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A Thyss

Publications and source records attributed to A Thyss.

At least 91 records · Page 5Linked to original sources
PubMed1993

Childhood cancer incidence in the south-east of France. A report of the Provence-Alpes-Côte d'Azur and Corsica Regions Pediatric Cancer Registry, 1984-1991.

A prospective registration of incident cancers in childhood in two south-east regions of France since 1 January 1984 allows us to collect pertinent data on 875 cases throughout a period of 8 years. World age-standardised overall incidence rate is 137.63 cases/million/year. It is close to that reported in other white European. North American and Oceanian populations. The age-adjusted (age-standardised) relative frequency of each pathological group is: leukaemias 29.71%; central nervous system tumours 20.61%; lymphomas 12.75%; sympathetic tumours 9.03%; soft tissues tumours 7.37%; bone tumours 5.89%; kidney tumours 4.82%; epithelial tumours 3.83%; germinal and gonadal tumours 3.24%; retinoblastomas 2.11%; liver tumours 0.45% and others 0.14%. The comparison of these results with international available data shows that we record the world highest adjusted incidence rates for neuroblastomas (15.46) and rhabdomyosarcomas (7.04) and a high rate for Ewing's sarcomas (3.30); this fact will need to be confirmed by a longer period of observation, but even now the total number of cases (particularly for neuroblastoma) is high when compared with the data of other children registries which give rates for longer periods and for similar or larger populations.

Adolescent↗
PubMed1993

Extracerebral toxoplasmosis in the acquired immunodeficiency syndrome (AIDS).

Although Toxoplasma gondii frequently causes lesions of the central nervous system in AIDS, the exact incidence of extracerebral toxoplasmosis in these immunodepressed patients remains difficult to determine. Isolation of the parasite outside the central nervous system is rarely performed ante mortem, and most diagnoses of extracerebral toxoplasmosis are made post mortem. This article describes 23 cases of extracerebral toxoplasmosis diagnosed between 1987 and 1991 in an autopsy series of 170 patients infected with the human immunodeficiency virus (HIV). Ante mortem diagnosis of extracerebral involvement was affirmed in 4 of these 23 patients by identification of trophozoites in bronchoalveolar lavage fluid (2 cases), a surgical pulmonary biopsy specimen, and a bladder biopsy. Clinical and paraclinical findings suggested cardiac involvement in 4 other patients. Post mortem examination demonstrated disseminated toxoplasmosis in 18 cases and extracerebral monovisceral involvement in 5 cases. Extracerebral toxoplasmosis was directly responsible for the death of 6 patients. The most frequent extracerebral sites of Toxoplasma gondii involvement were the heart (21/23 cases; 91%), the lungs (14/23 cases; 61%) and the pancreas (6/23 cases; 26%). The tissular consequences of toxoplasmic involvement varied considerably, from formation of pseudocysts or cysts without any surrounding inflammatory reaction to necrotic lesions rich in neutrophilic polynuclear cells containing numerous free parasites. Immunoperoxidase study using antitoxoplasmic antibodies contributed to the diagnosis of 8 extracerebral localizations. Electron microscopy examination of a surgical lung biopsy and myocardial specimens (2 cases) demonstrated the ultrastructural characteristics of Toxoplasma gondii trophozoites.(ABSTRACT TRUNCATED AT 250 WORDS)

Acquired Immunodeficiency Syndrome↗
PubMed1993

Dihydropyrimidine dehydrogenase activity in cancer patients.

Dihydropyrimidine dehydrogenase (DPD) is the major catabolic enzyme of pyrimidines and fluoropyrimidines. The clinical course of 2 patients with suspected DPD deficiency is described. Both patients had significantly delayed clearance of fluorouracil (5-FU), elevated plasma uracil concentrations, and subsequent lethal toxicity. The prevalence of DPD deficiency in the general population is unknown, but given the large number of cancer patients treated with 5-FU, it may be of great clinical significance. Lymphocytes have been previously shown to be a useful marker of systemic DPD activity. Because DPD activity has not been previously reported in a large population of cancer patients using 5-FU as the substrate, we determined DPD activity in lymphocytes from 66 patients with cancer. DPD activity was determined by a sensitive high performance liquid chromatography method. The mean DPD activity (S.D.) in 66 patients with head and neck cancer was 0.189 (0.071) nomol/min/mg protein with wide interpatient variability (range 0.058-0.357). DPD activity was not correlated to age (r = -0.164, P = 0.188). The mean DPD activity in men [0.192 (0.074)] was not significantly different from that in women [0.172 (0.057); t-test P = 0.418]. Likewise, there was no statistical difference in DPD activity in patients who had not received prior chemotherapy [0.195 (0.066)] to patients receiving one or more cycles of chemotherapy [0.186 (0.074); t-test P = 0.638].

Adult↗
PubMed1993

Prevalence of toxoplasma myocarditis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To evaluate the prevalence of cardiac toxoplasmosis in a series of 182 necropsies performed between 1987 and 1991 on patients infected with the human immunodeficiency virus (HIV), to correlate this prevalence with the ante mortem diagnosis of cardiac involvement, and to assess the role of such cardiac lesions in the immediate cause of death. PATIENTS AND METHODS: Complete necropsies of 182 HIV-infected patients (48 women, 134 men) were performed consecutively between 1987 and 1991. Risk factors, identified in 174 cases, included drug abuse (111/182), homosexuality (51/182), and blood transfusions (12/182). 16 samples were systematically obtained from each heart for histological study. If trophozoites or lymphocytic myocarditis were seen, immunohistochemical investigations were carried out with polyclonal antibodies for Toxoplasma gondii. An ultrastructural study was performed in four patients with toxoplasma myocarditis. Myocardial lesions were defined by the Dallas classification. Clinical data (and information on electrocardiograms and echocardiograms) were obtained from medical records. RESULTS: Cardiac toxoplasmosis was diagnosed at necropsy in 21 (12%) patients. Cardiac lesions were associated with toxoplasmic encephalitis in 18 patients and were solitary in three patients. Acute diffuse myocarditis was present in 6/21, rare foci of myocarditis were seen in 8/21, and intramyocytic toxoplasmic cysts without any inflammatory reaction or necrosis were seen in 4/21. Anti-toxoplasma immunolabelling showed cardiac toxoplasmosis in three patients with lymphocytic myocarditis. Particles with the ultrastructural characteristics of Toxoplasma gondii trophozoites were seen in four cases. Six patients had presented with cardiac symptoms, confirmed by electrocardiographic and echocardiographic abnormalities during their disease course, and their cardiac lesions were directly responsible for the death. CONCLUSION: Cardiac toxoplasmosis was common in this necropsy series of HIV-infected patients. Cardiac toxoplasmosis had been suspected clinically in four patients. Myocardial lesions were generally asymptomatic and were not discovered until necropsy. Solitary cardiac involvement was not uncommon reflecting parasite reactivation at a myocardial site. The incidence of cardiac toxoplasmosis in this group of immunodepressed subjects from an area with a high prevalence of this parasitic disease justifies regular follow up of such patients by electrocardiography and echocardiography as well as immediate administration of anti-toxoplasma treatment should sudden heart failure occur.

Acquired Immunodeficiency Syndrome↗
PubMed1993

Etoposide in relapsed or refractory Wilms' tumor: a phase II study by the French Society of Pediatric Oncology and the United Kingdom Children's Cancer Study Group.

PURPOSE: Despite a high cure rate of approximately 85% in Wilms' tumor by multimodality therapy, to date only four drugs are known to be active against such tumors. There is a clear need for new active drugs. PATIENTS AND METHODS: Thirty-one patients with relapsed or refractory Wilms' tumor from three British and 14 French centers were treated with intravenous (IV) etoposide 200 mg/m2 daily for 5 days. Original stage was I (n = 3), II (n = 7), III (n = 9), IV (n = 10), and V (n = 2). Prior chemotherapy, administered initially or at relapse, included vincristine and dactinomycin in all cases, doxorubicin or epirubicin in 30, and ifosfamide in 20. Sites of relapse or resistant disease were lung in 13, abdomen or pelvis in six, liver in one, and multiple in 11. When entered onto the study, 12 patients were in first relapse, 10 in second relapse, and four in third or more relapse. Five had never obtained a complete remission. All but two (progressing) patients received two courses of etoposide, the second course being administered at day 21. RESULTS: A complete response (CR) was documented in two patients, partial response (PR) in 11, stable disease in 10, and progressive disease (PD) in eight. The duration of response could not be evaluated, because all responding patients were subsequently treated with multimodality therapy. The major toxicities observed were neutropenia and thrombocytopenia, but most patients had been heavily pretreated. No toxic death clearly associated with etoposide was noted. CONCLUSION: It is concluded that etoposide in this schedule is an active agent in Wilms' tumor and should be considered for inclusion in regimens for high-risk patients, such as those with metastatic disease at diagnosis and those who relapse after multiagent chemotherapy.

Adolescent↗
PubMed1993

[l-folinic acid versus racemic folinic acid in the treatment of leukemia in children with high dose of methotrexate].

Until now, folinic acid (FA) has been available the racemic mixture d1 FA, whose biological activity is supported by natural 1 FA. The purpose of this trial was to compare, on a pharmacokinetic, biological, and clinical basis, the racemic mixture dl FA with the pure 1 FA in the rescue of high-dose methotrexate (MTX) therapy. Eighteen children with acute lymphocytic leukemia (ALL) were entered in this trial planned with a cross-over design. Four cycles of MTX (5 g/m2, 24h CVI) were administered to each patient, with a 2-week interval between cycles. The rescue was achieved orally every 6h, starting 12h after the end of the MTX infusion, at a dose of 12 mg/m2 for dl FA and 6 mg/m2 for pure 1 FA. dl FA and 1 FA rescues were alternated from one cycle to the next. d FA, 1 FA, and the active metabolite 5-methyltetrahydrofolate (5-MTHF) were measured in plasma using a stereospecific HPLC assay. After administration of dl FA, the accumulation of d FA in plasma was confirmed: mean residual concentrations were 420 and 652 nM after 2 and 6 intakes respectively. Total active folate concentrations (1 FA + 5-MTHF) were similar between the two types of rescue: 92 and 100 nM respectively for dl FA rescue and 1 FA rescue after two intakes, 186 and 184 nM respectively for dl FA rescue and 1 FA rescue after six intakes. Intra-individual statistical analysis of total active folates (1 FA + 5-MTHF) performed on 17 patients did not show any significant difference between dl FA rescue and 1 FA rescue. For both types of rescue, MTX terminal half-lives were identical (average value 13.9 h). Considering each type of toxicity (hematologic, hepatic, renal and digestive) there was no significant difference in the proportion of toxic cycles following l FA rescue or dl FA rescue. In conclusion, the administration of the pure l FA, as compared with the administration of the racemic mixture, results in comparable blood profiles of active folates and MTX, and leads to equivalent treatment tolerance.

Adolescent↗
PubMed1993

[Kaposi sarcoma of the lungs in patients with acquired immunodeficiency syndrome (AIDS). Thoracic radiography and scanning].

Twenty-four patients with AIDS presenting with Kaposi's sarcoma of the lung were retrospectively studied to assess the merits of thoracic radiographs and of CT for the diagnosis of this disease. Evidence for Kaposi's sarcoma of the lung was given by a characteristic fiberendoscopic appearance in 10 cases and by the histologic diagnosis in 14 cases. All patients had chest radiographs and 14 patients a concomitant thoracic CT study. Chest radiographs showed perihilar opacities in 18 patients, nodules in 8, mediastinal and/or hilar adenopathies in 2 and pleural effusion in 16. Comparison of the patients who had had thoracic radiographs and a CT scan showed better detection of adenopathies, described in 2 cases on chest radiographs and 7 on CT scans, and of nodules, detected in 5 cases on chest radiographs and 6 on CT scans. In 12 patients with perihilar opacities on thoracic radiographs, CT provided a better view of the peribronchovascular distribution of these opaque areas. In 1 patient, CT showed peribronchovascular thickening while radiographs were normal. In 1 patient, both examinations were normal. This study emphasizes the merits of thoracic radiographs and, even more, of CT for the diagnosis of Kaposi's sarcoma of the lung. Peribronchovascular thickening appears to be a characteristic sign that is well analyzed with computed tomography. Since histological evidence of Kaposi's sarcoma is rarely obtained because of the aggressive nature of biopsies in such patients, CT has an important role for the diagnosis of this condition.

AIDS-Related Opportunistic Infections↗
PubMed1993

[Primary lymphoma of the cranial vault. Apropos of a case].

Primary lymphomas of the cranial vault are most unusual lesions. Only six cases have been described in the literature. We report a case of a 71 year old female who was admitted with an occipital mass. A C.T. scan revealed a mainly extra cranial tumor with an osteolysis of the cranial vault and a small intracranial component. It was diagnosed as a phenotype B centroblastic lymphoma. Half of the patients reported in the literature had a subcutaneous mass as the main symptom. These neoplasms are usually highly malignant tumors. The treatment realized is neurosurgical excision followed by chemotherapy and radiotherapy.

Aged↗
PubMed1992

l-folinic acid versus d,l-folinic acid in rescue of high-dose methotrexate therapy in children.

BACKGROUND: At this time, folinic acid (FA) is commercially available as the racemic mixture d,l-FA, whose biological activity is supported by natural l-FA. The administration of d,l-FA results in the accumulation of d-FA in plasma relative to the active l-FA form; in vitro studies have shown that d-FA can compete with the polyglutamation of methotrexate (MTX). PURPOSE: Our purpose was to compare, on a pharmacokinetic, biological, and clinical basis, the racemic mixture d,l-FA with the pure l-FA in rescue of high-dose MTX therapy (5 g/m2) in children with acute lymphocytic leukemia (ALL). METHODS: Eighteen children with ALL were entered in this trial, which was planned with a crossover design. Four cycles of MTX were administered to each patient, and rescue was achieved orally every 6 hours at a dose of 12 mg/m2 for d,l-FA and 6 mg/m2 for pure l-FA. The d,l-FA and l-FA rescues were alternated from one cycle to the next. d-FA, l-FA, and the active metabolite 5-methyltetrahydrofolate (5-MTHF) were measured in plasma using a stereospecific high-performance liquid chromatography assay. RESULTS: Considering total active folate levels (l-FA + 5-MTHF), mean residual concentrations were similar for rescue by d,l-FA and l-FA, after two and six intakes, respectively: 92 and 186 nM for d,l-FA rescue versus 100 and 184 nM for l-FA rescue. Intra-individual comparison of total active folates (l-FA + 5-MTHF) did not show any significant difference between d,l-FA rescue and l-FA rescue. After administration of d,l-FA, the accumulation of d-FA in plasma was confirmed. For both types of FA rescue, MTX terminal half-lives were identical (average value, 13.9 hours). Considering each type of toxic effect (hematologic, hepatic, renal, and digestive), there was no significant difference in the proportion of toxic cycles following l-FA rescue or d,l-FA rescue. CONCLUSION: The administration of the pure l-FA, compared with the administration of the racemic mixture, results in comparable blood profiles of active folates and MTX, leads to equivalent treatment tolerance, and avoids the plasma accumulation of d-FA.

Adolescent↗
PubMed1992

Correlation between dihydropyrimidine dehydrogenase activity in peripheral mononuclear cells and systemic clearance of fluorouracil in cancer patients.

Dihydropyrimidine dehydrogenase (DPD) is the initial key enzyme in the catabolism of 5-fluorouracil (5-FU). We measured DPD activity in lymphocytes from 57 consecutive head and neck cancer patients while simultaneously monitoring 5-FU pharmacokinetics during 5-day, continuous infusion (1000 mg/m2/day) 5-FU therapy (82 cycles in total). The mean value for DPD activity was 0.186 +/- 0.068 (SD) nmol/min/mg of protein (range, 0.058 to 0.357). The mean value for 5-FU clearance was 2522.6 +/- 684.2 ml/min/m2 (range, 1052 to 4029). A significant linear correlation was observed between DPD activity and 5-FU clearance (r = 0.716, P less than 0.0001). DPD activity was poorly correlated to plasma uracil concentrations (r = -0.260, P = 0.0215). Likewise, plasma uracil concentrations were poorly correlated to 5-FU clearance (r = -0.214, P = 0.0595). In patients evaluated for more than one cycle (n = 18), there was large intrapatient variability in both DPD activity and 5-FU clearance. No significant difference was noted between cycles for DPD activity or 5-FU clearance (Kruskal-Wallis test). Monitoring DPD activity in lymphocytes may be useful in identifying patients at risk for altered 5-FU disposition.

Adult↗
PubMed1992

Methylated catecholamine metabolites for diagnosis of neuroblastoma.

Assays of urinary catecholamines and their metabolites (HVA, VMA, dopamine) permit biochemical diagnosis of neuroblastoma in approximately 80% of patients. The urinary methylated catecholamine metabolites normetanephrine (NMN), metanephrine (MN), and 3-methoxytyramine (3-MT) were analyzed in 18 patients with neuroblastoma and compared with reference values established for 69 healthy pediatric controls. All 18 neuroblastoma patients had raised urinary excretion of at least one of the three commonly assayed metabolites (HVA, VMA, dopamine). Similarly, raised urinary excretion of a methylated metabolite was noted in all but one of the neuroblastoma patients. The 3-MT level was pathologic in 16 of the 18 patients (89%). In this series, 3-MT assay sensitivity was sufficient to warrant trials on a larger population including comparison with patients considered nonsecretors by routine assay procedures.

Adolescent↗
PubMed1992

Doxorubicin weekly low dose administration: in vitro cytotoxicity generated by the typical pharmacokinetic profile.

The cytotoxic effects of prolonged exposure to low concentrations of doxorubicin or a doxorubicin bolus were examined in vitro on four human breast cancer cell lines to simulate the plasma concentration profile of weekly low-dose (WLD) doxorubicin in breast cancer patients. Cells were exposed to doxorubicin for various prolonged times (24, 72, 120 and 192 h) and with different drug concentrations (5, 10, 20, 50 and 80 nmol/l). In a series of parallel experiments, cell lines were placed in contact with the drug for short periods (1 h) before prolonged exposure to doxorubicin; the concentrations of these pulses were 150, 250 and 350 nmol/l. A constant decrease in tritiated thymidine incorporation was noted as a function of the drug concentration and the duration of the cell contact with the drug. Interestingly the lowest concentrations (5-10 nmol/l) produced marked cytotoxic effects. For equivalent concentration x time values, experiments including doxorubicin pulses resulted in greater cytotoxicity than continuous exposure alone, in a dose-related manner. This finding was related to differences in intracellular doxorubicin concentrations. Results suggest that the rather empirically designed WLD doxorubicin schedule can generate greater cytotoxic effects than continuous doxorubicin administration alone.

Breast Neoplasms↗
PubMed1992

No effect of dose, hepatic function, or nutritional status on 5-FU clearance following continuous (5-day), 5-FU infusion.

One hundred and eighty seven patients (155 males, 32 females) with histologically proven and previously untreated head and neck cancer were entered in the study. A total of 222 cycles of therapy were analyzed (cisplatin 100 mg m-2 on day 1 and 5-day continuous intravenous infusion of 5-FU 550-1069 mg m-2 day-1, mean 875.5 mg m-2 day-1). Significant interpatient variability for various 5-FU pharmacokinetic parameters was observed including an almost ten-fold range in 5-FU clearance (5-FU Cl, ml min-1 m-2 = 791-7769, mean 2820.7). Log 5-FU Cl was not modified by 5-FU dose (r = -0.1034, P = 0.124, n = 222). Poor linear correlations between log 5-FU Cl and hepatic function tests were observed (respective r and P values for 222 cycles, log AST:0.0526, 0.4365; Log ALT: -0.1167, 0.0842; Log A1K. Phos.:0.154, 0.0214; Log GGT: 0.0652, 0.3436; Log LDH: -0.0984, 0.1563; Log bilirubin: 0.1278, 0.0601). The log 5-FU Cl was also poorly correlated with the serum concentration of various nutritional proteins (respective r and P values for 222 cycles, Albumin: 0.0110, 0.8714; prealbumin: -0.1067, 0.1129; transferrin: 0.0439, 0.5226). Laboratory data including indices of hepatic function and nutritional status cannot account for the interpatient variability in 5-FU disposition.

Blood Proteins↗
PubMed1992

Vitiligo-like depigmentation and morpheas after specific intralymphatic immunotherapy for malignant melanoma.

We report the case of a patient with stage 2 malignant melanoma (MM), who received a specific immunotherapy consisting of intralymphatic injections of irradiated MM cells. She developed subsequently vitiligo-like leukoderma and several plaques of localized scleroderma. Simultaneously an increase in the patient's cytotoxic activity against MM cells was detected in vitro. The responsibility of immune phenomena and specific immunotherapy for the appearance of depigmentation and morpheas is discussed.

Aged↗
PubMed1992

Influence of sex and age on fluorouracil clearance.

PURPOSE: Currently, fluorouracil (5-FU) is one of the major drugs used in cancer chemotherapy. Several investigators, including ourselves, have demonstrated a link between abnormalities in 5-FU clearance (Cl) and the risk of developing more or less 5-FU-related toxicities. Age and sex are among the host factors that have been implicated in the pharmacokinetic variability of drugs. Presently, no data are available on the possible influence of sex and age on 5-FU Cl. PATIENTS AND METHODS: Three hundred eighty patients (mean age, 61.7 years; range, 25 to 91; 301 men and 79 women) with squamous cell carcinoma (sre) of the head and neck were treated in our institution between 1987 and 1991. 5-FU Cl was determined for a total of 1,092 chemotherapy cycles. Each cycle consisted of cisplatin and 5-day continuous intravenous infusion 5-FU (daily doses ranging between 365 and 1,224 mg/m2). RESULTS: 5-FU Cl values (L/h/m2) showed a wide dispersion for both men (median, 179; range, 29 to 739) and women (median, 155; range, 56 to 466). 5-FU Cl values were lower significantly for women compared with men (P = .0005). When adjusted for age and dose, the influence of sex on log Cl remained significant (P = .013). There was no evidence that age modified 5-FU Cl when adjusted for sex and dose. Interestingly, for both men and women, the oldest patients (greater than 70 years) maintained their ability to clear 5-FU with daily doses that ranged from 500 to 1,000 mg/m2. CONCLUSIONS: These data indicate that the capacities to clear 5-FU are lower in women compared with men and are not influenced by age. It would be of interest to know whether this sex-related difference in 5-FU Cl may be clinically relevant by considering both toxicity and tumor response to 5-FU treatment.

Adult↗
PubMed1992

Pharmacokinetics and pharmacodynamics of medroxyprogesterone acetate in advanced breast cancer patients.

PURPOSE: Medroxyprogesterone acetate (MPA) is one of the major drugs used in endocrine therapy for advanced breast cancer. However, its optimal dose still has not been clearly established. Response to treatment and drug-related side effects were analyzed as a function of plasma MPA concentrations during prolonged MPA treatment. PATIENTS AND METHODS: MPA plasma concentrations were measured (high-performance liquid chromatography [HPLC] assay) at steady state (Css min) in 129 patients (mean age, 63 years; range, 34 to 87) treated by MPA (86% were treated orally exclusively with daily doses ranging from 400 to 2,000 mg). RESULTS: A wide interpatient variability was noted in MPA Css min for the 70 patients who received 1,000 mg/d orally (median, 51 ng/mL; range, 10 to 269 ng/mL). Intrapatient analysis of the evolution of MPA Css min during prolonged treatment showed relative stability of MPA concentrations (mean CV, 20.6%). A weak but significant correlation was demonstrated between oral doses and MPA Css min (P = .016). Thirty-five percent of patients (45 of 129) developed MPA-related side effects that were associated with the highest plasma MPA concentrations; medians were 81 and 32 ng/mL for toxic and nontoxic treatments, respectively (P less than .001). Objective response was assessable in 55 patients who were treated by MPA exclusively. Plasma MPA concentrations were significantly different (P = .025) between patients with progressive disease (PD) (median, 46 ng/mL) and those with complete response (CR), partial response (PR), or stable disease (SD) (median 65 ng/mL). Comparison of CR plus PR versus SD versus PD showed only a tendency toward significant differences in MPA Css min (P = .07). Analysis of toxicity and response as a function of the oral dose did not show any significant relationship. These data suggested an optimal therapeutic window for MPA Css min located within 50 to 70 ng/mL. CONCLUSION: This study demonstrates that plasma MPA concentration, as opposed to the administered dose, is a determining factor for toxicity and response therapy [corrected].

Adult↗