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Biomedical subjects

B W Gillespie

Publications and source records attributed to B W Gillespie.

32 records · Page 2Linked to original sources

Phenotypic plasticity in skull and dental morphology in the prairie deer mouse (Peromyscus maniculatus bairdii).

Morphologists and systematists have long suspected that dietary consistency can affect skull and dental form in mammals. We examined plasticity of skull shape and tooth morphology in prairie deer mice (Peromyscus maniculatus bairdii) by feeding mice diets that differed in consistency but not nutritional quality. Shape differences were analyzed qualitatively and quantitatively, using both landmark-based morphometrics and traditional distance measurements. Mice fed a gruel made of laboratory chow soaked in water differed from those fed hard blocks of chow by a slight anterior shift in the incisor tips, a narrowed zygomatic plate, a reduction in size of the masseteric tubercles, an overall decrease in skull size in lateral view, and an increase in overall size in ventral view. Disparities between our results and previous studies may be due to the differences in behavior between the inbred, relatively inactive laboratory strains commonly used in experimental studies and the outbred, constantly active species used here. Also, in contrast to previous studies, the statistical analysis employed here took into account both family relationships of the animals and the large number of statistical comparisons performed. Failure to consider these factors would have resulted in an exaggerated estimate of the effects of diet on skull form and may taint other studies that have explored the same aspects of plasticity.

Animals↗

The epidemiology of scleroderma among women: assessment of risk from exposure to silicone and silica.

OBJECTIVE: To investigate the relationship between exposure to silicone (including breast implants) and silica and the development of scleroderma (systemic sclerosis, SSc) among women. METHODS: A population based case-control study was conducted among women in Michigan. 274 confirmed cases of SSc diagnosed between 1985 and 1991 were identified by contacting rheumatologists, hospitals, and a scleroderma support group. These cases and 1184 controls were interviewed by telephone to ascertain past exposures to silicone or silica. RESULTS: Silicone in the form of breast implants was not associated with significantly increased risk of SSc (adjusted odds ratio, 1.30; 95% confidence interval, 0.27 to 6.23). Among 20 other potential silicone exposure surveyed, self-reported exposure to silicone based glues, sealants, and caulks, manufacture or repair of windows or windshields, repairing or frequently using photocopy machines, consumption of simethicone-containing antacids, and implanted medication delivery pumps were significantly associated with SSc. However, blinded assessment of all job and hobby descriptions in terms of their potential for silicone exposure failed to support the first 3 associations, antacid consumption may have been confounded by esophageal dysmotility before the diagnosis of SSc, and other silicone containing device categories (pacemakers, central nervous system shunts, other shunts and catheters) were not significantly associated with SSc. Surgically implanted metallic fixation devices were associated with significantly reduced risk for SSc. No association was detected between SSc and silica dust exposure. CONCLUSION: Consistent with other studies, we found no increased risk of SSc among women with silicone breast implants, equivocal evidence of risk from other silicone exposures, and no evidence of risk from silica exposure.

Adolescent↗

The epidemiology of vulvovaginal candidiasis among university students.

Vulvovaginal candidiasis affects approximately 20% of women annually, but it is not well characterized epidemiologically. Of 1027 respondents to two mailed cross-sectional surveys at a large university, 37.5% reported a prior clinical diagnosis of vulvovaginal candidiasis. The frequency of first diagnosis increased rapidly after age 17, with an estimated 54.7% of women experiencing the condition by age 25. In a proportional hazards model of age at first diagnosis, vulvovaginal candidiasis was associated with initiation of sexual activity (rate ratio [RR] = 2.9; 95% confidence interval [CI] = 2.2, 3.8), oral contraceptive use (RR = 1.7; CI = 1.4, 2.2), and White (RR = 3.1; CI = 1.7, 5.7) and Black (RR = 5.9; CI = 3.0, 11.5) race vs Asian.

Adolescent↗

A meta-analysis of colorectal cancer and asbestos exposure.

A meta-analysis of the relation between asbestos exposure and colorectal cancer mortality was conducted, using published reports of 20 asbestos-exposed cohorts. Summary standardized mortality ratios (SMRs) for colorectal cancer were examined in relation to asbestos type and estimates of dust exposure (as direct estimators of asbestos exposure) and in relation to lung cancer SMR and the proportion of all deaths due to mesothelioma (as proxy estimators of asbestos exposure). An elevated summary SMR was observed in cohorts exposed to amphibole asbestos (summary SMR = 1.47; 95% confidence interval (CI) 1.09-2.00), but not in cohorts exposed to serpentine asbestos (summary SMR = 1.04; 95% CI 0.81-1.33) or in cohorts exposed to both serpentine and amphibole asbestos (summary SMR = 1.03; 95% CI 0.74-1.42). Cohorts having a lung cancer SMR greater than 2.00 had a summary SMR of 1.51 (95% CI 1.29-1.76), and cohorts in which more than 1% of all deaths were attributed to mesothelioma had a summary SMR of 1.24 (95% CI 0.94-1.64). After stratifying the cohorts based on mortality due to all cancers excluding those known or suspected to be associated with asbestos exposure, lung cancer mortality was not clearly associated with colorectal cancer mortality, suggesting that the crude association between these factors may be due to misdiagnosis of lung cancer as other types of cancer in the reported causes of death. These results suggest that exposure to amphibole asbestos may be associated with colorectal cancer, but these findings may reflect an artifact of miscertification of cause of death. The results also suggest that serpentine asbestos is not associated with colorectal cancer.

Asbestos↗

Patterns of absolute risk of lung cancer mortality in former smokers.

BACKGROUND: It is well known that the relative risk (RR) of lung cancer mortality decreases following smoking cessation compared with the risk in persons who continue to smoke. However, changes in the absolute risk of lung cancer death following smoking cessation are not well documented. Further, few studies have examined the effect of age at smoking cessation on subsequent lung cancer death risk. PURPOSE: The purpose of this study was to examine and compare absolute and relative lung cancer death risks in former smokers as a function of age at cessation. METHODS: Using the American Cancer Society's Cancer Prevention Study II, a prospective cohort study with 6 years of follow-up, we modeled absolute risk of lung cancer mortality in individuals who had never smoked and in current and former smokers. The model was fit with the use of person-years logistic regression analysis. RESULTS: Similar patterns of absolute risk of lung cancer death by age were found for all ages of smoking cessation up to the mid-60s. Lower lung cancer death risk was observed for those quitting earlier in life, and the risk for all former smokers was significantly lower than that for current smokers. For those quitting between ages 30 and 49, lung cancer death risk rose gradually with age at a rate slightly greater than that for those who had never smoked. Lung cancer death risk for former smokers quitting between ages 50 and 64 leveled off near the risk attained at the time of quitting until around age 75, when it rose sharply. At age 75, the RR for former smokers compared with current smokers was approximately 45% for those quitting in their early 60s, approximately 20% for those quitting in their early 50s, and less than 10% for those quitting in their 30s. For those who had never smoked, the RR at age 75 is less than 5%. CONCLUSIONS: In terms of reduced risk of lung cancer mortality, smoking cessation is beneficial at any age, with much greater benefits accruing to those quitting at younger ages. Unlike previous research, which has primarily examined the effects of cessation as a function of years since quitting, our results demonstrate that age at cessation has a major impact on subsequent lung cancer risks. IMPLICATIONS: Smokers of all ages should be encouraged to quit because cessation at any age decreases lung cancer risk relative to that of current smokers.

Adult↗

Neutron therapy in cervical cancer: results of a phase III RTOG Study.

Between October 1976 and May 1984, 156 patients with locally advanced cervical cancer were entered into a Phase III trial with the participation of five institutions. Patients were randomly assigned to receive photons only (50 Gy in 25 fractions over 5 weeks plus intracavitary applications or external-beam boost) or mixed-beam radiotherapy (2 fractions a week of neutrons, 3 fractions a week of photons to a total RBE-adjusted dose of 50 Gy over 5 weeks plus intracavitary applications or external mixed-beam boost). Only patients with squamous carcinoma of FIGO Stages IIB, III, or IVA with negative para-aortic nodes on lymphangiogram were eligible. Ten patients were excluded from the analysis because of ineligibility or cancellation. Of the 146 patients analyzed, 80 were treated with mixed-beam radiotherapy and 66 with photons. Patients were grouped by stage and institution. The percentage of patients undergoing intracavitary applications was 50% on mixed beam and 75% on photons (p less than 0.01). Tumor clearance was 52% and 72% for mixed beam and photons, respectively (p less than 0.03). Local control at 2 years was 45% for mixed beam and 52% for photons. Median survivals were 1.9 years on mixed beam and 2.3 years on photons. Severe complications occurred in 19% and 11% in mixed beam and photons respectively (p less than 0.13). The inferior outcome with neutron therapy in this study may have resulted from the use of horizontal neutron beams of varying energy and penetration. A new randomized trial using high-energy hospital-based cyclotrons with gantry-mounted beam-delivery systems has recently been activated to evaluate more rigorously the role of fast-neutron therapy for advanced cervical cancer.

Adult↗

An outcome study of the RTOG Cancer Control program.

The Cancer Control program, funded by the National Cancer Institute, was initiated with the goal of involving community hospitals in multi-institutional clinical trials. The Radiation Therapy Oncology Group (RTOG) began participating in this program in 1976. This investigation compares the survival of patients treated by protocol in RTOG Full Member versus Cancer Control institutions between 1976 and 1985. The RTOG has 28 Full Members which are major treatment centers and enter at least 50 patients on RTOG protocols each year. The 11 Cancer Control members, which are mostly community hospitals, must enter at least 12 patients on RTOG protocols each year. A comparison of survival between Full Members and Cancer Control members was made for five RTOG studies. No difference in data quality or protocol compliance was observed for these studies between Cancer Control and Full Member institutions. Overall survival comparisons, as well as comparisons adjusted for prognostic factors, were made for each of the five studies. No differences in survival between Cancer Control and Full Members were observed in either analysis.

Clinical Trials as Topic↗

Impact of tumor control on survival in carcinoma of the lung treated with irradiation.

The long-term results in tumor response, intrathoracic tumor control and survival are reported in patients with medically inoperable or unresectable non-oat cell and small cell carcinoma of the lung. In 376 patients with stages T1-3, NO-2 carcinoma of the lung tumors, accessioned to a Radiation Therapy Oncology Group (RTOG) randomized study to evaluate different doses of irradiation, a higher complete response rate (24%), intrathoracic tumor control (67%) and three year survival (15%) was observed with 6000 cGy, compared with lower doses of irradiation (4000 or 5000 cGy). Increased survival was noted in patients with complete tumor response. Three year survival in complete responders was 23%, in partial responders, 10%, and in patients with stable disease, 5%. Patients treated with 6000 cGy had an overall intrathoracic failure rate of 33% at 3 years, compared with 42% for those treated with 5000 cGy, 44% for patients receiving 4000 cGy with split course, and 52% for those treated with 4000 cGy continuous course (p = 0.02). Patients surviving 6 or 12 months exhibited a statistically significant increased survival when the intrathoracic tumor was controlled. Patients treated with 5000-6000 cGy, showing tumor control, had a three year survival of 22%, versus 10%, if they had intrathoracic failure (p = 0.05). In patients treated with 4000 cGy (split or continuous), the respective survival was 20% and 10%, if the intrathoracic tumor was controlled (p = 0.001). In patients surviving 12 months after treatment with 5000-6000 cGy, on whom the intrathoracic tumor was controlled, the median survival was 29 months, in contrast to 18 months, if they developed intrathoracic failure (p = 0.05). In patients treated with 4000 cGy, the median survival was 23 months with control and 18 months without control of the intrathoracic tumor [corrected] (p = 0.008). In another RTOG study for patients with more advanced tumors (T4 or N3), those with local tumor control at 12 months had a three year survival rate of 25%, compared with 5% for those with thoracic failures. These differences are statistically significant (p = 0.006). Higher doses of irradiation yield a greater proportion of complete response, higher intrathoracic tumor control and better survival in non-oat cell medically inoperable or unresectable carcinoma of the lung.(ABSTRACT TRUNCATED AT 400 WORDS)

Carcinoma, Bronchogenic↗

Predicting the response of head and neck cancers to radiation therapy with a multivariate modelling system: an analysis of the RTOG head and neck registry.

Two thousand and sixty-six patients with primary head and neck cancers were entered in the RTOG Head and Neck Cancer Registry between 1977 and 1980. Nine hundred and ninety-seven (997) evaluable patients were treated initially with radiation therapy alone. Tumor site, T-stage, N-stage, histology, degree of infiltration, degree of differentiation, patient age, sex and Karnofsky performance score were all prospectively recorded. T-stage (p less than .001), N-stage (p = .007), primary site (p less than .001), and initial Karnofsky performance score (p less than .001) proved to be significant factors independently predictive of primary tumor clearance. Using these factors, a multivariate response model was constructed to predict primary tumor response. The predictive accuracy of the model proved to be highly reliable, and was tested by comparing the predicted vs. observed complete tumor clearance rates for each independent variable. For primary sites, the predicted number of complete responses vs. observed were: oral cavity, 139.8 predicted vs. 139 observed; nasopharynx, 51.8 predicted vs. 51 observed; oropharynx, 174.8 predicted vs. 176 observed, supraglottic larynx, 314.4 predicted vs. 318 observed; glottic larynx, 314.4 predicted vs. 318 observed; and hypopharynx, 49.4 predicted vs. 46 observed. For the entire group of patients predicted to have a 90% or better complete primary tumor response (including T3 and T4 tumors), 94% remained in initial complete remission at the primary site at one year, and 87% at two years. An accurate multivariate response model, such as the one presented in this paper, should prove to be a useful tool in selecting patients with head and neck cancers suitable for treatment with radiation therapy alone.

Adult↗

Is misonidazole neurotoxicity altered by the use of phenytoin and/or dexamethasone in RTOG 79-18 and RTOG 79-16?

An analysis of Misonidazole (MISO) neurotoxicity in RTOG 79-16 and RTOG 79-18 was undertaken to evaluate the incidence of neurotoxicity relative to dexamethasone dose and phenytoin use. MISO was administered as follows: 79-16 arm A, 1 gm/m2 5 days a week for a total of 10 gm/m2 in 2 weeks; 79-16 arm B, 2 gm/m2 twice weekly for a total of 12 gm/m2 in 3 weeks; and 79-18, 2.5 gm/m2 once a week for a total of 15 gm/m2 in 6 weeks. Practically all patients were on dexamethasone, and 240 out of 550 were on phenytoin for seizures. CNS toxicity and ototoxicity rates were no different between treatment groups with overall rates of 2.7 and 1.1%, respectively. Peripheral neuropathy (PN) was 5.1% in 79-16 arm A, 5.9% in 79-16 arm B, and 8.7% in 79-18. Phenytoin did not significantly alter CNS and PN toxicity rates. All ototoxicities occurred in patients not on phenytoin. There was no correlation between dexamethasone dose and incidence of neurotoxicity within each study. However, the incidence of (PN) for the combined studies was 6.4% (35/550) which is lower than 18.9% (85/449) for non-brain Phase III protocols where patients are rarely, if ever, on dexamethasone or other corticosteroids. Four hour and 24 hour plasma MISO levels, and 24 hour/4 hour MISO ratios did not correlate with toxicity.

Brain Neoplasms↗

Interleukin-8 levels and activity in delayed-healing human thermal wounds.

There are numerous causes for slow or delayed wound healing. Because slowly healing wounds are often inflamed, we quantitated the inflammatory chemokine, interleukin-8, produced by slowly healing human burn wounds and compared this to interleukin-8 from healed wounds and normal intact skin. Interleukin-8 levels were increased significantly in unhealed wounds (19.7 ng/ml) compared to healed wounds (7.7 ng/ml) or normal skin (5.7 ng/ml). Interleukin-8 in these ranges was added to adult human keratinocytes and fibroblasts. Interleukin-8 significantly decreased keratinocyte replication but had no effect on fibroblast replication. The rate or final degree of fibroblast populated collagen lattice contraction was inhibited at interleukin-8 concentrations between 10 and 30 ng/ml, but not altered at concentrations below 10 ng/ml and above 100 ng/ml. The concurrent application of indomethacin at 10 microg/ml reversed this interleukin-8 induced inhibition. Interleukin-8 inhibited myosin ATPase activity, apparently by reducing the phosphorylation of nonmuscle myosin light chain. We conclude that elevated levels of interleukin-8 may be found during delayed healing, and these elevated interleukin-8 levels may directly contribute to retarded wound closure.

Adult↗

Sexual behaviors and other risk factors for Candida vulvovaginitis.

Sexual behaviors are associated with many genital infections, but the role of sexual variables as risk factors for Candida vulvovaginitis has not been clearly determined. To assess the association between sexual behaviors and other risk factors with the presence of Candida vulvovaginitis, we performed a case-control study comparing these potential risk factors in women with and without culture-documented Candida vulvovaginitis in two Midwestern community-based medical offices. Participants included 156 women with Candida vulvovaginitis and 92 controls, ages 18-60. Risk factors for Candida vulvovaginitis, including sexual and partnership behaviors, demographic data, past genital infections, exposures, and diet, were investigated using logistic regression. The presence of Candida vulvovaginitis was positively associated with recent cunnilingus (odds ratio [OR] = 2.22 for five times a month compared with no times, 95% confidence interval [CI] 1.36, 3.84), but was less likely in women who masturbated with saliva in the previous month (OR = 0.30 if masturbated five times vs. no times, 95% CI 0.09, 0.99). Other independent risk factors included knowing the sexual partner a shorter period of time (OR = 1.56 for 1 year vs. 5 years, 95% CI 1.16, 2.13) and lower milk ingestion (OR = 3.57 for no servings vs. two servings per day, 95% CI 2.00, 6.67). Increased number of sexual partners, early age at first intercourse, and increased frequency of intercourse are not related to risk.

Adolescent↗

Birthweight-adjusted Dubowitz methods: reducing misclassification of assessments of gestational age in a Zimbabwean population.

OBJECTIVE: To evaluate the performance and the utility of using birthweight-adjusted scores of the Dubowitz method of estimating gestational age in a Zimbabwean population. DESIGN: A validation study. SETTING: Harare Maternity Hospital, from October to December 1999. SUBJECTS: 364 African newborn infants with a known last menstrual period (LMP), within the first 56 hours of life. MAIN OUTCOME MEASURES: Differences between regression lines and variances explained by Dubowitz scores obtained by examining newborn infants compared to gestational age calculated from the last menstrual period, in models with and without the addition of birthweight. RESULTS: The Dubowitz method was a good predictor of gestational age, useful in differentiating term from pre-term infants. The beta coefficients from regression lines with and without addition of birthweight differed significantly from each other (z = 2.83, p < 0.01). Our regression line without adding birthweight was Y(LMP gestational age) = 23.814 + 0.301* score. Addition of birthweight to the regression models improved prediction of gestational age, Y(LMP gestational age) = 23.512 + 0.219* score + 0.0015* grams, and accounted for 69% of the variance compared to 66% in models without birthweight. CONCLUSION: The introduction of birthweight improves estimation of gestational age, correcting for the overestimation reported for the original Dubowitz methods and the error caused by low birthweight. We recommend the use of our birthweight-adjusted Dubowitz maturity scales for studies of prematurity, and for routine clinical practice.

Adolescent↗