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Biomedical subjects

C Weil

Publications and source records attributed to C Weil.

At least 19 recordsLinked to original sources
PubMed2001

Doxorubicin and paclitaxel versus fluorouracil, doxorubicin, and cyclophosphamide as first-line therapy for women with metastatic breast cancer: final results of a randomized phase III multicenter trial.

PURPOSE: This phase III trial compared the efficacy and safety of doxorubicin and paclitaxel (AT) to 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) as first-line therapy for women with metastatic breast cancer. PATIENTS AND METHODS: A total of 267 women with metastatic breast cancer were randomized to receive either AT (doxorubicin 50 mg/m(2) followed 24 hours later by paclitaxel 220 mg/m(2)) or FAC (5-fluorouracil 500 mg/m(2), doxorubicin 50 mg/m(2), cyclophosphamide 500 mg/m(2)), each administered every 3 weeks for up to eight cycles. Patients had to have measurable disease and an Eastern Cooperative Oncology Group performance status of 0 to 2. Only one prior non-anthracycline, nontaxane-containing adjuvant chemotherapy regimen was allowed. RESULTS: Overall response rates for patients randomized to AT and FAC were 68% and 55%, respectively (P =.032). Median time to progression and overall survival were significantly longer for AT compared with FAC (time to progression 8.3 months v 6.2 months [P =.034]; overall survival 23.3 months v 18.3 months [P =.013]). Therapy was generally well-tolerated (median of eight cycles delivered in each arm). Grade 3 or 4 neutropenia was more common with AT than with FAC (89% v 65%; P <.001); however, the incidence of fever and infection was low. Grade 3 or 4 arthralgia and myalgia, peripheral neuropathy, and diarrhea were more common with AT, whereas nausea and vomiting were more common with FAC. The incidence of cardiotoxicity was low in both arms. CONCLUSION: AT conferred a significant advantage in response rate, time to progression, and overall survival compared with FAC. Treatment was well-tolerated with no unexpected toxicities.

Adult↗
PubMed2001

Cardiac function following combination therapy with paclitaxel and doxorubicin: an analysis of 657 women with advanced breast cancer.

BACKGROUND: To determine the cardiotoxicity of paclitaxel (T) plus doxorubicin (A) combination therapy in women with advanced breast cancer. To define a dose range of A for use in AT. PATIENTS AND METHODS: The effect of cumulative A dose on risk of congestive heart failure (CHF) and alterations of myocardial contractility (left ventricular ejection fraction [LVEF] decrease > or = 20% or to <50%) was estimated from pooled data from 10 trials of AT. RESULTS: Thirty-one of 657 patients (4.7%) developed CHF at a median of 6.6 months (range 0.3-24.6) after initiation of AT. CHF was stabilized in 29 patients at a median of 17.3 months after diagnosis (range 4.1-31.2 months). The risk of developing CHF was < or = 5% at a total A dose < or = 380 mg/m2. In patients who received a total A dose > 440 mg/m2, the incidence of CHF was >25% but similar to that of A monotherapy. The risk of CHF was similar in women receiving AT or A monotherapy at a dose < or = 380 mg/m2 (2%-3%). LVEF progressively decreased in patients who received AT, especially at a cumulative A dose > 380 mg/m2. LVEF decreases were more frequent in patients who later developed CHF, but the majority of CHF patients did not experience LVEF alterations prior to symptoms. LVEF recovered after discontinuation of A in 25 of 67 women who developed LVEF < 50%. CONCLUSION: The reported cardiac effects are consistent with anthracycline-related cardiotoxicity. AT is associated with a cardiac risk similar to that of A monotherapy up to a cumulative A dose of 340-380 mg/m2.

Adult↗
PubMed1999

Growth hormone (GH) and gonadotropin subunit gene expression and pituitary and plasma changes during spermatogenesis and oogenesis in rainbow trout (Oncorhynchus mykiss).

In order to evaluate potential interactions between somatotropic and gonadotropic axes in rainbow trout (Oncorhynchus mykiss), changes in pituitary content of the specific messenger RNA of growth hormone (GH) and gonadotropin (GTH) alpha- and beta-subunits were studied during gametogenesis with respect to pituitary and plasma hormone concentrations. Quantitative analyses of mRNA and hormones were performed by dot blot hybridization and homologous RIA on individual fish according to stage of spermatogenesis and oogenesis. All transcripts were detectable in 9-month-old immature fish. GH, GTH IIbeta, and GTH alpha increased moderately throughout most of gametogenesis and then more dramatically at spermiation and during the periovulatory period. GTH Ibeta mRNA increased first from stage I to V in males and more abruptly at spermiation, while in females GTH Ibeta transcripts increased first during early vitellogenesis and again around ovulation. Pituitary GH absolute content (microgram/pituitary, not normalized with body weight) increased slowly during gametogenesis and more abruptly in males during spermiation. In the pituitary of previtellogenic females and immature males, GTH I beta peptide contents were 80- to 500-fold higher than GTH II beta peptide contents. GTH I contents rose regularly during the initial phases of vitellogenesis and spermatogenesis and then more abruptly in the final stages of gonadal maturation, while GTH II contents show a dramatic elevation during final oocyte growth and maturation, in postovulated females, and during spermiogenesis and spermiation in males. Blood plasma GTH II concentrations were undetectable in most gonadal stages, but were elevated during spermiogenesis and spermiation and during oocyte maturation and postovulation. In contrast, plasma GTH I was already high ( approximately 2 ng/ml) in fish with immature gonads, significantly increased at the beginning of spermatogonial proliferation, and then increased again between stages III and VI to reach maximal levels ( approximately 9 ng/ml) toward the end of sperm cell differentiation, but decreased at spermiation. In females, plasma GTH I rose strongly for the first time up to early exogenous vitellogenesis, decreased during most exogenous vitellogenesis, and increased again around ovulation. Our data revealed that patterns of relative abundance of GTH Ibeta mRNA and pituitary and plasma GTH I were similar, but not the GTH II patterns, suggesting differential regulation between these two hormones at the transcriptional and posttranscriptional levels. Pituitary and plasma GH changes could not be related to sexual maturation, and only a weak relationship was observed between GH and gonadotropin patterns, demonstrating that no simple connection exists between somatotropic and gonadotropic axes at the pituitary level during gametogenesis.

Animals↗
PubMed1999

A cholesterol-lowering diet does not produce adverse psychological effects in children: three-year results from the dietary intervention study in children.

The Dietary Intervention Study in Children (DISC), a 2-arm, multicenter intervention study, examined the efficacy and safety of a diet lower in total fat, saturated fatty acids, and cholesterol than the typical American child's diet. A total of 663 8- to 10-year-old children with elevated low-density lipoprotein cholesterol levels were randomly assigned to either an intervention or a usual-care group. Intervention included group and individual counseling sessions to assist participants in adopting a dietary pattern containing 28% or less of calories from total fat (<8% as saturated fat, up to 9% as polyunsaturated fat, and 11% as monounsaturated fat) and dietary cholesterol intake of less than 75 mg/1,000 kcal. The dietary intervention reduced low-density lipoprotein cholesterol levels, and 3-year results showed no adverse effects for children in the intervention group in terms of academic functioning, psychological symptoms, or family functioning.

Adaptation, Psychological↗
PubMed1999

Phase II study of oral platinum drug JM216 as first-line treatment in patients with small-cell lung cancer.

PURPOSE: This multicenter phase II trial was performed to determine tumor efficacy and tolerance of the oral platinum drug JM216 in patients with small-cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with SCLC limited disease unfit for intensive chemotherapy or those with extensive disease received JM216 120 mg/m(2)/d for 5 consecutive days every 3 weeks. Individual dose escalation to 140 mg/m(2)/d was allowed if toxicity was </= grade 2 according to the National Cancer Institute Common Toxicity Criteria. Tumor response was evaluated according to World Health Organization criteria. RESULTS: Twenty-seven patients were assessable for toxicity and 26 for tumor response. Eighty-eight cycles were administered. Common Toxicity Criteria grade 3 and 4 hematologic toxicities were neutropenia in 15.9% and 3.7%, lymphocytopenia in 47.6% and 17.1%, and thrombocytopenia in 19.5% and 10.3% of cycles, respectively. One patient suffered from neutropenic fever. Nausea, vomiting, and diarrhea were the most common nonhematologic toxicities. Except for grade 4 diarrhea in one patient, no grade 4 nonhematologic toxicity was observed. No severe neurotoxicity or nephrotoxicity was observed. Tumor response rate was 10 of 26 (38%; 95% confidence interval, 19% to 58%), excluding five unconfirmed partial responses. No complete responses were observed. Median overall time to progression was 110 days (range, 5 to 624 days). Median overall survival time was 210 days (range, 5 to 624 days). CONCLUSION: Oral JM216 is active in previously untreated patients with SCLC and shows mild toxicities.

Aged↗
PubMed1999

Differential effect of insulin-like growth factor I on in vitro gonadotropin (I and II) and growth hormone secretions in rainbow trout (Oncorhynchus mykiss) at different stages of the reproductive cycle.

The short-term effect of insulin-like growth factor I (IGF-I) on GTH I (FSH-like), GTH II (LH-like), and GH production by cultured rainbow trout pituitary cells was studied in immature fish of both sexes, at early gametogenesis and in spermiating and periovulatory animals. IGF-I had no effect on basal GTH I and GTH II release, whereas it always inhibited basal GH, showing decreasing intensity with the gonad maturation. In absence of IGF-I, GTH I and GTH II cells were always responsive to GnRH, whereas no response was observed for GH cells whatever the sexual stage. The action of IGF-I on the sensitivity to GnRH differs between GTH and GH cells. The former requires a coincubation with IGF-I (10(-6) M)/GnRH to show an increase in sensitivity, independent of the sexual stage. To be responsive to GnRH, the GH cells require longer exposure to IGF-I, the efficiency of which decreases with gonad maturation. The action of IGF-I (10(-6) M) on GTH cell sensitivity to GnRH does not seem to be related to a mitogenic effect or to an improvement in cell survival. It seems to be IGF-I specific, not passing via the insulin receptor. Certain hypotheses on the putative role of IGF-I and GnRH as a link between growth and puberty are suggested.

Animals↗
PubMed1998

Phase I clinical and pharmacokinetic study of the oral platinum analogue JM216 given daily for 14 days.

BACKGROUND: The oral bis (acetate) ammine dichloro cyclohexylamine platinum (IV) analogue (BMS-182751) was brought into clinical development because it was shown to be cytotoxic against some human tumour cell lines and to have an antitumor activity in murine tumours at least comparable to that of parenteral cisplatin and carboplatin. In early clinical studies in which the optimal schedule of treatment was daily for five consecutive days, dose-dependent nausea and vomiting occurred in about two-thirds of patients. PATIENTS AND METHODS: To evaluate if the use of lower daily doses for longer periods of time could result in a better tolerability, JM216 was given once daily for 14 consecutive days every four to five weeks to adult patients with solid tumors. Oral antiemetics were given prophylactically only at the highest doses. The pharmacokinetics of total and ultrafiltrable platinum were studied on days 1 and 14 of the first cycle by Inductively Coupled-Mass-Spectrometry (ICP-MS). RESULTS: Forty-six patients were treated at doses ranging from 10 mg/m2/d to 50 mg/m2/d and 39 were evaluable for hematologic toxicity over 74 cycles. MTDs were reached at 45 mg/m2/d and 50 mg/m2/d x 14 repeated every five weeks in patients with extensive, or limited/no prior treatment, respectively. The dose-limiting toxicity was neutropenia which was delayed and variable among patients. Other non-hematological toxicities were severe vomiting (22% of cycles), diarrhea (28% of cycles) and drug-associated fever (32% of patients), controlled with paracetamol. Subjective improvement with disappearance of tumour-related pain was observed in one patient with chemotherapy-resistant metastatic prostate cancer and in one previously untreated patient with malignant mesothelioma. Cmax and AUC values of both total and ultrafiltrable platinum on days 1 and 14 were highly variable among patients. Only Cmax on day 1 was linearly related to the dose. Total and ultrafiltrable platinum were still detectable two weeks after the last dose. No relationship could be established between AUC values and toxicities. CONCLUSIONS: Daily doses of JM216 of 40 mg/m2 and 45 mg/m2 for 14 consecutive days every five weeks with oral antiemetic prophylaxis are selected for phase II evaluation of single agent in patients with extensive or limited/no prior treatment, respectively. The administration of JM216 on a day x 14 schedule produced nausea and vomiting comparable to that observed with the day x 5 regimen but of longer duration. The variability of pharmacokinetics and pharmacodynamics, even though limited at the doses proposed for phase II evaluation of JM216 as single agent, recommend a careful monitoring of the patients.

Administration, Oral↗
PubMed1997

Psychosocial characteristics of inner-city children with asthma: a description of the NCICAS psychosocial protocol. National Cooperative Inner-City Asthma Study.

Previous research has demonstrated a significant reciprocal relationship between psychosocial factors and asthma morbidity in children. The National Cooperative Inner-City Asthma Study investigated both asthma-specific and non-specific psychosocial variables, including asthma knowledge beliefs and management behavior, caregiver and child adjustment, life stress, and social support. This article presents these psychosocial characteristics in 1,528 4-9-year-old asthmatic urban children and their caretakers. Caretakers demonstrated considerable asthma knowledge, averaging 84% correct responses on the Asthma Information Quiz. However, respondents provided less than one helpful response for each hypothetical problem situation involving asthma care, and most respondents had more than one undesirable response, indicating a potentially dangerous or maladaptive action. Both adults and children reported multiple caretakers responsible for asthma management (adult report: average 3.4, including the child); in addition, children rated their responsibility for self-care significantly higher than did adults. Scores on the Child Behavior Checklist indicated increased problems compared to normative samples (57.3 vs. 50, respectively), and 35% of children met the criteria for problems of clinical severity. On the Brief Symptom Inventory, adults reported elevated levels of psychological distress (56.02 vs norm of 50); 50% of caretakers had symptoms of clinical severity. Caretakers also experienced an average of 8.13 undesirable life events in the 12 months preceding the baseline interview. These findings suggest that limited asthma problem-solving skills, multiple asthma managers, child and adult adjustment problems, and high levels of life stress are significant concerns for this group and may place the inner-city children in this study population at increased risk for problems related to adherence to asthma management regimens and for asthma morbidity.

Adult↗
PubMed1997

Effects of steroids on GTH I and GTH II secretion and pituitary concentration in the immature rainbow trout Oncorhynchus mykiss.

Using specific radio-immunoassays for rainbow trout GTH I and GTH II, the effects of testosterone and estradiol 17 beta have been studied or reinvestigated on the regulation of the secretion and the synthesis of the these two pituitary gonadotropins in the immature rainbow trout. After steroid implantation, the GTH II pituitary concentration is stimulated by testosterone and estradiol 17 beta for the entire period during which the plasma levels of these hormones are maintained to values comparable to those measured in the adult vitellogenic female rainbow trout. On the other hand, only testosterone induced a transient increase in the GTH I pituitary content 15 days after implantation, and estradiol provoked a decrease at day 30. The secretion of both GTH I and GTH II is stimulated by testosterone but not by estradiol 17 beta. Altogether, these results show that in the immature rainbow trout, testosterone preferentially modifies GTH I secretion, but not that of GTH II. They confirm that the stimulation of GTH II accumulation after testosterone or estradiol treatment would correspond to a stimulation of hormone synthesis. They evidence a differential action of both steroids on the synthesis of the two gonadotropins, especially a possible inhibition of GTH I synthesis by estradiol. They let suppose that the regulation of GTH I synthesis would involve factors other than steroids.

Animals↗
PubMed1995

Preliminary evidence suggesting variations of GtH 1 and GtH2 mRNA levels at different stages of gonadal development in rainbow trout, Oncorhynchus mykiss.

To study the variations of alpha and beta GtH 1 and 2 gene expression during gonadal development in male and female rainbow trout, chum salmon alpha and beta GtH 1 and 2 probes were used. The alpha subunit cDNA probe used is identical to the cDNA encoding the alpha subunit common to both GtH 1 and 2. Total RNAs were prepared from pooled pituitaries and the validation of the use of these probes for studying the variation of GtH mRNAs was made by Northern blot analysis. The quantitative determination of GtH mRNAs employed slot blot hybridization. In males and females, beta GtH 1 predominates in early stages of gonadal development (spermatogonia A and previtellogenesis), beta GtH 2 being weakly expressed. Both beta GtH 1 and beta GtH 2 are expressed during prespermiation, spermiation, and the periovulatory period with a predominance of beta GtH 2. In both sexes alpha GtH variations follow beta GtH 2 variations.

Animals↗
PubMed1995

Role of IGF-I in the control of GH secretion in rainbow trout (Oncorhynchus mykiss).

To study the role of IGF-I on GH secretion, we looked firstly for IGF-I binding sites in the central nervous system. IGF-I presents a single class of binding sites on brain membranes and pituitary extracts. Their affinity constants (Ka) were 11.44 +/- 4.66 and 4.42 +/- 1.37 x 10(9) M-1, respectively and their capacity (Bmax) were 119.83 +/- 46.21 and 73.65 +/- 20.87 fmoles/mg, respectively. In a second step IGF-I and bGH action on GH release was tested in vitro and in vivo. IGF-I inhibited GH release by pituitary cell cultures while bGH did not, suggesting direct action of IGF at the pituitary level and indirect action of GH, possibly mediated by IGF-I. IGF-I injected into catheterization fish induced a rapid inhibition of GH release, while bGH induced a delayed one. This timing supports a direct effect of IGF-I on GH release and the indirect effect of bGH. So peripheral IGF-I can play a role on GH secretion, perhaps as a mediator of GH action. This could explain the delayed fluctuation of GH and IGF-I plasma levels previously observed. This strong relationship between plasma IGF and GH secretion in trout seems to be different from that in mammals in which systemic IGF does not seem to play a predominant role in regulating GH secretion.

Animals↗
PubMed1995

Case study of the anemic patient: epoetin alfa--focus on improving ventricular function.

Multiple factors, including chronic anemia, can impair left ventricular function and lead to serious or fatal consequences. Correcting anemia with Epoetin alfa is an important step in improving compromised left ventricular function. Continuous management of fluid status, blood pressure, and hematocrit is the best way for nephrology nurses to help patients improve their cardiac function and quality of life.

Anemia↗
PubMed1992

Effects of human insulin-like growth factor-I on release of growth hormone by rainbow trout (Oncorhynchus mykiss) pituitary cells.

A recombinant human IGF-I (rhIGF-I) was applied to primary cultures of rainbow trout pituitary cells. In wells containing 3 x 10(4) and 6 x 10(4) cells/well, rhIGF-I inhibited basal GH release both in short (6 h) and long (12 and 24 h) exposures. The decline in GH release was dose-dependent over the range of 0.01 and 100 mM. The combination of rhIGF-I and low concentrations of synthetic somatostatin (SRIF) enhanced the inhibitory effect of rhIGF-I in an additive manner. Any appreciable effect of rhIGF-I on PRL release was not evidenced. To our knowledge, this report demonstrates for the first time the participation of IGFs on the inhibitory component of fish GH regulation.

Animals↗
PubMed1992

In vitro bioactivities of various forms of GnRH in relation to their susceptibility to degradation at the pituitary level in the rainbow trout, Oncorhynchus mykiss.

In vitro potencies of native and modified forms of salmon and mammalian gonadotropin-releasing hormone (GnRH) were studied in relation with their susceptibility to degradation by intact pituitary cells maintained in culture. The kinetics of degradation and the origin of the proteases involved in this process were examined. All the molecules tested (native and modified forms) were equipotent at doses between 10(-6) and 10(-7) M in inducing GtH release by cultured pituitary cells. On the other hand, their effectiveness differed at 10(-9) and 10(-8) M leading to the establishment of the following hierarchy of bioactivity: the native forms, LHRH and sGnRH, were the less potent, the fish analogues (DAla6Pro9Net)sGnRH and (DArg6Pro9Net)sGnRH were the more potent, and mammalian analogues with substitutions at position 6 and/or 10 were intermediate in potency. The native form sGnRH was weakly degraded while no degradation of the modified molecules was observed. The degradation of the native sGnRH occurred after 12 and 24 hr of incubation and the results indicate that the peptidases involved are released from the cells into the incubation medium.

Animals↗
PubMed1992

Evidence of GnRH receptors in cultured pituitary cells of the winter flounder (Pseudopleuronectes americanus W.).

For continued studies of GnRH receptor regulation in the winter flounder, we have developed an in vitro system consisting of cultured pituitary cells dissociated by collagenase. Using immunocytochemical staining methods for gonadotropin, growth hormone, and prolactin, these cell types were represented at the levels of 25, 20, and 19.5% of total pituitary cell population, respectively. Receptors for GnRH were characterized in intact monolayered attached pituitary cells, maintained in RPMI culture medium. The cell GnRH receptor characteristics were compared with those previously described using pituitary homogenates. The cells were capable of binding GnRH in a similar manner on Day 2 or Day 3 of culture, indicating the integrity of GnRH receptors. The specificity of binding was demonstrated since only high doses of cold GnRHa competed with 125I-GnRHa uptake, different peptides being without effect. The specific binding is saturable and the data suggest the presence of a single class of high-affinity (apparent Ka = 1.50 x 10(9) M-1), high-capacity sites (binding capacity = 25.03 fmol/2.5 x 10(5) cells or 242.23 x 10(3) sites/gonadotroph) which is in accordance with the characteristics of GnRH receptors present in homogenates of pooled male and female pituitary glands. All these observations suggest that such an in vitro pituitary cell system would be appropriate for studying GnRH receptor characteristics under different physiological conditions.

Animals↗
PubMed1992

Effect of somatostatin on prolactin in rainbow trout (Oncorhynchus mykiss) pituitary cells in primary culture.

To study the control of prolactin secretion in fish, an in-vitro technique using a monolayer cell culture system of rainbow trout pituitary glands was developed. Such secretion was characterized by measurement of both prolactin release and prolactin mRNA content using a trout prolactin cDNA as a probe. This cell culture technique, already used to study the regulation of gonadotrophin secretion in rainbow trout, was further validated by measuring total DNA and protein content. Both parameters appeared to be stable after 2 days of culture. Studying the effect of somatostatin (SRIF) on prolactin cells indicated that a maximal inhibitory effect (62%) was observed after 24 h of treatment. Significant inhibition of prolactin release was obtained for SRIF doses ranging from 50 nM to 1 microM. However, in the same experiment, SRIF was much more potent as an inhibitor of growth hormone release. Short-term (< 12 h) incubation with SRIF did not induce a significant change in prolactin release, whereas growth hormone release was reduced at as early as 1 h after SRIF exposure. SRIF did not have a significant effect on total prolactin content or prolactin mRNA levels, suggesting the absence of an effect on prolactin synthesis. No increase in the magnitude of the inhibitory effect of SRIF was observed when using pituitary cells from immature, mature male or mature female trout. When comparing effects on primary cultures containing cells from the whole pituitary with a prolactin cell-enriched population, SRIF appeared to have the same inhibitory effect on prolactin release, supporting a direct action of SRIF on prolactin cells. These results provide further support for SRIF being a prolactin-inhibiting factor in rainbow trout and acting as a modulator of a dominant stimulatory control of prolactin release.

Actins↗