Reduction in oral corticosteroid use with mometasone furoate dry powder inhaler improves health-related quality of life in patients with severe persistent asthma.

Severe persistent asthma can have a substantial impact on a patient's health-related quality of life (HRQL), both as a result of symptoms and from side effects of treatment. The HRQL impact of two doses (400 and 800 microg twice daily) of mometasone furoate dry powder inhaler (MF DPI) was compared with placebo in patients with severe persistent asthma previously maintained on oral steroids as a component of a previously published randomized, 12-week, double-blind, placebo-controlled, multicenter trial. A 9-month open-label extension (OLE), with all patients treated with MF DPI, followed. Patients 12 years of age or older completed a generic HRQL measure, the Medical Outcomes Trust Short Form-36 (SF-36), and an asthma-specific measure, the Marks Asthma Quality of Life Questionnaire (AQLQ-M), at baseline, at endpoint (last evaluable visit) of the double-blind phase (EODBP), and after the first 3 months of the OLE. Of 132 patients enrolled in the study, 128 provided HRQL data at baseline and at EODBP. Mean SF-36 scores at baseline showed significant HRQL impairment compared with U.S. general population norms. With treatment, the reduction in oral corticosteroid (OCS) requirements of the MF-DPI-treated groups was accompanied by significant (p < 0.05) improvement over placebo in the physical domain of HRQL (SF-36 physical component summary score and the physical function subscale) at EODBP. MF-DPI-treated patients also showed significant improvements at EODBP in each of the four subscales of the AQLQ-M (p<0.05). From EODBP to the OLE 3-month endpoint, patients treated with MF DPI twice daily maintained, or improved, SF-36 scores in most domains. Symptomatic improvement and reduction in OCS use with MF DPI were accompanied by significant improvement in HRQL in patients with severe persistent asthma. These improvements were maintained during the 3-month period of the OLE in which HRQL was evaluated.     

Paget-von Schroetter syndrome: case description in the light of the literature

A 27 year old patient with a thrombosis of the subclavian vein (Paget- von Schroetter's-syndrome) was treated successfully with a systemic streptokinase thrombolysis. Indications and success of the different therapeutic ways in current literature (conventional management, systemic and local thrombolysis) are compared to each other. The authors prefer treatment with systemic thrombolysis, patients with contraindications should be treated with conservative management. Nevertheless no final conclusions can be drawn, as there are no controlled studies comparing the different concepts in treatment.     

Validating signals of ovulation: Do women who think they know,really know?

This study was carried out to test whether women who think they know when they ovulate, really know. Fifty-three women of age 18.7 to 46.1 (mean age 28.4 years) participated in initial interviews about ovulation. Criteria for recruitment included perceived ovulation, regular menstrual cycles, and not using hormonal contraception. Women collected and refrigerated urine samples from day 5 until they thought they ovulated. Samples collected within 48 h of the perceived signal were then tested for a pre-ovulatory LH surge. Of the 53 original participants, 36 women provided urine samples for 1-6 cycles, so that 87 cycles were tested. Subjective signals of ovulation varied between women and between cycles but included abdominal pain and changes in cervical discharge, libido, and mood. Of the 87 cycles tested, during which women identified one or multiple signals of ovulation, 37 of the 87 urine specimens tested positive for an LH surge for a concordance rate of 42.5%. Using the first tested cycle from the 36 women who provided urine specimens, 13 of those specimens demonstrated an LH surge, for a concordance rate of 36.1%. That rate dropped to 28% (7/25) when women who used basal body temperature as an ovulatory signal were excluded. Finally, the mean level of accuracy among the 15 women who contributed 3-6 urine specimens for testing was 48.9%. The results of this study demonstrate a low degree of concordance between LH surge and perceived ovulation among women who think they know when they ovulate. The most motivated study participants were right about half of the time. Although there is variation among women in their ability to know when they ovulate, this study suggests that, for most women, ovulation is concealed.     

Age and symptom experience at menopause in the Selska Valley, Slovenia

OBJECTIVE: To assess age and symptom experience at menopause in a high-altitude population in the Selska Valley of Slovenia. DESIGN: In four mountain villages, all houses were approached and 80% of eligible residents were interviewed. Additional women were interviewed for comparison in the valley below. Age at interview ranged from 32.7 to 85.5 years, with a mean of 58.2 years. The majority of women (62%) were aged 40 to 65 years. RESULTS: Of the 58 women interviewed, 7 had undergone menopause by hysterectomy (12%). Recalled age at natural menopause ranged from 42 to 54, with a mean of 50.3 (SD 2.9). By probit analysis, median age at natural menopause was 52.03. Fifty-five percent of participants reported ever having experienced a hot flash, although only 24% reported hot flashes during the 2 weeks before being interviewed. When the sample was limited to women aged 40 to 65, frequency of hot flashes in the 2 weeks before the interview was 39%. For all participants, the most frequent complaint was lack of energy (66%), followed by backaches (59%), and joint stiffness (53%). CONCLUSIONS: In contrast to expectations, age at menopause was not earlier and hot flash frequency was not significantly lower at higher elevations.     

Interlaboratory validation of a CD71-based flow cytometric method (Microflow) for the scoring of micronucleated reticulocytes in mouse peripheral blood

An interlaboratory study was performed to validate an anti-CD71/flow cytometry-based technique for enumerating micronucleated reticulocytes (MN-RETs) in mouse peripheral blood. These experiments were designed to address International Workshop on Genotoxicity Test Procedures validation criteria by evaluating the degree of correspondence between MN-RET measurements generated by flow cytometry (FCM) with those obtained using traditional microscopy-based methods. In addition to these cross-methods data, flow cytometric MN-RET measurements for each blood sample were performed at two separate sites in order to evaluate the reproducibility of data between laboratories. In these studies, groups of male CD-1 mice were treated with vehicle (saline or vegetable oil), a negative control (saline or vegetable oil), or four dose levels of five known genotoxicants (clastogens: cyclophosphamide, benzo[a]pyrene, 5-fluorouracil, methotrexate; aneugen: vincristine sulfate). Exposure occurred on 3 consecutive days via intraperitoneal injection, and blood samples were obtained approximately 24 hr after the final treatment. MN-RET frequencies were determined for each sample based on the analysis of 2,000 (microscopy) and 20,000 (FCM) reticulocytes. Regardless of the method utilized, each genotoxic agent was observed to cause statistically significant increases in the frequency of MN-RETs, and each response occurred in a dose-dependent manner. Spearman's correlation coefficient (rs) for FCM versus microscopy-based MN-RET measurements (nine experiments, 252 paired measurements) was 0.740, indicating a high degree of correspondence between methods. The rs value for all flow cytometric MN-RET measurements performed at the two independent sites was 0.857 (n = 248), suggesting that the automated method is highly transferable between laboratories. Additionally, the flow cytometric system offered advantages relative to microscopy-based scoring, including a greater number of cells analyzed, much faster analysis times, and a greater degree of objectivity. Collectively, data presented in this report suggest that the overall performance of mouse peripheral blood micronucleus tests is enhanced by the use of the flow cytometric scoring procedure.     

Tumor regression by anti-CD40 and interleukin-2: role of CD40 in hematopoietic cells and organ-specific effects.

CD40 stimulation can synergize with interleukin (IL)-2 for antitumor responses against mouse metastatic renal cell carcinomas, with coincident increases in tumor-specific CD8+ T-cell responses and dendritic cell numbers in both the spleen and liver. Because CD40 is present on various hematopoietic-derived cells, endothelial cells, and some tumors themselves, this study was performed to determine whether the antitumor effects of CD40 stimulation and IL-2 were primarily mediated by CD40+ hematopoietic-derived cells. Bone marrow chimeras were created by reconstituting lethally irradiated CD40+/+ recipients with bone marrow from CD40-/- or CD40+/+ mice. Chimeric mice were then implanted orthotopically with renal cancer cells, followed by treatment with anti-CD40 agonist monoclonal antibodies and IL-2. Immune parameters of the spleen and liver were assessed after therapy and correlated with antitumor responses. The antitumor effects in the CD40-/- bone marrow transplantation chimeras were almost completely abrogated after treatment, and this shows that hematopoietically derived CD40+ cells are the principal targets for CD40 stimulation in this model. Although both spleen and liver showed reductions in CD8+ T-cell and dendritic cell expansion in the CD40-/- versus CD40+/+ chimeras after therapy, only the liver exhibited no significant increases in either CD8+ T cells or dendritic cells after treatment. CD40 cells on hematopoietic cells are the primary target for anti-CD40 and IL-2 therapy. The results also suggest that the immunologic events in the liver may be more revealing that those in lymphoid organs with regard to critical events related to responses after therapy.     

The effect of bipolar electrosurgical coagulation waveform on a rat uterine model of fallopian tube sterilization

Laparoscopic bipolar electrosurgical sterilization has been employed for nearly two decades. This bipolar procedure was intended to reduce the incidence of unintended complications, such as bowel burns. However, compared to the monopolar procedure, it produced a higher failure rate. This study examines the role of the low power-high voltage coagulation waveform on the effectiveness of electrosurgical desiccation on the rat uterine model of the fallopian tube. Desiccations were performed with both Kleppinger and Storz forceps using generator settings from 2 to 6. Desiccations performed to the visual endpoint (blanch, swell, and collapse) required from 23.8 to 30.0 joules, although procedures performed at a generator setting of 2 required long application times, an average 15.4 sec (Storz) and 28.2 (Kleppinger). All bipolar procedures led to a loss of tissue at the desiccation site at 12 weeks postsurgery. Therefore, the electrosurgical coagulation waveform proved to be effective in producing adequate in vivo tissue destruction even at very low generator settings.