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Biomedical subjects

J Baron

Publications and source records attributed to J Baron.

At least 73 records · Page 4Linked to original sources
PubMed1997

Body size and risk of breast cancer.

The relation between body size and breast cancer remains uncertain, particularly with regard to differences between pre- and postmenopausal women. The authors examined whether height, weight, body mass index, and weight change were associated with breast cancer risk among pre- and postmenopausal women. This population-based case-control study included women aged 20-74 years (n = 6,548) who were diagnosed with invasive breast cancer during 1988-1991 in Maine, Massachusetts, New Hampshire, and Wisconsin. Similarly aged control women (n = 9,057) were selected at random from driver's license files and Health Care Financing Administration files. Height, weight, and information on other breast cancer risk factors were ascertained by telephone interview, and logistic regression was used to estimate multivariate-adjusted odds ratios and 95% confidence intervals. Among premenopausal women, the adjusted odds ratio for the upper quintile group of height relative to the lowest was 1.36 (95% confidence interval (CI) 1.05-1.76). The heaviest premenopausal women had a lower risk (odds ratio (OR) = 0.87, 95% CI 0.70-1.10). Among postmenopausal women, the adjusted odds ratios were higher for the upper quintile categories of both height (OR = 1.27, 95% CI 1.11-1.45) and weight (OR = 1.57, 95% CI 1.37-1.79). Weight gain since ages 18 and 35 years was associated with increased postmenopausal breast cancer risk, and risk was lower in women who had lost weight. These findings suggest that programs to avoid weight gain merit study as a means to reduce risk of postmenopausal breast cancer.

Adult↗
PubMed1997

Protected Values

Protected values are those that resist trade-offs with other values, particularly economic values. We propose that such values arise from deontological rules concerning action. People are concerned about their participation in transactions rather than just with the consequences that result. This proposal implies that protected values, defined as those that display trade-off resistance, will also tend to display quantity insensitivity, agent relativity, and moral obligation. People will also tend to experience anger at the thought of making trade-offs, and to engage in denial of the need for trade-offs through wishful thinking. These five properties were correlated with tradeoff resistance (across different values, within subjects) in five studies in which subjects answered several questions about each of several values, or in which they indicated their willingness to pay to prevent some harmful action. These correlations were found even when the subjects could not tell the experimenters which values they were responding to, so they cannot be ascribed entirely to subjects' desire to express commitment. We discuss implications for value measurement and public policy.

Journal Article↗
PubMed1997

Cancer risk after a hospital discharge diagnosis of endometriosis.

OBJECTIVES: Our goal was to determine the risk of cancer after hospitalization for endometriosis. STUDY DESIGN: Records of 20,686 women hospitalized with endometriosis during the period 1969 to 1983, as identified through the nationwide Swedish Inpatient Register, were linked against the National Swedish Cancer Registry through 1989 to identify all subsequent diagnoses of cancer. The study subjects were followed up for a mean of 11.4 years, with the cohort contributing 216,851 woman years of follow-up. Standardized incidence ratios were computed by the use of age- and period-specific incidence rates derived from the Swedish population. Because of the high proportion of subjects with gynecologic operations (55.6%), evaluation of the risk of gynecologic cancers involved truncation of person years at the time of any such operation. RESULTS: The overall cancer risk was 1.2 (95% confidence interval 1.1 to 1.3). Significant excesses were observed for breast cancer (standardized incidence ratio = 1.3, 95% confidence interval 1.1 to 1.4), ovarian cancer (1.9, 1.3 to 2.8), and hematopoietic malignancies (1.4, 1.0 to 1.8); this latter excess was largely driven by an excess risk of non-Hodgkin's lymphoma (1.8, 1.2 to 2.6). The risk of ovarian cancer was particularly elevated among subjects with a long-standing history of ovarian endometriosis (4.2, 2.0 to 7.7). Cervical cancer risk was slightly reduced (0.7, 0.4 to 1.3) whereas no association was observed for cancer of the endometrium (1.1, 0.6 to 1.9). CONCLUSIONS: These findings suggest that further attention be given to the risk of breast, ovarian and hematopoietic cancers among women with endometriosis and to exploring possible hormonal and immunologic reasons for the excess risks.

Breast Neoplasms↗
PubMed1997

Effects of smoking and clinical status on lung function in human immunodeficiency virus (HIV)-seropositive subjects.

Lung function was measured at 3-month intervals for up to 1 yr in a group of Caucasian HIV-seropositive subjects. The objective was to document any deterioration in lung function and seek correlations between such deterioration and smoking history and Centers for Disease Control (CDC) status. Ninety-nine subjects were studied at enrollment; 43 were followed-up (mean duration 9 +/- 3 months). Ninety-five of the 99 enrolled subjects remained free of HIV-related respiratory disease and were included in the analysis. At enrollment, carbon monoxide diffusing capacity (TLCO) was significantly lower than predicted in non-smokers, smokers and ex-smokers (88, 77 and 88%, respectively, P < 0.001). The TLCO measurements in the smoking group were significantly lower than those of the life-long non-smoking subjects (P < 0.01). Residual volume (RV) was significantly higher than predicted in smokers (111%, P = 0.02). During follow-up, all three groups demonstrated significant declines in TLCO (7%, P = 0.01; 9%, P = 0.005; 13%, P < 0.001, respectively), and increases in RV (9%, P = 0.03; 13.5%, P = 0.02, 22%, P = 0.02, respectively). At enrollment, significantly lower than predicted values of TLCO were observed in groups stratified by CDC criteria: in asymptomatic HIV-seropositive subjects (CDC 11) 89%, P = 0.01; persistent generalized lymphadenopathy (PGL) 84%; AIDS-related complex (ARC) 81%; and in non-pulmonary AIDS (IV C1) 69%, P = 0.0001, respectively. Residual volume was significantly higher than predicted in CDC II (114%, P = 0.05). During follow-up, TLCO fell in groups PGL and ARC by 7 and 9%, respectively, while RV increased in groups CDC II, PGL and ARC by 17, 15 and 8%, respectively. Only the TLCO decline in PGL showed any linkage to clinical deterioration. This study demonstrates deficits at enrollment, and a continuing decline of TLCO and increase in RV in HIV-seropositive subjects without overt lung disease.

AIDS-Related Complex↗
PubMed1997

A Ca(2+)-sensing receptor mutation causes hypoparathyroidism by increasing receptor sensitivity to Ca2+ and maximal signal transduction.

Activating mutations of the Ca(2+)-sensing receptor (CaR) gene cause autosomal dominant hypoparathyroidism. Functional expression studies have been reported for several mutations, but have produced conflicting results. Thus, the mechanism by which these mutations activate the receptor is unclear. We describe here a new family with autosomal dominant hypoparathyroidism. The mother and three daughters experienced muscle spasms and/or seizures from early childhood. They were treated with oral calcium and vitamin D analogs, and all four patients developed hypercalciuria, nephrocalcinosis, and renal insufficiency. In this family, we identified a heterozygous missense mutation (F612S) involving the extracellular region of the CaR. The mutation cosegregated with disease. It was not present in 50 normal control individuals. We used site-directed mutagenesis to introduce this mutation into the CaR cDNA, and then expressed the mutant receptor in human embryonic kidney (HEK)-293 cells. In these cells, the accumulation of inositol phosphates was measured as a function of extracellular Ca2+ concentration. Compared with the wild-type receptor, the mutant receptor showed a left-shift in the concentration-response curve and an increase in the maximal response to high Ca2+ concentration. These effects did not appear to be mediated by changes in levels of receptor expression, as judged by ELISA, or by changes in receptor glycosylation, as judged by Western analysis. We conclude that this CaR mutation causes hypoparathyroidism by a dual increase in receptor sensitivity to extracellular Ca2+ and maximal signal transduction capacity.

Adult↗
PubMed1997

Effects of fasting on the growth plate: systemic and local mechanisms.

Inadequate caloric intake inhibits longitudinal bone growth. This study was designed to investigate the mechanisms responsible for this suppression of growth plate function, focusing on the roles of systemic and local insulin-like growth factor 1 (IGF-1). Five week-old male rabbits were fasted for 48 h. Fasting significantly decreased proximal tibial growth velocity and growth plate width (both proliferative and hypertrophic zones). During the fast, systemic IGF-1 production was down-regulated. Serum IGF-1 levels and hepatic IGF-1 messenger RNA (mRNA) levels decreased despite increased GH levels. Serum levels of GH binding protein (a circulating fragment of the GH receptor) and hepatic GH receptor mRNA levels were not significantly changed. In contrast, the local, growth plate IGF-1 system appeared to be up-regulated. Growth plate GH receptor mRNA and IGF-1 mRNA levels were both increased during fasting. We conclude that, in the rabbit, fasting induces a rapid depletion of growth plate chondrocytes and inhibition of longitudinal bone growth. These effects appear to be mediated by systemic endocrine mechanisms; circulating IGF-1 levels are diminished because of hepatic resistance to GH. In contrast, the local, paracrine IGF-1 system in growth plate does not appear to contribute to the growth inhibition but instead appears to be up-regulated by fasting.

Animals↗
PubMed1997

Sporadic hypoparathyroidism caused by de Novo gain-of-function mutations of the Ca(2+)-sensing receptor.

Activating mutations of the Ca(2+)-sensing receptor (CaR) gene have been identified in families with autosomal dominant hypoparathyroidism and in one patient with sporadic hypoparathyroidism. Here, we describe two additional patients with sporadic hypoparathyroidism. One patient presented with mild symptoms at age 18 yr; the other was severely symptomatic from infancy. A heterozygous missense mutation was identified in each patient. One mutation (L773R) involved the fifth transmembrane domain of the CaR, the other (N118K) affected the amino-terminal, extracellular domain. In both cases, the probands' parents lacked the mutation, indicating that the mutations arose de novo. In expression studies the mutations shifted the concentration-response curve to the left and increased maximal activity. We conclude that 1) sporadic hypoparathyroidism can be caused by de novo gain-of-function mutations of the CaR; 2) the phenotype can vary from mild to life-threatening hypocalcemia; 3) gain-of-function mutations can involve not only extracellular regions, as previously reported, but also transmembrane domains of the CaR; and 4) the mechanism of activation can involve both increased receptor sensitivity to Ca2+ and increased maximal signal transduction.

Adult↗
PubMed1996

Energy, nutrient intake and prostate cancer risk: a population-based case-control study in Sweden.

The role of diet in the etiology of prostate cancer remains unclear, because results from several case-control and cohort studies on fat intake and risk of prostate cancer have been inconsistent; few of the studies have adjusted the results for caloric intake. To examine the relationship between energy, intake of several nutrients and risk of prostate cancer (all stages combined and advanced stages separately), we conducted a population-based case-control study in Orebro County, Sweden, from 1989 through 1994. A total of 526 patients with newly diagnosed prostate cancer and 536 controls, randomly selected from the population register and frequency-matched by age, were included in the analyses. Information about dietary intake was obtained from a self-administered semi-quantitative food frequency questionnaire. Odds ratios with 95% confidence intervals were estimated by unconditional logistic regression. In age-adjusted analyses, there were positive associations of prostate cancer (all stages combined) risk with total energy intake as well as intake of total fat (saturated and monounsaturated), protein, retinol and zinc. The positive association with energy intake was stronger for advanced cancer, with an excess risk of 70% for the highest quartile vs. the lowest. After adjustment for energy intake, there was no apparent association of prostate cancers (all stages combined) with any of the investigated nutrients. However, a weak positive association between intake of retinol and advanced cancer was observed. We conclude that our results provide some evidence that total energy intake is a risk factor for prostate cancer.

Adult↗
PubMed1996

A prospective study of smoking and risk of prostate cancer.

We evaluated the hypothesis that smoking increases the incidence of and mortality from prostate cancer. High-quality smoking information was collected in 1971-1975 in a nation-wide cohort of 135,006 male construction workers in Sweden. We achieved virtually complete follow-up through record linkages and ascertained as of December 1991 2,368 incident cases of prostate cancer and 709 deaths due to this disease. Rate ratios (RR) of prostate cancer incidence and mortality, with 95% confidence intervals (CI), were estimated in Poisson-based age-adjusted models, with amount and duration of smoking as independent variables. We found no convincing association between current smoking status, number of cigarettes smoked or years since onset and risk of prostatic cancer. The age-adjusted incidence RR among previous smokers was 1.09 and among current smokers 1.11 compared with non-smokers. Weak and inconsistent trends were seen with increasing number of cigarettes smoked per day and increasing duration among current smokers. Smokers of 15 or more cigarettes daily for at least 30 years experienced an incidence RR of 1.30. Mortality in ex-smokers was similar to that in never-smokers; it was, however, slightly increased among current smokers without any trend with amount smoked or duration. The weak and inconsistent associations between smoking and prostate cancer could easily have arisen due to bias or confounding. We therefore conclude that smoking is most likely not causally linked to the occurrence of prostate cancer.

Adult↗
PubMed1996

Cost-effectiveness analysis in a setting of budget constraints--is it equitable?

BACKGROUND: One of the promises of cost-effective analysis is that it can demonstrate how to maximize health benefits attainable within a specific limited budget. Many people argue, however, that when there are budget limitations, the use of cost-effectiveness analysis leads to health care policies that are inequitable. METHODS: We asked prospective jurors, medical ethicists, and experts in medical decision making to choose between two screening tests for a population at low risk for colon cancer. One test was more cost effective than the other but because of budget constraints was too expensive to be given to everyone in the population. With the use of the more effective test for only half the population, 1100 lives could be saved at the same cost as that of saving 1000 lives with the use of the less effective test for the entire population. RESULTS: Fifty-six percent of the prospective jurors, 53 percent of the medical ethicists, and 41 percent of the experts in medical decision making recommended offering the less effective screening test to everyone, even though 100 more lives would have been saved by offering the more expensive test to only a portion of the population. Most of the study participants justified this recommendation on the basis of equity. A smaller number stated either that it was not politically feasible to offer a test to only half the population or that the additional benefit of the more expensive test (100 more lives saved) was too small to justify offering it to only a portion of the public. CONCLUSIONS: People place greater importance on equity than is reflected by cost-effectiveness analysis. Even many experts in medical decision making -- those often responsible for conducting cost-effectiveness analyses -- expressed discomfort with some of its implications. Basing health care priorities on cost effectiveness may not be possible without incorporating explicit considerations of equity into cost-effectiveness analyses or the process used to develop health care policies on the basis of such analyses.

Colonic Neoplasms↗
PubMed1996

Folate and 10-formyltetrahydrofolate dehydrogenase in human and rat retina: relation to methanol toxicity.

Ocular toxicity, a well-recognized outcome of methanol poisoning in humans, correlates with formate accumulation in blood following the ingestion of methanol. Rodents, however, are a species known to be resistant to the toxicity of formate. The present study was designed to determine whether components of folate-dependent formate oxidation, e.g., folate and 10-CHO-H4-folate dehydrogenase (10-FDH), exist in retina and whether differences in these components might explain species-determined susceptibility to methanol intoxication. Total folate levels were determined in human and rat retinal tissues and were found to be much lower than the levels in liver. However, folate levels in human retina were only 14% of those determined in rat retina. Western blot analysis was used to quantify the amount of cytosolic and mitochondrial 10-FDH in retinal tissues. Results of these studies showed that comparable amounts of this enzyme were present in both cellular compartments in each species. However, the amount of 10-FDH in human retina was approximately three times the amount found in rat retina. In order to determine the cell type(s) within the retina that contained 10-FDH, immunohistochemical staining for 10-FDH was carried out. Confocal microscopic image analysis of human and rat retinae showed colocalization of 10-FDH primarily with Muller cell protein markers [glial fibrillary acidic protein (GFAP), vimentin, and carbonic anhydrase]. Therefore, 10-FDH was found to be preferentially localized in this cell type. Since Müller cells appear to represent the target for formate-induced ocular toxicity, our data suggest that formate oxidation reactions might serve two roles, first a protective role and then a role in methanol-induced toxicity in Müller cells.

Adenosine Triphosphate↗
PubMed1996

Recent oral contraceptive use and risk of breast cancer (United States)

We examined the association between recent oral contraceptive (OC) use and the risk of breast cancer in data from a large population-based case-control study in the United States. Cases (n = 6,751) were women less than 75 years old who had breast cancer identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls (n = 9,311) were selected randomly from lists of licensed drivers (if aged under 65 years) and from lists of Medicare beneficiaries (if aged 65 through 74 years). Information on OC use, reproductive experiences, and family and medical history was obtained by telephone interview. After adjustment for parity, age at first delivery, and other risk factors, women who had ever used OCs were at similar risk of breast cancer as never-users (relative risk [RR] = 1.1, 95 percent confidence interval [CI] = 1.0-1.2). Total duration of use also was not related to risk. There was a suggestion that more recent use was associated with an increased risk of breast cancer; use less than two years ago was associated with an RR of 1.3 (CI = 0.9-1.9). However, only among women aged 35 to 45 years at diagnosis was the increase in risk among recent users statistically significantly elevated (RR = 2.0, CI = 1.1-3.9). Use prior to the first pregnancy or among nulliparous women was not associated with increased risk. Among recent users of OCs, the risk associated with use was greatest among non-obese women, e.g., among women with body mass index (kg/m2) less than 20.4, RR = 1.7, CI = 1.1-2.8. While these results suggest that, in general, breast cancer risk is not increased substantially among women who have used OCs, they also are consistent with a slight increased risk among subgroups of recent users.

Adult↗
PubMed1996

Esophageal smooth muscle dysfunction in oculopharyngeal muscular dystrophy.

Oculopharyngeal muscular dystrophy (OPMD) is a rare genetic disorder with late-onset progressive myopathy affecting mainly head and neck striated muscles. It is more common in certain ethnic communities. Dysphagia was usually attributed to the malfunction of striated pharyngeal muscles. We studied a group of Bukharan immigrants affected by this disorder (N = 13). Esophageal studies, including endoscopy, manometry, and scintigraphic emptying were performed. Very low pharyngeal pressures were measured. Upper esophageal pressures (UEP) were in the normal range in eight patients, and above normal in three patients. Four also had low lower esophageal sphincter pressure. Esophageal body peristaltic activity was grossly impaired in all patients: mainly nonpropulsive, simultaneous, retrograde, and failed activity was recorded. Marked retention of isotopic material was demonstrated in all patients studied, usually in the middle and lower parts of the body, ranging from 17 to 100% retention. The dysphagia in OPMD is due not only to dysfunction of pharyngeal and upper esophageal striated muscle, but also has a significant smooth muscle component.

Adult↗
PubMed1996

Cognitive processes and the decisions of some parents to forego pertussis vaccination for their children.

Public health analyses suggest that, in spite of the possibility that pertussis vaccine may cause rare cases of neurological injury, catastrophic risks to individual children are lower if they are vaccinated. A number of parents, however, choose not to vaccinate their children. The purpose of this study was to investigate the decision processes of some parents who choose to vaccinate and some parents who choose not to do so. Surveys were mailed to 500 randomly selected subscribers of Mothering magazine. Two hundred and ninety-four completed questionnaires were returned (59%). In addition to well-recognized factors in vaccination decisions, perceived dangers of the vaccine, and of the disease and susceptibility to the disease, several cognitive processes not previously considered in vaccination decision studies were found to be important predictors in this population of parents: perceived ability to control children's susceptibility to the disease and the outcome of the disease; ambiguity or doubts about the reliability of vaccine information; a preference for errors of omission over errors of commission; and recognition that if many other children are vaccinated, the risk to unvaccinated children may be lowered. Although perhaps most cases of undervaccination for pertussis reflect more general problems of health care access, some parents choose to forego vaccination for their children for other reasons. Traditional risk-benefit arguments alone will be unlikely to persuade these parents to reassess their decisions. Efforts to increase childhood vaccination must incorporate an understanding of the cognitive processes that help drive these decisions.

Adult↗
PubMed1996

Mutations in the Ca(2+)-sensing receptor gene cause autosomal dominant and sporadic hypoparathyroidism.

Parathyroid hormone secretion is negatively regulated by a 7-transmembrane domain, G-protein coupled Ca(2+)-sensing receptor. We hypothesized that activating mutations in this receptor might cause autosomal dominant hypoparathyroidism (ADHP). Consistent with this hypothesis, we identified, in two families with ADHP, heterozygous missense mutations in the Ca(2+)-sensing receptor gene that cosegregated with the disorder. None of 50 normal controls had either mutation. We also identified a de novo, missense Ca(2+)-sensing receptor mutation in a child with severe sporadic hypoparathyroidism. The amino acid substitution in one ADHP family affected the N-terminal, extracellular domain of the receptor. The other mutations involved the transmembrane region. Unlike patients with acquired hypoparathyroidism, patients with these mutations had hypercalciuria even at low serum calcium concentrations. Their greater hypercalciuria presumably reflected activation of Ca(2+)-sensing receptors in kidney cells, where the receptor negatively regulates calcium reabsorption. This augmented hypercalciuria increases the risk of renal complications and thus has implications for the choice of therapy.

Adult↗
PubMed1996

Gastric emptying in Parkinson's disease: patients with and without response fluctuations.

Delayed gastric emptying may be an important pharmacokinetic mechanism underlying some of the response fluctuations that develop after long-term levodopa therapy. We performed a radionuclide gastric emptying study using a standard Tc-99m colloid-labeled solid meal in 30 patients with Parkinson's disease (PD), 15 fluctuators with "delayed-on" and "no-on" phenomena, and 15 nonfluctuators. Fasting patients were given the standard meal, and gastric emptying was monitored with a gamma camera positioned over the stomach, recording data for 1 hour. PD patients had prolonged gastric emptying measured after 60 minutes compared with the normal control subjects (70.7 +/- 16% versus < 60%). Gastric retention measured after 1 hour was increased in patients with fluctuations compared with patients without fluctuations (77.4 +/- 15.5% versus 64.0 +/- 14.3%; p < 0.05). Half-time emptying was significantly delayed in patients with, as compared with those without, response fluctuations (221 +/- 202 minutes versus 85 +/- 31 minutes; p < 0.05). This demonstrates that delayed gastric emptying is common in PD patients and is more marked in those with response fluctuations. The stomach is an important target organ in PD, affected either by the basic PD pathology, chronic drug administration, or both.

Adult↗
PubMed1996

Lifestyle factors and prostate cancer risk: a case-control study in Sweden.

We examined associations between lifestyle factors and subsequent risk of prostate cancer in a population-based case-control study. Information on smoking and alcohol habits, socioeconomic factors, marital status, family history, and sexual habits were obtained from a questionnaire and a face-to-face interview with 256 (74.6%) eligible patients and 252 (76.6%) selected controls, frequency matched by age and screened for prostate cancer with negative findings. Unconditional logistic regression was used to estimate the odds ratios (ORs). Risk was elevated among current smokers of cigarettes (OR, 1.8) and current users of hard liquor (OR, 1.4); however, the lack of dose-response trend for both of these exposures argues against a causal association. We found tentative evidence that early first intercourse, a larger number of sexual partners, and other indices of high sexual activity are associated with increased risk. Similarly, adult height, an indicator of nutrition during childhood and adolescence, was weakly positively associated with risk, although larger studies are needed to establish this link. Unmarried men had a lower risk than married men (OR, 0.3), and socioeconomic status did not appear to be strongly associated with prostate cancer. Men with a father who had prostate cancer had a more than 2-fold increased risk of prostate cancer, whereas those with a brother affected had about a 5-folk risk.

Adult↗