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Biomedical subjects

A Kaul

Publications and source records attributed to A Kaul.

At least 19 recordsLinked to original sources

Advances in the diagnosis and management of chronic pulmonary aspiration in children.

Chronic pulmonary aspiration (CPA) in children is an important cause of recurrent pneumonia, progressive lung injury, respiratory disability and death. It is sporadic, intermittent and variable, and often occurs in children with complicated underlying medical conditions and syndromes that produce symptoms indistinguishable from CPA. For most types of aspiration there is no gold-standard diagnostic test. The diagnosis of CPA is currently made clinically with some supporting diagnostic evaluations, but often not until significant lung injury has been sustained. Despite multiple diagnostic techniques, the diagnosis or exclusion of CPA in children is challenging. This is of particular concern given the outcome of unrecognised progressive lung injury and the invasiveness of definitive therapies. Although new techniques have been introduced since the 1990s and significant advances in the understanding of dysphagia and gastro-oesophageal reflux have been made, characterisation of the aspirating child remains elusive.

Child↗

Open anterior fracture dislocation of the hip: a case report and review of literature.

Open anterior fracture dislocation of the hip is an extremely rare injury and is the result of a violent trauma. Such a case is being reported in a 15-year-old female, who also had other adjacent bony injuries. In spite of early treatment, necrosis and infection could not be controlled, resulting in permanent disability in this young girl.

Accidents, Traffic↗

Relation between viral fitness and immune escape within the hepatitis C virus protease.

BACKGROUND: The hepatitis C virus (HCV) mutates within human leucocyte antigen (HLA) class I restricted immunodominant epitopes of the non-structural (NS) 3/4A protease to escape cytotoxic T lymphocyte (CTL) recognition and promote viral persistence. However, variability is not unlimited, and sometimes almost absent, and factors that restrict viral variability have not been defined experimentally. AIMS: We wished to explore whether the variability of the immunodominant CTL epitope at residues 1073-1081 of the NS3 protease was limited by viral fitness. PATIENTS: Venous blood was obtained from six patients (four HLA-A2+) with chronic HCV infection and from one HLA-A2+ patient with acute HCV infection. METHODS: NS3/4A genes were amplified from serum, cloned in a eukaryotic expression plasmid, sequenced, and expressed. CTL recognition of naturally occurring and artificially introduced escape mutations in HLA-A2-restricted NS3 epitopes were determined using CTLs from human blood and genetically immunised HLA-A2-transgenic mice. HCV replicons were used to test the effect of escape mutations on HCV protease activity and RNA replication. RESULTS: Sequence analysis of NS3/4A confirmed low genetic variability. The major viral species had functional proteases with 1073-1081 epitopes that were generally recognised by cross reactive human and murine HLA-A2 restricted CTLs. Introduction of mutations at five positions of the 1073-1081 epitope prevented CTL recognition but three of these reduced protease activity and RNA replication. CONCLUSIONS: Viral fitness can indeed limit the variability of HCV within immunological epitopes. This helps to explain why certain immunological escape variants never appear as a major viral species in infected humans.

Acute Disease↗

Lymphoproliferative disorder of the airway of an adolescent without immunodeficiency.

Epstein-Barr virus (EBV) is a ubiquitous viral pathogen in humans that has a unique ability to immortalize B-cells. In immunosuppressed individuals, EBV can produce non-neoplastic lymphoproliferative disorders involving various organs. We describe a case report of EBV-associated lymphoproliferative disorder in an immunocompetent 14-year-old male. The case provides a description of EBV-associated lymphoproliferation affecting the upper and lower respiratory tract. The massive submucosal infiltration of B-cells in the lingual tonsils, trachea, and bronchi produced near-complete airway obstruction resulting in tracheotomy. Neither surgical reduction of lingual tonsils nor treatment with steroids was of benefit. An extensive evaluation for immunodeficiency and neoplasia was normal. Treatment with rituximab, an anti-CD20 antibody, resulted in near-complete resolution of the infiltrative process, sufficient to allow decannulation. Rituximab is a treatment option for the rare occurrence of non-neoplastic, EBV-associated, lymphoproliferative disorders.

Adolescent↗

Tolerance of uncertainty, extroversion, neuroticism and attitudes to randomized controlled trials among surgeons and physicians.

BACKGROUND: Surgeons have a reputation for decisiveness and self-confidence, which suggests that they may tolerate uncertainty poorly and therefore be less capable than other doctors of experiencing clinical equipoise. Their 'typical' behaviour is characteristic of the stable extrovert personality and so they may prefer spontaneous clinical judgement over randomized trials. The aim of this study was to compare personality dimensions and tolerance of uncertainty among surgeons and hospital physicians, to determine whether differences in either property might help to explain the apparently poor performance of surgeons in conducting randomized controlled trials. METHODS: This was a postal questionnaire study of 1000 consultant general surgeons and 1000 consultant physicians. Respondents completed a short self-assessment of Eysenck personality dimensions, Budner's Intolerance of Ambiguity scale and a short questionnaire about attitudes to randomized trials. Correlation and multiple regression analyses were performed. RESULTS: The response rate was 36.5 per cent. Physicians were more likely to be women (P < 0.001) and had spent 1 more year in academic posts than surgeons (P < 0.030). Surgeons were significantly more extrovert (P < 0.001) and less neurotic (P < 0.001) than physicians. Surgeons were significantly more intolerant of uncertainty than physicians (P = 0.007). Multivariate analysis identified age (P < 0.030) and sex (P = 0.015) as independent predictors of intolerance of uncertainty. The attitudes of surgeons and physicians to randomized trials were no different. CONCLUSION: Surgeons are not prejudiced against randomized trials, but their intolerance of uncertainty may inhibit them from deciding that an individual patient is suitable for trial entry. If more surgeons were female, this difference between surgeons and physicians might disappear.

Attitude of Health Personnel↗

Anti-inflammatory activity of 'TAF' an active fraction from the plant Barleria prionitis Linn.

'TAF' fraction from the methanol-water extract of Barleria prionitis Linn. was evaluated for anti-inflammatory and anti-arthritic activities against different acute and chronic animal test models. It exhibited significant anti-inflammatory activity against different inflammagens like carrageenan, histamine and dextran. The anti-inflammatory activity in adrenalectomised rats was maintained showing that the effect of fraction 'TAF' is not activated by the pituitary-adrenal axis. Significant anti-arthritic activity was observed in adjuvant-induced polyarthritis test in rats. 'TAF' also showed inhibition of vascular permeability and leucocytes migration in vivo into the site of inflammatory insult.Ibuprofen (Cadilla India Ltd., Mumbai) was used as a standard reference drug. The oral (p.o.) LD(50) was more than 3000mg/kg, with no signs of abnormalities or any mortality observed for 15 days after single-dose drug administration. The intraperitoneal (i.p.) LD(50) was found to be 2530mg/kg (+/-87mg/kg S.E.) [Proceedings of Society of Experimental Biological Medicine 57 (1944) 261].

Acanthaceae↗

High virus loads in naturally and experimentally SIVagm-infected African green monkeys.

A quantitative RT-PCR assay was developed for SIVagm and was used to measure the levels of viral RNA in the plasma of experimentally and naturally infected African green monkeys. The number of productively infected PBMCs and the number of cells carrying integrated provirus were also measured. Plasma virus loads in experimentally infected animals peaked at 2 weeks postinfection, ranging from 2.9 x 10(5) to 4.2 x 10(7) RNA copies/ml plasma. Set points of 2.1 x 10(3) to 2.8 x 10(6) RNA copies/ml plasma were maintained for one year. Similarly, the number of cells carrying integrated SIVagm provirus remained relatively stable in individual animals for one year with set points ranging from 73 to 810 proviral copies per 10(6) PBMC. However, the number of productively infected cells fluctuated considerably during this period. Virus loads in the 26 naturally infected AGMs ranged from 8.3 x 10(3) to 1.1 x 10(7) (mean 1.7 x 10(6)) RNA copies/ml plasma. These levels of viremia are similar to those seen in pathogenic systems (HIV-1, SIVmac), indicating that control of SIVagm replication is not the reason for the natural host's resistance to disease progression.

Animals↗

Pathology of autoimmune myelofibrosis. A report of three cases and a review of the literature.

We identified 3 patients with autoimmune myelofibrosis (AM) lacking American Rheumatism Association criteria for systemic lupus erythematosus (SLE). They had 1 or 2 cytopenias and lacked serologic evidence for SLE. Autoimmune features included psoriatic arthritis and positive direct Coombs test (DCT) result, DCT-positive autoimmune hemolytic anemia, and synovitis with polyclonal hypergammaglobulinemia. Bone marrow biopsy specimens from each patient were evaluated by routine morphologic and immunohistochemical examination. They demonstrated marked hypercellularity (2 cases) or hypocellularity (1 case), moderate erythroid hyperplasia (all cases) with left-shifted maturation (2 cases), intrasinusoidal hematopoiesis (all cases), slightly to moderately increased megakaryocytes (2 cases), and grade 3 to 4 reticulin fibrosis (all cases). All lacked basophilia, eosinophilia, bizarre megakaryocytes, clusters of megakaryocytes, and osteosclerosis. Mild to moderate bone marrow lymphocytosis was noted in all cases. In 2 cases, increased small T cells and B cells formed nonparatrabecular, loose aggregates. AM is a clinicopathologic entity that may lack features of SLE. Loose aggregates of bone marrow T and B lymphocytes and the absence of morphologic and clinical features of myeloproliferative disease or low-grade lymphoproliferative disease are clues that distinguish AM from better known causes of bone marrow fibrosis.

Adult↗

I. The modulatory effect in genotoxic responses due to age and duration of PHT-therapy in epileptic patients.

Sister chromatid exchange (SCE) frequency has been studied from the peripheral blood lymphocyte cultures of 42 epileptic patients on the anticonvulsant drug phenytoin (PHT) for 3 months and their follow-up (6 and 9 months), of 33 epileptics who had not started therapy (PHT-untreated), and of 40 normal healthy controls, all in the same age group, i.e., 10-30 years. PHT-treated epileptic patients at all three durations of therapy (3, 6, and 9 months) showed higher SCE frequency (P < 0.001) than healthy controls and PHT-untreated patients. There was no significant difference in SCE frequency between control and PHT-untreated patients, suggesting that disease is not associated with an increased frequency of SCEs. The frequency of SCEs seems to be influenced by an age factor, when older treated patients (21-30 years) showed higher SCE frequencies at 3 and 6 months (P < 0.001) and 9 months (P < 0.05) than the younger age group (10-20 years). SCE frequency increased linearly with the duration of therapy, i.e., from 3 months to 9 months. No correlation was found between SCE frequency and sex with respect to controls, PHT-untreated, and PHT-treated subjects. In conclusion, the modulating effect on SCE frequencies elicited by age and duration of therapy has been clearly demonstrated by SCE mean analysis. Teratogenesis Carcinog. Mutagen. 21:135-149, 2001.

Adolescent↗

II. An altered proliferation response due to the anticonvulsant phenytoin (PHT) in epileptic patients.

Lymphocyte proliferation kinetics (LPK) is an end point used in genetic toxicology that was proposed as an alternative for the screening of anticonvulsant drugs. The effect of phenytoin (PHT) was investigated on the mitotic and proliferation indices in cultured blood lymphocytes of 33 sporadically collected untreated and 42 PHT-treated epileptics, where the duration of treatment was 3, 6, and 9 months, and 40 control subjects (age range 10-30 years). PHT induced mitotic delays and decreased the mitotic index. A significant heterogeneity of the first, second and the third metaphases between treated and untreated groups was revealed. A reduction of the proliferation index (P < 0.001) and proliferation delay per cycle (P < 0.001) was also observed. There was little variation between the controls and untreated patients (P > 0.05). The results have confirmed that PHT can affect responses leading to genotoxicity. Teratogenesis Carcinog. Mutagen. 21:151-164, 2001.

Adolescent↗

Polymer recycling in aqueous two-phase extractions using thermoseparating ethylene oxide--propylene oxide copolymers.

This is a study on the recovery and recycling of copolymer in aqueous two-phase systems containing random copolymers of ethylene oxide (EO) and propylene oxide (PO). The random copolymers separate from water solution when heated above the lower critical solution temperature (LCST). The primary phase systems were composed of EOPO copolymer and hydroxypropyl or hydroxyethyl starch. After phase separation the upper EOPO phase was removed and subjected to temperature induced phase separation. Copolymers with different EO/PO compositions have been investigated, EO50P050 [50% EO and 50% PO (w/w)], EO30PO70 and EO20P080. The temperature required for thermoseparation decreases when the PO content of the copolymer is increased. The effect on the recovery of copolymer after addition of salts, a second polymer or protein was investigated. The added components increased the recovery of copolymer after thermoseparation, e.g., increased the amount copolymer separated from the water phase after thermoseparation. Recycling of copolymer and measurements of polymer concentrations in the primary top and bottom phases after repeated recycling steps was performed. The fluctuation in polymer concentration of the phases was very small after recycling up to four times. Partitioning of the proteins BSA and lysozyme was studied in primary phase systems after recycling of copolymer. The partition coefficients of total protein and lysozyme was not significantly changed during recycling of copolymer. More than 90% of the copolymer could be recovered in the thermoseparation step by optimising the temperature and time for thermoseparation. In repeated phase partitionings in EOPO-starch systems the EO50PO50 copolymer could be recovered to 77% including losses in primary system and thermoseparation, which is equivalent to a total copolymer reuse of 4.3 times.

Polyethylenes↗

Expression of complement regulatory proteins-CD 35, CD 46, CD 55, and CD 59-in benign and malignant endometrial tissue.

OBJECTIVE: Complement system plays an important role in host defense mechanisms against microorganisms and tumor cells. To protect themselves from autologous complement-mediated damage, normal host tissues express cell membrane-associated complement regulatory proteins (CRPs). To investigate whether neoplastic endometrial tissues overexpress these proteins to escape complement damage, we examined the distribution of complement receptor type 1 (CR1, CD35), membrane cofactor protein (MCP, CD46), decay-accelerating factor (DAF, CD55), and protectin (MACIF, CD59) on frozen endometrial tissue samples. METHODS: A total of 54 endometrial tissue samples were collected. Cryosections were obtained of 31 benign and 23 malignant tissue specimens. Tissue sections were stained by immunohistochemical staining procedure using specific antibodies and employing the avidin-biotin technique. Quantitation of the protein content of these CRPs was determined using the Samba 4000 image analysis system. RESULTS: For all four of the CRPs studied, a statistically significant difference in protein expression between the benign and malignant endometrial tissue specimens (P < 0.0001) was observed. CONCLUSIONS: Overexpression of all the CRPs studied (CD35, CD46, CD55, CD59) was observed in the malignant as compared with the benign endometrial tissues. The upregulation of these CRPs may promote resistance of the endometrial malignant tissue to complement-mediated damage, thereby allowing the tumor cells to escape from cytolysis and thus promoting carcinogenesis.

Adult↗

Anti-inflammatory activity of the hydrosoluble fraction of Euphorbia royleana latex.

The hydrosoluble fraction of Euphorbia royleana latex (AER), administered by gavage at doses of 50-200 mg/kg, showed dose-dependent anti-inflammatory and anti-arthritic effects in different acute and chronic test models in rats and mice. It reduced the exudate volume and the migration of leukocytes and showed a poor inhibitory effect on the granuloma formation induced by cotton pellets, while it had a low ulcerogenic score. The oral LD(50) was more than 1500 mg/kg in both rats and mice.

Animals↗