Maternal sociodemographic characteristics and risk factors of antepartum fetal death

The objectives of this study were to assess the sociodemographic profile and to identify the risk factors of ante-partum fetal death which occurs after the age of viability of fetus. This prospective observational study was conducted in the Obstetrics department of Ad-din Women Medical College Hospital during the period of June, 2009 to July, 2010. A total of 14,015 pregnant patients were admitted in the study place after the age of viability, which was taken as 28 weeks of gestation for our facilities. Eighty-three (0.59%) of them were identified as intrauterine fetal death. Assessment of maternal sociodemographic characteristics and maternal-fetal risk factors were evaluated with a semi structured questionnaire pretested. Majority (81.92%, n=68) of the patients were below 30 years of age, 78.31% belonged to middle socioeconomic group. Almost 58% women had education below SSC level and 28.91% took regular antenatal checkup. About 61.45% patients were multigravida. Most (59.04%) ante-partum deaths were identified below 32 weeks of pregnancy. Out of 83 patients, maternal risk factors were identified in 41(49.59%) cases where fetal risk factors were found in 16(19.27%) cases; no risk factors could be determined in rests. Hypertension (48.78%), diabetes (21.95%), hyperpyrexia (17.3%), abruptio placentae (4.88%) and UTI (7.36%) were identified as maternal factors; and congenital anomaly (37.5%), Rh incompatibility (37.5%), multiple pregnancy (12.5%) and post-maturity (12.5%) were the fetal risk factors. Here, proximal biological risk factors are most important in ante-partum fetal deaths. More investigations and facilities are needed to explain the causes of antepartum deaths.     

Genetic polymorphisms and the risk of infection following esophagectomy. positive association with TNF-alpha gene -308 genotype

OBJECTIVE: To examine the association of single nucleotide polymorphisms (SNPs) in inflammation-related genes in the development of infections following esophagectomy. SUMMARY BACKGROUND DATA: Genetic polymorphisms for immunoregulatory cytokines may explain individual variation in response to trauma. Esophagectomy is associated with a high risk of postoperative infection and sepsis, and this study explored a number of SNPs in cytokine genes and their relationship to postoperative infection. METHODS:: In a prospective analysis of 197 patients with esophageal cancer undergoing resection, 55 developed postoperative infections. DNA was extracted and genotyping was performed for polymorphisms in genes encoding TNF-alpha, IL-1beta, IL-1 receptor antagonist, IL-10, and Toll-like receptor 4 (TLR-4) using Taqman chemistry and PCR/RFLP. In a blinded analysis, the cohort with infections was compared with the no complication cohort (n = 114) and a cohort that had noninfective complications (n = 28). RESULTS: No differences in polymorphisms for IL-1beta, IL-1 RN, IL-10, and TLR-4 genes were observed across groups. The frequency of TNF-alpha -308 GG homozygotes was significantly (P = 0.021) higher in the postoperative infection group. The G allele was significantly higher in the postoperative infection group compared with the no complication group (P = 0.017) and other complication group (P = 0.013). By multivariate analysis, this polymorphism as well as age and body mass index were predictors of infection. CONCLUSION: The TNF-alpha -308A allele has been shown to be associated with higher circulating levels of TNF-alpha and the -308 G allele is a comparative low secretor allele. We propose that the polymorphism in the promotor region of TNF-alpha gene may lead to altered expression and a possible suboptimal activity of TNF-alpha in persons with GG genotypes, and these data suggest a link with infection following major surgery.     

Memory T-Cell Responses to Vibrio cholerae O1 Infection

Vibrio cholerae O1 can cause diarrheal disease that may be life-threatening without treatment. Natural infection results in long-lasting protective immunity, but the role of T cells in this immune response has not been well characterized. In contrast, robust B-cell responses to V. cholerae infection have been observed. In particular, memory B-cell responses to T-cell-dependent antigens persist for at least 1 year, whereas responses to lipopolysaccharide, a T-cell-independent antigen, wane more rapidly after infection. We hypothesize that protective immunity is mediated by anamnestic responses of memory B cells in the gut-associated lymphoid tissue, and T-cell responses may be required to generate and maintain durable memory B-cell responses. In this study, we examined B- and T-cell responses in patients with severe V. cholerae infection. Using the flow cytometric assay of the specific cell-mediated immune response in activated whole blood, we measured antigen-specific T-cell responses using V. cholerae antigens, including the toxin-coregulated pilus (TcpA), a V. cholerae membrane preparation, and the V. cholerae cytolysin/hemolysin (VCC) protein. Our results show that memory T-cell responses develop by day 7 after infection, a time prior to and concurrent with the development of B-cell responses. This suggests that T-cell responses to V. cholerae antigens may be important for the generation and stability of memory B-cell responses. The T-cell proliferative response to VCC was of a higher magnitude than responses observed to other V. cholerae antigens.Vibrio cholerae is a gram-negative bacterium that can cause a severe, acute secretory diarrhea. Serological differentiation of V. cholerae strains is based on the O-side chain of the lipopolysaccharide (LPS) component of the outer membrane. Of the more than 200 serogroups of V. cholerae identified, only the O1 and O139 serogroups can cause epidemic cholera (44). These pathogens are noninvasive and colonize the mucosal surface of the small intestine (44).Natural infection with V. cholerae is known to provide protection against subsequent disease, but the mechanism of this protective immunity is not fully characterized. The vibriocidal antibody is a complement-dependent bactericidal antibody that is associated with protection from infection. However, no known threshold level of the vibriocidal antibody confers complete protection from V. cholerae infection, and some individuals with low serum vibriocidal antibody titers are still protected. This suggests that the vibriocidal titer may be a surrogate marker (16, 45). Elevated serum immunoglobulin A (IgA) antibody levels specific for the B subunit of cholera toxin (CTB), the major structural subunit of a type IV pilus (TcpA), and LPS are also associated with protective immunity in areas where cholera is endemic (19). However, after natural infection, the serum levels of these antibodies wane more rapidly than protective immunity (19). Patients with cholera develop memory B-cell responses of both the IgG and the IgA isotype to at least two V. cholerae protein antigens, CTB and TcpA. These responses are detectable for at least 1 year after infection and persist even after V. cholerae antigen-specific antibody-secreting cells and serum antibody titers have returned to baseline (18). B-cell memory responses also develop for the T-cell independent antigen LPS, but these responses wane more rapidly than memory B-cell responses to protein antigens, suggesting that durable memory B-cell responses to some V. cholerae antigens may be T-cell dependent (18).We have recently demonstrated that cholera patients mount a primed T-cell response in the mucosa after V. cholerae O1 infection (6). We hypothesize that protection from cholera may be mediated by memory B cells capable of an anamnestic response in the gut mucosa and that these memory B cells may depend on stimulation provided by memory T cells for their development and maintenance. T cells may contribute to the activation of B cells during V. cholerae infection by secreting stimulatory cytokines and direct contact with B cells in lymph nodes. Therefore, T cells may have an important role in protective immunity to V. cholerae infection.We characterized the memory T-cell responses to V. cholerae antigens following natural V. cholerae infection and compared these with serological responses to the same antigens. Previously, our group has studied various V. cholerae antigens, including mannose-sensitive hemagglutinin, TcpA, CTB, and LPS (22, 33, 37). We also included in the present study responses to a novel antigen, V. cholerae cytolysin/hemolysin (VCC) (31, 32). The hly gene that encodes the VCC protein is widespread across both pathogenic and environmental strains of V. cholerae, suggesting that VCC may impart an advantage to the organism (42). Although the precise role of VCC in V. cholerae infection is unknown, VCC is the primary virulence factor in V. cholerae infection with non-O1, non-O139 strains that do not produce cholera toxin (12, 46). The immune response to VCC is not well understood; however, recent studies suggest that VCC may promote a Th2 response in V. cholerae infection (2). In addition, the cytolytic activity of VCC may generate epithelial destruction that allows other V. cholerae antigens to penetrate the mucosa and promote the inflammatory response observed in V. cholerae infection (35, 39).     

Treatment of metastatic breast cancer during pregnancy: we need to talk!

Metastatic breast cancer during pregnancy is a challenging situation. The literature yield in this topic is poor given the rarity of the disease. Management strategies should be discussed in a multidisciplinary manner and each case have to be counselled separately and informed about the pros and cons of different treatment options. Here, we report a case of metastatic breast cancer initially diagnosed during pregnancy. We discuss the clinical course and dilemmas governing the management decisions.     

The preventative analgesic effect of preincisional peritonsillar infiltration of two low doses of ketamine for postoperative pain relief in children following adenotonsillectomy. A randomized, double-blind, placebo-controlled study

Background:  In literature, the use of ketamine for the preventative analgesia in the management of postoperative pain is controversial. The purpose of the present study was the clinical assessment of the efficacy of preincisional peritonsillar infiltration of two doses of ketamine on postoperative pain relief compared with peritonsillar saline in children undergoing adenotonsillectomy.
Methods/materials:  Seventy-five ASA physical status I and II patients, aged 3–12 years, scheduled for adenotonsillectomy were enrolled in this randomized, double-blind, placebo-controlled study. Patients were divided into three groups of 25 each and received a local peritonsillar infiltration of 0.9% saline (group S), ketamine 0.5 mg·kg⁻¹ (group K1), or ketamine 1 mg·kg⁻¹ (group K2). All medications were 2 ml in volume which was applied 1 ml per tonsil 3 min prior to tonsillectomy. The Children's Hospital of Eastern Ontario Pain Scale (CHEOPS) and Wilson sedation scale were used to evaluate pain levels and sedative conditions, respectively.
Results:  Group S had significantly higher CHEOPS scores than group K1 and K2. Both K1 and K2 groups had comparable scores, which were not statistically significant ( P  > 0.05). During 24 h after surgery, 16 patients in group S and no patients in groups K1 or K2 needed analgesics ( P  <   0.001).
Conclusions:  A 0.5 or 1 mg·kg⁻¹ dose of ketamine given at approximately 3 min before surgery by peritonsillar infiltration provides efficient pain relief during 24 h after surgery without side-effects in children undergoing adenotonsillectomy.     

Pronounced susceptibility to infection by Salmonella enterica serovar Typhimurium in mice chronically exposed to lead correlates with a shift to Th2-type immune responses

Persistent exposure to inorganic lead (Pb) is known to adversely affect the immune system. In the present study, we assessed the effect of chronic Pb exposure on susceptibility to infection by the facultative intracellular pathogen Salmonella enterica serovar Typhimurium. Mice were exposed to 10 mM Pb-acetate in drinking water for approximately 16 weeks, resulting in a significant level of Pb in the blood (106.2+/-8.9 microg/dl). Pb exposure rendered mice susceptible to Salmonella infection, manifested by increased bacterial burden in target organs and heightened mortality. Flow cytometric analysis of the splenic cellular composition in normal and Pb-exposed mice revealed no gross alteration in the ratios of B and T lymphocytes or myeloid cells. Similarly, the capacity of B and T cells to upregulate the expression of activation antigens in response to mitogenic or inflammatory stimuli was not hindered by Pb exposure. Analysis of the ability of ex vivo-cultured splenocytes to secrete cytokines demonstrated a marked reduction in IFN-gamma and IL-12p40 production associated with Pb exposure. In contrast, secretion of IL-4 by splenocytes of Pb-treated mice was 3- to 3.6-fold higher than in normal mice. The increased capacity to produce IL-4 correlated with a shift in the in vivo anti-Salmonella antibody response from the protective IgG2a isotype to the Th2-induced IgG1 isotype. We conclude that chronic exposure to high levels of Pb results in a state of immunodeficiency which is not due to an overt cytotoxic or immunosuppressive mechanism, but rather is largely caused by a shift in immune responsiveness to Th2-type reactions.     

Successful use of subcutaneous anakinra in hemophagocytic lymphohistiocytosis precipitated by candidiasis in a patient with systemic lupus erythematosus: A case report and description of a novel therapeutic regimen

Hemophagocytic lymphohistiocytosis (HLH) is a rare and often fatal condition characterized by inappropriate immune system activation leading to a “cytokine storm”, and ultimately resulting in end-organ damage. Causes include primary defects in genes involved in immune-mediated cytolytic pathways, or secondary triggers such as infection or malignancy. We describe a case of HLH precipitated by fungal infection which occurred as a consequence of immunosuppression for management of systemic lupus erythematosus (SLE) and necrotizing myopathy. The patient presented with immune-mediated disease of the muscles and lung which was treated with high-dose corticosteroids and aggressive immunosuppression. HLH emerged in the context of confirmed candidiasis and features of severe sepsis. The patient responded rapidly to antifungal therapy and high-dose anakinra, which was administered subcutaneously and progressively weaned over 4 weeks. She completed HLH treatment as an outpatient and remains well at 12 months with controlled SLE and no recurrence of HLH.     

Missed opportunities for noninvasive positive pressure ventilation: a utilization review

BACKGROUND: Although noninvasive positive pressure ventilation (NPPV) improves outcomes in patients who have acute respiratory failure due to chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF), it may be underutilized outside the controlled trial setting. PURPOSE: The purpose of this study is to determine the proportion of patients who met criteria for a trial of NPPV but were emergently intubated and mechanically ventilated without receiving a trial of NPPV. METHODS: We retrospectively reviewed charts of patients who were intubated and ventilated or who received NPPV on admission to one intensive care unit and who had an intensive care unit admitting diagnosis of either exacerbation of COPD or CHF during the period from November 1998 to July 2003. RESULTS: Of the 243 patients who had an admitting diagnosis of COPD or CHF, 59 (24.3%) met explicit criteria for a trial of NPPV. Only 20 (33.9%) of 59 had a trial of NPPV. The remaining 39 (66%) of 59 did not receive a trial of NPPV and were intubated. INTERPRETATION: Nearly two thirds of patients who appeared to meet criteria for NPPV did not receive a trial of this intervention. There is an opportunity to improve the use of NPPV in these patients. Systematic knowledge translation strategies such as guideline implementation and interactive educational interventions may optimize the appropriate use of NPPV.