Otic lesions and congenital hypothyroidism in the developing chick.

In an effort to elucidate the relation, if any, between thyroid abnormality and congenital deafness in Pendred's syndrome, an experiment was designed to study the effects of hypothyroidism on middle and inner ear hearing structures, including the auditory nerve and its central projection, in developing chick embryos. Propylthiouracil (PTU), 2 mg, was injected into the albumin of fertile chick eggs on the 10th incubation day. Single doses of L-thyroxine (range 1-100mug) were inoculated in a similar manner, either alone or with PTU. Control inocula included sterile saline or water. After hatching, each chick was examined for obvious malformations. The thyroid glands, middle and inner ear mechanisms, auditory nerve, and brainstem were studied grossly and with different histologic staining techniques. When compared to controls, chicks exposed to PTU on their 10th incubation day exhibited: increased mortality, delayed hatching, reduced size, incomplete yolk sac absorption, and death within 5 days unless exogenous thyroid hormone was provided in the first 24-48 hr after hatching. Specific, consistent, morphologic alterations were observed in their thyroid glands as well as in the sensory hair cells of the acoustic papilla and cells of the spiral ganglion of the cochlea. Our data also indicate that if 50-75 mug of L-thyroxine is given simultaneously with (or as long as 120 hr after) the PTU injection on the 10th incubation day, one cannot detect the gross defects, marked thyroid lesions, or abnormal histology in cells of the cochlea and its ganglion. A relationship between embryonic thyroid gland function and the hearing mechanism of the chick embryo is suggested.

Prevalence of diabetes in Mexican Americans. Relationship to percent of gene pool derived from native American sources.

We have estimated the prevalence of non-insulin-dependent diabetes mellitus (NIDDM) in Mexican Americans and Anglos in three San Antonio neighborhoods. The age-adjusted NIDDM rates (both sexes pooled) for Mexican Americans were 14.5%, 10%, and 5% for residents of a low-income barrio, a middle-income transitional neighborhood, and a high-income suburb, respectively. In Mexican American women, though not in men, obesity also declined from barrio to suburbs. We have previously shown, however, that, although obesity is an important cause of NIDDM in Mexican Americans, there is a two- to fourfold excess in the rate of NIDDM in this ethnic group over and above that which can be attributed to obesity. We therefore speculated that genetic factors might also contribute to excess NIDDM in this ethnic group. The percent native American admixture of Mexican Americans as estimated from skin color measurements was 46% in the barrio, 27% in the transitional neighborhood, and 18% in the suburbs. The NIDDM rates in Mexican Americans thus paralleled the proportion of native American genes. Furthermore, the San Antonio Mexican American rates were intermediate between the NIDDM rates of "full-blooded" Pima Indians (49.9%), who presumably have close to 100% native American genes, and the San Antonio Anglo population (3.0%) and the predominantly Anglo HANES II population (3.1%), both of which presumably have few if any native American genes. The association of genetic admixture with NIDDM rates suggests that much of the epidemic of NIDDM in Mexican Americans is confined to that part of the population with a substantial native American heritage.

A longitudinal analysis of hospitalization and emergency department use among human immunodeficiency virus-infected women reporting protease inhibitor use.

The impact of protease inhibitors (PIs) on emergency department (i.e., emergency room [ER]) visits and hospitalizations was examined among a cohort of human immunodeficiency virus (HIV)-infected and high-risk women followed-up in the HIV Epidemiology Research Study (HERS) from 1993 through 1999. The rates of hospitalization and ER visits were measured as a function of recent or current PI use, age, race, transmission risk category, HERS site, baseline CD4 cell count, and baseline virus load; the PI effect was estimated separately by baseline CD4 cell count. In the HERS, PI use was strongly associated with lower rates of ER visits and hospitalizations for patients with baseline CD4 cell counts of <200 cells/mL (for hospitalizations: rate ratio [RR], 0.54; 95% confidence interval [CI], 0.33-0.89; for ER visits: RR, 0.38; 95% CI, 0.24-0.61). Other factors associated with increased hospitalization and ER use included history of injection drug use, low CD4 cell counts, and high virus loads.

Effect of physician specialty on counseling practices and medical referral patterns among physicians caring for disadvantaged human immunodeficiency virus-infected populations.

Data regarding the care and management of human immunodeficiency virus (HIV)-infected patients provided by infectious diseases (ID)-trained physicians, compared with data for care and management provided by other specialists, are limited. Here, we report results of a self-administered survey sent to 317 physicians (response rate, 76%) in 4 metropolitan areas of the United States who were identified as providing care to disadvantaged HIV-infected patients. ID-trained physicians who responded that they strongly agreed or somewhat agreed that they had enough time to care for their HIV-infected patients were more likely than were non-ID-trained physicians to provide therapy-adherence counseling. Physicians with >or=50 patients in care and ID-trained physicians were less likely to always discuss condom use and risk reduction for HIV transmission. Factors significantly associated with referring rather than treating HIV-infected patients with hypertension or diabetes included having <50 patients in care, being an ID-trained physician, and practicing in a private practice. These results suggest the need for targeted physician training on the importance of HIV transmission prevention counseling, increasing the duration of patient visits, and improving strategies for generalist-specialist comanagement of HIV-infected patients.

Hypertensive virilizing adrenal hyperplasia with minimal impairment of synthetic route to cortisol.

One of the first described cases of hypertensive virilizing adrenal hyperplasia (VAH) (Pediatrics 8: 805, 1951) has been followed from age 2 1/2 until age 26. Blood pressure as an infant was 150/90, and at age 25 was 220/160. During childhood the patient was lost to follow-up for prolonged periods, and received no therapy from age 20 to 25. At this time 24 h urinary excretion of 17-ketosteroids was 89 mg; tetrahydro 11-deoxycortisol (tetrahydro S), 47 mg and pregnanetriol 5.7 mg. Hourly measurements of several plasma steroids utilizing sephadex LH 20 chromatography and competitive protein binding were made during 24 h; concentration ranges were made during 24 h; concentration ranges were as follows (mug/100 ml): 11-deoxycortisol 8-40; cortisol 0-48; corticosterone 0-15; deoxycorticosterone 1-18. Plasma cortisol, especially showed a significiant morning impairment, but reached normal and even markedly elevated levels during the day and early evening. Urinary cyclic AMP per 24 h ranged from 5.3 to 11.6 n mol/mg creatinine before therapy, and was 1.9 n mol after therapy. The results suggest either the formation of an alternate pathway to cortisol synthesis, or the existence of a form of VAH with two independent 11-B hydroxylating systems, exhibiting only minimal impairment of the synthetic route to cortisol. The latter would support the presence of two independent 11-B hydroxylating systems in the normal human adrenal. This has been suggested by Zachmann et al. (J Clin Endocrinol Metab 33: 501, 1971) to be true in infancy. Our observations on an adult indicate that these two systems may not be transitory, but persist into adulthood.

The dynamics of CD4+ T-lymphocyte decline in HIV-infected individuals: a Markov modeling approach.

We modeled the decline of CD4+ T-lymphocytes (T4 cells) in HIV-infected individuals with a continuous-time Markov process. The model partitions the HIV infection period into six progressive T4-cell count intervals (states), followed by a seventh state: a definitive HIV-infection end point, i.e., AIDS diagnosis or Walter Reed stage 6 (opportunistic infections). The Markov model was used to estimate the state-specific progression rates from data as functions of important progression cofactors. We applied the model to data on 1,796 HIV-positive individuals in the U.S. Army. The estimated mean waiting time from seroconversion to when the T4-cell count persistently drops below 500/mm3, but is greater than 349/mm3, is 4.1 years, and the waiting time to a T4-cell count of less than 200/mm3 is estimated at 8.0 years. The estimated rate of T4-cell decline was higher for HIV-infected individuals with initially high numbers of T4 cells, but the estimated rate of decline remains relatively uniform when the T4-cell count dropped persistently below 500/mm3. The opportunistic infection incubation period, i.e., the time from seroconversion to opportunistic infection diagnosis, is estimated at 9.6 years. Age is found to be an important cofactor. The estimated mean opportunistic infection incubation periods are 11.1, 10.0, and 8.9 years for the youngest (less than or equal to 25 years old), the middle (26-30 years old), and the oldest (greater than 30 years old) age groups, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Evidence for spread of the human immunodeficiency virus epidemic into low prevalence areas of the United States.

Reports of an increased proportion of AIDS cases occurring in small and medium-sized cities suggest that the HIV epidemic may be spreading into locations that were previously characterized by their low HIV antibody prevalences. Studying the question of the geographic spread of the HIV infection epidemic (rather than the AIDS epidemic) has been difficult largely because most serial seroprevalence data have been gathered from cohorts of high risk individuals (e.g., homosexual/bisexual cohorts) in New York City, San Francisco, and other geographically circumscribed areas. The U.S. military applicant HIV screening data were used in the current report to examine rates and 24 month temporal trends in geographic areas characterized by their HIV endemicities. The data examined concern the seven most populous states and four hyperendemic metropolitan areas located within those states (New York City, Miami, Houston, and San Francisco). In the nonepidemic regions, seroprevalence rates increased among black and white applicants. In the four epidemic urban areas, only young black applicants had higher HIV seroprevalence rates during the second 12 month period. Six of the seven nonepidemic regions had positive HIV seroprevalence trends, and these trends were significant in Florida, California, Texas, Illinois, and Ohio. The increases in these regions were greater for young blacks (30% excess for year 2 vs. year 1) compared to young whites (12% excess for year 2 vs. year 1). These data provide evidence of birth year specific increases in seroprevalence over time occurring in presumed low HIV prevalence areas. These increases cannot be due to, but are observed in spite of, biases associated with increasing self-selection over time.

Tracking the spread of the HIV infection epidemic among young adults in the United States: results of the first four years of screening among civilian applicants for U.S. military service.

Because the period from infection to clinically apparent disease is long, variable, and changing as new therapies are developed and applied, AIDS data are inadequate for tracking current values of critical parameters of HIV infection epidemics: prevalence of infection, rate of acquisition of new infections (incidence rate), and direction and rate of change of infection incidence over time (acceleration). These "vital signs" of infection epidemics can be tracked using serial cross-sectional seroprevalence data, however. From October 1985 through September 1989, more than 2.3 million applicants for U.S. military service were screened for antibody to HIV. The overall seroprevalence was 1.31 per 1,000 (3,014/2,300,675). Seroprevalences were highest near urban centers of the AIDS epidemic and were independently associated with age, race/ethnicity, and gender. Based on age seroprevalence trends, it was crudely estimated that at least one of 2,000 young men and one of 7,000 young women are infected with HIV annually in the U.S. Infection incidence rates, estimated from age and temporal trends, were estimated to be highest among black males (1.40/1,000/year) and lowest among white females (0.03/1,000/year). Poisson regression analysis of seroprevalence trends suggested that infection incidence rates accelerated among black females during the first 3 years of screening. Since selection factors undoubtedly changed over the period, estimates based on these data probably underestimate actual values in the general population, particularly near urban AIDS epicenters. Nonetheless, even crude estimates of these critical values, particularly among adolescents and young adults, are useful to guide policy development, to allocate resources, and to monitor program effects.

Predictors of HIV-1 disease progression in early- and late-stage patients: the U.S. Army Natural History Cohort. Military Medical Consortium for Applied Retrovirology.

HIV-infected individuals in both early and late stages of HIV disease were evaluated over 2 years to assess temporal trends and determinants of disease progression. The Walter Reed (WR) staging system was used to categorize patients into an early-stage cohort (WR Stages 1 and 2, N = 1183) and a late-stage cohort (WR Stage 5, N = 260) based on the initial clinical evaluation. Progression was defined as the occurrence of Stage 5 disease or beyond for the early cohort and Stage 6 disease or beyond for the late cohort. The cumulative incidence of progression was 15.7% (137 events) for the early-stage cohort, and 53.7% (85 events) for the late-stage cohort. Baseline CD4+ T lymphocyte (T4) count was the most significant marker of progression: 26% of WR Stage 1 or 2 patients with T4 lymphocytes below 500/mm3 progressed, compared with 12% with T4 lymphocytes at or above 500/mm3. In late-stage individuals, 83% with T4 lymphocytes under 200/mm3 progressed, compared with 27% with T4 lymphocytes at or above 200/mm3. Older age was associated with progression in both early- and late-stage groups. Differences in the rates of disease progression were not significant between blacks and whites or between men and women. Two-year rates of progression among the late-stage patients dropped from 78 to 47% between 1986 and 1988. This contrasted with progression rates in the early-stage cohort, which remained stable: 18% for those entering follow-up in 1986 and 17% for those entering follow-up in 1988. These data indicate a significant slowing of HIV disease progression rates and mortality rates among individuals with late-stage disease that is temporally associated with the increased availability and use of therapies. With control of T4 lymphocyte count, age, and calendar time, neither gender nor race was significantly associated with progression in either early- or late-stage patients.

Misclassification of physical work exposures as a design issue for musculoskeletal intervention studies.

OBJECTIVES: This study determined the impact of misclassification due to using job titles as surrogate variables for physical work exposures to assess confounding in a study of the preventive effect of back belts on back injury. The authors present retail merchandise data that quantify misclassification from residual confounding by physical work exposures on injury rate ratios when available administrative job titles are used. METHODS: Job title and direct observation data on 134 workers were used to calculate the percentage to which the job-title-adjusted rate ratio for back injury accounts for confounding by the true physical work exposures, awkward postures, and heavy weight handling. Workers' compensation data, an estimate of the effect of back belts from the literature, and the percentage of adjustment of the rate ratio due to the job title variable were used to calculate the magnitude of bias from the rate ratio adjusted for job title. RESULTS: The job title variable was found to have sensitivities of 97% and 85% and specificities of 68% and 58% for awkward postures and heavy weight handling, respectively. The magnitude of confounding bias remaining for the back-injury rate ratio when the job title surrogate was used was 24% for postures and 45% for heavy weight handling. CONCLUSIONS: The administrative job title performed poorly in this setting; residual confounding was sufficient to bias the rate ratio from 2.0 to 1.3. The effect of additional sources of misclassification and the need for better exposure measures than job title are discussed.

Highly active antiretroviral therapy associated with improved anemia among HIV-infected women.

Anemia is common during human immunodeficiency virus (HIV) infection and is associated with increased mortality. We conducted a study to examine the impact of highly active antiretroviral therapy (HAART) on anemia in a multicenter cohort of HIV-positive women, the Human Immunodeficiency Virus Epidemiology Research (HER) Study. Among women receiving HAART (n = 188), non-HAART monotherapy or combination antiretroviral therapy (ART) (n = 111), or who had no reported treatment (n = 62), the prevalence of anemia (hemoglobin, <120 g/L) at baseline was 38.3, 36.9, and 43.6%, respectively (p = 0.58) and at 1-year follow-up was 26.1%, 36.9%, 45.2%, respectively (p = 0.01); mean hemoglobin at baseline was 125 +/- 16, 122 +/- 16, and 122 +/- 18 g/L, respectively (p = 0.29) and at 1-year follow-up was 128 +/- 14, 123 +/- 16, and 119 +/- 20 g/L, respectively (p < 0.0001). Adjusted linear regression models showed that HAART was associated with an increase of hemoglobin of 0.20 g/L per month (p = 0.007). After 1 year of treatment, HAART was associated with a 32% reduction in anemia among HIV-infected women (p = 0.01), whereas there was no significant change in the prevalence of anemia among those on non-HAART ART or those who had no reported treatment. HAART is associated with a large reduction in anemia among HIV-infected women.

Ergonomic exposure assessment: an application of the PATH systematic observation method to retail workers. Postures, Activities, Tools and Handling.

This study examined biomechanical stressor variables (physical work exposures) in relation to job title, gender, and back-belt status in 134 retail store workers. The principal concerns were to quantitatively describe physical work exposures and to determine the degrees to which these quantitative variables correlated with job title and with the use of back belts. An additional objective was to assess the inter-rater reliability of the observation method. The systematic observation method employed was based on a modification of the PATH (Postures, Activities, Tools, and Handling) measurement method. Chi-square analysis indicated that the frequencies of bent or twisted postures followed the pattern of unloaders > stockers > department managers. For weight handled per lift, lower, or carry, the pattern was unloaders > department managers > stockers. The mean lifting frequencies per hour were 35.9 for department managers, 48.8 for stockers, and 137.4 for unloaders. Back-belt-wearing percentages were higher for unloaders (63%) compared with stockers (48%) and department managers (25%). Back-belt-wearing workers had higher levels of biomechanical stressor variables, including arm position, twisting, weight handled, and number of lifts per hour. Kappa statistics ranged from 0.5 to 0.63, a level of adequate or good reliability beyond chance. The method employed in this study is applicable in studies that require only fairly crude distinctions among biomechanical stressor variables. Nevertheless, this level of distinction may be sufficient when implementing intervention studies and control strategies for many material-handling-intensive jobs.

Activation of latent Graves' disease in children. Review of possible psychosomatic mechanisms.

In some children, psychological events have appeared to be important in the triggering of Graves' disease. This report examines the case histories of three children in whom the appearance of symptomatology of Graves' disease was associated with depression following the death of a loved one. An analysis of neuroendocrine and immunologie pathways suggests that depression, set off by bereavement, causes low levels of norepinephrine in the brain. The latter in turn may mediate an increase in ACTH and cortisol, leading to reductions in immune surveillance and resultant production of thyroid-stimulating immunoglobulins, hence the development of Graves' disease.

The X isochromosome-X syndrome [46,X,i(Xq)]. Report of three cases with review of the phenotype.

It is important not to confuse the 46,X,i(Xq) syndrome with the 45,X classical Turner's syndrome. There are profound cytogenetic and clinical differences between the two syndromes, which must be borne in mind in the differential diagnosis of amenorrhea and of infertility.