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Biomedical subjects

S Ram

Publications and source records attributed to S Ram.

At least 19 recordsLinked to original sources

Synthesis and biological activity of certain alkyl 5-(alkoxycarbonyl)-1H-benzimidazole-2-carbamates and related derivatives: a new class of potential antineoplastic and antifilarial agents.

A series of methyl and ethyl 5-(alkoxycarbonyl)-1H-benzimidazole-2-carbamates (7-19) and methyl 5-carbamoyl-1H-benzimidazole-2-carbamates (24-34) have been synthesized via the reaction of an appropriate alcohol or amine with the acid chloride derivatives 6a or 6b at room temperature. Reaction of an alcohol with acid chloride 6a at reflux temperature afforded transesterified products 20-23 in good yield. Treatment of methyl 5-amino-1H-benzimidazole-2-carbamate with substituted benzoyl chlorides furnished the methyl 5-benzamido-1H-benzimidazole-2-carbamates (36-38). Compounds 9, 16, 20, and 22 demonstrated significant growth inhibition in L1210 cells with IC50's less than 1 microM. Growth inhibition by this series of compounds appears to be associated with mitotic spindle poisoning. All the compounds tested, 9, 10, 19, 20, 22, and 23, caused significant accumulation of L1210 cells in mitosis. Compounds 7, 9, 19, 25, 26, 27, and 36 showed significant in vivo antifilarial activity against adult worms of Brugia pahangi, Litomosoides carinii, and Acanthocheilonema viteae in experimentally infected jirds.

Animals

Development of 3-iodophenylisothiocyanate for radioiodination of monoclonal antibodies.

A new radioiodination reagent, 3-iodophenylisothiocyanate (3-IPI) has been developed for coupling to monoclonal antibodies. The starting material, 3-tri-n-butylstannylphenylisothiocyanate was prepared via a reaction of hexabutylditin with 3-bromoaniline, followed by treatment with thiophosgene with an overall yield of 72%. The radioiodination of this tin precursor with Na[125I]I/iodogen in chloroform gave 3-[125I]IPI in 23-55% radiochemical yield and 81-99.6% radiochemical purity. Purification of the impure product by high pressure liquid chromatography increased the radiochemical purity of the product up to 99%. These results suggest that 3-IPI may be a useful ligand for radioiodination and coupling to a variety of monoclonal antibodies.

Antibodies, Monoclonal

Loss of some virulence factors of enterotoxigenic Escherichia coli on repeated subcultures.

Thirty enterotoxigenic Esch. coli (ETEC) strains of predominant serogroups, isolated from patients with diarrhoea in Ludhiana, Punjab were investigated for expression of heat labile (LT) enterotoxin and colonization factor antigens (CFAs) on repeated subculture. These belonged to serogroup 078 (10), 080 (2), 0114 (6), 020 (3), 0128 (3), 0153 (2) and 08 (4) respectively. The isolates exhibited a differential response for expression of LT and CFAs on repeated subculturing. All the strains were positive for both LT and CFA up to six subcultures. Three strains of serogroup 0114 and one of 080 failed to express CFA while one strain each of serogroups 080, 0114, 020 and 08 failed to elaborate LT in the 8th subculture. Only 25 and 19 isolates were detected as stable producer of LT and CFAs up to 10th subculture.

Antigens, Bacterial

Assessment of the modified internal gas generator system for isolation of Campylobacter.

The modified internal gas generator system (MIGGS) to create microaerophilic conditions for the isolation of Campylobacter was compared with two conventional methods viz., the Gaspak and the hydrogen and carbon dioxide gas mixture from gas cylinders. Ten reference strains of C. jejuni, C. coli and C. laridis were grown on Butzler's medium at optimum temperature under microaerophilic conditions. The MIGGS and Gaspak gave identical results which were better than with the compressed gas mixture. As the chemicals required for MIGGS are commonly available in the market, it works out to be less expensive than the commercial Gaspak. Further, investigations with MIGGS revealed Campylobacter in the faecal samples of 1.9 per cent (50 out of 2661) patients of diarrhoea visiting a Teaching Hospital in Ludhiana (Punjab). None of the 105 healthy volunteers excreted Campylobacter in their faeces. In the 50 positive patients, highest (22%) occurrence was observed in April followed by 16 per cent in May. High prevalence of Campylobacter diarrhoea was observed among infants and children up to 10 yr. Male patients were found to be more susceptible to infection than females (1.9:1). All strains were sensitive to the common antimicrobial agents tested.

Adolescent

ELISA for detection of heat stable enterotoxin producing Escherichia coli strains.

Among 557 strains of Esch. coli isolated from patients with acute diarrhoea, 392 (70.4%) isolates demonstrated ST production by ELISA. Predominant ST producing serogroups were 020 (45), 078 (40), 0128 (21), 061 (19), 0149 (9), 04, 055, 0106 and 0114 (8 each). The inhibition ELISA range was between 10.5 and 40.5 per cent. Visual difference between a negative and a positive ELISA test was distinct. A comparison of ELISA with classical suckling mouse assay for 100 strains showed 88 and 80 positive strains respectively for ST. ELISA proved a more specific, rapid and sensitive assay which may be useful for screening large number of isolates in epidemiological studies.

Acute Disease

Aeromonas-associated diarrhoea in north India.

The incidence of Aeromonas-associated diarrhoea in patients attending the hospital attached to the Dayanand Medical College, Ludhiana, India was investigated during May 1984-May 1987. Microbiological examination of single faecal samples from 2,661 patients showed the presence of various enteropathogens of which details of only Aeromonas isolations are given and discussed in the present article. A small control sample of 105 age-matched healthy volunteers were also examined. Only 55 patients (2.1% of all patients) showed Aeromonas spp. in their stool samples on culture. Aeromonas as a single pathogen was isolated from 37 patients and, from 18 patients it was mixed with other enteropathogens. Stools of healthy controls did not contain any pathogen. Seven of 25 isolates of A. caviae, all 18 isolates of A. sobria and all 7 isolates of A. hydrophilla were shown to be enterotoxigenic by rabbit ileal loop test. There was no immunological cross-reaction between Aeromonas enterotoxin and Escherichia coli labile toxin antiserum. The Aeromonas isolates were susceptible to most of the commonly used antimicrobial agents except ampicillin and cephalothin.

Adolescent

Incidence & outcome of aluminium phosphide poisoning in a hospital study.

A total of 418 patients with aluminium phosphide poisoning admitted during January 1981 to December 1987, were studied and analysed for various clinical parameters. A steady increase in the number of patients was seen during the last 7 yr. Maximum number belonged to the younger generation and nature of poisoning was suicidal in most of these patients. Dose of poison consumed varied, but most patients consumed two tablets (6 g). A wide range of symptoms and signs was seen, the commonest being gastrointestinal manifestations and shock. Cardiac arrhythmias and conduction disturbances were seen in 38.2 per cent patients. The overall mortality was 77.2 per cent. Indices of a bad prognosis included poor response to dopamine infusion and continuous increase in its dosage, chest infections, adult respiratory distress syndrome and disseminated intravascular coagulation. The complications noticed were pericarditis, congestive cardiac failure, acute gastrointestinal haemorrhage and acute respiratory arrest. Histopathology of various organs showed changes suggestive of cellular hypoxia but the mechanism of ECG changes and of the complications could not be elucidated.

Accidents

The effects of labetalol and prazosin on exercise haemodynamics in hypertensive patients.

The antihypertensive and haemodynamic effects of labetalol were compared with those of prazosin both at rest and during bicycle exercise in 38 moderate to moderately severe hypertensive patients (supine DBP 95 to 119 mmHg when untreated). Following a two week open placebo phase to establish baseline BP and baseline exercise performance, patients were randomly and double-blindedly assigned to receive labetalol or prazosin. Drug dose was titrated from 100 to 400 mg labetalol twice daily, or from one to 10 mg prazosin twice daily at weekly intervals until BP was controlled (supine DBP less than or equal to 90 mmHg with at least a 10 mmHg decrease from baseline). Eighteen labetalol and twenty prazosin patients achieved BP control and were subsequently reexercised to fatigue on a bicycle ergometer. The mean changes from baseline for heart rate and rate pressure product (heart rate x SBP) were reduced only in the labetalol group; the difference between the labetalol and prazosin groups was significant (P less than 0.01) both at rest and during exercise. This haemodynamic profile of labetalol may be important in selecting a vasodilating antihypertensive for patients with concomitant ischaemic heart disease.

Adult

Electrocardiographic abnormalities in aluminium phosphide poisoning with special reference to its incidence, pathogenesis, mortality and histopathology.

Ninety-five patients out of total 190 cases of aluminium phosphide (ALP) poisoning, who exhibited ECG changes were studied for incidence, type and pattern of ECG abnormalities, their effect on mortality and their relationship with histopathology of heart. Its incidence in the present study was 50%. The arrhythmias, conduction disturbances and ischaemic pattern occurred more or less in equal frequency. Certain ECG abnormalities which had not been reported previously ie, early repolarisation syndrome, varied sino-atrial blocks, bradycardia-tachycardia syndrome and electrical alternans were observed in this study. The clinical profile of these cases was similar irrespective of whether patients had ECG abnormalities or not. Shock was the cardinal feature. There was no effect of ECG abnormalities on mortality. The mortality which was otherwise high, depended upon severity of poisoning, dose of poison consumed, duration of shock, failure of response of shock to resuscitative measures and severe hypomagnesaemia. The pathogenesis of ECG abnormalities is still obscure. Hypomagnesaemia was observed in all the 18 cases studied, irrespective of ECG abnormalities. However, these were common when hypomagnesaemia was severe. Hypoxaemia and shock were not the contributory factors for these abnormalities. Autopsy revealed stereotyped histopathological changes of toxic myocarditis independent of ECG findings.

Adolescent

Bioecological factors & rotavirus diarrhoea.

Rotavirus was detected (using Rotalex) in 11.72 per cent (120 of 1024) children below 3 yr age with diarrhoea. None of the 25 healthy control children excreted rotavirus in their faeces. Group specific ELISA for 89 Rotalex positive samples revealed 30 subgroup I and 43 subgroup II whereas 10 were untypable. Rotavirus infection ranged from 2.8 to 22.20 per cent in different months. There was no correlation with mean minimum and maximum temperatures. However, the incidence showed a negative correlation (r = -0.645) with relative humidity. Children between the age of 10 to 12 months had the maximum incidence of rotavirus infection. Male patients were found to be more susceptible to infection than females (3.3:1).

Child, Preschool

Seasonal fluctuations in the occurrence of enteroinvasive Escherichia coli diarrhoea.

Enteroinvasive Esch. coli (EIEC) was implicated in 2.1 per cent (57 out of 2661) diarrhoeal patients investigated at Ludhiana (Punjab). The predominant serogroups isolated were 028, 0147, 0124 and 0112. High prevalence of EIEC infection was noticed among infants (50.6%) followed by children up to 10 yr (19.3%). The peak incidence (24.5%) occurred during the hot and dry month of May as compared to 1.7 per cent in February. The disease incidence was positively correlated with mean minimum temperature and mean maximum temperature. All strains gave Sereny's test positive and were mostly susceptible to cephalothin, gentamicin, nalidixic acid, furazolidine and neomycin.

Adolescent

Identification and antigenic typing of Rickettsia tsutsugamushi in naturally infected chiggers (Acarina: Trombiculidae) by direct immunofluorescence.

Rickettsia tsutsugamushi organisms were detected and typed antigenically by direct immunofluorescence in mites from laboratory-maintained infected colonies of Leptotrombidium (Leptotrombidium) fletcheri and L. (L.) arenicola. Rickettsiae were identified most readily in unengorged larvae, but were also discernable in engorged larvae and all post-larval stages of the vectors.

Antigens

Reconstruction of mammary hypoplasma associated with chest wall deformities.

Three young women who had significant unilateral hypoplasia of the breast, accentuated by marked rib deformities and hypoplasia of the pectoralis muscle, were treated by two-staged reconstructions. A custom-made chest wall implant and a breast prosthesis were used. In the absence of cardiorespiratory compromise, these are simpler operations than rib osteoplasties and the cosmetic result is better.

Adolescent