Biomedical subjects

S Chakrabarti

Publications and source records attributed to S Chakrabarti.

At least 55 records · Page 3Linked to original sources

PubMed2005

Myocilin gene implicated in primary congenital glaucoma.

Primary congenital glaucoma (PCG) has been associated with CYP1B1 gene (2p21), with a predominantly autosomal recessive mode of inheritance. Our earlier studies attributed CYP1B1 mutations to only 40% of Indian PCG cases. In this study, we included 72 such PCG cases where CYP1B1 mutations were detected in only 12 patients in heterozygous condition, implying involvement of other gene(s). On screening these patients for mutations in myocilin (MYOC), another glaucoma-associated gene, using denaturing high-performance liquid chromatography followed by sequencing, we identified a patient who was double heterozygous at CYP1B1 (c.1103G>A; Arg368His) and MYOC (c.144G>T; Gln48His) loci, suggesting a digenic mode of inheritance of PCG. In addition, we identified the same MYOC mutation, implicated for primary open angle glaucoma, in three additional PCG patients who did not harbor any mutation in CYP1B1. These observations suggest a possible role of MYOC in PCG, which might be mediated via digenic interaction with CYP1B1 and/or an yet unidentified locus associated with the disease.

Aryl Hydrocarbon Hydroxylases↗

PubMed2005

Cost of care of schizophrenia: a study of Indian out-patient attenders.

OBJECTIVE: To assess the cost of care of Indian out-patients with schizophrenia. METHOD: Cost of illness in 50 out-patients with schizophrenia was assessed over a 6-month period together with structured assessments of psychopathology and disability, and compared with 50 out-patients with diabetes mellitus. RESULTS: Total annual costs of care of schizophrenia were 274 US dollars; these were not significantly different from diabetes mellitus. Indirect costs (63%) were higher than direct costs. Drug costs were high. The main brunt of financial burden was borne by the family. Total treatment costs in schizophrenia were significantly higher in those who were unemployed, those who visited the hospital more often, and were more severely ill and disabled. CONCLUSION: Schizophrenia is an expensive illness to treat even in developing countries. Costs of care are similar to those of chronic physical illness, such as diabetes mellitus. Costs are higher in severely ill and disabled patients.

Adult↗

PubMed2005

Understanding cardiac arrhythmias.

This review highlights the applied science intrinsic to the interpretation of the electrocardiogram and cardiac arrhythmias in children.

Arrhythmias, Cardiac↗

PubMed2005

Cost of ambulatory care of diabetes mellitus: a study from north India.

BACKGROUND: Diabetes mellitus is a chronic and potentially disabling disease that represents an important public health and clinical concern because of the economic burden it imposes on the person, family, and society. Despite this, data regarding cost of care of diabetes mellitus from developing countries are scarce. This study aimed to assess the cost of care of Indian patients with diabetes mellitus. METHODS: Cost of illness in 50 outpatients with diabetes mellitus (diagnosed according to WHO criteria, Expert Committee, 1997) was assessed over a six month period using a specially designed questionnaire, together with structured assessments of disability. RESULTS: Total annual cost of care was 14 508 rupees (263.78 euros). The largest proportion of the total cost was made up of direct costs (68%), followed by indirect costs (28.76%) and provider's costs (2.8%). Drug costs were high. Total treatment cost was significantly higher in those who were more educated, those who visited the hospital more often, and those receiving a greater number of drugs. CONCLUSION: From this study it can be concluded that diabetes mellitus is an expensive illness to treat even in developing countries. The main brunt of financial burden is borne by the family. Any efforts at cost reduction should, therefore, have the family as its focus, and relieving the family of this financial burden needs to be prioritised.

Adult↗

PubMed2005

Photoluminescence and raman study of CdS-Al2O3 nanocomposite films prepared by sol-gel techniques.

The optical and microstructural properties of CdS-Al2O3 nanocomposite (CdS-Al2O3 = 20:80 to 50:50) thin films synthesized by sol-gel techniques were studied. Optical transmission spectra indicated a marked blue shift of the absorption edge due to quantum confinement. Band gaps of CdS-Al2O3 nanocomposites were found to vary in the range 3.69-2.61 eV. The sizes of the nanocrystals, estimated from the blue shift (0.2-1.2 eV) of the absorption edges and transmission electron microscopy, were found to vary in the range 2.8-7.0 nm. X-ray diffraction studies showed reflections from (111), (200), (220), and (311) planes of CdS in the cubic phase. Microstructural characterization by high-resolution transmission electron microscope (HRTEM) indicated well crystallinity of the nanoparticles and lattice fringes supported the cubic phase of CdS. Raman spectroscopy was carried out for CdS-Al2O3 nanocomposites, which indicated a prominent peak at approximately 299 cm(-1). Significant changes in the peak position and intensity of the Raman peak were observed with varying the annealing temperature (373-573 K). Photoluminescence measurements indicated a prominent broad peak at approximately 1.81 eV due to the surface defects in the CdS nanocrystallites. The present study revealed Al2O3 to be a good capping material for CdS nanoparticles.

Aluminum Oxide↗

PubMed2005

Sarcoma-like mural nodules in ovarian mucinous cystadenomas--a report of two cases.

Sarcoma-like mural nodule is a very rare occurrence in a mucinous tumour of the ovary. Two such nodules having morphologically benign features with osteoclastic giant cells, in the wall of mucinous cystadenoma are described. In addition, these nodules exhibited reactive vascular proliferations. The sarcoma-like nodules are associated with a favourable outcome and must be distinguished from other malignant nodules composed of sarcoma or anaplastic carcinoma that may also occur in the wall of mucinous ovarian tumours.

Adult↗

PubMed2004

Observation and properties of the X(3872) decaying to J/psipi(+)pi(-) in pp collisions at sqrt[s]=1.96 TeV.

We report the observation of the X(3872) in the J/psipi(+)pi(-) channel, with J/psi decaying to mu(+)mu(-), in pp collisions at sqrt[s]=1.96 TeV. Using approximately 230 pb(-1) of data collected with the Run II D0 detector, we observe 522+/-100 X(3872) candidates. The mass difference between the X(3872) state and the J/psi is measured to be 774.9+/-3.1(stat)+/-3.0(syst) MeV/c(2). We have investigated the production and decay characteristics of the X(3872) and find them to be similar to those of the psi(2S) state.

Journal Article↗

PubMed2004

Search for doubly charged higgs boson pair production in the decay to mu(+)mu(+)mu(-)mu(-) in pp collisions at sqrt[s]=1.96 TeV.

A search for pair production of doubly charged Higgs bosons in the process pp -->H(++)H(--) -->mu(+)mu(+)mu(-)mu(-) is performed with the D0 run II detector at the Fermilab Tevatron. The analysis is based on a sample of inclusive dimuon data collected at an energy of sqrt[s]=1.96 TeV, corresponding to an integrated luminosity of 113 pb(-1). In the absence of a signal, 95% confidence level mass limits of M(H(+/-+/-)(L))>118.4 GeV/c(2) and M(H(+/-+/-)(R))>98.2 GeV/c(2) are set for left-handed and right-handed doubly charged Higgs bosons, respectively, assuming 100% branching into muon pairs.

Journal Article↗

PubMed2004

Re-institution of good metabolic control in diabetic rats and activation of caspase-3 and nuclear transcriptional factor (NF-kappaB) in the retina.

Hyperglycemia is one of the major underlying factors in the development of retinopathy in diabetes. Retinal microvascular cells undergo accelerated apoptosis before other histopathological changes are detectable in diabetes. We examined the effect of re-institution of good metabolic control (GC) on the activation of retinal apoptosis executor enzyme, caspase-3, and nuclear transcriptional factor NF-kB. In streptozotocin diabetic rats, two or six months of poor metabolic control (PC) with glycated hemoglobin >11.0% was followed by seven additional months of GC (glycated hemoglobin <5.5%). Caspase-3 activity in retina was measured by the cleavage of its substrate, the expression of active 17 kD subunit, and cleavage of poly(ADP ribosyl) polymerase. NF-kB activation was determined by electrophoretic shift assay and by western blots for P65 subunit. Caspase-3 activity in diabetic rats kept in PC for 13 months was 175% that in normal rats. Re-institution of GC after two months of PC partially normalized the hyperglycemia-induced activation of caspase-3 (to 140% of normal values) while re-institution of GC after six months of PC had no significant effect on the activation of caspase-3 NF-kB activity was 2.5-fold higher in diabetic rats kept in PC than in normal rats. Re-institution of GC after 2 months of PC partially reversed this increase (X-fold over normal), but GC after 6 months of PC had no effect. Initiation of GC soon after induction of diabetes in rats prevented activation of retinal caspase-3 and NF-kB. These results suggest that the process of activation of apoptosis execution enzyme and NF-kB in retina that starts before appearance of histopathological changes is not easily reversed by re-institution of GC. Characterization of the abnormalities responsible for the resistance of retinopathy to halt after re-institution of GC will help identify potential therapies for inhibition of progression of diabetic retinopathy.

Animals↗

PubMed2004

Phosphatidylserine efflux and intercellular fusion in a BeWo model of human villous cytotrophoblast.

Phosphatidylserine (PS) efflux characterizes cytotrophoblast apoptosis and differentiation. To evaluate whether PS externalization and intercellular fusion were secondary to apoptosis, BeWo cells were induced to differentiate by forskolin or undergo apoptosis by staurosporine. PS externalization was measured by FITC-annexin V binding, and intercellular fusion was quantified by counting nuclei in syncytial cells. During forskolin treatment, vanadate decreased PS efflux by 78.0 per cent from 68.0 [5.3] (mean [SD]) to 15.0 [8.8] Lum (x10(3)) (P<0.001), whereas Z-VAD-fmk had no effect (66.5 [7.3]). Vanadate decreased intercellular fusion from 78.1 per cent [4.1] fusion in uninhibited cultures to 23.4 per cent [2.5], compared with 10.0 per cent [1.7] in media alone. Z-VAD-fmk did not affect fusion (80.4 per cent [6.8]). Staurosporine induced PS efflux was not affected by vanadate (69.6 [5.5] Lum x10(3)), but was inhibited 87.8 per cent by Z-VAD-fmk; from 71.5 [6.2] to 8.7 [3.6] Lum (x10(3)) (P<0.001). Apoptosis was measured by the TUNEL and COMET assays, lamin B fragmentation, activation of procaspase 3, mitochondrial membrane potential, and release of mitochondrial cytochrome c and apoptosis inducing factor. There was no indication of apoptosis associated with differentiation. Thus, PS efflux and intercellular fusion occurred through a vanadate-sensitive mechanism that was independent of apoptosis.

Amino Acid Chloromethyl Ketones↗

PubMed2004

Alemtuzumab (Campath-1H) in allogeneic stem cell transplantation: where do we go from here?

Alemtuzumab (Campath-1H) has been widely used for T-cell depletion following both conventional and reduced-intensity conditioning allografts. We studied the impact of alemtuzumab used in vivo and in vitro on infections, immune reconstitution, and allograft outcome. The use of alemtuzumab in vivo following reduced-intensity conditioning and unrelated donor conventional transplantation was associated with durable engraftment and significant reduction in graft-versus-host disease (GVHD) but at the cost of impaired immune reconstitution and increased infectious complications. Alemtuzumab exposure in vitro was associated with durable engraftment and reduced GVHD following conventional transplants without affecting immune recovery to the same extent. Improved results were obtained following a further reduction in the alemtuzumab dose in vitro from 20 mg to 10 mg. Subsequent pharmacokinetic studies on alemtuzumab demonstrated that the antibody persisted at a higher concentration at the time of transplant and for at least 2 months thereafter when used in vivo compared to persistence for less than 30 days when used at 20 mg in vitro. In this context; an antibody with a shorter half-life, like the original rat CD52 antibody Campath-1G, would be preferable. Otherwise, our cumulative experience with alemtuzumab suggests that better results might be achieved by tailoring the dose and mode of antibody use to match the clinical situation. Further studies are needed to optimize the dose of alemtuzumab in vivo and in vitro, determined by the type of conditioning and the graft.

Alemtuzumab↗

PubMed2004

Influence of cytomegalovirus (CMV) sero-positivity on CMV infection, lymphocyte recovery and non-CMV infections following T-cell-depleted allogeneic stem cell transplantation: a comparison between two T-cell depletion regimens.

We compared the incidence and outcome of preemptively treated cytomegalovirus (CMV) infection, lymphocyte recovery and non-CMV infections between two different TCD modalities, one employing CD34+ selection and T-cell add-back (TCAB), preceded by Campath-1H in vivo (CD34+/TCAB group, n=29), and the other using grafts incubated with Campath-1H in vitro (Campath-1H in vitro group, n=32). The probabilities of CMV reactivation and recurrence were 67 and 83.6% in the CD34+/TCAB group and 42.9 and 20% in the Campath-1H group (P=0.07 and 0.02). Donor sero-positivity reduced CMV reactivation in the Campath-1H group, but not in the CD34+/TCAB group. The durations of positive PCR/antigenemia positivity and antiviral therapy were also significantly longer in the CD34+/TCAB group. However, only two patients developed CMV disease in each group. The mean absolute lymphocyte counts (x 10(9)/l) at 30 days (0.27 vs 0.4, P=0.03) and 100 days (0.77 vs 1.4, P=0.01) were significantly lower in the CD34+/TCAB group along with a higher incidence of non-CMV infections in CMV at-risk patients, but not in the CMV low-risk group. These findings suggest that the modality of TCD should be tailored according to the CMV risk status, and CMV sero-positive patients should receive a less extensively T-cell-depleted graft and a CMV sero-positive graft if possible.

Adoptive Transfer↗

PubMed2004

Enterovirus infections following T-cell depleted allogeneic transplants in adults.

Anecdotally, enteroviruses have been reported to cause serious complications post BMT, but the exact impact of these viruses in the post transplant period has not been reported. We prospectively evaluated stool, urine and throat samples for enteroviruses by viral culture together with relevant body fluids by RT-PCR in 64 allograft recipients receiving grafts T-cell depleted by Campath-1H, following both conventional and reduced-intensity conditioning. Seven patients (10.4%) developed nine episodes of enterovirus infections at a median of 146 days post transplant. Four episodes were associated with symptomatic illnesses, which could be attributable to enteroviruses. There was no mortality directly related to enteroviruses. There was no correlation between dose and mode of Campath-1H use, lymphocyte recovery, IgG and IgA levels and enterovirus isolation. Although enteroviruses tended to be more frequent in TBI-based conventional conditioning recipients, the only significant risk factor for enterovirus infection was unrelated donor graft. The low incidence of the severe enterovirus infections could have been related to a low lymphocyte count in this cohort in the absence of GVHD, particularly CD4+ count, which has been implicated in tissue damage in experimental animals. Further studies are needed to define its impact in different allograft settings.

Adolescent↗

PubMed2004

Neurological complications following alemtuzumab-based reduced-intensity allogeneic transplantation.

We report the incidence, characteristics and outcome of neurological complications occurring following reduced-intensity conditioning (RIC) in 85 patients who received a related/unrelated donor stem cell transplantation following therapy with alemtuzumab, fludarabine and melphalan. Six patients (probability 8.9%) developed severe neurological complications at a median of 151 days (24-334 days). Five of them presented with progressive peripheral sensori-motor radiculo-neuropathy and/or myelitis, preceded by one or more viral reactivation/infection. Despite treatment with immunoglobulins/plasmapheresis/steroids, four died of respiratory failure due to progressive peripheral neurophathy. Viral infection was identified as the only risk factor for the development of neurological complications. Patients who are treated with alemtuzumab-based RIC may have a lower risk of developing regimen-related neurological complications, but are more susceptible to develop peripheral radiculo-neuropathy or myelitis. This phenomenon may be possibly related to viral infection associated with delayed immunological recovery or immunological dysregulation caused by alemtuzumab-induced T-cell depletion.

Adolescent↗

PubMed2004

A randomised study comparing peripheral blood progenitor mobilisation using intermediate-dose cyclophosphamide plus lenograstim with lenograstim alone.

We conducted a prospective randomised study to compare the efficiency of out-patient progenitor cell mobilisation using either intermediate-dose cyclophosphamide (2 g/m(2)) and lenograstim at 5 micrograms/kg (Cyclo-G-CSF group, n=39) or lenograstim alone at 10 micrograms/kg (G-CSF group, n=40). The end points were to compare the impact of the two regimens on mobilisation efficiency, morbidity, time spent in hospital, the number of apheresis procedures required and engraftment kinetics. Successful mobilisation was achieved in 28/40 (70%) in the G-CSF group vs 22/39 (56.4%) for Cyclo-G-CSF (P=0.21). The median number of CD34+ cells mobilised was 2.3 x 10(6)/kg and 2.2 x 10(6)/kg for G-CSF and cyclo-G-CSF arms following a median of two apheresis procedures. Nausea and vomiting and total time spent in the hospital during mobilisation were significantly greater after Cyclo-G-CSF (P<0.05). Rapid neutrophil and platelet engraftment was achieved in all transplanted patients in both groups. In conclusion, G-CSF at 10 micrograms/kg was as efficient at mobilising progenitor cells as a combination of cyclophosphamide and G-CSF with reduced hospitalisation and side effects and prompt engraftment. When aggressive in-patient cytoreductive regimens are not required to both control disease and generate progenitor cells, the use of G-CSF alone appears preferable to combination with intermediate-dose cyclophosphamide.

Adjuvants, Immunologic↗

PubMed2004

Detection and characterization of HIV type 2 in Calcutta, India.

Since the first report of HIV/AIDS in India in 1986, continuous serosurveillance has been undertaken in all Indian states. Recently, five cases of HIV-2 infection have been detected in Calcutta, situated in the eastern part of India. The full-length envelope gene (2.5 kb) of one of the strains was amplified, cloned, and sequenced. Phylogenetic analysis of the Calcutta HIV-2 envelope revealed a close relatedness to the HIV-2 Rod sequence isolated in offshore Senegal. This strain, however, showed a genetic diversity of 13.5% to other Indian HIV-2 isolates.

Adult↗

PubMed2004

Improved survival in steroid-refractory acute graft versus host disease after non-myeloablative allogeneic transplantation using a daclizumab-based strategy with comprehensive infection prophylaxis.

Approximately 15% of patients undergoing non-myeloablative allogeneic haematopoietical cell transplantation (NMHCT) develop steroid-refractory acute-graft versus host disease (aGVHD), a usually fatal complication. We encountered 18 cases of steroid-refractory aGVHD in 146 patients, undergoing NMHCT from a related human leucocyte antigen-compatible donor following cyclophosphamide/fludarabine-based conditioning. Our initial cohort of steroid-refractory aGVHD patients treated with antithymocyte globulin (ATG) and mycophenolate mofetil (regimen-1: n = 6) had high GVHD-related mortality. Therefore, we investigated an alternative strategy for subsequent patients developing this complication (regimen-2: n = 12), consisting of daclizumab (alone or combined with infliximab/ATG) and targeted broad spectrum antibacterial and aspergillus prophylaxis in conjunction with rapid tapering of steroids to minimize opportunistic infections. In a retrospective analysis, patients receiving regimen-2 were significantly more likely to have complete resolution of GVHD compared with those receiving regimen-1 [12/12 (100%) vs. 1/6 (17%); P < 0.001]. When compared with those receiving regimen-1, regimen-2 patients also had a higher probability of survival at day 100 (100% vs. 50%) and day 200 (73% vs. 17%) post-transplant, and improved overall survival (median 453 d vs. 42 d from aGVHD onset; P < 0.0001). GVHD-related mortality was 89% for regimen-1 patients vs. 17% for regimen-2 patients (P < 0.0001). These data suggest that a co-ordinated approach using immunoregulatory monoclonal antibodies, pre-emptive antimicrobial therapy and judicious steroid withdrawal can dramatically improve outcome in steroid-refractory aGVHD.

Adolescent↗

PubMed2004

The broad autism phenotype: findings from an epidemiological survey.

This study aimed to determine if relatives of children with autism and less severe pervasive developmental disorders (PDDs) have higher rates of various components of the broad autistic phenotype. Psychiatric and medical disorders were investigated. Parents of children with PDDs were selected from an epidemiological survey and compared with parents of control children with non-autistic developmental problems. Rates of abnormalities and disorders were compared in relatives of 79 cases and 61 controls. Medical and autoimmune disorders in both groups were endorsed by few relatives. Specific developmental disorders were commoner in parents of controls. Depression and anxiety were significantly more prevalent in mothers of children with PDDs. Significantly more PDD children had at least one first-degree relative with anxiety and one second-degree relative with OCD. PDDs were commoner in first-degree relatives. The implications of the findings for the definition of the broad phenotype of autism are discussed.

Adult↗