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Biomedical subjects

D H Ho

Publications and source records attributed to D H Ho.

At least 37 records · Page 2Linked to original sources
PubMed1993

In vitro activities of antimicrobial agents against clinical isolates of Flavimonas oryzihabitans obtained from patients with cancer.

We evaluated the in vitro activities of 21 different antimicrobial agents against nine clinical isolates of Flavimonas oryzihabitans obtained from patients with cancer. The organisms were susceptible to most agents commonly used for the empiric therapy (aminoglycosides, ureidopenicillins, extended-spectrum cephalosporins, monobactams, and carbapenems) and prevention of infections (quinolones and trimethoprim-sulfamethoxazole) in this patient population.

Anti-Bacterial Agents↗
PubMed1993

Depletion of patients' plasma tryptophan using tryptophan side-chain oxidase columns.

The use of the enzyme tryptophan side-chain oxidase, isolated from Pseudomonas XA, was explored in 3 patients with refractory acute lymphocytic leukemia. Patients were given either a low-tryptophan diet or tryptophan-free hyperalimentation, prior to and during therapy. Their plasma, separated by pheresis, was continuously passed through a tryptophan depletion column containing the immobilized tryptophan side-chain oxidase. Up to 4 plasma volumes were passed through the column daily, 5 days per week for 2-3 weeks, and plasma tryptophan levels, both free and total, were measured by high-performance liquid chromatography. Pre- and postcolumn plasma samples were collected throughout the pheresis procedure. All postcolumn plasma samples had unmeasurable tryptophan levels throughout the treatment period, whereas precolumn samples were always measurable. Generally, tryptophan levels of plasma isolated from peripheral blood decreased after therapy, but rebounded by the next day. The enzyme depletion column reduces circulating plasma tryptophan levels, and its use is well tolerated by patients. However, further development of this method will require study of the effects of diet and of the duration, interval, and frequency of use of this column on therapeutic efficacy. Problems include difficulties with extended diet compliance and apparently intensive mobilization of tryptophan from body stores, which may preclude the clinical application of this enzyme depletion column.

Chromatography, High Pressure Liquid↗
PubMed1993

L-asparaginase and PEG asparaginase--past, present, and future.

L-asparaginase is an enzyme which hydrolyses asparagine. Since the 1960s it has been known that some leukemic cells are deficient in asparagine synthetase and therefore cannot manufacture sufficient quantities of this essential amino acid to maintain cell viability. L-asparaginase is predominantly useful in acute lymphocytic leukemia (ALL) although responses have been noted in patients with acute myeloid leukemia, lymphoma, and rarely other tumors. L-asparaginase has been used in conjunction with methotrexate and ara-C in combination programs in leukemia. The major side-effect limiting the usefulness of L-asparaginase is allergic reactions. In addition, it is probable that neutralizing antibodies develop which shorten the half life of the drug so that the goal of depletion of plasma levels of asparagine cannot be attained or maintained. Polyethylene glycol (M.W. 5000) can be conjugated to L-asparaginase at sites not involving the active site of the enzyme. This enables free access of a small molecule, asparagine, to the active site of the enzyme but prevents uptake by the reticuloendothelial system, greatly decreasing the probability of developing antibodies against the asparaginase and prolongs the circulating half life of the drug. In a phase I/II study conducted at the M.D. Anderson Cancer Center, 37 heavily pretreated patients with refractory hematologic malignancy were treated. The age range from 15 to 73 years, median 49 years. Nineteen patients had ALL, 15 lymphoma, two myeloma, and one Hodgkin's disease. The dose levels of PEG L-asparaginase varied from 250 IU/m2 up to 8000 IU/m2. The pharmacokinetic profile demonstrated a monophasic half life consistent with a one compartment model with a single elimination phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Determination of plicamycin in plasma by radioimmunoassay.

This article describes a method for the determination of plicamycin in plasma by radioimmunoassay. The anti-plicamycin antibody was produced against a plicamycin-bovine serum albumin conjugate prepared by using diazotized p-aminobenzoic acid as a cross-linker. The radiolabeled ligand, 125I-plicamycin, was prepared by the chloramine-T method. The linear plicamycin concentration range was 7-400 ng/ml. The coefficients of variation for intra- and interday variabilities were 7.5 and 15%, respectively. No interference was observed from either the structurally related chromomycin A or concomitantly used drugs hydroxyurea or allopurinol. With this method of testing, plicamycin levels in plasma could be determined in patients receiving small (0.85-1.0 mg/m2) therapeutic plicamycin doses. Preliminary pharmacokinetic data in humans indicate that the plasma drug disappearance curve was biphasic with a mean elimination half-life of 10.6 +/- 1.7 h, total clearance rate of 11.1 +/- 0.4 ml/min/m2, and area under the plasma drug concentration-time curve of 1,289-1,546 ng-h/ml. This assay method is clinically useful for pharmacokinetic studies of plicamycin and may be helpful in the design of rational therapeutic drug trials.

Antibody Specificity↗
PubMed1992

In vitro activity of Ro 23-9424, a dual-action antibacterial agent, against bacterial isolates from cancer patients compared with those of other agents.

The in vitro activity of Ro 23-9424 against bacterial isolates from patients with cancer was compared with those of fleroxacin, ciprofloxacin, cefoperazone, and ceftazidime. Ro 23-9424 inhibited the majority of the members of the family Enterobacteriaceae and all Aeromonas isolates at a concentration of less than or equal to 1.0 micrograms/ml. It was also active against Acinetobacter spp. and Haemophilus influenzae, including beta-lactamase-producing strains. The MIC for 90% of isolates (MIC90) of Pseudomonas aeruginosa was 16.0 micrograms/ml. All group A and B streptococci were inhibited by less than or equal to 0.25 micrograms/ml, and 90% of group G streptococci and Streptococcus pneumoniae were inhibited by 1.0 micrograms/ml. All methicillin-susceptible strains of Staphylococcus aureus and 60% of methicillin-resistant strains were susceptible to 2.0 micrograms of Ro 23-9424 per ml, whereas the MIC90 for Staphylococcus epidermidis and Staphylococcus hominis isolates was 4.0 micrograms/ml. Staphylococcus haemolyticus and Enterococcus spp. were less susceptible; MIC90s for them were 16.0 and 32.0 micrograms/ml. Ro 23-9424 has a broad antibacterial spectrum and potential utility for therapy of infections in cancer patients.

Anti-Infective Agents↗
PubMed1991

Phase I trial of FK973: description of a delayed vascular leak syndrome.

FK973 is a novel, substituted dihydrobenzoxazine structurally similar to mitomycin. FK973 lacks cross-resistance with mitomycin, doxorubicin, and vincristine in murine tumor models. A phase I study of FK973 was initiated using a 30-minute infusion repeated every 4 weeks. Of 17 patients enrolled on the study, a minimum of three patients were entered at each dose level: 7, 14, 21, 30, and 45 mg/m2. The dose-limiting toxicity was a vascular leak syndrome (VLS) characterized by pericardial and pleural effusions, ascites, and subcutaneous edema. These conditions were observed in two patients treated with a dose of 30 mg/m2 and in four who received 45 mg/m2. VLS was observed 2 weeks after the third dose of 30 mg/m2 and one week after the second dose of 45 mg/m2. Of nine patients treated with a cumulative dose greater than 60 mg/m2, five experienced this toxic reaction. Reversible drug-related pneumonitis was noted in one patient after the third course of 30 mg/m2. Moderate nausea and vomiting were initially observed at a dose of 14 mg/m2 and alopecia at 30 mg/m2. Grade 3-4 granulocytopenia was observed in two patients treated with 45 mg/m2. Extensive myocardial degeneration was observed at autopsy in a patient who had received three courses of 30 mg/m2. One patient with metastatic colon carcinoma and another with metastatic pancreatic carcinoma experienced partial clinical responses. Although the drug's clinical activity appears promising, additional investigation is needed into the mechanism of toxicity prior to further clinical development.

Antineoplastic Agents↗
PubMed1990

[Activities of enzymes converting 5-fluorouracil to 5-fluorouridine-5' monophosphate and 5-fluorodeoxyuridine-5' monophosphate in subcultured cell lines and solid tumor tissues].

The activities of five enzymes, orotate phosphoribosyltransferase (OPRTase), uridine kinase (UR kinase), thymidine kinase (TdR kinase), uridine phosphorylase (UR Prylase) and thymidine phosphorylase (TdR Prylase), were examined in subcultured human acute leukemia cell lines (HL-60, CCRF-CEM), subcultured human solid tumor cell lines (Colo-205, HeLa-S3) and human cancerous tissues with a view to compare the activation of 5-fluorouracil in them. There was no significant difference in the activity of any enzyme between HL-60 and CCRF-CEM, Colo-205 and HeLa-S3, and human lung cancerous tissue and human colon cancerous tissue. Compared between the acute leukemia cell lines and the solid tumor cell lines, the UR kinase activity was high in both cell lines. The OPRTase and UR Prylase activities were low in the solid tumor cell lines. In the cancerous tissues, both the UR kinase and TdR kinase activities were low, but the UR Prylase and TdR Prylase activities were markedly high. The results suggest that the intracellular activation of 5-fluorouracil varies with different human cancerous cells. When the anti-cancer activity of 5-fluorouracil is tested in vitro, the difference of fluoropyrimidine metabolism in subcultured cell lines from that in the cancerous tissue should be taken in account.

Fluorouracil↗
PubMed1990

Comparative in vitro activity of the new erythromycin derivative dirithromycin against gram-positive bacteria isolated from cancer patients.

The in vitro activity of dirithromycin (LY-237216), a new macrolide erythromycin derivative, was compared to that of four other agents (clarithromycin, erythromycin, roxithromycin, clindamycin) against 334 gram-positive isolates obtained from cancer patients. Dirithromycin was similar in potency and antimicrobial spectrum to the other agents tested. It was very active against beta-haemolytic streptococci and Streptococcus pneumoniae, and moderately active against penicillin and methicillin susceptible Staphylococcus aureus, Bacillus spp., Listeria monocytogenes and Corynebacterium jeikeium. Erythromycin resistant organisms were also resistant to dirithromycin.

Anti-Bacterial Agents↗
PubMed1990

In-vitro activity of PD 117 596, a new quinolone, against bacterial isolates from cancer patients.

The in-vitro activity of PD117 596, a new 4-quinolone antimicrobial agent was compared with that of ciprofloxacin against 798 Gram-positive and Gram-negative distinct isolates from cancer patients. PD117 596 was found to have a broad antimicrobial spectrum with excellent activity against the Enterobacteriaceae (MIC90 0.03 mg/l) Acinetobacter spp. (MIC90 0.25 mg/l), Aeromonas spp. (MIC100 0.06 mg/l) and Pseudomonas spp. including Ps. aeruginosa (MIC90 0.5 mg/l). It was also extremely active against Gram-positive micro-organisms particularly Staphylococcus spp. (including methicillin-resistant and coagulase-negative isolates) Bacillus spp. and streptococci. PD117 596 had lower minimal inhibitory concentrations against most isolates tested than ciprofloxacin, the most active currently available 4-quinolone.

Anti-Infective Agents↗
PubMed1990

In vitro activity of sparfloxacin (CI-978; AT-4140) against clinical isolates from cancer patients.

The in vitro activity of sparfloxacin, a new quinolone, was compared with those of ciprofloxacin and fleroxacin against gram-positive and gram-negative bacteria, greater than 90% of which were isolated from blood culture specimens of cancer patients. Sparfloxacin was extremely active against Acinetobacter species, Aeromonas hydrophila, Citrobacter diversus, Enterobacter species, Escherichia coli, Klebsiella species, Proteus vulgaris, and Serratia marcescens (inhibiting greater than 90% of these isolates at a concentration of 0.5 microgram/ml) and moderately active against Pseudomonas species, other Proteus species, and Citrobacter freundii. Sparfloxacin inhibited greater than 90% of staphylococci (including methicillin-resistant and coagulase-negative strains) at a concentration of 0.12 microgram/ml and greater than 90% of streptococci (including Streptococcus pneumoniae) at a concentration of 1.0 microgram/ml. It was also active against Bacillus cereus, Enterococcus species, and Corynebacterium jeikeium, organisms that have become fairly common in cancer patients.

Anti-Infective Agents↗
PubMed1990

Comparative in vitro activities of newer quinolones against Pseudomonas species and Xanthomonas maltophilia isolated from patients with cancer.

The in vitro susceptibilities of three Pseudomonas species (Pseudomonas aeruginosa, Pseudomonas putida, and Pseudomonas fluorescens) and Xanthomonas maltophilia to quinolone antimicrobial agents were determined. Several newer agents, particularly PD117558, PD117596, PD127391, sparfloxacin (AT-4140), A-56620, and temafloxacin, were active against Pseudomonas species. X. maltophilia isolates were generally less susceptible than were Pseudomonas isolates but were inhibited by some of the newer quinolones.

4-Quinolones↗
PubMed1990

In vitro activity of PD127,391, a new quinolone against bacterial isolates from cancer patients.

The in vitro activity of PD127,391, a new 4-quinolone, was compared to that of ciprofloxacin against common clinical bacterial isolates from patients with cancer. PD127,391 was found to have a broad antimicrobial spectrum with excellent activity against gram-positive isolates (including multidrug-resistant organism such as Corynebacterium jeikeium, Enterococcus faecalis, Enterococcus faecium, methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus spp.). It was also extremely active against gram-negative bacilli including Pseudomonas aeruginosa. Against organisms such as Achromobacter xylosoxidans, Acinetobacter spp. and Xanthomonas maltophilia, which are frequently resistant to a variety of antimicrobial agents, PD127,391 exhibited good activity, inhibiting all such isolates at a concentration of 0.5 micrograms/ml. Overall, PD127,391 was far more potent than ciprofloxacin against gram-positive isolates and slightly more active against gram-negative isolates. No bacterium that we examined needed more than 2 micrograms/ml of PD127,391 for inhibition.

Anti-Infective Agents↗
PubMed1989

A comparison of the effects of tetraplatin and cisplatin on renal function and gentamicin pharmacology in rats.

Tetraplatin (tetrachloro[d,l-trans]1,2-diaminocyclohexane platinum IV (TTP)) is a new platinum analogue active against L1210 murine leukemia that is resistant to cisplatin (diamminedichloroplatinum II (DDP)). Since nephrotoxicity is a significant problem with DDP therapy, we compared the effects of equitherapeutic doses of TTP and DDP on renal structure and function in rats. We also studied the effects of the 2 platinum compounds on the distribution and excretion of gentamicin (GENT), an antibiotic that is excreted solely by the kidneys. Rats treated intravenously with 2.85 mg/kg of DDP on days 1, 5 and 9 had significantly different plasma urea nitrogen (BUN) levels and creatinine clearance rates on day 16 than those given the same doses of TTP. The renal function of TTP-treated rats did not differ from that of controls or rats given only GENT. Twenty-four hours after a single GENT dose (given on day 15), DDP-treated rats had higher GENT concentrations in the plasma, liver and spleen than rats given GENT alone. TTP-treated rats had higher GENT levels only in the spleen. DDP-treated rats retained a higher percentage of the injected platinum in the renal cortex than those treated with TTP. Light microscopic examination of renal tissue showed necrotic cells and dilated tubules in the proximal tubules of DDP-treated rats while the kidneys of TTP-treated rats were largely indistinguishable from those of controls. Thus, our results indicate that the distribution of platinum in the kidneys differs between rats treated with TTP and those treated with DDP. This may partly explain the considerably lower nephrotoxicity of TTP.

Animals↗
PubMed1989

In vitro activity of trospectomycin (U-63366F), a novel spectinomycin analog, against gram-positive isolates from cancer patients.

The in vitro activity of trospectomycin was compared to that of amikacin, cephalothin and vancomycin against gram-positive organisms, mostly isolated from cancer patients. Trospectomycin was considerably more active than amikacin against most isolates tested, particularly species of Staphylococcus and Streptococcus. Overall, vancomycin was the most active agent tested.

Amikacin↗
PubMed1989

In-vitro activity of PD 117558, a new quinolone against bacterial isolates from cancer patients.

The in-vitro activity of PD 117558, a new quinolone antimicrobial agent, was compared to that of four other quinolones, imipenem and ceftazidime against a variety of Gram-positive and Gram-negative isolates from cancer patients. PD 117558 was found to have a broad antimicrobial spectrum with excellent activity against all Gram-positive isolates (including methicillin-resistant Staphylococcus aureus, coagulase-negative staphylococci, Streptococcus faecalis and Group JK-corynebacteria). It was also extremely active against Gram-negative bacilli with the exception of Pseudomonas aeruginosa against which ciprofloxacin was more active. Fleroxacin was slightly less active and S-25930 and S-25932 considerably less active than PD 117558. PD 117558 also had lower minimal inhibitory concentrations for most organisms tested than either imipenem or ceftazidime.

4-Quinolones↗
PubMed1989

Antifungal susceptibility of 44 clinical isolates of Fusarium species determined by using a broth microdilution method.

The MICs and minimum fungicidal concentrations of amphotericin B, natamycin, miconazole, itraconazole, and flucytosine against 17 isolates of Fusarium solani, 14 isolates of Fusarium moniliforme, 10 isolates of Fusarium oxysporum, and 3 isolates of Fusarium semitectum were determined by a broth microdilution method. Amphotericin B and natamycin were the most active agents tested and failed to show any inoculum size effect. In contrast, miconazole and itraconazole showed poor inhibitory and fungicidal activities, and the inoculum size had a major effect on the results. Flucytosine had no activity against any of the isolates tested.

Antifungal Agents↗
PubMed1989

Metabolism and disposition of (R)-4-[3-(2-hydroxy-2-phenyl)ethylamino-3-methylbutyl]benzamide Hcl (LY 195448) in rodents.

The disposition and metabolism of (R)-4-[3-(2-hydroxy-2-phenyl)ethylamino-3-methylbutyl]benzamide HCl, or LY 195448 (LY), were studied in rodents 1 hr following a single iv injection of 14C-LY at 30 mg/m2 (10 mg/kg mice and 5 mg/kg rats), In all tissues and carcases, recovery of 14C was nearly complete. The majority of radioactivity was recovered from intestine (40%) whereas liver and urine accounted for 10% each, kidney for 3-5%, and plasma for 1-3% of total administered radioactivity. Analyzing by HPLC and TLC, para-hydroxy-LY (para-OH-LY) in addition to unchanged drug, was found in all tissues. Meta-OH-LY was detected only in urine, intestine and kidney. These metabolites were found to be conjugated with either glucuronide or sulfate moieties. Peaks coeluting with authentic para-OH-meta-methoxy-LY and di-OH-LY were also observed.

Animals↗