Biomedical subjects

Michael Weiss

Publications and source records attributed to Michael Weiss.

60 records · Page 4Linked to original sources

PubMed2002

Digoxin uptake, receptor heterogeneity, and inotropic response in the isolated rat heart: a comprehensive kinetic model.

The cardiac pharmacokinetics of digitalis glycosides is not well understood. In the present study, a mechanism-based pharmacokinetic/pharmacodynamic model was developed to describe the uptake kinetics, receptor interaction, and positive inotropic effect of digoxin in the single-pass isolated perfused rat heart. Three doses of digoxin (0.1, 0.2, and 0.3 micromol) were administered to the heart (n = 12) as consecutive 1-min infusions followed by 15-min washout periods. Outflow concentration and left ventricular developed pressure were measured and analyzed by the model. The uptake of digoxin by the heart was limited by capillary permeability with a permeation clearance of 2.35 ml/min/g (about one-third of perfusate flow). Binding kinetics was determined by a mixture of two receptor subtypes, a low-affinity/high-capacity binding site (K(D,1) = 20.9 nmol, 89% of total receptors) and a high-affinity/low-capacity binding site (K(D,2) = 1.5 nmol, 11%). The time course of inotropic response was linked to receptor occupation, with higher efficiency of the high-affinity receptor population. The results suggest that, in the rat heart, consecutive inhibition of first the alpha(2)- and then the alpha(1)-isoform of Na(+)/K(+)-ATPase mediates the positive inotropic effect of digoxin with increasing dosage.

Animals↗

PubMed2002

Detection of Cryptococcus neoformans DNA in tissue samples by nested and real-time PCR assays.

Two PCR protocols targeting the 18S rRNA gene of Cryptococcus neoformans were established, compared, and evaluated in murine cryptococcal meningitis. One protocol was designed as a nested PCR to be performed in conventional block thermal cyclers. The other protocol was designed as a quantitative single-round PCR adapted to LightCycler technology. One hundred brain homogenates and dilutions originating from 20 ICR mice treated with different azoles were examined. A fungal burden of 3 x 10(1) to 2.9 x 10(4) CFU per mg of brain tissue was determined by quantitative culture. Specific PCR products were amplified by the conventional and the LightCycler methods in 86 and 87 samples, respectively, with products identified by DNA sequencing and real-time fluorescence detection. An analytical sensitivity of 1 CFU of C. neoformans per mg of brain tissue and less than 10 CFU per volume used for extraction was observed for both PCR protocols, while homogenates of 70 organs from mice infected with other fungi were PCR negative. Specificity testing was performed with genomic DNA from 31 hymenomycetous fungal species and from the ustilaginomycetous yeast Malassezia furfur, which are phylogenetically related to C. neoformans. Twenty-four strains, including species of human skin flora like M. furfur and Trichosporon spp., were PCR negative. Amplification was observed with Cryptococcus amylolentus, Filobasidiella depauperata, Cryptococcus laurentii, and five species unrelated to clinical specimens. LightCycler PCR products from F. depauperata and Trichosporon faecale could be clearly discriminated by melting curve analysis. The sensitive and specific nested PCR assay as well as the rapid and quantitative LightCycler PCR assay might be useful for the diagnosis and monitoring of human cryptococcal infections.

Animals↗

PubMed2002

Enterohepatic circulation: physiological, pharmacokinetic and clinical implications.

Enterohepatic recycling occurs by biliary excretion and intestinal reabsorption of a solute, sometimes with hepatic conjugation and intestinal deconjugation. Cycling is often associated with multiple peaks and a longer apparent half-life in a plasma concentration-time profile. Factors affecting biliary excretion include drug characteristics (chemical structure, polarity and molecular size), transport across sinusoidal plasma membrane and canniculae membranes, biotransformation and possible reabsorption from intrahepatic bile ductules. Intestinal reabsorption to complete the enterohepatic cycle may depend on hydrolysis of a drug conjugate by gut bacteria. Bioavailability is also affected by the extent of intestinal absorption, gut-wall P-glycoprotein efflux and gut-wall metabolism. Recently, there has been a considerable increase in our understanding of the role of transporters, of gene expression of intestinal and hepatic enzymes, and of hepatic zonation. Drugs, disease and genetics may result in induced or inhibited activity of transporters and metabolising enzymes. Reduced expression of one transporter, for example hepatic canalicular multidrug resistance-associated protein (MRP) 2, is often associated with enhanced expression of others, for example the usually quiescent basolateral efflux MRP3, to limit hepatic toxicity. In addition, physiologically relevant pharmacokinetic models, which describe enterohepatic recirculation in terms of its determinants (such as sporadic gall bladder emptying), have been developed. In general, enterohepatic recirculation may prolong the pharmacological effect of certain drugs and drug metabolites. Of particular importance is the potential amplifying effect of enterohepatic variability in defining differences in the bioavailability, apparent volume of distribution and clearance of a given compound. Genetic abnormalities, disease states, orally administered adsorbents and certain coadministered drugs all affect enterohepatic recycling.

Aging↗

PubMedDate not supplied

Diabetic sclerosing lymphocytic lobulitis of the breast.

Diabetic sclerosing lymphocytic lobulitis of the breast (SLLB) as a complication of long standing diabetes is a benign disease without known tendency to malignant evolution. Clinically, it is characterized by solitary or multiple rock-hard discrete lesion(s) in one or both breasts, usually in a subareolar site, but may appear equally in any part of the breast. Mammographically and morphologically, this lesion simulates cancer. The lesion may recur after excision in the same site or in another location of the ipsilateral or the contralateral breast. Awareness of this entity, establishment of the diagnosis by open biopsy or by core needle biopsy may spare the need for repeated wide excisions and the resulting distortion of the breast architecture. The aim of this review is to arouse the awareness of the physicians and surgeons to this possibility when they find a similar lesion in the breast of a diabetic patient.

Algorithms↗

PubMedDate not supplied

Inflammatory pseudotumor of the breast: case report and literature review.

Inflammatory pseudotumor (IP) is a benign lesion that can affect any tissue in the body and which may be confused clinically and in imaging for malignancy. Despite the widespread performance of breast biopsy, the finding of inflammatory pseudotumor of the breast is exceedingly rare. Excision of the tumor is the treatment of choice, but there is a relatively high rate of recurrence. The aim of this report is to describe the clinical, imaging, and pathologic features in a case of breast IP, the first reported case in a postpartum woman still nursing her infant.

Adult↗

PubMedDate not supplied

Intravitreal triamcinolone treatment for macular edema associated with central retinal vein occlusion and hemiretinal vein occlusion.

PURPOSE: To assess the efficacy of intravitreal triamcinolone treatment for macular edema from central retinal vein occlusion (CRVO) and hemiretinal vein occlusion (HRVO). METHODS: This study was a retrospective medical records review of 24 eyes of 24 patients (mean age, 71 years) that were injected with 4 mg of intravitreal triamcinolone acetonide for treatment of macular edema due to CRVO (n = 21) and HRVO (n = 3). Of the 24 eyes, 14 were injected once, 6 were injected twice, 3 were injected 3 times, and 1 received 4 injections. Mean follow-up time was 10 months (range, 3-24 months). The average time between onset of symptoms and first injection was 5.4 months (range, 2-48 months). Available documents on pre- and postinjection optical coherence tomography central foveal thickness in 23 of 39 total injections were evaluated. RESULTS: All injections resulted in reduction in central foveal thickness as determined by optical coherence tomography. The mean central foveal thickness decreased to 55% of preinjection values ([n = 23] 635 vs. 352 mum, respectively; P < 0.001). The average gain in visual acuity was 1.3 Snellen lines (range, -3-7) over the course of the study period. Ten eyes gained > or =2 lines of visual acuity, 3 eyes improved 1 line, 7 eyes remained the same, and 4 eyes worsened. There was no correlation between improvement in foveal thickness and corresponding visual gain (P = 0.24). None of the eyes of diabetic patients (n = 6) or patients with ischemic CRVO (n = 2) improved in visual acuity. The difference in mean baseline (20/167) and mean final visual acuity (20/91) was statistically significant (P = 0.015). The mean best postinjection visual acuity (20/67) was also significantly higher than the mean final visual acuity (P = 0.019). When diabetic and ischemic CRVO patients were excluded, the difference between mean baseline visual acuity and mean final visual acuity was found to be highly significant ([n = 16] 20/133 vs. 20/67, respectively; P < 0.001), while mean final and best postinjection visual acuities (20/50) did not differ (P = 0.085). Eight of 16 phakic eyes showed progression of cataract, 2 of which underwent cataract extraction. Nine of 18 patients without a history of glaucoma developed ocular hypertension and required glaucoma medication during postinjection follow-up. Trabeculectomy was performed on two eyes with glaucoma. Two other eyes developed epiretinal membranes, one of which underwent vitrectomy. CONCLUSIONS: Intravitreal triamcinolone may be effective in treating macular edema from CRVO and HRVO. Subjects with concurrent diabetes or ischemic central retinal vein were less likely to have visual improvement.

Adult↗