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Biomedical subjects

B Audhuy

Publications and source records attributed to B Audhuy.

At least 37 records · Page 2Linked to original sources

A double-blind, randomised comparison of the anti-emetic efficacy of two intravenous doses of dolasetron mesilate and granisetron in patients receiving high dose cisplatin chemotherapy.

This multicentre, double-blind, double-dummy, randomised trial was designed to compare the efficacy and safety of single intravenous doses of dolasetron mesilate and granisetron in the prevention of acute emesis and nausea due to high-dose (> or = 80 mg/m2) cisplatin. Single intravenous doses of 1.8 or 2.4 mg/kg of dolasetron mesilate or 3 mg of granisetron hydrochloride were administered in a volume of 50 ml over a 5-min period, beginning 30 min prior to cisplatin (> or = 80 mg/m2) administration. The number and timing of emetic episodes, time to administration of escape anti-emetic medication, severity of nausea by visual analogue scale (VAS), and safety were monitored for 24 h after the start of cisplatin-containing chemotherapy. Investigators' evaluations of overall efficacy and patients' satisfaction with therapy were recorded at the end of the 24-h study period. Of the 474 patients evaluable for efficacy, complete responses were achieved by 54, 47 and 48% of patients given dolasetron mesilate 1.8 mg/kg, dolasetron mesilate 2.4 mg/kg and granisetron, respectively. Statistically, treatment groups had comparable complete and complete plus major responses, times to first emesis, and use of escape medication; patient maximum nausea severity and treatment satisfaction ratings; and physician nausea severity and overall efficacy assessments. For the majority of efficacy endpoints, 1.8 mg/kg dolasetron mesilate produced numerically superior responses compared with the 2.4 mg/kg dose. Gender and prior chemotherapy were significant predictors of complete response; males and chemotherapy-naive patients had higher responses. The overall incidences of adverse events were comparable among the treatment groups; headache and diarrhoea were most common. In conclusion, 1.8 and 2.4 mg/kg of dolasetron mesilate and granisetron (3 mg) were equally effective in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, because no additional benefit was observed with 2.4 mg/kg of dolasetron mesilate and numerically greater responses were observed with the 1.8 mg/kg dose, the lower dose of 1.8 mg/kg is optimal for further clinical development.

Adult↗

[Multiple keratosis induced by hydroxyurea].

INTRODUCTION: Specific skin manifestations including skin atrophy and stripes of erythema on the extremities have been reported in patients with long-term treatment with hydroxyurea (HU). CASE REPORT: A 60-year-old patient who had been treated with HU since 1986 for chronic myeloid leukaemia presented in March 1992 with lesions characteristic of HU-induced skin changes. Hydroxyurea was continued for two more years and the lesions worsened. Unusually encountered multiple skin keratoses developed rapidly creating a clinical picture compatible with carcinomatous transformation until the withdrawal of hydroxyurea. DISCUSSION: The chronology and the clinical signs were in favour of implicating hydroxyurea in the development of these keratoses. The literature on the subject revealed one comparable case with actinic keratoses and multiple skin carcinomas. The interactions between hydroxyurea and the keratinocytes of the basal layer could explain different aspects of hydroxyurea-related toxidermia. The most severe manifestation could be the development of epithelial skin cancer.

Female↗

Clinical and immunological follow-up of patients with AIDS-associated Kaposi's sarcoma treated with an anti-IL-6 monoclonal antibody.

Ten AIDS patients with Kaposi's sarcoma (four in stage II A, four in stage III A, one in stage III B and one in stage IV of the disease) were treated for 14 days with B-E8, an anti-IL-6 monoclonal antibody (IgG1), at a daily dose of 10 mg. No side-effects were observed, but no patients experienced a complete or partial response. No modification was noted in the analysis of lymphocyte subsets, except for a transient decline in the number of cells expressing CD56, accompanied by altered NK activity in four of the seven evaluable patients. Anti-IL-6 mAb prevented the binding of IL-6 to its cell membrane receptor, as documented by the decline in C reactive protein levels. However, anti-IL-6 mAb induced the circulation of significant amounts of IL-6, probably in the form of monomeric immune complexes. The sera, analysed on B9 cell line, demonstrated a stimulating activity, indicating that hypersensitive cells were able to cleave these complexes. This observation, together with the clinical inefficacy of the treatment, should prompt us to be careful with the use of unmanipulated single monoclonal antibodies, especially in cancer patients.

Acquired Immunodeficiency Syndrome↗

Intraperitoneal mitoxantrone as consolidation treatment for patients with ovarian carcinoma in pathologic complete remission.

BACKGROUND: Stages II-IV ovarian cancer in pathologic complete remission (pCR) at second-look surgery have a high relapse rate (50%) during the first 2 years. Considering relapse sites (abdomen and/or pelvis), intraperitoneal (IP) therapy is a logical approach. Mitoxantrone is an effective drug against ovarian cancer cells in vitro and is an attractive agent for IP therapy because of its very low peritoneal clearance. The value of IP mitoxantrone was studied as consolidation treatment of ovarian cancer in pCR at second-look surgery. METHODS: Fifty patients with Stages II-IV ovarian cancer (8, Stage II; 37, Stage III; 5, Stage IV) were included in this Phase II study, which began in June 1988. All patients had undergone initial cytoreductive surgery followed by 6 cyclophosphamide, doxorubicin, and cisplatin cycles. All patients were in pCR, as confirmed by second-look surgery. Consolidation treatment consists of 20 mg (total dose per cycle) IP mitoxantrone every 3 weeks for six cycles. RESULTS: Toxicity was limited to mild abdominal pain not requiring dose reduction (90% pain grade < or = 2). With a median follow-up of 2 years, the 5-year predicted survival is 59.8% (95% confidence interval [CI], 48.3 - 71.3), and the disease-free survival (DFS) rate is 47.3% (95% CI, 36.7 - 57.9). Patients with no or microscopic residual disease after initial surgery had a better 5-year DFS rate (75.8%) than those with macroscopic residual disease (31.2%) (P = 0.01). CONCLUSION: IP mitoxantrone (20 mg/cycle) is feasible with an acceptable abdominal toxicity. The results in terms of DFS are encouraging, but a randomized study versus no treatment is necessary to prove the value of this consolidation treatment.

Abdominal Pain↗

Intraperitoneal mitoxantrone as consolidation treatment for stage III ovarian carcinoma: a pilot study.

In June 1986 we initiated an intra-peritoneal (IP) mitoxantrone chemotherapy trial as consolidation treatment for ovarian carcinoma in CR or PR after induction therapy (surgery + CHAP combination chemotherapy). Thirty-two patients received 25 mg IP mitoxantrone every 3 wk for 6 months. The most frequent side-effects were abdominal pains; haematological toxicity was minimal. The response was assessed by third-look surgery. In group I patients (patients in histological complete remission at second-look surgery) 12 of 14 evaluable patients remained in CR at the time of third look. Ten of the 12 patients are still alive with no evidence of disease (NED) with a median follow-up of 9.7 months after completion of treatment. In group II patients (microscopic residual disease at second-look surgery), 7 of 9 evaluable patients entered in CR at the time of third look; 6 of the 7 are still alive with NED and with a median follow-up of 14.3 months. In 7 group III patients (macroscopic residual disease at the time of second look) no response to IP therapy was observed and all patients progressed. We conclude that IP mitoxantrone is a valuable consolidation treatment for patients in CR or with minimal residual disease; further follow-up is necessary to assess the impact on duration of remission and survival.

Adult↗

Zoladex as primary therapy in advanced prostatic cancer. A French cooperative trial.

From April 1984 to May 1986, 129 patients with prostate cancer entered a prospective trial with a new LH-RH agonist, Zoladex. Mean age was 72 years (range of 45-94 years) and, in most cases, patients had metastatic disease, not previously treated by chemotherapy or hormone therapy. Patients received a monthly injection of 3.6 mg. Serum testosterone was lowered into the range of castrate levels after 4 weeks of treatment. In 105 evaluable patients at 3 months, a 65% partial response (PR) rate was observed, with 11% stable and 24% progressive disease. Median time to progression was 37 weeks. Analysis of objective criteria revealed 30% PR for prostate volume and 51% CR-PR for prostatic acid phosphatases. Seventeen percent of lytic metastases had recalcified. One hundred twenty-nine patients were evaluable for toxicity. Endocrinological side effects were common: decrease in libido, 92%; impotence, 86%; hot flushes, 48%; and breast swelling or tenderness, 9%. Nonendocrinologic side effects were rare. The treatment is generally well accepted by patients owing to the convenient depot formulation and to the minor side effects.

Acid Phosphatase↗

High dose intravenous IgG followed by splenectomy versus splenectomy alone in idiopathic thrombocytopenic purpura refractory to steroids.

A total of twenty-six patients with idiopathic thrombocytopenic purpura ITP refractory to corticosteroids were alternately allocated to undergo splenectomy alone (N = 12) or to receive a 5 day course of high dose immunoglobulin G i.v. immediately followed by splenectomy (N = 14). Although there were less initial failures after splenectomy in patients receiving IgG, the proportion of sustained complete remission at 1 and 2 years was identical in both groups. It is concluded that high dose IgG infusions do not improve the results of splenectomy in refractory ITP.

Adolescent↗

[Acute myeloblastic leukemias and myelodysplasias: treatment with low doses of aracytine].

The anti-leukaemic effect of low-dose cytosine arabinoside was assessed in 36 patients; 15 patients presented with an acute myeloblastic leukaemia and were treated in first induction because of age or preexisting disease and clinical and biological stabilization was obtained in 7 cases, with a mean duration of 8.7 months. In 4 relapsed patients 2 complete remissions were obtained, 1 of which after several courses of cytosine arabinoside. In all cases an important haematopoietic and extra-haematopoietic toxicity was noticed. In 15 patients treated for a myelodysplastic syndrome terminating in acute myeloblastic leukaemia stabilization was obtained in 8 cases, but final conclusions were difficult. The cytotoxic effect of cytosine arabinoside even at low dosage remains important. The optimal modalities in the administration, and the actual advantages of this treatment compared with conventional chemotherapy have still to be defined.

Aged↗

[Insulin-dependent diabetes with acute onset. Remissions induced by early temporary blood glucose normalization].

Within 6 months of the acute onset of an insulin-dependent diabetes, remission of insulin-dependence was attempted in 30 hospital patients by strict control of glycaemia obtained in a few days with intravenous infusions of insulin, using a macropump. This was followed by an oral antidiabetic treatment, and the patients were considered in remission when metabolic control was achieved. By this method remission of insulin-dependence was obtained in 90% of the patients; it lasted for more than 1 year on average, and its degree seemed to depend on the time elapsed between the clinical onset of the disease and the beginning of the intravenous treatment but also, to a lesser extent, on the residual secretory capacity of the pancreas when this treatment was instituted. Thus, an intensive metabolic control increases the effectiveness of an oral treatment as regards both number of patients improved and duration of remission. When administered alone at the onset of the disease the oral treatment is only effective in about 30% of the cases.

Adolescent↗

[Evaluation of the biliary passage of beta-lactam antibiotics].

The present study is devoted to the biliary excretion of some beta-lactam antibiotics (6 derived from the penicillin group: Penicillin G, Ampicillin, Metampicillin, Carbenicillin, Mezlocillin, Apalcillin and 9 from the cephalosporin group: Cephalothin, Cephaloridine, Cephacetrile, Cefalexin, Cefazolin, Cefamandole, Cefuroxime, Cefaclor and Ceftizoxime). The biliary excretion of these antibiotics was assessed by 4 different procedures: 1) experimental study of their biliary elimination by a perfused isolated rabbit liver; 2) in humans, by evaluation of their passage: a) in aspirated duodenal fluid, b) in bile collected by external biliary drainage, c) and in bile obtained by puncture of the main bile duct and the gall bladder during surgery. The results of these different investigations were concordant and showed that the biliary excretion of Metampicillin, Apalcillin and Mezlocillin was definitely higher than that of the other studied beta-lactams; on account of their suitable antibacterial spectrum, these 3 derivatives should be used in preference for the treatment of biliary infection.

Animals↗

[Refractory anemia with an excess of blasts: evidence for 2 evolving groups in a group of 56 patients].

Cytological and kinetic findings in 56 patients with refractory anemia with excess blasts (RAEB) were studied. The different statistical methods used produce similar results: our group of patients can be separated by cytological parameters in two populations (overt leukemic or hematologically stable evolution). Different functional lesions may be responsible for these two types; pluripotential stem cell dysfunction in the first case and abnormality of the granulocytic committed stem cell in the second. A score, based on a small number of simple and reliable parameters, is able to distinguish these two populations.

Adolescent↗

[Clinical value of nephelometric assay of C-reactive protein].

Laser immunonephelometry is a sensitive, specific and rapid method for assaying plasma C-reactive protein (CRP). This "acute phase" protein has recently been shown to be of significance in the regulation of immunological responses. It is released from hepatocytes early during infection, inflammation or necrosis. Nephelometry provides a good means for detection, monitoring and evaluation of therapeutic efficiency in these conditions. The increase in CRP may precede the positivity of the usual biological tests and is of value in situations where these tests cannot be interpreted.

C-Reactive Protein↗

Auer rods in refractory anemia with excess of blasts: presence and significance.

Auer rods were found in the bone marrow of nine out of 56 patients having all the criteria of refractory anemia with excess of blasts (RAEB). No differences were found in Auer-positive or Auer-negative subgroups according to cytology, kinetics, type of growth in agar, or disease course. Therefore, the presence of Auer rods in the bone marrow of patients with RAEB does not imply overt leukemia.

Adult↗