Some properties of the specific androgen-binding activities in cultured human genital skin fibroblasts.

Specific 5 alpha-dihydrotestosterone (DHT)-binding activity in the cytosol (C) and 0.4 M KCl-extractable nuclear fraction (N) of cultured human fibroblast cell strains developed from preputial (n = 12) and labium majus (n = 12) skin were analyzed by gel exclusion chromatography, sucrose gradient sedimentation, and thermostability. Both fractions had activities that were excluded from Sephacryl S-200 columns; another component (mol wt, 20,000) was present in the N fraction. The C was more thermostable than a homologous N activity, and addition to the former of KCl to 0.4 M had no effect. There was large, overlapping variation in thermostability of the C and N activities among strains from either site, sister strains developed from a single skin biopsy, and even among serial subcultures within a strain; likewise, the variable sedimentability of the C (4-7S) and N (3.2-5.9S) activities prevented their consistent discrimination. Each type of variation occurred despite excellent intraexperimental replication. The thermostability of a given N activity varied directly with its sedimentation coefficient. By cluster analysis, the data relating thermostability of a given N activity with the percentage of 0.4 M KCl-resistant nuclear activity segregated into two populations; within each population these two measurements were related inversely. We suggest that these coordinate behaviors of the N activity reflect intrinsic properties of the androgen-receptor system in normal genital skin fibroblasts which may be useful for defining qualitative aberrations of the system in receptor-positive forms of congenital androgen insensitivity.

A radiologic survey of various configurations of the lumbar spine.

This paper reports an investigation to determine whether or not human spine configurations can be categorized into types by which one could predict the possibility of disablement at one specific level more than another. Configurations of the lumbar spine, the shape of the lower two lumbar discs, the anterior and posterior heights of discs, the sizes of the transverse processes of L4-5, the presence or absence of rudimentery ribs, and the presence of transitional vertebrae were studied in roentgenograms of 554 subjects. They concluded that the probable criteria for development of L4-5 degeneration were 1) high intercrestal line passing through the upper half of L4, 2) long transverse process on L5, 3) rudimentary rib, and 4) transitional vertebra. Criteria for development of L5-S1 degeneration were 1) intercrestal line passing through the body of L5, 2) short transverse process on L5, 3) no rudimentary rib, 4) no transitional vertebrae. A high intercrestal line and long transverse process probably act as antitorsional devices protecting the L5-S1 disc; hence the likelihood of degeneration at L4-5 is increased.

Mortality and occupational exposure to radiation: first analysis of the National Registry for Radiation Workers.

OBJECTIVE: To study cause specific mortality of radiation workers with particular reference to associations between fatal neoplasms and level of exposure to radiation. DESIGN: Cohort study. SETTING: United Kingdom. SUBJECTS: 95,217 radiation workers at major sites of the nuclear industry. MAIN OUTCOME MEASURE: Cause of death. RESULTS: Most standardised mortality ratios were below 100: 83 unlagged, 85 with a 10 year lag for all causes; 84 unlagged, 86 lagged for all cancers; and 80 for all known other causes, indicating a "healthy worker effect." The deficit of lung cancer (75 unlagged, 76 lagged) was significant at the 0.1% level. Standardised mortality ratios were significantly raised (214 unlagged, 303 lagged) for thyroid cancer, but there was no evidence for any trend with external recorded radiation dose. Dose of external radiation and mortality from all cancers were weakly correlated (p = 0.10), and multiple myeloma was more strongly correlated (p = 0.06); for leukaemia, excluding chronic lymphatic, the trend was significant (p = 0.03; all tests one tailed). The central estimates of lifetime risk derived from these data were 10.0% per Sv (90% confidence interval less than 0 to 24%) for all cancers and 0.76% per Sv (0.07 to 2.4%) for leukaemia (excluding chronic lymphatic leukaemia). These are, respectively, 2.5 times and 1.9 times the risk estimates recommended by the International Commission on Radiological Protection, but 90% confidence intervals are large and the commission's risk factors fall well within the range. The positive trend with dose for all cancers, from which the risk estimate was derived, was not significant. The positive association between leukaemia (except chronic lymphatic leukaemia) was significant and robust in subsidiary analyses. This study showed no association between radiation exposure and prostatic cancer. CONCLUSION: There is evidence for an association between radiation exposure and mortality from cancer, in particular leukaemia (excluding chronic lymphatic leukaemia) and multiple myeloma, although mortality from these diseases in the study population overall was below that in the general population. The central estimates of risk from this study lie above the most recent estimates of the International Commission on Radiological Protection for leukaemia (excluding chronic lymphatic leukaemia) and for all malignancies. However, the commission's risk estimates are well within the 90% confidence intervals from this study. Analysis of combined cohorts of radiation workers in the United States indicated lower risk estimates than the commission recommends, and when the American data are combined with our analysis the overall risks are close to those estimated by the commission. This first analysis of the National Registry for Radiation Workers does not provide sufficient evidence to justify a revision in risk estimates for radiological protection purposes.

Evaluating the role of primary care physicians in the treatment of latent tuberculosis: a population study.

SETTING: Latent tuberculous infection (LTBI) remains a significant source of new active tuberculosis cases. Recent guidelines encourage primary care physicians to prescribe LTBI treatment; however, there have been no investigations into the impact on treatment completion. OBJECTIVE: To estimate LTBI treatment initiation and completion rates by primary care physicians. DESIGN: A historical cohort study was conducted with Quebec residents dispensed isoniazid (INH) between 1 January 1998 and 31 December 2005. Information was obtained from administrative health insurance data. Regression modeling was used to estimate the association of completion rates with prescribing physician specialty, after adjustment for initial health status and other patient characteristics. RESULTS: A total of 14,753 people were dispensed INH for LTBI treatment. Primary care physicians initiated 3863 (26%) treatments. This proportion decreased from 28.7% in 1998 to 21.1% in 2005. Patients initiated on treatment by primary care physicians were less likely to complete treatment (OR 0.79, 95%CI 0.72-0.86). Only 5977 (40.5%) patients completed treatment; the average treatment duration of the primary care physician group was 11 days less (P < 0.0001). CONCLUSION: Primary care physicians initiated a substantial number of LTBI treatments, but less than half of patients completed treatment regardless of the physician specialty. Primary care physicians should be supported to enhance treatment completion.

Risk factors of squamous cell carcinoma of the skin. A case-control study in the Montreal region.

A matched case-control study was undertaken to assess the relative risk associated with known and suspected risk factors of squamous cell carcinoma of the skin among patients in the Montreal region. Three hundred eleven cases histologically diagnosed in 1977 and 1978 in 12 hospitals and meeting strict definition criteria were identified. With the exception of six cases, two controls were matched to each case for sex, age, and hospital of diagnosis. A logistic regression analysis was done. The known host risk factors (eye and hair color, complexion, descent) and nonoccupational sunlight exposure were found to be operative in the Montreal region. After adjusting for these factors, occupational sunlight exposure appeared to be a risk factor. An association was then observed between the risk of squamous cell carcinoma of the skin and tobacco smoking and the use of a sunlamp. Relative risks associated with the above-mentioned factors were estimated.

The distorted shell method for clustering for syndrome classification.

Syndrome classification may be described as the arrangement of individuals into groups on the basis of their phenotypic resemblance. This paper describes how phenotypic resemblance may be quantified and demonstrates a numerical method called distorted shell clustering, which isolates groups of phenotypically similar individuals representing syndromes. This new method takes into consideration apparent biological properties of syndromes. It allows for overlapping phenotypes between syndromes, and differing character association and variability within syndromes. This method is compared to four other clustering methods by using suspects for a syndrome of known etiology (Down syndrome). The numerical results based on the phenotype then can be compared with the actual diagnosis. Only the distorted shell method classifies patients, without error, into two major clusters: the Down and the non-Down, while maintaining a high level of efficiency.

A possible approach for discrimination between normal and pathological signals using the WFLC algorithm.

The discrimination between normal and pathological tremor is difficult when amplitude is relatively small. The WFLC algorithm, a time domain adaptive Fourier transform, is designed to control physiological tremor and to improve precision during microsurgery. We added two iterative optimization processes to initialize the following parameters: initial frequency weight (omega0), amplitude adaptation rate (mu) and frequency adaptation rate (mu0). Then, we applied the methods on data sets recorded on patients with different tremors (control, parkinsonian, cerebellar, and essential) sampled at 200 Hz. After filtering the data, the WFLC algorithm tracked the time-varying dominant frequencies and amplitudes of the transformed data sets. Our results illustrate the potential of using this algorithm as an approach to discriminate between normal and pathological signals even when amplitude is not a significant discriminating factor.

Predicting survival in adults with end-stage renal disease: an age equivalence index.

To quantify prognosis in patients with end-stage renal disease, we evaluated pretreatment clinical state and ascertained the outcome of all 220 patients who began therapy at two hospitals from 1970 to 1975. Each of three pretreatment characteristics made a statistically significant independent contribution to the relative risk of death: age (relative risk for 10-year increments = 2.2, p less than 0.001); duration of diabetes (relative risk for 10-year increments = 2.2, p less than 0.001); and left-sided heart failure (relative risk = 2.0, p less than 0.001). We combined the effects of these factors in an age-equivalence index that showed a strong gradient in survival rates from lower to higher values; the 5-year survival rate differed between 92% in patients with a score of 30 or less and 6% in patients with a score over 70. This index, which is simple to use, should prove helpful in patient care and can improve the scientific validity of therapeutic comparisons in patients with end-stage renal disease by identifying and adjusting for the selection biases that occur in the allocation of different treatments.

Change-point analysis of neuron spike train data.

In many medical experiments, data are collected across time, over a number of similar trials, or over a number of experimental units. As is the case of neuron spike train studies, these data may be in the form of counts of events per unit of time. These counts may be correlated within each trial. It is often of interest to know if the introduction of an intervention, such as the application of a stimulus, affects the distribution of the counts over the course of the experiment. In such investigations, each trial generates a sequence of data that may or may not contain a change in distribution at some point in time. Each sequence of integer counts can be viewed as arising from a Poisson process and are therefore independently distributed or as an integer-valued time series that allows for correlations between these counts. The main aim of this paper is to show how the ensemble of sample paths may be used to make inference about the distribution of the instantaneous times of change in a given population. This will be accomplished using a Bayesian hierarchical model for these change-points in time. A bonus of these models is they also allow for inference about the probability of a change in each unit and the magnitude of the effects, if any. The use of such change-point models on integer-valued time series is illustrated on neuron spike train data, although the methods can be applied to other situations where integer-valued processes arise.

Plasma amino acids in 3/sec spike-wave epilepsy.

Plasma levels of 14 amino acids were determined in 44 probands with 3/sec spike-wave epilepsy, 27 of their first-degree relatives, and 22 controls. Six ratios of metabolically related amino acids were also calculated. Statistically significant differences were found for 7/20 variables when the experimental and control probands were compared, and for 6/20 variables when the relatives were compared with controls. Tau, Asp, and Tau/Glu were decreased and Glu was was increased in both the experimental probands and their first degree relatives. When discriminant analysis was used, age- and sex-matched epileptic probands could be distinguished from the age- and sex-matched control probands with 100% accuracy employing only 3 amino acids (Asp, Glu, Val) and one ratio (Thr/Ser).