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Biomedical subjects

S Mahadevan

Publications and source records attributed to S Mahadevan.

At least 37 records · Page 2Linked to original sources

Cranial computed tomography in partial motor seizures.

OBJECTIVE: To identify the pattern of intracranial structural lesions in developmentally normal children with partial motor seizures by computed tomography and to monitor the behavior of single ring enhancing lesion (SREL) after a period of time with or without treatment. METHODS: Consecutive developmentally normal children between one year and twelve years with partial motor seizures in a tertiary care referral Hospital. After clinical examination and appropriate investigation for tuberculosis and cysticercosis, CT scan was performed. In addition to anticonvulsants, children received antituberculous or anticysticercal therapy if indicated. Repeat CT was performed on children with SREL after 6 months. RESULTS: Computed tomography was abnormal in 102 (68%) children. Majority of the children (75) had SREL. The lesions were located in decreasing order of frequency in the parietal lobe (65), frontal lobe (7), occipital lobe (1), temporal lobe (1) and cerebellum (1). Repeat CT scan was performed on 50 of the 75 children with SREL. Among these, in 41 children who were only on antiepileptic therapy, the SREL had decreased in size in thirty-two whereas in the rest (9), there was no change in the size. CONCLUSION: Awareness of the existence of disappearing SREL lesions is essential to avoid unnecessary treatment with antituberculous or anticysticercal therapy and provides ample justification in treating with anticonvulsant drugs only.

Algorithms↗

The value of human papillomavirus testing in the colposcopy clinic.

The aim of the study was to investigate if human papillomavirus (HPV) testing can help in treatment and management decision-making in patients referred to the colposcopy clinic with mildly dyskaryotic or borderline smears. Fifty-five patients referred to the colposcopy clinic in Benenden Hospital with mildly dyskaryotic or borderline smears had HPV testing in addition to colposcopy. Twenty-eight patients had a negative HPV test and normal colposcopy and were discharged back to their general practitioners for cytological surveillance. The most recent smear results of these 28 patients were obtained from their general practitioners to assess if any patient had progressed to a higher-grade smear. Twenty-one (75%) replies were obtained and in 17 (80.9%) patients smear results had regressed to normal. Three continued to have borderline or mildly dyskaryotic smear and one had progressed to moderate dyskaryosis. Our conclusion was that in the presence of normal colposcopic findings in patients with mildly dyskaryotic or borderline smears, negative HPV status justifies referral back to the general practitioner for cytological surveillance, thus reducing workload and cost.

Adult↗

The effect of different types of hysterectomy on urinary and sexual functions: a prospective study.

A prospective observational study was designed to evaluate the effect of the different techniques of hysterectomy on urinary and sexual function. One hundred and eighty-seven women aged 29-73 years and admitted for hysterectomy for various indications were recruited to the study. Women presenting primarily with major uterine prolapse and those requiring radical hysterectomy were excluded. Patients underwent one of four different techniques of hysterectomy: total abdominal, vaginal, laparoscopic or subtotal. All patients completed a standardised questionnaire addressing urinary and sexual symptoms and underwent urodynamic testing using the Lectromed 6000 System (Lectromed, Letchworth, Herts, UK) before and 6 months after surgery. Out of 187 women, 184 (98.4%) had completed data. Seventy-three patients (39%) had a total abdominal hysterectomy, 62 (34%) had vaginal, 38 (21%) had laparoscopic and 11 (6%) had subtotal hysterectomy. At 6 months after surgery, urinary symptoms occurred less frequently (P<0.01) and urodynamic studies remained unchanged. Moreover, patients reported significantly lower rates of stress incontinence (P=0.005), urgency (P=0.03) and deep dyspareunia (P<0.001) than before the operation, regardless of the hysterectomy technique used. The route of hysterectomy did not influence the outcome of surgery. We conclude that simple hysterectomy, whether performed abdominally, vaginally or laparoscopically, does not adversely affect urinary or sexual function at 6 months after surgery.

Adult↗

Paroxysmal nocturnal hemoglobinuria with onset in childhood: a case report.

A twelve-year-old boy presented with recurrent episodes of anemia. Complete blood counts showed pancytopenia. Bone marrow was hypercellular with erythroid hyperplasia and depleted stores of iron. Positive Ham's test and sucrose lysis test revealed that he had paroxysmal nocturnal hemoglobinuria. There was a delay of nearly two years in the diagnosis in this patient. Paroxysmal nocturnal hemoglobinuria is rare in childhood. It must however be considered in a child who presents with unexplained anemia or bone marrow failure so that an early and accurate diagnosis is reached.

Age of Onset↗

The beta-glucoside genes of Klebsiella aerogenes: conservation and divergence in relation to the cryptic bgl genes of Escherichia coli.

The ability to metabolize aromatic beta-glucosides such as salicin and arbutin varies among members of the Enterobacteriaceae. The ability of Escherichia coli to degrade salicin and arbutin appears to be cryptic, subject to activation of the bgl genes, whereas many members of the Klebsiella genus can metabolize these sugars. We have examined the genetic basis for beta-glucoside utilization in Klebsiella aerogenes. The Klebsiella equivalents of bglG, bglB and bglR have been cloned using the genome sequence database of Klebsiella pneumoniae. Nucleotide sequencing shows that the K. aerogenes bgl genes show substantial similarities to the E. coli counterparts. The K. aerogenes bgl genes in multiple copies can also complement E. coli mutants deficient in bglG encoding the antiterminator and bglB encoding the phospho-beta-glucosidase, suggesting that they are functional homologues. The regulatory region bglR of K. aerogenes shows a high degree of similarity of the sequences involved in BglG-mediated regulation. Interestingly, the regions corresponding to the negative elements present in the E. coli regulatory region show substantial divergence in K. aerogenes. The possible evolutionary implications of the results are discussed.

Bacterial Proteins↗

Keith Edwards score for diagnosis of tuberculosis.

OBJECTIVE: To evaluate the applicability of Keith Edwards scoring system for the diagnosis of childhood tuberculosis. METHODS: One hundred and one children aged 2 months to 12 years who fulfilled the inclusion criteria were evaluated with Keith Edwards score. The diagnosis of tuberculosis by Keith Edwards score and the definitive reference were compared. RESULTS: Among the 65 children diagnosed as having tuberculosis by the definitive reference, 59 had a Keith Edwards score of >7. Four children had a score of >7 but were not suffering from tuberculosis. The sensitivity and specificity of this score have been found to be 91% and 88% respectively. CONCLUSION: In select population with indicative clinical features, Keith Edwards score can be a definitive guideline for the diagnosis of childhood tuberculosis. However, more studies are required for the validation of this clinical score before it can be used as a definitive diagnostic reference standard for tuberculosis.

Child↗

Qualitative tuberculin response in the diagnosis of tuberculosis in apparently healthy schoolchildren.

SETTING: School-based cross-sectional study. OBJECTIVE: To assess the value of qualitative tuberculin responses (turgid and non-turgid type) in diagnosis of tuberculosis disease in apparently healthy schoolchildren. DESIGN: Qualitative tuberculin responses were assessed in 548 apparently healthy schoolchildren. Tuberculin-positive (> or = 10 mm) children were investigated for evidence of tuberculosis. The relationship between the types of qualitative tuberculin response and occurrence of tuberculosis was studied. RESULTS: Eighty-eight (16.1%) children were found to be tuberculin-positive. Of these, 68 had non-turgid reaction whereas 20 had turgid reaction. Most of the children with a reaction of 5-9 mm had a non-turgid type of tuberculin reaction. Only four children with non-turgid reaction had tuberculosis, while 18 children with turgid reaction had tuberculosis disease (P < 0.0001). A larger tuberculin reaction was found to be associated with a higher occurrence of tuberculosis (P = 0.016 by linear regression method). CONCLUSION: The observations indicate a possible relation between turgid reaction and tuberculosis disease.

Child↗

Predictive value of tuberculin induration at 24 h in healthy schoolchildren.

Tuberculin (1 TU PPD RT23 Tween 80) was administered to 500 healthy schoolchildren, aged 5-9 years. The induration at 24 h was compared with that at 72 h. The mean (standard deviation) induration of the tuberculin reaction at the end of 24,48 and 72 h was 4.5 (6.75), 4.4 (7.11) and 4.0 (6.91) mm, respectively. When the tuberculin reaction was 0-9 mm, a significant difference was noted between the 24- and 72-h reading (p = 0.0001). There was no difference in the size of the tuberculin reaction between the 24- and 72-h readings when the reaction size was > or = 10 mm (p > 0.05). Considering a tuberculin induration of < 10 mm as negative tuberculin reaction for our reference population in South India, the sensitivity, specificity, positive predictive value and the negative predictive value in our study for the 24-h reading were found to be high. The predictive value of 24-h induration was not affected by age. Reading and interpretation of tuberculin test after 24 h needs due consideration in clinical practice.

Child↗

Prognostic factors in childhood tuberculous meningitis.

The risk factors affecting the outcome in 50 children with tuberculous meningitis were evaluated over a period of 20 months. Five children (10 per cent) had stage 1 disease, 29 (58 per cent) had stage II disease, and 16 (32 per cent) had stage III disease at admission. Seventeen cases (34 per cent) showed complete recovery, five (10 per cent) had mild, 14 (28 per cent) had moderate, and nine (18 per cent) had severe neurological sequelae. Five children (10 per cent) died. Younger age, tonic posturing, papilloedema, focal neurological deficit and stage at presentation were found to affect adversely the prognosis independently in children with tuberculous meningitis.

Child↗

Differential spectrum of mutations that activate the Escherichia coli bgl operon in an rpoS genetic background.

The bgl promoter is silent in wild-type Escherichia coli under standard laboratory conditions, and as a result, cells exhibit a beta-glucoside-negative (Bgl-) phenotype. Silencing is brought about by negative elements that flank the promoter and include DNA structural elements and sequences that interact with the nucleoid-associated protein H-NS. Mutations that confer a Bgl+ phenotype arise spontaneously at a detectable frequency. Transposition of DNA insertion elements within the regulatory locus, bglR, constitutes the major class of activating mutations identified in laboratory cultures. The rpoS-encoded sigmaS, the stationary-phase sigma factor, is involved in both physiological as well as genetic changes that occur in the cell under stationary-state conditions. In an attempt to see if the rpoS status of the cell influences the nature of the mutations that activate the bgl promoter, we analyzed spontaneously arising Bgl+ mutants in rpoS+ and rpoS genetic backgrounds. We show that the spectrum of activating mutations in rpoS cells is different from that in rpoS+ cells. Unlike rpoS+ cells, where insertions in bglR are the predominant activating mutations, mutations in hns make up the majority in rpoS cells. The physiological significance of these differences is discussed in the context of survival of natural populations of E. coli.

Bacterial Proteins↗

Serodiagnosis of tuberculosis in children.

Serodiagnostic tests aid in clinical decision-making process while evaluating symptomatic children for active tuberculosis. Interpretation of test results must take into consideration the type of antigen used, stage of the disease in the child and prevalence of the disease in the population. Epitope specific serology and multi-antigen cocktail assays will render acceptable specificity and sensitivity to serodiagnostic tests in tuberculosis.

Child↗

The Escherichia coli antiterminator protein BglG stabilizes the 5'region of the bgl mRNA.

The beta-glucoside utilization (bgl) genes of Escherichia coli are positively regulated by the product of the bglG gene, which functions as an antiterminator by binding to specific sequences present within the bgl mRNA. BglG is inactivated by phosphorylation in the absence of beta-glucosides by BglF, the bgl-specific component of the phosphotransferase system (PTS). Here, we present evidence for an additional function for BglG, namely the stabilization of the 5' end of the bgl mRNA. Half-life measurements of the promoter-proximal region of the bgl mRNA indicate a five fold enhancement of stability in the presence of active (unphosphorylated) BglG. This enhancement is lost when the binding of BglG to mRNA is prevented by deletion of the binding site. Interestingly, stabilization by BglG does not extend to downstream sequences. The enhanced stability of the upstream sequences suggest that BglG remains bound to its target on the mRNA even after the downstream sequences have been degraded. Implications of these observations for the mechanism of positive regulation of the operon by BglG are discussed.

Bacterial Proteins↗

Childhood bacterial meningitis in Pondicherry, South India.

OBJECTIVE: To identify causative bacteria from cerebrospinal fluid (CSF) of children with meningitis and analyse various clinical and laboratory parameters. METHODS: Over a 20 month period, September 1994 to April 1996, one hundred episodes of acute bacterial meningitis in children aged 1 month-12 years were studied in a tertiary urban hospital in South India. Organisms were isolated from the cerebrospinal fluid (CSF) in 35% of cases. Among infants and children, the two major pathogens were H. influenzae (17%) and S. pneumoniae (12%). RESULTS: The illness at presentation was mild in 13% and severe in 36% of cases. The association of subdural effusion in children with Salmonella Gp B meningitis merits attention. The overall case fatality rate was 25%. S. pneumoniae had a higher case fatality rate than Salmonella Gp B and H. influenzae (50% vs 17% vs 12%). All the three infants below 3 months of age with S. pneumoniae meningitis died. On analysis of selected clinical and laboratory features by discriminant analysis, CSF culture was the significant (P = 0.02) variable in relation to outcome. In pneumococcal meningitis, CSF WBC count was a highly significant variable in relation to outcome (Wilk's Lambda 0.15, F = 24.64, P = 0.0002). CONCLUSION: Prevention of infections due to H. influenzae and S. pneumoniae should be given higher priority.

Analysis of Variance↗

Monoclonal antibodies to mycobacterial DNA gyrase A inhibit DNA supercoiling activity.

DNA gyrase is an essential type II topoisomerase found in bacteria. We have previously characterized DNA gyrase from Mycobacterium tuberculosis and Mycobacterium smegmatis. In this study, several monoclonal antibodies were generated against the gyrase A subunit (GyrA) of M. smegmatis. Three, MsGyrA:C3, MsGyrA:H11 and MsGyrA:E9, were further analyzed for their interaction with the enzyme. The monoclonal antibodies showed high degree of cross-reactivity with both fast-growing and slow-growing mycobacteria. In contrast, none recognized Escherichia coli GyrA. All the three monoclonal antibodies were of IgG1 isotype falling into two distinct types with respect to epitope recognition and interaction with the enzyme. MsGyrA:C3 and MsGyrA:H11 IgG, and their respective Fab fragments, inhibited the DNA supercoiling activity catalyzed by mycobacterial DNA gyrase. The epitope for the neutralizing monoclonal antibodies appeared to involve the region towards the N-terminus (residues 351-415) of the enzyme in a conformation-dependent manner. These monoclonal antibodies would serve as valuable tools for structure-function analysis and immunocytological studies of mycobacterial DNA gyrase. In addition, they would be useful for designing peptide inhibitors against DNA gyrase.

Antibodies, Monoclonal↗

Cold knife cone biopsy--a valid diagnostic tool and treatment option for lesions of the cervix.

We present a case series of cold knife cone biopsy with emphasis on validation of the technique for ongoing and future use. This involved: analysis of 100 cold knife cone biopsies performed between 1987 and 1997. Data were gathered relating to indications, technique, postoperative morbidity, histological findings and results of long-term follow-up. Mean age was 41.8 years, and mean parity 2. Smear abnormalities of moderate or severe dyskaryosis were present in 74% of cases, and glandular abnormalities in 8%. Colposcopic diagnosis of CIN II-III was made in 55% of cases, and invasion suspected in 12%. The main indications for conisation were inability to visualise the entire squamocolumnar junction (64%), disparity in cytological and colposcopic findings (26%), and colposcopic suspicion of invasion (12%). Mean blood loss was 90 ml. One patient (1%) required hysterectomy and blood transfusion to control secondary haemorrhage. Postoperative infection occurred in 5%, and cervical stenosis in 3%. All specimens were adequate for histopathological evaluation, including the margin, CIN was histologically proven in 67% of specimens, microinvasion in 4%, adenocarcinoma in-situ in 3%, and invasion in 3%. During a mean follow-up of 4.5 years (range 1.5-11 years), cure rate after complete excision was 97% and after incomplete excision was 85% (P > 0.05) Despite the advent of alternative methods of treatment, cold knife cone biopsy remains an acceptable option in the management of CIN and microinvasion of the cervix. There are valid indications for the technique. When properly performed, it gives accurate representation of the disease process, has low risk of complications and is curative in most cases.

Journal Article↗

Effect of different classes of inhibitors on DNA gyrase from Mycobacterium smegmatis.

Quinolones, coumarins, cyclothialidines, CcdB and microcin B17 inhibit DNA gyrase. Information regarding these various inhibitors comes from studies performed with the enzyme from Escherichia coli, and subsequent analyses have also primarily been confined to this system. We have carried out a detailed analysis of the effect of various groups of inhibitors on Mycobacterium smegmatis gyrase and demonstrate differential susceptibility of the E. coli and M. smegmatis gyrases. Interestingly, M. smegmatis gyrase was refractory to the plasmid-borne proteinaceous inhibitors CcdB and microcin B17. Ciprofloxacin, a fluoroquinolone, showed a 10-fold reduction in efficacy against M. smegmatis compared with E. coli gyrase. We have also shown that etoposide, an antineoplastic drug, inhibits DNA gyrase activity by trapping the gyrase-DNA complex. DNA gyrases from both E. coli and M. smegmatis were susceptible to etoposide at comparable levels.

Adenosine Triphosphatases↗