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Biomedical subjects

D G Kern

Publications and source records attributed to D G Kern.

17 recordsLinked to original sources

Rapid and precise quantification of HIV-1 RNA in plasma using a branched DNA signal amplification assay.

The level of human immunodeficiency virus type 1 (HIV-1) RNA in human plasma has been quantitated directly with use of a solid-phase nucleic acid hybridization assay, based on branched DNA (bDNA) signal amplification technology with chemiluminescent detection. Signal amplification is accomplished by the incorporation of sites for 1,755 alkaline phosphatase-labeled probes per genome of HIV-1, after successive hybridization of target-specific oligonucleotides and bDNA amplifier molecules. The assay is performed in microwells, much like an immunoassay, and is amenable to routine laboratory use. Reproducibility and specificity studies indicated that the bDNA method was precise and showed no reactivity with seronegative donors. HIV-1 RNA levels were quantitated for 348 seropositive specimens, with a detection rate of 83% for those specimens from patients with < 500 CD4+ T-cell counts. Plasma RNA levels were found to change with disease stage, and in response to antiviral therapy. Quantitation of HIV-1 RNA in the plasma of HIV-1-infected patients, with use of the bDNA assay, may be a useful method for monitoring HIV-1 disease progression and therapeutic response.

Acyclovir

Lead poisoning in precious metals refinery assayers: a failure to notify workers at high risk.

Lead poisoning in a precious metals refinery fire assayer and a routine OSHA inspection prompted an investigation of the index facility, a survey of the industry, and efforts to notify assayers of this previously unrecognized hazard. Air and blood samples were obtained at the index facility. Management personnel from all fire assay laboratories in Rhode Island and southern Massachusetts were interviewed. The industry's trade association, OSHA, NIOSH, trade unions, and the media were asked to assist in a nationwide notification effort. Assayers at the index facility had excessive exposures to lead due to an age-old, lead-based assaying method that remains the industry gold standard. Blood lead levels of the three assayers (mean 61.3 micrograms/dl, range 48-86 micrograms/dl) were considerably higher than those of 16 other refinery workers (mean 27.4 micrograms/dl, range 13-49 micrograms/dl). The industry survey revealed inadequate knowledge of both the lead hazard and the applicability of the OSHA lead standard. Notification efforts failed in large part due to economic obstacles. The notification of workers at high risk of lead exposure and the eradication of occupational lead poisoning will require greater attention to economic forces.

Humans

Occupational asthma following kapok exposure.

Whether a distinct kapok allergen exists or whether the fiber's allergenicity is due to contamination by other allergens has never been resolved. Several years ago, we evaluated a patient who appeared to develop occupational asthma to kapok. We performed an environmental assessment, cross-shift spirometric testing of the patient's co-workers, and the first reported bronchoprovocation challenge with kapok. The disappearance of the patient's asthma following cessation of kapok exposure, with now 7 years of follow-up, our inability to incriminate any other agent, and the patient's positive specific bronchoprovocation challenge strengthen the evidence, but do not prove definitively, that kapok fiber itself is allergenic.

Adult

Malignant mesothelioma in the jewelry industry.

We conducted a clinical, environmental, pathologic, and mineral lung burden investigation of a 61-year-old man with malignant mesothelioma. For 35 years, up until three weeks prior to pneumonectomy, the patient made asbestos soldering forms at a costume jewelry production facility. Only chrysotile asbestos was used at the plant during the last decade of the patient's employment, and recent environmental sampling of the work-place identified no other asbestos fiber type. Anticipating that the patient would add to the very small number of cases of mesothelioma attributable solely to chrysotile, we found instead that the patient's lung tissue contained large numbers of both coated and uncoated amosite asbestos fibers but, surprisingly, no chrysotile. We subsequently learned that a distributor of both chrysotile and amosite supplied the company during the first 25 years the patient was fabricating soldering forms. The findings underscore the futility of estimating environmental exposure to chrysotile on the basis of fiber counts in lung tissue. Although we previously described non-neoplastic asbestos-related disease among patients engaged in similar work, this case, to the best of our knowledge, represents the first report of mesothelioma in the commercial jewelry industry. As such, it prompted us to initiate a public health campaign to replace asbestos soldering forms in this industry with readily available, safer alternatives.

Air Pollutants, Occupational

Outbreak of the reactive airways dysfunction syndrome after a spill of glacial acetic acid.

The reactive airways dysfunction syndrome (RADS) defines a chronic asthmalike illness with airway hyperresponsiveness that develops within 24 h of a single, brief, highly irritating inhalation exposure. Support for the syndrome has been limited to case reports. A chemical spill, exposing hospital employees to 100% acetic acid, offered an opportunity to more convincingly establish the existence of RADS. All 56 exposed subjects were asked both to complete a questionnaire focusing on their preexposure health status, potential for exposure, and symptom development after the accident, 8 months after the spill, and to undergo methacholine challenge testing to detect airway hyperresponsiveness. An industrial hygienist, blinded to clinical data, estimated each subject's exposure. Preemployment health history forms were reviewed to assess recall bias. The study questionnaire was returned by 51 (91%) subjects; 24 (47%) consented to methacholine challenge, including 7 of the 8 with RADS-consistent symptoms. Diagnostic criteria for RADS were satisfied by none of 7 (0%) subjects with low exposure, 1 of 30 (3.3%) with medium exposure, and 3 of 14 (21.4%) with high exposure (test of trend p value = 0.021). The odds ratio estimate of the relative risk of RADS in subjects with high exposure was 9.8 (95% Cl, 0.902 to 264.6). Neither stratified analysis nor review of the preemployment health history forms revealed evidence of confounding or recall bias, respectively. The reactive airways dysfunction syndrome appears to be a valid clinical entity. Further study of RADS is especially appropriate given increasing evidence that airway inflammation may be etiologically important in all asthma.

Accidents, Occupational

Auscultated forced expiratory time as a clinical and epidemiologic test of airway obstruction.

OBJECTIVE: Seeking an inexpensive, readily available, clinical, screening, and field surveillance test of airway obstruction, we determined the validity of current dogma that forced expiratory time (FET) is a good clinical test of airway obstruction yet is of no epidemiologic use given excessive intrasubject variability. SUBJECTS AND METHODS: Two hundred twenty-nine white male plumbers and pipefitters were evaluated by spirometry, chest roentgenography, and a standardized respiratory questionnaire during a union-sponsored asbestos screening program. Subjects were classified as having large airway obstruction (LAO), small airway obstruction (SAO) alone, or no obstruction, on the basis of standard spirometric prediction equations. Two physicians, blinded to clinical and spirometric data, independently measured FET while auscultating the trachea with a stethoscope. The FET was defined as the time taken for an individual to forcefully exhale through an open mouth from total lung capacity until airflow became inaudible. Five such times were recorded for each subject. The mean of the three times having the narrowest range was deemed the FET for calculating test sensitivity and specificity. Based on previous literature, an FET greater than or equal to 6 s was considered abnormally prolonged. RESULTS: Two hundred five subjects completed both spirometry and FET testing; 67 had LAO, 5 SAO, and 133 no obstruction. A total of 83 percent had three FETs reproducible within a range of less than or equal to 1 s. The sensitivity and specificity of FET for LAO were 92 and 43 percent, respectively, while for SAO alone, 60 and 44 percent, respectively. Overall, FET misclassified 56 percent of nonobstructed subjects. Adjusting the normal-abnormal cutoff points for both FET and SAO minimally improved the performance of FET. CONCLUSION: Although FET is a simple, inexpensive, sensitive, and fairly reproducible clinical test of LAO, it cannot be recommended as a clinical or an epidemiologic tool because of its extremely low specificity.

Asbestosis

Treating asthma.

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Asthma

Asthma in respiratory therapists.

STUDY OBJECTIVE: To test the hypothesis that work as a respiratory therapist is associated with an increased risk of developing asthma. DESIGN: Cross-sectional questionnaire study comparing respiratory therapists with controls (physical therapists and radiologic technologists). Subsequent validation of reported asthma with methacholine challenge studies. SUBJECTS: All respiratory therapists and physical therapists and a random 50% sample of radiologic technologists working in the state of Rhode Island as of June 1986. METHODS: All subjects received a mail questionnaire with questions about the presence or absence of asthma, time of onset, and important covariates. Responses were analyzed for all subjects, and again after excluding those subjects with pre-existing asthma. Subjects who reported physician-diagnosed asthma were asked to have methacholine challenge testing. RESULTS: Respondents included 194 respiratory therapists (response rate, 69.5%) and 517 controls (response rate, 75.3%). After excluding respiratory therapists from the hospital at which the hypothesis was generated, there were 34 respiratory therapists (18.7%) and 30 controls (5.8%) reporting physician-diagnosed asthma. After controlling for age, smoking status, family history, atopic history, and other covariates using logistic regression, respiratory therapy carried an odds ratio of 3.2 (95% CI, 1.9 to 5.5). With analysis restricted to those who developed asthma after entering their profession, the odds ratio for respiratory therapy was 4.6 (95% CI, 2.0 to 10.4). In the validation study, 10 of 14 respiratory therapists (71%) and 6 of 10 controls (60%) had evidence of bronchial hyperreactivity. CONCLUSIONS: These results suggest a previously unrecognized excess of asthma in respiratory therapists. The excess develops after entry into the profession, and does not appear to be explained by confounding, information bias, or selection bias.

Adult

Identification of a galactose-binding lectin on Fusobacterium nucleatum FN-2.

A previous study has suggested that Fusobacterium nucleatum FN-2 contains a galactose-binding protein (lectin) on the cell surface (P. A. Murray, V. Matarese, C. I. Hoover, and J. R. Winkler, FEMS Microbiol. Lett. 40:123-127, 1987). In the present study, the molecular specificity and size of this lectin were investigated by several techniques. Whole-cell affinity chromatography with asialofetuin covalently coupled to Sepharose 6MB demonstrated that 81% of 3H-labeled F. nucleatum were specifically eluted by 0.5 M galactose. Specific binding was calcium dependent and did not occur in the presence of calcium chelators. Binding was inhibited by preincubation with galactose. Agglutination of human parotid saliva by F. nucleatum was also inhibited by galactose and its structural analogs. Inhibition by lactose was 2 times that of galactose, inhibition by p-aminophenyl galactosides was 4 times that of galactose, and inhibition by asialoglycopeptides was 100 times that of galactose. Similar inhibition results were obtained for hemagglutination of neuraminidase-treated erythrocytes. These findings suggest that the binding specificity of F. nucleatum FN-2 is more complex than simply the recognition of the monosaccharide galactose. This is consistent with the concept that lectins considered identical in terms of monosaccharide specificity can recognize fine differences in more complex structures. To identify the specific bacterial component(s) involved in galactose recognition, proteins of F. nucleatum FN-2 were separated on a 4 to 11% gradient sodium dodecyl sulfate slab gel, transferred to nitrocellulose paper to renature bacterial binding sites, and then incubated with 125I-labeled asialofetuin. Autoradiographs of the nitrocellulose revealed a band at a range of Mr 300,000 to 330,000 which was not present when the blots were preincubated with galactose. These data support the concept that F. nucleatum FN-2 possesses a lectin that recognizes galactose and galactose-containing substrates.

Asialoglycoproteins

Isolation of xanthophores from the goldfish (Carassius auratus L.).

A method is described for the isolation of milligram quantities of viable, hormone-responsive xanthophores from goldfish scales. The preparations are typically 70 to 90% pure and are useful for biochemical analyses or for establishing primary cultures.

8-Bromo Cyclic Adenosine Monophosphate

Developing a competency-based preventive medicine curriculum for medical schools.

Trends in patient morbidity and mortality, cost-effectiveness, and national recommendations mandate that we practice more preventive medicine. To address this need, we set out to develop a comprehensive curriculum in preventive medicine for medical schools. We constructed a competency-based (i.e., performance-based) curriculum with specific educational objectives defined by outcomes. Subject areas were subdivided by life stages, and learning objectives were created separately for epidemiology, assessment, and intervention. We hope that adoption of such an educational blueprint by medical schools will measurably enhance the attitudes, knowledge, and skills necessary for the incorporation of preventive principles into all aspects of clinical medicine.

Clinical Competence