Cesarean sections sometimes save the lives of mothers and babies; however, they are excessively used compared to medical necessity, which is influenced by various factors that are explored in this article. Since, in most cases the risks of cesarean sections are greater than the benefits, particularly in cesareans that are not medically indicated, it is astonishing that cesarean surgery is the most common surgical procedure, taking away resources from medically necessary care. While economic incentive is counted among the reasons for the increasing cesarean trend, the situation is not so simple since many factors interact to cause the trend. Since reversal of the vaginal birth after cesarean (VBAC) trend downward is correlated with revised policy statements by e.g. American College of Obstetricians and Gynecologists (ACOG), which have since been partially moderated, it became much more difficult for medical institutions to provide VBACs due to concerns about liability. Although whether to give birth by cesarean delivery is a matter for informed consent, yet childbearing women are influenced significantly by their health service providers' opinions. Even though the World Health Organization (WHO) recommends the most peripheral level of maternity care for normal pregnancy and childbirth that is safe using midwives, yet the percentage of midwife deliveries is low. Among other things, it has been suggested that more childbirth by midwife delivery and in out-of-hospital settings can reduce medically unnecessary cesareans and the undue risks associated with them, and free up medical resources for those in need.
Extramammary Paget's disease (EMPD) is a rare intraepidermal adenocarcinoma. The common sites of EMPD involvement are the vulva, perineal, perianal, scrotal and penile skin. Several studies have shown that HER-2/neu, also known as c-erbB-2, is amplified and overexpressed in many cancers. In this study, we investigated the expression and clinical significance of HER-2 in Japanese patients with EMPD. Keratinocytes in epidermis were slightly positive for HER-2. As for EMPD, 19 of 31 EMPD were positive for HER-2 (61%). There is significant correlation between the presence of invasion and strong positivity (3+) for HER-2 (p < 0.02). Furthermore, there is significant correlation between the presence of lymph node metastasis and strong positivity (3+) for HER-2 (p < 0.02). These results suggest that patients with EMPD strongly positive for HER-2 may have high risk for lymph node metastasis and should be followed up carefully. The observed overexpression of HER-2 in EMPD presents a potential therapeutic target for adjuvant treatment of this disease. Treatment with trastuzumab is well established in breast cancer with HER-2 overexpression and is recommended by several consensus statements. The results of the present study indicate that targeting therapies for HER-2, such as trastuzumab, may be used for EMPD particularly in patients with invasive and/or metastatic EMPD.
Once-daily tacrolimus (denoted here simply as OD) is a recently developed extended-release drug formulation. The purpose of the present study was to pharmacokinetically evaluate tacrolimus exposure and determine the feasibility of its de novo use in liver transplant recipients in the perioperative period. This was an open-label, single center study. Eligible patients were 18 to 65 years of age in the perioperative period after a liver transplant. Patients were initially treated with intravenous tacrolimus and then converted to the 10× milligram-for-milligram daily dose of OD administered once daily. Twenty-four-hour pharmacokinetic profiles were obtained on day 7 after the conversion. Laboratory and safety parameters were also evaluated. A total of 9 patients received OD, were successfully converted, and provided pharmacokinetic profiles. Intravenous tacrolimus and OD resulted in similar areas under the curve for 24 h (AUC0-24) of tacrolimus. OD was well tolerated with a safety profile comparable to that of intravenous tacrolimus. The AUC0-24 correlated with the minimum concentration of OD (R = 0.49). Renal and liver functions remained stable. None of the patients experienced acute rejection during the observation period. OD and intravenous tacrolimus provide equivalent drug exposure, allowing conversion of selected liver transplant recipients from intravenous tacrolimus to OD in the peri-operative period.
Pleural tuberculosis is an extra-pulmonary disease which poses a diagnostic dilemma. The detection of mycobacterial DNA by IS6110 polymerase chain reaction (PCR) in clinical samples is a promising approach for the rapid diagnosis of pleural tuberculosis infections. The aim of the present study is to evaluate the advantage of using IS6110 PCR for rapid detection of Mycobacterium tuberculosis (M. tuberculosis)from pleural fluid. 102 clinically suspected cases of pleural tuberculosis cases were enrolled from inwards and outwards of the Department of Pulmonary Medicine at Chattrapati Shahuji Maharaj Medical University, Lucknow from April 2007 to April 2010. The pleural fluids were processed at the Mycobacteriology Laboratory of Department of Microbiology at Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Pleural fluid samples were processed and examined by Ziehl Neelsen (ZN) staining for acid fast bacilli and detection of M. tuberculosis by BACTEC culture. We applied IS6110 PCR to detect specific M. tuberculosis complex in pleural fluid samples. We found a significant difference in sensitivity of different tests, acid fast bacilli were detected in 17 (16.6%) samples by ZN Staining , 47 (46.1%) by BACTEC culture and using IS6110 PCR, 62 (60.7%) were positive for IS6110 PCR for M. tuberculosis. We found IS6110 PCR was much more sensitive than ZN staining and BACTEC culture. IS6110 PCR detection of M. tuberculosis may be very useful in cases that are highly suspect as pleural tuberculosis and those that are negative for AFB and culture. IS6110 PCR may gain an immense prospective to better clinicians ability to improve diagnosis of pleural tuberculosis.
The relation has not been reported consistently between the polymorphisms in the gene of apolipoprotein A5 (APO A5) and coronary artery disease (CAD). To clarify the discrepancy, we conducted a comprehensive search of PubMed and EMBASE for all available case-control studies to explore the association between two APO A5 polymorphisms and CAD. Two reviewers independently selected studies. Statistical analyses were carried out using the STATA software package v 10.0. Thirteen studies investigated the association between the APO A5 -1131T>C polymorphism and risk of CAD were selected in this meta-analysis with 5,050 cases and 7,272 controls. For the S19W APO A5 gene polymorphism, 5 studies were included with 2,196 cases and 3,933 controls. We observed a significant statistical association between Apo A5 -1131T>C polymorphism and CAD (recessive genetic model: OR = 1.73, 95% CI = 1.37-2.19; dominant genetic model: OR = 1.42, 95% CI = 1.25-1.61; allelic contrast: OR = 1.31, 95% CI = 1.22-1.39, respectively). After restricting our analysis to Chinese individuals, we found that the association was stronger. We also observed strong association between the APO A5 S19>W polymorphism and risk of CAD under a recessive genetic model. This meta-analysis reveals that the minor allele of the -1131T>C polymorphism in the promoter of APO A5 gene significantly increases the susceptibility to CAD. This effect is more pronounced in Chinese subjects.
Our previous studies revealed that valsartan, an angiotensin II type I receptor blocker, exhibited renoprotective effects through decreasing urine protein excretion levels due to improving glomerular permeability in rats with diabetic nephropathy (DN). In this study, we sought to investigate the underlying mechanisms in perspectives of oxidative stress, transforming growth factor beta-1 (TGF-β1) and monocyte chemoattractant protein-1 (MCP-1) expressions in glomerular mesangial cells (GMCs) and glomerular epithelial cells (GECs) since their roles are well-established in the development and progression of DN. High-glucose levels significantly increased oxidative stress in GMCs and GECs, as evidenced by enhanced generation of reactive reactive oxygen species (ROS), reduced levels of glutathione (GSH) and antioxidant enzyme superoxide dismutase (SOD), and increased production of malondialdehyde (MDA). Treatment with valsartan significantly restored the levels of those oxidative stress relevant molecules. Furthermore, valsartan obviously diminished the expression of proinflammatory cytokine MCP-1 in GMCs and GECs induced by high-glucose levels both at mRNA and protein levels, as determined by real-time PCR, immunocytochemistry, western blotting, and ELISA. In addition, the increased expressions of TGF-β1 mRNA and protein induced by high-glucose level were also abrogated by valsartan treatment in GMCs, as evaluated by real-time PCR and ELISA. These results suggest that the renoprotective effects of valsartan may be related to its potential in decreasing oxidative stress and the expressions of MCP-1 and TGF-β1 in GMCs and GECs.
Recent studies indicate a circadian rhythm in blood pressure and heart rate and its association with various neurotransmitters. In the present study, we examine the circadian nature of blood pressure/heart rate and salivary cortisol in night shift workers and whether these circadian changes produced by night shifts are reversible. Sixteen healthy nurses of both genders, aged 20-40 years, performing day and night shift duties, were randomly selected out of 22 who volunteered for this study. Ambulatory blood pressure monitoring was done in all the subjects and salivary cortisol levels were analyzed during both day and night shift duties. There were clinically significant changes in the Acrophase of blood pressure and cortisol levels, indicating ecphasia (odd timing of systolic blood pressure) individually during night as well as day shifts. However, this pattern was statistically not significant. A reverse pattern of Acrophase was observed in 8 out of 16 subjects when they were posted on day shift. No significant change was found in midline estimating statistics of rhythm (MESOR) of blood pressure values. Changes in Double amplitude (Predictable change) were observed in 8 subjects during night shifts as well as in 7 subjects during day shifts. However, the pattern was not similar and night workers had an altered circadian pattern in the night as well as during day shifts. Changes in Double amplitude, Acrophase and Salivary cortisol were found during night as well as day shifts but these changes were not statistically significant (p > 0.05) due to incomplete recovery during day shifts (changes again seen when they came back to day shifts). Salivary cortisol levels were lowest in early morning, increased at midnight and further increased in the afternoon during night shifts along with ecphasia. It is possible that nurses working the night shift felt more tired due to the altered circadian cycle.