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Biomedical subjects
Publications and source records attributed to R Barnes.
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The authors evaluated risk factors potentially associated with the development of popliteal artery atherosclerosis in a population-based study and compared them with factors linked to carotid wall intimal-medial thickness. The Atherosclerosis Risk in Communities (ARIC) Study is a longitudinal investigation of cardiovascular disease in 15,800 individuals. The present analyses are based on the baseline popliteal and carotid ultrasonography examination in 10,002 subjects conducted in 1987-1989. After adjustment for covariates, both carotid and popliteal intimal-medial thicknesses were strongly associated with male sex and age (p < 0.01), having a graded relation with increasing quartiles of plasma total cholesterol and low density lipoprotein cholesterol and with plasma triglycerides (women only for popliteal) (p < 0.01). An inverse correlation was noted between plasma high density lipoprotein cholesterol and carotid (p < 0.01) and popliteal (women only) (p < 0.05) intimal-medial thicknesses. Cigarette use (p < 0.01), a history of diabetes mellitus (p < 0.01), alcohol use, elevated systolic pressures (p < 0.01), and fibrinogen levels (p < 0.01) were directly associated with both popliteal and carotid intimal-medial thicknesses. Although menopause was associated with thickened carotid (p < 0.01) and popliteal (p < 0.05) intimal-medial thicknesses, hormone replacement therapy was associated with thinner carotid walls only (p < 0.05). Although there were some differences, many of the classical risk factors associated with cardiovascular disease were also related to early thickening of both the popliteal and the carotid artery walls.
BACKGROUND: Endarterectomy benefits certain patients with carotid stenosis, but benefits are lessened by perioperative surgical risk. Acetylsalicylic acid lowers the risk of stroke in patients who have experienced transient ischaemic attack and stroke. We investigated appropriate doses and the role of acetylsalicylic acid in patients undergoing carotid endarterectomy. METHODS: In a randomised, double-blind, controlled trial, 2849 patients scheduled for endarterectomy were randomly assigned 81 mg (n=709), 325 mg (n=708), 650 mg (n=715), or 1300 mg (n=717) acetylsalicylic acid daily, started before surgery and continued for 3 months. We recorded occurrences of stroke, myocardial infarction, and death. We compared patients on the two higher doses of acetylsalicylic acid with patients on the two lower doses. FINDINGS: Surgery was cancelled in 45 patients, none were lost to follow-up by 30 days, and two were lost by 3 months. The combined rate of stroke, myocardial infarction, and death was lower in the low-dose groups than in the high-dose groups at 30 days (5.4 vs 7.0%, p=0.07) and at 3 months (6.2 vs 8.4%, p=0.03). In an efficacy analysis, which excluded patients taking 650 mg or more acetylsalicylic acid before randomisation, and patients randomised within 1 day of surgery, combined rates were 3.7% and 8.2%, respectively, at 30 days (p=0.002) and 4.2% and 10.0% at 3 months (p=0.0002). INTERPRETATION: The risk of stroke, myocardial infarction, and death within 30 days and 3 months of endarterectomy is lower for patients taking 81 mg or 325 mg acetylsalicylic acid daily than for those taking 650 mg or 1300 mg.
This article reviews the existing literature in the following areas of sports neuropsychology: Dementia Pugilistica, concussion and Post Concussion Syndrome, Second Impact Syndrome, and the emerging role of the sports neuropsychologist regarding return to play decisions. Dementia Pugilistica is discussed as a condition that exists along a continuum: Although many boxers will develop mild neurocognitive deficits, it is not yet known what percent of these mild presentations will progress to diagnosable Dementia Pugilistica. Factors contributing to both increased and reduced risk are detailed. The role of neuropsychological assessment in research and clinical management is reviewed. Existing studies of concussion incurred during contact sports provide evidence of an important role for neuropsychology in assessment and management of mild head injuries. Issues in clinical assessment of concussion are reviewed. The importance of grading of concussions, monitoring of postconcussive symptom resolution, and the use of neuropsychological test results in return to play decisions is detailed. The Second Impact Syndrome is discussed with regard to return to play decisions. Recommendations are proposed for research and for clinical application of findings in sports neuropsychology.
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Congenital generalized lipodystrophy (CGL, Berardinelli-Seip Syndrome, OMIM # 269700) is a rare autosomal recessive disorder characterized by near complete absence of adipose tissue from birth. Affected individuals have marked insulin resistance, hypertriglyceridemia and acanthosis nigricans, and develop diabetes mellitus during teenage years. The genetic defect for CGL is unknown. A semi-automated genome-wide scan with a set of highly polymorphic short tandem repeats (STR) was carried out in 17 well-characterized pedigrees and identified a locus for CGL to chromosome 9q34. The maximum two-point lod score obtained was 3.6 at D9S1818 (theta(max) = 0.05). There was evidence for genetic heterogeneity (alpha = 0.73) and 2 of the pedigrees were unlinked. Multipoint linkage analysis excluding the 2 unlinked families yielded a peak lod score of 5.4 between loci D9S1818 and D9S1826. The CGL1 critical region harbors a plausible candidate gene encoding the retinoid X receptor alpha (RXRA) that plays a central role in adipocyte differentiation. Identification of the CGL gene(s) will contribute to our understanding of the adipocyte differentiation and elucidation of the mechanisms of insulin resistance in disorders of adipose tissue.
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A survey of clinical audit in 21 trusts found wide variations in workload. The number of audits carried out in one year ranged from four to 218. Services most frequently audited were surgery, diagnostics, mental health and medicine. The average cost of an audit was 2,260 pounds. Most trusts reviewed progress on implemented agreed recommendations following an audit.
Obesity is strongly implicated in the pathophysiology of insulin resistance, diabetes mellitus and dyslipidemia. The mechanisms, however, by which obesity causes these complications are not known. The study of single-gene disorders affecting adipose tissue may elucidate some of the mechanisms involved in these processes. Familial partial lipodystrophy, Dunnigan variety, (FPLD, OMIM 308980) is an autosomal-dominant condition characterized by marked loss of subcutaneous adipose tissue affecting the trunk and extremities but with excess fat deposition in the head and neck areas. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus, dyslipidemia and acanthosis nigricans. The genetic basis of FPLD is unknown. We carried out a genome-wide scan with a set of highly polymorphic short tandem-repeats (STR) in individuals from five well-characterized pedigrees and mapped the FPLD locus to chromosome 1q21-22. The maximum two-point lod score obtained with a highly polymorphic microsatellite at D1S2624 at theta(max)=0 was 5.84. Multipoint-linkage analysis yielded a peak lod score of 8.25 between D1S305 and D1S1600. There was no evidence for genetic heterogeneity (alpha=1) in the pedigrees.
The effect of partial dietary replacement of linoleic acid (18:2n-6; linoleic acid-rich diet) with alpha-linolenic acid (18:3n-3; alpha-linolenic acid-rich diet) on plasma lipids was investigated in twenty-nine healthy young men. After a 2-week stabilization period subjects were randomly assigned to either the alpha-linolenic acid-rich diet group (n 15), receiving a mean of 10.1 g of alpha-linolenic acid and 12.1 g of linoleic acid/d, or the linoleic acid-rich diet group (n 14), receiving a mean of 1.0 g of alpha-linolenic acid and 21.0 g of linoleic acid/d, for a 6-week test period. Blood samples were taken at the commencement of the stabilization period and at the start (week 0), midpoint (week 3) and endpoint (week 6) of the test period and plasma lipids analysed. The changes occurring on the linoleic acid-rich diet and alpha-linolenic acid-rich diet were compared but no significant differences in the changes in plasma total cholesterol, LDL-cholesterol, HDL-cholesterol, the subfractions HDL2 and HDL3 or triacylglycerols were found. These results indicate that dietary replacement of linoleic acid with alpha-linolenic acid in the diet of healthy male subjects offers similar cardioprotective benefits with respect to lipid metabolism.
Alterations of BRCA2 result in increased susceptibility to breast cancer in both men and women (relative lifetime risks of 0.06 and 0.8 respectively). BRCA2 maps to 13q12-q13 and encodes a transcript of 10,157 bp. Other cancers that have been described in BRCA2 mutation carriers include those of the larynx. Human chromosome 13q has been shown previously by LOH studies to harbor several tumor suppressor genes for head and neck squamous cell carcinoma (HNSCCs). We therefore examined the role of BRCA2 in the development of these cancers. Only 6/22 (27%) of the laryngeal cancers we examined demonstrated LOH of the BRCA2-containing region. These and 10 other HNSCCs of different origins that were demonstrated by LOH studies to have lost the region of chromosome 13 containing BRCA2 were examined for alterations in this gene. SSCP analysis failed to reveal any alterations leading us to conclude that BRCA2 alterations are not frequently involved in the pathogenesis of HNSCCs and that the observed LOH of chromosome 13 loci is due to other, as yet, unidentified tumor suppressor gene(s). Interestingly tumors with LOH in this region (proximal to D13S118) were far more likely to be derived from women than men. This is unusual since HNSCCs are usually fourfold more common in men than in women.
Soil ingestion was evaluated in 10 adults as part of a larger study to evaluate soil ingestion in children. Each adult was followed for 4 weeks in a mass-balance study that was designed to evaluate the detection limit for soil ingestion in a similarly designed, concurrent children's study. After a baseline week, during Weeks 2 through 4, adults received daily soil capsules containing 20, 100, and 500 mg of soil, respectively. A 1-week period separated each study week. Based on the first 3 weeks of observation after subtracting the capsule ingestion amounts, the median, 75th percentile, and 95th percentile soil ingestion estimates were 1, 49, and 331 mg/day, with estimates calculated as the median of the three trace elements Al, Si, and Y. The average estimate of soil ingestion was 10 mg/day (SD = 94 mg/day). These findings augment sparse empirical data on adult soil ingestion, and suggest lower levels of soil ingestion in adults than previous studies.
We have generally encouraged living donation among our kidney recipients. However, an examination of our clinical practice revealed inconsistencies in the depth and content of information transmitted to kidney recipient families regarding living donation. We therefore initiated a structured education program, including an educational video, to ensure that all recipient families would receive a similar exposure to a standard block of information. After the program had been functioning for over a year, we compared the living donor (LD) volunteer rates between the 3-year period before (BEFORE) and the 18 months after (AFTER) initiation of the formal education program. There were 1,363 patients registered on our kidney transplantation waiting list during the 54-month study period (757 white [56%] and 580 black [43%]). We found that 33.4% of the kidney transplant candidates in the period BEFORE the LD education program had at least one potential LD tissue typed, compared with 39.4% in the period AFTER starting the program (P = 0.03). The increase in the proportion of patients with potential donors was greatest among the black (P < 0.05) and elderly (P < 0.01) registrants, which were the groups with the lowest volunteer rates before the program began. Among the registrants with at least one potential donor, the percentage of registrants who ultimately received an LD transplant was highly correlated with the number of donors (R = 0.98). The rate of LD kidney transplantation was significantly higher (P = 0.02) for the patients referred in the period AFTER initiation of the LD education program compared with the period BEFORE the program. The 1- and 3-year graft survival rates for the 170 LD transplants performed in these patients were 96.9% and 93.2%, respectively. These were significantly better than the corresponding 83.9% and 71.4% rates for the 341 kidney transplants from cadaver donors in these registrants (P < 0.001). Black recipients of LD transplants had graft survival rates comparable to whites; the 3-year graft survival rate for LD transplants was 93.9% in whites and 90.6% in blacks (P = NS). We conclude that living kidney donor volunteer rates can be improved by a formal family education program, especially for subgroups of patients with low volunteer rates. A substantial benefit is derived by black patients, who generally experience low graft survival rates with cadaver-donor kidneys. A local formal LD education program is a useful adjunct to national organ donation campaigns.
Peri-operative nausea and vomiting (PONV), remain a considerable problem. Ondansetron is being promoted currently as the drug of choice for the prevention and treatment of PONV. Experiments to investigate efficacy of ondansetron in PONV have been made with placebo or single doses of other drugs, e.g. metoclopramide, and often with different anaesthetic regimes with different emetic potential. This study investigated the relative benefits, in the prevention of PONV, of ondansetron compared with metoclopramide used at a dose higher than used in previous studies. Ninety-six patients undergoing minor gynaecological surgery were randomized to receive either ondansetron 4 mg or metoclopramide 0.4 mg kg-1. The patients were then assessed in the recovery room, in the day ward prior to discharge and the following day for the occurrence of PONV. Emetic symptoms occurred in similar proportions of patients who received ondansetron and metoclopramide. Nausea scores were similar between the groups in the recovery ward and 24-h follow-ups but there were higher post-operative nausea scores in the ondansetron group in the day ward (P = 0.001). There were no significant side effects due to either drug. We conclude that moderate dose metoclopramide is an effective alternative to ondansetron in the control of PONV.
This paper describes black/white differences in risk factors for atherosclerosis in the large multicenter Atherosclerosis Risk in Communities (ARIC) Project sponsored by the National Heart, Lung, and Blood Institute. It is based on data collected at baseline in ARIC's four geographically distinct clinical centers. Participants were randomly selected (4264 black and 11,479 white men and women, ages forty-five to sixty-four years at entry). There were striking differences in obesity between black and white women, higher fasting glucose and greater prevalence of diabetes in blacks, and lower high-density lipoprotein values in white men. Not unexpectedly, blood pressure in black participants exceeded that in whites. Clustering of multiple risk factors was more common in the black population. Conversely, prevalence of no risk factors was greatest among whites. In conclusion, while African-Americans and Caucasians share much the same group of risk factors for atherosclerosis, there are clinically important racial differences in emphasis.
Despite considerable efforts to improve the design of soil ingestion studies, substantial variability in daily soil ingestion rates based on different tracer estimates exists in the same subjects. The present study assessed the hypothesis that one of the unexplored causes of this intertracer variation in soil ingestion estimation was related to differences in soil tracer concentration by particle size. The study analyzed the tracer concentration in soil for children in the Anaconda, Montana soil ingestion study for the particle size fraction less than 250 microm [corrected] in diameter. Soil ingestion estimates for these children were recalculated based on the new soil concentration values and compared to previous findings (E. J. Calabrese, E. J. Stanek, P. Pekow, and R. M. Barnes, submitted, 1996) when the soil concentrations were determined for soil particle size diameter of <2 mm. The results indicated that five tracers (Al, Si, Ti, Y, and Zr) did not have their soil concentrations changed by particle size. However, for three tracers (La, Ce, and Nd) the concentration increased by two- to fourfold with the smaller particle size. Recalculation of soil ingestion estimates indicates that the soil ingestion estimates of the five tracers not varying by particle size did not change while those of the remaining three tracers were decreased by approximately 60%. The revised calculations provide a substantial improvement in intertracer estimates of soil ingestion and suggest that the children ingested soil of small particle size. These findings are of significance since they (1) identify an important potential cause of intertracer variability in soil ingestion estimates, (2) establish a new criterion for soil tracer selection, and (3) develop a method for not only providing improved soil ingestion estimates but also determining the particle size of the ingested soil. These findings offer important potential applications for risk assessment practices at contaminated sites since soil ingestion is frequently the dominant route of estimated contaminant exposure in children.