Corticosteroid-induced osteoporosis: effects of a treatment with slow-release sodium fluoride.
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Adrenal Cortex Hormones↗
Biomedical subjects
S Spector
Publications and source records attributed to S Spector.
Immediate and delayed type hypersensitivity to malathion.
Between December 1989 and June 1990, 1,874 reports of alleged malathion application related illness from repeated spraying of a mixture of malathion corn syrup bait to eradicate a Mediterranean fruit fly infestation in Southern California were received by the Toxics Epidemiology Program of Los Angeles County. Among these complaints were 47 reports of urticaria, 38 reports of angioedema and 213 reports of a nonspecific skin rash. In order to determine whether these alleged skin reactions were the result of an immediate or delayed type of hypersensitivity reaction to malathion or to the corn syrup bait we studied ten subjects referred for testing by the local health department. All ten subjects had no reaction on patch testing. One child exhibited a positive reaction to the bait and one child had irritant reactions to malathion and to the bait. This study documented one case of a possible immediate IgE reaction to malathion bait. Due to the low participation rates in this study, no specific conclusions concerning the rate of sensitivity in the population can be drawn, although it appears that such reactions are uncommon.
Adult↗
Effect of terfenadine in asthmatic patients.
The bronchodilator effect of terfenadine, 60-mg or 120-mg single dose, and 1 week twice daily dosing, was evaluated in 12 allergic asthmatic patients. When compared with baseline, FEV1 rose significantly for single dose 120 mg terfenadine at one, one and one-half, three, five and one-half, and six hours and for 60 mg terfenadine at three, five and one-half, six, and eight hours postdose. Variations in patient response were observed. At steady state, 120 mg terfenadine b.i.d. showed consistent improvement over placebo from three to 12 hours postdosing but no improvement in FEV1 was noted for terfenadine, 60 mg b.i.d. There no longer was a statistically significant difference in mean FEV1 or percent change from baseline. Thus, terfenadine proved to be a safe and a mild bronchodilator; however, tachyphylaxis might develop to the bronchodilator effect after 1 week of continuous b.i.d. dosing.
Asthma↗
Paradoxical bronchospasm after use of inhalation aerosols: a review of the literature.
Various formulations of beta-agonists and other bronchodilators have been associated with unexpected bronchoconstriction in certain individuals. Even though the number of affected individuals represents a relatively small percentage and the etiologies may differ among patients, it is important for the public to be aware of the potential for paradoxical bronchospasm and for the physician to investigate each case accordingly.
Administration, Inhalation↗
Changes of endogenous morphine and codeine contents in the fasting rat.
The alteration of endogenous opiate alkaloids during fasting state was investigated in rats. The concentrations of morphine and codeine in the cortex, midbrain, pons plus medulla, cerebellum, adrenal gland and pancreas were measured using radioimmunoassay for the opiates following high pressure liquid chromatography. The morphine and codeine contents of fasting rats showed maximum elevated levels in cortex, pons plus medulla and pancreas after 2 days of fasting, but after 1 day in midbrain. The opiate content of the cerebellum showed a tendency for a continuous increase during the 4 days. Adrenal glands of fasting rats had elevated levels at days 3 and 4, although there were great fluctuations within the groups.
Adrenal Glands↗
Peripheral-acting benzodiazepines inhibit the growth of human melanoma cells and potentiate the antiproliferative activity of recombinant human interferons.
In this study, we evaluated the effect of a series of peripheral-acting benzodiazepines (BZDs), alone and in combination with recombinant human leukocyte (IFN-alpha A), fibroblast (IFN-beta), or immune (IFN-gamma) interferon (IFN), on the growth of human melanoma cells. Specific peripheral-acting BZDs caused a marked suppression in the proliferation of human melanoma cells. The effect on melanoma cell growth required 72 h exposure to the peripheral-acting BZDs and was not observed if the compounds were removed by 48 h. The relative potency of antiproliferative activity of a series of peripheral-acting BZDs on human melanoma cell growth did not correlate with the reported ability of these agents to bind to peripheral sites on the cell membrane of Friend erythroleukemia cells (FELC), nor did they correlate with the ability of these agents to inhibit [3H]thymidine incorporation in FELC, induce differentiation in FELC, or inhibit neurite outgrowth in nerve growth factor-treated rat pheochromocytoma (PC12) cells. The growth of human melanoma cells was also inhibited by various recombinant human IFNs, with IFN-beta displaying greater antiproliferative activity than IFN-alpha A or IFN-gamma. When the peripheral-acting BZD Ro7-3351, which displays growth inhibitory properties when used alone, was combined with IFN, the antiproliferative activity of the combination was greater than either individual compound exerted independently. The combination of IFN-beta plus Ro7-3351 was more active in suppressing HO-1 melanoma cell growth than other IFN preparations in combination with this peripheral-type BZD. Even when combined with a peripheral-acting BZD, such as Ro5-4608, which displayed only marginal antiproliferative activity against human melanoma cells when applied alone, growth suppression of the combination of this peripheral-type BZD with all three types of IFNs was more than additive. These studies suggest that specific peripheral-acting BZDs, both alone and in combination with recombinant IFNs, display novel antiproliferative activity toward human melanoma cells which may involve a different genetic locus than previously observed in other model cell culture systems.
Antineoplastic Agents↗
Endogenous benzodiazepine receptor ligands in human and animal hepatic encephalopathy.
The role of endogenous benzodiazepine receptor ligands in the pathogenesis of hepatic encephalopathy was studied in humans and in rat models of hepatic encephalopathy. Endogenous benzodiazepine ligands were extracted from rat brain and human CSF by acid treatment and purification by HPLC. Detection and partial characterization of these endogenous benzodiazepine ligands were carried out using both radioreceptor binding assays and radioimmunoassays with anti-benzodiazepine antibodies. Four different benzodiazepine receptor ligands were identified in human and rat tissue, two of which may be diazepam and desmethyldiazepam, based on elution profiles and anti-benzo-diazepine antibody reactivity. Human CSF and serum from patients with hepatic encephalopathy contained approximately 10 times more endogenous benzodiazepine receptor ligand than CSF from controls or nonencephalopathic patients with liver disease. The levels of brain benzodiazepine receptor ligand compounds were also increased approximately 10-fold in rats suffering from fulminant hepatic failure, but not in rats with portacaval shunts, a model of chronic hepatic disease. The increased concentrations of these substances could be behaviorally significant and may contribute to the pathogenesis of hepatic encephalopathy.
Adult↗
Selectivity of some "specific" opioid ligands?
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Animals↗
Multicenter, double-blind, placebo-controlled trial of triamcinolone acetonide nasal aerosol in the treatment of perennial allergic rhinitis.
In a double-blind study involving 205 patients with perennial allergic rhinitis, statistically significantly greater symptomatic improvements were evident following the administration of 200 micrograms/day triamcinolone acetonide aerosol than following placebo. These improvements were evident as early as week 1 and were sustained throughout the 12-week study. They were accompanied by greater reductions in nasal eosinophils. Triamcinolone acetonide aerosol was well tolerated and had no effect on serum cortisol levels.
Administration, Intranasal↗
Phencyclidine blocks voltage-dependent potassium currents in murine thymocytes.
We investigated the effect of phencyclidine (PCP) on the voltage-dependent K+ current in whole cell recordings from murine thymocytes. PCP caused a dramatic, reversible and dose-dependent decrease of the current. An analysis of the dose-response relationship suggests a single site of action for PCP with an IC50 of 4.7 microM. Dextrorphan and naloxone also inhibited the current, although their effects were of a lower magnitude than those of PCP. Neither 10 microM dextrorphan nor 100 microM naloxone antagonized the inhibitory action of 10 microM PCP. The analysis of the dose-response curve for PCP in presence of 100 microM naloxone suggested that the two drugs act at the same site. We also investigated the effect of morphine on the K+ current. Morphine, in concentrations up to 100 microM, inhibited the K+ current less than dextrorphan or PCP. The kinetics and voltage dependence of the currents in the presence of morphine suggest that it interacts with a different site or different conformation of the channel than the other three compounds. Our findings show that certain opioids can act on thymocytes through a system completely different from the typical opioid receptors.
Animals↗
Presence of endogenous opiate alkaloids.
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Animals↗
Studies of HIV infection and the development of Epstein-Barr virus-related B cell lymphomas following transfer of human lymphocytes to mice with severe combined immunodeficiency.
Mice with severe combined immunodeficiency (C.B-17 scid, hereafter SCID) accept xenografts of adult human peripheral blood leukocytes (PBL). The transplanted human PBL expand in number and survive for at least thirteen months and have been shown to reconstitute human immune function at both the T and B cell levels. Human immunoglobulin production is restored, and secondary antibody responses to antigens such as tetanus toxoid can be induced. All SCID mice reconstituted with 50 x 10(6) or more PBL from donors with evidence of exposure to Epstein-Barr virus (EBV) have developed human B cell lymphomas at 8-16 weeks after PBL engraftment, whereas mice reconstituted with PBL from EBV-seronegative donors fail to develop tumors. These tumors involve both lymphatic and non-lymphatic organs, and histologically they resemble large cell or immunoblastic lymphomas. The tumors are associated with high levels of human immunoglobulin secretion and serum electrophoresis reveals oligoclonal immunoglobulin banding patterns. Analysis of tumor DNA shows the presence of EBV genomes and oligoclonal patterns of immunoglobulin JH gene rearrangement. Taken together, these observations suggest an EBV-related proliferation of B lymphocytes leading to the rapid appearance of oligoclonal B cell malignancies following transfer of B lymphocytes from "normal" donors to SCID mice. SCID mice reconstituted with PBL from EBV-seronegative donors have been infected with the LAV-1 strain of human immunodeficiency virus (HIV-1). Virus has been recovered from most infected animals by co-culture of mouse tissue with human T lymphoblasts. Some mice with high virus titers have developed an acute wasting syndrome and depletion of human T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Identification of the convulsant opiate thebaine in mammalian brain.
The convulsant opiate thebaine, an intermediate of morphine biosynthesis, was purified from bovine brain to homogeneity by gel filtration and high-performance liquid chromatography (HPLC) monitored by a radioimmunoassay. The immunoreactive material behaved identically to standard thebaine in two HPLC systems and was confirmed to be thebaine by combined gas chromatography/mass spectrometry. To our knowledge, the presence of thebaine in mammalian tissue has not been demonstrated previously. Codeine and morphine were also found to exist in ovine brain. The presence of thebaine in ovine brain provides strong evidence that morphine and codeine, in various mammalian tissues, are of endogenous origin and actually biosynthesized from a precursor.
Animals↗
Acquired immunodeficiency syndrome. Magnetic resonance patterns of brain involvement with pathologic correlation.
Magnetic resonance brain scans of 30 patients with either acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were reviewed. Twenty patients had focally abnormal neurological examination results at the time of scanning. Pathological diagnosis was available in nine. Four patterns of abnormality were observed on T2-weighted images. Multiple discrete high-signal foci (pattern A) were found in patients with toxoplasmosis and progressive multifocal leukoencephalopathy. Large, bilateral patchy to confluent high-signal areas within the white matter (pattern B) represented a white matter encephalitis secondary to cytomegalovirus or human immunodeficiency virus. Generalized enlargement of the cortical sulci and ventricles (pattern C) probably reflected atrophic changes from the chronic human immunodeficiency virus infection and prolonged debilitating illness. Solitary high-signal-intensity lesions (pattern D) suggested a nonviral opportunistic infection. Differential diagnosis of brain abnormalities in patients with AIDS can be assisted by recognition of these characteristic patterns.
Acquired Immunodeficiency Syndrome↗
One-year follow-up of cardiac and coronary artery disease in infants and children with Kawasaki disease.
Of 75 patients meeting clinical criteria for Kawasaki disease, 67 patients were followed with serial ECG and echocardiograms (echo) for at least 1 year. Sixteen patients had coronary artery aneurysms and three had dilated coronary arteries as assessed by initial two-dimensional (2D) echo and/or angiocardiographic studies. ECG findings of first and second-degree heart block and ST-T wave changes (36%) as well as M-mode echo abnormalities (45%) including pericardial effusion, decreased ventricular septal motion, and decreased left ventricular function were all normalized by 6 months, except in two infants who continued to have decreased function and flat ventricular septal motion. In four patients with single proximal coronary aneurysm and two with dilated coronary artery, resolution of lesions occurred by 1 year. Among 11 patients with multiple coronary aneurysms discovered by initial studies, the 2D echo became normal in seven and showed aneurysms in four as corroborated by angiogram. One patient with an isolated distal coronary aneurysm, not seen by initial or serial echo, had a normal follow-up angiogram. Our study suggests that in Kawasaki disease careful, serial, 2D echo is sufficient to monitor the course of coronary artery disease that tends to regress and follow a benign course. However, the long-term effects of this disease on cardiac and coronary arteries remain to be elucidated.
Child↗
Opioid binding site in EL-4 thymoma cell line.
Using EL-4 thymoma cell-line we found a binding site similar to the k opioid receptor of the nervous system. The Scatchard analysis of the binding of [3H] bremazocine indicated a single site with a KD = 60 +/- 17 nM and Bmax = 2.7 +/- 0.8 pmols/10(6) cells (51 pmols/mg total cell proteins). To characterize this binding site, competition studies were performed using selective compounds for the various opioid receptors. The k agonist U-50,488H was the most potent displacer of [3H] bremazocine with an IC50 value = 0.57 microM. The two stereoisomers levorphanol and dextrorphan showed the same affinity for this site (IC50 = 2.9 microM and 1.9 microM respectively). While morphine, [D-Pen2, D-Pen5] enkephalin and beta-endorphin failed to displace, except at very high concentrations, codeine demonstrated a IC50 = 60 microM, that was similar to naloxone (IC50 = 69 microM).
Analgesics↗
A multicenter evaluation of the clinical benefits of cromolyn sodium aerosol by metered-dose inhaler in the treatment of asthma.
The efficacy and safety of cromolyn sodium by metered-dose inhaler (MDI) (1 mg per actuation) was evaluated with a double-blind, placebo-controlled, parallel-study design. Subjects with asthma, aged 8 to 58 years, whose asthma was well controlled taking cromolyn sodium capsules by Spinhaler turboinhaler, plus beta 2-agonists, entered the study after being maintained with cromolyn sodium capsules for a minimum of 4 weeks. The investigation began with a 2-week control interval with cromolyn sodium capsules followed by a 4-week single-blind period with placebo capsules. Subjects whose asthma significantly worsened while they were receiving placebo therapy were then randomized to a 10-week double-blind phase in which they received either active cromolyn sodium or placebo by MDI. Efficacy variables included diary data, physician evaluation, and spirometry. Comparisons were made between baseline period scores and each assessment variable over time. Of 155 subjects entered, 93 qualified for the double-blind, randomized phase. Eighty-three subjects completed the study and were analyzed. At baseline there existed no significant differences between the active-treatment and placebo-treatment groups. Significant differences (p less than 0.05) in favor of the cromolyn sodium-treatment group, however, were noted at all time points for daily diary symptoms (cough, breathlessness, and overall asthma severity), physician's assessments at each clinic visit, physician's and patient's overall final assessments, FEV1 at each clinic visit, and FVC and peak expiratory flow rate at the final visit. Concomitant bronchodilator medication use was less in the cromolyn sodium-treatment group. Cromolyn sodium by MDI is highly effective for (1) controlling asthmatic symptoms, (2) improving lung functions, and (3) decreasing the need for concomitant bronchodilators.
Administration, Inhalation↗
Transformation of thebaine to oripavine, codeine, and morphine by rat liver, kidney, and brain microsomes.
Thebaine, an intermediate of morphine biosynthesis in the poppy plant, Papaver somniferum, was transformed to oripavine, codeine, and morphine by rat liver, kidney, and brain microsomes in the presence of an NADPH-generating system. The formation of morphine, codeine, and oripavine was identified by a specific RIA, HPLC, and GCMS. Thebaine also gave rise to four other compounds, which for the moment are unidentified. NADH dramatically increased the formation of both codeine and morphine when used together with an NADPH-generating system, especially in liver microsomes. NADPH is essential in the formation of oripavine from thebaine and morphine from codeine, while NADH is critical in the conversion of thebaine to codeine and from oripavine to morphine. Carbon monoxide or SKF 525A inhibited the conversion, indicating a role of cytochrome P-450. These results provide evidence for the enzymatic in vitro conversion by mammalian tissues of thebaine to morphine. The pathway is similar to that which exists in plants.
Animals↗