bluuebunny/crossref_metadata_2025_split huggingface dataset:
Two Consecutive Phase II Studies of 5-Fluorouracil/Leucovorin/Mitomycin C and of Gemcitabine in Patients with Advanced Biliary Cancer
Authors: Raderer M. , Hejna M.H.L. , Valencak J.B. , Kornek G.V. , Weinländer G.S. , Bareck E. , Lenauer J. , Brodowicz T. , Lang F. , Scheithauer W. 
Published: April 2003

<i>Introduction:</i> Carcinoma of the biliary system is a rare tumor entity, and patients with advanced disease face a dismal prognosis. Because of the absence of standard chemotherapy for advanced biliary carcinoma, we have performed two consecutive studies to evaluate the clinical potential of 5-fluorouracil, leucovorin and mitomycin C as well as the novel antimetabolite gemcitabine in this disease. <i>Patients and Methods:</i> A total of 39 consecutive patients suffering from locally inoperable or metastatic biliary cancer were enrolled in the study between March 1994 and October 1997. Twenty patients were treated with leucovorin 200 mg/m<sup>2</sup> and 5-FU 400 mg/m<sup>2</sup>, both given as intravenous bolus on days 1–4, and mitomycin C 8 mg/m<sup>2</sup> on day 1 (group A). Treatment cycles were repeated every 28 days. The second cohort included 19 patients, who received gemcitabine 1200 mg/m<sup>2</sup> on days 1, 8 and 15 with a 2-week interval before the next treatment cycle (group B). Treatment was continued for a maximum of 6 cycles in the absence of progressive disease in both groups, and endpoints of the study were responses rates, survival and toxicity. <i>Results:</i> In group A, 5 patients (25%) had a partial response (PR), 6 additional patients (30%) had stable disease (SD) and 9 patients (45%) progressed during treatment. The median survival was 9.5 months (range, 3–14.5) with the median time to progression being 4 months (range, 3–9). In group B, 3 patients achieved a PR (16%), 4 showed SD (21%), while the remaining 12 patients had progressive disease. A median survival of 6.5 months (range, 2–11.5) was obtained, and the median time to progression was 2.5 months (range, 1–6+). Toxicity was generally mild in both treatment arms, 6 patients in group A required dose reductions, while no dose adaptation had to be performed for gemcitabine. <i>Conclusion:</i> Our data suggest that treatment of advanced biliary cancer is feasible and can be safely performed with both regimens applied in our study. While administration of gemcitabine has resulted in only mild toxicities, its exact impact on the management of advanced biliary cancer should be evaluated in a controlled trial.
Outpatient Treatment of Neutropenic Fever with Oral Antibiotics and Granulocyte Colony-Stimulating Factor
Authors: Papadimitris Constantinos , Dimopoulos Meletios A. , Kostis Evangelos , Papadimitriou Christos , Anagnostopoulos Athanassios , Alexopoulos George , Papamichael Christos , Gika Dimitra , Mitsibounas Dimitrios , Stamatelopoulos Stamatios 
Published: April 2003

In recent years, several cancer patients who developed neutropenic fever were effectively treated on an outpatient basis with either intravenous or oral antibiotics. This approach is associated with reduced cost and improved patient convenience. However, the appropriate antibiotic regimen and the role of growth factors have not been established yet. In order to address these issues we performed a nonrandomized phase II study to assess the feasibility and efficacy of an oral antibiotic regimen in combination with granulocyte colony-stimulating factor (G-CSF) for the outpatient treatment of cancer patients with low-risk neutropenic fever. In 50 patients with solid tumors or lymphoma, 60 episodes of neutropenic fever were treated with the combination of oral ofloxacin 400 mg twice a day, oral amoxicillin 1 g 3 times a day and G-CSF 5 μg/kg/day subcutaneously. Patients receiving G-CSF prophylaxis were eligible for our study. Oral antibiotics were administered for at least 5 days and G-CSF was continued until resolution of neutropenia. Our patients were ambulatory, hemodynamically stable, and without significant comorbidity. Our combination was successful in 57 episodes (95%) with a median time for fever resolution of 3 days (range: 1–5 days). There was no significant toxicity associated with the antibiotic regimen with the exception of one case of reversible renal impairment. The role of G-CSF in the success of our antibiotic treatment is highly questionable since one half of our patients developed fever while on G-CSF prophylaxis. The combination of oral ofloxacin and amoxicillin with G-CSF is highly effective for the outpatient treatment of cancer patients who develop uncomplicated febrile neutropenia. The relative contribution of G-CSF needs clarification with a prospective randomized study.
Scintigraphic Imaging of Sarcomatous Tumors with [<sup>111</sup>In-DTPA-Phe-1]-Octreotide
Authors: Giannakenas C. , Kalofonos H.P. , Apostolopoulos D. , Petsas T. , Kalogeropoulou C. , Tzorakelefterakis E. , Skopa C.D. , Vassilakos P.J. 
Published: April 2003

The objective of the present study was to investigate the efficacy of <sup>111</sup>In-DTPA-octreotide (OC) for in vivo scintigraphic imaging of these relatively uncommon tumors. Thirteen patients (9 males, 4 females, mean age 59 years) with known sarcomatous lesions were studied. All patients had known lesions as demonstrated by previous investigation with other modalities, e.g. CAT, MRI. Following intravenous injection of 10 μg of OC labeled with 2.8–4.2 mCi <sup>111</sup>In, planar imaging was done at 6 ± 1 and 22 ± 2 h, respectively. Histologic verification was obtained in all cases, either from fine needle aspiration or from surgically removed tissue. Positive imaging was observed in 12/13 cases (92.3%). One scan was false-negative (7.7%). Occult lesions were demonstrated in two patients. The histologic typing and the scintigraphy results were: fibrosarcoma (1+/1), embryonic rhabdomyosarcoma (1+/1), leiomyosarcomas (3+/3), liposarcomas (2+/2), uterine sarcomas (2+/2), HIV (–) Kaposi sarcoma (1+/1), osteosarcoma (1+/1), chondrosarcoma (1–/1) and neurogenous sarcoma (1+/1). OC appears to have properties that lead to a new indication for its use. Other possible applications relate to the therapeutic use of octreotide either unlabeled or labeled with a beta-emitting radionuclide, as well as its use in radioimmunoguided surgery. Regarding the latter, our preliminary results are encouraging.
Sequential Trimetrexate, 5-Fluorouracil and Folinic Acid Are Effective and Well Tolerated in Metastatic Colorectal Carcinoma
Authors: Szelényi H. , Hohenberger P. , Lochs H. , Haboubi N. , Berdel W.E. , Thiel E. , Kreuser E.D. 
Published: April 2003

Trimetrexate (TMTX) is a new antifolate which avoids competition for cellular uptake with folinic acid (FA). A regimen of sequential TMTX, FA and 5-fluorouracil (5-FU) has shown efficacy in patients with colorectal cancer. Therefore, we treated 34 previously untreated patients with metastatic colorectal cancer with a weekly chemotherapy regimen consisting of 110 mg/m<sup>2</sup> of TMTX intravenously, then 24 h later 200 mg/m<sup>2</sup> of FA (i.v.) and 500 mg/m<sup>2</sup> of 5-FU (i.v.). Thereafter, 7 doses of oral FA (15 mg) were given at 6-hourly intervals. A treatment cycle consisted of 6 weeks of treatment, then 2 weeks of rest. All patients were treated as outpatients unless complications arose. Thirty-three patients were assessable for tumor response, and all 34 patients were assessable for toxicity. Twelve patients (36%; 95% confidence interval: 25–49%) achieved a partial response. The median duration of response was 8.5 months, and median survival was 14 months. The most common toxicity was diarrhea of grade 3/4, observed in 22% of treatment cycles; this decreased to 8% with early loperamide treatment. Hematologic toxicity was mild. The sequential administration of TMTX, FA and 5-FU is an active regimen in the first-line treatment of metastatic colorectal cancer and warrants further studies.
Risk-Adapted Chemotherapy of Germ Cell Tumors with Carboplatin, Etoposide and Bleomycin for Low-Risk and Cisplatin, Etoposide and Ifosfamide for High-Risk Patients
Authors: Tscherry G. , Jacky E. , Jost L.M. , Stahel R.A. 
Published: April 2003

The prognosis of germ cell tumors treated with chemotherapy depends on the presence of nonseminomatous tumor, clinical parameters based on the tumor volume and site, as well as on the level of the tumor markers AFP, βHCG and LDH. We report here on the results of a risk-adapted approach to the chemotherapy of germ cell tumors. Patients with low-risk tumors, defined as seminomatous disease and/or nonseminomatous disease with a tumor mass <10 cm, less than 20 lung metastases, no liver, bone, or CNS metastases, and levels of AFP <1,000 IU/ml and βHCG <10,000 IU/l, were to receive 4 cycles of carboplatin 400 mg/m<sup>2</sup> i.v. day 1, etoposide 120 mg/m<sup>2</sup> i.v. days 1–3 and bleomycin 30 IU i.v. days 1, 8 and 15 during the first 3 cycles (CEB<sub>90</sub>). Patients with high-risk disease were to receive 4 cycles of ifosfamide 1,500 mg/m<sup>2</sup> continuous infusion on days 1–4 together with mesna 1,200 mg/m<sup>2</sup> days 1–5, cisplatin 20 mg/m<sup>2</sup> i.v. days 1–5 and etoposide 100 mg/m<sup>2</sup> i.v. days 1–5 (VIP). Of the 60 patients treated with this risk-adapted approach, 51 had low-risk and 9 had high-risk disease. Forty-five of 51 patiens treated with CEB<sub>90</sub> achieved complete remission (CR), 4 achieved partial remission with marker negativity. Four patients with CR relapsed between 4 to 8 months after the start of chemotherapy. Of the 6 patients failing CEB<sub>90</sub>, 3 were treated successfully with surgery or further chemotherapy. With a median follow-up of 52 months, the estimated cause-specific 3-year survival is 93% (95% confidence interval, CI, 80–98%). Seven of 9 high-risk patients treated with VIP achieved a CR and 1 patient relapsed. All 3 patients failing VIP had successful salvage therapy. With a medium follow-up of 63 months all patients remain alive and free of disease. Forty-six patients receiving CEB<sub>90</sub> were retrospectively classified to be in the good prognosis group according to the international germ cell consensus classification. Their estimated 3-year survival was 95% (CI 81–99%). We thus confirm that CEB<sub>90</sub> is a well-tolerated outpatient regimen with good results in good prognosis germ cell tumors. Bleomycin at a cumulative dose of 270 U might contribute substantially to the inferior effect of carboplatin as compared to cisplatin. However, in view of the results of randomized studies favoring cisplatin over carboplatin, it is not recommended to use this regimen outside a clinical trial.
Gelatinase and Inhibitor Expression in Soft Tissue Sarcomas: Lack of Correlation with Distant Metastasis<footref rid="foot01"><sup>1</sup></footref>
Authors: Maguire Patrick D. , Qi Wen-Ning , Lallemand Roger , Scully Sean P. 
Published: April 2003

The predominant mode of death for most patients with soft tissue sarcomas (STS) remains distant metastasis (DM). Current clinical predictors of DM are unreliable. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) correlate with biologic aggression in other tumors. The gene expression of the gelatinase, MMP-2 and MMP-9, and their respective inhibitors, TIMP-1 and TIMP-2, in STS was evaluated. Twelve fresh-frozen surgical specimens from patients with large (>5 cm) STS were analyzed. Six patients developed DM while 6 survived disease-free (DFS) at a minimum follow-up of 13 months. Following mRNA isolation, reverse transcription-polymerase chain reaction was performed using primers for MMP-2, MMP-9, TIMP-1, and TIMP-2. Gene expression was determined by band densitometry. Ratios of MMP-9/TIMP-1 and MMP-2/ TIMP-2 gene expression as well as MMP-2 protein activation ratio (active/inactive enzyme determined by gelatin zymography) were analyzed for correlation with DM and DFS. MMP-2 gene was expressed in 12 specimens, while MMP-9 was detectable in 9. Relative levels of MMP-2 and MMP-9, MMP2/TIMP-2 ratio, and MMP-9/TIMP-1 ratio were not significantly correlated with DM. Poor DFS was significantly correlated with high MMP-9/TIMP-1 ratio (p = 0.02). Active MMP-2 protein was detected in 12 specimens, while active MMP-9 protein was detected in 2. No association was found between MMP-2 protein activation ratio and DM or DFS. While MMP-2 gene expression and protein activity occurred in these 12 specimens, gelatinase/inhibitor ratios (for both MMP-2 and MMP-9) appear to be poor predictors of DM in STS.
Fine Needle Aspiration May Shed Breast Cells into Peripheral Blood as Determined by RT-PCR
Authors: Hu X.C. , Chow Louis W.C. 
Published: April 2003

<i>Objective:</i> A diagnostic test applying reverse-transcriptase chain reaction (RT-PCR) assay targeted against cytokeratin 19 (CK19), cytokeratin 20 (CK20) and the β-subunit of human chorionic gonadotropin (β-hCG) mRNAs was used to evaluate the impact of fine needle aspiration (FNA) on breast cell shedding into peripheral blood. <i>Methods:</i> The sensitivity of this assay was based on the different degree of admix of MCF-7 breast cancer cell line with HL-60 leukemic cell line. For blood samples of 24 cases with benign breast diseases and 20 cases with malignant ones, 5 ml of peripheral blood was drawn before and within 10 min after puncture. Total RNA was extracted from peripheral blood mononuclear (PBMN) cells; β-actin was used to assess the quality of cDNA. RT-PCR products were run in ethidium bromide gel and observed under ultraviolet. RT-PCR products for β-hCG were digested with <i>Sty</i> I endonuclease to confirm the specificity. <i>Results:</i> The sensitivity of RT-PCR assay was 1 MCF-7 cell in 10<sup>5</sup> HL-60 cells for CK19 and CK20, and 1 in 10<sup>6</sup> for β-hCG. For 24 benign cases, none of the pre- FNA samples was positive for CK20 and β-hCG, and 3 cases (12.5%) were positive for CK19. As for 20 malignant cases, 1 pre-FNA sample was positive for all three markers and 2 other samples were positive for CK19. After aspiration, 3/21 benign cases and 1/17 malignant case with pre-FNA negative signals became positive for CK19, while 3/19 malignant cases with pre-FNA negative signals were converted to a positive result for CK20 and β-hCG. Of 6 pre-FNA positive cases, all cases remained positive for the respective marker. <i>Conclusion:</i> FNA to breast tumor may cause hematogenous dissemination of breast cells.
High-Density Exposure Therapy for Obsessive-Compulsive Inpatients: A 1-Year Follow-Up<footref rid="foot01"><sup>1</sup></footref>
Authors: Wetzel Claudia , Bents Hinrich , Florin Irmela 
Published: April 2003

<i>Background</i>: This study evaluates the effects of individual high-density exposure (2–3 weeks, all day) plus response prevention therapy on 85 unselected inpatients suffering from obsessive-compulsive disorder (OCD). <i>Methods</i>: Twenty-eight therapist practitioners performed treatment. <i>Results</i>: At 1-year follow-up, self-ratings indicated that patients on average felt much improved. Impairment by both obsessions and compulsions was significantly reduced (p < 0.001 in each case), and OCD symptoms as assessed by two OCD questionnaires had also decreased significantly, as had depressiveness and overall symptomatology (all p < 0.001). Defining improvements as >30% successes, as done in other OCD treatment outcome studies, success rates were 68 and 69%, respectively, for the two OCD questionnaire scores, 75% for self-rated impairment by obsessions and 84.5% for compulsions, 85.6% for overall psychopathology (General Symptom Index), and 75% for depressiveness (Beck Depression Inventory). Effect sizes were >1 SD for all of the measures included. <i>Conclusions</i>: We conclude that long-term effects for high-density treatment of unselected OCD patients bring about as good results as treatments with exposure and response prevention performed with selected patient samples in a research context.
Effects of Dietary Fish Oil Supplementation on the Phospholipid Composition and Fluidity of Cell Membranes from Human Volunteers
Authors: Lund Elizabeth K. , Harvey Linda J. , Ladha Shabirali , Clark David C. , Johnson Ian T. 
Published: April 2003

<i>Background:</i> Membrane fluidity is an important aspect of cellular physiology which may be manipulated by diet. <i>Methods:</i> We studied the effect of dietary fish oil on the membrane composition of erythrocytes and cheek cells, and on membrane fluidity of erythrocytes as assessed by fluorescence recovery after photobleaching (FRAP). Healthy volunteers received a daily supplement of fish oil (930 mg EPA, 630 mg DHA) for 42 days. <i>Results:</i> The intervention reduced the ratio of n-6 to total fatty acid in the phospholipid fraction of erythroctye membranes but the n-3 fraction remained stable and the ratio of cholesterol to phospholipid increased. The level of EPA and DHA in cheek cells increased significantly during the intervention period. The mean diffusion coefficient of the fluorescent probe in erythrocyte membranes increased from 7.2 ± 0.7 × 10<sup>–9</sup> cm<sup>2</sup>/s at the start to 9.8 ± 0.5 × 10<sup>–9</sup> cm<sup>2</sup>/s after 21 days. Membrane fluidity remained higher than the initial value 42 days after withdrawal of the supplement. Fish oil also reduced platelet aggregation in response to ADP but there was no effect on plasma lipid profiles. <i>Conclusion:</i> We conclude that n-3 fatty acids influence erythrocyte membrane composition at relatively low levels of supplementation by a mechanism which does not necessarily involve an increase in the level of EPA or DHA present in the membrane.
Protective Efficacy of Trypsin Inhibitor on the Gut following Rotavirus Infection in Malnourished Infant Mice
Authors: Katyal R. , Ojha S. , Rana S.V. , Vaiphie K. , Singh K. , Singh V. 
Published: April 2003

Epidemiologic data suggest a close relationship between protein energy malnutrition (or protein energy malnourished) (PEM) and development of infectious diarrheal diseases. In the present studies, the impact of trypsin inhibitor (TI) on the gut following rotavirus (RV) infection was investigated in PEM young growing inbred balb/c mice. The animals were divided into four groups: (1) control; (2) PEM; (3) PEM+RV and (4) PEM+ RV+TI. Control and PEM animals were orally inoculated with normal saline, PEM+RV animals were given 50 μl RV (100 ID<sub>50</sub>) and PEM+RV+TI animals were inoculated with 0.6 mg TI/g body weight + 50 μl RV. The body weight of each animal was recorded. Six animals from each group were sacrificed on days 0, 1, 3, 5, 7 and 10 post inoculation by cervical dislocation. The intestines were removed, everted and homogenized in ice-cold saline. Leucine aminopeptidase (LAP), glutathione (GSH) levels and <i>L</i>-leucine uptake were determined in the jejunum and ileum. Body weight was decreased in PEM and PEM+RV groups compared to the controls. LAP and leucine uptake levels were elevated in the PEM group but decreased in the PEM+RV group. GSH levels were decreased in the PEM+RV group. Enzyme activity, GSH and LAP uptake levels were restored in the PEM+RV+TI group. The study shows the protective role of soybean TI against RV infection in malnourished mice.
Oxidation of an Oil Rich in Docosahexaenoic Acid Compared to Linoleic Acid in Lactating Women
Authors: Fidler N. , Sauerwald T. , Demmelmair H. , Pohl A. , Koletzko B. 
Published: April 2003

<i>Background:</i> We studied the oxidation of an oil rich in docosahexaenoic acid (DHA; DHASCO<sup>®</sup>) in lactating mothers receiving a dietary DHA supplement or a placebo. The results were compared with the oxidation of linoleic acid. <i>Methods:</i> Breast-feeding mothers received a dietary supplement (DHASCO; 200 mg DHA/day, n = 5) or a placebo (n = 5) for 14 days. Six weeks post partum all 10 mothers received a single dose of 2 mg/kg body weight uniformly <sup>13</sup>C-labeled DHASCO. In a previously reported study 6 mothers received 1 mg/kg body weight uniformly <sup>13</sup>C-labeled linoleic acid. Breath samples were collected over 48 h after tracer application. The total CO<sub>2</sub> production was measured by indirect calorimetry and the <sup>13</sup>C isotopic enrichment of labeled CO<sub>2</sub> by isotopic ratio mass spectrometry. <i>Results:</i> The oxidation of <sup>13</sup>C-labeled DHASCO in the supplemented and placebo groups was similar. Maximal <sup>13</sup>C enrichment was reached earlier in the group receiving <sup>13</sup>C-DHASCO (median 1.0 vs. 3.0 h in the linoleic acid group). The cumulative <sup>13</sup>C recovery in breath was higher in the DHASCO versus the linoleic acid group until 10 h after tracer application and comparable thereafter. <i>Conclusions:</i> The difference in oxidation of DHASCO versus linoleic acid after tracer ingestion might be partly due to a faster absorption and oxidation of shorter chain saturated fatty acids contained in DHASCO. The cumulative oxidation of DHASCO and linoleic acid 24 and 48 h after tracer ingestion is similar.
Long-Term Oral β-Carotene Supplementation in Patients with Cystic Fibrosis – Effects on Antioxidative Status and Pulmonary Function
Authors: Rust Petra , Eichler Irmgard , Renner Sabine , Elmadfa Ibrahim 
Published: April 2003

To investigate the efficacy of long-term oral β-carotene supplementation for optimizing the antioxidant status and pulmonary function in patients with cystic fibrosis (CF), 24 patients (aged 12.8 ± 6.3 years) were randomized to a CF supplementation or to a CF placebo group. As controls 14 healthy age-matched subjects (aged 14.7 ± 6.2 years) were studied. Patients of the CF supplementation group received 1 mg β-carotene/kg body weight (BW)/day (maximally 50 mg β-carotene/day) for the first 12 weeks; during the following 12 weeks, dosage was reduced to 10 mg β-carotene/day. At study entry, plasma β-carotene concentrations were significantly lower in CF patients than in controls (p < 0.001). In the CF supplementation group, plasma β-carotene concentrations were significantly increased (baseline: 0.08 ± 0.04 μmol/l) at the end of high-dose treatment (12th week; 0.6 ± 0.4 μmol/l; p < 0.001), but decreased again during supplementation with 10 mg β-carotene/day to 0.3 ± 0.2 μmol/l at the end of the study (p < 0.001). β-Carotene supplementation did not affect plasma concentrations of other carotenoids and retinol, but an increase in plasma α- and γ-tocopherol concentrations was noticed. During high-dose treatment, a significant decrease in TBA-MDA complexes and a correction of total antioxidative capacity was observed. During the treatment, pulmonary exacerbation could be corrected significantly (p < 0.05). We conclude that CF patients can be efficiently supplemented with 1 mg β-carotene/kg BW/day (maximally 50 mg β-carotene/day) to achieve plasma concentrations of healthy control subjects and to minimize oxidative stress, improving the quality of life of CF patients.