Citations

Abstract Pulmonary lymphangioleiomyomatosis (LAM) is an uncommon disease reported to occur exclusively in women. We describe a phenotypically normal man with pulmonary LAM. Fluorescence in situ hybridization (FISH) studies performed on the lung biopsy confirmed a normal XY genotype. Our patient also had stigmata of tuberous sclerosis complex (TSC), including facial angiofibromas and renal angiomyolipoma. Immunohistochemical stains of both LAM and renal angiomyolipoma showed positive immunoreactivity for hamartin (TSC1) and loss of immunoreactivity for tuberin (TSC2). Loss of heterozygosity (LOH) for TSC2 was further demonstrated in the renal angiomyolipoma. Coupled with the results of immunostains, these findings are consistent with TSC2 mutation.

Objective To evaluate carbonic anhydrase IX ( CAIX ) expression as an independent prognostic marker for clear cell renal cell carcinoma ( ccRCC ). With recent smaller studies showing conflicting results, we aimed to update our initial analysis in 2007 with an additional 5‐year follow‐up. Patients and Methods We provided long‐term follow‐up of the same cohort used in our 2007 study (730 patients with unilateral, sporadic ccRCC treated surgically between 1990 and 1999). Associations of CAIX expression with RCC death and distant metastases were evaluated using C ox proportional hazards regression models. Results CAIX was expressed in 708 (97.0%) of the specimens; 163 tumours (22.3%) had low (≤85%) expression and 567 (77.7%) high (>85%) expression. There were 483 deaths and 265 RCC ‐specific deaths. The median follow‐up for the 247 patients still under observation was 13.8 years. Univariately, low CAIX expression was associated with an increased risk of RCC death vs high expression (hazard ratio 1.62; P < 0.001). Low CAIX expression was not statistically significantly associated with RCC death or distant metastases after adjusting for nuclear grade or coagulative tumour necrosis. Conclusion After additional long‐term follow‐up of our large cohort, our results continue to suggest that CAIX is not an independent prognostic marker for ccRCC .

AbstractChronic pain is common in persons with HIV and is often associated with psychiatric illness and substance abuse. Current literature links psychiatric illness and substance abuse with worse HIV outcomes; however, the relationship of chronic pain, alone and in the context of psychiatric illness and substance abuse, to outcomes in HIV has not been described. To develop this new area of inquiry, we propose an adapted biopsychosocial framework specifically for chronic pain in HIV. This framework will describe these relationships and serve as a conceptual framework for future investigations.

Abstract Background: Ovarian cancer is a leading cause of cancer-related death among women. In an effort to understand contributors to disease outcome, we evaluated single-nucleotide polymorphisms (SNP) previously associated with ovarian cancer recurrence or survival, specifically in angiogenesis, inflammation, mitosis, and drug disposition genes. Methods: Twenty-seven SNPs in VHL, HGF, IL18, PRKACB, ABCB1, CYP2C8, ERCC2, and ERCC1 previously associated with ovarian cancer outcome were genotyped in 10,084 invasive cases from 28 studies from the Ovarian Cancer Association Consortium with over 37,000-observed person-years and 4,478 deaths. Cox proportional hazards models were used to examine the association between candidate SNPs and ovarian cancer recurrence or survival with and without adjustment for key covariates. Results: We observed no association between genotype and ovarian cancer recurrence or survival for any of the SNPs examined. Conclusions: These results refute prior associations between these SNPs and ovarian cancer outcome and underscore the importance of maximally powered genetic association studies. Impact: These variants should not be used in prognostic models. Alternate approaches to uncovering inherited prognostic factors, if they exist, are needed. Cancer Epidemiol Biomarkers Prev; 22(5); 987–. ©2013 AACR.

Mycobacterium haemophilum is a slow growing, aerobic, fastidious mycobacterium requiring hemin and a temperature of 30–32° C for optimal growth that is ubiquitous in nature. Disease in immunocompromised adults typically manifests as skin lesions such as papules, pustules and ulcerations. This organism also causes lymphadenitis in immunocompetent children. Antitumour necrosis factor-α (anti-TNF-α) therapy with agents such as infliximab, etanercept and adalimumab is increasingly being used for immunosuppression in patients with various autoimmune conditions. These agents are known to place patients at increased risk for tuberculosis and other granulomatous diseases. However, little is known about illness caused by M haemophilum in patients on immunosuppression with anti-TNF-α therapy. We describe a case of disseminated M haemophilum manifesting as skin lesions in a 72-year-old man with rheumatoid arthritis on infliximab and methotrexate.

Aberrant connectivity is implicated in many neurological and psychiatric disorders, including Alzheimer’s disease and schizophrenia. However, other than a few disease-associated candidate genes, we know little about the degree to which genetics play a role in the brain networks; we know even less about specific genes that influence brain connections. Twin and family-based studies can generate estimates of overall genetic influences on a trait, but genome-wide association scans (GWASs) can screen the genome for specific variants influencing the brain or risk for disease. To identify the heritability of various brain connections, we scanned healthy young adult twins with high-field, high-angular resolution diffusion MRI. We adapted GWASs to screen the brain’s connectivity pattern, allowing us to discover genetic variants that affect the human brain’s wiring. The association of connectivity with the SPON1 variant at rs2618516 on chromosome 11 (11p15.2) reached connectome-wide, genome-wide significance after stringent statistical corrections were enforced, and it was replicated in an independent subsample. rs2618516 was shown to affect brain structure in an elderly population with varying degrees of dementia. Older people who carried the connectivity variant had significantly milder clinical dementia scores and lower risk of Alzheimer’s disease. As a posthoc analysis, we conducted GWASs on several organizational and topological network measures derived from the matrices to discover variants in and around genes associated with autism ( MACROD2 ), development ( NEDD4 ), and mental retardation ( UBE2A ) significantly associated with connectivity. Connectome-wide, genome-wide screening offers substantial promise to discover genes affecting brain connectivity and risk for brain diseases.