Dapsone hydroxylamine-mediated alterations in human red blood cells from endometriotic patients

Endometriosis, an estrogen-dependent chronic gynecological disease in women of reproductive age, is characterized by a systemic inflammation status involving also red blood cells (RBCs). In this study, we evaluated how the protein oxidative status could be involved in the worsening of RBC conditions due to dapsone intake in endometriotic women in potential treatment for skin or infection diseases. Blood samples from two groups of volunteers, control group (CG) and endometriosis patient group (PG), were analyzed for their content of band 3 tyrosine phosphorylation (Tyr-P) and high molecular weight aggregate (HMWA) in membranes, and glutathione (GSH) content and carbonic anhydrase (CA) activity in cytosol. In endometriotic patients, RBC showed the highest level of oxidative-related alterations both in membrane and cytosol. More interestingly, the addition of dapsone hydroxylamine (DDS-NHOH) could induce further increase of both membranes and cytosol markers, with an enhancement of CA activity reaching about 66% of the total cell enzyme amount. In conclusion, in PG the systemic inflammatory status leads to the inability of counteracting adjunctive oxidative stress, with a potential involvement of CA-related pathologies, such as glaucoma. Hence, the importance of the evaluation of therapeutic approaches worsening oxidative imbalance present in PG RBC is underlined.     

Metformin Decreases Circulating Androgen and Estrogen Levels in Nondiabetic Women With Breast Cancer

IntroductionDiabetic patients treated with metformin have a lower risk of developing BC or a better BC prognosis. Metformin might reduce cancer growth through direct antiproliferative effects or through indirect mechanisms, particularly the reduction of insulin. In a randomized study on nondiabetic BC patients in natural menopause with high testosterone levels, we observed a significant decrease in insulin and in testosterone levels with metformin 1500 mg/d compared with 1000 mg/d. We present the results of a new analysis of our study on the effect of metformin on the bioavailability of sex hormones.Patients and MethodsOne hundred twenty-four eligible women were initially invited to take metformin 500 mg/d for 3 months. The 108 women who completed the first 3 months continued the study using 1000 mg/d for 1 month. The women were then randomized into 2 groups, and, for the subsequent 5 months, 1 group increased the dose to 1500 mg/d, and the other group continued with 1000 mg/d.ResultsNinety-six women completed the study, 43 receiving metformin 1500 mg/day, and 53 receiving 1000 mg/day. The women receiving 1500 mg/d showed a greater and significant reduction of free testosterone (?29%) and estradiol (?38%), a borderline significant reduction of estrone and insulin-like growth factor-1, and a nonsignificant reduction of androstenedione. They also showed a nonsignificant increase of dehydroepiandrosterone sulfate.ConclusionMetformin does not interfere with the production of dehydroepiandrosterone sulfate. Besides, it decreases estradiol levels, basically through the reduction of testosterone. These hormonal changes might have clinical relevance.     

Long-term outcome of patients with spinal myxopapillary ependymoma: treatment results from the MD Anderson Cancer Center and institutions from the Rare Cancer Network

Background

Spinal myxopapillary ependymomas (MPEs) are slowly growing ependymal gliomas with preferential manifestation in young adults. The aim of this study was to assess the outcome of patients with MPE treated with surgery, radiotherapy (RT), and/or chemotherapy.

Methods

The medical records of 183 MPE patients (male: 59%) treated at the MD Anderson Cancer Center and 11 institutions from the Rare Cancer Network were retrospectively reviewed. Mean patient'' age at diagnosis was 35.5 ± 15.8 years. Ninety-seven (53.0%) patients underwent surgery without RT, and 86 (47.0%) were treated with surgery and/or RT. Median RT dose was 50.4 Gy. Median follow-up was 83.9 months.

Results

Fifteen (8.2%) patients died, 7 of unrelated cause. The estimated 10-year overall survival was 92.4% (95% CI: 87.7–97.1). Treatment failure was observed in 58 (31.7%) patients. Local failure, distant spinal relapse, and brain failure were observed in 49 (26.8%), 17 (9.3%), and 11 (6.0%) patients, respectively. The estimated 10-year progression-free survival was 61.2% (95% CI: 52.8–69.6). Age (<36 vs ≥36 y), treatment modality (surgery alone vs surgery and RT), and extent of surgery were prognostic factors for local control and progression-free survival on univariate and multivariate analysis.

Conclusions

In this series, treatment failure of MPE occurred in approximately one third of patients. The observed recurrence pattern of primary spinal MPE was mainly local, but a substantial number of patients failed nonlocally. Younger patients and those not treated initially with adjuvant RT or not undergoing gross total resection were significantly more likely to present with tumor recurrence/progression.     

Verhandlungen Ärztlicher Gesellschaften

Ohne Zusammenfassung     

Sarcopenia in Parkinson Disease: Comparison of Different Criteria and Association With Disease Severity

Objectives

In Parkinson disease (PD), sarcopenia may represent the common downstream pathway that from motor and nonmotor symptoms leads to the progressive loss of resilience, frailty, and disability. Here we (1) assessed the prevalence of sarcopenia in older adults with PD using 3 different criteria, testing their agreement, and (2) evaluated the association between PD severity and sarcopenia.

Clinicopathological risk factors of Stage II colon cancer: results of a prospective study

Aim Adjuvant 5‐fluorouracil based chemotherapy has demonstrated benefit in Stage III colon cancer but still remains controversial in Stage II. The aim of this study was to analyse the prognostic impact of clinicopathological factors that may help guide treatment decisions in Stage II colon cancer. Method Between 1996 and 2006 data from patients diagnosed with colorectal cancer at Hospital Universitari Bellvitge and its referral comprehensive cancer centre Institut Català d′Oncologia/L’Hospitalet were prospectively included in a database. We identified 432 patients with Stage II colon cancer operated on at Hospital Universitari Bellvitge. The 5‐year relapse‐free survival (RFS) and colon‐cancer‐specific survival (CCSS) were determined. Results The 5‐year RFS and CCSS were 83% and 88%, respectively. Lymphovascular or perineural invasion was associated with RFS [hazard ratio (HR) 1.84; 95% CI 1.01–3.35]. Gender (women, HR 0.48; 95% CI 0.23–1) and lymphovascular or perineural invasion (HR 3.51; 95% CI 1.86–6.64) together with pT4 (HR 2.79; 95% CI 1.44–5.41) influenced CCSS. In multivariate analysis pT4 and lymphovascular or perineural invasion remained significantly associated with CCSS. We performed a risk index with these factors with prognostic impact. Patients with pT4 tumours and lymphovascular or perineural invasion had a 5‐year CCSS of 61%vs the 93% (HR 5.87; 95 CI 2.46–13.97) of those without any of these factors. Conclusion pT4 and lymphatic, venous or perineural invasion are confirmed as significant prognostic factors in Stage II colon cancer and should be taken into account in the clinical validation process of new molecular prognostic factors.     

Programa de atención farmacéutica integrada en pacientes con enfermedades crónicas

ObjectivesTo assess whether an integrated pharmaceutical care programme (IPCP) improves clinical evolution, patient quality of life, and reduces health costs in chronic patients.Material and methodsA parallel, open, and multi-centre clinical trial of an IPCP in patients with heart failure (HF) and/or chronic obstructive pulmonary disease (COPD) in 8 different health areas in Cataluña. The intervened patient was monitored for pharmacotherapeutic evolution by hospital pharmacists, primary care physicians, and community pharmacists. Controls received normal follow-up. All patients were monitored for 12 months, with quality of life tests administered at the beginning and end of follow-up.ResultsWe had the participation of 8 different hospitals, 8 primary care centres, and 109 community pharmacies. 238 patients completed the study, with 2.9% of participants lost during the study period. There were no significant differences in terms of readmissions, visits to the doctors, or to emergency services. We detected 50 different medication-related problems (MRP) in 37 patients, with a statistically significant difference in terms of MRP between the control and treatment groups of patients with HF, and almost significant differences in COPD patients. MRP were moderate-severe in 36% of cases. MRP were avoidable in 94% of cases, and the pharmacist resolved the issue in 90% of cases. There were no differences in terms of patient quality of life or health costs between the start and end of the study.ConclusionsIntegrated pharmaceutical care programs facilitate an improvement in the quality of patient care, but electronic registries are necessary to promote communication between sections of the health care network.     

Intervención farmacéutica en pacientes quirúrgicos con alteraciones electrolíticas

ObjectiveTo qualitatively and quantitatively determine electrolyte imbalances (potassium, phosphorus, magnesium and calcium) in patients admitted for general and gastrointestinal surgery, the degree of these imbalances in percentage detected by medical staff, and the acceptance of the recommendations made by the Hospital Pharmacy Department.MethodSeven-month prospective study. Any alteration detected was recorded on a data collection form (personal data, hospital ward, type of alteration, detection by medical staff, type of pharmaceutical intervention, form of notification, acceptance of the intervention, date of imbalance correction, patient receiving parenteral nutrition).Results100 imbalances were detected in 66 patients (231 analytical tests revised). A total of 78 interventions were carried out. Most changes were due to hypokalaemia and hypomagnesaemia, hypophosphataemia being the most frequent abnormality in patients receiving parenteral nutrition.The acceptance of pharmaceutical intervention was higher if the information was oral (100% vs. 35% written). Twice the number of analytical tests were performed after interventions (RR: 2.1, 95% CI: 1.11 to 3.94, P = .006). When pharmaceutical intervention was accepted there was a greater number of imbalance resolutions in comparison with those cases which did not accept (RR: 1.5, 95% CI: 1.01 to 2.24, P = .04).ConclusionsThis study shows that electrolyte imbalances are common in surgical patients and the level of detection and monitoring by medical staff is low. Therefore, the pharmacist could help in improving this aspect.