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Biomedical subjects

A B Mehta

Publications and source records attributed to A B Mehta.

At least 55 records · Page 3Linked to original sources
PubMed1994

Sion thrombolysis trial--randomised trial of intravenous thrombolysis & primary percutaneous transluminal coronary angioplasty for acute myocardial infarction [AMI]--feasibility phase data of angioplasty limb.

Reperfusion in acute myocardial Infarction [AMI] can be realised by thrombolytic therapy or percutaneous transluminal coronary angioplasty [PTCA] has theoretical advantage but hardly any randomised trials have been published till recently to compare the two modalities. We started the STAT trial with this objective. Patients of AMI were randomised to thrombolytic therapy or PTCA. In the present article we present the phase I data of the PTCA limb. The procedural success rate was 100% with no procedural mortality. In-hospital mortality was 10% [Anterior Infarction 0%, Inferior infarction 20%]. Recurrence of angina occurred in 10% patients. Direct PTCA to left anterior descending artery appeared to be more rewarding than PTCA to right coronary artery.

Adult↗
PubMed1994

Recovery positive exercise stress test: an indication for coronary artery disease.

UNLABELLED: The significance of ST depression occurring during exercise treadmill stress test has been well established. However, at times there may be no ST segment changes during exercise with changes occurring during the recovery phase. Out of the 1234 patients who underwent exercise stress test, 17 patients had ST segment changes confined to recovery phase. Coronary angiography performed in these 17 patients showed 11 patients had significant coronary artery disease (CAD), with nine patients having triple vessel disease and 2 having double vessel disease. Analysis showed there was no significant difference in the two groups of CAD and no CAD with respect to sex ratio, mean duration of exercise, maximal heart rate and double product achieved. CONCLUSION: Although, patients with recovery positive stress test may have normal coronary angiography, a large number of patients (64.7%) in our study had significant CAD. Hence, such patients should be subjected to another noninvasive test such as thallium perfusion scan or coronary angiography.

Adult↗
PubMed1993

Recombinant interferon alfa 2a in the treatment of patients with early stage B chronic lymphocytic leukaemia.

18 patients with early stage, previously untreated B-CLL were given interferon alfa (IFN alpha) 2a. 3 MU thrice weekly, subcutaneously. The peripheral lymphocyte count decreased in all patients. Response was delayed in three patients until they had received a median of 5 months therapy, one of whom had an initial transient increase in lymphocytes. Two patients normalized their blood lymphocyte counts, but neither achieved complete remission (CR). Responses were transient in eight patients lasting a median of 5 months (3-21). Binding anti-IFN alpha antibodies were present in 9/17 patients tested (53%). Low titre binding antibodies (< 533 IBU/ml) were not associated with LHR, but high titre antibodies (> 4401 IBU/ml) were. Two of 12 patients assessed had a > 3 g/l increase in baseline serum IgG levels during IFN alpha therapy, one of whom reverted to pretreatment levels in association with LHR. Haematological toxicity was moderate, other than in two patients, one of whom developed autoimmune haemolytic anaemia and the other thrombocytopenia. We conclude that IFN alpha lowers the lymphocyte count in early stage CLL, that the response may be delayed and that anti-IFN alpha antibodies may play a role in a proportion of those in whom the response is transient.

Adult↗
PubMed1993

Flow cytometric assessment of multidrug resistance (MDR) phenotype in acute myeloid leukaemia.

Forty one patients with acute myeloid leukemia (AML), including 27 at presentation and 14 relapsed or resistant cases, were assessed for laboratory evidence of the MDR phenotype. Leukaemic cells from all 41 cases were studied by immunocytochemistry using the JSB-1 monoclonal antibody and simultaneously by reverse transcription polymerase chain reaction (RT-PCR) to evaluate expression of the mdr 1 gene. Cells from 32/41 cases were also assessed for daunorubicin (DNR) accumulation and retention by flow cytometry (FC). Nineteen of the 41 (46%) patients were positive for MDR by JSB-1 immunocytochemistry (11/27 [41%] at presentation and 8/14 [57%] relapsed or resistant cases). Nine of the 19 (47%) P-gp positive, de novo patients achieved complete remission. 22 patients were negative by JSB-1 immunocytochemistry (16/27 [59%] at presentation and 6/14 [43%] of the relapsed or resistant cases) and 11/22 (50%) P-gp negative patients achieved a complete remission. Of the 32 patients assessed by FC, 7 (22%) were positive for the MDR phenotype with increased DNR accumulation and retention in the presence of the MDR reversing agent verapamil (VPM). 6/7 of the FC positive cases were also JSB-1 positive, and 6 had additional poor risk features. Of the twenty five FC negative patients, 6 had received previous chemotherapy and 15 (60%) achieved complete remission. Mdr 1 mRNA levels were increased in all seven FC positive cases whereas only 7/19 JSB-1 positive cases had raised mdr 1 mRNA levels. These results suggest that the assessment of MDR status by immunocytochemistry using JSB-1 is not predictive of response to chemotherapy. Flow cytometric analysis of blast cells appears to correlate well with mdr 1 mRNA levels and may be a better predictor of treatment outcome.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Percutaneous transluminal coronary angioplasty in totally occluded arteries.

Out of 321 consecutive cases of Percutaneous Transluminal Coronary Angioplasty (PTCA), 28 (8.7%) patients underwent PTCA for nonacute total occlusion with no visible antegrade flow. All patients had evidence of reversible ischaemia in the territory of totally occluded artery. Overall initial success rate was 66% and was mainly related to the duration of the occlusion (85% for occlusion of 1 month or less, 70% for 1-6 months, and nil for more than 6 months duration). In 21 (75%) cases where collateral circulation to the occluded vessel could be demonstrated before PTCA, was not visible after successful PTCA. Failure was mainly due to inability to cross the lesion with the guide wire (8 out of 10 failures). Emergency Coronary Artery Bypass Graft (CABG) surgery was required in 2 cases where dissection of nontarget vessels occurred during manipulation of the guide wire. Acute reocclusion occurred in 2 cases, both were redilated successfully. There was no death. Although the primary success rate is lower than that associated with conventional stenotic lesions, with improvement in the hardware-balloon catheters and guide wires, coronary angioplasty can be performed successfully in majority of the patients with total coronary occlusion.

Adult↗
PubMed1993

Interferon-alpha inducible 2'-5' oligoadenylate synthetase transcripts in lymphoid and myeloid leukemias.

Alpha-interferon (IFN) is effective in the treatment of a proportion of patients with hairy cell leukemia (HCL). B-cell chronic lymphocytic leukemia (CLL), chronic myeloid leukemia (CML) and multiple myeloma (MM). One of the proteins induced by IFN is the enzyme 2'-5' oligoadenylate synthetase (2-5 AS). Peripheral blood or bone marrow samples treated with IFN in vitro, or from patients treated with IFN were studied for expression of the different 2-5 AS mRNA transcripts. A total of four normal individuals and 31 patients (nine HCL, five CLL, six MM, nine acute myeloid leukemia (AML) and two T-cell acute lymphoblastic leukemia (T-ALL) have been investigated. In normal peripheral blood lymphocytes, only the 1.8 kb transcript was induced with IFN in vitro. In HCL, CLL, and MM all four transcript sizes were induced by IFN in vivo and in vitro. The 1.6 and 1.8 kb forms were equally and predominantly expressed in HCL and B-CLL. On the other hand, the 1.8 kb transcript was predominantly expressed in MM and this increased expression was statistically significant. In acute leukemia, the majority of samples expressed all four transcripts equally but four of eleven samples expressed only the 1.8 kb transcript. These results suggest that the pattern of induction of specific 2-5 AS mRNA transcripts may be related to the underlying disease. Whether these different patterns of 2-5 AS induction have implications for response to IFN treatment, remains to be determined.

2',5'-Oligoadenylate Synthetase↗
PubMed1992

Increase in 2',5'-oligoadenylate synthetase caused by deoxycoformycin in hairy cell leukaemia.

2',5'-oligoadenylate synthetase (2-5OAS) has been studied in peripheral blood mononuclear cells from nine patients with hairy cell leukaemia (HCL) receiving therapy with the adenosine deaminase inhibitor deoxycoformycin (dCF) or alpha interferon (alpha-IFN). 2-5OAS mRNA was assayed by dot-blot hybridization. Increase of 2-5OAS mRNA level was seen in six patients with HCL treated with dCF and in one patient treated with alpha-IFN who responded to therapy. A patient with a variant form of HCL treated with dCF and the second patient treated with alpha-IFN did not show an increase of 2-5OAS mRNA and neither responded to therapy. The 15 other patients with T or B-chronic lymphoblastic leukaemia (CLL), T-acute lymphoblastic leukaemia (ALL), adult T-cell leukaemia lymphoma (ATLL), non-Hodgkins lymphoma (NHL), Sezary and T or B-prolymphocytic leukaemia (PLL) treated with dCF did not show an increase in 2-5OAS, though four patients, all with T-cell tumours, responded clinically. 2-5OAS activity is known to be stimulated by alpha-IFN and recent work suggests that this rise in 2-5OAS may result in increased cleavage of mRNA for tumour necrosis factor (TNF) and other cytokines on which autocrine growth and proliferation of the tumour cells are dependent. By analogy, we suggest that one mechanism of action of dCF in hairy cell leukaemia may be to break down an autocrine growth loop for TNF or other cytokines. An alternative explanation for these observations is that cytokines released from hairy cells in the bone marrow killed by dCF induce a rise in 2-5OAS in circulating leucocytes.

2',5'-Oligoadenylate Synthetase↗
PubMed1992

Effects of interferon-alpha (IFN) on the expression of interleukin 1-beta (IL-1), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF) in acute myeloid leukemia (AML) blasts.

Interferon-alpha (IFN) induces the enzyme 2-5 oligoadenylate synthetase (2-5 AS) in cells from patients with hairy cell leukemia and B-cell chronic lymphocytic leukemia and this is associated with a breakdown of certain species of cytokine messenger (m)RNA via the activation of a latent ribonuclease. We have studied the expression of the cytokines interleukin 1-beta (IL-1), interleukin 6 (IL-6), granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumour necrosis factor alpha (TNF) as well as of the ribonuclease activator 2-5 AS in the presence and absence of IFN in acute myeloid leukaemia (AML) blast cells from 26 patients. Before monocyte and T-cell depletion there was no expression of IL-1, IL-6 or GM-CSF, and only three of 13 patients studied expressed TNF mRNA. After cell depletion one or more cytokine was expressed in 31-62% of the 26 patients. Expression of one or more mRNA for IL-1, IL-6, GM-CSF and TNF after 18 h incubation was detected in 16 of 26 patients (63%) and this was particularly so in French-American-British (FAB) subtypes M4 and M5. Eight of nine patients with IL-6 mRNA expression and seven of 10 with IL-1 mRNA expression were in the FAB subtypes M4 and M5. Twenty-two of 26 patients showed induction of 2-5 AS mRNA in response to IFN in vitro. Exposure to IFN resulted in reduction of IL-1 mRNA in nine of 12 cases, of IL-6 mRNA in eight of nine, and GM-CSF mRNA in five of seven cases. TNF mRNA was unaffected by IFN despite 2-5 AS induction in 12 of 13 patients expressing this cytokine. In the presence of exogenous IFN, cells from six of seven patients studied showed inhibition of 3H-thymidine incorporation into DNA. DNA synthesis could also be abrogated in six of seven patients with anti-IL-1 monoclonal antibodies (MoAb) and in two of seven with anti-IL-6 MoAb. This inhibitory effect could be reversed in all patients when anti-IL-1 or anti-IL-6 was given in combination with their corresponding cytokine. These data suggest that IFN may exert a therapeutic effect in a proportion of AML patients by blocking IL-1 and IL-6 mediated growth, consequent on activation of the ribonuclease activator 2-5 AS.

2',5'-Oligoadenylate Synthetase↗
PubMed1992

Percutaneous transluminal coronary angioplasty in distal lesions.

Of 210 patients in whom percutaneous transluminal coronary angioplasties [PTCA] were performed during the period of 2 years (June 1987 to August 1989), 55 had distal lesions. These included 50 males and 5 females with the lesions in left anterior descending [LAD] artery after the origin of the second diagonal branch, circumflex [Cx] artery after the origin of the obtuse marginal [OM], and right coronary artery [RCA] after the acute marginal branch. There were a total of 71 distal lesions, involving the LAD [51%], Cx [20%], and RCA [29%]. The overall success rate with PTCA was 91%. There were 4 acute closures of vessels; all were redilated with balloon angioplasty. One of these was sent for emergency bypass surgery after balloon dilatation. There was no death. With improvement in balloon catheters and guidewires, the feasibility and success of PTCA in distal lesions have increased remarkably, thus expanding the horizon of PTCA.

Angioplasty, Balloon, Coronary↗
PubMed1991

Ewing's sarcoma t(11;22) in a case of acute nonlymphocytic leukemia.

Chromosome analysis of bone marrow cells from a patient with acute nonlymphocytic leukemia M2 revealed the translocation t(11;22)(q24;q12) usually associated with Ewing's sarcoma. Molecular investigations ruled out the possibility that this was a variant Philadelphia translocation with breakpoints in the major breakpoint cluster region. Although cytogenetic analysis was not available at diagnosis, this abnormality was found both pre- and postallogeneic bone marrow transplant.

Adolescent↗
PubMed1991

Fludarabine phosphate for the treatment of low grade lymphoid malignancy.

Thirty-four patients with previously treated, advanced, low grade NHL were treated with Fludarabine, a deamination-resistant analogue of adenosine arabinoside, at a dose of 25 mg m-2 intravenously, daily for 5 days (median number of cycles = 3, range 1-10). Complete remission (CR) was achieved in six and partial remission (PR) in a further seven. Overall, responses were seen in 11/23 patients (48%) with follicular lymphoma and in 2/11 (18%) with low grade, diffuse NHL. Fifteen patients with previously treated CLL and one patient with prolymphocytic leukaemia (PLL) were also treated as above (median no. of cycles = 3, range 1-6). A partial response was seen in three of the 11 evaluable patients with CLL and CR was achieved in the patient with PLL. There were four deaths due to infection and 19 further episodes requiring admission to hospital. No other significant toxicity was reported in a total of 164 cycles of Fludarabine. This agent is active in advanced low grade lymphoid malignancy. Further studies are required to assess its role in newly diagnosed patients.

Antineoplastic Agents↗
PubMed1991

Interleukin 2 infusion induces haemopoietic growth factors and modifies marrow regeneration after chemotherapy or autologous marrow transplantation.

Administration of interleukin 2 (IL2) to patients with minimal residual malignant disease following myeloablative chemo-radiotherapy may augment immune reconstitution and reduce the risk of relapse by increasing cytotoxic effector function and cytokine dependent killing directed at residual malignant cells. The ability of IL2 generated activated killer cells to inhibit haemopoietic progenitor cells and to release gamma-interferon (gamma IFN) and tumour necrosis factor (TNF) may, however, retard haemopoietic recovery, as both TNF and gamma IFN inhibit normal myelopoiesis in vitro. To determine the effect of IL2 infusion on myeloid regeneration in vivo, we have examined haemopoietic recovery in patients receiving this cytokine following autologous marrow transplantation or ablative chemotherapy. We find that IL2 infusion accelerates neutrophil recovery and that granulocyte-macrophage colony stimulating factor (GMCSF) and IL3 mRNA become detectable in circulating mononuclear cells. Induction of TNF by IL2 may also contribute to subsequent acceleration of myelopoiesis by initiation of GM-CSF mRNA synthesis in patient marrow fibroblasts. These results show that IL2 infusion may facilitate myeloid recovery when administered during the period of haemopoietic regeneration following ablative chemoradiotherapy.

Acute Disease↗
PubMed1991

Blood product support in patients undergoing chemotherapy and autologous or allogeneic bone marrow transplantation for haematological malignancies.

Three groups of patients with leukaemia and myelodysplasia were assessed with regard to the blood product support they required during their period of bone marrow hypoplasia following treatment. One group received myelo-ablative remission-induction chemotherapy followed by appropriate consolidation therapy (two courses in patients with acute myeloid leukaemia and one or two intensification courses in patients with acute lymphoblastic leukaemia); whilst the other two had 'conditioning' with chemotherapy and radiotherapy prior to autologous bone marrow transplantation (auto-BMT) or T cell depleted allogeneic bone marrow transplantation (allo-BMT). There was no statistically significant difference in blood product requirements between the three groups. However, platelet requirements during remission-induction chemotherapy alone were significantly less than for allo-BMT or auto-BMT. Platelet requirements for patients undergoing auto-BMT were also significantly higher than for patients receiving consolidation chemotherapy; and were required for a longer period than for patients receiving allogeneic-BMT. There was no difference in blood product support between ABO matched and mismatched transplants within the allogeneic group, but the presence of graft versus host disease and/or cytomegalovirus infection did significantly increase the requirements for blood product support.

Adolescent↗
PubMed1991

Failure of purged autologous bone marrow transplantation in high risk acute lymphoblastic leukaemia in first complete remission.

Patients in first remission of acute lymphoblastic leukaemia (ALL) considered to be at high risk of relapse were offered autologous bone marrow transplantation (ABMT) using purged marrow as a therapeutic alternative to cranial irradiation and maintenance chemotherapy. Twenty-seven bone marrows taken in remission, were purged using monoclonal antibodies (anti CD7 for T lineage and anti CD10 and/or anti CD19 for B lineage leukaemias) plus rabbit complement. Retrospective analysis of 19 purged marrows by immunophenotyping or immunoglobulin gene rearrangement studies demonstrated no evidence of disease. Engraftment was seen in 26 of the patients. No correlation was found between the numbers of infused nucleated cells or colony forming units-granulocyte-macrophage (CFU-GM) and subsequent engraftment kinetics. The actuarial disease-free survival (DFS) is 32% at 7 years (median follow-up 3.4 years). There were two transplant related deaths (actuarial risk 8%); the main cause of treatment failure has been disease recurrence with an overall actuarial risk of 67%; 76% for T-ALL (five of nine), 62% for common ALL (five of 10), two of five pre B and none of three patients with B-ALL. In these 27 high risk patients in vitro purging of remission marrow as part of ABMT appears not to improve patient outcome, although confirmation of this would require a randomized trial.

Adolescent↗
PubMed1990

Alpha interferon therapy for haematological malignancies: correlation between in vivo induction of the 2',5'oligoadenylate system and clinical response.

2',5'oligoadenylate (2-5A) synthetase mRNA and enzyme levels have been studied in peripheral blood mononuclear cells from 12 patients with chronic granulocytic leukaemia (CGL), 14 with essential thrombocythaemia (ET) and nine with chronic lymphocytic leukaemia (CLL), undergoing therapy with alpha interferon (alpha IFN). 2-5A synthetase mRNA was assayed by hybridization using the dot-blot technique and the enzyme activity was measured biochemically. A statistically significant difference was observed (P less than 0.05) between the degree of in vivo induction of mRNA by IFN alpha in the total patients between the good and intermediate responders and the poor responders. There was a similar pattern in each of the CGL, ET and CLL groups although this only reached statistical significance in the CGL group. In vitro induction of either mRNA or of enzyme activity, however, did not show a difference between the responders and poor responders in any of the patient groups. Our findings are consistent with the concept that 2-5A has an important role in the anti-tumour activity of alpha IFN and suggest that measurement of in vivo induction of 2-5A synthetase mRNA may be useful in predicting clinical response. In vitro studies, on the other hand, do not provide a reliable predictor of clinical response.

2',5'-Oligoadenylate Synthetase↗