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Biomedical subjects

M Brodsky

Publications and source records attributed to M Brodsky.

At least 37 records · Page 2Linked to original sources
PubMed1995

CNS levels of mu opioid receptor (MOR-1) mRNA during chronic treatment with morphine or naltrexone.

The CNS levels of mu opioid receptor (MOR-1) mRNA were determined by solution hybridization in rats treated chronically with morphine or naltrexone. Morphine treatment (2 x 75 mg pellets were implanted SC on Day 1 and 2 more on Day 4) resulted in the development of tolerance to morphine's antinociceptive (analgesic) effect, as assessed by the hot plate procedure on treatment Day 7. Following the hot plate test, selected CNS regions were obtained by microdissection. The levels of MOR-1 mRNA in pg/microgram RNA ranged from 0.7 in sensorimotor cortex to 15.3 in medial thalamus. MOR-1 mRNA levels were not altered in the dorsal horn of spinal cord, nucleus raphe magnus, periaqueductal grey, hypothalamus, medial thalamus, or sensorimotor cortex. In a separate experiment, a 2 day exposure to naltrexone (2 x 30 mg pellets) had no effect on CNS levels of MOR-1 mRNA; however, after an 8 day exposure a decrease was detected in the nucleus raphe magnus (by 28%), hypothalamus (by 21%), and medial thalamus (by 27%). Chronic exposure to morphine or naltrexone did not result in alterations in the size of full-length MOR-1 mRNA from rat brain, or in the size of the region protected by the MOR-1 riboprobe (i.e., the entire coding region). Thus, the neuroadaptive processes associated with the development of analgesic tolerance to morphine do not involve concurrent changes in the steady-state levels of MOR-1 mRNA. Chronic treatment with naltrexone appears to produce a region-specific downregulation of MOR-1 mRNA levels, which may be secondary to the naltrexone-induced increase in mu receptor binding.

Animals↗
PubMed1995

Dextromethorphan shows efficacy in experimental pain (nociception) and opioid tolerance.

The oral antitussive dextromethorphan is a clinically available N-methyl-D-aspartate receptor antagonist. Dextromethorphan has analgesic efficacy in the experimental formalin test, blocks the nociceptive activation of the immediate-early gene, c-fos proto-oncogene, and prevents and reverses the development of opiate analgesic tolerance in experimental models. These data suggest that dextromethorphan should be evaluated in a controlled clinical trial for analgesic efficacy in zoster-associated neuralgia.

Dextromethorphan↗
PubMed1994

Supraspinal delta opioid receptor mRNA levels are not altered in [D-Ala2]deltorphin II tolerant mice.

Delta opioid receptor (DOR) mRNA levels were studied in mice rendered tolerant to [D-Ala2]deltorphin II by 4 days of repeated intracerebroventricular administration (10 micrograms, [tid]). ED50 determinations on day 5 revealed a 10-fold loss in [D-Ala2]deltorphin II potency with the tail-flick test. Utilization of a microdissection technique followed by quantitative solution hybridization of RNA extracts from mouse brain revealed mean levels of DOR mRNA ranging from 3.9 pg/micrograms RNA in the caudate-putamen to 0.4 pg/micrograms RNA in the cerebellum. DOR mRNA levels were not different when RNA extracts from tolerant and non-tolerant mice were compared. These data suggest that altered DOR mRNA levels are not one of the adaptive changes that occur with delta opioid ([D-Ala2]deltorphin II) tolerance.

Animals↗
PubMed1994

Comparative effects of the combination of digoxin and dl-sotalol therapy versus digoxin monotherapy for control of ventricular response in chronic atrial fibrillation. dl-Sotalol Atrial Fibrillation Study Group.

To establish the value of adjuvant dl-sotalol to digoxin for control of the ventricular response in chronic atrial fibrillation, 60 patients were evaluated in a multicenter, randomized, double-blind, parallel, placebo-controlled study. Patients were evaluated with serial ambulatory ECG monitoring and exercise testing during stable digoxin dosing and then with the addition of either a placebo or dl-sotalol, 80 mg/day, or dl-sotalol, 160 mg/day. The combination of digoxin and dl-sotalol, at either 80 or 160 mg/day, resulted in a statistically significant reduction in heart rate at rest and with exercise during both exercise testing and ambulatory monitoring. No significant difference was observed between the two doses of dl-sotalol. There was no significant difference with regard to symptoms or side effects among the three groups. In summary, dl-sotalol was noted to be a safe and effective adjuvant to digoxin for control of the ventricular response in chronic atrial fibrillation.

Atrial Fibrillation↗
PubMed1994

Fluoxetine for childhood anxiety disorders.

OBJECTIVE: The objective of this open study was to determine the efficacy and safety of fluoxetine for the treatment of children and adolescents with anxiety disorders. METHOD: Twenty-one patients with overanxious disorders, social phobia, or separation anxiety disorder, who were unresponsive to previous psychopharmacological and psychotherapeutic interventions, were treated openly with fluoxetine for up to 10 months. Patients with lifetime histories of obsessive-compulsive disorder (OCD) or panic disorder, or with current major depression, were excluded. Beneficial and adverse effects of fluoxetine were ascertained using the improvement and severity subscales of the Clinical Global Impression Scale (CGIS) in two ways: (1) independent chart reviews by two child psychiatrists and (2) prospective assessments by the treating nurses and the patients' mothers. RESULTS: Eighty-one percent (n = 17) of patients showed moderate to marked improvement in anxiety symptoms. The severity of anxiety as measured by the CGIS was also significantly reduced from marked to mild (effect size: 2.3). There were no significant side effects. CONCLUSIONS: These results suggest that fluoxetine may be an effective and safe treatment for nondepressed children and adolescents with anxiety disorders other than OCD and panic disorder. Future investigations using double-blind, placebo-controlled methodologies are warranted.

Adolescent↗
PubMed1993

Metrazole induces the sequential activation of c-fos, proenkephalin, and tyrosine hydroxylase gene expression in the rat adrenal gland: modulation by glucocorticoid and adrenocorticotropic hormone.

The immediate-early gene c-fos (a nuclear transcription factor) has been viewed as a nuclear "third messenger" or cellular "master switch." Both in vitro and in vivo studies have suggested that the proenkephalin (Penk) and tyrosine hydroxylase (TH) genes are potential targets of this immediate-early gene. We investigated the relationships between the activation of the c-fos gene and the activation of the Penk and TH genes in both rat hippocampus and adrenal using a commonly used model, metrazole (MTZ)-induced convulsions. The administration of MTZ produced a sequential elevation in c-fos, preproenkephalin (PPenk), and TH mRNAs. One hour after MTZ administration, c-fos mRNA was increased about 10-fold in rat hippocampus and about 5-fold in rat adrenal, without a significant change in spinal cord levels. Immunocytochemistry revealed that Fos-like immunoreactivity was greatly increased in both hippocampus and adrenal medulla at 3 hr after MTZ administration. The levels of PPenk and TH mRNAs were significantly increased (5-fold and 3-fold, respectively) in the adrenal 6 hr after MTZ treatment. The effects of MTZ on c-fos, PPenk, and TH mRNAs were dose dependent in both adrenal and hippocampus. In the adrenal, both the basal levels and the MTZ induction of PPenk mRNA were significantly attenuated by hypophysectomy (hypox) and were partially reinstated by adrenocorticotropic hormone (ACTH) replacement. In contrast, the basal levels of c-fos and TH mRNAs were not altered in hypox rat adrenal. ACTH treatment completely blocked the MTZ induction of adrenal c-fos mRNA and the subsequent induction of Fos-like immunoreactivity, whereas MTZ increased PPenk and TH mRNAs nearly 3-fold. Thus, in hypox rats MTZ can increase adrenal c-fos and TH mRNA levels without a corresponding increase in PPenk mRNA, whereas in ACTH-treated rats PPenk and TH mRNA levels in adrenal can be increased by MTZ without a preceding increase in c-fos mRNA. The MTZ induction of c-fos appears neither sufficient nor always necessary for the subsequent MTZ induction of Penk and TH gene expression. We conclude that c-fos, Penk, and TH genes can be differentially regulated in the adrenal of hypox rats or animals treated with ACTH, although they are co-localized in the same medullary cells.

Adrenal Glands↗
PubMed1992

New-onset ventricular tachycardia during pregnancy.

During evaluation for palpitations, presyncope, or syncope, seven pregnant women had documented ventricular tachycardia. Before pregnancy none had a history of significant cardiac disease or symptomatic arrhythmia. The tachycardia rate ranged from 117 to 250 beats/min and lasted up to 65 seconds. Arrhythmia evaluation in five of the patients suggested catecholamine-sensitive ventricular tachycardia. This diagnosis was supported by either a positive relation to exercise or isoproterenol infusion, suppression of arrhythmia by beta-blockade or sleep, and lack of induction of arrhythmia by programmed electrical stimulation of the heart. The arrhythmias resolved in one patient soon after evaluation and in one other patient after 2 months of controlling therapy. Five other patients continued to receive therapy throughout pregnancy. Delivery was accomplished in all patients without significant maternal or neonatal complications.

Echocardiography↗
PubMed1992

The incidence of illicit drug use in the United States, 1962-1989.

Epidemiological descriptions of drug abuse in the US in the last three decades have generally not included data on the patterns and trends in the incidence of illicit drug use (i.e. new users). In this paper, estimates of illicit drug use incidence are presented, based on retrospective data from the National Household Survey on Drug Abuse. Incidence of marijuana use began increasing in the 1960s and reached a peak in 1973, after which a continuing decline was seen. Cocaine use incidence began to increase in the late 1960s and reached a peak in 1982, then declined.

Adolescent↗
PubMed1992

Beneficial effects of pimobendan on exercise tolerance and quality of life in patients with heart failure. Results of a multicenter trial. The Pimobendan Multicenter Research Group.

BACKGROUND: This multicenter trial was conducted to determine the efficacy and safety of pimobendan, an inotropic agent with calcium-sensitizing properties and activity as a phosphodiesterase inhibitor, in patients with heart failure. METHODS AND RESULTS: One hundred ninety-eight ambulatory patients with symptoms of moderate to severe heart failure despite therapy with digitalis and diuretics with or without a single vasodilator were randomly assigned to receive either placebo (n = 49) or pimobendan (n = 149) in a double-blind fashion for 12 weeks. A dose range of pimobendan was used including 2.5 (n = 49), 5 (n = 51), or 10 mg/day (n = 49). One hundred fifty-eight (80%) patients were taking a converting enzyme inhibitor (CEI) and 28 (14%) patients were taking a non-CEI vasodilator. At end point, the 5-mg dose of pimobendan significantly increase exercise duration compared with placebo (121.6 +/- 19.1 seconds, p less than 0.001), whereas the 10-mg dose produced an increase of borderline significance (81.1 +/- 19.5 seconds, p = 0.05). Peak VO2 was significantly increased by 2.23 +/- 0.58 ml/kg/min in the 5-mg group (p less than 0.01 versus placebo). Furthermore, quality of life measured with the Minnesota Living With Heart Failure Questionnaire improved by 8.5 +/- 2.3 units in the 5-mg group compared with 1.3 +/- 2.2 units in the placebo group (p less than 0.01). There were a total of 23 all-cause hospitalizations in the placebo group, which was significantly greater compared with 33 in the three groups treated with pimobendan (p less than 0.01). There were no significant differences between the placebo and pimobendan groups with respect to changes in ejection fraction and plasma norepinephrine measured at baseline and at the completion of the 12-week study, proarrhythmic effect, or the number of patients with a significant adjustment in background therapy. Eleven patients died, including three (6%) on placebo and eight (5%) on pimobendan (p = NS). Among all adverse events, headache tended to be more common in the pimobendan groups compared with placebo, with the incidence increasing with dose (p less than 0.05). CONCLUSIONS: These data demonstrate that pimobendan significantly increases exercise duration, peak VO2, and quality of life in patients with heart failure. Pimobendan appears to be useful adjunctive therapy when added to digitalis, diuretics, and vasodilators.

Analysis of Variance↗
PubMed1991

Cloning of the cDNA of the heme-regulated eukaryotic initiation factor 2 alpha (eIF-2 alpha) kinase of rabbit reticulocytes: homology to yeast GCN2 protein kinase and human double-stranded-RNA-dependent eIF-2 alpha kinase.

We have cloned the cDNA of the heme-regulated eIF-2 alpha kinase (HRI) of rabbit reticulocytes. In vitro translation of mRNA transcribed from the HRI cDNA yields a 90-kDa polypeptide that exhibits eIF-2 alpha kinase activity and is recognized by a monoclonal antibody directed against authentic HRI. The open reading frame sequence of the HRI cDNA contains all 11 catalytic domains of protein kinases with consensus sequences of protein-serine/threonine kinases in conserved catalytic domains VI and VIII. The HRI cDNA also contains an insert of approximately 140 amino acids between catalytic domains V and VI. The HRI cDNA coding sequence has extensive homology to GCN2 protein kinase of Saccharomyces cerevisiae and to human double-stranded-RNA-dependent eIF-2 alpha kinase. This observation suggests that GCN2 protein kinase may be an eIF-2 alpha kinase in yeast. In addition, HRI has an unusually high degree of homology to three protein kinases (NimA, Wee1, and CDC2) that are involved in the regulation of the cell cycle.

Amino Acid Sequence↗
PubMed1986

Cyclosporine eyedrops for the treatment of severe vernal keratoconjunctivitis.

Twelve children with severe chronic vernal keratoconjunctivitis participated in a pilot study aimed at evaluating the effect of 2% cyclosporine eyedrops on the clinical course and symptoms of this disease. Eleven of the 12 children showed improvement after the first week of treatment. Nine patients demonstrated persistent improvement at the completion of the treatment schedule after six weeks. However, although seven of the children were symptom-free while being treated, only three were free of disease two months after cessation of the cyclosporine eyedrops. The other nine showed rapid recurrence of their symptoms.

Child↗
PubMed1985

Treatment of blood hyperviscosity with calcium dobesilate in patients with diabetic retinopathy.

This double-blind randomized trial was carried out on 37 patients with diabetic retinopathy and blood hyperviscosity. 19 patients received calcium dobesilate in capsules of 500 mg 3 times daily for 3 months and 18 patients took 3 placebo capsules daily during the same period. Calcium dobesilate was found to reduce whole-blood viscosity in a statistically significant manner which was accompanied by a diminution of the albumin/globulin ratio and a significant reduction of fibrinogen and cholesterol levels. A statistically significant diminution of capillary fragility was also observed in the calcium dobesilate-treated group. These results indicate that calcium dobesilate, by restoring the integrity of the microvessels, and by lowering blood viscosity, could act favorably on the evolution of diabetic retinopathy.

Adult↗
PubMed1984

Magnesium therapy in massive digoxin intoxication.

A potentially fatal case of massive digitalis intoxication is presented. Recurrent ventricular fibrillation failed to respond to lidocaine or phenytoin, but responded dramatically to magnesium sulfate infusion. A review of the literature and previous clinical studies, as well as the case reported here, appears to indicate that magnesium sulfate given intravenously in adequate quantities (2 to 3 g in one minute followed by 2 g/h for 4 to 5 h) is effective in controlling ventricular irritability caused by toxic levels of digitalis preparations.

Digoxin↗