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Biomedical subjects

M Berman

Publications and source records attributed to M Berman.

At least 19 recordsLinked to original sources
PubMed1992

Radical hysterectomy in the elderly patient: analysis of morbidity.

OBJECTIVE: This study compares the perioperative morbidity and mortality following radical hysterectomy of patients older than 65 years with a younger age group who underwent radical hysterectomy and pelvic lymphadenectomy for cervical carcinoma stage IB or IIA. STUDY DESIGN: A retrospective analysis of morbidity and mortality for the first 60 postoperative days was conducted. The study population of 45 women greater than 65 years of age with cervical cancer treated by radical hysterectomy was compared with a control population of 90 women less than 65 years treated similarly. RESULTS: In the elderly group, 31 of 45 and 12 of 15 were American Society of Anesthesologists Physical Status II and III respectively; 68/90 and 19/90 were American Society of Anesthesiologists status I and II in the younger age group (p = 0.001). Transfusions of greater than 2 units were required in 14% of the elderly and 35% of younger patients (p = 0.02). No statistical differences were observed between groups for other parameters examined. CONCLUSION: Age alone should not be a contraindication for radical hysterectomy in the elderly patient with American Society of Anesthesiologists Physical Status I to III.

Age Factors↗
PubMed1992

Cytokeratin immunohistochemical examination of liver biopsies in infants with Alagille syndrome and biliary atresia.

Identifying bile duct epithelium is sometimes difficult with standard histologic techniques. The availability of antibodies to specific cytokeratin (CK) intermediate filaments has allowed identification of CK expressed by bile duct epithelium. Formalin-fixed, paraffin-embedded liver tissue from five infants (aged 1-12 months) with Alagille syndrome and five infants with biliary atresia (aged 1.5-11 months) were pepsin digested then reacted with a combination of anti-cytokeratin monoclonal antibodies using an avidin-biotin immunoperoxidase technique. Liver tissue obtained at autopsy from infants without primary liver disease (aged 22 weeks gestation to 24 months) was treated similarly for comparison. Control specimens showed progression from prominent immunoreactivity of the ductal plate cells at the rim of the portal tract (22-24 weeks gestation) to incorporation of tubular ductal structures into portal tract mesenchymal tissue (26-34 weeks gestation) and formation of intensely immunoreactive mature discrete interlobular ducts with progressive loss of cytokeratin immunoreactivity of the ductal plate cells (1-24 months). In contrast, biopsies from infants with Alagille syndrome showed few immunoreactive interlobular ducts. Biopsies from infants with Alagille syndrome less than 2 months old showed only immunoreactivity of single ductal plate cells or small ductules at the periphery of the portal tracts. Biopsies from some infants greater than 3 months old showed increased numbers of immunoreactive cells in groups and anastomosing bands lacking true lumens and extending into the fibrous bridges between adjacent portal areas (neoductular proliferation).(ABSTRACT TRUNCATED AT 250 WORDS)

Alagille Syndrome↗
PubMed1992

Lidocaine pretreatment effectively decreases the incidence of hiccups during methohexitone administration for dilatation and curettage.

The efficacy of lidocaine 1 mg.kg-1 for prevention of methohexitone-induced hiccups was assessed in a double-blind fashion in 200 patients undergoing dilatation and curettage for pregnancy interruption. The patients were randomly assigned to receive either lidocaine 1% or saline 0.9% in a similar way (1 ml for every 10 kg of body weight). The incidence of hiccups was 16% in the control group compared to 6% in the lidocaine group. We speculate that this reduction in the methohexitone-induced hiccup ratio is related to lidocaine's membrane-stabilizing properties, which decrease the excitability of all the nervous structures involved in this reflex.

Abortion, Induced↗
PubMed1992

Blocking factors (soluble membrane receptors) for tumor necrosis factor and lymphotoxin detected in ascites and released in short-term cultures obtained from ascites and solid tumors in women with gynecologic malignancy.

Studies were conducted to identify and establish the cell and tissue source of blocking factors (BF), materials that inhibit the bioactivity of human TNF and LT in vitro. Ascites and samples of solid tumors were collected from women with various gynecologic malignancies. Supernatants were collected from cultures of tumor and ascites cells after 24, 48, and 72 h. Cell-free ascites (CFA) and culture supernatants were tested for their ability to block human recombinant TNF and LT-induced lysis of L929 cells in vitro. Levels of soluble forms of the 55- and 75-kDa TNF/LT receptors were measured by ELISA assay in the same samples. CFA and culture supernatants contained TNF/LT blocking factors and high levels of one or both soluble 55- and 75-kDa TNF/LT membrane receptors. Levels of BF bioactivity and receptors appeared rapidly, peaked at 24 h, and declined thereafter. Soluble TNF/LT receptors may be the active BF in these samples, and tumor tissues and ascitic cells may be a source of these receptors in the ascites fluid of these patients.

Ascites↗
PubMed1991

A naturally occurring 6-9-kilodalton interleukin-1 (IL-1) inhibitor prevents IL-1-mediated islet cytotoxicity but not IL-1-mediated suppression of insulin secretion.

Earlier studies have shown direct effects of interleukin-1 (IL-1) on isolated pancreatic islets. Coculture of isolated rat pancreatic islets with human rIL-1 beta for 6 days resulted in dose-dependent cytotoxicity (up to 100%) and suppression of insulin secretion (up to 88.5%). The cytotoxic effects of rIL-1 beta beta were blocked by the simultaneous presence of a naturally occurring 6-9-kilodalton (kDa) inhibitor of IL-1-induced T-cell proliferation. However, the ability of rIL-1 beta to suppress insulin secretion was not blocked by the 6-9-kDa inhibitor of IL-1 activity. This IL-1 inhibitor is produced by mononuclear cells and is resistant to pH 2, sensitive to heating at 56 degrees C for 30 min, has a pI of 4.5-5.6, and appears to be different from other recognized IL-1 inhibitors in both composition and mechanism of action. Unlike this IL-1 inhibitor, a monoclonal antibody specific for rIL-1 beta was able to neutralize both the islet cytotoxic and insulin modulatory effects of rIL-1 beta. These results demonstrate the use of an IL-1 inhibitor to prevent at least one mechanism of islet destruction, and suggest separate pathways for IL-1 mediated islet cytotoxicity and suppression of insulin secretion.

Animals↗
PubMed1991

Pathogenesis of corneal epithelial defects: role of plasminogen activator.

Previous studies have suggested that the plasminogen activator (PA)/plasmin system has important roles in the pathogenesis of epithelial defects and stromal ulceration. The current studies were performed to localize PA species and identify them as tissue-type PA (tPA) or urokinase-like PA (uPA) as the two have distinct regulatory properties potentially related to the mechanisms of defect formation and ulceration. To determine the locations and types of PA species, antibodies to tPA or to uPA or the drug amiloride (a drug that inhibits uPA but not tPA) were incorporated into fibrin/fibronectin (Fn) clots overlying frozen sections to block regional fibrinolysis. Normal rabbit eyes showed tPA activity in association with corneal epithelium, corneal endothelium, and ciliary body/iris. After epithelial scrape or alkali burn, corneal tPA activity was detected initially in the defect zone colinear with fibrin/Fn and was symmetrical to resurfacing epithelium. The observation that initial fibrinolysis occurs in the defect zone, known to contain fibrin/Fn, suggests that tPA from blood (limbal vascular endothelium) and/or from corneal epithelium has become bound to (and activated on) the fibrin/Fn. PA activity was also associated with the leading edges of migrating epithelium post-scrape and post-burn and was not inhibited by antibodies to either tPA or uPA but was inhibited by amiloride. After complete closure of the primary defect post-scrape, only tPA appeared to be associated with the epithelium in that all PA activity was inhibited by antibodies to tPA. The observation that leading edge activity post-burn, in correlation with the formation of secondary defects, continues to be inhibitable by amiloride but not by antibodies to tPA suggests that uPA remains abnormally on the leading edge, and that sustained uPA activity in that location results in inappropriate degradation of subepithelial fibrin/Fn to result in a defect. Successful regulation of uPA activity at the leading edge of corneal epithelium post-burn would be expected to be useful therapeutically in the healing of epithelial defects and the prevention of stromal ulceration.

Animals↗
PubMed1979

Potassium-stimulated ATPase activity and hydrogen transport in gastric microsomal vesicles.

The Mg2+-dependent, K+-stimulated ATPase of microsomes from pig gastric mucosa has been studied in relation to observed active H+ transport into vesicular space. Uptake of fluorescent dyes (acridine orange and 9-aminoacridine) was used to monitor the generated pH gradient. Freeze-fracture electron microscopy showed that the vesicular gastric microsomes have an asymmetric distribution of intramembraneous particles (P-face was particulate; E-face was relatively smooth. Valinomycin stimulated both dye uptake and K+-ATPase (valinomycin-stimulated K+-ATPase); stimulation by valinomycin was due to increased K+ entry to some intravesicular activating site, which in turn depends upon the accompanying anion. Using the valinomycin-stimulated K+-ATPase and H+ accumulation as an index, the sequence for anion permeation was NO-3 greater than Br- greater than Cl- greater than I- greater than acetate approximately isethionate. When permeability to both K+ and H+ was increased (e.g using valinomycin plus a protonophore or nigericin), stimulation of K+-ATPase was much less dependent on the anion and the observed dissipation of the vesicular pH gradient was consistent with an 'uncoupling' of ATP hydrolysis from H+ accumulation. Thiocyanate interacts with valinomycin inhibiting the typical action of the K+ ionophore. But stimulation of ATPase activity was seen by adding 10 mM SCN- to membranes preincubated with valinomycin. From the relative activation of the valinomycin-stimulated K+-ATPase, it appears that SCN- is a very permeant anion which can be placed before NO-3 in the sequence of permeation. Valinomycin-stimulated ATPase and H+ uptake showed similar dependent correlations, including: dependence on [ATP] and [K+], pH optima, temperature activation, and selective inhibition by SH- or NH2-group reagents. These results are consistent with a pump-leak model for the gastric microsomal K+-ATPase which was simulated using Nernst-Planck conditions for passive pathways and simple kinetics for the pump. The pump is a K+/H+ exchange pump requiring K+ at an internal site. Rate of K+ entry would depend on permeability to K+ as well as the counterion, either (1) the anion to accompany K+ or (2) the H+ efflux path as an exchange ion. The former leads to net accumulation of H+ and anion, while the latter results in non-productive stimulation of ATP hydrolysis.

Adenosine Triphosphatases↗
PubMed1979

Mathematical model for adriamycin (doxorubicin) pharmacokinetics.

Adriamycin (doxorubicin), an active antineoplastic drug, is rapidly distributed across cell membranes and is concentrated within cells. Binding to protein and to tissue readily occurs. The drug is metabolized to both fluorescent and nonfluorescent compounds, the liver being the main organ of biotransformation and elimination. A multicompartment, open model that accounts for these processes has been derived. The model assumes an initial volume of distribution of 60% of body weight and includes two peripheral adriamycin compartments and a subsystem for adriamycinol, a major metabolite. Plasma and urine concentrations of adriamycin and adriamycinol were determined for four patients treated with adriamycin (60 mg/m2), and these concentrations were used to calculate rate constants for the model. Concentrations were measured by fluorescence assay after thin-layer chromatographic separation of parent compound and metabolites. Differential equations were solved by the SAAM computer program. Evaluation of adriamcinol pharmacokinetics suggests that the previously reported high concentrations of adriamycinol immediately after IV infusion of adriamycin are an artifact of the fluorescence method and that observed plasma concentrations of adriamycinol are the sum of adriamycinol concentrations and approximately 10% of the adriamycin concentrations. Corrected peak plasma concentrations of adriamycinol occur 2--12 h after infusion of adriamycin.

Doxorubicin↗
PubMed1979

A mathematical model for membrane transport of amino acid and Na+ in vesicles.

A model with a carrier having sites for both amino acid and Na+ can account for AIB (alpha-aminoisobutyric acid) transport kinetics observed in membrane vesicles from SV3T3 (simian virus 40-tranformed Balb/c33 cells) and 3T3 (the parent cell line). The main feature of this cotransport model is that Na+ binding to carrier decreases the effective Km for AIB transport. Na+ transport kinetics observed in both vesicle systems can be described by passive (possibly facilitated) diffusion. The lag of Na+ transport across the membrane compared to that for AIB, coupled to the Na+-dependent decrease in the Km for AIB, accounts for the overshoot in intravesicular AIB observed for SV3T3 in the presence of an initial Na+ gradient. Extra-vesicular Na+ maintains a decrease in the Km for AIB influx before intra-vesicular Na+ has accumulated to balance it with a comparable decrease in the Km for AIB efflux. 3T3 vesicles display little overshoot, and this finding can be explained mostly by a lower carrier affinity for Na+.

Aminoisobutyric Acids↗
PubMed1979

The composition and metabolism of high density lipoprotein subfractions.

The composition and metabolism of high density lipoprotein (HDL) subfractions were investigated in seven normal individuals. Mean HDL2 (d, 1.063-1.125 g/ml) composition (by weight) was 43% protein, 28% phospholipid, 23% cholesterol, and 6% triglyceride, and mean HDL3 (d, 1.125-1.21 g/ml) composition was 58% protein, 22% phospholipid, 14% cholesterol, and 5% triglyceride. The mean apoA-I; apoA-II weight ratio was 4.75 for HDL2 and 3.65 for HDL3. HDL2 protein was proportionally slightly richer in C apolipoproteins and higher molecular weight constituents (including apoE) than HDL3. Kinetic studies utilized radiolabeled HDLA (d, 1.09-1.21 g/ml), HDL2, and HDL3 demonstrated rapid exchange of apoA-I and apoA-II radioactivity among HDL subfractions, similar fractional rates of catabolism of apoA-I and apo A-II within HDL, and similar radioactivity decay within HDL subfractions. Mean plasma residence time was 5.74 days for radiolabeled HDL2 and 5.70 days for radiolabedled HDL3. Differences in HDL protein mass among individuals were largely due to alterations in catabolism, and in general both HDL2 and HDL3 were catabolized via a plasma and a nonplasma pathway. Data from simultaneous radiolabeled very low density lipoprotein and HDL studies in 2 individuals are consistent with the concept that apoC-II and apoC-III are catabolized at a different rate than are apo A-I and apo A-II within the HDL density range.

Adult↗
PubMed1979

Analysis of 47Ca kinetics in normal subjects by means of a compartmental model with a non-exchangeable plasma calcium fraction.

1. 47Ca kinetic studies were performed in eight normal young adult males. Plasma, urinary and faecal stable and radioactive calcium and whole-body radioactivity were measured for up to 40 days after intravenous administration of the tracer. 2. The plasma radioactivity data could be fitted to the sum of four exponentials corresponding to a four-compartment model, but this model did not account for the consistently greater 47Ca specific radioactivities in plasma relative to those in urine at the same time in five of the subjects. 3. A non-exchangeable fraction of plasma calcium estimated as 5% of the mass in the plasma compartment was postulated to account for this finding. 4. An estimate of the insensible losses of calcium was obtained from the whole-body radioactivity counting data.

Adult↗
PubMed1979

Zinc metabolism in humans: a kinetic model.

A quantitative model is developed that describes the kinetics of the early phases of zinc metabolism in humans. The model is based on averaged data obtained over 5 days from 17 atients with smell and/or taste dysfunction who were given 69mZn in trace amounts orally and intravenously. A function describing the rate of entry of 69mZn into systemic plasma following ingestion of the isotope is derived showing that about 37% of the ingested zinc enters plasma. Gastrointestinal absorption is essentially completed by 4 h. Sixty-seven percent of the absorbed zinc in the portal circulation is extracted by the liver before being released into the systemic circulation and agrees with the calculated extraction efficiency from the systemic circulation. There are both rapid and slow exchnage phases between plasma and liver and between plasma and red cells. The calculated steady-state zinc values for plasma, red cells, and liver agree with previously reported measured values implying there are no additional zinc pools in these tissues. The tracer data, however, account for only 10% of total body zinc, the remaining 90% in tissues whose kinetics are too slow to be resolved from a 5-day study.

Adult↗
PubMed1979

Kinetic model for production and metabolism of very low density lipoprotein triglycerides. Evidence for a slow production pathway and results for normolipidemic subjects.

A model for the synthesis and degradation of very low density lipoprotein triglyceride (VLDL-TG) in man is proposed to explain plasma VLDL-TG radioactivity data from studies conducted over a 48-h interval after injection of glycerol labeled with 14C, 3H, or both. The curve describing the radioactivity of plasma VLDL triglycerides reaches a maximum at about 2 h, after which the decay is biphasic in all cases; the late curvature becoming evident only after 8--12 h. To fit the complex curve, it was necessary to postulate two pathways for the incorporation of plasma glycerol into VLDL-TG, one much slower than the other. A process of stepwise delipidation of VLDL in the plasma compartment, previously proposed for VLDL apoprotein models, was also necessary. Predicted VLDL-TG synthesis rates calculated with this model can differ significantly from those based on experiments of shorter duration in which the slow VLDL-TG component is not apparent. The results of these studies strongly support the interpretation that the late, slow component of the VLDL-TG activity curve is predominantly due to the slowly turning-over precursor compartment in the conversion pathway and is not due either to a slow compartment in the labeled precursor, plasma free glycerol, or to an exchange of plasma VLDL-TG with an extravascular compartment. It also cannot, in these studies, be attributed to a slowly turning-over VLDL-TG moiety in the plasma. The model was tested with data from 59 studies including normal subjects and patients with obesity and(or) various forms of hyperlipoproteinemia. Good fits were obtained in all cases, and the estimated parameter values and their uncertainties for 13 normolipemic nonobese subjects are presented. Sensitivty testing was carried out to determine how critical various parameter estimations are to the assumptions introduced in the modeling.

Glycerol↗
PubMed1979

Transport of very low density lipoprotein triglycerides in varying degrees of obesity and hypertriglyceridemia.

Measurements of transport of triglycerides (TG) in very low density lipoproteins (VLDL) were carried out in 59 patients by injection of radioactive glycerol, determinations of specific activities of VLDL-TG for 48 h thereafter, and treatment of the data by multicompartmental analysis. The patients were divided into three groups: normal weight (89-120% ideal weight), mildly obese (120-135% ideal weight), and markedly obese (135% ideal weight). They had varying levels of VLDL-TG ranging from normal to markedly elevated. In many subjects, there was a positive correlation between concentrations and transport of VLDL indicating that overproduction of VLDL-TG contributed to hypertriglyceridemia. In others, and particularly in several markedly obese subjects, transport rates were greatly increased without significant hypertriglyceridemia, suggesting that they had enhanced capacity to clear TG. In all groups, however, there were patients whose degree of hypertriglyceridemia seemed out of proportion to their transport rates. This finding and the fact that many patients have increased secretion of VLDL-TG without elevated plasma TG suggests that both overproduction of VLDL-TG and insufficient enhancement of clearance contributed to the development of hypertriglyceridemia.The data showed a poor correlation between transport rates determined by our multicompartment analysis and single-exponential analysis used previously by other investigators (r = 0.46); this comparison was not improved by segregating patients according to their degree of obesity. Although two conversion pathways (fast and slow synthetic paths) were required to fit the data, there was no correlation between transport rates and the ratio of the two pathways. Also, despite the known pathway of conversion of VLDL to low density lipoprotein, no correlation was found between VLDL-TG transport rates and estimated low density lipoprotein-cholesterol concentrations.

Biological Transport↗