Polymorphisms of the androgen transporting gene SLCO2B1 may influence the castration resistance of prostate cancer and the racial differences in response to androgen deprivation.

BACKGROUND: Organic anion-transporting polypeptides (OATPs) encoded by SLCO mediate the cellular uptake of many compounds, including androgens. SLCO1B3 and SLCO2B1 are polymorphic, and single-nucleotide polymorphisms of those genes alter androgen transport efficiency. We aimed to investigate the association between genetic variations in SLCOs and the progression to castration-resistant prostate cancer (CRPC). METHODS: We studied the progression to CRPC for the SLCO1B3 rs4149117 and SLCO2B1 rs12422149 genotypes in 87 prostate cancer patients who received androgen deprivation therapy (ADT). Data were analyzed using the χ(2) test, Kaplan-Meier survival analysis and Cox proportional hazard model. RESULTS: SLCO3B1 genotypes were not significantly associated with the time to progression (TTP); however, patients carrying the active androgen transport SLCO2B1 genotype (GG allele) exhibited a median TTP that was 7 months shorter than that of patients with impaired androgen-transporting activity SLCO2B1 polymorphisms (GA/AA alleles) (10.0 vs 17.0 months, P=0.004). Active androgen transport genotypes of SLCO2B1 (GG allele) occurred more frequently in African and Caucasian populations than in Japanese and Han Chinese populations (P<0.001). CONCLUSIONS: These data suggest that SLCO2B1 rs12422149 variants could provide prognostic value for prostate cancer patients treated with ADT and influence ethnic differences in response to ADT. Active androgen import may be one of the underlying mechanisms of resistance to ADT, and androgen-transporting systems could provide novel biomarkers and targets for CRPC treatment.

[Coronary embolism due to an adherent right atrium thrombus through a patent foramen ovale]. / Embolies coronaires secondaires à un thrombus adhérent de l'oreillette droite par un foramen ovale perméable.

This observation relates to the discovery of native coronary paradoxical embolism secondary to thrombus adherent to the right atrium through a patent foramen ovale (PFO). A patient of 64 years, with a history of mitral regurgitation not followed, was hospitalized for acute respiratory distress due to a mitral insufficiency (MI) with a ruptured chordae and pulmonary embolism. Coronary angiography was performed and revealed two typical images of coronary embolism associated to a non-atheromatous coronary tree. The patient underwent a mitral valve replacement. After the establishment of cardiopulmonary bypass, adherent fibrin and cruoric thrombus of the right atrium and a PFO were found. The analysis of the valves did not reveal any arguments for infective endocarditis. A CT scan, performed as the patient remained unconscious after surgery, showed several cerebral infarcts. Paradoxical embolism coronary was diagnosed in front of the combination of adherent thrombus in the right atrium, pulmonary embolism and systemic coronary and cerebral embolism with a PFO. Coronary embolism rarely happens. It is mainly due to three causes: iatrogenic origin in most cases, direct causes due to micro emboli, particularly from infectious endocarditis and paradoxical embolic origin. There are two types of right atrial thrombus; the most common is the mobile thrombus from the peripheral venous system. The other one, which is more rare, is the adherent thrombus, which occurs in situ. Coronary embolism of paradoxical origin represents a small proportion of the causes of coronary embolism. However, this diagnosis must be considered.

[Peripheral arterial disease with lower limb claudication: Medical treatment]. / Artériopathie oblitérante chronique au stade d'ischémie d'effort : traitement médical.

Whereas the complaint from a patient with intermittent arterial claudication is walking impairment, prognosis is linked to an increased risk of cardiovascular ischemic events due to the diffuse nature of the atherosclerosis. The objectives of the medical treatment therefore include improvement of walking limit, prevention of myocardial infarction, stroke and cardiovascular death, and preventive measures to avoid progression to critical lower limb ischemia. The key areas of treatment focus on smoking cessation, exercise rehabilitation, with supervised therapy if possible, cardiovascular risk prevention with antiplatelet drugs, statins and angiotensin converting enzymes, and correction of atherosclerotic risk factors with well-defined targets (LDL less than 1g/L, HDL greater than 0.4g/L, HbA(1c) less than 6.5%, brachial blood pressure less than 140/90 or 130/80mmHg in case of diabetes or renal insufficiency, body mass index less than 25kg/m(2)). Limitation or avoidance of progression to local critical ischemia requires control of atherosclerotic risk factors and proper foot care. The patient with arterial claudication needs to understand the local and general risks of arterial atherosclerotic disease, and to be involved in his/her own treatment. Obtaining patient compliance to medical care is fundamental: specific educational workshops are of great value for this.

Tympanic membrane reconstruction using formaldehyde-formed autogenous temporalis fascia: twenty years' experience.

This study describes 20 years' experience with autogenous temporalis fascia that is formed and shaped by formaldehyde cross-linking with special Fasciaform (Hear America, Palo Alto, Calif.) molds in the repair of large tympanic membrane perforations. One hundred twenty operations in 113 patients were performed between 1973 and 1993 to close large perforations in patients with intact ossicular chains. All perforations were successfully closed by this technique. Audiometric studies indicated that the postoperative air-borne gap was closed to within 0 to 10 dB in 63% and to within 0 to 20 dB in 97%. One patient had a 15-dB sensorineural hearing impairment. Graft lateralization requiring revision occurred in three patients, two of whom had previous unsuccessful tympanoplasties. Comparisons of adult vs. pediatric groups and primary vs. revision groups were made. The technique ensures the removal of any ectopic epithelium on the medial surface of the tympanic membrane remnant and provides for easy graft placement and stability during healing without the use of middle ear Gelfoam (Upjohn Co., Kalamazoo, Mich.). The formaldehyde-formed fascia graft or Fasciaform graft technique provides an effective method of closing large perforations with excellent functional results and minimal complications.

An immunohistochemical study of the endolymphatic sac in patients with acoustic tumors.

Intraosseous endolymphatic sacs obtained from patients with acoustic neuromas who had undergone total labyrinthectomy during tumor removal were examined for the presence of T helper/inducer and T suppressor/cytotoxic lymphocytes, B lymphocytes, plasma cells, and macrophages. Immunoperoxidase staining of cryostat sections revealed the presence of T helper/inducer lymphocytes, T suppressor/cytotoxic lymphocytes, and macrophages. The number of B lymphocytes and plasma cells was much smaller than the number of T lymphocytes. The number of T suppressor/cytotoxic lymphocytes was higher than the number of T helper/inducer lymphocytes. This study supports the notion of local immune responsiveness in the human inner ear. This is the first immunohistochemical study to analyze lymphocyte subpopulations; specifically, to provide insight into T-cell function in the endolymphatic sac.

Histologic and statistical studies on hyalin bodies in the human endolymphatic sac.

Hyalin bodies are amorphous, eosinophilic masses that protrude from the subepithelial connective tissue into the lumen of the endolymphatic sac. In this study, hyalin bodies were analyzed in two groups of temporal bones: normal bones and bones with cochlear otosclerosis. The results revealed that bones with cochlear otosclerosis had significantly more and larger hyalin bodies that did normal bones. In addition, the hyalin bodies in cochlear otosclerosis were denser and associated with more edema and loose connective tissue in the surrounding areas. Foamy macrophages, concentric calcific structures, and bony ingrowth were frequent features of the hyalin bodies in the cochlear otosclerosis. Our current hypothesis is that these hyalin bodies are repository of membranous cellular debris phagocytized by the macrophages. If this is true, the hyalin bodies may further support the proposed resorptive and phagocytic functions of the endolymphatic sac and the enzymatic concept in cochlear otosclerosis.

Electron microscopy of hyalin bodies in the human intraosseous endolymphatic sac.

Hyalin bodies are amorphous, eosinophilic masses protruding from the subepithelial connective tissue into the lumen of the intraosseous endolymphatic sac (ES). We studied hyalin bodies at the electron microscopic level. Celloidin- embedded temporal bone sections known to have hyalin bodies were re-embedded into plastic and cut into thin sections appropriate for electron microscopy. The results revealed that the hyalin bodies are composed predominantly of thick bundles of collagenous fibers arranged in various directions. Fibroblasts and disintegrated macrophages were occasionally observed among the collagen fibers. Concentric calcific structures found within the hyalin bodies were composed of multiple smaller, concentric, lamellar calcifications. The results of this study support the hypothesis that the hyalin bodies are a repository of membranous cellular debris phagocytized by the macrophages.

Human endolymphatic sac: morphologic evidence of immunologic function.

The ultrastructure of ten normal human endolymphatic sacs (ES), fixed immediately after death and obtained at autopsy, was observed by transmission electron microscopy. The roles of the epithelium, subepithelial space, vasculature, and ES leukocytes were morphologically studied to evaluate possible immunologic functions of the human ES. In addition, five intraosseous ES biopsies from patients undergoing translabyrinthine acoustic neuroma resection were studied using the immunoperoxidase technique to identify specific leukocyte subpopulations. Evidence of phagocytic activity included the presence of phagocytic epithelial cells, monocytes, macrophages, and polymorphonuclear leukocytes. Immune surveillance was suggested by intraepithelial and subepithelial T-lymphocytes, numerous fenestrated blood vessels, and the presence of a homogeneously staining substance within the lumina of ES epithelial tubules. No B-lymphocytes were found. The findings support the existence of a local immune system of the normal human inner ear.