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Biomedical subjects

J Chang

Publications and source records attributed to J Chang.

At least 433 records · Page 24Linked to original sources
PubMed1990

Reduction of tetrachloro(dl-trans)1,2-diaminocyclohexaneplatinum(IV) (tetraplatin) toxicity by the administration of diethyldithiocarbamate (DDTC), S-2(3-aminopropylamino)ethylphosphorothioic acid (WR-2721), or sodium selenite in the Fischer 344 rat.

Diethyldithiocarbamate (DDTC), S-2(3-aminopropylamino)ethylphosphorothioic acid (WR-2721), and sodium selenite have all been shown to effectively reduce cisplatin toxicity. As a result, we have investigated the efficacy of these compounds to reduce the toxicity associated with tetrachloro(dl-trans)1,2-diaminocyclohexaneplatinum(IV) (tetraplatin), a second-generation platinum compound recently approved for phase I/II clinical trials. The dose-limiting toxicities associated with tetraplatin (16.5 mg/kg) in the Fischer 344 male rat were nephrotoxicity, myelosuppression, and gastrointestinal toxicity. The nephrotoxicity in Fischer 344 rats was effectively reduced by treatment with either DDTC (750 mg/kg ip) 0.5 hr after tetraplatin or WR-2721 (200 mg/kg ip) 0.5 hr before tetraplatin as determined by blood urea nitrogen and creatinine values. Diarrhea was evident in 95% of the rats treated with tetraplatin alone while it was not evident in any of the DDTC- or WR-2721-protected rats. Only DDTC was moderately effective in preventing tetraplatin-induced decreases in platelet and lymphocyte counts. Histopathology confirmed DDTC protection of renal, intestinal, and lymphoid tissues and WR-2721 protection of renal and intestinal tissues. Sodium selenite was ineffective in reducing tetraplatin-induced damage when administered 4 hr before tetraplatin at doses of 0.5, 1.0, or 2.0 mg/kg. The results suggest that DDTC may allow for increased dosages of tetraplatin by ameliorating the toxic side effects of the drug. WR-2721 may also have some usefulness in tetraplatin therapy, but it does not reduce as wide a variety of toxic side effects as DDTC.

Amifostine↗
PubMed1990

Early controlled active mobilization with dynamic splintage for treatment of extensor tendon injuries.

Early controlled active mobilization with a dynamic splint for treatment of repaired extensor tendon injuries was studied prospectively. Postoperative dynamic splintage started on the third postoperative day and involved elastic band extension and active flexion of the digits. Mobilization of the digits within the splint was done immediately under supervision. Range of motion was stepped up progressively and splintage was stopped after 5 to 6 weeks. Thirty-eight patients with 48 digits were reviewed. The average follow-up was 6.7 months (range, 4 to 10 months). Injuries involving the fingers showed an average final total active motion of 229 degrees (range, 95 to 270 degrees), whereas injuries involving the thumb was 118 degrees (range, 78 to 150 degrees). Lesions distal to the knuckles (zones II, III, IV) showed the worst results with an average total active motion of only 188 degrees (range, 95 to 270 degrees). The duration out of work was 8.5 weeks (range, 4 to 25 weeks). There was no infection or acute tendon rupture. One patient required reconstruction of a persistent button-hole deformity; two required tenolysis and capsulotomy. Of the six unsatisfactory results with poor total active motion, four had injuries distal to the metacarpophalangeal joint, three of which were crushing injuries.

Adolescent↗
PubMed1990

N-[(arylmethoxy)phenyl] carboxylic acids, hydroxamic acids, tetrazoles, and sulfonyl carboxamides. Potent orally active leukotriene D4 antagonists of novel structure.

Four series of N-[(arylmethoxy)phenyl] compounds were prepared as leukotriene D4 (LTD4) antagonists. In the hydroxamic acid series, methyl 3-(2-quinolinylmethoxy)benzeneacetohydroxamate (Wy-48,422, 20) was the most potent inhibitor of LTD4-induced bronchoconstriction with an oral ED50 of 7.9 mg/kg. Compound 20 also orally inhibited ovalbumin-induced bronchoconstriction in the guinea pig with an ED50 of 3.6 mg/kg. In vitro, against LTD4-induced contraction of isolated guinea pig trachea pretreated with indomethacin and 1-cysteine, 20 produced a pKB value of 6.08. In the sulfonyl carboxamide series, N-[(4-methylphenyl)sulfonyl]-3-(2-quinolinylmethoxy)-benzamide (Wy-49,353, 30) was the most potent antagonist. Compound 30 orally inhibited both LTD4- and ovalbumin-induced bronchoconstriction with ED50s of 0.4 and 20.2 mg/kg, respectively. In vitro, against LTD4-induced contraction of isolated guinea pig trachea, 30 produced a pKB value of 7.78. In the carboxylic acid series, which served as intermediates for the above two series, 3-(2-quinolinylmethoxy)benzeneacetic acid (Wy-46,016, 5) was the most potent inhibitor of LTD4-induced bronchoconstriction (99% at 25 mg/kg, intraduodenally); however, the pKB for this compound was disappointing (5.79). In the tetrazole series, the most potent inhibitor was 2-[[3-(1H-tetrazol-5-ylmethyl)phenoxy]methyl]quinoline (Wy-49,451, 41). The respective inhibitory ED50s were 3.0 mg/kg versus LTD4 and 17.5 mg/kg versus ovalbumin. In the isolated guinea pig trachea, 41 produced a pKB value of 6.70.

Animals↗
PubMed1990

Granulocyte-macrophage colony stimulating factor (GM-CSF) after high-dose melphalan in patients with advanced colon cancer.

Nine patients with progressive, metastatic disease from primary carcinoma of the colon were entered into a phase I/II study using continuous intravenous infusions of granulocyte-macrophage colony-stimulating factor (GM-CSF) and high dose melphalan (120 mg m-2). GM-CSF was given alone to six patients during the first part of the study to determine a dose that would produce a peripheral leucocyte count (WCC) greater than or equal to 50 X 10(9) 1(-1) and was initially given at 3 micrograms kg-1 day-1 and escalated to 10 micrograms kg-1 day-1 after 10 days. The infusion was discontinued when the WCC exceeded 50 X 10(9) 1(-1) and after a gap of one week, melphalan was given over 30 min. GM-CSF was recommenced 8 h later and was continued until the neutrophil count had exceeded 0.5 X 10(9) 1(-1) for greater than 1 week. One patient achieved a WCC greater than 50 X 10(9) 1(-1) with GM-CSF 3 micrograms kg-1 day-1, but the other five who entered this phase of the study required dose escalation to 10 micrograms kg-1. No toxicity attributed to GM-CSF was seen. After melphalan, the median times to severe neutropenia (less than 0.5 X 10(9) 1(-1] and thrombocytopenia (greater than 20 X 10(9) 1(-1] were 6 and 9 days respectively. The median durations of neutropenia and thrombocytopenia were 14 and 10 days respectively. All patients required intensive support with a median duration of inpatient stay of 24 days. There was one treatment related death due to renal failure. One complete and two partial remissions (33% response rate) were seen but these were of short duration (median of 10 weeks). This study demonstrates that GM-CSF given by continuous intravenous infusion produces significant increments of peripheral granulocyte counts at 3 and 10 micrograms kg-1 day-1 and is not associated with any toxicity. The duration of neutropenia and thrombocytopenia induced by high-dose melphalan appears to be reduced by the subsequent administration of GM-CSF to times which are at least as short as have been reported in historical series which have used autologous bone marrow rescue.

Adult↗
PubMed1990

Functional studies of bone marrow haemopoietic and stromal cells in the myelodysplastic syndrome (MDS).

Long-term bone marrow culture (LTBMC) was used to investigate the proliferative behaviour of marrow cells from a spectrum of cases of the myelodysplastic syndrome (MDS), and the results compared with those obtained in the conventional short-term clonal assay. Two broad patterns of growth were revealed in LTBMC. In one group the incidence of haemopoietic progenitor cells steadily declined to abnormally low levels at 4 weeks, while in a second group they were maintained near normal levels for periods of up to 7 weeks. These growth patterns, which were not predictable from clonogenic assays on the marrow cells prior to LTBMC, or from the morphology of the bone marrow, may reflect the stage of evolution of the disease. Further studies of clonality are required to establish whether or not patients exhibiting the second pattern have a potentiality to harbour residual normal haemopoiesis. LTBMC was also used to study the function of MDS marrow stroma in terms of its ability to sustain the growth of normal haemopoietic progenitor cells. Although the phenotype of the cultured adherent cell layer, obtained from some patients, was atypical, no consistent functional defect of MDS stroma could be identified by studying the level of haemopoiesis reached by normal cells seeded into MDS stroma.

Adolescent↗
PubMed1990

Long-term bone marrow damage after chemotherapy for acute myeloid leukaemia does not improve with time.

Thirteen patients with acute myeloid leukaemia (AML) who had been in unmaintained complete remission for at least 5 years following successful chemotherapy, were studied by marrow culture techniques regularly for periods of up to 5 years. In 10 patients, short-term clonal assay revealed the incidence of granulocyte-macrophage progenitor cells (GM-CFC) to be at the lower limit of the normal range; but three showed wide fluctuations in GM-CFC numbers. Moreover the generation of GM-CFC in long-term bone marrow culture (LTBMC) was impaired in eight of nine evaluable patients. These results suggest that, despite normal blood counts, impairment of haemopoiesis persists in patients who are long-term survivors of AML, and this does not improve with the passage of time.

Adult↗
PubMed1990

Roseola infantum and other syndromes associated with acute HHV6 infection.

Eight cases of acute human herpesvirus type 6 (HHV6) infection in infants were diagnosed serologically by the demonstration of IgM anti-HHV6 (8/8) and a significant change in total anti-HHV6 antibody titre (6/8). Four infants were sufficiently ill to require admission to hospital and further investigations: one with encephalitis and three with gross hepatosplenomegaly, two of whom had evidence of simultaneous infection with another herpes-virus. The remaining four infants had an illness compatible with roseola infantum, although this diagnosis had not been made clinically. Sera from two of those infants with rash had been sent for analysis to exclude rubella because the infants' mothers were pregnant. The other two had received antibiotics when febrile, and the subsequent appearance of the roseola rash had raised the possibility of antibiotic allergy. The data suggest that there are clinical syndromes in addition to roseola infantum associated with the presence of IgM anti-HHV6, in which serological screening for evidence of acute HHV6 infection may be useful.

Antibodies, Viral↗
PubMed1990

Intravenous therapy with high doses of ranitidine and omeprazole in critically ill patients with bleeding peptic ulcerations of the upper intestinal tract: an open randomized controlled trial.

Thirty-nine critically ill patients with actively bleeding peptic ulcerations--Forrest Ib--in the stomach or duodenum were randomly allocated to intravenous therapy with 400 mg ranitidine per day or 80 mg omeprazole per day (120 mg on the 1st day) for 5 days. Successful therapy was proven by control endoscopy on day 6 if less than 2.5 liters of blood had to be transfused from the start of therapy to maintain a hemoglobin value of 10g/l or above. Treatment failure meant that more than 2.5 liters of blood were necessary to maintain a hemoglobin level above 10 g/l. Of 20 patients in the ranitidine group bleeding stopped in only 3 patients (15%). Of 17 patients who continued bleeding under ranitidine therapy the bleeding could be controlled in 13 patients after changing to omeprazole treatment. Of 19 patients in the omeprazole group bleeding stopped in 16 patients (84%). These results demonstrate that the significantly more effective reduction of acidity by omeprazole is promising for the therapy of bleeding peptic ulcerations and may reduce the need for invasive therapy or operation.

Duodenal Ulcer↗
PubMed1990

Characterization of interleukin 1 induced rabbit chondrocyte phospholipase A2.

Stimulation of rabbit articular chondrocytes with interleukin 1 (IL-1) results in the activation of intracellular phospholipase A2 (PLA2) and the subsequent secretion of this enzyme into the extracellular milieu. Pretreatment of chondrocytes with actinomycin D or cycloheximide significantly inhibited IL-1 induced PLA2 activation and secretion, suggesting that the enzyme induction process is RNA and protein synthesis dependent. Chondrocyte PLA2 is highly calcium dependent with a 1 mM optimum CA++ concentration for hydrolytic activity; little or no hydrolysis is observed in the absence of calcium and the hydrolytic activity is abolished in the presence of 10 mM ethylenediamine tetraacetic acid. The enzyme is also pH sensitive with optimal PLA2 hydrolytic activity observed at pH 6.5-7. Further, chondrocyte PLA2 was sensitive to inhibition by mepacrine, a compound with PLA2 inhibitory activity. The IL-1 induced chondrocyte PLA2 has a molecular weight of approximately 10 kDa, as determined by molecular sieve G75 column chromatography. The apparent molecular weight and CA++, pH and drug sensitivity of the extracellular and intracellular forms of the IL-1 induced chondrocyte PLA2 are indistinguishable. Since this IL-1 induced enzyme has similar biochemical characteristics to PLA2 enzymes isolated from human rheumatoid and osteoarthritic synovial fluid, we suggest that the chondrocyte may be an important cellular source for this PLA2 enzymatic activity in inflamed joints.

Animals↗
PubMed1990

The use of cultured bone marrow cells in autologous transplantation.

The feasibility of ex vivo purging with long-term bone marrow cultures (LTBMC) for autologous transplantation in leukemia has been established. The procedure has been applied to patients with acute myeloid leukemia (in relapse or remission) and recently in one patient with chronic myeloid leukemia. The results in first remission AML are very encouraging with 4 out of 6 patients well and apparently disease free greater than 1 to 4 years post autograft. In patients transplanted with active disease, remissions of 6 to 8 months duration were seen in two patients transplanted in florid relapse. In a CML patient with 87% of his bone marrow cells Ph1 positive, there was a marked decline of karyotypically abnormal cells in culture. Reinfusion of the cultured cells into the patient resulted in engraftment with exclusively Ph1 negative cells. The therapeutic implications of LTBMC purging require further evaluation.

Bone Marrow Cells↗
PubMed1989

Wy-48,252 (1,1,1-trifluoro-N-[3-(2-quinolinylmethoxy)phenyl]methane sulfonamide) an orally active leukotriene D4 antagonist: pharmacological characterization in vitro and in vivo in the guinea pig.

The following communicates the pharmacology of Wy-48,252 (1,1,1-trifluoro-N-[3-(2-quinolinylmethoxy)phenyl]methanesulfonamide) a chemically novel and orally potent leukotriene (LT) D4 receptor antagonist. In the isolated guinea-pig trachea pretreated with indomethacin (5 microM) and L-cysteine (10 mM), Wy-48,252 antagonized TD4-induced contraction with a pKB = 7.6. Against LTC4 on tissues pretreated with IND and glutathione (10 mM), Wy-48,252 had a pKB greater than 5. Wy-48,252 (10 microM) did not antagonize pilocarpine-, histamine- or PGF2 alpha-induced tracheal contraction. Further, in the presence of indomethacin and chlorpheniramine (1 microM), Wy-48,252 dose-dependently inhibited the antigen-induced contraction of guinea-pig trachea in a manner consistent with antagonism at the LTD4 receptor and inhibition of LT synthesis. In the Konzett-Rossler model of i.v. LTD4-induced bronchoconstriction in indomethacin treated guinea pigs, intragastric Wy-48,252 (2 hr) had an ID50 of 100 micrograms/kg and a functional half-life of 5 hr. Against i.v. antigen-induced bronchoconstriction in guinea pigs treated with indomethacin and chlorpheniramine, intragastric Wy-48,252 (2 hr) had an ID50 of 0.6 mg/kg and a 5 hr half life. Intragastric Wy-48,252 also selectively blocked the cutaneous wheal reaction to intradermal LTD4 but not histamine. We conclude that Wy-48,252 is distinguished from other selective LTD4 receptor antagonists by its oral potency and should be useful in ascertaining the role of LTD4 mediated processes in asthma, allergy and animal models.

Animals↗
PubMed1989

N-[(arylmethoxy)phenyl] and N-[(arylmethoxy)naphthyl] sulfonamides: potent orally active leukotriene D4 antagonists of novel structure.

Two series of compounds, N-[(arylmethoxy)phenyl] sulfonamides and N-[(arylmethoxy)naphthyl] sulfonamides, were prepared as leukotriene D4 (LTD4) antagonists. In the phenyl series, N-[3-(2-quinolinylmethoxy)phenyl]-trifluoromethanesulfonamide (Wy-48,252, 16) was the most potent inhibitor of LTD4-induced bronchoconstriction in the guinea pig. With an intragastric ID50 of 0.1 mg/kg (2-h pretreatment), 16 was 300 times more potent than LY-171,883. Compound 16 also intragastrically inhibited ovalbumin-induced bronchoconstriction in the guinea pig with an ID50 of 0.6 mg/kg. In vitro against LTD4-induced contraction of isolated guinea pig trachea pretreated with indomethacin and L-cysteine, 16 produced a pKB value of 7.7. In the rat PMN assay 16 inhibited both 5-lipoxygenase and cyclooxygenase (IC50's = 4.6 and 3.3 microM). In the naphthyl series, N-[7-(2-quinolinylmethoxy)-2-naphthyl]trifluoromethanesulfonamide (Wy-48,090, 47) in addition to potent LTD4 antagonist activity (on isolated guinea pig trachea 47 had a pKB value of 7.04) also had antiinflammatory activity (63% inhibition at 50 mg/kg in the rat carrageenan paw edema assay and 34% inhibition of TPA-induced inflammation at 1 mg/ear in the mouse ear edema model). Perhaps the antiinflammatory activity of 47 was due to its additional activity of inhibiting both 5-lipoxygenase and cyclooxygenase enzymes (IC50's = 0.23 and 11.9 microM, respectively, in rat PMN).

Acetophenones↗
PubMed1989

Socioeconomic concerns in vascular surgery: a survey of the role of age, resource consumption, and outcome in treatment cost.

Surgical hospital payment issues and socioeconomic concerns are likely to attract more attention in the future, especially regarding access and the quality of surgical care. We analyzed all peripheral vascular surgical admissions (n = 1240) by age treated at the Long Island Jewish Medical Center from 1985 to 1987. Hospital cost and length of stay per patient increased with age, as did losses under diagnostic related group (DRG) prospective hospital payment. Hospital cost by hospital service showed considerable variation by age category; outliers, mortality, and the number of diagnoses and procedures generally rose with age. Use of hospital resources, such as emergency or surgical intensive care unit admission, or the need for blood or plasma products was high in general for patients undergoing peripheral vascular surgery. This study demonstrates a number of findings regarding the socioeconomic factors for hospitalized patients undergoing peripheral vascular surgery. Surgical health policy analysis of this specialty vis-a-vis current changes proposed to the federal medicare DRG system in the U.S. Congress and Health Care Financing Administration suggests a relatively greater impact on the specialty of peripheral vascular surgery demonstrated in this study by the use of higher resources of the same.

Adolescent↗
PubMed1989

The kinetics of human granulopoiesis following treatment with granulocyte colony-stimulating factor in vivo.

Cell proliferation in the bone marrow and blood of two patients with metastatic breast cancer who were treated with granulocyte colony-stimulating factor was studied by using [3H]thymidine labeling and autoradiography. Additionally, the fate of neutrophils labeled with 99mTc-hexamethylpropyleneamineoxime was observed following granulocyte colony-stimulating factor infusion. Proliferation increased in all stages of granulopoiesis, but a significant amount of the increased production stemmed from a greater input to the myeloblast compartment. Changes in the myelogram combined with the increased labeling indicated a faster throughput of cells, which resulted in labeled cells appearing in the circulation within 1 day compared to the normal 4 or 5 days. The 99mTc studies demonstrated no sequestration of circulating neutrophils by spleen, lungs, or liver. The half-life of the circulating neutrophils was not significantly changed, and calculations from the flow of labeled cells to the peripheral blood indicated an increase of 3.2 extra amplification divisions during neutrophil development. The dramatic neutrophil response to granulocyte colony-stimulating factor can therefore be accommodated by a relatively modest increase in granulopoietic activity.

Adult↗
PubMed1989

Prevention and reversal of aerosol LTD4-induced changes in guinea pig pulmonary mechanics by Wy-48252, an orally active LTD4/E4 receptor antagonist.

Anesthetized male albino guinea pigs were prepared for recording changes in the pulmonary mechanics parameters, dynamic compliance (Cdyn) and airway conductance (Gaw). Two aerosol leukotriene D4 (LTD4) challenges (0.125 microgram/ml, 3-7 breaths, 1 h apart) were administered via an ultrasonic nebulizer to each animal and, produced reductions in Cdyn that were approximately 60% of those of Gaw. Intraduodenal administration of the LTD4/E4 receptor antagonists Wy-48252 (30 min), Wy-45911 and Ly-171883 (15 min) produced dose-related inhibition of the second LTD4 challenge. From the data, ID50 values were calculated and, Wy-48252 was 8- to 17-fold more potent (mg/kg) than Wy-45911 or Ly-171883. Responses to histamine were not altered by the antagonists. In separate experiments, Wy-48252 (0.3 and 1 mg/kg i.v.) rapidly reversed aerosol LTD4-induced decreases of Cdyn and Gaw, but did not reverse pulmonary mechanics decreases produced by prostaglandin F2 alpha. The results indicate that systemically administered LTD4 receptor antagonists can both prevent and reverse bronchoconstriction produced by aerosol LTD4 in the guinea pig.

Animals↗
PubMed1989

Phase II study of cyclophosphamide, doxorubicin, and vincristine (CAV) and etoposide plus cisplatin (EP) alternating chemotherapy combined with radiotherapy in small cell lung cancer.

The development of drug resistance is the major limiting factor influencing the survival of patients with small cell lung cancer (SCLC). We have thus examined the activity of cyclophosphamide, doxorubicin and vincristine (CAV) alternating with etoposide and cisplatin (EP) in 35 patients with SCLC. The treatment courses were alternated every 3 or 4 weeks. After induction chemotherapy, patients with limited disease (LD) received thoracic radiotherapy (5000 cGy), prophylactic cranial irradiation (3000 cGy) and maintenance chemotherapy and patients with extensive disease (ED) received maintenance chemotherapy only. In this group of 35 patients, 13 had limited disease (LD) and 22 had extensive disease (ED). After completion of the therapy, 100% of the patients with LD achieved complete plus partial remission (CR + PR) and 68% of the patients with ED achieved CR + PR. The median survival time was 66 weeks (15.3 months) in patients with LD and 44 weeks (10.2 months) in patients with ED. The over all survival for patients with LD was superior to that for patients with ED (p less than 0.05). Also, median response duration for patients with LD (35 wks) was longer than that for patients with ED (17 weeks) (p less than 0.05). The primary site was the most vulnerable site to relapse (18 patients). Toxicity was mild to moderate and acceptable, and there were no treatment-related deaths. These results suggest that the alternation of CAV and EP is effective treatment strategy in the management of SCLC. A randomized controlled study will be required to discriminate the actual effect of this alternating regimen.

Adult↗