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Biomedical subjects

B Gerson

Publications and source records attributed to B Gerson.

At least 37 records · Page 2Linked to original sources
PubMed1988

Rapid antidepressant response to alprazolam in depressed patients with high catecholamine output and heterologous desensitization of platelet adenylate cyclase.

The present study examined the relationship between 24-hr urinary catecholamine (norepinephrine and epinephrine) output and measures of platelet adenylate cyclase (AC) activity in depressed patients (n = 17) and control subjects (n = 10). In both groups, significant inverse correlations were observed when 24-hr urinary catecholamine levels were examined in relation to measures of both receptor-mediated (prostaglandin D2 and alpha 2-adrenergic) and postreceptor-mediated (NaF) platelet AC enzyme activities, suggesting that circulating catecholamines may regulate platelet AC by heterologous (agonist-nonspecific) desensitization of the AC enzyme complex. Depressed patients who had favorable antidepressant responses to alprazolam had significantly higher pretreatment urinary catecholamine output and lower receptor-mediated platelet AC enzyme activities than control subjects, whereas the nonresponders did not. After 8 days of treatment with alprazolam, urinary catecholamine levels declined significantly. In responders, receptor-mediated measures of platelet AC activity increased significantly by day 8 to values comparable to those in control subjects; but similar changes were not observed in nonresponders. Prior to treatment, responders showed a strict linear relationship between receptor-mediated (prostaglandin D2) and postreceptor-mediated (NaF) stimulation of platelet AC activity through the stimulatory guanine nucleotide regulatory protein (Ns), whereas nonresponders did not. This suggests the presence of two distinct coupling interactions between platelet prostaglandin D2 receptors and the stimulatory guanine nucleotide regulatory protein in responders and nonresponders to the antidepressant effects of alprazolam prior to treatment. The authors propose that catecholamines, possibly acting through prostaglandins, may regulate platelet AC enzyme activity by heterologous desensitization occurring through postreceptor mechanisms.

Adenylyl Cyclases↗
PubMed1988

Stabilization of stannous pyrophosphate kits with gentisic acid.

We evaluated the ability of gentisic acid, an antioxidant, to stabilize stannous pyrophosphate (Sn:PPi) kits and extend the shelf-life of the kit after reconstitution. In vitro studies showed that gentisic acid (0.5 mg/mL) stabilized the stannous ion against oxidation by various levels of exogenous hydrogen peroxide. In patients who received stabilized Sn:PPi for in vivo red blood cell labelling, the left ventricle-to-background activity ratio was significantly higher than that in patients who received a standard formation of Sn:PPi. Gentisic acid is now used routinely in the Sn:PPi kit formulation in this institution.

Drug Stability↗
PubMed1988

Technetium-99m red blood cell labeling in patients treated with doxorubicin.

Radionuclide angiography is useful in monitoring cardiotoxicity of doxorubicin, but in vivo RBC labeling in these patients is believed to be poorer than that in general patients. The left ventricle-to-background activity ratio (R) was not significantly lower in patients treated with doxorubicin (3.24 +/- 1.15, N = 13) than in control patients (3.89 +/- 1.60, N = 14). With both modified in vivo and in vitro labeling, R was significantly improved in patients treated with doxorubicin (4.37 +/- 0.91, N = 8, and 4.37 +/- 1.22, N = 13, respectively). However, with the modified in vivo method, labeling efficiency remained a function of hematocrit, whereas the in vitro method removed this dependency. Both modified in vivo and in vitro labeling result in improved image quality over in vivo labeling in patients treated with doxorubicin, and the choice of method can be based on other factors.

Doxorubicin↗
PubMed1987

Cytoplasmic enzyme patterns in isolated hamster pulmonary alveolar type II cells.

Three cytoplasmic enzyme patterns were studied in pulmonary alveolar type II cells isolated from normal adult hamster lung: lactate dehydrogenase (total and isoenzymes), peroxidase, and beta-N-acetylglucosaminidase. Enzyme patterns of freshly-isolated type II cells were found to be different from those of freshly-isolated pulmonary hamster fibroblasts. After both types of cells had been cultured for seven days, no difference in cytoplasmic enzyme patterns remained. Lactate dehydrogenase isoenzyme patterns for type II cells were different from those obtained from polymorphonuclear leukocytes and alveolar macrophages. These data may be useful in detecting sources of lung injury by assessment of enzyme patterns in bronchoalveolar lavage fluid.

Acetylglucosaminidase↗
PubMed1987

The pulmonary toxicity of talc and granite dust as estimated from an in vivo hamster bioassay.

A short-term animal bioassay was used to assess the toxicity of occupational dusts. We quantified pulmonary responses in hamsters exposed to granite (12% quartz) and talc (quartz and asbestos-free) dust collected from worksites. Personal samples collected on workers showed similar quartz content and particle-size distributions to the high-volume samples collected for bioassays, thus demonstrating that the particulates were representative of worker exposure. We measured biochemical and cellular indicators of injury in bronchoalveolar lavage fluid (BAL) of animals exposed to dust suspensions by intra-tracheal instillation. The assays measured release of cytoplasmic and lysosomal enzymes into the cell-free supernatant of BAL; levels of albumin and red blood cells; changes in macrophage and polymorphonuclear neutrophil cell numbers; and in situ macrophage phagocytosis. Dose-response (0.15, 0.75, and 3.75 mg/100 g body wt) and time-course (1-14 days postexposure) studies were performed. One day after exposure, both talc and granite dust resulted in elevated enzyme levels, pulmonary edema, and increased cell numbers in BAL. Macrophage phagocytosis was also inhibited. Based on earlier studies, response levels were either intermediate between nontoxic iron oxide and toxic alpha-quartz or comparable with alpha-quartz. The response to granite dust diminished fairly rapidly over time. By contrast, after talc exposure, there was a more persistent elevation in enzyme levels, and macrophage phagocytosis remained depressed. These results indicate that, when a similar mass was deposited in the lungs, talc caused more lung injury than did granite. Better estimates of exposure-dose relationships in talc and granite workers as well as longer-term animal studies are required to evaluate the harmfulness of these work environments at present-day exposure levels.

Animals↗
PubMed1987

Technetium-99m diethyldithiocarbamate (DDC): comparison with thallium-201 DDC as an agent for brain imaging.

Technetium-99m diethyldithiocarbamate (99mTc-DDC) was prepared by reduction of [99mTc]pertechnetate with formamidine sulfinic acid in the presence of DDC at alkaline pH, both from extemporaneous solutions and in a kit formulation. The properties of 99mTc-DDC were compared in vitro and in vivo with those of 201Tl-DDC, an agent used for cerebral perfusion imaging (CPI). 99mTc-DDC is a lipophilic complex but its oil/water partition coefficient is lower than that of 201Tl-DDC. 99mTc-DDC also shows greater binding to plasma proteins. Studies in rabbits show that 99mTc-DDC enters the brain but is not retained to the same extent as 201Tl-DDC. This lack of retention may be because 99mTc-DDC does not decompose rapidly in lipid media as 201Tl-DDC does. These results suggest that 99mTc-DDC in its present formulation is not suitable for CPI with SPECT.

Animals↗
PubMed1987

Reliability and significance of increased creatine kinase MB isoenzyme in the serum of uremic patients.

The authors quantified creatine kinase MB (CK-MB) isoenzyme activity and mass in the serum of 81 uremic and 20 nonuremic (control) patients who had no clinical or electrocardiographic evidence of acute myocardial infarction. CK-MB was quantified by three methods: electrophoresis, the QuiCK-MB (International Immunoassay Labs), and the Tandem-E CK-MB (Hybritech, Inc.). The authors then followed all uremic patients for subsequent hospitalization for cardiac disease. Median CK-MB was increased in the serum of the uremic patients as compared with the control patients by all methods. Most uremic patients had CK-MB in serum above the median CK-MB of the control group. Seventeen (21%) uremic patients had CK-MB in serum elevated above the reference range by at least one method. All control patients had CK-MB in the serum within the reference range. Twelve of 81 (15%) uremic patients have subsequently developed acute myocardial infarction (six patients; four died) or angina pectoris (six patients; one died). Eleven patients were specifically hospitalized for cardiac symptoms. One patient had acute myocardial infarction three weeks after renal transplant. With the use of the chi-square test and 2 X 2 contingency tables, patients with CK-MB in serum above 5 U/L by electrophoresis (chi 2 = 5.47; P less than 0.05) or at least 2.9 EU/L by the QuiCK-MB (chi 2 = 6.56; P less than 0.01) appeared to be at increased risk of subsequent hospitalization. The authors conclude that a slight increase of CK-MB in serum is found in most uremic patients. However, CK-MB elevated above reference range in the serum of uremic patients without clinical or electrocardiographic evidence of acute myocardial infarction is not common. When found, elevated CK-MB isoenzyme appears to be associated with an increased risk of subsequent cardiac disease. Therefore, quantification of CK-MB in the serum of uremic patients is more reliable than is implied in the literature.

Adult↗
PubMed1987

Development of metabolic alkalosis after massive transfusion during orthotopic liver transplantation.

Five patients undergoing orthotopic liver transplantation were investigated for changes in acid-base homeostasis secondary to large volume transfusions. All patients developed a transient acidemia during the operative period, followed by alkalemia which persisted into the early postoperative period. The patients received an estimated mean of 750 mEq of citrate, which appeared to cause metabolic alkalosis. The biochemical basis underlying the regulation of citrate metabolism that may have led to the timing, extent, and duration of the subsequent metabolic alkalosis is presented. Finally, the time course for the development of metabolic alkalosis may be a potentially sensitive indicator of early allograft function.

Acid-Base Imbalance↗
PubMed1987

Free drug monitoring.

The principles, technique of measurement, and clinical significance of free drugs are reviewed. Albumin, alpha-1-acid glycoprotein, and lipoprotein are the main drug-binding proteins in blood. Variations of the concentrations of these proteins owing to disease would result in changes in the free drug levels. These levels may be determined by equilibrium dialysis, ultrafiltration, and other techniques.

Blood Proteins↗
PubMed1987

Flucytosine (5-fluorocytosine).

Monitoring of flucytosine (5-FC) concentration in serum is of great importance. It may be anticipated that demand for this service will increase in the near future, because this drug is used in situations involving immunocompromised patients, including those afflicted with AIDS.

Flucytosine↗
PubMed1987

Cyclosporine controversies.

Cyclosporine is a potent immunosuppressant with low myelotoxicity. It is approved for use to prevent rejection of kidney, liver, and heart transplants, and is being investigated for possible use for suppression of graft-versus-host disease in patients who have received bone marrow transplants. Although cyclosporine is generally thought of as an immunosuppressive agent for use in conjunction with transplantation, there are investigations underway that could result in wider applications.

Cyclosporins↗
PubMed1986

Trazodone: a simple, clean extraction and rapid quantification by high pressure liquid chromatography.

We have developed an HPLC technique which is precise, rapid and reliable. Sample preparation involves simple alkaline extraction into an organic solvent mixture. Trazodone elutes at 3.2 min in this reverse phase system. There is no requirement for elevated column temperature. The method is linear to 3000 ng/ml. The availability of a technique which is transferrable to the clinical laboratory may help to define the proper role of therapeutic monitoring of trazodone.

Chlordiazepoxide↗
PubMed1986

The biological activity in vivo of recombinant murine interleukin 1 in the rat.

The present study summarizes the biological response of rats to infusion with recombinant murine IL-1 (rIL-1) cloned in Escherichia coli. Thirty-seven male rats (135-180 g) were infused over a 6-hr period with either 0.008 M guanidine hydrochloride (the vehicle) or E. coli product (both groups are controls) or 1000, 3750, 7500, 15,000, or 37,500 LAF units/hr of rIL-1. The controls and the group receiving 1000 LAF units/hr of rIL-1 did not exhibit a change in body temperature during the experiment. A mild fever was noted with 3750 LAF units/hr which became significantly elevated with 7500 and 15,000 LAF units/hr. At a dose of 37,500 LAF units/hr of rIL-1 (in 0.08 M guanidine hydrochloride) the rats became hypothermic and died. An equivalent dose of guanidine hydrochloride alone (0.08 M) was not fatally toxic although the rats did become hypothermic. Plasma zinc levels were significantly depressed and white blood cell count elevated at 6 hr postinfusion onset. Resting energy expenditure (REE) was significantly depressed during an infusion of 7500 and 15,000 LAF units/hr of rIL-1 despite a concurrent elevation in body temperature. Whole-body leucine kinetics were unchanged by infusion with rIL-1. Plasma fibrinogen and serum haptoglobin and copper levels were not altered by rIL-1. In conclusion, murine rIL-1 is similar to monocytic-derived IL-1 in that it produces a fever, hypozincemia, and leukocytosis; however, rIL-1 does not induce changes in protein metabolism.

Animals↗
PubMed1985

In vitro activity and mechanism of action of A21978C1, a novel cyclic lipopeptide antibiotic.

The in vitro activity of A21978C1, a novel cyclic polypeptide antibiotic, was compared with those of vancomycin, teichomycin, and several beta-lactam antibiotics against gram-positive bacteria. The new drug was at least as active as vancomycin against all species of streptococci and staphylococci tested, including methicillin-resistant Staphylococcus aureus and penicillin-resistant pneumococci. Activity of the drug was found to be strongly correlated with the calcium concentration in test media. Against enterococci, A21978C1 was bactericidal at concentrations near the MIC (MIC for 100% of the strains, 2 micrograms/ml), but combining that drug with gentamicin resulted in bactericidal synergism by time-kill methods. Studies were undertaken to examine the mechanism of action of the drug. A21978C1 did not interact with penicillin-binding proteins of bacterial cell membranes. No direct effect of the drug on the synthesis of DNA, RNA, or protein by a susceptible strain of Streptococcus faecalis could be demonstrated. However, A21978C1 inhibited peptidoglycan synthesis in early-log-phase cultures of both Streptococcus faecalis and Staphylococcus aureus.

Anti-Bacterial Agents↗