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Biomedical subjects

R Bugat

Publications and source records attributed to R Bugat.

At least 109 records · Page 6Linked to original sources
PubMed1989

Rapid quantitative determination of doxorubicin and its metabolites in biological samples.

A rapid sensitive and selective method is developed for the plasma analysis of doxorubicin and its metabolites, doxorubicinol and doxorubicinone with daunorubicin as the internal standard, by using high performance liquid chromatography (HPLC) with fluorescence detection and a "zorbax ODS" column. An eluent containing tetrahydrofuran and trietylamine afforded improved efficiency and resolution and was used to resolve the four anthracycline derivatives in a sole isocratic run. An example of the plasma levels obtained in a cancerous patient after two different administrations is shown.

Chromatography, High Pressure Liquid↗
PubMed1988

Association of the Philadelphia chromosome and 5q- in secondary blood disorder.

A patient developed a secondary blood disorder 7 years after radiotherapy for a gastric lymphoma. The initial myelodysplastic syndrome evolved to a myeloproliferative phase with transient polycythemia, progressive thrombocythemia, and hyperleukocytosis. Chromosome analysis performed in the terminal phase showed del(5)(q13q31),t(9;22)(q34;q11), and a complex rearrangement involving chromosomes #2 and #3. A correlation between chromosomal abnormalities and hematologic findings could be established. In this case, we have assumed that the Philadelphia translocation is a late event, due to prior mutagen exposure, and its association with a common secondary abnormality (5q-), followed by a progressively developing myeloproliferative phase. Furthermore, the association of Ph and 5q- in a single clone seems to indicate that the same stem cell is affected by these two abnormalities.

Anemia, Refractory, with Excess of Blasts↗
PubMed1988

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↗
PubMed1987

[The phenomenon of relative resistance to heparin].

In a prospective clinical study heparin half-life and in vitro and ex vivo heparin sensitivity, as assessed by activated partial thromboplastin time prolongation, was evaluated in 8 healthy volunteers and in 21 patients with malignant tumor. In the patients, coagulation activation was evaluated by determining the fibrinogen half-life and the level of the fibrin-fibrinogen degradation products. The results were comparable in the two groups of subjects, and in the patients there was no correlation with the degree of activation of the coagulation system. In both groups large interindividual variations were recorded. These results confirm those obtained in patients with deep venous thrombosis. They suggest that the relative heparin resistance phenomenon encountered in some patients during heparin therapy is unrelated to the presence of the thromboembolic disease (P.M.).

Adult↗
PubMed1987

Uptake and binding of teniposide (VM26) in Krebs II ascites cells.

With [3H] VM26 as marker, the uptake and binding of teniposide have been made in cells of Krebs II ascitic tumors. The intracellular accumulation of drug displayed a passive diffusion and a saturation kinetics with an apparent Michaelis-Menten constant of 37.54 10(-6) M and a flux of 13.4 nM/min/mg of protein. VM26 was rapidly taken and an equilibrium was established with the extracellular drug in about 30 min. The steady-state accumulation was diminished by Na+ and Ca2+ absence and VP16-213, whereas, K+ and Mg2+ have no effect. Energy dependence of the system was characterized by a Q10 of 1.75 +/- 0.2 and the uptake was reduced by ouabain and iodoacetamide, when 2-4-dinitrophenol and glucose absence were without appreciable change. The study of the efflux showed that about 87% of the uptaken drug was removed, the residual amount being probably irreversibly bound. The intracellular accumulation of the drug was associated with various cell organelles, however, only the nuclear fraction demonstrated a high affinity binding.

Animals↗
PubMed1987

Pharmacokinetics of high-dose i.v. alizapride in prevention of cisplatin-induced emesis.

Alizapride is a new antidopaminergic-related benzamide with specific antiemetic properties. Pharmacokinetics at a high repetitive dose (16 mg/kg) shows a biexponential plasma decay with T1/2 alpha of 8.33 +/- 2.47 min and T1/2 beta 2.8 +/- 0.7 hr. Large Vdss and high total body clearance are apparent. We demonstrate an increase in drug exposure during the first 6 hr after CDDP infusion by shortening the interval between injections. We conclude that the rate of infusion of alizapride could be important in the efficacy of the drug.

Antiemetics↗
PubMed1986

Synchronous abdominotrans-sphincteric resection of low rectal cancer: new technique for direct colo-anal anastomosis.

Sixty-five patients with low rectal cancer 4-9 cm from the anal margin were treated by rectal resection and direct colo-anal anastomosis. The procedure simultaneously combined abdominal dissection with the patient in the lateral position with a trans-sphincteric approach. In 57 cases a temporary defunctioning colostomy was performed. There were no postoperative deaths. Six patients (9 per cent) developed pelvic sepsis or anastomotic leakage. Faecal continence was normal in 46 of 51 patients (91 per cent) who were operated on at least 1 year previously. The remaining 5 complained of occasional minor soiling. No patients require a permanent colostomy for incontinence. Of 29 patients treated for potential cure greater than 3 years previously, 24 (82 per cent) were alive without recurrence. Local recurrence occurred in four patients (6 per cent). Direct colo-anal anastomosis using a combined abdominotrans-sphincteric approach has produced good functional results without impairing the patient's life expectancy.

Adult↗
PubMed1986

Pharmacokinetics and efficacy of i.v. and i.p. VM26 chemotherapy in mice bearing Krebs II ascitic tumors.

The pharmacokinetics and the efficacy of VM26 are studied following i.p. or i.v. administration in mice bearing Krebs II ascitic tumors. The i.p. inoculation of 30.10(6) Krebs II cells in Swiss mice leads to the formation of ascites. The effects of VM26 were dependent upon the route of administration. A 2 mg/kg i.p. single dose induces an equivalent per cent increase of median survival time than a 20 mg/kg i.v. single dose. The survival advantage of i.p. VM26 was found to be related to the pharmacologic benefit of i.p. administration. If local toxicity does not prove to be a major problem, i.p. VM26 may constitute a safe and practical mode of therapy in patients with intraabdominal tumors.

Animals↗
PubMed1985

Platelet regeneration time after aspirin ingestion and platelet survival time after labelling with 51chromium or 111indium oxine--a comparative study.

A simultaneous investigation of platelet regeneration time (PRT) based upon malondialdehyde (MDA) recovery after a single oral intake of 500 mg of aspirin and of platelet survival time (PST) after labelling with 51chromium or 111indium oxine was performed in 25 cancerous patients. A pilot study conducted with 9 healthy volunteers demonstrated that the MDA assay was highly reproducible and specific for the platelet cycloxygenase activity. The pattern of MDA recovery after aspirin ingestion was linear in the healthy volunteers and in the patients presenting both a normal and an accelerated platelet turnover. PST were calculated using the four mathematical models recommended by the International Committee for Standardization in Hematology; the best fit was given by the multiple hit model in 22 cases and by the linear regression model in 3 cases. The mean results obtained in the patients investigated with the 51chromium were consistently shorter than those obtained in the patients investigated with the 111indium oxine while the mean PRT were almost identical in the two groups. An excellent correlation between PRT and PST was observed after 111indium oxine labelling and using the weighted mean method for PST determination. These results suggest that the 111indium oxine technique is a better method for platelet labelling and that the results provided by the weighted mean method reflect more closely the in vivo platelet turnover than those provided by the multiple hit model.

Adult↗
PubMed1985

Pharmacokinetics of teniposide (VM 26) after IV administration in serum and malignant ascites of patients with ovarian carcinoma.

Nine patients with ovarian carcinoma and malignant ascites treated with IV teniposide chemotherapy (30 mg/m2/30 min) entered this study. Plasma and peritoneal fluid levels were measured by an HPLC method with electrochemical detection. Plasma decay kinetics followed a triexponential function. A high variability of drug diffusion in ascites was noticed. Peak concentrations in ascites ranged from 1.6% to 20.5% of serum peak concentration. The concentration in peritoneal fluid reached a maximum level 6 h after the infusion ended. Teniposide was less slowly eliminated from ascites than from serum. The exposure of the inflammatory peritoneal fluid to the drug expressed by area under the concentration-time curve (AUC) was also subject to significant interindividual variation, ranging from 223 to 2332 micrograms/ml X min. However, the peritoneal AUC was correlated with serum AUC and with the systemic clearance of the drug. A significant relationship between gamma glutamyltranspeptidase and both systemic clearance and either the serum or the peritoneal AUC was found, suggesting that liver plays a role in drug disposition.

Aged↗
PubMed1985

[Merkel cell carcinoma of the skin. Anatomoclinical, ultrastructural and immunohistochemical study of 14 cases].

The clinical and pathological features of 14 cases of Merkel cell carcinoma are reported. They commonly arise in the skin of elderly patients, particularly on the face and pelvis. They have a loco-regional aggressivity (nodal metastases in 4 cases) but some patients die with disseminated metastases (2 cases). These tumors are composed of round cells with scanty cytoplasm, arranged in solid or trabecular sheets. Mitotic figures are usually numerous. The ultrastructural study reveal secretory granules and paranuclear collection of intermediate filaments. Immunohistochemical phenotype is highly characteristic: cytoplasmic diffuse positivity with an anti-neuron-specific enolase polyclonal antibody; polar and/or diffuse positivity with anti-cytokeratin, anti-epithelial membrane antigen and anti-S100 protein monoclonal antibodies; polar positivity with an anti-neurofilament monoclonal antibody. The negativity with an anti-common leucocyte antigen monoclonal antibody is helpful to differentiate Merkel cell carcinoma from cutaneous malignant lymphoma.

Adult↗
PubMed1985

[Second-look laparotomy or the search for curable stage III FIGO ovarian epitheliomas. Apropos of a series of 35 cases].

The authors report their experience in 35 cases of second-look laparotomy performed on 35 patients in the Claudius Regaud Centre. The actuarial survival rate at 3 years of patients who had undergone this surgery has been shown to be 41% as against 13% for all Stage III and IV cases randomly taken in this same period (194 cases). Indications for a second-look laparotomy are generally reserved for patients who have responded to chemotherapy after a mean of 6 treatments unless there in an obvious indication to go in. The reasons for this procedure include the idea of assessing completely the state of affairs and if necessary carrying out a large excision operation, knowing full well that the results will depend mainly on the quality of the first treatment given. Survival after second-look laparotomy depends on the mass of neoplastic tissue that is left behind, its size and its position in the peritoneal cavity or in the lumbo-aortic lymph nodes. This makes it possible to define that privileged group of patients that have a good prognosis. These patients who can be cured are those who have no disease in the peritoneal cavity or in the lymph glands. The combination of different ways of treating residual disease in the peritoneum or behind the peritoneum are derived from decisions made following second-look laparotomy. There is no place for radiotherapy of the abdomen and pelvis when there is residual lymph gland disease.

Actuarial Analysis↗