Biomedical subjects
Publications and source records attributed to A K Goyal.
Wavelength beam combining of five ytterbium fiber lasers is demonstrated in a master-oscillator power-amplifier configuration at combined powers up to 6 W. The combined beam profile has an M2 value of 1.14, which is equal to that of an individual fiber. Beam steering in one dimension over 140 resolvable spots is also demonstrated.
Areflexic quadriplegia due to barium carbonate (rat poison) poisoning is described in two young patients. These cases very closely resembled Guillain-Barre syndrome. The various effects of barium carbonate along with the pathogenesis of hypokalaemic paralysis are highlighted.
Fifty-eight Indian patients with visceral leishmaniasis who did not respond or relapsed after 30 days of consecutive sodium stibogluconate therapy were randomised to treatment with amphotericin B lipid complex (ABLC) using a total dose of 7.5 or 10 mg/kg. Treatment induced a prompt clinical response in all patients with resolution of fever and regression in spleen size. Fever and chills developed during ABLC infusion, but it diminished with successive infusions. Fourteen days after treatment, 26 of 28 (93%) patients in the 7.5 mg/kg group and all 30 (100%) in the 10 mg/kg group had splenic aspirate parasite density scores of 0 and were considered apparent clinical and parasitologic responders. Four and three patients in the 7.5 and 10 mg/kg groups respectively relapsed during six months of followup; thus, overall 22 of 28 (79%) patients treated with 7.5 mg/kg and 27 of 30 (90%) treated with 10 mg/kg were definitive cures. All initial non-responders and relapses were retreated successfully with higher dose of ABLC. These results confirm the efficacy of short-course ABLC therapy for antimony-unresponsive Indian patients with visceral leishmaniasis. Since treatment with a total dose of 7.5 mg/kg did not appear to increase efficacy (79% vs. 84% induced by 5 mg/kg in a prior study), initial treatment with a total dose of 5 mg/kg followed by retreatment of any non-responders represents a potentially less costly approach in patients who fail antimony therapy. Though high cure rates are achieved with > or = 10 mg/kg total dose of ABLC, treatment using lower doses with retreatment of non-responders or relapses with higher dose can result in considerable savings.
BACKGROUND: There is no effective oral treatment for visceral leishmaniasis (kala-azar), a disseminated intracellular protozoal infection that occurs worldwide. Miltefosine, an alkyl phospholipid developed as an oral antineoplastic agent, is active against visceral infection in animal models. We tested safety, tolerance, and efficacy of miltefosine in kala-azar. METHODS: Oral doses of miltefosine were given to six groups of five Indian men for 28 days: 50 mg every second day (group 1), 100 mg every second day (group 2), 100 mg/day (group 3), 150 mg/day (group 4), 200 mg/day (group 5), and 250 mg/day (group 6). Assessment for apparent cure--taken as an afebrile state with decreased spleen size and a splenic-aspirate parasite-density score of 0--was done on days 14 and 28. Definitive cure at 8 months required a parasite-free bone-marrow aspirate and no clinical evidence of relapse. FINDINGS: 21 of 30 patients were apparently cured on day 14. Transient episodes of vomiting and diarrhoea, were common during weeks 1-2 and were seen in 22 patients. Four other patients in groups 5 and 6 had miltefosine withdrawn after 7-10 days because of vomiting. One patient in group 6 developed renal insufficiency and severe diarrhoea and died on day 21. On day 28, all 29 remaining patients were apparently cured. By 8 months, seven of ten patients in groups 1 and 2 had relapsed; however, 18 of 19 patients treated daily (groups 3-6) appeared to be cured. Among the 21 definitive cures were the four patients treated for 10 days or less and 12 for whom previous therapy with pentavalent antimony had failed. INTERPRETATION: Treatment with miltefosine at 100-150 mg/day for 4 weeks has promise as an effective oral treatment of visceral leishmaniasis including antimony-resistant infection.
OBJECTIVE: This study evaluated the usefulness of gadolinium (Gd) chelates in magnetic resonance imaging (MRI) of extracranial pediatric mass lesions. MATERIALS AND METHODS: Seventy-five MRI studies were obtained on 60 children (mean age 5.06 years) with pathologically proven mass lesions. Post-contrast T1-weighted (T1W) images were compared with pre-contrast T1-weighted, T2-weighted (T2W) and both T1W and T2W images. They were evaluated for their ability to demonstrate lesion margins and extent, to add additional information, and to increase confidence in or change a diagnosis. In all patients post-contrast images were also evaluated for degree and pattern of enhancement. RESULTS: Malignant lesions enhanced much more intensely than benign lesions (P<0.0005). Lack of enhancement was seen only in benign lesions. A heterogeneous pattern of enhancement was more frequently seen in malignancy (P<0.05). Additional information was provided on Gd-enhanced T1W images in 36% of cases compared to unenhanced T1 and T2W images. Diagnostic confidence was improved in 29%. The Gd-enhanced images changed the diagnosis correctly in 5% and incorrectly in 1%. CONCLUSION: Post-contrast images clarified specific issues, better defined lesion extent and margins in a majority of cases, and gave additional useful information in selected cases.
High cost is the principal drawback of treating visceral leishmaniasis (VL; kala-azar) with any of the new lipid formulations of amphotericin B. The aim of the present study was to see if the costs of treatment with such drugs could be reduced by using ultra-short courses. Amphotericin-B-lipid complex (ABLC) was given to 77 Indian patients with antimony-unresponsive VL, either as a single infusion of 5 mg/kg (Group A) or two infusions, each of 5 mg/kg, given 5 days apart (Group B) or on consecutive days (Group C). Other than the anticipated higher fever and chills, treatment was well-tolerated. On day 19 after first infusion, 72 patients were considered apparent cures: 24 (89%) of the 27 in Group A; all 24 (100%) in Group B; and 24 (92%) of the 26 patients in Group C. Six months after treatment, 19 (70%) of 27 in Group A, 19 (79%) of 24 in Group B, and 21 (81%) of 26 in Group C were healthy, relapse-free and considered definitive cures. These cure rates were not statistically different. All 18 treatment failures (five initial non-responders and 13 relapses) were cured after treatment with a 5-day course of ABLC at a higher dose (10-15 mg/kg.day). In a related analysis of hospital plus drug costs for treating antimony-unresponsive VL, short-course ABLC (1-5 days) was compared with conventional amphotericin B (0.75-1.0 mg/kg on alternate days over 30-34 days). This analysis, which included the cost of re-treatment, identified one short-course ABLC regimen with an overall estimated expense which was only modestly higher than that of amphotericin B. Together, the present results provide further support for the use of ABLC in the management of VL patients who fail antimony therapy.
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The ggh-A gene, encoding a 1,4-beta-D-glucan glucohydrolase/beta-glucosidase, of Microbispora bispora (Mb) was subcloned and expressed from a 4.0-kb XhoI DNA fragment. The nucleotide sequence of this fragment was determined. Analysis of the sequence revealed one open reading frame (ORF) which encodes a 986-amino-acid (aa) protein with a calculated molecular weight of 107,510. The ggh-A ORF has features typical of an actinomycete gene including high GC content (70.5%) and corresponding biased codon usage. Comparison of the aa sequence of the Mb 1,4-beta-D-glucan glucohydrolase (Mbggh-A) with other glycosidases reveals high overall homology to several beta-glucosidases and a 1,4-beta-D-glucan glucohydrolase belonging to the glycosyl hydrolase family 3. The aa sequence alignments of Mbggh-A and beta-glucosidases show that the active site region potentially involves two Asp residues. The aa sequence homology studies revealed a potential two-domain structure for Mbggh-A and other beta-glucosidases. Furthermore, Mbggh-A has localized homology to a cellulose-binding domain present in some xylanases. This report is significant, as, to date, 1,4-beta-D-glucan glucohydrolases have rarely been reported, though they are assumed to have a critical role in cellulolysis.
Three strains of Comamonas testosteroni were isolated from river sediment for the ability to degrade phenanthrene; two of the strains also grew on naphthalene, and one strain also grew on anthracene. The homology of the genes for polycyclic aromatic hydrocarbon degradation in these strains to the classical genes (nah) for naphthalene degradation from Pseudomonas putida NCIB 9816-4 was determined. The three C. testosteroni strains showed no homology to the nah gene probe even under low-stringency conditions. The genes for naphthalene and phenanthrene degradation were cloned from one of the three C. testosteroni strains. Two cosmid clones expressing polycyclic aromatic hydrocarbon dioxygenase activity were identified from a library prepared with genomic DNA from C. testosteroni GZ39. The genes coding for the first two enzymes in the catabolic pathway, phenanthrene dioxygenase and cis-phenanthrene dihydrodiol dehydrogenase, were localized to a 5.4-kb NcoI-PstI fragment by subcloning and gene expression experiments. Further subcloning and analysis revealed a novel organization of the genes, with the gene for cis-phenanthrene dihydrodiol dehydrogenase located between the genes for the individual phenanthrene dioxygenase components. A Southern blot with the cloned genes from C. testosteroni GZ39 confirmed that these genes are distinct from those found in P. putida NCIB 9816-4. Southern blots also demonstrated that C. testosteroni GZ38A possesses genes for phenanthrene degradation that are similar to those cloned from C. testosteroni GZ39. However, C. testosteroni GZ42 possesses genes for phenanthrene degradation that are not homologous to those cloned from C. testosteroni GZ39. This suggests that there are at least two different sets of genes for the degradation of phenanthrene among the three C. testosteroni strains.
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Genomic DNA fragments encoding beta-glucosidase activities of the thermophilic actinomycete Microbispora bispora were cloned into Escherichia coli. Transformants expressing beta-glucosidase activity were selected by their ability to hydrolyze the fluorogenic substrate 4-methylumbelliferyl-beta-D-glucoside. Two genes encoding beta-glucosidase activity were isolated and distinguished by restriction analysis, Southern hybridization, and the substrate specificities of the encoded enzymes. One gene, bglB, encoded a beta-glucosidase that was expressed intracellularly in E. coli. It exhibited a molecular mass of approximately 52,000 Da by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE) and 51,280 Da by nondenaturing gradient PAGE, a pI of 4.6, and temperature and pH optima of 60 degrees C and 6.2, respectively. Cloned BglB showed greater activity against cellobiose than against aryl-beta-D-glucosides and was thermostable, retaining about 70% of its activity after 48 h at 60 degrees C. BglB activity is activated two- to threefold in the presence of 2 to 5% (0.1 to 0.3 M) glucose. The DNA sequence of the 2.2-kb insert carrying bglB has been determined. An open reading frame which codes for a protein of 473 amino acids with a predicted molecular mass of 52,227 Da showed significant homology (40 to 47% identity) with beta-glucosidases from glycosal hydrolase family 1.
Hepatic echo patterns and "right lobe to left lobe longitudinal diameter ratio" were compared in age- and sex-matched 100 normal subjects and 76 patients with diffuse liver diseases (38 cirrhotics and 38 noncirrhotics) in a prospective sonographic study. Various echo patterns, assigned to cirrhotic livers (bright liver, micronodulation, beam attenuation), could not differentiate cirrhosis from other diffuse liver diseases. In cirrhotic livers, the right lobe manifested a significant shrinkage, while the left lobe exhibited almost no alteration. Considering the right to left lobe ratio of 1.30 as a discriminatory value, the cirrhosis could be diagnosed with a sensitivity of 74%, a specificity of 100%, and an accuracy of 93%; the sensitivity rates were seen to be higher in postnecrotic cirrhosis than in alcoholic cirrhosis.
In a prospective ultrasound study, the various factors possibly influencing the portal vasculature were evaluated in normal subjects; the correlation of portal diameters with physical factors such as age, sex, and body texture was poor, whereas the caliber variation was significant with respiration, posture, and meal. Considering the fasting state, supine decubitus, and deep inspiration as suitable and standard variables, the diameters were compared in 100 healthy subjects and 50 patients with portal hypertension. The upper normal limits of portal, splenic, and superior mesenteric vein diameters were reported as 16, 12, and 11 mm, respectively, and the dimensions above these values provided an overall sensitivity of 72%, an accuracy of 91%, and a specificity of 100% in diagnosing the patients with suspected portal hypertension.
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A prospective sonographic study was undertaken in age- and sex-matched normal subjects and patients with portal hypertension to evaluate the effects of a meal on the portal venous system. Postprandial increase in portal vessel diameters was proved to be statistically significant in normal individuals, with mean variations of 27.9% (16-60%), 46.5% (25-83%), and 45.2% (20-75%), respectively, for portal, splenic, and superior mesenteric veins. In contrast, this effect was insignificant in the hypertensive portal venous system. A diminished meal-related caliber variation in portal, splenic, and mesenteric veins less than 16%, 25%, and 20%, respectively, could be diagnostic of portal hypertension.
Early fibre-optic oesophago-gastroduodenoscopy was performed in 23 portal hypertensive patients with acute upper gastrointestinal haemorrhage to evaluate the source of bleeding. Oesophageal varices grade II or more were documented in all patients. None of the patients showed a source of bleeding other than the ruptured oesophageal varices, probably because, unlike western countries, the alcoholic cirrhosis as a source of portal hypertension is rather uncommon in India. Hence, we could presume that most of the emergency endoscopies are unnecessary in bleeding patients with portal hypertension.