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Objective To compare viral load on care HPV DNA testing in self-collected vaginal (VHPC) and clinician-collected cervical (CHPC) samples for the detection of high-grade cervical intra-epithelial neoplasia (CIN). Study design Cross-sectional study. Ever-married women aged 30–59 years were targeted for cervical screening. On attendance for screening, vaginal self-sampling was performed by the woman, and an auxiliary nurse midwife subsequently performed a per-speculum examination, collected a CHPV sample and a Pap smear, and made a visual inspection of the cervix with acetic acid. The ratio of viral load expressed in relative light units to positive controls set at a cut-off of 1 pg/ml was used for care HPV quantitative assessment. The median viral load was compared using non-parametric tests. Receiver operating characteristic (ROC) curves were constructed for the detection of CINII+ and CINIII+ in CHPV and VHPV samples. Results Overall, the median viral load in the 4658 women screened was higher in CHPV samples compared with VHPV samples (9.8-fold higher in cases of high-grade CIN). The median viral load was significantly higher among Pap-positive women compared with Pap-negative women in both CHPV and VHPV samples ( p < 0.01). Assessment by ROC analysis for the detection of high-grade CIN did not differ significantly between CHPV and VHPV samples. Conclusion Viral load on care HPV testing was comparable between self- and clinician-collected samples for the detection of high-grade CIN. The self-sampling approach may be an option for screening in low-resource countries. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare cervical careHPV screening in a rural community setting with other methods of cervical screening for the detection of high-grade cervical intra-epithelial neoplasia (CIN). Study design: Cross-sectional study. All ever-married women aged 30–59 years surveyed in an administrative area of Uttar Pradesh, India were targeted for screening by careHPV (cervical and vaginal samples), Pap test and visual inspection of the cervix following application of acetic acid (VIA). Women who screened positive were referred for colposcopy and the results were confirmed histologically. Sensitivity, specificity and predictive values for the detection of histological CINII+ and CINIII+ were assessed for each screening test. Results: Sixty-five percent (5032/7704) of the women invited for cervical screening agreed to participate in the study. Screen-positive rates for cervical careHPV, vaginal careHPV, Pap test and VIA were 3%, 2%, 3% and 6%, respectively. Data for women who did not complete all screening modes, women lost to follow-up and women with missing histological results were excluded before data analysis, resulting in a final sample size of 4658. Cervical careHPV had high sensitivity (85%) for the detection of CINIII+ lesions and moderate sensitivity (53%) for the detection of CINII+ lesions. Sensitivities for the detection of CINIII+ and CINII+ were 54% and 41% for vaginal careHPV, 62% and 44% for Pap test, and 8% and 22% for VIA, respectively. Conclusion: Cervical careHPV testing is superior to VIA and Pap test for the detection of high-grade CIN in a rural community setting. [Copyright &y& Elsevier]

Abstract: Aim: To review the experience with hilar cholangiocarcinoma and to determine the results of a radical surgical approach in a UK centre. Methods: A 10-year review of all patients treated surgically for proximal bile duct carcinoma at a single surgical unit was conducted. Patient demographics, disease details and histopathology reports were reviewed. From January 1993 through December 2003, 106 patients were admitted with the diagnosis of hilar cholangiocarcinoma and 61 patients received surgical exploration. Results: Tumours were staged as follows (UICC 6th edition): stage IB, n =10 IIA, n =9; IIB, n =20; III, n =8; IV, n =14. Out of 61 patients, 44 had a resection (3 bile duct resection alone, 41 liver resection with bile duct resection), 5 were considered unresectable and 12 underwent liver transplantation (LT). The caudate lobe was excised in 34 of the patients and regional lymphadenectomy was systematically carried out. Para-aortic lymphadenectomy was performed in 17 cases. Portal vein resection was needed in 17 and hepatic artery resection was performed in 4 cases. Negative histologic margins (R0) were achieved in 20 patients and microscopic margin involvement (R1) was seen in 16. In the remaining 8 resected patients, localised metastasis were found (peritoneal deposits in 2, liver metastasis in 4 and positive para-aortic lymph nodes in 2); nevertheless the resection was performed and it was considered R2. Overall survival at 3 and 5years for patients who underwent a resection was 43% and 28% including postoperative deaths. The 1-, 3- and 5-year actuarial survival rates for patients who underwent R0 resection were 78%, 64% and 45% respectively, including the postoperative deaths (n =3). The median survival time was 41.1months. The 1-, 3- and 5-year actuarial survival rates for R1 resection and R2 were 60%, 26%, 26% and 25% and 0% respectively, while the median survival time for these groups was 15.4 and 6.8months respectively. The actuarial survival rate at 1, 3 and 5years for well-differentiated tumours (G1) was 73%, 54% and 40% (median 39.7months). The figures for G2 were 60%, 48% and 0%. The figures for G3 (poorly differentiated) were 16% and 0% at three years (p =0.03).The overall survival at 3 and 5years for those patients who had a liver transplant was 41% and 20% including early postoperative mortality. The tumour grading (presence of poorly differentiated tumour) was found to be the only independent factor affecting the survival time producing a hazard ratio of 4.3 (p =0.0034, 95% confidence interval 0.1007–6.342). Conclusions: Radical surgical resection is the best treatment for hilar cholangiocarcinoma. R0 resection provides acceptable 5-year survival, but R1 resection may also provide acceptable palliation. In our experience TNM stage and tumour grade were the main determinants of long-term survival. [Copyright &y& Elsevier]

Objectives: Cardiovascular mortality in patients with chronic critical lower limb ischaemia (CCLI) is high and early risk stratification in these patients may aid clinical management improving outcomes. Cardiac troponin I (cTnI) has prognostic significance in patients with unstable angina. The aim of this study was to evaluate the prognostic significance of cardiac troponins in CCLI patients who had no clinical evidence of unstable coronary heart disease. Methods: Patients (n =152) admitted with CCLI to a single vascular unit over a two-year period were included prospectively in this study. Patients with clinical evidence of unstable coronary disease were excluded from the study. Patient demographics, clinical history, co-morbidity and risk factors for peripheral vascular disease were documented. Admission cTnI levels were recorded using a threshold, 0.1ng/ml. The primary endpoint was mortality. Results: Fifty-two patients (34.2%) had an elevated cTnI, whilst 100 (65.8%) had cTnI <0.1ng/ml. Sixty-two patients died during the follow-up period, 38 with an elevated admission cTnI. Death rate in patients with cTnI >0.1ng/nl was 73% compared with 24% in those with levels below the threshold (p <0.0001). Patients with elevated cTnI were significantly older than those with normal level (median age 76 years vs 71 years, p <0.001). An elevated cTnI was found to independently predict disease-specific mortality on Cox regression analysis (Hazard Ratio 4.2; 95% Confidence Interval 1.3–12.7). Conclusion: In this series of patients with CCLI the measurement of cTnI on admission was a significant independent predictor of survival. cTnI has potential as a prognostic test to stratify patients with a high cardiovascular risk and may enable further optimisation of these high-risk patients. [Copyright &y& Elsevier]

Objectives: Previous literature has suggested an association between AAA and the presence of elevated plasma homocysteine levels (HCY). Homocysteine can stimulate elastolysis in the arterial media via activation of elastase and matrix metalloproteinases. No evidence in the literature exists correlating aneurysm expansion and HCY. The study objective is to identify whether the rate of AAA expansion is related to HCY. Methods: 108 patients undergoing surveillance for AAA were identified at our vascular surgical unit. AAA size and growth rate were assessed by serial ultrasongraphic measurements. Fasting total HCY levels were measured using fluorescence polarisation immunoassays. Demographic details and atherosclerotic risk factors were noted all AAA patients. A multivariate analysis was performed for growth rate vs. HCY, hypertension and hypercholesterolaemia. The correlation between AAA growth rate, AAA size and HCY levels were calculated. Results: 60% of patients with AAA had some degree of hyperhomocysteinaemia (>15μmol/l). Multivariate analysis showed HCY to be the only significant factor affecting AAA growth rate. A positive correlation was demonstrated between HCY levels and AAA growth rate using a linear regression model (R=0.28, p =0.003). Median growth rate among patients with hyperHCY was double that of patients with normal HCY (0.5mm/month vs. 0.25mm/month, p =0.003). A growth rate of >10mm/year was seen in 25% of hyper HCY patients and in only 2% of patients with normal HCY. In addition patients with hyper HCY and larger AAAs (>4cm) had a growth rate twice as fast as patients with hyper HCY and AAAs <4cm. Conclusions: A correlation between HCY and growth rate exists, although this is weak due to the multifactorial aetiology of AAAs. HyperHCY patients have faster expansion rates than patients with normal HCY, with significant numbers demonstrating rapid expansion (>10mm/year) and therefore an increased risk of rupture. [Copyright &y& Elsevier]

For a variety of purposes it is increasingly necessary to establish the health needs of local populations. Following a critique of existing proxies of need, this paper presents and evaluates an alternative which draws upon epidemiological evidence concerning the age, sex and social class distribution of morbidity in order to estimate the prevalence of specific conditions in designated populations. By way of demonstrating the insights to be gained through the use of these indicative prevalence rates, the paper considers the treatment of ischaemic heart disease in a sample of 539 practices and presents evidence regarding the significance of deprivation and rurality in determining health service use relative to needs. [Copyright &y& Elsevier]

Abstract: Factors contributing to increased risk for Alzheimer''s disease (AD) include age, sex, genes, and family history of AD. Several risk factors for AD are endogenous; however, accumulating evidence implicates modifiable risk factors in the pathogenesis of AD. Although the continued task of identifying new genes will be critical to learning more about the disease, several research findings suggest that potentially alterable environmental factors influence genetic contributions, providing targets for disease prevention and treatment. Here, we review midlife risk factors for AD, and address the potential for therapeutic intervention in midlife. [Copyright &y& Elsevier]

Abstract: This study examined the functionality of the medial temporal lobe (MTL) and posterior cingulate (PC) in mild cognitive impairment amnestic type (MCI), a syndrome that puts patients at greater risk for developing Alzheimer disease (AD). Functional MRI (fMRI) was used to identify regions normally active during encoding of novel items and recognition of previously learned items in a reference group of 77 healthy young and middle-aged adults. The pattern of activation in this group guided further comparisons between 14 MCI subjects and 14 age-matched controls. The MCI patients exhibited less activity in the PC during recognition of previously learned items, and in the right hippocampus during encoding of novel items, despite comparable task performance to the controls. Reduced fMRI signal change in the MTL supports prior studies implicating the hippocampus for encoding new information. Reduced signal change in the PC converges with recent research on its role in recognition in normal adults as well as metabolic decline in people with genetic or cognitive risk for AD. Our results suggest that a change in function in the PC may account, in part, for memory recollection failure in AD. [Copyright &y& Elsevier]

Background. Our laboratory has previously reported that testosterone (T) administration to older men significantly improves cognitive function. This study examined potential changes in insulin-like growth factor (IGF) IGF-I, IGF-II and IGF-related binding proteins in response to T administration in older men and their relationship to cognitive functioning.Methods. Twenty-five healthy community dwelling volunteers, ranging in age from 50–80 years were randomized to receive weekly intra-muscular (i.m.) injections of either 100 mg T enanthate or placebo (saline) for 6 weeks. Serum hormone levels and cognitive functioning was assessed at baseline and twice during treatment.Results. Significant positive associations between IGF-I and IGF-II and spatial memory, spatial reasoning, and verbal fluency were observed after 6 weeks of T administration. Increased serum T levels from treatment were positively associated with improvement in spatial reasoning performance, whereas estradiol was associated with a decline in divided attention performance. Serum IGF-I, IGF-II and IGFBPs did not change in response to T treatment.Conclusions. Our results suggest that T, estradiol and IGF-I may have independent and selective effects on cognitive functioning. Positive associations between T levels and cognition are consistent with an effect of androgen treatment, whereas positive associations between IGF-I levels and cognition are reflective of a relationship between endogenous IGF-I levels and cognition. [Copyright &y& Elsevier]