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Biomedical subjects

T Ahmed

Publications and source records attributed to T Ahmed.

At least 217 records · Page 12Linked to original sources
PubMed1986

Phase II trial of 10 deaza-aminopterin in patients with bladder cancer.

Deaza-aminopterin is a folate analog which is transported more rapidly than methotrexate into cells and appears to be more active than methotrexate against human and animal tumor in vitro. Fifteen patients with advanced urothelial tract cancer were given deaza-aminopterin 30-37.5 mg/m2 IV QW. In responding patients drug was given QOW after 4-6 consecutive doses. Doses were escalated or de-escalated by 7.5 mg/m2 depending on toxicity. Twelve patients had received prior chemotherapy which included methotrexate in nine. Three patients achieved a partial remission lasting 1, 3, and 3 months respectively: all responders had previously failed methotrexate after an initial response to a methotrexate containing regimen. None of the six patients who were methotrexate naive responded to deaza-aminopterin; 3 subsequently received methotrexate without response. Mild mucositis was universal and in 5 was severe. Six patients had an increase in liver transaminases probably secondary to anti-folate hepatotoxicity. Other toxicities included diarrhea, nausea, skin rash and fever. Further studies are needed to define the precise efficacy of deaza-aminopterin in patients with urothelial tract cancers.

Aged↗
PubMed1986

Treatment of colorectal hepatic metastases by intrahepatic chemotherapy alone or as an adjuvant to complete or partial removal of metastatic disease.

Because of the wide variation in reported benefits from the use of intrahepatic chemotherapy for colorectal hepatic metastases, the authors performed their own phase II studies comparing the use of intrahepatic chemotherapy alone and intrahepatic chemotherapy as an adjuvant to complete or partial removal of metastatic colorectal cancer to the liver. Techniques for partial removal included unilateral and bilateral wedge resection, peripheral presinusoidal embolization of the liver, and portal vein branch ligation. Patients were staged using the per cent hepatic replacement method of Pettavel and Taylor, and patients with bilateral metastases were included in the study. Twenty-seven patients, mean age 60.3 years, were examined. There were 19 males, mean age 60.4 years, and eight females, mean age 60 years. The patients were divided into four groups. Group A had an implantable pump only; Group B had an implantable pump and resection; Group C had an implantable pump and arterial embolization and portal vein branch ligation; and Group D had an implantable pump, partial resection, arterial embolization, and portal vein branch ligation. Kaplan-Meyer survival curves were calculated for all of these groups. A separate analysis was carried out for each of the stages, and a comparison was made. The study indicated that the overall median survival time was 18 months and that the more radical the treatment in addition to chemotherapy, the better the results. Such results were not totally dependent on the staging of the tumor volume but were dependent on the degree of extirpation of the tumor. In Group C, consisting primarily of Stage IIa, IIIa, and IV patients (i.e., unresectable patients), a doubling of expected median survival to 12 months could be achieved, compared to those in Group A, which achieved a median survival of only 6 months.

Adult↗
PubMed1986

Suppression of pulmonary and systemic vascular histamine H2-receptors in allergic sheep.

We have previously demonstrated a depression of airway H2-receptor function in sheep allergic to Ascaris suum antigen. To investigate whether this is a generalized defect, we studied the H1- and H2- histamine receptor functions in the pulmonary and systemic circulations of allergic and nonallergic sheep. Pulmonary arterial pressure, and cardiac output were measured for calculation of pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) before and immediately after a rapid intrapulmonary infusion of histamine (10 micrograms/kg), with and without pretreatment with H1- (chlorpheniramine) and H2- (metiamide) antagonists. Histamine alone increased mean PVR to 435 and 401% of base line and decreased mean SVR by 51 and 54% in the nonallergic and allergic sheep, respectively (P less than 0.001). In the nonallergic sheep following pretreatment with chlorpheniramine (selective H2 stimulation) or metiamide (selective H1 stimulation), histamine decreased SVR by 18 and 36%, respectively, suggesting that approximately two-thirds of the vasodepressor response was mediated by H1-receptors and one-third by H2-receptors. Combined H1- and H2-antagonists completely blocked the histamine response. In allergic sheep the histamine-induced decrease in SVR was primarily mediated by H1-receptors, because the response was blocked by H1-antagonist, chlorpheniramine, and the H2-antagonist, metiamide, had no effect. In the pulmonary circulation selective H1-stimulation caused a similar increase in PVR in allergic (365%) and nonallergic sheep (424%), whereas selective H2-stimulation caused a significant decrease in PVR in the nonallergic group (14%) but not in the allergic group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Endotoxin-induced changes in pulmonary hemodynamics and respiratory mechanics. Role of lipoxygenase and cyclooxygenase products.

We investigated the role of leukotrienes and cyclooxygenase products in endotoxin-induced pulmonary vascular and airway changes. In 11 conscious sheep, measurements of pulmonary vascular resistance (PVR), lung resistance (RL), arterial PO2, leukocyte count (WBC), and plasma thromboxane B2 (TxB2), 6-keto-PgF1 alpha and PgF2 alpha were obtained, before and at predetermined intervals after a 10-min infusion of E. coli endotoxin (0.3 microgram/kg). On a separate occasion, 5 sheep received an infusion of the leukotriene end-organ receptor antagonist FPL-57231 (0.7 to 1 mg/kg/min), before and for as long as 4 h after endotoxin infusion; and 6 sheep received a single injection of the cyclooxygenase inhibitor indomethacin (2 mg/kg) 1 h before endotoxin infusion. Endotoxin caused a biphasic response with an increase in mean PVR and RL to 441 and 353% of baseline, respectively, during the early phase (0 to 1 hr), and lesser increases to 168 and 195% of baseline during the late phase (1.5 to 4 h). These changes were associated with mild hypoxemia, marked leukopenia, and marked increases in plasma TxB2, 6-keto-PgF1 alpha and PgF2 alpha. The FPL-57231 completely blocked the endotoxin-induced changes in PVR, RL, and PaO2 during both phases without preventing the increases in TxB2; however, it partly attenuated the increases in 6-keto-PgF1 alpha and enhanced the generation of PgF2 alpha. Indomethacin, which blocked the endotoxin-induced increases in TxB2, 6-keto-PgF1 alpha, PgF2 alpha, and RL, only partly blocked the increase in PVR during the early phase, followed by an exaggerated increase of PVR during the late phase.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Suppression of gastric H2-receptor mediated function in patients with bronchial asthma and ragweed allergy.

We have previously demonstrated a depression of airway, vascular, and cutaneous H2-histamine receptor function in sheep with experimental allergic asthma. In the present investigation, we wished to determine if there is a depression of gastric H2-receptor function in subjects with allergic bronchial asthma. In eight normal subjects and seven subjects with allergic bronchial asthma and bronchial reactivity to ragweed antigen, gastric H2-receptor function was assessed by measuring basal and maximal stimulated acid output following pretreatment with a placebo or the H2-antagonist, cimetidine. Maximal stimulated acid output was defined as the peak acid output (PAW mEq/hr) of hydrochloric acid following a subcutaneous injection of histalog (1.5 mg/kg), and selective H2-stimulation as delta PAO = PAOplacebo-PAOcimetidine. While basal acid output was not different between the two groups, mean (+/- SD) PAO was significantly lower in the asthmatic group (14.0 +/- 8.2 mEq/hr) than the normal group (27.9 +/- 9.4 mEq/hr) (p less than 0.01). Mean PAO expressed as percent of predicted maximum was 112 +/- 36 percent in the normal group and 61 +/- 34 percent in the asthmatic group (p less than 0.01). Mean delta PAO was significantly higher in the normal group (17.1 +/- 4.8 mEq/hr) than in the asthmatic group (7.0 +/- 5.3 mEq/hr) (p less than 0.005) indicating suppressed selective H2-receptor stimulation in the latter. We conclude that in subjects with bronchial asthma and marked bronchial hyperreactivity to ragweed antigen, there is a depression of gastric H2-histamine receptor function.

Adult↗
PubMed1985

Teratoma with malignant transformation in germ cell tumors in men.

Pathology reports of over 580 male patients with germ cell tumors treated between 1972 and 1982 were screened for teratomas in which malignant transformation was apparent. The diagnosis was established in 17 cases. The median age was 28 years (range, 14-52). For patients with disease limited to the testis, the median survival has not been reached, with all five patients surviving disease-free at 22+ to 120+ months. Among the 12 patients with metastatic disease, the median survival was 30.5 months (range, 12-69). All 12 patients were treated with cisplatin-containing regimens. Six had complete responses either to chemotherapy alone or to chemotherapy plus resection of residual disease. Four of the six complete responders relapsed, and three died of progressive disease. One patient with sarcomatous differentiation was treated with a doxorubicin-based regimen and had a partial remission, which lasted 8 months. Teratoma with malignant transformation, when found in metastatic sites, appeared to be a poor prognostic pathologic variant in male patients with germ cell tumors.

Adolescent↗
PubMed1985

Phase-II trial of 4-demethoxydaunorubicin (DMDR) for advanced hypernephroma.

A phase-II trial of 4-demethoxydaunorubicin (4-DMDR) was performed in 21 patients with advanced renal cell carcinoma. The drug had demonstrated a broader spectrum of activity with less cardiotoxicity in preclinical evaluation than the parent compound daunorubicin. The starting dose was 12.5 mg/m2, with escalations to 15 and 17.5 mg/m2 in the absence of toxicity. Myelosuppression was the primary toxicity and cardiac toxicity was not seen in four patients who received four or more doses of DMDR. No responses were seen in 19 adequately treated patients, including 14 who had received no prior therapy.

Aged↗
PubMed1985

Preliminary results of M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) for transitional cell carcinoma of the urothelium.

The M-VAC (methotrexate, vinblastine, doxorubicin and cisplatin) regimen was used to treat 25 patients with transitional cell carcinoma of the urothelial tract. Treatment consisted of monthly cycles of 30 mg. per m.2 methotrexate, followed 24 hours later by 3 mg. per m.2 vinblastine, 30 mg. per m.2 doxorubicin and 70 mg. per m.2 cisplatin, and concluded with repeat vinblastine and methotrexate on days 15 and 22. Significant tumor regression was noted in 71 per cent of the patients. Complete clinical remission was observed in 12 of 24 patients (50 per cent, 95 per cent confidence limits 30 to 70 per cent) with bidimensionally measurable indicator lesions, 6 of whom had pathological confirmation. After surgical exploration 4 patients required downstaging to a partial remission. The median duration of response has not yet been reached at 9.5 plus months, range 4.5 plus to 16 plus. Five patients (21 per cent) had a partial clinical remission for 4 to 8 plus months, 1 had a minor response for 4 months and 1 had stable disease for 11 months. All metastatic sites responded, including bone (6 of 8 cases), liver (3 of 5), locoregional (12 of 17) and intravesical (6 of 7) disease. Toxicity included moderately severe myelosuppression that resulted in nadir sepsis in 4 patients and a drug-related death in 1, mild to moderate anorexia, vomiting, alopecia and renal dysfunction. These preliminary results suggest that treatment with methotrexate, vinblastine, doxorubicin and cisplatin is extremely effective against locoregional and disseminated urothelial tract tumors, with the expectation (95 per cent confidence limits) of inducing objective tumor regression in 53 to 89 per cent of the cases.

Adult↗
PubMed1985

Vinblastine and methotrexate for advanced bladder cancer.

Fifty-seven patients with advanced measurable urothelial tract cancer, 52 of whom had an adequate trial, were treated weekly with 3 to 4 mg. per m.2 vinblastine and 30 to 40 mg. per m.2 methotrexate. Of 3 patients with unidimensional parameters 2 showed improvement lasting 16 and 27 months, which was documented by serial cystoscopic examinations. An additional 2 patients had measurable disease that could have been encompassed in a preoperative radiotherapy field. Both patients are free of disease at more than 12 and 14 months, respectively. Of the 47 patients with bidimensionally measurable parameters 19 (40 per cent) achieved a complete or partial remission lasting a median of 8 months, with a range of 1 to 24 months. Of 25 patients with intra-abdominal or pelvic disease 7 achieved a complete or partial remission and 5 also had a minor remission. Of note, 18 of 38 patients who had received no prior chemotherapy achieved a remission versus 1 of 9 who had been treated previously (p equals 0.06). Responders frequently obtained another remission with subsequent chemotherapy (4 of 9 versus 0 of 16, p equals 0.03). Responders lived 14 months versus 8 months for nonresponders (p equals 0.02). Four responders had brain metastases compared to none of 28 nonresponders. The combination of vinblastine and methotrexate is a well tolerated, effective outpatient regimen for patients with urothelial tract cancers.

Adult↗
PubMed1985

Pulmonary edema with nifedipine in primary pulmonary hypertension.

Despite occasional case reports, vasodilator therapy of primary pulmonary hypertension remains unsatisfactory. Nifedipine, a calcium channel antagonist, has recently been recommended for the treatment of primary pulmonary hypertension. Transient mild side effects to this drug have been known. In this report we describe a case of primary pulmonary hypertension in whom oral nifedipine use was followed by fatal pulmonary edema. We suggest that nifedipine has the potential of causing life-threatening complications of pulmonary edema in patients with severe primary pulmonary hypertension, and in this condition it should be used cautiously.

Adult↗
PubMed1985

Increased serum copper in primary pulmonary hypertension: a possible pathogenic link?

In conscious sheep, we showed that intravenous infusion of copper sulfate produced a marked increase in pulmonary vascular resistance which was prevented by alpha-adrenergic blockade or catecholamine depletion. Because of these observations, we measured serum copper in 7 patients with primary pulmonary hypertension, and in 6 normal women. The 5 female patients had taken contraceptive and appetite-suppressant medication in the past. The mean serum copper level was significantly higher in patients with pulmonary hypertension, indicating that increased serum copper may be a cause or a marker of this entity.

Adult↗
PubMed1985

Direct and indirect effects of leukotriene D4 on the pulmonary and systemic circulations.

We investigated direct (vascular leukotriene receptor stimulation) and indirect (generation of cyclooxygenase metabolites) hemodynamic effects of leukotriene D4 (LTD4) in 6 conscious sheep. Pulmonary artery, pulmonary arterial wedge and systemic arterial pressures, and cardiac output were measured. From these parameters, pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) were calculated before and immediately after a rapid injection of LTD4 into the pulmonary artery. Injection of 0.1 micrograms/kg of LTD4 increased mean PVR to 421% of baseline (p less than 0.001). It produced a biphasic effect on SVR that, after an initial decrease of 18% (p less than 0.05), increased to 143% of baseline (p less than 0.05). Both PVR and SVR returned to baseline within 10 min. The same results were obtained when the dose of LTD4 was increased to 0.5 micrograms/kg. Dose-response curves with increasing doses of LTD4 )0.025 micrograms/kg to 0.5 micrograms/kg) revealed that the optimal dosage for maximal effect was 0.1 micrograms/kg. The effects of LTD4 (0.1 micrograms/kg) on the pulmonary circulation were completely blocked by the SRS-A antagonist, FPL-57231, as well as by indomethacin. In the systemic circulation, FPL-57231 blocked the biphasic effects of LTD4 on SVR, whereas indomethacin prevented the initial decrease without attenuating the subsequent increase in mean SVR (135% of baseline, p less than 0.05). We conclude that there are direct and indirect hemodynamic effects of LTD4: the systemic vasoconstrictor response is directly related to vascular leukotriene receptor stimulation, whereas activation of cyclooxygenase pathway products is responsible for the pulmonary vasoconstrictor and systemic depressor responses.

Animals↗
PubMed1985

Hypoxia enhances nonspecific bronchial reactivity.

Enhancement of nonspecific bronchial reactivity has been observed after antigen-induced bronchoconstriction, a mast-cell-mediated phenomenon. Because hypoxia also causes degranulation of mast cells, we tested the hypothesis that alveolar hypoxia produces nonspecific bronchial reactivity. In 11 conscious sheep, we determined specific lung resistance (SRL) (mean pulmonary flow resistance times thoracic gas volume) before and after exposure to either air-sham or a hypoxic gas mixture (13% O2, balance N2), with and without cromolyn sodium pretreatment. The sheep then received 50 breaths of 5% histamine or 10 breaths of 2.5% carbachol on different days. Inhalation of histamine and carbachol after air-sham caused a significant increase in mean SRL to 350 and 403% of baseline, respectively (p less than 0.01). A 30-min exposure to the hypoxic gas mixture, which per se had no effect on SRL, enhanced the histamine and carbachol-induced increases in SRL to 519 and 472% of baseline (p less than 0.01). These increases were significantly greater than those observed after air-sham exposure (p less than 0.05). Infusion of cromylyn sodium (3 mg/kg/min) before and during exposure to hypoxia prevented the posthypoxia enhancement of histamine-induced (n = 7) and carbachol-induced (n = 5) bronchoconstriction, without affecting the airway responsiveness to these agents during normoxia. These data suggest that alveolar hypoxia enhances nonspecific bronchial reactivity in sheep, which may be related to hypoxia-induced release of mast-cell mediators.

Airway Resistance↗
PubMed1985

Methylglyoxal-bis(guanylhydrazone) in hormone-resistant adenocarcinoma of the prostate.

Methylglyoxal-bis(guanylhydrazone) (MGBG), an inhibitor of polyamine synthesis, was administered to 35 patients with hormone-resistant advanced adenocarcinoma of the prostate in doses of 500 or 600 mg/m2 per week intravenously. Of 31 patients with bidimensional measurable soft-tissue lesions, 25 had an adequate trial, defined as four or more doses. Six (24%; 95% confidence limits, 8% to 32%) patients achieved a partial remission (greater than or equal to 50% reduction in tumor size) in soft-tissue disease. Response was noted to start after one to two doses and persisted for a median of three months (range, 1 to 4 months). Toxicity was tolerable, and significant myelosuppression was not observed. The lack of response in osseous metastases may be secondary to the short duration of remission or to the presence or inducibility of the enzyme ornithine decarboxylase in bone. Since some animal prostatic cancer tumor models are sensitive to cytotoxic drugs that produce polyamine inhibition, clinical trials of MGBG combined with other inhibitors of the polyamine pathway should be explored.

Adenocarcinoma↗