Influence of HIV-1 and/or HIV-2 infection and CD4 count on cervical HPV DNA detection in women from Senegal, West Africa.

BACKGROUND: HIV infection is associated with greater risk of precancerous lesions and cervical cancer in women. However, several factors remain unclarified regarding the association between HIV infection and HPV detection, especially among those with HIV type 2 versus type 1 infection and severely immunocompromised persons. OBJECTIVES: To evaluate HPV overall and type-specific detection among HIV-infected and uninfected women in Senegal. STUDY DESIGN: Detection of HPV DNA for 38 genotypes in cervical swabs using PCR-based methods was evaluated in HIV-positive (n=467) and HIV-negative (n=2139) women participating in studies in Senegal. Among HIV-1 and/or HIV-2 positive women, CD4 counts were assessed. Adjusted multivariable prevalence ratios (PR) were calculated. RESULTS: The prevalence of any HPV DNA and multiple HPV types was greater among HIV-infected individuals (78.2% and 62.3%, respectively) compared with HIV-negative women (27.1% and 11.6%). This trend was also seen for HPV types 16 and 18 (13.1% and 10.9%) compared to HIV-negative women (2.2% and 1.7%). HIV-infected women with CD4 cell counts less than 200 cells/µl had a higher likelihood of any HPV detection (PRa 1.30; 95% CI 1.07-1.59), multiple HPV types (PRa 1.52; 95% CI 1.14-2.01), and HPV-16 (PRa 9.00; 95% CI 1.66-48.67), but not HPV-18 (PRa 1.20, 95% CI 0.45-3.24) compared to those with CD4 counts 500 cells/µl or above. CONCLUSION: HIV-infected women, especially those most severely immunocompromised, are more likely to harbor HPV. Measures to prevent initial HPV infection and subsequent development of cervical cancer through focused screening efforts should be implemented in these high risk populations.

Knowledge of Pap screening and human papillomavirus among women attending clinics in Medellín, Colombia.

This study evaluated Pap screening and human papillomavirus (HPV) knowledge in a population of Colombian women as a possible contributing factor of low cervical cancer screening success. This is a descriptive, cross-sectional analysis of 454 women who were approached in five different hospitals and clinics throughout Medellín, Colombia. Of them, 449 females agreed to participate and answered a standardized face-to-face questionnaire regarding Pap screening and HPV knowledge. Using logistic regression, predictors of both Pap and HPV knowledge were examined. Overall, 76.3% of the participants exhibited a high level of Pap screening knowledge, while only 7.8% showed high level of HPV knowledge. Of the 449 women, 71.5% reported that it had been 1 year or less since their last Pap test, while 7.8% reported never having had a Pap test or not having had a recent test. Factors influencing Pap screening knowledge included education level and insurance; factors influencing HPV knowledge included education level and age. The high level of Pap screening knowledge and use do not explain the high cervical cancer rates in Colombia. The results of this study suggest that educational efforts should be focused on increasing women's knowledge and awareness of HPV in anticipation of the availability of HPV vaccines and HPV tests for screening.

Use of oral contraceptives and risk of breast cancer in young women.

Many studies have shown that oral contraceptive (OC) use increases a young woman's risk of breast cancer, although some studies suggest that the risk may be limited to recent use. The objective of this study was to determine what particular aspects of OC use could be important for breast cancer development at an early age in the cohort of women who had the opportunity to use OCs all of their reproductive life. The cases were first diagnosed with breast cancer at age 40 or younger between 1983 and 1988, and identified by the Los Angeles County Cancer Surveillance Program. Control subjects were individually matched to participating cases on birth date (within 36 months), race (white), parity (nulliparous versus parous), and neighborhood of residence. Detailed OC histories were obtained during in-person interviews with subjects. In general the risk estimates were small, and not statistically significant. Compared to no use, having used OCs for 12 years or more was associated with a modest non-significant elevated breast cancer risk with an odds ratio (OR) of 1.4 (95% confidence interval (CI) = 0.8-2.4). Long-term (12 years or more) users of high-dose estrogen pills had a non-significant 60% higher breast cancer risk than never users (CI = 0.9-3.2). Early use was associated with slightly higher ORs among young women (age < or =35), and among parous women. Recent use was associated with somewhat higher ORs among parous women and women above age 36. Analyses by stage, body weight, and family history yielded similar results. This study is consistent with a modest effect of early OC use on breast cancer risk in young women.

PIP: The relationship of breast cancer risk in young women to particular patterns of oral contraceptive (OC) use was investigated in a case-control study conducted in Los Angeles County, California (US), in 1983-89. Enrolled as cases were 744 White women 40 years or younger at the time of breast cancer diagnosis who were located through a population-based cancer registry. One community control was matched to each of these cases on birth date, race, parity, and neighborhood of residence. OCs had been used by 83.3% of breast cancer cases and 84.4% of controls; 68.6% of cases and 69.3% of controls had used OCs for 12 months or more. In general, the results revealed only a modest effect of early OC use on breast cancer risk in young women. Compared to never use, OC use for 12 or more years was associated with a small, nonsignificant elevated breast cancer risk (odds ratio (OR), 1.40; 95% confidence interval (CI), 0.81-2.40). Women who used high-dose estrogen formulations for 12 years or more had a nonsignificant increased risk compared with nonusers (OR, 1.64; 95% CI, 0.85-3.18). Among women below age 35 years at diagnosis, compared with never users, women who had used OCs for 1 year or more before the age of 18 years were at almost twice the risk of developing breast cancer (OR, 1.97; 95% CI, 0.90-4.32). Among women over age 35 years at diagnosis, compared with never users, those who had used OCs for 3 or more years during the past 5 years were at a 2.54-fold increased risk (95% CI, 0.94-6.88). Analyses by cancer stage, body weight, and family history failed to detect any significant effects.

Treatment with human chorionic gonadotropin and risk of breast cancer.

Studies of the induction of mammary tumors by 7,12-dimethylbenz(a)anthracene in a rat model show that human chorionic gonadotropin (hCG) administration reduces tumor incidence in a manner comparable to that of a completed pregnancy. On the basis of their studies, Russo and Russo (Cancer Epidemiol., Biomarkers & Prev., 3: 353-364, 1994) have proposed that hCG treatment of young nulliparous women would reduce their breast cancer risk in a manner similar to that of a term pregnancy. As part of a population-based, case-control study of breast cancer among women ages 40 years or younger, we asked women whether they had received hCG injection as part of a weight loss regimen or as a component of infertility treatment. Participants in this study were 744 women newly diagnosed with breast cancer between July 1983 and December 1988 and 744 controls individually matched on birthdate (within 36 months), race (white), parity (nulliparous/parous), and neighborhood of residence. Forty-five cases and 65 controls reported exposure to hCG (multivariate odds ratio = 0.77, 95% confidence interval = 0.50-1.19). Risk was reduced significantly among women whose maximum nonpregnant body mass index was less than 27.5 kg/m2 but no reduction in risk was observed among more obese women. Although the odds ratios were reduced substantially for both nulliparous and parous women with maximum nonpregnant body mass indices less than 27.5, only the result for nulliparous women was statistically significant. These results are consistent with the effects proposed by Russo and Russo based on their animal model. Although not definitive, these results suggest that hCG may be a means for reducing breast cancer risk.

Physical exercise and reduced risk of breast cancer in young women.

BACKGROUND: Epidemiologic evidence strongly suggests that cumulative exposure to ovarian hormones is a determinant of breast cancer risk. Because physical activity can modify menstrual cycle patterns and alter the production of ovarian hormones, it may reduce breast cancer risk; yet few epidemiologic studies have assessed this relationship. PURPOSE: The major objective of this study was to determine whether young women (aged 40 and younger) who regularly participated in physical exercise activities during their reproductive years had a reduced risk of breast cancer. METHODS: Using a case-control design, we conducted personal interviews of a total of 545 women (aged 40 and younger at diagnosis) who had been newly diagnosed with in situ or invasive breast cancer between July 1, 1983, and January 1, 1989, and a total of 545 control subjects. Case patients and control subjects were individually matched on date of birth (within 36 months), race (white), parity (nulliparous versus parous), and neighborhood of residence. Lifetime histories of participation in physical exercise activities on a regular basis were obtained during the personal interview. RESULTS: After adjustment for potential confounding factors, we found that the average number of hours spent in physical exercise activities per week from menarche to 1 year prior to the case patient's diagnosis was a significant predictor of reduced breast cancer risk (two-sided P for trend < .0001). The odds ratio (OR) of breast cancer among women who, on average, spent 3.8 or more hours per week participating in physical exercise activities was 0.42 (95% confidence limits [CLs] = 0.27, 0.64) relative to inactive women. The effect was stronger among women who had had a full-term pregnancy. Comparing most active (> or = 3.8 hours/wk of exercise) women to inactive women, the ORs were 0.28 (95% CL = 0.16, 0.50) for parous and 0.73 (95% CL = 0.38, 1.41) for nulliparous women. CONCLUSIONS: Most previously identified risk factors for breast cancer are reproductive and menstrual events that cannot be readily altered. The protective effect of exercise on breast cancer risk in the women whom we studied suggests that physical activity offers one modifiable lifestyle characteristic that may substantially reduce a woman's lifetime risk of breast cancer. IMPLICATIONS: Whether the protective effects of exercise on breast cancer risk are due to alterations in ovarian function and whether they extend into women's menopausal years need to be established. Our results suggest that implementation of regular physical exercise programs as a critical component of a healthy lifestyle should be a high priority for adolescent and adult women.

Phase I and pharmacologic study of liposomal daunorubicin (DaunoXome).

We have completed a phase I and pharmacology study of liposomally-encapsulated daunorubicin (DaunoXome). Of 32 patients entered, 30 were evaluable. No toxicity was encountered at the initial dose-escalation steps from 10 to 60 mg/m2. At 80 mg/m2, two patients manifested grade 2 neutropenia. At least grade 3 neutropenia occurred in all patients receiving 120 mg/m2. Alopecia and subjective intolerance were mild. Cardiotoxicity was not observed except for an episode of arrhythmia in a patient with lung cancer and prior radiation. Only one minor objective response was observed in this population of refractory solid tumors. Pharmacokinetics differed from those of the free drug with no detection of daunorubicinol. We recommend future phase II studies with a dose of 100 mg/m2 in previously treated and 120 mg/m2 of DaunoXome in previously untreated patients with solid tumors.

Serum hormone levels in pre-menopausal Chinese women in Shanghai and white women in Los Angeles: results from two breast cancer case-control studies.

To assess whether risk of breast cancer in young women is associated with differences in luteal-phase hormone production and to attempt to explain differences in risk of breast cancer of young Shanghai Chinese and Los Angeles white women, two concurrent case-control studies of serum hormone concentrations were conducted. Both studies were carefully controlled for the possible confounding effects of age, weight, height, pregnancy history, and day of the menstrual cycle, by individually matching cases and controls on these factors. Case eligibility was limited to women with localized breast cancer. Sixteen of 39 Shanghai breast-cancer cases were sampled prior to the histologic diagnosis of their disease. The remaining 23 Shanghai cases and all 42 Los Angeles cases were diagnosed, and treated by surgery only, at least six months prior to hormonal evaluation. All subjects were sampled on day 22 of the menstrual cycle. Overall, cases had 13.5% higher serum estradiol concentrations (p = 0.038) with a case-to-control excess of 16.6% in Shanghai subjects (p = 0.089) and 10.8% in Los Angeles subjects (p = 0.23). There were no appreciable differences in amounts of sex-hormone binding globulin between cases and controls. Cases had lower progesterone levels than controls, but the situation was reversed when the analysis was restricted to subjects with evidence of ovulation. Los Angeles controls had 20.6% greater estradiol concentrations than Shanghai controls (p = 0.036); adjustment for body weight accounted for only 25.7% of this difference.(ABSTRACT TRUNCATED AT 250 WORDS)

[Treatment of newly diagnosed type II diabetic patients with special reference to prescribing glibenclamide in low doses]. / Die Behandlung neuerfasster Typ-II-Diabetiker unter besonderer Berücksichtigung der Verordnung von Glibenclamid in niedriger Dosierung.

In the period of 15 months 90% of all newly registered type II diabetics of a district area (70 males, 122 females) were prospectively thoroughly examined above all in hospital, standardizedly stabilized and have been followed up for 1 year with regard to their therapy behaviour. From the features obtained (age, body weight, heredity, symptomatology, blood glucose and insulin concentrations basally and after 75 g oGTT) subgroupings were worked out relevant for the therapy. 64% of the newly registered type II diabetics could be stabilized purely dietetically (males 70%, females 60.7%). Female type II diabetics revealed the worse course of therapy. Younger age, overweight, genetic load and higher insulin concentrations are markers of the importance of the insulin resistance and a domain of the basis therapy. Older age, normal weight in connection with higher blood glucose and lower insulin concentrations as an expression of the insulin deficit of higher degree render in most cases possible a treatment with SH-preparations. Small doses of glibenclamide proved to be very favourable both in not purely dietetically manageable younger patients and in older patients. 68% of all SH-cases did with a dosage of 1-3 mg glibenclamide a day, 28% with 1 mg a day. The pathophysiologic and pharmacologic mechanisms are discussed.

A case-control study of male breast cancer.

A case-control study was conducted in Los Angeles County, CA, of 75 male breast cancer cases aged 20-74 yr at diagnosis to investigate the role of a number of suspected risk factors. The study involved both interviews and laboratory measurements. Factors under study included fertility and marital history, obesity, alcohol and cigarette consumption, use of drugs known or suspected of causing gynecomastia, family history of breast cancer, history of radiation exposure to the upper body, sex chromatin analysis, serum levels of prolactin, testosterone, estrone, estradiol and sex-hormone-binding globulin, as well as urinary levels of estrone, estradiol, and estriol. Two patients versus no controls tested positive for sex chromatin and were excluded from further analyses. The only statistically significant risk factor identified was greater weight of the cases at age 30; a man who weighed 80 or more kg at age 30 had twice the risk of breast cancer of a man weighing less than 60 kg at that age. Serum estrone levels were positively, and sex-hormone-binding globulin levels were negatively, related to body weight, and we interpret the greater weight of the cases as suggesting that the underlying risk factor is an increased exposure to bioavailable estrogen. None of the differences observed between cases and controls for either the serum or urinary hormone levels was, however, statistically significant and there did not appear to be any large absolute excess of estrogens or deficit of testosterone in the cases. This apparent contradiction may be explained by the fact that there was little difference in weight between the cases and controls at the time of sampling.

The effects of moderate physical activity on menstrual cycle patterns in adolescence: implications for breast cancer prevention.

Girls who engage in strenuous physical activity are often amenorrheic and have recently been reported to be at a reduced risk of breast cancer. To determine whether moderate amounts of exercise affect menstrual cycle patterns and ovulatory frequency in young postmenarcheal girls, the menstrual cycles and physical activity patterns of 168 high school girls were monitored for a 6 month period. Anovulatory cycles were associated with later age at menarche, fewer elapsed years since menarche and greater levels of energy expended per week in physical activity. After adjusting for age at menarche and years since menarche, there was a significant dose-related trend in the risk of anovular menstrual cycles associated with increasing levels of physical activity (1-sided P = 0.03). Major determinants of average cycle length were weekly average energy expenditure (less than or equal to 750 kcal wk-1 associated with cycles that were on average 2.4 days longer), age at menarche (an increase of 0.7 days per year of age) and race (Asians having cycles about 1.9 days longer than Caucasians). Because a major determinant of breast cancer risk may be the cumulative number of ovulatory cycles, these data suggest that regular participation in moderate physical activity, by reducing the frequency of ovulatory cycles in adolescence, may provide an opportunity for the primary prevention of breast cancer.

Cigarette smoking, obesity, diuretic use, and coffee consumption as risk factors for renal cell carcinoma.

One hundred sixty incident cases of renal cell carcinoma under the age of 55 years and an equal number of age-(within 5 yr), race-, and sex-matched neighborhood controls were interviewed. Cigarette smoking was a risk factor for renal cell carcinoma in males [relative risk (RR) = 2.1, one-sided P = .02] but not in females (RR = 1.1, P = .50). Obesity was a significant risk factor in both males and females: The RR for a 4th quartile compared to a 1st quartile Quetelet's Index 10 years ago was 2.5 for males and 3.3 for females. Additional risk factors in females were diuretic use (RR = 4.5, P = .002) and daily coffee consumption (RR = 2.3, P = .06).

Serum testosterone levels in healthy young black and white men.

Blacks in the United States have the highest prostate cancer rate in the world and nearly twice that of whites in the United States. The 2:1 black-to-white ratio in prostate cancer rates is already apparent at age 45 years, the age at which the earliest prostate cancer cases occur. This finding suggests that the factor(s) responsible for the difference in rates occurs, or first occurs, early in life. Testosterone has been hypothesized to play a role in the etiology of prostate cancer, because testosterone and its metabolite, dihydrotestosterone, are the principal trophic hormones that regulate growth and function of epithelial prostate tissue. This report gives the results of assays of circulating steroid hormone levels in white and black college students in Los Angeles, CA. Mean testosterone levels in blacks were 19% higher than in whites, and free testosterone levels were 21% higher. Both these differences were statistically significant. Adjustment by analysis of covariance for time of sampling, age, weight, alcohol use, cigarette smoking, and use of prescription drugs somewhat reduced the differences. After these adjustments were made, blacks had a 15% higher testosterone level and a 13% higher free testosterone level. A 15% difference in circulating testosterone levels could readily explain a twofold difference in prostate cancer risk.

Pancreas cancer and smoking, beverage consumption, and past medical history.

Four hundred and ninety pancreas cancer patients representative of confirmed cases in Los Angeles County residents of working age were compared to healthy controls individually matched by age, sex, race, and neighborhood. Home interviews were conducted on occupation, smoking, food and beverage consumption, and medical history. Cigarette smoking was a strong and consistent predictor of pancreas cancer occurrence; the effect disappeared after a decade of nonsmoking, and there was no increase in risk among current smokers as daily dose increased. There was no link between pancreas cancer and past consumption of tea, carbonated beverages, beer, or spirits; and an association with coffee consumption was inconsistent. A strong association between pancreas cancer and history of subtotal gastrectomy at any past time could not be explained by chance or any other factor. Pancreas cancer patients had experienced fewer allergies of any kind.

Pancreas cancer is unrelated to the workplace in Los Angeles.

From 1975 to 1981, 490 cases of exocrine adenocarcinoma of the pancreas, representative of those occurring in the working-age population of Los Angeles County, were compared to matched neighborhood controls. Among the items of information obtained from each subject was a lifetime job history and a history of specific workplace exposures; this came directly from both case and control in 124 pairs. Although the matched cases and controls were generally comparable, they were not matched with respect to job history. While other strong risk factors for pancreas cancer were found in the same study, no significant or suggestive differences in the jobs or perceived chemical or process exposures between cases and controls were found. Those minor differences which were found did not suggest credible mechanisms of carcinogenesis when examined in detail. Our study does not point to the workplace as an important determinant of pancreas cancer in the economically diversified urban area of Los Angeles.

Hepatitis, alcohol consumption, cigarette smoking, and hepatocellular carcinoma in Los Angeles.

Seventy-eight black patients and white patients with primary hepatocellular carcinoma (PHC), 70 years or younger at diagnosis, and 78 age-, sex-, and race-matched neighborhood controls were interviewed. Information sought included usual dietary and drinking habits, cigarette smoking habits, prior medical conditions including a history of hepatitis, prior exposure to blood products, and occupational history. Cigarette smoking was a risk factor for PHC; the relative risk (RR) for current smokers of more than one pack/day compared to nonsmokers was 2.6. Alcohol consumption was also a significant risk factor for PHC; individuals who drank 80 g or more of ethanol per day had a RR of 4.2 compared to those drinking less than 10 g/day. In addition, a history of hepatitis (RR = 13.0) and a history of blood transfusions (RR = 7.0) were significant risk factors for PHC. Each of these factors remained significant after adjustment was made for the others.

Evaluation of gel permeation chromatography for clean up of human adipose tissue samples for GC/MS analysis of pesticides and other chemicals.

Gel permeation chromatography (GPC) has been evaluated for clean up of human adipose tissue sample extracts in preparation for confirmatory analysis by gas chromatography-mass spectrometry (GC/MS). Studies were conducted with standard solutions, fortified chicken fat, and actual human adipose tissue samples. Nearly quantitative removal of lipid material was achieved with minimal losses of 16 organochlorine pesticides and metabolites: two polychlorinated biphenyl (PCB) mixtures, two chlorinated naphthalene (PCN) mixtures, and a polybrominated biphenyl (PBB) mixture. Mass spectra free from interferences were obtained over the mass range from 46 m/z to 560 m/z.