The Hidden Source of Testosterone Hypersecretion in a Female-A 30-Year Journey.

A Sertoli-Leydig cell tumor (SLCT) is a rare ovarian tumor that often excessively secretes testosterone and its precursor, leading to virilization in females. We present a case of a female patient with persistent, severe hyperandrogenism. Our patient had a history of left oophorectomy due to an ectopic pregnancy and initially presented with amenorrhea at the age of 30. Biochemical evaluations suggested ovarian hyperandrogenism. Despite the absence of an ovarian mass, she underwent a right oophorectomy and remained hyperandrogenic postoperatively. When she established care with our endocrinology clinic at the age of 58, she had more virilizing features and total testosterone levels ranging from 10.1 to 12.0 nmol/L (292-346 ng/dL; normal reference range for women: 0.07-1.56 nmol/L; 2-45 ng/dL). While biochemical evaluations were consistent with tumorous ovarian hyperandrogenism, ultrasound and computed tomography again failed to identify the source. Finally, an 18F-fluorodeoxyglucose-positron emission tomography/computed tomography revealed a mass in the left adnexa, and she underwent removal of the mass. The final pathology confirmed SLCT. The case highlights that SLCT may be small and slow-growing and not readily visible on conventional imaging modalities.

Transgenic overexpression of the transcription factor Nkx6.1 in ß-cells of mice does not increase ß-cell proliferation, ß-cell mass, or improve glucose clearance.

The loss or dysfunction of the pancreatic endocrine ß-cell results in diabetes. Recent innovative therapeutic approaches for diabetes aim to induce ß-cell proliferation in vivo by pharmacological intervention. Based on the finding that overexpression of the transcription factor Nkx6.1 in islets in vitro increases ß-cell proliferation while maintaining ß-cell function, Nkx6.1 has been proposed as a potential target for diabetes therapy. However, it is unknown whether elevated Nkx6.1 levels in ß-cells in vivo have similar effects as observed in isolated islets. To this end, we sought to investigate whether overexpression of Nkx6.1 in ß-cells in vivo could increase ß-cell mass and/or improve ß-cell function in normal or ß-cell-depleted mice. Using a bigenic inducible Cre-recombinase-based transgenic model, we analyzed the effects of Nkx6.1 overexpression on ß-cell proliferation, ß-cell mass, and glucose metabolism. We found that mice overexpressing Nkx6.1 in ß-cells displayed similar ß-cell proliferation rates and ß-cell mass as control mice. Furthermore, after partial ß-cell ablation, Nkx6.1 overexpression was not sufficient to induce ß-cell regeneration under either nondiabetic or diabetic conditions. Together these results demonstrate that sustained Nkx6.1 overexpression in vivo does not stimulate ß-cell proliferation, expand ß-cell mass, or improve glucose metabolism in either normal or ß-cell-depleted pancreata. Thus, raising cellular Nkx6.1 levels in ß-cells in vivo is unlikely to have a positive impact on type 2 diabetes.

Molecular epidemiology of carbapenem-resistant Pseudomonas aeruginosa carrying metallo-beta-lactamase genes in Taiwan.

Seventy-two isolates of carbapenem-resistant Pseudomonas aeruginosa (CRPA) collected through the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program in 2000 and 2002 were studied for carriage of metallo-beta-lactamase (MBL), integrase genes, and integrons. Epidemiologic relatedness was determined using pulsed-field gel electrophoresis. The prevalence of the MBL genes among CRPA was 36.0% (9 of 25) in TSAR II and 17.0% (8/47) in TSAR III, with prevalence in surveyed hospitals being 19.1% (4/21, TSAR II) and 23.1% (6 of 26, TSAR III). The bla(VIM-3) was detected in 15 of the 17 MBL-positive isolates; the remainder possessed bla(VIM-2). The bla(IMP) was not evident. Class 1 integron was detected in all MBL-positive isolates; amplicon DNA sequences containing the bla(VIM-3) regions were all identical. All MBL-positive isolates remained susceptible to colistin. Molecular typing revealed a predominant strain that comprised 14 of the isolates among the various surveyed hospitals.