PubMed HealthSearch

Biomedical subjects

P Goldberg

Publications and source records attributed to P Goldberg.

At least 19 recordsLinked to original sources

[Potential role of environmental and domestic exposure to tremolite in pleural cancer in New Caledonia].

A previous study of respiratory cancers in New Caledonia (1978-1987) showed an excess risk of pleural cancer in this South Pacific French Territory, leading to the identification of an environmental pollution. In some villages, the residents use for their houses a whitewash made from a rock derived from local outcroppings. Analysis of samples of rock and whitewash showed that they consisted of tremolite asbestos. High levels of tremolite were detected in airborne samples collected in these villages and in biological specimens of patients with pulmonary cancer or mesothelioma; the concentrations of fibers are up to 78,000 fibers per litre of air and 44 millions of fibers per gramme of dry tissue. Besides the whitewash, the environmental exposure to tremolite fibers could also be associated with certain occupations. A case control study under process will allow the estimation of respiratory cancer risks associated with the exposure to tremolite.

Air Pollutants

The effectiveness of regulations requiring periodic occupational hygiene monitoring.

The passing of regulations requiring periodic occupational hygiene monitoring surveys is one way of controlling workers' exposure to hazardous materials. The results of this study showed that this control is ineffective. The source of data was Occupational Hygiene Survey (OHS) records which were archived in the Institute for Occupational Health, Tel Aviv University and related only to workplaces that requested an OHS. The mean frequency of surveys carried out in the workplaces studied was significantly lower than the required one. Although the main factors required to ensure effective implementation of the regulations exist in Israel, i.e., monitoring services and enforcement authorities, excursions above permitted levels (overexposure) are still widely occurring. From all the measurements made over the study period (1989-1991) the ranges of overexposure were 31-75% for silica, 26-32% for talc, and 19-41% for lead. The results of the study highlighted the need to strengthen the authority of the bodies involved in occupational hygiene by increasing intervention. This could be achieved by enlarging the capabilities of the enforcement authorities by giving authority to occupational health physicians and to the organization carrying out the survey.

Environmental Monitoring

A worldwide study of the Huntington's disease mutation. The sensitivity and specificity of measuring CAG repeats.

BACKGROUND: Huntington's disease is associated with an expanded sequence of CAG repeats in a gene on chromosome 4p16.3. However, neither the sensitivity of expanded CAG repeats in affected persons of different ethnic origins nor the specificity of such repeats for Huntington's disease as compared with other neuropsychiatric disorders has been determined. METHODS: We studied 1007 patients with diagnosed Huntington's disease from 565 families and 43 national and ethnic groups. In addition, the length of the CAG repeat was determined in 113 control subjects with a family history of Alzheimer's disease (44 patients), schizophrenia (39), major depression (16), senile chorea (5), benign hereditary chorea (5), neuroacanthocytosis (2), and dentatorubropallidoluysian atrophy (2). The number of CAG repeats was also assessed in 1595 control chromosomes, with the size of adjacent polymorphic CCG trinucleotide repeats taken into account. RESULTS: Of 1007 patients with signs and symptoms compatible with a diagnosis of Huntington's disease, 995 had an expanded CAG repeat that included from 36 to 121 repeats (median, 44) (sensitivity, 98.8 percent; 95 percent confidence interval, 97.7 to 99.4 percent). There were no significant differences among national and ethnic groups in the number of repeats. No CAG expansion was found in the 110 control subjects with other neuropsychiatric disorders (specificity, 100 percent; 95 percent confidence interval, 95.2 to 100 percent). In 1581 of the 1595 control chromosomes (99.1 percent), the number of CAG repeats ranged from 10 to 29 (median, 18). In 12 control chromosomes (0.75 percent), intermediate-sized CAG sequences with 30 to 35 repeats were found, and 2 normal chromosomes unexpectedly had expanded CAG sequences, of 39 and 37 repeats. CONCLUSIONS: CAG trinucleotide expansion is the molecular basis of Huntington's disease worldwide and is a highly sensitive and specific marker for inheritance of the disease mutation.

Adult

Geographical distribution of haplotypes in Swedish families with Huntington's disease.

This study was planned to determine the number of origins of the mutation underlying Huntington's disease (HD) in Sweden. Haplotypes were constructed for 23 different HD families, using six different polymorphisms [(CCG)n, GT70, 674, BS1, E2 and 4.2], including two within the gene. In addition, extensive genealogical investigations were performed, and the geographical origin of the haplotypes was studied. Ten different haplotypes were observed suggesting multiple origins for the HD mutation in Sweden. Analysis of the two polymorphic markers within the HD gene (the CCG repeat and GT70) indicates that there are at least three origins for the HD mutation in Sweden. One of these haplotypes (7/A) accounts for 89% of the families, suggesting that the majority of the Swedish HD families are related through a single HD mutation of ancient origin. Furthermore, three of the families that were previously considered to be unrelated could be traced to a common ancestor in the 15th century, a finding that is consistent with this hypothesis.

Alleles

A 10-year incidence survey of respiratory cancer and a case-control study within a cohort of nickel mining and refining workers in New Caledonia.

The incidence of lung, pleural, nasal, larynx, and pharynx cancer in relation to work in the nickel mining and refining industry was studied from 1978 to 1987 in the male population of the French territory of New Caledonia in the South Pacific. The results showed no greater risk in the population of nickel workers than in the general male population. The incidence of respiratory cancer in New Caledonia was found to be comparable to that of industrialized countries, except for pleural cancer for which there was an excess risk in New Caledonia. A case-control study within the cohort of nickel industry workers comprised 80 lung cancer, 12 larynx cancer, 20 pharynx cancer cases, and 298 controls, and took account of 18 substances to which workers were exposed, five of them nickel compounds. None of the substances, or any other occupational variable, was shown to increase the risk of respiratory cancer, except for cancer of the larynx in relation to level and duration of exposure to dust and engine exhaust fumes on mining sites (odds ratios ranged from five to 5.4 and were significant). These results provide no evidence that exposures specific to the nickel industry in New Caledonia increase the risk of respiratory cancer. This might be due to the involvement of less airborne nickel than the amount observed in positive studies elsewhere. The high incidence of respiratory cancer in New Caledonia, compared with other South Pacific islands, might be attributable to an environmental risk connected with the presence of mineral fibers in the geologic strata, as well as to tobacco and alcohol consumption levels similar to those prevailing in France.

Age Factors

Respiratory mechanics in status asthmaticus. Effects of inhalational anesthesia.

The incidence and severity of bronchial asthma has increased considerably in recent years. As a result, the number of patients requiring mechanical ventilation and more intensive medical therapy for treatment of refractory asthma has also increased. Despite this, available information concerning the quantitative changes in respiratory mechanics and the response to treatment that occur in such patients is limited. The present study describes the abnormalities in respiratory mechanics and the response to isoflurane anesthesia observed in three adults mechanically ventilated for treatment of status asthmaticus. Airway pressure, flow, and volume were measured during controlled mechanical ventilation in which the airway was periodically occluded in order to determine respiratory system mechanics. In two patients, the volume of hyperinflation and expiratory volume-flow relationship were also obtained. Inspiratory and expiratory indices of respiratory resistance were markedly abnormal. These abnormalities were associated with significant dynamic hyperinflation and high levels of intrinsic PEEP. Expiratory flow limitation was also identified in two patients by failure of low levels of applied positive end-expiratory pressure (PEEP) to alter the expiratory volume-flow relationship. Indices of respiratory resistance as well as the magnitude of dynamic hyperinflation and intrinsic PEEP improved considerably with isoflurane administration, after having been refractory to intensive conventional bronchodilator therapy. In summary, these results demonstrate the severity of abnormalities in respiratory mechanics present in ventilated patients with status asthmaticus and the potential therapeutic efficacy of inhalational anesthesia in this setting.

Adult

Assessment of the extent of implementation of the recommendations made in occupational hygiene survey reports.

The extent of implementation of recommendations contained in field reports from the Occupational Hygiene Unit of the Institute for Occupational Health at the Tel Aviv University, was investigated. The results show that 33% were not carried out at all and 16% were only partially carried out. A number of factors influenced the extent of implementation, in particular the degree of involvement of the management in worker health and welfare, an active safety system in operation, the professional skill and seniority of the person in charge of safety, awareness by the workers of health and safety matters, the existence of a specific budget for health and safety and a regulatory system concerning occupational exposure.

Health Knowledge, Attitudes, Practice

Effect of partial substitution of invert sugar for sucrose in combination with Duraphat treatment on caries development in preschool children: the Malmö Study.

The aim was to study the effect of substitution of invert sugar for sucrose, in combination with fluoride varnish (Duraphat) treatment twice a year, on caries development in preschool children. One hundred and eighty-seven 4-years-olds were divided randomly into four sugar groups: (1) sucrose (S), (2) sucrose-Duraphat (SD), (3) invert sugar (I), and (4) invert sugar-Duraphat (ID). All families were asked to buy beverages, biscuits, breakfast cereals, marmalade, ice cream, jam, ketchup, sweets and table sugar, totally 32 different food items, sweetened with invert sugar or sucrose. The substitution was, thus, restricted to a number of sugar-rich between-meal products. The study was carried out double-blind for 2 years. The children of those parents who did not want to participate in the sugar groups were divided randomly into one of the following two groups: (5) Duraphat (D), and control (C). Because of lack of cooperation, only 114 of the 187 children (61%) were considered to have completed the study. The mean caries increment, including initial lesions, was 3.86 dmfs in the combined groups S and SD (n = 63) and 3.10 dmfs in the combined groups I and ID (n = 51) during the 2 years (p = 0.34). The corresponding values for the 2nd year only were 1.84 and 0.67 dmfs, respectively (p = 0.09). The mean caries increment was 2.86 dmfs in group D (n = 113) and 4.10 dmfs (p = 0.08) in group C (n = 93). If initial caries lesions were excluded from the index, the difference between groups D and C was significant (p = 0.008).(ABSTRACT TRUNCATED AT 250 WORDS)

Cariogenic Agents

Assessment of respiratory muscle dysfunction in chronic obstructive lung disease.

In COLD, the inspiratory muscles are severely disadvantaged by virtue of the hyperinflation that accompanies this disorder. Such mechanical disadvantage will lead clinically, in the stable patient, to the active recruitment of the accessory muscles of inspiration and to a pattern of rapid, shallow breathing that may be due to either peripheral (muscle) or central (neurogenic) influences thought to be linked to a critical tension-time index of the inspiratory muscles. This pattern appears to be all the more pronounced in the patient with acute respiratory failure and is frequently accompanied by disordered rib cage-abdominal movements. While these movements may reflect the muscles' attempts to stave off fatigue, they may also imply that if the imposed mechanical stress is unrelieved, muscle failure will ensue. In the laboratory, mechanical disadvantage is marked by diminished inspiratory mouth pressures. Because of wide scatter, a low mouth pressure beyond that which can be explained by hyperinflation alone should be confirmed by an assessment of Pesosniff or by the measurement of transdiaphragmatic pressure. Muscle endurance, also compromised in this condition, can be assessed indirectly by the measurement of MVV or MSVC, or more directly by an invasive assessment of the tension-time index and endurance time of the diaphragm or noninvasively by the Endurance Index of McKenzie and Gandevia. And finally, once muscle failure is pending or has been established, a program of muscle rest, either complete or partial, pharmacotherapy, and goal-specific training should be instituted.

Acute Disease

Single-dose effects of ibopamine hydrochloride on renal function in patients with congestive heart failure.

To examine the renal effects of ibopamine HCl we evaluated 15 patients with New York Heart Association Class II-III congestive heart failure and mild renal insufficiency (creatinine clearance [CLcr] = 45-85 ml min-1). Diuretics and vasodilators were withheld and a sodium (Na+)-restricted diet was initiated. All patients exhibited positive Na+ balance at the time of evaluation. Hourly urine volumes, urine chemistries, serum chemistries, PAH and inulin/iothalamate clearances were determined 2 h pre and 4 h post a single 200 mg oral dose of ibopamine. Effective renal plasma flow, creatinine clearance, filtration fraction, and the fractional excretion of sodium and potassium were not significantly altered postdose. A significant increase in urine output and decrease in urine osmolality were seen at all time points postdose. A significant reduction in serum potassium (2 and 3 h) and blood urea nitrogen (1, 3 and 4 h) concentrations occurred. Measurements of glomerular filtration rate by inulin or [125I]-iothalamate produced differing results in the patient groups studied. We conclude that a single dose of ibopamine does not produce significant improvements in renal function in patients with congestive heart failure, mild renal insufficiency and positive sodium balance.

Acute Kidney Injury

Continuous positive airway pressure reduces work of breathing and dyspnea during weaning from mechanical ventilation in severe chronic obstructive pulmonary disease.

Dynamic hyperinflation and the development of intrinsic positive end-expiratory pressure (PEEPi) are commonly observed in patients with severe chronic obstructive pulmonary disease (COPD) and acute respiratory failure. The presence of intrinsic PEEP acts as an inspiratory threshold load, and contributes significantly to the observed increase in work and oxygen cost of breathing. The present study examined the effects of continuous positive airway pressure (CPAP) (at 5, 10, and 15 cm H2O) and its ability to reduce the mechanical load imposed by PEEPi on breathing pattern, work of breathing, and dyspnea in seven patients with severe COPD during weaning from mechanical ventilation. Tidal volume remained stable at all levels of applied pressure. Breathing frequency was also stable except for a small (12%) decrease during CPAP of 15 cm H2O. Inspiratory pulmonary resistance and elastance were unaltered by the application of CPAP. There were progressive reductions in the inspiratory work of breathing as the level of CPAP increased. At the highest level of CPAP, the amount of inspiratory work performed per minute and per liter of ventilation decreased by 49.8 and 41.8%, respectively. Similar progressive reductions were also obtained in the pressure-time product for the inspiratory muscles and the diaphragm, which amounted to decreases of 42.9 and 42.2%, respectively, at the highest level of CPAP. End-expiratory lung volume remained stable at the lowest level of CPAP, with only modest increases occurring at the higher levels. In addition, all patients reported a reduction in dyspnea during the administration of CPAP.(ABSTRACT TRUNCATED AT 250 WORDS)

Dyspnea

ESR dates for the hominid burial site of Es Skhul in Israel.

The Middle East has been critical to our understanding of recent human evolution ever since the recovery of Neanderthal and early anatomically modern fossils from the caves of Tabun and Skhul (Mount Carmel) over 50 years ago. It was generally believed, on archaeological and morphological grounds, that middle eastern Neanderthals (such as those from Tabun, Amud and Kebara) probably dated from more than 50,000 years ago, whereas the earliest anatomically modern specimens (from Skhul and Qafzeh) probably dated from about 40,000 years. Recent thermoluminescence and electron spin resonance (ESR) determinations, however, have supported biostratigraphy in dating the Qafzeh deposits to an earlier part of the late Pleistocene, probably more than 90,000 years ago. These dates have been questioned on unspecified technical grounds, and it has also been argued that they create explanatory problems by separating the morphologically similar Qafzeh and Skhul samples by some 50,000 years, thus implying a long-term coexistence of early modern humans and Neanderthals in the area. Here we report the first radiometric dating analysis for Skhul, using ESR on bovine teeth from the hominid burial levels. Early uptake and linear uptake ages average 81 +/- 15 and 101 +/- 12 kyr respectively. These analyses suggest that the Skhul and Qafzeh samples are of a similar age and therefore it is possible that the presence of early modern humans in the area was episodic, rather than long-term during the early late Pleistocene.

Animals

Determinants of weaning and survival among patients with COPD who require mechanical ventilation for acute respiratory failure.

The decision to institute MV in patients with COPD and ARF is difficult because the risk of complications is high and the long-term prognosis is poor. We reviewed our experience with 95 COPD patients with ARF requiring MV. Fifty-five patients required MV for more than two weeks, 72 were weaned successfully, and 59 died within one year of follow-up. Survival was associated with premorbid level of activity (p less than .001), FEV1 (p less than .01), serum albumin level (p less than .05), and severity of dyspnea (p less than .01). Cor pulmonale on ECG, premorbid hypercarbia, and history of left ventricular failure were also more common among those who died. Weaning from MV was associated with premorbid level of activity (p less than .001), FEV1 (p less than .001), albumin level (p less than .05), and negative inspiratory pressure (p less than .001) and respiratory rate during T-piece trial (p less than .01). The duration of intubation was associated only with premorbid level of activity (p less than .01). Predictive models for the weaning success and the one-year survival were developed.

Actuarial Analysis

Direct effect of alpha-human atrial natriuretic peptide on human vasculature in vivo and in vitro.

1. The effect of a alpha-human atrial natriuretic peptide (1-28) (ANP) on human vasculature was investigated in vivo and in vitro. Possible involvement of vascular dopamine receptors and the renin-angiotensin system in the response to ANP was also studied in vivo. 2. Forearm blood blow was measured by venous occlusion plethysmography. Isolated human blood vessels were studied using conventional organ bath techniques. 3. ANP (0.1-1 microgram/min, intra-arterially) produced a dose-dependent increase in forearm blood flow, corresponding to a 163% increase in net forearm blood flow in the study arm. This action of ANP was not antagonized by (R)-sulpiride (100 micrograms/min, intra-arterially), a selective vascular dopamine receptor antagonist, or 50 mg of oral captopril, an inhibitor of angiotensin-converting enzyme. 4. ANP (1 nmol/l-1 mumol/l) produced concentration-dependent relaxation of isolated human arteries, including brachial artery, but was without effect on isolated human saphenous vein. 5. ANP produces vasodilatation in vivo and relaxes isolated human arterial smooth muscle. This action of ANP may contribute to its reported hypotensive effects in vivo.

Adult

Epidemiology of respiratory cancers related to nickel mining and refining in New Caledonia (1978-1984).

The incidence rate of respiratory (lung and upper respiratory tract) cancer related to the nickel industry was studied in the male population of New Caledonia over a 7-year period (1978-1984). The findings show no excess incidence of lung or upper respiratory tract (larynx, pharynx, nasal cavities) cancer cases in the population of nickel workers compared with the rest of the male population in New Caledonia. This result was corroborated by a case-control study which does not indicate any particular role of hazards specific to the nickel mining and refining industry. Our findings, which may be specific for the type of ore processed in New Caledonia, must nevertheless be confirmed by extending the study to a total of 10 years (1978-1987). The incidence rate of male respiratory cancer in New Caledonia was also compared to that of cancers of this type reported in certain regions of industrialized countries (Australia, France, U.K., USA). Such findings are very similar to those observed in New Caledonia, thereby confirming a predominant role of tobacco and alcohol consumption in a territory which, despite certain characteristics of a developing country, has life-style habits similar to those of industrialized countries.

Adult

No evidence for a direct vasodilatory effect of celiprolol on human vasculature in vivo or in vitro.

Celiprolol is reported to be a new cardioselective beta blocker with novel ancillary properties including vasodilator effects. The purpose of this study was to investigate whether celiprolol possesses a direct vasodilatory effect on human vasculature in vivo and in vitro. We studied the in vivo effects of intra-arterial celiprolol (1-100 micrograms/min i.a.) on forearm blood flow (FBF). Forearm blood was measured by venous occlusion plethysmography. Possible vasorelaxant actions of celiprolol on human vascular smooth muscle were studied using segments of isolated human saphenous vein in vitro. The effect of celiprolol was investigated on resting tone or noradrenaline induced tone. Possible alpha 2-adrenoceptor antagonist effects of celiprolol were assessed using celiprolol as an antagonist of BHT933 induced constriction. Celiprolol was without significant effect on FBF and failed to relax isolated saphenous vein segments preconstricted with noradrenaline. The weak alpha 2-adrenoceptor antagonist action of celiprolol was demonstrable in human saphenous vein. This study does not provide evidence for a direct vasodilatory effect of celiprolol on human vasculature.

Adrenergic beta-Antagonists

The actions of calcitonin gene related peptide and vasoactive intestinal peptide as vasodilators in man in vivo and in vitro.

1 The two peptides calcitonin gene related peptide (CGRP) and vasoactive intestinal peptide (VIP) produced marked dilatation of the forearm vascular bed when infused via the brachial artery. 2 CGRP relaxed preconstricted segments of human radial, coronary, gastric and cerebral arteries in an endothelium dependent manner. 3 VIP relaxed human gastric and transverse cervical arteries in an endothelium dependent manner, but relaxation of the human pulmonary artery was not dependent on endothelium. 4 The characteristics of the endothelium dependent relaxation of these medium-sized muscular arteries indicated involvement of the endothelium derived relaxing factor in vitro. 5 Caution is expressed in drawing comparisons between the mechanisms involved in the in vivo and in vitro vascular responses.

Adult