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Biomedical subjects

T Ahmed

Publications and source records attributed to T Ahmed.

At least 127 records · Page 7Linked to original sources
PubMed1994

TMJ: a well-tolerated high-dose regimen for the adjuvant chemotherapy of high risk breast cancer.

Following local treatment and doxorubicin-containing standard chemotherapy, 42 patients with surgical Stage II or IIIA breast cancer containing ten or more involved axillary nodes and 13 patients with Stage IIIB disease were treated with high-dose chemotherapy (TMJ) consisting of thiotepa (750 mg/m2), mitoxantrone (40 mg/m2), and carboplatin (1000 mg/m2), with autologous bone marrow (ABM) and peripheral stem cell (PSC) transplant, followed by irradiation and/or hormone therapy. Sargramostim (GM-CSF) support was given to most patients. The median time to transfusion independence was two weeks. Severe non-hematologic toxicity was uncommon, with no intensive care admission or treatment-related death. At a median follow-up of 17 months, eight patients have relapsed and five have died of tumor progression. No statement can yet be made regarding adjuvant efficacy, but this high-dose regimen is very well tolerated.

Adult↗
PubMed1994

Phase I-II trial of high dose Ara-C, carboplatinum, etoposide and steroids in patients with refractory or relapsed lymphomas.

Thirty-three patients, including 20 with non-Hodgkin's lymphomas (NHL) and 13 patients with Hodgkin's disease, were treated with a combination of high dose Ara-C 3 gm/m2 over 3 h, carboplatinum 300 mg/m2 over 15 min, etoposide 300-750 mg/m2 continuous infusion over 24 h and solumedrol 1250 mg. Probantheline was given prophylactically. The etoposide dose was escalated from 300 mg/m2 to 600 mg/m2 to 750 mg/m2. The median age was 44 years (range 28-63). Median Karnofsky performance status was 80 (range 60-100). Patients treated included: primary refractory six, first relapse 14, > first relapse seven, and resistant relapse six. Responses were seen in 11 patients (33%; 95% CI 17-49). Of note, no responses were seen in ten patients receiving < 750 mg/m2 etoposide vs. 11/23 patients receiving 750 mg/m2 etoposide (p = 0.013). Responses were seen in patients who were refractory to previous chemotherapy and occurred in all sites. Toxicity was tolerable with most patients not requiring hospitalization following chemotherapy. Two patients died on study: one of Guillain-Barre syndrome and the other of a sudden death. Severe mucositis was not observed. High dose etoposide based salvage chemotherapy offers a greater probability of response than lower dose etoposide. This regimen is well tolerated and can be administered with relatively brief hospitalization.

Adult↗
PubMed1994

Clinical and laboratory comparison study of refrigerated and cryopreserved bone marrow for transplantation.

Refrigerated storage for short-term preservation of bone marrow is an alternative to cryopreservation where chemotherapeutic regimens include drugs with short in vivo half-lives. We performed a clinical and laboratory comparison of bone marrow stored at 4 degrees C for up to 9 days to bone marrow cryopreserved at -90 degrees C for autotransplantation. After adjusting for the confounding effects of disease type or sex, no clinically meaningful variation in post-transplant course between refrigerated storage and cryopreserved was found. Therefore, the data presented in this study suggest that the clinical recovery indices following transplantation between the two storage groups are essentially equivalent. One potential advantage to refrigerated storage, however, is that it may provide an opportunity for extended exposure to growth factors and/or purging agents in vitro prior to transplantation. To prepare for an in vitro analysis of this hypothesis, we concentrated the stem cell population and compared the nucleated cell recovery, viability and colony forming potential following refrigerated storage of whole bone marrow and buffy coat to cryopreserved bone marrow stored for the same interval. While the nucleated cell recovery for cryopreserved marrow was significantly greater than for refrigerated storage, the viability and colony forming potential of the refrigerated storage was superior or equivalent, independent of prior processing.

Adolescent↗
PubMed1993

Preventing bronchoconstriction in exercise-induced asthma with inhaled heparin.

BACKGROUND: We have previously reported that inhaled heparin prevents allergic bronchoconstriction in sheep and inhibits the anti-IgE-mediated release of histamine from mast cells in vitro. Since the release of such mediators has been implicated in exercise-induced asthma, we investigated whether inhaled heparin could also attenuate the bronchoconstrictor response in this disease. METHODS: On five days we studied 12 subjects with a history of exercise-induced asthma. On day 1 they underwent a standardized exercise challenge on a treadmill to document the presence of exercise-induced asthma. Minute ventilation was estimated with a calibrated respiratory inductive plethysmograph. The workload was increased until the heart rate reached 85 percent of the predicted maximal value, and was sustained for 10 minutes. The magnitude of bronchoconstriction was assessed by measuring specific airway conductance before and after the exercise. On day 2 the partial-thromboplastin time was measured in plasma obtained before and after the subjects inhaled a nebulized solution of heparin (1000 U per kilogram of body weight). On days 3 through 5 the subjects were pretreated with 4 ml of inhaled heparin (1000 U per kilogram), cromolyn sodium (20 mg), or placebo according to a single-blind, randomized, crossover design and underwent exercise challenge 45 minutes later. To exclude the possibility that heparin had any direct effect on airway smooth muscle, bronchial provocation with histamine was induced in five subjects on two further days after pretreatment with either heparin or placebo. RESULTS: Inhaled heparin and cromolyn sodium had no effect on specific airway conductance at base line, but did attenuate the exercise-induced decreases in this variable: the mean (+/- SE) maximal decrease five minutes after exercise was 9 +/- 5 percent after pretreatment with heparin, as compared with 22 +/- 5 percent after pretreatment with cromolyn and 35 +/- 2 percent after pretreatment with placebo. Heparin did not change the partial-thromboplastin time and did not modify the bronchoconstrictor response to histamine. CONCLUSIONS: Inhaled heparin prevents exercise-induced asthma without influencing histamine-induced bronchoconstriction. This non-anticoagulant action of heparin is more likely to be related to a modulation of mediator release than to a direct effect on smooth muscle.

Administration, Inhalation↗
PubMed1993

Systemic lupus erythematosus evolving into systemic vasculitis: a report of five cases.

Five patients with systemic lupus erythematosus are described who developed the disease in their second or third decade. The pattern of their disease then changed markedly and they developed the clinical features of a systemic vasculitis. The possible explanations for this transition of one connective tissue disease to another is discussed.

Adolescent↗
PubMed1993

Inhibition of antigen-induced airway and cutaneous responses by heparin: a pharmacodynamic study.

We have previously shown that heparin attenuates the acute bronchoconstrictor response and immediate cutaneous reaction (ICR) to antigen in allergic sheep. In the present investigation, we studied the pharmacodynamics of the antiallergic action of heparin. Specific lung resistance (sRL) was measured in eight sheep, allergic to Ascaris suum antigen, before and 5 min after inhalation challenge with the antigen. On different experiment days, antigen challenge was repeated after pretreatment with 1) aerosol heparin (1,000 U/kg) administered < or = 20 min, 6 h, 12 h, and 24 h and 2) intravenous heparin (1,000 U/kg) administered < or = 20 min, 1 h, 6 h, and 12 h before antigen challenge. sRL increased by 374 +/- 116% (SE) above baseline with antigen alone. Both aerosol and intravenous heparin attenuated the antigen effects on sRL in a time-dependent fashion. Prolonging the lag time between pretreatment and antigen challenge decreased the inhibitory effect of aerosol heparin; delta sRL was 31 +/- 29, 99 +/- 38, 142 +/- 40, and 306 +/- 60% for < or = 20-min, 6-h, 12-h, and 24-h pretreatment protocols, respectively. In contrast, prolonging the lag time increased the inhibitory effect of intravenous heparin: delta sRL was 246 +/- 64, 66 +/- 26, and 76 +/- 32% for < or = 20 min, 1 h, and 6 h, respectively. In seven additional sheep pretreatment with intravenous heparin (1,000 U/kg) attenuated the ICR also in a time-dependent manner; the inhibitory effect of heparin on ICR to antigen was enhanced 60% by increasing the heparin pretreatment interval from 20 to 60 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerosols↗
PubMed1993

Ovine tracheal muscle contraction in vitro: inhibition by calcium channel blockers gallopamil and verapamil.

We compared the inhibitory effects of calcium channel blockers, gallopamil and verapamil on acetylcholine (Ach)-induced contractions of ovine tracheal muscle in vitro. Adult sheep were sacrificed and tracheal strips were obtained by cutting the single tracheal rings from the mid-trachea. Tracheal strips were suspended in Krebs-Henseleit solution and isometric tension measured upon stimulation with cumulative doses of Ach (10(-7) to 10(-4) M) without and after pretreatment with gallopamil (10(-7) to 10(-6) M) or verapamil (10(-6) to 10(-5) M). In untreated tissues, the mean concentration of Ach required to produce 50% of maximal response (EC50) was 4.3 x 10(-6) M Ach. Both gallopamil and verapamil inhibited the Ach-induced contractions of ovine tracheal smooth muscle, by shifting the dose-response curves to Ach to the right. EC50 Ach for gallopamil (10(-6) M) and verapamil (10(-6) M) was 2.6 x 10(-5) and 5.2 x 10(-6) M, respectively. Dose ratio defined as postantagonist EC50 Ach/control EC50 Ach, was 7.7 for gallopamil and 2.0 for verapamil. Thus, the inhibitory effect of gallopamil was approximately 4-fold more potent than that of verapamil. Gallopamil was 17-fold more potent than verapamil in relaxing precontracted tracheal strips. The dose of calcium antagonists required to produce 25% relaxation (EC25) of tracheal strips precontracted with 10(-4) Ach was 3.7 x 10(-5) M for verapamil and 2.2 x 10(-6) M for gallopamil. These results indicate that gallopamil is effective against Ach-induced contractions of ovine trachealis muscles, and is more potent than verapamil.

Acetylcholine↗
PubMed1993

Experimental antiasthmatic activity of RWJ 22108: a bronchoselective calcium entry blocker.

RWJ 22108 (N-benzyl-N-methylaminoethyl 9-(2-chloro-6-fluorophenyl)-2,3,4,5,6,9-hexahydro-7-methyl-1, 1-dioxothiacyclohepteno-[3,2-b]pyridine-8-carboxylate) is a new bronchoselective calcium entry blocker with potential use as an antiasthmatic agent. Previous studies have shown that RWJ 22108 is a potent calcium entry blocker in vitro and demonstrates tissue selectivity for airway smooth muscle over vascular smooth muscle. The current study demonstrates the in vivo activity of RWJ 22108 in several different models of airway obstruction and asthma. RWJ 22108 relaxes preconstricted airways in dogs with little effect on blood pressure when administered by aerosol. In addition, it inhibits airway obstruction induced by antigen, histamine and exogenous leukotriene D4 in guinea pigs. In a conscious sheep model of allergic asthma, aerosol RWJ 22108 inhibits antigen-induced early and late phase airway obstruction and also the cellular infiltration associated with late phase. Total leukotrienes production is decreased in the guinea pig model probably as a result of fewer inflammatory cells infiltrating the lungs as shown in the sheep model of late phase. These data suggest that RWJ 22108 may have pharmacological potential in the clinical management of asthma.

Airway Obstruction↗
PubMed1993

Phase I clinical and pharmacokinetic evaluation of high-dose mitoxantrone in combination with cytarabine in patients with acute leukemia.

PURPOSE: To determine the maximally tolerated dose of mitoxantrone in combination with cytarabine in patients with acute leukemia and advanced phases of chronic myelogenous leukemia (CML), and to assess the pharmacokinetics of high-dose mitoxantrone in this patient population. PATIENTS AND METHODS: In a phase I study, 68 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and accelerated- and blastic-phase CML received induction therapy consisting of cytarabine 3 g/m2 by infusion over 3 hours daily for 5 days, with escalating doses of mitoxantrone 40 to 80 mg/m2 over 1 to 2 days by intravenous infusion over 15 minutes. Mitoxantrone pharmacokinetics were evaluated by high-performance liquid chromatography (HPLC) in 15 patients given a single dose of mitoxantrone ranging from 40 to 80 mg/m2 in combination with cytarabine. RESULTS: Severe, but reversible hyperbilirubinemia (> three times normal) was considered the dose-limiting toxicity, and was observed in 25% of all patients and in 35% of those who received 70 to 80 mg/m2 of mitoxantrone. Other extramedullary toxicity, including cardiac dysfunction, was mild. Myelosuppression was universal and the median time to complete remission (CR) was 28 days (range, 19 to 77). The CR rate for previously untreated and relapsed patients with AML was 85% (17 of 20) and 38% (seven of 18), respectively. Eighty-three percent (15 of 18) of patients with ALL achieved a CR, including all patients with previously untreated disease. Eight of 12 patients with advanced-phase CML achieved a CR. No significant changes in mean mitoxantrone plasma elimination rates (ie, terminal plasma half-life and total-body clearance rate) occurred as the mitoxantrone dose doubled, indicating linear pharmacokinetics. CONCLUSIONS: The recommended phase II dose of mitoxantrone is 80 mg/m2 administered over 15 minutes as a single intravenous infusion in combination with cytarabine 3 g/m2/d for 5 days. At this dose, high concentrations of mitoxantrone are achievable in vivo to levels that have been shown to be extremely cytotoxic in vitro.

Adolescent↗
PubMed1993

Restrictive chest bellows disease and frontometaphyseal dysplasia.

We describe a patient with frontometaphyseal dysplasia (FMD), restrictive chest bellows disease, hypercapnic respiratory failure, and cor pulmonale. Treatment with intermittent supplemental oxygen, nocturnal nasal volume ventilation, and posture modification was successful in partial resolution of chronic hypoventilation and excessive daytime somnolence.

Abnormalities, Multiple↗
PubMed1993

Antiseptic mouthwashes in modern dental practice.

This article is based on the winning entry of the Oraldene Student Essay Competition which was announced in Dental Update in the November 1992 issue. On the opposite page Miss Ahmed can be seen accepting her prize of 500 pounds from Professor C.E. Renson and Professor F.C. Smales.

Humans↗
PubMed1993

Propantheline prevention of mucositis from etoposide.

Mucosal toxicity is dose limiting for etoposide. This may be related to the direct effects of etoposide on the mucosa. Twelve patients receiving etoposide 1800 mg/m2 as part of a myeloablative pre-transplant regimen were randomized to receive propantheline 30 mg or placebo orally every 6 h for six doses. Mucositis was less frequent (2 of 6 vs 5 of 6) and less severe (p = 0.05) in the propantheline arm. There were no differences in tumor response or survival between the two groups. Propantheline is an anticholinergic that causes xerostomia by decreasing salivation. Propantheline may reduce the salivary excretion of etoposide and could reduce its toxic effects on the mucosa. Propantheline is effective in reducing the incidence and severity of mucositis in patients receiving high-dose etoposide.

Adult↗
PubMed1993

Induction of DNA strand breaks associated with apoptosis during treatment of leukemias.

A new flow cytometric method is described to detect DNA strand breaks associated with apoptosis, by labeling the 3'-OH termini in the breaks with biotinylated dUTP in a reaction employing exogenous terminal deoxynucleotidyl transferase. The method has been applied in studies on leukemic HL-60 and MOLT-4 cell lines to reveal whether it is specific to apoptotic cells, and whether it can be used in the clinic to detect DNA breakage in leukemic cells during chemotherapy. There was labeling of mononuclear cells in peripheral blood of all 11 patients studied during chemotherapy for acute lymphoblastic, acute myelogenous, or chronic myelogenous leukemia (ALL, AML, or CML) in blastic crisis, indicating induced DNA damage; the number of labeled cells increased from 1-8% before treatment up to 80% during the course of treatment. The DNA topoisomerase inhibitors mitoxantrone, VP-16 (etoposide), and m-AMSA (amsacrine) were more effective in inducing DNA breaks than was hydroxyurea or cytosine arabinoside (AraC). Cells with DNA breaks were identified in peripheral blood for up to 5 days following administration of Mitoxantrone and VP-16. In the case of DNA aneuploid leukemias, the DNA breaks were predominant in the aneuploid cell subpopulations, whereas presumably non-neoplastic diploid cells were unlabeled. In one case of ALL there were two distinct subpopulations of aneuploid cells: one responded to the treatment (by DNA breakage) and the other was non-responding. Thus, cells undergoing apoptosis can be detected by this method of labeling DNA strand breaks and the technique is applicable for analysis of response of leukemic cells to chemotherapy. With this method it may be possible to identify tumor cell sensitivity or resistance to particular drugs early in the course of treatment.

Adult↗