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Biomedical subjects

V K Sharma

Publications and source records attributed to V K Sharma.

At least 37 records · Page 2Linked to original sources

An Indian child with Kindler syndrome resulting from a new homozygous nonsense mutation (C468X) in the KIND1 gene.

Kindler syndrome is an inherited skin condition that presents with blistering followed by photosensitivity and a progressive poikiloderma. The disorder results from mutations in the KIND1 gene, encoding the protein kindlin-1, a recently characterized 677-amino acid protein involved in anchorage of the actin cytoskeleton to the extracellular matrix. We report the clinical features of an 11-year-old boy with Kindler syndrome from a consanguineous Indian family and the identification of a homozygous nonsense mutation (C468X) in exon 12 of the KIND1 gene in his genomic DNA. This mutation has not been described previously but is similar to the 17 previously published KIND1 mutations that are all predicted to lead to loss of kindlin-1 protein expression and function. The clinical features in this boy highlight the relevance of kindlin-1 in skin biology, specifically to epidermal adhesion and response to acute and chronic sun exposure. Delineation of this new pathogenic mutation in KIND1 is also useful for genetic counselling in this family and in assessing carrier status in unaffected family members.

Base Sequence↗

Invasive dermatophytosis with lymph node involvement in an immunocompetent patient.

A 23-year-old man presented with annular and arcuate, hyperpigmented, itchy, scaly plaques over the trunk and lower extremities for 5 years progressing to verrucous papules and nodules for the last 1.5 years. He also had nontender, inguinal and axillary lymphadenopathy. Skin and lymph node biopsies showed granulomatous inflammation and special stains demonstrated long septate hyphae. Tissue cultures grew Trichophyton verrucosum. The patient was treated with itraconazole 100 mg twice daily for 8 months, resulting in complete clearance of the lesions.

Adult↗

The NORSE (new-onset refractory status epilepticus) syndrome: defining a disease entity.

INTRODUCTION: To characterise a homogeneous group of patients with new-onset refractory status epilepticus (NORSE syndrome). MATERIALS AND METHODS: This is a descriptive, semiprospective review of all cases of NORSE syndrome seen between 2000 and 2004 at a tertiary care public hospital in Singapore. A review of the literature was performed to identify possible additional similar cases for comparison. RESULTS: Seven patients with NORSE syndrome were identified. Characterising features were female gender, young age, previous good health, cerebrospinal fluid pleocytosis (in 4), antecedent febrile illness (in 5), extraordinarily prolonged status epilepticus (average 32 days), failure of extensive investigations to reveal an underlying cause, catastrophic outcome as well as temporal lobe and leptomeningeal abnormality on brain magnetic resonance imaging. A review of the literature identified 12 similar patients, comprising both adults and children. CONCLUSIONS: Based on our patients and those described in the literature, we characterise the NORSE syndrome. Increased recognition of this clinical entity is needed to help delineate the underlying aetiology of this unique severe illness.

Adult↗

In vitro activity of ceftriaxone plus tazobactam against members of Enterobacteriaceae.

AIMS: To study the in vitro activity of ceftriaxone alone and in combination with the beta-lactamase inhibitor tazobactam against bacterial isolates belonging to the Family Enterobacteriaceae. METHODS: One hundred and five consecutive isolates of Escherichia coli and Klebsiella spp. that had been recovered from various high-risk areas of the hospital were included in the study. MIC estimation to ceftriaxone and a combination of ceftriaxone and tazobactam was performed by the agar dilution method. RESULTS: By the MIC studies, 88.6% of the strains appeared to be resistant to ceftriaxone with the MIC90 value being > 256 microg/ml. When the MIC were done to ceftriaxone in combination with tazobactam, the resistance rate dropped to 4.8% with the MIC90 value being 4.0 microg/ml. CONCLUSION: The combination of ceftriaxone and tazobactam appears to be an excellent therapeutic alternative with 94.6% of ceftriaxone resistant strains being susceptible in vitro to this combination.

Anti-Bacterial Agents↗

Seroprevalence of Chalmydia trachomatis infection amongst patients with pelvic inflammatory diseases and infertility.

Chlamydia trachomatis (C. trachomatis) is a common cause of pelvic inflammatory disease in female population. This infection can be diagnosed both by culture and serology. The present study evaluated the seroprevalence of chlamydial infection in patients with pelvic inflammatory disease (ND) and infertility and in control population of healthy normal females. The seroprevalence was found to be 82.7% in patients and 32% in controls by Enzyme Linked Immuno Sorbent Assay (ELISA) for any one or more class of antichlamydial antibodies (IgG/IgM/ IgA). The study demonstrates the importance of serology to monitor trends of chlamydial infections in women with PID and infertility.

Adult↗

Atmospheric deposition of polycyclic aromatic hydrocarbons (PAHs) in mosses (Hypnum cupressiforme) in Hungary.

The atmospheric deposition of polycyclic aromatic hydrocarbons (PAHs) was investigated in Hungary by analyzing a moss (Hypnum cupressiforme) species as a bioindicator. In the autumn of 1997, samples were collected at 29 sites distributed across Hungary. The concentrations of total PAH at these sites were in the range of 0.1567-10.45 x 10(4) microg kg(-1) with a mean value of 1.87 x 10(4) microg kg(-1). More than 99% of the total PAHs atmospheric deposition were low molecular weight PAHs (up to 3 ring compounds). The total PAH values showed no correlation with metal concentrations. However, most of the sites in this region showed a positive linear relationship between PAHs levels and traffic volume (r2 = 0.83; P < 0.001) while no relationship existed between PAH levels and population (r2 = 0.01; P > 0.1). Atmospheric deposition of PAHs at different regions in Hungary may be due to incomplete combustion of fuel. The total concentrations of PAHs were compared to the PAH levels in vegetation samples collected from different regions around the world. The highest PAHs concentrations accumulated were found in Hypnum cupressiforme than other vegetation species. A greater affinity for PAH compounds by Hypnum cupressiforme than other moss species probably caused larger amounts of accumulation. A relationship between accumulations of PAH compounds in Hypnum cupressiforme and octanol-air partition coefficients was obtained and is briefly discussed.

Air Pollutants↗

Proton pump inhibitor treatment for acute peptic ulcer bleeding.

BACKGROUND: Peptic ulcer (PU) bleeding is associated with substantial morbidity, mortality and healthcare cost. Randomised controlled trials (RCTs) evaluating the clinical effect of proton pump inhibitors (PPIs) in peptic ulcer bleeding have yielded conflicting results. OBJECTIVES: To evaluate the efficacy of PPIs in the management of acute bleeding from PU using evidence from RCTs. SEARCH STRATEGY: We performed a search of CENTRAL, The Cochrane Library (Issue 3, 2003), MEDLINE (1966 to February 2003) and EMBASE (1980 to February 2003) and proceedings of recent major meetings through to February 2003. We searched the reference lists of articles and contacted pharmaceutical companies and experts in the field for additional published or unpublished data. SELECTION CRITERIA: RCTs of PPI treatment (oral or intravenous) compared with either placebo or H(2)-receptor antagonist (H(2)RA) in patients with acute bleeding from PU were included if they met pre-defined criteria. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data independently on a purpose-designed data extraction form. Validity of included studies was assessed by adequacy of randomisation method and other pre-defined criteria. Studies were summarised and meta-analysis was undertaken. The influence of factors on the outcomes was assessed. MAIN RESULTS: Twenty-one RCTs with a total of 2915 participants were included. Statistical heterogeneity was found among trials for rebleeding (P = 0.05), but not for mortality (P = 0.26) or surgery (P = 0.42). There was no significant difference in mortality rates between PPI and control treatment; pooled rates were 5.2% on PPI versus 4.6% on control (odds ratio (OR) 1.11; 95% CI 0.79 to 1.57). PPI treatment significantly reduced rates of surgical intervention compared with control; pooled rates were 8.4% on PPI versus 13.0% on control (OR 0.59; 95% CI 0.46 to 0.76). PPIs significantly reduced rebleeding compared to control; pooled rates were 10.6% with PPI (range: 0% to 24.4%) versus 18.7% with control treatment (range: 2.3% to 39.1%), the OR was 0.46 (95% CI 0.33 to 0.64). Results on mortality and rebleeding rates were independent of route of PPI administration, type of control treatment or application of initial endoscopic haemostatic treatment. Surgical intervention rates varied with type of control (PPI significantly reduced surgical intervention rates compared with placebo and not when compared with H(2)RA) but not with route of PPI administration or application of initial endoscopic haemostatic treatment. REVIEWERS' CONCLUSIONS: PPI treatment in PU bleeding reduces rebleeding and surgical intervention rates in studies comparing treatment with placebo or H(2)RA, but there is no evidence of an effect on mortality.

Acute Disease↗

Use of iron(VI) and iron(V) in water and wastewater treatment.

Fe(VI) (Fe(VI)O4(2-)) and Fe(V) (Fe(V)O4(3-)) have high oxidizing power, selectivity, and upon decomposition produce a non-toxic by-product, Fe(III), which makes them potential oxidants in water and wastewater treatment. Rates of oxidation increase with a decrease in pH and are related to protonation of Fe(VI)O4(2-) and Fe(V)O4(3-). Oxidation of sulfur- and nitrogen-containing pollutants by Fe(VI) can be accomplished in seconds to minutes with formation of non-hazardous products. Fe(VI) can easily oxidize the amino acid components of microcystins and is a suitable disinfectant for detoxifying toxins in water. The oxidation of pollutants and amino acids with Fe(V) is 3-5 orders of magnitude faster than with Fe(VI). The use of ionizing radiation and photocatalytic techniques in the presence of Fe(VI) results in Fe(V) formation and may have synergistic effects on the oxidation of pollutants and removal of toxins in water and wastewater. This paper summarizes the results of multi-functional properties of Fe(VI) and Fe(V) to treat water and wastewater.

Amino Acids↗

Changing face of septicaemia and increasing drug resistance in blood isolates.

In a retrospective study conducted between January, 2000 and December 2000, 7157 adults and children were studied. Amongst these, 1071 patients had positive blood cultures. Of these, 575 (53.6%) cases were community acquired septicaemia and 486 (46.4%) cases had developed septicaemia of nosocomial origin. Gram negative aerobes accounted for 708 (66.1%) isolates. Amongst them, Klebsiella pneumoniae predominated (23%), followed by Escherichia coli (14%). Acinetobacter spp. emerged as the next common pathogen (9%), followed by Salmonella typhi (5.4%). Staphylococcus aureus (9%) and coagulase negative staphylococci (9%) were the most common gram positive isolates followed by Enterococcus faecalis (4.7%). Antibiotic susceptibility of all these isolates was performed by the modified Stokes' method. Both Klebsiella pneumoniae and Escherichia coli showed alarmingly high resistance to all groups of antibiotics with 70-80% resistance to amoxicillin and cephalexin. Minimum resistance was observed against cefotaxime (23%) and ciprofloxacin (12%). Majority of Enterococcus faecalis were multidrug resistant. Streptococcus pneumoniae exhibited 26% resistance to penicillin. Thus, the study clearly highlights the rising level of drug resistance amongst the bacterial isolates from blood and hence the need to update and formulate newer drug policies.

Adult↗

Community based study on sero-prevalence of syphilis in New Delhi (India).

Syphilis continues to be a major health problem in India. Data regarding sero-prevalence of syphilis is largely hospital based. Majority of community based studies have been conducted on select groups. Therefore, these studies do not reflect the true prevalence of syphilis in general population. The objective of the study was to determine the sero-prevalence of syphilis in the urban and rural communities of New Delhi, using both VDRL and TPHA for screening and FTA-ABS for confirmation and discrepant analysis. Serum specimens from 178 males and 227 females aged between 15-49 years were tested. VDRL test was put up using VDRL antigen from serologist, Kolkata. TPHA and FTA-ABS were performed using commercially available kits. 6.91% (28/405) subjects were found to be seropositive for syphilis (males 10.11%, females 4.40%). Syphilis seropositivity was found to be significantly associated with low income (p=0.02) and presence of symptoms suggestive of STIs (p=0.00) among males. Positive syphilis serology was significantly associated with trichomoniasis in females (p=0.00). Community based studies utilizing one non-treponemal test plus one treponemal test for screening purpose and an additional specific test for confirmation should be used for designing a control programme.

Adolescent↗

Plasma cortisol levels in acute asthma.

OBJECTIVE: The study was undertaken with the aim to determine correlation between the initial plasma cortisol level and severity of asthma attack and the response to standard treatment for acute exacerbation of bronchial asthma in pediatric age group. METHODS: The study was performed in 33 asthmatic patients between 5-12 years of age, presenting to pediatric emergency with acute exacerbation of bronchial asthma. None of the patients included in the present study was on steroids. Venous blood sample for determination of plasma cortisol level was taken and patients were nebulized with salbutamol every 20 minutes, up to 1 hour. The patients who failed to respond even after three nebulizations were labeled as nonresponders and repeat venous blood sample for plasma cortisol estimation was taken before giving injection hydrocortisone. In responders sample was taken 1 hour after last nebulization. RESULTS: The mean plasma cortisol value at the time of admission in responders (12.42 +/- 1.9 microg/dl) was not found to be significantly different from that in nonresponders (13.1 +/- 2.74 microg/dl). Children with severe attack of asthma had significantly higher plasma cortisol levels both at the time of admission (p=0.03) and at the end of study (p=0.001), as compared to patients with moderate attack. The mean percentage change in plasma cortisol levels in nonresponders was an increase of 80.65 +/- 60.64%, whereas, in responders it decreased by 16.49 +/- 21.7% and this difference was statistically significant (p<0.05). CONCLUSION: The hypothalamo pituitary adrenal axis functions normally in asthmatic patients, producing a rise in cortisol levels corresponding to degree of stress; and from initial cortisol level alone, it cannot be predicted, whether a patient will respond to beta-2 agonist (salbutamol) nebulization alone or will require exogenous corticosteroids.

Acute Disease↗

Optimization of RNA yield, purity and mRNA copy number by treatment of urine cell pellets with RNAlater.

BACKGROUND: We have shown that measurement of mRNA for cytotoxic attack proteins perforin and granzyme B in urinary cells is a noninvasive means of diagnosing acute rejection of human renal allografts. Urinary cell mRNA studies have yielded useful information in other patient populations such as patients with cancer. The isolation of sufficient and high quality ribonucleic acid (RNA) from urinary cells however is problematic. RNAlater, an RNA stabilization solution, has been reported to optimize RNA isolation from tumor tissues stored at room temperature and from pigment-rich ocular tissues. METHODS: We explored whether the addition of RNAlater to urine cell pellets improves RNA yield, enhances purity and facilitates measurement of low abundance mRNAs. We measured, with the use of real-time quantitative polymerase chain reaction (PCR) assay, levels of expression of a constitutively expressed gene 18S rRNA and mRNA for granzyme B and transforming growth factor-beta(1) (TGF-beta(1)) in urine specimens and renal biopsies obtained from renal allograft recipients. RESULTS: RNA yield (P<0.01, Wilcoxon signed rank test) and the A260/A280 ratio (P<0.01) were both higher with urine cell pellets treated with RNAlater prior to snap freezing compared to cell pellets that were not treated with RNAlater prior to snap freezing. Levels (copy number per 1 microg of total RNA) of 18S rRNA (P<0.02), granzyme B mRNA (P=0.002) and TGF-beta(1) (P=0.02) were all higher with treated urine cell pellets compared to untreated cell pellets. Kruskall-Wallis one way analysis of variance and pair-wise comparisons with Student-Newman-Keuls test showed that the levels of mRNA for granzyme B (P<0.05) and TGF-beta(1) (P<0.05) are significantly different between renal allograft biopsies and untreated urine cell pellets but not between the biopsy specimens and RNAlater-treated urine cell pellets. CONCLUSIONS: The addition of RNAlater to urine cell pellets improves RNA isolation from urinary cells and facilitates measurement of low abundance mRNAs.

Adolescent↗

Role of Joshi's external stabilisation system fixator in the management of idiopathic clubfoot.

PURPOSE: To explore the role of Joshi's external stabilisation system fixator in correcting cases of clubfoot peculiar to India, we studied cases of neglected clubfoot, dropout cases of plaster-of-paris cast treatment, or failed surgical procedures that had been followed for a minimum period of 2 years. METHODS: 26 children underwent 44 Joshi's external stabilisation system procedures at the Central Institute of Orthopaedics at the Safdarjung Hospital, New Delhi, between January 1998 and December 1999 for the conditions of interest. Three-dimensional correction was achieved by use of the distractor device. RESULTS: Excellent results were obtained in 77% of the cases, good results in 13%, and poor results in 9% of the cases. Complications in half of the cases were pintract infections, which eventually healed on an outpatient basis without any residual sequelae. CONCLUSION: The Joshi's external stabilisation system frame is ideally suited for the child in whom clubfoot deformities remain uncorrected by plaster-of-paris casts and manipulation, as well as for recurrent clubfoot. Casting after complete correction not only protects the osteopenic bones while the pin-tracts heal, but also maintains correction and allows gradual weightbearing.

Child↗