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Biomedical subjects

C Atkinson

Publications and source records attributed to C Atkinson.

At least 19 recordsLinked to original sources

Cardiac metastasis from a bronchial carcinoid: report of a case presenting with diffuse thickening of the left ventricular wall.

Bronchial carcinoids are low grade malignancies with an excellent prognosis and a low incidence of metastases. This report describes a case of a typical carcinoid tumour with metastases to the spine after four years and to the heart after eight years. Carcinoid tumours rarely metastasise to the heart and previous reports have identified gastrointestinal primaries as the source in most cases. This is the first published case of typical carcinoid tumour that metastasised to the heart from a bronchial primary.

Bronchial Neoplasms↗

Familial correlations, segregation analysis, and nongenetic correlates of soy isoflavone-metabolizing phenotypes.

Particular intestinal bacteria metabolize the soy isoflavone daidzein to equol and O-desmethylangolensin (O-DMA), metabolites that can be identified in urine. Individuals that harbor bacteria capable of producing equol or O-DMA are known as equol producers (approximately 30%-50% of the population) and O-DMA producers (approximately 80%-90% of the population), respectively. The equol-producer phenotype has been associated with sex hormone-related outcomes in several studies. However, the bacteria responsible for these phenotypes have not yet been identified and factors that influence the manifestation of these phenotypes are not well understood. To evaluate familial clustering of and nongenetic factors associated with these phenotypes, 410 individuals from 112 families participated in phenotyping (3-day soy challenge and Day 4 spot urine collection). In segregation analyses of the equol-producer phenotype, the Mendelian dominant model provided the most parsimonious fit to the data, suggesting that the pattern of inheritance of the equol-producer phenotype is consistent with an autosomal dominant trait. This phenotype was positively associated with education (p trend = 0.01), but not with sex, smoking, or several dietary factors. Results of the segregation analyses of the O-DMA-producer phenotype were inconclusive; no other models provided a more parsimonious fit to the data than the general model. This phenotype was inversely associated with age in a nonlinear model (p = 0.01), positively associated with age- and sex-adjusted height (odds ratio [OR] 10-cm increase = 0.38, 95% confidence interval [CI] = 0.15, 0.95) and body mass index (kg/m(2)) (OR = 0.91, 95% CI = 0.85, 0.96), but not with sex, education, smoking, or several dietary factors. These results suggest the equol-producer phenotype may be under some degree of genetic control and that there are likely other environmental factors not evaluated in the present analysis that contribute to both of these phenotypes. These results provide a foundation for further work to refine our understanding of heritable and environmental determinants of daidzein-metabolizing phenotypes.

Female↗

The evaluation of liquid-based 'Cyto-SED' cytology of bronchioalveolar lavage specimens in the diagnosis of pulmonary neoplasia against conventional direct smears.

Historically, bronchioalveolar lavage (BAL) samples have been prepared by a direct smear (DS) technique. Recent advances in liquid-based cytology have led to a revolution in cytological specimen preparation. Cyto-SED system (CS) is a manual liquid-based cytology system, designed for small-scale use. A total of 137 samples from patients with radiographically detectable lesions underwent BAL procedures at Papworth Hospital NHS Trust over a 4-month period. After preparation for diagnostic purposes with the DS method, the remaining sample was prepared using the CS system. The slides produced were allocated a blind study number and screened by three independent screeners. The cellular morphology was well preserved and comparable between both techniques. Of the 137 patients, 38% were confirmed as malignant by cytology or histology; 71% of these malignant diagnosis were confirmed by the DS technique and 91% confirmed by the CS. The results demonstrate that the CS is a viable alternative to the DS technique. The cytological detail is clearly defined without a loss of three-dimensional information, thus aiding the differential diagnosis of malignancy. Cyto-SED cytology system yields a higher diagnostic accuracy than the conventional direct smear technique without compromising on cytological detail.

Bronchoalveolar Lavage↗

Clinical and molecular genetic features of pulmonary hypertension in patients with hereditary hemorrhagic telangiectasia.

BACKGROUND: Most patients with familial primary pulmonary hypertension have defects in the gene for bone morphogenetic protein receptor II (BMPR2), a member of the transforming growth factor beta (TGF-beta) superfamily of receptors. Because patients with hereditary hemorrhagic telangiectasia may have lung disease that is indistinguishable from primary pulmonary hypertension, we investigated the genetic basis of lung disease in these patients. METHODS: We evaluated members of five kindreds plus one individual patient with hereditary hemorrhagic telangiectasia and identified 10 cases of pulmonary hypertension. In the two largest families, we used microsatellite markers to test for linkage to genes encoding TGF-beta-receptor proteins, including endoglin and activin-receptor-like kinase 1 (ALK1), and BMPR2. In subjects with hereditary hemorrhagic telangiectasia and pulmonary hypertension, we also scanned ALK1 and BMPR2 for mutations. RESULTS: We identified suggestive linkage of pulmonary hypertension with hereditary hemorrhagic telangiectasia on chromosome 12q13, a region that includes ALK1. We identified amino acid changes in activin-receptor-like kinase 1 that were inherited in subjects who had a disorder with clinical and histologic features indistinguishable from those of primary pulmonary hypertension. Immunohistochemical analysis in four subjects and one control showed pulmonary vascular endothelial expression of activin-receptor-like kinase 1 in normal and diseased pulmonary arteries. CONCLUSIONS: Pulmonary hypertension in association with hereditary hemorrhagic telangiectasia can involve mutations in ALK1. These mutations are associated with diverse effects, including the vascular dilatation characteristic of hereditary hemorrhagic telangiectasia and the occlusion of small pulmonary arteries that is typical of primary pulmonary hypertension.

Activin Receptors↗

Hypnosis as a modulator of cellular immune dysregulation during acute stress.

To assess the influence of a hypnotic intervention on cellular immune function during a commonplace stressful event, the authors selected 33 medical and dental students on the basis of hypnotic susceptibility. Initial blood samples were obtained during a lower stress period, and a second sample was drawn 3 days before the first major exam of the term. Half of the participants were randomly assigned to hypnotic-relaxation training in the interval between samples. Participants in the hypnotic group were, on average, protected from the stress-related decrements that were observed in control participants' proliferative responses to 2 mitogens, percentages of CD3+ and CD4+ T-lymphocytes, and interleukin 1 production by peripheral blood leukocytes. More frequent hypnotic-relaxation practice was associated with higher percentages of CD3+ and CD4+ T-lymphocytes. These data provide encouraging evidence that interventions may reduce the immunological dysregulation associated with acute stressors.

Adult↗

The long-term results of Anderson-Hynes pyeloplasty.

OBJECTIVES: To examine the durability of open pyeloplasty for pelvi-ureteric junction obstruction. PATIENTS AND METHODS: The records of 56 Anderson-Hynes pyeloplasties undertaken by two surgeons between 1981 and 1994 were examined. Attempts were made to trace all patients and for them to undergo diuretic renography to examine the current status of the operated renal unit. RESULTS: In all, 41 evaluable patients were identified; 24 agreed to return for reassessment. The mean (range) time from surgery was 10.6 (6-19) years. The results showed an improvement over the preoperative split renal function in 19 patients (79%) and an improvement in drainage in 23 (96%). CONCLUSIONS: The Anderson-Hynes pyeloplasty is an excellent procedure for treating pelvi-ureteric junction obstruction, and produces a lasting improvement in function and drainage in most patients. It is the 'gold standard' against which newer techniques should be compared.

Adolescent↗

The choice of timing for diuresis renography: the F + 0 method.

OBJECTIVE: To investigate a method of diuresis renography where the radiopharmaceutical and frusemide (diuretic) are given simultaneously, in contrast to conventional renography which involves an intravenous injection with frusemide 20 min after administering the radiopharmaceutical (F + 20) or 15 min before (F - 15), with particular interest in the effect of this change on assessing split renal function and interpreting upper tract drainage dynamics. PATIENTS AND METHODS: In a prospective study, 29 patients (18 women and 11 men, mean age 47 years, range 21--86) were assessed. Each patient had two renograms taken over a 48-h period, either by the F + 20 or F - 15, and the F + 0 method: Data for split renal function and drainage curves were obtained in the usual way. Two independent assessments of the drainage curves were obtained and the results compared. RESULTS: The split function assessments were identical (< 5% variation) in all but two patients; 26 of 29 (90%) gave identical conclusions about the drainage curves. The three patients with discrepancies between the studies had either hugely dilated upper tracts or otherwise had multiple complicating factors, e.g. impaired renal function, neuropathic bladder. CONCLUSIONS: F + 0 renography has been used in paediatric urological practice before, but there are no comparative studies and no data on its use in adults. This prospective study confirmed that in investigating dilated upper tracts, the F + 0 technique gives similar results to the conventional techniques. The F + 0 method has the potential to reduce the time required to undertake standard F + 20 renography but it may not be useful in evaluating the grossly dilated upper tract, where the F-15 technique has the best record in terms of reducing equivocal results.

Adult↗

Daidzein and genistein content of fruits and nuts.

Dietary phytoestrogens such as the isoflavones daidzein and genistein are thought to protect against chronic diseases that are common in Western societies, such as cancer, osteoporosis, and ischemic heart disease. In addition, there are concerns regarding the deleterious effects of hormone-like compounds, especially with respect to the development of infants. However, there is little information regarding the phytoestrogen content of foods, and therefore epidemiologic investigations of phytoestrogens are limited. As part of a study quantifying the consumption of phytoestrogens, the objective of this work was to assess the daidzein and genistein content of fruits and nuts commonly eaten in Europe. Eighty different fruits and nuts were sampled, prepared for eating, and freeze-dried. Daidzein and genistein were extracted from the dried foods, and the two isoflavones were quantified after hydrolytic removal of any conjugated carbohydrate. Completeness of extraction and any procedural losses of the isoflavones were accounted for using synthetic daidzin (7-O-glucosyl-4'-hydroxyisoflavone) and genistin (7-O-glucosyl-4'5-dihydroxyisoflavone) as internal standards. Of the 80 foods assayed, 43 contained no detectable daidzein or genistein, at a limit of quantification of 1 microg/kg dry weight of food. Nine foods contained more than 100 microg of the two isoflavones combined per kilogram wet weight, and 28 contained less than this amount. Currants and raisins were the richest sources of the isoflavones, containing 2,250 microg and 1,840 microg of the two isoflavones combined per kilogram of wet weight of food. Although fruits and nuts are not as rich in isoflavone phytoestrogens as are soy and other legumes, this is the first documentation of levels of daidzein and genistein occurring in these foods.

Journal Article↗

Daidzein and genistein contents of vegetables.

Food samples (n 114) were prepared from vegetables commonly eaten in Europe. The glycosidic forms of the phyto-oestrogens daidzein and genistein were extracted from the dried foods into aqueous methanol. The isoflavones were quantified by GC-MS after hydrolytic removal of any conjugated carbohydrate. Completeness of extraction and any procedural losses of the isoflavones were accounted for using synthetic daidzin (7-O-glucosyl-4'-hydroxyisoflavone) and genistin (7-O-glucosyl-4'5-dihydroxyisoflavone) as internal standards. Of the 114 foods assayed, at a limit of quantification of 0.1 microg/kg dry weight, forty-eight contained no detectable daidzein or genistein, forty-one contained less than 100 microg/kg of the two isoflavones combined and the remaining twenty-five contained more than this amount. Soyabean products contained between 470 and 1420 mg (average of 960 mg) daidzein and genistein combined per kg wet weight of food, and legumes contained between 20 and 5750 microg/kg wet weight of food, with an average of 620 microg/kg. Cooking by boiling in water caused a decrease in the daidzein and genistein content of food in twenty-four of twenty-eight foods. The extent of the decrease was variable and warrants further investigation. The present paper comprises the first comprehensive description of the content of daidzein and genistein in vegetables.

Estrogens, Non-Steroidal↗

Simultaneous adjuvant radiotherapy and chemotherapy for stage I and II breast cancer.

The purpose of the present paper was to evaluate treatment outcome after conservative breast surgery or mastectomy followed by simultaneous adjuvant radiotherapy and cyclophosphamide, methotrexate and fluorouracil (CMF) therapy. Two hundred and sixty eight (268) patients were treated at two Australian and two New Zealand centres between 1981 and July 1995. One hundred and sixty-nine patients underwent conservation surgery and 99 had mastectomies. Median follow-up was 53 months. Conventionally fractionated radiation was delivered simultaneously during the first two cycles of CMF, avoiding radiation on the Fridays that the intravenous components of CMF were delivered. In conservatively treated patients, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 34.5 +/- 5.2%, 25.4 +/- 4.5% and 75.5 +/- 4.8%, respectively. Crude incidence of local relapse at 4 years was 6.3% and at regional/distant sites was 26.3%. Highest grades of granulocyte toxicity (< 0.5 x 10(9)/L), moist desquamation, radiation pneumonitis and persistent breast oedema were recorded in 10.7, 8.5, 8.9 and 17.2%, respectively. In patients treated by mastectomy, 5-year actuarial rates of any recurrence, distant recurrence and overall survival were 59.7 +/- 7.3%, 56.7 +/- 7.4% and 50.1 +/- 7%. The crude incidence of local relapse at 4 years was 5.6% and at regional/distant sites it was 45.7%. The issue of appropriate timing of adjuvant therapies has become particularly important with the increasing acknowledgement of the value of anthracycline-based regimens. For women in lower risk categories (e.g. 1-3 nodes positive or node negative), CMF may offer a potentially better therapy, particularly where breast-conserving surgical techniques have been used. In such cases CMF allows the simultaneous delivery of radiotherapy with the result of optimum local control, without compromise or regional or systemic relapse rates. Further randomized trials that directly address the optimal integration of the two modalities, such as the one carried out in Boston, are clearly necessary.

Adult↗

Randomized controlled trial of a comprehensive stroke education program for patients and caregivers.

BACKGROUND AND PURPOSE: We report the findings of a randomized controlled trial to determine the effectiveness of a multidisciplinary Stroke Education Program (SEP) for patients and their informal carers. METHODS: Two hundred four patients admitted with acute stroke and their 176 informal carers were randomized to receive an invitation to the SEP or to receive conventional stroke unit care. The SEP consisted of one 1-hour small group educational session for inpatients followed by six 1-hour sessions after discharge. The primary outcome measure was patient- and carer-perceived health status (SF-36) at 6 months after stroke. Knowledge of stroke, satisfaction with services, emotional outcome, disability, and handicap and were secondary outcome measures. RESULTS: Only 51 of 108 (47%) surviving patients randomized to the SEP completed the program, as did 20 of 93 (22%) informal carers of surviving patients. Perceived health status (Short Form 36 [SF-36] health survey) scores were similar for SEP patients and controls. Informal carers in the control group scored better on the social functioning component of the SF-36 than the SEP group (P=0.04). Patients and informal carers in the SEP group scored higher on the stroke knowledge scale than controls (patients, P=0.02; carers, P=0. 01). Patients in the SEP group were more satisfied with the information that they had received about stroke (P=0.004). There were no differences in emotional or functional outcomes between groups. CONCLUSIONS: Although the SEP improved patient and informal carer knowledge about stroke and patient satisfaction with some components of stroke services, this was not associated with an improvement in their perceived health status. Indeed, the social functioning of informal carers randomized to the SEP was less than in the control group.

Adult↗

Mammographic patterns as a predictive biomarker of breast cancer risk: effect of tamoxifen.

Mammographic breast density has been shown to be associated with up to a 4- to 6-fold increase in risk of breast cancer, whereas tamoxifen therapy increases disease-free survival and reduces mortality. We have therefore investigated whether these effects are related. To determine the effects of tamoxifen on mammographic density, mammograms from 94 women who had received tamoxifen for breast cancer and 188 women (without breast cancer) who had not received tamoxifen were visually classified according to the criteria of Wolfe. Two controls were age-matched to each case. All of the women were postmenopausal (ages, 50-64 years), neither group was taking hormone replacement therapy, and none of the cases had received chemotherapy. There were significant differences in breast density between cases and controls at the initial mammogram (P = 0.0001) but no significant differences at the follow-up mammogram (P = 0.51). A significant change to a more lucent pattern had occurred among the case group (P = 0.0001). The odds ratio for cancer that was associated with the more dense (P2 and DY) patterns with respect to the more lucent (N1 and P1) patterns was 3.6 (95% confidence interval, 2.11-6.18) at the initial mammogram. This was significantly reduced to 1.5 (95% confidence interval, 1.32-1.70) after treatment with tamoxifen (P = 0.019; chi2 = 5.52). The substantial reduction in breast density with tamoxifen provides evidence that tamoxifen has the capacity to favorably alter postmenopausal breast density toward a more lucent pattern, which is associated with reduced risk of breast cancer. Mammographic pattern is, thus, a potential biomarker of breast cancer risk.

Antineoplastic Agents, Hormonal↗