Hypertension detection and follow-up program study of serum retinol, retinol-binding protein, total carotenoids, and cancer risk: a summary.

In a recently reported study by us, no significant associations were found between retinol, retinol-binding protein (RBP), and total carotenoid levels in prediagnositic serum and the incidence of cancer at all sites combined. Inasmuch as other investigators, in addition to us, have not been able to confirm the two original reports of an inverse association between serum retinol and overall cancer incidence, the relationship, if it exists at all, is probably complex and limited to certain population subgroups. Such subgroups may be defined by extreme values of serum retinol, certain levels of other nutrients, or specific types of cancer. In the present study an inverse association was observed between serum retinol levels and cancer among subjects with low serum selenium levels and for subjects with gastrointestinal cancer. In addition, the risk of cancer was elevated for those individuals with the combination of low serum retinol and high RBP. However, since significant associations will arise by chance alone when many subgroups are examined, these findings are difficult to interpret. Additional studies will be needed to determine whether they are reproducible or are simply the results of chance.

Serologic precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate cancer.

We investigated the associations of serum retinol, the carotenoids beta-carotene and lycopene, and tocopherol (vitamin E) with the risk of prostate cancer in a nested case-control study. For the study, serum obtained in 1974 from 25,802 persons in Washington County, MD, was used. Serum levels of the nutrients in 103 men who developed prostate cancer during the subsequent 13 years were compared with levels in 103 control subjects matched for age and race. Although no significant associations were observed with beta-carotene, lycopene, or tocopherol, the data suggested an inverse relationship between serum retinol and risk of prostate cancer. We analyzed data on the distribution of serum retinol by quartiles, using the lowest quartile as the reference value. Odds ratios were 0.67, 0.39, and 0.40 for the second, third, and highest quartiles, respectively.

Effect of HIV antibody disclosure on subsequent sexual activity in homosexual men.

During a prospective study of the natural history of AIDS, 1001 homosexual or bisexual men were offered the opportunity to learn their HIV antibody status. Six hundred and seventy (67%) of the population who elected to do so were similar to the 331 (33%) people who declined in a number of baseline characteristics. All were counselled to practice safe sex. To determine whether disclosure of HIV serologic status affects subsequent sexual behavior, we examined changes at four time-points in three sexual activities during the previous 6 months: the number of male partners with whom the participant had (1) sexual intercourse, (2) unprotected anal receptive intercourse, and (3) unprotected anal insertive intercourse. All activities decreased strikingly over the 18-month study period. Following disclosure, the mean number of partners dropped to 47% of the baseline number in people remaining unaware of their antibody status, to 45% in people told that they were seropositive, and to 55% in people told that they were seronegative. The mean number of partners for younger seropositives declined less than that for older seropositives. The mean number of partners with whom unprotected anal receptive intercourse was practiced declined to 57% of baseline in unaware people, 42% in aware seropositives, and 62% in aware seronegatives. The mean number of partners with whom unprotected anal insertive intercourse was practiced declined to 52% of baseline in unaware people, 42% in aware seropositives and 59% in aware seronegatives. Disclosure of a negative test result led to a significantly smaller decline in these sexual activities.(ABSTRACT TRUNCATED AT 250 WORDS)

Transmission of HIV-1 within a statewide prison system.

To assess the incidence of infection with HIV-1 in the Maryland state prison system, inmates with excess sera stored from specified intake periods between April and June 1985 and 1986 were approached in May 1987 to volunteer for venipuncture. Of the 2286 inmates for whom intake specimens were stored, 1038 (45.4%) no longer incarcerated as of April 1987 were excluded from the study; another 319 missed the survey. Of the 929 eligible inmates approached for the study, 446 (48%) consented and 422 (94.6%) provided a specimen. Twenty-nine (6.6%) were confirmed seropositive at time of entry into prison, indicating that infection had occurred prior to incarceration. Baseline seropositives were more likely (P less than 0.05) to be non-violent offenders, committed in Baltimore City, and black. The 393 participants seronegative at baseline provided a total of 482 prison-years of potential exposure to infection. Two inmates seroconverted with baseline specimens seronegative on Western blot and follow-up sera confirmed positive; their duration of pre-incarceration detention was 69 and 146 days, respectively. No interruption of incarceration was recorded for these two inmates. The rate of infection in this prison sample, which does not include an average of 2 months of pre-incarceration detention for the study sample, was 0.41% per prison-year.

Seasonal and annual variation of antibody to HIV-1 among male inmates entering Maryland prisons: update.

Previous serosurveys of antibody to HIV-1 among incoming male inmates in Maryland between April and June of 1985, 1986 and 1987 have shown a prevalence of 7.0, 7.7 and 7.0%, respectively, with stability persisting after multivariate adjustment. To investigate seasonality and update annual trends, excess sera were obtained from incoming male inmates between August 1987 and August 1988. Correctional personnel also provided demographic variables of age, race, offense, category, and jurisdiction. Once rendered anonymous, specimens were assayed for antibody to HIV-1 using enzyme-linked immunosorbent assay and Western blot. For the 12-month study period, 415 (7.9%) of 5262 consecutive male entrants were seropositive. On univariate and multivariate analyses, no significant change in seroprevalence or risk by subgroup was noted by month or season. For data from April to June 1988, 113 (8.1%) of 1398 consecutive entrants demonstrated anti-HIV-1; seropositivity was associated with age greater than 25 years, Black race, and Baltimore jurisdiction. No significant change was found over time in seroprevalence or risk of HIV-1 infection by subgroup in multivariate analysis combining data for 1985-1988. These data provide additional evidence to suggest stability of HIV-1 seroprevalence in Maryland male prison entrants.

Clinical manifestations of acute infection with human immunodeficiency virus in a cohort of gay men.

During a prospective study of the natural history of human immunodeficiency virus (HIV) infection in a cohort of gay/bisexual men, information on self-reported symptoms lasting for 3 or more days during the previous 6 months was collected without knowledge of the subject's HIV serological status. Twenty-two people were retrospectively found to have seroconverted to HIV during the interval. Each seroconverter was matched to two seronegative and two seropositive controls. Matched case-control analyses using the seronegative controls determined that the following symptoms lasting for 3 or more days were associated with new HIV infection: fever greater than 37.7 degrees C, swollen lymph nodes, night sweats and headaches. Matched case-control analyses using the seropositive controls determined that the following symptoms lasting for 3 or more days were associated with new HIV infection: fatigue, fever greater than 37.7 degrees C, swollen lymph nodes, night sweats and headaches. It was notable that the majority of seroconversions were not associated with any symptoms lasting for 3 or more days. Due to their non-specificity, symptoms associated with seroconversion are not likely to have a high positive predictive value. In high risk populations, however, appearance of these symptoms may facilitate identification of early infection that may be important for studies of natural history or for optimal timing for initiating antiviral therapy.

An evaluation of the Vita-Stat automatic blood pressure measuring device.

Four Vita-Stat (VS) automatic, coin-operated, blood pressure measuring devices were evaluated for accuracy and precision. Under field conditions, 342 adults had two blood pressure measurements with both the VS device and with the Random-Zero (RZ) device. Two of the VS machines gave significantly higher systolic (SBP) and diastolic blood pressure (DBP) values, compared to the RZ values. The mean difference between these two units and the RZ device were clinically important (14.0 and 6.9 mm Hg SBP; 7.5 and 6.8 mm Hg DBP), and resulted in the misclassification of 23% of normotensives as hypertensives. We observed a significant order effect on SBP with the VS device, with a mean decrement of 4.9 mm Hg between the first and second SBP values, compared to 0.6 mm Hg with the RZ device. Even after adjusting for this bias, all four VS devices gave significantly more variable SBP readings than the RZ unit; two of the four also gave more variable DBP values. These data suggest that the VS device is neither accurate nor precise enough at the present time to be recommended for widespread use. These findings also raise questions concerning the monitoring of performance of this and similar devices in the field.

Temporal trends of human immunodeficiency virus type 1 (HIV-1) infection among inmates entering a statewide prison system, 1985-1987.

Acquired immune deficiency syndrome (AIDS) became the leading cause of death among Maryland State prisoners in 1985. To identify the prevalence, risk factors, and temporal trends for infection with the human immunodeficiency virus type 1 (HIV-1) in the statewide prison system, excess sera were obtained from incoming male inmates during specified periods between April and June 1985, 1986, and 1987. Correctional medical personnel also provided demographic variables of age, race, offense category, sentence, jurisidiction, and an indicator of intravenous drug use. Once rendered anonymous, specimens were assayed for antibody to HIV-1, using ELISA and Western blot techniques. For data from April to June 1985, 1986, and 1987, the crude prevalence of anti-HIV-1 was 7.1, 7.7, and 7.0%, respectively. Although one-third of incoming inmates were identified as intravenous drug users (IVDUs), the drug use variable was missing for 70% of the 1985 sample, and 40% of the 1986 sample. Several strategies were used to examined temporal trends in the context of missing data. Univariate analyses suggested no substantial change over time for either HIV-1 seroprevalence or risk of infection among IVDUs.(ABSTRACT TRUNCATED AT 250 WORDS)

HIV-1, sexual practices, and contact with foreigners in homosexual men in Colombia, South America.

From October 1985 to November 1987, a sample of 294 Colombian homosexual men volunteered to answer a questionnaire on sexual practices and consented to HIV-1 testing. Testing for HIV-1 was performed using an ELISA and those positive were confirmed with envelope- and core-specific ELISAs. Statistical methods for data analysis included Mantel-Haenszel methods on contingency tables. The overall seropositivity rate was 21.1%. Subjects who reported a receptive role (either as predominantly receptive or as mixed receptive-insertive intercourse) had a seropositivity rate of 23.7%, which was significantly higher than the 10.3% found in those reporting predominantly insertive intercourse (RR = 2.30, 95% C.I. = 1.16-4.57). For subjects reporting receptive intercourse, sexual contact with foreign visitors was a significant risk factor for HIV-1 infection (RR = 1.84, 95% C.I. = 1.13-3.00). Factors of borderline significance included having had more than ten homosexual partners in the preceding year (RR = 1.53) and a history of international travel (RR = 1.43). These associations did not hold for those reporting predominantly insertive intercourse. The data indicate the need to monitor the spread of HIV-1 at the international level and provide information on subgroups of high transmission rates.

Predictors of decline in CD4 lymphocytes in a cohort of homosexual men infected with human immunodeficiency virus.

Longitudinal data on four visits scheduled at 6 month intervals were available on a cohort of 1,827 homosexual men who were human immunodeficiency virus (HIV) seropositive at entry. To identify predictors of the rate of decline of CD4 T-lymphocytes, we used an autoregressive model that relates CD4 counts to predictor variables, while adjusting for previous CD4 counts. Significant predictors of steeper decline of CD4 counts were high CD8 count, low hemoglobin, low platelets, high serum IgA, high cytomegalovirus (CMV) antibody, and low HIV antibody. Using the fitted model, a subject with an initial deficit of 314 CD4 cells (median value of study sample) with respect to seronegative subjects and with average values in all other predictors is estimated to lose approximately 53 cells in a 6 month period (95% C.I. = 45-61 cells). Contrasting this estimate to the one obtained with similar methods in intravenous drug users, it is suggested that a faster rate of decline is present among i.v. drug users. This analysis provides evidence that several covariates in addition to previous number of CD4 counts have significant predictive power for estimating the decline in CD4 counts in HIV seropositive subjects.

Incidence of Kaposi's sarcoma in a cohort of homosexual men infected with the human immunodeficiency virus type 1. The Multicenter AIDS Cohort Study Group.

Longitudinal data on 2,125 participants in the Multicenter AIDS Cohort Study (MACS) with documented antibodies to the human immunodeficiency virus type 1 (HIV-1) were used to examine the incidence of acquired immune deficiency syndrome (AIDS)-related Kaposi's sarcoma (KS) over time and to determine if sexual practices and hematologic variables prior to diagnosis differed for participants who develop KS vs. non-KS AIDS (NKS). In the first 4 years of the study, 84 seropositive men were observed to develop KS and 307 presented with an AIDS diagnosis other than KS. A systematic trend in the incidence of KS over time was not apparent in this population. The number of anal-receptive intercourse partners prior to diagnosis declined in a similar fashion for both AIDS groups. Although the number of partners with whom the men performed rimming decreased prior to diagnosis for both AIDS groups, a greater proportion of the KS AIDS group had performed this activity with multiple partners than had the non-KS AIDS group. Furthermore, history of oral gonorrhea was significantly (p = 0.027) more prevalent in the KS group. In addition, the KS AIDS group had lower cytomegalovirus antibody levels prior to diagnosis and higher levels of total immunoglobulin G. The groups did not differ with respect to baseline hematological measures, temporal trends in helper and suppressor T cells, or hepatitis B surface antigen or antibody. Given this profile of factors associated with the occurrence of KS, an infectious agent, in addition to HIV-1, is plausible as a proposed cofactor in the development of KS.

The effect of fresh lymphocytes on increased sensitivity of HIV-1 isolation: a multicenter study.

A multicenter study was undertaken to determine the sensitivity and reproducibility of markers for human immunodeficiency virus type 1 (HIV-1) viral growth and the effect of various preparations of lymphocytes on the sensitivity of standard and routinely used procedures for HIV-1 isolation. In phase 1, cocultivated culture supernatants obtained from 10 HIV-1 cultures were transported to three Multicenter AIDS Cohort Study (MACS) Virology Laboratories. Three commercial HIV-p24 antigen capture (AC) tests and two reverse transcriptase (RT) assays were used to ascertain the replication of HIV-1. The Du Pont and Abbott AC assays were found to be most sensitive (85-100%), and the RT assay with 24-h incubation period had comparable sensitivity (75-100%). In phase II, the sensitivity of standard cocultivation procedure for HIV-1 isolation was compared using freshly phytohemagglutinin-P (PHA-P)-stimulated, stimulated-frozen, and frozen-thawed and then stimulated normal human peripheral blood mononuclear cells (PBMCs) as cocultivating cells. Blood samples from 13 HIV-1 infected individuals with various CD4+ cell counts were cocultivated in each of the three MACS laboratories using one of the aforementioned normal PBMCs. The PHA-P-stimulated fresh normal PBMC showed a maximum isolation rate of 100% (13 of 13) with an average of 8 days to positivity. This rate of isolation was significantly greater than other rates using any one of the other PBMC preparations. These findings demonstrated that the use of freshly PHA-P stimulated PBMCs maximized HIV-1 isolation from blood when a sensitive HIV-1 p24 AC assay or RT assay with overnight incubation is employed for the detection of HIV in culture supernatant.

Endocrine disorders in men infected with human immunodeficiency virus.

Gonadal, adrenal, and thyroid functions were evaluated in 70 men seropositive for human immunodeficiency virus (HIV) infection, clinically categorized as asymptomatic (n = 19), AIDS-related complex (ARC) (n = 9), or acquired immunodeficiency syndrome (AIDS) (n = 42). Twenty of 40 men (50 percent) with AIDS were hypogonadal. Mean serum testosterone concentrations in both ARC (292 +/- 70 ng/dl) and AIDS (401 +/- 30 ng/dl) men were significantly less than in asymptomatic (567 +/- 49 ng/dl) or normal men (608 +/- 121 ng/dl). Of these hypogonadal men, 18 of 24 (75 percent) had hypogonadotropic hypogonadism. Seven of eight hypogonadal men (88 percent) had a normal gonadotropin response to gonadotropin-releasing hormone administration. Hypogonadism correlated with lymphocyte depletion and weight loss. Adrenal cortisol reserve, evaluated by adrenocorticotropin stimulation, was normal in 36 of 39 patients (92 percent) with AIDS. Indices of thyroid function were normal with the exception of one ARC man with a low free thyroxine index. In conclusion, hypogonadism is common in men with HIV infection and may be the first or most sensitive endocrine abnormality.

Seroepidemiology of hepatitis B virus infection in the United States. 1976 to 1980.

The prevalence of hepatitis B virus (HBV) infection was determined using sera from persons participating in the second National Health and Nutrition Examination Survey, conducted from 1976 to 1980. Of 14,488 scientifically selected participants aged 12 to 74, 821 had evidence of past or present infection with HBV. In the white population, the weighted estimate of hepatitis B infection was 3.2 percent (95 percent confidence interval, 3.1 to 4.2). A steady increase with age was seen; by ages 65 to 74, the prevalence was 6.9 percent (95 percent confidence interval, 5.2 to 8.5). In the black population, the overall weighted estimate of prevalence was 13.7 percent (95 percent confidence interval, 11.6 to 15.8). In this racial group, there was a dramatic increase with age, with the oldest age groups having a prevalence of 39.6 percent (95 percent confidence interval, 29.1 to 50.0). In both racial groups, there was a low prevalence of infection in young children that began to rise between ages 12 and 18. In a multivariate analysis of factors associated with infection, there was an interaction of race with age; therefore, the odds ratio for race is presented for four ages. This ratio ranged from 3.0 (95 percent confidence interval, 1.8 to 4.2) for a 15-year-old to 8.2 (95 percent confidence interval, 6.5 to 10.3) for a 70-year-old. These relative odds estimates were not substantially affected by adjustment for the available information on risk factors for HBV infection. The results of this study in a representative sample of the United States population show that adult black Americans are at high risk for hepatitis B infection. Other independent predictors of HBV positivity include male sex; residing in the South, Northeast, or West; residing in a city of 250,000 or more people; serving in the armed forces; living below the poverty level; and having a positive treponemal test for syphilis. These data suggest that the immunization practices for controlling this disease should be re-examined.

Flow cytometric quantitation of T cell phenotypes in cerebrospinal fluid and peripheral blood of homosexual men with and without antibodies to human immunodeficiency virus, type I.

Two-color flow cytometry was used to analyze T cell subsets (total (CD3), helper-inducer (CD4), and suppressor-cytotoxic (CD8] in paired specimens of cerebrospinal fluid (CSF) and peripheral blood of 66 homosexual men, including 62 with antibodies to human immunodeficiency virus, type 1 (HIV-1). With the exception of one traumatic specimen, all of the CSF specimens, 52 of which had less than or equal to 5 lymphocytes/mm3, were evaluated fully, with the number of lymphocytes counted for each antibody ranging from 200 to 2933 (mean = 1129). Proportions of CD3, CD4, and CD8 lymphocytes in CSF were very highly correlated with the proportions of these cells in the peripheral blood (r = 0.87, 0.96, and 0.94, respectively), as was the CD4/CD8 ratio (r = 0.98). These strong correlations were present in each of seven subgroups of study subjects defined on the basis of detailed neurologic examination, neuropsychological testing, and the presence or absence of antibodies to HIV-1. In the population studied, T cell phenotypes in CSF as analyzed by two-color flow cytometry were largely determined by the corresponding proportions in the peripheral blood.

Response of preterm infants to diphtheria-tetanus-pertussis vaccine.

The American Academy of Pediatrics recommendation that immunization of preterm infants with diphtheria-tetanus-pertussis (DTP) vaccine should begin at 2 months after birth, regardless of gestational age, is based on limited data. A prospective study was conducted to determine the immunogenicity and safety of DTP vaccine in preterm infants. One hundred ten preterm and 146 full term infants received doses of DTP at 2, 4 and 6 months after birth. Adjusted analysis of the antibody responses indicated that after three doses mean titers among preterm infants to each vaccine component were comparable to those of full term infants. Adjusted analysis of the incidence of adverse events indicated that the risk of adverse events in preterm infants was not significantly higher than that in full term infants. DTP vaccine is immunogenic and safe in preterm infants when the series is initiated at 2 months after birth, and this study supports the current recommendation of the American Academy of Pediatrics.

Immunogenicity and safety of measles vaccine in ill African children.

A concurrent prospective study was conducted in Rwanda to compare the immunogenicity and safety of live, attenuated measles vaccine in ill and well children. Five hundred and eighteen children aged 8 to 19 months were selected from children attending the acute care and immunization services of two clinics. Two hundred and sixty-seven ill children and 251 well children were enrolled and examined. Serological tests were performed on blood samples obtained before and 40 days after measles immunization. Among the 208 ill children and 215 well children who were seronegative at baseline and had unequivocal follow-up serological results, seroconversion rates were 81% and 80%, respectively. Side effects were modest and were equally frequent in the two study groups (15.4% among ill children versus 15.1% among well children). These results support a change in measles immunization policy in developing countries with respect to immunization of children with acute illnesses. Such a change would make a great contribution to decreasing the enormous burden of measles in the developing world through increased immunization coverage.

Prevention of catheter-associated urinary tract infection: a cost-benefit analysis.

A cost-benefit analysis was used to assess four strategies to prevent catheter-associated urinary tract infections in an acute care setting. Routine use of catheters with sealed collection junctions, selective use of these catheters, and oral antibiotic prophylaxis all result in fewer deaths, fewer infections, and lower overall costs than not using any of these. Routine use of sealed junction catheters results in fewer infections and deaths than does selective use. When the cost of a nosocomial urinary tract infection is +500, routine use of sealed junction catheters is also less expensive than selective use in many circumstances. Oral antibiotic prophylaxis would result in the lowest net cost and the fewest deaths and infections, if it were as effective as parenteral prophylaxis, if more than 72% of patients received it, and if important negative factors such as selection of antimicrobial resistance and adverse drug reactions are not considered. When there is no extra cost of sealed junction catheters, their use is less expensive than the oral prophylaxis strategy if the total cost of oral prophylaxis, including the cost of adverse reactions, is greater than +15. If the extra cost of sealed junction catheters is +4 per unit, their use is less expensive than oral prophylaxis when its cost exceeds +35. Prevention of catheter-associated urinary tract infection reduces the overall cost of patient care, even when the prevention itself incurs costs. This analysis supports the routine use of sealed junction catheters in most acute care situations that require indwelling catheter drainage. Currently, we do not recommend routine antibiotic prophylaxis.

Hepatitis B: a controllable disease.

Major advances have been made in understanding the epidemiology and biology of the hepatitis B virus. Two particular developments--hepatitis B immune globulin and a new hepatitis B virus vaccine--are of special interest to obstetricians, gynecologists, and others who provide health care to women. The appropriate use of hepatitis B immune globulin and hepatitis vaccine can prevent hepatitis B virus infections.

Rarity of cesarean delivery in cases of juvenile-onset respiratory papillomatosis.

Papillomas of the respiratory and genital tracts are caused by the same papillomavirus genotypes, and mothers of children with respiratory papillomatosis often have a history of genital warts. Only one of 109 cases reviewed gave a history of birth by cesarean section, whereas ten cesarean deliveries would have been the expected number for this group on the basis of national rates. The single case was delivered by elective cesarean section before the rupture of the membranes, and the child developed respiratory papillomatosis in the first year of life. These findings suggest that in juvenile-onset disease, the transmission of infection from mother to child occurs most often during passage through an infected birth canal, but that intrauterine infection of the fetus is also possible. Papillomavirus infection of the female genital tract is common, but respiratory papillomatosis is rare. On the basis of crude estimates of annual number of children born to infected mothers and of new cases of juvenile-onset disease, the risk of developing disease for a child born to an infected mother was calculated to be one in several hundred exposures.