Biomedical subjects

A Srivastava

Publications and source records attributed to A Srivastava.

At least 55 records · Page 3Linked to original sources

PubMed2005

The discriminant power of bleeding history for the diagnosis of type 1 von Willebrand disease: an international, multicenter study.

OBJECTIVE: The aim of this study was the validation of the criteria defining a significant mucocutaneous-bleeding history in type 1 von Willebrand disease (VWD). SUBJECTS AND METHODS: To avoid selection bias, 42 obligatory carriers (OC) of type 1 VWD were identified from a panel of 42 families with type 1 VWD enrolled by 10 expert centers. OC were identified by the presence of an offspring and another first degree relative with type 1 VWD (affected subjects, AFF). A standardized questionnaire was administered to evaluate hemorrhagic symptoms at the time of first examination, using a bleeding score ranging from 0 (no symptom) to 3 (hospitalization, replacement therapy, blood transfusion). Sensitivity, specificity, diagnostic likelihood ratios, positive and negative predictive values for the diagnosis of type 1 VWD were calculated from the data collected in OC and in 215 controls. RESULTS: Having at least three hemorrhagic symptoms or a bleeding score of 3 in males and 5 in females was very specific (98.6%) for the bleeding history of type 1 VWD, although less sensitive (69.1%). None of the misclassified OC had life-threatening bleeding episodes after diagnosis. CONCLUSIONS: We suggest that the use of a standardized questionnaire and bleeding score may be useful for the identification of subjects requiring laboratory evaluation for VWD.

Adult↗

PubMed2005

The nutrient intakes of mothers of low birth weight babies - a comparison of ethnic groups in East London, UK.

The objective of this paper was to compare the nutrient intakes of mothers of different ethnic origins after they had given birth to a low birth weight (LBW) baby (< 2.5 kg). A total of 165 participants from East London, UK completed a prospective 7-day diet diary using household measures, between 8 and 12 weeks post-partum. The data were originally collected as baseline data prior to two separate nutrition intervention studies and were combined and re-interrogated for the purpose of this paper. Folate and iron intakes were low in all ethnic groups compared to the Reference Nutrient Intakes (RNI). Half did not meet the RNI for folate and 88% did not meet the RNI for iron. Nearly a quarter of the group did not achieve the Lower Reference Nutrient Intake (LRNI) for iron. The mean vitamin D and calcium intakes were significantly different between the ethnic groups (P = 0.007, P = 0.001, respectively). African women had the highest vitamin D intakes (4.72 microg d(-1)) and Caucasians and Asians the lowest (2.4 microg d(-1)). Caucasians had the highest calcium intakes (780 mg d(-1)) and Africans the lowest (565 mg d(-1)). Over two-thirds of African, Asian and African-Caribbean women did not meet the RNI for calcium. Thirty-one per cent of Africans did not meet the LRNI for calcium. Our data show a high prevalence of inadequate nutrition among women who deliver LBW babies with differences in nutrient intake between ethnic groups. This information can be used to target specific appropriate dietary advice to ethnic minorities for the prevention or repetition of LBW.

Adult↗

PubMed2005

Unidirectional whole body turning: a new lateralising sign in complex partial seizures.

BACKGROUND: The lateralising significance of unidirectional whole body turning in patients with complex partial seizures (CPS) arising from the temporal lobe was evaluated. METHODS: A total of 330 patients undergoing long term video-EEG study were included. "Unidirectional whole body turning" was defined as rotation of the trunk, head, and limbs by >90 degrees and lasting >10 s. EEG correlates, MRI, and SPECT findings were compared and outcome after surgery was noted for patients with follow up data for >1 year. RESULTS: Unidirectional whole body turning was observed in 13 patients with a mean age of 18+/-8 years. Concordance of the side of whole body turning with the EEG focus and MRI findings was observed in 11 of the 13 patients (84.7%) and in 26 of 28 seizures (92.8%). The six patients who underwent temporal lobectomy or resection of lesion, opposite to the direction of body turning, had good seizure outcome. CONCLUSION: Unidirectional whole body turning is a new lateralising sign in temporal lobe CPS with good predictive value for epileptogenic focus contralateral to the direction of turning.

Adolescent↗

PubMed2005

Cytochrome P4501A1 and glutathione S transferase gene polymorphisms in patients with aplastic anemia in India.

The etiology of acquired aplastic anemia (AA) in most patients remains unclear. It is believed that patients with a reduced ability to detoxify environmental toxins are at increased risk of developing AA. Cytochrome P450 (CYP450) and glutathione S transferase (GST) are the major phase I and phase II xenobiotic-metabolizing enzymes. We analyzed the impact of the polymorphisms in CYP4501A1 and GSTM1 and GSTT1 genes on the susceptibility and disease severity in 200 patients with AA and compared the frequency with the normal population. There was a significantly increased frequency of the CYP1A1m4 allele in AA patients compared with normal controls (odds ratio = 3.01; 95% confidence interval 1.76-5.17; p = 0.00001). None of the other CYP1A1 genotypes or the GST genotypes were significantly different between AA patients and controls. Altered metabolism of benzo(a)pyrene due to the polymorphism in the CYP1A1 gene might be an etiologic factor in the increased incidence of AA in these patients. The CYP1A1m4 allele may play a role in determining the risk of AA in India.

Adolescent↗

PubMed2004

Hematological and molecular remission with combination chemotherapy in a patient with PLZF-RARalpha acute promyelocytic leukemia (APML).

Patients with acute promyelocytic leukemia (APML) with the t(11;17) translocation usually respond poorly to all-trans retinoic acid (ATRA) and chemotherapy. We describe a patient with promyelocytic leukemia zinc finger/retinoic acid receptor alpha (PLZF/RARalpha) APML who was treated with combination chemotherapy after poor response to arsenic trioxide. He achieved hematological remission in 4 weeks followed by achievement of molecular remission in 8 weeks. Four cycles of consolidation chemotherapy followed by four cycles of maintenance therapy were given over a period of 9 months. At a follow-up of 32 months after achieving hematological remission, he continues to remain in hematological and molecular remission with normal blood parameters and negative reverse transcriptase polymerase chain reaction (RT-PCR) results. Combination chemotherapy can achieve sustained remission in patients with PLZF/RARalpha APML.

Adult↗

PubMed2004

Effect of glycosylation on the structure of Erythrina corallodendron lectin.

The three-dimensional structure of the recombinant form of Erythrina corallodendron lectin, complexed with lactose, has been elucidated by X-ray crystallography at 2.55 A resolution. Comparison of this non-glycosylated structure with that of the native glycosylated lectin reveals that the tertiary and quaternary structures are identical in the two forms, with local changes observed at one of the glycosylation sites (Asn17). These changes take place in such a way that hydrogen bonds with the neighboring protein molecules in rECorL compensate those made by the glycan with the protein in ECorL. Contrary to an earlier report, this study demonstrates that the glycan attached to the lectin does not influence the oligomeric state of the lectin. Identical interactions between the lectin and the non-covalently bound lactose in the two forms indicate, in line with earlier reports, that glycosylation does not affect the carbohydrate specificity of the lectin. The present study, the first of its kind involving a glycosylated protein with a well-defined glycan and the corresponding deglycosylated form, provides insights into the structural aspects of protein glycosylation.

Binding Sites↗

PubMed2004

Carbon nanotube filters.

Over the past decade of nanotube research, a variety of organized nanotube architectures have been fabricated using chemical vapour deposition. The idea of using nanotube structures in separation technology has been proposed, but building macroscopic structures that have controlled geometric shapes, density and dimensions for specific applications still remains a challenge. Here we report the fabrication of freestanding monolithic uniform macroscopic hollow cylinders having radially aligned carbon nanotube walls, with diameters and lengths up to several centimetres. These cylindrical membranes are used as filters to demonstrate their utility in two important settings: the elimination of multiple components of heavy hydrocarbons from petroleum-a crucial step in post-distillation of crude oil-with a single-step filtering process, and the filtration of bacterial contaminants such as Escherichia coli or the nanometre-sized poliovirus ( approximately 25 nm) from water. These macro filters can be cleaned for repeated filtration through ultrasonication and autoclaving. The exceptional thermal and mechanical stability of nanotubes, and the high surface area, ease and cost-effective fabrication of the nanotube membranes may allow them to compete with ceramic- and polymer-based separation membranes used commercially.

Equipment Design↗

PubMed2004

Synthesis of galactopyranosyl amino alcohols as a new class of antitubercular and antifungal agents.

The galactopyranosyl amino alcohols (3-16) were synthesised by regioselective oxirane ring opening of compound 2 with variety of amines and screened for antitubercular and antifungal activities. One of the compounds (16) showed potent activity against Mycobacterium tuberculosis H37 Rv in vitro and also displayed activity in MDR TB. The compound (16) was found to be superior to ethambutol clinically used anti TB drug in in vitro screen.

Amino Alcohols↗

PubMed2004

Predictors of survival end points in patients with cancer of the cervix on long-term follow-up: inferences and implications from an audit of patients treated with a specific radiotherapy protocol.

AIMS: An audit of patients with cancer of the cervix treated with a specified protocol of external beam radiotherapy (EXRT) followed by intracavitary brachytherapy (ICBT) was carried out to determine the prognosticators for major survival end points. MATERIALS AND METHODS: Patients treated between 1991 and 2003 with a uniform protocol of EXRT (50 Gy/25 fractions/5 weeks) followed by high-dose-rate ICBT (18 Gy/3 fractions/3 weeks) were selected from the database. Various clinical and treatment parameters were evaluated for extent of locoregional response at completion of EXRT, namely absence or presence of gross residual tumour (AGRT and PGRT, respectively) and survival end points. These included locoregional disease-free survival (LDFS), disease-free survival (DFS) and overall survival (OS). RESULTS: Of the 157 evaluable patients, 145 (92%) belonged to FIGO stages II and III. Eighty-three (53%) at completion of EXRT had AGRT, which was influenced by age and gross tumour features. The estimated 10-year LDFS, DFS and OS were 38.6%, 33.1% and 38.5%, respectively. Factors significant on univariate analysis for these survival end points were EXRT duration, ICBT time, overall treatment time (OTT) and EXRT response. On multivariate analysis, AGRT to EXRT, an OTT of < or = 67 days, and patients older than 50 years were the significant favourable determinants for all the above survival end points. CONCLUSION: The audit highlights that younger people, especially those with bulky tumours that determine response to EXRT, are poor prognosticators for survival end points. They could perhaps benefit from treatment intensification regimens using chemoradiotherapy, provided that OTT is not unduly prolonged.

Adult↗

PubMed2004

Selective use of mycophenolate mofetil in renal transplant patients in Indian scenario.

PURPOSE: Although mycophenolate mofetil (MMF) has emerged as a valuable immunosuppressive in renal transplantation, its high cost demands that it be used selectively. MATERIALS AND METHODS: This retrospectively study included 55 renal transplant patients on MMF for rescue therapy after treatment of acute vascular rejection (n = 45), acute/chronic liver disease with elevated transaminases (n = 4), early chronic rejection (n = 2), cyclosporine toxicity (n = 3), and cyclosporine-induced hemolytic-uremic syndrome (n = 1). The patients were given 1.5 to 2 g MMF in divided doses for at least 6 months, depending upon the tolerability, adverse effects, and finances, and followed for 1 year. The patients on MMF following treatment of acute rejections were compared with controls who received azathioprine-based triple immunosuppression after treatment of an acute rejection episode. RESULTS: The incidence of recurrent acute rejection in the first year was 18% in the MMF group compared to 42% in the control group (P < .005). The serum transaminases in the acute/chronic liver disease group reached normal levels at 3 to 6 months. The serum creatinine remained stable for a mean duration of 8 months in the early chronic rejection patients. The patients with cyclosporine toxicity showed stable graft function on low-dose cyclosporine. The patient with hemolytic-uremic syndrome showed stable graft function for 4 years. The MMF-based triple regimen is two times more expensive than an azathioprine-based regimen. CONCLUSION: MMF significantly decreases the recurrence of acute rejection. It is a good alternative agent in special situations like acute/chronic liver diseases with elevated transaminases, early chronic rejection, cyclosporine toxicity, and cyclosporine-induced hemolytic-uremic syndrome. Because of the high cost it should be used selectively in our population.

Acute Disease↗

PubMed2004

Infections among allogeneic bone marrow transplant recipients in India.

SUMMARY: Infections are a major cause of morbidity and mortality in patients undergoing high-dose therapy and allogeneic bone marrow transplantation (BMT) despite prophylaxis, use of growth factors and newer antimicrobial drugs. We report the clinical profile of infections among 297 patients who underwent 304 allogeneic transplants between 1986 and December 2001. All patients developed febrile neutropenia. There were 415 documented infections among 304 transplants. This included bacterial (34.9%), viral (42.9%), fungal (15.9%) and other infections (6.3%) including tuberculosis. Bacterial pathogens were mainly Gram-negative bacteria (80%) as compared to Gram-positive (20%) bacteria. The common Gram-negative bacteria were nonfermenting Gram-negative bacteria (NFGNB) (24.9%), Pseudomonas (17.9%), Escherichia coli (17.9%) and Klebsiella (9.7%). The major source of positive cultures was blood (53.7%) followed by urine (25.5%) and sputum (8.9%). In all, 133/304 (43.7%) transplants had 178 documented viral infections. The common viral infections were due to cytomegalovirus, herpes group of viruses and transfusion-related hepatitis; and 60/304 (19.7%) transplants had 66 documented fungal infections. Common fungi included Aspergillus species (69.7%), Candida (22.2%) and Zygomycetes (8.1%). Tuberculosis was documented in 2.3% of the transplants. Catheter infections were suspected or documented in 7.8% of the transplants (24/304). The incidence of infections in this series from developing countries is not significantly different from reports from the West. Bone Marrow Transplantation (2004) 33, 311-315. doi:10.1038/sj.bmt.1704347 Published online 1 December 2003

Adult↗

PubMed2004

Improved transduction of primary murine hepatocytes by recombinant adeno-associated virus 2 vectors in vivo.

Adeno-associated virus 2 (AAV) vectors are currently in use in Phase I/II clinical trials for gene therapy of cystic fibrosis and hemophilia B. Although 100% of murine hepatocytes can be targeted by AAV vectors, the transgene expression is limited to approximately 5% of hepatocytes. Since the viral genome is a single-stranded DNA, and single strands of both polarities are encapsidated with equal frequency, it has been suggested that failure to undergo DNA strand-annealing accounts for the lack of efficient transgene expression. We and others, on the other hand, have proposed that failure to undergo viral second-strand DNA synthesis attributes to the observed low efficiency of transgene expression. We have previously documented that a cellular protein, designated FKBP52, when present in phosphorylated forms, inhibits the viral second-strand DNA synthesis, and consequently, limits transgene expression in nonhepatic cells, whereas unphosphorylated forms of FKBP52 have no effect. To further evaluate whether phosphorylated FKBP52 is also involved in regulating AAV-mediated transgene expression in murine hepatocytes, we generated transgenic mice overexpressing the cellular T-cell protein tyrosine phosphatase (TC-PTP) protein, known to catalyze dephosphorylation of FKBP52, as well as mice deficient in FKBP52. We demonstrate here that dephosphorylation of FKBP52 in TC-PTP transgenic (TC-PTP-TG) mice, and removal of FKBP52 in FKBP52-knockout (FKBP52-KO) mice results in efficient transduction of murine hepatocytes following tail-vein injection of recombinant AAV vectors. We also document efficient viral second-strand DNA synthesis in hepatocytes from both TC-PTP-TG and FKBP52-KO mice. Thus, our data strongly support the contention that the viral second-strand DNA synthesis, rather than DNA strand-annealing, is the rate-limiting step in the efficient transduction of hepatocytes, which should have implications in the optimal use of recombinant AAV vectors in human gene therapy.

Animals↗

PubMed2004

Treatment of children with newly diagnosed acute promyelocytic leukemia with arsenic trioxide: a single center experience.

A total of 11 children (five males and six females) with hypergranular type of acute promyelocytic leukemia (APML) were treated with intravenous arsenic trioxide (As(2)O(3)) between December 1998 and October 2003. Eight cycles of As(2)O(3) (0.15 mg/kg/day) were administered (induction, consolidation and six cycles of maintenance) over a period of 12 months. The median WBC count at diagnosis was 3400/mm(3) (range: 800-9800). In all, 10 patients (91%) achieved hematological remission at a mean duration of 48 days (range: 41-60) with all 10 patients achieving molecular remission at a median duration of 81 days (range: 64-109). Toxicity was minimal with leukocytosis in six patients, ichthyosis and hyperpigmentation of skin in five and mild peripheral neuropathy in one patient. One patient who relapsed 6 months after completing therapy achieved a second hematological and molecular remission with As(2)O(3). With a median follow-up of 30 months (range: 4-62), the overall (OS) survival is 91% with a relapse-free survival (RFS) of 81%. As(2)O(3) achieves hematological and molecular remission in majority of newly diagnosed children with APML with minimal toxicity, but long-term follow-up is required to evaluate late effects of As(2)O(3) and study the minimum dose and duration required for a sustained remission.

Adolescent↗

PubMed2004

External fixators in haemophilia.

External fixators (EF) are not commonly used for patients with haemophilia. We describe the use of EF (Ilizarov, AO- uni- and bi-planar fixators and Charnley clamp) in nine patients (mean age: 19.2 years; range: 9-37) with haemophilia for the following indications - arthrodesis of infected joints, treatment of open fractures and osteoclasis. EF required an average of nine skin punctures [range: 4-17 were maintained for a period of 15 weeks (range: 8-29.5), without regular factor replacement, till bone healing was adequate and were removed with a single dose of factor infusion]. The mean preoperative factor level achieved was 85% (range: 64-102%). Much lower levels were subsequently maintained till wound healing. The average total factor consumption was 430 IU kg(-1) (range: 240-870), administered over a period of 17 days (range: 9-44). There were no major complications related to EF except in a patient who developed inhibitors. In conclusion, EF can be used safely in haemophilic patients who do not have inhibitors and does not require prolonged factor replacement.

Adolescent↗

PubMed2004

Seizures among families of Indian probands with different epileptic syndromes.

OBJECTIVES: To investigate the contribution of hereditary factors in the causation of different epilepsy syndromes. MATERIAL AND METHODS: Occurrence of seizures among first- and second-degree relatives of 5628 Indian probands with epilepsy, and 3357 probands with non-epilepsy neurological disorders (who acted as control population) was documented. Syndromic concordance between epilepsy probands and affected relatives was investigated. RESULTS: Twenty percent epilepsy probands (1129) had affected relatives. Relatives of epilepsy probands were more often affected compared with relatives of non-epilepsy probands (OR: 3.4). Probands with some epilepsy syndromes more often had a positive family history. Relatives of younger probands were at greater risk of having epilepsy. Sibs were more often affected compared with other first- and second-degree relatives (OR: 1.3 and 4.6). Sibs having generalized epilepsies and syndromes and febrile convulsions (FC) were at greater odds of syndromic concordance with probands compared with second-degree relatives. Sibs and second-degree relatives having idiopathic/cryptogenic epilepsy had greater odds for concordance compared with those with symptomatic epilepsies. CONCLUSIONS: One-fifth of probands with all types of epileptic syndromes have family history of seizures. Familial risk of epilepsy correlated with the epilepsy syndrome among probands and their age at presentation. Risk of relatives being affected varied as a function of the relation with probands. Concordance of epilepsy syndromes varied both as a function of the epilepsy syndrome and relation with the probands.

Adolescent↗

PubMed2004

Informativeness of linkage analysis for genetic diagnosis of haemophilia A in India.

The objective of this study was to assess the frequency of factor VIII (FVIII) gene intron 1 and intron 22 inversions and the informativeness of polymorphic markers for the genetic diagnosis of patients with haemophilia A (HA). Fifty unrelated patients with HA were first assessed for the intron 1 and intron 22 inversion mutations. Inversion-negative families were then screened for the bi-allelic intragenic markers--intron 7 G-->A polymorphism, HindIII site in intron 19 and XbaI site in intron 22 and the multiallelic dinucleotide CA repeat alleles in introns 13 and 22. The extragenic, multiallelic VNTR DXS52 (st14) was also analysed. Intron 22 inversion mutation was found in 38% (n = 19) of all patients and 46% of those with severe HA. Intron 1 inversion was found in one (2%) patient. Of the 30 inversion-negative families, XbaI site polymorphism was the single most informative marker (70%, n = 21/30) followed by HindIII (60%, n = 18/30), intron 13 CA repeats (56.66%, n = 17/30), intron 22 CA repeats (50%, n = 15/30), DXS52 VNTR (23.33%, n = 7/30) and intron 7 G-->A polymorphism (6.66%, n = 2/30). The combined use of these markers was informative in 92% (n = 46/50) of HA families. Based on the informativeness of these markers a comprehensive algorithm has been proposed for genetic diagnosis of HA in India.

Chromosome Inversion↗

PubMed2004

Comprehensive care for haemophilia around the world.

Comprehensive haemophilia care has been defined as the continuing supervision of all medical and psychosocial factors affecting the person with haemophilia family. Services offered by haemophilia treatment centres (HTCs) adopting the comprehensive care model include establishing prophylaxis and other treatment protocols, development of psychosocial, education and research programme, maintenance of a patient registry, genetic and reference diagnostic services and orchestration and management of a wide variety of multidisciplinary interventions. Most centres practising this model of care are based in developed countries and can meet costs for plentiful treatment products through government or insurance-company funding. Not all the programmes are dependent on the level of product supply, however, and many have been supported in countries with emerging economies as part of national healthcare systems, particularly in relation to blood management. In this paper we present perspectives from different areas of the world on how to adopt, adapt and achieve economically appropriate models of comprehensive care.

Comprehensive Health Care↗

PubMed2004

Dose and outcome of care in haemophilia--how do we define cost-effectiveness?

Severe haemophilia (factor [F]VIII/FIX activity < 0.01 IU mL(-1)) is characterized by repeated haemarthroses resulting in severe arthropathy in adulthood. In 1958, Professor Nilsson in Sweden introduced prophylactic infusions with clotting factor concentrates at regular intervals in order to maintain clotting factor levels above 0.01 IU mL(-1) and to prevent bleeding. Since then, evidence of the long-term beneficial effects of prophylactic treatment for severe haemophilia has been increasing and it has become the recommended treatment strategy for children with severe haemophilia by both the World Health Organization and the US National Hemophilia Foundation Medical and Scientific Advisory Committee. However, the implementation of this recommendation has been hampered by issues of cost and venous access. The high costs of prophylaxis have largely prevented its use in major parts of the world. The question therefore is whether the current models of replacement of clotting factor concentrates, while certainly being effective, are also optimal. Can the data on outcome at different levels of factor replacement be used to assess their cost-effectiveness?

Adolescent↗