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Biomedical subjects

A Bastian

Publications and source records attributed to A Bastian.

At least 37 records · Page 2Linked to original sources
PubMed1996

[Comparative study of the cost-/effectiveness relationship of initial therapy with imipenem/cilastatin in nosocomial pneumonia. Group study].

AIM OF THE STUDY: The present study assessed the total cost involved in the therapy of nosocomial pneumonia. Cost for patients receiving Imipenem as initial antibiotic therapy was compared with that for patients treated by selected alternative regimens. Secondary objectives included the evaluation of fever days, days of antibiotic therapy, days at ICU and days of overall hospitalisation required for the treatment of the nosocomial pneumonia for both methods of treatment. METHODS: A prospective randomised open study involving multiple study sites was conducted. Total cost, efficacy and safety of an initial therapy with Imipenem were compared to results achieved with selected other antibiotic regimens. Altogether 109 patients were enrolled into the study; 85 patients could be assessed. RESULTS: Both treatment methods showed equal clinical efficacy. Total cost of the therapy of nosocomial pneumonia for all patients was in the range between 1,616 DM and 82,141 DM, the arithmetic mean was calculated to be 11,307 DM and the median was found to be 6,507 DM. Imipenem-treated patients incurred lower cost (median 5,649 DM, mean 10,009 DM) than patients treated with other antibiotics (median 9,334 DM, mean 12,701 DM). CONCLUSION: The total cost of treatment of nosocomial pneumonia was lower for Imipenem-treated patients than for patients receiving initially other selected antibiotic regimens. The savings are apparently due to a faster recovery of the patients resulting in reduced duration of therapy. The study shows that assessment of cost of therapy per day might be misleading in the economic analysis of antimicrobial chemotherapy.

Adolescent↗
PubMed1995

Phase I clinical trial of continuous infusion cyclopentenyl cytosine.

Cyclopentenyl cytosine (CPE-C) is an investigational drug that is active against human solid tumor xenografts. The 5'-triphosphate of CPE-C inhibits CTP synthase, and depletes CTP and dCTP pools. We conducted a phase I clinical trial of CPE-C given as a 24-h continuous i.v. infusion every 3 weeks in 26 adults with solid tumors. The starting dose rate, 1 mg/m2 per h, was selected on the basis of both preclinical studies and pharmacokinetic data from two patients obtained after a test dose of 24 mg/m2 CPE-C as an i.v. bolus. Dose escalation was guided by clinical toxicity. A total of 87 cycles were given, and ten patients received four or more cycles. The mean CPE-C steady-state plasma levels (Cpss) increased linearly from 0.4 microM to 3.1 microM at dose levels ranging from 1 to 5.9 mg/m2 per h (actual body weight); the mean total body clearance was 146 +/- 38 ml/min per m2. CPE-C was eliminated by both renal excretion of intact drug and deamination to cyclopentenyl uracil in an apparent 2:1 ratio. CTP synthase activity in intact bone marrow mononuclear cells was inhibited by 58% to 100% at 22 h compared to matched pretreatment samples at all CPE-C dose levels. When all data were combined, flux through CTP synthase was decreased by 89.6% +/- 3.1% at 22 h (mean +/- SE, n = 16), and remained inhibited by 67.6% +/- 7.7% (n = 10) for at least 24 h post-CPE-C infusion. Granulocyte and platelet toxicities were dose-dependent, and dose-limiting myelosuppression occurred during the initial cycle in two of three patients treated with 5.9 mg/m2 per h. Four of 11 patients (4 of 20 cycles) who received 4.7 mg/m2 per h CPE-C experienced hypotension 24-48 h after completion of the CPE-C infusion during their first (n = 2), third (n = 1) and sixth cycles (n = 1), respectively. Two of these patients died with refractory hypotension despite aggressive hydration and cardiopulmonary resuscitation. One of 12 patients (28 total cycles) treated with 3.5 mg/m2 per h CPE-C experienced orthostatic hypotension during cycle 1, and this patient had a second episode of orthostatic hypotension at a lower dose (3.0 mg/m2 per h). Hypotension was not seen in patients receiving < or = 2.5 mg/m2 per h CPE-C.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1994

Chimeric fusion protein toxin DAB486IL-2 in advanced mycosis fungoides and the Sezary syndrome: correlation of activity and interleukin-2 receptor expression in a phase II study.

DAB486IL-2 is a recombinant toxin with the cell surface-binding domain of diphtheria toxin (DT) replaced by interleukin-2 (IL-2). To correlate clinical response with expression of components of the IL-2 receptor (IL-2R), 14 patients with cutaneous T-cell lymphoma (CTCL) received five daily 90-minute infusions every 21 days. There were no complete responses, 1 partial response (PR), 2 major biologic effects (major cutaneous improvement without change in circulating neoplastic cells), 3 stable disease (SD), and 8 progressive disease (PD). Responders had easily detected expression of CD25 (Tac; alpha-chain of IL-2R) in skin, and in two responders expression of the beta chain of the IL-2 receptor (beta-IL-2R) was detectable by reverse transcriptase-polymerase chain reaction. CD25 was also detected in 8 of 11 SD or PD patients, with beta-IL-2R in 3 of 8 SD or PD patients. Two of the three responders had anti-DT antibodies before treatment. Reversible increased hepatic transaminases occurred in 13 of 14 patients during the first course, with decreased frequency in repeated courses. The maximal serum concentration after the first infusion of DAB486IL-2 varied (1,369 +/- 1,155 ng/mL [mean +/- SD]; n = 14; range, 55 to 3,999 ng/mL) with a short half-life (T1/2 beta = 0.21 +/- 0.12 h [mean +/- SD]; range, 0.099 to 0.57 h). The area under the concentration curve varied inversely with anti-DT antibody titer. We conclude that DA-B486IL-2 has valuable activity in certain patients with CTCL. Expression of the IL-2R may be necessary but is not sufficient to predict response.

Diphtheria Toxin↗
PubMed1994

A dose intensity study of FLAC (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) chemotherapy and Escherichia coli-derived granulocyte-macrophage colony-stimulating factor (GM-CSF) in advanced breast cancer patients.

BACKGROUND: It has been demonstrated that granulocyte-macrophage colony-stimulating factor (GM-CSF) can ameliorate chemotherapy-induced neutropenia. The extent to which GM-CSF can increase the actual delivered dose intensity of combination chemotherapy over multiple cycles of therapy to patients with advanced breast cancer has not been well defined. We conducted a phase I/II study of dose-intensive FLAC chemotherapy (5-fluorouracil, leucovorin, doxorubicin, cyclophosphamide) in combination with GM-CSF in patients with locally advanced and metastatic breast cancer to study the acute and cumulative toxicities, anti-tumor activity and dose-intensity achievable with this regimen. METHODS: Eighty-one patients with newly diagnosed stages IIB, III and IV breast cancer who were previously untreated with chemotherapy and who had measurable disease received multiple cycles of FLAC chemotherapy plus E. coli-derived GM-CSF administered every three weeks. RESULTS: FLAC plus GM-CSF as associated with significant cumulative hematologic toxicity. Ninety-eight percent of patients developed grade 4 neutropenia; 29% of all cycles administered required hospitalization for fever and neutropenia; 41% and 22% of cycles required red blood cell and platelet transfusions, respectively. Other significant toxicities with E. coli-derived GM-CSF included mild to moderate first dose effects (hypotension, dyspnea, abdominal cramping) in 30% of patients; late occurring anaphylactoid reactions in 11% of patients; and vascular thromboses. The average delivered dose intensities over all cycles were cyclophosphamide, 210 mg/m2/week; doxorubicin, 14.8 mg/m2/week and 5-fluorouracil, 342 mg/m2/week. The overall clinical response rates were 100% and 83% for LABC and metastatic patients, respectively. There were 23% (6/26) pathologic CR's in the LABC patients given neoadjuvant FLAC and 22% (12/54) clinical CR's in the stage IV patients. The median survival of the LABC patients has not been reached (> 26 months) and is 30 months for the stage IV patients. CONCLUSIONS: The administration of multiple cycles of FLAC plus E. coli-derived GM-CSF therapy is associated with cumulative, dose-limiting myelosuppression, especially thrombocytopenia, as well as significant clinical toxicity. A modest increase in FLAC dose intensity over the starting doses was achievable with the addition of GM-CSF. FLAC chemotherapy has substantial antitumor activity in the treatment of advanced breast cancer. The potential usefulness of FLAC plus GM-CSF must be balanced by its considerable cost and alteration in patients' quality of life due to toxicity. Combination hematopoietic growth factor strategies may be able to reduce the toxicity of FLAC and to allow further increase dose intensity.

Adult↗
PubMed1994

Phase II trial of fludarabine phosphate and interferon alfa-2a in advanced mycosis fungoides/Sézary syndrome.

PURPOSE: This phase II study was undertaken to assess the efficacy and toxicity of the addition of continuous low-dose interferon alfa-2a (IFN) to fludarabine in patients with advanced or refractory mycosis fungoides (MF) or the Sézary syndrome (SS). PATIENTS AND METHODS: Thirty-five patients were treated with fludarabine 25 mg/m2 intravenously (IV) on days 1 to 5 every 28 days along with IFN 5 x 10(6) U/m2 subcutaneously three times per week continuously for up to eight cycles. IFN doses were escalated to 7.5 x 10(6)/m2 at day 29 if constitutional toxicities were less than grade 3. Twenty-one patients had not responded to prior chemotherapy or total-skin electron-beam irradiation (TSEB), and 10 of these had received prior deoxycoformycin (pentostatin; DCF) and intermittent high-dose IFN; seven had received only topical therapies, and seven were untreated. RESULTS: Four patients achieved a complete response (CR) and 14 achieved a partial response (PR) for an overall response rate of 51% (95% confidence interval, 35% to 70%). Four of 11 patients with visceral involvement responded. The median progression-free survival duration of the patients who responded was 5.9 months, and three of the complete responders are in unmaintained response after 18 to 35 months. Grade 3 or 4 hematologic toxicity occurred in 21 patients, including two who developed persistent bone marrow aplasia. Eighteen patients developed infections during therapy, including five with herpes zoster, one with Pneumocystis carinii, one with extrapulmonary tuberculosis, and two with disseminated toxoplasmosis. CONCLUSION: The combination of fludarabine with continuous low-dose IFN is an active regimen in patients with advanced MF/SS, including patients with visceral involvement and patients who progressed after prior therapy with DCF and IFN. This regimen has induced unmaintained remissions in a small subset of patients.

Adult↗
PubMed1993

Phase I trial of dihydrolenperone in lung cancer patients: a novel compound with in vitro activity against lung cancer.

Antitumor activity of the butyrophenone dihydrolenperone in non-small cell lung cancer was initially suggested by in vitro screening against tumor cells derived from fresh surgical samples using the human tumor colony-forming assay. We have completed a directed phase I trial in patients with lung cancer. Thirty-two patients with lung cancer have completed 25 courses of therapy at doses of 10 to 60 mg/square meter orally on a twice daily schedule. Twenty-three men and 9 women with a median age of 55 (range 24-69) were entered. Twenty-four were performance status 0 or 1 and 8 were 2. The maximum tolerated dose was 50 mg/square meter orally twice daily and the dose limiting toxicity was somnolence. Of the 32 patients, 18 developed symptomatic hypotension (grade 1 or 2). There was no significant hematologic, renal, or hepatic toxicity. In vitro drug testing using the MTT [3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (thiazolyl blue)] assay confirmed 50% inhibition of non-small cell and small cell lung cancer cell line growth at 70-450 micromolar concentrations. Plasma dihydrolenperone levels were at least 75-fold less than levels at which in vitro activity was observed. We conclude: 1) the maximum tolerated dose in our study is 50 mg/square meter orally twice daily, 2) the dose-limiting side effect of dihydrolenperone is somnolence, and 3) the concentrations of dihydrolenperone observed in plasma are significantly lower than those associated with in vitro activity.

Adult↗
PubMed1993

The covalent linkage of secretory component to IgA. Structure of sIgA.

Immunoglobulin A which is secreted into external fluids is synthesized in plasma cells as an (IgA)2-J-chain complex. This complex docks on to the polyimmunoglobulin receptor which is located at the basolateral surface of epithelial cells. After docking the (IgA)2-J-receptor complex is internalized and processed. The polyimmunoglobulin receptor loses its C-terminal tail and thus becomes the secretory component. This secretory component is then covalently linked to the (IgA)2-J-chain complex by a disulfide bond, and protects the so formed sIgA from denaturation and proteolysis in external fluids. In order to establish this disulfide bond between IgA and the secretory component, sIgA, purified from human colostrum, was subjected to several enzymatic and chemical fragmentation reactions. One of the resulting polypeptides allowed us to characterize the covalent linkage of the secretory component to IgA in sIgA. IgA was found to be covalently linked to the secretory piece by a single disulfide bond between Cys 311 of one alpha-chain and Cys 467 of the secretory component. Cys 501 of the secretory component and Cys 311 of the other alpha-chain are blocked by cysteines. With this last paper of a series the structure of an entire sIgA molecule has been elucidated.

Amino Acid Sequence↗
PubMed1992

Intra- and interchain disulfide bridges of the human J chain in secretory immunoglobulin A.

All intra J chain disulfide bridges of human sIgA, the disulfide bonds between the J chain and the two IgA monomers, and one inter IgA monomer disulfide bridge were determined. sIgA was isolated from colostrum of healthy women and digested with IgA1-specific protease followed by cyanogen bromide cleavage. This procedure generated fragments of 140 kDa, 60 kDa, and 28 kDa. The 28-kDa polypeptide comprised the complete J chain covalently bound to two alpha 1 chain octapeptides derived from the C-termini of two alpha 1 chains. The 28-kDa fragment was digested with trypsin. The resulting peptides were purified by RP-HPLC, and subsequently characterized by amino-acid analysis, mass spectrometry, and gas phase sequencing. These data unequivocally show that the J chain cysteines C1-C6, C4-C5, and C7-C8 form intra chain disulfide bridges. The second (C2) and the third (C3) J chain cysteines are disulfide linked to two alpha chain cysteines (C17) joining the two IgA monomers of sIgA tail to tail. The remaining two alpha chains of the two monomers are directly bound to each other via their ultimate cysteines (C17-C17). A new model for the J chain in sIgA is presented.

Amino Acid Sequence↗
PubMed1987

[Risk factors for the occurrence of eye damage following ethambutol treatment].

The present paper deals with two cases of severe irreversible visual disturbances (bilateral opticus atrophy) after combined antituberculous chemotherapy including ethambutol following unilateral nephrectomy because of tuberculosis of the kidneys and with farther complications as damages of the blood vessels and diabetes mellitus. Damages of the kidneys are especially predisposing to side effects by ethambutol and inclusion into an ophthalmological dispensary at short intervals is necessary.

Aged↗
PubMed1978

[Results of lens extractions in defective light projection (author's transl)].

It is demonstrated by means of a series of 84 lens extractions in 80 patients that cataract extraction can be meaningful and successful even with defective light projection. Indications discussed are those which are considered urgent (Cataracta hypermatura or primary and secondary glaucoma with concomitant cataract), purely functionally urgent (desire on the part of the patient to have his vision restored) and relative.

Cataract Extraction↗