Proliferative responses in the placenta after endotoxin exposure in preterm fetal sheep

OBJECTIVES: Antenatal infections are associated with an increased risk of perinatal morbidity and mortality. Systemic application of endotoxins to the fetus results in an increase in placental vascular resistance and chronic reduction in umbilical blood flow. We studied morphological alterations of the placenta in response to fetal inflammation in the preterm sheep. STUDY DESIGN: Therefore, 14 fetal sheep were chronically instrumented at a mean gestational age of 107+/-1 days (term is 147 days). Four days after surgery fetuses received 100 ng lipopolysaccharide (LPS; n=8) or saline (control; n=6) intravenously. Fetal heart rate and arterial blood pressure were monitored continuously while blood gases and acid-base balance were measured at time points 0, +1, +3, +6, +12, +24, +48 and +72 h. Three days after LPS application placental cotyledons were analyzed by immunohistochemistry and morphometry. Different primary antibodies like AE 1 and AE 3 against cytokeratins were used. Secondary antibodies were visualized with 3-amino-9-ethylcarbazole (AEC) or using the Vectastain kit (Vector Laboratories, Burlingame, CA). Double staining was carried out first by utilizing Vectastain kit (black), followed by AEC staining (red). Counterstaining was performed with haematoxylin. RESULTS: Fetal tachycardia and hypertension were induced transiently during the first 12h after LPS application. Fetuses suffered from mild hypoxaemia while acidemia was absent. Morphometry revealed a non-significant shift in the relation of maternal and fetal placental compartments towards the maternal parts in response to LPS treatment. Endotoxin induced an increased proliferation in both compartments of the placenta with a 3.2-fold increase on the maternal and a 1.8-fold increase on the fetal side. CONCLUSIONS: Systemic endotoxin exposure of the preterm fetal sheep leads to a change in the gross organization of the placenta and changes in the proliferation patterns in both placental compartments. These rearrangements inside the placenta may disturb its organ function and subsequently lead to fetal morbidity associated with the fetal inflammatory response syndrome and chronic placental dysfunction, respectively.     

Uterine receptivity and cytokines: new concepts and new applications

The implantation process, currently thought to be the most critical step in achieving a successful early pregnancy, remains one of the most important unsolved processes in reproductive medicine. It depends on uterine-dependent and embryo-specific events, which need to be critically coordinated. Early embryo signaling following a maternal hormonal or cytokine-mediated preparation phase seems to be involved in stages immediately before, during and just after the apposition step to permit adequate proliferation of the stroma. Our objective is to develop guidelines and diagnostic tools pertinent to appreciate uterine receptivity. We will focus our attention on the uterine luminal environment at the time of oocyte retrieval and on the monitoring of the endometrium using three-dimensional ultrasound associated with digital technology and cytokine quantification by real-time PCR during the implantation window in an IVF/ICSI population. There is an accumulating body of data which strongly suggests that both implantation and uterine receptivity are controlled, primarily, though not exclusively, by locally acting growth factors and cytokines, some under steroid control. Some specific cytokines (IL-12, IL-15 and IL-18) in the luminal environment and in the endometrium allow a distinct pattern of abnormal uterine receptivity. The identification of these distinct patterns of abnormal uterine receptivity and of the mechanisms leading to the abnormal angiogenesis before implantation strongly suggest that no single therapeutic scheme can correct all cases of implantation failure and should be adapted for each patient especially in the case of unexplained infertility.     

Does the source of laser energy influence the coagulation of chorionic plate vessels? Comparison of Nd:YAG and diode laser on an ex vivo placental model

OBJECTIVES: To compare the histological effects of diode and Neodymium-Yttrium Aluminium Garnet (Nd:YAG) laser coagulation of chorionic plate vessels. METHODS: In selected chorionic plate vessels in an ex vivo term placenta perfused with warm saline solution, diode (wavelength 940 nm) and Nd:YAG (wave length 1,064 nm) laser were used with an output of 30, 40, and 50 W, and 55 and 70 W respectively using preset energy and duration of impact. All vessels were examined histologically blindly to the procedures' characteristics. RESULTS: A total of 23 vessels were coagulated. Similar histological lesions were observed using diode and Nd:YAG lasers. The lesions were compatible with an acceptable clinical effect at all power outputs tested. The results were not related to the diameter or type of vessels. Lesions of the endothelium and reduction of the vessel lumen were best achieved with a diode laser at 40 W. CONCLUSION: Nd:YAG and Diode laser induce significant and comparable changes in chorionic plate vessels compatible with an efficient coagulation process under the experimental condition used.     

Muscle strength in obese elderly women: effect of recreational physical activity in a cross-sectional study

BACKGROUND: Muscle strength (MS) may be impaired in obese persons, and this impairment may be a consequence of both obesity and low physical fitness. OBJECTIVE: We investigated whether MS differed between obese [body mass index (BMI; in kg/m2 > 29], normal-weight (BMI = 24-29), and lean (BMI < 24) elderly subjects and compared the MS of sedentary and active subjects according to their BMI group. DESIGN: The study included 215 obese [ (+/- SD) age: 80.0 +/- 3.5 y; BMI: 31.9 +/- 2.6], 630 normal-weight (age: 80.2 +/- 3.7 y; BMI: 26.3 +/- 1.4), and 598 lean (age: 80.7 +/- 3.5 y; BMI: 21.6 +/- 1.8) women with good functional ability. A cross-sectional design was used. Anthropometric measures (weight, height); measures of appendicular skeletal muscle mass (by dual-energy X-ray absorptiometry), isometric knee and elbow extension (by statergometer), and isometric handgrip strength (by dynamometer); and data on health status and self-reported recreational physical activity (RPA: walking, gymnastics, cycling, swimming, gardening) were collected. RESULTS: Absolute (unadjusted) MS was higher in obese than in lean women (P < 0.01), except for handgrip strength (P > 0.05). When adjusted for age, height, RPA, pain, depression, and appendicular skeletal muscle mass, MS did not differ significantly between obese, normal-weight, and lean subjects, except for knee extension (significant interaction effect with RPA; P = 0.01). With increasing BMI, lower limb strength did not change in the sedentary women but increased in active (> or = 1 h/wk in > or = 1 RPA for > or = 1 mo) women. All adjusted MS measures in active participants were significantly higher (P < 0.001) than those in their sedentary peers. CONCLUSION: The adjusted MS of elderly women is not associated with obesity but is higher in active subjects than in sedentary ones, especially in the lower limbs of obese subjects.     

How do general practitioners recognize the definition of multimorbidity? A European qualitative study

Background: Multimorbidity is a challenging concept for general practice. An EGPRN working group has published a comprehensive definition of the concept of multimorbidity. As multimorbidity could be a way to explore complexity in general practice, it was of importance to explore whether European general practitioners (GPs) recognize this concept and whether they would change it.

Objectives: To investigate whether European GPs recognize the EGPRN concept of multimorbidity and whether they would change it.

Methods: Focus group meetings and semi-structured interviews as data collection techniques with a purposive sample of practicing GPs from every country. Data collection continued until saturation was reached in every country. The analysis was undertaken using a grounded theory based method. In each national team, four independent researchers, working blind and pooling data, carried out the analysis. To ensure the internationalization of the data, an international team of 10 researchers pooled the axial and selective coding of all national teams to check the concept and highlight emerging themes.

Results: The maximal variation and saturation of the sample were reached in all countries with 211 selected GPs. The EGPRN definition was recognized in all countries. Two additional ideas emerged, the use of Wonca’s core competencies of general practice, and the dynamics of the doctor–patient relationship for detecting and managing multimorbidity and patient’s complexity.

Conclusion: European GPs recognized and enhanced the EGPRN concept of multimorbidity. These results open new perspectives regarding the management of complexity using the concept of multimorbidity in general practice.

Key Messages

• European general practitioners recognize the EGPRN enhanced, comprehensive concept of multimorbidity.

• They add the use of Wonca’s core competencies and the patient–doctor relationship dynamics for detecting and managing multimorbidity.

• The EGPRN concept of multimorbidity leads to new perspectives for the management of complexity.

     

Inhibition of bone turnover by milk intake in postmenopausal women

Increased postmenopausal bone turnover leads to bone loss and fragility fracture risk. In the absence of osteoporosis, risk preventive measures, particularly those modifying nutritional lifestyle, are appropriate. We tested the hypothesis that milk supplementation affects bone turnover related to biochemical markers in a direction that, in the long term, may be expected to reduce postmenopausal bone loss. Thirty healthy postmenopausal women aged 59.3 (SD 3.3) years were enrolled in a prospective crossover trial of 16 weeks. After a 4-week period of adaptation with diet providing 600 mg calcium plus 300 mg ingested as 250 ml semi-skimmed milk, participants were maintained during 6 weeks under the same 600 mg calcium diet and randomized to receive either 500 ml semi-skimmed milk, thus providing a total of 1200 mg calcium, or no milk supplement. In the next 6 weeks they were switched to the alternative regimen. At the end of the each period, i.e. after 4, 10 and 16 weeks, blood and urinary samples were collected. The changes in blood variables between the periods of 6 weeks without and with milk supplementation were: for parathyroid hormone, -3.2 pg/ml (P=0.0054); for crosslinked telopeptide of type I collagen, -624 pg/ml (P<0.0001); for propeptide of type I procollagen, -5.5 ng/ml (P=0.0092); for osteocalcin, -2.8 ng/ml (P=0.0014). In conclusion, a 6-week period of milk supplementation induced a decrease in several biochemical variables compatible with diminished bone turnover mediated by reduction in parathyroid hormone secretion. This nutritional approach to postmenopausal alteration in bone metabolism may be a valuable measure in the primary prevention of osteoporosis.     

Gender-specific Differences in Clinicopathologic Outcomes Following Radical Cystectomy: An International Multi-institutional Study of More Than 8000 Patients

Background

The impact of gender on the staging and prognosis of urothelial carcinoma of the bladder (UCB) is insufficiently understood.

Objective

To assess gender-specific differences in pathologic factors and survival of UCB patients treated with radical cystectomy (RC).

Design, setting, and participants

Data from 8102 patients treated with RC (6497 men [80%] and 1605 women [20%]) for UCB between 1971 and 2012 were analyzed.

Outcome measurements and statistical analysis

Multivariable competing-risk regression analyses were performed to evaluate the relationship of gender on disease recurrence (DR) and cancer-specific mortality (CSM). We also tested the interaction of gender and tumor stage, nodal status, and lymphovascular invasion (LVI).

Results and limitations

Female patients were older at the time of RC (p = 0.033) and had higher rates of pathologic stage T3/T4 disease (p < 0.001). In univariable, but not in multivariable analysis, female gender was associated with a higher risk of DR (p = 0.022 and p = 0.11, respectively). Female gender was an independent predictor for CSM (p = 0.004). We did not find a significant interaction between gender and stage, nodal metastasis, or LVI (all p values >0.05).

Conclusions

We found female gender to be associated with a higher risk of CSM following RC. However, these findings do not appear to be explained by gender differences in pathologic stage, nodal status, or LVI. This gender disparity may be due to differences in care and/or the biology of UCB.