PubMed Health⌕ Search

Biomedical subjects

N Jain

Publications and source records attributed to N Jain.

At least 19 recordsLinked to original sources

Phenotypic switching in Cryptococcus neoformans.

Phenotypic switching has been described in serotype A and D strains of Cryptococcus neoformans. It occurs in vivo during chronic infection and is associated with differential gene expression and changes in virulence. The switch involves changes in the polysaccharide capsule and cell wall that affect the yeast's ability to resist phagocytosis. In addition, the phenotypic switch variants elicit qualitatively different inflammatory responses in the host. In animal models of chronic cryptococosis, the immune response of the host ultimately determines which of the switch variants are selected and maintained. The importance of phenotypic switching is further underscored by several findings that are relevant in the setting of human disease. These include the ability of the mucoid colony variant of RC-2 (RC-2 MC) but not the smooth variant (RC-2 SM) to promote increased intracerebral pressure in a rat model of cryptococcal meningitis. Furthermore, chemotherapeutic and immunological antifungal interventions can promote the selection of the RC-2 MC variant during chronic murine infection.

Animals↗

Management of minor head injuries according to NICE guidelines and changes in the number of patients requiring computerised tomography imaging in a district general hospital: a retrospective study.

The objective of this study was to investigate how many patients with minor head injury would have required computerised tomography (CT) imaging if they were to be managed according to the National Institute of Clinical Excellence (NICE) guidelines (June 2003) and the difference in workload for patients presenting out of hours at Calderdale Royal Hospital, Halifax. The study was a retrospective cohort analysis of patient's notes presenting with head injury at Calderdale Royal Hospital, Halifax. The data set comprised case notes of 844 patients with head injuries, 400 adults and 444 children attending the Accident and Emergency department from January to June 2003. The case notes were evaluated according to the NICE guidelines for the indications for CT imaging for the time that they presented to the Accident and Emergency department, and how many of them actually underwent CT imaging. The number of patients who required CT imaging and how many of them presented out of hours (between 17:00 and 21:00 hours on weekdays and at any time on weekends). Ten patients underwent CT imaging for minor head injuries from January to June 2003. Eighty-eight patients required CT imaging if they were to be managed according to the NICE guidelines. Sixty-three per cent of these patients presented out of hours when a radiologist was not available in the hospital. Adhering to the NICE guidelines would significantly increase the number of patients requiring CT imaging. A significant proportion of these patients would present out of hours.

Adult↗

Phenotypic switching in a Cryptococcus neoformans variety gattii strain is associated with changes in virulence and promotes dissemination to the central nervous system.

This is the first report of a Cryptococcus neoformans var. gattii strain (serotype B) that switches reversibly between its parent mucoid (NP1-MC) colony morphology and a smooth (NP1-SM) colony morphology. Similar to C. neoformans var. grubii and C. neoformans var. neoformans strains, the switch is associated with changes in the polysaccharide capsule and virulence in animal models. In murine infection models, NP1-MC is significantly more virulent than NP1-SM (P < 0.021). In contrast to the serotype A and D strains, the serotype B strain switches in vivo reversibly between both colony morphologies. The polysaccharide of NP1-MC exhibits a thicker capsule, and thus NP1-MC exhibits enhanced intracellular survival in macrophages. Consistent with this finding, switching to the mucoid variant is observed in pulmonary infection with NP1-SM. In contrast, the thin polysaccharide capsule of NP1-SM permits better crossing of the blood-brain barrier. In this regard, only smooth colonies were grown from brain homogenates of NP1-MC-infected mice. Our findings have important implications for the pathogenesis of cryptococcosis and suggest that phenotypic switching affects host-pathogen interactions in the local microenvironment. This altered interaction then selects for specific colony variants to arise in a pathogen population.

Animals↗

Maintaining standards in surgical training: how effective is the accreditation by the Specialist Advisory Committee in the United Kingdom?

In order to assess the efficacy of inspection and accreditation by the Specialist Advisory Committee for higher surgical training in orthopaedic surgery and trauma, seven training regions with 109 hospitals and 433 Specialist Registrars were studied over a period of two years. There were initial deficiencies in a mean of 14.8% of required standards (10.3% to 19.2%). This improved following completion of the inspection, with a mean residual deficiency in 8.9% (6.5% to 12.7%.) Overall, 84% of standards were checked, 68% of the units improved and training was withdrawn in 4%. Most units (97%) were deficient on initial assessment. Moderately good rectification was achieved but the process of follow-up and collection of data require improvement. There is an imbalance between the setting of standards and their implementation. Any major revision of the process of accreditation by the new Post-graduate Medical Education and Training Board should recognise the importance of assessment of training by direct inspection on site, of the relationship between service and training, and the advantage of defining mandatory and developmental standards.

Accreditation↗

Impact of post-methanation distillery effluent irrigation on groundwater quality.

Molasses-based distilleries generate large quantities of effluent, which is used for irrigation in many countries including India. The effluent is rich in organic and inorganic ions, which may leach down and pollute the groundwater. An on-farm experiment was conducted to assess the impact of long-term irrigation with post-methanation distillery effluent (PMDE) on nitrate, sulphate, chloride, sodium, potassium, and magnesium contents in the groundwater of two sites in northwest India. Electrical conductivity (EC), pH, total dissolved solids (TDS), sodium adsorption ratio (SAR) and colour were also determined to assess the chemical load in the groundwater. Nitrate content in the groundwater samples ranged from 16.95 mg L(-1) in the unamended fields to 59.81 mg L(-1) in the PMDE-amended fields during the 2-year study (2001-2002). Concentrations of TDS in water samples from tubewell of the amended field was higher by 40.4% over the tubewell water of the unamended field. Colour of the water samples of the amended fields was also darker than that of the unamended fields. The study indicated that the organic and inorganic ions added through the effluent could pose a serious threat to the groundwater quality if applied without proper monitoring.

Agriculture↗

Impact of a "direct approach" to live kidney donation in the British Indo-Asian community.

Although a general imbalance exists between the demand for renal transplants and the supply of suitable organs, the shortfall is particularly severe for patients from the Indo-Asian (I-A) community. It seems unlikely that this will be remedied by any increase in cadaveric donation. Our aim was to increase the rate of live donor transplantation (LDT) in the I-A population through a direct approach to patients and their families, in a culturally acceptable environment by an Asian transplant coordinator. Whereas an increase in LDT was seen in the I-A population over the period of review, 1997 to 2003, 15 compared with none prior to 1997, significant attrition was seen within the program, with only 10% of the original cohort coming to donation. There are multiple reasons for this including medical, social and psychological.

Asia↗

Cutaneous metastasis from glioblastoma.

A rare case of glioblastoma with isolated cutaneous metastasis adjacent to the scar site is described. Its pathogenesis and clinical significance are discussed.

Brain Neoplasms↗

Molecular epidemiology of clinical Cryptococcus neoformans strains from India.

Little is known about the molecular epidemiology of the human pathogenic fungus Cryptococcus neoformans in India, a country now in the midst of an epidemic of AIDS-related cryptococcosis. We studied 57 clinical isolates from several regions in India, of which 51 were C. neoformans var. grubii, 1 was C. neoformans var. neoformans, and 5 were C. neoformans var. gattii. This strain set included 18 additional sequential isolates from 14 patients. Strains were characterized phenotypically by measuring the polysaccharide capsule and by determining the MICs of standard antifungals. Molecular typing was performed by a PCR-based method using the minisatellite-specific core sequence (M13), by electrophoretic karyotyping, by restriction fragment length polymorphisms with the C. neoformans transposon 1 (TCN-1), and by URA5 DNA sequence analysis. Overall, Indian isolates were less heterogeneous than isolates from other regions and included a subset that clustered into one group based on URA5 DNA sequence analysis. In summary, our results demonstrate (i) differences in genetic diversity of C. neoformans isolates from India compared to isolates from other regions in the world; (ii) that DNA typing with the TCN-1 probe can adequately distinguish C. neoformans var. grubii strains; (iii) that TCN-1 sequences are absent in many C. neoformans var. gattii strains, supporting previous studies indicating that these strains have a limited geographical dispersal; and (iv) that human cryptococcal infection can be associated with microevolution of the infecting strain and by simultaneous coinfection with two distinct C. neoformans strains.

Adolescent↗

Transdermal delivery of an analgesic agent using elastic liposomes: preparation, characterization and performance evaluation.

The aim of the present study was to prepare and characterize novel vesicular carrier elastic liposomes, of most commonly used non-steroidal anti-inflammatory agent diclofenac for its sustained and targeted delivery. Elastic liposomes of diclofenac were prepared and characterized in vitro and in vivo. The effect of different formulation variables like type of surfactant, concentration of surfactant and dose of drug on transdermal flux, amount of drug deposited into the skin, muscle and plasma concentration was investigated. The biological activity of optimized formulation was evaluated using carrageenan induced rat paw edema model and results were compared with commercial hydrogel formulation. The elastic liposomal formulations achieved muscle drug concentration between 2.2+/-0.14 to 5.3+/-0.22 microg/g at 12 hr. The same dose of commercial hydrogel formulation produced drug levels between 0.41+/-0.07 to 1.1+/-0.09 microg/g in the muscle. Plasma concentration study showed regiospecificity of elastic liposomal formulation. The results of in vivo study revealed that incorporation of diclofenac in elastic liposomes increased its biological activity two fold as compared to commercial hydrogel formulation. The results of the present study demonstrated greater effectiveness of dermaly applied diclofenac elastic liposomal formulation in comparison to conventional delivery system. The optimized elastic liposomal formulation offers a promising means for the non-invasive treatment of local pain and inflammation by topical application.

Administration, Cutaneous↗

Third generation cephalosporins versus conventional antibiotics for treating acute bacterial meningitis.

BACKGROUND: Antibiotic therapy for suspected acute bacterial meningitis (ABM) needs to be started immediately, even before the results of cerebrospinal fluid culture and antibiotic sensitivity are available. It is not clear whether the available evidence supports the choice of third generation cephalosporins over the conventional antibiotic combination of ampicillin and chloramphenicol. Immediate institution of effective treatment through intravenous route may reduce death and disability in survivors. OBJECTIVES: The objective of this review is to determine the effectiveness and safety of the third generation cephalosporins and conventional treatment with penicillin/ampicillin-chloramphenicol in patients with community-acquired acute bacterial meningitis. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2003) which contains the Cochrane Acute Respiratory Infections Group trials register, MEDLINE (January 1966 to November 2003), and EMBASE (January 1990 to November 2003). We also searched the reference list of review articles and textbook chapters and contacted experts for any unpublished trials. SELECTION CRITERIA: Randomised controlled trials comparing ceftriaxone or cefotaxime with conventional antibiotics as empirical therapy of acute bacterial meningitis. DATA COLLECTION AND ANALYSIS: Two independent reviewers applied the study selection criteria, assessed methodological quality and extracted data. MAIN RESULTS: Eighteen trials included 993 patients in the analysis. The kappa (chance-corrected agreement) between the observers in study selection and data extraction was substantial. There was no heterogeneity of results among the studies in any outcome except diarrhoea. There was no statistically significant difference between the groups in the risk of death (risk difference -1%; 95% confidence interval (CI) -4% to +3%), risk of deafness (risk difference -4%; 95% CI -9% to +1%), risk of treatment failure (risk difference -2%; 95% CI -5% to +2%). However, there were significantly decreased risk of culture positivity of CSF after 10-48 hours (risk difference -6%; 95% CI -11% to 0%) and statistically significant increased in the risk of diarrhoea between the groups (risk difference +8%; 95% CI +3% to +13%) with the third generation cephalosporins. The risk of neutropenia and skin rash were not significantly different between the two groups. However, all the studies have been conducted in the eighties except two, which have been conducted in 1993 and 1996. REVIEWERS' CONCLUSIONS: Although the review shows no clinically important difference between ceftriaxone or cefotaxime and conventional antibiotics, the studies are done decades ago and may not apply to current routine practice. However, in situations where ceftriaxone or cefotaxime are not available or affordable, ampicillin-chloramphenicol combination may be used as an alternative. The antimicrobial resistance pattern against various antibiotics needs to be closely monitored in developing as well as developed countries. The factors determining overuse of antibiotics in developing countries and educational interventions to limit such practice are priority area for research in developing countries.

Acute Disease↗

Fluconazole and itraconazole susceptibility of clinical isolates of Cryptococcus neoformans at a tertiary care centre in India: a need for care.

OBJECTIVES: In cryptococcosis, fluconazole is a standard prophylactic, therapeutic and maintenance option, particularly in the expanding HIV/AIDS group. However, its excessive use may lead to resistance in Cryptococcus neoformans. Variations in clinical response to fluconazole have already been noted elsewhere, and cases of post-therapy relapse are not uncommon. To assess azole antifungal susceptibility profiles of clinical cryptococcal isolates in India, the All India Institute of Medical Sciences (AIIMS) has recently initiated preliminary studies using NCCLS M27-A. MATERIALS AND METHODS: Twenty-eight randomly chosen AIIMS clinical isolates (spanning 1997-2000), 16 isolates from other institutions in North India, and six reference strains of C. neoformans were subjected to susceptibility testing to fluconazole and itraconazole. RESULTS: Among clinical isolates, susceptibilities to fluconazole and itraconazole were 84.1% and 93.2%, respectively. MICs for all clinical isolates were 0.25-32 mg/L for fluconazole and <0.03-0.25 mg/L for itraconazole. MIC50 and MIC90 values for fluconazole were 4 and 16 mg/L, respectively, and those for itraconazole were 0.032 and 0.125 mg/L, respectively. Out of 28 AIIMS clinical isolates, 22 had minimum fungicidal concentrations (MFCs) of fluconazole at 128 mg/L. Moderately high fluconazole MICs (16-32 mg/L) were observed in 16% of clinical isolates--probably the first such report from India. MIC/MFC ratios for fluconazole and itraconazole were 1:32 or more in 16 AIIMS clinical isolates, indicating possible azole tolerance. There was good agreement between MIC values obtained by the micro- and macro-broth dilution techniques of M27-A compared in this study. CONCLUSIONS: The observed MIC data warrant continued surveillance of susceptibility values of clinical cryptococcal isolates in India.

Confidence Intervals↗

Non-ligation of the hernial sac during herniotomy: a prospective study.

Herniotomy is performed for the surgical repair of hernia and along with orchiopexy for the closure of associated patent processus vaginalis. Ligation of the hernial sac has been considered mandatory for a successful repair. The present report was designed to study the results of non-ligation of the hernial sac before excision at the neck. It was found that non-ligation has no untoward effect on early complications and recurrence rate on long-term follow-up. It is suggested that it is not necessary to ligate the hernial sac during herniotomy in children.

Child↗

Nosocomial outbreak of diarrhoea by enterotoxigenic Escherichia coli among preterm neonates in a tertiary care hospital in India: pitfalls in healthcare.

An outbreak of watery diarrhoea accompanied by low-grade fever and weight loss in 16 preterm neonates (age range 2-20 days) admitted to a neonatal intensive care unit (NICU) over four days in August 2000 is reported. Escherichia coli having similar antibiograms were identified on routine bacterial stool cultures in 14 (87.5%) neonates and none of the other known enteropathogens were detected. An investigation was undertaken to trace the source of infection. Surveillance cultures of swabs from the utensils used to prepare milk feed, culture of the formula feed and all items handled by one particular cook yielded growth of E. coli as did culture of his hand swabs and faecal sample. The causative agent was identified as enterotoxigenic E. coli (ETEC) as toxin production could be demonstrated by reverse passive latex agglutination in all the strains of E. coli isolated both from the infected neonates and the source of infection. The outbreak was effectively controlled by appropriate therapy and institution of proper measures of hygiene after identification of the source of infection.

Animals↗

Pulmonary arteriovenous fistula presenting as multiple brain abscess.

Pulmonary arteriovenous fisula is a rare condition in which there is abnormal connection between pulmonary arteries and veins. We describe this condition is an 18-year-old male who presented with cyanosis, clubbing, polycythemia and multiple brain abscesses. The patient was diagnosed as pulmonary arteriovenous fistula based on CT scan and on pulmonary angiography. The patient had a complete recovery after surgical drainage of brain abscess and excision of right upper lobe. After one year of follow up, there are no symptoms and there is complete reversal of cyanosis and polycythemia.

Adolescent↗

Liquid crystalline pharmacogel based enhanced transdermal delivery of propranolol hydrochloride.

A novel pharmacogel was developed for the enhanced transdermal delivery of propranolol hydrochloride (PH). The synthesized prodrugs, propranolol palmitate hydrochloride (PPH) and propranolol stearate hydrochloride (PSH) self-assembled to form gel simply upon mixing alcoholic solution of prodrug with an aqueous solution in a specified ratio. By varying the ratio of prodrug, alcohol and water, three-component phase diagram was constructed which revealed isotropic-gel-vesicular dispersion regions, respectively concomitant to increasing the ratio of water. The gel phase is termed 'Pharmacogel' and exhibits birefringence under plane-polarized light corroborating the presence of lamellar liquid crystals. The pharmacogel by virtue of high chemical potential gradient and improved physicochemical properties showed the enhanced in-vitro skin permeation flux of 51.5+/-3.7 and 42.5+/-3.1 microg/cm(2)/h from PPH and PSH gel, respectively, as compared to 1.9+/-0.1 microg/cm(2)/h for control; and decrease in lag time (1.8 and 2.8 h for PPH and PSH gel, respectively) compared to control (7.6 h) was observed. The admixing of egg lecithin (EL) in increasing ratio concomitantly decreased the flux values to 31.7+/-2.1 microg/cm(2)/h (at a mole ratio of 50:50 PPH:EL) and increased the lag time. In the gel containing 50% EL, the addition of span 40 and cholesterol slightly reduced the permeation while sodium deoxycholate and Tween-80 improved it. The plasma drug levels following transdermal application of control were low (C(max)=23 ng/ml) while in PPH gel, it increased with time reaching C(max) of 94 ng/ml at 8 h post-application of PPH gel (C(max) of 75 ng/ml at 12 h post application of PL5 gel) and maintained for longer times. The AUC(0-32 h) for PPH gel was much higher (1968 ng h/ml) than control (AUC(0-18 h) was 239 ng h/ml), while EL mixed gel also showed better absorption (AUC(0-32 h) was 1707 ng h/ml). The gel formulations also caused less irritation than control, while mixed gel showed least irritation. This novel self-assembled pharmacogel providing high transdermal permeation with many variables to regulate the delivery is therefore having a great potential in percutaneous delivery.

Administration, Cutaneous↗

Sodium valproate in the management of painful neuropathy in type 2 diabetes - a randomized placebo controlled study.

OBJECTIVE: To study the effectiveness and safety aspects of sodium valproate in the management of painful neuropathy in patients of type 2 diabetes mellitus. MATERIAL AND METHODS: A randomized double-blind placebo controlled trial of sodium valproate was done in type 2 diabetic patients to assess its efficacy and safety in the management of painful neuropathy. We screened 60 patients but eight patients could not complete the study; hence, the present study was done on 52 patients. Each patient was assessed by clinical examination, pain score by short form of the McGill pain questionnaire (SF-MPQ) and electrophysiological examination, which included motor and sensory nerve conduction velocity, amplitude and H-reflex initially and at the end of 1 month of treatment. RESULTS: Significant improvement was noticed in the pain score of patients receiving sodium valproate in comparison to patients receiving placebo at the end of 1 month (P < 0.05). The changes in electrophysiological data were not significant. The drug was well tolerated by all patients except one who developed a raised aspartate transaminase (AST)/alanine transaminase (ALT) level after 15 days of treatment. CONCLUSION: Sodium valproate is a well-tolerated drug and provides significant subjective improvement in painful diabetic neuropathy. These data provide a basis for future trials of longer duration in a larger group of patients.

Adult↗