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Biomedical subjects

M Kuhn

Publications and source records attributed to M Kuhn.

At least 73 records · Page 4Linked to original sources
PubMed1999

Provocative use tests in CAPB-allergic subjects with CAPB-containing product.

Cocamidopropyl betaine (CAPB) has been identified as a cause of contact allergy in personal care products. Furthermore, it has been suggested that chemicals responsible are impurities, especially dimethylaminopropylamine (DMAPA). However, skin contact concentrations with these impurities, especially DMAPA, are very low. The aim of the study was to analyse whether subjects with previous positive patch tests to CAPB would react in provocative use tests of a product containing CAPB. 10 individuals with a clinical history of contact allergy to CAPB (by positive patch test and history) took part in a ROAT which used a CAPB-based shower gel at 25% (DMAPA concentration < 1 ppm). None of the subjects showed positive allergic reactions. 1 of the test subjects did experience a flare of atopic dermatitis at the treatment site. Later, all 10 subjects were patch tested to 3 different concentrations of CAPB and DMAPA (0.1%, 0.3%, 1%) to verify the threshold that was capable of inducing a positive test reaction. 5/10 showed clear + reactions to 1% CAPB (typically at D3), whilst a further 3 gave marginal and/or irritant reactions. Only 1 of the subjects showed an allergic reaction to DMAPA. Finally, in uncontrolled use testing with the shower gel, none of the test subjects reported any adverse skin reactions. Thus, the study confirmed that CAPB-sensitive individuals can use a CAPB-based rinse-off product without the risk of experiencing an allergic reaction to CAPB.

Adult↗
PubMed1999

Regulated, side-directed secretion of proguanylin from isolated rat colonic mucosa.

Guanylin, an activator of the guanylyl cyclase C receptor in the apical membrane of intestinal epithelium, modulates intestinal fluid and electrolyte transport. The bioactive 15-amino acid peptide originally isolated from rat intestine represents the C-terminal part of a longer, 115-residue prepropeptide. The aim of the present study was to characterize the direction and molecular form in which guanylin is secreted from the colonic mucosa, as well as the mechanisms that trigger its secretion. Isolated rat colonic mucosa was mounted in Ussing chambers, allowing the separate determination of apical and basolateral release. After HPLC purification, two different molecular forms of guanylin were identified in the apical incubation media by combining a bioassay for guanylyl cyclase C activation, a specific guanylin enzyme-linked immunosorbent assay and mass spectrometry, as well as sequence analysis: a bioactive form coeluting with synthetic 15-residue guanylin and the 94-residue propeptide, guanylin-22-115. The basal concentration of proguanylin at the apical side of epithelia was about 15-fold higher, compared with that of the small, bioactive peptide. In the basolateral incubation media, no proguanylin and only very low amounts of bioactive guanylin were detected. Incubation with carbachol led to a significant increase of about 7-fold in the release of proguanylin to both sides of the isolated epithelia. On the apical side, a concomitant increase of the small, bioactive peptide was observed; whereas, on the basolateral side, its concentration remained unchanged. Vasoactive intestinal peptide or the NO-donor S-nitroso-N-acetylpenicillamine did not affect guanylin secretion. Our results suggest that, in the intestine, guanylin is secreted mainly to the luminal side of the epithelium. The peptide is released as a 94-residue propeptide, which is then processed to a smaller, bioactive form (luminocrine secretion). Carbachol stimulates the release of proguanylin to both sides of the intestinal mucosa, but a parallel increase in the bioactive C-terminal derivative only occurs on the apical side. In vivo, the basolateral release could be a source of circulating proguanylin, which might be processed proteolytically to the active peptide in distant target tissues (endocrine secretion).

Amino Acid Sequence↗
PubMed1999

Imaging in the 21st century.

The drive for cost reduction and increased quality of therapy (patient outcome) will lead to increasingly less-invasive procedures. As a result, imaging will become essential in the operating theatre environment, simply because the site of the intervention is not visible to the clinician performing it.

Cost Control↗
PubMed1998

[Drug-induced discoloration of the teeth and gingiva].

For this article all cases of suspected drug-induced discolouration of teeth and gingiva reported between 1.1.1989 and 31.5.1997 have been collected. As far as documented all discolourations were reversible and represented exclusively undesired but not serious adverse drug effects. In the literature such events are usually not mentioned. Thus, sense and intention of this work is to draw attention to certain adverse effects that are hitherto not well known.

Adolescent↗
PubMed1998

The microtubule depolymerizing drugs nocodazole and colchicine inhibit the uptake of Listeria monocytogenes by P388D1 macrophages.

Uptake of Listeria monocytogenes by different mammalian cells like macrophages and epithelial cells is dependent on functional actin filaments and hence susceptible to inhibition by cytochalasin. Here we show that phagocytic uptake of L. monocytogenes by P388D1 macrophages is also highly sensitive to treatment with the microtubule depolymerizing drugs nocodazole and colchicine. This sensitivity is cell type specific and much less pronounced in bone marrow-derived macrophages and Caco-2 epithelial cells. In contrast to nocodazole and colchicine, the microtubule stabilizing drug taxol has no significant effect on the uptake of L. monocytogenes by all three cell types tested.

Actins↗
PubMed1998

[Differences in the relative incidence of adverse drug reactions in relation to age? An evaluation of the spontaneous reporting system of SANZ (Swiss Drug Monitoring Center)].

The risk of presenting adverse drug reactions (ADR) is greater for elderly patients. Chronological age is not an independent risk factor for ADRs, but age-dependent factors such as polymedication, multiple diseases and changes in pharmacokinetics and pharmacodynamics seem to be responsible for the risk of developing more adverse drug reactions. We analyzed the ADRs spontaneously reported to the Swiss Drug Monitoring Centre (SANZ) between 1981 and 1995. Age-specific relative incidences of the reported ADRs affecting different organ systems were calculated. For elderly patients we found a decrease in the relative incidence of dermatological ADRs and an increase in neuropsychic and hematological ADRs. The incidence of serious ADRs increased by 8.7% in older patients (> 70 years). The results of this analysis of spontaneous reports were inconsistent with results from epidemiological studies. The possibility and reasons for under-reporting ADRs occurring in elderly patients are discussed.

Adolescent↗
PubMed1998

Guanylin stimulates regulated secretion from human neuroendocrine pancreatic cells.

BACKGROUND & AIMS: Gastroenteropancreatic neuroendocrine cells secrete chemical messengers in a calcium-dependent fashion. So far, other second messenger systems involved in regulated secretion have gained little attention. The aim of this study was to characterize guanosine 3',5'-cyclic monophosphate (cGMP)-mediated vesicular secretion in pancreatic neuroendocrine cells. METHODS: In a human pancreatic cell line, BON, cyclic nucleotide levels and chromogranin A release were monitored with specific immunoassays. Uptake and release of gamma-aminobutyric acid were measured. Intracellular Ca2+ concentration was monitored with fura-2. Guanylyl cyclase C was analyzed by reverse-transcription polymerase chain reaction. RESULTS: Guanylin increased cGMP concentrations in BON cells via guanylyl cyclase C. Stimulation of the cGMP pathway by guanylin or Escherichia coli heat-stable enterotoxin increased the release of chromogranin A and gamma-aminobutyric acid from BON cells. This effect was mimicked by the cGMP analogue 8-bromo-cGMP. CONCLUSIONS: Guanylin and STa stimulate the regulated secretion from BON cells via guanylyl cyclase C and cGMP. Our study yields novel information about secretory properties of guanylin, mediated via a signal transduction pathway, increasing cGMP and leading to regulated secretion of neuroendocrine cells.

Bacterial Toxins↗
PubMed1998

Tobacco smoke-induced alterations of cytokeratin expression in the rat nasal activity cavity following chronic inhalation of room-aged sidestream smoke.

In a 12-month inhalation study on rats using room-aged sidestream smoke (RASS, 12 microg total particulate matter (TPM)/l) as an experimental surrogate for environmental tobacco smoke (ETS), we investigated differentiation changes, i.e. altered cytokeratin (CK) expression, in the epithelial lining at nasal cavity level 1 (NL1) (anterior portion of nasal cavity), and their correlation with histomorphological changes. In addition to conventional histopathological examination, routine paraffin sections were immunohistologically stained for various rat CK and evaluated. Changes in CK expression were observed in the nonciliated respiratory epithelium of maxilloturbinate, lateral wall, and nasoturbinate: in basal cells, increase of CK14 and CK18 and decrease of CK15; in nonciliated columnar cells, increase of CK15 and CK19. These CK changes had histomorphological correlates, i.e. reserve cell hyperplasia and squamous metaplasia. CK expression changes were also seen at sites without histomorphological changes, e.g. enhanced expression of CK14, CK18 in ciliated cells at the dorsal meatus, and CK15 at the septum. Most of the CK expression changes seen after 1 year of RASS exposure resembled the changes previously seen after 8 days of exposure.

Administration, Inhalation↗
PubMed1998

Host cell signalling during Listeria monocytogenes infection.

Macrophages and other mammalian cells respond to infection with Listeria monocytogenes by the transient or persistent activation of host cell signal transduction pathways. In addition, L. monocytogenes infection influences expression of various host cell genes, some of which may hinder or favour bacterial replication. The observed host cell responses vary with the different subcellular locations inhabited by L. monocytogenes during its intracellular life cycle.

Animals↗
PubMed1998

Lethal pulmonary hypertension in a young woman caused by unrecognized haemangiosis carcinomatosa.

A 38-year-old female is described, who was admitted with increasing respiratory distress, cough and visible blood stasis in the jugular veins. The most likely diagnosis in this young women taking oral contraceptives was pulmonary embolism, however, a ventilation-perfusion lung scan was normal. Echocardiography showed a dilated right ventricle and increased systolic pulmonary pressure. Despite administration of oxygen and intravenous heparin the patient died in circulatory collapse before further investigations could be initiated. Post-mortem examination revealed diffuse adenocarcinoma of the stomach (linitis plastica) with metastasis to local lymphnodes, lymphangiosis carcinomatosa of the liver, pancreas and spleen and tumour cell masses within the lumen of small pulmonary arteries leading to variable occlusions of the vessels. Fibrocellular intimal proliferation was found, leading to further obstruction and increased resistance to flow through the pulmonary vascular bed and to subacute cor pulmonale.

Adenocarcinoma↗
PubMed1998

Patch tests versus use tests in skin irritation risk assessment.

In the risk assessment of the ability of a substance or preparation to cause skin irritation, a patch test involving human volunteers is often seen as providing definitive information. However, the skin exposure conditions found in an occluded patch may be far removed from those in a particular use situation, not least for such reasons as the high dose per unit area, the duration of exposure and the maceration of the skin. Whilst these factors may enhance sensitivity in the identification of intrinsic hazard, they may do little to ensure accurate safety evaluation for real use. In this paper, we report data from a series of studies with an unmarketed facial skin cosmetic product. Whilst the product was unexpectedly highly irritating in a standard patch test in 30 volunteers, subsequent use tests, including a 6x daily open application to the elbow for 3 weeks and 2x daily application in a half-face test lasting 3 to 4 weeks and involving 52 volunteers failed to show any evidence of skin irritation. It is concluded that the most meaningful results for skin irritation risk assessment are likely to come from studies which involve relevant patterns of exposure.

Adult↗
PubMed1998

Interaction of Listeria monocytogenes with human brain microvascular endothelial cells: InlB-dependent invasion, long-term intracellular growth, and spread from macrophages to endothelial cells.

Invasion of endothelial tissues may be crucial in a Listeria monocytogenes infection leading to meningitis and/or encephalitis. Internalization of L. monocytogenes into endothelial cells has been previously demonstrated by using human umbilical vein endothelial cells as a model system. However, during the crossing of the blood-brain barrier, L. monocytogenes most likely encounters brain microvascular endothelial cells which are strikingly different from macrovascular or umbilical vein endothelial cells. In the present study human brain microvascular endothelial cells (HBMEC) were used to study the interaction of L. monocytogenes with endothelial cells, which closely resemble native microvascular endothelial cells of the brain. We show that L. monocytogenes invades HBMEC in an InlB-dependent and wortmannin-insensitive manner. Once within the HBMEC, L. monocytogenes replicates efficiently over a period of at least 18 h, moves intracellularly by inducing actin tail formation, and spreads from cell to cell. Using a green fluorescent protein-expressing L. monocytogenes strain, we present direct evidence that HBMEC are highly resistant to damage by intracellularly growing L. monocytogenes. Infection of HBMEC with L. monocytogenes results in foci of heavily infected, but largely undamaged endothelial cells. Heterologous plaque assays with L. monocytogenes-infected P388D1 macrophages as vectors demonstrate efficient spreading of L. monocytogenes into HBMEC, fibroblasts, hepatocytes, and epithelial cells, and this phenomenon is independent of the inlC gene product.

Adult↗
PubMed1998

High prevalence of bronchial hyperresponsiveness and asthma in ice hockey players.

The prevalence of asthma was studied in a ice hockey team compared with both a floor ball team and the Swiss population. Lung function, bronchial hyperresponsiveness to methacholine, asthma symptoms and exercise-induced asthma were measured in a cross-sectional prospective study. A positive response to the methacholine bronchial provocation test was found in 34.6% of the ice hockey players and 20.8% of the floor ball players (Swiss population 16.4%). The provocative dose causing a 20% fall in the forced expiratory volume in one second (PD20) was significantly lower in ice hockey players than in floor ball players, but there was no significant difference in the dose-response slopes between the two groups. Asthma was diagnosed in 19.2% of the ice hockey players and in 4.2% of the floor ball players (Swiss population 6.8%), whereas exercise-induced asthma was found in 11.5% of the ice hockey players and in 4.2% of the floor ball players. In conclusion, asthma and bronchial hyperresponsiveness seemed to be more common in ice hockey players than in floor ball players and in the Swiss population. Strenuous exercise at lower temperatures may be a risk factor for the higher prevalence of asthma and bronchial hyperresponsiveness, as well as the increased severity of bronchial hyperresponsiveness, particularly in ice hockey players.

Adolescent↗
PubMed1998

A randomized comparison of exercise training in patients with normal vs reduced ventricular function.

BACKGROUND: Exercise training is recommended after myocardial infarction (MI) or bypass surgery in order to improve exercise tolerance. In some patients, the decrement in exercise capacity secondary to deconditioning and the left ventricular stunning associated with MI or coronary artery bypass graft (CABG) spontaneously improves after the event. However, the impact of the status of the left ventricle on these improvements is unknown. METHODS: Sixty-seven patients 1 month after MI or CABG were randomized to a training (n=34; age, 59+/-7 years) or a control group (n=33; age, 55+/-6 years). Forty-two patients had an ejection fraction >50% (22 in the training group and 20 in the control group), and 25 patients had an ejection fraction <40% (12 in the exercise group and 13 in the control group). After stabilization for approximately 1 month after the event, patients in the exercise group underwent 8 weeks of twice daily exercise at a residential rehabilitation center, while control patients received usual care. Initially and after 8 weeks, patients in both groups underwent maximal exercise testing with gas exchange and lactate analysis. RESULTS: Exercise training increased peak oxygen consumption (VO2) only in the reduced ejection fraction group (19.4+/-3.0 to 23.9+/-4.8 mL/kg/min; p<0.05); the exercise group with normal ventricular function did not change significantly. Changes in VO2 at the lactate threshold paralleled those of peak VO2 for both groups. Conversely, control patients with normal ventricular function increased peak VO2 spontaneously (20.8+/-3.9 to 24.8+/-3.5 mL/kg/min; p<0.01), whereas control patients with reduced ventricular function did not improve peak VO2. CONCLUSION: These data suggest that patients with depressed left ventricular function strongly benefit from rehabilitation, whereas most patients with preserved left ventricular function following MI or CABG tend to improve spontaneously 1 to 3 months after the event.

Coronary Artery Bypass↗