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Biomedical subjects

U Malik

Publications and source records attributed to U Malik.

At least 19 recordsLinked to original sources

Multi-day radon signals with a radioactive decay limb -- occurrence and geophysical significance.

Multi-day signals, generally with duration of 2-10 days, are a prominent temporal variation type of radon (Rn) in geogas in the unsaturated zone. Rare multi-day Rn signals have been found which are characterized by: (a) a declining limb lasting up to 10 days which conforms to the radioactive decay of Rn, (b) recurs at the same location and (c) is recorded in diverse situations-volcanic and seismogenic. It suggested that a Rn blob is injected at a lower level on a steady upward flow of geogas whereby the rise and final fall of the signal are attributed to the edges of the blob while the central Rn-decay segment records the passing of the decaying blob itself. Rn-decay signals are a small subset of multi-day Rn signals which are considered as highly irregular and unusable for the understanding of geophysical processes. In difference, it is concluded that multi-day Rn signals are probably proxies of subtle geodynamic processes at upper crustal levels and are therefore significant for studying such processes.

Journal Article↗

Phase I trial of pegylated liposomal doxorubicin and docetaxel in advanced breast cancer.

PURPOSE: To develop a combination of pegylated liposomal doxorubicin (Doxil; Alza Pharmaceuticals, Palo Alto, CA) and docetaxel (Taxotere; Aventis Pharmaceutical, Parsipanny, NJ) that can be safely used for the treatment of advanced breast cancer. PATIENTS AND METHODS: Forty-one patients with locally advanced (n = 10) or metastatic (n = 31) breast cancer received Doxil (30-, 40-, or 45-mg/m(2) intravenous [IV] infusion over 30 to 60 minutes), followed 1 hour later by docetaxel (60 or 75 mg/m(2) by IV infusion over 1 hour) in cohorts of three to six patients. Dose-limiting toxicity (DLT) was defined as febrile neutropenia, prolonged neutropenia, or grade 3 to 4 nonhematologic toxicity that occurred during cycle 1. RESULTS: In conjunction with docetaxel 75 mg/m(2) every 4 weeks, the MTD of Doxil was 30 mg/m(2) and required granulocyte colony-stimulating factor (G-CSF) to prevent febrile neutropenia. Without G-CSF, the MTD was docetaxel 60 mg/m(2) and Doxil 30 mg/m(2) every 3 weeks; only 1 (7%) out of 15 patients treated at this dose level had cycle 1 DLT. Infusion reactions were common with Doxil with the recommended infusion schedule during the first cycle (55%) but were reduced with a modified schedule (7%). There was no clinically significant cardiac toxicity. Objective response occurred in eight of nine assessable patients with stage III disease and in 16 (52%) of 31 patients (95% confidence interval, 34% to 70%) with stage IV disease. CONCLUSION: The recommended dose and schedule of this combination for further evaluation is Doxil 30 mg/m(2) and docetaxel 60 mg/m(2) given every 3 weeks without G-CSF. When used with G-CSF, it is Doxil 30 mg/m(2) and docetaxel 75 mg/m(2) every 4 weeks.

Adult↗

Therapeutic efficacy of theophylline in chronic lymphocytic leukemia.

Theophylline, a methylxanthine commonly used as a treatment for asthma, has been shown to induce apoptosis in chronic lymphocytic leukemia (CLL) cells both in vitro and in vivo. We have treated three advanced CLL patients with theophylline, and seen responses in two. The clinical courses of the responders are presented, and the literature concerning theophylline as therapy for CLL is reviewed.

Antineoplastic Agents↗

Acquired Glanzmann's thrombasthenia associated with Hodgkin's lymphoma: a case report and review of the literature.

BACKGROUND: Acquired Glanzmann's thrombasthenia is a rare hemorrhagic diathesis resulting from impaired adhesive function of the platelet receptor GPIIb/IIIa (alpha(IIb)beta3). Typically, this disorder develops during adulthood, with patients manifesting fluctuating clinical and laboratory findings. To date, the underlying defect of most if not all cases of acquired Glanzmann's thrombasthenia results from an autoantibody or plasma protein inhibitor directed toward a demonstrably normal GPIIb/IIIa glycoprotein. METHODS: In this report, a patient with a history of treated Hodgkin's lymphoma presented with a severe hemorrhagic diathesis characterized by mild thrombocytopenia, a prolonged bleeding time, and defective platelet aggregation. RESULTS: Examination of the patient's platelet GPIIb/IIIa by Western blot analysis revealed no abnormality. Mixing studies demonstrated a non-immunoglobulin G plasma inhibitory factor, whereas flow cytometry analysis revealed elevated platelet-associated immunoglobulin (Ig) M. After an emergency colectomy for severe hemorrhage, the patient's qualitative and quantitative platelet parameters significantly improved. Pathology of the resected colonic segment demonstrated atypical lymphoid hyperplastic lesions. CONCLUSIONS: To the authors' knowledge, this is the first reported case of acquired Glanzmann's thrombasthenia associated with a putative IgM autoantibody. Furthermore, this report verifies the association of acquired thrombasthenia with lymphoproliferative disease. Although rare, awareness of this hemorrhagic diathesis as a possible sequelae of active or treated lymphoid disorders should encourage clinical vigilance of these patients.

Antibodies, Neoplasm↗

Intravenous gamma-globulin inhibits binding of anti-GM1 to its target antigen.

In this study, we preincubated the sera of 3 patients with neuropathies associated with elevated titers of IgM anti-GM1 antibodies, with increasing concentrations of intravenous Ig (IVIg) and assayed the inhibitory effect of this mixture on antibody binding to immobilized GM1 by an enzyme-linked immunosorbent assay. Pharmacologic concentrations of IVIg, ranging from 0.1 microgram/ml to 100 mg/ml, inhibited anti-GM1 binding to its target antigen from 26 +/- 3 to 71 +/- 7%, respectively, in a dose-dependent manner. A similar inhibition of binding was also observed with IVIg F(ab')2 fragments. These findings provide a possible mechanism for the clinical efficacy of IVIg in motor neuropathies.

Dose-Response Relationship, Drug↗

Phase I trial of high-dose mitoxantrone plus cyclophosphamide and filgrastim in patients with advanced breast carcinoma.

PURPOSE: To determine the maximum-tolerated dose (MTD) of mitoxantrone that could be safely used in combination with cyclophosphamide and filgrastim in patients with advanced breast carcinoma. PATIENTS AND METHODS: Twenty-seven patients with metastatic (n = 24) or locally advanced (n = 3) breast carcinoma received escalating doses of mitoxantrone (16, 20, 24, 28, or 32 mg/m2) plus cyclophosphamide at one of three dose levels: group 1, 1,200 mg/m2; group 2, 2,400 mg/m2; and group 3,600 mg/m2. All patients also received filgrastim 5 micrograms/kg administered subcutaneously beginning on day 2 and continuing until the post-nadir absolute neutrophil count (ANC) was > or = 10,000/microL. Treatment was repeated every 3 weeks if the ANC was > or = 2,000/microL and platelet count > or = 90,000/microL for a maximum of six cycles. Dose escalation occurred within each group if zero of three or one of four patients had dose-limiting toxicity during the first cycle. RESULTS: The MTD of mitoxantrone was 24 mg/m2 in group 1, less than 16 mg/m2 in group 2, and 28 mg/m2 in group 3. Neutropenia was dose-limiting, and cumulative neutropenia and thrombocytopenia occurred with continued therapy. Nonhematologic toxicity consisted predominantly of nausea, vomiting, alopecia, and fatigue. Three patients (11%) had a > or = 10% decrease in the left ventricular ejection fraction (LVEF), one patient (4%) had a decrease in the LVEF below normal, and none developed clinical congestive heart failure. Of patients with stage IV breast carcinoma who had not received prior chemotherapy for advanced disease, objective responses occurred in nine of 20 (45%), and the median response duration was 5 months. CONCLUSION: In combination with 600 mg/m2 of cyclophosphamide and filgrastim, the MTD of mitoxantrone is 28 mg/m2, a dose that is approximately twofold to 2.8-fold higher than the conventional dose used without a hematopoietic growth factor.

Adult↗

Endoscopic injection for the treatment of bleeding ulcers: local tamponade or drug effect?

Fifty-two patients with Forrest Ia or Ib bleeding ulcers were randomized to receive endoscopic injection therapy with either 1:10,000 epinephrine in water (Group I) or distilled water (Group II). Twenty-five out of 27 patients in group I, versus 22 out of 25 patients in group II, achieved initial hemostasis after endoscopic injection therapy (p > 0.05). Five patients who did not respond to local injection had bleeding controlled by heater probe thermocoagulation or surgical intervention. Three patients in each group developed rebleeding after initial hemostasis. Four of these patients had bleeding controlled by surgical intervention, while the other two died of underlying diseases. No change in systemic blood pressure, but a significant drop in the pulse rate were noted in both groups after injection therapy. Patients with shock at admission or ulcer size greater than 2 cm had a significantly higher rebleeding rate after initial hemostasis than patients with normal blood pressure and ulcers under 2 cm (p < 0.05). No serious complications were observed after injection therapy, and no significant difference in the amounts of solution required for successful hemostasis was noted between the two groups. We conclude that a local tamponade with distilled water is as effective and safe as diluted epinephrine solution for endoscopic injection therapy.

Double-Blind Method↗

Health, attitudes and beliefs of working women.

A cross-sectional case-control study was conducted comparing working women employed by the Women's Work Centres of the Orangi Pilot Project with non-working matched controls. Differences in the knowledge, attitude and practice of several variables were elicited. Working women's families had significantly higher immunization rates, 73% vs 55%, and shorter duration of illness, 5.9 days vs 8.8 days, compared to controls. More working than non-working women supported contraception, 100% vs 74%, desired equal education for sons and daughters (P less than 0.005), and had a dominant role in family health decision-making, 48% vs 12%. We conclude that these working women in Orangi have a different set of beliefs and practices than non-working women and this may be one important factor responsible for the lower morbidity in their children.

Attitude↗

Macromolecular biosynthesis in Mycobacterium smegmatis ATCC 607 in the presence of antibodies to mannophosphoinositides.

The biosynthesis of DNA, proteins, RNA and phospholipids in Mycobacterium smegmatis ATCC 607 was investigated by studying the incorporation of radiolabelled components in the presence of antiserum to mannophosphoinositides. The antiserum had an inhibitory effect on the rate of synthesis of these macromolecules. However, the inhibition was greater when antibody was present together with complement.

Antibodies, Bacterial↗

Antibody response to sulfolipids in experimental tuberculosis.

Live Mycobacterium tuberculosis H37Rv, when injected into guinea pigs, induced antibodies to sulfolipids whereas antibodies were not detected in animals injected with heat killed cells. The antibody titre was found to be related to the degree of infection. A significant decrease in the titre was noted after streptomycin treatment, suggesting that antibodies were produced in response to an increasing bacterial load that occurred as the infection progressed.

Agglutination Tests↗

Immunological studies with sulpholipids of mycobacteria.

Antibodies to sulpholipids of mycobacteria were produced in rabbits when injected as sulpholipid-MBSA complexes and were detected by kaolin agglutination and double diffusion techniques. Sulpholipid antibodies did not cross react with any other lipids of mycobacteria except cord-factor. The antigenicity of sulpholipids appears to be due to alpha-D-trehalose and sulphate groups. Guinea pigs immunized with sulpholipid-MBSA complexes showed partial protection against tuberculous infection with M. tuberculosis H37Rv, as revealed by mortality rate and score of lesions.

Animals↗