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Biomedical subjects

B McKnight

Publications and source records attributed to B McKnight.

At least 73 records · Page 4Linked to original sources

Vaginal douching and the risk of tubal pregnancy.

To explore the possible association between vaginal douching and tubal pregnancy, we interviewed 273 women who were diagnosed with tubal pregnancy at Group Health Cooperative between September 31, 1981 and October 1, 1986. Their responses were compared with responses of a random sample of 722 female members of Group Health Cooperative who were assumed to be at risk of becoming pregnant at the time the cases conceived. After adjusting for differences between cases and controls with regard to other measured risk factors, we found a modest increase in risk associated with having douched more than two times per year in the past (RR = 1.3, 95% CI: 0.9-1.8). Among women who had more than one sexual partner during their lifetime, however, the risk for those who had douched more than twice per year was somewhat higher (RR = 1.6, 95% CI: 1.1-2.3). There was an indication that women who had been exposed to Chlamydia trachomatis, as indicated by elevated antibody titers, may further increase their risk for tubal pregnancy by douching (RR = 2.4, 95% CI: 0.8-7.3). The associations found in other studies between douching and pelvic inflammatory disease, and between pelvic inflammatory disease and subsequent tubal pregnancy, argue that a relation between douching and tubal pregnancy might be anticipated. Our results offer further support for this hypothesis.

Adolescent↗

Linkage of a nasopharyngeal carcinoma susceptibility locus to the HLA region.

The frequency of nasopharyngeal carcinoma is nearly 100-fold higher in southern Chinese than in most European populations. Earlier studies have suggested that an increased risk of nasopharyngeal carcinoma is associated with specific haplotypes in the HLA region: relative risks slightly over twofold were found for haplotypes A2, Bw46 and the antigen B17. We now report a linkage study based on affected sib pairs which suggests that a gene closely linked to the HLA locus confers a greatly increased risk of nasopharyngeal carcinoma. The maximum likelihood estimate is of a relative risk of approximately 21. The relationship between this suspected disease susceptibility gene (or genes) and known viral and environmental aetiological factors remains to be elucidated.

China↗

Islet function and insulin sensitivity in the non-diabetic offspring of conjugal type 2 diabetic patients.

To determine whether the genetic predisposition towards Type 2 diabetes was associated with a defect in either islet-cell function or insulin action, 12 non-diabetic offspring each of whose parents both had Type 2 diabetes were studied, together with 12 control subjects matched for age, sex, and weight. Fasting plasma glucose was higher in the offspring (5.5 +/- 0.1 mmol l-1 (mean +/- SE)) than in the matched controls (5.1 +/- 0.1 mmol l-1) (p less than 0.05). Using an IVGTT insulin sensitivity was not significantly lower in the offspring compared with their controls (3.1 +/- 0.5 vs 3.8 +/- 1.0 min-1 mU-1 l 10(-4)). There was no significant difference in any of the measures of insulin secretion (first- and second-phase response to IV glucose, slope of glucose potentiation, and maximal glucose regulated insulin secretory capacity). Glucagon secretion measured before and after a stimulus of IV arginine at varying plasma glucose concentrations was virtually identical in the offspring and their controls. Among a total of 28 non-diabetic subjects of differing body-weights there was a significant inverse relationship between insulin sensitivity and insulin secretion. When adjusted for their generally lower insulin sensitivity, maximal insulin secretory capacity was reduced in the offspring (p = 0.038, one-tailed t-test). The results suggest that the genetic predisposition to Type 2 diabetes is not associated in young adults with any major pre-morbid impairment in insulin secretion or insulin action but the relationship between the two may be abnormal. Islet A-cell function appears to be normal.

Adult↗

Diet and pharyngeal cancer.

A population-based case-control study was conducted to examine the effect of ingestion of vitamin C, carotenoids and retinol on risk of pharyngeal cancer. Data were available from 166 cases of pharyngeal cancer or their next-of-kin, and from 547 controls similar in age and sex to the cases. Odds ratios (ORs) relating consumption of vitamin C, carotenoids and retinol from foods and vitamins C and A from supplements to risk of pharyngeal cancer were calculated using multiple logistic regression analysis. After adjustment for smoking and alcohol consumption, a significant increase in risk associated with low intake of vitamin C from foods was observed. Compared to the highest quartile, the OR for the lowest quartile of intake was 2.5 (95% confidence interval, 1.5-4.2). No overall effect of dietary carotenoid or retinol consumption was noted after adjustment for smoking and alcohol. Decreasing use of either vitamin C or vitamin A supplements was associated with increasing cancer risk among the case group as a whole. However, the effect of vitamin C supplement use was substantially lower when next-of-kin respondents were excluded from analysis. Also, the OR for use of vitamin A supplements is based on a very small number of cases reporting use, and must be viewed with caution. The results of our study suggest that intake of vitamin C may be protective against pharyngeal cancer, and are consistent with the results of previous studies which reported a decreased risk of pharyngeal cancer associated with intake of fruits and vegetables.

Adult↗

Induced abortion and the risk of subsequent ectopic pregnancy.

This study assessed the effect of legal induced abortion on ectopic pregnancy risk by using a comparison group of reproductive-age women who were at risk of becoming pregnant during the same time period the women with ectopic pregnancy conceived. Cases were members of Group Health Cooperative of Puget Sound who were hospitalized for ectopic pregnancy from October 1981 through September 1986 (N = 211). Controls were randomly selected members matched to cases on age and county of residence (N = 457). All subjects in this analysis had had one or more prior pregnancies. Eighty-eight cases (41.7 per cent) and 177 controls (38.7 per cent) had a history of one or more induced abortions. The relative risk of ectopic pregnancy associated with one abortion was 0.9 (95 per cent confidence interval 0.6, 1.3), adjusted for age, county, reference date, religion, gravidity, age at first pregnancy, lifetime number of sexual partners, and miscarriage history. Among women with two or more prior pregnancies, the risk associated with two or more abortions was 1.2 (0.6, 2.4). Controlling for pelvic inflammatory disease and use of intrauterine devices did not alter these risks. We conclude that legal abortion as performed in the US since 1970 has little or no influence on a woman's risk of ectopic pregnancy in subsequent pregnancies.

Abortion, Legal↗

A guide to the statistical analysis of long-term carcinogenicity assays.

Statistical methods for analyzing data from chronic carcinogenicity bioassays are reviewed. When treatment groups do not show marked differences in tumor-free death rates, methods that compare the crude proportions of animals that develop tumors can be recommended as valid and powerful comparisons of age-specific tumor incidence rates. When the age at tumor onset can be observed, techniques of survival analysis such as the logrank test can adjust for differing tumor-free mortality rates. If tumors are strictly nonlethal, the age-adjusted comparison of tumor prevalence among dying animals compares age-specific tumor incidence rates. When tumors are occult or of intermediate lethality and when tumor-free death rates differ substantially, a variety of techniques are available, but most are computationally intensive and rely either on the collection of additional data or on additional assumptions that may not be met.

Animals↗

Multiple primary tumours in women with vulvar neoplasms: a case-control study.

We sought to determine whether women with in situ or invasive squamous cell vulvar cancer were more likely than other women to have had a previous or concurrent tumour at other anogenital sites. One hundred and fifty-eight women with vulvar cancer were identified who were first diagnosed during 1980-1985, were ages 18-79 years at that time, and were residents of one of three counties in western Washington. Two control groups were selected: (1) from records of hospital pathology departments, a sample of 113 women with certain benign conditions of the vulva; (2) through random digit dialing, a sample of 212 women from the general population of these counties. Information on a history of other cancers, and on sexual, reproductive, medical, and demographic characteristics was collected from cases and controls in at-home interviews. Cases were more likely to report a history of other anogenital cancers than were controls, with relative risks of 3.5-29.8, depending on the type of case group and type of control. These associations were not explained by case-control differences in demographic characteristics or frequency of cervical screening. On the other hand, prior or concurrent non-anogenital cancers were equally common in cases and controls. These results support the hypothesis that the different anogenital cancers have at least one aetiology in common.

Adolescent↗

Cryptorchism, orchiopexy, and the risk of testicular cancer.

Adult white male residents of 13 counties of western Washington State in whom germ cell testicular cancer was diagnosed between 1977 and 1983 (n = 333) were interviewed by telephone regarding their history of cryptorchism and its treatment. The same interview was given to a sample of 675 men selected from the population of these counties by dialing telephone numbers at random. Men who reported a history of cryptorchism were 5.9 times (95 per cent confidence interval 3.4-10.2) more likely than men without such a history to develop testicular cancer. Compared with noncryptorchid men, those with unilateral cryptorchism were at greater risk of developing a tumor on the side of nondescent (relative risk = 8.0) than on the opposite side (relative risk = 1.6). The size of the increased risk tended to be smaller among cryptorchid men who had undergone orchiopexy by age 10 than for other cryptorchid men, but the influence of orchiopexy in early childhood could not be evaluated in this population. These observations offer support for the hypothesis that one or more local factors (e.g., temperature elevation) account for the major part of the increased risk of germ cell testicular tumors in cryptorchid men.

Adult↗

Reliability of transcutaneous oxygen tension (TcPO2) measurements in elderly normal subjects.

This study was conducted to evaluate the reliability of TcPO2 measurements in a well characterized group of 10 elderly normal subjects with an age distribution typical for the population with peripheral vascular disease (PVD) and amputation. The TcPO2 values were obtained on three separate occasions at 2-week intervals at seven anatomic sites commonly measured in patients with PVD. The TcPO2 values were comparable to those previously reported for similar sites in normal elderly subjects. Measurement to measurement variation averaged 1.1 kPa (8 mmHg) for a coefficient of variation (CV) of 14.4%. Confidence intervals ranging from 2.1 kPa (16 mmHg) above a single TcPO2 value to 2.1 kPa (16 mmHg) below were necessary to contain the true value 95% of the time. While TcPO2 measurement is assuming an important role in the evaluation of disease states in both paediatric and adult medicine, our observations emphasize the importance of using such measurements as an adjunct in clinical decision making and not basing such decisions on a single TcPO2 value alone. The size of the confidence intervals can be reduced substantially for a given site by taking the mean of two or more TcPO2 measurements taken at separate times.

Aged↗

Correlates of placental abruption.

All cases (884) of placental abruption reported on Washington State birth or fetal death certificates in 1980 and 1981 were compared with 789 randomly selected births from the same time period. The incidence of reported cases of placental abruption was 6.5 per 1000 total births. The combined stillbirth and first month death rate of all abruption cases was 21%. Increased risks of placental abruption were associated with pre-eclampsia, diabetes, and unmarried status. Neither parity nor maternal age was associated with an increased risk. Infants born after abruption were significantly smaller-for-gestation than control infants, more likely to be male, and had malformations more frequently than control infants. Apgar scores of liveborn abruption infants were significantly lower than those of controls after adjustment for infant weight, gestational age, and sex.

Abruptio Placentae↗

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.

Adult↗

A cluster of injuries at a water slide in Washington State.

Interviews were conducted with 46 people injured on a newly opened water slide in Washington State during the summer of 1983, and 46 age-matched controls. The injuries included nine concussions and eight spinal fractures. The odds ratio associated with being 10 per cent over ideal body weight, adjusted for age and sex, was 1.6 (95% C.I. 1.1-2.5). Three of eight people with spinal fractures were riding with another person between their legs, compared with two of 38 other injured riders (OR = 10.8, 95% C.I. 1.8-63.5).

Adolescent↗

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.

Adult↗

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.

Age Factors↗

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.

9,10-Dimethyl-1,2-benzanthracene↗

Prognostic value of serum lactic dehydrogenase level in Hodgkin's disease.

The serum LDH level determined at time of diagnosis provides important prognostic information about patients with Hodgkin's disease. The median survival of patients with a normal value was 129 months, whereas those with elevated values had a median survival of only 39 months. The prognostic power of LDH persisted after adjustment for age, symptom class, stage, or histology. When the Cox proportional hazards regression method was used to simultaneously adjust for age, histology, symptom class, and stage, elevated enzyme levels still were correlated with short survival. (J Lab Clin Med 99:382, 1982.)

Female↗

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.

9,10-Dimethyl-1,2-benzanthracene↗

Challenges posed by non-random missing quality of life data in an advanced-stage colorectal cancer clinical trial.

Effects of variations in agent, dose, and route of treatment administration on patient reported quality of life (QOL) were examined for 279 patients enrolled on a seven-arm randomized clinical trial (S8905) of 5-FU and its modulation for advanced colorectal cancer. Patients completed QOL questionnaires at randomization and weeks 6, 11, and 21 post-randomization with five QOL endpoints considered primary: three treatment-specific symptoms (stomatitis, diarrhea, and hand/foot sensitivity); physical functioning; and emotional functioning. Patient compliance with the QOL assessment schedule was good, supporting the feasibility of including QOL measures in cooperative group trials. However, death and deteriorating health produced substantial missing data. Cross-sectional analyses indicated that the seven therapeutic arms did not differ in their impact on QOL. Unfortunately, longitudinal analyses of the QOL data were inappropriate given non-random missing data. Graphical presentation of non-random missing data identified the seriousness of this problem and its effect on potential conclusions about QOL during treatment. This problem appears to be particularly challenging in the context of advanced-stage disease. Failure to recognize the presence of non-random missing data can lead to serious overestimates of patient QOL over time.

Adult↗