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Biomedical subjects

B C Pestalozzi

Publications and source records attributed to B C Pestalozzi.

33 records · Page 2Linked to original sources
PubMed1998

Pharmacokinetic studies of mitoxantrone and one of its metabolites in serum and urine in patients with advanced breast cancer.

OBJECTIVE: Mitoxantrone (MTO) was administered to patients with advanced breast cancer either as free MTO (f-MTO) or liposomal MTO (1-MTO). The intra- and interindividual variations in serum pharmacokinetics of MTO were analysed. In addition, the excretion of MTO and its metabolite mitoxantrone dicarboxylic acid (MTOD) in urine was determined. METHODS: The concentration of MTO was measured by high-performance liquid chromatography in serum over a period of 24 h and the amount of MTO and the metabolite MTOD excreted in urine over 18 h was determined. Pharmacokinetic parameters of f-MTO and 1-MTO were calculated. RESULTS: 1-MTO had a significantly longer half-life of distribution in the deep (third) compartment and thus a larger area under the curve (AUC) than f-MTO. No difference was found with respect to distribution in the peripheral (second) compartment. The kinetics of MTO in serum did not significantly differ between patients. In four patients repeated pharmacokinetic analyses gave superimposable results. Thus, there was no enzyme induction during therapy. By contrast, two patients with oedema had a much longer mean residence time (MRT) and AUC for MTO in serum. Despite the altered pharmacokinetics of f-MTD and 1-MTO, no toxic adverse effects occurred in these two patients. CONCLUSIONS: f-MTO and 1-MTO exhibited different distribution patterns in the deep compartment with a significantly increased half-life for 1-MTO. There is no need to monitor MTO for treatment of breast cancer patients with f-MTO. In patients with oedema, the MRT of MTO is prolonged. The clinical relevance of this observation is as yet unclear.

Adult↗
PubMed1997

Hepatic lesions of chronic disseminated candidiasis may become invisible during neutropenia.

We describe the phenomenon of waning of focal hepatic and/or splenic lesions on abdominal computed tomographic (CT) scan during neutropenia in patients with chronic disseminated candidiasis. After observation of the phenomenon in one patient, a total of five cases were prospectively monitored with serial CT scans. After the diagnosis of disseminated candidiasis, hepatic lesions decreased in size and conspicuousness in three patients, while in two others they disappeared completely during a subsequent chemotherapy-induced neutropenia. After recovery of the neutrophils, the lesions reappeared or increased in conspicuousness in all five patients. Of three patients treated with a second cycle of myeloablative chemotherapy, lesions again decreased in two patients during neutropenia and increased again in one patient after neutrophil recovery. In all five patients, candidiasis eventually resolved after prolonged antifungal treatment. In chronic disseminated candidiasis, hepatic or splenic lesions may transiently disappear during neutropenia. Thus, antifungal therapy should not be discontinued on the basis of radiologic findings alone.

Adolescent↗
PubMed1997

[Quality of treatment in operable breast carcinoma. Comparison of the years before 1987, 1987-1990 and 1991-1994].

BACKGROUND: Has progress in the treatment of breast cancer been translated into routine practice? What can be further ameliorated? We present a first step in quality assurance by examining the quality of care in early-stage breast cancer during recent years. METHODS: Retrospective analysis of actual care in 300 patients with operable invasive breast cancer. Analysis and comparison of treatment in 3 time-periods based on date of diagnosis (before 1987, 1987-1991, 1991-6/1994). RESULTS: Staging, surgical treatment and histopathological analysis have become more complete over these years. There is, however, no tendency to diagnose smaller tumors in our series. The percentage of patients undergoing breast-conserving surgery has not increased since 1987. Overall, 25% of cancers were treated by breast-conserving surgery. The rate of ipsilateral breast recurrences after breast-conserving surgery was 19% if the breast was irradiated, and 67% when radiation had been omitted (median follow-up 50 months). Adjuvant systemic therapy is now given to many node negative patients. Combined adjuvant therapy (endocrine plus chemotherapy) was rarely used. Early consultation of medical oncology has increased in recent years. CONCLUSION: Progress in the treatment of early-stage breast cancer has only partially been translated into clinical practice. To ensure that treatment decisions conform to the most recent standards, quality controls are necessary. The simplest form of quality control is a multidisciplinary approach, which should be used early, in every case, and if necessary, repeatedly.

Adult↗
PubMed1997

Prognostic importance of thymidylate synthase expression in early breast cancer.

PURPOSE: To assess the prognostic importance of thymidylate synthase (TS) expression in breast tumors of patients with early-stage breast cancer, and to determine whether the benefit of chemotherapy (CT) is associated with TS expression. PATIENTS AND METHODS: The level of TS expression was evaluated in 210 node-negative and 278 node-positive patients enrolled onto Trial V of the International Breast Cancer Study Group ([IBCSG] formerly the Ludwig Breast Cancer Study Group) with a median follow-up time of 8.5 years. TS expression was assessed using the immunohistochemical method with the monoclonal antibody TS 106 on paraffin-embedded tissue specimens. RESULTS: High TS expression was associated with a significantly worse prognosis in node-positive but not in node-negative breast cancer patients. Twenty-seven percent of node-positive patients with high TS expression were disease-free at 10 years, compared with 44% of node-positive patients with low TS expression (P = .03). Forty-one percent of patients with node-positive high-TS-expressing tumors were alive after 10 years, compared with 49% of those with low TS expression (P = .06). The association between TS and disease-free survival (DFS) and overall survival (OS) was independent of other prognostic factors such as tumor size, tumor grade, nodal status, vessel invasion, estrogen receptor (ER)/ progestin receptor (PR) status, c-erb B-2, or Ki-67 expression. In node-positive patients, six cycles of standard adjuvant cyclophosphamide, methotrexate, and fluorouracil ([5-FU] CMF) CT improved DFS and OS compared with one cycle of perioperative CMF therapy. The magnitude of this benefit was greatest in patients whose tumors had high TS expression (P < .01 for DFS; P < .01 for OS). Node-negative patients demonstrated no difference in outcome to CT based on TS expression; however, the power to detect differences was limited by the small number of events in this group. CONCLUSION: In early-stage breast cancer, high TS expression is associated with a significantly worse prognosis in node-positive patients. Node-positive patients with high TS levels demonstrate the most significant improvement in DFS and OS when treated with six cycles of conventional adjuvant CMF therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Breast carcinoma: state of the art].

Diagnosis and therapy of breast cancer are briefly reviewed for the general internist. He should know what triple diagnosis, breast-conserving surgery, radiotherapy and adjuvant systemic therapy involve. He should know when to perform a screening mammography, what follow-up examinations after breast cancer are indicated and what dangers loom in metastatic breast cancer. He should know of new therapeutic avenues such as bisphosphonates, new aromatase inhibitors, taxanes, and high-dose chemotherapy with stem cell support. Since advances in the treatment of breast cancer have been achieved mostly through randomized studies, a positive attitude toward such studies and a willingness to take part in them are desirable.

Biopsy, Needle↗
PubMed1995

Increased thymidylate synthase protein levels are principally associated with proliferation but not cell cycle phase in asynchronous human cancer cells.

We have analysed cell cycle variations in thymidylate synthase (TS) protein in asynchronously growing NCl H630 and HT 29 colon cancer and MCF-7 breast cancer cell lines. Western immunoblot analysis using the TS 106 monoclonal antibody revealed a 14- to 24-fold variation in TS levels between the peak exponential and confluent growth phase in the three cell lines. Similar variations in TS levels and TS activity were detected using the 5-fluorodeoxyuridine monophosphate and deoxyuridine monophosphate biochemical assays. The percentage of cells in S-phase, which paralleled changes in TS levels, reached a maximum of 38-60% in asynchronous exponentially growing cells compared with 5-10% in confluent cells. In asynchronous exponential cells, analysis of TS levels in each cell cycle phase using two-parameter flow cytometric analysis revealed that TS protein levels were 1.3- to 1.5-fold higher in S than in G0/G1 phase cells, and 1.5- to 1.8-fold higher in G2/M than G0/G1 cells. Similar differences of 1.1- to 1.5-fold between G0/G1 and S-phase and 1.6- to 1.9-fold between G0/G1 and G2/M-phase were detected by Western immunoblot and biochemical assays. TS protein was not detectable by Western blot analysis, flow cytometry or biochemical analysis in the G0/G1 population of confluent cells. Twenty-six per cent of cells in this population were G0 cells compared with 2% in exponentially growing cells. In contrast to TS, a 4-fold difference in thymidine kinase (TK) was detected between G0/G1 and S-phase cells in exponentially growing MCF-7 cells. The level of TS enzyme is associated with cellular proliferation and the percentage of cells in S-phase; however, TS protein is not exclusively associated with S-phase in asynchronously growing cells. The variation in TS levels between exponentially growing and confluent cell population appears to be due to differences in TS levels between G0 and G1 cells.

Breast Neoplasms↗
PubMed1993

Typhlitis resulting from treatment with taxol and doxorubicin in patients with metastatic breast cancer.

BACKGROUND: Typhlitis is being recognized with increasing frequency as a serious complication of aggressive chemotherapy for hematologic and solid malignancies. METHODS: In this report the authors describe two cases of typhlitis in patients with metastatic breast cancer treated with taxol and doxorubicin. RESULTS: Both cases occurred during the first cycle of treatment with taxol (180 mg/m2) and doxorubicin (75 mg/m2), being given simultaneously as 72-hour continuous intravenous infusions. CONCLUSION: Two cases of typhlitis have occurred after combined treatment with taxol and doxorubicin, while typhlitis has not been described after treatment with either drug alone.

Adult↗
PubMed1986

[Group poisoning by belladonna].

A case is reported of collective intoxication in nine youths through self-brewed belladonna tea. Apart from peripheral anticholinergic symptoms, some of them had delirious states with visual hallucinations. The self-made tea was re-brewed in the laboratory and from the measured concentration of atropine the ingested total dose of atropine was estimated at up to 3 mg or more per person. In delirious states of unclear origin in young people, especially drug abusers, the possibility of intentional intoxication with atropine-containing plants should be considered. Intravenous physostigmine is the antidote of choice.

Adolescent↗
PubMed1984

Graft-versus-host reactions in F1 hybrid mice: MHC-restriction-independent generalized depression of virus-specific cytotoxic T cell response.

A graft-versus-host reaction (GVHR) was induced in F1 hybrid mice by intravenous injection of parental spleen cells. A possible effect generated by recipient F1 mice of a GVHR on the restriction specificities of anti-viral cytotoxic T cells was investigated. (A/J X C57BL/6) F1 recipients were injected with 1 X 10(8) or 2 X 10(7) spleen cells from either parent. Zero to two weeks later during an acute GVHR or 12 to 26 weeks later during a chronic GVHR, spleen cells from these F1 recipients were assayed for their capacity to generate vaccinia (or lymphocytic choriomeningitis) virus-specific cytotoxic T cells. No effect was seen when parental cells were injected with virus on the same day. During the acute phase of the GVHR, recipients of spleen cells of both doses or from either parent injected 7 or 14 days previously generated markedly fewer cytotoxic T cells with respect to both parental restriction specificities. In the more chronic situation only, recipients of 1 X 10(8) parental spleen cells showed depressed virus-specific cytotoxic responses, again both restriction specificities were affected comparably. Therefore, a GVHR depresses generation of virus-specific cytotoxic T cells in a dose- and time-dependent way, but does not measurably disturb the balance of parental 1 versus parental 2 restriction specificity in an F1 recipient.

Animals↗
PubMedDate not supplied

Hemolytic uremic syndrome in prostatic carcinoma.

BACKGROUND: Disseminated intravascular coagulation is a well-known complication of adenocarcinoma of the prostate, while hemolytic uremic syndrome (HUS) is not. CASE REPORT: We describe the unusual case of a 61-year-old patient with adenocarcinoma of the prostate. Prior to any systemic therapy he developed hemolytic uremic syndrome (HUS) necessitating dialysis. Renal function has fully recovered and he is alive and well 7 years later. CONCLUSION: HUS is a rare complication of adenocarcinoma of the prostate and has a far better prognosis than chemotherapy-associated HUS.

Adenocarcinoma↗
PubMedDate not supplied

Cell cycle regulation of the G0/G1 transition in 5-fluorouracil-sensitive and -resistant human colon cancer cell lines.

PURPOSE: Resistance to 5-fluorouracil (5-FU) has been associated with thymidylate synthase (TS) gene amplification and increased TS protein levels. Increased TS protein expression has also been found to be a significant independent prognostic factor for disease-free survival and overall survival in patients treated with adjuvant 5-FU-based chemotherapy. In these studies and in our prior preclinical studies, TS has been considered a marker of proliferative capacity. The purpose of the current study was to further evaluate the association between TS levels and cell cycle regulation, by investigating cell cycle kinetics in a 5-FU-resistant cell line with constitutive overexpression of TS. The influence of increased TS levels on cell cycle progression may provide insight into methods to overcome 5-FU resistance. MATERIALS: 5-FU-sensitive NCI H630(WT) and 5-FU-resistant NCI H630(R1) (with 15- to 20-fold higher TS protein levels) were utilized in this investigation to determine the influence of constitutive overexpression of TS on cell cycle kinetics. RESULTS: There was no apparent influence of increased TS levels on cell cycle distribution during asynchronous growth, and both cell lines reach plateau growth phase in 120 hours, arresting in G0/G1 as determined by flow cytometry. In the H630(WT) cells, this G0/ G1 arrest was associated with a 14- to 17-fold reduction in TS activity and protein levels (using the TS-106 monoclonal antibody), whereas in the H630(R1) cells, only a two- to fivefold reduction was noted. Flow cytometry analysis utilizing Ki-67 indicated that there was no evidence of a G0 population in the confluent H630(R1), whereas 26% +/- 7% of confluent H630(WT) cells were Ki-67 negative (G0) and the remainder had low Ki-67 signal intensity. Analysis of pRb phosphorylation and p16 and p21 expression suggested that the arrest point for both cell lines was before the point at which Rb phosphorylation takes place, yet the confluent H630(R1) cells had threefold higher p21 than confluent H630(WT) cells. DISCUSSION: These data suggest that the 5-FU-resistant H630(R1) cell lines arrest at a later point in G0/G1 and have a potentially greater capacity for proliferation.

Antimetabolites, Antineoplastic↗