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Biomedical subjects

H Gelband

Publications and source records attributed to H Gelband.

At least 19 recordsLinked to original sources

The science and politics of dental amalgam.

Dental amalgam--a mixture of elemental mercury and a silver-dominated metal alloy--has been the most widely used dental filling material for well over a century. Alternative materials exist but are not well suited for some important applications, and all are more expensive than amalgam. The toxic effects of occupational mercury exposure have long been known, but it was not until about 1980 that serious consideration was given to the possibility that mercury vapor escaping from amalgam fillings might be affecting health, specifically producing subtle effects on the central nervous system. Such effects have been reported among dentists and other dental personnel, whose exposures are well below industrial levels but above those from fillings alone. No large studies have been completed that examine the effects of mercury exposure from dental amalgam fillings. In the face of inadequate evidence on the possible risks of dental amalgam, countries have reacted desperately. Sweden is phasing out amalgam entirely, possibly by the end of 1997. Germany has produced guidelines for limiting its use, other countries have signaled their intention to reduce it, and others--the United States and Canada--have studied the matter but taken no action. Policy differences within Europe have made dental amalgam a test case for the European Community's new medical device regulations. Relatively little epidemiologic research has been initiated to try to answer the question of dental amalgam's possible health effects. An international effort to define and carry out a research agenda to guide public policy is called for.

Central Nervous System Diseases

Ca2+ release from intracellular stores is an initial step in hypoxic pulmonary vasoconstriction of rat pulmonary artery resistance vessels.

BACKGROUND: A reduction in oxygen tension in the lungs is believed to inhibit a voltage-dependent K+ (Kv) current, which is thought to result in membrane depolarization leading to hypoxic pulmonary vasoconstriction (HPV). However, the direct mechanism by which hypoxia inhibits Kv current is not understood. METHODS AND RESULTS: Experiments were performed on rat pulmonary artery resistance vessels and single smooth muscle cells isolated from these vessels to examine the role of Ca2+ release from intracellular stores in initiating HPV. In contractile experiments, hypoxic challenge of endothelium-denuded rat pulmonary artery resistance vessels caused either a sustained or transient contraction in Ca2+-containing or Ca2+-free solution, respectively (n=44 vessels from 11 animals). When the ring segments were treated with either thapsigargin (5 micromol/L), ryanodine (5 micromol/L), or cyclopiazonic acid (5 micromol/L) in Ca2+-containing or Ca2+-free solution, a significant increase in pulmonary arterial tone was observed (n=44 vessels from 11 animals). Subsequent hypoxic challenge in the presence of each agent produced no further increase in tone (n=44 vessels from 11 animals). In isolated pulmonary resistance artery cells loaded with fura 2, hypoxic challenge, thapsigargin, ryanodine, and cyclopiazonic acid resulted in a significant increase in [Ca2+]i (n=18 cells from 6 animals) and depolarization of the resting membrane potential (n=22 cells from 6 animals). However, with prior application of thapsigargin, ryanodine, or cyclopiazonic acid, a hypoxic challenge produced no further change in [Ca2+]i (n=18 from 6 animals) or membrane potential (n=22 from 6 animals). Finally, application of an anti-Kv1.5 antibody increased [Ca2+]i and caused membrane depolarization. Subsequent hypoxic challenge resulted in a further increase in [Ca2+]i with no effect on membrane potential (n=16 cells from 4 animals). CONCLUSIONS: In rat pulmonary artery resistance vessels, an initial event in HPV is a release of Ca2+ from intracellular stores. This rise in [Ca2+]i causes inhibition of voltage-dependent K+ channels (possibly Kv1.5), membrane depolarization, and an increase in pulmonary artery tone.

Animals

Diethylcarbamazine salt in the control of lymphatic filariasis.

Where lymphatic filariasis has diminished since about the 1950s, it has most frequently, though not always, been a direct result of chemotherapeutic intervention against the parasite. Diethylcarbamazine (DEC), a well-established drug, has been the single agent of chemotherapeutic control and has been successful in a wide variety of regimens. This paper reviews the experience with one strategy: long-term, low-dose treatment through DEC-medicated common salt. Diethylcarbamazine-medicated salt played a major role in the Chinese filariasis control program and has been successful in more limited trials in India, Brazil, and Tanzania. It is not being used today in any endemic area, but the evidence suggests that it is safe, effective, and relatively inexpensive. Enough is already known about the beneficial effects of DEC-medicated salt from community-wide studies to develop specific guidelines for its use in community programs.

Animals

Social and economic factors and the control of lymphatic filariasis: a review.

Formal control programmes do not exist for lymphatic filariasis in much of the endemic world. The literature on the social, economic and clinical impacts of the disease is so sparse as to provide virtually no guidance on whether the disease should be accorded more importance in national or local public health programmes. This type of research is a major priority. Putting together what little is known about the socioeconomic determinants of filariasis with the fairly extensive experience in control leads to a finding that control programmes must be undertaken at the community level to be effective. Diethylcarbamazine (DEC) is a readily available and apparently safe drug that can be deployed successfully for community control. While research currently is exploring the potential for individuals to protect themselves with DEC or a newer drug, ivermectin, community-wide control is unlikely to be achieved in that way. Under some special circumstances, controlling the mosquito vectors may be sufficient to control the disease, and in other cases, it may complement chemotherapy, but in general, it cannot be relied upon as a primary measure. DEC may be used in a variety of regimens which vary in their cost, duration, incidence of side effects and degree of community participation. Some, including DEC-medicated salt, are particularly attractive alternatives for many filariasis-endemic areas. The search for less expensive, yet effective, control options must continue, and this requires research not only into the costs of the various options, but also into the determinants of community acceptance, compliance and participation.

Animals

Selective pulmonary and systemic vasodilator effects of amrinone in children: new therapeutic implications.

OBJECTIVES: The present study was performed to determine the systemic and pulmonary hemodynamic effects of amrinone in infants and children with a cardiac left to right shunt to determine if there is a beneficial effect on the pathophysiology of this condition. BACKGROUND: Amrinone is a bipyridine derivative with inotropic and vasodilator effects that have not been systematically evaluated in the pediatric patient with increased pulmonary blood flow. METHODS: Nineteen patients (aged 2 months to 8.3 years) with one or more left to right shunts were evaluated during cardiac catheterization with direct hemodynamic measurements made before and 10 min (peak effect) after administration of a bolus injection of amrinone, 3 mg/kg body weight. The Fick method was used to calculate pulmonary and systemic blood flow, and resistances were then calculated. RESULTS: In group A, five patients with normal pulmonary artery pressure and resistance, amrinone significantly reduced mean pulmonary artery pressure by 19%, mean left atrial pressure by 39% and systemic vascular resistance by 17%. In group B, seven patients with pulmonary artery hypertension (mean pulmonary artery pressure > 20 mm Hg) and normal pulmonary vascular resistance (total pulmonary resistance < or = 3 Wood U.m2), amrinone significantly reduced the pulmonary artery pressure by 27%, systolic aortic pressure by 5%, mean aortic pressure by 12%, pulmonary arteriolar resistance by 36% and total pulmonary vascular resistance by 26%. In group C, seven patients with pulmonary artery hypertension (mean pulmonary artery pressure > 20 mm Hg) and elevated pulmonary vascular resistance (total pulmonary resistance > 3 Wood U.m2), amrinone significantly reduced the pulmonary arteriolar resistance by 49%, total pulmonary resistance by 47% and pulmonary arteriolar/systemic vascular resistance ratio by 45% and increased the heart rate by 15%. CONCLUSIONS: In children with a cardiac left to right shunt, amrinone 1) appears to have selective vasodilator effects depending on the pulmonary artery pressure and resistance, 2) has a beneficial hemodynamic effect in children with normal pulmonary artery pressure and resistance, and 3) may have a role in the treatment of patients with pulmonary artery hypertension without causing systemic hypotension.

Amrinone

Methodology of OTA's report on drug labeling in developing countries.

This article discusses the methodology of the OTA Project on Drug Labeling in Developing Countries. This report describes (a) the process of the project; (b) observations from a field visit to Thailand; (c) the development of the multinational pharmaceutical industry; and (d) influences on multinational pharmaceutical companies from their home countries, host countries, international organizations, self-regulation, and public interest groups. The results of the assessment will appear in the final report to Congress.

Consumer Advocacy

Relation of age to effects of phentolamine and phenylephrine on heart.

In the present study, the responses of neonatal and adult dog hearts to phenylephrine (PE) and phentolamine (PA) were investigated in order to determine the influence of age factors. PA resulted in the slowing of the heart rate, the prolongation of corrected sinus node recovery time, atrial refractory period (ARP), ventricular effective refractory period (VERP), and ventricular functional refractory period (VFRP), and a significant inhibition of conducting tissues in neonatal dogs. In contrast, no such effects were seen in adult dogs. PE had a positive chronotropic effect in neonatal dogs but no such effect in adult dogs. In conclusion, alpha-adrenoceptors played an important excitatory role in the neonatal dog heart.

Age Factors

Synergistic hypotensive effect of vasoactive intestinal polypeptide and alpha-blockade with phentolamine. Evidence for vasoactive intestinal peptide alpha-adrenoceptor coupling in the cardiovascular system of newborn dogs.

Vasoactive intestinal polypeptide (VIP) is a neuropeptide with potent circulatory effects in the adult animal and human. Little is known about its effects or mechanism of action in the immature animal. These series of experiments evaluated the effects and possible mechanism of action of VIP on the developing canine cardiovascular system. In all three series, measurements of mean heart rate and blood pressure were taken in the control state, after parasympathetic denervation with bilateral cervical vagotomies, and after autonomic blockade with propranolol (1 mg/kg) and phentolamine (0.5 mg i.v.). In series 1, we characterized the role of alpha-adrenergic receptors in early newborn puppies by investigating the hemodynamic effects of phentolamine alone in five early newborn puppies. In series 2, the hemodynamic effects of intravenous VIP infusion (0.2 microgram/kg/min) were recorded and compared in six early newborn puppies and in 10 late newborn puppies. In series 3, the hemodynamic effects of phentolamine in the presence of VIP receptor binding inhibitor were studied. In early newborn puppies, VIP had essentially no effect on heart rate or blood pressure until phentolamine was given; then, blood pressure decreased by 17% (p less than 0.005). In late newborn puppies, VIP resulted in an increase in heart rate in the control state but not after parasympathetic or sympathetic denervation. In early newborn puppies, phentolamine alone resulted in a 24% decrease (p less than 0.005) in blood pressure, compared with a 54% decrease (p less than 0.005) in early newborn puppies preexposed to VIP infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Comparisons of the electrophysiological effects of intravenous sotalol and propranolol on the immature mammalian heart.

Sotalol is a beta blocker that has also been reported to exert class III antiarrhythmic effects. To evaluate the effects of sotalol on the immature heart, and specifically to assess the relative importance of its class III action, the electrophysiologic effects of incremental doses of intravenous dl-sotalol (cumulative dose of 8 mg/kg) were studied in 11 intact canines (ages 4-15 days) utilizing intracardiac programmed stimulation and electrogram recording techniques. These results were compared to the electrophysiologic effects obtained in an additional 14 neonatal canines given 0.6 mg/kg of the beta blocker propranolol intravenously. Sotalol caused a greater increase than propranolol in the resting sinus cycle length (45 vs. 4%). Importantly, sotalol resulted in greater increases in atrial and ventricular muscle refractoriness than did propranolol (AERP--77 vs. 4%, AFRP--57 vs. 6%; VERP--53 vs. 4%, VFRP--51 vs. 7%). Thus, the electrophysiologic effects of sotalol include large changes in myocardial refractoriness that are not observed with simple beta blockade induced by propranolol. These results suggest that sotalol exerts a significant class III effect in the immature mammalian heart, and thus may be useful as an antiarrhythmic agent in the neonate.

Analysis of Variance

Effects of hypoxia on calcium fluxes and force development in the neonatal rat atrium.

The effects of hypoxia on 45calcium fluxes and force development were studied in the resting and stimulated (high potassium/low sodium solutions or Bay K 8644) neonatal rat atrium. Under normoxic conditions, high potassium (100 mmol.litre-1)/low sodium Tyrode solution and Bay K 8644 (2.5 X 10(-5) mol.litre-1) significantly increased calcium uptake above that measured in normal Tyrode solution. High potassium/low sodium Tyrode solution elicited a sustained tonic contracture. Bay K 8644 did not increase resting tension but induced spontaneous phasic contractions in some preparations. Hypoxia failed significantly to alter resting calcium uptake but partially inhibited (50-90%) the high potassium/low sodium and Bay K 8644 induced calcium uptake (that is, the calcium uptake above that measured in normal Tyrode solution). The magnitude of the high potassium/low sodium induced contracture was increased by hypoxia (15 min). Bay K 8644 had no effect on resting tension (in five out of six experiments) after 15 min of hypoxia. Acidosis failed to affect resting (with the exception of the 210 min time point), high potassium/low sodium induced, and Bay K 8644 induced calcium uptakes and had little effect on the high potassium/low sodium induced contracture. It is hypothesised that hypoxia reduces the cells' ability to regulate calcium. Furthermore, it appears that hypoxia's effects on calcium fluxes and the high potassium induced contracture involve other mechanisms besides the associated acidosis.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy

The non-catecholamine-mediated electrophysiological effects of intravenous bethanidine sulfate on the immature mammalian heart.

In a preliminary study, we found that bethanidine sulfate had important electrophysiologic effects on the neonatal canine heart, specifically that bethanidine increased atrial effective and functional refractory periods. Other effects (increase in heart rate blood pressure and enhanced atrioventricular conduction) were thought to be due to a release of endogenous catecholamines. To investigate the non-catecholamine-mediated effects of bethanidine, we administered 10 mg/kg i.v. bethanidine to eight neonatal puppies ages 6-14 days pretreated with 0.6 mg/kg of propranolol and compared them with a control group of six neonates that received propranolol followed by a placebo. In the bethanidine group, the mean atrial effective and functional refractory periods increased significantly from 58 to 109 ms and from 108 to 185 ms, respectively (p less than 0.0001). Bethanidine also caused a decrease in resting heart rate (from 154 beats/min postpropranolol to 144 beats/min postbethanidine, p less than 0.002). These effects were not observed in the placebo group. Wenckebach periodicity during incremental atrial pacing did not change significantly. There was a modest increase in the ventricular refractory periods following bethanidine. Thus, the direct electrophysiologic effects of bethanidine in the neonate include a significant prolongation of atrial refractoriness and a decrease in sinus node automaticity. Ventricular refractory periods, while increased, did not show the dramatic prolongation exhibited by the atrium. The atrial specificity of bethanidine is unique and may prove useful in the treatment of supraventricular arrhythmias in the neonatal period.

Animals

Electrophysiologic and hemodynamic effects of bethanidine sulfate on the immature mammalian heart.

The cumulative electrophysiologic and hemodynamic effects of bethanidine sulfate (2.5, 5, 10 and 15 mg/kg i.v.) were studied in 9 canine neonates and 7 adult dogs. Increased heart rate, blood pressure and enhanced atrioventricular nodal function, observed in both groups, and decreased ventricular refractory periods and inducibility of ventricular arrhythmias seen in the adult, are probably related to a bethanidine-mediated release of catecholamines. However, in spite of the catecholamine release, bethanidine sulfate results in a significant prolongation of atrial refractoriness, this effect being quantitatively more important in the neonate than in the adult.

Aging

Atrioventricular nodal function in the immature canine heart [corrected and republished article orginally printed in Pediatr Res 1987 Nov;22(5):616-20].

Previous studies have suggested that the atrioventricular nodal functional refractory period in the neonate is equal to or shorter than that of the ventricle, providing little or no protection to the ventricle against rapid atrial rates and allowing closely coupled atrial beats to fall within the ventricular vulnerable period. We evaluated atrioventricular node function in 21 mongrel neonatal puppies, 3-15 days old, and 15 adult dogs utilizing intracardiac His bundle recording and stimulation techniques. The mean atrioventricular nodal functional refractory period (173.1 +/- 20.0 ms) exceeded both the ventricular effective refractory period (139.5 +/- 14.3) and ventricular functional refractory period (163.3 +/- 14.5) in the neonates. Furthermore, the atrioventricular node was the site of limiting antegrade conduction in all neonates. No ventricular arrhythmias were induced by atrial extrastimulation in any of the neonates. The site of conduction delay during atrial extrastimulation was confined to the atrioventricular node in 15/16 neonates (94%) while 1/16 (6%) had combined nodal and infranodal delay. The neonates developed Wenckebach, at significantly faster heart rates than the adults, but both groups developed Wenckebach at approximately twice the resting heart rate. Retrograde conduction was a consistent finding in the neonates. However, antegrade Wenckebach occurred at a significantly faster heart rate than retrograde Wenckebach suggesting different functional properties. Our data suggest that in the neonatal canine, the atrioventricular node functional refractory period is longer than both the ventricular effective refractory period and ventricular functional refractory period. Furthermore, the degree of protection offered by the neonatal atrioventricular node to the ventricle appears to be comparable to that of the adult.

Animals

In vivo demonstration of maturational changes of the chronotropic response to alpha-adrenergic stimulation.

In vitro studies suggest that neonates and adults may have different cardiac chronotropic responses to alpha-adrenergic stimulation. To investigate these differences in vivo, three groups of dogs were studied. Group I = 12 puppies, ages 3-7 days; group II = 12 puppies ages 8-15 days, and group III = seven adult dogs. Heart rate and blood pressure determinations were made in the control setting and then after combined beta-adrenergic and parasympathetic blockade (propranolol 0.6 mg/kg and bilateral vagotomies). Alpha-stimulation was then achieved with phenylephrine given in doses of 0.5, 1.0, and 10.0 micrograms/kg/min. A second, high dose of propranolol (1.0 mg/kg intravenously) was administered after the highest phenylephrine infusion dosage to assure complete beta-blockade. Finally, alpha-blockade was achieved with phentolamine (groups I and II: 0.5 mg intravenously; group III: 5.0 mg intravenously). An alpha-mediated positive chronotropic effect was observed in 42 and 100% of subjects in groups I and II, respectively, but never observed in the adults. Whereas alpha-blockade with phentolamine resulted in a large decrease in heart rate of all puppies (groups I and II), it had no effect on adults. Blood pressure responses were similar in all three groups. Thus, there are important maturational changes in the chronotropic response to alpha-adrenergic stimulation and blockade demonstrable in the intact neonatal canine.

Aging