A systematic review of Demand-based & Supply-based Interventions on continuum of maternal and child healthcare in south Asian countries

Journal of Public Health - In this study, we conduct a systematic review of literature to understand the effectiveness of interventions on continuum of maternal and child healthcare services, the...     

Enolase 1 of Candida albicans binds human CD4+ T cells and modulates naïve and memory responses

To obtain a better understanding of the biology behind life-threatening fungal infections caused by Candida albicans, we recently conducted an in silico screening for fungal and host protein interaction partners. We report here that the extracellular domain of human CD4 binds to the moonlighting protein enolase 1 (Eno1) of C. albicans as predicted bioinformatically. By using different anti-CD4 monoclonal antibodies, we determined that C. albicans Eno1 (CaEno1) primarily binds to the extracellular domain 3 of CD4. Functionally, we observed that CaEno1 binding to CD4 activated lymphocyte-specific protein tyrosine kinase (LCK), which was also the case for anti-CD4 monoclonal antibodies tested in parallel. CaEno1 binding to naïve human CD4⁺ T cells skewed cytokine secretion toward a Th2 profile indicative of poor fungal control. Moreover, CaEno1 inhibited human memory CD4⁺ T-cell recall responses. Therapeutically, CD4⁺ T cells transduced with a p41/Crf1-specific T-cell receptor developed for adoptive T-cell therapy were not inhibited by CaEno1 in vitro. Together, the interaction of human CD4⁺ T cells with CaEno1 modulated host CD4⁺ T-cell responses in favor of the fungus. Thus, CaEno1 mediates not only immune evasion through its interference with complement regulators but also through the direct modulation of CD4⁺ T-cell responses.     

Age and the onset of desaturation in apnoeic children

Most patients undergoing general anaesthesia are apnoeic during laryngoscopy and tracheal intubation. This study determined the time until the onset of desaturation following preoxygenation in apnoeic infants, children, and adolescents. Fifty ASA physical status I patients, 2 days to 18 yr of age, were studied. The patients were stratified into one of five groups according to age: Group I, 0–6 mo; Group II, 7–23 mo; Group III 2–5 yr; Group IV, 6–10 yr; and Group V, 11–18 yr. Following induction of anaesthesia with halothane via mask or intravenous barbiturates, the ability of the anaesthetist to ventilate the lungs via the mask was ascertained and paralysis was accomplished with vecuronium 0.1 mg · kg^?1. Manual mask ventilation was maintained with oxygen and halothane. When end-tidal N₂ decreased below 3% (minimum time two minutes), the face mask was removed. The time between the removal of the face mask and a decrease in oxygen saturation (SpO₂ from 99–100% to 90% was measured. Manual ventilation was then resumed and the trachea intubated. Desaturation started earlier in infants than in two-to five-year-old children (96.5 ± 12.7 sec vs 160.4 ± 30.7 sec, P < 0.0001). Children became desaturated faster than adolescents (160.4 ± 30.7 vs 382.4 ± 79.9 sec, P < 0.0001). The time required to reach 90% saturation correlated well with age by linear regression analysis (r² = 0.88, P < 0.0001). We conclude that the time to onset of desaturation following pre-oxygenation with mask ventilation increases with age in healthy apnoeic children. Adolescents can tolerate apnoea for longer than children, and infants exhibit desaturation faster than children.     

An intrasubject comparison of two doses of succinylcholine in modified electroconvulsive therapy.

The electroconvulsive therapy (ECT) guideline of the Royal College of Psychiatrists recommends a 0.5 mg/kg of succinylcholine for ECT modification. Our clinical experience suggests that this dose is insufficient for Indian patients. The dose recommended by the Royal College of Psychiatrists (0.5 mg/kg) and a larger dose (1 mg/kg) were compared in 50 patients referred for ECT. In one ECT session, patients were equally randomized to receive one of the two doses and in the next session they were switched to the other dose. The extent of motor seizure modification was rated on a five-point scale by two independent raters who were blinded to the succinylcholine dose. The interrater reliability was good (K = 0.85). "Poor" seizure modification occurred in 48% and 12% of patients with the 0.5 and 1 mg/kg doses, respectively. Of the 24 patients who had poor modification with 0.5 mg/kg, 20 had "good" modification in the session with 1 mg/kg (P < 0.001). A small delay (mean = 55 s) occurred in time to recover from the respiratory paralysis with the 1 mg/kg dose of succinylcholine. No patient, however, had prolonged apnea requiring special measures. We recommend 1 mg/kg of succinylcholine dose be used in the first ECT session. For subsequent sessions, the dose may be altered, depending on the response for optimal motor seizure modification. IMPLICATIONS: The dose of muscle relaxant (succinylcholine) recommended in modified electroconvulsive therapy is not based on empirical research. In the same patients (n = 50), two doses-0.5 mg/kg and 1 mg/kg-were compared during different electroconvulsive therapy sessions. The larger dose was more effective in modifying the peripheral convulsion.     

Chronic berylliosis of the lung: report of a case

We report a case of chronic berylliosis of the lung in a patient who was exposed to copper beryllium alloy, which was mistaken and being treated as miliary tuberculosis. The relevant literature is reviewed.     

Deletions in the ligand for CD40 in X-linked immunoglobulin deficiency with normal or elevated IgM (HIGMX-1)

Patients with X-linked Ig deficiency with normal or elevatedIgM (HIGMX-1) fail to switch from IgM/IgD to other Ig isotypes.Interaction between the B cell antigen CD40 and the CD40 ligandexpressed on activated T cells is critical for T cell drivenisotype switching. We have reported that T lymphocytes fromthree unrelated male patients with HIGMX-1 failed to expressCD40 ligand on their surface, but the mRNA for CD40 ligand wasof an apparently normal size and level. Analysis of CD40 ligandcDNA from two of the patients revealed deletions that alterthe reading frame. Patient 1 displayed two mutations: a C Atransversion at nucleotide 590 and the deletion of an adjacentC nucleotide. The second patient had a 58 bp deletion from nucleotides289–346. Furthermore, neither patient expressed a proteinproduct detectable by the CD40L mAb, 5c8.     

Papillary thyroid carcinoma in a thyroglossal cyst

The incidence of Papillary Thyroid Carcinoma in a Thyroglossal Cyst is rare. Only about 160 cases have been reported in the last 85 years. We report a case of Thyroglossal Cyst who underwent Sistrunk &#x2019;s Operation. The Cyst was reported to contain a focus of papillary thyroid carcinoma. In the absence of metastases in thyroid gland and neck nodes, only thyroid suppression with Thyroxine was given. After I year of follow-up there are no metastases. The importance of Sistrunk&#x2019;s operation lies not only in complete removal of Thyroglossal Cyst but also in management of small foci of Papillary thyroid Carcinoma.     

Poloxamer gel as vehicle for transdermal iontophoretic delivery of arginine vasopressin: evaluation of in vivo performance in rats

The present study describes the formulation and evaluation for pharmacokinetic and pharmacodynamic activity of arginine vasopressin (AVP), a nanopeptide with antidiuretic activity on being delivered by transdermal iontophoresis. Poloxamer 407 was used to form stable gels that did not reduce the release of AVP. The release rate from the gel followed Higuchi kinetics indicating that the dominant mechanism of release is diffusion. Iontophoresis alone and in combination with chemical enhancers was used to augment the transdermal permeation of AVP. The results of both pharmacokinetic and pharmacodynamic studies emphasize the dimension of 'rapid onset' achieved by iontophoresis. The correlation between pharmacokinetic data and pharmacodynamic activity was only qualitative. Histopathological studies revealed that skin toxicity caused by either iontophoresis or chemical enhancers when used alone could be reduced by using a combination of both the techniques in tandem.     

Effect of iontophoresis and fatty acids on permeation of Arginine Vasopressin through rat skin

The aim of this study was to assess the effects of fatty acids and iontophoretic mode of penetration enhancement on transdermal delivery of Arginine Vasopressin (AVP). Sprague-Dawley (SD) rat skin was pretreated with fatty acids (e.g. 5% w/v, lauric acid, oleic acid, and linoleic acid in ethanol:water (EtOH:W, 2:1 system) for 2h and iontophoresis in vitro, separately or together. The results indicate that all fatty acids studied increased (P<0.05) the flux of AVP in comparison to control (not pretreated with enhancer) and their effectiveness in flux enhancement was comparable. Further, oleic acid in combination with iontophoresis significantly increased the permeation of AVP both in comparison to pretreatment with fatty acids and iontophoresis alone. However, iontophoresis did not further increase the permeation of AVP through linoleic acid pretreated skin. Fourier transform infrared (FT-IR) spectroscopic studies revealed that EtOH:W (2:1) system is not effective in lipid extraction. The shift to higher wavenumbers of the symmetric and asymmetric stretching peaks at 2850 and 2920cm(-1) revealed that at the concentration used, oleic acid and linoleic acid caused fluidization of stratum corneum (SC) lipids. This study provides direct evidence that oleic acid in EtOH:W (2:1) system causes disruption of the SC lipid lamellae and that a combination of oleic acid with iontophoresis further enhances the effects of oleic acid in a synergistic manner.     

A randomized controlled trial of fluorouracil plus leucovorin, irinotecan, and oxaliplatin combinations in patients with previously untreated metastatic colorectal cancer.

PURPOSE: Three agents with differing mechanisms of action are available for treatment of advanced colorectal cancer: fluorouracil, irinotecan, and oxaliplatin. In this study, we compared the activity and toxicity of three different two-drug combinations in patients with metastatic colorectal cancer who had not been treated previously for advanced disease. PATIENTS AND METHODS: Patients were concurrently randomly assigned to receive irinotecan and bolus fluorouracil plus leucovorin (IFL, control combination), oxaliplatin and infused fluorouracil plus leucovorin (FOLFOX), or irinotecan and oxaliplatin (IROX). The primary end point was time to progression, with secondary end points of response rate, survival time, and toxicity. RESULTS: A total of 795 patients were randomly assigned between May 1999 and April 2001. A median time to progression of 8.7 months, response rate of 45%, and median survival time of 19.5 months were observed for FOLFOX. These results were significantly superior to those observed for IFL for all end points (6.9 months, 31%, and 15.0 months, respectively) or for IROX (6.5 months, 35%, and 17.4 months, respectively) for time to progression and response. The FOLFOX regimen had significantly lower rates of severe nausea, vomiting, diarrhea, febrile neutropenia, and dehydration. Sensory neuropathy and neutropenia were more common with the regimens containing oxaliplatin. CONCLUSION: The FOLFOX regimen of oxaliplatin and infused fluorouracil plus leucovorin was active and comparatively safe. It should be considered as a standard therapy for patients with advanced colorectal cancer.