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Biomedical subjects

P Schmid

Publications and source records attributed to P Schmid.

At least 109 records · Page 6Linked to original sources
PubMed1996

Prostaglandin E1 increases binding of 123I-low-density lipoprotein to the human liver in vivo.

Previous in vitro radioligand binding data have shown that prostaglandin E1 (PGE1) increases the number and the binding affinity of low-density lipoprotein (LDL) receptors of the human liver. Experimental data in normo- and hypercholesterolaemic rabbits have confirmed these findings, showing a significant increase in LDL-binding to the liver in vivo after prolonged PGE1 therapy. METHODS. This study aimed to confirm the experimental and animal data in human in vivo. 123I-LDL binding to the liver was quantified in vivo in patients suffering from peripheral vascular disease, seven of them with heterozygous familial hypercholesterolaemia (HC) and five with normal total plasma cholesterol, after PGE1 administration (5 ng.kg-1.min-1; 6 h daily for 5 days/week for 5 weeks). LDL uptake by the liver was quantified by single photon emission computer tomography (SPECT). RESULTS. The amount of LDL trapped by the liver in normocholesterolaemics (45.6%) was significantly higher than in hypercholesterolaemics (22.0%). PGE1 induced an increase in liver LDL binding, which was more pronounced in HC (+38.2%) than in normocholesterolaemic patients (+8.11%).

Aged↗
PubMed1996

Airborne exposure to polycyclic aromatic hydrocarbons (PAHs) and urinary excretion of 1-hydroxypyrene of carbon anode plant workers.

Workers in plants producing carbon anodes for aluminium electrolysis are exposed to PAHs containing coal tar pitch volatiles, pitch and coke. The aim of this study was to evaluate the suitability of urinary 1-hydroxypyrene to characterize respiratory exposure to PAH, which is most relevant for assessing individual health risks. Six workers in a carbon anode plant volunteered to take part in a personal air sampling and a biological monitoring programme lasting five consecutive 8-h shifts to determine occupational exposure to airborne PAHs and urinary excretion of 1-hydroxypyrene. Exposure to total PAH for all worksites varied from 3.99 to 120.6 micrograms PAH m-3 and for benzo(a)pyrene (BaP) from 0.17 to 4.88 micrograms BaP m-3. The concentration of 1-hydroxypyrene in post- and pre-shift urine samples was in the range (0.5- 61.8 mumol 1-OHP per mol creatinine) and depended on the worksite. The Spearman rank correlation test showed a low but significant (P<0.005) correlation of urinary 1-hydroxypyrene in the post-and pre-shift samples with respiratory pyrene exposure. The quantitative aspects of biological monitoring for the evaluation of respiratory PAH exposure were tested with a pharmacokinetic model. On the basis of individual pyrene exposure, excretion of urinary 1-hydroxypyrene during the working week was calculated for each worker. The results presented in this investigation indicate that biological monitoring of the pyrene metabolite 1-hydroxypyrene is a useful indicator of a general PAH exposure, but cannot replace personal air sampling for assessing the lung cancer risk of individuals.

Air Pollutants, Occupational↗
PubMed1996

The use of toxic equivalency factors in assessing occupational and environmental health risk associated with exposure to airborne mixtures of polycyclic aromatic hydrocarbons (PAHs).

The health risk associated with inhalatory exposure to PAHs either in the occupational atmosphere or in outdoor air is commonly assessed on the basis of benzo(a)pyrene (BaP) concentrations in air. The PAH-related health risk is calculated with the help of epidemiological data from coke oven workers. The proportion of individual carcinogenic PAHs to BaP has been shown to vary in different environments by one to two orders of magnitude. Despite this, the unit risk value for BaP derived from epidemiological studies of coke oven workers is used for risk estimation of these environments. Toxic equivalency factors (TEFs) for individual PAHs were used to estimate human health risk associated with inhalatory exposure to PAHs. Given the uncertainties involved in risk assessment in general, a variability of risk estimation for PAH mixtures based on the toxic equivalency factor concept by a factor 2.6 is low and rather unreasonably precise. This underlines the importance of BaP as a surrogate compound of a PAH mixture.

Air Pollutants, Occupational↗
PubMed1996

Occurrence of nitro and non-nitro benzenoid musk compounds in human adipose tissue.

Nitro benzenoid musk compounds (Musk tibetene [CAS no. 145-39-1], Musk ambrette [83-66-9], Musk moskene [116-66-5], Musk ketone [81-14-1] and Musk xylene [81-15-2]) and non-nitro benzenoid musks (Celestolide [13171-00-1], Galaxolide [1222-05-5]) and Fixolide [1506-02-1] [21445-77-7] were analysed in 15 human adipose tissue samples from Switzerland by gas chromatography/high resolution mass spectrometry. The levels of Musk xylene and Galaxolide ranged up to 288 ng/g lipids and 171 ng/g lipids, respectively. The concentrations of non-nitro benzenoid musks found in human adipose tissue raise concern since very few toxicological data are available.

Adipose Tissue↗
PubMed1996

Phase II trial of intravenous endotoxin in patients with colorectal and non-small cell lung cancer.

We report the immunological and clinical results of a phase II trial with intravenously administered highly purified endotoxin (Salmonella abortus equi) in patients with advanced cancer. 15 patients with non-small cell lung cancer and 27 with colorectal cancer were entered into the study. 37 evaluable patients received at least four injections of endotoxin (4 ng/kg body weight) and 1600 mg ibuprofen orally in 2-week intervals. Transient renal (WHO grade 0-1) and hepatic (WHO grade 0-4) toxicities occurred in several patients. Constitutional side-effects such as fever, chills and hypotension could not be prevented completely by pretreatment with ibuprofen. 3 patients in the colorectal cancer group demonstrated objective responses (1 complete remission (CR), 2 partial remission (PR)). The complete remission has been maintained for more than 3 years, while the partial remissions were stable for 7 and 8 months, respectively. Only marginal antitumour effects were seen in the lung cancer group. Tolerance of the macrophage system to the stimulatory effect of endotoxin, as measured by human necrosis factor alpha (TNF-alpha) release into serum, built up after the first administration and remained at a steady-state level after each subsequent injection. In constrast, rising CD4:CD8 ratio and release of tumour necrosis factor beta (TNF-beta) indicated the continuing activation of the lymphocyte system by repetitive injections of endotoxin.

Adult↗
PubMed1996

Force transmission and stress distribution in a computer-simulated model of the kidney: an analysis of the injury mechanisms in renal trauma.

Injury mechanisms in renal trauma were investigated by analyzing the stress distributions within a two-dimensional computer-simulated model of the kidney. In biomechanics, damage to biological tissue is primarily caused by stresses resulting in tissue deformation beyond recovery limits. Segmental surface force was applied to the model and the resulting stress distributions were analyzed. Maximum stress concentrations were found at the periphery of the kidney model. Stresses were caused by the combined effect of the applied force and the reaction generated by the liquid-filled inner compartment as a function of its hydrostatic pressure. Maximum stress concentrations corresponded to typical injury sites observed clinically. Our findings suggest that a similar mechanism may play a crucial role in renal trauma. Renal injuries as well as the higher trauma susceptibility of hydronephrotic kidneys and renal cysts could thus be explained. The role of computer models in injury biomechanics research is discussed.

Biomechanical Phenomena↗
PubMed1996

Excretion and metabolism of remikiren, a potent orally active inhibitor of primate renin.

1. Following intravenous administration of 14C-remikiren to the male rat, 78% of the administered radioactivity was recovered in faeces, indicating high biliary elimination. Of the 25 +/- 0.1% of the dose recovered in urine, the majority (16.5% of dose) was intact drug. 2. After oral administration to the male rat the urinary recovery was markedly reduced (8.5 +/- 2.0% of dose), and virtually all of the material was excreted as an inactive hydrolysis product. Intact drug was non-detectable, suggesting extensive first-pass metabolism. 3. Perfusion of isolated rat liver confirmed high biliary elimination, coupled with extensive metabolism. Although intact remikiren was the major component in bile (20% of the 'dose'), the majority of the radioactivity was recovered as a series of mono- and di-hydroxylated metabolites. 4. When screened against human renin, only one of the metabolites in bile and urine (mono-hydroxylated in the t-butyl side chain, and synthesized as Ro 44-0444) showed comparable activity to remikiren. The remaining ten metabolites tested were at least one order of magnitude less active than the parent drug. 5. In comparative in vitro studies Ro 44-0444 was formed by rat, but not human or cynomolgus monkey, liver microsomes. The primate microsomes also produced more of the remaining mono- and di-hydroxy products, suggesting that metabolites make little contribution to the oral activity of remikiren which is observed in these species in vivo.

Administration, Oral↗
PubMed1996

In situ analysis of transforming growth factors-beta (TGF-beta 1, TGF-beta 2, TGF-beta 3) and TGF-beta type II receptor expression in basal cell carcinomas.

Transforming growth factor-beta (TGF-beta) consists of a highly homologous family of multifunctional peptides which are differentially expressed and function in a wide range of target cells. Aberrant expressions of TGF-beta s have been implicated in a number of disease processes, particularly those involving fibrotic and inflammatory lesions, and loss of TGF-beta growth inhibition may play a part in the progression of certain neoplasms. In the present study, we have analysed and compared, by in situ hybridization, mRNA expression of transforming growth factors-beta (TGF-beta 1, TGF-beta 2, TGF-beta 3) and TGF-beta type II receptor (T beta R II), and, by immunohistochemistry, the distribution of TGF-beta 3 protein in normal human skin and in basal cell carcinoma (BCC). The stroma of most BCCs revealed enhanced TGF-beta 1 and T beta R II mRNA expression when compared with normal dermis. A minority of BCCs also showed stromal overexpression of TGF-beta 2 and/or TGF-beta 3 mRNA. However, tumour tissues of all BCCs revealed weaker TGF-beta 3 mRNA and protein expression than normal interfollicular epidermis and hair follicle epithelia, whereas expression of TGF-beta 1 mRNA was comparably weak in tumour tissues and normal skin epithelia. Expression of TGF-beta 2 mRNA, which was clearly detectable in distinct hair follicle epithelia, was only barely detectable in normal interfollicular epidermis and in tumour tissues. In contrast, abundant T beta R II mRNA expression was observed both in normal skin epithelia and tumour tissues. From these findings, we suggest that increased stromal TGF-beta activity induces fibrotic alterations which promote tumour survival and/or progression via paracrine mechanisms, whereas lack of TGF-beta 3 expression by tumour cells may contribute to an autocrine growth control defect in BCCs.

Basal Cell Carcinoma↗
PubMed1995

Isradipine increases vascular prostaglandin I2-formation while the thromboxane B2-synthesis is diminished.

PGI2- and TXA2-synthesis from vascular tissue samples derived from cultured (endothelial and smooth muscle) cells, rabbit aorta and human bypass surgery were determined using specific radioimmunoassays for the stable derivatives (6-oxo-PGF1a and TXB2, respectively) of these compounds. Cultured cells were incubated in presence of isradipine, rabbits were pretreated for 4 weeks receiving 0.3 mg isradipine/kg*day, while patients were on isradipine (5-10 mg total dose/day, per os twice daily) since 6-19 weeks. In presence of isradipine, cultured cells produced significantly (p < 0.01) more 6-oxo-PGF1a and significantly less TXB2 (p < 0.05). 6-oxo-PGF1a-formation in rabbit aorta was significantly (p < 0.01) higher in isradipine treated normocholesterolemic animals while no significant changes were seen in isradipine treated hypercholesterolemic animals. TXB2 was significantly (p < 0.01) depressed in the abdominal and the thoracic aortic segment of isradipine treated hypercholesterolemic animals and was not significantly influenced in isradipine treated normocholesterolemic animals. Similarly, PGI2-synthesis in human arterial specimen was significantly (p < 0.01) enhanced as compared to the untreated controls. These findings indicate a beneficial behaviour of isradipine on vascular wall eicosanoid profile, which may contribute to a variety of antiatherosclerotic actions at the vascular wall level and to an improvement in hemostatic balance already described.

Aged↗
PubMed1995

Quantifying HIV-1 RNA using the polymerase chain reaction on cerebrospinal fluid and serum of seropositive individuals with and without neurologic abnormalities.

We quantified HIV-1 RNA levels (copies per milliliter) in cerebrospinal fluid (CSF) and serum from subjects at various stages of HIV-1 disease and determined the relationship of RNA levels to clinical and neurologic disease status (HND) and to laboratory values. Ninety-seven HIV-1-seropositive men without CNS opportunistic infections, tumors, or neurosyphilis and 13 high-risk seronegative controls were included in the study. Each individual underwent a structured interview and physical and neurologic examinations, followed by standardized collection of blood and CSF. A custom-designed, fully automated polymerase chain reaction (PCR) system was used to perform a minimum of four separate amplifications per specimen, using two HIV-1 gag primer pairs. Southern blotting followed by hybridization with product-specific probes was used for post-PCR detection. The number of copies per milliliter was determined by relating unknowns to a built-in dilution-series standard curve using an image analysis system. HIV-1 RNA was detectable in 96% of the sera, 78% of the concentrated CSF samples, and 54% of the unconcentrated CSF samples. Serum RNA levels were significantly higher than in CSF. Serum RNA levels were significantly inversely correlated with CD4+ cell counts (p = -0.34; p = 0.03): i.e., higher RNA levels in seropositive subjects were associated with lower numbers of CD4+ cells. Serum RNA levels correlated positively with number of AIDS-related symptoms, dysfunction scores for total neurological examination, mental status score, cranial nerve score, and CNS motor signs score. Serum RNA levels did not correlate significantly with length of time on zidovudine therapy, intrathecal IgG synthesis rate, or albumin leakage. RNA levels in CSF significantly correlated only with intrathecal IgG synthesis rate and with serum RNA levels. These results confirm that serum levels of HIV-1 RNA correlate with HND and inversely correlate with CD4 counts, demonstrating that HND occurs predominantly in late stages of HIV-1 disease, although HIV-1 RNA can be detected in CSF from a majority of HIV-1-seropositive individuals at all stages of disease, which suggests that there can be early penetration of HIV into the CNS. However, HND can occur in the absence of high levels of CSF HIV-1 RNA. We also found that the concentration of HIV-1 in CSF is correlated with intrathecal IgG synthesis rate.

AIDS Dementia Complex↗
PubMed1995

Passive smoking and cardiovascular risk.

A possible relationship between passive smoking and coronary heart disease has been widely debated during the past decade. Convincing evidence links environmental (passive) tobacco smoke exposure to heart disease morbidity as well as mortality. In the United States, 37,000 coronary heart disease deaths per year are attributed to environmental tobacco smoke exposure, accounting for 70% of all deaths caused by environmental tobacco smoke. The analysis of 10 epidemiologic studies indicated a consistent dose-response effect related to exposure, but more proof is still needed. Evidence indicates that nonsmokers are more sensitive to smoke, including cardiovascular effects, and that sidestream smoke contains higher concentrations of gas constituents, including carbon monoxide. Pathophysiological and biochemical data after short- and long-term environmental tobacco smoke exposure show changes in endothelial and platelet function as well as exercise capacity similar to those in active smoking. Therefore, passive smoking is a relevant risk factor for heart disease morbidity and mortality.

Animals↗
PubMed1995

Heart rate deflection related to lactate performance curve and plasma catecholamine response during incremental cycle ergometer exercise.

The correlation between the behaviour of the heart rate/work performance (fc/W) curve and blood lactate ([la]b) and plasma adrenaline/noradrenaline concentrations ([A]/[NA]) during incremental cycle ergometer exercise was investigated. A group of 21 male sports students was divided into two groups: group I, with a clear deflection of the fc/W curve; group II, without or with an inverse deflection of the fc/W curve. The aerobic threshold (Thaer) and the lactate turn point (LTP) were defined. Between Thaer and maximal work performance (Wmax) the behaviour of the fc/W curve as well as the behaviour of [la-]b and [A]. [NA] were described mathematically. The fc, systolic blood pressure (BPs), W, [la-]b, [A] and [NA] at rest, Thaer, LTP, Wmax, after 3 and 6 min of recovery (Re3/Re6) were calculated. A significant difference between the two groups could only be detected for fc at LTP, Re3 and Re6 (P < 0.05). No significant correlation could be found between individual fc/W-behaviour and individual time course of [la-]b, [A] and [NA]. However, a significant correlation was visible between [la-]b/W-behaviour and individual catecholamine response. These results and the fact that the different flattening at the top of the fc/W curve was related to diminished stress-dependent myocardial function led us to the conclusion that it is possible that sympathetic drive is not directly involved in mechanisms of regulation between load dependent fc and myocardial function. In addition, individual fc/W behaviour was independent of BPs and Wmax, or individual conditions of energy supply.

Adult↗
PubMed1995

In situ analysis of transforming growth factor-beta s (TGF-beta 1, TGF-beta 2, TGF-beta 3), and TGF-beta type II receptor expression in malignant melanoma.

We have analysed, by in situ hybridization, mRNA expression of TGF-beta 1, TGF-beta 2, TGF-beta 3, and of TGF-beta type II receptor in benign melanocytic naevi, primary melanomas, and in skin metastases of malignant melanomas. Our results show that melanoma progression correlates with overexpression of TGF-beta. All skin metastases and most primary melanomas invasive to Clark's level IV-V revealed specific TGF-beta 2 mRNA and protein expression. However, expression of this cytokine was not observed in benign melanocytic lesions and was detected only in one of five early primary melanomas investigated. Some primary melanomas and skin metastases also revealed specific TGF-beta 1 mRNA signals although expression of this isoform was not found in benign naevi. TGF-beta 3 expression, which was only barely detectable in benign melanocytic lesions, was enhanced in some skin metastases. Interestingly, the epidermis overlaying melanomas revealed lower levels of TGF-beta 3 mRNA expression than epidermis of healthy skin or epidermis adjacent to benign naevi, thereby suggesting that paracrine mechanisms between tumour cells and keratinocytes may influence melanoma development. In primary melanomas TGF-beta type II receptor mRNA signals were much more heterogeneously distributed when compared to benign melanocytic naevi, suggesting variable degrees of TGF-beta resistance among melanoma cells within individual lesions. However, melanoma progression appeared not to be correlated with a complete loss of TGF-beta type II receptor gene expression, since all skin metastases revealed clearly detectable although heterogeneous levels of TGF-beta type II receptor mRNA expression.

Disease Progression↗
PubMed1995

In vitro efficacy of cefquinome (INN) and other anti-infective drugs against bovine bacterial isolates from Belgium, France, Germany, The Netherlands, and the United Kingdom.

The in vitro antibacterial activity of cefquinome (INN), an aminothiazolyl-cephalosporin of the fourth generation of cephalosporins, was investigated by determining the minimal inhibitory concentration (MIC, microgram/ml) for 714 bacterial isolates of bovine origin and comparing it with those of amoxicillin, amoxicillin and clavulanic acid, ceftiofur, cephapirin, enrofloxacin, gentamicin, kanamycin and oxytetracycline. Drug resistance was determined by using break-points, which consider the dosage regimen and pharmacokinetics of the veterinary antimicrobials investigated. Cefquinome demonstrated a very high in vitro activity against bacterial isolates of Pasteurella spp., Escherichia coli and Salmonella spp. Overall, the level of resistance against the different anti-infectives tested was lowest for cefquinome. For the remaining substances examined, in vitro activity and the level of resistance showed considerable differences. The chemical and pharmaceutical features of cefquinome are discussed.

Animals↗
PubMed1995

Detection of occult melanoma cells in blood with a multiple-marker polymerase chain reaction assay.

PURPOSE: The objective of the study was to develop a sensitive multimarker polymerase chain reaction (PCR) assay to detect circulating melanoma cells in patient blood. The rationale was that malignant melanoma is heterogeneous in regards to antigen expression. PATIENTS AND METHODS: A PCR assay that uses four melanoma-associated gene markers (tyrosinase, p97, MUC18, and MAGE-3) was developed. Sensitivity and specificity of the PCR assay for individual markers were assessed using 10 melanoma cell lines and peripheral-blood lymphocytes (PBL) from 39 normal volunteers as controls. The assay's sensitivity and specificity were improved using nested primers and Southern blot analysis. Patients (N = 119) with American Joint Committee on Cancer (AJCC) stages I to IV disease were evaluated for circulating melanoma cells using the four gene markers under optimal conditions. RESULTS: All melanoma-associated gene markers were expressed in at least 80% of the melanoma lines, whereas 37 of 39 normal PBL tested negative for all markers; the remaining two PBL were positive for MUC18. Using four markers in the PCR assay was significantly better than using tyrosinase alone. There was a significant correlation between the number of positive PCR markers, AJCC stage of disease, and progression of disease. In all AJCC stages, there were more PCR-positive patients with disease than without disease. CONCLUSION: A multimarker PCR assay is more reliable and sensitive than a single-marker assay for detection of melanoma cells in blood of patients. This assay can provide important insight into tumor progression kinetics without major surgical or conventional radiologic diagnostic procedures.

Antigens, Neoplasm↗
PubMed1995

[Susceptibility of bacterial isolates from the equine respiratory tract to trimethoprim, sulfadoxine, sulfadimethoxine and combinations of these compounds].

Using a broth microdilution technique, the in vitro susceptibility of bacterial isolates from the equine respiratory tract to trimethoprim, sulfadoxine, sulfadimethoxine, and combinations of these compounds was determined. The bacterial strains (n = 88) isolated recently from horses with respiratory symptoms belonged to the following species: Streptococcus equi subsp. zooepidemicus (n = 34), Streptococcus equi subsp. equi (n = 22), Staphylococcus aureus (n = 9), Klebsiella pneumoniae (n = 7), Rhodococcus equi (n = 4), Pseudomonas spp. (n = 3) and Escherichia coli (n = 3). In addition, two isolates of Enterobacter spp. and one isolate of Streptococcus equisimilis, Staphylococcus intermedius, Proteus mirabilis and Serratia marcescens were examined. For determination of susceptibility of an organism the following minimal inhibitory concentrations (MIC) were fixed as limiting values: Trimethoprim < or = 0.5 microgram/ml, sulfadoxine < or = 32 micrograms/ml, sulfadimethoxine < or = 32 micrograms/ml, trimethoprim/sulfadoxine < or = 0.5/32 micrograms/ml, trimethoprim/sulfadimethoxine < or = 0.5/32 micrograms/ml. As expected, Rhodococcus-equi-isolates were resistant to the antimicrobials tested. However, most of the clinically more common isolates showed a high degree of susceptibility to the combinations. The fractional inhibitory concentration (FIC) indices indicated synergism of the combination-partners in a wide range. According to these in vitro results, application of trimethoprim/sulfonamide combinations for the initial therapy of equine respiratory tract infections can be recommended.

Animals↗