Biomedical subjects
Publications and source records attributed to J Gallagher.
This article describes some of the issues relevant to the different kinds of contracts that are likely to be offered to physicians entering private practice upon completion of residency programs or in the early years of practice and discusses how such issues can be resolved in the course of negotiating those contracts.
Viral infections are more frequent and more severe in patients with cancer. As treatments for malignancy become ever more aggressive, the supportive care must also advance or the gains from innovative antineoplastic treatments will be lost to morbidity and mortality from secondary immune suppression and opportunistic infections. While empiric antibacterial and antifungal therapies for neutropenic leukemia patients were improving patients' survival, viral infections in cancer patients were often relegated to a clinical footnote in review articles since little could be done about them. Recently, however, acyclovir, ganciclovir, immunoglobulins, and ribavirin have given new opportunities for successful management of severe viral opportunistic infections in patients with leukemia and in bone marrow and other transplant patients.
The goals of this article are to provide an overview of the research process and highlight some of the most important aspects. In the process, the definition of research and some general terminology will be reviewed. Discussions of how to define a problem, reviewing the literature, types of study designs, sampling, types of measurement, reliability and validity, limitations and assumptions, data analysis, ethical concerns with human subjects, and time management are included, as are examples of published research.
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A cross-sectional medical evaluation was conducted to determine respiratory and dermatological effects of platinum salts sensitization among workers in a secondary refinery of precious metals. Fifteen of 107 current employees and eight (28%) of 29 former employees, who had been terminated from employment on average for 5 years because of respiratory symptoms, had positive skin reactivity to platinum salts. Platinum salts skin reactivity was significantly associated with average air concentrations of platinum salts in employees' present work area. Workers with positive platinum salts skin tests had significantly higher prevalences of reported rhinitis, asthma, and dermatitis than negative skin test workers. They also had increased bronchial response to cold air challenge and elevated levels of total serum IgE. Platinum salts sensitization was not associated with atopic tendency as measured by sensitivity to common aeroallergens, but was strongly associated with cigarette smoking status. The findings indicate that cigarette smoking may be a risk factor for the development of platinum salts allergy. The persistence of platinum salts sensitization and high prevalence of adverse health outcomes among former workers demonstrate the importance of regular medical monitoring so that sensitized workers can be removed from exposure before they develop long-term health problems.
Familial defective apolipoprotein B-100 (FDB) is a recently identified, dominantly inherited genetic disorder, which leads to increased serum concentration of low density lipoprotein (LDL) cholesterol with reduced affinity for the LDL receptor. This disorder is associated with a G to A mutation in exon 26 of the apolipoprotein B (apo B) gene which creates a substitution of glutamine for arginine in the codon for amino acid 3500. We have searched for this mutation in 374 unrelated individuals with hyperlipidaemia from the United Kingdom, and in 371 unrelated individuals with a primary clinical diagnosis of atherosclerosis from the United Kingdom and Scandinavia. Ten individuals, 9 from the U.K. and 1 from Denmark, were identified. The frequency of the mutation was 3% in individuals classified clinically as having familial hypercholesterolaemia (FH) and 3% in individuals with type IIa hyperlipidaemia without FH, and was not found in patients with types IIb and III hyperlipidaemia. The mutation was rare in individuals with a primary clinical diagnosis of atherosclerosis. Plasma lipid levels and clinical characteristics of the ten patients identified in the present study are similar to those reported for heterozygous FH. Thus, in our study, FDB is associated with moderate to severe hypercholesterolaemia, and appears to be a serious disorder causing premature cardiovascular disease. Individuals with this mutation can be identified unambiguously using routine molecular screening techniques.
Corynebacterium pseudotuberculosis produces a sphingomyelin-specific phospholipase D exotoxin that is a major determinant in the pathogenesis of caseous lymphadenitis. We assessed the changes induced in the morphology and sphingomyelin concentration of ovine erythrocytes after incubation with broth culture filtrates or purified exotoxin. Sphingomyelin was hydrolysed nearly in parallel with shape change. Morphologically, spherostomatocytes were seen initially, and later these contained numerous vacuoles at the periphery. Vacuoles seen in thin sections with transmission electron microscopy appeared as pits with scanning electron microscopy. Pitting became progressively worse with time, leading to extensive scalloping of the membrane surface. Chemically, significant decreases (P less than or equal to 0.05) in erythrocyte membrane sphingomyelin content and significant increases (P less than or equal to 0.05) in the content of glycerophospholipids (i.e. phosphatidylglycerol) were observed in erythrocytes incubated with broth culture filtrates or purified exotoxin. These alterations may contribute to the pathophysiology of acute infections induced by C. pseudotuberculosis.
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An investigation of a platinum refinery operation consisted of an administered questionnaire, spirometry, skin prick testing with platinum salts and common aeroallergens, serum total IgE, radioallergosorbent test for platinum salts, and measurement of nonspecific airway hyperresponsiveness by cold air challenge testing. Among 136 employees examined, there were 107 current and 29 medically terminated workers; 23 (17 percent) subjects had a positive platinum salts prick skin test and 19 (14 percent) displayed a positive cold air challenge. RAST binding for platinum salts IgE antibodies showed a high level of agreement with platinum skin prick test results. A proportion (63 percent) of the population (74 current and 12 terminated workers) underwent repeat platinum skin testing one year later. Among current workers, there was conversion of the platinum skin test from negative to a positive test in five employees, with three conversions occurring in workers who showed only a positive cold air challenge test the year before. Platinum skin sensitivity, asthma symptoms, and nonspecific airway hyperresponsiveness persisted for years after termination of exposure in some medically terminated workers presumably because of a delay in removal from work of employees who became sensitized to platinum salts. It is suggested that proper surveillance for occupational asthma involves the use of several testing procedures. Prompt removal from work of individuals found to become sensitized to platinum salts is important in this industry.
We previously reported IgE-mediated occupational asthma among workers exposed to airborne egg protein at a plant that produces liquid and dried powdered egg products. To demonstrate that our original observations are generalizable to other facilities that process eggs, and to estimate the prevalence of IgE-mediated occupational asthma among egg-exposed workers, we conducted surveys at two additional plants. We administered a questionnaire to 188 employees to identify workers with symptoms suggestive of occupational asthma. We further evaluated 88 workers with and without symptoms by a clinical examination by a physician blinded to results of other tests, serial peak expiratory flow rate (PEFR) determinations every three hours while awake for one week, and skin prick tests and serum specific IgE levels to extracts of factory egg products, commercial egg test reagents, and egg white protein fractions. Fourteen workers had work-related asthmalike symptoms by questionnaire, a physician diagnosis of occupational asthma, and evidence of IgE-mediated sensitization to one or more egg proteins. Workers exposed exclusively to liquid egg aerosol, as well as workers exposed primarily to dried airborne egg protein, developed occupational asthma. This study replicated our original observations and demonstrated that workers in all areas of liquid and powdered egg production are at risk of developing occupational asthma from exposure to airborne egg proteins.
Current research on the cancer risks of complex mixtures of urban air pollutants addresses the identification and comparative assessment of mutagenic and carcinogenic chemicals and emission sources. To identify genotoxic compounds in urban air, micromutagenesis methods are coupled to analytical fractionation and new chemical characterization methods. Among polar mutagenic compounds, many appeared to be nitrated and or oxygenated aromatic compounds. Source apportionment of the mutagenic activity observed in urban air shows that vehicles and residential heating are major contributors to the ambient mutagenicity of the aerosol fraction. Comparative tumorigenesis and DNA adduct dosimetry studies are also being conducted with these same combustion emission sources and urban aerosols. The potential hazard and sources of the gaseous emissions have not been determined, but appear to be significantly increased by atmospheric transformation by ozone and nitrogen oxides.
The purpose of this article is to provide an overview of the research process and highlight some of the most important aspects. The definition of research and some general terminology are reviewed. Included in this article are discussions of the following: defining a problem, reviewing the literature, types of study designs, sampling, types of measurement, reliability and validity, limitations and assumptions, data analysis, ethical concerns with human subjects, and time management. Examples of published research are used to illustrate the points where necessary. A supplemental bibliography is provided to direct the interested reader to more in-depth discussions of the various aspects of the research process.
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We have determined the frequencies of the alleles at the EcoRI (E), XbaI (X) and PvuII (P) polymorphic restriction sites in the apo B gene in 124 white men with coronary artery disease (CAD) and in 146 white men free from CAD. The frequencies of the E- (restriction site absent) and X- alleles were both significantly higher in normocholesterolaemic men with CAD than in those without CAD, but the frequency of the P+ allele (restriction site present) was similar in the 2 groups. The frequency of the E- allele was significantly higher in CAD men with hypertriglyceridaemia than in normal men without hypertriglyceridaemia. In the normocholesterolaemic men without CAD, the mean serum cholesterol concentration was higher in those with genotype X++ than in those with genotype X--. Mean serum LDL-apo B and LDL-cholesterol concentrations did not differ significantly between men with different XbaI or EcoRI genotypes. Serum apo A-I levels differed significantly between normal men with different XbaI genotypes. Serum HDL-cholesterol levels differed significantly between CAD men with different XbaI genotypes. These results suggest that in white men the E- and X- alleles are in linkage disequilibrium with a nearby allele that is causally related to CAD. It is also possible that the amino acid substitution at position 4154 in apo B, brought about by the nucleotide change responsible for the EcoRI polymorphism, has a direct effect on the atherogenicity of LDL.
We have investigated the association between serum high density lipoprotein-cholesterol (HDL-C) and apo A-I concentration and the PstI and XmnI restriction fragment length polymorphisms of the apolipoprotein AI-CIII-AIV multigene complex. Two groups of subjects were examined. The first comprised 174 unrelated male patients under 60 years of age with angiographic evidence of coronary artery disease (CAD). Of this group 34 were non-North European. The second group consisted of 104 unrelated healthy male North European subjects aged under 60 and free from demonstrable CAD, who attended a health screening clinic in London. For the PstI polymorphism, the frequency of the rarer P2 allele was 0.12 in both the North European and non-North European patients and this was higher than in the control group (P2 frequency 0.06, P less than 0.05). Healthy individuals with the genotype P1P2 had higher levels of apo A-I but similar levels of HDL-C compared to those with the genotype P1P1. However, CAD patients with the genotype P1P2 had lower serum levels of apo A-I and significantly lower serum levels of HDL-C compared to those with the genotype P1P1 (0.85 mmol/l vs. 1.0 mmol/l, P less than 0.05). The allele frequencies of the XmnI polymorphisms were not significantly different in the control group and the group of North European patients, although within the sample of non-North European patients, the frequency of the X2 allele was significantly higher than that found in the North European controls (0.26 vs. 0.09). Patients with the genotype X1X2 had a higher mean serum concentration of HDL-C and apo A-I compared with patients with the genotype X1X1 (1.14 and 0.93 mmol/l for HDL-C, P less than 0.05; 147 and 123 mg/dl for apo A-I, P less than 0.05). Associations between HDL-C and apo A-I levels and PstI and XmnI genotype were similar in patients taking and not taking beta-blockers. The data show that genetic variation in the apo AI-CIII-AIV gene cluster is associated with coronary artery disease although only weakly, and suggest that the mechanism of this association may operate through an effect in determining the serum concentration of apo A-I and HDL-cholesterol.
One hundred twenty-five consecutive admissions in 102 patients hospitalized for acute bronchospasm were studied to determine the need for routine admission chest radiography in asthmatics. Patients were categorized as complicated or uncomplicated asthmatics based on data recorded in the emergency department. Thirteen admission chest radiographs in 44 complicated asthmatics had an impact on management, whereas none of the 81 radiographs in the uncomplicated group affected patient care (P less than .001). Our study suggests that routine admission chest radiographs in uncomplicated asthmatics may be unnecessary.
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