Successful management of pregnancy-associated severe aplastic anemia.
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Biomedical subjects
Publications and source records attributed to Neelam Varma.
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Renal transplantation may be complicated by persistent fever and cytopenia. Bone marrow examination, though painful and invasive, may be of value because it can be performed in most peripheral hospitals, and the results are rapidly available. In a retrospective analysis, clinical records, marrow aspirates, and trephine biopsies were assessed to determine the indications for bone marrow examination and the findings in 132 patients over a 9-year period. In 7 of 61 (11%) patients with fever, a specific infection or a malignancy was identified, and hypocellularity was seen in 85% of cases. Nutritional deficiency with megaloblastosis or diminished iron stores was noted in 29% of cases. Malignancies were relatively infrequent (3%). Overall, in 12% of the cases, bone marrow examination provided useful information. Examination of the bone marrow may be a useful diagnostic test in pyrexia of unknown origin and cytopenia, particularly in developing countries.
BACKGROUND: Available evidence suggests that the regulation of telomerase activity primarily depends on the transcriptional control of the human telomerase reverse transcriptase (hTERT) gene. Although several activators and repressors of hTERT gene transcription have been identified, the exact mechanism by which hTERT transcription is repressed in normal cells and activated in cancer cells remains largely unknown. In an attempt to identify possible novel mechanisms involved in the regulation of hTERT transcription, the present study examined the role of Receptor Ck, a cell surface receptor specific for cholesterol, in the transcription of hTERT gene in normal human peripheral blood mononuclear cells. RESULTS: Activated Receptor Ck was found to down-regulate hTERT mRNA expression by repressing the transcription of c-myc gene. Receptor Ck-dependent signaling was also found to down-regulate the mRNA expression of the gene coding for the ligand inducible transcription factor, peroxisome proliferator-activated receptor gamma (PPARgamma). The ligand activation of PPARgamma resulted in the down-regulation of c-myc and hTERT mRNA expression. By using specific activator and inhibitor of protein kinase C (PKC), it was demonstrated that Receptor Ck dependent down-regulation of hTERT gene transcription involved inhibition of PKC. In addition, 25-hydroxycholesterol was found to contribute to the transcriptional regulation of hTERT gene. CONCLUSION: Taken together, the findings of this study present evidence for a molecular link between cholesterol-activated Receptor Ck and hTERT transcription, and provide new insights into the regulation of hTERT expression in normal human peripheral blood mononuclear cells.
Posttransplant lymphoproliferative disorders (PTLD) are commonly caused by Ebstein-Barr Virus infection. The role of hepatitis C virus (HCV) in the genesis of lymphomas has been recognized recently. We report a HCV infected renal transplant recipient who developed PTLD 11 months after transplantation. Reduction of immunosuppression led to disappearance of viremia and clearance of PTLD. This is the first such report in the world literature.
BACKGROUND AND OBJECTIVES: A large number of patients diagnosed with bone marrow failure syndromes (BMFS), comprising aplastic anaemia (AA) and myelodysplastic syndromes (MDS), remain aetiologically uncharacterized worldover, especially in resource constrained set up. We carried out this study to identify a few constitutional causes in BMFS patients attending a tertiary care hospital in north India. METHODS: Peripheral blood lymphocyte cultures were performed (with and without clastogens) in a cohort of 135 consecutive BMFS patients, in order to detect Fanconi anaemia (FA), Down's syndrome (+21), trisomy 8 (+8) and monosomy 7 (-7). RESULTS: Constitutional factors were detected in 17 (12.6%) patients. FA defect was observed in 24.07 percent (13/54), 16.66 percent (1/6) and 2.85 percent (1/35) paediatric aplastic anaemia, paediatric MDS and adult MDS patients respectively. Down's syndrome was detected in 5.00 percent (2/40) adult aplastic anaemia patients. None of the patients revealed trisomy 8 or monosomy 7. INTERPRETATION AND CONCLUSION: Presence of an underlying factor determines appropriate management, prognostication, family screening and genetic counselling of BMFS patients. Special tests required to confirm or exclude constitutional aetiological factors are not available to majority of the patients in our country. Diepoxybutane (DEB) test yielded better results than mitomycin C (MMC) test in our experience.
French-American-British classification for leukemias had been widely accepted due to its objectiveness and good reproducibility. WHO classification of leukemias was formulated in 1997 with a purpose of further enhancing the objectivity. However, the requirement of cytogenetics and immunophenotyping makes it difficult for many countries like India to put WHO classification in routine use. This study was carried to know the effectiveness of FAB classification in an era of technical advancement. A retrospective analysis of all acute leukemias over a period of 2 years was done. Out of total of 469 cases of acute leukemias, 193 were diagnosed as Acute Lymphoblastic Leukemia (ALL), 200 as Acute Myeloid Leukemia (AML), and 76 cases diagnosed as Acute Leukemia, cytochemically undifferentiated. Hence, only 16% of all leukemias remained unclassifiable. Subclassification of AML cases revealed a much higher percentage of AML-M3, as compared to western literature. In conclusion, FAB classification, based on morphology and simple cytochemical stains, remains effective enough, although cytogenetics and immunophenotyping can add to diagnostic accuracy in some cases.
Pure red cell aplasia sometimes accompanies thymoma. Herein we report a PRCA patient with malignant thymoma. Only two Indian cases of PRCA with malignant thymoma have been reported so far and six cases in the world literature, to the best of our knowledge. This paper describes a malignant thymoma in a 40 year old male who later on developed pure red cell aplasia 7 months after thymectomy.
Aplastic anemia is characterized by pancytopenia with hypoplastic bone marrow. Various factors including viral infections have been implicated as the precipitating factors. Human parvovirus B19 has been associated with red-cell aplasia, leukopenia, and thrombocytopenia. The present study was carried out to determine the role of parvovirus B19 in aplastic anemia patients. Twenty-seven aplastic anemia patients and 20 healthy controls were tested for the presence of parvovirus B19 infection by detecting parvovirus B19-specific IgM by ELISA and viral DNA by PCR. Parvovirus B19 IgM and viral DNA were detected in significantly higher numbers of patients in comparison to the controls (40.7% vs. 5%, P < 0.01; 37% vs. 0%, P < 0.001, respectively). The presence of parvovirus DNA in aplastic anemia patients indicates active or recent infection. However, more studies are needed to explore the mechanism of bone-marrow aplasia due to human parvovirus B19 infection.
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A total of 239 cases of Down syndrome (DS) were seen in the genetic clinic between 1992 and 2003, of which of 15 had hematological manifestations at presentation. These comprised 4 cases of transient myeloproliferative disorder (TMD), 3 cases of TMD/acute leukemia, 4 cases of acute leukemia (AL), 2 of dual deficiency anemia, and 1 case each of myelofibrosis and idiopathic thrombocytopenia. This study emphasizes the fact that an abnormal hemogram in a DS patient does not necessarily indicate AL/TMD, as a considerable number of the cases in this study had other hematological abnormalities. TMD can be differentiated from acute leukemia only on follow-up.
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Hairy-cell leukemia-variant (HCL-V) is a rare B-cell disorder which accountsfor 10% of HCL cases. The main features are splenomegaly, lymphocytosis and cytopenias without monocytopenia. The circulating cells have a morphology intermediate between prolymphocytes and hairy cells. The immunophenotype shows a mature B-cell phenotype with expression of B-cell antigens CD11c and CD103 but unlike typical hairy cell the cells are negative for CD25. The histology of bone marrow and spleen shows a pattern of infiltration similar to that in HCL. We present a case of HCL-V in a 66-year-old male. The bone marrow findings, immunophenotypic profile and electron microscopic features are described. The patient underwent splenectomy which also revealed infiltration by leukemia. Patients are resistant to alkylating agents and alpha-interferon (á-IFN). Splenectomy may be beneficial for long-lasting partial responses in some of the patients and is a good palliative treatment.
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Combined liver and kidney transplantation is the ideal treatment for patients with end-stage renal failure secondary to primary hyperoxaluria and systemic oxalosis, with a functioning liver providing replacement of the deficient enzyme and a functioning kidney providing the route of excretion for the oxalate crystals. Pancytopenia from bone marrow infiltration of oxalate crystals is a rare complication of primary hyperoxaluria, and its reversal following transplant has not been described. We report the first case of pancytopenia from marrow infiltration by oxalate crystals reversing following a successful kidney transplant alone. Although kidney alone transplants do not provide the best chance of survival or quality of life as compared to a combined kidney and liver transplant, a well functioning kidney transplant is able to take care of the systemic oxalate load and ameliorate, at least for a period of time, the systemic complications of oxalosis.
This study assessed the efficacy of stanozolol in acquired aplastic anaemia (AA) in children, who were unable to opt for alternative therapies due to financial constraints. It uses a retrospective case-record analysis. Medical records of children with AA who received stanozolol were analysed. Their clinical and haematological profile was studied and the outcome assessed. Forty-nine children with acquired AA received stanozolol (1 mg/kg/day) in the period between January 1991 and December 2000. The median age at diagnosis was 9 years (range: 1.5-13). Thirteen (26.5%) defaulted therapy after periods of 1-4 weeks and 11 (22.4%) died within 2 months of starting treatment. Ten (20.4%) responded, whilst 15 (30.6%) did not. None of the patients with very severe AA responded, two (28.6%) with severe AA responded and eight (38%) with non-severe AA had a response. All responses were partial except one. Median time taken to respond was 11 weeks (range: 1-20). Responders were treated for a median duration of 25 weeks (range: 13-155), and they were followed-up for a median duration of 25 months (range: 3-144). Eight (80%) responders were off drugs for a median duration of 18 months (range: 6-110). Stanazolol is ineffective for severe and very severe AA. As it induced remission in 38% of our patients with non-severe AA, it can be tried in this group if other methods of treatment are unaffordable or have failed. A short history of presentation (< 3 months) and > or = 70% lymphoid cells in marrow correlated with poor prognosis.