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Biomedical subjects

D Müller

Publications and source records attributed to D Müller.

At least 703 records · Page 39Linked to original sources
PubMedDate not supplied

Comparative study of the teratogenicity of phenobarbitone, diphenylhydantoin and carbamazepine in mice.

Three selected anticonvulsants, phenobarbitone (PHB), diphenylhydantoin (DPH) and carbamazepine (CAA) were examined for embryotoxic and teratogenic activity in albino mice. After oral treatment of the dams during the period of organogenesis (days 6-15 of gestation) with both PHB and DPH in doses causing marked symptoms and signs of toxicity (40 and 170 mg/kg/day respectively), an abnormally high incidence of cleft palate was observed in the foetuses (4.3% and 9.3% resp.). In a cumulative control group of foetuses, the incidence of this particular malformation was only 0.13%. No significant change in the malformation rate was seen after the administration of CAA in doses up to 250 mg/kg/day. Slight to moderate retardation of foetal growth was noted after treatment with DPH and CAA, but only at the higer and toxic dose levels. DPH also increased the incidence of early embryonic deaths (deciduomata).

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Superior temporal gyrus and P300 in schizophrenia: a combined ERP/structural magnetic resonance imaging investigation.

Decrement of the auditory P300 component of the event-related potentials (ERP) is a robust finding in schizophrenic patients and seems to be most pronounced in the left temporal region. Structural MRI studies support the hypothesis that regional structural brain differences in this patient group include reduced volume in temporal lobe structures. The aim of the presented study was to investigate the possible gray matter volume reductions in the left posterior superior temporal gyrus (STG) and the P300 reduction and left <right topographic asymmetry in schizophrenic patients. Therefore, in 50 male schizophrenic patients and 50 age- and educational level-matched male controls, auditory ERPs and structural MRI measurements of the gray matter volume of the STG were assessed. In the group of patients, the psychopathological symptom of thought disorder was correlated with the electrode site T3 and underlying gray matter of the left posterior superior temporal gyrus. The subgroup of patients with pronounced negative symptoms was analyzed with respect to ERP and structural MRI measurements. Our data revealed no evidence for a reduction of P300 amplitude or left STG gray matter volume in schizophrenic patients. However, the higher amount of thought disorders was related to a small T3 amplitude. No associations between the electrophysiological and structural measurements could be detected. There were also no significant reductions of ERP and MRI measurements within the subgroup of patients with pronounced negative symptoms.

Adult↗
PubMedDate not supplied

Assessment of intake from the diet.

Exposure assessment is one of the key parts of the risk assessment process. Only intake of toxicologically significant amounts can lead to adverse health effects even for a relatively toxic substance. In the case of chemicals in foods this is based on three major aspects: (i) how to determine quantitatively the presence of a chemical in individual foods and diets, including its fate during the processes within the food production chain; (ii) how to determine the consumption patterns of the individual foods containing the relevant chemicals; (iii) how to integrate both the likelihood of consumers eating large amounts of the given foods and of the relevant chemical being present in these foods at high levels. The techniques used for the evaluation of these three aspects have been critically reviewed in this paper to determine those areas where the current approaches provide a solid basis for assessments and those areas where improvements are needed or desirable. For those latter areas, options for improvements are being suggested, including, for example, the development of a pan-European food composition database, activities to understand better effects of processing on individual food chemicals, harmonisation of food consumption survey methods with the option of a regular pan-European survey, evaluation of probabilistic models and the development of models to assess exposure to food allergens. In all three areas, the limitations of the approaches currently used lead to uncertainties which can either cause an over- or underestimation of real intakes and thus risks. Given these imprecisions, risk assessors tend to build in additional uncertainty factors to avoid health-relevant underestimates. This is partly done by using screening methods designed to look for "worst case" situations. Such worse case assumptions lead to intake estimates that are higher than reality. These screening methods are used to screen all those chemicals with a safe intake distribution. For chemicals with a potential risk, more information is needed to allow more refined screening or even the most accurate estimation. More information and more refined methods however, require more resources. The ultimate aims are: (1) to obtain appropriate estimations for the presence and quantity of a given chemical in a food and in the diet in general; (2) to assess the consumption patterns for the foods containing these substances, including especially those parts of the population with high consumption and thus potentially high intakes; and (3) to develop and apply tools to predict reliably the likelihood of high end consumption with the presence of high levels of the relevant substances. It has thus been demonstrated that a tiered approach at all three steps can be helpful to optimise the use of the available resources: if relatively crude tools - designed to provide a "worst case" estimate - do not suggest a toxicologically significant exposure (or a relevant deficit of a particular nutrient) it may not be necessary to use more sophisticated tools. These will be needed if initially high intakes are indicated for at least parts of the population. Existing pragmatic approaches are a first crude step to model food chemical intake. It is recommended to extend, refine and validate this approach in the near future. This has to result in a cost-effective exposure assessment system to be used for existing and potential categories of chemicals. This system of knowledge (with information on sensitivities, accuracy, etc.) will guide future data collection.

Animals↗
PubMedDate not supplied

Induction of c-fos during myelomonocytic differentiation and macrophage proliferation.

Previous studies have suggested a role for c-fos in cellular differentiation in fetal membranes, haematopoietic cells and teratocarcinoma stem cells. In other cell types, such as fibroblasts, c-fos expression is normally very low, but is rapidly induced by peptide growth factors, implicating c-fos in growth control mechanisms. Here, we show that the TPA (12-O-tetradecanoylphorbol-13-acetate)-induced macrophage-like differentiation of HL60 human promyelocytic precursor cells is accompanied by the induction of both c-fos mRNA and protein within 15 min after treatment, suggesting a functional role for c-fos in this differentiation system. In quiescent terminally differentiated macrophages, expression of c-fos is inducible by the macrophage-specific growth factor colony-stimulating factor-1 (CSF-1). The kinetics of c-fos induction, however, are entirely different from those in growth factor-stimulated fibroblasts, supporting the view that the c-fos gene product may serve different functions in different cell types.

Cell Differentiation↗
PubMedDate not supplied

[Age- and weight-related dosage of dDAVP in the treatment of primary nocturnal enuresis].

BACKGROUND: In treating primary nocturnal enuresis the dosages recommended for an intranasal application of dDAVP are 20, 30 or 40 microgram depending on the response. Dosages that take the patient's weight or age into account are not commonly used until now. PATIENTS AND METHODS: In the present prospective study including 43 children therapeutic success was therefore evaluated on the basis of the dosage that was standardized according to both age and weight of the patients. The patients' weight ranged from 16.5 to 98 kg, their age from 6 to 14.9 years. RESULTS: The dDAVP dosages that were applied ranged from 0.3 and 2.4 microgram/kg and 3.74 and 15.3 microgram x age/kg respectively. Therapeutic efficacy was at 63 %. CONCLUSIONS: The results suggest an ideal weight-related dosage of 1 microgram x weight or rather an age- and weight-related dosage of 8 microgram x weight/age. A higher dosage evidently is of little use since there was a significant difference between the non-responders and the responders (p < 0.01) with the non-responders not even reacting to higher dosages.

Administration, Intranasal↗
PubMedDate not supplied

[Spontaneous elimination of helicobacter pylori infection in children].

BACKGROUND: With the (13)C-urea-breath test, 6.6 % of 3 372 preschool children of the Leipzig area tested H. pylori positive in 1998. PATIENTS: In 2000, 5.6 % of 3 854 grade-two pupils of the same area tested positive. METHOD: 2 235 children participated in both tests campaigns. Therefore, their H. pylori state could be reinvestigated after two years. RESULTS: 30 of the 104 children, who were tested positive in 1998 were negative in 2000. Using questionnaires completed by the corresponding parents and family physicians, possible reasons of individual elimination were analysed. It was found that 18 of the 25 children received a H. pylori triple therapy. Three children had been tested false-positive in 1998. Four children received antibiotics for other reasons and H. pylori was obviously eradicated too. Only three children were not treated with any antibiotics between 1998 and 2000. For these children, spontaneous elimination is assumed. CONCLUSIONS: Conclusions about spontaneous elimination of H. pylori infections are problematic. Further investigations are needed in consideration of this object.

Anti-Bacterial Agents↗
PubMedDate not supplied

Tremorlytic activity of budipine in Parkinson's disease.

To objectively quantify the tremorlytic activity of budipine in Parkinson's disease (PD), we performed long-term tremor recordings in addition to the Columbia University Rating Scale (CURS) in a subset of patients (n = 14) who enrolled in a multicenter, double-blind, placebo-controlled study. Tremor occurrence improved in the budipine group (n = 7) from 24.7 +/- 15.5% to 14.8 +/- 14.5% (p < 0.05). Tremor intensity decreased from 9.1 +/- 2.5 (signal-to-noise ratio) to 7.2 +/- 1.6. The CURS sum score improved from 5.7 to 3.0 in the budipine group, whereas there was only a small improvement in the placebo group (from 7.1 to 5.5). These data suggest that budipine is an effective tremorlytic agent in PD and that it may be used as an alternative to anticholinergics.

Aged↗
PubMedDate not supplied

Characteristics and regulation of Na/Pi cotransport in a SV-40-transformed rabbit proximal tubular cell line.

An SV-40-transformed cell line of rabbit S2 proximal tubular origin (RKPC-2 cells) was used to characterize Na/P(i) cotransport. P(i) saturation experiments showed simple Michaelis-Menten behaviour and an apparent Km of 106 microM; Hill analysis of Na+ concentration dependence results in an apparent Km for Na+ of about 130 mM and suggests a stoichiometry exceeding unity. Exposure of confluent monolayers to low P(i) medium induced an increase in Na/P(i) cotransport. Incubation with 10(-9) M parathyroid hormone produced a 'paradoxical' stimulation of Na/P(i) cotransport, mimicked by pharmacological activation of protein kinase A or protein kinase C. The above regulatory events, observed on Na/P(i) cotransport, were not observed for Na(+)-dependent amino acid transport (L-proline and/or L-glutamic acid).

Animals↗
PubMedDate not supplied

[Neonatal Bartter disease diagnosed with the detection of a mutation of the KCNJ1 gene which codifies the synthesis of the renal ROMK1 potassium channel].

We report clinical data of a female patient with Bartter's syndrome who was initially diagnosed with idiophatic hypercalciuria and, subsequently, with hyperprostaglandin E, syndrome. The patient was born after premature delivery with a history of polyhydramnios. During the first two years of life, in spite of evidence for significant failure to thrive, polyuria and special tendency to dehydration, she had no hypokalemia. The acid-base balance was normal except metabolic acidosis during the first few days after she was born. When hypercalciuria was observed, she was treated with thiazides and a low-salt diet. With such treatment she frequently showed hypokalemic alkalosis. Afterwards, once it was possible to determine the levels of renin and aldosterone and the urinary excretion of PGE2, we suspected the diagnosis. DNA sequencing analysis showed that the patient carried a homozygotic mutation in the KCNJ1 gene, coding for the potassium channel ROMK, which results in the premature termination of the protein. It is the first time that this mutation has been found in Spain. The detection of this mutation confirmed a disease that was initially of uncertain diagnosis.

Bartter Syndrome↗
PubMedDate not supplied

[Chondrocalcinosis and hypomagnesaemia in a patient with a new mutation in the gene of the thiazide-sensitive Na-Cl cotransporter].

We report the clinical history of an adult patient that debuted during adolescence with sharp episodes of arthritis several joints, with affectation of big articulations of superior and inferior members, in absence of renal symptoms. An X-ray showed calcification of the menisci in both knees, the symphysis of the pubis and of other joints. When the presence of hypomagnesaemia was demonstrated, we observed that he also had hypokalemia, hypocalciuria, increment of the urinary elimination of magnesium, slightly high levels of renin, dilution defect and a moderate reduction of the NaCl tubular distal reabsorption, all compatible with the diagnosis of Gitelman syndrome. We sequenced the exons and intron flanking regions of the SLC12A3 gene, encoding the thiazide-sensitive Na-Cl cotransporter, and showed that the patient is homozygous for a new mutation in intron 7. This mutation consisted of a G to A transition at position +1 of the donor splice site of intron 7.

Adolescent↗
PubMedDate not supplied

[Coverage rates of influenza vaccine in Italy during the 2002/3 and 2003/04 seasons: a cross-sectional study].

The objective of this survey was to assess the level of influenza vaccination coverage in the season 2002/ 2003 compared with the season 2003/2004 in Italy, to understand the drivers and barriers to vaccination and to determine the intention for vaccination for the following winter. We conducted a random-sampling, telephone-based household survey among non-institutionalised individuals representative of the population aged 14 years and above. The surveys for 2002/2003 and 2003/2004 used the same questionnaire and were subsequently pooled. Four target groups were determined for analysis: (1) persons aged 65 years and above; (2) people working in the medical field; (3) persons suffering from a chronic illness and (4) all other groups. The overall sample consisted of 4010 people. The influenza vaccination coverage rate in Italy increased from 19.6% in season 2002/2003 to 22.2% in season 2003/2004. The most frequent reasons mentioned by vaccinees to get vaccinated were advice received from the family doctor or nurse (48.9%), influenza being considered a serious illness which people did not want to contract (38.5%) and not wanting to pass the influenza bug to family and friends (29.2%). Reasons mentioned by never vaccinated people for not getting vaccinated were the fact that people did not consider it before (34.9%), the opinion that one was not very likely to catch influenza (32.2%) and influenza not being a serious illness (23.4%). Options encouraging an influenza vaccination are a recommendation by the family doctor or nurse (58.4%), more available information on the vaccine regarding efficacy and tolerance (34.4%) and more available information on the disease (24.3%). We therefore suggest that family doctors be better informed on influenza vaccine and the disease itself in order to enable them to actively inform their patients on these topics accordingly.

Adult↗