Age of the floor of the eastern Indian ocean.

Deep sea drilling in the eastern Indian Ocean shows that the oceanic crust off Western Australia is approximately 140 million years old and becomes younger to the west; this dates the initial opening of the Indian Ocean.

Vasomotor symptoms and the risk of incident venous thrombosis in postmenopausal women.

Essentials Vasomotor symptoms have been proposed as markers of changing cardiovascular risk. In this cohort study, we evaluated these symptoms as markers of venous thrombosis (VT) risk. We found no evidence that vasomotor symptom presence or severity were associated with VT risk. Among these postmenopausal women, vasomotor symptoms are not a useful marker of VT risk. SUMMARY: Background Vasomotor symptoms may be markers of changes in cardiovascular risk, but it is unknown whether these symptoms are associated with the risk of venous thrombosis (VT). Objective To evaluate the association of vasomotor symptom presence and severity with incident VT risk among postmenopausal women, independent of potential explanatory variables. Methods This cohort study included participants of the Women's Health Initiative (WHI) Hormone Therapy Trials (n = 24 508) and Observational Study (n = 87 783), analyzed separately. At baseline, women reported whether hot flashes or night sweats were present and, if so, their severity. Using Cox proportional hazards models, we estimated the VT risk associated with vasomotor symptom presence and severity, adjusted for potential explanatory variables: age, body mass index, smoking status, race/ethnicity, and time-varying current hormone therapy use. Results At baseline, WHI Hormone Therapy Trial participants were aged 64 years and WHI Observational Study participants were aged 63 years, on average. In the WHI Hormone Therapy Trials over a median of 8.2 years of follow-up, 522 women experienced a VT event. In the WHI Observational Study, over 7.9 years of follow-up, 1103 women experienced a VT event. In adjusted analyses, we found no evidence of an association between vasomotor symptom presence (hazard ratio [HR]adj  0.91, 95% confidence interval [CI] 0.75-1.1 in the WHI Hormone Therapy Trials; HRadj  1.1, 95% CI 0.99-1.3 in the WHI Observational Study) or severity (HRadj for severe versus mild 0.99, 95% CI 0.53-1.9 in the WHI Hormone Therapy Trials; HRadj  1.3, 95% CI 0.89-2.0) in the WHI Observational Study) and the risk of incident VT. Conclusions Although vasomotor symptoms have been associated with the risk of other cardiovascular events in published studies, our findings do not suggest that vasomotor symptoms constitute a marker of VT risk.

Diminished B cell secretory capacity in patients with noninsulin-dependent diabetes mellitus.

In order to assess whether patients with noninsulin-dependent diabetes mellitus (NIDDM) possess normal insulin secretory capacity, maximal B cell responsiveness to the potentiating effects of glucose was estimated in eight untreated patients with NIDDM and in eight nondiabetic controls. The acute insulin response to 5 g intravenous arginine was measured at five matched plasma glucose levels that ranged from approximately 100-615 mg/dl. The upper asymptote approached by acute insulin responses (AIRmax) and the plasma glucose concentration at half-maximal responsiveness (PG50) were estimated using nonlinear regression to fit a modification of the Michaelis-Menten equation. In addition, glucagon responses to arginine were measured at these same glucose levels to compare maximal A cell suppression by hyperglycemia in diabetics and controls. Insulin responses to arginine were lower in diabetics than in controls at all matched glucose levels (P less than 0.001 at all levels). In addition, estimated AIRmax was much lower in diabetics than in controls (83 +/- 21 vs. 450 +/- 93 microU/ml, P less than 0.01). In contrast, PG50 was similar in diabetics and controls (234 +/- 28 vs. 197 +/- 20 mg/dl, P equals NS) and insulin responses in both groups approached or attained maxima at a glucose level of approximately 460 mg/dl. Acute glucagon responses to arginine in patients with NIDDM were significantly higher than responses in controls at all glucose levels. In addition, although glucagon responses in control subjects reached a minimum at a glucose level of approximately 460 mg/dl, responses in diabetics declined continuously throughout the glucose range and did not reach a minimum. Thus, A cell sensitivity to changes in glucose level may be diminished in patients with NIDDM. In summary, patients with NIDDM possess markedly decreased maximal insulin responsiveness to the potentiating effects of glucose. Such a defect indicates the presence of a reduced B cell secretory capacity and suggests a marked generalized impairment of B cell function in patients with NIDDM.

Spinopelvic mobility and acetabular component position for total hip arthroplasty.

AIMS: Posterior tilt of the pelvis with sitting provides biological acetabular opening. Our goal was to study the post-operative interaction of skeletal mobility and sagittal acetabular component position. MATERIALS AND METHODS: This was a radiographic study of 160 hips (151 patients) who prospectively had lateral spinopelvic hip radiographs for skeletal and implant measurements. Intra-operative acetabular component position was determined according to the pre-operative spinal mobility. Sagittal implant measurements of ante-inclination and sacral acetabular angle were used as surrogate measurements for the risk of impingement, and intra-operative acetabular component angles were compared with these. RESULTS: Post-operatively, ante-inclination and sacral acetabular angles were within normal range in 133 hips (83.1%). A total of seven hips (4.4%) had pathological imbalance and were biologically or surgically fused hips. In all, 23 of 24 hips had pre-operative dangerous spinal imbalance corrected. CONCLUSIONS: In all, 145 of 160 hips (90%) were considered safe from impingement. Patients with highest risk are those with biological or surgical spinal fusion; patients with dangerous spinal imbalance can be safe with correct acetabular component position. The clinical relevance of the study is that it correlates acetabular component position to spinal pelvic mobility which provides guidelines for total hip arthroplasty. Cite this article: Bone Joint J 2017;99-B(1 Supple A):37-45.

Cross-sectional association of endogenous steroid hormone, sex hormone-binding globulin, and precursor steroid levels with hemostatic factor levels in postmenopausal women.

Essentials Endogenous hormone levels' influence on hemostatic factor levels is not fully characterized. We tested for associations of endogenous hormone with hemostatic factor levels in postmenopause. Estrone levels were inversely associated with the natural anticoagulant, protein S antigen. Dehydroepiandrosterone sulfate levels were inversely associated with thrombin generation. SUMMARY: Background Oral use of exogenous estrogen/progestin alters hemostatic factor levels. The influence of endogenous hormones on these levels is incompletely characterized. Objectives Our study aimed to test whether, among postmenopausal women, high levels of estradiol (E2), estrone (E1), testosterone (T), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), and androstenedione, and low levels of sex hormone-binding globulin (SHBG), are positively associated with measures of thrombin generation (TG), a normalized activated protein C sensitivity ratio (nAPCsr), and factor VII activity (FVIIc), and negatively associated with antithrombin activity (ATc) and total protein S antigen (PSAg). Methods This Heart and Vascular Health study cross-sectional analysis included 131 postmenopausal women without a prior venous thrombosis who were not currently using hormone therapy. Adjusted mean differences in TG, nAPCsr, FVIIc, ATc and PSAg levels associated with differences in hormone levels were estimated using multiple linear regression. We measured E2, E1, total T, DHEAS, DHEA and androstenedione levels by mass spectrometry, SHBG levels by immunoassay, and calculated the level of free T. Results One picogram per milliliter higher E1 levels were associated with 0.24% lower PSAg levels (95% Confidence Interval [CI]: -0.35, -0.12) and 1 µg mL-1 higher DHEAS levels were associated with 40.8 nm lower TG peak values (95% CI: -59.5, -22.2) and 140.7 nm×min lower TG endogenous thrombin potential (ETP) (95% CI: -212.1, -69.4). After multiple comparisons correction, there was no evidence for other associations. Conclusions As hypothesized, higher E1 levels were associated with lower levels of the natural anticoagulant PSAg. Contrary to hypotheses, higher DHEAS levels were associated with differences in TG peak and ETP that suggest less generation of thrombin.

Population-based study of tamoxifen therapy and subsequent ovarian, endometrial, and breast cancers.

BACKGROUND: The success of tamoxifen in reducing the occurrence of contralateral breast cancer among breast cancer patients in clinical trials has prompted the study of its use in the primary prevention of breast cancer. Long-term risks associated with tamoxifen therapy, however, are still being evaluated, particularly with respect to subsequent cancer occurrence at sites other than the breast. PURPOSE: This population-based, nested case-control study investigated the risks of second primary cancers of the ovary, endometrium, and contralateral breast among women receiving tamoxifen for breast cancer in conventional medical practice. METHODS: A cohort of women diagnosed with breast cancer during 1978 through 1990 was identified from a population-based cancer registry. Case subjects included all women in the cohort who subsequently developed second primary ovarian (n = 39), endometrial (n = 42), or contralateral breast (n = 234) cancer prior to 1992. Control subjects were a random sample of the cohort who did not develop a second primary malignancy; they were matched to the case subjects on age, disease stage, and year of initial breast cancer diagnosis (approximately two control subjects per case subject). Information on tamoxifen use as well as on potential risk factors for the second primary cancers was obtained through medical record abstractions and physician questionnaires. RESULTS: The percentage of women who had received tamoxifen was 18% and 20%, respectively, among ovarian cancer case subjects and control subjects; 26% and 31%, respectively, among endometrial cancer case subjects and control subjects; and 10% and 18%, respectively, among contralateral breast cancer case subjects and control subjects. The mean duration of tamoxifen use was less than 2 years for all groups. The relative risks for ovarian and endometrial cancers in women who took tamoxifen were relatively low but were consistent with no association (for ovarian cancer, matched odds ratio [mOR] = 0.6 and 95% confidence interval [CI] = 0.2-1.8; for endometrial cancer, mOR = 0.6 and 95% CI = 0.2-1.9). Tamoxifen therapy was associated with a decreased risk of contralateral breast cancer (mOR = 0.5; 95% CI = 0.3-0.9), especially if the drug had been taken for more than 1 year (mOR = 0.4; 95% CI = 0.2-0.9) or if the women were postmenopausal at initial breast cancer diagnosis (mOR = 0.4; 95% CI = 0.2-0.8). CONCLUSIONS AND IMPLICATIONS: These data suggest that short durations of tamoxifen therapy are not associated with an increased risk of endometrial or ovarian cancer but are associated with a reduction in contralateral breast cancer risk. It would not be appropriate, however, to generalize these results to women who receive tamoxifen for longer periods.

Cofactors with human papillomavirus in a population-based study of vulvar cancer.

BACKGROUND: Human papillomavirus (HPV) has been previously associated with vulvar cancer. In a population-based study, we examined whether exposure to HPV, cigarette smoking, or herpes simplex virus 2 (HSV2) increases the risk of this cancer. METHODS: Incident cases of in situ (n = 400) and invasive (n = 110) squamous cell vulvar cancer diagnosed among women living in the Seattle area from 1980 through 1994 were identified. Serum samples were analyzed for antibodies against specific HPV types and HSV2. HPV DNA in tumor tissue was detected by means of the polymerase chain reaction. In most analyses, case subjects were compared with population-based control subjects (n = 1403). Relative risks of developing vulvar cancer were estimated by use of adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Increased risks of in situ or invasive vulvar cancer were associated with HPV16 seropositivity (ORs = 3.6 [95% CI = 2.6-4.8] and 2.8 [95% CI = 1.7-4.7], respectively), current cigarette smoking (ORs = 6.4 [95% CI = 4.4-9.3] and 3.0 [95% CI = 1.7-5.3], respectively), and HSV2 seropositivity (ORs = 1.9 [95% CI = 1.4-2.6] and 1.5 [95% CI = 0.9-2.6], respectively). When the analysis was restricted to HPV16 DNA-positive tumors (in situ or invasive), the OR associated with HPV16 seropositivity was 4.5 (95% CI = 3.0-6.8). The OR for vulvar cancer was 18.8 (95% CI = 11.9-29.8) among current smokers who were HPV16 seropositive in comparison with never smokers who were HPV16 seronegative. CONCLUSIONS: Current smoking, infection with HPV16, and infection with HSV2 are risk factors for vulvar cancer. Risk appears particularly strong among women who are both current smokers and HPV16 seropositive.

Interaction of dimethylbenzanthracene and diethylstilbestrol on mammary adenocarcinoma formation in female ACI rats.

It has been reported that X-irradiation and diethylstilbestrol (DES) act synergistically on mammary adenocarcinoma formation in female ACI rats. The physical carcinogen, X-irratiation, was replaced by a chemical carcinogen, dimethylbenzanthracene (DMBA), and their interaction was studied in this system. Thirty-three female ACI rats were given 13.3 mg of DMBA per 100 grams of body weight. A total of 10 mammary adenocarcinomas were found, 8 in rats with a single mammary adenocarcinoma and 2 in a single rat, over a 266-day study period. Twenty-nine rats were implanted with a cholesterol pellet containing 5 mg of DES, and a total of 47 mammary adenocarcinomas were found, 5 in rats with a single mammary adenocarcinoma and 42 in 5 rats with 2 or more mammary adenocarcinomas. Twenty-four rats were given a combined treatment of both compounds, DES 2 days before DMBA, and a total of 12l mammary adenocarcinomas were found, 2 in rats with a single mammary adenocarcinoma and 124 in 18 rats with 2 or more mammary adenocarcinomas. The interaction between DMBA and DES was interpreted to be synergistic in regard to the proportion of rats with one or more mammary adenocarcinomas, the proportion of rats with two or more mammary adenocarcinomas, and the median times of appearance of both first and second mammary adenocarcinomas. These interactions between DMBA and DES resemble the previously reported synergistic interactions between radiation and DES on mammary adenocarcinoma formation in female ACI rats.

Evidence for a new model of tumor progression from carcinogenesis and tumor promotion studies with 7-bromomethylbenz[a]anthracene.

7-Bromoethylbenz[a]anthracene (BrMeBA) has been shown previously to be a modest initiator of tumors in mouse skin and a powerful promoter. Evidence has also been presented that carcinomas and papillomas arising in mouse skin from a two-stage induction regimen (initiation and promotion) originate in two separate populations, rather than representing progressive stages on a single pathway. In this report, we show that 10 nmol of BrMeBA applied biweekly to female SENCAR mice initiated with 7,12-dimethylbenz[a]anthracene (DMBA) is an effective promoting dose. The question of whether BrMeBA or its solvolysis product, 7-hydroxymethylbenz[a]anthracene, is the effective promoter was tested in Charles River CD-1 mice, in which 90 nmol of BrMeBA applied weekly following a single dose of 200 nmol of DMBA induced papillomas in 17 weeks (median induction time) and carcinomas in 43 weeks after beginning of promotion. Without DMBA initiation, papillomas appeared 11 weeks later in much lower yield, while carcinomas appeared 14 weeks later. Animals treated with 7-hydroxymethylbenz[a]anthracene for 82 weeks had developed only 16 tumors in eight animals (initiated) or six tumors in five animals (uninitiated), with survivals of 18 of 30 and 19 of 30, respectively. In SENCAR mice treated with 90, 30, or 10 nmol of BrMeBA biweekly, the ratio of total carcinomas to total papillomas in initiated mice was about half that in uninitiated mice, due primarily to a large reduction in papilloma incidence in uninitiated mice. When adjusted for the number of papillomas, the risk of developing the first carcinomas at any time was dependent only on the dose of BrMeBA and not on whether DMBA was given first. An attempt to inhibit BrMeBA promotion with the antiinflammatory steroid fluocinolone acetonide resulted in inhibition of DMBA-initiated papillomas but had no effect on the carcinoma latent period of incidence. The results are explained in terms of new models of tumor progression which suggest either that promotors with the capabilities of 12-O-tetradecanoylphorbol-13-acetate can divert cells at a minimum level of initiation from progression to cancer or that initiation can create at least two populations of altered cells, one (or more) of which is less likely to progress to cancer than normal cells.

Circulating microRNAs and sudden cardiac arrest outcomes.

AIM: MicroRNAs (miRNAs) have regulatory functions in organs critical in resuscitation from sudden cardiac arrest due to ventricular fibrillation (VF-SCA); therefore, circulating miRNAs may be markers of VF-SCA outcome. METHODS: We measured candidate miRNAs (N=45) in plasma using qRT-PCR among participants of a population-based VF-SCA study. Participants were randomly selected cases who died in the field (DF, n=15), died in hospital (DH, n=15), or survived to discharge (DC, n=15), and, age-, sex-, and race-matched controls (n=15). MiRNA levels were compared using ANOVA, t-tests, and fold-changes. RESULTS: Mean age of groups ranged from 66.9 to 69.7. Most participants were male (53-67%) and white (67%). Comparing cases to controls, plasma levels of 17 miRNAs expressed in heart, brain, liver, and other tissues (including miR-29c, -34a, -122, -145, -200a, -210, -499-5p, and -663b) were higher and three non-specific miRNAs lower (miR-221, -330-3p, and -9-5p). Among DH or DC compared with DF cases, levels of two miRNAs (liver-specific miR-122 and non-specific miR-205) were higher and two heart-specific miRNAs (miR-208b and -499-5p) lower. Among DC vs. DF cases, levels of three miRNAs (miR-122, and non-specific miR-200a and -205) were higher and four heart-specific miRNAs (miR-133a, -133b, -208b, and -499-5p) lower. Among DC vs. DH cases, levels of two non-specific miRNAs (miR-135a and -9-3p) were lower. CONCLUSIONS: Circulating miRNAs expressed in heart, brain, and other tissues differ between VF-SCA cases and controls and are related to resuscitation outcomes. Measurement of miRNAs may clarify mechanisms underlying resuscitation, improve prognostication, and guide development of therapies. Results require replication.

The association of statin therapy with the risk of recurrent venous thrombosis.

UNLABELLED: Essentials A lowered risk of recurrent venous thrombosis (VT) with statin treatment is controversial. Among observational inception cohort of 2,798 adults with incident VT, 457 had recurrent VT. Time-to-event models with time-varying statin use and adjustment for potential confounders was used for analysis. Compared to nonuse, current statin use was associated with 26% lower risk of recurrent VT. Click to hear Prof. Büller's perspective on Anticoagulant Therapy in the Treatment of Venous Thromboembolism SUMMARY: Background Meta-analyses of randomized controlled trials suggest that treatment with hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) lowers the risk of incident venous thrombosis (VT), particularly among those without prevalent clinical cardiovascular disease (CVD). Whether this is true for the prevention of recurrent VT is debated. We used an observational inception cohort to estimate the association of current statin use with the risk of recurrent VT. Methods and Results The study setting was a large healthcare organization with detailed medical record and pharmacy information at cohort entry and throughout follow-up. We followed 2798 subjects 18-89 years of age who experienced a validated incident VT between January 1, 2002, and December 31, 2010, for a first recurrent VT, validated by medical record review. During follow-up, 457 (16%) developed a first recurrent VT. In time-to-event models incorporating time-varying statin use and adjusting for potential confounders, current statin use was associated with a 26% lower risk of recurrent VT: hazard ratio 0.74, 95% confidence interval 0.59-0.94. Among cohort members free of CVD (n = 2134), current statin use was also associated with a lower risk (38%) of recurrent VT: hazard ratio 0.62, 95% confidence interval 0.45-0.85. We found similar results when restricting to new users of statins and in subgroups of different statin types and doses. Conclusions In a population-based cohort of subjects who had experienced an incident VT, statin use, compared with nonuse, was associated with a clinically relevant lower risk of recurrent VT. These findings suggest a potential secondary benefit of statins among patients who have experienced an incident VT.

Cardiovascular disease mortality in familial forms of hypertriglyceridemia: A 20-year prospective study.

BACKGROUND: Familial combined hyperlipidemia (FCHL) and familial hypertriglyceridemia (FHTG) are 2 of the most common familial forms of hyperlipidemia. There is a paucity of prospective data concerning the risk of cardiovascular disease (CVD) in such families. The purposes of this study were to estimate 20-year total and CVD mortality risk among relatives in these families and to evaluate plasma triglyceride as a predictor of death. METHODS AND RESULTS: The study was based on lipid and medical history data from 101 families ascertained in 2 studies conducted in the early 1970s. Vital status and cause of death was determined during 1993 to 1997 for 685 family members, including first-degree relatives of the probands and spouse control subjects. Compared with spouse control subjects, 20-year CVD mortality risk was increased among siblings and offspring in FCHL (relative risk 1.7, P=0.02) after adjustment for baseline covariates. In FHTG families, the relative risk was also 1.7 but was not statistically significant (P=0.39). Baseline triglyceride was associated with increased CVD mortality risk independent of total cholesterol among relatives in FHTG families (relative risk 2.7, P=0.02) but not in FCHL families (relative risk 1.5, P=0.16) after adjustment for baseline covariates. CONCLUSIONS: This prospective study establishes that relatives in FCHL families are at increased risk for CVD mortality and illustrates the need for effective prevention strategies in this group. Baseline triglyceride level predicted subsequent CVD mortality among relatives in FHTG families, adding to the growing evidence for the importance of hypertriglyceridemia as a risk factor for CVD.

Prognostic value of blood glucose in Hodgkin's disease.

Subjects with Hodgkin's disease and an initial blood glucose greater than 115 mg/dL had an impressively shorter survival than those with a glucose below that level. The same is true if the groups are formed from those having glucose above or below 100. The correlation between glucose and survival persisted after allowing for the survival effects of histology, stage, symptom class, and age.

Human papillomavirus and prognosis of invasive cervical cancer: a population-based study.

PURPOSE: To determine the association between human papillomavirus (HPV) type and prognosis of patients with invasive cervical carcinoma. PATIENTS AND METHODS: Patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB to IV cervical cancer between 1986 and 1997 while residents of three Washington State counties were included (n = 399). HPV typing was performed on paraffin-embedded tumor tissue using polymerase chain reaction methods. Patients were observed for a median of 50.8 months. Total mortality (TM) and cervical cancer-specific mortality (CCSM) were determined. Hazards ratios (HR) adjusted for age, stage, and histologic type were estimated using multivariable models. RESULTS: Eighty-six patients had HPV 18-related tumors and 210 patients had HPV 16-related tumors. Cumulative TM among patients with HPV 18-related tumors and among patients with HPV 16-related tumors were 33.7% and 27.6%, respectively; cumulative CCSM in these two groups were 26.7% and 18.1%, respectively. Compared with patients with HPV 16-related cancers, patients with HPV 18-related cancers were at increased risk for TM (HR(TM), 2.2; 95% confidence interval [CI], 1.3 to 3.6) and CCSM (HR(CCSM), 2.5; 95% CI, 1.4 to 4.4). The HPV18 associations were strongest for patients with FIGO stage IB or IIA disease (HR(TM), 3.1; 95% CI, 2.3 to 4.2; and HR(CCSM), 5.8; 95% CI, 3.9 to 8.7), whereas no associations were observed among patients with FIGO stage IIB to IV disease. Virtually identical associations were found in the subset of patients with squamous cell carcinoma (n = 219). CONCLUSION: HPV 18-related cervical carcinomas, particularly those diagnosed at an early stage, are associated with a poor prognosis. Elucidating the mechanism or mechanisms underlying this association could lead to new treatment approaches for patients with invasive cervical carcinoma.

Beta-cell function and insulin sensitivity in nondiabetic HLA-identical siblings of insulin-dependent diabetics.

Insulin secretion and insulin sensitivity were compared in 12 HLA-identical siblings of insulin-dependent diabetics and nondiabetic controls. Only the maximum acute insulin response to intravenous arginine was lower in the siblings than in the matched controls (P less than .05); other measures of insulin secretion, including the acute insulin response to glucose or arginine, the second-phase insulin response to glucose, and the slope of glucose potentiation, were not significantly different. Insulin sensitivity, derived from an intravenous glucose tolerance test with a minimal-modeling technique, was lower in the siblings (P less than .01). In a large group of nondiabetic controls of various adiposity, insulin secretion and insulin sensitivity were inversely related. In view of the difference in insulin sensitivity between siblings and matched controls, a direct comparison of beta-cell function tests may be inappropriate, and the measures of insulin secretion were compared with those of nondiabetics when adjusted for differences in insulin sensitivity. This analysis revealed that all measures of insulin secretion were significantly lower in the siblings. We conclude that HLA-identical siblings of insulin-dependent diabetics show evidence of both insulin resistance and impaired beta-cell function and that analysis of beta-cell function in relation to insulin sensitivity shows a greater frequency of beta-cell secretory abnormalities than previously appreciated.

Randomized prospective trial of pure porcine and conventional bovine/porcine insulin.

Use of pure porcine insulin versus partially purified insulin of bovine/porcine origin might be expected to have certain clinical benefits, e.g., a lower incidence of skin reactions, a lower insulin dosage, better diabetes regulation, and greater preservation of endogenous insulin secretion. To test this hypothesis, we randomly assigned 112 newly diagnosed, untreated, insulin-dependent diabetic children to therapy with either pure porcine or partially purified bovine/porcine insulin. They were followed for 1 yr, data being available on at least 90 subjects at each visit. More skin reactions were found in the group treated with the bovine/porcine insulin. This insulin was of higher antigenicity, and binding of radiolabeled insulin (mean +/- SE) by serum from bovine/porcine insulin treatment was 35.5 +/- 2.6 versus 16.8 +/- 1.4% (P less than .001) for pure porcine insulin treatment 12 mo after initiation of insulin therapy. However, throughout the 12 mo of observation the levels of glycosylated hemoglobin, insulin dosage, fasting plasma glucose, and C-peptide concentration were similar for the groups. Reported incidences of hypoglycemia and nocturia were also similar. Thus, insulin-antibody formation and skin reactions were minimized by the use of pure porcine versus partially purified bovine/porcine insulin, but no other clinical advantages were apparent.

Colorectal cancer in patients with esophageal adenocarcinoma.

The incidence of adenocarcinoma of the esophagus and gastric cardia has been rising rapidly in Western Europe and the United States, especially among white males. Previous reports, based on case series, have suggested an association between colonic neoplasia and Barrett's esophagus, a metaplastic condition of the lower esophagus that can lead to adenocarcinoma. We analyzed cancer incidence data from 1973 to 1989 from the nine population-based registries of the Surveillance, Epidemiology, and End Results program of the United States National Cancer Institute to investigate this association, using malignancies as an outcome. Using a case-control design, we measured the odds of being diagnosed with colorectal adenocarcinoma some time in life among persons diagnosed with adenocarcinomas of the esophagus or gastric cardia relative to persons diagnosed with squamous cell carcinomas of the esophagus. Among white males the odds ratio was 1.44 (95% confidence interval, 1.03-2.02). This association appeared to be independent of which cancer occurred first. In contrast, white females with adenocarcinomas were less likely to be diagnosed with colorectal cancer than those with squamous cell carcinomas (odds ratio, 0.39; 95% confidence interval, 0.19-0.78). These associations appeared to be specific for colorectal tissue because there was no relationship between histological type of esophageal cancer and prostate cancer in men or breast cancer in women. We conclude that men with esophageal adenocarcinoma may be more likely to be diagnosed with colorectal cancer in their lifetime than expected; the opposite association may exist for women.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasectomy and risk of prostate cancer.

Most studies do not support an association between vasectomy and prostate cancer, but a few have suggested a link. Vasectomy is a common birth control method, and prostate cancer is the most frequently diagnosed solid tumor in men, making this a major public health question. This study was specifically designed to determine whether or not vasectomy is associated with risk of prostate cancer. To examine this issue, we conducted a population-based case-control study in King County, Washington. Interviews were completed with men ages 40-64 years newly diagnosed with prostate cancer between January 1993 and December 1996 who were ascertained through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results (SEER) cancer registry (n = 753) and with comparison men without prostate cancer identified from the same general population (n = 703). The odds ratio (OR) for prostate cancer in relation to vasectomy was assessed. The prevalence of vasectomy was similar in cases (39.4%) and controls (37.7%), resulting in no association (adjusted OR, 1.10; 95% confidence interval, 0.9-1.4). There was no consistent evidence that risk varied by the age at which vasectomy was performed, the time since vasectomy, or the calendar period when the vasectomy was performed. The OR in relation to vasectomy was higher in men with less aggressive prostate cancer. Risk estimates did not differ according to age, race, or family history of prostate cancer. This study suggests that vasectomy is not associated with the risk of developing prostate cancer. It also provides evidence that vasectomized men may be more likely to present with earlier-stage, lower-grade prostate tumors.

The association of human papillomavirus antibodies with cervical cancer risk.

The association between viral human papillomavirus (HPV) DNA and cervical carcinoma has been well documented. However, less is known about the immune response to HPV infections and its relationship to cervical cancer risk. A higher prevalence of antibodies to HPV16 E7 among women with cervical cancer compared with controls has been reported, but reactivity to other antigens has not been systematically examined. Prevalence of serum IgG antibody reactivities to HPV6-encoded L1 and L2 and to HPV16- and HPV18-encoded E2, E4, E6, E7, L1, and L2 bacterial fusion proteins in a Western immunoblot assay were measured among cases with invasive cervical cancer (n = 69) and control women (n = 81). The intensities of the Western blot bands were graded as +1, +2, or +3 (0 = negative). Antibodies to HPV6 L1 and L2, HPV16 E7 and L2, and HPV18 L2 fusion proteins were observed among 39-62% of cases and 33-71% of controls. After systematic sampling for antibody reactivity to this range of fusion proteins, the sample was expanded to include 150 cases and 145 controls tested exclusively for reaction to HPV6 L1 and L2, HPV16 E7, and HPV16 and HPV18 L2. Relative risk was estimated for > or = +1, +1, and > or = +2 levels of reactivity after adjustment for confounding factors. Except for HPV16 E7, reactivity at the > or = +1 level did not distinguish cases from controls.(ABSTRACT TRUNCATED AT 250 WORDS)

The p53 Arg72Pro polymorphism, human papillomavirus, and invasive squamous cell cervical cancer.

A. Storey et al. [Nature (Lond.), 393: 229-234, 1998)] reported a 7-fold increased risk of cervical cancer associated with having an Arg/Arg polymorphism at codon 72 of p53 compared with the Pro/Arg heterozygotes (odds ratio, 7.4; 95% confidence interval, 2.1-29.4). Complementary in vitro studies suggested that the HPV E6 oncoprotein more readily targets the arginine form, as opposed to the proline form, of p53 for degradation. We investigated the impact of this polymorphism in a population-based case-control study of invasive cervical cancer. Using a PCR assay to detect the p53 codon 72 polymorphism, we tested blood samples from 111 women with invasive squamous cell cancer of the cervix identified by a population-based registry and 164 random-digit telephone-dialed controls. The distribution of the genotype among control women was 38% heterozygous, 7% proline homozygous, and 55% arginine homozygous, and among the cases was 38%, 6%, and 56%, respectively. There was no increased risk of squamous cell invasive cervical cancer associated with homozygosity for the arginine allele (odds ratio, 1.0; 95% confidence interval, 0.6-1.7). Furthermore, there was no modification of this result by human papillomavirus (HPV) DNA status of the tumor, age, or smoking status. Among controls, there was no association between the polymorphism and HPV-16 L1 seropositivity. However, among case subjects, the codon 72 polymorphism may be related to HPV 16L1 seropositivity status.