Bone turnover in postmenopausal women after withdrawal of estrogen/gestagen replacement therapy

Bone turnover before and after withdrawal of estrogen/gestagen treatment was studied in a randomized trial with 110 healthy female volunteers, who had passed a natural menopause 6 months to 3 years before the start of the study. Urinary excretion of intravenously injected 99m-technetium diphosphonate was measured as an index of bone turnover; plasma bone Gla protein and serum alkaline phosphatase were measured as indices of bone formation; and fasting urinary excretion of hydroxyproline and calcium were measured as estimates of bone resorption. During 2 years of hormone treatment, all variables decreased highly significantly (p less than 0.001) to a constant low level. Three months after withdrawal all variables increased highly significantly (p less than 0.001) towards, but not above, pretreatment and placebo levels. We conclude that withdrawal of estrogen/gestagen replacement therapy in postmenopausal women increases bone turnover, but not in excess of pretreatment values. This indicates that bone loss (after withdrawal) is similar to that seen in the placebo group and that a rebound phenomenon is unlikely.     

Brachytherapy in France in 2002: results of the ESTRO-PCBE questionnaire]

The authors report the results of the Patterns of Care for Brachytherapy in Europe (PCBE) throughout France. Responses were obtained for 91% of the Radiation Oncology departments, which have declared using brachytherapy for 67, and gave detailed data for 49 ones. The equipments and treated tumours were recorded. LDR brachytherapy remained the most often used (53.5%), followed by HDR (28%). PDR represented 5.5% and permanent implants 11%. The authors discuss the development of new equipment, with an aggregation of the structures, and an increase of the PDR and prostate implants use.     

Oxidative metabolism of lung macrophages exposed to sodium arsenite

Arsenic pollution has become increasingly severe. It occurs as the result of geological processes and different human activities. Arsenic toxicity at the respiratory level occurs mainly by inhalation of products of coal combustion. The aim of this study was to evaluate sodium arsenite (As³⁺) toxicity in murine alveolar macrophages (AMs) in vitro and its association with the alterations in cell metabolism.

No changes in viability, apoptosis or cell area were detected in AMs treated with As³⁺ concentrations up to 2 μM for 24–96 h. A marked decrease in these end-points was observed for As³⁺ concentrations ranging from 2.5 μM to 10 μM.

Regarding the dynamics of the endo-exocytic process triggered by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell incorporation, no variations were detected for As³⁺ concentrations lower than 2 μM while higher concentrations markedly modified this response.

MTT specific activity, as a measure of cell metabolic activity, was not modified irrespective of the As³⁺ concentration assayed. However, nitroblue tetrazolium (NBT) specific activity, as a measure of superoxide anion generation, is responsive but only to low As³⁺ doses.

Although this study focuses on lung macrophages, the effects of As³⁺ described herein may also apply to the response of macrophages residing in other organs.

Arsenite modifies the metabolic and the oxidative status of AMs in vitro. When macrophages are in an As³⁺ rich medium, they exhibit a reduction in respiratory burst levels and lose their intrinsic capacity to respond to toxicants.     

Frequency, nature and determinants of pharmaceutical consultations provided in private by Dutch community pharmacists

OBJECTIVE: According to a report published by the federation of Dutch patients' associations, patients would like to see a pharmacist, who acts more as a personal adviser. This raised the question, how often Dutch community pharmacists have personal consultations with their patients in daily practice, on which factors this depends, and what kind of topics are discussed during these meetings. SETTING: Community pharmacies in the Netherlands. METHOD: A questionnaire was distributed among 800 randomly selected pharmacies. Questions were restricted to consultations characterized by one-to-one contact, drug therapy related content, and adequate privacy. These consultations were labelled as pharmaceutical consultations in private to distinguish them from other contacts between pharmacists and patients. MAIN OUTCOME MEASURE: Number, content, and character of consultations. RESULTS: 198 (24.8%) community pharmacies responded. The pharmacists provide an average of roughly 1.2 consultations in private per working day. The vast majority of respondents provided face-to-face and telephone consultations (94.4 and 91.9%, respectively), only a minority gave consultations by e-mail (30.8%). These consultations primarily dealt with topics related to medication safety. The mean overall time spent was 290 min per month. A relatively high frequency of personal consultations was significantly associated with the absolute number of full-time equivalent pharmacists in the pharmacy. CONCLUSION: The frequency of pharmaceutical consultations in private is low, but may be improved by reorganisation of the pharmacist's activities. The possibility of personal consultations by e-mail is not yet well-developed. Further research is needed to assess the patient's view of pharmaceutical consultations in private.     

Effects of conjugated equine estrogens or raloxifene on lipid profile, coagulation and fibrinolysis factors in postmenopausal women.

OBJECTIVES: To compare the effect of conjugated equine estrogens (CEE) and raloxifene on lipid profile and hemostasis. MATERIALS AND METHODS: A double-blind, randomized and parallel study was performed with 90 healthy postmenopausal women, aged 54 +/- 5 years, divided into three groups and submitted to daily therapy with either CEE 0.625 mg, raloxifene 60 mg or placebo for 4 months. The lipid profile, coagulation and fibrinolytic factors were analyzed. RESULTS: CEE increased the levels of high density lipoprotein cholesterol (HDL-C) from 49.0 to 56.8 mg/dl (p < 0.001), very low density lipoprotein cholesterol (VLDL-C) from 17.2 to 22.3 mg/dl (p < 0.001), and triglycerides from 86.0 to 111.7 mg/dl (p < 0.001), and decreased the levels of low density lipoprotein cholesterol (LDL-C) from 121.0 to 106.5 mg/dl (p < 0.001). The only significant effect of raloxifene was an increase in the levels of HDL-C from 46.0 to 47.8 mg/dl (p = 0.019). There was no significant reduction in LDL-C, from 115.5 to 110.2 mg/dl (p = 0.06), VLDL-C, from 21.7 to 20.0 mg/dl (p = 0.201), and triglycerides, from 108 to 100 mg/dl (p = 0.201). CEE decreased the levels of fibrinogen, from 370.5 to 326.8 g/l (p = 0.039) and the levels of antithrombin III, from 99.5 to 93.2% (p < 0.001). Raloxifene decreased the levels of fibrinogen, from 354.7 to 302.0 g/l (p = 0.009) and the levels of antithrombin III, from 102.4 to 98.5% (p = 0.039). CEE increased levels of protein C from 103.7 to 115.3 mg/l (p < 0.001) and raloxifene did not change the levels of protein C (107.9 to 105.1 mg/l; p = 0.158). CEE decreased the antigen levels of tissue plasminogen activator (t-PA) from 8.8 to 6.8 U/ml (p < 0.001), and of plasminogen activator inhibitor (PAI-1) from 30.8 to 21.6 U/ml (p < 0.010), whereas raloxifene had no significant effect on either t-PA, from 9.6 to 9.2 U/ml (p = 0.235) or PAI-1 antigen levels, from 32.1 to 30.4 U/ml (p = 0.538). CONCLUSION Both CEE and raloxifene exert significant effects on the lipid and coagulation profile. CEE had a more significant effect on fibrinolysis than raloxifene. These effects may have a significant impact on the cardiovascular risk that needs to be confirmed in larger studies.     

Gallibacterium anatis-secreted metalloproteases degrade chicken IgG.

Gallibacterium anatis (previously named Pasteurella haemolytica-like) is considered a normal inhabitant of genital and upper respiratory tracts of healthy chickens, but it is also associated with different pathological conditions. Secreted metalloproteases from field and reference G. anatis cultures were obtained by methanol precipitation and were characterized. Proteins of molecular mass higher than 100 kDa showing proteolytic activity were observed in 10% polyacrylamide gels copolymerized with 1% bovine casein. They were active at alkaline pH, and inhibited by ethylenediamine tetraacetic acid. Their activity was stable at 50 degrees C, but partially inhibited at 60 degrees C, and totally inhibited at higher temperatures. Secreted proteins were able to degrade chicken IgG after 24 h of incubation, and cross-reacted with a polyclonal antibody against purified protease from Actinobacillus pleuropneumoniae. Secreted metalloproteases could play a role in infections caused by G. anatis.     

Adjuvant radiotherapy in carcinomas of the uterine cervix: the prognostic value of hemoglobin levels

Anemia has been associated with a poorer treatment response and reduced survival in women undergoing primary radiotherapy (RT) or radiochemotherapy for advanced cervical carcinoma. This study aimed to determine the influence of anemia on outcome in patients with cervical carcinoma undergoing adjuvant RT. Medical records were reviewed for 183 cervical cancer patients who had received adjuvant RT because of risk factors after radical surgery (n= 109) or inadequate primary surgery (simple hysterectomy; n= 74). Kaplan-Meier and Cox regression analyses were used to study hemoglobin levels before and during adjuvant RT in relation to recurrence-free and overall survival. Hemoglobin values > or =11 g/dL were considered normal, while those <11 g/dL indicated anemia. Hemoglobin levels before RT influenced significantly overall survival and recurrence-free survival across the whole group (overall survival--log rank(all patients)= 7.5; df = 1; P= 0.006). However, subgroup analysis showed that the observed difference was mainly due to the group of women who had undergone inadequate primary surgery (overall survival--log rank(inadequate surgery)= 10.8; df = 1; P= 0.001). Multifactorial regression analyses comparing hemoglobin before RT with grading and tumor stage confirmed the prognostic value of hemoglobin values. Maintaining normal hemoglobin values before and during adjuvant RT seems to be important, especially in patients who have had inappropriate simple hysterectomy, which may resemble a therapeutic situation.     

Is neighbourhood deprivation a risk factor for gestational diabetes mellitus?

AIMS: To assess the relationship between neighbourhood deprivation and the rate of gestational diabetes mellitus (GDM) using routinely collected data from a clinical information system, in Plymouth, UK. METHODS: Between 1 January 1996 and 31 December 1997, 3933 women residing within the Plymouth Primary Care Trust (PCT) were screened for GDM using indices of neighbourhood deprivation and prevalence of GDM. Areas (n = 43) were classified according to the Townsend index, measuring material deprivation. Pregnant women with and without GDM were compared. RESULTS: The prevalence of GDM was 1.7%[95%, confidence interval (CI) 1.20, 2.11]. The prevalence of GDM ranged from 1.05% (95% CI 0.60, 1.70) in the most deprived to 2.10% (95%, CI 1.34, 3.13), in the least deprived neighbourhood. Crude rates decreased by 50%[relative prevalence (RP) (95% CI) 0.50 (0.27, 0.94); P = 0.06] amongst those living in the most-deprived compared with those living in the least-deprived areas. Using a stepwise binary logistic regression model, older age at delivery significantly increased the risk of developing GDM. [RP (95%, CI) 1.09, (1.04, 1.13)]. Townsend deprivation score had no significant independent association with GDM when other covariates were considered. CONCLUSION: These data suggest that the neighbourhood context in which women live has no impact on the risk of GDM. Diabet.