Allelic variants of the estrogen receptor genes and frailty phenotype in postmenopausal women.

OBJECTIVE: The prevalence of frailty has been related to menopause. Our main objective was to investigate whether single nucleotide polymorphisms (SNPs) of the estrogen receptor (ER) ERα and ERß genes were related to the frailty phenotype in a population of community-dwelling postmenopausal women. METHODS: A cross-sectional study was performed in which we selected five SNPs, three in the ERα gene and two in the ERß. Linear regression was used to estimate the percentage of phenotypic variance after adjusting for confounding variables. RESULTS: A total of 470 women (mean ± standard deviation age 63.83 ± 8.16 years) were included, of whom 137 women were frail. The SNP rs3798577 of the ERα gene was the only variant associated with frailty, but this significance faded in the multivariant analysis. Body mass index (p = 0.012), number of comorbidities (0 vs. ≥2, p = 0.002) and two reproductive variables, number of miscarriages (none vs. ≥2, p = 0.036) and of childbirths (one vs. ≥3, p = 0.008), were independently related to frailty. CONCLUSION: The five SNPs of the ERα and ERß genes tested were not correlated with frailty. Other SNPs of the ER warrant analysis to clarify whether variance in the gene response affects frailty status.

Nerve gaps repaired with acellular nerve allografts recellularized with Schwann-like cells: Preclinical trial.

BACKGROUND: Acellular nerve allografts (ANA) recellularized with mesenchymal stem cells (MSC) or Schwann cells (SC) are, at present, a therapeutic option for peripheral nerve injuries (PNI). This study aimed to evaluate the regenerative and functional capacity of a recellularized allograft (RA) compared with autograft nerve reconstruction in PNI. METHODS: Fourteen ovines were randomly included in two groups (n=7). A peroneal nerve gap 30 mm in length was excised, and nerve repair was performed by the transplantation of either an autograft or a recellularized allograft with SC-like cells. Evaluations included a histomorphological analysis of the ANA, MSC pre differentiated into SC-like cells, at one year follow-up functional limb recovery (support and gait), and nerve regeneration using neurophysiological tests and histomorphometric analysis. All evaluations were compared with the contralateral hindlimb as the control. RESULTS: The nerve allograft was successfully decellularized and more than 70% of MSC were pre differentiated into SC-like cells. Functional assessment in both treated groups improved similarly over time (p <0.05). Neurophysiological results (latency, amplitude, and conduction velocity) also improved in both treated groups at twelve months. Histological results demonstrated a less organized arrangement of nerve fibers (p <0.05) with an active remyelination process (p <0.05) in both treated groups compared with controls at twelve months. CONCLUSIONS: ANA recellularized with SC-like cells proved to be a successful treatment for nerve gaps. Motor recovery and nerve regeneration were satisfactorily achieved in both graft groups compared with their contralateral nontreated nerves. This approach could be useful for the clinical therapy of PNI.

[How to manage risk in the surgical area. A Modal Analysis of Failures and Surgical Effects]. / Cómo gestionar el riesgo en el área quirúrgica. Análisis modal de fallos y efectos quirúrgicos.

OBJECTIVE: First to identify the areas of improvement in the surgical area before and during the performance of a surgical procedure in general surgery through the application of a Modal Analysis of Failures and Effects. Second to establish preventive measures to avoid adverse events in the surgical area. METHOD: A multidisciplinary working group was created in a university hospital for risk management in the General Surgery Operating Room Unit. The Modal Analysis of Faults and Effects was used. Potential risks for the patient in the ante-surgery and within the operating room were identified. The Risk Priority Index was calculated and preventive measures were established for all of them, with special interest when the Risk Priority Index was higher than 100. Preventive measures were developed based on the detected risks as well as those responsible for them. RESULTS: We identified a greater number of risks when the patient is in the operating room than in the ante-surgery room. Those with a higher risk priority index were: anticoagulated or antiaggregated patients, urinary tract infections, osteoarticular or neuropathic problems, patients not prepared for colon surgery, errors in laterality and leaving compresses in the operative field. CONCLUSIONS: A risk map has been developed in our organization, allowing the design of strategies to improve Patient Safety in the Surgical area. Training is a key aspect to improve Patient Safety.

The appearance of malnutrition in hematological inpatients prolongs hospital stay: the need for nutritional surveillance during hospitalization.

INTRODUCTION: Introduction: oncohematological diseases are associated with a high prevalence of malnutrition during hospitalization. Our aim was to analyze the appearance and repercussions of malnutrition in well-nourished hematological inpatients at admission. Method: a prospective one-year study conducted in hematology inpatients. The Malnutrition Screening Tool (MST) was used at admission and repeated weekly. Patients with a negative screening at admission who developed malnutrition during hospitalization constituted our study sample. A nutritional evaluation and intervention was performed. We also analyzed the effect of newly diagnosed malnutrition on patients' outcomes in comparison with the outcomes of patients that remained well-nourished during hospitalization. Results: twenty-one percent of hematological inpatients who were well nourished at admission developed malnutrition during hospitalization. Of the patients, 62.4% needed a nutritional intervention (100% oral supplements, 21.4% diet changes, 5.2% parenteral nutrition). After intervention, an increase in real intake was achieved (623 kcal and 27.3 g of protein/day). Weight loss was slowed and visceral protein was stabilized. Length of stay was 8.5 days longer for our sample than for well-nourished patients. Conclusions: newly diagnosed malnutrition appeared in one in five hematological well-nourished inpatients, leading to a longer length of stay. Nutritional intervention improved intake and nutritional status. Nutritional surveillance should be mandatory.

INTRODUCCIÓN: Introducción: las enfermedades oncohematológicas asocian una elevada prevalencia de malnutrición, especialmente durante la hospitalización. Objetivo: analizar la aparición de malnutrición y su repercusión en pacientes normonutridos al ingreso. Métodos: estudio prospectivo de un año en una cohorte de ingresados hematológicos. El Malnutrition Screening Tool (MST) se realizó al ingreso, repitiéndose semanalmente. Los pacientes con cribado negativo al ingreso que desarrollaron malnutrición durante la hospitalización constituyeron nuestra muestra. Se realizó evaluación e intervención nutricional, analizando el efecto de la aparición de malnutrición en el pronóstico, comparado con los pacientes que permanecieron normonutridos. Resultados: el 21% de los pacientes normonutridos al ingreso desarrolló malnutrición en la hospitalización. El 62.4% precisó intervención nutricional (100% suplementos orales, 21,4% cambios dietéticos, 5.2% nutrición parenteral). La intervención logró un aumento de ingesta real de 623 kcal y 27,3 g proteína/día, frenando la pérdida de peso y estabilizando las proteínas viscerales. La estancia fue 8,5 días mayor en nuestra muestra que en los pacientes que permanecieron normonutridos. Conclusiones: uno de cada cinco ingresados normonutridos al ingreso desarrolló malnutrición en la hospitalización, asociando mayor estancia. La intervención nutricional puede mejorar la ingesta y el estado nutricional, por tanto, la vigilancia nutricional debería ser obligatoria.

How to Improve Speaking Skills in Plastic Surgery Training? Survey in Residents Participants in Pecha Kucha Contest.

BACKGROUND: Little is known about educational games in Plastic Surgery training. Pecha kucha game has proved to be helpful tool to improve communicative skills. This study survey in resident participants in Pecha Kucha contest assessed how to improve speaking skills in plastic surgery training. METHODS: In the second edition of Pecha Kucha contest of the Mexican Society of Plastic Surgery, a survey was conducted with the residents to know the utility of this educational game. RESULTS: Twenty-six residents participated in the survey. Most of them from the Universidad Nacional Autonoma de México. Most of the residents considered it to be a good tool in order to improve communication skills and helpful for their future practice. The amount of time to present an idea was considered enough to express an idea. The most common proportion between words and images was 20-80% in the presentation. CONCLUSION: Pecha Kucha helped to improve communication skills during residents' training. We encourage other plastic surgery societies to incorporate educational games in their national and international meetings.

The hip fracture surgery in elderly patients (HIPELD) study to evaluate xenon anaesthesia for the prevention of postoperative delirium: a multicentre, randomized clinical trial.

BACKGROUND: Postoperative delirium occurs frequently in elderly hip fracture surgery patients and is associated with poorer overall outcomes. Because xenon anaesthesia has neuroprotective properties, we evaluated its effect on the incidence of delirium and other outcomes after hip fracture surgery. METHODS: This was a phase II, multicentre, randomized, double-blind, parallel-group, controlled clinical trial conducted in hospitals in six European countries (September 2010 to October 2014). Elderly (≥75yr-old) and mentally functional hip fracture patients were randomly assigned 1:1 to receive either xenon- or sevoflurane-based general anaesthesia during surgery. The primary outcome was postoperative delirium diagnosed through postoperative day 4. Secondary outcomes were delirium diagnosed anytime after surgery, postoperative sequential organ failure assessment (SOFA) scores, and adverse events (AEs). RESULTS: Of 256 enrolled patients, 124 were treated with xenon and 132 with sevoflurane. The incidence of delirium with xenon (9.7% [95% CI: 4.5 -14.9]) or with sevoflurane (13.6% [95% CI: 7.8 -19.5]) were not significantly different (P=0.33). Overall SOFA scores were significantly lower with xenon (least-squares mean difference: -0.33 [95% CI: -0.60 to -0.06]; P=0.017). For xenon and sevoflurane, the incidence of serious AEs and fatal AEs was 8.0% vs 15.9% (P=0.05) and 0% vs 3.8% (P=0.06), respectively. CONCLUSIONS: Xenon anaesthesia did not significantly reduce the incidence of postoperative delirium after hip fracture surgery. Nevertheless, exploratory observations concerning postoperative SOFA-scores, serious AEs, and deaths warrant further study of the potential benefits of xenon anaesthesia in elderly hip fracture surgery patients. CLINICAL TRIAL REGISTRATION: EudraCT 2009-017153-35; ClinicalTrials.gov NCT01199276.

A modified chemical protocol of decellularization of rat sciatic nerve and its recellularization with mesenchymal differentiated schwann-like cells: morphological and functional assessments.

The functional reconstruction of large neural defects usually requires the use of peripheral nerve autografts, though these have certain limitations. As a result, interest in new alternatives for autograft development has risen. The acellular peripheral nerve graft is an alternative for peripheral nerve injury repair, but to date there is not a standardized chemical decellularization method widely accepted. The objective of this study was to propose a modified chemical protocol of decellularization of rat sciatic nerve and its recellularization in vitro with mesenchimal differentiated Schwann-like cells. After the transplantation, an evaluation of its regeneration was performed using morphological and functional tests. The study consisted of two phases; in phase 1, different concentrations and times of exposure of rat sciatic nerves to detergents were tested, to establish a modified chemical protocol for nerve decellularization. The chemical treatment with 3% triton X-100 and 4% sodium deoxycholate for 15 days allowed a complete decellularization whilst conserving the extracellular matrix of the harvested nerve. In phase 2, the decellularized and recellularized alografts were compared against autografts. The morphological analysis showed a higher positivity to specific myelin antibodies in the recellularized group compared to the autograft. There were no differences in this parameter between the control limb and the experimental limb (recellularized group). The functional analysis showed no statistical differences at week 15 in the Sciatic Function Index in the autograft group vs the other groups. This study sets the morphological and functional bases for posterior studies about nerve defects regeneration in humans.

Endometrial response to concurrent treatment with vaginal progesterone and transdermal estradiol.

ABSTRACT Objective To describe the effect of the intermittent administration of vaginal progesterone and a low-dose estradiol patch on endometrial stability, as assessed by the rate of amenorrhea and endometrial stimulation. Methods This was an open study in which 64 moderately symptomatic, postmenopausal women were treated in the outpatient clinic of our University Hospital for different intervals up to 1 year. The treatment consisted of a combination of patches delivering 25 µg/day estradiol and intravaginal pills containing 100 mg of micronized progesterone. Patches and pills were administered concomitantly in a twice-a-week protocol. The endometrial response was assessed by endovaginal ultrasound completed with suction biopsy when required. Results Both cumulative amenorrhea and no-bleeding rates increased progressively and reached 88.9% and 100.0%, respectively, by the 12th month. Isolated or repetitive episodes of bleeding, bleeding and spotting, or only spotting were reported by three, four, and 12 women, respectively. Endometrial thickness remained unaltered. Endometrium was atrophic in the seven women in whom a biopsy was performed. Conclusion The substantially reduced progestogen load determined by this combination achieved an acceptable incidence of spotting or bleeding when associated with a low estrogenic dose. There was no apparent endometrial stimulation. Additional studies are required to confirm this observation.

Gene-gene interaction between CD40 and CD40L reduces bone mineral density and increases osteoporosis risk in women.

SUMMARY: We have analysed the association of single-nucleotide polymorphisms (SNPs) in CD40 and CD40L genes with bone mineral density (BMD) in our women. Results showed that women with TT genotype for rs1883832 (CD40) and for rs1126535 (CD40L) SNPs displayed reduced BMD and increased risk for osteopenia/osteoporosis. Our data notwithstanding, the results need to be replicated. INTRODUCTION: Recent data have revealed that the CD40/CD40L system can be implicated in bone metabolism regulation. Moreover, we previously demonstrated that rs1883832 in the CD40 gene was significantly associated with BMD and osteoporosis risk. The objective of the present work was to determine whether polymorphisms in CD40 and CD40L genes are associated with BMD and osteoporosis risk. METHODS: We conducted an association study of BMD values with SNPs in CD40 and CD40L genes in a population of 811 women of which 693 and 711 had femoral neck (FN) and lumbar spine (LS) densitometric studies, respectively. RESULTS: Women with the TT genotype for rs1883832 (CD40) showed a reduction in FN-BMD (P = 0.005) and LS-BMD (P = 0.020) when compared with women with the CC/CT genotype. Moreover, we found that rs1126535 (CD40L) was significantly associated with LS-BMD so that women with the TT genotype displayed lower BMD (P = 0.014) than did women with the CC/CT genotype. Interestingly, we have found a strong interaction between polymorphisms in these genes. Thus, women with the TT genotype for both rs1883832 and rs1126535 SNPs (TT + TT women) showed a lower age-adjusted BMD (Z-score) for FN (P = 0.0007) and LS (0.007) after adjusting by years since menopause, body mass index, smoking and menopausal status, densitometer type, hormone replacement therapy (HRT) use and HRT duration and after making the Bonferroni adjustment for multiple comparisons than did the remaining women. Logistic regression analysis adjusted by these covariates showed that TT + TT women had increased risk for FN (odds ratio (OR) = 2.76; P = 0.006) and LS (OR = 2.39; P = 0.020) osteopenia or osteoporosis than did the other women. CONCLUSIONS: Our results suggest that interaction between genetic variants in the CD40 and CD40L genes exerts a role on BMD regulation. Further studies, which we welcome, are needed to replicate these data in other populations.

Progestogens reduce thromboxane production by cultured human endothelial cells.

OBJECTIVES: Progestogens have been poorly studied concerning their roles in endothelial physiology. Prostanoids are vasoactive compounds, such as thromboxane A2, a potent vasoconstrictor, and prostacyclin, a vasodilator. We examined the effects of two progestogens used clinically, progesterone and medroxyprogesterone acetate, on thromboxane A2 production by cultured human umbilical vein endothelial cells (HUVEC) and investigated the role of progesterone receptors and the enzymes involved in production of thromboxane A2 and prostacyclin. METHODS: Cells were exposed to 1-100 nmol/l of either progesterone or medroxyprogesterone acetate, and thromboxane A2 production was measured in culture medium by enzyme immunoassay. Gene expression of prostacyclin synthase and thromboxane synthase was analyzed by quantitative real-time polymerase chain reaction. Expression of prostacyclin synthase protein was analyzed by Western blot. RESULTS: Both progestogens decreased thromboxane A2 release after 24 h. Protein and gene expression of prostacyclin synthase were increased after exposure to both progestogens, without changes in thromboxane synthase expression. These effects induced by progestogens were mediated through progesterone receptors, since they were decreased in the presence of the progesterone receptor antagonist RU486. The cyclo-oxygenase-1 selective inhibitor reduced thromboxane release. CONCLUSION: Progesterone and medroxyprogesterone acetate decreased HUVEC thromboxane release in a progesterone receptor-dependent manner, without changes in thromboxane synthase expression and enhanced prostacyclin synthase gene and protein expression.

[Evaluation of urinary cortisol levels in women with fibromyalgia]. / Evaluación de la cortisoluria en mujeres diagnosticadas de fibromialgia.

OBJECTIVE: We propose a comparative study of urinary cortisol in a controlled simple group of patients diagnosed with fibromyalgia (FM) during a minimum time frame (3 years) vs. a normal group with the same characteristics of age and gender. Our objective is to demonstrate if urinary cortisol at lower levels than those found in the normal population, as long as FM is regarded, could help to evaluate the fatigue. METHODS: We determined the urinary cortisol in a group of 47 women with a clinical diagnosis of FM using the criteria from the American College of Rheumatology (ACR) 1990, with ages between 29 and 64 years, in whom an accurate sample was collected and cortisol was determined using an FPIA method. The results were compared with the urinary cortisol obtained in a group of 88 healthy women within the same age range as those with FM. RESULTS: Urinary cortisol in FM was 65.0 microg/l (median), which was significantly lower than that of the healthy group (80.0 microg/l), p<0.001. CONCLUSION: 33.4% of patients with FM displayed urinary cortisol concentrations significantly lower than the group of women without FM.

A C >T polymorphism located at position -1 of the Kozak sequence of CD40 gene is associated with low bone mass in Spanish postmenopausal women.

UNLABELLED: This study evaluated the association of a polymorphism in the CD40 gene with BMD and risk of osteopenia or osteoporosis in a population of 602 postmenopausal women. Results showed that women with the TT genotype had lower BMD at femoral neck and spine sites and increased risk of osteopenia or osteoporosis. INTRODUCTION: Recent findings have demonstrated that the CD40/CD40L system, which is of main importance for the immune system, can also be implied in the regulation of bone metabolism. The main objective of the present work has been to clarify whether single nucleotide polymorphisms (SNPs) affecting genes of CD40/CD40L system could be linked with abnormalities in the level of bone mineral density (BMD) in menopausal women. METHODS: We performed an association study of BMD values with a SNP located at position -1 of the Kozak consensus sequence of CD40 gene (rs1883832; C>T) in a population of 602 postmenopausal women. RESULTS: Women with the TT genotype (8.6% of women) displayed a reduction in femoral neck BMD (FN BMD) and lumbar spine BMD (LS BMD) of 6.2% and of 6.3%, respectively, as compared to women with CC + CT genotype. Logistic regression analysis adjusted for age, weight, and height showed that women with the TT genotype had increased risk for FN (odds ratio: 2.34; 95% CI: 1.12-4.89) and LS (odds ratio: 2.49; 95% CI: 1.19-5.24) osteopenia or osteoporosis. CONCLUSIONS: Women with the TT genotype in rs1883832 SNP affecting to Kozak consensus sequence of CD40 gene had lower BMD at FN and at LS sites and increased risk of osteopenia or osteoporosis.

Comparative effects of 17beta-estradiol, raloxifene and genistein on bone 3D microarchitecture and volumetric bone mineral density in the ovariectomized mice.

UNLABELLED: This study assessed the effect of estradiol, raloxifene and genistein on the preservation of bone 3D-microarchitecture and volumetric bone mineral density (vBMD) in the ovariectomized mouse model. Our results indicated that raloxifene was more effective in preserving bone ovariectomized-induced changes, the advantage being concentrated in both bone microarchitecture and vBMD. INTRODUCTION: This study assessed the effect of different estrogen receptor (ER) agonists on the preservation of bone 3D-microarchitecture and volumetric bone mineral density (vBMD) in the ovariectomized (OVX) mouse model. METHODS: Twelve-week-old female C57BL/6 mice were randomly assigned to one of five groups: (1) SHAM-operated + vehicle; (2) OVX + vehicle; (3) OVX + 17beta-estradiol (5 microg/kg); (4) OVX + raloxifene (1 mg/kg); (5) OVX + genistein (25 mg/kg), during 4-weeks. Bone microarchitecture and trabecular, cortical and total vBMD of distal femur were imaged by ex vivo microcomputed tomography (micro-CT). RESULTS: Ovariectomy produced a global deterioration involving both trabecular and cortical 3D-microarchitecture and vBMD. Raloxifene maintained both microarchitecture and vBMD, whereas estradiol prevented deterioration of some microstructural parameters, such as trabecular thickness (Tb.Th), trabecular bone pattern factor (Tb.Pf), and cortical periosteal perimeter (Ct.Pe.Pm), but did not completely block the loss in vBMD. Mice treated with genistein exhibited the less favourable profile in both vBMD and microstructural parameters preserving only cross-sectional bone area (B.Ar) and Ct.Pe.Pm in cortical bone. CONCLUSION: Our data indicate that, at the selected doses, raloxifene was more effective in preserving bone OVX-induced changes than either estradiol or genistein, the advantage being concentrated in both bone microarchitecture and vBMD.

Effects of prone position on alveolar dead space and gas exchange during general anaesthesia in surgery of long duration.

BACKGROUND AND OBJECTIVE: We investigated the effects of prone position on respiratory dead space and gas exchange in 14 anaesthetized healthy patients undergoing elective posterior spinal surgery of more than 3 h of duration. METHODS: The patients received a total intravenous anaesthetic with propofol/remifentanil/cisatracurium. They were ventilated at a tidal volume of 8-10 mL kg(-1), zero positive end-expiratory pressure and an inspired oxygen fraction of 0.4. Physiological, airway and alveolar dead spaces were calculated by analysis of the volumetric capnography waveform. Measurements were made in supine position (20 min after the beginning of mechanical ventilation) and 30, 120 and 180 min after turning to prone position. RESULTS: We found that the alveolar dead space/tidal volume ratio did not change. PaO(2)/F(i)O(2) increased, although not statistically significantly. Dynamic compliance was reduced due to a reduction in tidal volume and an increase in plateau pressure. CONCLUSIONS: Patients undergoing surgery in prone position for a duration of 3 h under general anaesthesia including muscle relaxation and mechanical ventilation without positive end-expiratory pressure have stable haemodynamics and no significant changes in the alveolar dead space to tidal volume ratio. Oxygenation tended to improve.

Estrogen receptor agonists and immune system in ovariectomized mice.

Several data implicate the immune system in bone lost after estrogen deficiency, however, some of the effects on the immune system of estrogen deficiency or of estrogen receptor (ER) modulation are not well established. In this study, the effect of ER agonists on the immune system in ovariectomized mice is analyzed. Mice were ovariectomized and were administered 17beta-estradiol (E2), raloxifene (RAL) or genistein (GEN). The effect of a 4-week treatment on bone turnover and on several parameters that reflect the status of the immune system was studied. Results show that ovariectomy provoked both uterine atrophy and thymic hypertrophy. Although RAL corrected thymic hypertrophy, only E2 corrected both. Ovariectomized mice showed increased levels of serum calcium and cathepsin K gene expression and decreased levels of serum alkaline phosphatase (ALP) activity, which suggests that there is a persistent alteration in bone metabolism. Moreover, ovariectomy increased B-cells and CD25+ cells, and decreased the percentages of T-cells and Cbfa1 gene expression in bone marrow (BM). All ER agonists corrected, although to different degrees, changes induced by the ovariectomy. Furthermore, results showed that it is essential to adjust ER agonist doses to avoid immunosuppression, since all ER agonists decreased BM T-cell levels.

Alterations in the phenotype and function of immune cells in ovariectomy-induced osteopenic mice.

BACKGROUND: Within the last few years, much evidence has been presented on the involvement of the immune system in certain types of bone loss, such as activated T cells in rheumatoid arthritis and in periodontitis. Estrogen deficiency induces bone loss; however, how this deficiency affects the immune system has not been sufficiently studied. METHODS: To evaluate the effects of estrogen withdrawal on the status and functionality of the immune system, mice were ovariectomized or sham-operated, and 5 weeks after surgery, when osteopenia had developed, several parameters were analysed in spleen and in bone marrow. We analysed bone turnover, cell phenotype by flow cytometry, cell function by cell proliferation assays, and the expression of several genes related to the process. RESULTS: Five weeks after ovariectomy, augmented osteoclastogenesis persisted in the bone marrow. In addition, the ovariectomized mice had more B-cells and CD3+ T-cells expressing the receptor activator of NF-kappaB ligand (CD3+/RANKL+). The ovariectomized mice had lower serum alkaline phosphatase activity, a normal amount of T cells, lower percentages of CD11b+ and CD51+ cells in the bone marrow, and a lower serum interferon-gamma level compared with sham-operated controls. CONCLUSIONS: The data suggest that, 5 weeks after ovariectomy, bone turnover remains imbalanced, with increased osteoclastogenesis and a decreased rate of bone formation. Moreover, there is an increase in B-cell formation, with normal and decreased percentages of T cells and myelomonocytic cells (CD11b+), respectively, in the bone marrow. Decreased serum interferon-gamma levels could be involved in the increased osteoclastogenesis found in the present work.

Progestogens stimulate prostacyclin production by human endothelial cells.

BACKGROUND: The effects of progestogens on endothelial physiology are poorly studied. Prostacyclin is a potent vasodilator synthesized by two isoforms of cyclooxygenase (COX) in endothelium. We examined the effects of two clinically used progestogens, progesterone and medroxyprogesterone acetate (MPA), on prostacyclin production by cultured human umbilical vein endothelial cells (HUVEC) and the possible role of progesterone receptors and both COX enzymes. METHODS: Cells were exposed to 1-100 nmol/l of either progesterone or MPA and prostacyclin production was measured in culture medium. RESULTS: Both progestogens significantly increased prostacyclin release in a time- and dose-dependent manner, being higher than control after 24 h. Progesterone and MPA, both at 10 nmol/l, increased mRNA expression and protein content of both COX. All these effects were mediated through progesterone receptor activation, since they were abolished by treatment of cells with the progesterone receptor antagonist RU-486. Selective inhibitors of COX-1 and -2 (SC-560 and NS-398 respectively) reduced basal prostacyclin release, and eliminated increased production in response to progestogens. In combination with estradiol, progestogens had an additive effect without eliminating estradiol-induced prostacyclin production. CONCLUSIONS: Our results support the hypothesis that progesterone and MPA increased HUVEC prostacyclin production in a progesterone receptor-dependent manner, by enhancing COX-1 and COX-2 expression and activities.

Closed-system anaesthesia for laparoscopic surgery: is there a risk for carbon monoxide intoxication?

BACKGROUND AND OBJECTIVE: One of the complications of laparoscopic surgery is carbon monoxide production during electrocautery. The aim of our study was to ascertain the relationship between intraperitoneal and alveolar concentrations of carbon monoxide and systemic carboxyhaemoglobin in patients undergoing laparoscopic cholecystectomy and anaesthetized with a closed system, where the carbon monoxide excreted through the lungs is accumulated in the circuit and thus re-inhaled. METHODS: Nine consecutive patients undergoing laparoscopic cholecystectomy were studied. Patients' lungs were ventilated with a closed anaesthesia breathing system (Physioflex). Measurements were taken after establishing pneumoperitoneum (baseline) and at 5, 15 and 30 min after starting electrocautery. RESULTS: Mean duration of pneumoperitoneum was 42 +/- 13 min with cumulative electrocautery time of 2.4 +/- 1.8 min. Intraperitoneal carbon monoxide concentrations increased significantly at 5, 15 and 30 min reaching peak values of 481 +/- 151 ppm at 15 min. No significant differences were found in alveolar carbon monoxide and carboxyhaemoglobin concentrations with respect to baseline. CONCLUSIONS: No significant increase in carboxyhaemoglobin is produced during laparoscopic surgery, even under closed-system anaesthesia without pulmonary carbon monoxide elimination. This is most likely due to a low peritoneal absorption of carbon monoxide. We conclude that in adult patients, no carbon monoxide intoxication is caused if reasonable periods of electrocautery are used and the intraperitoneal gas is regularly renewed.

Bone turnover markers and PTH levels in surgical versus natural menopause.

In order to assess similarities and differences in women that suffer surgical versus natural menopause, a series of bone, clinical, and biochemical parameters was assayed in a clinical sample of 35 women with surgical menopause and 112 women with natural menopause. Biochemical parameters included hormones [parathyroid hormone (PTH) and the sex steroids estradiol and testosterone] and several markers of bone turnover measured in urine (N-telopeptide and calcium/creatinine ratio) or serum (osteocalcin, total alkaline phosphatase, total and ionic calcium, phosphate, and magnesium). In addition to type of menopause, women were divided by years since menopause (ysm 2). To detect differences and relationships between variables, ANOVA, ANCOVA, and linear regression analyses were used. Only N-telopeptide, one resorption marker, was significantly affected by the variable years since menopause 2 ( P <0.01), but not by type of menopause. The age-corrected level of PTH was significantly decreased in the surgical menopause group ( P < 0.05). In conclusion, type of menopause did not impose significant differences in bone turnover markers. PTH, one powerful resorption hormone, was diminished in surgical menopause.

[Extracorporeal shock-wave lithotripsy. An established treatment]. / Litotricia extracorpórea por ondas de choque. Un tratamiento establecido.

Extracorporeal shock wave lithotripsy (ESWL) is the most required urinary stone therapy in our country and in the rest of the world. In a way it has replaced the alternative treatments (open surgery, percutaneous nephrolithectomy, ureteroscopy). Nevertheless these therapeutic approaches have still its own indications. Although there is no a definitive agreement, it should be desirable a world-wide consensus where each therapy will have a exactly defined land with all potential of each management improved. We review ESWL technical aspects, its literature-based most accepted indications, adverse bioeffects and last, future improvements are considered.