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Biomedical subjects

T Ahmed

Publications and source records attributed to T Ahmed.

At least 181 records · Page 10Linked to original sources
PubMed1990

PAF-induced airway responses in sheep: effects of a PAF antagonist and nedocromil sodium.

Platelet-activating factor (PAF) is a potent inflammatory mediator that can cause bronchoconstriction and airway hyperresponsiveness in selected human subjects and animals. The mechanism by which PAF induces these changes is not clearly understood. We therefore studied the effects of intratracheal instillation of PAF (30 micrograms/kg) on airway resistance and airway responsiveness in allergic sheep (n = 7) and attempted to modulate these effects with the specific PAF antagonist, WEB-2086, and the antiasthmatic agent, nedocromil sodium (NED). Specific lung resistance (SRL) was measured to assess bronchial responses to PAF, and airway responsiveness was determined by deriving a provocative dose of carbachol in breath units causing an increase in SRL to 4 L times centimeters of H2O per liters per second (PD4) from carbachol dose-response curves. PAF instillation increased mean +/- SD SRL to 228 +/- 134% above baseline. Two to 4 hours after PAF instillation, PD4 decreased by 55 +/- 9% from a baseline of 39 +/- 9 breath units (p less than 0.05). Airway responsiveness remained increased at 24 hours but returned to baseline by 48 hours. Pretreatment with WEB-2086 (3 mg/kg, intravenously) or NED (1 mg/kg, nebulized) blocked (p less than 0.05) PAF-induced bronchoconstriction and PAF-induced airway hyperresponsiveness. Instillation of lyso-PAF (30 micrograms/kg) did not cause bronchoconstriction or airway hyperresponsiveness. Thus, instilled PAF causes bronchoconstriction and airway hyperresponsiveness in allergic sheep by a receptor-mediated mechanism that likely involves the release of secondary mediators, the latter process being sensitive to NED.

Aerosols↗
PubMed1990

Active specific immunotherapy in patients with melanoma. A clinical trial with mouse antiidiotypic monoclonal antibodies elicited with syngeneic anti-high-molecular-weight-melanoma-associated antigen monoclonal antibodies.

In two clinical trials the mouse antiidiotypic monoclonal antibody (MAb) MF11-30, which bears the internal image of human high-molecular-weight-melanoma-associated antigen (HMW-MAA) was administered by subcutaneous route without adjuvants to patients with stage IV malignant melanoma on day 0, 7, and 28. Additional injections were administered if anti-antiidiotypic antibodies were not found or their titer decreased. In the first phase I trial with 16 patients the initial dose was 0.5 mg per injection and escalated to 4 mg per injection. Neither toxicity nor allergic reactions were observed despite the development of anti-mouse Ig antibodies. Minor responses were observed in three patients. In a second clinical trial MAb MF11-30 was administered to 21 patients at a dose of 2 mg per injection, since this dose had been shown in the initial study to be effective in inducing anti-antiidiotypic antibodies. Two patients were inevaluable; in the remaining 19 patients, the average duration of treatment was 34 wk. In this trial as well, neither toxicity nor allergic reactions were observed. 17 of the 19 immunized patients increased the levels of anti-mouse Ig antibodies and 16 developed antibodies that inhibit the binding of antiidiotypic MAb MF11-30 to the immunizing anti-HMW-MAA MAb 225.28. One patient increased the level of anti-HMW-MAA antibodies. One patient achieved a complete remission with disappearance of multiple abdominal lymph nodes for a duration of 95 wk. Minor responses were observed in three patients. These results suggest that mouse antiidiotypic MAb that bear the internal image of HMW-MAA may be useful reagents to implement active specific immunotherapy in patients with melanoma.

Adult↗
PubMed1990

Autologous marrow transplantation for Hodgkin's disease current techniques and prospects.

Hodgkin's disease is a chemotherapeutically curable malignancy, but cure is rare if a complete remission is not achieved with initial therapy. Drugs that have myelosuppression as a major dose-limiting toxic effect, can be given at high doses and may be combined together at close to the maximum tolerated dose with marrow rescue. Multiple chemotherapy drugs given at high doses with marrow rescue are best utilized if they possess dissimilar extramedullary toxicity. The use of growth factors and improved storage methods may also help reduce hematopoietic toxicity. There is currently no consensus on the ideal treatment regimen, although combinations of etoposide, carmustine, and cyclophosphamide are frequently used and are associated with decent disease-free survival. The frequency of pulmonary complications is higher with regimens containing higher doses of carmustine. There are no prospective comparative randomized trials between standard chemotherapy and high dose chemotherapy with marrow support. Patients transplanted earlier in the course of their disease appear to do best, as do patients with good performance status and low tumor burden who have had less than two prior regimens. In such patients the long-term disease-free survival after autologous bone marrow transplantation may be in excess of 80%. Patients with Hodgkin's disease refractory to front line chemotherapy do poorly with high dose chemotherapy with autologous marrow rescue and often do not achieve remission. Newer regimens need to be explored and developed for patients at high risk of relapse.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Clostridium perfringens type C in bloody and watery diarrhea in Bangladesh.

A two-week age-matched case-control survey to detect Clostridium perfringens type C-associated illness was conducted among diarrheal patients hospitalized following the consumption of high protein meals on the occasion of an annual religious festival. From the stool of 33 patients screened, C. perfringens type C was isolated from one patient with bloody diarrhea and from two patients with watery diarrhea. In Bangladesh, C. perfringens type C has been isolated in both bloody and watery diarrhoeal illness and is not necessarily associated with necrotizing enteritis (pigbel).

Bangladesh↗
PubMed1989

Contraceptive method choice in the Philippines, 1973-83.

Contraceptive use and method mix were analysed using Philippines national survey data of 1973, 1978, and 1983. The analyses suggest that the reported decline in contraceptive prevalence between 1978 and 1983 was due to under-reporting of use in 1973 and 1983. The shifts in contraceptive method mix were also partly from under-reporting of rhythm and other methods in 1973 and 1983. Nevertheless, the determinants of method choice were similar in all three sets of data. Filipino couples were making rational choices in terms of their contraceptive goals, access, evaluation, and competence. Modifications in the directions and magnitude of the relationships in determining method choice also occurred, partly reflecting the increased use of sterilization by older, higher parity women.

Adult↗
PubMed1989

Bacteremia and urinary tract infection associated with CDC group Vd biovar 2.

A case of urinary tract infection and bacteremia caused by CDC group Vd biovar 2 in a 23-year-old woman with Hodgkin's disease is described. This is the first report of CDC group Vd biovar 2 isolated from a clinical specimen and considered as a pathogen. Detailed antimicrobial susceptibility data are presented.

Adult↗
PubMed1989

Lack of protection against bacterial infections in patients with advanced cancer treated by biologic response modifiers.

A survey of patients with advanced cancer treated by biologic response modifiers (BRMs), including (i) recombinant interleukin-2 and lymphokine-activated killer cells, (ii) recombinant interleukin-2 and alpha interferon, and (iii) tumor necrosis factor, was done. A total of 52 patients were reviewed. A total of 73 courses of BRMs were administered. Prior to the initiation of therapy, all patients were infection free and not receiving antibiotics. Twelve patients developed bacteremia during treatment with these BRMs. Five of these 12 patients had catheter-related bacteremia. Six patients had bacteremic infections without an obvious source, and one patient had a urinary tract infection with bacteremia. Staphylococcus epidermidis accounted for six of the isolates. Other organisms were Staphylococcus aureus, group B streptococci, viridans group streptococci, and gram-negative bacilli. This was an unexpectedly high incidence of bacterial infections in patients treated with BRMs. These BRMs have been previously shown to be efficacious against infections (by bacteria and other intracellular organisms) in experimental animals. In this study BRMs did not influence host defense mechanisms or offer protection against bacterial infections.

Bacterial Infections↗
PubMed1989

Acute promyelocytic leukemia: a 5-year experience with new antileukemic agents and a new approach to preventing fatal hemorrhage.

Forty-six induction courses were administered to 32 patients with acute promyelocytic leukemia. There were 28 males and 18 females with a median age of 39.5 (range 19-68). Twelve patients were previously untreated, 32 were in relapse, and 2 were refractory to primary induction chemotherapy. Heparin 7.5-10 units/kg/h by continuous infusion, 4-6 units of platelets and 1-2 units of fresh-frozen plasma (FFP) every 12 h were given to all patients. Previously untreated patients received either daunorubicin, idarubicin or mitoxantrone in combination with cytarabine (Ara-C). For relapsed and refractory patients, regimens included amsacrine with high-dose cytarabine (Amsa/HiDac), homoharringtonine (HHT) alone, or with Ara-C, mitoxantrone and bisantrene. Hemorrhagic complications occurred in only 1 out of 46 courses (2%). Complete remission rates (CR) were as follows: previously untreated 83% (10/12), relapsed 66% (21/32), primary refractory 50% (1/2). Amsa/HiDac resulted in a 71% (10/14) CR and HHT-based regimens achieved a 46% (6/13) CR. These regimens are effective and the value of their incorporation into primary therapy should be studied. The use of heparin with platelet and FFP transfusions every 12 h reduces the risk of hemorrhage during induction therapy.

Adult↗
PubMed1989

Philadelphia chromosome (Ph1)-positive acute lymphoblastic leukemia (ALL) is resistant to effective therapy for Ph1-negative ALL.

Amsacrine with high-dose cytarabine is effective therapy for Philadelphia chromosome (Ph1)-negative acute lymphoblastic leukemia (ALL). We examined the effectiveness of this regimen in 19 patients with Ph1-positive lymphoblastic leukemia. Four had an antecedent chronic phase of chronic myelogenous leukemia and 15 presented with ALL. There were no complete responders in either group. All 14 patients whose bone marrow could be assessed after completion of therapy showed persistent leukemia. We conclude that patients with Ph1-positive lymphoblastic leukemia have a disease that is resistant to treatment that is highly effective in patients with Ph1-negative ALL.

Adolescent↗
PubMed1989

Effect of calcium antagonist gallopamil on antigen-induced early and late bronchoconstrictor responses in allergic sheep.

Calcium channel blockers have been shown to modify acute antigen-induced bronchoconstriction in allergic animals and in some human subjects with bronchial asthma; however, the effects of calcium antagonists on late-phase bronchial responses are not known. In this investigation, we studied the effects of calcium antagonist gallopamil on antigen-induced early- and late-phase bronchial responses in sheep allergic to Ascaris suum antigen. In 11 unsedated sheep, specific lung resistance (SRL) was measured before, immediately after, and serially up to 8 h after inhalation challenge with A. suum antigen. On different experiment days, at least 3 wk apart, the sheep were pretreated with gallopamil, administered either as an aerosol (5 mg, n = 10; 10 mg, n = 9) or as an intravenous injection (20 micrograms/kg, n = 10), and the antigen challenge was repeated. For the control experiments (n = 11), mean +/- SE SRL increased immediately after antigen challenge (early response) to 533 +/- 72% of baseline and again 6 to 8 h after challenge (late response) to 304 +/- 31% of baseline (p less than 0.05). Neither intravenously administered nor aerosolized gallopamil had a significant effect on baseline SRL. Both aerosolized and intravenously administered gallopamil blunted the early response and completely blocked the late-phase bronchoconstrictor response (p less than 0.05). Mean SRL during early phase increased to 208 +/- 39% and 245 +/- 39% of baseline with 5 mg and 10 mg of aerosolized gallopamil and to 191 +/- 35% of baseline with intravenously administered gallopamil, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Is there loss of protective muscarinic receptor mechanism in asthma?

We investigated the hypothesis that prior airway muscarinic receptor stimulation (with aerosolized methacholine) would modify the bronchoconstrictor response to histamine, which is, in part, vagally mediated. On four different experiment days, the following combinations of methacholine and histamine inhalation challenges were performed in 15 subjects (nine normal and six asthmatic) in a random fashion: methacholine-histamine, histamine-methacholine; methacholine-methacholine and histamine-histamine. Cumulative provocative dose of each agonist which caused a 50 percent decrease in SGaw was estimated (PD50). The second challenge was performed approximately 1 hour after the first challenge, when SGaw had returned to baseline. In normal subjects, prior muscarinic stimulation with methacholine suppressed the subsequent bronchoconstrictor response to histamine (mean +/- SE PD50 histamine increased from 13.7 +/- 3.1 to 28.4 +/- 7.2 breath units), without modifying the bronchoconstrictor response to methacholine. In asthmatic subjects, prior methacholine exposure failed to modify the bronchoconstrictor responses to histamine and methacholine. In contrast, prior challenge with histamine did not modify the subsequent bronchoconstrictor responses to histamine and methacholine in both normal and asthmatic subjects. Pretreatment with ipratropium bromide attenuated the histamine-induced bronchoconstriction, suggesting that airway effects of histamine, in part, are vagally mediated. These data suggest that prior muscarinic stimulation has a protective effect on histamine-induced bronchoconstriction in normal subjects and the absence of this inhibitory effect in asthmatic patients may represent loss of a protective muscarinic receptor mechanism.

Adult↗
PubMed1989

Inhibition of hydrolytic enzymes by gold compounds. I. beta-Glucuronidase and acid phosphatase by sodium tetrachloroaurate (III) and potassium tetrabromoaurate (III).

Purified bovine liver beta-glucuronidase (beta-D-glucuronide glucuronohydrolase, EC 3.2.1.32) and wheat germ acid phosphatase (orthophosphoric monoesterphosphohydrolase, EC 3.1.3.2) were inhibited with freshly dissolved and 24 h aquated tetrahaloaurate (III) compounds. Rate and equilibrium inhibition constants were measured. From this data two acid phosphatases species were observed. Equilibrium inhibition constants ranged from 1 to 12.5 microM for the various gold compounds toward both enzymes. The first order rate constants ranged between 0.005 and 0.04 min.-1 for most reactions with the exception of the fast reacting acid phosphatase which had values as high as 2.6 and 2.8 min.-1. It is observed that the beta-glucuronidase is rapidly inhibited during the equilibrium phase before the more slower reaction covalent bond formation takes place. The acid phosphatases form the covalent bonds more rapidly, especially the faster reacting species suggesting a unique difference in the active site geometry to that of the more slowly reacting species. The tightly bonded gold (III)-enzyme complex is probably the reason for its toxicity and non-anti-inflammatory use as a drug.

Acid Phosphatase↗
PubMed1989

Inhibition of several enzymes by gold compounds. II. beta-Glucuronidase, acid phosphatase and L-malate dehydrogenase by sodium thiomalatoraurate (I), sodium thiosulfatoaurate (I) and thioglucosoaurate (I).

Bovine liver beta-D-glucuronide glucuronohydrolase, EC 3.2.1.32), wheat germ acid phosphatase (orthophosphoric monoesterphosphohydrolase, EC 3.1.3.2) and bovine liver L-malate dehydrogenase (L-malate: NAD oxidoreductase, EC 1.1.1.37) were inhibited by a series of gold (I) complexes that have been used as anti-inflammatory drugs. Both sodium thiosulfatoaurate (I) (Na AuTs) and sodium thiomalatoraurate (NaAuTM) effectively inhibited all three enzymes, while thioglucosoaurate (I) (AuTG) only inhibited L-malate dehydrogenase. The equilibrium constants (K1) ranged from nearly 4000 microM for the NaAuTM-beta-glucuronidase interaction to 24 microM for the NaAuTS-beta-glucuronidase interaction. The rate of covalent bond formation (kp) ranged from 0.00032 min-1 for NaAuTM-beta-glucuronidase formation to 1.7 min-1 for AuTG-L-malate dehydrogenase formation. The equilibrium data shows that the gold (I) drugs bind by several orders lower than the gold (III) compounds, suggesting a significantly stronger interaction between the more highly charged gold ion and the enzyme. Yet the rate of covalent bond formation depends as much on the structure of the active site as upon the lability of the gold-ligand bond. It was also observed that the more effective the gold inhibition the more toxic the compound.

Acid Phosphatase↗
PubMed1989

High-dose, potentially myeloablative chemotherapy and autologous bone marrow transplantation for patients with advanced Hodgkin's disease.

Twenty three patients with Hodgkin's disease were treated with BCNU (carmustine), etoposide, and cyclophosphamide at doses of 450-600 mg/m2, 1500-2000 mg/m2, and 120 mg/kg respectively. Bone marrow refrigerated at 4 degrees C for 2-5 days or cryopreserved at -80 degrees C was used to reconstitute bone marrow function. The median age was 28 (range 16-48), and the median Karnofsky performance status was 70. Nineteen patients had progressive disease while on chemotherapy. The median number of prior regimens was three (1-7), and the median number of prior chemotherapy drugs was 10 (range 4-12). Ten patients had received at least two of the drugs used in this study and four had had all three. Indicator lesions included lung (10), peripheral lymph nodes (9), retroperitoneal nodes (8), liver (3), and chest wall masses (2). Ten patients achieved a complete remission (43.5%; 95% confidence limits 23-64%), and five patients had a partial remission (21.7%; 95% confidence limits 5-39%). The median duration of complete remission was 6 months (range 2-13+ months). Responses were shorter in duration for patients with primary refractory disease. Liver function abnormalities were noted in nine (39%) cases. Post transplant, the recovery time was 18 days (range 11-43) for WBC and 24 days (11-77) for platelets. Two patients died of septic episodes while neutropenic. The median number of RBC units used was seven (range 1-45). Ten patients had evidence of pulmonary dysfunction. In seven patients there was symptomatic improvement with steroid therapy, but three patients who were not treated with steroids died as a result of interstitial pneumonia. Future programs should consider bone marrow transplantation in patients with Hodgkin's disease earlier in the course of disease, at the time of minimal residual disease, and employ newer, potentially less toxic drugs.

Adolescent↗
PubMed1989

Staphylococcal scalded skin syndrome mimicking acute graft-vs-host disease in a bone marrow transplant recipient.

A 33-year-old man with mild acute graft-vs-host disease after an allogeneic bone marrow transplant for chronic myelogenous leukemia developed a necrolytic rash 90 days after transplant. A diagnosis of staphylococcal scalded skin syndrome was made when a skin biopsy specimen revealed a split in the granular layer and phage group 2, type 71 Staphylococcus aureus was cultured from the blood.

Acute Disease↗