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Biomedical subjects

T Ahmed

Publications and source records attributed to T Ahmed.

At least 145 records · Page 8Linked to original sources
PubMed1992

Peripheral blood stem cell mobilization by cytokines.

Hematopoietic stem cells circulate in the peripheral blood. These cells can be collected by apheresis techniques either in the unperturbed state, after mobilization following the administration of cytokines like G-CSF or GM-CSF, or during the phase of early blood count recovery following chemotherapy-induced myelosuppression. The number of cells collected following mobilization is greater than that obtained after apheresis in the unperturbed state. There are, however, qualitative differences between unperturbed and mobilized cells. Chemotherapy related mobilization can be potentially dangerous in that severe myelosuppression necessary to achieve mobilization can have serious consequences. There are no controlled studies that evaluate the relative merits of each method of collection. Regardless of the techniques employed peripheral blood stem cells can reliably accelerate hematologic recovery after potentially myeloblative therapy and provide an alternative to bone marrow support.

Blood Cell Count↗
PubMed1992

A phase I pharmacokinetic study of recombinant human tumor necrosis factor administered by a 5-day continuous infusion.

Nineteen patients with advanced cancer were entered into a phase I clinical trial of Tumor Necrosis Factor (TNF) which was designed to determine the pharmacokinetic profile, safety, and maximal tolerated dose (MTD) of the recombinant human cytokine in vivo. TNF was administered by continuous infusion for 24 hours followed by pharmacokinetics and a 120-hour infusion repeated every 3 weeks. The initial dose was 40 micrograms/m2 and was ultimately escalated to 200 micrograms/m2. A total of forty 5-day cycles were administered to 18 of these patients; and all were evaluable for toxicity. Toxicities in this trial included fever, chills, rigors, hypotension, headaches, seizures, lethargy, weight loss, and malaise. At all dose levels, but more significantly at the highest doses, hematological toxicities were observed and grade 3 neurotoxicity (headache and confusion), and hypotension were noted. Two patients expired during the study, and this was felt to be related to septic episodes. Because of these severe toxicities, 160 micrograms/m2 was defined as the MTD. At 160 micrograms/m2 peak serum levels occurred within 5-20 minutes of initiation and were not detectable 1 hour later. No anti-tumor responses were observed. No measurable plasma levels of TNF were observed with the administration of doses of 80 micrograms/m2. This dose level could be further studied in phase II studies alone and in combination with other agents, utilizing a continuous infusion schedule.

Adenocarcinoma↗
PubMed1992

Phase I trial of ImuVert (natural membrane vesicles associated with ribosomes) in patients with advanced cancer.

ImuVert, a new biological response modifier, was evaluated for toxicity and potential efficacy in patients with advanced cancer. This agent consists of sized, labile, natural membrane vesicles associated with ribosomes derived from Serratia marcescens. ImuVert induces enhanced in vitro macrophage and natural-killer-cell-mediated cytotoxicity, and has demonstrated antitumor activity in palpable animal tumor systems. A group of 39 patients with a variety of tumors, 25 men, 14 women, with a mean performance status (Karnofsky) of 80% and median age of 57 years were entered into this trial. ImuVert was administered subcutaneously weekly for a minimum of 3 weeks. A total of 183 treatments were evaluated. Flu-like systemic toxicities, including fever, chills, nausea, vomiting, diarrhea and hypotension were observed. Erythema, induration and tenderness developed at the injection sites. Myelosuppression, thrombocytopenia, anaphylaxis, rental and hepatic toxicities did not occur. All symptoms resolved within 24 h. Two patients with nodular lymphoma achieved a partial response and two minor responses were seen in patients with glioblastoma and melanoma. On the basis of ImuVert's biological activity, and tolerable toxicity it warrants further clinical investigation.

Adult↗
PubMed1992

Higher cure rates in acute leukemia: now more probable with increasingly effective induction therapy.

Traditional therapy of acute myelogenous leukemia has not cured more than 10% of patients and, of acute lymphoblastic leukemia not more than 30% of adults. In part, this is due to the lack of agents effective enough to induce remissions of such quality that cure is possible. The introduction of mitoxantrone and its use in high dose with high-dose cytarabine for induction therapy, raises the possibility of an increased cure rate of acute myelogenous leukemia and acute lymphoblastic leukemia.

Acute Disease↗
PubMed1992

Case report: acute polymyositis in a patient with chronic graft vs. host disease.

Chronic graft versus host disease (cGVHD) is a multisystemic condition which occurs in 25 to 40% of patients undergoing allogeneic bone marrow transplantation. A 31 year old male developed acute polymyositis one year in the setting of cGVHD etc. after allogeneic bone marrow transplantation. A viral etiology could not be proven. This presumably represented a manifestation of cGVHD. His clinical condition improved with immunosuppression and he remains asymptomatic, off therapy.

Acute Disease↗
PubMed1992

Utilization review savings at the micro level.

Utilization review (UR) programs have become an integral part of efforts to contain health care costs for private health insurers, employers, and health care organizations. While some studies have measured the overall performance of these programs, important information in the prior level of the health care utilization has not been used in estimating the effectiveness of the program for micro units (e.g., employer groups). In this article, the authors present a model to determine how the impact of the hospital UR program on health care utilization for specific groups varies with historical use patterns. The estimation approach used in this article can be used to determine the effect of UR for specific employer groups without having to rely on the average effectiveness measures for all. Claims obtained from Aetna Health Plans provided data for more than 5,300 employer accounts covering approximately 580,000 employees, 44% of whom had the UR program sometime during the period 1987 to 1990. Because of regression to the mean, UR savings were greater for units with higher prior use and smaller for units with lower use. In addition to prior use, the size of the group also determined the extent of regression to the mean. Groups with smaller number of enrollees had greater potential to save from the UR because of UR's ability to reduce the outliers.

Adolescent↗
PubMed1992

Complement factor 2 deficiency: a clinical and serological family study.

Inherited complement deficiencies are associated with a variety of connective tissue diseases. A family with inherited deficiency of complement factor 2 (C2) is described in which two family members with homozygous C2 deficiency developed cutaneous vasculitis and sicca syndrome. The other family members had heterozygous C2 deficiency and each member had the HLA-A25, B18, DR2 (w15) haplotype. The mother had seropositive rheumatoid arthritis. Further studies showed the presence of cryoglobulins, antibodies against endothelial cells, and anticardiolipin antibodies.

Adult↗
PubMed1992

Effects of food with two oral rehydration therapies: a randomised controlled clinical trial.

To evaluate the impact of food on the efficacy of oral rehydration solution (ORS), a randomised, controlled clinical trial was conducted in 182 adults with cholera. After initial rehydration with an intravenous polyelectrolyte solution for four hours, the patients were randomised to receive one of four rehydration therapies: glucose based ORS and no food for the first 24 hours (group A), glucose based ORS plus food from the beginning of treatment (group B), rice based ORS with no food for the first 24 hours (group C), and rice based ORS plus food from start of therapy (group D). Tetracycline was given after 72 hours to all patients. No significant differences in ORS intake, stool output, and duration of diarrhoea were noted between groups A and B and between groups C and D. A substantial and significant reduction in stool output was, however, shown in the groups who received rice based ORS irrespective of feeding. These results show that food does not potentiate the efficacy of either glucose based or rice based ORS in adults with cholera. Rice based ORS compared with glucose ORS substantially reduces purging in cholera patients.

Adolescent↗
PubMed1992

Attenuation of platelet-activating factor-induced airway responses with methylprednisolone succinate in sheep.

Intratracheal instillation of platelet-activating factor (PAF) in sheep produces bronchoconstriction and airway hyperresponsiveness (AHR) by a two-stage process that involves the initial stimulation of PAF receptors followed by the secondary generation of proinflammatory mediators. Because the biological effects of PAF may be mediated by these proinflammatory metabolites, it is possible that a steroidal anti-inflammatory agent would modify the airway responses of PAF. We measured specific lung resistance (sRL) in sheep (n = 11) before, immediately after, and serially for up to 2 h after intratracheal instillation of PAF (30 micrograms/kg). Airway responsiveness was measured 2 h post-PAF when sRL had returned to baseline and was expressed as the cumulative provocating dose of carbachol that increased sRL to 4 l.cmH2O.l-1.s (PD4). PD4 was determined on a control day and on different experiment days without or after treatment with intravenous methylprednisolone (MPS; 1 mg/kg) administered 3 h before (n = 6), 20 min before PAF (n = 7), or 20 min after PAF challenge (n = 7). PAF increased sRL by 222 +/- 44% (SE) above baseline and decreased PD4 of carbachol by 44 +/- 5% (P less than 0.05). Pretreatment (both 3 h and 20 min) with MPS attenuated the PAF-induced increases in sRL, whereas its administration 20 min post-PAF had no effect. Irrespective of the effects on sRL, MPS administration inhibited the PAF-induced AHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1992

Immunologic mast cell-mediated responses and histamine release are attenuated by heparin.

Heparin has been shown to act as a competitive inhibitor of inositol 1,4,5-triphosphate (InsP3) receptors in various cell types. Because InsP3 is one of the second messengers involved in stimulus-secretion coupling in mast cells, it is possible that heparin may inhibit mast cell-mediated reactions. Therefore, in allergic sheep, we tested this hypothesis in two mast cell-mediated reactions induced by immunologic and nonimmunologic stimuli: immediate cutaneous reaction (ICR) and acute bronchoconstrictor response (ABR). In 12 sheep allergic to Ascaris suum antigen, the surface area of the skin wheal was determined 20 min after intradermal injection (0.05 ml) of increasing concentrations of specific antigen, compound 48/80, and histamine, without and after pretreatment with heparin (100, 300, or 1,000 U/kg i.v.). Antigen, compound 48/80, and histamine produced concentration-dependent increases in ICR. Heparin "partially" inhibited the ICR to antigen and compound 48/80 in a dose-dependent manner without modifying the ICR to histamine. The heparin preservative benzyl alcohol was ineffective. In 11 additional sheep, specific lung resistance was measured before and after inhalation challenges with antigen, compound 48/80, and histamine without and with aerosol heparin pretreatment (1,000 U/kg). Heparin blocked the antigen- and compound 48/80-induced bronchoconstriction without modifying the airway effects of histamine. In isolated human uterine mast cells, heparin inhibited the anti-immunoglobulin E- but not the calcium ionophore- (A23187) induced histamine release. These data suggest that heparin inhibits the ICR and ABR induced by stimuli that produce immunologic and nonimmunologic mast cell degranulation without attenuating the effects of histamine.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Modification of histamine- and methacholine-induced bronchoconstriction by calcium antagonist gallopamil in asthmatics.

We studied the comparative modification of histamine- and methacholine-induced bronchoconstriction by a calcium antagonist, gallopamil, in 8 subjects with bronchial asthma. Dose-response curves to aerosolized methacholine or histamine were performed, without and following pretreatment with inhaled gallopamil (10 mg), on 6 different experiment days to determine the cumulative provocative dose (PD50) of each agonist in breath units which caused a 50% decrease in specific airway conductance (SGaw). Baseline values of SGaw were similar on different experiment days and gallopamil had no significant effect on SGaw. PD50 values for histamine on control and placebo days were 6.8 +/- 2.8 and 5.2 +/- 2.8 breath units (mean +/- SE), respectively. Pretreatment with gallopamil increased histamine PD50 to 19.8 +/- 7.5 breath units, which was significantly greater than on control and placebo days (p < 0.01). PD50 values for methacholine on control and placebo days were 9.5 +/- 5.6 and 8.8 +/- 5.8 breath units, respectively. Gallopamil pretreatment had no significant effect on methacholine-induced bronchoconstriction; methacholine PD50 increased to 13.4 +/- 5.5 breath units (p = NS). The mean dose ratio (ratio of PD50 for the agonist in the presence and absence of gallopamil) for histamine was 6.9, which was 3.7-fold higher than the dose ratio of 1.9 methacholine in the same subjects. These data suggest that gallopamil causes greater inhibition of histamine- versus methacholine-induced bronchoconstriction. This suggests that calcium influx in airway smooth muscle through voltage-dependent channels primarily occurs in response to histamine and not to methacholine.

Adult↗
PubMed1992

Effects of inhaled heparin on immunologic and nonimmunologic bronchoconstrictor responses in sheep.

The glycosaminoglycan heparin has been shown to block inositol triphosphate (IP3) receptors in various tissues. Because IP3 is one of the pathways involved in stimulus-secretion coupling in mast cells, it is possible that heparin may inhibit airway anaphylaxis. Thus, the purpose of the present investigation was to study the effect of inhaled heparin on immunologically and nonimmunologically induced bronchoconstriction in allergic sheep. Specific lung resistance (SRL) was measured in 15 sheep allergic to Ascaris suum antigen, before and after inhalation challenge with the specific antigen, compound 48/80, histamine, and carbachol. On a different day, the animals were pretreated with inhaled heparin and airway challenges with the antigen and agonists were repeated. Antigen alone increased SRL by 367 +/- 119% (mean +/- SE) above baseline (p less than 0.05). Inhaled heparin had no effect on baseline SRL, but attenuated antigen-induced bronchoconstriction in a dose-dependent fashion: mean SRL increased by 313 +/- 87, 151 +/- 69, and 24 +/- 20% above baseline with 100, 300, and 1,000 U/kg of heparin, respectively. Inhaled benzyl alcohol preservative, dextran sulfate, and de-N-sulfated heparin failed to inhibit antigen-induced bronchoconstriction. The dose of heparin (1,000 U/kg) that completely blocked antigen-induced bronchoconstriction also attenuated the bronchoconstriction induced by compound 48/80 (delta SRL = 374 +/- 72 versus 35 +/- 12%), but failed to block the bronchoconstrictor effects of histamine and carbachol. These data suggest that inhaled heparin prevents bronchoconstrictor responses induced by by stimuli that produce immunologic and nonimmunologic mast-cell degranulation in sheep, without attenuating agonist-induced bronchoconstriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1992

Factors associated with child mortality in Pakistan and implications for the national health programs.

"This study attempts to establish the levels of infant and child mortality in Pakistan using an indirect estimation technique to analyze data from the 1984-85 Pakistan Contraceptive Prevalence Survey....[Results indicate] that children's survival chances have hardly improved in recent years.... Suggestions are offered on ways to improve the effectiveness of rural health programs."

Asia↗
PubMed1992

Alternate scenarios for population control in Pakistan: the issue of contraceptive method mix.

The authors review Pakistan's population program, with a focus on the ideal mix of contraceptive methods needed to slow population growth. "Our objective in this exercise is to estimate the extent of services required to achieve a certain level of the Contraceptive Prevalence Rate (CPR) necessary to bring fertility down to a level desired by women." Comparison is made between single- and multiple-method approaches.

Asia↗