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Biomedical subjects

T Ahmed

Publications and source records attributed to T Ahmed.

At least 235 records · Page 13Linked to original sources
PubMed1985

Influence of an antagonist of slow-reacting substance of anaphylaxis on the cardiovascular manifestations of hypoxia in piglets.

Leukotrienes have been implicated in the pathogenesis of hypoxic pulmonary hypertension in adult animals and in persistent pulmonary hypertension with accompanying hypoxemia in the neonate. In order to elucidate the role of leukotrienes in hypoxic pulmonary hypertension in a young animal model, the effects of a leukotriene antagonist, FPL 57231, were evaluated in anesthetized piglets. Cardiac output and vascular pressures were measured and pulmonary and systemic vascular resistances calculated prior to and during hypoxia. These measurements were compared during continued hypoxia between a control and treatment group which received FPL 57231. FPL 57231 infusion resulted in significant decreases in mean pulmonary artery pressure (p less than 0.04), pulmonary vascular resistance (p less than 0.01) and the ratio of pulmonary/systemic vascular resistance (p less than 0.01). Systemic vascular resistance fell approximately 25% from hypoxic baseline (p less than 0.01) while PVR decreased 54%. There were no differences between groups in mean systemic arterial pressure, cardiac output, pH, or PaCO2. In addition, pretreatment with FPL 57231 attenuated the hemodynamic response to hypoxia. These data suggest that leukotrienes may, in part, mediate hypoxic pulmonary vasoconstriction in piglets.

Animals↗
PubMed1985

Comparative modification of antigen-induced bronchoconstriction by the calcium antagonists, nifedipine and verapamil.

We compared the effects of the two calcium antagonists, nifedipine and verapamil, on baseline airway function and antigen-induced bronchoconstriction in asymptomatic subjects with ragweed hypersensitivity and a history of bronchial asthma. Twelve subjects received a single oral dose of 20 mg of nifedipine or 160 mg of verapamil before inhalation with ragweed antigen. Mean specific airway conductance, a measurement of airway obstruction, was not affected by either agent; nifedipine caused bronchodilatation in two subjects, and verapamil was followed by slight bronchoconstriction in another subject. Nifedipine partially or completely blocked the antigen-induced bronchoconstriction in 67 percent (8/12) of the subjects (p less than 0.05). Two of the subjects who were protected by nifedipine were also protected by pretreatment with verapamil, while this drug was without effect in the others. This study demonstrates that both nifedipine and verapamil in a single oral dose may attenuate antigen-induced bronchoconstriction in some subjects with allergic bronchial asthma and that nifedipine may be more effective than verapamil.

Adult↗
PubMed1985

Comparative effects of oral and inhaled verapamil on antigen-induced bronchoconstriction.

We investigated the comparative effects of oral and inhaled verapamil on specific airway conductance (SGaw) and allergic bronchial reactivity. Ten asymptomatic subjects with ragweed hypersensitivity and a history of bronchial asthma were studied on four different days, without and with pre-treatments by oral (160 mg) or inhaled (20 mg) verapamil. Bronchial reactivity was measured as the cumulative provocative dose of ragweed antigen which caused a 35 percent decrease in SGaw, ie PD35. The amount of inhaled verapamil actually deposited in the tracheobronchial tree was estimated to be 0.56 mg. Mean SGaw was not affected by either mode of administration; mean SGaw (SE) was 0.13(.02) and 0.12(.02) L/sec-1 before and .14(.02) and 0.12(.02) L/sec-1 after oral and inhaled verapamil, respectively. Mean (SE) PD35 was reproducible on two control days, ie 0.9(.4) and 0.8(.4) breath units, respectively. Inhaled verapamil increased mean PD35 to 18.8 (10.8) breath units (p less than 0.02), while oral verapamil had no significant effect on mean PD35. This study demonstrates that route of administration of calcium antagonist verapamil is an important factor in protection against antigen-induced bronchoconstriction. Inhalation of verapamil appears to be more effective than oral administration.

Administration, Oral↗
PubMed1985

Treatment of acute leukemia with amsacrine and high-dose cytarabine.

We varied the number of doses of high-dose cytarabine (3 g/m2) given to patients with acute leukemia in relapse who were receiving therapeutic doses of amsacrine (600 mg/m2/course). Twelve patients received 13 courses of therapy. Two of six patients with acute nonlymphocytic leukemia and one of three with acute lymphoblastic leukemia achieved remission. Dose-limiting toxicity (diarrhea) was seen in patients receiving more than five daily doses of high-dose cytarabine. We conclude that therapeutic doses of amsacrine can be combined safely with five daily doses of high-dose cytarabine and that a formal study is now required to assess the efficacy of this regimen.

Acute Disease↗
PubMed1984

Estrogen, progesterone, and androgen-binding sites in renal cell carcinoma. Observations obtained in Phase II trial of flutamide.

A Phase II disease-oriented drug trial using flutamide (4'-nitro-3'trifluoro-methylisobutyranilide) 250 mg by mouth three times a day was undertaken in 28 patients with advanced, bidimensionally measurable renal cell carcinoma. Of 25 adequately treated cases, 1 (4%, 95% confidence limits 0-12%) had a partial remission lasting 9+ months, and 2 had stabilization of disease lasting 6 and 15 months, respectively. Flutamide demonstrated no significant antitumor activity in patients with disseminated renal cell carcinoma. Including patients entered in this study, 62 specimens were evaluated for steroid binding sites using a fluorescent method: 33 of 62 specimens assayed showed no hormone-binding sites, and only 12 cases had androgen binding. Of the 12 of 23 patients receiving flutamide who were biopsied and had an adequate sample for steroid-binding site determination, estrogen binding was demonstrated in 6, androgen binding in 3, and progesterone binding in 4. Since this study did not obtain a sufficient number of cases with androgen-binding positivity, the possible efficacy of flutamide in such cases cannot be excluded.

Adenocarcinoma↗
PubMed1984

Inhibition of antigen-induced bronchoconstriction by methylprednisolone succinate.

We investigated whether the glucocorticoid methylprednisolone succinate mg/kg) could prevent antigen-induced bronchoconstriction in conscious sheep. Ten allergic ewes were subjected to inhalation challenge with Ascaris suum antigen, with and without methylprednisolone pretreatment, administered intravenously either 20 min or 3 hr before antigen challenge. Antigen challenge alone resulted in increased airflow resistance, pulmonary hyperinflation, and decreases in dynamic lung compliance and arterial oxygen tension. Methylprednisolone administered 20 min before antigen challenge had no effect on these antigen-induced changes. In contrast, administration of methylprednisolone 3 hr before antigen challenge effectively prevented all the responses to antigen challenge. We suggest that pretreatment with glucocorticoids can attenuate airway anaphylaxis if sufficient time is allowed between the pretreatment and the antigen challenge.

Animals↗
PubMed1984

Sequential trials of methotrexate, cisplatin and bleomycin for penile cancer.

Methotrexate, bleomycin or cisplatin was used to treat 21 patients with advanced bidimensionally measurable epidermoid carcinoma of the penis. Patient characteristics were similar in all 3 drug trials. Drug therapy was continued with each agent until the disease progressed. Significant tumor regression was observed in 8 of 13 men (61 per cent) treated with methotrexate, 3 of 12 (25 per cent) treated with cisplatin and 3 of 14 (21 per cent) treated with bleomycin. Responders tended to be younger than nonresponders (median age 48 versus 59 years, respectively, p less than 0.05) and lived a median of 8 versus 2 months, respectively (p equals 0.03). Cross-resistance was not encountered among the 3 drugs. Future trials might investigate combination regimens of all 3 agents.

Adult↗
PubMed1984

Activity of sequential low-dose methotrexate and fluorouracil in advanced colorectal carcinoma: attempt at correlation with tissue and blood levels of phosphoribosylpyrophosphate.

Forty-five patients with metastatic colorectal carcinoma were treated with low-dose methotrexate (MTX) and 5-fluorouracil (5-FU) given sequentially. The dose of MTX was 40 mg/m2 intravenously (IV) on days 1 and 8 followed 24 hours later by 5-FU at 600 mg/m2 IV on days 2 and 9; the drugs were recycled every 28 days. Fourteen (32%) of 43 adequately treated patients had a complete or partial response lasting a median of nine months (range, 6-15 + months). Four patients had a minor response and seven patients had stable disease for a median of nine and 10 months, respectively. Toxicity included mucositis in 28 (65%) patients, diarrhea in 18 (40%), nausea in 11 (24%), and vomiting in seven (16%). Hematologic toxicity was mild: six patients had nadir white blood cell counts less than 3.5 X 10(3) cells/microL, and seven patients had a nadir platelet count less than 100 X 10(3) cells/microL. Serial biopsies and blood samples were obtained in selected patients to evaluate the effect of MTX on tissue and lymphocyte phosphoribosylpyrophosphate (PRPP) and PRPP synthetase levels.

Adult↗
PubMed1984

Genetic variation for West Nile virus susceptibility in Culex tritaeniorhynchus.

Mutant and geographical strains of Culex tritaeniorhynchus were compared for West Nile (WN) virus susceptibility by feeding on a high-titered blood-virus suspension. Eleven strains also were selected from 2-21 generations for an increase and/or a reduction of oral susceptibility using 90% and 10% infective virus doses, respectively. Only one of the 20 strains tested, e ma, was significantly less susceptible than the control strain. In the selection experiments, none of the strains showed a consistent decrease in susceptibility, but the Changa Manga II (CM) strain showed a sustained increase in susceptibility from generations F11-F21 when selection was discontinued. Reciprocal cross-matings and back-crosses were set up between the selected CM strain and two of the morphological mutant strains, e ma and re e ae, carrying homozygous recessive markers. The resulting progeny were tested for susceptibility to WN virus infection and the ability to replicate virus to high-titers after infection. These results suggest that the trait of increased susceptibility is dominant over resistance. The enhanced ability of infected mosquitoes to replicate WN virus showed partial dominance. Both of these traits appear to be polyfactorial, and are apparently associated with more than one chromosome in Cx. tritaeniorhynchus.

Animals↗
PubMed1984

Similar specificity of membrane transport for folate analogues and their metabolites by murine and human tumor cells: a clinically directed laboratory study.

Mediated transport of folate compounds exhibited similar kinetic characteristics and structural specificity in a series of cultured murine and human tumor cells examined in a parallel fashion. In each case, influx was characterized by a single saturable component with an approach to steady-state conforming to a single exponential, while efflux was first order (poorly saturable). Both mediated fluxes exhibited high temperature dependence (Q10 27-37 degrees = 6 to 8). During competition studies with various analogues, it was found that positions 4, 5, 7, and 10 and the gamma-carboxyl position of the folate molecule were specified for influx in tumor cells from each species. Also, short-chain alkyl substitution at position 10 was specified in the case of N10, but not in the case of C10. None of the modifications at position 10 affected mediated efflux in either cell type. The linkage of additional glutamyl residues at the gamma-carboxyl-position resulted in reduced saturability (increased value for Ki) of influx in both murine and human tumor cells in a manner proportional to the number of glutamyl residues. Mediated influx in human ovarian carcinoma cells obtained from malignant effusions in several patients and in an established cell line derived from one of these patients showed similar kinetics for folate analogue transport and specificity for modification at position 10 of the 4-amino-folate molecule. Mediated entry of 10-deazaaminopterin and its 10-ethyl derivative compared to entry of methotrexate was 4- to 11-fold greater in murine tumor cells and 4- to 9-fold greater in human tumor cells in culture or when clinically derived. Mediated efflux was not specified for position 10 on the 4-amino folate structure in any tumor cell type. These findings appear to provide some basis for concluding that the results of studies of this type in model murine systems or with tumor cell lines established in culture have relevance to clinical cancer.

Animals↗
PubMed1983

Histamine receptor blocking effects of cimetidine in the airways.

We investigated the modification of histamine-induced bronchoconstriction by the H2-antagonist cimetidine in conscious sheep. One hundred breaths of 5% histamine aerosol increased mean (SD) pulmonary resistance (RL) by 5.6 (1.4) cmH2O/l/sec. This increase in RL was completely blocked by intravenous clemastine (0.5 mg), a specific H1-antagonist, indicating that the histamine-induced bronchoconstriction was mediated by H1-receptors. Intravenous cimetidine caused a dose-dependent enhancement of the histamine response between 1 and 1000 mg with a mean peak delta RL of 15.3 (5) cmH2O/l/sec (p less than 0.05) at the 1000 mg dose, while it blocked the histamine response at a dose of 2400 mg [delta RL = 1.9 (2) cmH2O/l/sec, p = NS]. This paradoxic effect was not related to an anticholinergic mechanism as intravenous cimetidine (2400 mg) failed to block carbachol-induced (25 breaths of 1% solution) bronchoconstriction. We conclude that in the ovine airway, cimetidine is a selective H2-histamine receptor blocker at lower tissue concentrations, and a combined H2- and H1-histamine receptor blocker at high tissue concentrations.

Airway Resistance↗
PubMed1983

Functional depression of H2 histamine receptors in sheep with experimental allergic asthma.

We tested the hypothesis that airway hyperresponsiveness to histamine in the allergic sheep is related to functional depression of H2 histamine receptors. Thirteen of 32 sheep responded with bronchoconstriction to inhaled Ascaris suum antigen (allergic sheep), and the remainder served as controls (nonallergic sheep). In the allergic sheep, 50 and 100 breaths of 5% histamine solution increased mean pulmonary resistance (RL) to 235% and 438% of baselines, respectively. The corresponding values in nonallergic sheep were 200% and 211%, indicating a greater response to the higher dose of histamine in allergic sheep. Selective H1-receptor stimulation with 50 breaths of histamine (pretreatment with the H2-receptor antagonist metiamide) failed to enhance the effect of histamine in allergic sheep (mean RL increased to 239% of baseline) whereas it enhanced the histamine response in nonallergic sheep (RL increased to 438% of baseline). Selective H2-receptor stimulation (pretreatment with the H1-receptor antagonist chlorpheniramine) caused histamine to decrease RL by 31% in the nonallergic sheep group; it blocked but did not reverse the histamine effect in the allergic sheep. Similar observations were made in a different group of animals when selective H1- or selective H2-receptor stimulation was produced by 100 breaths of histamine. The cutaneous wheal response to intradermal histamine dilutions of 0.0001. 0.001, 0.01, and 1 mg/ml was similar in both groups. In nonallergic sheep, both chlorpheniramine and metiamide blunted the cutaneous wheal response. In allergic animals, only chlorpheniramine blunted the cutaneous wheal response, whereas metiamide was without effect. We conclude that airway hyperresponsiveness to histamine in allergic sheep is related to a functional depression of H2 receptors and that such a defect is observed both in the airways as well as in the skin.

Animals↗