Pediatric cardiovascular effects of imipramine and desipramine

Electrocardiograms were evaluated in 39 children and adolescents before and after the clinical use of imipramine and desipramine. The average increase in PR interval was 0.01 seconds. The PR interval increased by 0.02 seconds in 11 subjects, and a new first-degree atrioventricular block developed in two subjects. These changes were not related to the choice between imipramine and desipramine, the dose, or the method of administration. An increase in PR interval by 0.02 seconds or more did correlate with having an abnormality disclosed on a pretreatment electrocardiogram. The average increase in PR interval was 0.007 seconds for subjects with normal baseline electrocardiograms and 0.019 seconds for subjects with conduction and nonconduction abnormalities disclosed in baseline tracings. None of the electrocardiogram changes resulted in adverse clinical consequences.     

A patient with lambda type light-chain disease associated with Crow-Fukase syndrome and autoimmune thrombocytopenia]

A 67-year-old woman, who presented polyneuropathy, pleural effusion, ascites and sclerosing changes in the ribs, was admitted to our hospital on June 17, 1987. On admission, cerebrospinal examination showed a marked protein-cell dissociation and a delay in nerve conduction velocity. Bence-Jones protein was detected in urine, and the immunohistochemical study of biopsied bone marrow of the rib revealed lambda-chain positive plasmacytoma. Serum immunoelectrophoresis, however, showed no monoclonal gamma-globulinemia. From the findings described above, she was diagnosed as having Crow-Fukase syndrome associated with lambda-type light chain disease. Even with a therapy by prednisolone, platelet counts progressively declined to 10,000/ml3. Bone marrow aspiration showed normal number of megakaryocytes. Since platelet-associated IgG was increased to 452 ng/1.0 x 10(8) plt, a diagnosis of autoimmune thrombocytopenia was considered. Melphalan and cyclophosphamide to plasmacytoma resulted in a marked improvement of platelets. In addition, the level of platelet-associated IgG returned to normal range. Polyneuropathy, however, didn't respond to those therapies. It was suggested that both Crow-Fukase syndrome and thrombocytopenia were closely concerned with plasmacytoma but developed in a different manner.     

Retrospective analysis of Naval Special Boards of Flight Surgeons, 1974-83

The Naval Special Board of Flight Surgeons was established in 1956 for the evaluation of Navy, Marine Corps, and Coast Guard problem aeromedical cases. This paper examines a sample 248 of these cases for the period of 1974-83 with respect to the characteristics of those referred, their referral diagnostic category, and the recommendation of the Special Board regarding return to a flying status. Those cases with a referral diagnostic category of ENT and Ophthalmology were less likely to be returned to flight status. Older, more senior pilots, and pilots with more total flight time were less likely to be returned to unrestricted flying than were their younger, more junior, and less experienced counterparts. Otherwise, no significant difference in outcome based on age, rank, marital status, branch of service, specialty, or flight hours was detected. Overall, 61% of those evaluated by the SBFS were returned to flight status.     

Effects of early reperfusion on the mechanical and biochemical characteristics of ischemic myocardium

Coronary reperfusion of ischemic myocardium may be beneficial but is highly dependent upon occlusion and reperfusion times. To study the effects of early reperfusion on ischemic myocardium, 24 open chest pigs underwent coronary occlusion; one group was occluded for 40 min, and the other was occluded for 30 min followed by 10 min of reperfusion. Left ventricular wall thickness during systole and diastole was determined by ultrasound. Mitochondrial energy production and calcium content were evaluated from ischemic and nonischemic areas. Results showed: There was an absence of systolic thickness, a slight decrease of diastolic thickness from baseline, and a decrease in energy production in the ischemic myocardium. Reperfusion resulted in a diverse pattern of systolic and diastolic wall thickness in the ischemic area and a variable Ca2+ accumulation and mitochondrial ATP production. The variability of myocardial Ca2+ accumulation in the ischemic reperfused group correlated inversely with mitochondrial ATP production (r = -0.94) and directly with diastolic wall thickness (r = 0.65). Similarly, calcium accumulation, ATP production, and diastolic wall thickness correlated with mean blood pressure during reperfusion. These results suggest that many factors including individual characteristics of the animal and experimental conditions such as the level of blood pressure and the degree of calcium accumulation may determine outcome of reperfusion even in as brief a period as 10 min.     

Direct observation in vitro of how neuroblasts migrate: medulla and cochleovestibular ganglion of the chick embryo

The hypothesis that neuroblasts migrate in the nervous system by a locomotory process was tested experimentally. An in vitro preparation permitted direct observation of postmitotic cells migrating from the rhombic lip of the medulla and the anlage of the cochleovestibular ganglion. Cell locomotion was not seen. Instead migration was produced by elongation of a leading process, followed by translocation of the nucleus (perikaryal translocation). On the basis of comparisons with previous observations in situ, we propose that this represents a common mode of migration in the developing nervous system. Cell clusters were explanted from the rhombic lip at the developmental stage when they migrate from the ventricular zone to the acoustico-vestibular anlage in the medulla. Cells from the cochleovestibular ganglion were explanted after migration from the otocyst, but before ganglionic differentiation. Each neuroblast's migration route was formed by an elongating leading process ending in a growth cone. The growth cone attached to other cells and processes or ended freely on an acellular substrate. Nonneuronal cells usually migrated as has been described for fibroblasts, yet with some of the features of perikaryal translocation, but some nonneuronal precursor cells may migrate the way neuroblasts do. Neuroblasts did not migrate preferentially on the processes of nonneuronal cells, although the reverse could be observed. In fact a variety of interactions between migratory cells, neuronal and nonneuronal, were observed. The advantage of the experimental system described here is that one can observe cells migrating spontaneously at the times in development when they normally do so, while preserving the cellular populations present in situ.     

Lack of effect of the calcium antagonist isradipine on cyclosporine pharmacokinetics in renal transplant patients.

Hypertension has emerged as a frequent side effect in transplant recipients on effective doses of cyclosporine (CsA). To control hypertension in renal transplant patients, calcium channel blockers have been used; some of these, however, have been shown to cause significant increases in CsA levels. These findings point out that possible interactions of each calcium antagonist with CsA deserve investigation. We performed an open, placebo-controlled study in 12 stable renal transplant recipients to determine whether short-term isradipine influences CsA pharmacokinetics. All patients had mild to moderate hypertension and received triple immunosuppressive therapy with CsA, azathioprine, and prednisolone. Throughout a 4-week period of isradipine treatment, blood CsA levels (specific and nonspecific monoclonal antibodies) remained stable. The mean trough specific level was 121 +/- 14 micrograms/L following placebo, compared to 120 +/- 14 micrograms/L during isradipine. Corresponding non-specific values were 465 +/- 68 and 474 +/- 63 micrograms/L. Also, values for Cmax, AUC, and t1/2 were not significantly changed following 4 weeks of isradipine. Mean arterial pressure was significantly reduced at the end of the study. This study implies that isradipine does not influence CsA metabolism. Further studies should be carried out to determine its long-term effects on CsA pharmacokinetics and renal function in transplanted patients.     

Regulatory control of indoor Rn

Regulation of indoor Rn is explored in the context of cost-effectiveness of regulatory action. Evaluation of cost (i.e., mitigation expenses) and benefits (i.e., savings associated with medical expenses and lost productivity related to lung cancer) at various action levels indicate that regulatory programs would be economically inefficient and unreasonable if standards were established at or below the current EPA action guide (150 Bq m-3 or less). For the approximately 95% of U.S. homes with Rn levels near or below 150 Bq m-3, government programs should continue to focus on public information and consumer protection. For the small number of homes with high Rn levels, government programs should focus on identifying high risk homes and encouraging homeowners to reduce Rn levels. Because of the potential for substantial risk reduction, such efforts would be cost-effective in these homes.     

A general multiple-compartment model for the transport of trace elements through animals.

Multiple-compartment models employed in the analysis of trace element transport in animals are often based on linear differential equations which relate the rate of change of contaminant (or contaminant concentration) in each compartment to the amount of contaminant (or contaminant concentration) in every other compartment in the system. This has the serious disadvantage of mixing intrinsic physiological properties with the geometry of the animal. The basic equations on which the model presented here is developed are derived from the actual physical process under way and are capable of separating intrinsic physiological properties from geometry. It is thus expected that rate coefficients determined through this model will be applicable to a wider category of physiologically similar animals. A specific application of the model for the study of contamination of sheep--or indeed for any ruminant--is presented, and the temporal evolution of contaminant concentration in the various compartments of the animal is calculated. The application of this model to a system of compartments with changing geometry is also presented.     

Dioxin treatment of rats results in increased in vitro induction of sister chromatid exchanges by alpha-naphthoflavone: an animal model for human exposure to halogenated aromatics

Recent reports have shown that alpha-naphthoflavone (alpha-NF) in vivo enhances the sister chromatid exchange (SCE) frequency in lymphocytes from human populations exposed to cigarette smoke or polychlorinated biphenyls and dibenzofurans. In this study, female Sprague-Dawley rats (9-11 weeks old) were administered a single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and killed 6 days after treatment. Blood cultures were established with or without alpha-NF. The baseline and alpha-NF-induced SCE frequencies were assessed in lymphocytes after a 72-hr culture period. No effect on the SCE baseline frequency (cultures without alpha-NF) was detected in rats exposed to 0-30 micrograms TCDD/kg. However, the SCE frequencies from cultures incubated in the presence of alpha-NF were significantly higher in lymphocytes from rats treated with TCDD. Moreover, delta SCE values (SCE alpha-NF minus SCE baseline) were significantly higher in lymphocytes from rats treated with TCDD than in controls. A dose-dependent increase in delta SCE values was observed between 0 and 3 micrograms TCDD/kg, followed by a plateau at higher doses. This induction pattern closely resembled the induction of the liver microsomal aryl hydrocarbon hydroxylase activity by TCDD. In contrast to TCDD, phenobarbital treatment of rats (75 mg/kg/day) had no effect on alpha-NF-induced SCE frequencies in lymphocytes. Liver microsomes from TCDD-treated rats metabolized alpha-NF at a rate much faster than that of control microsomes. These studies indicate that TCDD-exposed rats provide a useful model to investigate the mechanism of enhanced in vitro induction of SCE frequency in lymphocytes from humans exposed to toxic halogenated aromatics or cigarette smoke.     

Monitoring of intracellular Ca2+ elevation in a single neural cell using a fluorescence microscope/video-camera system

For monitoring the changes in intracellular free Ca2+ concentration ([Ca2+]i), we developed a simple system combining a fluorescence microscope, an image intensifier, a video-camera, a cathode ray tube display and a photodiode, employing quin2 as a Ca2+ indicator. We recorded increases of the fluorescence intensity due to [Ca2+]i rises, when high K+ medium, neurotransmitter and Ca2+ ionophore were applied to the single cells of nervous system origin in culture. The present system is capable of simultaneous detection of the [Ca2+]i changes from multiple separate cells.