Influence of body mass index on measured and calculated androgen parameters in adult women with Hirsutism and PCOS.

There is growing evidence that obesity in women lead to a more severe form of hyperandrogenism and other endocrine abnormalities which may have some health implications later in life. Obese females are at higher risk for metabolic syndrome due to severe hyperandrogenemia. Calculated values for free testosterone are equivalent to those obtained by equilibrium dialysis, which is one of the reference measurement procedures (RMP) for estimation of free testosterone and may be capable of replacing values estimated using RMP's. For adult women correlations of body mass index (BMI) with calculated free (cFT) and bioavailable testosterone (cBT) are still rare, while these data are reported for peripubertal and adolescent girls. In this study we aimed to investigate the association between BMI and different androgen parameters (including calculated free and bioavailable testosterone, free androgen index, and sex hormone-binding globulin [SHBG]) in adult women with Hirsutism and with PCOS. In hirsute women with BMI > or = 25 kg/m2 measured total testosterone (TT) was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were significantly higher compared to women with BMI < 25 kg/m2. In PCOS women with BMI > or = 25 kg/m2 TT was significantly higher, SHBG was significantly lower and the calculated androgen parameter (FAI, cFT and cBT) were also significantly higher compared to women with BMI < 25 kg/m2. In both the Hirsutism and PCOS-group there was a positive correlation between BMI and TT, cFT, and cBT, while BMI was negatively correlated with SHBG. In summary, in adult women with Hirsutism and PCOS obesity is associated with increased levels of TT and decreased levels of SHBG resulting in significant elevated calculated free and bioavailable testosterone levels. Obesity might lead to a more severe form of hyperandrogenism with elevated calculated free and bioavailable testosterone in the study population.     

Low urine citrate excretion as main risk factor for recurrent calcium oxalate nephrolithiasis in males.

To better define the relative role of metabolic factors in the recurrence of stone formation, we studied the 24-hour urinary excretion of calcium (uCa), citrate (uCit), oxalic acid (uOx) and uric acid (uUa) in 73 male patients with primary calcium oxalate urolithiasis. According to the episodes of stone formation per year, we identified 51 recurrent stone formers (RSF) and 22 single stone formers (SSF). 20 normal adult males constituted the control group (C). uCa and uOx were higher in RSF than in C, but quite similar in SSF and RSF. The only difference between RSF and SSF was uCit, significantly lower (2.06 +/- 1.04 mmol/24 h) in RSF than in SSF (3.22 +/- 1.18 mmol/24 h, p less than 0.001) and in C (3.42 +/- 1.33 mmol/24 h, p less than 0.001). Hypocitraturia (uCit less than 1.5 mmol/24 h) was found in 16 of 51 RSF (31.4%) and in 1 of 22 SSF (4.5%). These data confirm that high levels of uCa and uOx represent a risk factor for lithogenesis, but also strongly indicate the low uCit excretion as the most important urinary abnormality accounting for the recurrence of calcium oxalate stones.     

In vivo measurements of fibrin formation and degradation in nephrotic patients

Summary Intraglomerular fibrin deposition has been implicated as an important pathogenetic mechanism in patients with glomerular diseases and the nephrotic syndrome. To investigate fibrin formation and degradation in nephrosis, we measured fibrinopeptide A by radio-immunoassay and D-dimer by enzyme-linked immunosorbent assay in the plasma of 30 consecutive adult patients with the nephrotic syndrome; in 10 the serum creatinine was more than 2 mg/dl. Both fibrinopeptide A and D-dimer were abnormally elevated in the majority of nephrotics (P<0.001 vs. healthy controls), providing evidence of increased fibrin generation and lysis “in vivo.” A positive correlation was found between fibrinopeptide A and D-dimer (correlation coefficient 0.64,P<0.001), suggesting a close relationship between fibrin formation and degradation. Calcium heparin, administered to 12 nephrotics, caused a marked decrease in plasma fibrinopeptide A, due to a reduction of in vivo thrombin activity. As enhanced thrombin activity can favor fibrin deposition within the renal parenchyma, as well as vascular complications, it is reasonable to assume that an antithrombotic treatment aimed at controlling thrombin generation may ameliorate the natural history of nephrosis.     

Ergebnisse des seletiven venösen Etagenkatheters (SVK) beim okkulten C-Zell-Karzinom der Schilddrüse

Background: Medullary thyroid carcinoma (MTC) can — even in recurrent cases — only be treated surgically. Therefore, preoperative localization of the tumor is essential.Methods: From April 1986 through April 1997, 137 patients with MTC were operated on at our clinic. In 22 patients with recurrent tumor which had not been radiologically localized, 28 selective venous catheterizations (SVC) with determination of calcitonin levels were carried out.Results: In 23 examinations a suspected tumor could be identified (nine cervical unilateral, seven mediastinal, four cervical unilateral and mediastinal, one cervical bilateral and mediastinal, one liver, one cervical unilateral and liver). In 18 cases surgery was performed for recurrence (nine cervical revisions, one mediastinal dissection, six cervicomediastinal dissections, two laparotomies). In 15 of 18 cases, tumor tissue was found in the previously suspected area. In ten cases serum calcitonin levels dropped postoperatively by 6%–75%. A normalization of the hormone level was achieved only once by yet another operation. During further follow-up, five of the reoperated patients died from their disease. The other 17 patients are being followed up, whereby calcitonin levels are elevated but there is no clinical or radiological evidence of tumor.Conclusions: Although in the patient cohort presented a normalization of serum calcitonin could be achieved only once, the authors consider SVC useful because it is the only means of localization of tumor tissue in cases of negative radiologic studies and therefore allows a planned approach to the operation procedure in these cases.     

Effects of Intramuscular Testosterone Undecanoate on Body Composition and Bone Mineral Density in Female-to-Male Transsexuals

IntroductionThe most common treatment regimen in female-to-male transsexuals is administration of short-acting testosterone esters intramuscularly every 2 weeks.AimThe aim of this study was to evaluate the effect of long-acting intramuscular testosterone undecanoate on body composition and bone mineral density during cross-sex hormone therapy in female-to-male transsexuals.MethodsForty-five female-to-male transsexuals (FtMs) were treated with injections of testosterone undecanoate 1,000 mg intramuscularly every 12 weeks over 24 months.Main Outcome MeasuresBody composition, bone mineral density, hormone parameters, and lipids were compared after 12 months and after 24 months with baseline values. Sonographic findings in the ovaries and endometrium, clinical and adverse effects during the study period were recorded.ResultsThere was a significant increase in lean mass in the FtMs during the study period in comparison with baseline values, whereas no change in BMI, fat mass, and bone mineral density was observed. There was a significant decline in gonadotropins, estradiol, dehydroepiandrosterone sulphate, sex hormone-binding globulin, and high-density lipoprotein, while testosterone and triglyceride levels increased significantly after 12 and 24 months. Ovaries remained unchanged and no noticeable endometrial pathology was observed. No mortality or morbidity was observed during the study period. We observed a cessation of menstrual bleeding, an increase in clitoral growth, libido, body and beard hair growth, deepened voices and decline in breast size. There was a significant increase in hemoglobin, hematocrit, glutamic-pyruvic transaminase, gamma-glutamyl transferase, and an increase in systolic blood pressure during the study period.ConclusionsThere was an increase in lean mass during the study period in FtMs treated with testosterone undecanoate. Transsexual patients should be monitored for adverse effects on lipid profiles, blood pressure, and erythrocytosis during intramuscular testosterone undecanoate therapy. Mueller A, Haeberle L, Zollver H, Claassen T, Kronawitter D, Oppelt PG, Cupisti S, Beckmann MW, and Dittrich R. Effects of intramuscular testosterone undecanoate on body composition and bone mineral density in female-to-male transsexuals.     

Effect of heparan sulphate on kidney tissue expression of TGF-beta,rhoA, laminin and fibronectin in subtotally nephrectomized rats

BACKGROUND: Different mitogens are involved in the pathogenesis of kidney damage after subtotal nephrectomy. One of them, TGF-beta, controls mesangial cell proliferation and interstitial fibrosclerosis. The transduction of the TGF-beta signal is controlled by intracellular signalling molecules such as Ras G monomeric proteins. Renal damage after subtotal nephrectomy (5/6 Nx) can be prevented by heparins, but so far no immunohistochemical correlation between TGF-beta, TGF-beta induced matrix molecules and Rho proteins has been investigated. Since the Ras transduction pathway has recently been associated with progression of renal damage, we evaluated the effect of heparan sulphate (HS) on the expression of TGF-beta, laminin, fibronectin and a Ras protein, RhoA, in the rat remnant kidney model. METHODS: The immunoperoxidase technique was employed to reveal the antigens on 18 remnant kidneys from 5/6 nephrectomized rats, nine untreated and nine treated with oral HS, and on seven normal kidneys from sham-operated rats. Data were semiquantitatively analyzed by an image analyzer (Quantimet, Leica). RESULTS: The expression of the antigens was significantly higher in the remnant kidneys than in normals. The high TGF-beta, laminin, fibronectin and RhoA expression observed in subtotally nephrectomized rats suggests a role for these molecules in the pathogenesis of progressive renal damage. However, apart from RhoA, HS-treated rats had significantly lower levels of the antigens than the untreated rats. CONCLUSIONS: HS treatment is associated with significantly lower renal expression of TGF-beta, laminin and fibronectin, but not of RhoA. This suggests that the renal-protective effect of HS may be obtained by modulating the TGF-beta pathway, independently of RhoA-mediated transduction.     

Endothelial dysfunction and oxidative stress in chronic renal failure

Uremic patients have an increased incidence of cardiovascular disease (CVD), endothelial dysfunction and oxidative stress that can contribute to cardiovascular (CV) events. To assess the relationship between endothelial dysfunction, oxidative stress and renal failure severity, we studied 40 patients (age 57 +/- 7 yrs, 24 males) affected by chronic kidney disease (CKD) K/DOQI stage 3-5 (serum creatinine (Cr) 5.6 +/- 2.2 mg/dL) on conservative treatment, 20 uremic patients (age 57 +/- 12 yrs, 13 males) on hemodialysis (HD) and 30 healthy controls (56 +/- 12 yrs, 20 males). Before and 2 hr after oral vitamin C (2 g) administration, we measured brachial artery endothelium-dependent vasodilation (flow mediated dilation (FMD)) to reactive hyperemia following 5 min of forearm ischemia and the response to sublingual glyceril trinitrate (GTN). Measurements were made by high-resolution ultrasound and computerized analysis. FMD was lower in CKD patients than in controls (5.3 +/- 2.2 vs. 6.9 +/- 2.8%; p<0.01) and was further reduced in HD patients (3.6 +/- 2.7; p<0.01 vs. CKD patients). Response to GTN was similar in all groups. FMD was related to Cr clearance (r=0.42; p<0.01) in CKD patients, while it related inversely to Kt/V(urea) (r=-0.52; p<0.05) in HD patients. After vitamin C administration, FMD was significantly enhanced in HD (4.7 +/- 2.4%; p<0.01 vs. baseline), but not in CKD patients. Response to GTN was unaffected. However, vitamin C load reduced oxidative stress markers, and increased plasma antioxidant capability in both groups. In conclusion, the reduced endothelium-dependent dilation in the brachial artery of CKD patients is related to renal failure severity. HD patients showed a more marked alteration, which seems to be related, at least in part, to increased oxidative stress.     

Ultrasonic tissue characterization of the myocardium in anorexia nervosa

AIM: To determine the systodiastolic variations in the integrated backscatter (IBS) signal of the myocardium in patients with anorexia nervosa. METHODS: 25 young women (aged 22.4 +/- 4.3 y) with overt anorexia nervosa, compared with 25 age-matched thin and 25 age-matched control women with body mass index >20 kg m(-2), underwent either conventional two-dimensional echocardiography or analysis of IBS cyclic variations. RESULTS: Compared with thin and control subjects, anorectic patients showed reduced left ventricular mass (LVM: 82.9 +/- 17.1 vs 119.9 +/- 13.8 and vs 126.12 +/- 16.4 g, p < 0.0001; LVM indexed 21.4 +/- 3.3 vs 29.4 +/- 2.5 and vs 31.2 +/- 3.1 g m(-2.7), p < 0.0001), and IBS cyclic variations (septum: -0.49 +/- 2.18 vs 6.86 +/- 1.3 and vs 6.61 +/- 1.74 dB p < 0.0001; posterior wall: 2.77 +/- 2.12 vs 7.15 +/- 2.12 and vs 7.48 +/- 2.23 dB, p < 0.01). CONCLUSION: Anorexia nervosa is associated with a significant reduction in the cyclic variation in IBS, which is also related to left ventricular hypotrophy. Ultrasonic tissue characterization could give an objective approach for the detection of myocardial structural properties and represent a preclinical index of myocardial dysfunction in anorexia nervosa.     

Sequential FISH analysis of oocytes and polar bodies reveals aneuploidy mechanisms

OBJECTIVES: Constitutional aneuploidy occurs in at least 5% of recognised pregnancies, with apparent preferential involvement of the X chromosome and the smaller autosomes. Molecular cytogenetic investigations of cleavage-stage embryos have revealed anomalies affecting all sizes of chromosomes. The aim was to investigate the variety of anomalies arising during maternal meiosis I by analysis of unfertilised oocytes and polar bodies to gain insight into aneuploidy mechanisms. METHODS: Sequential FISH analysis was carried out with specific probes derived from eight chromosomes, representing all sizes. Only imbalance due to a gain of a whole chromosome or chromatid, represented by extra signals, was counted to avoid artefact. RESULTS: Data were obtained on 236 eggs from 124 patients of average age 32.5 years (range 22-44). Ten patients (average 32.6 years) had abnormal eggs. The abnormality rate for oocytes and for polar bodies was close to 4% for each. Fourteen hyperploidies were found, seven involving additional single chromatids. The abnormalities affected chromosomes 13,16,18, 21 and X but not chromosomes 1, 9 or 12. CONCLUSION: The data provide evidence for several mechanisms leading to aneuploidy, including classical non-disjunction of whole univalents; pre-division of chromatids prior to anaphase I, leading to imbalance detected at metaphase II; gonadal mosaicism for a trisomic cell line and preferential involvement of the smaller chromosomes. Monosomy for the large autosomes is not uncommon in cleavage-stage embryos and may additionally arise from anaphase lag preferentially affecting such chromosomes.     

QT interval dispersion in young women with anorexia nervosa

OBJECTIVES: To evaluate the degree of QT dispersion in a group of young women in the starvation phase of anorexia nervosa (AN) and its relation to left ventricular (LV) mass. STUDY DESIGN: Sixteen patients with self-induced starvation were matched with 16 women of normal weight and 16 constitutionally thin women (body mass index <20 kg/m2). Starving patients and control patients underwent an electrocardiogram and echocardiogram. QT intervals were measured from surface electrocardiograms and QT dispersion was defined as the difference between maximum QT and minimum QT occurring in any of the 12 leads. RESULTS: LV-chamber mass was significantly less in women with AN than in thin and normal-weight women. QT dispersion was significantly greater in AN than in the thin and control groups (QT dispersion: 50 +/- 14 vs 34 +/- 9 and 37 +/- 11 ms, P <.001; QT interval dispersion corrected for heart rate: 49+12 vs 34 +/- 9 and 36 +/- 7 ms, P <.01, respectively). A significant relation between QT dispersion and LV-mass index (r = -0.726, P <.01), and between QTc dispersion and LV mass index (r = -0.693, P < 0.01) were found only in the patients with AN. CONCLUSION: Starving patients show an increased QT dispersion related to reduced LV mass. This result could represent a useful indicator of arrhythmic risk and sudden death in AN.