Serum androgen dynamics in young women aged 18-40 treated with chemotherapy for breast cancer: an observational, multicentric, prospective study in France.

Although the deleterious impact of chemotherapy regimen used to treat women of reproductive age with breast cancer on ovarian reserve has been extensively studied, hardly anything has been reported on the effect of these protocols on theca cell function and ovarian androgen secretion. The aim of this prospective multicentric cohort study was to describe serum levels of total testosterone and androstenedione during chemotherapy and 24-month follow-up in 250 patients <40 years treated for breast cancer. Mean basal levels of androstenedione and total testosterone at diagnosis were 1.68 ng/mL and 0.20 ng/mL respectively. No correlation with age was found. Serum levels of androstenedione and total testosterone rapidly decreased after chemotherapy completion, before slowly increasing and almost returning to basal levels in all patients during 2-year follow-up. In conclusion our study demonstrates a chemotherapy-induced alteration of ovarian thecal function, resulting in a significant decrease in serum androgen levels. This alteration of theca cell function adds to the well-known alteration of granulosa cell function, resulting in a global, but partly transient, ovarian failure in young women treated for breast cancer. These data bring new insight into ovarian physiology and emphasize the need for pre and post-treatment ovarian follow-up. Trial registration: ClinicalTrial.gov identifier NCT01114464.

[Check-list "Patient Safety" in the operating room: one year experience of 40,000 surgical procedures at the university hospital of Nice]. / Check-list "Sécurité du patient au bloc opératoire": une année d'expérience sur 40 000 interventions au centre hospitalier universitaire de Nice.

OBJECTIVES: The implementation of the check-list "Safe surgery saves live" (CL) has proven effective to reduce morbidity and perioperative mortality. Since 1st January 2010 it is a requirement of the HAS as part of the process of certification of hospitals. The CL has been established on all the operating rooms of our hospital after the onset of a near accident. METHODS: The CL has been computerized to facilitate its adoption by professionals. An internal benchmarking was immediately implemented to allow each surgical specialty to benchmark themselves with other teams. We conducted an audit concerning the CL and periodic assessments in order to learn more precisely concerning the expectations and feelings of medical and nursing teams. RESULTS: Nearly 40 000 CL were collected in the patient record. The completeness of information of some items seems to reflect the difficulty for professionals to realize the difference between traceability and information sharing within the team on the implementation of a protocol. This audit has confirmed the difficulty in sharing information orally. CONCLUSIONS: The CL is involved in developing a safety culture in the operating room and led to the establishment of a risk mapping in the operating room and the recovery room and participation in the program error prevention procedure and surgical site through international program "High 5s" whose purpose is to improve the safety of care.

Anti-mullerian hormone: clinical relevance in assisted reproductive therapy.

Anti-Müllerian Hormone (AMH) is a member of the transforming Growth Factor-B (TGF-B) family synthesized exclusively by the gonads of both sexes. Over the last four years, numerous studies have examined the clinical usefulness of serum AMH levels as a predictor of ovarian response and pregnancy in assisted reproductive technology cycles. Assessment of ovarian reserve in women undergoing assisted reproduction is useful in optimising the treatment protocol. Availability of a reliable measure of ovarian reserve is essential. Currently, serum AMH level seems to be more strongly related to the ovarian reserve and to be a more discriminatory marker of assisted reproductive technology outcome than follicle-stimulating hormone, inhibin B or estradiol, which are more commonly used markers. Our study involving 69 women undergoing a cycle of in vitro fertilisation (IVF) or intracytoplamic sperm injection (ICSI) treatment, confirmed these results. We have shown in this study that AMH is significantly correlated with the number of eggs collected and is of great interest as a negative predictive value for the success of assisted reproductive technology (ART). Further studies are needed to determine AMH cut-off values.

IGFBP-1 inhibits EGF mitogenic activity in cultured endometrial stromal cells.

The properties of the insulin-like growth factor-binding proteins (IGFBP-1 to 6) are not limited to modulation of IGF actions. IGFBP-1, which shares an Arg-Gly-Asp (RGD) motif in its C-terminal domain, modulates cell motility by binding to integrin alpha5beta1. The cross-talks between integrins and growth factor receptor signalling pathways are extensively documented, particularly in the case of the epidermal growth factor receptor (EGFR). However, whether IGFBP-1 can modulate growth factor signalling through its interaction with integrin alpha5beta1 has not yet been studied. As EGF is involved in the decidualisation of endometrial stromal cells (ESCs) and as decidualised ESCs are a source of IGFBP-1, we investigated if IGFBP-1 can modulate EGF effects on ESCs. RGD- and IGF-independent inhibition of EGF mitogenic activity and EGFR signalling by IGFBP-1 were demonstrated in ESC primary cultures, A431, cells and in mouse fibroblasts lacking IGF receptors.

Simultaneous infection with multiple strains of Mycobacterium tuberculosis.

Drug-susceptible and drug-resistant isolates of Mycobacterium tuberculosis were recovered from 2 patients, 1 with isoniazid-resistant tuberculosis (patient 1) and another with multidrug-resistant tuberculosis (patient 2). An investigation included patient interviews, record reviews, and genotyping of isolates. Both patients worked in a medical-waste processing plant. Transmission from waste was responsible for at least the multidrug-resistant infection. We found no evidence that specimens were switched or that cross-contamination of cultures occurred. For patient 1, susceptible and isoniazid-resistant isolates, collected 15 days apart, had 21 and 19 restriction fragments containing IS6110, 18 of which were common to both. For patient 2, a single isolate contained both drug-susceptible and multidrug-resistant colonies, demonstrating 10 and 11 different restriction fragments, respectively. These observations indicate that simultaneous infections with multiple strains of M. tuberculosis occur in immunocompetent hosts and may be responsible for conflicting drug-susceptibility results, though the circumstances of infections in these cases may have been unusual.

Two methods of estimating health costs linked to alcoholism in France (with a note on social costs).

The health costs of alcohol-related problems in France were estimated using two cost evaluation approaches: (1) estimate based on the proportion of cases attributable to alcohol abuse (the alcohol abuse factor); (2) estimate based on prevalence of alcohol abuse for in- and out-patients. For a 10% prevalence of alcohol abuse in the general population, the minimum cost in 1996 was about US$ 2300 million; for a prevalence of 15% it was US$ 2700 million. This cost concerns the health disorders that are linked directly or indirectly to alcohol abuse. It did not allow for injuries from accidents caused by alcohol intoxication and undervalued the cost of out-patient care. Based on the prevalence of alcohol-related disorders seen at hospitals, a percentage of the total in-patient and out-patient costs due to effects of alcohol could be estimated. However, this did not permit an estimate of the cost of care in which alcohol abuse was a risk factor only. Based on the available data showing that between 3% and 10% of inpatients have a directly alcohol-related condition, estimates of in-patient treatment costs varied from US$ 1300 to 2100 million. Among adult out-patients, 20% present with a disorder in which alcohol is a factor or suffer from an alcohol-related illness, which corresponds to a cost of about US$ 1600 million. Thus, these methods yield minimum year's cost estimated between US$ 2500 and 3300 million. These costs are high, compared to the low level of financing for the specialized facilities offering treatment to people in difficulty due to alcohol excess, which was US$ 23 million in that year. As regards social and total costs, estimates from four Western countries have found that about 75% of the total costs of alcohol abuse was attributable to social harm, and 25% to medical costs. Applying this ratio to the French data gives an estimated total cost to French society of about US$ 13 200 million, i.e. 1.04% of the gross national product.

Transmission of Mycobacterium tuberculosis from medical waste.

CONTEXT: Washington State has a relatively low incidence rate of tuberculosis (TB) infection. However, from May to September 1997, 3 cases of pulmonary TB were reported among medical waste treatment workers at 1 facility in Washington. There is no previous documentation of Mycobacterium tuberculosis transmission as a result of processing medical waste. OBJECTIVE: To identify the source(s) of these 3 TB infections. DESIGN, SETTING, AND PARTICIPANTS: Interviews of the 3 infected patient-workers and their contacts, review of patient-worker medical records and the state TB registry, and collection of all multidrug-resistant TB (MDR-TB) isolates identified after January 1, 1995, from the facility's catchment area; DNA fingerprinting of all isolates; polymerase chain reaction and automated DNA sequencing to determine genetic mutations associated with drug resistance; and occupational safety and environmental evaluations of the facility. MAIN OUTCOME MEASURES: Previous exposures of patient-workers to TB; verification of patient-worker tuberculin skin test histories; identification of other cases of TB in the community and at the facility; drug susceptibility of patient-worker isolates; and potential for worker exposure to live M tuberculosis cultures. RESULTS: All 3 patient-workers were younger than 55 years, were born in the United States, and reported no known exposures to TB. We did not identify other TB cases. The 3 patient-workers' isolates had different DNA fingerprints. One of 10 MDR-TB catchment-area isolates matched an MDR-TB patient-worker isolate by DNA fingerprint pattern. DNA sequencing demonstrated the same rare mutation in these isolates. There was no evidence of personal contact between these 2 individuals. The laboratory that initially processed the matching isolate sent contaminated waste to the treatment facility. The facility accepted contaminated medical waste where it was shredded, blown, compacted, and finally deactivated. Equipment failures, insufficient employee training, and respiratory protective equipment inadequacies were identified at the facility. CONCLUSION: Processing contaminated medical waste resulted in transmission of M tuberculosis to at least 1 medical waste treatment facility worker. JAMA. 2000;284:1683-1688.

[Estimation of health care cost for alcoholism in France: advantages and limitations of two evaluation methods]. / Estimation du coût sanitaire de l'alcoolisme en France: intérêts et limites de deux méthodes d'évaluation.

TWO CALCULATION SCHEMES: We estimated the cost of health care related to alcoholism using two different medicoeconomic approaches. PREVALENCE OF ALCOHOLISM: Corresponding costs of alcohol-related conditions can be calculated from the prevalence of alcoholism in hospitalized and ambulatory patients. It is however impossible to calculate the alcohol-related cost, even for heavy drinkers, when alcohol is involved as a risk factor. METHOD ONE: For a 10% prevalence of excessive alcohol intake in the general population, the minimal cost in 1996 would be approximately 14 billion francs ($2.2 billion). For a 15% prevalence, it would reach 16 billion ($2.6 billion). This cost only concerns diseases directly or indirectly related to alcoholism. The estimated hospital cost of diseases directly related to alcoholism, that is alcoholic dependence and psychosis, cirrhosis, and upper airway-digestive cancers, reaches 6 to 6.5 billion francs ($1-$1.03 billion) respectively for a 10 or 15% prevalence. Total costs (hospital and ambulatory costs) are between 6.4 and 6.9 billion francs ($1.02-$1.04 billion). For diseases where alcohol is only a risk factor, the minimal cost varies between 7.5 and 9.5 billion francs ($1.20-$1.51 billion). METHOD TWO: With this method, the minimal total cost is to the order of 20 billion francs ($3.75 billion) with half being hospital costs and half ambulatory costs. This cost only concerns alcohol in overt disease states. Costs related to alcohol as a risk factor are not included in this estimation as there is no known coefficient for attribution. HIGH COST OF ALCOHOLISM: Both of our methods used a minimizing estimation scheme and found total costs to lie in the range of 15 ñ 20 billion francs ($2.38-$3.75 billion). Extrapolating from studies conducted in other countries where social costs amounted to 75% of total costs, it can be considered that alcoholism in France costs more than 80 billion francs ($12.7 billion) a figure exceeding 1% of the GNP.

Improvement of blood glucose control in Type 1 diabetic patients treated with lispro and multiple NPH injections.

AIMS: To evaluate a multiple daily injections (MDI) regimen combining lispro with multiple NPH insulin injections in order to replace basal insulin optimally. METHODS: Twenty-five C-peptide negative Type 1 patients already trained to MDI were randomized to lispro (lispro + NPH 5 min before breakfast and lunch, lispro before dinner, NPH at bedtime) or soluble insulin (20-30 min before each meal and NPH at bed-time) for 3 months before crossing over to the other regimen for another 3 months. The mean initial HbA1c level was 8.32+/-1.5%. RESULTS: The variability of capillary blood glucose values was significantly lower with lispro (MAGE 0.75+/-0.36 g/l vs. 0.99+/-0.50, P<0.01; MODD 0.64+/-0.26 g/l vs. 0.80+/-0.40, P<0.05). There was a nonsignificant reduction in HbA1c with lispro: -0.40+/-0.86 vs. -0.08+/-0.71. Mean daily blood glucose levels were significantly lower with lispro (1.53+/-0.48 g/l vs. 1.82+/-0.57 g/l, P<0.05). The frequency of all hypoglycaemic episodes was the same with both regimens but the number of severe hypoglycaemic events was reduced with lispro, P = 0.048. At the end of the study, 75% of the patients chose the lispro associated with multiple NPH regimen for their own treatment. The total insulin doses was the same with both regimens but the proportion of NPH was higher with lispro (53% vs. 34%). CONCLUSIONS: An MDI regimen using lispro combined with multiple NPH compared to a standard MDI regimen using soluble insulin reduced day-to-day blood glucose fluctuations, was generally preferred by patients and was associated with a reduced incidence of severe hypoglycaemia with no loss of overall control.

Weight gain and cardiovascular risk factors in the post-menopausal women.

Cardiovascular disease is the leading cause of mortality and morbidity in the post-menopausal woman. The natural menopause does not appear to be an independent risk factor (or a minor one) for coronary heart disease. Obesity, more precisely excessive intra-abdominal fat, is a cardiovascular risk factor especially with regard to the metabolic risk factors associated with this type of obesity. There is a progressive increase in weight gain at the age of menopause but this weight gain is related to ageing independent of whether women are post-menopausal or not, or treated with oestrogens or not. At the same time, there is a central redistribution of fat with a decrease in gluteo--femoral fat and an increase in intra-abdominal fat with an associated muscle mass loss. This trend to central obesity obviously favours an increased cardiovascular risk. With regard to weight gain, these changes in body composition are related to ageing. Different factors (e.g., diet, physical activity, GH secretion, etc.) may be involved. Are these changes related to menopause? Can hormonal replacement therapy prevent them? The results of the studies in this field are not consistent and these questions remain under debate.