Drug-induced gynecomastia

Drugs are a very common cause of gynecomastia and should always be entertained as the possible causal agent of such a condition. This drug side-effect is due to an impaired balance in the serum estrogen/serum androgen ratio, whatever the mechanism, or a rise in prolactin level. Sex hormones, antiandrogens, are frequently involved as well as spironolactone, cimetidine, verapamil and cancer chemotherapy (especially alkylating agents). Diazepam, tricyclic antidepressants, neuroleptics, calcium channel blockers, captopril, digitalis glycosides, omeprazole, some antibiotics and growth hormone are all possibly, but less often, the responsible agent. Criteria of the French method for determining drug causality are discussed.     

Genomic association analysis suggests chromosome 12 locus influencing antihypertensive response to thiazide diuretic

We conducted a genome-wide association study to identify novel genes influencing diastolic blood pressure (BP) response to hydrochlorothiazide, a commonly prescribed thiazide diuretic preferred for the treatment of high BP. Affymetrix GeneChip Human Mapping 100K Arrays were used to measure single nucleotide polymorphisms across the 22 autosomes in 194 non-Hispanic black subjects and 195 non-Hispanic white subjects with essential hypertension selected from opposite tertiles of the race- and sex-specific distributions of age-adjusted diastolic BP response to hydrochlorothiazide (25 mg daily, PO, for 4 weeks). The black sample consisted of 97 "good" responders (diastolic BP response [mean+/-SD]=-18.3+/-4.2 mm Hg; age=47.1+/-6.1 years; 51.5% women) and 97 "poor" responders (diastolic BP response=-0.18+/-4.3; age=47.4+/-6.5 years; 51.5% women). Haplotype trend regression identified a region of chromosome 12q15 in which haplotypes constructed from 3 successive single nucleotide polymorphisms (rs317689, rs315135, and rs7297610) in proximity to lysozyme (LYZ), YEATS domain containing 4 (YEATS4), and fibroblast growth receptor substrate 2 (FRS2) were significantly associated with diastolic BP response (nominal P=2.39 x 10(-7); Bonferroni corrected P=0.024; simulated experiment-wise P=0.040). Genotyping of 35 additional single nucleotide polymorphisms selected to "tag" linkage disequilibrium blocks in these genes provided corroboration that variation in LYZ and YEATS4 was associated with diastolic BP response in a statistically independent data set of 291 black subjects and in the sample of 294 white subjects. These results support the use of genome-wide association analyses to identify novel genes influencing antihypertensive drug responses.     

Urinary complaints in nondisabled elderly people with age-related white matter changes: the Leukoaraiosis And DISability (LADIS) Study

OBJECTIVES: To investigate, in a cohort of nondisabled elderly people, the association between urinary complaints and severity of age‐related white matter changes (ARWMC). DESIGN: Cross‐sectional data analysis from a longitudinal multinational study. SETTING: The Leukoaraiosis And DISability Study, assessing ARWMC as an independent predictor of the transition from functional autonomy to disability in elderly subjects. PARTICIPANTS: Six hundred thirty‐nine subjects (288 men, 351 women, mean age 74.1±5.0) with magnetic resonance imaging (MRI)‐detected ARWMC of different severity. MEASUREMENTS: ARWMC severity was graded on MRI as mild, moderate, and severe (Fazekas scale). MRI assessment also included ARWMC volumetric analysis and the count of infarcts. Urinary complaints (nocturia, urinary frequency, urgency, incontinence) were recorded based on subjects' answers to four questions. RESULTS: In comparing the three ARWMC severity groups, there was a significant difference only in prevalence of urgency, with 16% of subjects in the mild severity group, 17% in the moderate severity group, and 25% in the severe group (P=.03). Adjusting for age, sex, lacunar and nonlacunar infarcts, diabetes mellitus, and use of diuretics, severe ARWMC retained an independent effect in the association with urinary urgency (odds ratio=1.74, 95% confidence interval=1.04–2.90, severe vs mild group). Subjects with urinary urgency also had higher ARWMC volumes (25.2, vs 20.4 mm³ in those without urinary urgency; P<.001). Urgency was confirmed to be associated with the severe degree of ARWMC, irrespective of complaints of memory, gait disturbances, or history of depression. CONCLUSION: In a cohort of nondisabled elderly people, severe ARWMC were associated with urinary urgency, independent of other potential confounders and vascular lesions of the brain.     

In vitro tests that predict tumor-associated idiotype levels in the serum of patients with B cell lymphomas and leukemias

The presence of circulating tumor idiotype interferes with the in vivo effectiveness of anti-idiotype antibodies. We developed two assays that permit identification of patients with high levels of serum idiotype without the need for first producing an anti-idiotype antibody. A cell suspension made from the tumor was cultured for seven days with or without phytohemagglutin (PHA) and/or phorbol myristic acetate (PMA). Ig secretion in vitro by patients' tumor cells varied. In 4 patients, no secretion in vitro occurred, 5 patients had low levels, and 5 patients had high levels of Ig secretion. In three patients, Ig secretion occurred only after stimulation with PHA, PMA, or both. Spontaneous or induced immunoglobulin secretion in vitro is related to the levels of tumor idiotype secretion that exist in vivo. Eight patients with serum idiotype levels greater than 100 micrograms/mL (mean 265 micrograms/mL), had a minimum of 1.0 microgram/10(6) cells of idiotype secretion in vitro. Nine patients with serum idiotype levels less than 30 micrograms/mL (mean 3.7 micrograms/mL), had less than or equal to 0.5 microgram/10(6) cells of idiotype secretion in vitro. In another assay, the levels of IgM kappa and IgM lambda in patients' sera were compared with those in normal serum. An imbalance in the relative amounts of IgM kappa and IgM lambda indicated high levels of circulating idiotype in the serum, but this assay was less sensitive than the in vitro secretion assay and limited to IgM-secreting tumors. These assays will be useful for future clinical studies using anti- idiotype antibodies.     

Validation of a new immunoblot assay (LiaTek HIV III) for confirmation of human immunodeficiency virus infection

BACKGROUND: Used as a supplemental assay, new anti-human immunodeficiency virus (HIV) immunoblots, employing recombinant and synthetic antigens, appeared to resolve the majority of samples with false-reactive Western blot results. Would it be possible to completely replace the Western blot by an immunoblot for confirmation and exclusion of HIV infection? STUDY DESIGN AND METHODS: The sensitivity of the new LiaTek HIV III immunoblot assay (Organon Teknika, Turnhout, Belgium) was tested on 416 Western-blot positive samples (386 HIV-1, 22 HIV-2, 1 HIV-1/2, and 7 HIV-O) and on 45 HIV-1 seroconversion samples. The specificity was tested on 146 samples from noninfected donors with false-positive results on a HIV screening test. RESULTS: All Western- blot-positive samples tested positive in the immunoblot (sensitivity: 100%). The immunoblot could not discriminate between HIV-1 and HIV-2 infection in 22 of 416 (5%) samples. The LiaTek assay showed reactivity in 28 of 45 seroconversion samples, whereas the Western blot reacted in 30 of 45 seroconversion samples. With false-positive donor samples, the immunoblot was indeterminate in 10 of 146 samples (specificity: 93%), and the Western blot was indeterminate in 44 of 146 samples (specificity: 70%). CONCLUSION: Like the Western blot, the immunoblot runs the risk of missing samples that are reactive by enzyme immunoassay during the early stage of HIV infection. Nevertheless, considering its superior specificity on false-positive donor samples, it appears that the immunoblot offers a cost-effective alternative to the Western blot assay for confirmation and exclusion of HIV infection.     

Do differences in baseline characteristics or in management account for the poorer in-hospital and subsequent outcome after myocardial infarction in diabetics? Data from a large unselected cohort

OBJECTIVE: There is an excess mortality after myocardial infarction in diabetics, but also documented significant differences in the characteristics of MI and in management between diabetics and non-diabetics. The aim of this prospective study in a large unselected patient cohort in a single French region was to determine if baseline characteristics, management, or in-hospital and one-year mortality differed in diabetic and non-diabetic patients with myocardial infarction. METHODS AND RESULTS: Data were prospectively collected in consecutive patients with myocardial infarction admitted to all hospitals in three departments in the Rhone-Alpes region between September 1, 1993 and January 31,1995. Among the 2,297 patients, 410 patients (17.8%) were diabetic. Although diabetics were older than non-diabetics (70.3 vs. 67.8 years; p < 0.0004), and less likely to receive thrombolysis (31% vs. 36%; p = 0.043), in-hospital mortality was not significantly higher (17.3% vs. 14.7%) than in non-diabetics. In multivariate analysis, diabetes was a significant predictor of one-year mortality (relative risk: 1.41; 95% CI = 1.10 - 1.79; p = 0.0063) but not of in-hospital mortality (relative risk: 1.2; 95% CI = 0.9 - 1.7; p = 0.25). Multivariate predictors of in-hospital and one-year mortality in diabetics were age and Killip class at admission. CONCLUSIONS: In this large unselected French cohort, diabetes mellitus was a significant predictor of one-year but not of in-hospital mortality after myocardial infarction in a French region.This negative effect of diabetes on mortality was not related to differences in baseline characteristics, or in initial or post-discharge management between diabetics and non-diabetics.     

Distal pancreatectomy for rectal metastatic adenocarcinoma 6 years after proctectomy

We report the case of a 77 year old man treated with a distal pancreatectomy for rectal metastatic cancer. Diagnosis was made based on increased CEA levels following excision of the rectal tumor discovered during treatment follow up of liver and pulmonary metastases. Eight months after pancreatectomy the patient was asymptomatic and CEA levels were normal. Pancreatic resection for metastatic colonic adenocarcinoma of the pancreas may be considered in selected patients without extrapancreatic disease. Long-term survival or good palliation may be achieved after surgery.