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Biomedical subjects

H Gelband

Publications and source records attributed to H Gelband.

At least 19 recordsLinked to original sources
PubMed2000

Vaccines for preventing malaria.

BACKGROUND: Despite continued efforts to control the disease, malaria remains a major health problem in many regions of the world, especially sub-Saharan Africa, and new ways to control or eradicate the disease are urgently needed. Two types of vaccine, SPf66 vaccine against the asexual stages, and NANP vaccines against the sporozoite stages of the Plasmodium parasite, have been tested in randomised clinical trials in endemic areas. OBJECTIVES: To assess the effects of malaria vaccines. SEARCH STRATEGY: The Cochrane Infectious Diseases Group trials register, the Cochrane Controlled Trials Register, Medline, Embase and reference lists of articles were searched. Organisations and researchers in the field were contacted. SELECTION CRITERIA: Randomised trials comparing vaccines against Plasmodium falciparum, P. vivax, P. malariae or P. ovale, and placebo. DATA COLLECTION AND ANALYSIS: Two independent reviewers assessed trial quality and conducted data extraction. MAIN RESULTS: Thirteen efficacy trials involving about 7700 people were included. There were nine trials of the Spf66 vaccine and four trials of the NANP vaccines. There was large heterogeneity between trials when investigating the effect of SPf66 in reducing incidence of the first attack of P. falciparum malaria. When trials were subcategorised by location, there was no evidence for effect of SPf66 in reducing incidence of P. falciparum in four African trials conducted in children under 5 years of age (Peto odds ratio [OR] = 0.96, 95% confidence interval [CI] 0.81 to 1.14). In five trials outside Africa with participants aged 2 years to adult, there was a reduction in incidence by SPf66 vaccine (Peto OR = 0.77, 95% CI 0.67 to 0.88, fixed effects model). Significant heterogeneity remained between trials conducted outside Africa. Using a random effects model for these five trials, the OR was 0.74 (95% CI 0.54 to 1.01). In five trials, there was no evidence for effect of the SPf66 vaccine on the incidence of the first attack of P. vivax malaria (OR 1.01, 95% CI 0.87 to 1.17). Trials to date have not indicated any severe adverse effects of SPf66 vaccine. In three trials of NANP-based vaccines, there was no evidence for protection by these vaccines against P. falciparum malaria (OR 1.12, 95% CI 0.64 to 1.93). REVIEWER'S CONCLUSIONS: There is no evidence for protection by SPf66 vaccines against P. falciparum in Africa. There is a modest reduction in attacks of P. falciparum malaria following vaccination with SPf66 in other regions. Further research with SPf66 vaccines in South America may be justified. Trials to date have not been of sufficient size to evaluate the effect of malaria vaccines on mortality or on severe malaria requiring admission to hospital. There was not enough evidence to evaluate the use of NANP vaccines.

Adult↗
PubMed2000

Regimens of less than six months for treating tuberculosis.

BACKGROUND: WHO recommends 6 months of treatment in TB programmes. OBJECTIVES: The purpose of this review is to assess the effects of regimens lasting less than 6 months compared with longer regimens in the treatment of active TB. SEARCH STRATEGY: Search strategy: MEDLINE 1955-, Cochrane Infectious Diseases Trials Register, existing reviews, and researchers in the field. Date of the most recent search: January 1999. SELECTION CRITERIA: Randomized trials comparing two or more TB drug regimens, in which at least one regimen was <6 months and it was compared with at least one regimen that lasted longer, in any patients with active TB. DATA COLLECTION AND ANALYSIS: One reviewer extracted data and assessed trial quality. MAIN RESULTS: Seven trials with a total of 9 comparisons of <6 months (range: 2-5 months) versus longer treatment were included. About 2200 patients were in the shorter regimens and about 1900 in the longer regimens (the same comparison groups were used for more than one shorter regimen, in two studies). Relapse rates were consistently higher after shorter duration treatment regimens, regardless of the comparison made, though they were all relatively low. Results were significantly better in the longer groups in the meta-analyses of 2, 3, and 4 months of treatment vs longer treatment (Peto OR = 6.1 [95%CI 2.19,17.01], 3.67 [2.42,5.58], 3.64 [1.71,7. 75] but not in the single trial of 5 vs. 7 months (Peto OR = 2.24 [0. 90,5.59]. Relapse rates after longer (comparison) regimens ranged from 0-7% at one year (or more), and in the shorter treatment arms, they ranged from 1-9% in 8 trials, and18% relapsed in the one remaining. There was little or no difference in the rates of adverse reactions or toxicity requiring a change of regimen or discontinuation of treatment. The "sterilizing efficacy" at the end of treatment varied little among treatments, providing no predictive value for relapse rates. Few or no deaths were reported in the individual trials, and in no case did enough deaths occur for a comparison of short vs. long regimens. REVIEWER'S CONCLUSIONS: Longer periods of treatment (at least up to 6 months) result in higher success rates in patients with active TB, but the differences are small. Under field conditions, where adherence to treatment is a big problem, and shorter regimens might improve adherence, these differences may not be evident. A comparison of <6 months vs. 6 months of treatment under programme conditions would be needed to determine this.

Antitubercular Agents↗
PubMed1999

Treating neurocysticercosis medically: a systematic review of randomized, controlled trials.

OBJECTIVE: To summarize the evidence from randomized controlled trials on the effects of cysticidal therapy used for treating human cysticercosis. METHODS: Published and unpublished studies in any language identified through MEDLINE (1966 - June 1999) specialized databases, abstracts, proceedings and contact with experts were analysed. Those which compared, using randomized or quasi-randomized methods, any cysticidal drug with placebo or symptomatic therapy were entered in the study. Data were extracted independently by two reviewers and trial quality assessed. Meta-analysis using fixed effects models calculated provided there was no significant heterogeneity, expressed as relative risk. RESULTS: Four trials met the inclusion criteria, treating intraparenchymatous neurocysticercosis with either albendazole or praziquantel compared to placebo or no treatment. In the two trials reporting clinical outcomes, treatment was not associated with a reduction in the risk of seizures, although numbers were small (RR 0.95, 95% CI 0.59-1.51). Four trials reported radiological outcomes, and cysticidal treatment was associated with a lower risk of cyst persistence of scans taken within six months of start of treatment (RR 0.83, 95% CI 0.70-0.99). Subsidiary analysis assuming different outcomes in patients lost to follow-up did not alter the findings of the main analysis. CONCLUSIONS: There is insufficient evidence to determine whether cysticidal therapy is of any clinical benefit to patients with neurocysticercosis. The review does not exclude the possibility that more patients remain seizure-free when treated with cysticidal drugs. Further testing through placebo-controlled trials is required.

Albendazole↗
PubMed1998

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↗
PubMed1997

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↗
PubMed1994

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1993

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↗
PubMed1991

Pediatric cardiac electrophysiology.

Over the past year, many advances have been made in the management of cardiac arrhythmias in the pediatric patient. It has become evident that the new surgical procedures for congenital cardiac disease can result in arrhythmia-associated morbidity and mortality. New pharmacologic agents such as adenosine have been shown to be efficacious in treating supraventricular tachycardias, and other agents such as flecainide, beta-blockers, and amiodarone are also of significant value in young patients with acute and chronic arrhythmias. Along with advances in the use of pharmacologic agents, pacing catheter techniques for the diagnosis and treatment of cardiac arrhythmias have also significantly progressed. Transcatheter ablation is safe and effective in our patient population, and an understanding of various pacemaker modalities and the physiologic parameters for optimum use have been defined. This review outlines the advances in all modes of treatment of cardiac arrhythmias.

Anti-Arrhythmia Agents↗
PubMed1990

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↗
PubMed1989

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↗
PubMed1988

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↗