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Biomedical subjects

M Weiss

Publications and source records attributed to M Weiss.

At least 307 records · Page 17Linked to original sources

[Syncope of unclear origin--role of 2 diagnostic tests with high specificity].

We report the diagnostic evaluation of an elderly woman admitted with recurrent syncopes induced by head rotation. A cardiac origin was exclude by Holter ECG, echocardiography and carotid sinus compression. Angiography showed unilateral vertebral artery hypoplasia, suggesting the possibility of hemodynamic vertebrobasilar insufficiency. This origin, however, could be ruled out by monitoring of blood flow velocities in both posterior cerebral arteries with transcranial Doppler, which showed no alteration during syncope induced by head rotation. Detailed analysis of the course of the syncope recorded on videotape suggested a psychogenic event. Furthermore, the syncopes could be prevented with a "protective" placebo despite head rotation, and induced by a "provocative" placebo without head rotation while EEG monitoring showed normal brain activity. This finding underscored the suggestion of a psychogenic cause.

Aged↗

Preoperative diagnosis of thyroid papillary carcinoma by reverse transcriptase polymerase chain reaction of the MUC1 gene.

As thyroid nodules are common, it is imperative to recommend operation only to those with a high risk of malignancy. Fine-needle aspiration (FNA) biopsy, which is widely used for this purpose, is limited by the considerable rate of non-diagnostic or non-interpretable conclusions. Therefore, it is highly desirable to acquire a new diagnostic means for thyroid cancer. We have recently described a marked over-expression of the MUC1 gene in thyroid papillary-carcinoma tissue, as compared with various benign thyroid pathologies. As the amount of mRNA obtainable by FNA is not amenable to hybridization analysis, we amplified the mRNA sequence of the MUC1-gene upstream of the variable number tandem repeat array using the reverse-transcription polymerase chain reaction (RT-PCR). Seven out of 8 FNA samples obtained from thyroid papillary carcinoma resulted in 336 and 309 base-pair products. In contrast, in all 13 FNA samples obtained from various benign pathologies, only the smaller RT-PCR product was observed. Sequence analysis of the RT-PCR products indicates that alternative splicing of the exon 2 acceptor site accounts for the difference between the 2 amplification products. It is suggested that RT-PCR of the MUC1-gene transcript may add a biomolecular diagnostic dimension to the routine cytological preoperative FNA diagnosis.

Adult↗

Autoregulatory properties of dorsal raphe 5-HT neurons: possible role of electrotonic coupling and 5-HT1D receptors in the rat brain.

In the present study, the hypothesis that somatodendritic availability of 5-hydroxytryptamine (5-HT) could be regulated independently of the firing activity of dorsal raphe 5-HT neurons was tested. The 5-HT pathway was electrically stimulated at the level of the ventromedial tegmentum and the ensuing action potentials, recorded in the dorsal raphe, met all criteria for antidromic invasion of 5-HT neurons. The latency of antidromic spikes was current-dependent and the changes in latency were of quantal nature. This observation suggests an electrotonic coupling between 5-HT neurons. Stimulation of the ventromedial tegmentum also induced a decrease in the probability of firing of 5-HT neurons. This reduction in 5-HT neuron firing activity is a 5-HT-mediated response, due to an increased bioavailability of the neurotransmitter in the biophase of somatodendritic 5-HT1A autoreceptors. The intravenous administration of the 5-HT1 agonists TFMPP and RU 24969 reduced the duration of suppression of firing induced by the 5-HT-pathway stimulation, without altering the spontaneous firing rate of 5-HT neurons. The effect of TFMPP and RU 24969 on duration of suppression was blocked by (+-)mianserin, a drug with high affinity for the rat 5-HT1D, but not 5-HT1B, receptors. On the other hand, (-)propranolol, a mixed 5-HT antagonist also blocked the effect of TFMPP. However, the selective 5-HT1A antagonist (+)WAY 100135 did not alter the effect of TFMPP. These results, in keeping with previous anatomical studies, suggest the existence of electrotonic coupling of 5-HT neurons and indicate that 5-HT release in the rat dorsal raphe nucleus may be controlled independently of firing-regulating 5-HT1A autoreceptors. They also suggest that 5-HT1D receptors may play a role in this regulatory function of 5-HT neurons.

Action Potentials↗

Pharmacokinetics of trapidil in patients with chronic liver disease.

The pharmacokinetics of trapidil were studied in 15 patients with chronic liver disease (12 with hepatic cirrhosis, 2 with alcoholic fatty liver, 1 with liver fibrosis). Trapidil was administered intravenously as a 100-mg bolus. Serum samples were analyzed for trapidil by means of high-performance liquid chromatography. Mean pharmacokinetic parameters were compared with those found in a previous study of 12 healthy volunteers. Total plasma clearance was decreased significantly in patients with hepatic cirrhosis (96 mL/ min versus 258 mL/min in healthy individuals and 252 mL/min in patients with noncirrhotic liver disease). No difference in clearance was observed between patients with compensated or decompensated cirrhosis, and portal hypertension did not affect this clearance of trapidil. It can be concluded that trapidil clearance is a parameter that is very sensitive to alterations in hepatic clearance caused by liver cirrhosis, and that the dosage of trapidil should be adjusted accordingly in such patients.

Adult↗

Filgrastim (RHG-CSF) related modulation of the inflammatory response in patients at risk of sepsis or with sepsis.

Over a period of 14 days a longitudinal analysis was performed on the effects of filgrastim (recombinant human granulocyte colony stimulating factor, rhG-CSF) administered to 20 postoperative/posttraumatic patients at risk of or with sepsis. The following parameters were determined: leukocyte counts, serum cytokine levels and the surface expression of functional antigens and adhesion molecules. Filgrastim (1 mu g/kg.day) was infused continuously on the first 3 days and tapered to 0.5 mu g/kg.day on the following 4 days or until discharge from the surgical intensive care unit. During infusion of filgrastim, G-CSF levels increased in 16 out of the 20 patients within 48 h. In these 16 patients, leukocyte counts increased in 15 out of 16 patients. Expression of CD64 was upregulated within 24 h. The expression of CD32 was upregulated in 8 out of 9 patients with an initial expression < 55%. LAM-1 expression was downregulated in all patients revealing an initial expression of LAM-1 > 40%. Soluble ICAM increased in 9 out of 11 patients. IL-8 decreased in all 6 patients presenting initial values of IL-8 > 90 pg/ml. IL-1RA increased in 10 patients. Filgrastim had no effect on the expression of CD14, CD16 and CD34 and on the levels of TNF-alpha and sTNF-R type I (p55). In conclusion, infusion of filgrastim in postoperative/post traumatic patients at risk of and with sepsis resulted in improved generation and function of neutrophils and appeared to counterregulate hyperactivation of proinflammatory processes.

Antigens, Surface↗

Electroencephalogram activity, catecholamines, and lymphocyte subpopulations after resistance exercise and during regeneration.

We examined the effect in ten male sports students of 30-min resistance exercise followed by either 45-min regeneration with massage treatment on a massage bench or supine rest serving as control, on plasma catecholamine concentration, number and distribution of circulating white blood cells and central activity. Resistance exercise increased free plasma adrenaline (A) and noradrenaline (NA), whereas sulphoconjugated catecholamine concentration remained unchanged as determined by high performance liquid chromatography. Exercise induced leucocytosis and lymphocytosis measured by flow cytometry was predominantly manifested by an increase in the number of lymphocytes, monocytes, CD3+ cells, CD8+ cells and CD3- CD16/56+ cells. Computer-aided electroencephalography (EEG) revealed significant increases in absolute EEG band power. The increase was highest in alpha 2 with 51.6 (SD 40.2)% (P < 0.01), followed by beta 1 with 33.3 (SD 21.0)% (P < 0.01), alpha 1 with 31.9 (SD 25.2)% (P < 0.01), beta 2 with 30.8 (SD 26.7)% (P < 0.01), delta with 26.1 (SD 28.7)% (P < 0.05), and theta with 19.8 (SD 16.5)% (P < 0.01). All hormone and immunological variables returned to pre-exercise values 45 min after exercise with no differences between massage and control treatments. However, during regeneration differences in absolute EEG-band power were observed between massage and control treatments. In central (Cz, C3, C4) and fronto-lateral (F3, F4) electrode positions absolute beta 1 spectral power density was significantly lower during massage treatment than during control (Wilcoxon test: P < 0.01). Overall, these data demonstrated that an influence of massage treatment on deactivation characteristics could be observed in EEG measurements but not in plasma catecholamine concentration or blood lymphocytes, indicating that computer-aided topographical EEG may be a useful technique for studying activation and regeneration characteristics.

Adult↗

Tissue distribution kinetics as determinant of transit time dispersion of drugs in organs: application of a stochastic model to the rat hindlimb.

A stochastic theory of drug transport in a random capillary network with permeation across the endothelial barrier is coupled with a model of tissue residence time of drugs assuming radial intratissue diffusion. Axial diffusion is neglected both in tissue as well as in the radially well-mixed vascular phase. The convective transport through the microcirculatory network is characterized by an experimentally determined transit time distribution of a nonpermeating vascular indicator. This information is used to identify three adjustable model parameters characterizing permeation, diffusion, and steady-state distribution into tissue. Predictions are made for the influence of distribution volume, capillary permeability, and tissue diffusion on transit time distributions. The role of convection (through the random capillary network), permeation, and diffusion as determinants of the relative dispersion of organ transit times has been examined. The relationship to previously proposed models of capillary exchange is discussed. Results obtained for lidocaine in the isolated perfused hindleg in rats indicate that although the contribution of intratissue diffusion to the dispersion process is relatively small in quantitative terms, it has a pronounced influence on the shape of the impulse response curve. The theory suggests that the rate of diffusion in muscle tissue is about two orders of magnitude slower than in water.

Anesthetics, Local↗

Degenerative disk vascularization on MRI: correlation with clinical and histopathologic findings.

OBJECTIVE: This prospective study was designed to determine the MRI features, clinical significance, and correlation to histopathologic findings of secondary vascularized degenerative intervertebral disks. MATERIALS AND METHODS: Fifty-three patients with localized painful spine syndrome were investigated prospectively by contrast-enhanced MRI. Pain was not predominantly radiating and there was no clinical evidence of spinal infection. In all patients sagittal SE T1-weighted, fast SE T2-weighted or turbo-STIR, and T1-weighted frequency-selective fat-suppressed images were obtained. RESULTS: We identified 37 vascularized disks in 26 patients. In 18 patients the changes had occurred spontaneously, in 6, the affected disk had been operated on previously, and 2 patients had spondylolisthesis. In 15 patients, vascularization was accompanied by medullary edema adjacent to the vertebral endplates. In one of the vascularized disks, herniation was also found. In seven patients, ventral diskectomy was performed. Histopathologic findings confirmed disk vascularization in six of seven cases. CONCLUSIONS: Degenerative, band-like disk vascularization is a feature which is associated with local pain. It was demonstrated by contrast-enhanced MRI. Degenerative disk vascularization is an important differential diagnosis to bacterial spondylodiskitis. It can be a cause of pain in patients with postdiskectomy syndrome.

Diagnosis, Differential↗

Wiskott-Aldrich syndrome: no strict genotype-phenotype correlations but clustering of missense mutations in the amino-terminal part of the WASP gene product.

The Wiskott-Aldrich syndrome protein (WASP) gene was found to be mutated in patients presenting with WAS and in patients showing X-linked thrombocytopenia. Mutation analysis in 19 families of German, Swiss and Turkish descent by single-strand conformation polymorphism and sequencing resulted in the detection of seven novel and 10 known mutations. A striking clustering of missense mutations in the first four exons contrasted with a random distribution of nonsense mutations. More than 85% of all known missense mutations were localized in the amino-terminal stretch of the WASP gene product; this region contained a mutational hot spot at codon 86. No genotype-phenotype correlation emerged after a comparison of the identified mutations with the resulting clinical picture for a classical WAS phenotype. A substitution at codon 86 resulted in an extremely variable expression of the disease in a large Swiss family. An extended homology search revealed a distant relationship of this stretch to the vasodilator-stimulated phosphoprotein (VASP), which is involved in the maintenance of cyto-architecture by interacting with actin-like filaments.

Adult↗

Filariasis in northern Ghana: some cultural beliefs and practices and their implications for disease control.

This article reports on how some endemic rural communities in northern Ghana perceive and manage lymphatic filariasis. The disease was mainly attributed to supernatural and spiritual factors. Except for a few instances of neglect, the community was generally caring towards people with the disease. Issues related to marriage, stigma, concealment and leadership are discussed. On the whole, the importance of social and cultural perceptions of a disease and its relevance to control cannot be over emphasized.

Culture↗

Pathophysiologic features of a pneumoperitoneum at laparoscopy: a swine model.

OBJECTIVE: The aim of this study was to examine local and systemic reactions of the body to a pneumoperitoneum to elucidate potential dangers and risks of laparoscopic procedures. STUDY DESIGN: Laparoscopy was performed on 25 pigs. The pigs were divided into five groups by level of intraabdominal pressure (14 and 18 mm Hg) and gas used (carbon dioxide and air). The effects of the pneumoperitoneum on cardiopulmonary condition and the peritoneal milieu were observed. These effects should be the result of various changes as the mechanical, ventilatory, cellular, hormonal, and immunologic levels. RESULTS: In this animal study marked changes in the peritoneal milieu were observed, and we demonstrated that these changes were dependent on the gas used, intraabdominal pressure, and duration of application. Locally these changes are manifest in the development of severe peritoneal acidosis, hypercapnia, and the release of various mediators. Systemic changes, in particular cardiopulmonary changes, also depend on the intraabdominal pressure and the gas used. CONCLUSION: During conventional pneumoperitoneum the peritoneum might change to a large extent so that the development of new risks are possibly encouraged. A reduction in intraabdominal pressure with the use of carbon dioxide as the insufflation gas should result in normal acid-base balance.

Abdomen↗

Management of complicated neurologic injuries.

Despite measures based on the Monro-Kellie principles for ICP reduction and optimization of cerebral perfusion pressure, the outcome from complicated neurologic injuries remains unsatisfactory. Many patients are "pulled through" the acute event only to remain minimally functional or vegetative for the remainder of their lives. Pharmacologic interventions to protect the brain against the toxic and metabolic consequences of neurologic injury seem to be the future of neurotrauma.

Brain Edema↗

A novel extravascular input function for the assessment of drug absorption in bioavailability studies.

PURPOSE: Flexible parametric models describing the input process after extravascular drug administration are needed for the assessment of absorption rate and the use of population methods in bioavailability and bioequivalence studies. METHODS: The oral concentration-time curve modeled as the product of the input and disposition function in the Laplace domain was obtained by numerical inversion methods for parameter estimation. The utility of the inverse Gaussian input density was examined using bioavailability data of an extended-release dosage form. Measures of rate of absorption and the cumulative absorbed amount profile were defined in terms of the estimated model parameters. RESULTS: Accurate estimation of absorption parameters was achieved by simultaneous fitting of the extravascular and intravascular data (describing the latter by a triexponential function). The new input function allowed a direct estimation of both extent of absorption and mean absorption time. CONCLUSIONS: The findings suggest that the inverse Gaussian density is a useful input function. Its flexibility may reduce the effect of model misspecification in parameter estimation. All parameters can be readily interpreted in terms of the absorption process.

Absorption↗

Effects of cardiac output on disposition kinetics of sorbitol: recirculatory modelling.

1. The purpose of this study was to determine the effects of cardiac output on distribution and elimination kinetics of the marker compound sorbitol. 2. The disposition kinetics of sorbitol were investigated after rapid intravenous injection and arterial sampling in nine patients who had undergone cardiac catheterization whereby the cardiac output was measured. 3. A minimal circulatory model consisting of pulmonary and systemic subsystems, both of which were characterized by an inverse Gaussian transit time density function, fitted the data very well. The method involves numerical inverse Laplace transform of the model equations. 4. The mixing clearance introduced as a novel non-compartmental parameter of distribution dynamics was significantly correlated with cardiac output. The steady-state volume of 14 l matched the extracellular volume. The systemic extraction ratio of 23% may reflect the fractional liver blood flow. 5. This pharmacokinetic model can be applied when an independent observation of cardiac output is available. In contrast to the conventional compartmental (or sum of exponential) approach it contains fewer adjustable parameters which can be more readily interpreted in physiological terms.

Aged↗

Radical scavenger activity of three flavonoid metabolites studied by inhibition of chemiluminescence in human PMNs.

3,4-Dihydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, and 3-(4-hydroxyphenyl)-propionic acid, metabolites which arise from quercetin glycosides, respectively, from flavones and probably from procyanidins by the human intestinal microflora, have been tested for their effects on oxygen radical production by human PMNs stimulated with FMLP or opsonized zymosan. Oxygen radicals were detected by luminol-augmented chemiluminescence measurements. Furthermore free radical scavenging activity of these metabolites was investigated in a cell-free system in which oxygen radicals were generated by horseradish peroxidase with H2O2 as substrate. 3,4-Dihydroxyphenylacetic acid reduced considerably chemiluminescence in PMNs in an amount which was much more pronounced than those of the other two metabolites. Concentrations of 1 mumol/l showed an inhibition by 84% with FMLP as stimulant and by 15% with opsonized zymosan, indicating that different signal transduction pathways are influenced in PMNs. Using the same conditions the unmetabolized quercetin showed an inhibition of chemiluminescence by 74% (FMLP), resp. 20% (opsonized zymosan). In the cell free system 3,4-dihydroxyphenylacetic acid suppressed much more effectively chemiluminescence than 3-hydroxyphenylacetic acid. In contrast, 3-(4-hydroxyphenyl)-propionic acid led to an increase of chemiluminescence generated in the cell-free system (FMLP and zymosan), i.e. by 30% by 25%, at the highest concentration of 4 mumol/l. In conclusion, flavonoid metabolites differ in their effects on free radical production of PMNs and their radical scavenging potencies.

Flavonoids↗