Search PubMed⌕ Search

Biomedical subjects

J Klastersky

Publications and source records attributed to J Klastersky.

At least 181 records · Page 10Linked to original sources
PubMed1986

Subrenal capsule assay of fresh human tumors: problems and pitfalls.

The 6 day subrenal capsule (SRC) assay was performed in normal mice using 20 fresh human non-small cell lung cancers and nine fresh ovarian cancers. Different multi-agent chemotherapy regimens administered intravenously on days 2 + 3 of the assay were evaluated for activity against these two tumor types. Macroscopic results measured via an ocular microscope showed high activity for some combinations as well as for single agents. However, when subjected to microscopic examination, the SRC implants in the untreated control animals did not show viable tumor growth on day 6. Detailed histologic evaluation of over 800 SRC grafts reveals an intense inflammatory and fibrotic reaction in the majority of the grafts. These results indicate that drug sensitivity patterns obtained with this assay using only macroscopic criteria do not correlate with actual tumor regression. Microscopic analysis of the grafts prior to transplant shows absence or only minimal presence of tumor in many cases which also contributes to the poor growth observed in these two tumors.

Animals↗
PubMed1986

Placebo controlled pneumococcal immunization in patients with bronchogenic carcinoma.

Pneumococcal vaccine [heptadecavalent types 1, 2, 3, 4, 6A, 7F, 8, 9N, 11A, 12F, 14, 15F, 17F, 18C, 19F, 23F and 25 pneumococcal capsular polysaccharide vaccine (Moniarix)] or placebo were evaluated in 26 and 21 patients with bronchogenic carcinoma, most of whom did not receive prior radiotherapy or chemotherapy. No difference was detected as far as clinical outcome is concerned: 3 vaccinated patients out of 26 (11.5%) developed pneumococcal infections (1 fatal bacteremia) and 4/21 (19%) of those who received a placebo presented such an infection (1 fatal bacteremia). The antibody response was significantly increased in the vaccines for types 1, 2, 7F, 8, 9N, 12F, 14, 17F, 18C, 23F and 25.

Adult↗
PubMed1986

In vitro activity of menogaril and N-demethylmenogaril in a human tumor cloning assay.

The activity of menogaril and its major metabolite in animals and humans, N-demethylmenogaril, has been investigated in the human stem cell assay as developed by Salmon et al. Among 31 evaluable samples, four were sensitive to menogaril, including one which responded to N-demethylmenogaril. Three samples resistant to menogaril responded to N-demethylmenogaril. None was sensitive to doxorubicin. Overall, one out of seven ovarian samples and one out of three breast samples responded to menogaril. Our data confirm the in vitro activity of menogaril in ovarian and breast cancer; in addition, they suggest incomplete cross-resistance between doxorubicin and menogaril and, considering the concentrations of N-demethylmenogaril in animals and humans, a minor role for this metabolite in the overall antitumor activity of the parent compound.

Breast Neoplasms↗
PubMed1986

Nephrotoxicity induced by cancer chemotherapy with special emphasis on cisplatin toxicity.

Renal failure in cancer patients is a common problem in oncology; this complication is frequently multifactorial in origin. Several antineoplastic agents are potentially nephrotoxic; previous renal impairment as well as combinations with other nephrotoxic drugs may increase the risk of nephrotoxicity during administration of chemotherapy. Methotrexate-related renal damage most frequently occurs with high-dose therapy and can be avoided by forced alkaline diuresis and administration of folinic acid. Renal dysfunction secondary to semustine (CH3-CCNU) is clearly related to cumulative doses in excess to 1,200 mg/m2; the onset may be delayed and renal failure progress despite drug discontinuation. Streptozotocin is also nephrotoxic and may cause proteinuria and renal tubular acidosis; progressive renal failure can be predicted by a close monitoring of proteinuria and prevented by drug discontinuance. Mitomycin-associated renal failure frequently presents with signs of microangiopathic hemolytic anemia; renal failure is usually delayed but occasionally, it may be rapidly progressive despite drug discontinuance. Cisplatin nephrotoxicity is clearly dose-related and used to be considered dose limiting. Renal insufficiency can be prevented by hydration and forced diuresis; in addition, hyperhydration with mannitol-induced saline diuresis may allow administration of high doses and thus circumvent the dose-limiting effect of cisplatin-induced renal toxicity. Cisplatin-induced renal magnesium wasting occurs frequently and should be supplemented. Other approaches to reduce cisplatin nephrotoxicity are currently under investigation and are discussed.

Animals↗
PubMed1986

Cephalosporins, vancomycin, aminoglycosides and other drugs, especially in combination, for the treatment of methicillin-resistant staphylococcal infections.

Methicillin-resistant staphylococci (MRS) have become major nosocomial pathogens during the last decade. The infections caused by these organisms occur predominantly in intensive care units, where extensive use of antibiotics takes place. Because of their multiresistant nature, these microorganisms frequently pose difficult therapeutic problems. Emergence of resistance during single-drug therapy further complicates the management of these infections. The use of combination therapy provides theoretically, at least, an answer to some of these difficulties; however, in-vitro and experimental studies need to be confirmed by adequately-controlled clinical trials. Aminoglycosides occasionally may play an important role as companion drugs for cephalosporins or vancomycin in the management of MRS infections. Other drugs such as rifampicin, teicoplanin, fluoroquinolones, and imipenem are to be more extensively investigated, as single-drug therapy or part of a combination regimen, for these difficult staphylococcal infections.

Aminoglycosides↗
PubMed1986

Empirical antimicrobial therapy with Timentin plus amikacin in febrile granulocytopenic cancer patients.

Timentin (ticarcillin plus clavulanic acid) plus amikacin was administered as an empirical regimen to 52 febrile granulocytopenic patients with cancer and appeared as effective as the other commonly recommended combinations of antimicrobial agents. A favourable response was observed in 61% of episodes with bacteraemia and in 83% of the episodes without bacteraemia. However, the efficacy in Gram-positive bacteraemia was suboptimal and the emergence of superinfections caused by Gram-positive cocci may represent a clinical challenge.

Adult↗
PubMed1986

Comparison of pharmacokinetics and bactericidal activity of teicoplanin and vancomycin.

Teicoplanin (0.2 g) or vancomycin (1 g) were infused over 3 and 50 min respectively to six male volunteers in a cross-over study. Each drug was administered twice at a 14 h interval. The pharmacokinetics of both drugs were accurately described using a two-compartment model. Vancomycin had a shorter half-life (5.8 +/- 1.8 h) compared to teicoplainin (33.2 +/- 5.1 h; P less than 0.001). One hour serum was tested for serum bactericidal activity against ten strains each of Staphylococcus aureus (median serum bactericidal activity 1:16 for teicoplanin; 1:32 for vancomycin), Staph. epidermidis (1:32 for teicoplanin and for vancomycin) and Streptococcus faecalis (1:2 for both drugs). Serum killing rate studies showed a slower rate of killing of Staph. aureus with teicoplanin (less than 1 log10 cfu/ml over 6 h) than with vancomycin (4 log10 cfu/ml over 6 h).

Adult↗
PubMed1986

Clinical evaluation of teicoplanin for therapy of severe infections caused by gram-positive bacteria.

Teicoplanin was evaluated in 47 patients with severe infections, including 14 patients with bone infections, 11 patients with soft-tissue infections, 7 patients with endocarditis, 5 patients with pneumonia, 3 patients with septic thrombophlebitis, 3 patients with septicemia of unknown origin, and 4 patients with miscellaneous infections. Overall, bacteremia was documented in 24 patients. The pathogens isolated were 35 strains of Staphylococcus aureus (including 8 methicillin-resistant strains), 4 strains of Staphylococcus epidermidis, 4 strains of Streptococcus faecalis, 2 strains of Streptococcus pneumoniae, 5 strains of other streptococci, and 1 Micrococcus luteus strain. A total of 22 patients (46.8%) were clinically cured, 8 patients (17.0%) improved, 2 patients (4.3%) had relapses after initial improvement, and 15 patients (31.9%) failed to respond. The results were better in nonbacteremic patients (19 of 23 patients [82.6%] were cured or improved) than in patients with bacteremia (12 of 24 patients [50%] were cured or improved). Bacteriological cure occurred in 25 patients (53.2%), and superinfections were documented in 6 patients (12.8%). No major adverse effects were observed. We conclude that teicoplanin is a potentially effective and well-tolerated antimicrobial agent for therapy of nonbacteremic infections caused by gram-positive bacteria.

Adult↗
PubMed1986

Bactericidal activity and killing rate of serum from volunteers receiving pefloxacin alone or in combination with amikacin.

Serum bactericidal activities (SBAs) were studied after intravenous administration of pefloxacin (8 mg/kg) and amikacin (7.5 mg/kg) alone or in combination to 15 human volunteers. About 10 strains each of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Staphylococcus aureus were tested. The serum levels of pefloxacin were measured microbiologically by using E. coli KP 1976-712 as the test organism at 0, 30, 60, 120, and 720 min after infusion; at 0, 30, 60, and 720 min these levels were 7 +/- 1.4, 5 +/- 0.8, 4.5 +/- 0.7, and 2.1 +/- 0.6 mg/liter (mean +/- standard deviation), respectively, with a terminal half-life of 10 h. The serum levels of pefloxacin in the presence of amikacin were measured similarly; 1% sodium polyanethol sulfonate was added to the agar to inactivate amikacin. Treatment with pefloxacin alone resulted in high SBAs against E. coli, K. pneumoniae strains susceptible to cephalothin, and Staphylococcus aureus at the peak concentration; 81 to 100% of the sera had SBAs of greater than or equal to 1:8. However, treatment with pefloxacin alone resulted in low SBAs against K. pneumoniae strains resistant to cephalothin and P. aeruginosa; only 34% of the sera had SBAs of greater than or equal to 1:8. At trough concentrations the percentages of sera with SBAs greater than or equal to 1:8 were 75 to 83% (E. coli), 9 to 27% (K. pneumoniae), 0% (P. aeruginosa), and 10% (S. aureus). The combination of pefloxacin plus amikacin was most often additive; the peak activity was due to amikacin, and the trough activity was due to pefloxacin. Occasionally antagonism occurred with P. aeruginosa, K. pneumoniae, and S. aureus strains. These observations were confirmed by the killing curves in pooled serum obtained at peak and trough levels. Regrowth was observed for seven strains of P. aeruginosa treated with pefloxacin alone; amikacin seemed to prevent this phenomenon.

Amikacin↗
PubMed1986

Prospective randomized comparison of three antibiotic regimens for empirical therapy of suspected bacteremic infection in febrile granulocytopenic patients.

The standard regimen used by members of the European Organization for Research on Treatment of Cancer Antimicrobial Therapy Cooperative Group for empiric therapy of febrile neutropenic cancer patients has been treatment with ticarcillin plus amikacin. A three-arm prospective randomized controlled trial was performed to determine whether the extended-spectrum antipseudomonal penicillin azlocillin or the extended-spectrum cephalosporin cefotaxime had more or less efficacy than the beta-lactam in the ticarcillin-plus-amikacin regimen. A total of 742 patients from 22 institutions were evaluated. Single gram-negative rod bacteremias accounted for 83 episodes, and it was among these patients that the prognosis was least satisfactory, leading to a more intensive evaluation of this patient group. In these patients the azlocillin-plus-amikacin regimen resulted in a 66% response rate, compared with a 37% response rate for patients who received cefotaxime plus amikacin (P = 0.080) and a 47% response rate for patients who received ticarcillin plus amikacin (P = 0.207). The patients with gram-negative rod bacteremias and persistently profound granulocytopenia had substantially poorer response rates (37%) than the patients with rising granulocyte counts (73%; P = 0.004). A logistic regression analysis indicated that the following factors also affected infection resolution: beta-lactam utilization in the regimen (azlocillin was better than ticarcillin or cefotaxime), resolution of profound granulocytopenia (less than 100 cells per microliter) during therapy, and susceptibility to the beta-lactam antibiotic.

Adolescent↗
PubMed1986

BRL-36650: in vitro studies and assessment of serum bactericidal activity after single-dose administration in volunteers.

Ten healthy volunteers received 1 g of BRL-36650, a new formamido-penicillin derivative, given by intravenous infusion over 15 min. Levels in serum were measured microbiologically 30, 60, and 120 min after the start of the 15-min infusion and were (mean +/- standard deviation) 102.7 +/- 28.4, 59.7 +/- 11.5, and 9.6 +/- 1.9 mg/liter, respectively. A total of 10 strains each of Escherichia coli, Klebsiella pneumoniae, Serratia spp., and Enterobacter spp. and 14 strains of Pseudomonas aeruginosa were selected according to their susceptibility or resistance to piperacillin for the study of serum bactericidal activity (SBA). The MICs and MBCs of these strains were influenced by the choice of medium. Median SBA against E. coli and K. pneumoniae were greater than or equal to 1:2,048 and 1:512, respectively. The SBA against piperacillin-susceptible Serratia spp. (1:256), Enterobacter spp. (1:128), and P. aeruginosa (1:32) were significantly higher than against piperacillin-resistant strains (1:32, 1:8, and 1:4, respectively). Killing curves confirmed the high bactericidal activities obtained against the majority of strains. In the case of one Enterobacter sp. and one P. aeruginosa isolate with an MBC greater than or equal to 32, the absence of killing was noted.

Female↗
PubMed1986

Serum bactericidal activity and killing rate for volunteers receiving imipenem, imipenem plus amikacin, and ceftazidime plus amikacin against Pseudomonas aeruginosa.

Serum bactericidal activity against 20 strains of Pseudomonas aeruginosa was studied in 10 volunteers after administration of imipenem (25 mg/kg), imipenem (25 mg/kg) plus amikacin (7.5 mg/kg), and ceftazidime (25 mg/kg) plus amikacin (7.5 mg/kg). Eight strains were susceptible and 12 were resistant to ticarcillin. Serum levels were measured microbiologically after 30 and 60 min and were, respectively, 97 and 46 micrograms/ml for imipenem given alone and 79 and 45 micrograms/ml for imipenem given with amikacin. Despite the very large dose of imipenem used, imipenem and imipenem plus amikacin appeared slightly less active than ceftazidime plus amikacin (P less than or equal to 0.1; Wilcoxon matched-pairs test), with respective median titers at 30 min of 1:128, 1:128, and 1:256 against ticarcillin-susceptible strains and 1:32, 1:32, and 1:64 against ticarcillin-resistant strains; however, more than 90% of the serum determinations, regardless of the regimen, had a serum bactericidal activity greater than or equal to 1:8. Amikacin significantly increased the rate of killing in serum of P. aeruginosa by imipenem. Imipenem plus amikacin appeared as effective as ceftazidime plus amikacin in reducing the viable counts of P. aeruginosa after 24 h of incubation.

Amikacin↗
PubMed1986

Bactericidal activity and killing rate of serum in volunteers receiving ciprofloxacin alone or in combination with vancomycin.

Ten healthy volunteers received the following regimen on different days: vancomycin, 500 mg intravenously; ciprofloxacin, 200 mg intravenously; vancomycin plus ciprofloxacin. Concentrations in serum measured microbiologically at the end of infusion and 1 and 6 h after the end of infusion were, respectively (mean [standard deviation] in milligrams per liter): 32.3 (5.5), 14.2 (2.6), and 4 (0.9) for vancomycin and 3.12 (0.86), 0.78 (0.18), and 0.19 (0.05) for ciprofloxacin. Vancomycin concentration was not affected by the simultaneous administration of ciprofloxacin. The serum bacteriostatic and bactericidal (SBA) activities were measured 1 and 6 h after the end of infusion against five strains each of Staphylococcus aureus susceptible and resistant to oxacillin, Staphylococcus epidermidis susceptible and resistant to oxacillin, Corynebacterium strain JK, and Listeria monocytogenes and three strains of Mycobacterum fortuitum. Ciprofloxacin alone provided low SBAs against the tested strains even 1 h after administration. Vancomycin provided adequate SBAs against staphylococci and Corynebacterium strain JK 1 h after administration. None of the regimens tested showed adequate bactericidal activity against L. monocytogenes and M. fortuitum. The combination of vancomycin with ciprofloxacin was indifferent. This was confirmed by studying the rate of killing in serum. Vancomycin plus ciprofloxacin appeared to be promising for the empiric treatment of infection in immunocompromised patients.

Ciprofloxacin↗
PubMed1986

A randomized study comparing a high and a standard dose of cisplatin in combination with etoposide in the treatment of advanced non-small-cell lung carcinoma.

We conducted a randomized trial comparing a high (120 mg/m2 day 1) v a standard (60 mg/m2 day 1) dose of cisplatin in combination with etoposide (120 mg/m2 days 3, 5, and 7) in advanced non-small-cell lung carcinoma (NSCLC). Two hundred forty-one patients were evaluable for survival and 207 for response. We obtained a 25% objective response rate in the standard-dose arm and 29% in the high-dose arm; this difference was not statistically significant. There was no significant improvement in the overall survival or survival of responders with the high-dose regimen. However, toxicity (mainly myelosuppression) was significantly increased in the patients receiving the higher dose of cisplatin. An analysis of prognostic factors showed that disease progression, loss of body weight, performance status, and prior therapy were predictive parameters of survival.

Actuarial Analysis↗
PubMed1986

Nonsurgical combined modality therapies in non-small cell lung cancer.

Nonsurgical combined approaches of non-small cell lung cancer represent a concept that has only been investigated so far with chemotherapy and radiation therapy. Thoracic irradiation of locoregional disease is associated with a high rate of local control and a 5-10% long-term (5-year) survival; however, distant metastases remain the main cause of failure. This observation suggests that the tumor is often microscopically disseminated at the time of diagnosis. Systemic therapy therefore must be associated to radiation therapy to try to control both the undetectable metastases and the local disease. However, the results reported so far have been disappointing, probably because of the modest activity of the available chemotherapy. Further progress with the combined approach requires new developments in the chemotherapy of non-small cell lung cancer, particularly the introduction of new active drugs.

Antineoplastic Agents↗
PubMed1986

Influence of various antibiotics on superoxide generation by normal human neutrophils.

Among the several killing mechanisms displayed by human neutrophils, the oxidative system is the most efficient. We have studied the influence of various antibiotics on the generation of superoxide by isolated human polymorphonuclear leukocytes (PMNL) stimulated by phorbol-myristate acetate. Among the antibiotics tested, only coumermycin significantly inhibited superoxide generation; this effect was dose-related, it depended on extracellular calcium concentration and was potentiated by sub-inhibitory concentrations of calcium channel-blocking agents. Coumermycin inhibited the influx of calcium produced by the ionophore A23187 as well as directed chemotaxis in agar and the intracellular killing of a highly susceptible strain of S. aureus. These inhibitory effects required at least 15 min of preincubation of the PMNL. Coumermycin, at clinically achievable serum concentrations, significantly impaired several PMNL functions. The mechanism could be a specific or a non-specific interaction with calcium-channels.

Aminocoumarins↗
PubMed1986

In vitro activity of coumermycin alone or in combination against Staphylococcus aureus and Staphylococcus epidermidis.

The in vitro activity of coumermycin was tested against oxacillin-susceptible and resistant strains of Staphylococcus aureus and Staphylococcus epidermidis, and compared with that of penicillin G, oxacillin, minocyclin, erythromycin, vancomycin, teicoplanin, rifampicin and LM 427. The MICs were measured using the agar dilution method with an inoculum of 10(5) cfu/spot. Coumermycin was the most active antibiotic with MIC90 of 0.025-0.2 mg/l. The MICs of coumermycin remained unchanged by further incubation for 48 h. The combination of coumermycin with ciprofloxacin, an inhibitor of subunit A of the DNA gyrase, was studied by the time-kill curve method and resulted in a synergistic effect when subinhibitory concentrations of either antibiotic were used. The combination of coumermycin with rifampicin or LM 427 was antagonistic.

Aminocoumarins↗