CR1 Knops blood group alleles are not associated with severe malaria in the Gambia

The Knops blood group antigen erythrocyte polymorphisms have been associated with reduced falciparum malaria-based in vitro rosette formation (putative malaria virulence factor). Having previously identified single-nucleotide polymorphisms (SNPs) in the human complement receptor 1 (CR1/CD35) gene underlying the Knops antithetical antigens Sl1/Sl2 and McC(a)/McC(b), we have now performed genotype comparisons to test associations between these two molecular variants and severe malaria in West African children living in the Gambia. While SNPs associated with Sl:2 and McC(b+) were equally distributed among malaria-infected children with severe malaria and control children not infected with malaria parasites, high allele frequencies for Sl 2 (0.800, 1,365/1,706) and McC(b) (0.385, 658/1706) were observed. Further, when compared to the Sl 1/McC(a) allele observed in all populations, the African Sl 2/McC(b) allele appears to have evolved as a result of positive selection (modified Nei-Gojobori test Ka-Ks/s.e.=1.77, P-value <0.05). Given the role of CR1 in host defense, our findings suggest that Sl 2 and McC(b) have arisen to confer a selective advantage against infectious disease that, in view of these case-control study data, was not solely Plasmodium falciparum malaria. Factors underlying the lack of association between Sl 2 and McC(b) with severe malaria may involve variation in CR1 expression levels

Widening socio-economic inequalities in oral cancer incidence in Scotland, 1976–2002

Oral cancer incidence was investigated among 10 857 individuals using Scottish Cancer Registry data. Since 1980 the incidence of oral cancer among males in Scotland has significantly increased, the rise occurring almost entirely in the most deprived areas of residence

A survey of physicians knowledge regarding awareness of maternal alcohol use and the diagnosis of FAS.

BACKGROUND: Alcohol is the most widely used drug in the world that is a human teratogen whose use among women of childbearing age has been steadily increasing. It is also probable that Fetal Alcohol Syndrome is under diagnosed by physicians. The objectives of this study were twofold: 1) to evaluate the experience, knowledge and confidence of family physicians with respect to the diagnosis of FAS and 2) to evaluate physicians awareness of maternal drinking patterns. METHODS AND PARTICIPANTS: A multiple choice anonymous questionnaire was sent to a randomly selected group of family physicians in the Metropolitan Toronto area. RESULTS: There was a 73% (75/103) total response rate; Overall, 6/75 (8%) of family physicians reported that they had actually diagnosed a child with FAS. 17.9% had suspicions but did not make a diagnosis and 12.7% reported making a referral to confirm the diagnosis. Physician rated confidence in the ability to diagnosis FAS was low, with 49% feeling they had very little confidence. 75% reported counselling pregnant women and 60.8% reported counselling childbearing women in general on the use of alcohol. When asked what screening test they used to detect the use of alcohol, 75% described frequency/quantity. Not a single respondent identified using the current accepted screening method for alcohol use (TWEAK) which is recommended by The Centre for Addiction and Mental Health. CONCLUSIONS: Family physicians do not feel confident about diagnosing FAS. None of the physicians were aware of the current screening methods to accurately gage alcohol use in pregnant and childbearing wome

Hybrid management of a spontaneous ilio-iliac arteriovenous fistula: a case report

<p>Abstract</p> <p>Introduction</p> <p>Spontaneous iliac arteriovenous fistulae are a rare clinical entity. Such localized fistulation is usually a result of penetrating traumatic or iatrogenic injury. Clinical presentation can vary greatly but commonly includes back pain, high-output congestive cardiac failure and the presence of an abdominal bruit. Diagnosis, therefore, is often incidental or delayed.</p> <p>Case presentation</p> <p>We report a case of a spontaneous ilio-iliac arteriovenous fistula in a 68-year-old Caucasian man detected following presentation with unilateral claudication and congestive cardiac failure. Following computed tomography evaluation, the fistula was successfully treated with a combined endovascular (aorto-uni-iliac device) and open (femoro-femoral crossover) approach.</p> <p>Conclusion</p> <p>Endovascular surgery has revolutionized the management of such fistulae and we report an interesting case of a high-output iliac arteriovenous fistulae successfully treated with a hybrid vascular approach.</p

Impact of deprivation and rural residence on treatment of colorectal and lung cancer

For common cancers, survival is poorer for deprived and outlying, rural patients. This study investigated whether there were differences in treatment of colorectal and lung cancer in these groups. Case notes of 1314 patients in north and northeast Scotland who were diagnosed with lung or colorectal cancer in 1995 or 1996 were reviewed. On univariate analysis, the proportions of patients receiving surgery, chemotherapy and radiotherapy appeared similar in all socio-economic and rural categories. Adjusting for disease stage, age and other factors, there was less chemotherapy among deprived patients with lung cancer (odds ratio 0.39; 95% confidence intervals 0.16 to 0.96) and less radiotherapy among outlying patients with colorectal cancer (0.39; 0.19 to 0.82). The time between first referral and treatment also appeared similar in all socio-economic and rural groups. Adjusting for disease stage and other variables, times to lung cancer treatment remained similar, but colorectal cancer treatment was quicker for outlying patients (adjusted hazard ratio 1.30; 95% confidence intervals 1.03 to 1.64). These findings suggest that socio-economic status and rurality may have a minor impact on modalities of treatment for colorectal and lung cancer, but do not lead to delays between referral and treatment

Kinetic modelling of competition and depletion of shared miRNAs by competing endogenous RNAs

Non-conding RNAs play a key role in the post-transcriptional regulation of mRNA translation and turnover in eukaryotes. miRNAs, in particular, interact with their target RNAs through protein-mediated, sequence-specific binding, giving rise to extended and highly heterogeneous miRNA-RNA interaction networks. Within such networks, competition to bind miRNAs can generate an effective positive coupling between their targets. Competing endogenous RNAs (ceRNAs) can in turn regulate each other through miRNA-mediated crosstalk. Albeit potentially weak, ceRNA interactions can occur both dynamically, affecting e.g. the regulatory clock, and at stationarity, in which case ceRNA networks as a whole can be implicated in the composition of the cell's proteome. Many features of ceRNA interactions, including the conditions under which they become significant, can be unraveled by mathematical and in silico models. We review the understanding of the ceRNA effect obtained within such frameworks, focusing on the methods employed to quantify it, its role in the processing of gene expression noise, and how network topology can determine its reach.Comment: review article, 29 pages, 7 figure

Rural factors and survival from cancer: analysis of Scottish cancer registrations

In this survival study 63 976 patients diagnosed with one of six common cancers in Scotland were followed up. Increasing distance from a cancer centre was associated with less chance of diagnosis before death for stomach, breast and colorectal cancers and poorer survival after diagnosis for prostate and lung cancers. © 2000 Cancer Research Campaig

Definitive chemoradiation in patients with inoperable oesophageal carcinoma

We performed a retrospective study of 90 consecutive cases with inoperable carcinoma of the oesophagus treated with definitive chemoradiation at a single cancer centre between 1995 and 2002. For the last 4 years, 73 patients have received therapy according to an agreed protocol. This outpatient-based regimen involves four cycles of chemotherapy, cycles 3 and 4 given concurrently with 50 Gy external beam radiotherapy (XRT) delivered in 25 fractions over 5 weeks. Cisplatin 60 mg m-2 day-1 is given every 3 weeks together with continuous infusional 5-fluorouracil 300 mg m-2 day-1, reduced to 225 mg m-2 day-1 during the XRT. In all, 45 (50%) patients suffered one or more WHO grade 3/4 toxicity, grade 3 in 93% cases. Patients received more than 90% of the planned chemoradiation schedule. The median overall survival was 26 (15, >96) months, 51% (41, 64) and 26% (13, 52) surviving 2 and 5 years, respectively. Advanced stage, particularly T4 disease, was associated with a worse prognosis. Patients considered not suitable for surgery for reasons other than their disease, mainly co-morbidity, had a significantly better outcome, median survival 40 (26, >96) months, 2- and 5-year survivals 67% (54, 84) and 32% (13, 79), respectively (P<0.001). This schedule is a feasible, tolerable and effective treatment for patients with oesophageal cancer considered unsuitable for surgery

Factors influencing time from presentation to treatment of colorectal and breast cancer in urban and rural areas

Stage at diagnosis and survival from cancer vary according to where people live, suggesting some may have delays in diagnosis. The aim of this study was to determine if time from presentation to treatment was longer for colorectal and breast cancer patients living further from cancer centres, and identify other important factors in delay. Data were collected on 1097 patients with breast and 1223 with colorectal cancer in north and northeast Scotland. Women with breast cancer who lived further from cancer centres were treated more quickly than those living closer to cancer centres (P = 0.011). Multilevel modelling found that this was largely due to them receiving earlier treatment at hospitals other than cancer centres. Breast lump, change in skin contour, lymphadenopathy, more symptoms and signs, and increasing age predicted faster treatment. Screen detected cancers and private referrals were treated more quickly. For colorectal cancer, time to treatment was similar for people in rural and urban areas. Quicker treatment was associated with palpable rectal or abdominal masses, tenesmus, abdominal pain, frequent GP consultations, age between 50 and 74 years, tumours of the transverse colon, and iron medication at presentation. Delay was associated with past anxiety or depression. There was variation between general practices and treatment appeared quicker at practices with more female general practitioners