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Biomedical subjects

N Verma

Publications and source records attributed to N Verma.

At least 19 recordsLinked to original sources
PubMed1997

Profile of ocular trauma in Papua New Guinea.

BACKGROUND: Ocular trauma is a significant cause of blindness in Papua New Guinea (PNG). This study was done to determine the pattern and rates of ocular and adnexal injuries so as to determine the size and extent of the problem. METHODS: A retrospective study of 4157 cases presenting with ocular trauma in three regions of PNG was carried out. The data were analysed with respect to the age, sex, province, type and cause of injury, time interval between injury and presentation to the hospital and the final visual outcome after treatment. RESULTS: Ocular trauma rates in PNG were alarmingly high (39.1 per 100,000). The commonest cause of injury in the younger age group was due to lime. Alcohol-related violence and fights resulted in injuries in the adult age group. Most of the injuries were grievous and 60.7% of patients were left with a visual acuity of less than 6/60 in the injured eye. In addition, 78.7% of the patients were under 30 years of age. CONCLUSIONS: Ocular injuries in PNG are an important cause of visual disability. Some specific injuries, such as those due to lime in children, can easily be prevented by health education.

Adolescent↗
PubMed1996

Trabeculectomy and manual clot evacuation in traumatic hyphaema with corneal blood staining.

BACKGROUND: The management of traumatic hyphaema with raised intraocular pressure and corneal blood staining is difficult. Residual blood clots after anterior chamber washout are responsible for sustained postoperative elevation of intraocular pressure, even after trabeculectomy and clot evacuation. METHODS: Thirty-five patients with traumatic hyphaema, elevated intraocular pressure and varying degrees of corneal blood staining underwent a combined trabeculectomy with manual clot evacuation from the anterior chamber in a general hospital. RESULTS: The postoperative control of intraocular pressure was found to be adequate in all patients at the end of two months. Examination of the posterior segment was made possible earlier. Although the procedure is more complex, no significant complications were encountered. CONCLUSION: In patients presenting with traumatic hyphaema, secondary glaucoma and corneal blood staining, trabeculectomy with manual extraction of the clot through a large incision appears to be a safe and reliable procedure where medical therapy fails to control the intraocular pressure.

Adolescent↗
PubMed1996

Prognostic markers in amebic liver abscess: a prospective study.

OBJECTIVES: Amebic liver abscess (ALA) is being increasingly recognized with the progressive spread of AIDS. The prognosis of ALA needs to be determined to decide whether aggressive intervention therapy should be used. A prospective study was conducted to determine the factors that predicted mortality in patients with ALA. METHODS: The study population consisted of 135 consecutive patients with ALA who were treated with 80 mg/kg/day of metronidazole for 10 days if they survived. Needle aspiration or open surgical drainage was performed in patients who deteriorated despite drug therapy or had an abscess that clinically appeared to be at risk of impending rupture. Survivors and nonsurvivors were compared by univariate and multivariate analysis to identify predictors of outcome. These predictors were then prospectively evaluated in a subsequent cohort of patients with ALA. RESULTS: Twenty-four patients died during the acute phase. Significant differences between survivors and nonsurvivors were observed. A stepwise logistic regression suggested that a bilirubin level >3.5 mg/dl, encephalopathy, volume of abscess cavity, hypoalbuminemia (serum albumin level <2.0 g/dl), and the number of abscesses were independent risk factors for mortality. The duration of symptoms and type of treatment did not influence mortality. The regression equation derived was then applied prospectively to 64 subsequent patients with ALA, and the validity of the prediction rule was confirmed. The qualities of simplicity, availability, low cost of derivation, and good discriminating power suggest that this index would be useful in assessing prognosis in patients with ALA.

Adult↗
PubMed1995

Sensitive high-performance liquid chromatographic assay method for the determination of guggulsterone in serum.

Guggulsterone (I) is a new hypolipidemic agent, being developed at CDRI (Lucknow, India). A sensitive high-performance liquid chromatographic assay in serum has been developed and validated for the determination of guggulsterone in serum for pharmacokinetic studies. This assay method consists of extraction of the drug with hexane from spiked human serum samples. Separation was achieved using C18 reversed-phase column coupled with photodiode array detector, and an acetonitrile-water mixture as mobile phase. The method described herein is simple and has limit of quantitation of 10 ng/ml as compared to 200 ng/ml by the previous reported method. The standard curve was linear over the range of 10-1000 ng/ml in mobile phase as well as in normal human serum. Analytical recovery of I added to serum was > 90%. The reproducibility was determined by the inter- and intra-assay variations which were < 10%.

Administration, Oral↗
PubMed1995

Pharmacokinetic evaluation of percutaneous hepatic venous isolation for administration of regional chemotherapy.

Hepatic artery infusion (HAI) chemotherapy has been used to treat patients with unresectable liver tumours. We report a preclinical study of the pharmacokinetics of HAI combined with hepatic venous drug extraction (HVDE) for regional administration of doxorubicin. HVDE was aided by a double balloon catheter inserted via femoral vein cutdown into the inferior vena cava to collect all hepatic vein blood. Pigs received doxorubicin 0.5-9.0 mg kg-1 over 90 min via HAI or systemic infusion (SYSI). HVDE was performed for 240 min. SYSI pigs underwent hepatic venous isolation without drug filtration. Doxorubicin levels were assayed using high-pressure liquid chromatography (HPLC). HAI/HVDE reduced systemic exposure to doxorubicin with equivalent hepatic exposure at all doses. Pharmacokinetic enhancement ranged from 7.0 to 22.3 for peak concentration, 8.8-23.2 for the area under the curve and 2.9-4.2 for tissue concentration. HAI/HVDE also prevented the mortality which was observed with SYSI administration of high-dose (5.0 and 9.0 mg kg-1) doxorubicin. We conclude that HAI/HVDE reduces systemic exposure to doxorubicin as compared with SYSI of equivalent doses. Pharmacokinetic enhancement indices suggest that HAI/HVDE may allow equivalent hepatic drug exposure with reduced systemic exposure. This method may be applicable to other drugs and to other anatomic settings in which enhanced regional drug delivery is desirable.

Animals↗
PubMed1995

An evaluation of hepatic extraction and clearance of doxorubicin.

A swine model was developed to study quantitatively the pharmacokinetics of hepatic extraction and clearance of doxorubicin (DOX). Systemic and hepatic artery infusions of DOX (0.5-9 mg kg-1) were administered to 34 pigs. Pharmacokinetic analysis was simplified by use of a double-balloon catheter in the inferior vena cava to collect hepatic venous effluent. During hepatic artery infusion only, DOX in hepatic venous blood was extracted using activated carbon filters to prevent drug recirculation. Hepatic extraction and clearance of DOX were independent of dose and route of administration. Extraction ratios varied from 0.75 to 0.91 during hepatic artery infusion and from 0.50 to 0.72 during systemic infusion. Clearance results were analogous. After cessation of drug infusions, hepatic extraction and clearance of DOX was negative, suggesting that the liver serves as a drug reservoir during DOX infusion and subsequently is a net source of unmetabolised drug. Liver extraction and clearance of DOX in pigs are substantial. During either systemic or hepatic artery infusion of DOX, the liver serves as a drug reservoir. Subsequent mobilisation of this hepatic pool of DOX may cause prolonged systemic exposure to drug.

Animals↗
PubMed1995

Characterisation and starvation induced regulation of methionine uptake sites in mouse mammary gland.

The sites of methionine uptake by 10 day lactating mouse mammary gland were determined in vitro. Four modes of methionine entry characterised were: (i) A sodium-dependent, N-(methylamino) isobutyric acid (MeAIB)--sensitive system with a Vmax of 18.8 nmol/g cells/min (this mode of entry was similar to the A site in other tissues); (ii) A sodium-dependent, MeAIB--insensitive uptake system with a Vmax of 12.4 nmol/g cells/min); this mode of entry was inhibited by substrates preferred by ASC system); (iii) A sodium-independent, 2-amino-bicyclo heptane 2-carboxylic acid (BCH)-sensitive system L with a Vmax of 30 nmol/g cells/min; and (iv) A sodium-independent entry which was not inhibited by high concentrations of MeAIB or BCH. The Km value of each of the former three carrier mediated transport systems was 0.46 mM. Starvation of animals brought about important increase in the Vmax of the A system by 97% and that of ASC system by 1003% which was accompanied by similar increases in the Km values of these systems. These results show an adaptive regulation of these two sodium-dependent sites as a result of starvation.

Animals↗
PubMed1994

Hepatic artery infusion of doxorubicin with hepatic venous drug extraction.

Hepatic artery infusion (HAI) has been used to take advantage of the steep dose-response relationship characteristic of chemotherapeutic agents. Systemic toxicity, however, remains the dose limiting factor for HAI of low hepatic extraction drugs. This investigation compared the pharmacokinetics of doxorubicin administered using a system that combines HAI and hepatic venous drug extraction (HVDE) versus systemic administration without HVDE. HAI was accomplished by transfemoral cannulation of the hepatic artery. HVDE was aided by use of a double-balloon catheter inserted fluoroscopically via femoral vein cutdown into the inferior vena cava. Inflation of the balloons above and below the hepatic veins allowed collection of hepatic venous effluent. Hepatic venous blood was pumped through the double-balloon catheter into an extracorporeal circuit with activated carbon filters to extract drug prior to return to the systemic circulation. Domestic female swine (25-35 kg) received 3 mg/kg doxorubicin over 90 min via HAI. HVDE was performed for 240 min following initiation of HAI (Time 0-240 min). Control swine underwent hepatic venous isolation using the double-balloon catheter without drug filtration and received 3 mg/kg doxorubicin over 90 min via systemic vein (SYSI). Serum and myocardial doxorubicin and doxorubicinol levels were assayed using HPLC. Blood was serially sampled from hepatic vein blood, from the extracorporeal circuit after filtration, and from a systemic artery. Area under the curve (AUC) was integrated from time-concentration plots over Time 0-180 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

AroD deletion attenuates Shigella flexneri strain 2457T and makes it a safe and efficacious oral vaccine in monkeys.

The aromatic-dependent live Shigella flexneri 2a vaccine strain SFL1070, with a deleted aroD gene, had a much reduced intracellular growth in HeLa cells compared with its parent strain S. flexneri 2457T. S. flexneri SFL1070 gave no adverse effects in eight Macaca fascicularis monkeys orally vaccinated with four doses of 1 x 10(11) live bacteria within a 5-week period, whereas S. flexneri 2457T caused dysentery in all eight non-vaccinated monkeys. Thus the aromatic dependency rendered S. flexneri SFL1070 significantly attenuated (p = 0.00008). Significant intestinal S. flexneri lipopolysaccharide (LPS)-specific sIgA responses were seen in seven of eight vaccinated monkeys (p < 0.01) after four doses with SFL1070. However, serum IgG or IgA responses to various S. flexneri LPS antigens and the invasion plasmid antigens (Ipa-s) were seen in only four of eight vaccinated monkeys. The serum IgG titre increases against S. flexneri Y and 2a LPS reached significant levels (p < or = 0.05). All but one of the vaccinated monkeys were protected against oral challenge with 1 x 10(10) or 1 x 10(11) live S. flexneri 2457T given 2 weeks after the last vaccination. The protection was highly significant (p = 0.0007) as all non-vaccinated monkeys challenged with equal doses of strain 2457T developed dysentery. Three of them succumbed. Challenge infection of vaccinated monkeys elicited serum IgA and IgG responses to the homologous S. flexneri 2a LPS in three monkeys each (0.005 < or = p < or = 0.025). Serum IgA and IgG responses to the Ipa-s were seen in five and four monkeys each (0.01 < p < or = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Characterisation of the routes of methionine transport in mouse mammary glands.

The sites of methionine uptake by mammary glands from late pregnant and lactating mice were studied in vitro. Using the specific A system inhibitor, N-(methylamino) isobutyric acid (MeAIB) and the specific L system inhibitor, 2-amino-bicyclo (2.2.1) heptane 2-carboxylic acid (BCH), we have defined four modes of methionine entry into these tissues. (i) A sodium-dependent A system with a Vmax of 13.4 and 18.8 n mol/g cells/min in pregnant and lactating mice, respectively. This mode of entry was completely inhibited by MeAIB and its Km value was similar (0.45 mM) in both groups. (ii) A sodium-dependent mode with a Vmax of 6.7 and 12.4 n mol/g cells/min and a Km of 0.24 and 0.46 mM in pregnant and lactating mice, respectively. This mode of entry was insensitive to inhibition by MeAIB, and was similar to the ASC (alanine, serine, cysteine) system in other tissues. (iii) A sodium-independent L system with a Vmax of 13.8 and 30.0 n mol/g cells/min and a Km of 0.27 and 0.46 mM in pregnant and lactating mice, respectively. This mode of entry was completely inhibited by BCH. (iv) A sodium-independent non-specific entry amounting to 25 per cent of the total entry at 0.1 mM external methionine which was not inhibited by high concentration of BCH. The results of our studies show an increase in the number of active carriers of the A, ASC and L systems of methionine uptake in mammary glands of mouse during lactation.

Amino Acids↗
PubMed1992

Enzymatic synthesis and isolation of thymidine diphosphate-6-deoxy-D-xylo-4-hexulose and thymidine diphosphate-L-rhamnose. Production using cloned gene products and separation by HPLC.

A two-step enzymatic synthesis of dTDP-L-rhamnose is developed using enzymes from sonicated extracts of cultures of Escherichia coli K12 strains harboring plasmids containing different parts of the rfb gene cluster of Salmonella enterica LT2. The intermediate dTDP-6-deoxy-D-xylo-4-hexulose was isolated after a 1-h reaction, using only dTDP-D-glucose and dTDP-D-glucose 4,6-dehydratase, followed by protein precipitation and desalting by gel chromatography (yield 89%). In a two-step reaction using dTDP-D-glucose and dTDP-D-glucose 4,6-dehydratase in the first step, and with NADPH, dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase and NADPH:dTDP-6-deoxy-L-lyxo-4-hexulose-4-reductase in the second hour of incubation, the dTDP-D-glucose was fully converted to dTDP-L-rhamnose. The hexoses of both products were identified by mass spectroscopy. The molar yield of dTDP-L-rhamnose, after protein precipitation, anion-exchange chromatography and desalting by gel chromatography, was 62%, corresponding to more than 150 mg, starting from 250 mg of dTDP-D-glucose. When stored lyophilysed under nitrogen, these products were found to be stable for several months. Both dTDP-6-deoxy-D-xylo-4-hexulose and dTDP-L-rhamnose have light absorption maxima at 267 nm, with molar absorption coefficients close to that of dTMP. However, the absorption coefficient of dTDP-6-deoxy-D-xylo-4-hexulose at the absorption maximum of 320 nm (specific for sugars containing keto groups) was found to be approximately 20% higher than values presented earlier. Furthermore, an HPLC technique is presented for determining the net activity of dTDP-6-deoxy-D-xylo-4-hexulose 3,5-epimerase and NADPH:dTDP-6-deoxy-L-lyxo-4-hexulose-4-reductase, based on separation of dTDP-6-deoxy-D-xylo-4-hexulose and dTDP-L-rhamnose. The HPLC technique is also suitable for determination of all the nucleotide components involved in the synthesis.

Bacterial Proteins↗
PubMed1992

Induction of a humoral immune response to a Shiga toxin B subunit epitope expressed as a chimeric LamB protein in a Shigella flexneri live vaccine strain.

Shigella flexneri vaccine strain (SFL124) given orally, evokes humoral immune response in human volunteers. Such a strain, expressing antigenic epitope of B subunit of Shiga toxin, would also provide immunity to the toxin produced by some species of Shigella. A synthetic oligonucleotide, specifying an epitope [13-26 amino acids (aa)] of the B subunit of Shiga toxin, was inserted into the lamB gene of Escherichia coli and expressed in the S. flexneri vaccine strain. The chimeric LamB protein functioned normally and the epitope was expressed at the surface of the bacteria. The animals immunized with the live bacteria, expressing the epitope or sonicated lysates, showed a humoral response that was specific to the peptide (13-26 aa) and to the whole B subunit molecule. The elicited antisera neutralized the toxin activity on HeLa cells up to 40%, while the purified IgG fractions from the sera gave 90% neutralization.

Amino Acid Sequence↗
PubMed1990

Clinical profile of multiple amoebic liver abscesses.

Of 70 consecutive patients with amoebic liver abscess admitted over a 3 year period, 15 (21.4%) had multiple abscesses. This condition, like solitary abscess, was a disease of the 2nd to 5th decade with a male preponderance. Multiple abscesses were more frequently associated with fever, jaundice, upper abdominal pain, pneumonitis and tender hepatomegaly. The left lobe of the liver was always enlarged in patients with multiple abscesses and 86% of patients required drainage of an abscess cavity. The presence of more severe clinical course, jaundice and left lobe hepatomegaly should raise the suspicion of multiple abscesses. After confirmation of the diagnosis by imaging technique, the abscess cavity should be aspirated for quick relief and cure.

Adolescent↗
PubMed1989

Identification and sequence of rfbS and rfbE, which determine antigenic specificity of group A and group D salmonellae.

Salmonella group A, group B, and group D strains have paratose, abequose, and tyvelose, respectively, as the immunodominant sugar in their O antigens, which are otherwise identical; only the final steps differ in the biosynthetic pathways of these sugars. The gene rfbJ from a group B strain, encoding abequose synthase, the final and only unique step in the biosynthesis of CDP-abequose, has been cloned and sequenced (P. Wyk and P. Reeves, J. Bacteriol. 171:5687-5693, 1989). In this study, we locate and sequence rfbS and rfbE from serovars typhi and paratyphi, representative of groups A and D. Gene rfbS is present in both groups and encodes paratose synthase, which carries out a step parallel to that of abequose synthase, but the product is CDP-paratose. The DNA and inferred amino acid sequences are compared with those of rfbJ. We conclude that the genes are homologous, but the divergence is extremely ancient. Gene rfbE encodes CDP-tyvelose epimerase, which converts CDP-paratose to CDP-tyvelose in group D strains; the gene is active in group D strains, and we find it to be present in a mutant form in group A strains. These two genes encode the steps unique to groups A and D and, like rfbJ of group B, are of low G+C content, suggesting transfer from outside of salmonellae. The evolutionary origin of these genes is discussed.

Amino Acid Sequence↗