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Biomedical subjects

M Chandy

Publications and source records attributed to M Chandy.

At least 55 records · Page 3Linked to original sources
PubMed2000

A zebrafish ftz-F1 (Fushi tarazu factor 1) homologue requires multiple subdomains in the D and E regions for its transcriptional activity.

A zebrafish Ftz-F1 homologue, zFF1A (zebrafish Ff1a or Nr5a2, a member of nuclear receptor superfamily) and its C-terminally truncated variant (zFF1B) were previously identified. Due to lack of the identity box (I-box) and activation function 2 (AF-2) domain, zFF1B lacks transactivation function and fails to synergize with estrogen receptor (ER) in regulating promoters. It was speculated that the I-box might be involved in the zFF1A/ER interaction. In the present study, the function of the I-box was examined. In the absence of the I-box or with an altered heptad 9, the AF-2 of zFF1A was not functional, either in the presence or absence of ER. The GST pull-down assay showed that zFF1A and its mutants exerted similar physical contacts with ER-LBD, suggesting that the "dimerization" domain (I-box) is essential for the transcriptional activity of zFF1A. Moreover, nuclear receptor coactivator selectively activated zFF1 with the I-box but exerted no effect on zFF1B, indicating that the I-box is able to interact with the coactivators. By deletion study and analysis of the identified domains in GAL4-DNA binding domain, other regions of zFF1A critical for its AF were also delineated. Consistent with the mutation analysis, AF-2 was active only in the presence of the I-box. We also identified a novel AF domain (AF-3) located in the hinge region (amino acids 155-267), although the activity of AF-3 was inhibited by its flanking region. We suggest that the D and E regions of zFF1A possess both positive and negative transactivation functions, and interdomain "cross-talk" may confer the full transcriptional activity of the protein.

Amino Acid Sequence↗
PubMed2000

Unusual association of Kikuchi's disease and dengue virus infection evolving into systemic lupus erythematosus.

Kikuchi's disease is a histologically alarming self-limiting condition typically affecting the lymph nodes of young females. A 13-year-old girl was presented with fever, skin rash and cervical lymphadenopathy. On examination she was found febrile, mild pallor was present and she had lymphadenopathy. Liver was palpable. Cervical lymph node biopsy showed histiocytic necrotising lymphadenitis (Kikuchi's disease). Dengue virus serology for IgG blot showed evidence of seroconversion in serial samples. She was treated with antibiotics and fluconazole and cyclosporin A. During hospitalisation she developed retinal vasculitis. She was reviewed after one month and showed rashes of subacute cutaneous lupus erythematosus. This case can be described to be a triggering event by dengue viral infection causing abnormal immune response leading initially to Kikuchi's disease and later on to systemic lupus erythematosus.

Adolescent↗
PubMed2000

Systemic bacterial infections in bone marrow transplant patients.

The clinical microbiology department at CMC&H, Vellore in conjunction with the haematology department carries out routine surveillance of patients admitted to the hematology department. Since 1994 in a sample population of 55 patients with various underlying clinical conditions who have had bone marrow transplant, sepsis was observed in 16 patients (29%). The predominant Gram negatives associated with sepsis were non-fermenting Gram negative bacilli and all the 5 Gram positives were coagulase negative staphylococci. These organisms were susceptible to most of the routinely used antimicrobial agents. Continued surveillance is needed to determine changing trends with respect to organisms causing systemic infections and their susceptibility to antimicrobials.

Adolescent↗
PubMed1999

High-performance liquid chromatographic method for quantification of busulfan in plasma after derivatization by tetrafluorothiophenol.

A high-performance liquid chromatographic (HPLC) method was developed and validated for the determination of busulfan in plasma. Busulfan was extracted in toluene, derivatized by 2,3,5,6-tetrafluorothiophenol to obtain di-TFTP-butane, the derivatization product was then re-extracted in toluene and injected into the HPLC system with ultraviolet detection (wavelength: 275 nm). Recovery from extraction was 80%, the limit of quantification was 50 ng/ml and linearity ranged from 50 to 2000 ng/ml. In addition, forty-two samples obtained from pediatric patients treated with busulfan were analyzed by the HPLC and GC-MS assays based on the same derivatization procedure. The correlation between the di-TFTP-butane concentrations was highly significant (p<0.0001), demonstrating that the two methods were in good agreement.

Antineoplastic Agents, Alkylating↗
PubMed1999

Evaluation of uroprotective efficacy of amifostine against cyclophosphamide induced hemorrhagic cystitis.

The role of amifostine in the prevention of cyclophosphamide-induced hemorrhagic cystitis (HC) was evaluated in the rat model. Urinary bladders from control rats that received no drugs (group I) were compared with those from rats receiving cyclophosphamide alone at a dose of 150 mg/kg (group II), and two other groups receiving amifostine at 100 mg/kg (group III) and 200 mg/kg (group IV), 15 min prior to cyclophosphamide. Bladders were assessed macroscopically and histologically at 24 h and after 7 days. All the animals that received cyclophosphamide alone developed severe HC. On the basis of the scores of macroscopic and histologic changes, animals that received amifostine showed excellent uroprotection. Only 2/6 rats in group III and 1/6 rats in group IV developed mild HC at 24 h. None of the rats in either of these groups showed any evidence of HC at 7 days. It is concluded that amifostine protects the urothelium against cyclophosphamide-induced HC.

Amifostine↗
PubMed1999

Pharmacokinetics of oral busulphan in children with beta thalassaemia major undergoing allogeneic bone marrow transplantation.

The pharmacokinetics of busulphan were studied in 23 thalassaemic children undergoing BMT. Patients received busulphan at a dose of either 16 mg/kg with cyclophosphamide and ATG (Group A) or 600 mg/m2 (with cyclophosphamide alone) (Group B) in 16 divided doses every 6 h over 4 days. Busulphan levels were analyzed by a modified GC-MS method. The dose of busulphan/kg for patients in group B was 64% (range 56-71%) higher than that for patients in group A. The mean AUC, Css, Cmax and MRV were significantly higher in group B as compared with group A for both doses 1 and 13. There was no significant difference in Vd/F, T1/2 and Kel between the two groups. A significant decrease in AUC and Css was found between 1st and 13th doses in group B, but not in group A. The Cl/F values in group A were significantly higher than those in group B after dose 1, but not after dose 13. No increase in toxicity due to the higher dose of busulphan was noted. We conclude that busulphan at 600 mg/m2 results in much higher systemic exposure to the drug as compared to 16 mg/kg, without increase in toxicity in children with beta thalassaemia major.

Administration, Oral↗
PubMed1998

Quantification of busulfan in plasma by gas chromatography-mass spectrometry following derivatization with tetrafluorothiophenol.

A specific and highly sensitive method has been developed for the determination of busulfan in plasma by gas chromatography-mass spectrometry using a deuterium-labeled busulfan (busulfan-d8) as internal standard. Plasma containing busulfan and busulfan-d8 were extracted with ethyl acetate and derivatized with 2,3,5,6-tetrafluorothiophenol prior to the monitoring of specific ions. The limit of quantification of the assay was 20 ng/ml and the calibration curve was linear over the range of 10 to 2000 ng/ml of derivatized busulfan. This method was in good agreement with the GC-MS assay using derivatization with sodium iodide and measuring diiodobutane. In addition, a pharmacokinetic study of busulfan was conducted in six children. The apparent oral clearance was 5.7+/-1.9 ml/kg/min and the volume of distribution was 1.0+/-0.4 l/kg and were similar to those previously reported in pediatric patients.

Alkylating Agents↗
PubMed1998

Otogenic intracranial abscess: concurrent craniotomy and mastoidectomy--changing trends in a developing country.

OBJECTIVES: To evaluate (1) the clinical profile, treatment, and outcome of adult and pediatric patients presenting with intracranial abscess of otogenic origin and (2) the advantages of concurrent craniotomy and mastoidectomy. DESIGN: A prospective case series. SETTING: An academic tertiary referral center in India. PATIENTS: Thirty-six patients clinically diagnosed as having intracranial abscess that was secondary to suppurative otitis media and confirmed by computed tomographic scanning. INTERVENTION: Concurrent craniotomy and mastoidectomy. RESULTS: Children were more commonly affected than adults, and there was a male preponderance. All patients had cholesteatoma at surgery, although one third of the children had only granulation tissue on otoscopy. More than two thirds of the patients in both the groups presented with more than one intracranial complication and definitive surgical intervention was done later than 24 hours. Meningitis was the most frequent intracranial complication, followed by cerebellar abscess. There was no significant intraoperative or postoperative morbidity, mortality, recurrence of intracranial complications, or residual neurological deficits. Three children (14%) showed evidence of recidivism cholesteatoma requiring revision surgery. CONCLUSIONS: In suppurative otitis media with intracranial complications, it is accepted practice to treat the neurosurgical complication first, followed by mastoidectomy at a later date after the patient has been stabilized. Craniotomy with concurrent mastoidectomy is not only safe, but it also removes the source of infection at the same time the complications are being treated, thus avoiding reinfection while the patient is awaiting the ear surgery. In addition, the treatment is completed with a single, shorter hospital stay, which is more economical for the patient.

Adolescent↗
PubMed1998

Low-dose intermittent factor replacement for post-operative haemostasis in haemophilia.

Recommendations for factor replacement therapy for postoperative haemostasis in haemophilia are often empirical and based on the physiological understanding of haemostatic requirements. This report describes the haemostatic management of patients with severe haemophilia undergoing major surgery using lower than usually recommended levels of factor replacement therapy. Eighteen adults (11 with FVIII and seven with FIX deficiency) with an average weight of 52 kg (range: 27-69) underwent 20 major surgical procedures. Factor concentrates were administered by intermittent bolus infusions. The dose of FVIII infused before surgery was 76 mu kg-1 (range: 51-113) and that of FIX was 77 mu kg-1 (range: 50-104). The preoperative levels achieved were 107% (range: 80-180) and 73% (range: 60-90), respectively. Between days 1 and 3 after surgery, an average of 29 mu kg-1 day-1 (range: 20-46) of FVIII and 23 mu kg-1 day-1 (range: 12-42) of FIX was used resulting in mean trough levels of 36% (range: 12-62) and 34% (range: 11-52), respectively. After day 4, an average of 19 mu kg-1 day-1 (range: 15-25) of FVIII and 18 mu kg-1 day-1 (range: 10-37) of FIX was administered until wound healing. The average duration of factor replacement was 11 days (range: 8-16). The mean dose of factor concentrate per patient was 260 mu kg-1 (range: 179-338) of FVIII and 300 mu kg-1 (range: 183-524) of FIX. The total amount of factor used per patient ranged from 12,380 to 19,980 units of FVIII and 8000 to 23,600 units of FIX. Only one patient had post-operative bleeding which was due to a surgical cause. It is concluded that it may be possible to use much lower than recommended levels of factor replacement therapy for postoperative haemostasis in severe haemophilia.

Adolescent↗
PubMed1998

Management of haemophilia in the developing world.

The problems with management of haemophilia in developing countries are poor awareness, inadequate diagnostic facilities and scarce factor concentrates for therapy. The priorities in establishing services for haemophilia include training care providers, setting up care centres, initiating a registry, educating affected people and their families about the condition, providing low-cost factor concentrates, improving social awareness and developing a comprehensive care team. A coagulation laboratory capable of reliably performing clotting times with correction studies using normal pooled, FVIII and FIX deficient patient plasma and factor assay is most essential for diagnosis. More advanced centralized laboratories are also needed. Molecular biology techniques for mutation detection and gene tracking should be established in each country for accurate carrier detection and antenatal diagnosis. Different models of haemophilia care exists. In India, there is no support from the government. Services, including import of factor concentrates, are organized by the Haemophilia Federation of India, with support from other institutions. Haemophilia is managed with minimal replacement therapy (about 2000 i.u./PWH/year). In Malaysia, where the system is fully supported by the government, facilities are available at all public hospitals and moderate levels of factor concentrates are available 'on-demand' (about 11,000 i.u./PWH/year) at the hospitals. Haemophilia care in South Africa is provided through major public hospitals. Intermediate purity factor concentrates are locally produced (about 12,000 i.u./PWH/year) at low cost. The combined experience in the developing world in providing haemophilia services should be used to define standards for care and set achievable goals.

Developing Countries↗
PubMed1997

Non-Hodgkin's lymphoma presenting with prominent splenomegaly--clinicopathologic diversity in relationship to immunophenotype.

Splenomegaly is an uncommon presenting feature of non-Hodgkin's lymphoma. This is a study of 16 cases of non-Hodgkin's lymphoma presenting with prominent splenomegaly, which includes ten B-cell lymphomas and six T-cell lymphomas. There were distinct clinical and morphologic differences between these two immunologic types of splenic lymphomas, the B-cell types being predominantly low grade and occurring in older individuals whereas the T-cell lymphomas were predominantly high grade and occurred in adolescents and young adults.

Adolescent↗
PubMed1996

NESTROFT as a screening test for the detection of thalassaemia & common haemoglobinopathies--an evaluation against a high performance liquid chromatographic method.

The NESTROFT method (Naked Eye Single Tube Red Cell Osmotic Fragility Test) was evaluated against a high performance liquid chromatographic (HPLC) method for its usefulness in screening for beta-thalassaemia and some of the common haemoglobinopathies. Blood samples (137) from patients with suspected haemoglobin disorders were analyzed by both methods. Among the 63 patients with heterozygous beta-thalassaemia on HPLC, NESTROFT was positive for 49, 'doubtful' for 13 and negative for 1. Of the 32 patients with other haemoglobin disorders, 28 were positive on NESTROFT and 4 were 'doubtful'. Of the 42 'normal' samples, NESTROFT was positive for 6, 'doubtful' for 8 and negative for 28. This test showed an overall sensitivity of 98.7 per cent, specificity of 66.6 per cent, positive predictive value of 87 per cent and negative predictive value of 96.5 per cent. We conclude that, NESTROFT is a suitable test for screening for beta-thalassaemia and the common haemoglobinopathies seen in India. It is easy to perform, simple, inexpensive and does not require sophisticated equipment. Subjects who are NESTROFT 'positive' or 'doubtful' deserve further investigation.

Chromatography, High Pressure Liquid↗
PubMed1995

Childhood acute lymphoblastic leukemia in India: an approach to management in a three-tier society.

Within a population of 882 million, six thousand children will develop acute lymphoblastic leukemia each year in India. These children come from three socio-economic backgrounds: Profile I (70%) being extremely poor who cannot afford any treatment unless it is provided free, Profile II (25%) from the middle class, and Profile III (5%) who can afford to have the best possible treatment. Current protocols for childhood ALL range from simple low-cost regimes like UKALL VIII, intermediate intensity regimes like BFM 76/79, and aggressive regimes aimed at increasing cure rates in the high risk groups. Since state resources are limited, the pediatric oncologist in India has to decide on the appropriate treatment protocol for the individual child in each of these profiles. This paper suggests an approach to managing childhood ALL in developing countries like India.

Child, Preschool↗