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Biomedical subjects

S Nand

Publications and source records attributed to S Nand.

At least 19 recordsLinked to original sources
PubMed2004

Lymphoproliferative disorders in chronic hepatitis C.

Chronic hepatitis C virus (HCV) infection is associated with the development of lymphoproliferative disorders (LPDs). The aim of this investigation was to determine the prevalence and characterization of monoclonal gammopathy and benign and malignant LPDs in individuals with chronic hepatitis C. A total of 233 subjects diagnosed with chronic hepatitis C (male/female ratio: 131/102, median age; 49 years) were studied. Serum and urine were examined for the presence of a monoclonal gammopathy. A bone marrow aspirate and biopsy was obtained in individuals with a monoclonal gammopathy. Thirty-two patients (13.7%, 32 of 233) had a monoclonal gammopathy; 75% of them were benign and were not associated with malignant disorders (24 of 32) while 25% were associated with malignant LPDs or a plasma cell disorder (eight of 32). Two additional subjects without monoclonal gammopathy were diagnosed as having a malignant LPDs. The prevalence of malignant LPDs/plasma cell disorder in individuals with HCV-induced chronic liver disease was 4.3%. No difference was found in terms of disease duration, HCV genotype, viral load, alanine aminotransferase level or histopathologic score between the subjects with or without a monoclonal gammopathy. The presence of mixed cryoglobulinaemia was strongly associated with the presence of an underlying malignant disorder. Hence a monoclonal gammopathy is found in 14% of patients with chronic hepatitis C and is associated with malignant B-cell LPD in more than a quarter of such patients. The prevalence of LPDs in individuals with HCV-induced chronic liver disease is greater than that of the normal healthy population.

Adult↗
PubMed2003

Herpes zoster during treatment with arsenic trioxide.

In vitro data suggest that arsenic compounds can suppress cell-mediated immunity by inducing apoptosis of T helper lymphocytes. We describe an occurrence of herpes zoster during treatment with arsenic trioxide (ATO) in two patients who were already in remission from acute promyelocytic leukemia and received ATO as consolidation treatment. During this complication, their leukocyte counts and differentials were within normal limits. Our report suggested the immunosuppressive effect of ATO in vivo. Both patients responded well to an oral antiviral. Clinicians should be aware of this complication during treatment with ATO since early antiviral treatment may help avoid complications including post-herpetic neuralgia.

2-Aminopurine↗
PubMed1999

A phase III comparison of high dose ARA-C (HIDAC) versus HIDAC plus mitoxantrone in the treatment of first relapsed or refractory acute myeloid leukemia Southwest Oncology Group Study.

The aim of this study is to determine whether the addition of mitoxantrone to high dose cytarabine improves the outcome of treatment in patients with relapsed or refractory acute myeloid leukemia (AML). One hundred and sixty-two eligible patients, 14-76 years of age, with AML either in first relapse or that failed to respond to initial remission induction therapy, with no CNS involvement were randomized to receive therapy with cytarabine 3 gm/M2 i.v. over 2 h every 12 h for 12 doses on days 1-6 (Arm I) (HIDAC); or HIDAC plus mitoxantrone 10 mg/M2 i.v. daily on days 7 9 (Arm II) (HIDAC + M). Patients achieving complete remission were treated with three courses of consolidation including HIDAC (Ara-C 3 gm/M2 i.v. 12 h days 1 3; 2 gm/M2 over age 50) alone (ARM I) or with mitoxantrone (10 mg/M2 i.v. day 1) (ARM II). Among 162 patients (81 HIDAC, 81 HIDAC + M) evaluated for induction toxicity, there were 10 (12%) induction deaths with HIDAC and 13 (17%) with HIDAC + M (2-tailed P = 0.65). Most early deaths were due to infection and/or hemorrhage. Among 162 patients evaluated for responses to induction therapy, 26/81 (32%) HIDAC and 36/81 (44%) HIDAC + M patients achieved complete remission (two-tailed P = 0.15). Although this difference was not statistically significant in univariate analysis, it was after adjusting for the effects of WBC and PMN percentage in multivariate analysis (P=0.013). Median survivals from study entry were 8 months (HIDAC) and 6 months (HIDAC + M); 2-tailed logrank P = 0.58. Among 48 patients registered for consolidation, the median disease-free survivals from that registration were 8 months with HIDAC and 11 months with HIDAC + M (P = 0.60). There were three treatment-related deaths during consolidation (1 HIDAC, 2 HIDAC + M), all due to infections. In this randomized trial, the addition of mitoxantrone to high-dose cytarabine was associated with a trend toward a higher CR rate. There was less evidence for an advantage in disease-free or overall survival, although any such conclusion is limited by the size of the study.

Acute Disease↗
PubMed1998

A phase II trial of interleukin-2 in myelodysplastic syndromes.

Patients with myelodysplastic syndromes (MDS) show a decrease in the number and function of natural killer (NK) cells, including lymphokine activated killer (LAK) cell activity. Interleukin-2 (IL-2) stimulates the proliferation and activity of these lymphocytes. Anecdotal clinical experience has shown haematological and cytogenetic improvement in myelodysplasia by low-dose IL-2 treatment. A total of 10 patients with MDS were treated with 1 million units of IL-2 subcutaneously daily for 12 weeks. Even though improvement in CD16+/CD56+ cell numbers was seen in a majority of the patients, the haematological status and transfusion requirements remained unchanged. There was minimal toxicity from this therapy.

Adult↗
PubMed1998

MR of leptomeningeal spinal and posterior fossa amyloid.

We report an unusual cause of leptomeningeal MR enhancement, amyloid, along the surfaces of the spinal cord and brain stem and in the spinal subarachnoid space, with sacral intradural and epidural deposition. Type I familial amyloid polyneuropathy may cause amyloid deposition along the leptomeninges of the spinal cord and brain in addition to the visceral organs and the peripheral somatic and autonomic nerves.

Adult↗
PubMed1997

Heparin-induced thrombocytopenia with thrombosis: incidence, analysis of risk factors, and clinical outcomes in 108 consecutive patients treated at a single institution.

Heparin-induced thrombocytopenia with thrombosis (HITT) can lead to serious morbidity and may be potentially fatal. We reviewed our experience with this entity over a 4-year period, to determine the following: 1) incidence and type of thrombosis in patients with heparin-induced thrombocytopenia (HIT), 2) clinical consequences of thrombosis, i.e., amputation, cerebrovascular accidents and death, 3) risk factors associated with development of thrombosis, and 4) impact of therapy on clinical outcomes in patients with HITT. Between 1991-1994, 108 patients were diagnosed to have HIT by heparin-induced platelet aggregation test. Thirty-two (29%) of these developed thrombotic complications, of which 20 were venous, 8 arterial, and 4 both. Five of the 32 died, 3 underwent amputations, and 3 had cerebrovascular accidents. The patients who developed thrombotic complications, when compared to those with HIT alone, were older (68.7 +/- 11.5 vs. 63.3 +/- 16 years, P = .05), had more severe thrombocytopenia (platelet count 46,300 +/- 30,400/mm3 vs. 62,500 +/- 34,400/mm3, P = .02), and developed it earlier (6.0 +/- 2.9 vs. 7.4 +/- 3.1 days, P = .03). Multivariate analysis showed that severity of thrombocytopenia and early fall in platelet count were independent risk factors for development of thrombotic complications. We did not find an association between development of thrombosis and clinical events (myocardial infarction, cardiac procedures or surgery, noncardiac surgery, and sepsis) that occurred immediately prior to onset of thrombocytopenia. Heparin was stopped in all 32 patients with HITT. Six received no additional therapy, and one received a single dose of aspirin. Three of these 7 died. The other 25 received anticoagulant or multiagent therapy, with 2 deaths. The death rate was lower in those who were treated with anticoagulant or multiagent therapy (P = .05). We conclude that: 1) Thrombotic complications occur in about 29% of hospitalized patients who develop HIT. 2) Early, severe fall in platelet count in elderly patients receiving heparin appears to be associated with development of thrombotic complications. 3) Our data do not show an association between development of thrombotic complications and clinical events immediately preceding the diagnosis of HIT. 4) In addition to discontinuation of heparin, anticoagulant or thrombolytic therapy should be considered in patients with HITT.

Anticoagulants↗
PubMed1997

Therapeutic apheresis in malignancy.

Plasmapheresis (PP), staphylococcal protein A immunoadsorption (SPI), and extracorporeal photochemotherapy (EP) have been utilized in cancer treatment for about 20 years. PP removes immune complexes and induces a temporary increase in T4/T8 ratio, natural killer cell activity, and blastogenic responses. SPI removes immune complexes, enhances lymphocytic responses, and activates complement. EP increases lysis of circulating lymphoma cells by CD8+ cytotoxic T cells and increases tumor necrosis factor production by host monocytes. PP induces partial remission in about 28% of patients, but this remission is short lived. SPI gives similar results. Addition of PP to chemotherapy has been reported to prolong survival in patients with multiple myeloma. EP appears useful in treating cutaneous T cell lymphomas with 25% of patients achieving complete response and 50% of patients attaining partial remission. Thus, PP and SPI induce short-lived immune responses, but have no proven clinical utility. EP may be useful in the treatment of cutaneous T cell lymphomas.

Humans↗
PubMed1996

Leukemogenic risk of hydroxyurea therapy in polycythemia vera, essential thrombocythemia, and myeloid metaplasia with myelofibrosis.

In polycythemia vera (PV), treatment with chlorambucil and radioactive phosphorus (p32) increases the risk of leukemic transformation from 1% to 13-14%. This risk has been estimated to be 1-5.9% with hydroxyurea (HU) therapy. When compared with historical controls, the risk with use of HU does not appear to be statistically significant. The leukemogenic risk of HU therapy in essential thrombocytosis (ET) and in myelofibrosis with myeloid metaplasia (MMM) is unknown. HU remains the main myelotoxic agent in the treatment of PV, ET, and MMM. We studied 64 patients with these three disorders, seen at our institution during 1993-1995. The patients were studied for their clinical characteristics at diagnosis, therapies received, and development of myelodysplasia or acute leukemia (MDS/AL). Forty-two had PV, 15 ET, and 6 MMM, and 1 had an unclassified myeloproliferative disorder. Of the 42 patients with PV, 18 were treated with phlebotomy alone, 16 with HU alone, 2 with p32, 2 with multiple myelotoxic agents, and 2 with interferon-alpha (IFN-alpha). Two patients from the phlebotomy-treated group, one from the HU-treated group, and 1 from the multiple myelotoxic agent-treated group developed MDS/AL. In the larger group, 11 received no treatment or aspirin alone, 18 were treated with phlebotomy alone, 25 with HU, 5 with multiple myelotoxic agents, 2 with p32, 2 with IFN-alpha, and 1 with melphalan. Study of the entire group of 64 patients showed that only one additional patient (total of 5 out of 64) developed MDS/AL. This patient had been treated with HU alone. Statistical analysis did not show any association between clinical characteristics at diagnosis, or HU therapy, and development of MDS/AL (P=0.5). Thus, our data provide no evidence suggestive of increased risk of transformation to MDS/AL with HU therapy in PV, ET, and MMM. Larger, prospective studies are needed to study this issue further.

Acute Disease↗
PubMed1996

Dual use of silver for management of chronic bone infections and infected non-unions.

Broad spectrum antibacterial effect of electrically generated silver ions has been fully established. Present work consists of clinical evaluation of beneficial antibacterial effect of silver ions liberated electrically with the help of locally manufactured power pack in 920 proved cases of chronic osteomyelitis with or without pathological fractures and septic non-unions. Wound debridement, silver iontophoresis, proper immobilisation and subsequent wound care yielded not only control of bone infections in 85% cases, but also produced healing of pathological fractures in 83% patients. Results remained unaffected by age or sex of patient, type of bone involved, duration of previous illness or type of previous treatment. Follow-up varied from 6 months to 10 years. This technique is likely to open a new chapter in treatment of chronic resistant bone infections and septic non-unions due to open fractures particularly in developing countries of the world.

Adolescent↗
PubMed1994

A phase I/II study of sequential interleukin-3 and granulocyte-macrophage colony-stimulating factor in myelodysplastic syndromes.

In this phase I/II study, 9 patients with myelodysplastic syndromes (MDS) were treated with interleukin-3 (IL-3) followed by granulocyte-macrophage colony-stimulating factor (GM-CSF). Each treatment cycle was 28 days long and administered as follows: 1 microgram/kg/d IL-3 on days 1 through 7 and 3 micrograms/kg/d GM-CSF for days 8 through 21, followed by a 7-day rest period. IL-3 dose escalations were planned, but the dose of GM-CSF was fixed. Three patients had refractory anemia, 4 had refractory anemia with ringed sideroblasts, and 2 had refractory anemia with excess blasts. Six patients were dependent on red blood cell transfusions, 1 on platelet transfusions, and 2 on both. The absolute neutrophil count improved in 7 (77%) patients and the platelet count improved in 3 (33%) patients during therapy. Hemoglobin levels were unchanged. A clinically relevant response was seen in only 1 patient with thrombocytopenia, and he received five cycles of therapy. The neutrophil count decreased in 2 patients and the platelet count decreased in 4 patients during treatment. The toxicity of the treatment was significant. In the first cohort of 3 patients, 1 patient developed supraventricular tachycardia and congestive heart failure. In the second group, 1 patient developed progressive granulocytopenia and died of gram-negative septicemia. Because of the disparate toxicity, 3 more patients were treated at the same dose level. One of these experienced a high fever and bone pain requiring hospitalization. Because of these adverse effects, the IL-3 dose was not escalated and all patients received 1 microgram/kg/d for 7 days. We believe that sequential therapy with IL-3 and GM-CSF at these dose levels causes unacceptable toxicity in patients with MDS. The major toxic events occurred during weeks 4 and 5 after starting treatment and may have been primarily caused by GM-CSF therapy. Although neutrophil counts improve in most patients, the effect on red blood cells and platelets is minimal. At present, this form of therapy remains problematic and appears to have a limited potential in the management of MDS.

Adult↗
PubMed1994

Pulmonary hypertension in polycythemia vera.

Thromboembolic events occur in about 27% of the patients with polycythemia vera and account for 31% of the deaths. These include cerebrovascular accidents, myocardial infarction, peripheral vascular occlusions, pulmonary infarctions, and venous thrombosis. We report two cases with polycythemia vera who presented with pulmonary hypertension in the absence of previous thromboembolic complications of any kind. One patient died suddenly, with evidence of extensive bilateral thrombosis of prelobular pulmonary arteries at autopsy. In the second patient, local thrombosis in the pulmonary vasculature or recurrent silent pulmonary emboli appear to be responsible for the development of pulmonary hypertension. After institution of anticoagulant therapy, he is able to maintain his functional status. The purpose of this report is to alert clinicians to the development of this insidious, but potentially fatal complication in patients with polycythemia vera.

Humans↗
PubMed1992

Phase II trial of recombinant human interferon alpha in myelodysplastic syndromes.

Twenty patients with myelodysplastic syndromes were treated with daily subcutaneous injections of interferon alpha 2a, at the initial dose of 3 x 10(6) U/m2. Hemogram, chemistry profile, natural killer (NK) cell activity and lymphokine-activated killer (LAK) cell cytotoxicity were monitored serially. Bone marrow with cytogenetic analysis was done before therapy and every three months afterwards. Normalization to the complete blood count, and wherever applicable, decrease in blast count of 5% or less were defined as a complete response. Improvement in hemoglobin level to 12 g/dl, neutrophil count to 1000/mm3 and platelets to 100,000/mm3 was considered a partial response. The median age was 71 (range 59-83) years and 16 of the patients were males. Two patients withdrew from the treatment in the first week and were considered ineligible. Among the other 18, two had refractory anemia, two refractory anemia with ringed sideroblasts, four chronic myelomonocytic leukemia, eight refractory anemia with excess blasts, and two refractory anemia with excess blasts in transformation to acute leukemia. Twelve patients were treated for six months, the other six were taken off the treatment after six to eight weeks because of disease progression. Only one patient with chronic myelomonocytic leukemia had a partial response for two months. NK cell activity remained unchanged before (18.3 +/- 4.6 lytic units) and during interferon therapy (19.6 +/- 5.3 lytic units). LAK cytotoxicity was not detected in any patient before therapy and was seen in only one patient (not the responder) during therapy (5.7 lytic units). The toxicity of the interferon therapy was substantial. Seventeen patients required a dose reduction and fifteen lost greater than 10% of body weight. Eleven patients (61%) developed infections requiring antibiotic therapy, and eight (44%) required hospitalization. Seven patients developed neurologic toxicity. Interferon alpha 2a is an ineffective but toxic therapy in these elderly patients with myelodysplastic syndromes.

Aged↗
PubMed1991

Primary lymphoma of the heart. Prolonged survival with early systemic therapy in a patient.

Primary lymphoma of the heart is an uncommon malignancy usually recognized at autopsy or fatal within a few weeks of diagnosis. Recently, it was reported in patients with acquired immune deficiency syndrome. A patient with diffuse large cell lymphoma of the heart is reported who had chest pain and rapidly evolving cardiac arrhythmias. The human immune deficiency virus antibody test was negative. Because of an aggressive diagnostic approach, therapy with cyclophosphamide, doxorubicin, vincristine, and prednisone was started on the third day after diagnosis. The patient has survived 18 months with an objective response. To the authors' knowledge, this is the longest reported survival in primary cardiac lymphoma. The diagnosis in this patient was aided by excellent tumor delineation by nuclear magnetic resonance scanning. The authors believe that better survival in this patient was a result of prompt diagnosis and treatment because the behavior of the lymphoma was similar to aggressive lymphomas arising elsewhere.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Granulocyte-macrophage colony stimulating factor for the treatment of drug induced agranulocytosis.

Drug induced agranulocytosis is an uncommon but potentially fatal complication. In some cases, it may be associated with hypoplasia and depletion of granulocytic precursors in the marrow, leading to prolonged neutropenia. We report on the use of granulocytic-macrophage colony stimulating factor (GM-CSF) in two such cases, at a dose of 10 micrograms per kilogram per day subcutaneously. The absolute neutrophil count rose above 500/mm3 in 3 days in both cases. We believe that GM-CSF expedited the recovery of granulocyte counts in our patients and warrants further study in the management of drug induced neutropenia.

Agranulocytosis↗