[Economic and organizational impact of the use of a disposable sheath with a flexible cystoscope]. / Cystoscope flexible à gaine stérile à usage unique: impact organisationnel et économique et sécurité bactériologique.

PURPOSE: To assess both economical and organizational impact as well as bacteriologic safety of a flexible cystoscope with sterile disposable sheath (FCSDS) compared to standard flexible cystoscopy (SFC) in two French urologic academic units. PATIENTS: Two-center prospective study, comparing the use of the FCSDS to the SFC on two consecutive periods of time. Two hundred and five patients were included and divided into each group. Duration procedures and costs were analysed in the two techniques. The urinary tract infection rate was also described. A dedicated sheaths leaks test after use was performed systematically. RESULTS: The preparation time of the fibroscope was longer for the sheathed cystoscopy group: 16.2 minutes versus 10.9 minutes for the standard group. The mean duration of disinfection was significantly shorter for the sheathed cystoscopy group: 53.8 minutes saved compared to the standard group; 99.01% of the tested sheaths, after their use, had no breaches. Urinary tract infections rate were similar in the two groups. The average cost of a sheathed cystoscopy compared to the standard was significantly cheaper in Lyon and almost equivalent in Marseille. CONCLUSION: The FCSDS allows significant saving over the disinfection duration, consumable costs and staff costs, while ensuring patient bacteriologic safety similar to SFC.

[Female stress incontinence treatment: urethral slings]. / Traitement de l'incontinence urinaire d'effort féminine : les bandelettes sous-urétrales.

Female stress incontinence is often the consequences of obstetrical traumatisms. They are responsible of a weakness of perineal musculoaponevrotic structures. Until 1996, the reference treatment of this pathology was the "Burch" colposuspension, by laparotomy, then laparoscopic way. After 1996, a new procedure was developped by Ulmten, reproducible, easy, safe and mini-invasive: the tension free-vaginal-tape (TVT) followed by the trans-obturator-tape (TOT). This therapeutic tool has become the reference for the treatment of the female stress incontinence. There are now 15 years from the beginning of this procedure and still 80% of the patients are improved.

Intermediate chains of exopolysaccharides from Lactobacillus rhamnosus RW-9595M increase IL-10 production by macrophages.

AIMS: To evaluate the immunosuppressive properties of the exopolysaccharide (EPS) from high-EPS producer Lactobacillus rhamnosus RW-9595M on inflammatory cytokines produced by macrophages. METHODS AND RESULTS: The conditioned media (CM) were produced by macrophages treated with parental Lact. rhamnosus ATCC 9595 and its isogenic variant, the high-EPS producer Lact. rhamnosus RW-9595M, and the levels of TNF-alpha, IL-6, IL-10 and IL-12 were evaluated. Results revealed that CM from parental Lact. rhamnosus induced higher levels of TNF-alpha, IL-6 and IL-12 but inhibited IL-10 production, whereas its mucous variant induced low or no TNF-alpha and IL-6. Addition of purified EPS to macrophages treated with parental Lact. rhamnosus decreased the inflammatory cytokines and inhibited the metabolic activity of lymphocytes. The intermediate polysaccharide chains (16-30 units) produced by time-controlled hydrolysis of EPS increased the IL-10 produced by macrophages. CONCLUSIONS: Polysaccharide chains of EPS induced immunosuppression by the production of macrophagic anti-inflammatory IL-10. SIGNIFICANCE AND IMPACT OF THE STUDY: These results indicate that the EPS from Lact. rhamnosus RW-9595M may be useful as a new immunosuppressive product in dairy food.

[Economic evaluation of deflexible ureteroscopy with laser]. / Evaluation économique de l'urétéroscopie souple laser.

PURPOSE: The purpose of our study was to make an evaluation of the effective cost of a session of deflexible ureteroscopy with laser to cure kidney stones and kidney urothelials tumors. MATERIAL: This cost was calculated based on 103 sessions (83 kidney stones, 18 urothelials tumors, one cyst and one endopyelotomy) carried out on 73 patients and was including (1) staff expenses in the operation room (based on work time stated on the anesthesia sheet); (2) material expenses: technically specific or not. Reusable or single use; (3) amortisement of medical supply calculated on a seven year basis; (4) hospital stay. In this study medical logistic expenses and administrative expenses were not taken into account as well as structural expenses which were considered apart of this activity. RESULTS: Cost of a laser deflexible ureteroscopy was estimated by more or less 4237.3euro, including 1677.6euro for hospital charges. The cost of a session was 4490.5euro for a tumor and 4141.4euro for a stone, however the difference was not significant. Cost without hospital charges was estimated by 1196.5euro. CONCLUSION: The main part of a laser deflexible ureteroscopy session cost was the consequence of hospital expenses. It could only be obtained in a structure running a sufficient activity level depend on amortisement of medical supply.

Structure-property relationships of trimetazidine derivatives and model compounds as potential antioxidants.

Twenty-five compounds (trimetazidine derivatives and other compounds, mostly having a free phenolic group) were examined for their radical scavenging and antioxidant properties. Their reaction with DPPH (2,2-diphenyl-1-picrylhydrazyl) as a measure of radical scavenging capacity was assessed by two parameters, namely EC50 (the concentration of antioxidant decreasing DPPH by 50%), and log Z, a kinetic parameter proposed here and derived from initial second-order rate constants and antioxidant/DPPH ratios. Antioxidant activities were determined by the inhibition of lipid peroxidation and albumin oxidation. The most active compounds were derivatives having a trolox or hydroquinone moiety. Physicochemical and structural properties were determined by molecular modeling as lipophilicity (virtual log P calculations) and H-Surf (solvent-accessible surface of hydroxyl hydrogen) and by quantum mechanical calculations (deltaH(ox) = oxidation enthalpy; deltaH(abs) = enthalpy of hydrogen abstraction). QSAR models were derived to identify molecular mechanisms responsible for the reactivity toward the DPPH radical and for the inhibition of lipid peroxidation. A useful prediction of antioxidant capacity could be achieved from calculated molecular properties and the kinetic parameter developed here.

Vitamin B1, B2, B6, and C status in hospital inpatients.

The status of vitamin B1, B2, B6 and C was investigated in 656 hospital inpatients by means of a dietary interview, biochemical studies, and clinical investigation. The daily intake was lower than the Recommended Dietary Allowance for vitamin B1 in 57%, B2 in 47%, B6 in 53%, and C in 9% of the patients; it was less than half the Recommended Dietary Allowance in 19, 12, 15, and 3%, respectively. A biochemical deficiency was observed in 25% of the patients for vitamin B1, in 11% for B2, in 25% for B6, and in 14% for C. On the basis of the parameters selected for this study, the biochemical vitamin status, the dietary vitamin intake, and the clinical symptoms correlated significantly with each other except in the case of vitamin B6.

[Interaction of thiamine diphosphate with magnesium ion]. / Etude de l'interaction de la thiamine diphosphate avec l'ion magnésium.

The action of magnesium ion on the exchange rate of the proton in C2 of thiamine and thiamine diphosphate is studied at different values of pD. Above pD 5 the ion Mg2+ increases this exchange rate. The phenomenon is markedly enhanced for TDP rather than thiamine and increases with pD. Below pD 5 magnesium decreases the exchange rate. This decrease is greater for TDP than for thiamine. The maximum effect is reached at a magnesium concentration of 0.5/1 for thiamine and of 1/1 for TDP. T1 measurements are made for different pH values with and without magnesium ion. Results seem to prove that an increase in pD values from 3.9 to 5.9 leads to an accentuation of the molecules "folded" form. Nevertheless for a given pD value the TDP-Mg complex seems to have a more "folded" form than TDP.

Differential effects of zidovudine and zidovudine triphosphate on mitochondrial permeability transition and oxidative phosphorylation.

1. The effects of zidovudine (ZDV) and zidovudine triphosphate (ZDV-3P) on Ca2+-induced mitochondrial permeability transition (MPT), respiratory control ratio (RCR) and ATP synthesis have been investigated on isolated rat liver mitochondria. 2. ZDV slightly but significantly decreased RCR and ATP synthesis but was ineffective in inhibiting MPT. In contrast, ZDV-3P did not alter RCR and ATP synthesis but strongly inhibited MPT (IC50 = 3.0 +/- 0.9 microM). 3. The effect of ZDV-3P on mitochondrial swelling required a preincubation time. When incubated 10 min with mitochondria, ZDV-3P (8 microM) totally inhibited the rate of swelling. 4. ADP, ATP and atractyloside, which are agents known to interact with the mitochondrial adenine nucleotide carrier (ANC), antagonized the effect of ZDV-3P on mitochondrial swelling. Indeed, the IC50 value of ZDV-3P increased from 3.0 to 17.4, 93.6 and 66.5 microM, in the presence of 20 microM, ADP, ATP or atractyloside, respectively. 5. ZDV-3P did not displace [3H]-ATP from its mitochondrial binding site(s) whereas ADP and atractyloside did, suggesting that ZDV-3P and [3H]-ATP do not share the same binding sites. 6. ZDV-3P did not affect either mitochondrial respiration or ATP synthesis but inhibited Ca2+-dependent mitochondrial swelling. It was concluded that mitochondrial toxic effects observed during the chronic administration of ZDV cannot be related to its active metabolite (ZDV-3P).

The in vitro effect of some nitroimidazoles on microtubule formation.

The in vitro effects of some nitroimidazoles (metronidazole, ornidazole) and their metabolites on microtubule formation have been tested. Cyclic metabolites are without effect. Metabolites proceeding from cleavage of the imidazole ring inhibit microtubule formation and reduce the polymerization rate of tubulin. This inhibitory effect might be correlated to some of the side-effects of these drugs. Isaxonine phosphate corrects this effect.

The restoration of ATP synthesis may explain the protective effect of calcium antagonists against cyclosporine A nephrotoxicity.

Cyclosporine A at pharmacological doses decreases the rate and yield of ATP synthesis in rat mitochondria. This action seems to be due to the mitochondrial calcium storage induced by the drug. If such an effect occurs in vivo, the ATP deficit will affect calcium extrusion pumps, so triggering vasoconstriction which is the major side effect of Cyclosporine A. Calcium antagonists (Nifedipine and Verapamil) at least partially correct this effect on ATP synthesis: this finding may be related with the beneficial clinical effect conferred on Cyclosporine A toxicity by calcium antagonists. This effect of calcium antagonists may be due to an interaction with Cyclosporine A at the level of mitochondrial calcium efflux.

1H nuclear magnetic resonance and clinical studies of interaction of calcium antagonists and hypoglycemic sulfonylureas.

The hypoglycemic effect of gliclazide is mainly due to its action on ATP stimulated K+ channels, but the calcium ionophoretic effect of this drug may also be involved in its physiological properties. Using 1H NMR we demonstrated the antiionophoretic effect of nifedipine and diltiazem. We attempted to verify whether this in vitro interaction also occurs in vivo. A clinical trial, was performed on patients treated concomitantly with gliclazide and nifedipine or diltiazem. Results showed that no in vivo interaction occurred. The discrepancy between in vivo and in vitro results may be explained by a too weak plasma concentration in the case of nifedipine and by a large plasma protein binding in the case of diltiazem.

Lack of pharmacodynamic interaction between trimetazidine and cyclosporin A in human lymphoproliferative and mouse delayed hypersensitivity response models.

The hypothesis of an interaction between trimetazidine and the immunosuppressive effect of cyclosporin A was investigated in two models: a) ex vivo, the lymphoproliferative response of normal human lymphocytes to phytohemagglutinin and a murine monoclonal antibody against the CD3 T-lymphocyte membrane complex; b) in vivo, the delayed hypersensitivity response model in mouse. The uptake of methyl-3H-thymidine was measured in both models. For the lymphoproliferative response, statistical analysis showed that there was a significant inhibitory effect of cyclosporin A on cell proliferation (P < 0.001) and confidence intervals obtained by ANOVA showed the equivalence of the results when trimetazidine was combined with cyclosporin A (all CI95% < or = 10). In the delayed hypersensitivity model, cyclosporin A was also found to be very effective in inhibiting the immune response (P < 0.001), while trimetazidine did not interfere with cyclosporin A's effect. It was concluded that trimetazidine exerted neither an immunostimulatory nor an immunosuppressive effect in the two models, suggesting of the absence of interaction between trimetazidine and cyclosporin A's effectiveness when both drugs are given in combination.

Comparison of the effects of cyclosporine A and trimetazidine on Ca(2+)-dependent mitochondrial swelling.

Cyclosporine A (CsA) is a known potent inhibitor of pro-oxidant-induced mitochondrial swelling. In the present study we show that CsA's effect is only transient when the liver mitochondrial swelling in induced by Ca2+ plus tert-butylhydroperoxide (t-BH). After an initial inhibition, swelling is worsened by CsA as evidenced by an extent of mitochondrial swelling that exceeds that of the control. Unlike CsA, trimetazidine (TMZ), an anti-ischemic drug decreases both the extent and the rate of the swelling with an IC50 value of 214 +/- 24 microM. Its inhibition effect on the initial swelling rate mimicks that of CsA but the mechanism may be independent. During long-term swelling. TMZ counteracts the worsening effect of CsA. The inhibition of swelling induced by TMZ is assessed by the fact that TMZ significantly increases the EC50 of Ca(2+)-induced mitochondrial swelling (46.6 +/- 6.0 to 85 +/- 10 microM, P < 0.01), without affecting its cooperativity. Apparently, TMZ seems to behave like trifluoperazine (TFP), a phospholipase A2 inhibitor that, under our experimental conditions, inhibits the mitochondrial swelling induced by Ca2+ and t-BH with an IC50 value of 25 +/- 10 microM. Both drugs are able to protect mitochondria from both phases (early and late) of the swelling, especially the late, which is enhanced in the presence of CsA. TFP and other phospholipase A2 inhibitors were able to displace [3H]TMZ from its mitochondrial binding sites whereas CsA was ineffective. We suggest that TMZ, like TFP, inhibits the CsA insensitive mechanism involved in the swelling process which is responsible for the worsening effect observed in the presence of CsA when the swelling is generated by Ca2+ and t-BH.

1H-NMR study of suloctidil-A23187 calcium ionophore interaction.

Suloctidil is a molecule with calcium antagonist properties, whose anti-ionophoretic effect has previously been reported. In the presence of A23187 calcium ionophore free acid (A+), the NMR spectra of suloctidil (S +/-) are modified at the level of H-1 protons and to a lesser degree in the CH3-3 and aromatic regions. Experiments with one of the enantiomers of suloctidil and decoupling investigations led us to postulate the existence of diastereoisomers S+/A+, S-/A+ in the suloctidil +/-/A23187 + mixture. Moreover our results allow the hypothesis that suloctidil and calcium compete for the same binding site of the ionophore molecule.

Calcium anti-ionophoretic effect of some calcium channel blockers in rat liver mitochondria.

Beyond their classical action on calcium channels, some calcium channel blockers also exhibit a calcium anti-ionophoretic effect. We studied this effect on respiratory control and Ca2+ fluxes in a mitochondrial model to compare calcium antagonists chosen among three clinical classes: vascular, cardiac, and mixed effects. Synthetic calcium ionophore A23187 decreases respiratory control and modifies Ca2+ fluxes. We show that calcium antagonists partially restore the parameters altered by A23187. By calculating the percentage of restoration, we found that vascular drugs exhibit a strong anti-ionophoretic effect, cardiac drugs exert no significant effect, and mixed calcium antagonists exert an intermediate effect. Thus, it appears possible to link the intensity of calcium anti-ionophoretic effect with the clinical interest of a calcium antagonist.

Inhibition in vitro of the polymerization of tubulin by uremic middle molecules: corrective effect of isaxonine.

The polymerization of tubulin leads to the formation of microtubules which are one of the components of the axons of nerve cells. This reaction is the limiting factor in the growth of axons. Uremic middle molecules inhibit in vitro the polymerization of tubulin in a dose dependent way. It is possible that a similar phenomenon could occur in vivo in uremic patients, and this might be involved in the development of neuropathy. In addition, isaxonine phosphate counteracts the inhibitory effect of uremic middle molecules on the polymerization of tubulin.

Protective effect of some calcium antagonists against mitochondrial calcium injury.

Ischaemia induces an increase in calcium cytosolic concentration, leading to a mitochondrial Ca2+ overload. As Ca2+ uptake and storage into mitochondria are the alternative route to oxidative phosphorylation, the Ca2+ overload induces a decrease in ATP synthesis. We have tested in vitro the ability of certain calcium antagonists to restore the ATP synthesis inhibited by mitochondrial calcium overload. Our results showed that diltiazem and bepridil, clinically used as antiischaemic agents, each can restore the ATP synthesis. It is suggested that our in-vitro results might serve to explain the antiischaemic properties of some calcium antagonists.

[Sclerosing cholangitis following surgical treatment of hydatid cysts of the liver. Probable role of the formol injection of bile ducts]. / Cholangite sclérosante après traitement chirurgical de kystes hydatiques du foie. Rôle probable de la formolisation des voies biliaires.

Three cases of secondary sclerosing cholangitis which developed during the early postoperative phase of surgical treatment of hydatid liver cysts are reported. The cysts had ruptured into the biliary tree and the treatment consisted of infection of formol into the cysts. Evolution was pejorative since one patient died within 3 months and the remaining two underwent liver transplantation following biliary sclerosis. An experimental protocol using dogs has shown that the injection of 5, 10 and 20 p. 100 formalin into normal bile ducts rapidly causes sclerosing cholangitis which often leads to death. In man, it is very likely that the contact of 2 p. 100 formalin with mucosal tissue damaged by episodes of cholangitis could result in sclerosing cholangitis. These observations should be sufficient to discourage the use of formalin to sterilize hydatid cysts of the liver.

[Adenocarcinoid of the stomach. Histochemical and immunohistochemical study using optical and electron microscopy]. / Adénocarcinoïde de l'estomac. Etude histochimique et immunohistochimique en microscopie optique et électronique.

A case of gastric adenocarcinoid was described by light and electron microscopy and immunohistochemistry. The tumor contained exocrine, endocrine and amphicrine cells. In endocrine cells, serotonin and pancreatic polypeptide were demonstrated. It was suggested that these gastric adenocarcinoid cells originate from totipotent immature cells of endodermal origin.