PubMed HealthSearch

Biomedical subjects

B Gerson

Publications and source records attributed to B Gerson.

At least 19 recordsLinked to original sources

Urinary 3-methoxy-4-hydroxyphenylglycol and the depression-type score as predictors of differential responses to antidepressants.

Pretreatment 24 hr urinary 3-methoxy-4-hydroxyphenylglycol (MHPG) levels and the Depression-type (D-type) scores (derived from a multivariate discriminant function equation based on levels of urinary catecholamines and metabolites) were examined as possible predictors of antidepressant responses to either imipramine or alprazolam. In the case of imipramine, the responders had significantly lower pretreatment urinary MHPG levels (p = 0.002) and D-type scores (p less than 0.001) than did nonresponders. In contrast, responders to the antidepressant effects of alprazolam had significantly higher pretreatment urinary MHPG levels (p less than 0.05) and D-type scores (p = 0.02) than did nonresponders. For each antidepressant treatment, D-type scores appeared to provide a better separation of responders from nonresponders than did urinary MHPG levels. For each drug, the effect size for the difference in mean log-transformed D-type scores between responders and nonresponders was greater than the effect size for the difference in mean log-transformed MHPG levels. The difference between the effect sizes was statistically significant for imipramine (p = 0.02) and tended toward significance for alprazolam using two-tailed tests. These results suggest that the D-type equation, which was initially derived to separate bipolar manic-depressive depressions from other subgroups of depressive disorders, can also be used to predict differential responses to certain antidepressant drugs in patients with unipolar depressions.

Adult

In vitro comparison of HMPAO and gentisic acid for labelling leukocytes with 99mTc.

Leukocytes can be labelled with 99mTc using HMPAO and gentisic acid methods. We compared the two methods with respect to labelling efficiency on mixed leukocytes and isolated polymorphonuclear (PMN) and mononuclear (MN) cells, and the in vitro stability of the label. HMPAO produced approximately 70% labelling efficiency on mixed or PMN cells and the label was stable in saline or plasma. Labelling efficiency on MN was only 14% and was less stable. Gentisic acid produced a labelling efficiency of 52% on PMN and 35% on MN; both were stable in saline but less stable in plasma. In conclusion, HMPAO produces higher labelling efficiency and the label shows greater in vitro stability in plasma. However, gentisic acid is much less expensive to use, allows labelling of MN cells, and should result in more favourable microdosimetry. Preliminary clinical results suggest that gentisic acid is equivalent to HMPAO but has the advantage of being much cheaper.

Costs and Cost Analysis

A kit for labelling erythrocytes or leukocytes with technetium-99m.

A pretinning method for labelling erythrocytes with technetium-99m (99mTc) in vitro has been developed using a kit which contains stannous chloride stabilized with gentisic acid. Labelling efficiency was 97.3% (SD 1.4%) for 80 patients. The method requires less time than the Brookhaven kit and results in a smaller volume for reinjection but provides equivalent clinical results. We have previously shown that leukocytes labelled with 99mTc using the same gentisic acid kit are clinically equivalent to those labelled with HMPAO; thus, the kit is versatile and cost-effective.

Erythrocytes

Alcohol.

Ethyl alcohol is readily available and is, therefore, a frequent cause of poisoning. Alcohol is also an important substance of abuse. The author discusses the approaches to medicolegal alcohol determinations. The pharmacokinetics of alcohol are explained, and ramifications for substance abuse testing are examined.

Adult

Technical aspects of quantification of aluminum.

Aluminum has been implicated as a contributing factor to dialysis encephalopathy syndrome (DES) and osteomalacic osteodystrophy. Monitoring of its level together with i-PTH, desferoxamine infusion test, or bone biopsy gives the degree of intoxication. Specimens for aluminum must be collected in containers washed in nitric acid or disodium EDTA to avoid contamination. Determination is made with flameless atomic absorption spectrometry or neutron activation. Various experimental conditions for the former together with discussion on their merits and shortcomings are given. Included are protein precipitation, matrix modification, background correction, and sampling technique.

Aluminum

Lead.

This article reviews historical and current uses of lead and sources of absorbed lead, such as water, lead-based paint, cookware, and bullet wounds. The means of absorption, collection of specimens, quantification methods, and effects of lead toxicity are discussed.

Absorption

Understanding digoxin use in the elderly patient.

There are many disease states in the elderly that mandate the use of drugs with extremely narrow therapeutic indexes and potentially fatal toxicity. Digoxin is one example of such drugs. It is extensively used for the treatment of congestive heart failure of diverse origin and of cardiac arrhythmias of supraventricular origin. Aging can produce changes in essentially all organ systems, which as a whole render geriatric patients particularly vulnerable to the toxic effects of digoxin. Among all age-related pharmacokinetic and pharmacodynamic changes, declining renal function is perhaps the most important factor that must be considered. This often means a significantly less efficient renal digoxin clearance, which necessitates a reduction in dosage. The geriatric population tends to consume more drugs and are more at risk for undesirable multidrug interactions than their younger counterparts. To name a few, quinidine, verapamil, amiodarone, and non-K(+)-sparing diuretics are notorious for predisposing the patient to digoxin toxicity when administered concurrently with digoxin. Therefore, digoxin must be prescribed to elderly patients with great judiciousness, with careful interpretation of serum digoxin assay, and due consideration of its intrinsic limitations.

Aged

Toward a biochemical classification of depressive disorders. X. Urinary catecholamines, their metabolites, and D-type scores in subgroups of depressive disorders.

Data on 24-hour urinary levels of catecholamines and metabolites were determined in 114 depressed patients. For each patient, a D-type score was calculated, using a discriminant function equation that was previously derived using data from an independent group of depressed patients. Of all measures, D-type scores provided the highest sensitivity and specificity for separating bipolar/schizoaffective-depressed patients from all remaining patients or from those patients with unipolar nonendogenous depressions. Using Research Diagnostic Criteria (RDC), bipolar I patients demonstrated significantly lower D-type scores than did all other RDC depressive subtypes, including bipolar II disorders. Similar findings were observed using the Clinical Inventory for the Diagnosis and Classification of Affective Disorders (CIDCAD) system: bipolar/schizoaffective patients demonstrated significantly lower D-type scores than all remaining subtypes, including diagnostically unclassifiable, probable bipolar patients (a category somewhat akin to RDC bipolar II disorder). Data pointed to the heterogeneity of bipolar disorders. Catecholamine and metabolite data in this study were compared with recent studies of others.

Adolescent

Technetium-99m dithiocarbamates as potential brain agents: evaluation of aliphatic and amine-containing analogues.

Technetium-99m forms a lipophilic complex with diethyldithiocarbamate (DDC) but this complex is not retained in the brain as is thallium-201 DDC. We therefore prepared a series of aliphatic and amine-containing analogues of DDC and evaluated the properties of their 99mTc complexes in vitro and in vivo. The ethyl acetate/buffer partition coefficients of the amine-containing derivatives showed a response to pH. Four of the five complexes were less stable than DDC in vitro and showed greater retention in rabbit brain. These agents warrant further investigation for cerebral perfusion imaging with SPECT.

Animals

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

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

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

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

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

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

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