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     

The tarsal pillar technique for narrowing and maintenance of the interpalpebral fissure.

We describe a tarsorrhaphy technique whereby an ipsilateral upper-eyelid tarsal pillar is sutured to a corresponding lower-eyelid recipient site. This technique allows maintenance of a narrowed interpalpebral fissure indefinitely, yet is easy to reverse without incurring lid-margin damage. Additionally, the procedure can be adjusted postoperatively to either narrow or widen the initial surgical result. We report our combined surgical experience in 35 consecutive procedures using this technique to treat eyes with exposure-related keratopathy of varied etiology, including facial nerve palsies, combined facial nerve palsy and trigeminal neuropathy with an anesthetic cornea, Graves' disease, congenital craniofacial anomalies, and severe keratitis sicca syndrome. The procedure was successful in improving exposure keratopathy symptoms in all 35 cases. Complications, reflecting the authors' learning curve with this new procedure, included intermarginal pyogenic granulomas, stretching of the tarsal pillar, minor lower-eyelid-margin eversion, and tarsal pillar dehiscence.     

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.     

Adenomyosis:common and uncommon manifestations on sonography and magnetic resonance imaging.

OBJECTIVE: The purpose of this presentation is to show the imaging findings of the common and uncommon variants of adenomyosis as seen on sonography and magnetic resonance imaging (MRI). METHODS: A 3-year database search was performed to identify women who had pelvic sonography and pelvic MRI within a 6-month interval. Images of these cases were retrospectively reviewed. RESULTS: Eighty women were identified. Adenomyosis was diagnosed on MRI, which was used as the reference standard, in 45 of these women. The correct diagnosis was made on sonography in 73% of the cases. CONCLUSIONS: Awareness of the spectrum of imaging features of adenomyosis is important to use sonography effectively for diagnosing this entity and to help avoid misdiagnosis.     

Blepharochalasis.

Blepharochalasis is an uncommon disorder distinguished by recurrent episodes of eyelid oedema in young patients. A hypertrophic form, manifested as fat herniation, and an atrophic form, manifested as fat atrophy, have been described. Ptosis with excellent levator function, laxity of the lateral canthal structures with rounding of the lateral canthal angle, nasal fat pad atrophy, and redundant eyelid skin develop after many episodes of eyelid swelling. Fine wrinkling, atrophy, and telangiectasias characterise the excess eyelid skin. We describe four cases of this syndrome in which external levator aponeurosis tuck, blepharoplasty, lateral canthoplasty, and dermis fat grafts were used to correct atrophic blepharochalasis after the syndrome had run its course.     

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.     

Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia

To determine the timing of pubertal development and the frequency of gonadal dysfunction in children who survive acute lymphoblastic leukemia, we assessed pubertal status and the plasma levels of sex steroids, gonadotropin, and inhibin in 45 children (20 girls and 25 boys) who had received combination chemotherapy along with 24 Gy of irradiation to the cranium (modified LSA2L2 protocol). We also reexamined testicular biopsy specimens, obtained at the time of the cessation of chemotherapy, for the presence of germ cells. Germ-cell damage, indicated by marked elevations in the plasma level of follicle-stimulating hormone (P less than 0.001 for the comparison with normal children), was evident in both sexes and was confirmed in the boys by the absence of germ cells in the testicular biopsy specimens and by the small size of the testes for pubic-hair stage. Only 44 percent of the pubertal girls had measurable plasma inhibin levels, as compared with more than 93 percent of normal pubertal girls. Although plasma sex-steroid levels were normal, the secretion of luteinizing hormone in response to stimulation with gonadotropin-releasing hormone was elevated in the pubertal children (P less than 0.01 for the comparison with normal controls)--a finding that suggests compensation for decreased gonadal function. Despite clear evidence of gonadal damage, girls had early menarche at a mean age (+/- SD) of 11.95 +/- 0.91 years, as compared with the Australian standard of 12.98 +/- 1.11 years (P less than 0.01). Thus, in girls, puberty was early despite primary gonadal damage. Thirteen of 23 boys reached puberty at a mean age of 12.36 +/- 0.73 years. We conclude that treatment for acute lymphoblastic leukemia may lead to primary gonadal damage in both sexes, regardless of the age at treatment, but that the secondary characteristics of puberty develop at a normal age or, in girls, relatively early.     

Brain volumes in familial and non-familial schizophrenic probands and their unaffected relatives

Structural brain abnormalities are consistently reported in schizophrenic subjects but the etiology of these abnormalities remains unclear. We tested the contribution of genetic predisposition and obstetric complications to the structural brain abnormalities found in schizophrenic probands and their relatives. MRI scans were carried out on 35 schizophrenic probands from families multiply affected with the disorder, and 63 of their unaffected relatives, including 10 parents who appeared to transmit genetic risk to their children; as well as 31 schizophrenic probands from families with no other affected members, 33 of their unaffected relatives; and finally 68 controls. Volumetric measurements of whole brain, lateral ventricles, third ventricle, cerebellum, and temporal lobes were completed for each subject. The impact of obstetric complications on brain structure was assessed across the gradient of presumed genetic predisposition. Both groups of schizophrenic probands displayed enlargement of the lateral and third ventricles, and there was a gradient of ventricular enlargement amongst the unaffected relatives in proportion to their likelihood of carrying schizophrenic genes. Ventricular enlargement was largely confined to males in both probands and unaffected relatives. Obstetric complications were associated with ventricular enlargement only in the familial probands. Non-familial probands displayed reduced volume of the temporal lobes bilaterally. In families with several schizophrenic members, ventricular enlargement is a marker for genetic liability, particularly in males. Individuals inheriting the susceptibility to schizophrenia appear particularly prone to develop ventricular enlargement in response to obstetric complications.