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Biomedical subjects

P Meier

Publications and source records attributed to P Meier.

At least 19 recordsLinked to original sources
PubMed1992

Absence of sensorineural hearing loss in treated infants and children with congenital toxoplasmosis.

Educationally significant hearing loss has been reported in 10% to 15% of children with congenital toxoplasmosis. As part of a pilot study to assess feasibility and safety of prolonged therapy for congenital toxoplasmosis, 30 congenitally infected infants and children were evaluated for auditory function. Serial testing, beginning within 2 months of birth, was performed. Availability of auditory brainstem response (ABR) testing made evaluation at an earlier age than previously possible. Six (20%) of the 30 infants had mild to moderate conductive type hearing loss associated with otitis media. No infant or child had sensorineural hearing loss. The better outcome we observed compared to previous reports of a 15% to 26% incidence of sensorineural hearing loss and 10% to 15% incidence of educationally significant, bilateral hearing impairment may be related to early initiation and/or prolonged institution of antimicrobial therapy. Continued followup to exclude progressive hearing impairment and study of larger numbers of children are needed to verify these preliminary findings.

Audiometry, Evoked Response↗
PubMed1991

Inhibition by cyclosporine A of the prooxidant-induced but not of the sodium-induced calcium release from rat kidney mitochondria.

The use of the immunosuppressive drug cyclosporine A (CSA) is restricted by its nephrotoxicity. Perturbation of Ca2+ homeostasis has been implicated in chemical toxicity. Mitochondria, a key regulator of Ca2+ homeostasis, may be a target of the drug. Here we show that CSA inhibits at low concentrations the prooxidant-induced but not the sodium-induced Ca2+ release from rat kidney mitochondria. CSA does not affect Ca2+ uptake by mitochondria. Inhibition of Ca2+ release is due to inhibition of intramitochondrial enzymatic hydrolysis of NAD+ to ADP-ribose and nicotinamide. These findings suggest a very specific effect of CSA on mitochondrial Ca2+ release by which the drug interferes with cellular Ca2+ homeostasis. This is possibly the basis of CSA nephrotoxicity.

Adenosine Diphosphate Ribose↗
PubMed1991

Determination of thiopental in human serum and plasma by high-performance capillary electrophoresis-micellar electrokinetic chromatography.

The quantitation of thiopental in human serum and plasma was investigated using high-performance capillary electrophoresis (HPCE) in a micellar configuration and the results were compared with reversed-phase high-performance liquid chromatography (HPLC). Thiopental and an internal standard (carbamazepine for HPCE and thiamylal for HPLC) were extracted from serum or plasma using pentane and a phosphate buffer (pH 6.4). HPCE analysis took place in a phosphate-borate buffer with 50 mM sodium dodecyl sulphate using an automated instrument and HPLC was performed with a C8 column and a mobile phase of phosphate buffer-acetonitrile (65:35, v/v). HPCE and HPLC data from 66 patient samples compared well based on linear regression analysis. However, estimates obtained with the inclusion of the internal standard were lower than those based on the sample peak only. This example allows the elucidation of the advantages of using HPCE as an assay methodology for the therapeutic monitoring of thiopental and other drugs.

Chromatography↗
PubMed1991

Analysis of barbiturates in human serum and urine by high-performance capillary electrophoresis-micellar electrokinetic capillary chromatography with on-column multi-wavelength detection.

The analysis of barbiturates in human serum (or plasma) and urine by high-performance capillary electrophoresis-electrokinetic capillary chromatography with on-column fast-scanning multi-wavelength detection is discussed. The use of a buffer of ca. pH 8 and containing sodium dodecyl sulphate provides a medium suitable for fast and high-resolution separations of barbiturates. Seven barbiturates are characterized by their retention and absorption spectra between 195 and 320 nm. Comparison of these computer-stored data with those of unknown samples is shown to allow the identification of barbiturates in samples of patients undergoing pharmacotherapy and in toxicological urine and serum specimens. Three-dimensional electropherograms provide reliable information on the requirement and suitability of sample pretreatment procedures. With urine, extraction of barbiturates prior to analysis is necessary. With human serum several barbiturates, including phenobarbital, are shown to elute in an interference-free window in front of uric acid and the proteins, allowing these substances to be determined by direct sample injection. The need for multi-wavelength detection over a relatively wide wavelength range as a means of peak confirmation in electrokinetic capillary analyses is demonstrated and limitations of this technique for compounds with similar retention behaviour and absorption spectra are discussed.

Barbiturates↗
PubMed1990

Inhibition of pro-oxidant-induced mitochondrial pyridine nucleotide hydrolysis and calcium release by 4-hydroxynonenal.

Intra- and extra-mitochondrial Ca2+ participates in vital cellular processes. This work investigates the influence of 4-hydroxynonenal (HNE) on pro-oxidant-induced Ca2+ release from rat liver mitochondria. Ca2+ movements across the mitochondrial inner membrane, the pyridine nucleotide redox state and pyridine (nicotinamide) nucleotide hydrolysis were analysed. HNE did not influence Ca2+ uptake by mitochondria, but inhibited in a concentration-dependent manner Ca2+ release induced by t-butylhydroperoxide (tbh). Total inhibition was achieved with about 50 microM-HNE. Ca2+ release induced by the pro-oxidant alloxan was also inhibited by HNE. Oxidation of pyridine nucleotides, induced by tbh through the concerted action of glutathione peroxidase, glutathione reductase and the energy-linked transhydrogenase, was not affected by up to 50 microM-HNE. In contrast, HNE inhibited pyridine nucleotide hydrolysis in a concentration-dependent manner. The data suggest that HNE toxicity may be in part attributed to an impaired intramitochondrial Ca2+ homeostasis.

Adenosine Diphosphate Ribose↗
PubMed1990

[Chronic hepatitis B: diagnostic value of hepatitis-B-virus DNA analysis in serum and liver tissue].

The diagnostic value of hybridization analyses for the detection of hepatitis B virus (HBV) DNA in serum and liver tissue was investigated in 79 patients with chronic liver disease. Active viral replication was demonstrated by the detection of HBeAg or HBV-DNA in serum or liver tissue. However, HBV-DNA was also detected in the absence of HBeAg in serum. No correlation was found between the presence of HBV-DNA in serum or liver tissue and clinico-chemical or histological disease. In HBsAg-negative patients no HBV-DNA was detected in serum or liver tissue. These data indicate that serological markers are sufficient for the diagnosis of HBV infection. However, detection of HBV-DNA in serum or active viral replication in liver tissue is important in selecting patients for antiviral therapy (e.g. interferon) and monitoring its efficacy.

Adolescent↗
PubMed1990

[Bulk-forming agents as laxatives in geriatric patients].

Constipation in elderly long-care patients is an important problem. We compared the daily administration of three bulk-forming agents, semen psyllii (Effersyllium), wheat bran with karaya gum (Crusca di Fior) and bruised linseed, with the routine laxative therapy in our clinic based on lactulose (Duphalac) and a combination of paraffin oil and phenolphthalein (Agarol). To evaluate these two laxative regimens the following parameters were monitored: quantity and quality of the feces and of additional laxatives used for regular defecation; acceptance by the patient; costs per patient and day. The results of this study show that daily administration of a laxative is significantly more efficient than periodic administration, and that daily administration of a bulk-forming agent is, at the same level of effectiveness, less expensive (-35%) than therapy with lactulose alone.

Aged↗
PubMed1990

[Acute hepatitis following administration of fansidar].

Since 1971 pyrimethamine-sulfadoxine (Fansidar, Roche) has been used worldwide for prophylaxis and therapy of chloroquine resistant Plasmodium falciparum malaria. The drug monitoring team of the producing firm has received reports of a number of cutaneous adverse reactions, some severe, and a few even with fatal outcome. Liver reactions were also encountered, with severe cases only in the recent literature. We report on two patients with hepatitis in temporal relationship to pyrimethamine-sulfadoxine, the first with a second event after later exposure to the same drug. After discontinuing the medication the liver function abnormalities returned to normal limits within a few weeks. Liver biopsy and a positive lymphocyte transformation test against sulfadoxine, a component of Fansidar, strongly suggest that Fansidar was the cause of hepatic injury.

Adult↗
PubMed1990

Patterns of contact phase proteins indicating neuropathy in diabetic patients.

In 42 outpatients of the diabetology division, coagulation and fibrinolysis variables were determined in order to detect typical patterns of results with which it was possible to discriminate between three groups with different diabetic complications (17: no complication, 7: angiopathy alone, 18: neuropathy with or without other complications). There was a statistically significant discriminatory function involving C1-inhibitor concentration, high molecular weight kininogen coagulant activity and fibrinogen as the most decisive variables. The neuropathy group was appropriately separated from the others with an 81% correct reclassification. Heparin cofactor II, histidine-rich glycoprotein, alpha 2-macroglobulin, pre-kallikrein and factor XII had no discriminative power.

Adult↗
PubMed1989

[Giant adenoma of Brunner's glands].

Bleeding, obstruction and invagination are the common symptoms of large polyps in the duodenal bulb. We present 2 patients with a large ulcerated Brunner's gland adenoma. The clinical findings were acute bleeding and nonspecific upper gastrointestinal symptoms. The treatment was surgical due to a suspect histological finding in one case, a thick stalk in the other, and the fact that endoscopic polypectomy is a much higher risk procedure in the duodenum than in the colon.

Adenoma↗
PubMed1989

A controlled trial of extended radical versus radical mastectomy. Ten-year results.

In view of increasing debate over possible benefit of more complete surgery compared to conservative procedures, a randomized controlled trial contrasting the then standard Halsted radical (RDL) operation with the more complete extended radical (EXT) mastectomy was initiated in 1973. Between November 1973 and July 1982, 123 women younger than 70 years of age and at clinical Stages I and II were enrolled. Of the total series, 112 were treated by the same surgeon and confirmed pathologically as having invasive mammary carcinoma. In this more homogeneous subgroup, the 10-year survival rates (and standard errors) were for RDL, 60% (+/- 7%) and for EXT, 74% (+/- 6%) (P value for comparison of survival curves = 0.13). In patients from this subgroup with central-medial tumors, comprising 62% of the total, survival after RDL at 10 years was 60% (+/- 8%), and after EXT 86% (+/- 6%) (P = 0.025). In the remaining patients with lateral tumors, survival rates were unaffected by treatment: 58% (+/- 13%) and 56% (+/- 11%), respectively (P = 0.62). Comparison of a nonrandomized series of 266 RDL and 124 EXT patients treated between 1960 and 1978 found differences consistent with those of the randomized study, although not statistically significant.

Aged↗
PubMed1989

Choosing covariates in the analysis of clinical trials.

Much of the literature on clinical trials emphasizes the importance of adjusting the results for any covariates (baseline variables) for which randomization fails to produce nearly exact balance, but the literature is very nearly devoid of recipes for assessing the consequences of such adjustments. Several years ago, Paul Canner presented an approximate expression for the effect of a covariate adjustment, and he considered its use in the selection of covariates. With the aid of Canner's equation, using both formal analysis and simulation, the impact of covariate adjustment is further explored. Unless tight control over the analysis plans is established in advance, covariate adjustment can lead to seriously misleading inferences. Illustrations from the clinical trials literature are provided.

Computer Simulation↗
PubMed1989

Chain configuration and flexibility gradient in phospholipid membranes. Comparison between spin-label electron spin resonance and deuteron nuclear magnetic resonance, and identification of new conformations.

The electron spin resonance spectra of 1-myristoyl-2-[n-(4,4-dimethyloxazolidine-N-oxyl)myristoyl]-sn- glycero-3-phosphocholine spin-label positional isomers (n = 6, 10, and 13) have been studied in oriented, fully hydrated bilayers of dimyristoylphosphatidylcholine, as a function of temperature and magnetic field orientation. The spectra have been simulated using a line-shape model which incorporates chain rotational isomerism, as well as restricted anisotropic motion of the lipid molecules as a whole, and which is valid in all motional regimes of conventional spin-label electron spin resonance (ESR) spectroscopy. At least one component of the lipid motion is found to lie in the slow-motion regime for all label positions, even in the fluid liquid crystalline phase, well above the phase transition. In the gel phase, the chain isomerism lies in the slow-motional regime, and the overall motions are at the rigid-limit. In the fluid phase, the chain isomerism is in the fast-motional regime, and the chain axis motions are in the slow regime. This indicates that the commonly used motional-narrowing theory is not appropriate for the interpretation of spin-label spectra in biological membranes. The simulation parameters yield a consistent description for the chain order and dynamics for all label positions. The correlation times and order parameters for the overall motion are the same at all positions down the chain, whereas the chain conformation and trans-gauche isomerism rate display a characteristic flexibility gradient, with increasing motion towards the terminal methyl end of the chain. Significantly, it is found that all six distinct tetrahedral orientations of the hyperfine tensor at the labeled segment are required for a consistent description of the chain isomerism. For the C-6 segment only the 0 degree (trans) and two 60 degrees (gauche) orientations are significantly populated, for the C-10 position two further 60 degrees orientations are populated, and for the C-13 position all orientations have non-vanishing populations. Detailed comparisons have been made with the results of 2H nuclear magnetic resonance (NMR) measurements on dimyristoylphosphatidylcholine labeled at the same position in the sn-2 chain, and using an identical motional model. The parameters of overall reorientation, both order parameter and correlation times, have very similar values as determined by ESR and NMR. The major difference between the results from the two methods lies in the conformational populations at the labeled chain segment and the trans-gauche isomerization rate in the gel phase. The conformational order is much lower for the spin-labeled chain segments than for the corresponding deuterium-labeled segments, and the isomer interconversion rates in the gel phase(although displaying a mobility gradient in both cases) are found to be much slower in the former case. In addition the spin-label measurements provide information on the macro order (chain tilt), which is only available from oriented samples. These results are consistent between the different spin label positions and are in agreement with the findings from x-ray diffraction.

Dimyristoylphosphatidylcholine↗
PubMed1989

Constructive thinking: a broad coping variable with specific components.

The structure of constructive thinking and the development of an instrument for measuring it, the Constructive Thinking Inventory (CTI), were discussed. Scales were derived from a factor analysis of an item domain of people's everyday automatic thinking. When the CTI and other tests were factor analyzed, separate intellective and nonintellective factors were found, with the CTI loading more strongly on the nonintellective factor than any other test. Only measures of IQ loaded on the intellective factor. The global constructive thinking scale correlated significantly with success in work, love, social relationships, and in maintaining emotional and physical well-being, but not with academic achievement, the only criterion with which the measures of IQ correlated strongly. The patterns of correlations between the CTI scales and the various criteria as well as the factor analysis demonstrated that the construct of constructive thinking is differentiated as well as integrated.

Achievement↗