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Biomedical subjects

J A Hanley

Publications and source records attributed to J A Hanley.

At least 73 records · Page 4Linked to original sources

Prediction of airway reactivity from responses to a standardized respiratory symptom questionnaire.

A standardized respiratory symptom questionnaire was administered to 200 male insulators who then underwent inhalational bronchial challenge to measure their airway reactivity. The results were analyzed to determine the value of questionnaire information in predicting airway reactivity measured objectively. Questionnaire information was grouped according to topic, scored according to severity, and then combined to create several airway reactivity indices by stepwise multivariate analysis. The final index selected for testing contained information on a history of "asthma," "wheeze," "episodes of cough with sputum," and "pneumonia." It had a sensitivity ranging from 5% to 67% and positive predictive value from 67% to 28% depending on the cutoff point chosen as indicative of increased airway reactivity. These results indicate that questionnaire information is not adequate for discriminating between those with and those without increased airway reactivity in population screening.

Adult↗

The Montreal Type A Intervention Project: major findings.

This article reports a comparison of three short-term treatments (aerobic exercise, cognitive-behavioral stress management, and weight training) in modifying behavioral and cardiovascular reactivity to laboratory psychosocial stressors in healthy Type A men. One hundred seven men completed the treatments and evaluations, 33 in the aerobic exercise group, and 37 each in the cognitive-behavioral stress management and weight-training groups. The stress management group showed significantly greater changes in behavioral reactivity (reductions of 13% to 23% below initial values) than the two physical exercise groups, which did not differ significantly from each other. For physiological reactivity, changes attributable to intervention were trivial for all three treatment groups. The positive finding of reduced behavioral reactivity as a result of the stress management intervention is of potential clinical significance and warrants further exploration. The lack of meaningful reductions in physiological reactivity also requires further exploration in that it raises questions concerning the ability of behavioral treatments in general to modify physiological reactivity, the ability of existing measures to assess accurately changes that are produced and, most fundamental of all, the relevance of physiological reactivity as an outcome measure for treatment efforts with Type As.

Adaptation, Psychological↗

The decreased incidence of aseptic necrosis in renal transplant recipients--a case control study.

Before 1971 the incidence of aseptic necrosis in renal transplant recipients was 29%, and after 1971 it was 5%. To investigate the reasons for this decreased incidence and to elucidate the causes of aseptic necrosis we studied all 26 transplant patients with aseptic necrosis and 42 controls matched for year of transplantation, age, and sex. Development of aseptic necrosis was not related to duration of dialysis before transplant, severity of uremia at the time the patient started dialysis, adequacy of dialysis before transplantation, transplant dysfunction at the time aseptic necrosis was diagnosed, hyperparathyroidism before or after transplantation, lack of Vitamin D supplementation after transplantation, or fatty infiltration of liver. Total steroid dose 1 month after transplantation was actually lower in aseptic necrosis compared with the control group (2.47 +/- 0.3 g vs. 3.6 +/- 0.3 g SEM g) and was similar after 4 months (6.72 +/- 0.55 g vs. 7.14 +/- 0.6 g), as were total numbers of i.v. doses of methylprednisolone or hydrocortisone. However, blood urea nitrogen (BUN) during the dialysis period was significantly higher in the aseptic necrosis group. Of the aseptic necrosis group, 27% had a previous transplant compared with 5% of controls. Half the aseptic necrosis group (5/10) had parenchymal iron on liver biopsy one year after transplant compared with 15% (2/13) of those without aseptic necrosis. Patients transplanted before 1971 (with and without aseptic necrosis) received significantly more i.v. hydrocortisone and less i.v. methylprednisolone, had higher BUN levels at the time of starting dialysis, and had lower serum calcium and higher serum phosphate at transplantation compared with patients transplanted in or after 1971. The incidence of aseptic necrosis following transplantation has decreased during the past 13 years for reasons that are unclear. Risk factors for aseptic necrosis may include previous transplantation, severe iron overload that may lead to marrow fibrosis and osteopenia, and increased protein catabolism/turnover during dialysis.

Adult↗

Cardiovascular involvement in osteogenesis imperfecta.

While aortic root dilatation and valvular dysfunction have been well-documented in osteogenesis imperfecta (OI), the nature and extent of cardiovascular involvement in OI have not been clearly delineated. A clinical and echocardiographic survey involving 109 individuals with various nonlethal OI syndromes from 66 separate families was undertaken. Clinically discernible valvular dysfunction was encountered in only four of the 109 individuals (aortic regurgitation in two, aortic stenosis in one, and mitral valve prolapse in one), none of whom were related. Aortic root dilatation was recognized echocardiographically in eight (12.1%) of 66 individuals comprising a subset of the sample in which each family was represented by a single individual. The extent of the aortic root dilatation was mild (the largest dimension measuring 4.3 cm) and was unrelated to the age of the individual. Dilatation was seen in each of the different OI syndromes but was strikingly segregated within certain families (p less than .001). In the same subset of 66 individuals, mitral valve prolapse was encountered in two or 6.9% of the 29 individuals aged 15 years or greater in whom adequate studies were obtained. This observed frequency was not different from that seen in a normal adult population. Aortic root dilatation appears to represent a distinct phenotypic trait in patients with OI that is nonprogressive and occurs in about 12% of affected individuals. Whether mitral valve prolapse should be considered as a part of the cardiovascular phenotype in OI, or alternately segregates as an independent autosomal dominant trait has yet to be determined.

Adolescent↗

Evaluating primary prevention programmes against cancer.

Based on current knowledge, roughly one third of all cancers worldwide are preventable, and primary prevention is increasingly seen as an important cancer control strategy. Interventions to reduce the exposure to known causes can be effected through legislation or education, or by means of vaccination or chemoprevention. Since primary prevention actions can be costly and will compete for resources needed for other disease control activities, and since there is no guarantee that they will be successful, they should not be introduced haphazardly but on the basis of scientific evaluations. This paper presents the main principles to be followed in designing such evaluations; the illustrations often, of necessity, come from other diseases (particularly cardiovascular disease), where there is considerably more experience. Because the interventions involve changes in lifestyle and behaviour, and because a long time is necessary to observe the ultimate endpoints, controlled intervention studies against cancer present many scientific and logistical difficulties. Some interventions, such as vaccination and chemoprevention (to test suspected protective agents) may be evaluated by traditional clinical trial methodology, using intermediate as well as final (cancer incidence and/or mortality) endpoints. Active, target-directed and preferably controlled health service research studies will definitely be needed to assess community or population interventions based on legislation or education.

Evaluation Studies as Topic↗

A Bayesian approach for predicting judged hearing disability.

A method of determining the cutoff point for an administrative decision to award compensation is proposed. To construct the predictive system a Bayesian approach and discriminant analysis were employed. Judged hearing disability was used as the criterion with audiometric scores as the determining variables. The common law doctrine of the balance of probability was used as the criterion, namely the 50th centile, on which to propose a cutoff point. The highest precision in predicting judged hearing disability was obtained with an average audiometric score at 1,000, 2,000, 3,000, 4,000 Hz in the worse ear. Assuming that judged hearing disability is a valid predictor of handicap, the cutoff point based on the balance of probability (50th centile) was obtained at 25 dB. The study also confirmed results from previous studies: hearing sensitivity in frequencies higher than 2,000 Hz is required to predict hearing disability and handicap, judged hearing disability is better correlated with hearing sensitivity in the worst ear, and the audiometric cutoff point for a medical legal definition of impairment should be lower than what certain technical groups have proposed in the past.

Audiometry↗

Exaggerated psychophysiological reactivity: issues in quantification and reliability.

Marked physiological reactivity to challenging mental tasks has been associated with elevated risk for, as well as the presence of, coronary heart disease. However, little systematic enquiry into the reliability and quantification of such exaggerated reactivity has emerged. Subjects were 32 male, managerial employees, ranging in age from 22 to 56 yr, who satisfied the following criteria: no history or current signs of heart disease, presence of Type A behavior pattern as revealed by the Structured Interview, and an increase during an initial psychosocial stress testing of at least 25% over baseline in at least three out of five psychophysiological indices. Heart rate, systolic blood pressure, diastolic blood pressure, plasma epinephrine and plasma norepinephrine levels were monitored while challenging mental tasks were performed in three sessions (screening, pretraining and posttraining) spaced several weeks apart. Psychophysiological reactivity during the tasks emerged as a consistent trait. For all five measures, change scores from baseline during the screening session were significantly correlated with change scores during the pretraining session. Moreover, the magnitude of the change scores were similar in the screening and pretraining sessions. Analysis of cross correlations within and between indices provided little support for the use of data transformations such as residual scores or analysis of covariance. Finally, on four out of five measures, the challenging tasks were found to be comparable in the degree of reactivity elicited. These findings suggest that, for selected Type A men, exaggerated psychophysiological reactivity occurs reliably when monitored with multiple indices, appears insensitive to mere passage of time, and can be uniformly elicited by a variety of tasks.

Adult↗

Protocol variations and their influence on the final outcome: critical review of the split-course base of tongue study of the RTOG.

A critical review of the protocol variations in an RTOG prospective randomized multi-institutional clinical trial has been conducted. The objective of the review was to identify variables that might have affected the results of the study. Compliance with general guidelines and specific technical treatment parameters of the Split-Course Radiation Therapy Protocol for Carcinoma of the Base of the Tongue (RTOG #71-02) was analyzed. A +/- 5% variation of the time-dose-fractionation factors, using the NSD and TDF formulae and their respective protocol ratios (ratio between actual case NSD and TDF level and what the protocol recommended), has been defined as fully acceptable. Seventy-two percent of the 141 study cases were within this category. Minor variation has been defined as one resulting in a +/- 6% to +/- 15% deviation from the study values (15.3% of cases). Major and unacceptable variation was a deviation of +/- 16% or more from the research plan (12.7% of cases). After identifying the different variations and correlating them with the clinical results, we conclude that these deviations did not affect the final results to a significant or identifiable degree.

Clinical Trials as Topic↗

The spectrum of diseases associated with necrotizing glomerulonephritis and its prognosis.

Necrotizing glomerulonephritis (NGN) represents small-vessel vasculitis in the kidney. To assess the diseases associated with necrotizing glomerular changes and their prognosis we studied all 32 patients who had this histologic finding on kidney biopsy from 1969 to 1982 and compared them to those patients who had crescentic, diffuse, or focal and segmental glomerulonephritis without necrosis (n = 29). The diseases associated with NGN were systemic lupus erythematosus (n = 6/15), Henoch-Schönlein purpura (n = 3/4) Goodpasture's syndrome (n = 4/7), Wegener's granulomatosis (n = 6/6), polyarteritis (n = 4/5), infective endocarditis (n = 2/3), and idiopathic rapidly progressive glomerulonephritis (n = 7/21). Necrotizing glomerulonephritis occurred significantly more often in the vasculitides than in all the other disorders put together. The most difficult diagnosis problem occurred in patients with renal disease and pulmonary hemorrhage (n = 9), in three of whom diagnosis was uncertain even after autopsy (two autopsies done within one month and one within three months of presentation). A fourth patient had a linear staining for IgG along the glomerular basement membrane (GBM) on kidney biopsy but was subsequently diagnosed as having Wegener's granulomatosis. Comparison of patients with without NGN revealed no difference in outcome (death or dialysis) one year after biopsy (38% v 43%) or in serum creatinine levels one year later (4.6 v 4.8 mg/dL). The prognostic effect of NGN was not obscured by unequal distribution of other adverse prognostic factors in the two groups. The most important prognostic characteristics we identified for outcome were serum creatinine at biopsy (chi 2 = 24.0, P less than .0004) and the sum of activity and chronicity indexes on biopsy (chi 2 = 12.7, P = .0004). These variables were similarly distributed in patients with and without necrosis, mean serum creatinine levels at biopsy being 4.3 v 4.2 mg/dL and sum of indexes 7.8 v 8.0. Other factors such as clinical diagnosis and therapy were not important prognostically and therefore could not explain our results. We conclude that NGN in patients with active proliferative glomerulonephritis has multiple causes. Diagnostic difficulties occurred in those with anti-GBM-negative pulmonary hemorrhage. The appearances of small-vessel vasculitis in the kidney did not appear to have prognostic significance.

Adolescent↗

Split-course radiotherapy of carcinoma of the urinary bladder stages C and D1. A Radiation Therapy Oncology Group Study.

One hundred forty-eight patients with advanced carcinoma of the urinary bladder Stages C or D1 were randomized between continuous-course radiotherapy (6,000 cGy in 30 fractions of 200 cGy each, over 6 weeks) and split-course radiotherapy (2,750 cGy in 10 fractions of 275 cGy each, over 2 weeks; a rest period of 3 weeks; 2,750 cGy in 2 weeks); 139 are analyzed in this report. Ninety-four percent of the patients have been followed at least 5 years or until death. The patients ranged in age from 45 to 80 with a median of 69. Seventy-six percent of the patients were males and 58% had Stage C disease. In patients with information on the size of the tumor, in 66% the lesion measured 5 cm or larger; 26% had a diameter of 8 cm or larger. In general, the treatment groups were well balanced with respect to patient characteristics. Both treatment groups tolerated therapy well. Eighty-seven percent of the patients completed therapy, 66% as planned. Fifty-four percent experienced at least one severe reaction, with the most common types being diarrhea (28%), frequency of urination (24%), soreness or burning on urination (25%), and urgency of urination (19%). Late effects of therapy were minimal. Median survival times were 11.5 months and 9.4 months for continuous-course and split-course, respectively. The treatment differences were not significant (p = 0.88; Mantel-Haenszel stratified by stage and sex). Forty percent of the patients became free of all clinically detectable disease following radiotherapy either alone or in combination with additional surgery (40% for continuous-course, 4% cleared by surgery, and 39% for split-course, 3% cleared by surgery). When the tumor measured less than 5 cm, the clearance rate was 61% (20/33) vs. 33% (13/39) for 5-7.9 cm, and 24% (6/25) for 8 cm or larger (p less than 0.01; chi2 test for linear trend). For those who became disease free, median time disease free within the irradiated volume was 72 months for continuous-course and is currently undefined for split-course; median time disease free was 28 months and undefined, respectively. There were no significant treatment differences in tumor control for any of these endpoints. The ultimate long-term tumor control in the pelvis was 28% (19/68) for continuous- and 25% (18/71) for split-course therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗

Relations between asbestos exposure and lung cancer SMRs in occupational cohort studies.

It has long been accepted that excessive exposure to asbestos may produce lung cancer but not that there is a consistent "biological gradient." This can only be evaluated reliably in studies where, for every individual, exposure has been measured in terms of both duration and intensity. Even now, there are only at most eight such cohort studies of asbestos workers, while femoral methods of analysis have been available only recently. These methods, applied in these studies, yield good evidence that the "exposure-response" relation between accumulated exposure to asbestos and standardised mortality ratios (SMRs) for lung cancer may be taken as linear, but that at zero exposure the lung cancer SMR is not always unity--not surprising, because of well known difficulties with the choice of reference population and selection problems. This leads to a concept of "relative slopes" that take account of the background mortality in the cohort and make what appears to be the best use of the available data. Other approaches to the same data, and indeed to all cohort data known, are also considered. Each study is examined as closely as is possible in a short review, and the concepts of linearity and relative slopes appear justified. The relative slopes (b/a) in the line SMR = a[1 + (b/a) . (exposure)] vary much more widely than can be accounted for by differences in epidemiological methodology; as discussed elsewhere, reasons for the variation seem to lie rather in type and dimensions of asbestos fibre, industrial process, etc. Slopes in the line SMR = 1 + b1 . (exposure) vary about twice as much as do the relative slopes.

Asbestos↗

The diagnostic and prognostic value of renal allograft biopsy.

We prospectively studied 89 patients to assess the diagnostic use of renal allograft biopsy in the first three months after transplantation. These biopsies were done in patients in whom diagnosis was not clear or clinical rejection was deemed to be severe. Clinical diagnosis at initial biopsy was compared with the morphological diagnosis. To determine if morphological data improved the prognostic usefulness of the clinical data, we performed multiple logistic regression relating clinical variables at initial biopsy and histological changes in the transplant to the outcome of 120 patients one year after biopsy. The clinical and morphological diagnosis differed in 41 of 89 patients (46%). Of 120 patients in the prognostic study, 35 returned to dialysis during the first year following transplantation. Using multiple logistic regression, a categorical variable that took into account both the serum creatinine and its rate of change before biopsy was the best clinical predictor of return to dialysis. Further increase in chi 2 occurred with type of donor, number of transfusions, and age. Using the clinical variables we produced an index, from 0 to 1 to predict outcome. Only 8 had index less than 0.2, of whom 7 returned to dialysis. The best morphological predictor of outcome was interstitial hemorrhage. Further increase in chi 2 was obtained with vascular endothelial proliferation, glomerular endothelial swelling, and glomerular necrosis. With an index derived from the morphological variables only 11 had index less than 0.2, of whom 9 returned to dialysis. Combining both clinical and morphological data, the best predictor of return to dialysis was interstitial hemorrhage, followed by creatinine, glomerular endothelial swelling, and type of donor. Using both clinical and morphological variables we produced another index to predict outcome. A group of 65 patients had index greater than 0.8, of whom 63 (94%) did not return to dialysis, and 18 patients had index less than 0.2, 17 of whom returned to dialysis. The remaining 12 patients in the dialysis group and 15 in the nondialysis group had indices greater than 0.2 less than 0.8. We conclude that a transplant biopsy yields important diagnostic and prognostic information. Unexpected diagnoses were made in 46% of cases. The addition of morphological data to the clinical data available at time of biopsy greatly improved the prediction of return to dialysis.

Biopsy↗

Statistical approaches to the analysis of receiver operating characteristic (ROC) curves.

In this article we review published and some unpublished work in statistical analyses of ROC curves. We describe both single and joint indices and indicate the approaches that have been taken to consider between-reader variations and correlations, within-reader variations, and variations and correlations between cases. We then discuss in detail a single index, the TP ratio at a fixed FP ratio (designated TPFP), or the FP ratio at a fixed TP ratio (designated FPTP). We show how to calculate confidence limits around any point on the curve; we further show, using the conventional Dorfman and Alf program and the jackknifing technique, how to calculate these confidence limits for multiple curves derived from the same sample of patients.

Diagnosis↗