (Ad12)-transformed cells, from Ad12-induced tumor cells, or from a symmetric recombinant between Ad12 DNA and human cell DNA. One important precondition for the generation of recombinants between host and foreign DNAs might be the establishment of a chromatin configuration that permits access of foreign DNA and of the recombination machinery to cellular DNA. Such favorable chromatin structures might arise during cellular DNA replication or transcription or both. As a first approach toward investigating these more complex problems of foreign DNA insertion, we determined transcriptional activities of cellular DNA sequences at viral junction sites. The sites of linkage investigated in this study with respect to their transcriptional activities were those previously cloned and sequenced (W. Doerfler, R. Gahlmann, S. Stabel, R. Deuring, U. Lichtenberg, M. Schulz, D. Eick, and R. Leisten, Curr. Top. Microbiol. Immunol. 109:193-228, 1983). In addition, a site from cell line HA12/7 which is described in this paper was also analyzed. The results presented demonstrate that the cellular DNA sequences involved in linkage to viral DNA at five completely different sites in DNA from three different species are transcribed into RNAs even in cells which have not been transformed or infected by adenovirus. Some of these RNAs were cytoplasmic and were not poly(A)+. Human cell DNA sequences at the junction to Ad12 DNA in SYREC2 DNA were transcribed into poly(A)+ cytoplasmic RNA which could be translated in vitro. These results are consistent with the notion that at least some of the cellular DNA sequences at sites of insertion of adenovirus (foreign) DNA are transcriptionally active and thus provide an opportunity for recombination.

Adenoviruses, Human↗
PubMed1987

Monoethylglycinexylidide formation kinetics: a novel approach to assessment of liver function.

A novel quantitative liver function test is described which is based on monoethylglycinexylidide (MEGX) formation after lidocaine bolus injection. Following the administration of small single doses of lidocaine hydrochloride (1 mg/kg), monoethylglycinexylidide serum concentration-time curves were determined by a novel highly sensitive fluorescence polarisation immunoassay (FPIA) in healthy volunteers, liver donors and patients with liver cirrhosis. The FPIA allowed rapid and reliable monoethylglycinexylidide determinations in serum and urine (between-days coefficient of variation: less than 10.3%, recovery: 80-113%). Monoethylglycinexylidide concentrations measured by FPIA in 32 serum samples from patients correlated well those determined by HPLC. The monoethylglycinexylidide concentration in serum determined 15 min after a lidocaine bolus injection proved to be a highly sensitive and specific indicator of hepatic dysfunction. Average monoethylglycinexylidide concentrations in serum obtained 15 min after lidocaine injection were substantially lower in patients with liver cirrhosis than in healthy volunteers. The average monoethylglycinexylidide concentrations in serum were also substantially lower in liver donors with ballooning or fatty changes of hepatocytes than in donors without relevant alterations of liver histology. By means of monoethylglycinexylidide formation in the liver donors, primary function of the transplanted liver was correctly predicted in 32/37 cases and initial non-function in 4/6 cases.

Chromatography, High Pressure Liquid↗
PubMed1987

[Chemical synthesis of phenylbutazone hydroperoxide and testing of the substance for heart action under in vitro and in vivo conditions].

Phenylbutazone (4-n-butyl-1,2-diphenyl-pyrazolidine-3,5-dione) 1 is an easily autoxidable substance which forms a crystalline and stable hydroperoxide 3. The decomposition of 3 yields products which were investigated as metabolites of the drug. In isolated heart preparations of guinea pigs and rabbit hearts in vivo the hydroperoxide 3 shows a significantly stronger cardiodepressive and coronary constricting effect compared to phenylbutazone 1, 4-hydroxy-phenylbutazone 4 and the open-ring decomposition product of the hydroperoxide 5. The results indicate the significance of the hydroperoxide 3 for the total efficiency of phenylbutazone and explain the side effects of the substance.

Animals↗