Analysis of the epsilon-sarcoglycan gene in familial and sporadic myoclonus-dystonia: evidence for genetic heterogeneity.

The epsilon-sarcoglycan gene (SGCE) on human chromosome 7q21 has been reported to be a major locus for inherited myoclonus-dystonia. Linkage to the SGCE locus has been detected in the majority of families tested, and mutations in the coding region have been found recently in families with autosomal dominant myoclonus-dystonia. To evaluate the relevance of SGCE in myoclonus-dystonia, we sequenced the entire coding region of the epsilon-sarcoglycan gene in 16 patients with either sporadic or familial myoclonus-dystonia. No mutations were found. This study suggests that epsilon-sarcoglycan does not play an important role in sporadic myoclonus-dystonia and supports genetic heterogeneity in familial cases.     

Association of markers of insulin and glucose control with subsequent colorectal cancer risk.

We evaluated the association of plasma insulin and other markers of insulin and glucose control with subsequent colorectal cancer. Incident colon (n = 132) and rectal (n = 41) cancer cases and matched controls (n = 346) were identified between baseline in 1989 and 2000 among participants in a community-based cohort in Washington County, Maryland. Circulating markers of insulin and glucose control were measured in baseline blood samples. Body mass index (BMI) and use of medications to treat diabetes mellitus were self-reported at baseline. Conditional logistic regression was used to estimate matched odds ratios (ORs). Compared with the lowest fourth, participants with insulin concentrations in the highest fourth were not at an increased risk of colorectal cancer [OR, 0.78; 95% confidence interval (CI), 0.45-1.35; P(trend) = 0.24]. Similarly, no associations were observed for the ratio of total cholesterol:HDL-cholesterol, triglycerides, and insulin-like growth factor binding protein 1. However, those in the highest fourth of glycosylated hemoglobin (HbA(1c)) level had a slightly increased risk of colorectal cancer (OR, 1.57; 95% CI, 0.94-2.60; P(trend) = 0.02). The OR of colorectal cancer was 1.70 (95% CI, 1.01-2.86; P(trend) = 0.08) comparing BMI >/=30 kg/m(2) to <25 kg/m(2). The OR of colorectal cancer was 2.43 (95% CI, 1.10-5.38) for the use of medications to treat diabetes. The associations of higher HbA(1c), higher BMI, and the use of medications to treat diabetes, with colorectal cancer lend support to the hypothesis that perturbations in insulin and glucose control may influence colorectal carcinogenesis. It is possible that HbA(1c), BMI, and the use of medications to treat diabetes, as a surrogate for protracted or severe type 2 diabetes mellitus, may have been better time-averaged indicators of hyperinsulinemia and hyperglycemia than the plasma markers that were measured once prediagnostically in a nonfasting population.     

Pain and pain management in newborn infants: a survey of physicians and nurses

BACKGROUND: Despite an increased awareness among clinicians regarding pain and pain management for infants undergoing surgery, pain associated with procedures performed outside the operating room may not be adequately managed. PURPOSE: To examine the beliefs and self-described behavior of physicians and nurses regarding the management of procedural pain in newborn infants. METHODS: A survey was distributed to 467 clinicians (nurses and physicians) working in 11 level II and 4 level III nurseries in a large metropolitan area. Respondents were asked to rate the painfulness of 12 common bedside nursery procedures and how often pharmacologic and nonpharmacologic (comfort) measures are currently used and should be used for those procedures. Demographic data were also collected. RESULTS: Surveys were completed by 374 clinicians (80% response rate). Physicians and nurses believe infants feel as much pain as adults and that 9 of the 12 listed procedures are moderately to very painful. Neither pharmacologic nor comfort measures are believed to be used frequently, even for the most painful procedures. Physicians and nurses believe both pharmacologic and comfort measures should be used more frequently, but nurses believe comfort measures should be used more frequently than do physicians. Beliefs about infant pain and procedural pain were related to pain management preferences. Physicians' but not nurses' ratings were associated with significant personal pain. CONCLUSIONS: Despite their beliefs that infants experience significant procedure-related pain, clinicians believe pain management for infants remains below optimal levels. Barriers to more consistent and effective pain management need to be identified and surmounted.     

Bacterial and mammalian DNA alkyltransferases sensitize Escherichia coli to the lethal and mutagenic effects of dibromoalkanes

Here we confirm and extend our previous studies demonstrating that the mutagenic potency of 1,2-dibromoethane (DBE) and dibromomethane (DBM) is markedly enhanced (not prevented) in bacteria expressing the O6- alkylguanine-DNA alkyltransferase (ATase) encoded by the Escherichia coli ogt gene. We demonstrate that, in close parallel with mutagenesis, the Ogt ATase sensitizes the bacteria to the lethal effects of these carcinogens, suggesting that one or more of the potentially mutagenic lesions induced by DBE and DBM in the presence of Ogt has additional lethal capacity. We further demonstrate that the sensitization to both lethality and mutagenesis by DBE and DBM is a property shared by other DNA alkyltransferases. This objective was accomplished by quantifying the induction of mutations and lethal events in ogt- ada- E. coli expressing an exogenous bacterial or mammalian ATase from a multicopy plasmid. Mammalian recombinant ATases enhanced the lethal and mutagenic actions of DBE and suppressed the lack of sensitivity of the vector- transformed bacteria to DBM. In most cases the order of effectiveness of the ATases ranked: murine > human > Ogt > rat. Further comparisons included the full-length Ada ATase from E. coli and a truncated Ada version (T-ada) that retains the O6-methylguanine binding domain of the protein. The full-length Ada ATase was effective in enhancing the lethality but not the mutagenicity induced by DBE and DBM. The T-ada ATase provided less sensitization than Ada to lethality by DBE, but of the three bacterial ATases T-ada yielded the highest sensitization to mutagenesis by this compound. T-ada and Ada ATases were in general less effective than the mammalian versions, with the exception of the rat recombinant ATase. The effectiveness of the different mammalian and bacterial ATases in promoting the deleterious actions of dibromoalkanes was compared with the effectiveness of these proteins in suppressing the lethal and mutagenic effects induced by N-nitroso-N-methylurea. The ability to sensitize E. coli to the lethal and mutagenic effects of DBE and DBM seems restricted to DNA alkyltransferase, since overexpression of thioredoxin (Trx) or glutaredoxin (Grx1) in ogt- ada- cells showed no effect, in spite of the reported potential of bioactive dihaloethane- derived species to alkylate Trx.      

Incident type 2 diabetes mellitus in African American and white adults: the Atherosclerosis Risk in Communities Study

Context  Although the excess prevalence of type 2 diabetes mellitus in African Americans is well established, few studies have compared incident diabetes in African American and white persons. Objectives  To compare risk of incident diabetes in African American vs white adults and to identify explanatory factors for racial disparities. Design  Prospective cohort study using baseline data collected from 1986 to 1989 from the ongoing Atherosclerosis Risk in Communities (ARIC) Study, with 9 years of follow-up. Setting and Participants  A total of 2646 African American and 9461 white adults aged 45 to 64 years without diabetes at baseline, sampled from 4 US communities. Main Outcome Measures  Incident type 2 diabetes, ascertained by self-report of physician diagnosis, use of diabetes medications, or fasting glucose level of at least 7.0 mmol/L (126 mg/dL), compared among white and African American subjects and by presence of potentially modifiable risk factors. Results  Diabetes incidence per 1000 person-years was about 2.4-fold greater in African American women (25.1 [95% confidence interval {CI}, 22.4-28.1] vs 10.4 [95% CI, 9.4-11.4]) and about 1.5-fold greater in men (23.4 [95% CI, 19.9-27.2] vs 15.9 [95% CI, 14.6-17.2]) than in their white counterparts (P<.001). Results from proportional hazards regression models indicated that racial differences in potentially modifiable risk factors, particularly adiposity, accounted for 47.8% of the excess risk in African American women but accounted for little excess risk in African American men. Compared with their white counterparts, African American men and women had higher blood pressures before diabetes onset (diastolic blood pressure difference=5.6 mm Hg in women and 8.4 mm Hg in men; P=.005). Conclusions  Our data indicate that compared with their white counterparts, middle-aged African Americans are at greater risk of developing type 2 diabetes and have higher blood pressure prior to development of diabetes. In women, almost 50% of this excess risk might be related to potentially modifiable factors.      

The prevalence and etiology of elevated aminotransferase levels in the United States

Chronic liver disease is a major cause of morbidity and mortality in the United States. Although often used to detect liver disease, the prevalence and etiology of elevated aminotransferases are unknown.We analyzed data on adults ages 17 yr and older (N = 15,676) from the Third National Health and Nutrition Examination Survey (1988-1994). Participants were classified as having elevated aminotransferase levels if either aspartate aminotransferase or alanine aminotransferase was elevated above normal. Aminotransferase elevation was classified as "explained" if there was laboratory evidence of hepatitis B or C infection, iron overload, or if there was a history of alcohol consumption. Analyses were weighted to provide national estimates.The prevalence of aminotransferase elevation in the United States was 7.9%. Aminotransferase elevation was more common in men compared to women (9.3% vs 6.6%, p = 0.002), in Mexican Americans (14.9%) and non-Hispanic blacks (8.1%) compared to non-Hispanic whites (7.1%, p < 0.001). High alcohol consumption, hepatitis B or C infection and high transferrin saturation were found in only 31.0% of cases. Aminotransferase elevation was unexplained in the majority (69.0%). In both men and women, unexplained aminotransferase elevation was significantly associated with higher body mass index, waist circumference, triglycerides, fasting insulin, and lower HDL; and with type 2 diabetes and hypertension in women (all p < 0.05).Aminotransferase elevation was common in the United States, and the majority could not be unexplained by alcohol consumption, viral hepatitis or hemochromatosis. Unexplained aminotransferase elevation was strongly associated with adiposity and other features of the metabolic syndrome, and thus may represent nonalcoholic fatty liver disease.     

Patient priorities and needs for diabetes care among urban African American adults

PURPOSE: This study was conducted to determine diabetes care priorities and needs in a group of urban African American adults with type 2 diabetes mellitus. METHODS: One hundred nineteen African American adults with type 2 diabetes, aged 35 to 75, received behavioral/educational interventions from a nurse case manager, a community health worker, or both. Priorities and needs were assessed during 3 intervention visits. RESULTS: The most frequently reported priorities for diabetes care were glucose self-monitoring (61%), medication adherence (47%), and healthy eating (36%). The most frequently addressed diabetes needs were glucose self-monitoring and medication adherence. Most of the intervention visits (77%) addressed non-diabetes-related health issues such as cardiovascular disease (36%) and social issues such as family responsibilities (30%). CONCLUSIONS: Participants' self-reported priorities for diabetes care directly reflected the diabetes needs addressed. Needs beyond the focus of traditional diabetes care (social issues and insurance) are important to address in urban African Americans with type 2 diabetes. Interventions designed to address comprehensive health and social needs should be included in treatment and educational plans for this population.