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Biomedical subjects

T I Mughal

Publications and source records attributed to T I Mughal.

18 recordsLinked to original sources

Primary thrombocythemia: a current perspective.

The relationships among thrombocytosis, abnormal platelet aggregation and altered hemostasis in primary thrombocythemia remain poorly understood. Consequently, the appropriate management of asymptomatic patients is controversial and needs to be individualized. For symptomatic patients, conventional therapy, usually hydroxyurea, is directed primarily at lowering the platelet count by suppression of megakaryocyte activity. Recombinant interferon alpha can selectively lower platelet counts and may offer a reasonable alternative. Recent experience with anagrelide is also most promising in both symptomatic and asymptomatic patients. Current thoughts on the pathogenesis and management guidelines are presented here.

Aspirin

Efficacy of Ondansetron and Lorazepam in controlling emesis associated with cytotoxic chemotherapy.

A phase II study using a combination of Ondansetron and Lorazepam to treat patients receiving either highly or moderately emetogenic chemotherapy regimens has recently been completed. A total of 56 patients were enrolled and data from 53 is amenable to analysis. The overall response rates were 100% and 91% for the highly and moderately emetogenic regimens respectively, with 16 out of 20 patients (80%) and 18 out of 33 patients (54.5%) achieving a complete or major response respectively. Toxicity was mild and no dose modifications were necessary.

Adolescent

A phase II study of recombinant granulocyte macrophage colony stimulating factor in patients with non-Hodgkin's lymphoma.

Myelosuppression is often the major limiting factor that prevents timely administration of cytotoxic chemotherapeutic agents, particularly in chemoresponsive malignancies. A study was designed to assess the role of GM-CSF in preventing myelosuppression in patients with intermediate-grade non-Hodgkin's lymphoma receiving combination chemotherapy (Cyclophosphamide, Vincristine, Prednisone and Epirubicin or Mitozantrone, +/- Bleomycin). A total of 24 patients were entered and data collated from 20 of them are amenable to analysis. All patients received the first chemotherapy cycle without GM-CSF and the second with GM-CSF (250 mg/m2 subcutaneously twice daily for 5 days commencing on the 5th day following chemotherapy). By entering only those patients who had suffered myelosuppression following chemotherapy, an internal control was established. GM-CSF administration significantly reduced the degree of neutropenia and leucopenia. The mean nadir white blood cell (WBC) and absolute neutrophil counts (ANC) were 2.88 x 10(9)/L and 0.97 x 10(9)/L in cycle 1 as compared to 5.95 x 10(9)/L and 2.92 x 10(9)/L respectively, in cycle 2 (p = 0.05 and 0.02, respectively). Eight patients (40%) had febrile neutropenias and 13 patients (65%) experienced a treatment delay by a median of 8 days during cycle 1. Six patients (30%) had febrile neutropenias and 2 patients (10%) had a treatment delay of 3 days during cycle 2. Reversible toxicity was seen in the majority of patients: bone pains (60%), skin rashes (35%), arthralgias (25%), and altered taste sensation (10%). No patient developed the capillary leak syndrome. This study demonstrates the efficacy of GM-CSF in preventing chemotherapy-induced myelosuppression.

Adolescent

Role of recombinant alpha-interferon in the treatment of advanced cutaneous malignant melanoma.

A total of 65 patients with advanced cutaneous malignant melanoma (MM) have now been treated with interferon alpha-2b (Intron A) at a dose of 10 million IU/m2 administered subcutaneously thrice weekly. Fifty-one patients were evaluable for response, and 4 of these (7.8%) achieved complete remission; 2 of these 4 remain so at 37 + and 54 + months. Six additional patients achieved a partial remission. All responders had subcutaneous, lymph node and/or pulmonary metastases only. In all responders, therapy was continued for a total of 12 months. The vast majority of patients experienced side effects, largely flu-like symptoms, mild leukopenia and mild hepatocellular dysfunction. No evidence of cumulative toxicity was observed. Our experience indicates that interferon alpha-2b is active in patients with advanced cutaneous MM.

Adult

Chronic leukaemias: can they be cured? Part II: Chronic lymphocytic leukaemia.

Despite improved understanding of the chronic lymphoid leukaemias, the long-term outcome for the majority of patients remains dismal. An alkylating agent, usually chlorambucil, with or without prednisone, remains the standard palliative treatment for chronic lymphocytic leukaemia. More recently, two new drugs have emerged, 2'deoxycoformycin and alpha-interferon, which appear to offer substantial benefit to patients with hairy cell leukaemia.

Adult

Role of recombinant interferon alpha 2 and cimetidine in patients with advanced malignant melanoma.

Following recent reports suggesting that the addition of cimetidine to interferon may enhance response rates in patients with metastatic malignant melanoma, we have completed a Phase II study of the use of recombinant alpha 2 interferon and cimetidine in patients with advanced malignant melanoma and who had progressive disease following interferon therapy alone. We observed two partial responses, no complete responses, and two patients had stable disease. Toxicity encountered was analogous to that of interferon alone. We conclude that the additional of cimetidine to alpha interferon is not beneficial in the treatment of advanced metastatic malignant melanoma.

Antineoplastic Combined Chemotherapy Protocols

Malignant melanoma--profile of an epidemic.

Cutaneous malignant melanoma is occurring in epidemic proportions in the United States. To provide a profile of persons at risk and the epidemiologic features of malignant melanoma, we reviewed the records of 325 patients with cutaneous malignant melanoma seen at the University of Colorado Health Sciences Center between 1973 and 1983. Most patients had fair skin, brown or blonde hair, blue or green eyes, and had difficulty in suntanning. The majority of melanomas (72%) developed in preexisting nevi. In women, melanomas were most common on the extremities, and in men they occurred most frequently on the trunk, head or neck. The most frequently noted depth of invasion was Clark's level IV. At diagnosis, most of the patients (77%) were at stage I. We conclude that malignant melanoma constitutes a major disease problem in the western United States that is largely preventable with appropriate physician and patient education.

Adolescent

Phase I clinical trial of intracarotid bis-chloroethylnitrosourea (BCNU) and 2' dioxy-5-fluorouridine (FUDR) in malignant astrocytomas.

Systemic chemotherapy has been of limited benefit in the treatment of intracranial neoplasms, due, in part, to the inability to deliver effective drug doses to the neoplasm without systemic toxicity. We have completed a clinical trial of intracarotid BCNU and FUDR using an implantable pump in patients with unilateral malignant astrocytomas (Grade III and IV) in the hope of obtaining better tumor control with less systemic toxicity. Six patients had in-dwelling catheters placed in the internal carotid artery attached to a percutaneous refillable pump (Infusaid 400). The treatment program consisted of bolus BCNU 400 mg every 6 weeks and FUDR by continuous infusion at dosages ranging from 0.5 mg/24 h to 2.5 mg/24 h. The maximum tolerable dose of FUDR was 1 mg/24 h with ipsilateral mucositis and conjunctivitis being dose limiting factors. Flow studies demonstrated significant perfusion of the ipsilateral eye and surrounding face secondary to ophthalmic artery collaterals. No patient had systemic toxicity and the lowest WBC encountered was 2 400 with normal differential and platelets.

Aged

Treatment of metastatic malignant melanoma with recombinant interferon alpha 2.

Fifty-nine patients with metastatic malignant melanoma were entered into a phase II trial of recombinant alpha-2 interferon given in a dosage of 10 million IU/M2 subcutaneously three times per week for one year. Forty-five of these were evaluable for response. Of five evaluable patients with ocular primaries, none responded to interferon treatment. Four of 40 patients (10%) with cutaneous primaries achieved complete remission, and 6 further patients (15%) had partial remissions for a combined response rate of 25%. Two patients remain in complete remission 15+ and 32+ months after starting treatment. Responses were limited to subcutaneous, lymph node and lung metastases. The treatment schedule was well tolerated with the majority of patients receiving more than 70% of their predicted doses. Flu-like symptoms were the most common side effect. No evidence of cumulative toxicity was seen. We conclude that interferon is an active agent in metastatic malignant melanoma of cutaneous origin and that further trials are indicated.

Adult

Recovery of blood and bone marrow stem cells following intense chemotherapy and autologous bone marrow transplantation.

Sixteen patients with advanced (stage III) malignant melanoma were treated with escalating doses of intravenous BCNU and melphalan starting at 400 and 35 mg/m2, respectively, and escalating to 1,000 and 110 mg/m2, respectively, combined with autologous marrow transplantation. The duration of granulocytopenia and time to granulocyte recovery was similar in all groups regardless of chemotherapy dose. Platelet recovery was delayed in patients receiving the highest doses of chemotherapy. This study showed that bone marrow colony-forming units in culture took as long as 6 months to recover. This was adequate to bring peripheral blood counts to normal but not to pretreatment levels. These studies indicate that autologous bone marrow transplantation is beneficial in enhancing short-term recovery, but may not be beneficial in the long-term hematopoietic recovery.

Agranulocytosis

Adult Hodgkin's disease in Saudi Arabia.

Hodgkin's disease (HD) has variable clinical and pathologic features in different geographic regions. The reasons behind this are not completely clear. We reviewed 81 cases of adult HD who presented to the Adult Oncology Unit of the King Faisal Specialist Hospital, Riyadh, Saudi Arabia between 1975 and 1982. Fifty-seven (70.4%) were males and 24 (29.6%) were females with median ages of 29.9 and 23 years, respectively. The male:female ratio was 2.38:1. Two distinct age peaks at 18 and 48 years were seen in both sexes, with bimodality being more striking in females. The most common histologic subtype encountered was mixed cellularity (59.3%). Most of the patients (67.9%) were either Stage III or Stage IV at the time of diagnosis. These patterns differ significantly from those seen in reported Western series, but are similar to those reported from other areas in the Middle East.

Adolescent

Tumor lysis syndrome following VP-16-213 in chronic myeloid leukemia in blast crisis.

Several recent reports have emphasized the potentially serious and often fatal acute metabolic complications following cytotoxic chemotherapy in both solid tumors and leukemias. We present here a case of chronic myeloid leukemia in blast crisis who developed an acute tumor lysis syndrome following a single dose of VP-16-213 (Etoposide).

Adult

Bladder carcinoma presenting as a solitary bony metastasis.

Although bony involvement by transitional cell carcinoma of the bladder occurs frequently, its presentation as a symptomatic solitary bony metastasis is rare. Furthermore, presentation as a solitary distal metastasis with osteolytic and osteoblastic components is almost a novelty. We present such a case, which is additionally unusual in that the primary lesion in the bladder and the metastasis were resectable.

Aged

Improved tolerance of cytotoxic chemotherapy with lorazepam. A pilot study.

Nausea and vomiting may be the most distressing part of cytotoxic chemotherapy for malignant disease and frequently leads to default from treatment. Furthermore, in some patients, anxiety associated with chemotherapy precipitates anticipatory vomiting. 24 patients with refractory vomiting associated with chemotherapy were selected from a homogeneous group of malignancies. 25% of these also had anticipatory vomiting. Lorazepam, a benzodiazepine, in a dose of 3 mg/m2, was given by mouth in conjunction with a standard centrally acting antiemetic 30 min before chemotherapy. Vomiting was totally abolished in 70% of patients; in only 4% two vomiting episodes occurred. In addition, 17% of patients had complete amnesia of the events of chemotherapy. This pilot study suggests that lorazepam in conjunction with standard antiemetic therapy may be an effective means of controlling refractory nausea and vomiting.

Adult