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G Fournier

Publications and source records attributed to G Fournier.

At least 55 records · Page 3Linked to original sources
PubMed1998

Substitution of acetic acid for hydrochloric acid in the bicarbonate buffered dialysate.

In a multicenter study including 5 dialysis units, blood acetate changes during 4 h dialysis sessions in 141 patients treated with a 4 mM acetate-containing bicarbonate dialysate (ABD) were evaluated and compared to the values of 114 patients using an acetate-free bicarbonate dialysate (AFD). Acetate-free bicarbonate dialysate was delivered by a dialysis machine from the mixing with water for dialysis of a 1/26.2 bicarbonate concentrate, and a 1/35 acid-concentrate in which acetic acid was substituted for hydrochloric acid (Soludia, Fourquevaux, France). This new type of dialysate was routinely in use for 3 years on average (range, from 2 to 5 years). All patients fasted before and during dialysis. Blood samples were withdrawn at the start and at the end of dialysis sessions. The acetate plasma concentration was determined using the acetyl-CoA synthetase enzymatic method (Boehringer, Manheim, Germany). In patients treated with ABD whose predialysis blood acetate levels were in the physiologic range of < or = 100 microM (n = 113), the acetate plasma concentration increased from a predialysis mean value of 22+/-3 microM to a postdialysis mean value of 222+/-11 microM in 88 patients (78% of patients) whereas the acetate plasma concentration changes remained in the range of physiologic values from 21+/-6 to 58+/-7 microM in the other 25 patients. In contrast, patients treated with AFD whose predialysis blood acetate levels were in the physiologic range (n = 108), acetate plasma concentration increased from a predialysis mean value of 49+/-6 microM to 160+/-19 microM in only 13 patients (12% of patients) whereas acetate plasma concentration changes remained in the range of physiologic values of 23+/-2 to 41+/-3 microM in most of the patients of this group. In this study, a significant number of patients, whether receiving standard or acetate-free bicarbonate dialysates, exhibited an extremely high acetate plasma concentration at the start of the dialysis session. Hyperacetatemia was controlled with AFD in patients whose predialysis acetate plasma concentration of 316+/-82 decreased to 55 +/-23 microM (n = 6) at the end of the dialysis session whereas the acetate plasma concentration remained high when the predialysis concentration was 580+/-76 microM, with a postdialysis concentration of 233+/-39 microM (n = 28). It is concluded that in patients whose predialysis blood acetate levels were in the physiologic range, acetate-containing bicarbonate dialysate induces hyperacetatemia whereas postdialysis blood acetate remains in the normal range in such dialysis patients treated with acetate-free dialysate. Chronic hyperacetatemia, which could be found in dialysis patients, is well controlled by dialysis using an acetate-free dialysate.

Acetate-CoA Ligase↗
PubMed1998

Predisposing gene for early-onset prostate cancer, localized on chromosome 1q42.2-43.

There is genetic predisposition associated with >=10% of all cancer of the prostate (CaP). By means of a genomewide search on a selection of 47 French and German families, parametric and nonparametric linkage (NPL) analysis allowed identification of a locus, on chromosome 1q42.2-43, carrying a putative predisposing gene for CaP (PCaP). The primary localization was confirmed with several markers, by use of three different genetic models. We obtained a maximum two-point LOD score of 2.7 with marker D1S2785. Multipoint parametric and NPL analysis yielded maximum HLOD and NPL scores of 2.2 and 3.1, respectively, with an associated P value of . 001. Homogeneity analysis with multipoint LOD scores gave an estimate of the proportion of families with linkage to this locus of 50%, with a likelihood ratio of 157/1 in favor of heterogeneity. Furthermore, the 9/47 families with early-onset CaP at age <60 years gave multipoint LOD and NPL scores of 3.31 and 3.32, respectively, with P = .001.

Age of Onset↗
PubMed1998

Hereditary prostate cancer and other genetic predispositions to prostate cancer.

The incidence of prostate cancer (CaP) and its increase in the last 10 years vary both from country to country and according to the ethnic group, with the highest incidence reported for Afro-Americans and the lowest for Asian men. To date, only three risk factors have been established for CaP: age; familial aggregation of CaP, and ethnic origins. No dietary or environment-related cause has been established. However, some variations in endogenous genetic factors may help explain differences in risk among ethnic groups or geographic areas. Similarly, certain genetic polymorphisms of genes encoding for 5alpha-reductase, androgen receptor or vitamin D, have been associated with different levels of CaP risk, and could explain the variations observed between populations. Different studies support the view that familial CaP may truly be hereditary, and not due to a similar lifestyle. Thus, familial inheritance is a parameter that needs to be considered in recommending screening for high-risk families. Indeed, when 1, 2, and 3 first-degree relatives are affected, the relative risk of first-degree relatives of CaP patients may increase to 2, 5, and 11%, respectively. Some familial forms appear to be associated with transmission of a rare putative dominant gene with a high penetrance (88% at age 85), with the cumulative proportion of CaP attributable to this gene being more marked for younger patients (a 43 versus a 34% risk of CaP appearing before the age of 55 versus 70 years). Using this transmission model and linkage analysis, a predisposing locus on chromosome 1q24-25 (HPC-1) has been described. Moreover, recessive and X-linked transmission has been suggested, showing that a large proportion of familial CaP may not be due to segregation of a few major gene mutations, but rather to familial sharing of alleles at many loci, each contributing to a small increase in cancer risk. Candidate genes may be the same suppressor genes that are involved in other cancers and in sporadic CaP.

Aged↗
PubMed1998

Thrombolysis with intravenous rtPA in a series of 100 cases of acute carotid territory stroke: determination of etiological, topographic, and radiological outcome factors.

BACKGROUND AND PURPOSE: Although new, large, double-blind, randomized studies are needed to establish the efficiency of intravenous thrombolysis, open trials of sufficient size may also provide novel data concerning specific outcomes after thrombolysis. METHODS: An open study of intravenous rtPA in 100 patients with internal carotid artery (ICA) territory strokes between 20 and 81 years of age, with a baseline Scandinavian Stroke Scale (SSS) score of <48 at entry was conducted. Inclusion time was within 7 hours after stroke onset. rtPA (0.8 mg/kg) was infused for 90 minutes, with an initial 10% bolus. Heparin was given according to 3 consecutive protocols. The SSS evaluation was done on days 0, 1, 7, 30, and 90. CT scan was performed before treatment, on days 1 and 7. Etiological investigations included echocardiography and carotid Doppler sonography and/or angiography. Outcome at 1 year was documented by SSS score, the modified Rankin Scale (mRS) score, and a 10-point invalidity scale. Multivariate logistic regression was used to identify predictors of poor versus good outcome. RESULTS: At day 90, 45 patients (45%) had a good result, defined as complete regression or slight neurological sequelae (mRS score of 0-1), 18 patients had a moderate outcome (mRS 2-3), and 31 patients had serious neurological sequelae (mRS 4-5). Six patients died, 2 with intracerebral hematoma after immediate heparin. Five of 11 patients (45.5%) treated between 6 and 7 hours had a good result. The overall intracerebral hematoma rate was 7%. Higher values of fibrin degradation products at 2 hours were observed in the subgroup with intracerebral hematomas. Significant predictors of poor outcome on multivariate logistic regression analysis were baseline SSS score of <15 (odds ratio [OR], 3.38; 95% confidence interval [CI], 1.07 to 10. 74; P=0.04), indistinction between white and gray matter on CT scan (OR, 6.59; 95% CI, 2.19 to 19.79; P=0.0008), and proximal internal carotid thrombosis (OR, 3.29; 95% CI, 0.99 to 10.95; P=0.05). CONCLUSIONS: Our study confirms the safety of intravenous rtPA at a dose of 0.8 mg/kg and suggests efficacy for this drug even within 7 hours. Outcome and hematoma rates were at least as favorable as for trials of therapy with a 3-hour time window. Subgroups with a poor prognosis include low baseline neurological score, baseline CT changes, and proximal ICA thrombosis. However, approximately 30% of patients with each of these characteristics show a good outcome, so their inclusion in future routine rtPA protocols is still justified.

Adult↗
PubMed1998

Doxorubicin prodrugs with reduced cytotoxicity suited for tumour-specific activation.

The three new hydrophilic prodrugs 2, 3 and 4 have been prepared from methyl (4-hydroxymethyl-2-nitrophenyl 2,3,4-tri-O-acetyl-beta-D-glucopyranosid)uronate (5) and doxorubicin. Their low cytotoxicity, efficient release of doxorubicin after hydrolysis by beta-D-glucuronidase, and in the cases of 2 and 3 stability at pH 7.2 fulfil the preliminary requirement for their use in antibody-directed enzyme prodrug therapy or prodrug monotherapy.

Antibiotics, Antineoplastic↗
PubMed1998

[Clinical stage T3 prostate cancer: natural history, therapeutic choices and their results].

Clinical stage T3 prostate cancer is ambiguous both in terms of its definition and its place in the natural history of the disease, and there is no consensus concerning its treatment. In a review of the literature, 148 articles were selected and analysed from the Medline database over a 14-year period (1983-1997). Single-agent therapy: Radiotherapy and radical prostatectomy: it is unlikely that these treatments can cure clinical stage T3 prostatic cancer, except perhaps for a small minority of patients actually presenting with overstaged pT2 disease or certain forms of low-grade pT3. Neither treatment appears to have any advantage over the other-Endocrine therapy: it has been proposed as exclusive treatment at this stage. Few studies have been reported. However, many authors consider this choice to be legitimate, because one-half of patients already have lymph node involvement. Combination therapy: Radiotherapy and endocrine therapy: recent studies comparing exclusive external beram radiotherapy with endocrine therapy show an advantage in favour of combination therapy. Total prostatectomy and endocrine therapy: neoadjuvant endocrine therapy does not provide any advantage. Adjuvant endocrine therapy improves local control and progression-free survival. Adjuvant radiotherapy and radical prostatectomy provides no advantage for T3. The choice of treatment for stage T3, N0, M0 obviously depends on the patient's general state and life expectancy. If the option of a curative treatment in a young subject can be reasonably considered, combination therapy should be preferred.

Adult↗
PubMed1997

Cytochrome P450 4A and 2E1 expression in human kidney microsomes.

Laurate and arachidonate omega and (omega-1)-hydroxylase activities, cytochrome P450 2E1 (CYP2E1), and CYP4A content were measured in 18 human kidney microsomal samples. The rates of laurate and arachidonate were found to be very different from those measured in human liver samples, with a laurate omega/omega-1 ratio of approximately 22 in human kidney vs 0.75 in human liver. Immunoblot analysis of the 18 human kidney microsomal samples identified 1 CYP4A electrophoretic band, but CYP2E1 was not detectable in human kidney, contrary to liver. Laurate and arachidonate omega-hydroxylase activities were significantly correlated with CYP4A content (r = 0.86 and 0.75, respectively). Polyclonal antirat CYP2E1 antibody did not affect omega-hydroxylase activity, whereas the polyclonal antirat CYP4A1 antibody inhibited it by 60%. These results suggest that, in contrast to other species, human kidney microsomes do not contain significant amounts of CYP2E1, but possess CYP4A and fatty acid omega-hydroxylase activity.

Adult↗
PubMed1997

Loss of heterozygosity at chromosome 16q in prostate adenocarcinoma: identification of three independent regions.

Loss of heterozygosity (LOH) on chromosome arm 16q is one of the most consistent genetic alterations in sporadic prostate cancer and may be involved in cancer development through inactivation of tumor suppressor genes. A candidate tumor suppressor gene on this chromosome arm, CDH1 at 16q22.1, is dysregulated in prostate cancer. However, no specific deletion map has been constructed from prostate tumors to determine whether CDH1 is the potential target gene for the observed LOH on 16q. To narrow down the region of 16q loss, we constructed a detailed deletion map that incorporates CDH1. We examined the pattern of allelic imbalance in prostate tissue from 22 patients with confined prostate tumors, 22 with local extracapsular extension, and 15 with metastatic forms, using 14 CA microsatellite repeats on 16q. Thirty-five of the 59 tumors tested showed LOH for at least one marker. We found evidence of 16q monosomy in 5 cases and partial allelic loss in 30. Our data provide evidence that three different target regions on 16q might be involved in the pathogenesis of prostate cancer. The first region is telomeric and lies at 16q24.3 between markers D16S520 and D16S413; the second, the most centromeric region in the 16q22.1 band, and limited by markers D16S347 and D16S318, is close to the CDH1 gene; the third, intermediate region, at 16q23.2, is bracketed by loci D16S518 and D16S507. The rate of LOH at 16q24.3 was significantly higher in metastatic forms (80%; 12 of 15) than localized forms (32%; 7 of 22), pointing to a gene related to invasiveness in prostate cancer.

Adenocarcinoma↗
PubMed1997

Facial mask noninvasive mechanical ventilation reduces the incidence of nosocomial pneumonia. A prospective epidemiological survey from a single ICU.

OBJECTIVE: To evaluate the impact of noninvasive positive pressure mechanical ventilation (NPPV) on ventilator-associated pneumonia (VAP). DESIGN: Prospective observational study. SETTING: Medical intensive care unit (ICU) of a university teaching hospital. PATIENTS: Cohort of 320 consecutive patients staying in the ICU more than 2 days and mechanically ventilated for > or = 1 day. MEASUREMENTS AND RESULTS: VAP was diagnosed when, satisfying classical clinical and radiological criteria, fiberoptic bronchoalveolar lavage and/or protected specimen brush grew > or = 10(4) and > or = 10(3) CFU/ml, respectively, of at least one microorganism. Patients were classified into four subgroups according to the way in which mechanical ventilation was delivered: NPPV then tracheal intubation (TI) (n = 38), TI then NPPV (n = 23), TI only (n = 199), and NPPV only (n = 60). Occurrence of VAP was estimated by incidence rate and density of incidence. Risk factors for VAP were assessed by logistic regression analysis. Twenty-seven patients had 28 episodes of VAP. The incidence rates for patients with VAP were 18% in NPPV-TI, 22% in TI-NPPV, 8% in TI, and 0% in NPPV (p < 0.0001). The density of incidence of VAP was 0.85 per 100 days of TI and 0.16 per 100 days of NPPV (p = 0.04). Logistic regression showed that length of ICU stay and ventilatory support were associated with VAP. CONCLUSIONS: There is a significantly lower incidence of VAP associated with NPPV compared to tracheal intubation. This is mainly explained by differences in patient severity and risk exposure.

APACHE↗
PubMed1997

Small airway closure and positive end-expiratory pressure in mechanically ventilated patients with chronic obstructive pulmonary disease.

The effects of positive end-expiratory pressure (PEEP) on alveolar recruitment and closing volume were studied in ten supine, sedated, and paralyzed patients with chronic obstructive respiratory disease and acute respiratory failure. We applied PEEP (0, 5, 10, and 15 cm H2O) and constructed inflation static volume-pressure (V-P) curves. In all patients, the static V-P curves obtained at different PEEP levels were superimposed on each other, indicating that with PEEP there was no recruitment of previously atelectatic lung units. However, the static V-P curves exhibited an inflection point, which should reflect the critical pressure (Po) required to reopen all closed airways, whilst the corresponding lung volume (Vo) reflects the opening volume. On average, Vo was 0.71 L above the relaxation volume of the respiratory system (Vr). All patients, however, exhibited dynamic hyperinflation, i.e., with zero PEEP (ZEEP) the end-expiratory lung volume (EELV) was 0.54 L above Vr. Nevertheless, in seven patients the EELV on ZEEP was below Vo, resulting in cyclic reopening and closure of small airways with each breathing cycle, with concomitant mechanical stresses on the peripheral airways that may lead to low-volume barotrauma. Such barotrauma may be prevented by increasing with PEEP the EELV to Vo.

Acute Disease↗
PubMed1997

Flutamide versus orchidectomy in the treatment of metastatic prostate carcinoma.

PURPOSE: To compare in a randomized clinical trial the therapeutic efficacy of the nonsteroidal antiandrogen flutamide 250 mg tid to testicular androgen suppression by orchidectomy in patients with metastatic prostate cancer. PATIENTS AND METHODS: Between 1989 and 1991, 104 patients aged 74 +/- 8 years with newly diagnosed metastatic prostate cancer, an ECOG performance status 0-2 and no prior hormone manipulation or chemotherapy, were randomized to receive flutamide 250 mg tid (54 patients) or orchidectomy (50 patients). Patients were evaluated at entry and at months 3, 6, 12, 18 and 24. The primary endpoint was duration of progression-free survival, progression being defined as an increase in PSA> 50% over the nadir value at 2 consecutive months or a single PSA rise > 50% over the nadir value with another objective parameter. At progression, the treatment was left to the discretion of the attending urologist. RESULTS: 16 patients (10 flutamide, 6 orchidectomy) are not evaluable. 86 had a minimum follow-up of 36 months, 36/42 and 41/44 have progressed in the orchidectomy and flutamide group with a time of failure of 419 and 496 days (p = 0.32); median time to progression was almost identical in both groups (370 vs. 396 days p = 0.9); overall survival at 69 months irrespective of treatment at relapse was identical in both groups. Side effects were dominated by gynecomastia, hot flushes in both groups, breast tenderness and diarrhea in the flutamide group. Overall, 4 (10%) of the patients in the flutamide group withdrew from therapy because of side effects. The impact of flutamide on sexual potency was not assessed because of the advanced age of the patients. Serum testosterone rose by 50% over baseline level at month 3 to plateau at 25% over baseline level at month 12. CONCLUSION: Although affected by the lack of a clear statistical power due to the small number of patients in each arm, this study shows that in spite of a constant elevation of serum testosterone (25% over baseline) flutamide 250 mg tid may be a reasonable alternative to castration in highly selected patients with well to moderately differentiated low volume metastatic prostate cancer and wishing to avoid the side effects of androgen deprivation, provided they are closely monitored and ready to switch to standard androgen deprivation in the presence of untolerable side effects or suboptimal treatment efficacy as assessed by the inability to achieve a low PSA nadir.

Aged↗
PubMed1996

Serum and erythrocyte magnesium in critically ill patients.

OBJECTIVES: To evaluate the prevalence of serum and erythrocyte magnesium (Mg) abnormalities in patients on admission to the intensive care unit (ICU) and to test the hypothesis that low levels of Mg are associated with a higher mortality. DESIGN: Prospective study. SETTING: 14-bed ICU in a 1000-bed teaching hospital. PATIENTS: 179 consecutive patients admitted over a 4-month period. MEASUREMENTS: Total serum Mg (Mgs) and erythrocyte Mg (Mge) were determined on admission by atomic absorption spectrophotometry. Severity of illness was assessed by Acute Physiology and Chronic Health Evaluation (APACHE) II and the number of organ system failures (OSF) during the first 24 h. The patients were followed up until discharge from hospital. MAIN RESULTS: On admission, 79 patients (44%) were hypomagnesemic and 10 (6%) were hypermagnesemic. A low level of Mge was observed in 119 patients (66%). In patients with similar APACHE II scores and OSF numbers, more of those with hyperMgs died during their ICU stay. However, the Mge value on admission did not correlate with patient outcome. CONCLUSIONS: We confirm the high prevalence of Mgs abnormalities as well as Mg deficiency on admission to a medical ICU. Low levels of Mgs and Mge are not associated with higher fatality. HyperMgs was associated with patient death.

APACHE↗
PubMed1996

Nephrogenic adenoma of the bladder in renal transplant recipients: a report of 9 cases with assessment of deoxyribonucleic acid ploidy and long-term followup.

PURPOSE: We evaluated the outcome of nephrogenic adenoma, a benign tumor rarely encountered in renal transplant recipients. MATERIALS AND METHODS: Between 1985 and 1993, 9 renal transplant recipients with a nephrogenic bladder adenoma removed by endoscopic resection were followed for 24 to 88 months (mean 40). Tumor deoxyribonucleic acid ploidy was assessed by flow cytometry at diagnosis and/or relapse. RESULTS: The relapse rate was 88%. The tumors were diploid and of low proliferating potential, and showed no malignant transformation. CONCLUSIONS: Our study confirms the lack of premalignant potential of nephrogenic adenomas. However, since transplant recipients might be at increased risk for bladder cancer, they should be followed closely.

Adenoma↗
PubMed1996

Treatment of hormone-refractory prostate carcinoma.

OBJECTIVES: To review the treatment of hormone-refractory prostate cancer (HRPC). INTRODUCTION: Almost all patients with metastatic prostatic cancer will eventually escape the control of the first-line endocrine therapy, and relapse. This escape occurs in the majority of patients after a median time of 12-18 months, and 1-year median survival is only 50%. Therefore, additional treatments are needed for men who have disease progression in the presence of castrate levels of serum testosterone. SECOND-LINE TREATMENT: Available second-line therapeutic modalities in relapsed prostatic cancer include endocrine manipulations, chemotherapy, combined endocrine and cytotoxic therapy, and new drugs like suramin. Despite relieving symptoms in some patients, these treatments have a limited capacity to prolong survival. Moreover, potential toxicity of these therapeutic regimens must also be taken into account in order to maintain quality of life. Finally, other palliative adjunctive treatments like analgesic support, radiation therapy for painful bone metastasis (either external beam or isotopic radiotherapy), or locoregional procedures for symptomatic primary tumors (transurethral resection, urinary diversion) have a central role in the therapeutic strategy.

Androgen Antagonists↗
PubMed1996

Open trial of intravenous tissue plasminogen activator in acute carotid territory stroke. Correlations of outcome with clinical and radiological data.

BACKGROUND AND PURPOSE: Pilot studies using early thrombolytic therapy in stroke have suggested that recombinant tissue plasminogen activator (rTPA) might be effective. While large, double-blind, randomized studies are needed, open trials could generate hypotheses concerning (1) the clinical correlations of outcome, (2) the significance of CT scan data during the first week, and (3) the use of adjunctive therapies. METHODS: We performed an open trial of intravenous rTPA on patients referred to our emergency service with all types of ischemic stroke in the carotid territory. All patients between 20 and 81 years hospitalized during 1994 with completed stroke in the internal carotid artery territory and a baseline Scandinavian Stroke Scale score lower than 48, even with severe disturbances of consciousness, were included. The inclusion time was within 7 hours after stroke onset. A 0.8-mg/kg dose of rTPA was infused for 90 minutes. Intravenous heparin was given either immediately at efficient dosage or after 24 hours. Mannitol was used in patients with severe presentation. The Scandinavian Stroke Scale evaluation was done at baseline, 3 hours, and 1, 7, 30, and 90 days. The CT scan was performed before the treatment and at days 1 (24 +/- 6 hours) and 7. RESULTS: Forty-three consecutive patients met the criteria of the protocol. The mean age at inclusion was 65 +/- 10.4 years, and the mean interval to treatment was 232 +/- 79 minutes. At day 90, 25 patients (58.1%) exhibited a complete regression of symptoms, and 3 had moderate neurological sequelae. Thirteen patients had severe neurological sequelae, 11 with infarcts and 2 with secondary parenchymal hematomas. Two patients died (4.6%), 1 with hematoma. The overall hematoma rate was 6.9%. Excellent outcome at day 90 was significantly correlated with major neurological improvement at day 1. Intravenous immediate heparin versus delayed heparin after 24 hours improved the ischemic outcome but not the overall outcome. Reinfarction syndromes after major neurological improvement, likely to be rethrombosis syndromes, were observed in 3 patients (6.9%). For the day 1 CT scan, poor outcome was associated with the presence of structured and homogeneous hypodensities likely to represent classic infarcts, as confirmed by day 7 CT scan. Conversely, total recovery was significantly associated with the absence of any image or with unstructured hypodensities, a particular type of image characterized by its heterogeneous darkness and often polylobar shape. This type of image disappeared at day 7 in 17.6% of the cases and is likely to represent reperfusion images and/or incomplete ischemic damage. CONCLUSIONS: The results obtained in this open, small study suggest safety and effectiveness of rTPA thrombolysis at the dose of 0.8 mg/kg within 7 hours in acute strokes of the carotid territory, including highly serious baseline neurological presentations, until age 81 years and under special therapeutic conditions. Complete recovery is significantly associated with major neurological improvement during the first 24 hours and the presence of a particular type of image at day 1 CT scan characterized by an unstructured hypodensity, often polylobar and heterogeneous, which is likely to correspond to reperfusion images.

Adult↗