An information strategy for radiotherapy patients.
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Biomedical subjects
Publications and source records attributed to S Edwards.
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RheothRx (Glaxo Wellcome Inc, Research Triangle Park, NC; poloxamer 188) Injection is a nonionic surfactant with hemorrheologic properties that suggest it may be useful in treating acute painful episodes (vasoocclusive crises) of sickle cell disease (SCD). We conducted a randomized, double-blind, placebo-controlled pilot study to evaluate the safety and efficacy of poloxamer, formulated as RheothRx Injection, in 50 patients with SCD. Patients with moderate to severe painful episodes requiring parenteral analgesics were randomized to receive a 48-hour infusion of either RheothRx or placebo. Pain was assessed every 4 hours. Efficacy endpoints included: (1) painful episode duration, (2) days of hospitalization, (3) quantity of analgesics used, and (4) pain intensity scores. Three subgroups of patients were considered for efficacy analyses based on the actual duration of the study drug infusion and the completeness of pain score data collection. Compared with placebo and depending on the subgroup, RheothRx-treated patients showed a 16% to 45% decrease in duration of painful episodes, a 1- to 2-day reduction in hospital stay, a threefold to fivefold reduction in analgesic requirements, and a 1-point reduction (using a 5-point scale) in average pain intensity scores at 72 hours. RheothRx was well tolerated; no clinically significant differences were observed between treatments with respect to adverse experiences or other safety measures. In addition, there were no differences between treatment groups in the incidence of recurrent painful episodes. In this study, RheothRx significantly reduced total analgesic use and pain intensity and showed trends to shorter duration of painful episodes and total days of hospitalization. In patients with moderate to severe vasoocclusive pain, RheothRx was safe and may offer a therapeutic benefit.
Smoking cigarettes has been consistently associated with adenomatous polyps. However, only a few studies have reported associations between smoking cigarettes or using other forms of tobacco and colon cancer. A population-based case-control study of colon cancer was conducted in 3 areas in the United States: northern California, Utah and Minnesota. We observed approximately a 50% increase in colon cancer risk from smoking over a pack of cigarettes per day among both men and women. Those who stopped smoking remained at increased risk, even if they stopped over 10 years ago. Our data suggest that the amount smoked may be a more important factor than the total number of years smoked. Smoking neither cigars nor pipes was associated with an increased risk of colon cancer. Among female participants only, those who smoked over 20 cigarettes per day and had a large body mass index were at greater risk of colon cancer than participants who smoked the same amount but were smaller (p for interaction among women = 0.04).
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Low levels of physical activity and high levels of energy intake and body mass have all been directly associated with colon cancer. The purpose of this study was to determine how physical inactivity interacts with other components of energy balance (energy intake and body mass) in determining colon cancer risk. Data were obtained from 2073 first primary cases of colon cancer and 2466 age- and sex-matched controls identified from 8 counties in Utah, the Northern California Kaiser Permanente Medical Care Program, and the Twin Cities metropolitan area in Minnesota. Recent and lifetime physical activity was assessed by intensity of activities performed at home, leisure, and at work; energy intake was estimated from an extensive diet history questionnaire; and body mass index (BMI) was calculated from measured height at the time of interview and reported weight for the referent year. For both men and women, lack of lifetime vigorous leisure-time activity was associated with increased risk of colon cancer [odds ratio (OR), 1.63 and 95% confidence interval (CI), 1.26-2.12 for men and OR, 1.59 and 95% CI, 1.21-2.10 for women, comparing the lowest to highest level of activity]. There were no differences in risk associated with physical activity by tumor site within the colon or by age at diagnosis. High levels of energy intake were also associated with increased risk of colon cancer in men and women (OR, 1.74 and 95% CI, 1.14-2.67 for men and OR, 1.70 and 95% CI, 1.07-2.70 for women). A large BMI was more associated with increased risk in men (OR, 1.94 and 95% CI, 1.49-2.54) than in women (OR, 1.45 and 95% CI, 1.08-1.94). Those at greatest risk of colon cancer were those who had the most unfavorable energy balance in that they were physically inactive, had high energy intakes, and had a large BMI (OR, 3.35 and 95% CI, 2.09-5.35). However, when physical activity was high, having a high energy intake and large BMI resulted in a nonsignificant increased colon cancer risk (OR, 1.28 and 95% CI, 0.81-2.03). This pattern was consistent between the sexes, but there was some evidence that men may be at higher risk than women, especially older women, as a result of unfavorable energy balance. These results support previous findings that physical inactivity, high energy intake, and large body mass are associated with increased risk of developing colon cancer. However, energy balance as a whole seems to be associated with risk of colon cancer. These findings suggest systemic metabolic influences on carcinogenesis and have important implications for prevention.
A pestivirus was transmitted by contact from a persistently infected (P.I.) bullock to pregnant sheep. This resulted in the birth of P.I. lambs, one of which in turn was able to transmit virus by contact to pregnant cattle. Two of these animals gave birth to P.I. calves, from one of which the virus was again transmitted by contact with pregnant sheep, leading to another generation of P.I. lambs. The expression of one or more epitopes on the E2 glycoprotein of the viruses isolated from this series of alternate cattle-sheep transmissions appeared to depend on the host species. Thus, several monoclonal antibodies which bound strongly to, and neutralised, viruses isolated from the bovine hosts, failed to bind or neutralise in the case of sheep isolates. The viral consensus sequences of the E2 gene as well as parts of the 5' untranslated region and of the Npro and capsid genes were compared between the different isolates. This revealed a high degree of genetic stability. However, a single codon change at amino acid position 9 of the E2 gene correlated with and was able to cause the loss of particular epitopes.
BACKGROUND: Pulmonary autografts offer many theoretical advantages. However, the operation is complex, may interfere with right ventricular and pulmonary outflow function, and requires a longer operative time than does the homograft operation. The effects of these potential disadvantages are unknown. METHODS: To clarify these issues we randomized 70 patients undergoing aortic valve replacement to an aortic homograft group (group A = 37 patients; 53%; 34 male, 3 female) or a pulmonary autograft group (group B = 33 patients; 47%; 28 male, 5 female). Ages varied from 12 to 65 years (mean 39 +/- 15 years) for group A and from 3 to 54 years (mean 29 +/- 15 years) for group B (p = not significant). Eleven patients in group A (30%) and eight in group B (24%) had previous aortic valve surgery. All patients were operated on by the same surgeon. The mean cardiopulmonary bypass time was 113 +/- 29 minutes (range 66 to 175 minutes) for group A and 151 +/- 31 minutes (range 115 to 226 minutes) for group B (p < 0.002). Mean aortic crossclamp time was 85 +/- 19 minutes (range 45 to 140 minutes) for group A and 109 +/- 20 minutes (range 74 to 164 minutes) for group B (p = 0.02). In 32 patients (86.5%) the aortic homograft was implanted as a root with coronary reimplantation. All pulmonary autografts were implanted as a root. RESULTS: No early or late deaths had occurred in this series at a mean follow-up time of 16 months (range 3 to 21 months). Two patients (one in each group) required reexploration for bleeding. No statistically significant differences were observed between the two groups with regard to ventilatory support (group A, mean 10 +/- 8.5 hours; group B, mean 29 +/- 85 hours), total blood loss (group A, mean 471 +/- 347 ml; group B, mean 543 +/- 404 ml), intensive care unit stay (group A, mean 1.2 +/- 0.6 days; group B, mean 2 +/- 3.7 days), and hospital stay (group A, mean 9.5 = 3.2 days; group B, mean 12 +/- 6 days). Postoperatively, all patients are in New York Heart Association class I (93%) or II (7%) (p = not significant). Ejection fraction for the two groups did not change significantly over the follow-up period. Left ventricular mass and diastolic diameter showed progressive regression, with no apparent difference between the two treatment groups to date. Echocardiographic evaluation of aortic valve function at 6 months showed good valve function in all patients with no evidence of aortic regurgitation in 80% of both groups. In group B the right ventricular outflow gradient was below 15 mm Hg over the follow-up period. Holter monitoring, available only in 44 patients (63%), showed most of the arrhythmias to be grade 0 to 1 of the modified Lown grading system. CONCLUSION: Although the pulmonary autograft requires a significantly longer operating time, this does not seem to affect early and medium-term outcome when compared with results obtained with aortic homografts. Continued patient evaluation is warranted, particularly with regard to evidence of valve degeneration and right ventricular function and arrhythmias in the long term.
Hormonal factors have been inconsistently associated with colon cancer risk in women. The associations between reproductive events, menstrual factors, exogenous hormones, and colon cancer were evaluated in a large case-control study (894 female cases and 1,120 female age-matched population-based controls) in the United States, stratifying by age at diagnosis, tumor site, family history and other potential risk factors. Overall, higher parity was associated with a marginally decreased risk of colon cancer (five or more births compared with nulliparous: odds ratio [OR] = 0.75, 95 percent confidence interval [CI] = 0.53-1.06) after adjusting for age at diagnosis, family history of colorectal cancer, vigorous lifetime physical activity, body mass index (BMI) (wt/ht1.5), total energy intake, and aspirin use. No important associations were observed for other reproductive or menstrual events. An inverse association between recent use of hormone replacement therapy (HRT) and colon cancer was observed (OR = 0.71, CI = 0.56-0.89). Although interaction terms were not significant, this inverse association appeared to be more pronounced for those with an older age at diagnosis; for those without a first-degree relative with colorectal cancer; and for those with a relatively low BMI. The reduced risk associated with HRT use did not appear to be explained by other behaviors related to HRT use.
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Opportunistic fungal infections account for a significant amount of morbidity associated with HIV disease. We report here a case of localised oral histoplasmosis without evidence of disseminated disease in a patient who lacked stigmata of HIV disease at the time of initial presentation. The diagnosis is based on histology with special stains, complement fixing antibodies in serum, and culture of the organism from fresh tissues. Activation of subclinical disease following an infection in Uganda may explain the development of these exophytic oral lesions in this British resident.
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OBJECTIVE: To investigate the benefits of the focal use of botulinum toxin in spasticity in the forearm seen after incomplete spinal cord injury. DESIGN: A single case study with standardized assessment before and at three-week intervals after injection. INTERVENTION: EMG-guided selective injection of botulinum toxin. SUBJECT: A 23-year-old man, 18 months post injury. MEASURES: Rivermead Motor Assessment; grip strength; Jebsen hand tests; visual analogue scale; Ashworth spasticity scale. RESULTS: Weakness was seen as expected with some functional losses, but the patient made gains in the areas of concern: shaking hands, typing, using the hand to drink. These gains were sustained at 12 weeks. CONCLUSION: Selective use of botulinum toxin to weaken muscles can lead to functional benefit.
Examined the contribution of particular stressors and resources to inner-city children's adjustment. Fourth, 5th, and 6th graders (N = 315; 66% from ethnic minority groups) reported on their recent exposure to stressful events and neighborhood disadvantage, their perceptions of self-worth and social support, and their behavioral and academic adjustment. Hierarchical regressions indicated unique contributions of stressful events and neighborhood disadvantage to predicting antisocial behavior; higher levels of self-worth and family support were related to lower levels of antisocial behavior, but higher levels of peer support were related to higher levels of antisocial behavior. Furthermore, whereas family support buffered the relation between stressful events and antisocial behavior, peer support exacerbated the effect of stressors on behavioral maladjustment.
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The blood pressure can reveal much about a patient's state of health. A number of variables can affect blood pressure measurement.
BACKGROUND: Site of the carcinoma within the colon in relation to age and sex may provide clues into the etiology of the disease. Incidence of colon carcinoma by age, sex, and tumor site at a population-based level are reported infrequently. The goal of this study was to describe the distribution of colon carcinoma (excluding cancers of the rectosigmoid junction and rectum) by age at diagnosis, sex, and site of the tumor within the colon. These factors were also evaluated in conjunction with disease stage at the time of diagnosis. METHODS: Data from three geographically distinct populations were used to describe rates of colon carcinoma and the distribution of tumors by age, tumor site, and stage at diagnosis. All colon carcinoma cases diagnosed within a 3-year period within the areas are included. RESULTS: Approximately 50% of all cancers in men and greater than 50% of cancers in women were in the proximal segment of the colon. Men who were diagnosed prior to age 50 and both men and women diagnosed at age 70 or older had predominantly proximal cancers. People with proximal cancers and people diagnosed prior to age 50 were more likely to have more advanced disease. CONCLUSIONS: Both men and women have more proximal cancers with advancing age, which are associated with more advanced disease. Observed trends in cancer site distributions could reflect screening practices, environmental and genetic factors, or a combination of these variables.
The synthesis of mevalonate, a molecule required for both sterol and isoprene biosynthesis in eukaryotes, is catalysed by 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase. Using a gene dosage approach, we have isolated the gene encoding HMG-CoA reductase hmgl+, from the fission yeast Schizosaccharomyces pombe (Accession Number L76979). Specifically, hmgl+ was isolated on the basis of its ability to confer resistance to lovastatin, a competitive inhibitor of HMG-CoA reductase. Gene disruption analysis showed that hmgl+ was an essential gene. This result provided evidence that, unlike Saccharomyces cerevisiae, S. pombe contained only a single functional HMG-CoA reductase gene. The presence of a single HMG-CoA reductase gene was confirmed by genomic hybridization analysis. As observed for the S. cerevisiae HMGlp, the hmgl+ protein induced membrane proliferations known as karmellae. A previously undescribed 'feed-forward' regulation was observed in which elevated levels of HMG-CoA synthase, the enzyme catalysing the synthesis of the HMG-CoA reductase substrate, induced elevated levels of hmgl+ protein in the cell and conferred partial resistance to lovastatin. The amino acid sequences of yeast and human HMG-CoA reductase were highly divergent in the membrane domains, but were extensively conserved in the catalytic domains. We tested whether the gene duplication that produced the two functional genes in S. cerevisiae occurred before or after S. pombe and S. cerevisiae diverged by comparing the log likelihoods of trees specified by these hypotheses. We found that the tree specifying post-divergence duplication had significantly higher likelihood. Moreover, phylogenetic analyses of available HMG-CoA reductase sequences also suggested that the lineages of S. pombe and S. cerevisiae diverged approximately 420 million years ago but that the duplication event that produced two HMG-CoA reductase genes in the budding yeast occurred only approximately 56 million years ago. To date, S. pombe is the only unicellular eukaryote that has been found to contain a single HMG-CoA reductase gene. Consequently, S. pombe may provide important opportunities to study aspects of the regulation of sterol biosynthesis that have been difficult to address in other organisms and serve as a test organism to identify novel therapies for modulating cholesterol synthesis.