Risk factors for male breast cancer.

To investigate risk factors in male breast cancer, a case-control study of 52 histologically diagnosed cases and 52 controls--matched for age, race, marital status, and hospital--was conducted in 5 U.S. metropolitan areas. Cases were significantly more likely to be Jewish than were the controls, supporting earlier suggestions of an increased risk in Jewish males. A significant association of male breast cancer with mumps infections at age 20 years or older, along with the possible association with antecedent testicular injury and the excess frequency of mumps orchitis among cases, suggests that testicular factors may be important in the development of breast cancer among males. An increased frequency of breast cancer among persons who have worked in blast furnaces, steel works, and rolling mills is of interest because of the possible testicular effect of high environmental temperatures. The observed association between breast cancer and a prior history of swollen breast is difficult to interpret because of potential recall bias, and a possible relationship with military service needs further confirmation.

Effects of blood transfusion on exercise capacity in patients with sickle-cell anemia.

Although sickle cells have increased intracellular viscosity, the viscosity of patient's blood is usually not increased, because of the low hematocrit typically found in such patients. When patients receive transfusions, their exercise capacity increases, but it is unclear whether the change is due primarily to increased hemoglobin concentration, or also reflects improved flow properties of the blood due to dilution of sickle cells with normal erythrocytes. To evaluate the relative importance of these two factors, submaximal exercise studies were performed before and after a series of transfusions. Exercise capacity improved and the patients were able to perform increased amounts of work at lower heart rates. Regression analyses indicated that the percent of sickle cells in patient's blood did not have a significant effect on exercise capacity after the transfusion-induced increase in hemoglobin concentration was taken into account. At the hematocrits typically found in patients, altered viscosity of blood due to the presence of sickle cells is much less important than hemoglobin concentration as a determinant of exercise capacity.

Risk factors in interstitial pneumonitis following allogenic bone marrow transplantation.

Total body irradiation is part of the preparatory regimen for allogeneic bone marrow transplantation because of its cytotoxic and immunosuppressive properties. A major toxicity of bone marrow transplantation has been interstitial pneumonitis, which may be, in part, related to the lung irradiation. One hundred and sixty-one consecutive patients receiving allogeneic bone marrow transplantation for leukemia and aplastic anemia at Johns Hopkins Hospital (1968-1979) were retrospectively studied. The present study demonstrated that lung shielding to 600 rad maximum in single dose total body irradiation, fractionation of total body irradiation in comparison to single dose total body irradiation, and absence of graft versus host disease in the leukemia patients, each reduced the risk of interstitial pneumonitis. Total body irradiation significantly reduced the leukemia recurrence rate and/or the failure of remission induction.

Multimodality treatment of patients with advanced ovarian carcinoma.

A multimodality treatment program has been applied to ovarian carcinoma at the Johns Hopkins Hospital since August 1975. Forty-nine patients were subdivided into 23 patients with maximally resected Stage III micrometastatic, and 26 patients with significant retained disease, 20 with Stage III macrometastatic and 6 with Stage IV. After initial pilot studies, those patients with minimally retained disease entered a randomized prospective study. Antiovarian antiserum was used in one arm of the study; in both study arms colloidal P-32, delayed split whole abdominal irradiation, and maintenance melphalan were used. For the 23 patients with micrometastatic disease the cumulative survival and survival without evidence of disease at four years is 78 and 34% respectively. Twenty-six patients with macrometastatic disease were treated with or without intraperitoneal antiserum and multiagent chemotherapy; their cumulative one year survival is 50%. The lack of significant toxicity of intraperitoneal antiovarian antiserum and the results of multimodality therapy indicate the feasibility of this therapeutic approach to further improve ovarian cancer therapy.

A parametric method for comparing cumulative pregnancy curves following infertility therapy.

When evaluating the results of infertility therapy, it is often of interest to know whether differences exist between a new form of therapy and the established one, between medical and surgical therapy, or between patient groups that differ in severity of disease, age, parity, and so on. In this paper, a likelihood-ratio test is developed to evaluate differences between cumulative pregnancy curves of different patient groups. The test takes into account variation in patient follow-up and can be applied to any type of infertility therapy. It is illustrated by consideration of a group of patients who underwent artificial insemination by donor (AID) and determination of whether pregnancy outcome differed according to parity. It was found that the cure rate for both nulliparous and parous patients was virtually 100% and that the monthly probability of pregnancy was not significantly different between the two groups.

Assessing the efficacy of The American Fertility Society's classification of endometriosis: application of a dose-response methodology.

In order to promote uniform reporting of endometriosis. The Americal Fertility Society (AFS) recently proposed a classification in which severity was categorized on the basis of both location and extent of disease. The results of this study indicate that the AFS scale poorly specifies the relation between severity of disease and pregnancy outcome after therapy, because of the arbitrary point scores assigned to each classification category, and the arbitrary cutoff points chosen to divide patients into severity groupings. A nonparametric monotonic estimator, which generates a dose-response relationship between AFS score (dose) and pregnancy following treatment (response) is shown to improve the discriminatory power of the AFS scale; however, in order to obtain the full benefit of the detail provided by the AFS classification, it is recommended that the current arbitrary individual-category weights be replaced by empirically derived weights.

The effect of mixed distributions on the methods of survival analysis.

A study of the effectiveness of preoperative radiation as an adjuvant for surgery for patients with invasive bladder carcinoma revealed a subpopulation of patients having advanced disease who could not benefit from radiation treatment. The effect of such a group of patients on the efficiency of 2 common nonparametric tests is investigated here. Both Gehan's tests and Greenwood's tests were shown to have a very low efficiency when compared with a parametric test when this group of patients is present.

Direct and indirect associations of five factors with infant mortality.

The relationship between several factors including maternal age, race, education and prior obstetric experience to infant mortality was investigated using vital statistics data from four regionalized networks in 1974 and 1975 and applying the log-linear model. By making a causal assumption, these relationships can be decomposed into a direct component and an indirect component acting through the association of the variables with birth weight. Detailed examination of the interactions between these factors revealed that all of the factors except education could demonstrate a direct component at the 5% significance level in their relationship to neonatal death, while all but birth order had a direct component relating to postneonatal deaths. The strength of the direct components was expressed in the form of odds ratios, leading to a conclusion confirming some earlier reports from these data, but suggesting that births to mothers over 35 years of age have smaller increased neonatal risk relative to those aged 18-34 years than had been reported previously. In addition, the direct component associated with first births does not show a higher risk than those of birth order 2 and 3. Added risk in this group is traceable to the indirect component. The disadvantage associated with having a prior fetal death is only found among low birth orders, with a possible reversal of the pattern in the high parity group. Analysis of postneonatal risks shows an interaction between maternal age and race, in which births to mothers under age 18 had increased risks only for whites.

Evaluation of an Alaskan streptococcal control program: importance of the program's intensity and duration.

Prospective follow-up information from the throat culturing results of 1,653 Eskimo children in 12 Alaskan villages was used to evaluate the effect of duration and intensity of a streptococcal control program begun in 1971 while controlling for several other risk factors related to streptococcal colonization. Relative risks of colonization for each of the subsequent study years relative to the first year indicate that the risk of colonization decreased over the duration of the study by 42% in Year 2 to 55% in Year 4 (P less than 0.0001). Cost-cutting measures such as lengthening the time interval between routine throat cultures led to a 37% increase in the risk of colonization (P = 0.0002). A comparison of the number of cases of acute rheumatic fever during the 5-year period before the streptococcal control program with the number of cases during the 5-year program period showed that cases in villages with the program decreased from 11 to 0. In a similar group of comparison villages without the program, the number of cases decreased from 7 to 4. A benefit-cost study of the program indicates that benefit exceeds cost. These findings and the changes in the carriage of streptococcal organisms during the control program underscore the importance of such long-term programs with regularly scheduled culturing in high-risk populations of children.

Epidemiology of cancer of the vulva. A case-control study.

Few epidemiologic studies have been undertaken to investigate the etiology of cancer of the vulva. To identify risk factors associated with this cancer, a case-control study was conducted in 149 patients with histologically proven vulvar carcinoma and the same number of control patients matched for age, race, marital status, and hospital from five U.S. metropolitan areas. As previously suspected, we found prior histories of leukoplakia of the vulva, inflammation of the vulva or vagina, and urogenital cancer to be significantly associated with vulvar cancer. In addition, we found moderately high odds ratios associated with occupational histories of private household maids and servants, and work in laundry, cleaning, and other garment services. A slightly increased odds ratio was associated with coffee consumption and a dose-response effect was demonstrated. The findings suggest that environmental exposures may play a role in vulvar carcinogenesis.

Cigarette smoking and nasopharyngeal carcinoma.

A case-control study was undertaken to investigate possible etiologic factors in nasopharyngeal cancer, a rare tumor in the United States. Data from 39 nasopharyngeal cancer cases and the same number of matched controls showed significantly more cases born in Asia than controls, supporting the notion that exposure in early life has a prolonged carcinogenic effect. Cases also smoked significantly more cigarettes than controls, indicating a need for investigating the role of cigarette smoking and other exposures in the etiology of nasopharyngeal cancer in western countries.

Comparison of postoperative mortality and morbidity in VA and nonfederal hospitals.

We compared postoperative mortality and morbidity rates in the Veterans Health Administration (VA) to those in nonfederal hospitals, using multivariate analysis to adjust for the patient characteristics of age, diagnosis, comorbidity, and severity of illness. We used a total of 544,000 patient discharge records (330,000 nonfederal and 214,000 VA) from 1987 through 1988 and compared 118 surgical procedures or procedure groups composed of 314 individual surgical procedures. We found no significant differences in postoperative mortality rates between the VA and nonfederal hospital systems for 110 of 118 surgical procedures or procedure groups. Endarterectomy, cervical esophagostomy, and esophageal anastomosis or esophagocolostomy showed significantly lower postoperative mortality in the VA hospitals compared to nonfederal hospitals (P = 0.05). VA postoperative mortality rates that were higher than those in nonfederal hospitals and could not be entirely explained by adjusting for patient characteristics were found for suture of ulcer, cholecystostomy, colon surgery, small intestine surgery, and reopening of recent thoracotomy site (P = 0.05). Respiratory, gastrointestinal, and urinary postoperative morbidity were generally lower in the VA hospitals than in nonfederal hospitals (P = 0.05). Infections were generally higher in the VA hospitals than in nonfederal hospitals. Pulmonary embolism, deep venous thrombosis, shock due to surgery or anesthesia, mediastinitis, hemorrhage, cardiac, and central nervous system morbidity showed no significant differences. These data demonstrate that VA postoperative mortality and morbidity in 118 surgical procedures or procedure groups is comparable to those in nonfederal hospitals.

Comparison of postoperative mortality in VA and private hospitals.

OBJECTIVE: This study compared unselected VA (Department of Veterans Affairs) and private multi-hospital postoperative mortality rates. In the absence of national standards for postoperative mortality rates and in view of the unique volume and range of surgical procedures studied, the second objective is to help establish national standards through the dissemination of these postoperative mortality norms. SUMMARY BACKGROUND DATA: Public Law 99-166, Section 204, enacted by Congress December 3, 1985, required that the VA compare postoperative mortality and morbidity rates for each type of surgical procedure it performs with the prevailing national standard and analyze any deviation between such rates in terms of patient characteristics. METHODS: The authors compared postoperative mortality in the VA to that in private hospitals, adjusting for the patient characteristics of age, diagnosis, comorbidity, or severity of illness. We used a total of 830,000 patients discharge records (323,000 VA and 507,000 private patients) from 1984 through 1986 among 309 individual surgical procedures within 113 comparison surgical procedures or procedure groups. RESULTS: The authors found no significant differences in postoperative mortality rates between the VA and private hospital systems for 105 of the 113 surgical procedures or procedure groups. VA postoperative mortality rates that were higher than those in private hospitals were found for suture of ulcer, revision of gastric anastomosis, small-to-small intestinal anastomosis, appendectomy, and reclosure of postoperative disruption of abdominal wall (p = 0.05). Vascular bypass surgery, portal systemic venous shunt, and esophageal surgery showed a significantly lower postoperative mortality in the VA as compared with that in private hospitals (p = 0.05). CONCLUSIONS: VA postoperative mortality in 113 surgical procedures or procedure groups is comparable to that in private hospitals.

Anthropometric predictors of low birth weight outcome in teenage pregnancy.

The highest relative risks of low birth weight are found among births to teenage mothers. An analysis of anthropometrics (weight, mid-arm circumference, and triceps skinfold) among black teenagers attending an adolescent prenatal program was studied. The sample consisted of 100 girls under 17 years. Data were collected from 19 to 35 weeks gestation. Adolescent mothers who delivered low birth weight (LBW) infants demonstrated different patterns of anthropometric changes than teen mothers who delivered normal birth weight (NBW) infants. Mean mid-arm circumference increases in the LBW group (0.05 mm/wk) were significantly less than mean increases in the NBW group (0.80 mm/wk) (p less than 0.05). Arm fat area estimates of the LBW mothers demonstrated weekly depletion (-24.9 mm2/wk), which was significantly less than those of the NBW group, who accumulated fat (+15.3 mm2/wk) (p less than .05). Changes in maternal nutritional status may in part mediate the birthweight outcome in adolescent pregnancy. Anthropometrics may be useful in predicting those teens at highest risk of bearing LBW infants.

PIP: The highest relative risks of low birth weight are found among births to teenage mothers. An analysis of anthropometrics (weight, mid-arm circumference, and triceps skinfold) among black US teenagers attending an adolescent prenatal program was studied. The sample consisted of 100 girls under 17 years. Data were collected from 19 to 35 weeks gestation. Adolescent mothers who delivered low birth weight (LBW) infants demonstrated different patterns of anthropometric changes than teen mothers who delivered normal birth weight (NBW) infants. Mean mid-arm circumference increases in the LBW group (0.05 mm/wk) were significantly less than mean increases in the NBW group (0.80 mm/wk) (p 0.05). Arm fat area estimates of the LBW mothers demonstrated weekly deplection (-24.9 mm squared/wk), which was significantly less than those of the NBW group, who accumulated fat (+15.3 mm squared/wk)(p 0.05). Changes in maternal nutritional status may in part mediate the birthweight outcome in adolescent pregnancy. Anthropometrics may be useful in predicting those teens at highest risk of bearing LBW infants. In conclusion, the LBW phenomenon in young teenagers may be due to an inadequate maternal accumulation of fat stores and/or an excessive mobilization of fat during gestation. Marginal fat reserves and a habitually limited food intake and/or stage of life cycle, despite a weight gain that is apparently compatible with successful adult pregnancy outcome, may diminish a teen mother's ability to sustain the rapid fetal weight gain during the 3rd trimester beyond approximately 35 weeks gestation. Appropriate nutrition and psychosocial and medical intervention may alter the LBW outcome.

Anticonvulsant toxicity in vitro: possible role of arene oxides.

Human lymphocytes incubated with a mouse hepatic microsomal drug metabolizing system were used to study the cytotoxicity of four anticonvulsants. In vitro toxicity assessed by trypan blue dye exclusion was significantly greater for compounds with relatively high clinical toxicity (mephenytoin and phenacemide) than those with only rare cytotoxic complications (phenytoin and phenobarbital). No toxicity occurred in the absence of microsomes and toxicity was enhanced by inhibitors of epoxide hydrolase suggesting that the cytotoxicity of the drugs may result from arene oxide metabolites. In vivo, the covalent binding of such metabolites to cell macromolecules could lead to cell death and, by acting as haptens, to secondary hypersensitivity reactions. The method may be useful in assessing the potential of a drug for toxicity, the mechanism of cell damage and individual differences in cell defenses within the human population.

Predictive factors for acute graft-versus-host disease in patients transplanted with HLA-identical bone marrow.

To identify predictive parameters for incidence and severity of acute graft-versus-host disease (GVHD), 136 patients, transplanted with histocompatible marrow as therapy for aplastic anemia and hematologic malignancies, were examined using univariate and multivariate analyses. The risk of GVHD increased in patients with acute lymphocytic leukemia (p less than 0.05), in sex-mismatched donor-recipient pairs (p less than 0.01), and in patients older than 23.7 yr (p less than 0.05). No other commonly observed factors appeared to have any relationship to GVHD except the presence of certain alleles. The presence of a Cw4 allele or of the Bw21 specificities B49 and B50 were associated with significantly increased risks of GVHD (p less than 0.05), whereas the presence of Aw19 (or the related specificities A29, Aw30, Aw31 , Aw32, Aw33 ) was associated with a significantly decreased risk (p less than 0.01). Using these factors, a regression equation can be constructed that estimates the risk of a given patient to develop clinically significant acute GVHD.