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Biomedical subjects

L Das

Publications and source records attributed to L Das.

At least 19 recordsLinked to original sources

Role of cognitive function in assessing informed consent for endoscopy.

BACKGROUND: Patient understanding of the consent process is often suboptimal and the reasons for this are poorly understood. In particular the role of cognitive function in assessing the level of understanding of consent has not been evaluated. AIMS: This study aims to assess the level of patient understanding of the informed consent process and the role of cognitive function in those with low levels of understanding. METHODS: The study was prospective, interviewing patients immediately after they had given consent but before undergoing their procedure. Understanding of the reason for the procedure, the risks attendant upon it, details of the procedure itself and post procedure care was scored with the total representing overall level of understanding. A mini mental state examination (MMSE) was then performed with the score recorded. RESULTS: 100 patients were interviewed. A low level of understanding was shown in 36%. Ninety two patients had a MMSE score greater than 24. All patients with a high level of understanding had MMSE scores greater then 24 compared with 78% of those with a low level of understanding. All patients (n = 8) who displayed a MMSE score less than 24 had a low level of understanding. Men displayed poorer levels of understanding than women. A subnormal MMSE only identified 22% of those with low levels of understanding. CONCLUSIONS: Understanding of the consent process is suboptimal. Adequate cognitive function does not predict a high level of understanding of the informed consent process while cognitive impairment precludes it. It is evident, however that factors other than cognitive dysfunction are at play when attempting to explain low levels of understanding.

Adult↗

Successful therapy of lethal murine visceral leishmaniasis with cystatin involves up-regulation of nitric oxide and a favorable T cell response.

The virulence of Leishmania donovani in mammals depends at least in part on cysteine proteases because they play a key role in CD4(+) T cell differentiation. A 6-fold increase in NO production was observed with 0.5 microM chicken cystatin, a natural cysteine protease inhibitor, in IFN-gamma-activated macrophages. In a 45-day BALB/c mouse model of visceral leishmaniasis, complete elimination of spleen parasite burden was achieved by cystatin in synergistic activation with a suboptimal dose of IFN-gamma. In contrast to the case with promastigotes, cystatin and IFN-gamma inhibited the growth of amastigotes in macrophages. Although in vitro cystatin treatment of macrophages did not induce any NO generation, significantly enhanced amounts of NO were generated by macrophages of cystatin-treated animals. Their splenocytes secreted soluble factors required for the induction of NO biosynthesis, and the increased NO production was paralleled by a concomitant increase in antileishmanial activity. Moreover, splenocyte supernatants treated with anti-IFN-gamma or anti-TNF-alpha Abs suppressed inducible NO generation, whereas i.v. administration of these anticytokine Abs along with combined therapy reversed protection against infection. mRNA expression and flow cytometric analysis of infected spleen cells suggested that cystatin and IFN-gamma treatment, in addition to greatly reducing parasite numbers, resulted in reduced levels of IL-4 but increased levels of IL-12 and inducible NO synthase. Not only was this treatment curative when administered 15 days postinfection, but it also imparted resistance to reinfection. These studies provide a promising alternative for protection against leishmaniasis with a switch of CD4(+) differentiation from Th2 to Th1, indicative of long-term resistance.

Animals↗

Role of ureogenesis in the mud-dwelled Singhi catfish (Heteropneustes fossilis) under condition of water shortage.

The air-breathing Singhi catfish Heteropneustes fossilis was kept inside moist peat for 1 month mimicking their normal habitat in summer and the role of ureogenesis for their survival in a water-restricted condition was studied. The ammonia excretion rate by the mud-dwelled fish increased transiently between 6 and 12 h of re-immersion in water to approximately between eight and 10-fold, followed by a sharp decrease almost to the normal level at the later part of re-immersion. The urea-N excretion by the mud-dwelled fish increased to approximately 11-fold within 0-3 h of re-immersion, followed by a gradual decrease from 9 h onwards. The rate of urea-N excretion by the mud-dwelled fish, however, remained significantly higher (approx. threefold more) than the control fish even after 36-48 h of re-immersion. Although there was a significant increase of both ammonia and urea levels in the plasma and other tissues (except ammonia in the brain), the level of accumulation of urea was higher than ammonia in the mud-dwelled fish as indicated by the decrease in the ratio of ammonia: urea level in different tissues including the plasma. The activities (units/g tissue and /mg protein) of glutamine synthetase and three enzymes of the urea cycle, carbamyl phosphate synthetase, argininosuccinate synthetase and argininosuccinate lyase increased significantly in most of the tissues (except the brain) of the mud-dwelled fish as compared to the control fish. Higher accumulation of ammonia in vivo in the mud-dwelled Singhi catfish is suggested to be one of the major factors contributing to stimulation of ureogenesis. Due to this physiological adaptive strategy of ureogenesis, possibly along with other physiological adaptation(s), this air-breathing amphibious Singhi catfish is able to survive inside the moist peat for months in a water-restricted condition.

Ammonia↗

Biodegradation of pentachlorophenol (PCP) by white rot fungal strains screened from local sources and its estimation by high-performance liquid chromatography.

White rot fungal strains screened from local sources (wood trunks and from effluents of pulp and paper industry) were tested for their ability to biodegrade polymeric compounds, viz. polymeric dyes (crystal violet and brilliant green) and chlorinated phenol (pentachlorophenol). Two of the most promising strains showing maximum degradation of polymeric dyes were selected to study the biodegradation potential and pattern of biodegradation of pentachlorophenol (PCP), a commonly used leather preservative and a potential carcinogen. PCP was quantitatively estimated and analysed by high-performance liquid chromatography (HPLC). Conditions were optimized for the measurement of PCP on HPLC, which were: mobile phase, 60% acetonitrile and 40% water; flow rate, 1 mL/ min; column, mu Bondapack C18 RP and UV detector at 238 nm. One of the white rot fungal strains isolated from wood trunk showed a maximum 68% biodegradation of PCP in liquid-buffered medium in 16 days. The biodegradation pattern of PCP followed a pseudo-first-order kinetics. Studies on enhancement of biodegradation of polymeric dyes and PCP showed that the kinetics of biodegradation is greatly improved by the presence of manganese ions, H2O2 and glucose in the medium. This strongly suggests the involvement of peroxidase enzyme machinery of white rot fungus in the biodegradation process of PCP.

Biodegradation, Environmental↗

Synergistic effect of interferon-gamma and mannosylated liposome-incorporated doxorubicin in the therapy of experimental visceral leishmaniasis.

Active targeting of doxorubicin to macrophages was studied by incorporating it in mannose-coated liposomes by use of visceral leishmaniasis in BALB/c mice as the model macrophage disease. Mannosylated liposomal doxorubicin was more effective than liposomal doxorubicin or free doxorubicin. Because leishmaniasis is accompanied by immunosuppression, immunostimulation by interferon (IFN)-gamma was evaluated to act synergistically with mannosylated liposomal doxorubicin therapy. Combination chemotherapy with a suboptimal dose of IFN-gamma resulted in possibly complete elimination of spleen parasite burden. Analysis of mRNA levels of infected spleen cells suggested that targeted drug treatment together with IFN-gamma, in addition to greatly reducing parasite numbers, resulted in reduced levels of interleukin (IL)-4 but increased levels of IL-12 and inducible nitric oxide synthase. Such combination chemotherapy may provide a promising alternative for the cure of leishmaniasis, with a plausible conversion of antiparasitic T cell response from a Th2 to Th1 pattern indicative of long-term resistance.

Animals↗

Family coping with pediatric leukemia: ten years after treatment.

As part of a longitudinal study of family coping with pediatric leukemia, 28 former patients (16 male; 12 female; M age = 19.1 years) and their parents (23 mothers; 12 fathers) participated in a follow-up study at 10 years posttreatment. Measures included the Current Adjustment Rating Scale, the Brief Symptom Inventory, the Ways of Coping Scale, the Family Coping Scale, and a semistructured interview. Long-term survivors and their parents continued to be well-adjusted to life posttreatment. Coping and perceived adjustment in long-term survivors were positively related to socioeconomic status and mother's coping and negatively related to academic problems. A strong bidirectional relationship was found between survivors' and mother's adjustment. Coping strategies were variable and not significantly correlated with coping adequacy or adjustment.

Adaptation, Psychological↗

Site-selected transposon mutagenesis at the hcf106 locus in maize.

The High chlorophyll fluorescence106 (Hcf106) gene in maize is required for chloroplast membrane biogenesis, and the hcf106-mum1 allele is caused by the insertion of a Robertson's Mutator Mu1 element into the promoter of the gene. Seedlings homozygous for hcf106-mum1 are pale green and die 3 weeks after germination, but only in the presence of Mutator activity conferred by active, autonomous Mu regulatory transposons elsewhere in the genome. When Mutator activity is lost, the mutant phenotype is suppressed, and homozygous plants have an almost wild-type phenotype. To isolate derivative alleles at the hcf106 locus that no longer require Mutator activity for phenotypic expression, we have developed a method for site-selected transposon mutagenesis in maize. This procedure, first described for Caenorhabditis elegans and Drosophila, involves using polymerase chain reaction (PCR) to screen pools of individuals for insertions and deletions in genes of known sequence. Pools of seedlings segregating for the progenitor allele hcf106-mum1 were screened by PCR for insertions and deletions associated with Robertson's Mutator. In a 360-bp target region, two new insertions and one deletion were identified in only 700 Mu-active gametes screened. One of the insertions was in the progenitor hcf106-mum1 allele and the other was in the wild-type allele, but all three new alleles were found to have break-points at the same nucleotide in the first intron. Unlike the hcf-106-mum1 progenitor allele, the deletion and one of the insertions conferred pale green seedling lethal phenotypes in the absence of mutator activity. However, the second insertion had a weak, viable phenotype under these conditions.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

Chromosomal aberrations in mouse lymphocytes exposed in vitro and in vivo to benzidine and 5 related aromatic amines.

Mouse lymphocytes were exposed in vitro for 2 h or in vivo for 24 h to benzidine and related aromatic amines to test for chromosome aberrations (CA) and mitotic indices. Uninduced mouse S9 was used to activate the amines for the in vitro tests to be consistent with the in vivo tests. Contrary to a previous report, no difference could be established in the genotoxicity of benzidine following activation with uninduced S9 compared to induced S9. There were concentration related increases in CA for benzidine and all the amines in vitro except for 4,4'-diaminostilbene which exhibited the greatest cellular toxicity towards cultured lymphocytes. Benzidine and its derivatives showed significant increases in CA in vivo compared to its negative control. The CA values for 4-aminostilbene were significantly higher than the other amines in both in vivo and in vitro studies. These genotoxicity results for 4-aminostilbene are consistent with our previous report of the pronounced CA effects in murine bone-marrow cells but would not be predicted from Salmonella mutagenicity tests.

Aminobiphenyl Compounds↗

Carboplatin-induced regression of an optic pathway tumor in a child with neurofibromatosis.

Optic pathway tumors are common in children with neurofibromatosis-1 (NF-1). The optimal management of these tumors is unknown, particularly when the optic chiasm and other brain structures are involved. We report the dramatic response to carboplatin in a 10-year-old girl with NF-1 and a progressive optic pathway tumor. Tumor shrinkage was accompanied by striking improvement in visual fields, return of color discrimination, and marked improvement in visual acuity. No significant toxicity was observed. One year following completion of chemotherapy the glioma remains as small or smaller than it was at the conclusion of therapy, and there has been no deterioration of vision. Carboplatin is a promising agent for the treatment of optic pathway tumors in children with NF-1.

Carboplatin↗

Chromosomal aberrations in mouse lymphocytes exposed in vivo and in vitro to aliphatic epoxides.

Mouse lymphocytes in vivo or in vitro were exposed for 24 h to 4 aliphatic epoxides, glycidyl 1-naphthyl ether, glycidyl 4-nitrophenyl ether, 1-naphthyl-propylene oxide and trichloropropylene oxide (TCPO), and tested for the induction of chromosomal aberrations (CA). These epoxides were among the most genotoxic aliphatic epoxides in our previous studies. With the exception of TCPO, the test epoxides caused significant increases in CA in vivo compared to a negative control. There were concentration related increases in CA for all 4 epoxides in vitro and TCPO produced the greatest cellular toxicity and genotoxic effects towards cultured lymphocytes. The difference in the order of genotoxicity for the two test systems can be explained on the basis of a much shorter half-life for TCPO than for the other epoxides.

Alkylating Agents↗

Bone metastases of medulloblastoma in childhood; correlation with flow cytometric DNA analysis.

Thirty children with medulloblastoma who were treated between 1980 and 1986 are presented. Flow cytometric DNA analysis using formalin-fixed and paraffin-embedded tissues showed that 15 were DNA aneuploid, 13 diploid and 2 tetraploid. After homogeneous treatment with a combination of radical resection and radiation therapy, patients with DNA aneuploid medulloblastoma showed significantly better outcome (p = 0.003). Among these 30 patients, 6 (20%) had bone metastases of medulloblastoma during a minimum of 2-year follow-up period. DNA ploidy of these patients was diploid in 5 and aneuploid in 1. Incidence of bone metastases appears to correlate with DNA ploidy (p = 0.046). At the time of discovery of bone metastases, 4 had no demonstrable recurrence in the central nervous system (CNS). Radionuclide bone scan was more sensitive in disclosing these lesions, while only one patient had positive results of bone marrow aspirates/biopsy. Three patients were treated with chemotherapy, two had a combination of regional irradiation and chemotherapy and one refused treatment. All treated bone metastases in 5 patients responded clinically and radiographically, but only one patient is alive 66 months after therapy. Four patients died due to either CNS recurrence of septic complication of chemotherapy. Early detection of bone metastases by use of frequent bone scans is important. Patients with diploid medulloblastoma should be treated with adjuvant chemotherapy in order to prevent recurrences and metastases.

Adolescent↗

Influence of duodenal secretions and its components on release and activities of human brush-border enzymes.

The in vitro effects of human duodenal secretions and various combinations of its components on activity and release of enzymes from the human brush border were examined. Sucrase retained activity for 90 min in duodenal secretions, and maltase was almost as stable; lactase lost activity rapidly and alkaline phosphatase was of intermediate stability. Inactivation of lactase could only be partly (50%) attributed to luminal proteases, bile salts and phospholipids played no role. Rate of release of an enzyme from the brush border bore no relationship to its rate of inactivation. When individual proteases were studied, elastase was the most potent for releasing disaccharidases from the brush border; trypsin was ineffective alone but augmented the effect of elastase. Sucrase and maltase were activated by proteolytic release, but activation was abolished by simultaneous exposure of brush borders to bile salts. Lactase was released and rapidly inactivated by proteinases, while alkaline phosphatase appeared to be inactivated without significant release. These results show that there are significant interactions between luminal factors which have been inapparent when studying them in isolation. Loss of functionally useful enzyme does not follow release of sucrase or maltase from the brush border into the lumen but does follow release of lactase. Study of the susceptibility of lactase to inactivation by luminal factors in the various forms of lactose intolerance is warranted.

Alkaline Phosphatase↗

Secondary leukemia following successful treatment of Wilms' tumor.

Leukemia accounts for 15-20% of the secondary malignancies among survivors of Wilms' tumor. We report three patients who developed leukemia after the successful treatment of Wilms' tumor, each of whom demonstrates the importance of close long-term medical surveillance. The first patient developed Philadelphia chromosome positive chronic myelogenous leukemia (CML) 6 years after the diagnosis of Wilms' tumor. This is the second report of CML occurring after Wilms' tumor. The other two patients developed acute nonlymphocytic leukemia (ANLL) 3 and 18 years after successful treatment of Wilms' tumor. In one patient, the clinical manifestations were subtle, and in the other the latency period was the longest reported for secondary leukemia following Wilms' tumor. We conclude that survivors of childhood cancer require frequent medical surveillance even in their adult years.

Alkylating Agents↗