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Biomedical subjects

P Goldberg

Publications and source records attributed to P Goldberg.

At least 37 records · Page 2Linked to original sources
PubMed1998

Role of inducible nitric oxide synthase in endotoxin-induced acute lung injury.

The role of nitric oxide (NO) in lung injury remains unclear. Both beneficial and detrimental roles have been proposed. In this study, we used mutant mice lacking the inducible nitric oxide synthase (iNOS) to assess the role of this isoform in sepsis-associated lung injury. Wild-type and iNOS knockout mice were injected with either saline or Escherichia coli endotoxin (LPS) 25 mg/kg and killed 6, 12, and 24 h later. Lung injury was evaluated by measuring lactate dehydrogenase activity in the bronchoalveolar lavage, pulmonary wet/dry ratio, and immunostaining for nitrotyrosine formation. In the wild-type mice, LPS injection elicited more than a 3-fold rise in lactate dehydrogenase activity, a significant rise in lung wet/dry ratio and extensive nitrotyrosine staining in large airway and alveolar epithelium, macrophages, and pulmonary vascular cells. This was accompanied by induction of iNOS protein and increased lung nitric oxide synthase activity. By comparison, LPS injection in iNOS knockout mice elicited no iNOS induction and no significant changes in lung NOS activity, lactate dehydrogenase activity, lung wet/dry ratio, or pulmonary nitrotyrosine staining. These results indicate that mice deficient in iNOS gene are more resistant to LPS-induced acute lung injury than are wild-type mice.

Animals↗
PubMed1998

Intrathoracic and extrathoracic sources of exhaled nitric oxide in porcine endotoxemic shock.

OBJECTIVES: Nitric oxide (NO), a highly reactive species produced by the activity of NO synthases (NOS), is normally present in the exhaled air of humans and animals. Exhaled NO concentration increases significantly in humans with sepsis and animals, but neither the source nor NOS isoforms responsible for this rise in pulmonary NO production are known. The main objective of this study is to determine the sites and the mechanisms of enhanced NO production in the exhaled air of endotoxemic pigs. DESIGN: Randomized, controlled, animal study. SETTING: University-based animal research facility. SUBJECTS: Thirteen pathogen-free adult female pigs (22 to 27 kg). INTERVENTIONS: Anesthetized pigs were divided into two groups: control and lipopolysaccharides (LPS) (septic) groups. In both groups, extrathoracic (upper airways, nasal, and paranasal) and intrathoracic (bronchi, bronchioles, and alveoli) compartments were ventilated equally with two separate ventilators connected to two tracheal tubes. The LPS group received slow infusion (over 2 h) of Escherichia coli endotoxin (10 microg/kg/h), whereas saline solution was infused into the control group. Expired air of the two compartments was collected throughout the 2-h observation period. The animals were then killed and the lungs were quickly excised and frozen. MEASUREMENTS: Hemodynamic variables were measured in both groups. NO concentration in the exhaled air of both compartments was measured with a chemiluminescence analyser. Pulmonary NOS activity was evaluated by measuring the conversion of L-[2,3H]-arginine to L-[2,3H]-citrulline, and pulmonary expression of NOS was evaluated by immunoblotting. RESULTS: Baseline NO concentration in both groups was significantly higher in the extrathoracic vs intrathoracic compartment (average of 5.2 vs 3.4 parts per billion). Endotoxin infusion elicited a significant and early (after 45 min) rise in exhaled NO concentration in the extrathoracic compartment. Exhaled NO in the intrathoracic compartment also rose significantly but after 90 min of endotoxin infusion. Measurement of lung NOS activity showed a substantial rise in Ca++/calmodulin-dependent activity in the LPS group with no rise in Ca++/calmodulin-independent activity. Immunoblotting of lung tissue samples indicated the absence of the inducible isoform in both groups of animals. Moreover, LPS injection elicited no significant alterations in the pulmonary expression of the endothelial and the neuronal isoforms. CONCLUSIONS: Both extrathoracic and intrathoracic compartments contribute to the rise in exhaled NO production in experimental septic shock. The rise in exhaled NO production is due to increased activity of constitutive NOS isoforms as a result of increased cofactor availability and/or downregulation of the endogenous inhibitors of NOS.

Animals↗
PubMed1998

Mechanical ventilation for respiratory failure postthoracotomy.

Although the exact incidence of postthoracotomy respiratory failure is unknown, it can be estimated to lie between 5% and 15%, given that many of these patients suffer from comorbid cardiopulmonary disease. Preoperative assessment is essential to more accurately predict those patients at increased risk for the development of respiratory failure. Efforts to minimize these risks include the aggressive use of analgesics. In the event of respiratory failure, the clinician must have a clear understanding of the underlying cardiopulmonary pathology, if any, and of the impact of the anesthetic and surgical procedures on cardiopulmonary performance. The twin goals of mechanical ventilation should be to provide inspiratory muscle assistance and rest while preventing the onset of muscle atrophy. To that extent, the limitations of the various modes of mechanical ventilation must be appreciated as to their impact on patient ventilatory performance. Weaning, which should be regarded simply as an extension of mechanical ventilation, should be approached with an appreciation of the pathophysiologic basis underlying ventilatory failure, the factors responsible, and a rational approach to their repair.

Humans↗
PubMed1997

The variability of exposure over time: a prospective longitudinal study.

Four hundred and forty personal air measurements were carried out on 54 workers, employed in the main processes in six different factories (6-13 in each). Potential exposure was to lead, benzene and dust. Ten randomly repeated hygiene surveys were carried out over 1 year. In order to estimate the magnitude of the variability in workers' exposure over time, its sources, the variance between workers and the variance within a worker, a nested unbalanced analysis-of-variance model was fitted to the log-transformed data. Of the total exposure variance, the within variance of a worker's exposure over time was 51% (geometrical standard deviation, GSD = 3.1) and the between workers, factories and air contaminants variance was 49%. The exposure variance between all the workers was due mainly to variance between workers within the same factory (67%). Outdoor locations, mobility of the worker and mobility of the sources of exposure result in a positive influence on both the variance between (26%, ANOVA) and the variance of a worker over time (39%, regression). These variables are therefore important in the sampling strategy of workers' exposure. For valid compliance testing and assessment of workers' exposure the mean and the within- and between-variance of the workers' exposure over time should be considered. The exposure should be measured several times a year randomly in order to prevent workers misclassification. To assess yearly exposure, a GSD = 3.1 can be used to calculate confidence limits for the arithmetic mean of worker's exposure measurements, in circumstances similar to those in this study.

Air Pollution↗
PubMed1997

Laryngeal and hypopharyngeal cancer and occupation: results of a case control-study.

OBJECTIVES: To ascertain whether certain occupations are associated with laryngeal or hypopharyngeal cancer. METHODS: A hospital based case-control study was carried out in 15 hospitals in France. It included 528 male cases diagnosed between January 1989 and April 1991, and 305 male controls with various other types of cancer. Interviews were carried out to obtain lifetime job histories and information on potential confounders. Logistic regression was used to compute the odds ratios (OR) for each of about 80 occupations and industries. RESULTS: There was an excess risk of laryngeal and hypopharyngeal cancer among service workers (OR 2.2, 95% confidence interval (95% CI) 1.3 to 3.9), agricultural and animal husbandry workers (OR 1.6, 95% CI 0.9 to 2.8), miners and quarrymen (OR 2.0, 95% CI 0.9 to 4.3), plumbers and pipe fitters (OR 2.6, 95% CI 0.8 to 8.1), glass formers and potters (OR 4.3, 95% CI 1.0 to 18) transport equipment operators (OR 1.5, 95% CI 1.0 to 2.5), and unskilled workers (OR 1.7, 95% CI 1.0 to 2.9). Analysis by industrial branch showed an excess risk for coal mining (OR 2.1, 95% CI 1.1 to 4.1), manufacture of metal products (OR 1.9, 95% CI 1.0 to 3.3), and administration and sanitary services (OR 1.7, 95% CI 1.1 to 2.5). CONCLUSION: These results suggest that occupational exposure might have a role in generating laryngeal and hypopharyngeal cancer, and indicate the need for further evaluation of these findings, an for the identification of the carcinogens which might account for the excess risks found for certain occupations.

Aged↗
PubMed1996

Proportional assist ventilation in acute respiratory failure: effects on breathing pattern and inspiratory effort.

Proportional assist ventilation (PAV) is a new mode of assisted ventilation which, by applying pressure in proportion to volume (volume assist, VA) and flow (flow assist, FA), should specifically reduce the inspiratory effort needed to overcome respiratory system elastance (Ers) and resistance (Rrs), respectively. The aims of this study were to determine (1) the effects of varying the level of VA on breathing pattern, inspiratory effort, and work of breathing, and (2) the interaction between VA and FA. In eight intubated patients with acute respiratory failure, four levels of VA (20 to 80% Ers) with and without a fixed amount of FA (approximately 50% Rrs) were evaluated. Compared with spontaneous breathing, VA increased tidal volume (VT) while respiratory rate (RR) was unchanged or fell slightly. The increase in minute ventilation (VE) was small and not significant. The addition of FA further increased VT while RR was significantly reduced so that VE remained unchanged. Increasing VA produced a graded reduction in inspiratory effort, reflected by decreases in the pressure-time integral of the diaphragm and the inspiratory muscles. These were further reduced when FA was added. VA decreased the elastic work of breathing (Wel) whereas resistive work (Wres) tended to increase so that the fall in total work (W/tot) was less than expected. At each VA setting, the addition of FA significantly reduced Wres and, as a result, Wtot. These results demonstrate that PAV can improve breathing pattern while reducing inspiratory effort by specifically decreasing Wel and Wres, and that VA and FA should be used together to optimize reductions in Wtot and the efficacy of assistance provided.

Acute Disease↗
PubMed1996

Work conditions and mental health among prison staff in France.

OBJECTIVES: A cross-sectional epidemiologic survey was conducted among prison staff in France to investigate the relationships between work conditions and mental health. METHODS: The sample included men and women 20 to 64 years of age belonging to all categories of prison personnel (prison guards, administrative staff, socioeducational workers, technicians, health care workers, and managers). A postal self-administered questionnaire was used to assess sociodemographic factors, work conditions, and physical and mental disorders. Multiple logistic regression analyses were conducted to determine the effects of work conditions and social relationships on the mental health of prison staff. RESULTS: The results presented in this report only concern depressive symptomatology (measured by the French version of the Center for Epidemiologic Studies Depression Scale), anxiety (measured by the state version of the State-Trait Anxiety Inventory), and sleep disorders. The percentage of mental disorders was higher among prison staff than that determined for other occupational samples. Guards comprised the prison staff least affected by these symptoms. CONCLUSIONS: The results show that, in our sample, the factors concerning the subjective evaluation of work conditions and social support were more closely related to mental disorders than work conditions. In addition, seniority was associated with depressive symptoms and anxiety among the men.

Adult↗
PubMed1996

[Working conditions, living conditions and physical health problems declared among penitentiary administration personnel in France].

A cross-sectional epidemiological survey was conducted among prison staff in France to investigate the relationships between working conditions and health. The sample included men and women 20 to 64 years old belonging to all categories of prison personnel: prison guards, administrative staff, socioeducational workers, technicians, health care workers, and managers (n = 4587, response rate 45.7%). A mailed self-administered questionnaire was used to assess sociodemographic characteristics, working conditions, and physical and mental disorders. Multiple logistic regression analyses were conducted to determine the effects of working conditions and social relationships on health of prison staff. However, the results reported here only concern 17 health disorders: body mass index, sick leave, medication use, accidents, digestive disorders, lower extremities and back disorders, hypertension, hemorrhoids, arthritis, skin disorders, urinary infections, chronic bronchitis, cholesterol, gastric ulcer, respiratory infections, ocular disorders. The living non professional conditions mostly associated with health disorders were financial difficulties (OR: 1.9 for digestive disorders, 1.8 for gastric ulcer, 1.7 for medication use) and irregularity of meals (OR = 1.5 for digestive disorders, and hypertension). In the occupational environment, the factors most associated with health disorders are seniority (OR = 4.2 for arthritis, 2.3 for cholesterol) and constraints (OR = 1.7 for lower extremities disorders). In spite of some limits associated to this kind of study, relationships between occupational and non occupational factors and physical health conditions were observed; the results also pointed out the protective role of the social relationships for health conditions.

Administrative Personnel↗
PubMed1995

Efficacy of noninvasive CPAP in COPD with acute respiratory failure.

Dynamic hyperinflation and the development of intrinsic positive end-expiratory pressure (PEEPi) are commonly observed in patients with severe chronic obstructive pulmonary disease (COPD) in acute respiratory failure. Previous studies have shown that externally applied PEEP reduces PEEPi and its adverse effects in mechanically-ventilated COPD patients. The purpose of this study was to determine the effects of graded amounts of continuous positive airway pressure (CPAP) on the degree of inspiratory effort, pattern of breathing, gas exchange, and level of dyspnoea in a group of spontaneously breathing, nonintubated COPD patients in acute hypercapnic respiratory failure. Ten COPD patients admitted to the intensive care unit in acute hypercapnic respiratory failure were studied. Inspiratory effort was measured by the tidal excursions of oesophageal (Poes) and transdiaphragmatic (Pdi) pressure. Inspiratory effort and both the pressure-time product for the diaphragm (integral of Pdi-dt) and for the inspiratory muscles (integral of Poes.dt) were measured during the application of 5, 7.5, and 10 cmH2O of CPAP. Dyspnoea, gas exchange and pattern of breathing were also assessed. Inspiratory effort and the pressure-time product both for the diaphragm and the inspiratory muscles fell significantly with CPAP in a dose-dependent fashion. Both the pattern of breathing and level of dyspnoea improved with CPAP. End-expiratory lung volume remained stable at the lower levels of CPAP, with only modest increases at the higher levels. Arterial oxygen tension (Pa,O2) and arterial carbon dioxide tension (Pa,CO2) either improved or remained stable with CPAP. We conclude that the noninvasive application of CPAP to spontaneously breathing patients with severe COPD in acute respiratory failure decreases inspiratory effort and dyspnoea whilst improving breathing pattern. It is conceivable that the early institution of CPAP in this setting may obviate the need for intubation and conventional mechanical ventilation.

Adult↗
PubMed1995

[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↗
PubMed1995

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗
PubMed1994

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↗