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Biomedical subjects

V Shah

Publications and source records attributed to V Shah.

At least 19 recordsLinked to original sources

The use of irradiated allograft in a paediatric population: an Indian experience.

Lyophilised, irradiated bone allografts available for the first time in the country from the Tata Memorial Hospital Tissue Bank were used in 30 paediatric patients from January 2001 to August 2004. They included 20 patients of scoliosis of various origin and ten with assorted orthopaedic conditions including one congenital kyphosis, two Pott's spine, one Perthes disease, one developmental dysplasia of the hip (DDH), one infective non-union, one fibrous dysplasia and three with bone defects either due to trauma, a cyst or removal of hardware. Morsellised allograft was used in 28 patients. In those cases of scoliosis in which ribs were resected out during costectomy, the morsellised allograft was mixed with morsellised rib autograft. Non-morsellised femoral head grafts were used in two patients, one a case of varus open derotation osteotomy in Perthes disease and the other an acetabuloplasty in DDH. Patients were followed at intervals of 8-12 weeks and radiological evaluation was done periodically. The follow up period ranged from 1 to 4 years post surgery. All patients with scoliosis showed excellent union at the grafting site with non-progression of curve and no signs of loosening at implant site. The two patients, in whom non-morsellised femoral head grafts were used, both showed incorporation of the graft with good fusion within a 4 month period. None of the patient had infection, non-union, pseudoarthrosis, fracture at the graft site, or any other complication.

Adolescent↗

Compact phase delay technique for increasing the amplitude of coherent population trapping resonances in open Lambda systems.

We propose and demonstrate a novel technique for increasing the amplitude of coherent population trapping (CPT) resonances in open Lambda systems. The technique requires no complex modifications to the conventional CPT setup and is compatible with standard microfabrication processes. The improvement in the CPT resonance amplitude as a function of intensity of the excitation light agrees well with the theory based on ideal open and closed Lambda systems.

Journal Article↗

Breastfeeding or breast milk for procedural pain in neonates.

BACKGROUND: Physiological changes brought about by pain may contribute to the development of morbidity in neonates. Clinical studies have shown reduction in the changes in physiological parameters and pain score measurements following pre-emptive analgesic administration in situations where the neonate is experiencing pain or stress. Nonpharmacological measures (such as holding, swaddling, breastfeeding) and pharmacological measures (such as acetaminophen, sucrose and opioids) have been used for this purpose. OBJECTIVES: The primary objective of this review was to evaluate the effectiveness of breastfeeding or supplemental breast milk in reducing procedural pain in neonates. The secondary objective was to conduct subgroup analyses based on the type of control intervention, type of painful procedure, gestational age and the amount of supplemental breast milk given. SEARCH STRATEGY: A literature search was performed using MEDLINE (1966 - Feb 2006), EMBASE (1980 - Feb 2006), CINAHL (1982 - Feb 2006), Cochrane Central Register of Controlled Trials (Issue 4, 2005 of Cochrane Library), abstracts from the annual meetings of the Society for Pediatric Research (1994 - 2006) and major pediatric pain conference proceedings. No language restrictions were applied. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of breastfeeding or supplemental breast milk versus no treatment/other measures in neonates were eligible for inclusion in this review. The study must have reported on either physiologic markers of pain or validated pain scores. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the authors. Data on relevant outcomes were extracted and the effect size was estimated and reported as relative risk (RR), risk difference (RD) and weighted mean difference (MD) as appropriate. MAIN RESULTS: Eleven eligible studies were identified. Marked heterogeneity in terms of control intervention and pain assessment measures were noted among the studies. Neonates in the breastfeeding group had statistically significantly less increase in the heart rate, reduced proportion of crying time and reduced duration of crying compared to swaddled group or pacifier group. Neonates in the breastfeeding group had a significant reduction in duration of crying compared to fasting (no intervention) group, but there was no significant difference when compared to glucose group. Premature Infant Pain Profile scores were significantly different between the breastfeeding group when compared to placebo group and the group positioned in mother's arms. However, these scores were not statistically significantly different in the breastfeeding group when compared to the no treatment group and the glucose group. Douleur Aigue Nouveau-ne scores were significantly different in the breastfeeding group when compared to the placebo group and the group positioned in mother's arms, but not when compared to the glucose group. Neonates in the supplemental breast milk group had significantly less increase in the heart rate and Neonatal Facial Coding Score compared to the placebo group. The differences in the duration of crying time and oxygen saturation change between supplemental breast milk group and the placebo group were not statistically significant. Neonates in the supplemental breast milk group had significantly higher increase in the heart rate changes and duration of crying time compared to glucose/sucrose group. No study was identified that has evaluated safety/effectiveness of repeated administration of breastfeeding or supplemental breast milk for pain relief. AUTHORS' CONCLUSIONS: If available, breastfeeding or breast milk should be used to alleviate procedural pain in neonates undergoing a single painful procedure compared to placebo, positioning or no intervention. Administration of glucose/sucrose had similar effectiveness as breastfeeding for reducing pain. The effectiveness of breast milk for repeated painful procedures is not established and further research is needed. These studies should include various control interventions including glucose/ sucrose and should target preterm neonates.

Breast Feeding↗

Nasal continuous positive airway pressure from high flow cannula versus Infant Flow for Preterm infants.

OBJECTIVE: To compare the feasibility of continuous positive airway pressure (CPAP) support generated by high flow nasal cannula with conventional CPAP for prevention of reintubation among preterm infants with a birth weight of <or=1,250 g. STUDY DESIGN: Preterm infants were randomized to CPAP generated via high flow cannula or the Infant Flow Nasal CPAP System (VIASYS, Conshohocken, PA, USA) at extubation. Primary outcome was incidence of reintubation within 7 days. Secondary outcomes included change in oxygen use and frequency of apnea and bradycardias postextubation. RESULTS: Forty neonates were randomized. Twelve of 20 infants randomized to high flow cannula CPAP were reintubated compared to three of 20 using Infant Flow (P=0.003). The high flow cannula group had increased oxygen use and more apneas and bradycardias postextubation. CONCLUSIONS: CPAP delivered by high flow nasal cannula failed to maintain extubation status among preterm infants <or=1,250 g as effectively as Infant Flow CPAP.

Apnea↗

Atomic-based stabilization for laser-pumped atomic clocks.

We describe a novel technique for stabilizing frequency shifts in laser-interrogated vapor-cell atomic clocks. The method suppresses frequency shifts due to changes in the laser frequency, intensity, and modulation index as well as atomic vapor density. The clock operating parameters are monitored by using the atoms themselves, rather than by using conventional schemes for laser frequency and cell temperature control. The experiment is realized using a chip-scale atomic clock. The novel atomic-based stabilization approach results in a simpler setup and improved long-term performance.

Journal Article↗

Silencing of epithelial CXCL12 expression by DNA hypermethylation promotes colonic carcinoma metastasis.

Cellular metastasis is the most detrimental step in carcinoma disease progression, yet the mechanisms that regulate this process are poorly understood. CXCL12 and its receptor CXCR4 are co-expressed in several tissues and cell types throughout the body and play essential roles in development. Disruption of either gene causes embryonic lethality due to similar defects. Post-natally, CXCL12 signaling has a wide range of effects on CXCR4-expressing cells, including the directed migration of leukocytes, lymphocytes and hematopoietic stem cells. Recently, this signaling axis has also been described as an important regulator of directed carcinoma cell metastasis. We show herein that while CXCR4 expression remains consistent, constitutive colonic epithelial expression of CXCL12 is silenced by DNA hypermethylation in primary colorectal carcinomas as well as colorectal carcinoma-derived cell lines. Inhibition of DNA methyltransferase (Dnmt) enzymes with 5-aza-2'-deoxycytidine or genetic ablation of both Dnmt1 and Dnmt3b prevented promoter methylation and restored CXCL12 expression. Re-expression of functional, endogenous CXCL12 in colorectal carcinoma cells dramatically reduced metastatic tumor formation in mice, as well as foci formation in soft agar. Decreased metastasis was correlated with increased caspase activity in cells re-expressing CXCL12. These data constitute the unique observation that silencing CXCL12 within colonic carcinoma cells greatly enhances their metastatic potential.

Animals↗

Systemic vasculitis: a cause of indeterminate intestinal inflammation.

OBJECTIVES: Indeterminate intestinal inflammation may result from a variety of inflammatory conditions in addition to ulcerative colitis and Crohn disease. The primary systemic vasculitides may present with intestinal inflammation and an indeterminate colitis. We set out to describe a series of children with primary systemic vasculitis who initially presented with clinical features suggestive of inflammatory bowel disease (IBD) to establish criteria that might help discriminate between IBD and primary systemic vasculitis. METHODS: Ten children (6 boys, median age at presentation 8.9 years, range 0.9-14.5 years) satisfied inclusion criteria. RESULTS: All had abdominal pain, weight loss, diarrhea (6 of 10 bloody) and laboratory evidence of a severe acute phase response. Extraintestinal clinical features included vasculitic rash, renal impairment, myalgia, testicular pain and polyarthritis. Endoscopy showed vascular changes or other macroscopic findings suggestive of vasculitis in 5 of 10 patients. Gut histology revealed indeterminate chronic inflammatory mucosal changes and one patient with small artery fibrinoid necrosis in the submucosal vessels. Extraintestinal biopsy was performed in 6 patients and had a higher yield for the demonstration of vasculitis than intestinal biopsy. The results of selective visceral angiography was suggestive of vasculitis in all patients, but was normal in 7 cases of treatment-unresponsive classic IBD. Treatment comprised corticosteroid and azathioprine in all patients. Cyclophosphamide was given to 7 of 10 patients. CONCLUSIONS: Extraintestinal manifestations and inflammatory responses that may be disproportionate to the degree of intestinal inflammation provide clues to the presence of an underlying primary systemic vasculitis, and these data suggest that selective visceral angiography plays a key role in the diagnosis of vasculitis in this context. It is important to identify and treat any vasculitic component because failure to do so may result in consequential morbidity or mortality.

Abdominal Pain↗

Atomic vapor cells for chip-scale atomic clocks with improved long-term frequency stability.

A novel technique for microfabricating alkali atom vapor cells is described in which alkali atoms are evaporated into a micromachined cell cavity through a glass nozzle. A cell of interior volume 1 mm3, containing 87Rb and a buffer gas, was made in this way and integrated into an atomic clock based on coherent population trapping. A fractional frequency instability of 6 x 10(-12) at 1000 s of integration was measured. The long-term drift of the F=1, mF=0-->F=2, mF=0 hyperfine frequency of atoms in these cells is below 5 x 10(-11)/day.

Journal Article↗

Continuous heparin infusion to prevent thrombosis and catheter occlusion in neonates with peripherally placed percutaneous central venous catheters.

BACKGROUND: Peripherally placed percutaneous central venous catheters (PCVC) are used in neonates to provide long-term vascular access. Major complications associated with these catheters include mechanical complications (catheter thrombosis, occlusion or dislodgement) and infection. Strategies to prevent catheter thrombosis and occlusion include the use of heparin. Systematic review has revealed that heparin is effective in prolonging the umbilical arterial catheter stay in neonates. However, heparin is known to be associated with complications such as bleeding and thrombocytopenia which may result in serious long-term sequelae. OBJECTIVES: The primary objective is to assess the effectiveness of heparin for prevention of catheter related thrombosis. The secondary objectives are to assess the effectiveness of heparin on catheter occlusion, duration of catheter patency, catheter related sepsis and complications associated with the use of heparin. SEARCH STRATEGY: A literature search was performed using the following databases: MEDLINE (1966-February 2005), EMBASE (1980-February 2005), CINAHL (1982-February 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2005) and abstracts from the annual meetings of the Society for Pediatric Research/American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2005). No language restrictions were applied. SELECTION CRITERIA: Selection criteria applied to the clinical trials were: the population had to be neonates, intervention had to be heparin infusion compared to placebo or no treatment for prevention of any of the complications related to peripherally placed PCVC, the trial had to be randomized or quasi-randomized and at least one of the primary or secondary outcomes reported. DATA COLLECTION AND ANALYSIS: The methodological quality of included trials was assessed using criteria for masking of randomization, masking of intervention, completeness of follow-up and masking of outcome measurement. Data on relevant outcomes were extracted and the effect size was estimated by calculating relative risk (95% CI), risk difference (95% CI) and weighted mean difference (95% CI). MAIN RESULTS: Two randomized trials on the use of heparin for peripherally placed PCVC were identified . One trial (Kamala et al) of 66 neonates of adequate methodology met the eligibility criteria. There was no statistically significant differences in the incidence of thrombosis (RR 0.79, 95% CI 0.35, 1.79), occlusion (RR 0.63, 95% CI 0.22), catheter related sepsis (RR 0.89, 95% CI 0.06, 13.57), extension of intraventricular hemorrhage (RR 0.87, 95% CI 0.25, 3.03), mortality (RR 0.59, 95% CI 0.18, 1.90) or duration of catheter patency (WMD 1.50 days, 95% CI -1.35 days, 4.35 days) between heparin and no heparin groups. Another trial (Betremieux et al) was excluded due to several methodological issues: 1. randomization was at the time of umbilical catheter placement rather than later PCVC placement 2. multiple PCVC were used in some infants, with reported results based on number of catheters rather than infants. AUTHORS' CONCLUSIONS IMPLICATIONS FOR PRACTICE: Prophylactic use of heparin for prevention of complications related to peripherally placed PCVC has been examined in only one randomized controlled clinical trial that was eligible for inclusion in this review. No significant differences in the incidence of thrombosis, occlusion, sepsis, mortality and duration of catheter patency were observed. With the current state of knowledge, routine use of heparin for this purpose can not be recommended. Implication for research: Increasing survival of extremely low birth weight infants may be accompanied by prolonged intravenous access for nutrition. Well designed randomized controlled trials of sufficient power to determine the benefits and risks of continuous infusion of heparin in neonates with peripherally inserted PCVC are warranted.

Anticoagulants↗

False diagnosis of renal agenesis on fetal MRI.

We report a twin pregnancy in which prenatal ultrasound revealed anhydramnios and bilateral absence of the kidneys in both fetuses. To overcome the difficulties faced in obtaining accurate information on fetal ultrasound in cases with oligohydramnios, an attempt was made to use fetal magnetic resonance imaging (MRI) to confirm the renal status. However, while the fetal MRI showed renal agenesis in both twins, postnatal follow-up revealed that one twin, which survived, had a small unilateral kidney not seen antenatally on fetal ultrasound or MRI. The second twin had bilateral renal agenesis and died of pulmonary hypoplasia. Care should be taken when using fetal MRI to replace fetal ultrasound in cases with poor visibility.

Adult↗

Observer variability in the histopathological reporting of core biopsies of papillary breast lesions is reduced by the use of immunohistochemistry for CK5/6, calponin and p63.

AIM: To investigate agreement on core biopsy diagnosis of papillary breast lesions, which is acknowledged as a difficult area, and to determine the effect of the use of immunohistochemistry (IHC) to assist diagnosis. STUDY DESIGN: Haematoxylin and eosin (H&E) sections of 129 core biopsies of papillary breast lesions were circulated to four observers who categorized each case as: B2 (benign), B3a (epithelial proliferation, probably benign but requiring biopsy), B3b (epithelial proliferation with cytological or architectural atypia), B4 (probably malignant but insufficient material or artefact to allow diagnosis), B5 (malignant papillary lesion). In all cases (n = 127) IHC was performed for cytokeratin (CK) 5/6, calponin, p63 (myoepithelial markers), and slides recirculated. RESULTS: There was unanimous agreement in 44% of cases on H&E only which rose to 91% after the use of IHC. Overall, unweighted kappa (Ku; five categories) rose from 0.54 to 0.91. The main effect of IHC was to reduce the use of intermediate categories (B3a, B3b and B4) and allow definitive diagnosis (B2 or B5). CONCLUSION: Agreement on H&E sections alone in papillary core biopsies of breast is only 44% (Ku = 0.54) but is significantly increased to 91% (Ku = 0.91) by the use of IHC for CK5/6, calponin and p63.

Biomarkers, Tumor↗

Venepuncture versus heel lance for blood sampling in term neonates.

BACKGROUND: Heel lance has been the conventional method of blood sampling in neonates for screening tests. Neonates undergoing this procedure experience pain. Despite various studies evaluating the role of pharmacological and non-pharmacological interventions to date, there are no effective and practical methods to alleviate pain from heel lance. OBJECTIVES: To determine whether venepuncture or heel lance is less painful and more effective for blood sampling in term neonates. SEARCH STRATEGY: Systematic search in accordance with the Cochrane Neonatal Collaborative Review Group. All randomized controlled trials which compared pain response to venepuncture vs. heel lance were identified using MEDLINE (1966-June 2004), EMBASE (1980-June 2004), CINAHL (1982-June 2004, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2004), reference lists of identified trials and personal files. No language restrictions were applied. SELECTION CRITERIA: Randomized controlled trials which compared pain response to venepuncture vs. heel lance were selected for this review. DATA COLLECTION AND ANALYSIS: Data regarding the primary outcome of pain response to venepuncture vs. heel lance as assessed by validated pain measures were abstracted. Secondary outcomes including the need of repeat blood sampling, bruising/hematoma at local site, and parental perception of their own anxiety and infant's pain were abstracted. All data were analysed using RevMan 4.2. When possible, meta-analysis was done using relative risk (RR) and risk difference (RD), along with their 95% confidence intervals (CI). If RD was significant, number needed to treat (NNT) was calculated. Weighted mean difference (WMD) was used for continuous data. When present, statistically significant between study heterogeneity was reported including the I(2) test. MAIN RESULTS: Four trials were eligible for inclusion in the review. Pain assessments were made using validated pain measures including Neonatal Infant Pain Scale (NIPS), Neonatal Facial Action Coding System (NFCS), Premature Infant Pain Profile (PIPP) score and cry characteristics. Two trials did not report on outcomes for all enrolled infants (not intention to treat analyses). Despite the heterogeneity in the pain measures used, all studies showed statistically significantly lower pain scores for venepuncture as compared to heel lance. A meta-analysis of the NIPS scores during the first minute of the procedure (reported in two studies) was statistically significantly decreased in the VP group compared to the HL group [WMD -1.84 (95% CI -2.61, -1.06)]. There was no statistically significant heterogeneity for this outcome (p = 0.22; I(2) 33.3%). The RR for requiring more than one skin puncture for venepuncture vs. heel lance (reported in 3 studies) was 0.30 (95% CI 0.18, 0.49. The risk difference was -39% (95% CI -50%, -28%). For this outcome there was statistically significant between study heterogeneity (for RR, p=0.02, I(2 )74.3%; for RD, p=0.0001, I(2) 88.9%). The number needed to treat (NNT) to avoid one repeat skin puncture was 3 (95% CI 2, 4). In one study, maternal anxiety was noted to be higher in the venepuncture group as compared to heel lance group prior to the procedure; however, after observing the procedure, mothers rated their infant's pain to be lower in the venepuncture group. REVIEWERS' CONCLUSIONS: Venepuncture, when performed by a skilled phlebotomist, appears to be the method of choice for blood sampling in term neonates. For each three venepunctures instead of heel lance, the need for one additional skin puncture can be avoided. Further well designed randomized controlled trials need to be conducted. The interventions should be compared in settings where several individuals perform the venepuncture and/or the heel lance.

Blood Specimen Collection↗

Arginine supplementation for prevention of necrotising enterocolitis in preterm infants.

BACKGROUND: Immaturity, ischemia, and disturbances in gut mucosal integrity due to infections or hyperosmolar feeds are some of the suspected mechanisms in the development of necrotising enterocolitis (NEC) in preterm infants. Decreased concentration of nitric oxide is proposed as one of the possible cellular mechanisms for NEC. Plasma arginine concentrations were found to be lower in infants who developed NEC. Arginine can act as a substrate for the production of nitric oxide in the tissues and arginine supplementation may help in preventing NEC. OBJECTIVES: This review examines the efficacy and safety of arginine supplementation in decreasing the incidence of NEC among preterm neonates. SEARCH STRATEGY: A literature search was performed using the following databases: MEDLINE (1966 - June 2004), EMBASE (1980 - June 2004), CINAHL (1982 - June 2004), Cochrane Controlled Trials Register (Issue 2, 2004 of Cochrane Library) and abstracts from the annual meetings of the Society for Pediatric Research, American Pediatric Society and Pediatric Academic Societies published in Pediatric Research (1991-2004). No language restrictions were applied. SELECTION CRITERIA STUDY DESIGN: randomized or quasi-randomized controlled trials. POPULATION: preterm neonates. INTERVENTION: enteral or parenteral arginine supplementation (in addition to what an infant may be receiving from enteral or parenteral source), compared to placebo or no treatment; arginine administered orally or parenterally for at least 7 days in order to achieve adequate plasma arginine levels (145 umol/l). OUTCOMES: any of the following outcomes - NEC, death prior to discharge, death due to NEC, surgery for NEC, duration of total parenteral nutrition, plasma concentrations of arginine and glutamine at baseline and seven days after intervention, side effects of arginine. DATA COLLECTION AND ANALYSIS: The methodological quality of the trials was assessed using the information provided in the studies and by personal communication with the author. Data on relevant outcomes were extracted and the effect size was estimated and reported as relative risk (RR), risk difference (RD) and mean difference (MD) as appropriate. MAIN RESULTS: Only one eligible study was identified. The methodological quality of the included study was good. There was a statistically significant reduction in the risk of developing NEC (any stage) in the arginine group compared with the placebo group (RR 0.24 [95% CI 0.10, 0.61], RD -0.21 [95% CI -0.32, -0.09]). No significant side effects directly attributable to arginine were observed. REVIEWERS' CONCLUSIONS: The data are insufficient at present to support a practice recommendation. A multicentre randomized controlled study of arginine supplementation in preterm neonates is needed, focusing on the incidence of NEC, particularly stage 2 or 3.

Arginine↗

Intraventricular antibiotics for bacterial meningitis in neonates.

BACKGROUND: Neonatal meningitis may be caused by bacteria, especially gram-negative bacteria, which are difficult to eradicate from the cerebrospinal fluid (CSF) using safe doses of antibiotics. In theory, intraventricular administration of antibiotics would produce higher antibiotic concentrations in the CSF than intravenous administration alone, and eliminate the bacteria more quickly. However, ventricular taps may cause harm. OBJECTIVES: To assess the effectiveness and safety of intraventricular antibiotics (with or without intravenous antibiotics) in neonates with meningitis (with or without ventriculitis) as compared to treatment with intravenous antibiotics alone. SEARCH STRATEGY: MEDLINE, EMBASE, The Cochrane Library, Issue 2, 2004, Science Citation Index, and the Oxford Database of Perinatal Trials were searched in June 2004. Pediatric Research (abstracts of proceedings) were searched (1990 - April 2004) as were reference lists of identified trials and personal files. No language restrictions were applied. SELECTION CRITERIA: Selection criteria for study inclusion were: Randomized or quasi-randomized controlled trials in which intraventricular antibiotics with or without intravenous antibiotics were compared with intravenous antibiotics alone in neonates (< 28 days old) with meningitis. One of the following outcomes was required to be reported: mortality during initial hospitalization, neonatal and/or infant mortality, neurodevelopmental outcome, duration of hospitalization, duration of culture positivity of CSF and side effects. DATA COLLECTION AND ANALYSIS: All reviewers abstracted information for outcomes reported and one reviewer checked for discrepancies and entered data into RevMan 4.2. Relative risk (RR), risk difference (RD), number needed to treat (NNT) or number needed to harm (NNH), and mean difference (MD), using the fixed effects model are reported with 95% confidence intervals (CI). The fixed effect model was used for meta-analysis. MAIN RESULTS: One study was included in the review. This study assessed the effect of intraventricular gentamicin in a mixed population of neonates (69%) and older infants (31%) with gram negative meningitis and ventriculitis. Mortality was statistically significantly higher in the group that received intraventricular gentamicin in addition to intravenous antibiotics compared to the group receiving intravenous antibiotics alone [RR 3.43 (95% CI, 1.09, 10.74; RD 0.30 (95% CI, 0.08, 0.53); NNH was 3 (95% CI; 2 ,13)]. Duration of CSF culture positivity did not differ significantly (MD -1.20 days (95% CI, -2.67, 0.27). REVIEWERS' CONCLUSIONS: In one trial, enrolling infants with gram negative meningitis and ventriculitis, the use of intraventricular antibiotics in addition to intravenous antibiotics resulted in a 3 fold increased RR for mortality compared to standard treatment with intravenous antibiotics alone. Based on this result, intraventricular antibiotics as tested in this trial should be avoided. Further trials comparing these interventions are not justified in this population.

Anti-Bacterial Agents↗

Vaginal chlorhexidine during labour to prevent early-onset neonatal group B streptococcal infection.

BACKGROUND: Early-onset group B beta-hemolytic streptococcus (GBS) infection accounts for approximately 30% of neonatal infections, has a high mortality rate and is acquired through vertical transmission from colonized mothers. Several trials have demonstrated the efficacy of intrapartum chemoprophylaxis (IPC) for preventing early-onset disease (EOD). Vaginal disinfection with chlorhexidine during labour has been proposed as another strategy for preventing GBS EOD in the preterm and term neonate. Chlorhexidine has been found to have no impact on antibiotic resistance, is inexpensive, and applicable to poorly equipped delivery sites. OBJECTIVES: To determine the effectiveness of vaginal disinfection with chlorhexidine during labour for preventing early-onset GBS infection in preterm and term neonates. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth trials register (October 2003), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 3, 2003), MEDLINE (1966 to October 2003), EMBASE (1980 to March 2003), CINAHL (1982 to March 2003) and LILACS (1982 to September 2003). SELECTION CRITERIA: Randomized and quasi-randomized trials comparing vaginal disinfection with chlorhexidine to placebo, or no treatment. DATA COLLECTION AND ANALYSIS: We extracted information from the results sections of the included studies. We reported relative risk (RR) and risk difference (RD) with 95% confidence intervals (CI) for dichotomous outcomes. We calculated the number needed to treat (NNT) with 95% CIs when a statistically significant RD was found. We used a chi square test (chi2) and the I2 analysis to test for heterogeneity, and applied a fixed or random effects model accordingly. MAIN RESULTS: Five studies, including approximately 2190 term and preterm infants, met the inclusion criteria and reported on at least one of the outcomes of interest for this systematic review. When all studies were combined there was a statistically significant (p = 0.005) reduction in colonisation (RR 0.72, 95% CI 0.56 to 0.91); RD -0.16 (95% CI -0.26 to -0.05); NNT 6 (95% CI 4 to 20). There was no statistically significant between-study heterogeneity. There was no statistically significant between-study heterogeneity both for RR (chi(2) = 3.21 [p = 0.2], I(2) = 37.8%) and for RD (chi(2) = 1.66 [p = 0.44], I(2) = 0%). There was no statistically significant reduction in EOD including GBS infection, GBS pneumonia, GBS meningitis or mortality. REVIEWERS' CONCLUSIONS: Vaginal chlorhexidine resulted in a statistically significant reduction in GBS colonisation of neonates, but was not associated with reductions in other outcomes. The review currently does not support the use of vaginal disinfection with chlorhexidine in labour for preventing EOD. Results should be interpreted with caution as the methodological quality of the studies was poor.

Administration, Intravaginal↗

Vbeta-restricted T cell adherence to endothelial cells: a mechanism for superantigen-dependent vascular injury.

OBJECTIVE: To investigate the potential for endothelial cells to operate as superantigen-presenting cells for T cells and the potential for such an interaction to cause endothelial cell activation and injury. METHODS: Class II major histocompatibility complex (MHC)-positive human umbilical vein endothelial cells (HUVECs) were cocultured for 4 hours with purified T cells and the superantigens staphylococcal enterotoxin B (SEB) or toxic shock syndrome toxin 1 (TSST-1). After staining with fluorescence-conjugated monoclonal antibodies, flow cytometric analysis was performed on the HUVECs and T cells to examine V(beta)-restricted T cell adherence to the endothelial cell monolayer, V(beta)-restricted T cell activation (CD69 up-regulation), surface expression of endothelial cell activation markers, and generation of endothelial microparticles (EMPs). RESULTS: Coculture of purified T cells with class II MHC-positive HUVECs and either TSST-1 or SEB resulted in V(beta)-restricted CD69 up-regulation by CD4 and CD8 cells (V(beta)2 activation for TSST-1; V(beta)3, V(beta)5.1, and V(beta)12 activation for SEB). Additionally, there was CD4 and CD8 T cell V(beta)-restricted adherence to the HUVEC monolayer at 4 hours. Expression of intercellular adhesion molecule 1, E-selectin, and vascular cell adhesion molecule 1 was up-regulated on the class II MHC-positive HUVECs following exposure to superantigen in the presence of T cells, and there was increased EMP release from activated HUVECs, which occurred earlier and was of greater magnitude than that observed in response to tumor necrosis factor alpha. CONCLUSION: Class II MHC-positive endothelial cells operate as competent superantigen-presenting cells for CD4 and CD8 lymphocytes in vitro. Dual signaling between endothelial cells and T cells results in V(beta)-restricted activation and adherence to endothelial monolayers and endothelial cell activation and release of EMPs expressing inducible cell adhesion molecules. It is proposed that this mechanism could account in part for the vascular injury associated with superantigen-mediated diseases including Kawasaki disease.

Antigen-Presenting Cells↗

Endothelial and platelet microparticles in vasculitis of the young.

OBJECTIVE: Microparticles are released from endothelial cells in response to a variety of injurious stimuli and recently have been shown to be increased in a number of diseases associated with endothelial dysfunction. This study examined endothelial microparticle (EMP) and platelet microparticle (PMP) profiles in children with systemic vasculitis to test the hypothesis that EMPs may provide a noninvasive means of examining endothelial activation or injury. METHODS: The study cohort comprised 39 children with systemic vasculitis at various stages of disease activity, 24 control children with febrile disease, and a control group of 43 healthy subjects. Plasma was ultracentrifuged at 17,000g for 60 minutes, and the microparticle pellets were examined using flow cytometry. RESULTS: Plasma from patients with active systemic vasculitis contained significantly higher numbers of E-selectin-positive EMPs compared with that from patients in remission, healthy controls, or febrile disease controls (P = 0.000 for each). A similar result was obtained for the numbers of EMPs expressing the marker CD105. There was also a significant increase in PMPs expressing CD42a in the active vasculitis group as compared with the other groups, but this difference was not significant for PMPs expressing P-selectin. The EMP counts correlated with the Birmingham Vasculitis Activity Score and the acute-phase reactant levels in the patients with systemic vasculitis, but there was a poor correlation overall between EMP counts and the acute-phase reactant levels in the febrile disease controls. CONCLUSION: EMPs may provide a window to the activated endothelium and could provide important pathophysiologic insights into the vascular injury associated with vasculitis of the young.

Acute-Phase Proteins↗