Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank

Background Although prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank.Methods A range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure.Results After an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death.Conclusion We found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.Subject terms: Predictive markers, Prostate cancer, Risk factors     

Osteochondral Fracture of the Fourth Metatarsal Head Treated by Open Reduction and Internal Fixation

Fracture of the metatarsal head is uncommon, and reports of isolated osteochondral fracture of the metatarsal head are rare. Because of the distal location of the fracture, it is difficult to achieve and maintain reduction, and potential complications include avascular necrosis and subchondral fatigue fracture. The authors present a case of an osteochondral fracture in a 40-year-old man, which was treated by open reduction and internal fixation with a single twist-off screw, with good results 12 months postoperatively.     

Improved diagnostic effectiveness with a sequential diagnostic paradigm in idiopathic pediatric sensorineural hearing loss.

OBJECTIVES: To determine whether a stepwise diagnostic paradigm is more diagnostically efficient and cost-effective than a simultaneous testing approach in the evaluation of idiopathic pediatric sensorineural hearing loss (SNHL). DESIGN: Prospective prevalence study. SETTING: Tertiary referral children's hospital. PATIENTS: Consecutive children (n = 150) presenting with idiopathic SNHL in the last 2 years. INTERVENTIONS: All children were evaluated with full diagnostic evaluations including GJB2 screens, temporal bone computed tomography scans, and laboratory investigations. MAIN OUTCOME MEASURES: 1) Diagnostic yields of GJB2 screens, imaging, and laboratory results per SNHL category; 2) Cost analysis comparing a sequential versus a simultaneous testing approach. RESULTS: Overall, 12.0% of patients had biallelic mutations in the GJB2 gene, whereas 30% of patients had an abnormality on temporal bone scan. Laboratory testing did not reveal the SNHL etiology in any patient. While maintaining diagnostic accuracy, significant cost savings were inferred by using a sequential diagnostic algorithm. Our data show children with severe to profound SNHL should first be tested with a GJB2 screen, as opposed to those with milder SNHL, who should undergo imaging as the initial testing step. In patients with initially positive GJB2 or imaging screens, logistic regression analysis significantly predicted negative results on further testing. CONCLUSIONS: A stepwise diagnostic paradigm tailored to the level of the hearing loss in children with bilateral SNHL is more diagnostically efficient and cost effective than the more commonly used full, simultaneous testing approach. Laboratory investigation should not be routine but based on clinical history.     

Experimental columnar metaplasia in the canine oesophagus

Regeneration of canine oesophageal mucosa was studied under basal conditions and in the presence of gastro-oesophageal reflux. In normal circumstances mucosal defects in the oesophagus regenerate by squamous epithelium. In the presence of gastro-oesophageal reflux of either acid or a combination of acid and bile, regeneration was frequently by columnar epithelium (Barrett's oesophagus). This columnar regeneration was not seen with bile reflux alone. By the use of squamous barriers to proximal migration of columnar epithelium in the stomach, it was demonstrated that columnar re-epithelialization may occur from cells intrinsic to the oesophagus and is not dependent on proximal migration of cardiac columnar epithelium. The cell of origin of this epithelium may be located in oesophageal gland ducts and is likely to be a multipotential stem cell since the regenerated columnar epithelium may contain goblet and parietal cells not normally found in the oesophagus. This epithelium is morphologically distinct on mucin histochemistry from cardiac columnar epithelium. These findings support the concept that Barrett's epithelium is metaplastic.     

Functional genomics and schizophrenia: endophenotypes and mutant models.

This article summarizes the rationale, methods, and results of gene discovery programs in schizophrenia research and describes functional methods of investigating potential candidate genes. It focuses next on the most prominent current candidate genes and describes (1) evidence for their association with schizophrenia and research into the function of each gene; (2) investigation of the clinical phenotypes and endophenotypes associated with each gene, at the levels of psychopathologic, neurocognitive, electrophysiologic, neuroimaging, and neuropathologic findings; and (3) research into the ethologic, cognitive, social, and psychopharmacologic phenotype of mutants with targeted deletion of each gene. It examines gene-gene and gene-environment interactions. Finally, it looks at future directions for research.     

The apolipoprotein C-II variant apoC-IILys19→Thr is not associated with dyslipidemia in an affected kindred

The rare apolipoprotein C-II (apoC-II) mutation, apoC-II_Lys19→Thr, also known as apoC-II-v, has been found previously in association with hyperlipoproteinemia. From a lipid clinic screening we identified three unrelated individuals who had the apoC-II_Lys19→Thr mutation. Among eight family members of one proband, we have found another four who were affected. None of the inviduals in this kindred is dyslipidemic and there is no difference in lipid levels between affected and unaffected family members. Therefore, we conclude that the presence of this apolipoprotein variant by itself has no effect on lipoprotein levels. In addition, the apolipoprotein E (apoE) isoform, apoE4 does not have a synergistic effect on lipoprotein levels in this kindred, in contrast to observations on the interaction of apoE4 with another apoC-II mutant (apoC-II_Toronto). The single nucleotide substitution that causes the apoC-II_Lys19→Thr variant introduces a previously unrecognized restriction site (for Mae III), that provides for easy screening.