A case of hippocampal laminar necrosis following complex partial status epilepticus

Cortical laminar necrosis (CLN) is a metabolic injury pattern usually observed after cerebral hypoxia, hypoglycemia, or ischemia. We report serial magnetic resonance imaging findings in a patient with complex partial status epilepticus (SE) developing a band-like, T1-hyperintense lesion consistent with CLN along the surface of the left hippocampus without concurrent other causes of CLN. This observation suggests a direct pathogenetic link between SE and CLN involving combined damage to neurons and glia.     

Genetic variability of the fatty acid synthase pathway is not associated with prostate cancer risk in the European Prospective Investigation on Cancer (EPIC)

A western lifestyle, characterised by low rates of energy expenditure and a high-energy diet rich in animal protein, saturated fats and refined carbohydrates, is associated with high incidence of prostate cancer in men. A high-energy nutritional status results in insulin/IGF signalling in cells, which in turn stimulates synthesis of fatty acids. We investigated whether the genetic variability of the genes belonging to the fatty acid synthesis pathway is related to prostate cancer risk in 815 prostate cancer cases and 1266 controls from the European Prospective Investigation on Cancer (EPIC). Using a tagging approach and selecting 252 SNPs in 22 genes, we covered all the common genetic variation of this pathway. None of the SNPs reached statistical significance after adjusting for multiple comparisons. Common SNPs in the fatty acid synthase pathway are not major contributors to prostate cancer risk.     

Serum levels of C-peptide, IGFBP-1 and IGFBP-2 and endometrial cancer risk; results from the European prospective investigation into cancer and nutrition

We conducted a case-control study nested within the European Prospective Investigation into Cancer and Nutrition, to examine the associations between prediagnostic serum concentrations of C-peptide, insulin-like growth factor binding protein (IGFBP)-1 and IGFBP-2, and endometrial cancer risk. Among pre- and post-menopausal women, who were not currently using exogenous hormones, 286 women developed incident endometrial cancer during an average 5.1 years follow-up. Using risk set sampling, 555 matched control subjects were selected. In conditional logistic regression models adjusted for matching factors only, endometrial cancer risk increased with increasing serum levels of C-peptide (relative risks (RR) for the top vs. bottom quartile = 2.13 [95% confidence interval (CI) 1.33-3.41], p(trend) = 0.001, and decreasing serum levels of IGFBP-2 (RR for the top vs. bottom quartile = 0.56 [95% CI 0.35-0.90], p(trend) = 0.03, but was not significantly associated with IGFBP-1 levels (RR for the top vs. bottom quartile = 0.76 [95% CI 0.47-1.21], p(trend) = 0.25). In BMI-adjusted models, only the C-peptide association remained marginally statistically significant (RR for the top vs. bottom quartile = 1.56 [95% CI 0.94-2.57], p(trend) = 0.05 for C-peptide; 0.84 [95% CI 0.50-1.40], p(trend) = 0.74 for IGFBP-2; and 1.08 [95% CI 0.65-1.78], p(trend) = 0.86 for IGFBP-1 levels). These associations were stronger among nonfasting women (< or =< or =6 hr since last meal; 63% of subjects) but were not evident among fasting women, although the interactions were not statistically significant. The C-peptide-risk association was substantially attenuated after adjustment for free estradiol in postmenopausal women (RR for the top vs. bottom quartile = 1.28 [95% CI 0.67-2.45], p(trend) = 0.42. Our results provide modest support to the hypothesis that hyperinsulinaemia is a risk factor for endometrial cancer.     

Three-year randomized controlled trial of dipyridamole and low-dose warfarin in patients with IgA nephropathy and renal impairment

Summary: Activation of platelets and the coagulation pathway are factors which may contribute to the progression of renal disease in IgA nephropathy (IgAN). Of 21 patients with IgAN and serum creatinines between 1.6 and 3.0 mg/dL, 10 were assigned to treatment with dipyridamole and low-dose warfarin (keeping the thrombotest between 30 and 50%) and 11 to no treatment in a prospective randomized 3-year study. At entry into the trial, patients in the treatment group were younger (35 ± 6 years vs 42 ± 9 years) and had worse histological scores for tubular atrophy (1.7 ± 0.7 vs 1.1 ± 0.5) and arteriolar hyperplasia (1.4 ± 0.7 vs 0.7 ± 0.8) than those in the non-treatment group. There were no differences in serum creatinine values, creatinine clearances, urinary protein excretions, serum albumins or urinary erythrocyte counts. At the end of the trial, patients on treatment did not experience a significant increase in serum creatinine values (1.9 ± 0.3 mg/dL to 2.5 ± 1.2) or reduction in creatinine clearances (52 ± 20mL/min to 52 ± 27). Untreated patients, however, experienced a significant rise in serum creatinine values (2.1 ± 0.5 mg/dL to 3.3 ± 1.1, P < 0.01) and a fall in creatinine clearances (51 ± 26 mL/min to 31 ± 22, P = 0.06). There was no significant change in the proteinuria in either group (treatment group: 1.2 ± 1.2 g/day to 1.3 ± 1.1, non-treatment group: 1.9 ± 1.4 to 1.5 ± 1.1) and there was also no change in serum albumins and urinary erythrocyte counts. Four untreated and one treated patient developed end-stage renal failure during the course of the trial. This study suggests that treatment of patients with IgAN and renal impairment with dipyridamole and low-dose warfarin retards the deterioration of renal function, as measured by the serum creatinine and creatinine clearance.     

Improving Risk Assessment: Hip Geometry, Bone Mineral Distribution and Bone Strength in Hip Fracture Cases and Controls. The EPOS Study

Hip geometry and bone mineral density (BMD) have previously been shown to relate independently to hip fracture risk. Our objective was to determine by how much hip geometric data improved the identification of hip fracture. Lunar pencil beam scans of the proximal femur were obtained. Geometric and densitometric values from 800 female controls aged 60 years or more (from population samples which were participants in the European Prospective Osteoporosis Study, EPOS) were compared with data from 68 female hip fracture patients aged over 60 years who were scanned within 4 weeks of a contralateral hip fracture. We used Lunar DPX ‘beta’ versions of hip strength analysis (HSA) and hip axis length (HAL) applied to DPX(L) data. Compressive stress (Cstress), calculated by the HSA software to occur as a result of a typical fall on the greater trochanter, HAL, body mass index (BMI: weight/(height)²) and age were considered alongside femoral neck BMD (FN-BMD, g/cm²) as potential predictors of fracture. Logistic regression was used to generate predictors of fracture initially from FN-BMD. Next age, Cstress (as the most discriminating HSA-derived parameter), HAL and BMI were added to the model as potentially independent predictors. It was not necessary to include both HAL and Cstress in the logistic models, so the entire data set was examined without excluding the subjects missing HAL measurements. Cstress combined with age and BMI provided significantly better prediction of fracture than FN-BMD used alone as is current practice, judged by comparing areas under receiver operating characteristic (ROC) curves (p<0.001, deLong’s test). At a specificity of 80%, sensitivity in identification was improved from 66% to 81%. Identifying women at high risk of hip fracture is thus likely to be substantially enhanced by combining bone density with age, simple anthropometry and data on the structural geometry of the hip. HSA might prove to be a valuable enhancement of DXA densitometry in clinical practice and its use could justify a more pro-active approach to identifying women at high risk of hip fracture in the community. Received: 16 March 2001 / Accepted: 3 August 2001     

Family history of heart attack: a modifiable risk factor?

A family history of heart attack is reported to be an independent predictor of cardiovascular death in men. In a 9 year follow-up of 4014 adults from 40 to 79 years old in the Rancho Bernardo Study, men under 60 years of age with a family history of heart attack were at fivefold increased risk. In this study, we sought to determine whether modifiable risk factors, i.e., blood pressure, plasma cholesterol, obesity, and cigarette smoking, have a differential effect on cardiovascular risk in those with and without a family history of heart attack. For both sexes, cigarette smoking was a stronger predictor of cardiovascular disease in those with a family history of heart attack (relative risk of smokers vs nonsmokers was 2.5 for men and 4.0 for women) than in those with no such family history (relative risk of smokers vs nonsmokers was 1.1 for men and 1.7 for women). Conversely, an increased risk of cardiovascular mortality in men with a family history of heart attack was present predominantly in smokers (relative risk related to positive family history was 1.2 in nonsmokers, and 3.3 in smokers). An estimated 68% of the excess deaths in men with a family history of heart attack were attributable solely to the interaction of family history with smoking habit and were therefore potentially avoidable. The risk of cardiovascular disease associated with an apparently inherited predisposition appears to be profoundly affected by modifiable behavior.     

More acidic dietary acid-base load is associated with reduced calcaneal broadband ultrasound attenuation in women but not in men: results from the EPIC-Norfolk cohort study

BACKGROUND: Dietary patterns that promote mild metabolic acidosis may have a negative effect on bone density. OBJECTIVE: We investigated the relation between a measure of dietary acid-base load, potential renal acid load (PRAL), and calcaneal broadband ultrasound attenuation (BUA) after adjustment for confounders and also compared the results with different estimates of acid-base load. DESIGN: A cross-sectional study was conducted in 14 563 men and women aged 42-82 y living in Norfolk, United Kingdom, in which measures of calcaneal BUA and dietary PRAL were estimated by using the European Prospective Investigation into Cancer and Nutrition Norfolk (EPIC-Norfolk) food-frequency questionnaire. RESULTS: A more acidic dietary intake (high PRAL) was significantly associated with lower calcaneal BUA in women but not in men; there was a difference of approximately 2% in BUA between the highest and lowest quintiles of PRAL, independent of age, body mass index, smoking habit, physical activity, diagnosed osteoporosis, and history of fracture, and (in women) hormone replacement therapy. No relation was observed between history of fracture or incident fracture and PRAL. Those with the greatest PRAL had higher intakes of meat, fish, eggs, and cereal and cereal products and lower intakes of fruit and vegetables, tea, and coffee. CONCLUSION: PRAL was inversely associated with bone ultrasound measures in women, but the magnitude of the association was relatively small compared with other known risk factors. Further longitudinal studies are required to establish whether, in the long term, these small effects are important in overall fracture risk in populations.