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Biomedical subjects

T Ahmed

Publications and source records attributed to T Ahmed.

At least 91 records · Page 5Linked to original sources
PubMed1997

Phase I clinical and laboratory evaluation of topotecan and cytarabine in patients with acute leukemia.

PURPOSE: To determine the maximal-tolerated dose (MTD) of topotecan with cytarabine in acute leukemia patients, and to evaluate leukemia cell apoptosis in these patients. PATIENTS AND METHODS: Fifty-three patients with acute leukemia not responsive to standard therapy were treated at eight dose levels of topotecan (2.5 mg/m2/d to 7.75 mg/m2/d). Topotecan was given as a 30-minute infusion daily with cytarabine 1 g/m2/d, both for 5 days. Using a flow-cytometric technique, the percent apoptotic cells in blood and bone marrow samples was determined, and the cell cycle distribution of the leukemic cells studied. RESULTS: Oropharyngeal mucositis was dose-limiting. The MTD of topotecan was 4.75 mg/m2/d for 5 days in high-risk patients and 7.0 mg/m2/d for 5 days in low-risk patients. The mean percent apoptotic cells in the peripheral blood reached a peak of 18.8%, a median of 48 hours following the first dose of topotecan. Patients with higher S-phase fractions, either before treatment or following cytarabine, were more likely to achieve bone marrow aplasia than those with lower S-phase fractions (P = .01 and P < .05, respectively). Clinical responses were seen in four of 39 patients with acute myelogenous leukemia (AML; of whom 32 had received prior high-dose cytarabine), three of six with acute lymphoblastic leukemia (ALL), and one of eight with chronic myelogenous leukemia in blast phase (CML-BP). CONCLUSION: The recommended phase II dose of topotecan with intermediate-dose cytarabine is 4.75 mg/m2/d for high-risk patients and 7.0 mg/m2/d for low-risk patients. The percentage of cells in S phase was important in determining response to treatment.

Adult↗
PubMed1997

Granulocyte-macrophage colony-stimulating factor/interleukin-3 fusion protein versus granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for non-Hodgkin's lymphoma: results of a randomized double-blind trial.

PURPOSE: A phase III trial to compare PIXY321 with granulocyte-macrophage colony-stimulating factor (GM-CSF) following high-dose therapy and autologous bone marrow transplant (ABMT) was conducted to evaluate the time to hematopoietic recovery. PATIENTS AND METHODS: One hundred seventy-seven patients with non-Hodgkin's lymphoma (NHL) receiving ABMT were randomized to receive either PIXY321 750 micrograms/m2/d divided into two subcutaneous (SC) doses or GM-CSF 250 micrograms/m2/d as a 2-hour intravenous (IV) infusion starting on day 0 post-ABMT for a maximum of 28 days. RESULTS: The median time to reach an absolute neutrophil count (ANC) > or = 500/microL in the PIXY321 group was 17 days versus 19 days in the GM-CSF group (P = .07) and the median time to reach platelet transfusion independence in the PIXY321 group was 25 days versus 23 days in the GM-CSF group (P = .30). The toxicity profiles of the two agents appeared to be equivalent with the exception of more patients in the PIXY321 group with a rash (64%) compared with the GM-CSF group (48%) (P = .028). A logistic regression model identified the use of a non-total-body irradiation (TBI) regimen and/or receipt of unpurged marrow and a body-surface area greater than 2.0 m2 as predictive of faster neutrophil engraftment, and those three factors, as well as the receipt of < or = two prior chemotherapy regimens as predictive for rapid platelet engraftment. CONCLUSION: There was a trend toward a slight improvement in neutrophil engraftment post-ABMT with the PIXY321 administered by an SC route compared with GM-CSF administered by an IV route. However, no differences could be identified between the two agents with respect to the time to platelet transfusion independence. Patient, regimen, and graft characteristics were most predictive of the engraftment tempo.

Adolescent↗
PubMed1997

Circulating antibodies to common food antigens in Japanese children with IDDM.

OBJECTIVE: To investigate the humoral immune response to common food antigens in Japanese children with IDDM. RESEARCH DESIGN AND METHODS: IgG antibodies to cow's milk, beta-lactoglobulin, bovine serum albumin (BSA), alpha-lactalbumin, and hens egg ovalbumin were examined by enzyme-linked immunosorbent assay in the sera of 33 patients with IDDM, ages 11.8 +/- 3.4 years. The data were compared with that of 50 normal subjects, ages 10.3 +/- 5.1 years, who acted as control subjects. A positive antibody to a food antigen was defined as an antibody titer greater than the 95th percentile value in normal subjects. RESULTS: Children with IDDM had significantly higher median titers of IgG antibodies to beta-lactoglobulin and ovalbumin (P = 0.03 and P = 0.0005 respectively). More children with IDDM than control subjects had positive IgG antibody to ovalbumin (21 vs. 6%, P = 0.04). Titers, as well as the number of positive antibodies to other food antigens, including BSA, did not differ between the two groups. CONCLUSIONS: Japanese children with IDDM show an enhanced humoral immune response to beta-lactoglobulin and ovalbumin, a phenomenon that may be related to the pathogenesis of the disease.

Adolescent↗
PubMed1997

The role of osmotic diuretics in the management of eclampsia in Karachi women.

In the present work, out of eighty (80) patients selected, suffering from eclampsia, thirty-five (35) were subjected to the combined therapy of diazepam (7-Chloro-1,3-dihydro-1-methyl-5-phenyl-2H-1, 4-benzo-diazepin-2-one) and mannitol (Osmotic diuretic) and forty-five (45) patients were administered diazepam only. Consequently it was inferred that osmotic diuretic (mannitol) exhibits beneficial effects on the management of eclampsia, thereby lowering the mortality and morbidity.

Journal Article↗
PubMed1997

Value of clinical features in the diagnosis of enteric fever.

There is no objective data on the value of individual clinical symptoms or signs in the diagnosis of enteric fever in a febrile patient. The purpose of the study was to assess the value of some clinical and simple laboratory features in the diagnosis of enteric fever. One hundred & six patients with microbiologically confirmed enteric fever and 170 patients with other established febrile illnesses were included in the evaluation. History of stepladder pattern of rise of temperature, loose motions, relative bradycardia and coated tongue proved to be powerful markers of enteric fever with high specificity (100%, 94.71%, 94.71%, 94.12% respectively), positive and negative predictive values. Headache, hepatomegaly and splenomegaly were moderately powerful. ESR and WBC count appeared to have little value in the diagnosis of enteric fever. Pattern of onset and loose motions did not discriminate between typhoid and paratyphoid fever. Most of these patients had illness persisting beyond one week by which viral infections and infectious enterocolitides were largely excluded. Elucidation of power of these markers in distinguishing enteric fever from other febrile illnesses with the help of better designed prospective studies would lessen our dependence on expensive and time consuming laboratory investigations.

Adolescent↗
PubMed1997

Gastrointestinal allergy to food: a review.

Gastrointestinal food allergy still poses a challenge to the clinician because of its variable symptomatology and lack of reliable diagnostic tests. Its prevalence is estimated at 2 approximately 5%, higher in children than in older age-groups. Allergy to food usually diminishes with advancing age. Although a wide variety of foods can cause allergic reactions, cow's milk is the most common cause of food allergy in infants and young children. Depending upon the speed of onset of symptoms, immediate and delayed types of food allergy have been described. Gastrointestinal symptoms in food allergy have been explained by alterations in transport across the intestinal wall (increased secretory and/or decreased absorptive functions), increased permeability, and motility of the intestine. The exact pathogenesis of food allergy is still not clear. However, immediate type of food allergy is believed to be mediated by type I hypersensitivity reaction, involving mast cells and food-specific IgE antibodies. The diagnosis of food allergy is based upon a favorable response to an elimination diet and a response to a challenge with the suspected food. The condition is treated by eliminating the allergenic food from diet for as long as 9-12 months in case of cow's milk allergy. While exclusive breast-feeding for the initial four months or more reduces the chances of development of food allergy, the role of diet restrictions in the mother in reducing the incidence of food allergy in the infant is controversial. Data on food allergy from developing countries are limited. This may be due to lack of diagnosis or less attention given to the condition relative to other diseases including infectious diarrheas and acute respiratory infections. The role of cow's milk allergy in the pathogenesis of persistent diarrhoea, a major problem in the developing world, remains speculative. Frequent intestinal infections and reduced secretory IgA, which are associated with malnutrition, alter intestinal permeability and result in an increased uptake of food antigens. The increased antigenic load combined with factors such as an atopic predisposition may initiate an abnormal mucosal immune response resulting in chronic enteropathy.

Adult↗
PubMed1996

Graft-versus-host disease. Possible higher risk for African American patients.

BACKGROUND: Race is not generally recognized as a factor in the severity or incidence of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation. The impression that African American patients had more frequent and severe GVHD prompted this retrospective survey. METHODS: The records of 75 consecutive patients treated with a human leukocyte antigen-identical sibling bone marrow transplant from 1985 to 1993 were reviewed. GVHD prophylaxis uniformly employed cyclosporine and steroids. Treatment of GVHD included cyclosporine and high dose steroids in all cases. Antithymocyte globulin and other immunosuppressants were used in severe cases. RESULTS: Of 75 patients, 56 (75%) were white, 11 (15%) were listed as "Hispanic", 7 (9%) were African Americans, and 1 was of Far-Eastern origin. Four of the African American patients had chronic myelogenous leukemia and 2 had acute leukemia, whereas 21 of the other 68 patients (31%) had chronic myelogenous leukemia, 31 (46%) had acute leukemia, and the remainder (33%) had miscellaneous hematologic malignancies. Transplants from a female donor to a male recipient were performed in 2 of 7 African Americans and 19 of 68 patients (28%) of other origins. Five of the 6 evaluable African American patients (83%; 95% confidence interval, 36-100%) had Grade 4 GVHD, as opposed to 5 of 61 patients of other racial origins (8%; 95% confidence interval, 3-18%). All African American patients died within 90 days of transplant. CONCLUSIONS: Patients of African American origin possibly have a greater risk of GVHD.

Adult↗
PubMed1996

The differentiation and maturation mediator for human myeloid leukemia cells shares homology with neuroleukin or phosphoglucose isomerase.

The identity of the maturation inducer capable of mediating the differentiation of human myeloid leukemic HL-60 calls to terminal monocytic cells was investigated. One of such inducers from T cells was purified as a 54.3-kD peptide. The amino acid sequence of a tryptic peptide and the enzyme cleavage sites revealed 100% homology to neuroleukin or phosphoglucose isomerase (PGI). Neuroleukin mediates differentiation of neurons and is homologous to PGI, which catalyzes the interconversion of glucose-6-phosphate and fructose-6-phosphate. The 54.3-kD inducer was shown to have PGI enzymatic activity. Separately purified PGI by substrate-elution exhibited identical specificity as the maturation inducer for HL-60 cell differentiation. They mediated a reduction of proliferating S and G2M cells, and the mature monocytic calls acquired complement receptors, phagocytic capacity, and adherence morphology. The magnitude of differentiation was dosage dependent on the inducer, with a bell-shaped curve. At the excess dose range cells did not undergo differentiation and remained in a proliferating cycle. Abnormally elevated PGI enzyme activities were detected in the plasma of acute myelogenous leukemia patients. Whether they represent an excess of the differentiation regulator in patients and are important in leukemogenesis remain to be investigated.

Aged↗
PubMed1996

Initial experience using Prostar: a new device for percutaneous suture-mediated closure of arterial puncture sites.

A new device that enables closure of the femoral artery puncture site by percutaneous placement of two nonabsorbable sutures (Prostar) was evaluated. Our initial experience included 32 insertion attempts at 29 femoral arterial puncture sites and one femoral venous puncture site. The device was applied at arterial puncture sites that had been used to carry out 12 balloon angioplasties (41%), seven intracoronary stent placements (24%), five intraaortic balloon pump insertions (17%), four diagnostic angiographies (14%), and one rotational ablation (3%). The venous access site closed was in a patient who had undergone balloon angioplasty and intracoronary thrombolysis. Most patients were anticoagulated with an average activated clotting time (ACT) of 306 +/- 123 sec (12 patients) or an average PTT of 68 +/- 29 sec (14 patients). There were four failures to achieve hemostasis using the device due to: inability to place the device because of peripheral vascular disease, entrapment of cutaneous tissue in the suture, a suture break that prevented hemostasis from being achieved, and avulsion of the sutures from the needles. Although three other suture breaks occurred, these did not prevent hemostasis from being achieved. Thus, 88% (28/32) of attempted uses were successful, and by using a second device in two of the failed attempts, 94% (30/32) of the puncture sites were successfully closed using the device. There was one late rebleed that required 1 hr of groin clamp pressure in an angioplasty patient who had received intracoronary urokinase. An ooze of blood occurred in 4 patients, but in only 2 was this more than trivial, resulting in discontinuation of heparin in one patient and a small hematoma in the other. We conclude that this device can be used safely and effectively, even in fully anticoagulated patients who have undergone complex procedures. The ultimate role of the device will require further experience and appropriate randomized studies.

Aged↗
PubMed1996

Studies on the basis for the toxicity of acrolein mercapturates.

Acrolein, 3-oxopropyl glutathione (oxoPrGSH), and S-3-hydroxypropyl N-acetylcysteine (hydroxyPrMCA) are confirmed metabolic products of cyclophosphamide. Other potential metabolites include the mercapturic acid S-3-oxopropyl N-acetylcysteine (oxoPrMCA), its sulfoxide, and their corresponding diacid forms. The reactivity of acrolein would appear to preclude its movement from the main site of formation (liver) to the sites of toxicity (lung and bladder). However, the rerelease of acrolein from various thiol conjugates via a beta-elimination reaction is possible. It is also possible that the parent conjugate is directly toxic. The current study examined the toxicity of various acrolein-thiol conjugates and related analogs to human lung adenoma A549 cells. The expected enhancement of acrolein, oxoPrMCA, and oxoPrMCA S-oxide toxicity (assessed as cell proliferation by the alamarBlue assay) following a 2-hr exposure of cells treated with diethyl maleate (DEM) to deplete GSH was observed. OxoPrGSH was toxic when present for 24 hr, and this toxicity was also enhanced by pretreatment with DEM. When treated with these conjugates alone, the depletion of intracellular GSH only occurred at doses above those needed to significantly inhibit cell proliferation. There were no changes in protein thiols as determined using the membrane impermeant fluorescent thiol probe para-sulfobenzoyloxybromobimane. The diacid conjugate was not toxic to A549 cells indicating further oxidation products of the mercapturic acids are not a factor in toxicity. ButanoneMCA, an analog of oxoPrMCA that cannot exist in the geminal diol form, inhibited A549 cell growth only slightly less effectively than oxoPrMCA, suggesting the geminal diol is not toxicologically significant. OxoBuMCA, which cannot undergo beta-elimination of acrolein, showed no toxicity to these cells, suggesting that the release of acrolein could be required. Exogenous GSH provided protection from all toxic compounds suggesting that the toxic species is electrophilic. Overall, the data suggest that toxicity, in terms of an inhibition of cell proliferation, is not due to the parent molecule but rather is the result of rereleased acrolein that then affects factors necessary for cell proliferation.

Acetylcysteine↗
PubMed1996

Conformational changes associated with activation of bee venom phospholipase A2.

Bee venom PLA2 possesses a binding site for long-chain fatty acids that can be acylated by long-chain fatty acid imidazolides [Drainas, D. and Lawrence, A.J. (1978) Eur. J. Biochem. 91, 131-138]. Occupation of the site either by oleic acid or the oleoyl residue enhances the catalytic activity by 45.7-fold in the presence of 20% 1-propanol and occupation of the site by the oleoyl residue increases the lytic activity against rabbit erythrocytes by 60-fold. Treatment of the enzyme with oleic acid and glutaraldehyde is known to produce irreversible activation [Lawrence, A.J. and Moores, G.R. (1975) FEBS Lett. 49, 287-291]. Here we show that reduction of the glutaraldehyde-treated enzyme with borohydride stabilizes the activated state and enables the fatty acid to be removed, revealing that a large proportion of the induced activation does not require the presence of oleic acid and indicating that activation is due to a change in the conformation rather than the hydrophobicity of the protein. A kinetic study of enzyme activated by oleoyl imidazolide showed that this modification stabilizes the protein against reversible inactivation by 1-propanol. Comparison of the CD spectra of native and oleoyl imidazolide-activated enzyme shows a change in secondary structure with apparent increase in both alpha-helix and beta-sheet content. During reaction of the enzyme with oleoyl imidazolide, the protein fluorescence shows a biphasic response with an initial fall attributed to occupation of the binding site followed by a progressive decrease with a shift of the emission maximum from 341 to 348 nm. The rate of the second phase closely matched the rate of increase in catalytic activity of the enzyme. Free oleic acid caused a rapid fall in fluorescence emission without the subsequent slow change. These results support the proposal that oleic acid or the oleoyl residue occupy a very similar site on the protein and that occupation of this site increases the exposure of one or both of the Trp residues to the aqueous environment. Binding studies show that activation by oleoyl imidazolide does not increase the affinity of the enzyme for the erythrocyte membrane. It is proposed that occupation of a long-chain fatty acid binding site on the enzyme enhances catalytic activity by changing the conformation of the protein rather than acting as a hydrophobic anchor to the substrate surface.

1-Propanol↗
PubMed1996

Mucinous (colloid) carcinoma of urinary bladder following long-term cyclophosphamide therapy for Waldenstrom's macroglobulinemia.

Carcinoma of the urinary bladder is a known complication of cyclophosphamide therapy. Almost all such cases have been transitional cell carcinomas. We report here the second example of an adenocarcinoma of bladder and the first purely mucinous (colloid) carcinoma of urinary bladder developing after long-term cyclophosphamide therapy. The patient, a 77-year-old woman, had been treated for Waldenstrom's macroglobulinemia for at least 24 years, during which time treatment for this disease varied from 50 to 100 mg per day. The disease terminated in acute myelogenous leukemia, and she died of severe disseminated intravascular coagulopathy associated with hypermacroglobulinemia. The mucinous (colloid) carcinoma of the urinary bladder was an incidental finding at autopsy.

Adenocarcinoma, Mucinous↗
PubMed1996

Protective effect of heparin on immunologically induced tracheal smooth muscle contraction in vitro.

Our previous studies have shown that heparin, a competitive inhibitor of inositol triphosphate receptors, inhibits airway anaphylaxis in vivo. In the present study, we tested the hypothesis that heparin blocks immunologically induced tracheal smooth muscle (TSM) contraction in vitro. TSM was obtained from sheep allergic to Ascaris suum antigen, and was suspended in an organ bath containing oxygenated (95% O2, 5% CO2) Krebs-Henseleit buffer at 39 degrees C. After an equilibration period, the tissues were treated with heparin dissolved in 10 microliters DMSO, at concentrations of 1, 10, or 100 U/ml (final concentration in the bath). Two types of controls were used: vehicle (10 microliters DMSO)-treated tissues and tissues treated with the anti-asthmatic nedocromil sodium (10(-5) M). After 30 min pretreatment, tissues were challenged with 10, 30 and 100 microliters of antigen. Contractions induced by antigen were expressed as percentage of the contraction elicited by the maximum effective concentration of acetylcholine (ACh, 10(-2) M). Antigen produced dose-dependent increases in tension, which were blocked by heparin and nedocromil sodium; maximal inhibition was 43 and 52%, respectively. Neither heparin nor nedocromil sodium affected the dose-response curve or the maximum response to Ach. The addition of the heparin preservative (benzyl alcohol) did not reverse ACh-induced contractions, or inhibit antigen-induced contractile responses. These results suggest that heparin blocks immunologically induced TSM contraction, without affecting the contractile response to the airway smooth muscle agonist, ACh. This action of heparin is similar to that of the anti-asthmatic nedocromil sodium and may be related to inhibition of mast cell mediator release.

Animals↗
PubMed1996

Time course of the protective effect of inhaled heparin on exercise-induced asthma.

We have previously shown that heparin attenuates allergic bronchoconstriction in sheep, inhibits anti-IgE mediated histamine release in isolated mast cells, and prevents the bronchoconstrictor response in subjects with exercise-induced asthma (EIA). The purpose of the present study was to determine the pharmacokinetics of anti-asthmatic activity of inhaled heparin in EIA and compare it with cromolyn sodium, a mast cell stabilizing agent with established efficacy in EIA. Nine subjects with a history of EIA were studied on 10 different experiment days. After obtaining baseline pulmonary functions on day 1, subjects performed a standardized exercise challenge to document the presence of EIA. While monitoring minute ventilation and heart rate, exercise challenge was performed on a treadmill with increasing workload, until 85% of predicted maximum heart rate was achieved. The subjects then continued the exercise at that workload for 10 min. EIA was assessed by measurements of specific airway conductance (SGaw) before and after exercise. On experiment days 2-10, the exercise challenge was performed after the subjects inhaled 4 ml of either heparin (20,000 u/ml), cromolyn (20 mg), or placebo solutions with increasing pretreatment intervals of 15 min, 1 h, 3 h, or 6 h in a single-blind, randomized fashion. Maximum decreases in SGaw (mean +/- SE) at 3 to 5 min after exercise on control (39 +/- 2.1%) and placebo (37 +/- 2.6%) days were reproducible. Heparin and cromolyn had no effect on baseline SGaw but attenuated the EIA in a time-dependent fashion. Heparin inhibited the bronchoconstrictor responses to exercise by 58%, 78%, and 67% (p < 0.05) when nebulized 15 min, 1 h and 3 h, respectively, before exercise; cromolyn attenuated the responses by 37%, 46%, and 41%, respectively, (p < 0.05). Although heparin offered greater protection than cromolyn (at 1 to 3 h), both agents were ineffective when administered 6 h before exercise. These data demonstrate that inhaled heparin prevents EIA for up to 3 h and is more effective than cromolyn.

Administration, Inhalation↗
PubMed1996

Heterogeneity of allergic airway responses in sheep: differences in signal transduction?

In preliminary studies we have observed that inhaled heparin blocks antigen-induced airway responses in sheep that develop only acute responses to inhaled antigen (acute responders), but not in sheep that develop both acute and later responses (dual responders). Because heparin is an antagonist of inositol triphosphate (IP3) (one of the pathways involved in stimulus-secretion-coupling in mast cells), the differential effect of inhaled heparin in acute responders and dual responders might indicate the involvement of different signaling pathways during IgE-mediated mast cell reactions. Therefore, in this study we compared the effects of heparin on antigen-induced bronchconstriction, allergic cutaneous reaction, and histamine release into bronchoalveolar lavage fluid (BAL) in sheep that develop only acute responses or dual responses to inhaled Ascaris suum antigen. Specific lung resistance (SRL) was measured in 21 sheep (eight acute responders; 13 dual responders) before and after inhalation challenge with antigen, without and after pretreatment with inhaled heparin (1,000 units/kg). Histamine in BAL was measured by RIA before and after segmental antigen challenge, without and after pretreatment with inhaled heparin (eight acute responders; eight dual responders). In acute responders, mean +/- SE SRL increased by 197 +/- 21% with antigen; this was prevented by inhaled heparin (deltaSRL = 15 +/- 7%; p < 0.05). In dual responders, inhaled heparin had no effect on antigen-induced early (deltaSRL = 328 +/- 51% versus 305 +/- 76%) or late (deltaSRL = 201 +/- 33% versus 163 +/- 15%) responses. After segmental antigen challenge, BAL mean +/- SE histamine increased from 2.09 +/- 0.8 nM to 75.4 +/- 21.1 nM in acute responders and 1.58 +/- 0.7 nM to 66.8 +/- 27.3 nM in dual responders (p < 0.01). Inhaled heparin inhibited the increase in BAL histamine by 81% in acute responders (p < 0.05) and by only 19% in dual responders (p = NS). As was seen in the airways, heparin attenuated the allergic cutaneous reaction in acute responders by 46% (p < 0.05), but it was ineffective in dual responders. In contrast, H-7, a nonspecific protein kinase C inhibitor, attenuated the cutaneous reaction in dual responders by 28% (p < 0.05), but it was ineffective in acute responders. These data suggest that heterogeneity of allergic airway response is related to difference in mast cell signal transduction; IP3 is the predominant second messenger in acute responders, whereas non-IP3 pathways may be involved in dual responders.

Animals↗
PubMed1996

Homoharringtonine in patients with myelodysplastic syndrome (MDS) and MDS evolving to acute myeloid leukemia.

Current anti-leukemic chemotherapy in patients with myelodysplastic syndromes (MDS) and MDS evolving to acute myeloid leukemia (AML) is associated with low response rates and high treatment-related toxicity. Homoharringtonine (HHT) is a novel cephalotaxime alkaloid with reported efficacy in relapsed and de novo AML and more recently, chronic myeloid leukemia. Although its mechanism(s) of action is not completely understood, in vitro studies have demonstrated both cytotoxic and differentiating activity in leukemic cells, as well as intra-cellular changes suggestive of apoptotic cell death. In a phase II trial, HHT was administered at a dose od 5 mg/m2 by 24-h continuous infusion daily for 9 days to patients with MDS and MDS evolving to AML (MDS/AML). Twenty-eight patients (MDS 16, MDS/AML 12) with a median age of 67 years (range 23-83) were entered. A complete remission was achieved in seven patients, a partial remission was achieved in one patient for an overall response rate of 28% (8/28). There were four of 13 responders in MDS/AML patients and four of 15 in patients with MDS. The median duration of complete response was 7 months (range 2-10). Significant myelosuppression was universal and resulted in a high incidence of induction deaths (13/28) due to neutropenic-related infections. Extramedullary toxicity was mild and consisted of hypo-tension, fluid retention, hypoglycemia, diarrhea, nausea and vomiting. HHT given in this dose and schedule demonstrated limited activity in MDS and MDS/AML and was associated with prolonged pancytopenia and marrow hypoplasia in many patients. Administration of HHT at a lower dose or in combination with hematopoietic growth factors may lead to better results, but treatment with HHT as single agent at this dose and schedule is not currently recommended for these patients.

Adult↗
PubMed1996

A study of prolonged pyrexia in Dhaka.

In a prospective study conducted in the Institute of Postgraduate Medicine & Research (IPGMR), Dhaka, 212 patients with prolonged pyrexia were thoroughly evaluated clinically and with the help of laboratory investigations with a view to reaching the diagnosis. Their clinical and laboratory data were recorded. Clinical features pertaining to a particular organ gave appropriate clue in 52% cases. Imaging techniques were instrumental in 24%, microbiological or serological investigations in 35%, invasive procedures were diagnostic in 42%, laparotomy had to be resorted to in five cases. Infectious diseases were the commonest causes of prolonged pyrexia accounting for about 63.21% of cases followed by neoplasms (12.74%) and connective tissue disorders (10.85%). Tuberculosis was the most common infection (24.53% of all cases) followed by enteric fever (12.74%) and visceral leishmaniasis (9.43%). Pleura was the commonest seat for tuberculosis followed by lymph nodes and abdomen. Leukemias were the commonest neoplasm and SLE the commonest connective tissue disorder presenting with prolonged fever. Several fundamental observations were made in the study. Infections are the commonest cause of prolonged fever in our community, neoplasms and connective tissue disorders are also not rare. Secondly, patients with temperature between 100 to 101 degrees F should not be denied evaluation with the apprehension of unnecessarily investigating for habitual hyperthermia, as the condition was distinctly rare in the series. Thirdly, analysis of materials from organs or systems suspected to be abnormal clinically or by simple imaging techniques had high diagnostic yield. Finally, usual causes of prolonged fever are illnesses ordinarily encountered in clinical practice, pyrexia becomes protracted either because the presentation is atypical or incomplete, or because we fail to make proper use of available clinical or paraclinical information.

Adolescent↗