Referral to autopsy: effect of antemortem cardiovascular disease: a population-based study in Olmsted County, Minnesota.

PURPOSE: Autopsy studies can provide insight into disease trends and their determinants, including data on the prevalence of atherosclerosis. However, such studies are subject to autopsy bias, which limits their generalizability to the source population. The impact of this bias on autopsy based estimates of time trends in heart disease prevalence is unknown. To report on the trends over time in autopsy rates in Olmsted County, MN, to examine the association between clinical diagnoses of cardiovascular diseases (CVDs) and referral to autopsy and how this association may have changed over time. METHODS: We examined the trends in autopsy rates between 1979 and 1994 in Olmsted County, and the association between antemortem characteristics including cardiovascular diagnoses and autopsy referral. RESULTS: From 1979 to 1994, a total of 9110 residents died in Olmsted County. The average annual autopsy rate was 30%. Autopsy rates declined from 36% in 1979 to 23% in 1994, corresponding to an average decline of 0.6%/year (p < 0.01). Referral to autopsy was positively associated with younger age, male sex, in-hospital place of death, antemortem diagnoses of myocardial infarction (MI) or peripheral vascular disease (PVD), and earlier calendar period. There was no evidence of an interaction between calendar period and any of these predictor variables. Antemortem diagnosis of heart failure was associated with a decrease in the odds of referral to autopsy over time as compared to persons without such diagnosis. CONCLUSIONS: In Olmsted County, autopsy rates, although declining over time, have remained on average approximately 30%. Antemortem diagnoses of MI or PVD are associated with autopsy referral but this association did not change over time. While the greater decline overtime in the use of autopsy observed among decedents with an antemortem diagnosis of congestive heart failure (CHF) deserves further studies, the present findings reduce the concern for bias of time trends in the prevalence of atherosclerosis by changes in the clinical characteristics of decedents referred to autopsy.

Prostate cancer: the stage disadvantage in the black male.

In an effort to determine the impact of race on the stage of prostate cancer at presentation, the records of 2102 patients diagnosed in Chicago between 1985 and 1987 were reviewed. For each of three age groups (less than 65, 65 to 75, and greater than 75 years), blacks had a significantly (P less than .05) lower percentage of localized stage disease than whites. Inasmuch as stage at diagnosis is inversely related to survival, these data may explain in part why prostate cancer mortality in every age category is higher for blacks than whites nationally.

Bilateral orchiectomy in the management of stage D-2 prostate cancer.

The records of 115 patients with stage D-2 prostate cancer treated with bilateral orchiectomy were reviewed to determine the effect of this procedure in previously untreated patients and in patients who had prior hormone therapy. Previously untreated patients survived 22.8 months while those who had prior hormone therapy survived 39.3 months (p < 0.001). Bilateral orchiectomy may be of additional clinical benefit in patients with advanced prostate cancer who have had prior hormone therapy.

White blood cell telomerase activity and incident respiratory illness among community-dwelling elderly vaccinated against seasonal influenza.

Immune cell telomerase activity may impact vaccine response in the elderly. Fifty persons aged 60-100 years were tested for post-influenza vaccination telomerase RNA expression (TERT) in peripheral blood mononuclear cells to assess for an association with influenza antibody levels and influenza-like illness or incident respiratory infection (IRI) in the year following vaccination. High rates of seroprotective influenza antibody (> or = 1:40 titers) were observed post-vaccination (86-92% to vaccine viral strains), with no association to TERT. No IRI occurred among persons in the top quartile of TERT expression, whereas the IRI rate was 33% in the lower three quartiles (Kaplan-Meier P=0.028). TERT expression was also IRI significantly higher in those who did not experience IRI than those who did in the follow-up period (0.845 vs. 0.301, P=0.024). These data suggest that telomerase expression may correlate with immune capacity for vaccine response in the elderly and could represent a target for recognizing risk for vaccine failure.

Effect of environmental molds on risk of death from asthma during the pollen season.

OBJECTIVE: Many studies have noted an association of ambient aeroallergen levels with exacerbation of asthma. This study was undertaken to examine the relationship of aeroallergen levels with asthma-related mortality in Chicago. METHODS: The association of environmental aeroallergen levels with death caused by asthma among 5- to 34-year-olds in Chicago was examined for the period of 1985 through 1989. Logistic regression analysis was used to compare the probability of a death caused by asthma occurring on the basis of environmental tree, grass, or ragweed pollen and mold spore levels. RESULTS: Mean mold spore levels but not tree, grass, or ragweed pollen levels were significantly higher for days on which asthma-related death occurred than for days on which no deaths occurred (z = 2.80, p < 0.005). The odds of a death caused by asthma occurring on days with mold spore counts of 1000 spores per cubic meter or greater was 2.16 times higher (95% confidence interval = 1.31, 3.56, p = 0.003) than on days on which mold spore counts were less than 1000 spores per cubic meter. The association with mold spore levels remained significant on multivariate logistic regression with mold spore counts measured as a continuous variable and controlling for pollens, with the odds of an asthma-related death occurring being 1.2 times higher (95% confidence interval = 1.07-1.34) for every increase of 1000 spores per cubic meter in daily mold spore levels. CONCLUSION: Although death caused by asthma also involves personal, social, and medical access factors, these data suggest that exposure to environmental molds may play a role in asthma-related mortality and should be considered in prevention strategies.

Evaluation of cytokeratin markers to differentiate between benign and malignant prostatic tissue.

Cytokeratins are intermediate filaments found within basal and secretory epithelial cells. Antisera raised against cytokeratins are available but frequently differ in specificity. Many are incompletely characterized for their reactivity against epithelial components. Cytokeratin (Cyto) P is a polyclonal antisera specific for 56 and 64 kd cytokeratins. Cyto M is a pool of monoclonals reacting against 40, 46, 50, 52, 58, and 65-67 kd cytokeratins. Initially, utilizing immunohistologic techniques, we evaluated these two antisera for their ability to distinguish between prostatic tissues of benign (benign prostatic hypertrophy [BPH]) or malignant (carcinoma of the prostate [CAP]) origin in the 34 cases evaluated. Specimens were analyzed for both Cyto P and Cyto M reactivity, as well as for the degree of reactivity. Lastly, in an effort to determine the morphologic relationship of atypical hyperplasia (AH) with either BPH or CAP, nine additional prostate specimens were analyzed. Cyto P was reactive in 8 of 8 (100%) BPH specimens and in 2 of 26 (8%) CAP specimens. Mean Cyto P degree of reactivity in the positive specimens was greater in BPH than in CAP (2.6 vs. 1.0). Cyto M reactivity was present in 8 of 8 (100%) BPH specimens and in 23 of 25 (92%) CAP specimens. Mean Cyto M degree of reactivity in the positive specimens was greater in CAP than in BPH (3.6 vs. 2.8). Cyto P was reactive in 3 of 9 (33%) AH specimens, with a mean degree of reactivity of 2.7. Cyto M was reactive in 9 of 9 (100%) AH specimens, with a mean degree of reactivity of 3.9. Cyto P reacted with only the basal cells, whereas Cyto M reacted with basal as well as secretory cells. These differences appeared to be the result of the differential reactivity of basal cells, which are present in BPH but absent in CAP. In summary, Cyto P and Cyto M are potentially useful markers in differentiating BPH from CAP, and it appears that AH is immunohistopathologically related to both.

Characteristics of hospitalization for asthma among persons less than 35 years of age in Chicago.

Mortality from asthma in Chicago is among the highest in the nation for 5-34-year-olds. Data for all hospitalizations among Chicago residents less than 35 years of age were examined to define characteristics that may be contributing to morbidity and mortality from asthma. From 1987 through 1989, the average annual age-adjusted hospitalization rate among persons less than 35 years of age in Chicago was 3.57 per 1000 persons. There were significant associations of community hospitalization rate with median income (r = -0.61, p < 0.001) and with proportion of community asthma hospitalizations using Medicaid, Medicare, or self-payment (r = 0.69, p < 0.001). Among 18-34-year-old men, asthma hospitalization rates for Medicaid recipients were 17.4-34.1-fold higher than among men using other forms of insurance. Asthma admissions using Medicaid, Medicare, or self-payment were more likely than those using other forms of insurance to present through the emergency department (79.3% and 66.4%, respectively, p < 0.001) and be discharged against medical advice (1.8% vs. 0.7%, respectively, p < 0.001). These data suggest that differential access to or utilization of health care may be contributing to asthma morbidity in Chicago.

GM-CSF restoration of a differentiated (growth factor-regulated) phenotype in an anaplastic tumor.

GM-CSF (granulocyte-macrophage-derived colony-stimulating factor) is a differentiation agent that stimulates bone marrow activity in patients receiving chemotherapy. GM-CSF (1 microgram/ml daily for 10 days), administered intralesionally, was evaluated to determine whether it would restore a more differentiated phenotype to an anaplastic, rapidly growing, hormone-independent variant (R3327 MAT-LyLu) of the Dunning prostatic adenocarcinoma. Immunohistology was used to quantitate the expression of epithelial growth factor receptors (rEGF) and the tissue testosterone content. GM-CSF therapy significantly (P less than 0.05) restored rEGF expression and tissue testosterone to levels associated with better differentiated, slower growing, androgen-dependent Dunning variants (R3327 H and G). GM-CSF may have a role in treatment of prostatic cancers by promoting androgen and epithelial growth factor regulation.

Cytoreductive surgery impedes metastasis and enhances the immune response: a preliminary report.

In an effort to determine the effect of cytoreductive surgery on the metastatic process, MAT-LyLu flank tumors were excised from Copenhagen x Fischer rats and the effects of this surgery on metastatic lung lesions were observed. Cytoreduction resulted in a decrease in lung lesions (P less than 0.05). Adjuvant cyclophosphamide (CTX) further enhanced this beneficial effect. A concurrent increase in the helper/suppressor ratios suggested that this beneficial response might be mediated by the host's immune response.

Trends in asthma mortality among African Americans and whites in Chicago, 1968 through 1991.

Death certificate data were used to examine asthma mortality among African Americans and Whites aged 5 through 34 years in Chicago from 1968 through 1991. African Americans experienced consistently higher asthma mortality throughout the period. Asthma mortality remained stable among Whites from 1968 through 1991 but increased by 337% among African Americans from 1976 through 1991 (P < .001). The increase was greatest among 20- through 34-year-olds. Between 1979 and 1991, outpatient and emergency department deaths increased significantly, while the proportion of dead-on-arrival cases remained stable at 51%. This shift to non-inpatient deaths suggests that lack of access to health care may play a role in increasing asthma mortality.

Coordinate loss of growth regulatory factors following castration of rats carrying the Dunning R3327 G prostatic tumor.

Hormonal manipulation of prostate cancer is an effective therapy for metastatic disease. Unfortunately, following an initial response tumors reestablish themselves as hormone independent variants and progress. This study was designed to assess the interrelationship of cytokeratin P (Cyto P), vimentin, epidermal growth factor receptor (rEGF) and tissue testosterone following androgen deprivation therapy. Animals bearing the hormone dependent Dunning R3327 G subline prostatic adenocarcinoma were surgically castrated and progressing tumors from both hormone intact and castrated groups were quantitatively assayed for immunohistologic reactivity against the described markers. The results demonstrate a significant (p < 0.05) decrease in cytokeratin (Cyto P), rEGF and testosterone levels following castration. When the expression of both rEGF and Cyto P are related to the tissue testosterone content, it is observed that the ratio between rEGF and testosterone remains essentially unchanged (0.65 +/- 0.21 to 0.65 +/- 0.41), suggesting that in the Dunning R3327 G subline, rEGF expression is coordinately under androgen control. At least some cytokeratin expression also appears to be particularly sensitive to androgen levels, since the ratio between Cyto P and testosterone decreased from 0.92 +/- 0.39 to 0.35 +/- 0.41 following castration. In contrast, following castration, the expression of vimentin was unaffected.

Value of tumor size in predicting survival from renal cell carcinoma among tumors, nodes and metastases stage 1 and stage 2 patients.

Results in the literature are inconsistent regarding the value of tumor size in predicting survival from renal cell carcinoma, and its use as a staging variable in the current tumors, nodes and metastases system has been questioned. In this study tumor size had no prognostic significance in Kaplan-Meier or Cox regression models examining survival differences between 93 patients with stage T1N0M0 and T2N0M0 renal cell carcinoma dichotomized by tumor size cutoffs at 2.5, 5, 7.5 or 10 cm. In multivariate Cox regression models for 122 patients with stage T1NallMall or T2MallMall renal cell carcinoma, metastatic disease was the strongest predictor of survival, and patients with smaller tumors had significantly longer survival than those with larger tumors at all cutoffs except 2.5 cm., for which differences were insignificant. A 5 cm. cutoff maximized the value of tumor size in predicting survival. If tumor size is to remain the variable by which tumors, nodes and metastases stages T1 and T2 disease are differentiated, a 5 cm. cutoff should replace the current 2.5 cm. definition.

Prevention of perinatal transmission of the hepatitis B virus. Outcome of infants in a community prevention program.

OBJECTIVE: To assess the outcome of infants born to hepatitis B surface antigen (HBsAg)-positive mothers who received prenatal and infant care in a large, public health care system. DESIGN: Follow-up of a cohort of infants born to HBsAg-positive mothers. SETTING: Large, urban hospital providing prenatal care and obstetric services to county health departments. PARTICIPANTS: Forty-two infants born to HBsAg-positive women. INTERVENTIONS: Prenatal testing of women and immunoprophylaxis of infants with hepatitis B immune globulin at birth and hepatitis B vaccine at birth and ages 1 and 6 months. RESULTS: All 42 infants received hepatitis B immune globulin and the first dose of vaccine. Of forty-one infants (98%) who received the second dose of vaccine, 37 received it by age 4 months. Thirty-two infants (76%) completed the three-dose vaccine series by age 12 months, and 34 infants (81%) completed the series by age 18 months. The rate of completion of the hepatitis B vaccine series was comparable to that of infants receiving the third dose of diphtheria-pertussis-tetanus vaccine. Of 26 infants who completed the hepatitis B vaccine series and had follow-up serologic testing, 24 (92%) had adequate levels of antibody to HBsAg. Only one infant who did not complete the vaccine series had serologic evidence of hepatitis B virus infection. No infant was HBsAg-positive. CONCLUSIONS: Public programs serving urban populations can effectively deliver hepatitis B immunoprophylaxis to infants born to HBsAg-positive mothers.

Bone scan as a stratification variable in advanced prostate cancer.

The serial technetium 99 (99Tc) bone scans of 76 patients with Stage D-2 prostate cancers were reviewed. Sites of metastases in skeletal areas in decreasing order were vertebrae, ribs, pelvis, long bones, and skull. Patients with one or two involved skeletal areas had a significantly longer progression-free interval and survival time than patients with three or more bony areas of uptake. Bone scans might be used as a stratification variable in future prospective clinical trials of Stage D-2 prostate cancer.

The epidemiology of Wegener's granulomatosis. Estimates of the five-year period prevalence, annual mortality, and geographic disease distribution from population-based data sources.

OBJECTIVE: To estimate the prevalence, annual mortality, and geographic distribution of Wegener's granulomatosis. METHODS: Analysis of national vital statistics data and hospitalization data from a national survey and from all New York State inpatient facilities. RESULTS: Between 1979 and 1988, 1,784 death certificates in the United States listed Wegener's granulomatosis as a cause of death. Nationally, an estimated 10,771 hospitalizations included Wegener's granulomatosis among the discharge diagnoses. In New York State, there were 978 hospitalizations among 571 individuals with Wegener's granulomatosis. CONCLUSION: The prevalence of Wegener's granulomatosis in the United States is approximately 3.0 per 100,000 persons. Clear differences in the geographic distribution of Wegener's granulomatosis are apparent when analysis consider rates of disease in individual counties. Contrary to previous reports, associations between disease exacerbations and season were not apparent.

Identification of multiple quantitative trait loci linked to prion disease incubation period in mice.

Polymorphisms in the prion protein gene are known to affect prion disease incubation times and susceptibility in humans and mice. However, studies with inbred lines of mice show that large differences in incubation times occur even with the same amino acid sequence of the prion protein, suggesting that other genes may contribute to the observed variation. To identify these loci we analyzed 1,009 animals from an F2 intercross between two strains of mice, CAST/Ei and NZW/OlaHSd, with significantly different incubation periods when challenged with RML scrapie prions. Interval mapping identified three highly significantly linked regions on chromosomes 2, 11, and 12; composite interval mapping suggests that each of these regions includes multiple linked quantitative trait loci. Suggestive evidence for linkage was obtained on chromosomes 6 and 7. The sequence conservation between the mouse and human genome suggests that identification of mouse prion susceptibility alleles may have direct relevance to understanding human susceptibility to bovine spongiform encephalopathy (BSE) infection, as well as identifying key factors in the molecular pathways of prion pathogenesis. However, the demonstration of other major genetic effects on incubation period suggests the need for extreme caution in interpreting estimates of variant Creutzfeldt-Jakob disease epidemic size utilizing existing epidemiological models.