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Biomedical subjects

M Haran

Publications and source records attributed to M Haran.

16 recordsLinked to original sources

Pharmacological interventions for treating acute heterotopic ossification.

BACKGROUND: Heterotopic ossification (HO) is the formation of mature lamellar bone in soft tissue sites outside the skeleton. HO frequently complicates burns, arthroplasty, fractures, and spinal cord and brain injuries. It can impair joint function. OBJECTIVES: To determine the efficacy of medications to treat acute HO on radiological, symptomatic, functional impairment, and disability outcomes. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group specialised register, the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 2, 2004), MEDLINE (1966 to August 2004), EMBASE (1980 to August 2004), CINAHL (1982 to August 2004), other databases, reference lists of articles, and contacted trialists and drug companies. No language restrictions were applied. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials that assessed the efficacy of any medication for treating acute HO (confirmed by bone scintigraphy, radiography, ultrasonography, or biopsy) and which used radiography to grade post-treatment HO severity. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the study quality and extracted data. We analysed two dichotomous outcomes: no progression in HO grade (versus progression) and improvement in HO grade (versus no improvement). MAIN RESULTS: Two randomised trials comparing disodium etidronate versus placebo were included (Ono 1988; Stover 1976), from which ninety-two participants with spinal cord injury had radiographically-proven HO at baseline. At the completion of the 12 week intervention, the Ono study but not the Stover study, suggested that disodium etidronate was associated with a significantly greater likelihood of successfully preventing the progression of radiographic HO grade, (relative risk (RR) 1.50; 95% confidence interval (CI) I 1.16 to 1.93; and RR 1.48; 95% CI 0.78 to 2.84 respectively) and a significantly greater likelihood of improvement in HO grade (RR 2.78; 95% CI 1.66 to 4.66; and RR 0.71; 95% CI 0.20 to 2.53 respectively). There was evidence of statistical heterogeneity for the latter outcome. Longer term radiographic, clinical or side effect outcomes were unavailable. Data was not pooled due to this heterogeneity and the inadequate duration of follow up. REVIEWERS' CONCLUSIONS: Given the absence of long term radiographic outcomes in the included studies, there is insufficient evidence to recommend the use of disodium etidronate or other pharmacological agents for the treatment of acute HO. It has been previously suggested that disodium etidronate acts by delaying, rather than preventing, the mineralization of HO, and that mineralization may occur after treatment cessation in many cases, thereby negating the benefit of disodium etidronate on eventual HO grade. Further studies are required to assess all pharmacological treatments for acute HO with sufficient follow-up duration.

Etidronic Acid↗

Grb7 expression and cellular migration in chronic lymphocytic leukemia: a comparative study of early and advanced stage disease.

Grb7, a noncatalytic intracellular adaptor protein involved in cell migration, is overexpressed in certain invasive and metastatic solid tumors. We found a highly significant difference in the level of expression of Grb7 between chronic lymphocytic leukemia (CLL) cells obtained from stage I and stage IV patients (P<0.001). Using semiquantitative RT-PCR, we detected high levels of Grb7 in 88% of stage IV patients vs only 18% in stage I patients. A corresponding increase was found in the in vitro migration of stage IV CLL cells in comparison to stage I cells. The statistically significant difference in the expression of Grb7 between stage IV and stage I patients was preserved even when tested specifically in the ZAP70-positive group (P<0.01). These findings show that Grb7 levels reflect the severity of the disease, and may be used, in conjunction with ZAP70, to predict disease progression.

Case-Control Studies↗

Successful treatment of aggressive HIV-associated non-Hodgkin's lymphoma with combination chemotherapy, biotherapy with rituximab and HAART: presentation of a therapeutic option.

The incidence of non-Hodgkin's lymphoma (NHL) in individuals infected with human immunodeficiency virus (HIV) is more than 60 times higher than in matched controls. In the vast majority of cases aggressive pathological subtypes and advanced stages prevail, extranodal sites are involved and systemic symptoms are present. The prognosis of HIV-NHL remains poor and the optimal therapeutic approach has yet to be defined. We report a 48-year-old Ethiopian woman with advanced-stage HIV infection, who developed diffuse large cell, immunoblastic type B-cell NHL and was treated with a modified CHOP-like chemotherapy combined with Rituximab and supported with growth factor. Highly active antiretroviral therapy (HAART) and opportunistic infections prophylaxis were administered concomitantly. The patient completed 6 cycles of therapy and currently, 76 weeks after diagnosis, is in complete clinical remission. Despite the fact that there was a transient decrease in the CD4-positive cell number and a 1.5 log increase in plasma viral load there were no opportunistic infections, nor was life-threatening toxicity seen. Rituximab seems a well-tolerable and advantageous adjunct to chemotherapy and HAART in the treatment of aggressive HIV-associated NHL andshould be investigated in large trials in the future.

Antibodies, Monoclonal↗

[Effective treatment with Lamivudine of patients with reactivation of hepatitis B following chemotherapy administration].

Chemotherapy administration to patients with lymphoproliferative diseases that are carriers of hepatitis B can be complicated by reactivation of Hepatitis B. This may lead to morbidity and mortality due to liver failure. We report 2 cases, treated recently. The first case is that of a 63-year-old female with a diagnosis of immunoblastic lymphoma. The patient was treated with the ProMACE-CytaBOM protocol. During treatment Hepatitis B was reactivated and after termination, of chemotherapy she developed fulminant hepatitis with hyperbilirubinemia, coagulopathy, hypoalbuminemia and ascites. The second case is that of a 34 years old male with a diagnosis of T-ALL who was treated according to the BFM 95 protocol. He had reactivation of Hepatitis B during induction therapy. These two patients were treated with Lamivudine with resolution of the hepatitis and disappearance of HBV DNA from the sera. Prophylactic administration of Lamivudine enabled reinduction of chemotherapy in the first case after relapse of the lymphoma and continuation of BFM 95 protocol in the second patient. Lamivudine inhibits replication of hepatitis B virus and prevents reactivation of Hepatitis B during immunosuppression induced by chemotherapy and probably ameliorates the severity of already reactivated hepatitis.

Adult↗

A case of transvaginal evisceration.

We present a case of spontaneous evisceration of the small bowel through the vaginal vault in a 61-year-old women. The predisposing factors and management are discussed.

Female↗

The recognition of haemoglobin by antibodies raised for the immunoassay of beta-amyloid.

Canine and porcine cerebrospinal fluid (CSF) were fractionated by size exclusion chromatography and analysed by a luminescence enzyme linked immunosorbent assay (ELISA) configured to detect beta-amyloid. A peak of activity was observed in the CSF consistent with the molecular weight of beta-amyloid. When CSF contaminated with blood was analysed an additional peak of immunoreactivity at a higher molecular weight was observed. The peak of activity was found to be derived from cross-reactivity of the immunoglobulins employed in the ELISA with haemoglobin. These findings are discussed with reference to primary and structural sequence homology between beta-amyloid and haemoglobin from a number of species, the known properties of beta-amyloid and recent clinical reports.

Amyloid beta-Peptides↗

Overexpression in Escherichia coli, folding, purification, and characterization of the first three short consensus repeat modules of human complement receptor type 1.

We have developed a simple expression, isolation, and folding protocol for an SCR oligomer comprising the first three SCRs of complement receptor Type 1 (C3b/C4b receptor, CD35). A T7 RNA polymerase expression system in Escherichia coli was used to express the oligomer as inclusion bodies. The oligomer was recovered from solubilized inclusion bodies using batch adsorption on SP-Sepharose. The oligomer was folded by one-step dilution in 20 mM ethanolamine/1 mM EDTA supplemented with 1 mM GSH/0.5 mM GSSG. The folded material was processed to a concentrated (> 20 mg/ml), usable product of greater than 98% purity using a combination of ultrafiltration, ammonium sulfate treatment, hydrophobic interaction, and size-exclusion chromatography. The yield of folded material varied between 6 and 15 mg/liter culture. The oxidation states of the 12 cysteine residues in SCR(1-3) were identified by HPLC of peptide fragments from a tryptic digest using dual UV/fluorescence detection, collection of selected peaks, and N-terminal sequencing. This methodology confirmed the expected location of disulfide bridges. Equilibrium and velocity sedimentation studies are interpreted in terms of a single sedimenting species with molecular weights of 21,629 and 21,063 by these respective techniques. These values compare to the predicted molecular weight, from amino acid composition, of 21,817. The hydrodynamic properties of the molecule indicate that it is asymmetric with an axial ratio of 1:5.2 or equivalent dimensions of 21 x 110 A. SCR(1-3) has an unusual CD spectrum exhibiting a broad maximum at 220-230 nm and a minimum at 190 nm. There was little evidence of classical secondary structure. The product exhibited concentration-dependent inhibition of complement-mediated lysis of sensitized sheep red blood cells.

Amino Acid Sequence↗

The effect of phytic acid on the resolution of peptides and proteins in capillary electrophoresis.

Studies are reported on the effect of the sodium salt of phytic acid on the resolution of peptides and proteins. Improved separation in the case of peptides is shown to be due to ion-ion pairing interactions between the positively charged peptides and the phytic acid polyanionic species. The improved peak shapes related to the proteins can be interpreted in terms of the sample preconcentration due to injection of analytes from a water medium to one of high ionic strength.

Amino Acid Sequence↗

Jacalin, a lectin with anti-HIV-1 properties, and HIV-1 gp120 envelope protein interact with distinct regions of the CD4 molecule.

Jacalin is a multimeric plant lectin able to interact with the lymphocyte cell-surface molecule CD4, a known receptor for the human immunodeficiency virus type 1 (HIV-1). Moreover, jacalin is able to block HIV-1 infection of CD4+ lymphoblastoid cells. Here we studied whether jacalin prevents HIV-1 gp120-CD4 interactions. We found (i) that jacalin did not inhibit HIV-1 Lai-induced syncytium formation that requires gp120-CD4 interactions; (ii) that jacalin prevented neither rgp120 binding to cell-surface CD4 nor sCD4 binding to viral envelope proteins expressed at the surface of HIV-1-infected lymphoblastoid cells; (iii) that jacalin did not compete for binding to CD4 with anti-CD4 mAb specific for the CDR2- or CDR3-like regions of the D1 domain of CD4; (iv) that jacalin did not bind a recombinant soluble molecule containing the D1/D2 domains of CD4; and, (iv) that jacalin binding to CD4 is inhibited by sugars known to interact with the lectinic-site of jacalin. These data have implications for the understanding of the mechanism by which jacalin blocks HIV-1 infection of CD4+ cells.

Acetylgalactosamine↗

Staphylococcal septicaemia after endometrial destruction.

Two cases of staphylococcus aureus septicaemia secondary to endometritis following endometrial destruction are presented. After surgical endometrial destruction, endometritis has been reported rarely, but there are no previous reports of staphylococcal septicaemia.

Adult↗

The effect of substituted aminoalkylaminoanthraquinones on eukaryotic cells.

Nine aminoalkylaminoanthraquinones (I-IX) were evaluated for their cytotoxic potency against normal and malignant mammalian cells. The 1.8-di-(aminopropylamino) derivative (VIII) exhibited significant activity against several tumor cell systems and had some selectivity. The toxicity of this compound was also tested in growing chick embryos.

Animals↗

The effect of diaminoalkyl-anthraquinone derivatives on the growth of the promastigotes of Leishmania tropica minor, L. t. major, L. donovani and L. aethiopica.

By combining knowledge of polyamine biosynthesis and its inhibition by various analogues with that on the activity of synthetic anthraquinones, a series of six anthraquinone derivatives were synthesized. Their ability to inhibit the growth of leishmanial promastigotes in vitro was used as a preliminary screen to check their potential as new antileishmanial chemotherapeutics. They were tested against four strains, representing four different species; Leishmania tropica major, L. tropica minor, L. aethiopica and L. donovani, associated with four separate disease syndromes. All six derivatives exhibited a fair degree of antileishmanial activity, some being more effective than others. They all inactivated cultures at 100 micrograms/ml and some did so at 10 micrograms/ml and even 1 microgram/ml; but taking different lengths of time to achieve this. Antileishmanial activity associated with anthraquinone derivatives might provide a new approach to the chemotherapy of leishmaniasis.

Anthraquinones↗