Synthesis and characterization of substituted benzoylhydrazones of naloxone.

Naloxone benzoylhydrazone (NalBzoH) has proved a valuable tool in the investigation of opioid receptor subtypes. In the present study, we have examined a series of derivatives of NalBzoH in which substitutions have been made on the benzoyl ring. Overall, we see dramatic effects on the binding affinities of derivatives against the various opioid receptor subtypes. Although the range of affinities against the mu receptors is quite modest, ranges of the others vary almost 30-fold for kappa 3, 50-fold for kappa 1 and 100-fold for delta and kappa 2 binding. Few substituted derivatives display greater affinity than NalBzoH for any of the receptors, except for delta sites where several derivatives have affinities almost tenfold greater than NalBzoH. Along with the wide variations in affinity, the compounds also appear to exhibited widely divergent activities in traditional bioassays.

Urinary tract infection prophylaxis in transurethral surgery: oral lomefloxacin versus parenteral cefuroxime.

The purpose of this study was to compare the efficacy and safety of single-dose oral lomefloxacin and single-dose parenteral cefuroxime for the prevention of urinary tract infection following transurethral surgery. A total of 63 patients were enrolled in this prospective, randomized open-label study, which was conducted at two medical centers in France. Patients were randomized to receive either 400 mg of oral lomefloxacin 2-6 hours before surgery or 1.5 g parenteral cefuroxime 30-90 minutes before surgery. Postoperative clinical evaluation was performed daily, and bacteriologic evaluation included urine cultures performed 24 hours after surgery, just before and 1 day after removal of the indwelling catheter, and 3-5 days after surgery. Another urine culture was optionally performed 1-3 months after surgery. Infection was defined as a urinary bacteria count greater than or equal to 10(5) colony-forming units (CFU)/mL of urine. Of the 63 patients enrolled, 54 were evaluable for efficacy, 27 in each group. The success rate of prophylaxis was 88.9% in the lomefloxacin group and 88.5% in the cefuroxime group (p = nonsignificant). None of the 16 lomefloxacin-treated patients who were re-cultured at 1-3 months was found to be infected. Adverse events were minor in both groups. A single oral dose of lomefloxacin was as efficacious and as safe as a single intravenous dose of cefuroxime for prevention of postoperative urinary tract infection in patients undergoing transurethral surgery.

Antagonists as "affinity probes" for peptide hormone receptors: QSAR studies on oxytocin receptor in the rat myometrium.

The use of competitive antagonists in receptor investigations has been based mainly on empirically established abilities to suppress biological effects of certain agonists. This information serves primarily for classification of receptors according to ligand specificities. Methods of quantitative structure-activity analysis can extend their use for investigations of preference substituent in the desired position, estimates of ligand-receptor affinities, etc., when a set of antagonists differing solely in the substituents in that position and characterized by their pA2 values, is available. In the case of a multiple substitution, contributions of single substituents on individual positions can be estimated by the Free-Wilson method and then subjected to correlation analysis. The approach is demonstrated on a group of oxytocin analogues acting as uterotonic inhibitors of oxytocin; the "intramolecular force" descriptors are used for correlation analysis.

Use of antibiotics in the conjunction with extracorporeal lithotripsy.

The first 400 patients treated on an inpatient basis at our center underwent bacteriological follow-up after extracorporeal lithotripsy (ECL) for ureteric or renal stones. 278 patients did not have any urinary tract infection on the urine culture before ECL. They did not receive any antibiotic prophylaxis and 4.8% of the patients developed infectious problems, with significant bacteriuria in only 1.5% of the cases. 89 patients had urinary tract infection on the preoperative cultures. 21.3% developed either fever or significant bacteriuria and this virtually always occurred in patients who were treated for less than 4 days before ECL, with septicemia in 4.5% of the cases. 33 patients with sterile urine received flush antibiotic prophylaxis and none of them developed postoperative infection. Two of these patients had infection at the time of the flush: one of them, who, by error, did not receive antibiotic treatment prior to ECL, developed bacteremia after the procedure. The rational use of antibiotics in conjunction with ECL should ensure effective prevention of urinary tract infections without requiring the excessive use of antibiotics.

In vivo diffusion of enoxacin in healthy renal and adenomatous prostate tissue in man.

Enoxacin is a new quinolone derivative that is well absorbed after oral administration and shows good efficacy against the pathogenic bacteria usually isolated in urinary infections. We studied the diffusion of enoxacin in healthy renal tissue (13 patients) and adenomatous prostate tissue (16 patients) in surgical patients dosed with enoxacin preoperatively. The plasma and parenchymal concentrations were measured by high-performance liquid chromatography after 5 successive oral doses of 400 mg given at 12-hour intervals. The mean concentrations for the prostatic series were: 5.15 +/- 2.68 micrograms/g of adenomatous prostatic tissue and 2.07 +/- 1.38 mg/l of plasma 2 h after the last dose (r = 2.54); 2.5 +/- 1.7 micrograms/g and 0.98 +/- 0.8 mg/l, respectively, 15 h after the last dose (r = 2.61). The mean concentration of enoxacin in the kidney 3 h after the last dose was 13.93 micrograms/g (r = 7.35); the concentrations 12 h after the last dose ranged from 9.70 to 14.35 micrograms/g of tissue and from 1.1 to 2.3 mg/l of plasma (r = 7.76). Consequently, enoxacin appears to have interesting possibilities for the treatment of urological parenchymal infections.

[Functional renal failure caused by vascular diversion. The role of a hypervascular renal tumor]. / Insuffisance rénale fonctionnelle par détournement vasculaire. Rôle d'une tumeur rénale hypervascularisées.

Tumorectomy was performed in a patient with hypervascular renal carcinoma on a solitary kidney. Prior to surgery, this patient had mild renal impairement (plasma creatinine 195 mumol/l, creatinine clearance 48 ml/min), but it was noted that 45 days after surgery his renal function had improved (plasma creatinine 142 mumol/l, creatinine clearance 63 ml/min). The hypothesis of a prerenal model of renal impairment is put forward, the probable physiopathological mechanism being a diversion of blood flow from the healthy kidney to the hypervascularized tumoral kidney.

Amino acid side chain parameters for correlation studies in biology and pharmacology.

Fifteen physicochemical descriptors of side chains of the 20 natural and of 26 non-coded amino acids are compiled and simple methods for their evaluation described. The relevance of these parameters to account for hydrophobic, steric, and electric properties of the side chains is assessed and their intercorrelation analyzed. It is shown that three principal components, one steric, one bulk, and one electric (electronic), account for 66% of the total variance in the available set. These parameters may prove to be useful for correlation studies in series of bioactive peptide analogues.

Piezoelectric extracorporeal lithotripsy by ultrashort waves with the EDAP LT 01 device.

A total of 433 extracorporeal lithotripsy procedures was performed for renal, ureteral and bladder stones by means of a system of ultrasonographic detection and piezoelectric destruction in 386 patients. The stones were detected easily in 87 per cent of the patients, difficult to detect in 10 per cent and impossible to detect in 3 per cent. Mean duration of treatment was 35 minutes. Mean number of piezoelectric waves was 2,700 at 1.25 per second. With a frequency of 1.25 to 5 per second, extracorporeal lithotripsy was performed without any local, regional or general anesthesia, and without premedication in 210 patients. Of the 217 patients with a renal stone reviewed at 3 months 161 (74 per cent) had successful results and 56 (26 per cent) failed therapy. Thirty patients (14 per cent) underwent 2 or 3 sessions. The morbidity was low: 2 per cent of the patients suffered ureteral obstruction, 1.5 per cent had subcapsular hematoma and 4 per cent had fever. No significant modifications of laboratory tests were necessary and no patient suffered renal failure. Of the stones 31 in the lumbar ureter, 15 in the pelvic ureter and 8 in the bladder were treated, with success rates of 87, 46 and 50 per cent, respectively. A total of 103 patients was treated on an outpatient basis. This outpatient treatment, together with the low cost and minimal maintenance of the apparatus, and the absence of anesthesia constitute a new progress in the treatment of renal stones.

Antibiotic prophylaxis of urinary tract infection after transurethral resection of the prostate: a randomized study.

Transurethral resection of the prostate is associated with a major risk of postoperative infection. To evaluate the clinical and bacteriological efficacy of antibiotic prophylaxis with a single dose of netilmicin sulfate, we conducted a randomized study in 100 patients with sterile preoperative urine undergoing transurethral resection of the prostate. Of these patients 95 were evaluated: 47 were randomized to the control group and received an intramuscular injection of 1.5 ml. of a 0.9 per cent solution of sodium chloride 1 hour preoperatively and 48 were given an intramuscular injection of 150 mg. netilmicin sulfate in a volume of 1.5 ml. 1 hour preoperatively. Of the patients 16 in the control group (34 per cent) and only 1 in the treated group (2 per cent) had bacteriuria (greater than 10(5) bacteria per ml.) (p less than 0.001). This difference also was significant 2 and 5 days postoperatively (p less than 0.05 and p less than 0.001, respectively). One patient in the control group had bacteremia compared to none in the treated group. Clinical signs of infection were less common in the treated group. Sensitivity studies revealed that all of the organisms tested were sensitive to netilmicin sulfate. High concentrations of netilmicin sulfate were found in the urine collected at operation (162 +/- 112 micrograms per ml. urine).

[Prevention of postoperative infections in non-endoscopic urologic surgery by a single dose of cefotiam]. / Prévention des infections post-opératoires en chirurgie urologique non endoscopique par une dose unique de céfotiam.

We report on the results of a randomized study of 1 g céfotiam flash pre-operative antibioprophylaxis to prevent post-operatory infection complications in non-endoscopic urologic surgery. Thirty-seven patients (17 controls and 20 treated) have had a prostatic adenomectomy: treatment has lead to decrease the number of post-operatory wall complications (47% vs 20%) and hospitalisation staying (p less than 0.03). Seventy-eight patients have had a urologic surgery with lumbar or abdominal incision (37 treated and 41 controls). In this group, there was not gain on post-operatory infections complications nor on hospital staying, since this surgery has a little number of infections complications. During the study, we have not noted an abnormal part of cefotiam resistant germs.

[Piezo-electric lithotripsy technic with echographic guidance (EDAP LT 01)]. / Technique de la lithotripsie piézo-électrique avec repérage échographique (EDAP LT 01).

Piezo-electric extracorporeal lithotripsy with ultrasonographic detection is performed with the following material according to the following technique: 1) A mobile firing head connected to the lumbar region by a simple inflatable cushion filled with sterile water. At the centre of the firing head, a 5 MHz real time transducer is used to locate the stone. 320 piezo-electric elements, arranged around the transducer, can induce, when focussed, a pressure of about 900 bars at the focal point in vitro. The focus is 15 mm X 5 mm. The generators are electronic. 2) The technique requires: understanding of ultrasonography in order to precisely locate the stone which, when it is intrarenal, is only missed in 1% of cases in our experience. Stones of the iliac ureter are not visible. Treatment requires the patient's confidence so that, due to the quality of the piezo-electric wave, no anaesthesia is necessary. The firing time should be relatively long (45 min to 1 hr) in order to ensure good fragmentation. 26% of patients require retreatment. Secondary complications are rare (3% of endoscopic treatments). The technique is now proposed in 90% of cases without admission to hospital. The simplicity of the manipulation of the apparatus must not mask the fact that it is a technique which requires perfect mastery. Only urologists familiar with stone pathology and who are able to treat the complications of lithotripsy by endoscopy or by surgery should perform extracorporeal lithotripsy.

[Obstruction of the upper excretory tract associated with primary urinary infection. Diagnosis, treatment and course. Apropos of 196 cases]. / Obstacle des voies excrétrices supérieures associé à une infection urinaire primitive. Diagnostic, traitement et évolution. A propos de 196 cas.

The association of upper urinary tract obstruction and urinary tract infection is a relatively common disease which requires early diagnosis and systematic treatment. The diagnosis of this disease can be difficult as many patients present with totally asymptomatic forms which may be revealed suddenly and totally unpredictably by an episode of severe infection. 196 (16%) of the 1,225 patients operated between January 1977 and June 1985 for upper urinary tract obstruction also presented with urinary tract infection at the time of admission. Suggestive urological signs were present in only 49% of the patients and infectious signs were present in 39%. 26 patients had acute renal failure and 9 presented at least 3 signs of severity. The bacteria most frequently isolated were E. coli (29% of M.S.U.s and 11% of blood cultures) and Proteus mirabilis (30% of M.S.U.s and 11% of blood cultures). Treatment always consisted of a combination of surgery and antibiotic therapy. Surgery was conservative in only 71% of patients at the first operation. 23 patients required specific symptomatic treatment due to the presence of signs of severity. Renal function, evaluated on the basis of the serum creatinine, was considerably improved by treatment, particularly in patients with acute renal failure on admission. In terms of bacteriological results, 92% of patients were discharged from hospital with sterile urine. 20% of the patients reviewed as outpatients had persistent urinary tract infection, generally caused by Proteus mirabilis. Three patients (1.5%) died, including 2 from the initial infectious syndrome.

[Extracorporeal piezoelectric lithotripsy by ultra-short waves using the EDAP LT01 device]. / Lithotripsie extra-corporelle piézo-électrique par ondes ultracourtes avec le EDAP LT01.

Three hundred and sixty one extracorporeal lithotripsies for renal, ureteric and bladder stones have been performed by means of a system of ultrasonographic detection and piezoelectric destruction (EDAP LT01). The localisation of the stone is achieved by a 5 MHz real time sectorial transducer situated in the centre of a small dish containing 320 piezoelectric elements concentrated in a source 5 mm wide by 15 mm high. The pressure recorded in vitro is 900 bars. The stone is easily detected in 87.2% of cases, difficult to detect in 10% of cases and impossible to detect in 28% of cases. By using a frequency of 1.25 to 5 per second, extracorporeal lithotripsy can be performed without any local, regional or general anaesthesia and without premedication in the 120 patients with a renal stone, reviewed between 1 and 3 months, 88 (73%) were considered to be complete successes. Ten (8%) were considered to be failures and 19 (21%) were considered to be partial successes. The best results were obtained in stones of the renal pelvis less than 20 mm in diameter. These results relate to a mean series which must take into account the successive improvements made to the lithotripter. Today, stone fragmentation is obtained in 93% of cases. Thirty six stones of the lumber and pelvic ureter were treated with success rates of 93% and 50%, respectively. Six bladder calculi were treated with a 50% success rate. Forty two patients were treated without being admitted to hospital.(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitative description of side chain effects on binding to protein.

Values of delta delta G previously reported for transition state binding of ATP and tyrosine by tyrosyl-tRNA synthetase as a function of side chain structure are quantitatively described by the intermolecular force (IMF) equation. Polarizability, ionic side chains, and steric effects seem to be the major factors in determining delta delta G. A contribution from hydrogen bonding cannot be excluded but is at best probably small. Binding is apparently due to dispersion forces and ion/dipole and ion-induced/dipole interactions.

Can transabdominal ultrasonography of the bladder replace cystoscopy in the followup of superficial bladder tumors?

Transabdominal ultrasonography of the bladder was performed on 100 patients 3 to 9 months after endoscopic resection of stage Pa or Pl transitional cell carcinoma of the bladder. In 81 patients there was a close correlation between the results of suprapubic ultrasonography and cystoscopy. In 19 patients the ultrasonography results were incorrect: 4 had false positive and 15 had false negative findings. Specificity for the diagnosis of recurrence was 90 per cent and sensitivity was 74 per cent. Transabdominal ultrasonography combined with cytology studies should be part of the diagnostic approach for recurrent superficial bladder tumors. When performed before cystoscopy these studies should reduce greatly without eliminating the frequency of this investigation.