Hormonal profile in women with polycystic ovarian syndrome with or without type 1 diabetes mellitus

CONTEXT: Anti-Müllerian hormone (AMH) levels are increased in polycystic ovarian syndrome (PCOS), but it is not known whether other forms of hyperandrogenism, such as PCOS observed in women with type 1 diabetes mellitus (DM1), are also associated with elevated AMH levels. OBJECTIVE: Our objective was to compare AMH and steroid levels in women with PCOS with and without DM1. DESIGN: We compared the clinical, hormonal, and ultrasonographic characteristics of 17 women with PCOS and DM1 (DM1+PCOS), 20 women with PCOS without DM1 (PCOS), and 35 normal women (control) in a cross-sectional study. RESULTS: The Ferriman-Gallwey score, serum testosterone, free androgen index, 17OH-progesterone, and ovarian volume were elevated in both groups of PCOS women compared with controls. Serum androstenedione, LH/FSH ratio, and follicle number, however, were higher and SHBG was lower in PCOS compared with DM1+PCOS and controls. AMH levels were higher in PCOS (76.0 +/- 36.3 pmol/liter) than in DM1+PCOS (18.8 +/- 7.4 pmol/liter) and controls (13.9 +/- 8.3 pmol/liter). AMH levels correlated with follicle number in the three groups. Serum AMH/follicle number ratio was higher in PCOS than in DM1+PCOS and controls. CONCLUSIONS: Women with DM1+PCOS have normal levels of AMH, inhibin B, estradiol, SHBG, and LH/FSH, suggesting that the pathophysiology of hyperandrogenism in PCOS patients with DM1 appears to be different from that in PCOS without DM1. However, hirsutism score and androgen levels were similar in both groups of women with PCOS. We postulate that insulin treatment acts as a co-gonadotropin increasing follicle recruitment, hence not increasing AMH levels.     

The oncology acute toxicity unit (OATU): an outpatient facility for improving the management of chemotherapy toxicity

Objective To provide an outpatient facility to improve the management of chemotherapy toxicity in cancer patients. Patients and methods We set up an oncology acute toxicity unit (OATU) to improve toxicity management. A telephone helpline was the initial contact which filters out inappropriate non-toxicity-related events. Patients were provided an information booklet describing the possible side effects of the chemotherapy and the helpline telephone number. A specialist nurse received the calls and consulted the doctor if necessary. Depending on requirements, the patient’s problem was resolved by telephone, or a consultation visit at the OATU was arranged. Results Between February 1999 and August 2001, 1126 patients made 2007 contacts with the OATU. The most common tumours were breast (26%), colorectal (20%) and lung (20%). The telephone helpline was used in 87% of contacts and 37% were considered inappropriate. Of the 1263 appropriate contacts, the most frequent chemotherapy schedules that had been administered were 5FU-leucovorin (11.2%) and CMF (10.4%). The most frequent side effects were fever (35.5%), diarrhoea (18.5%), mucositis (16.2%) and emesis (13%). The problem was resolved by telephone in 48% of cases and 52% required attendance in the OATU, of which 40% required hospital admission, i.e., 21.1% of the initial appropriate helpline contacts. The most frequent reason was Grade 3–4 neutropenic fever (56.5%). Conclusions The OATU enables prompt and efficient access of patients to medical oncology facilities in the event of toxicity due to chemotherapy. Unnecessary emergency room use is avoided while oncology outpatient and hospitalisation facilities are optimised.     

Effects of <Emphasis Type="Italic">S</Emphasis>-Nitrosoglutathione on Electrophysiological Manifestations of Mechanoelectric Feedback

Electromechanical coupling studies have described the intervention of nitric oxide and S-nitrosylation processes in Ca²⁺ release induced by stretch, with heterogeneous findings. On the other hand, ion channel function activated by stretch is influenced by nitric oxide, and concentration-dependent biphasic effects upon several cellular functions have been described. The present study uses isolated and perfused rabbit hearts to investigate the changes in mechanoelectric feedback produced by two different concentrations of the nitric oxide carrier S-nitrosoglutathione. Epicardial multielectrodes were used to record myocardial activation at baseline and during and after left ventricular free wall stretch using an intraventricular device. Three experimental series were studied: (a) control (n?=?10); (b) S-nitrosoglutathione 10 µM (n?=?11); and (c) S-nitrosoglutathione 50 µM (n?=?11). The changes in ventricular fibrillation (VF) pattern induced by stretch were analyzed and compared. S-nitrosoglutathione 10 µM did not modify VF at baseline, but attenuated acceleration of the arrhythmia (15.6?±?1.7 vs. 21.3?±?3.8 Hz; p?<?0.0001) and reduction of percentile 5 of the activation intervals (42?±?3 vs. 38?±?4 ms; p?<?0.05) induced by stretch. In contrast, at baseline using the 50 µM concentration, percentile 5 was shortened (38?±?6 vs. 52?±?10 ms; p?<?0.005) and the complexity index increased (1.77?±?0.18 vs. 1.27?±?0.13; p?<?0.0001). The greatest complexity indices (1.84?±?0.17; p?<?0.05) were obtained during stretch in this series. S-nitrosoglutathione 10 µM attenuates the effects of mechanoelectric feedback, while at a concentration of 50 µM the drug alters the baseline VF pattern and accentuates the increase in complexity of the arrhythmia induced by myocardial stretch.     

Concentration of adipogenic and proinflammatory cytokines in the bone marrow supernatant fluid of osteoporotic women

Osteoporosis is characterized by low bone mass, microarchitectural deterioration of bone tissue leading to increased bone fragility, and a resulting susceptibility to fractures. Distinctive environmental bone marrow conditions appear to support the development and maintenance of the unbalance between bone resorption and bone formation; these complex bone marrow circumstances would be reflected in the fluid surrounding bone marrow cells. The content of regulatory molecules in the extracellular fluid from the human bone marrow is practically unknown. Since the content of cytokines such as adiponectin, leptin, osteoprogeterin (OPG), soluble receptor activator of nuclear factor κB ligand (s‐RANKL), tumor necrosis factor α, and interleukin 6 (IL‐6) may elicit conditions promoting or sustaining osteoporosis, in this work we compared the concentrations of the above‐mentioned cytokines and also the level of the soluble receptors for both IL‐6 and leptin in the extracellular fluid from the bone marrow of nonosteoporotic and osteoporotic human donors. A supernatant fluid (bone marrow supernatant fluid [BMSF]) was obtained after spinning the aspirated bone marrow samples; donors were classified as nonosteoporotic or osteoporotic after dual‐energy X‐ray absorptiometry (DXA) measuring. Specific commercially available kits were used for all measurements. The cytokines' concentration in BMSF showed differently among nonosteoporotic and osteoporotic women; this last group was characterized by higher content of proinflammatory and adipogenic cytokines. Also, osteoporotic BMSF differentiated by decreased leptin bioavailability, suggesting that insufficient leptin action may distinguish the osteoporotic bone marrow. © 2010 American Society for Bone and Mineral Research     

Nitric Oxide-Mediated Toxicity in Paraquat-Exposed SH-SY5Y Cells: A Protective Role of 7-Nitroindazole

The precise mechanism underlying the role of nitric oxide (NO) or nitric oxide synthases (NOSs) in paraquat-mediated toxicity is yet to be fully elucidated. The importance of the NADPH-diaphorase activity of NOSs in paraquat toxicity, in addition to the production of NO, has previously been reported as a mechanism of toxicity. However, other studies have highlighted the toxicity of NO alone and, conversely a protective role of NO in paraquat-mediated toxicity has also been described. The goal of this study was to clarify the involvement of NO and NOS in paraquat-mediated toxicity in an SH-SY5Y cell system, and to evaluate the putative role of 7-nitroindazole as a protective agent in human neural cells. Our results indicate that the three previously described isoforms of NOS are expressed in SH-SY5Y cells, with the data showing that these synthases act as paraquat diaphorases. While this process could occur at the expense of NO production, NO alone does play a toxic role, with its production leading to the formation of the toxicant peroxynitrite. Although the efficacies of the different inhibitors tested cannot be directly compared because the various NOS forms were probably inhibited to differing extents, the results support the idea that endogenous and inducible NO is a neurotoxic mediator of the effects of paraquat. The NADPH-diaphorase activity of NOS and NO production are therefore factors implicated in the toxicity mediated by the herbicide paraquat.     

Tratamiento radioterápico exclusivo en el carcinoma del pabellón auricular. Análisis de una serie de 104 casos

We assessed the role of the radiation therapy as the exclusive treatment of the epithelial tumours of the pinna, evaluating the control disease, the rate of late complications and the cosmetic results. One hundred and four patients with epidermoid carcinoma of the pinna and radical treatment with radiotherapy were analyzed retrospectively. 53 (51%) were squamous cell carcinoma and 51 (49%) basocelular carcinoma. Classification according to tumours size was as follows: ≤1 cm, 22 (21.2%); 1–2 cm, 47 (45.2%); 2–3 cm, 19 (18.3%), and >3 cm, 11 (10.6%). Eighty eight patients (84.6%) were treated with⁶⁰Co, 15 (14.4%) with ortovoltage and one patient with 9 MeV electron. The median follow up is 55 month (14–257). The local control, complication like condritis, condronecrosis and audition damage, and the cosmetic result were the factors analyzed. The 5 and 10 years actuarial local control rate is 89.8% and 87.6%, respectively. In an univariate analysis including variables like size, localization, histologic type, differentiation grade, energy type, irradiation technique, doses and response to treatment, the bad prognostic factors regarding to local control, were found to be the size (>3 cm) (p=0.013), localization (posterior sulcus) (p=0.012) and response to treatment (not complete) (p=0.046). In a multivariate analysis only the size showed this tendency (p=0.05). After the intent of rescue in the 11 patients that failed locally, the final local control rate was 95.19% (99/104). Four patients with squamous cell carcinoma had nodal regional recurrence, which didn't occur in the patients with basocelular carcinoma. Eight (7.7%) patients presented some degree of condritis, which was resolved medically in all the cases except one patient that evolved to condronecrosis. The cosmetic results in the 76 patients evaluated was excellent in 53 (69.7%) and acceptable in 12 (22.6%). Radiotherapy is recommended for treatment of the epithelial tumour of the pinna, mainly in tumors less than 3 cm, getting local control rate similar to surgery but avoiding its cosmetic and functional sequelae.     

Quercetin and naringenin reduce abnormal development of mouse embryos produced by hydroxyurea

Objectives There is limited evidence about the impact of quercetin and naringenin on embryonic development. The purpose of this work was to evaluate in vitro their direct teratogenic potential as well as their protective activity against teratogenesis mediated by oxidative damage on mouse embryos. Methods Quercetin and naringenin toxicity on whole mouse cultured embryos, as well as their ability to protect embryos against hydroxyurea‐induced insult were evaluated. Key findings Quercetin 100 µm and naringenin 300 µm produced significant reduction of developmental and growth parameters, in comparison with those of the control group. Embryos exposed to the concurrent administration of quercetin or naringenin with hydroxyurea (2 µm , 2 h) were significantly protected from growth and developmental retardation, and abnormalities induced by hydroxyurea. Interestingly, embryos exposed to hydroxyurea and dimethyl sulfoxide 0.1%, the vehicle employed to dissolve flavonoids, also showed significant damage amelioration. Conclusions These results indicate that quercetin and naringenin have not only a minor toxic effect on development, but also a protective effect against hydroxyurea‐induced embryonic damage.     

Radioimmune imaging of bone marrow in patients with suspected bone metastases from primary breast cancer

Radioimmune imaging of bone marrow was performed by technetium-99m- (99mTc) labeled antigranulocyte monoclonal antibody BW 250/183 (AGMoAb) scans in 32 patients with suspected bone metastases from primary breast cancer. AGMoAb scans showed bone marrow defects in 25/32 (78%) patients; bone invasion was subsequently confirmed in 23 (72%) patients. Conventional bone scans performed within the same week detected bone metastases in 17/32 (53%) patients (p less than 0.001). AGMoAb scans detected more sites indicating metastatic disease than bone scans in 12 of these 17 patients (71%). All patients with bone metastases in the axial skeleton had bone marrow defects at least at the sites of bone metastases. Of 15 patients with normal, or indicative of, benign disease bone scans, 8 patients (53%) presented with bone marrow defects in the AGMoAb scans. Bone invasion was confirmed in six of them. AGMoAb bone marrow scans provide a method for the early detection of bone metastatic invasion in patients with breast cancer and suspected bone metastases.     

Quantitative morphometry of electrophysiologically identified CA3b interneurons reveals robust local geometry and distinct cell classes

The morphological and electrophysiological diversity of inhibitory cells in hippocampal area CA3 may underlie specific computational roles and is not yet fully elucidated. In particular, interneurons with somata in strata radiatum (R) and lacunosum‐moleculare (L‐M) receive converging stimulation from the dentate gyrus and entorhinal cortex as well as within CA3. Although these cells express different forms of synaptic plasticity, their axonal trees and connectivity are still largely unknown. We investigated the branching and spatial patterns, plus the membrane and synaptic properties, of rat CA3b R and L‐M interneurons digitally reconstructed after intracellular labeling. We found considerable variability within but no difference between the two layers, and no correlation between morphological and biophysical properties. Nevertheless, two cell types were identified based on the number of dendritic bifurcations, with significantly different anatomical and electrophysiological features. Axons generally branched an order of magnitude more than dendrites. However, interneurons on both sides of the R/L‐M boundary revealed surprisingly modular axodendritic arborizations with consistently uniform local branch geometry. Both axons and dendrites followed a lamellar organization, and axons displayed a spatial preference toward the fissure. Moreover, only a small fraction of the axonal arbor extended to the outer portion of the invaded volume, and tended to return toward the proximal region. In contrast, dendritic trees demonstrated more limited but isotropic volume occupancy. These results suggest a role of predominantly local feedforward and lateral inhibitory control for both R and L‐M interneurons. Such a role may be essential to balance the extensive recurrent excitation of area CA3 underlying hippocampal autoassociative memory function. J. Comp. Neurol. 515:677–695, 2009. © 2009 Wiley‐Liss, Inc.