Biomedical subjects

U R Malik

Publications and source records attributed to U R Malik.

3 recordsLinked to original sources

PubMed2001

Interferon-mediated fatigue.

Fatigue is a common side effect of interferon (IFN) therapy, reported in 70-100% of patients treated with IFN. The etiology of IFN-mediated fatigue (IMF) is multifactorial, with endocrine failure, neuropsychiatric disturbance, autoimmunity, and cytokine dysregulation potentially being contributors. Thyroid dysfunction, associated with the development of autoantibodies, is seen in 8-20% of patients receiving IFN-alpha. IFN-alpha also suppresses the hypothalamic-pituitary-adrenal axis. In addition, IFN-alpha therapy leads to depression and cognitive slowing, and depressed patients are predisposed to develop fatigue. Clinical management of IMF is challenging because the syndrome is variable in onset and severity and the pathophysiology is poorly understood. Current management typically centers on dose reduction, but ancillary nonpharmacologic measures may help improve symptoms. Other strategies include antidepressant or anxiolytic therapy and treatment of coexisting hypothyroidism. Future studies utilizing IFN should include quantitative guidelines for grading and managing IMF.

Antineoplastic Agents↗

PubMed1996

Atypical clonal T-cell proliferation in infectious mononucleosis.

An atypical case of infectious mononucleosis characterized by fever, acute tonsillitis, and bilateral cervical adenopathy is reported in a previously healthy young man. Although serology was positive for the Epstein-Barr virus, the patient did not display peripheral blood lymphocytosis or atypical, reactive lymphocytes. The patient's tonsilar tissue revealed an expanded T-zone of diffuse, monomorphous lymphocytes suggestive of lymphoma. Immunophenotypic analysis of the tonsilar tissue demonstrated more than 90% expression of pan-T markers, while pan-B markers were positive in 5-10% of the interfollicular T-zone cells and in 90% of germinal centre cells. In situ hybridization with a probe specific for EBER1 demonstrated positive staining in approximately 1% of the interfollicular tonsilar lymphocytes. Finally, Southern blot analysis of tonsilar tissue demonstrated a clonal rearrangement of the T-cell receptor gene. The patient recovered from his infection and remains in good health years after presenting with his illness. This case illustrates that T-cell clonality must be evaluated with caution in the setting of a viral infection and can occur in association with benign, self-limited infectious mononucleosis.

Adult↗

PubMedDate not supplied

Phase II trial of merbarone in patients with malignant brain tumors.

The standard treatment for patients with primary malignant glioma includes surgical resection, radiotherapy, and nitrosourea. Despite this multimodality approach, adults with newly diagnosed glioblastoma multiforme (GBM) and high-grade astrocytoma have a median survival duration of 50 weeks and 150 weeks respectively. Chemotherapy has had a limited impact on the survival of these patients. Merbarone (5-phenylcarboxamide-2-thiobarbituric acid) is a nonsedating derivative of barbituric acid that crosses the blood brain barrier. Antitumor activity of merbarone has been described against L1210, B16 melanoma cell line and the M5076 sarcoma cells in phase I studies. Merbarone inhibits DNA synthesis and tumor growth by inducing single strand breaks in DNA. It also inhibits RNA and protein synthesis. We evaluated merbarone in a phase II trial in patients (pts) with recurrent or refractory GBM (7 pts) and high grade anaplastic astrocytoma (7 pts). Fourteen patients (nine males, five females) were treated with merbarone at a dose of 1000 mg per m2 per day by continuous intravenous infusion for 5 days every 3 weeks. Every patient received at least two cycles of treatment. No complete or partial responses were observed, although one patient had stable disease lasting 20 weeks. Our conclusion is that merbarone is ineffective against GBM and high-grade anaplastic astrocytoma at the dose and schedule in which it was administered in this trial.

Adult↗