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Biomedical subjects

M Weiss

Publications and source records attributed to M Weiss.

At least 235 records · Page 13Linked to original sources
PubMed1998

Occupational sitting and low hip mineral density.

In order to evaluate the contribution of habitual physical activity to bone remodeling, we determined bone mineral density (BMD) at the lumbar spine (L2-4) and the hip by dual energy X-ray absorptiometry in 55 clerks and 44 nurses. Our data indicate similar L2-4 BMD in both groups due to equal weight load of the upper part of the body on the spinal column in both study groups, but higher femur BMD in the nurse group (0.6-0.8 SD, at various hip measurement sites) than in the clerk group. The age-adjusted hip BMD was correlated with serum osteocalcin levels, and was related to the duration of standing at work, indicating a cause and effect relationship. We conclude that prolonged working in a sitting position may induce a low hip BMD, and thereby increase the risk for osteoporotic hip fracture.

Adult↗
PubMed1998

[Fibrillary glomerulonephritis. Case report for differential nephrotic syndrome diagnosis].

A 67-year-old male patient presented with a nephrotic syndrome. Biopsy of the kidney revealed the characteristic of fibrillary glomerulopathy on light and electron microscopy. Other non-nephritic causes of a nephrotic syndrome (e.g. amyloidosis, immunotactoid glomerulopathy, light-chain glomerulopathy, cryoglobulinaemia, collagen-III glomerulopathy, fibronectin glomerulopathy) could be excluded. Besides the case report, differential diagnosis of fibrillary glomerulopathies is presented.

Actin Cytoskeleton↗
PubMed1998

Effect of increasing running velocity on electroencephalogram in a field test.

This study was designed to measure the electroencephalogram (EEG) after exercise with increasing intensity. In a field test with increments in running velocity a 2-min EEG was recorded, together with blood lactate concentration and heart rate, after each stage. An individual protocol was used, with up to six stages of running to ensure comparability of exercise intensity among the subjects, in each of 19 athletes (17 men, 2 women) experienced in leisure-time running. The exercise consisted initially of three running stages of aerobic exercise intensity without blood lactate accumulation followed by stages with an increase of lactate concentration. The protocol of the field test led to a progressive increase in cortical activity directly after the stages without blood lactate accumulation mainly in the delta frequency band, followed by theta and alpha-1 frequency band, and less pronounced in the alpha-2 and in the beta frequency bands. After the stages with an onset and further increase of blood lactate accumulation significant decreases in the beta-2, beta-1 and alpha-1 frequency bands occurred predominantly in temporal (T3, T4, T5, and T6) and occipital (O1, and O2) electrode positions, indicating a stage-by-stage decrease of activity. This decrease may be explained by feed-back from working muscle, via afferents to the cortex from intero- and proprio-receptors and affective processes. This could suggest that through a higher running intensity indicated by an onset of blood lactate accumulation metabolic and mechanical changes led to alterations within the afferent systems influencing the level of cortical activity.

Adult↗
PubMed1998

Outcome of patients with sepsis and septic shock after ICU treatment.

OBJECTIVE: Today, sepsis syndrome is the leading cause of death in adult, non-coronary intensive care units (ICUs) and is of great clinical importance. The purpose of this review was to evaluate recent prospective studies concerning the short- and long-term prognosis of patients suffering from systemic inflammatory-response syndrome (SIRS), sepsis, severe sepsis and septic shock. It has been shown in multicentre prospective surveys that 1% and 0.3% of all patients admitted to hospitals suffer, respectively, from bacteraemia alone and bacteraemia with severe sepsis. This rate increases, of course, when only admissions to the ICUs are considered: the above-mentioned rates increase then by a factor of 8 and 30, respectively. Thus, approximately 10% of patients in the ICU suffer from sepsis, 6% from severe sepsis and 2-3% from septic shock. SIRS occurs more frequently and its occurrence ranges from 40% to 70% of all patients admitted to ICUs. Thereby, 40-70% suffering from SIRS progress to a more severe septic-disease state. The overall prognosis is still poor, despite the recent advances in ICU treatment. The mortality rate of SIRS ranges from 6% to 7% and in septic shock amounts to over 50%. In particular, abdominal sepsis exhibits the highest mortality rate with 72%. The long-term prognosis is equally poor; only approximately 30% survived the first year after hospital admission. CONCLUSION: The prognosis of sepsis and septic shock remains poor, despite the advances in ICU treatment. Although prognostic factors have been identified for some patients, groups have not yet been able to identify the immediate or long-term prognosis for the majority of these septic patients.

Adult↗
PubMed1998

Pharmacokinetics of morphine-6-glucuronide and its formation from morphine after intravenous administration.

BACKGROUND: Morphine-6-beta-glucuronide is a primary morphine metabolite with potent opioid action. However, its low and slow brain permeability eventually prevents its central opioid effects after short-term intravenous administration. Research is needed to establish whether morphine-6-beta-glucuronide qualifies as an analgesic; this study provides the pharmacokinetic bases for such studies. METHODS: Plasma concentration-time data of morphine-6-beta-glucuronide and morphine obtained from 20 healthy volunteers after short-term intravenous administration of either morphine-6-beta-glucuronide or morphine were described by a biexponential disposition curve. Disposition parameters of morphine-6-beta-glucuronide and morphine were estimated by nonlinear regression, and basic pharmacokinetic parameters (clearance, volume of distribution at steady state, and mean disposition residence time) were derived. A new model of metabolite kinetics was applied, and the disposition parameters of morphine and morphine-6-beta-glucuronide were then used to fit the plasma concentration-time profile of morphine-6-beta-glucuronide formed from morphine. Thereby the fraction of morphine metabolized to morphine-6-beta-glucuronide and the mean transit time of morphine across the site of metabolism were estimated. RESULTS: The extent and time course of morphine-6-beta-glucuronide formation from morphine could be well described by a parametric model, with a fraction of morphine metabolized to morphine-6-beta-glucuronide of 7.55% +/- 1.24% and a mean metabolic transit time for morphine to morphine-6-beta-glucuronide of 0.28 +/- 0.21 hour. The underlying disposition of morphine and morphine-6-beta-glucuronide was characterized by clearance (morphine clearance, 32.7 +/- 6 ml.min-1.kg-1, morphine-6-beta-glucuronide clearance, 2.2 +/- 0.4 ml.min-1.kg-1), volume of distribution at steady state (morphine, 1.8 +/- 0.3 L.hr-1; morphine-6-beta-glucuronide, 0.12 +/- 0.02 L.hr-1), and mean disposition residence time (morphine, 1.8 +/- 0.4 hours; morphine-6-beta-glucuronide, 1.7 +/- 0.4 hours). CONCLUSIONS: The time course of morphine-6-beta-glucuronide formation kinetics was analyzed with use of the information on the disposition kinetics of both morphine and preformed morphine-6-beta-glucuronide, which was obtained by separate data fits. The transformation of morphine to morphine-6-beta-glucuronide could be described by two parameters characterizing the extent and delay of metabolite formation. The results of this study will serve as pharmacokinetic bases of future investigations of morphine-6-beta-glucuronide in human beings.

Adult↗
PubMed1998

Effect of acute, short- and long-term milnacipran administration on rat locus coeruleus noradrenergic and dorsal raphe serotonergic neurons.

The effect of milnacipran on the firing activity of dorsal raphe serotonin (5-HT) neurons and locus coeruleus norepineprine (NE) neurons was assessed using extracellular unitary recording in chloral hydrate anesthetized rats. A 2-day treatment with milnacipran (20 or 60 mg/kg/day, s.c.) markedly decreased the firing rate of NE neurons, and it remained reduced after a 7- or a 14-day treatment. Although the suppressant effect of the alpha2-adrenergic agonist clonidine on the firing rate of NE neurons was markedly reduced following long-term milnacipran (60 mg/kg/day x 14 days, s.c.), that of NE remained unchanged. The firing rate of 5-HT neurons was reduced following a 2-day treatment with milnacipran (20 mg/kg/day, s.c.), but there was a partial recovery after a 7-day treatment (20 mg/kg/day, s.c.) and a complete one after a 14-day treatment (20, 40 or 60 mg/kg/day, s.c.). The suppressant effect of 5-HT and of the 5-HT1A agonist 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin) on the firing rate of 5-HT neurons was also unaltered after milnacipran (60 mg/kg/day x 14 days, s.c.). The latter milnacipran treatment did not affect the uptake of [3H]5-HT but it inhibited that of [3H]NE by 30% in hippocampal slices. The NE system was thus investigated in an attempt to explain the effects of milnacipran on the firing activity of 5-HT neurons. Acute injection of milnacipran suppressed the firing activity of 5-HT neurons (with an ED50 of 5.7+/-1.5 mg/kg, i.v.), but not in NE-denervated rats. Furthermore, the inhibitory effect of clonidine on 5-HT neuron firing activity was markedly reduced by the long-term milnacipran treatment, whereas the inhibition of electrically evoked release of [3H]NE as well as that of [3H]5-HT produced by the alpha2-adrenoceptor agonist UK 14.304 from preloaded mesencephalic slices containing the dorsal raphe was unaltered. The latter results indicate that the alpha2-adrenergic autoreceptor and heteroreceptor were unaffected in the raphe area by milnacipran. In conclusion, milnacipran had profound effects on the function of 5-HT and NE neurons, and the mechanism by which 5-HT neurons regained their normal firing during milnacipran treatment appeared to implicate the NE system.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1998

Kinetic analysis of vascular marker distribution in perfused rat livers after regeneration following partial hepatectomy.

BACKGROUND/AIMS: Liver clearance models are based on information (or assumptions) on solute distribution kinetics within the microvasculatory system. The aim was to study albumin distribution kinetics in regenerated livers and in livers of normal adult rats. METHODS: A novel mathematical model was used to evaluate the distribution space and the transit time dispersion of albumin in livers following regeneration after a two-thirds hepatectomy compared to livers of normal adult rats. Outflow curves of albumin measured after bolus injection in single-pass perfused rat livers were analyzed by correcting for the influence of catheters and fitting a long-tailed function to the data. RESULTS: The curves were well described by the proposed model. The distribution volume and the transit time dispersion of albumin observed in the partial hepatectomy group were not significantly different from livers of normal adult rats. CONCLUSIONS: These findings suggest that the distribution space and the transit time dispersion of albumin (CV2) is relatively constant irrespective of the presence of rapid and extensive repair. This invariance of CV2 implies, as a first approximation, a similar degree of intrasinusoidal mixing. The finding that a sum of two (instead of one) inverse Gaussian densities is an appropriate empirical function to describe the outflow curve of vascular indicators has consequences for an improved prediction of hepatic solute extraction.

Albumins↗
PubMed1998

Hepatic disposition and metabolite kinetics of a homologous series of diflunisal esters.

The hepatic disposition and metabolite kinetics of a homologous series of diflunisal O-acyl esters (acetyl, butanoyl, pentanoyl, and hexanoyl) were determined using a single-pass perfused in situ rat liver preparation. The experiments were conducted using 2% BSA Krebs-Henseleit buffer (pH 7.4), and perfusions were performed at 30 mL/min in each liver. O-Acyl esters of diflunisal and pregenerated diflunisal were injected separately into the portal vein. The venous outflow samples containing the esters and metabolite diflunisal were analyzed by high performance liquid chromatography (HPLC). The normalized outflow concentration-time profiles for each parent ester and the formed metabolite, diflunisal, were analyzed using statistical moments analysis and the two-compartment dispersion model. Data (presented as mean +/- standard error for triplicate experiments) was compared using ANOVA repeated measures, significance level P < 0.05. The hepatic availability (AUC'), the fraction of the injected dose recovered in the outflowing perfusate, for O-acetyldiflunisal (C2D = 0.21 +/- 0.03) was significantly lower than the other esters (0.34-0.38). However, RN/fu, the removal efficiency number RN divided by the unbound fraction in perfusate fu, which represents the removal efficiency of unbound ester by the liver, was significantly higher for the most lipophilic ester (O-hexanoyldiflunisal, C6D = 16.50 +/- 0.22) compared to the other members of the series (9.57 to 11.17). The most lipophilic ester, C6D, had the largest permeability surface area (PS) product (94.52 +/- 38.20 mL min-1 g-1 liver) and tissue distribution value VT (35. 62 +/- 11.33 mL g-1 liver) in this series. The MTT of these O-acyl esters of diflunisal were not significantly different from one another. However, the metabolite diflunisal MTTs tended to increase with the increase in the parent ester lipophilicity (11.41 +/- 2.19 s for C2D to 38.63 +/- 9.81 s for C6D). The two-compartment dispersion model equations adequately described the outflow profiles for the parent esters and the metabolite diflunisal formed from the O-acyl esters of diflunisal in the liver.

Algorithms↗
PubMed1998

Hepatic structure-pharmacokinetic relationships: the hepatic disposition and metabolite kinetics of a homologous series of O-acyl derivatives of salicylic acid.

1. The hepatic disposition and metabolite kinetics of a homologous series of O-acyl (acetyl, propionyl, butanoyl, pentanoyl, hexanoyl and octanoyl) esters of salicylic acid (C2SA, C3SA, C4SA, C5SA, C6SA and C8SA, respectively) was determined using a single-pass, in-situ rat liver preparation. 2. The hepatic venous outflow profiles for the parent esters and the generated metabolite, salicylic acid (SA) were analysed by HPLC. Non-parametric moments analysis was used to determine the area under the curve (AUC'), mean transit time (MTT) and normalized variance (CV2) for the parent esters and generated SA. 3. Pregenerated SA ([14C]-salicylic acid) was injected into each liver with the parent ester to determine its distribution characteristics. 4. The overall recovery of ester plus metabolite was 89% of the ester dose injected and independent of the ester carbon number, suggesting that ester extraction was due to hepatic metabolism to salicylic acid. 5. The metabolite AUC' value increased directly with the lipophilicity of the parent ester (from 0.12 for C2SA to 0.95 for C8SA). By contrast, the parent AUC' decreased with the lipophilicity (from 0.85 for C2SA to zero for C8SA). The metabolite MTT value also showed a trend to increase with the lipophilicity of the parent ester (from 15.72 s for C3SA to 61.97 s for C8SA). However, the parent MTT value shows no significant change across the series. 6. The two-compartment dispersion model was used to derive the kinetic parameters for parent ester, pregenerated SA and generated SA. Consequently, these parameters were used to estimate the values of AUC', MTT and CV2 for the parent ester and metabolite. The moments values obtained using the two-compartment dispersion model show similar trends to the corresponding moments values obtained from the outflow profiles using a non-parametric approach. 7. The more lipophilic aspirin analogues are more confined to the portal circulation after oral administration than aspirin due to their more extensive hepatic elimination avoiding systemic prostacyclin inhibition. Given that aspirin's selectivity as an anti-thrombotic agent has been postulated to be due to selective anti-platelet effects in the portal circulation, the more lipophilic and highly extracted analogues are potentially more selective anti-thrombotic agents than aspirin.

Animals↗
PubMed1998

Characterization of the murine immune response to the murine TSH receptor ectodomain: induction of hypothyroidism and TSH receptor antibodies.

The thyrotropin receptor (TSHR) is the major autoantigen of human Graves' disease. In order to define the antigenicity of the TSHR in a defined model, we examined the immune response of BALB/c mice to immunization with a new bioactive, recombinant preparation of the ectodomain of the murine TSHR (mTSHR-ecd). Mice (n = 10) were immunized with 25-50 microg of insect cell expressed, purified and refolded, mTSHR-ecd in alum adjuvant containing pertussis toxin, on days 0, 21, 36, 50 and 70. Control mice received wild-type baculovirus-infected insect cell protein lysate, in a similar way. After 28 days, murine serum contained high titres of antibodies specific to mTSH-ecd and their titres continued to increase over 90 days. Antibody epitope mapping, using 26 peptides spanning the human TSHR-ecd, showed that a variety of regions of the ectodomain were antigenic. The earliest epitope included aa 22-41, but later two regions of reactivity were noted clustered towards the mid portion and carboxyl terminus of the ectodomain. The murine TSHR autoantibodies (TSHR-Abs) inhibited up to 78% of the binding of labelled TSH to native TSHR, demonstrating the presence of antibodies capable of blocking the native TSHR. We showed that these TSHR antibodies acted, in vitro, as TSH blocking antibodies, inhibiting TSH-induced generation of cyclic AMP in chinese hamster ovary (CHO) cells transfected with the hTSHR. Hence, the antibody response to mTSHR-ecd was potentially antagonistic in its influence on the TSHR. Assessment of thyroid function in the immunized mice showed a fall in serum total T3 by 90 days and markedly elevated murine TSH levels (from 64.0 to 239.6 ng/ml), confirming the onset of thyroid failure. However, thyroid histology remained grossly normal. These data demonstrate that mTSHR-ecd is a potent antigen with three major immunogenic regions. The induced mTSHR-Abs blocked TSH action in vivo and reduced murine thyroid function.

Animals↗
PubMed1998

[Differential diagnosis of erosive osteochondrosis and bacterial spondylitis: magnetic resonance tomography (MRT)].

PURPOSE: To evaluate retrospectively criteria in the differential diagnosis of erosive osteochondrosis (EO) and infectious spondylitis (IS) on the basis of MRI. METHODS: T1-weighted sagittal images before and after Gd-DTPA application, T2-weighted TSE or T-STIR images of 23 patients with proven 15 and 41 patients with EO were evaluated. Criteria for this evaluation were morphology and extension of bone marrow edema, visibility of the low-intensity vertebral endplate, contrast enhancement and signal intensity in the disc space on T2-weighted and T-STIR images. RESULTS: Bone marrow edema was more extensive in IS than in EO. The mean rated value for bone marrow edema on a four-level scale (0-3) was for IS 2.91 (+/- 0.29), for EO 1.32 (+/- 0.76, p < 0.001). In 37/41 cases of EO and in 22/23 cases of IS Gd-DTPA enhancement was found in the disc space (n.s.). In EO the low intensity endplate was visible in all parts in 36/41 cases (87.8%) on T1-weighted images, in IS not in a single case (0%). On T2-weighted or STIR images signal intensity of the discs was decreased in 82.1% of EO, 82.6% of segments in IS had water-equivalent signal intensity (p < 0.001). CONCLUSION: If all the criteria are taken into consideration differential diagnosis of EO and IS on the basis of MRI findings is possible.

Adult↗
PubMed1998

Development and characterization of monoclonal antibodies specific for the murine thyrotropin receptor.

We have characterized 10 monoclonal antibodies (Mabs) to recombinant murine thyrotropin receptor extracellular domain (mTSHR-ecd). Affinity purified mTSHR-ecd (amino acids 22-415), expressed in a baculovirus-insect cell system, was refolded in vitro and used to hyperimmunize female Balb/c mice. Spleens were removed 10 days after a final boost of 25 microg mTSHR-ecd intraperitoneally and intravenously, and the cells were fused to SP-2 cells and cloned. Hybridoma supernatants were screened by enzyme-linked immunosorbent assay (ELISA) with folded mTSHR-ecd antigen. Ten of 18 higher affinity hybridomas were selected at random and ascites fluids prepared. Nine of the monoclonals were of IgG 1 isotype, and one was IgM. Five Mabs (M3, M4, M5, M6, and M9) inhibited the binding of 125I-TSH to functional hTSHR expressed on Chinese hamster ovary (CHO) cells, and four (M1, M3, M5, and M9) blocked the TSH-stimulated generation of cyclic adenosine monophosphate (cAMP), using the same cells. The remaining Mabs appeared to be neutral in their interaction with native TSHR. The Mabs were also compared for their reactivity to mTSHR-ecd under folding (ELISA) and unfolding (reducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis [SDS-PAGE]) conditions. Most Mabs demonstrated reactivity to both conformational (folded) and linear (unfolded) forms of mTSHR-ecd, suggesting that they were generated primarily against linear epitopes although one Mab (M4) showed affinity for only folded antigen indicating a preference for a conformational epitope. Mapping the Mab epitopes using 26 overlapping peptides spanning the human (h)TSHR-ecd showed that 6 bound peptide 397-415, 1 bound peptide 352-371, and 1 peptide 22-41. These epitope mapped Mabs to the mTSHR-ecd, both receptor blocking and receptor neutral, will provide further insight into the structure-function of the TSHR ectodomain.

Animals↗
PubMed1998

Role of ultrasound-guided fine-needle aspiration biopsy in evaluation of nonpalpable thyroid nodules.

To determine the role of ultrasound-guided fine-needle aspiration biopsy (US-FNAB) in the evaluation of incidentally diagnosed nonpalpable thyroid nodules (NP-TN), we compared the diagnostic yield of US-FNAB in NP-TN larger than 10 mm in diameter, with palpation-guided (P-FNAB) in palpable thyroid nodules (P-TN) in the same hospital setting. Of 108 consecutive patients with NP-TN (female/male: 97/11, age: 55.2 +/- 14.3, mean +/- SD), malignancy was identified in 8 patients (7 with thyroid papillary carcinoma, 4 of which had extrathyroidal spread, and 1 patient had metastasis of pulmonary adenocarcinoma). Male gender was associated with higher prevalence of malignancy (p = 0.09) while calcification and/or cystic degeneration of the nodule did not predict the cytological findings. Malignancy was identified in 16 of 151 consecutive patients with P-TN (female/male: 139/12, age: 44.1 +/- 9.5, mean +/- SD) indicating a similar rate of malignancy in both NP-TN and P-TN. In the P-TN group thyroid cancer was more common in males (p = 0.007), and the US properties of the nodule did not predict its cytological diagnosis. In conclusion, because similar rates of cancer are detected by FNAB in both NP-TN and P-TN, an FNAB is recommended for NP-TN larger than 10 mm.

Adenocarcinoma↗
PubMed1998

Video-intuboscopy: a new aid to routine and difficult tracheal intubation.

Video-intuboscopy gives a video display of the view from the tip of the tracheal tube during conventional laryngoscopy, and was developed particularly to assist the immediate management of unexpected difficult intubation. A lightweight, malleable video-optical intubation stylet transmits the view from the stylet tip onto a monitor. It is inserted in the tracheal tube before starting anaesthesia, and the view from the tracheal tube tip enables the anaesthetist to verify tracheal tube position in the trachea. During difficult intubation the video view is used to guide the tracheal tube into the trachea. When used to allow confirmation of tracheal placement, the system did not interfere with conventional intubation procedures. The method showed the subglottic airway, gave immediate confirmation of tracheal tube position, and aided teaching and supervision. The method was used to guide intubation in two patients with unanticipated grade 3 laryngoscopic views. Intubation was simple, rapid and atraumatic, without the need for head, neck or laryngeal manipulation. Tracheal placement was instantly confirmed using the video view from the stylet tip. Clinical studies are required to define the value of this new intubation technique.

Anesthesia, General↗
PubMed1998

Meiotic differentiation of germinal cells in three-week cultures of whole cell population from rat seminiferous tubules.

The aim of the present study was to set up a culture system allowing most of the meiotic phase of rat spermatogenesis to occur in vitro. For that purpose, the differentiation of spermatogenic cells was monitored by three criteria: 1) examination of expression of genes specifically expressed at a high level in pachytene spermatocytes (the phosphoprotein p19 [p19] and the testis-specific histone TH2B) or in round spermatids (transition protein 1 [TP1] and transition protein 2 [TP2]) by reverse transcription-polymerase chain reaction (RT-PCR); 2) ploidy analysis; and 3) cytological and immunocytochemical study of the germ cells. In the first trial, we determined the changes in the ratios of p19:TP1 and TH2B:TP2 mRNA-related PCR products in the whole testis of rats between 18 and 60 days postpartum and related those results to the sequential appearance of the various types of spermatogenic cells during that period. In the second trial, our aim was to reproduce, in a culture system using seminiferous tubules from 23- to 25-day-old rats, the changes observed in vivo. The p19:TP1 and TH2B:TP2 ratios decreased dramatically in testicular extracts of rats between 32 and 40 days postpartum, i.e., at the time period during which round spermatids become more and more numerous in the testis. When seminiferous tubules were seeded in bicameral chambers, cell viability remained close to 70% of total cells throughout the 3-wk culture period. Both p19:TP1 and TH2B:TP2 ratios decreased during the first week of culture. This was attributable to a decrease in the levels of p19 and TH2B mRNAs and also to an enhancement in the relative amounts of TP1 and TP2. These changes were correlated with the appearance of a 1C cell population in the culture. Histological examination of the culture demonstrated that under the conditions of the present study, 5-bromo-2'-deoxyuridine-labeled pachytene spermatocytes of stages IV-VI were able to differentiate into secondary spermatocytes, then into round spermatids.

Animals↗