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Biomedical subjects

A Manoharan

Publications and source records attributed to A Manoharan.

At least 37 records · Page 2Linked to original sources

Streptococcus pneumoniae from ophthalmic infections: serotype distribution and penicillin susceptibility.

Streptococcus pneumoniae is one of the pathogens causing infection of the conjunctiva and the uveal tract. The present study began with the observation of two ophthalmic S. pneumoniae isolates showing intermediate resistance to penicillin. Among the 25 isolates of S. pneumoniae from 617 ophthalmic specimens, during the period of 14 months, four were found to exhibit an intermediate resistance to penicillin. Minimum Inhibitory Concentration values ranging from 0.125 microg/mL to 0.25 microg/mL was observed. No multidrug resistant strains were isolated. Serogrouping/typing of the S. pneumoniae revealed the following serogroups/types; 6A (n = 3), 6B (n = 2), 22 (n = 3), 14 (n = 3), 23A (n = 2), and 1 each of 23B, 19A, 7B, 32, 9, 42, 21, 39, 10, 3, and 34. One strain showed cross reaction in pool 29, 35, and 47. These findings represent the first such observation of ophthalmic isolates from India.

Anti-Bacterial Agents↗

An unusual case of chylothorax complicating non-Hodgkin's lymphoma.

A 64 year old man with non-Hodgkin's lymphoma developed extremely troublesome chylous pleural effusions following effective chemotherapy. With the pre-operative use of olive oil, a diffuse leakage of lymph was seen at thoracotomy. Oversewing was performed eventually resulting in an excellent outcome.

Chylothorax↗

Systemic bacterial infections in bone marrow transplant patients.

The clinical microbiology department at CMC&H, Vellore in conjunction with the haematology department carries out routine surveillance of patients admitted to the hematology department. Since 1994 in a sample population of 55 patients with various underlying clinical conditions who have had bone marrow transplant, sepsis was observed in 16 patients (29%). The predominant Gram negatives associated with sepsis were non-fermenting Gram negative bacilli and all the 5 Gram positives were coagulase negative staphylococci. These organisms were susceptible to most of the routinely used antimicrobial agents. Continued surveillance is needed to determine changing trends with respect to organisms causing systemic infections and their susceptibility to antimicrobials.

Adolescent↗

Decitabine (SuperGen).

Decitabine, a potent DNA methyltransferase inhibitor, which was originally under development by Pharmachemie, is being developed by SuperGen. Pharmachemie had been studying decitabine in phase II clinical trials for several leukemia indications in Europe and the US. Preliminary results indicated that the compound was active in the treatment of myelodysplasia, relapsed leukemia, acute myeloid leukemia and postallogeneic progenitor cell transplant relapse. The compound is in phase II clinical trials with phase III trials scheduled to begin shortly. Decitabine has been used to treat myelodysplastic syndrome in a total of 125 patients, with an overall response rate of 49%. In a study using decitabine to treat chronic myelogenous leukemia in 81 patients, a response rate of 62% among patients in chronic phase of the disease was achieved. In a phase I/II trial designed to establish safety and efficacy in the treatment of sickle cell anemias treatment with decitabine generated a response in 100% of the patients tested: a total of eight patients were enrolled, each experienced elevated levels of fetal hemoglobin. Side effects were minimal and the drug was well tolerated. Plans for additional clinical studies of decitabine as a treatment for sickle cell anemia are underway. A phase II trial using a low dose of decitabine in patients with myelodysplastic syndrome has been completed. Of 66 patients entered, 62 were evaluable. The response rate was 48%, with a median response duration of 40 weeks. The mean survival from the start of therapy was 13 months. In a study with 37 CML patients, a 25% overall response rate was seen in those patients in the blastic phase of the disease, and a 52% response rate was observed in the accelerated phase patients. The most significant side effect was prolonged myelosuppression. The drug suppresses cellular growth in seven human tumor cell lines, possibly by reactivation of certain growth suppressor genes.

Journal Article↗

Thrombosis and bleeding in myeloproliferative disorders: identification of at-risk patients with whole blood platelet aggregation studies.

Seventy-five patients with chronic myeloproliferative disorders were studied to investigate platelet function by simultaneous measurement of platelet aggregation by the impedance method and ATP dense granule release using a whole blood platelet lumi-aggregometer, in an attempt to identify patients at risk for thrombosis and bleeding. Thirty-nine patients had at least one abnormal result indicating platelet hyperactivity (i.e. impedance or release with one agonist being above the reference range); 16 patients had platelet hypoactivity (i.e. at least one result was below the reference range), whilst 14 had co-existence of hyper- and hypoactivity. Six patients had normal results. 20/53 patients with platelet hyperactivity (alone or mixed) had a positive history of venous and/or arterial thrombosis; in comparison, only two of the other 22 patients had a positive history. During a median follow-up of 33 months, nine patients with and one patient without platelet hyperactivity respectively developed new thrombotic events before the addition of specific therapy. A total of 50 patients with and eight patients without platelet hyperactivity respectively received specific treatment including aspirin and/or cytotoxic therapy. All but one elderly patient with platelet hyperactivity have remained free of new thrombotic events on specific therapy. Two of the 17 patients with platelet hypoactivity had major clinical bleeding. These observations highlight the need to test platelets for hyper- as well as hypo-function and suggest a useful role for routine whole blood platelet aggregation studies to identify the patients at risk for thrombosis or bleeding.

Aged↗

A variant of pyothorax-associated lymphoma.

A case of pleural lymphoma that developed after an episode of empyema is described. This may be a variant presentation of the rare yet distinct condition termed pyothorax-associated lymphoma. This condition was first recognised in Japan; there have been only a few reports in Western countries to date. A feature of this case is the relatively short interval between diagnosis of empyema and subsequent development of lymphoma.

Aged↗

A phase I/II study of intensive dose escalation of cytarabine in combination with idarubicin and etoposide in induction and consolidation treatment of adult acute myeloid leukemia. Australian Leukaemia Study Group (ALSG).

To determine the safety and efficacy of the combination of idarubicin, cytarabine and etoposide ("ICE") for induction and consolidation treatment of acute myeloid leukemia (AML), and of dose-intensification of cytarabine in this setting, 54 previously untreated patients in three cohorts were studied by sequential dose escalation of cytarabine, in combination with standard doses of idarubicin and etoposide. Cytarabine was given to Cohort 1 at the conventional dosage of 100 mg/m2 per day by continuous infusion for 7 days in induction and 5 days in consolidation; to Cohort 2 at high-dose (HiDAC) (3 g/m2 intravenously twice daily on days 1, 3, 5 and 7) during induction with conventional dosage during consolidation; to Cohort 3 HiDAC was given for both induction and consolidation. In addition, Cohort 3 patients received lenograstim (Granocyte; rHuG-CSF) after both induction and consolidation courses. We found that there was no significant difference between the three cohorts in hematological toxicity in induction, but that HiDAC was associated with a greater incidence of gastro-intestinal toxicities. There was no difference in induction mortality between the three cohorts, which was 11% overall. Consolidation with HiDAC led to a significant increase in hematological toxicity. Overall, the complete remission (CR) rate was 80% with no significant difference between the three regimens. The estimated disease free survival at 3 years was 28%, 67% and 54% respectively for Cohorts 1, 2 and 3 with an estimated overall survival of 38%, 63% and 47%. We conclude that cytarabine dosage can be escalated safely in combination with idarubicin and etoposide in both induction and consolidation. The combination is effective for induction treatment of AML and its side-effects appear similar to those of standard regimens. Whether its use offers long-term benefits compared with standard regimens is the subject of ongoing controlled randomized studies.

Adolescent↗

Changing trend in susceptibility pattern of Streptococcus pneumoniae to penicillin in India.

Prior to 1995 all strains of Streptococcus pneumoniae isolated at a tertiary care hospital in south India were uniformly susceptible to penicillin. However, since late 1995 strains of S. pneumoniae with intermediate resistance to penicillin have been observed. Altogether there were 25 such isolates, 9 from invasive (5 from CSF as well as blood, 1 from pleural fluid and 3 from CSF alone) and 16 from noninvasive sites (6 from throat, 6 from sputum, 3 from eye and 1 from ear) respectively, thus 4.6 per cent of S. pneumoniae showed intermediate resistance of a total of 535 strains studied so far. The minimum inhibitory concentration (MIC) values of penicillin, erythromycin, chloramphenicol and cefotaxime were determined by agar dilution method and for confirmation, E test was carried out for penicillin alone. The MIC range obtained for penicillin was between 0.125-1.0 microgram/ml. Kirby-Bauer disc diffusion method was adopted for testing of erythromycin, chloramphenicol, co-trimoxazole, cefotaxime, tetracycline and vancomycin. We observed that none of the strains with intermediate resistance to penicillin were multidrug resistant. These strains belonged predominantly to serotype 14 (n = 10), 7B (n = 9), 19A (n = 3), 7F (n = 2) and 23F (n = 1). Clonality was not observed in the 5 representative strains subjected to Box A finger printing method.

Anti-Bacterial Agents↗

Acute myeloblastic leukaemia in the elderly: biology, prognostic factors and treatment.

Elderly patients (> 60 years) with acute myeloblastic leukaemia (AML) have significantly inferior remission rates (around 50%) and median survival times (5-6 months) despite intensive therapy, compared with younger AML patients. This observation emanating from several large clinical studies has made treatment of elderly AML patients a highly controversial issue, with clinicians largely polarizing to one extreme viewpoint or the other. This article summarises the current understanding of the biology and the resultant justification for the assertion that AML in elderly patients is a distinct clinical entity; provides a useful list of prognostic factors to enable a rational therapeutic decision in individual patients; reviews the encouraging results with low-dose combination chemotherapy in small, non-randomized studies from four different centres; and draws attention to the possible significance of drug scheduling and pharmacokinetics in the treatment of elderly patients.

Aged↗

Idiopathic myelofibrosis: a clinical review.

Idiopathic myelofibrosis (MF) is a chronic myeloproliferative disorder (MPD) in which a clonal haemopoietic stem cell proliferation is accompanied by reactive fibrosis. Despite this clear understanding of pathogenesis, the majority of patients with MF are still poorly treated in comparison to those with other types of MPD. This article reviews the clinical and laboratory features in light of our current knowledge on the pathogenesis and pathopathology of MF; discusses the various prognostic factors to enable stratification of patients to the 'long-lived' group (median survival around 10 years) or the 'short-lived' group (median survival around 2 years); highlights the need to treat patients more effectively with specific therapy directed against the underlying neoplastic clonal stem cell proliferation; argues for long-term, if intermittent, maintenance therapy to improve the quality of life and hopefully, also their life-span; and, provides a summary of the various treatment options currently available for patients with MF.

Humans↗

PCR-Enzyme immunoassay for detection of Streptococcus pneumoniae DNA in cerebrospinal fluid samples from patients with culture-negative meningitis.

A PCR-based assay was developed to amplify a conserved region of the pneumococcal autolysin gene. The amplified product was labelled with digoxigenin-labelled dUTP and was detected with a biotin-labelled probe in an enzyme immunoassay (EIA). The assay was initially tested with suspensions of various serotypes of Streptococcus pneumoniae and other gram-positive and gram-negative bacteria and was then applied to cerebrospinal fluid (CSF) specimens from patients with meningitis and those with other neurological disorders. The assay detected all the serotypes of S. pneumoniae tested, whereas all the other bacterial strains tested were negative. Seven of the 8 CSF specimens positive for pneumococcus by culture or latex agglutination (LA) were positive by PCR-EIA, whereas all 10 specimens positive for other organisms were negative. Among 11 patients with clinically diagnosed meningitis but with negative culture and LA results, 5 were positive by PCR-EIA. The assay was negative for all but one patient without meningitis; it was positive with the CSF from a child with immunodeficiency and pneumococcal abscesses on the scalp. PCR-EIA is a useful tool for the diagnosis of meningitis, especially when culture and LA are negative because of prior antibiotic treatment.

Child↗