PubMed Health⌕ Search

Biomedical subjects

C Cote

Publications and source records attributed to C Cote.

14 recordsLinked to original sources
PubMed2004

The 6-min walk distance: change over time and value as a predictor of survival in severe COPD.

The 6-min walk distance (6MWD) is used to evaluate the functional capacity of patients with chronic obstructive pulmonary disease (COPD). The change in 6MWD over time and its correlation with changes in spirometry and survival are unclear. Patients (n=198) with severe COPD and 41 age-matched controls were followed for 2 yrs, and anthropometrics, spirometry, 6MWD and comorbidities were measured. The 6MWD decreased in the COPD group from 238 +/- 107 m to 218 +/- 112 m (-26 +/- 37 m x yr(-1)), and increased in the control group from 532 +/- 82 m to 549 +/- 86 m (12 +/- 25 m x yr(-1)). In both groups, there was a poor correlation with changes in forced expiratory volume in one second (FEV1). Nonsurvivors in the COPD group (42%) had a more pronounced change in the 6MWD (-40 versus -22 m x yr(-1)) but a similar change in FEV1 (118 versus 102 mL x yr(-1)). The 6MWD independently predicted survival, after accounting for age, body mass index, FEV1 and comorbidities. In severe chronic obstructive pulmonary disease, the 6-min walk distance predicts mortality better than other traditional markers of disease severity. Its measurement is useful in the comprehensive evaluation of patients with severe disease.

Anthropometry↗
PubMed1999

Clinical activity and benefit of irinotecan (CPT-11) in patients with colorectal cancer truly resistant to 5-fluorouracil (5-FU).

The aim of this prospective study was to assess the efficacy, clinical benefit and safety of CPT-11 (irinotecan) in patients with stringently-defined 5-fluorouracil-resistant metastatic colorectal cancer (CRC). 107 patients with documented progression of metastatic CRC during 5-FU were treated with CPT-11 350 mg/m2 once every 3 weeks in a multicentre phase II study. Tumour response and toxicity were assessed using WHO criteria. Changes in performance status (PS), weight and pain were also measured. The WHO response rate was 13/95 (13.7%, 95% CI 7.5% to 22.3%) eligible patients with a median duration of response of 8.5 months (37 weeks, range: 18-53+). There was also a high rate of disease stabilisation (44.2%) with a median duration of 4.8 months. The probability of being free of progression at 4 months was 50%. Median survival from first administration of CPT-11 was 10.4 months or 45 weeks (range: 3-66+ weeks). There was weight stabilisation or gain in 81% (73/90) of patients, a favourable outcome in PS in 91% (82/90) (improvement of WHO PS 2 or stabilisation of PS 0-1), and pain relief in 54% (26/48). There were no toxic deaths. Neutropenia was short-lasting and non-cumulative. Diarrhoea grade > or = 3 occurred in 7% of cycles and 28/107 (26%) of patients. CPT-11 350 mg/m2 once every 3 weeks has an encouraging degree of activity in progressive metastatic CRC truly resistant to 5-FU with a relatively high rate of tumour growth control translated into clinical benefit. The toxicity profile of CPT-11 is becoming better understood and has been considerably improved.

Adult↗
PubMed1998

A phase II study of irinotecan alternated with five days bolus of 5-fluorouracil and leucovorin in first-line chemotherapy of metastatic colorectal cancer.

PURPOSE: This multicenter phase II study was designed to assess the efficacy of the alternating schedule of irinotecan (CPT-11) with bolus 5-fluorouracil (5-FU) and leucovorin (LV) in first-line chemotherapy for metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Patients with histologically proven metastatic colorectal cancer, and at least one bidimensionally measurable lesion, aged 18-70, with performance status < or = 2, normal baseline biological values and no prior chemotherapy (or only adjuvant chemotherapy completed > or = 6 months before study entry) were selected. Treatment was irinotecan 350 mg/m2, i.v., day 1, alternating with leucovorin 20 mg/m2 i.v. and 5-FU 425 mg/m2, i.v. daily for five consecutive days, day 22-26 (Mayo Clinic regimen). One alternating cycle was to be performed every six weeks. Patients were evaluated for efficacy every alternating cycle. Treatment was administered until five alternating cycles, disease progression, unacceptable toxicity or patient refusal. RESULTS: Thirty-three patients (28 chemotherapy-naïve and five with prior adjuvant treatment completed > 1 year prior to accrual) were enrolled. The objective response rate (RR) was 30% (95% CI: 16-49; 10 patients/33; nine partial response and one complete response). All responses were reviewed by an independent external review committee. An additional 49% of patients had stable disease. The median survival was 16 months, the one year survival amounted to 58% and the median progression free survival was 7.2 months. Relative dose intensity was nearly 90% for both drugs. Grade 3-4 diarrhea and neutropenia were the most frequent severe toxic events, seen in 24% and 64% of patients, respectively. CONCLUSIONS: The alternating schedule of CPT-11 350 mg/m2 with five days bolus of 5-FU and low dose LV is an active and feasible regimen as front-line therapy for metastatic CRC. It is well tolerated, without evidence of overlapping toxicity. The response rate appears promising with regard to that expected with either single agent. This regimen warrants further assessment in randomized trials.

Adult↗
PubMed1998

Pathophysiology and therapy of irinotecan-induced delayed-onset diarrhea in patients with advanced colorectal cancer: a prospective assessment.

PURPOSE: Irinotecan (CPT-11), a camptothecin derivative, has shown efficacy against colorectal cancer. Delayed-onset diarrhea is its main limiting toxicity. The aim of this study was to determine the pathophysiology of CPT-11-induced delayed-onset diarrhea and assess the efficacy of combined antidiarrheal medication in a phase II, prospective, successive-cohorts, open study. PATIENTS AND METHODS: Twenty-eight patients with advanced colorectal cancer refractory to fluorouracil (5-FU) therapy received CPT-11 350 mg/m2 every 3 weeks. The first cohort of 14 consecutive patients explored for the mechanism of diarrhea received acetorphan (a new enkephalinase inhibitor) 100 mg three times daily; the second 14-patient cohort received, in addition to acetorphan, loperamide 4 mg three times daily. Before treatment, and if late diarrhea occurred, patients underwent colon mucosal biopsies for CPT-11 and topoisomerase I levels; intestinal transit time; fecalogram; fat and protein excretion; alpha1-antitrypsin clearance; D-xylose test; blood levels for vasoactive intestinal polypeptide, glucagon, gastrin, somatostatin, prostaglandin E2, and carboxylesterase; CPT-11/SN-38 and SN-38 glucuronide pharmacokinetics; and stool cultures. RESULTS: Delayed-onset diarrhea occurred during the first three treatment cycles in 23 patients (82%). Electrolyte fecal measurements showed a negative or small osmotic gap in nine of nine patients and an increased alpha1-antitrypsin clearance in six of six patients. There were no modifications in stool cultures or hormonal dysfunction. Four of 11 patients (36%) with delayed-onset diarrhea in the first cohort responded to acetorphan, whereas nine of 10 patients (90%) responded to the combination of acetorphan and loperamide (P < .02). CONCLUSION: CPT-11-induced delayed-onset diarrhea is caused by a secretory mechanism with an exudative component. Early combined treatment with loperamide and acetorphan seems effective in controlling the diarrheal episodes.

Adult↗
PubMed1995

Phase I and pharmacokinetic study of irinotecan (CPT-11) administered daily for three consecutive days every three weeks in patients with advanced solid tumors.

BACKGROUND: We conducted a phase I and pharmacokinetic study to determine the maximum tolerable dose (MTD), toxicities, pharmacokinetic profile, and antitumor activity of Irinotecan (CPT-11) in patients with refractory solid malignancies. PATIENTS AND METHODS: Forty-six patients were entered in this phase I study. CPT-11 was administered intravenously over 30 minutes for 3 consecutive days every 3 weeks. Dose levels ranged from 33 mg/m2/day to 115 mg/m2/day on days 1 through 3. The pharmacokinetics of total CPT-11 and its active metabolite SN-38 were assayed by HPLC. RESULTS: The combination of leukopenia and diarrhea was dose-limiting toxicity at 115 mg/m2/day dose level, since 50% of the patients (5/10) experienced either grade 3-4 leukopenia, or diarrhea, or both. Leukopenia appeared to be a cumulative toxicity, with a global increase in its incidence and severity upon repeated administration of CPT-11. Other toxicities included nausea, vomiting, fatigue and alopecia. CPT-11 and active metabolite SN-38 pharmacokinetics were determined in 21 patients (29 courses). Both CPT-11 and SN-38 pharmacokinetics presented a high interpatient variability. CPT-11 mean maximum plasma concentrations reached 2034 ng/ml at the MTD (115 mg/m2). The terminal-phase half-life was 8.3 h and the mean residence time 10.2 h. The mean volume of distribution at steady state was 141 l/m2/h. CPT-11 rebound concentrations were observed in many courses at about 0.5 to 1 hour following the end of the i.v. infusion, which is suggestive of enterohepatic recycling. Total body clearance did not vary with increased dosage (mean = 14.3 l/h/m2), indicating linear pharmacokinetics within the dose range administered in this trial. The total area under the plasma concentration versus time curve (AUC) increased proportionally to the CPT-11 dose. Mean metabolite SN-38 peak levels reached 41 ng/ml at the MTD. A significant correlation was observed between CPT-11 area under the curve (AUC) and its corresponding metabolite SN-38 AUC (r = 0.52, p < 0.05). SN-38 rebound concentrations were observed in many courses at about 0.5 to 1 hour following the end of the i.v. infusion, which is suggestive of enterohepatic recycling. Mean 24-h urinary excretion of CPT-11 accounted for 10% of the administered dose by the third day, whereas SN-38 urinary excretion accounted for 0.18% of the CPT-11 dose. In this phase I trial, the hematological toxicity correlated with neither CPT-11 nor SN-38 AUC. Diarrhea grade correlated significantly with CPT-11 AUC. Two partial (breast adenocarcinoma and carcinoma of unknown primary) and 2 minor (hepatocarcinoma and pancreatic adenocarcinoma) responses were observed. CONCLUSION: The MTD for CPT-11 administered in a 3 consecutive-days-every-3 weeks schedule in this patient population is 115 mg/m2/day. The recommended dose for phase II studies is 100 mg/m2/day.

Adult↗
PubMed1994

Irinotecan (CPT-11) high-dose escalation using intensive high-dose loperamide to control diarrhea.

BACKGROUND: Diarrhea is a serious side effect that may prevent the administration of high doses of the antitumor drug Irinotecan (CPT-11). PURPOSE: Intensive, high-dose loperamide was used in an attempt to control or downstage CPT-11-induced diarrhea and thus permit the use of higher dose intensities of CPT-11. METHODS: Twenty-three patients with various cancers were treated with doses of CPT-11 ranging from 400 to 600 mg/m2, administered as a 30-minute intravenous infusion every 3 weeks. Starting 8 hours or more after the administration of CPT-11, any episode of diarrhea was treated with 2 mg of loperamide taken every 2 hours. Patients stopped taking loperamide only after a 12-hour diarrhea-free period. If diarrhea was not controlled after 3 consecutive days of nonstop loperamide intake, or if the patient was dehydrated, loperamide was stopped and the patient was hospitalized for intravenous fluids. If blood or mucus were found in the stools at any time during diarrhea, loperamide was stopped and the patient was hospitalized. RESULTS: Seventeen of 23 patients had diarrhea while on CPT-11 treatment. Eighty-two CPT-11 cycles were administered to these 17 patients, and diarrhea occurred in 49 of these cycles, at a median time-to-onset of 6 days after CPT-11 administration. The loperamide protocol was followed in 46 of the 49 episodes of diarrhea, with 21 capsules of loperamide the median number being taken (range, 5-72). Only one patient was hospitalized for failure to respond to loperamide, and no major toxicity was associated with loperamide use. Fourteen of the 17 patients who experienced diarrhea were rechallenged with CPT-11 three or more times, and seven patients six or more times. CONCLUSIONS: High-dose loperamide controlled diarrhea in patients receiving CPT-11 and allowed administration of higher doses of CPT-11. IMPLICATIONS: The effectiveness of CPT-11 might be increased by higher dose intensities, which can be made tolerable by control of diarrhea with loperamide.

Adult↗
PubMed1993

Swimming activity in dystonia musculorum mutant mice.

Dystonia musculorum (dt) mutant mice, characterized by degeneration of spinocerebellar fibers, were evaluated in a visible platform swim test. It was found that dt mutants were slower to reach the platform than normal mice. However, the number of quadrants traversed was not higher in dt mutants. It is concluded that spinocerebellar fibers to the vermis are important in limb control during swimming but not in visuo-motor guidance (navigational skills) of the animal towards a visible goal, at least in regard to the quadrant measure. It is not excluded that a measure tracing their path may find a mild deviation from the goal.

Animals↗
PubMed1993

Behavioral effects of non-NMDA glutamate receptor antagonists.

Non-NMDA receptor antagonists decrease motor activity in some situations, alter the sleep-wake cycle, possess anticonvulsant and neuroprotectant actions, and appear to impair some learning tasks but not others. NMDA receptor antagonists affect these same functions but often in different and even opposite ways. NMDA receptor antagonists impair many different spatial learning tasks, including the Morris water maze, the Olton radial maze, and the hole-board task. Non-NMDA receptor antagonists are either ineffective in these spatial tasks or have not yet been evaluated. However, non-NMDA receptor antagonists may impair associative processes required in a bar-press response and in discrimination learning. Further research is needed in the context of comparing NMDA as opposed to non-NMDA receptor antagonists within the same paradigm.

Animals↗
PubMed1989

Two TFIIIA activities regulate expression of the Xenopus 5S RNA gene families.

Immunoblotting experiments with polyclonal and monoclonal anti-transcription factor IIIA (TFIIIA) antibodies reveal different electrophoretic forms of TFIIIA in extracts from immature and mature oocytes of Xenopus laevis. The well-characterized 39-kD TFIIIA species is present in approximately 10(12) copies per cell in stage I-III previtellogenic oocytes and declines in abundance by 10- to 20-fold during oogenesis. An immunologically related protein of apparent molecular mass of 42 kD is present at 2-4% of the level of 39-kD TFIIIA in immature oocytes, and the level of this protein increases dramatically during oogenesis. Both the 39- and 42-kD proteins are complexed with 5S RNA in 7S ribonucleoprotein (RNP) particles. High-level transcription of the oocyte-type 5S genes in vitro requires 39-kD immature oocyte TFIIIA, whereas both 39-kD TFIIIA and the mature oocyte TFIIIA species of 42 kD support somatic-type 5S transcription. TFIIIA of 42 kD does not support oocyte-type 5S transcription in a fractionated transcription system derived from mature oocytes. Both proteins, however, bind the oocyte-type and somatic-type genes with comparable affinities and exhibit similar DNase footprints on both genes. These results suggest a model for the developmental regulation of 5S RNA gene transcription where 42-kD TFIIIA serves as an activator of somatic-type 5S transcription and as a repressor of oocyte-type transcription during early embryogenesis.

Animals↗
PubMed1989

Muscle genetic variants and relationship with performance and trainability.

Samples were obtained in a maximum of 295 males and females from the vastus lateralis muscle and proteins fractionated by thin-layer isoelectric focusing. Muscle creatine kinase (CKM) and adenylate kinase (myokinase) (AK1M) were studied for the presence of variants. Six individuals exhibited a CKM variant described here for the first time, for a frequency of the variant gene of 1%. For AK1M, 21 individuals were heterozygotes for an inherited variant protein, an allele frequency of 3.5%. CKM (N = 5) and AK1M (N = 18) variant individuals were paired with control subjects who had the common CKM or AK1M muscle phenotype and compared for several performance indicators. There was no significant difference between the CKM and AK1M common and variant phenotypes for any of the performance measurements. However, the CKM variant subjects tended to be more effective than controls in a 90-min performance test (by about 22%) and had less percent decline over 60 s in force generation (by about 26%). In a subsequent experiment, a few variant subjects could be compared to controls in terms of response to exercise training. Although trends were observed, the CKM and AK1M variant subjects had a response to training generally comparable to that of the nonvariant individuals. While human variation in performance and trainability cannot be accounted for by the genetic polymorphism of the two kinase enzymes, the trends in the data suggest that allelic variation at these two gene loci may be of some functional significance.

Adenylate Kinase↗
PubMedDate not supplied

[Cholesterol biliary lithiasis (risk factors)].

The prevalence of gallstone disease in the world is heterogenous, it exist a wide range between different geographic areas, sex and age groups. Its distribution seems to be influenced by various factors such as age, sex, socieconomic class, genetic and ethnic influences and diseases like diabetes mellitus and obesity. Therefore, in this study, we will analyse the importance of each of those factors in the development of cholesterol gallstone disease.

Cholelithiasis↗