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Biomedical subjects

J R Harris

Publications and source records attributed to J R Harris.

At least 127 records · Page 7Linked to original sources
PubMed1997

Genetic and environmental contributions to the correlation between alcohol consumption and symptoms of anxiety and depression. Results from a bivariate analysis of Norwegian twin data.

Two thousand five hundred seventy pairs of Norwegian MZ and like-sexed and unlike-sexed DZ twins aged 18-25 years completed questionnaires with information about symptoms of anxiety and depression and alcohol consumption. The aim of the study was to estimate sex-specific genetic and environmental effects unique to symptoms of anxiety/depression and to alcohol consumption and effects common to the two phenotypes. Five models fitted the data almost equally well. The heritability estimate from these models ranged from .23 to .57 for male alcohol consumption, from .39 to .59 for female alcohol consumption, from .25 to .48 for male anxiety/depression, and from .45 to .56 for female anxiety/depression. The phenotypic correlation between alcohol and anxiety/depression in males (r = .23) could be fully explained by common genetic effects. The correlation in females (r = .18) was caused by individual environmental factors together with either genetic effects or family environment.

Adolescent↗
PubMed1997

Are genetic determinants of weight gain modified by leisure-time physical activity? A prospective study of Finnish twins.

A large number of studies have shown that obesity is both under genetic control and influenced by several environmental factors, including energy expenditure and intake. Several studies in animals and humans have furthermore suggested that certain environmental factors, such as a high fat intake, may modify the expression of the genes responsible for weight gain. The present study examined whether physical activity, measured at the baseline examination in 1975, was likely to play a differential role in subsequent weight changes in the following 6 y in 1571 monozygotic and 3029 dizygotic, same-sex twin pairs from the Finnish Twin Cohort Study. A hierarchical multiple-regression analysis was used to test for gene-environment interactions by identifying significant three-way interactions between genetic factors, physical activity, and weight change. The results showed that associations between weight change in twin A and twin B were significantly stronger for monozygotic than for same-sex dizygotic twins at all levels of physical activity. Additionally, in the monozygotic men the strength of the association varied with physical activity level, and the association between the change in body mass index between the twin pairs with the highest physical activity level was about three times stronger (beta = 0.40) than the association in twin pairs with the lowest physical activity level (beta = 0.15, P for trend = 0.002). In pairs of dizygotic men, and in both monozygotic and dizygotic women, similarity in body mass index change was independent of physical activity level (all P > 0.14). The present study showed that genetic factors may modify the effects of physical activity on weight change, and suggests that a sedentary lifestyle may have an obesity-promoting effect in men with a genetic predisposition.

Adult↗
PubMed1997

Radiation therapy and breast cancer.

Although the role of radiation therapy in the management of ductal carcinoma in situ is somewhat controversial, the benefit of radiation therapy in breast-conserving treatment of early stage invasive breast cancer is well established. Patients undergoing tumor excision with clear margins have low rates of recurrence with radiation therapy whether there is an extensive intraductal component or not. In all patients, there is a significantly higher risk of recurrence without radiation therapy. In patients receiving systemic therapy, the optimal sequence of chemotherapy and radiation therapy is still being defined; however, in patients with positive nodes and negative margins it is now clear that it is preferable to start chemotherapy first.

Breast Neoplasms↗
PubMed1997

Misclassification of smoking status and lung cancer risk from environmental tobacco smoke in never-smokers.

Lung cancer risk estimates for exposure to environmental tobacco smoke remain controversial, a major unresolved issue being misclassification of smokers. We studied misclassification rates in two large cohorts using information on smoking obtained several years apart. Cohort I included Swedish twins born between 1886 and 1925 who answered questionnaires in 1961 and again in 1967 or 1970. Cohort II was a random stratified population sample of individuals born between 1894 and 1945 who responded to postal smoking surveys in 1963 and 1969. We considered those who stated that they had never smoked in the second questionnaire, but who reported smoking or former smoking in the first questionnaire, to be misclassified. In cohort I, 4.9% of male and 4.5% of female ever-smokers were misclassified, corresponding to 11.1% and 1.3% of reported never-smokers, respectively. Cohort II yielded similar results. A follow-up through 1992 of cohort I showed a relative risk for lung cancer among misclassified men of 1.9 [95% confidence interval (CI) = 0.4-9.1], as compared with 4.5 (95% CI = 2.0-9.9) and 13.3 (95% CI = 6.5-27.0) for former and current smokers, respectively. No case occurred among misclassified women. Although misclassification of smokers exists, our results indicate that it mainly concerns light smokers or long-time ex-smokers, who have only a very moderately elevated risk of lung cancer. It therefore appears unlikely that confounding by smoking explains the increased risk for lung cancer related to environmental tobacco smoke exposure.

Bias↗
PubMed1997

Description and primary results from an audiometric study of male twins.

OBJECTIVE: The purpose of this study is to present descriptive results from an audiometric examination of a male twin sample, compare the values with normative databases, and explore whether there are age differences in genetic and environmental contributions to variation in hearing. DESIGN: Audiometric and questionnaire data were collected on a subsample of male twins who were identified through the population-based Swedish Twin Registry. Hearing examinations were completed for a total of 557 intact pairs, comprised of 250 identical (monozygotic [MZ] pairs and 307 fraternal (dizygotic [DZ] pairs aged 36 to 80 yr. A scale measuring hearing in the high-tone ranges was constructed by calculating the mean for the hearing threshold values obtained for both ears combined at 3000, 4000, 6000, and 8000 Hz for air conduction. RESULTS: To assess whether the twin values are representative of genera hearing function, the hearing thresholds were compared with values from two normative databases. Results suggest that these twin data provide a valid representation of hearing function in a cross-section of the Swedish male population, aged 35 and older. The mean values for hearing ability decreased across age, and variation increased. Twin similarity, estimated across four age groups using intraclass correlations, decreased from 0.716 to 0.516 for the MZ pairs and increased from 0.131 to 0.279 for the DZ pairs. These results suggest that variation in hearing ability in the high ranges is due to genetic and environmental factors and that environmental effects become more important with age. CONCLUSIONS: These data reflect typical age-related deterioration in hearing ability accompanied by greater individual differences in hearing function with age. Across all ages, genetic and environmental effects are important sources of variation in hearing. However, preliminary analyses suggest that the relative influence of environment increases with age. These environmental effects are of the nonshared type that are not associated with shared family environments but rather are explained by unique exposures.

Adult↗
PubMed1997

The complete set of predicted genes from Saccharomyces cerevisiae in a readily usable form.

Nearly all of the open reading frames (ORFs) of the yeast Saccharomyces cerevisiae have been synthesized by PCR using a set of approximately 6000 primer pairs. Each of the forward primers has a common 22-base sequence at its 5' end, and each of the back primers has a common 20-base sequence at its 5' end. These common termini allow reamplification of the entire set of original PCR products using a single pair of longer primers-in our case, 70 bases. The resulting 70-base elements that flank each ORF can be used for rapid and efficient cloning into a linearized yeast vector that contains these same elements at its termini. This cloning by genetic recombination obviates the need for ligations or bacterial manipulations and should permit convenient global approaches to gene function that require the assay of each putative yeast gene.

DNA Primers↗
PubMed1997

Latency versus persistence or intermittent recurrences: evidence for a latent state of murine cytomegalovirus in the lungs.

The state of cytomegalovirus (CMV) after the resolution of acute infection is an unsolved problem in CMV research. While the term "latency" is in general use to indicate the maintenance of the viral genome, a formal exclusion of low-level persistent productive infection depends on the sensitivity of the assay for detecting infectious virus. We have improved the method for detecting infectivity by combining centrifugal infection of permissive indicator cells in culture, expansion to an infectious focus, and sensitive detection of immediate-early RNA in the infected cells by reverse transcriptase PCR. A limiting-dilution approach defined the sensitivity of this assay. Infectivity was thereby found to require as few as 2 to 9 virion DNA molecules of murine CMV, whereas the standard measure of infectivity, the PFU, is the equivalent of ca. 500 viral genomes. Since murine CMV forms multicapsid virions in most infected tissues, the genome-to-infectivity ratio is necessarily >1. This assay thus sets a new standard for investigating CMV latency. In mice in which acute infection was resolved, the viral DNA load in the lungs, a known organ site of CMV latency and recurrence, was found to be 1 genome per 40 lung cells, or a total of ca. 1 million genomes. Despite this high load of CMV DNA, infectious virus was not detected with the improved assay, but recurrence was inducible. These data provide evidence against a low-level persistent productive infection and also imply that intermittent spontaneous recurrence is not a frequent event in latently infected lungs.

Animals↗
PubMed1997

Pancreatic abnormalities and AIDS related sclerosing cholangitis.

OBJECTIVES: Biliary tract abnormalities are well recognised in AIDS, most frequently related to opportunistic infection with Cryptosporidium, Microsporidium, and cytomegalovirus. We noted a high frequency of pancreatic abnormalities associated with biliary tract disease. To define these further we reviewed the clinical and radiological features in these patients. METHODS: Notes and radiographs were available from two centres for 83 HIV positive patients who had undergone endoscopic retrograde cholangiopancreatography for the investigation of cholestatic liver function tests or abdominal pain. RESULTS: 56 patients had AIDS related sclerosing cholangitis (ARSC); 86% of these patients had epigastric or right upper quadrant pain and 52% had hepatomegaly. Of the patients with ARSC, 10 had papillary stenosis alone, 11 had intra- and extrahepatic sclerosing cholangitis alone, and 35 had a combination of the two. Ampullary biopsies performed in 24 patients confirmed an opportunistic infection in 16. In 15 patients, intraluminal polyps were noted on the cholangiogram. Pancreatograms were available in 34 of the 45 patients with papillary stenosis, in which 29 (81%) had associated pancreatic duct dilatation, often with associated features of chronic pancreatitis. In the remaining 27 patients, final diagnoses included drug induced liver disease, acalculous cholecystitis, gall bladder empyema, chronic B virus hepatitis, and alcoholic liver disease. CONCLUSION: Pancreatic abnormalities are commonly seen with ARSC and may be responsible for some of the pain not relieved by biliary sphincterotomy. The most frequent radiographic biliary abnormality is papillary stenosis combined with ductal sclerosis.

Acquired Immunodeficiency Syndrome↗
PubMed1997

No evidence for effects of family environment on asthma. A retrospective study of Norwegian twins.

The risk of developing asthma contingent upon the co-twins' history of asthma was analyzed in a population-based study of 5,864 Norwegian twins. A primary aim was to assess the significance of shared environment for the development of asthma from infancy through age 25. Retrospective reports were collected when the twins were 18 to 25 yr of age. The risk of developing asthma, contingent upon the co-twin's history of asthma, was estimated using survival analyses, and genetic and environmental sources of variation in liability for asthma were analyzed with structural equation models. The cumulative incidence of asthma was 6% for males and 5.4% for females. The relative risk of developing asthma among twins whose co-twin had a positive history of asthma compared with those whose co-twin had no history of asthma was 17.9 (95% CI, 10.3 to 31.0) for identical, and 2.3 (95% CI, 1.2 to 4.4) for fraternal twins. Although shared environment encompasses many of the exposures that are putative risk factors for asthma in this age range, there is no evidence of shared environmental influences for asthma. Rather, 75% of the variation in liability for asthma was explained by genetic effects and the remaining variation was due to nonshared environmental influences. These results suggest that the familial risk for asthma is primarily, genetic.

Actuarial Analysis↗
PubMed1997

Distribution and heritability of recurrent ear infections.

The distribution of recurrent ear infections was obtained from a population-based sample of 2,750 pairs of Norwegian twins born between 1967 and 1974. The lifetime prevalence of self-reported recurrent ear infections was 8.9%, with a significant predominance of female cases. The mean age of onset was 4.2 years, with a gradual decrease in occurrence from 2 to 7 years of age. Among monozygotic pairs, the rate of tetrachoric correlation between co-twins was almost identical in males (0.73, SE 0.08) and females (0.74, SE 0.06), but among the dizygotic pairs the correlation was clearly higher in males (0.53, SE 0.12) than in females (0.20, SE 0.12). The value in the unlike-sexed dizygotic twins (0.25, SE 0.05) was intermediate to that of the like-sexed male and female dizygotic pairs. The relative contribution of genes and environment to variability in the predisposition to develop otitis media was estimated by means of structural equation modeling. Variation in liability to ear infections was mainly explained by additive genetic and dominance factors in females, for whom heritability was estimated at 74%. The remaining 26% of the variation in liability was explained by individual environmental factors. In males, 45% of the variation could be accounted for by genetic factors, 29% by common familial environment, and the remaining 26% by individual environmental effects.

Acute Disease↗
PubMed1997

Patient preferences concerning the trade-off between the risks and benefits of routine radiation therapy after conservative surgery for early-stage breast cancer.

PURPOSE: To assess patients' preferences regarding the trade-off between risks and benefits of radiation therapy after conservative surgery for early-stage breast cancer. PATIENTS AND METHODS: Utilities (measures of preference) of 97 early-stage breast cancer patients treated with conservative surgery and radiation therapy and 20 medical oncology nurses were assessed for five health states using standard gambles. RESULTS: Patients had the highest mean utility for treatment with conservative surgery and radiation therapy without a local recurrence (0.92), intermediate utilities for treatment with conservative surgery alone followed either by no local recurrence or by a local recurrence salvaged by conservative surgery and radiation therapy (0.88 and 0.87, respectively), and the lowest utilities for treatment with or without radiation therapy followed by a local recurrence salvaged by mastectomy and reconstructive surgery (0.82 and 0.81, respectively). All differences between health states' utilities were significant (P < .0001), except between the two intermediate and two lowest rated health states. None of the clinical or sociodemographic factors examined explained more than 5% of the variability in the patients' utilities or their differences. Nurses' utilities were similar to those of the patients. CONCLUSIONS: These results strongly suggest that fear of a local recurrence and an actual local recurrence leading to mastectomy have such a negative impact on quality of life that patients are willing to accept the risks and inconvenience of radiation therapy to avoid them. There is also considerable interpatient variability that was not explained by the clinical or sociodemographic factors examined.

Adult↗
PubMed1997

Recombinant human interferon-beta in the treatment of condylomata acuminata.

The number of clinic consultations for condylomata acuminata (genital warts) has increased substantially during the last 30 years. Most infections produce benign lesions but a few types may be associated with cervical and penile cancers. Interferons (IFN) have shown antiviral properties to these infections and IFN-beta in particular has demonstrated a specific cytopathic effect in humans. A total of 124 patients with condylomata acuminata, the majority of whom had failed previous therapy, were treated intralesionally with either recombinant human interferon-beta la (r-hIFN-beta-1a) or placebo. Up to 6 lesions were treated in each patient, and injections were made 3 times per week for a total of 9 injections. The patients were then followed up for 3 months. Efficacy assessments at all time points (day 19, week 6 and month 3) showed a clear advantage for the r-hIFN-beta-1a interferon-beta treatment. Patients receiving r-hIFN-beta-1a showed a greater proportion of treatment success in terms of the complete or partial reduction (at least 50%) of the total area of the treated lesions. The treatment was also well tolerated. Headache, flu-like symptoms and asthenia were more common in patients receiving r-hIFN-beta-1a, but these adverse events were generally mild in severity and rarely led to patient withdrawal. It was concluded that r-hIFN-beta-1a has good efficacy in condylomata acuminata, and therefore presents a useful therapeutic alternative in this hard-to-treat condition.

Adult↗
PubMed1997

Prevalence of sexual dysfunction in heterosexual patients attending a central London genitourinary medicine clinic.

Our objective was to determine the prevalence of sexual dysfunction among new heterosexual attendees at a central London genitourinary medicine (GUM) clinic. We carried out a cross-sectional study in which patients completed a self-administered questionnaire-the Golombok-Rust Inventory of Sexual Satisfaction (GRISS) and participated in a brief interview during which additional information was sought regarding the patient's sexual history. An overall transformed score of >5 on the GRISS was defined as indicative of overall sexual dysfunction and a score of >5 on any of the subscales as indicative of a specific sexual dysfunction. Twenty-five (24%) men and 10 (9%) women had a GRISS score in keeping with overall sexual dysfunction, the prevalence being significantly lower in women (P=0.01, chi2=6.56, 1df). Sixty-three men (59%) and 63 (60%) women produced scores indicative of significant abnormality on at least one subscale, including, in men: erectile dysfunction 20 (19%), premature ejaculation 23 (22%), and in women: vaginismus 26 (25%) and anorgasmia 23 (22%). Neither an abnormal overall or subscale score on the GRISS was associated with a current STD on KC60 diagnosis or a history of sexual assault for either men or women. There is a substantial prevalence of sexual dysfunction in new heterosexual attendees at our clinic, the service implications of which need to be addressed.

Adolescent↗
PubMed1997

The provision of psychosexual services by genitourinary medicine physicians in the United Kingdom.

A postal questionnaire survey, enquiring about the provision of psychosexual services, was sent to each GUM clinic in the UK. Of the 246 questionnaires distributed, replies were received from 166 directors responsible for 171 (69.5%) clinics. Of the 140 (84%) who supported the provision of a sexual dysfunction service, 59 (42%) currently provided such a service. Doctors and psychologists were the health care professionals most commonly involved in sexual dysfunction services for patients who were referred both internally and from external sources such as general practice and diabetic clinics. Patients with a variety of dysfunctions were being treated with a broad range of therapies, a reflection probably of the multidisciplinary nature of the team providing the service. However, it appears that junior doctors are not being trained in this field at present.

Female Urogenital Diseases↗
PubMed1997

Managed care--issues and opportunities: a view from the CDC.

Major changes are occurring in the health system in the United States. Currently the term managed care is most synonymous with this era of change. The Centers for Disease Control, as the nation's federal agency responsible for prevention of morbidity and premature mortality, offers its perspective on the issues and opportunities for prevention and community health promotion presented in managed care, describes some of its collaborative projects with public health agencies and managed care organizations, and discusses some of the prevention aspects of HEDIS 3.0.

Aged↗
PubMed1996

Pathologic margin involvement and the risk of recurrence in patients treated with breast-conserving therapy.

BACKGROUND: The relationship between the microscopic margins of resection and ipsilateral breast recurrence (IBR) after breast-conserving therapy for carcinomas with or without an extensive intraductal component (EIC) has not been adequately defined. METHODS: Of 1,790 women with unilateral clinical Stage I or II breast carcinoma treated with radiation therapy as part of breast-conserving therapy, 343 had invasive ductal histology evaluable for an extensive intraductal component (EIC), had inked margins that were evaluable for an review of their pathology slides, and received > or = 60 Gray to the tumor bed; these 343 women constitute the study population. The median follow-up was 109 months. All available slides were reviewed by one of the study pathologists. Final inked margins of excision were classified as negative > 1 mm (no invasive or in situ ductal carcinoma within 1 mm of the inked margin); negative-1 mm, or close carcinoma < or = 1 mm from the inked margin but not at the margin); or positive (carcinoma at the inked margin). A focally positive margin was defined as invasive or in situ ductal carcinoma at the margin in three or fewer low-power fields. The first site of recurrent disease was classified as either ipsilateral breast recurrence (IBR) or distant metastasis/regional lymph node failure. RESULTS: Crude rates for the first site of recurrence were calculated first for all 340 patients evaluable at 5 years, then separately for the 272 patients with EIC-negative cancers and the 68 patients with EIC-positive cancers. The 5-year rate of IBR for all patients with negative margins was 2%; and for all patients with positive margins, the rate was 16%. Among patients with negative margins, the 5-year rate of IBR was 2% for all patients with close margins (negative < or = 1 mm) and 3% for those with negative > 1 mm margins. For patients with close margins, the rates were 2% and 0% for EIC-negative and EIC-positive tumors, respectively; the corresponding rates for patients with negative margins > 1 mm were 1% and 14%. The 5-year rate of IBR for patients with focally positive margins was 9% (9% for EIC-negative and 7% for EIC-positive patients). The 5-year crude rate of IBR for patients with greater than focally positive margins was 28% (19% for EIC-negative and 42% for EIC-positive patients). CONCLUSIONS: Patients with negative margins of excision have a low rate of recurrence in the treated breast, whether the margin is > 1 mm or < or = 1 mm and whether the carcinoma is EIC-negative or EIC-positive. Among patients with positive margins, those with focally positive margins have a considerably lower risk of local recurrence than those with more than focally positive margins, and could be considered for breast-conserving therapy.

Breast Neoplasms↗
PubMed1996

Relationship of tumor grade to other pathologic features and to treatment outcome of patients with early stage breast carcinoma treated with breast-conserving therapy.

BACKGROUND: Although histologic grade has previously been described as a predictor of distant failure, it is uncertain whether histologic grade should be used to decide which patients should undergo axillary lymph node dissection and whether grade should be considered as a selection factor for breast-conserving therapy. METHODS: The authors retrospectively analyzed data from 1081 patients with American Joint Committee on Cancer Stage I or II infiltrating ductal carcinoma treated with breast-conserving therapy at the Joint Center for Radiation Therapy between 1970 and 1986. All patients had pathology slides reviewed by one of two study pathologists. Using the Elston modification of the Bloom-Richardson grading system, patients were divided by histologic grade into 3 groups (219 with Grade I, 482 with Grade II, and 380 with Grade III). The median follow-up time for 716 survivors was 134 months. The incidence of various pathologic features was examined with respect to histologic grade. In addition, the 10-year crude rates of failure (by first site) were examined as they related to grade. A polychotomous logistic regression model was used to determine the effect of grade on local and distant failure. RESULTS: High grade tumors tended to be larger, to exhibit more mononuclear cellular reaction and necrosis, and were more likely to be estrogen receptor negative. Patients with high grade tumors were also younger than those with lower grade tumors. The incidence of an extensive intraductal component and lymphatic vessel invasion did not vary significantly by histologic grade. The incidence of pathologic lymph node metastases also did not vary by grade, even when stratified by tumor size. In both univariable and multivariable analyses, the 10-year crude rate of local recurrence was not related to histologic grade (P = 0.44). Distant recurrence rates, however, were significantly higher as grade increased (p = 0.002). CONCLUSIONS: Higher histologic grade predicted an increased incidence of distant recurrence, but not a greater likelihood of axillary lymph node metastases or local recurrence after breast-conserving therapy. The authors conclude that grade should not be used to make decisions regarding local management.

Breast Neoplasms↗