New aspects of urolithiasis in France. GERBAP: Groupe d'Evaluation et de Recherche des Biologistes de l'Assistance Publique des Hôpitaux de Paris.

OBJECTIVE: To confirm epidemiological studies showing a continuous progression of calcium oxalate nephrolithiasis in western countries, we investigated some aspects of the evolution of stone disease in France. METHODS: Calculi collected from 1977 to 1993 in 10,438 adult French patients were analyzed by infrared spectroscopy. Only 8,631 well-documented cases were available. The anatomical location, the removal mode of calculi, and the time evolution of stone composition were studied. RESULTS: The stones were more often retained in the upper urinary tract in females than in males and needed urological removal. Uric acid stones were more frequently observed on the left side in both sexes (p < 0.0001). Extracorporeal shock wave lithotripsy seems to have been used for a time in calculi which would have been spontaneously discharged. Calcium oxalate stones were preponderant, but their proportion did not change in both sexes. A significant decrease of the proportion of calcium phosphate stones was observed in females (p < 0.0001), probably responsible for the increase of the male/female sex ratio from 1.7 to 2.4. CONCLUSIONS: From our observations and from the evolution of dietary habits in France, it can be deduced that urolithiasis trends to a plateau.

High dose chemotherapy with ifosfamide, carboplatin, and etoposide combined with autologous bone marrow transplantation for the treatment of poor-prognosis germ cell tumors and metastatic trophoblastic disease in adults.

BACKGROUND: A Phase I-II trial to assess the toxicity and efficacy of a tandem high dose chemotherapy combining ifosfamide, carboplatin, and etoposide in germ cell tumors and metastatic trophoblastic disease was performed. METHODS: Thirty-nine patients, with a total of 22 testicular tumors, 9 extragonadal germ cell tumors, 3 ovarian germ cell tumors, and 5 cases of metastatic trophoblastic disease, received tandem high dose therapy combining ifosfamide (7500-12,500 mg/m2), carboplatin (875-1225 mg/m2), and etoposide (1000-1250 mg/m2), followed by bone marrow reinfusion. Among the 39 patients, 33 were refractory to cisplatin- or carboplatin-based regimen and the response of 37 could be evaluated; 69 cycles of this tandem high dose therapy were administered. RESULTS: The overall response rate was 46%, including a complete response (CR) rate of 35%. Of 21 patients with testicular tumors who could be evaluated, 10 (47%) achieved a CR. No CRs were obtained in patients with refractory extragonadal germ cell tumors. Nine partial responders after the first cycle became complete responders after the second. Nine (23%) of the patients were long term survivors (> 18 months), 7 of them in continuous CR. Side effects primarily were renal toxicity and enterocolitis. Seven patients (18%) died of therapy-related be explored and the maximum tolerated doses of this three-drug regimen remain to be determined. CONCLUSION: This tandem therapeutic regimen is able to overcome resistance to a platinum-based regimen in highly refractory germ cell tumors and gestational trophoblastic disease and to cure a number of patients.

Sex- and age-related composition of 10 617 calculi analyzed by infrared spectroscopy.

A series of 10 617 calculi were analyzed by stereomicroscopy and infrared spectroscopy. This first study of French calculi was compared with large series in the literature. That the frequency of pure calculi was the lowest ever observed can be related to the methodology routinely used in our laboratory, which includes microsampling. We described more than 70 components among the 10 617 calculi. The overall sex ratio male to female patients was high (2.27) and increased over the period 1981-1993. Calcium oxalate was the most frequent component (86.48%), followed by calcium phosphate (79.75%) and purines (18.64%). We found a low occurrence of "infection" stones. The sex ratio was related to stone composition and differed according to the main component. For instance, calcium oxalate dihydrate (COD) was more frequent in men than in women, with a sex ratio of 4.97 versus 2.57 for calcium oxalate monohydrate (COM). On the contrary, calcium phosphate was more frequent in female patients (sex ratio 0.72 versus overall ratio). The high frequency of COD calculi (23.17%) suggests that hypercalciuria is particularly frequent in French patients susceptible to stone formation. For each main component, a specific profile was observed in relation to the sex and age of the patients with stones.

Phase I-II study of two consecutive courses of high-dose epipodophyllotoxin, ifosfamide, and carboplatin with autologous bone marrow transplantation for treatment of adult patients with solid tumors.

We describe a phase I-II study of two consecutive 5-day courses of a three-drug regimen of ifosfamide (IFM), carboplatin (CBDCA), and either etoposide (VP-16) (regimen 1) or teniposide (VM-26) (regimen 2) in high doses together with autologous bone marrow transplantation (ABMT), for previously treated patients with ovarian carcinoma (OC), germ cell tumors (GCT), gestational trophoblastic disease (GTD), or oat cell carcinoma (OCC). Forty-four patients entered the study. Two patients with OC received regimen 1, and 22 were given regimen 2. Sixteen patients with GCT, two with GTD, and two with OCC were treated with regimen 1. Six patients (13%) died of toxicity. Nephropathy and esophagitis were the dose-limiting toxic effects. The maximum-tolerated doses (MTDs) were 1,500 and 200 mg/m2/d for 5 days for IFM and CBDCA, respectively, in combination with VP-16 250 mg/m2/d for 5 days (regimen 1), and 150, 1,500, and 200 mg/m2/d for 5 days for VM-26, IFM, and CBDCA, respectively (regimen 2). The response rate of patients with OC was 78% (complete response [CR], 14%). For patients previously resistant to chemotherapy, the response rate was 70%. There were no long-term disease-free survivors among patients with OC. The response rate of patients with GCT was 60% (CR, 33%). All responders with GCT were resistant to previous chemotherapy. Unmaintained CRs lasted 2, 6, 8+, 27+, and 37+ months. Of the two patients with GTD, one with previous resistance to chemotherapy attained a CR of 18+ months. One patient with OCC attained a CR lasting 6 months. The regimen possesses great antitumor activity. It produced CRs of long duration in a number of patients with GCT and GTD who were previously resistant to chemotherapy.

[Evaluation of enzymuria as a tracer in nephrotoxicity: results of a multicenter study]. / Evaluation de l'enzymurie comme marqueur de néphrotoxicité: résultats d'une expérience multicentrique.

Urinary excretion of three enzymes of different subcellular location in kidney tissue, alanine aminopeptidase (AAP), gammaglutamyltransferase (GGT), N acetyl-beta-D glucosaminidase (NAG), was carried out in 79 healthy adults and 108 healthy children and in 69 adults with various therapies: antibiotics (32 cases), non steroidal anti-inflammatory drugs (NSAIDs) (22 cases), cisplatinum (12 cases) and cyclosporine (3 cases). A circadian rhythm has been shown in children. In patients treated with antibiotics, the importance and duration of the increased enzymes urinary excretion were variable but the excretion of AAP was always higher than that of GGT and NAG. Short term therapies by NSAIDs were without influence on enzymuria but long term therapies produced a moderate increase of NAG excretion. Enzymuria increased immediately after cisplatinum administration and decreased after each daily dose, except in patients with previously high creatininemia. Cyclosporine induced a slight increase in AAP and NAG excretion. Enzymuria, thus, increased early reflecting a toxic effect of the drug at the cellular level whereas creatininemia increase, marker of renal fonctionnal insufficiency, occurs only occasionally and lately.

[Measurement of maternal plasma volume during pregnancy]. / Mesure du volume plasmatique maternel au cours de la grossesse.

An increased maternal plasma volume (PV) is a characteristic phenomenon of normal pregnancy, which may be related to a physiological decrease of peripheral resistances. The authors have studied the plasma volume of 1,105 patients distributed as follows: normal (387), permanently hypertensive patients (84), hypertensive patients during pregnancy (390), patients with apparently isolated RCIU (154) or with a pathological past-history during previous pregnancies (90). It appears that the PV is a sign of a severe HBP, and presents a rather early and good predictive value regarding the weight of the fetus and some complications such as severe UCIU and fetal death in utero. In case of pathological past events or pre-existing hypertension, the PV enables to differentiate rather well patients who will be prone to a complicated pregnancy. In view of these results, utilization and interpretation criteria of this parameter during pregnancies with hypertension or pregnancies in which there is a suspicion or a risk of intra-uterine growth delay, are defined.

Study of beta-glucosidase from Helix pomatia by active site-directed inhibitors.

This work describes the purification of a beta-glucosidase (beta-D-glucoside-glucohydrolase EC 3.2.1.21) from the digestive juice of Helix pomatia and the study of the enzyme's active site by using different reversible and irreversible inhibitors. The catalytic constants of arylglycosides and their pH-dependent variations have also been determined. The inhibition studies demonstrate that conduritol epoxides are irreversible inhibitors of beta-glucosidase from the digestive juice of H. pomatia, and that nojirimicin shows tight binding with glucosidase: the formation and dissociation of the enzyme-inhibitor complex (dissociation constant 1.1 mumol/1) required several minutes.

Prevention of pre-eclampsia by early antiplatelet therapy.

102 patients at high risk of pre-eclampsia and/or fetal growth retardation were randomly allocated to treatment with 300 mg dipyridamole and 150 mg aspirin daily from 3 months' gestation onwards (group A) or to the control group (group B, no treatment). Group A was twice as likely as group B to have a normal pregnancy. Pre-eclampsia occurred in 6 patients in group B and none in group A. Major complications (fetal death or severe growth retardation) occurred in 9 patients in group B and none in group A. Platelet count and plasma volume were significantly higher in group A than in group B throughout pregnancy. The treatment did not produce serious adverse effects. Antiplatelet therapy given early in pregnancy to high-risk patients may thus protect against pre-eclampsia and fetal growth retardation.

[Controlled trial of preventive treatment of preeclampsia. Preliminary results]. / Essai contrôle d'un traitement préventif de la prééclampsie. Résultats préliminaires.

We selected 100 patients at high risk for having preeclampsia and/or intrauterine growth retardation, on the basis of their past obstetrical history. At three months, they were randomly allocated to treatment group (group A) receiving dipyridamole (300 mg/day) and low dose aspirin (150 mg/day) until delivery, or control group (group B). Age and parity were similar in both groups. 90 patients have delivered at this time. The pregnancy was normal in 54% of patients in group A and 23% in group B (p less than 0.01). Preeclampsia occurred in 6 patients in group A, none in group B (p less than 0.01). Fetal loss occurred in 5 patients in group B, none in group A (p less than 0.01). Duration of pregnancy, as well as fetal and placental weights were significantly higher in group A, and IUGR significantly less frequent. It is concluded that inhibition of platelet aggregation, when used early in pregnancy, may have a significant protective effect against preeclampsia and IUGR in high risk subjects.

Two successive pregnancies in a woman with xanthinuria: unexpected increase in serum uric acid levels.

Two successive pregnancies were observed in a patient with xanthinuria. In each of them, maternal serum uric acid (SUA) level rose progressively during the third trimester, reaching a subnormal value just before delivery. The level of UA was slightly higher in arterial cord blood than in maternal blood. There was no difference between levels in arterial and venous cord blood. It is suggested that xanthine oxydase may be present in the placenta.