Incidence and microbiology of post-operative infections after radical cystectomy and ureteral stent removal; a retrospective cohort study.

BACKGROUND: Post-operative infections are frequent after radical cystectomy with urinary diversion surgery (UDS). Reduction of post-operative infections necessitates appropriate peri-operative antimicrobial prophylaxis targeting causative bacteria. We assessed the incidence and microbiology of infections in the 30-day post-operative period after UDS and investigated effectiveness of the currently used peri-operative antibacterial prophylaxis. METHODS: Retrospective cohort study of all patients undergoing UDS in a tertiary university medical center from January 2014 until September 2016. Antibiotic prophylaxis consisted of cefazolin plus metronidazol according to the Dutch national guideline. Primary outcome was the incidence of post-operative infections within 30 days. Risk factors for post-operative infections and antimicrobial susceptibility profiles of cultured bacteria were also assessed. RESULTS: 147 patients were included. 69 patients (46.9%) had 82 post-operative infections, 27 of which were patients with bacteremia (18.4%). Highest incidence of infections was on day 4-5 and on day 8-10 postoperatively. The second peak was associated with ureteral stent removal. 4.8% of 147 study patients developed bacteremia 24 h after stent removal, which counted for 25.9% of all bacteremia episodes found in this study. Enterobacteriaceae were cultured in 67.9% of blood cultures and were only highly susceptible to ciprofloxacine, piperacillin-tazobactam (90%), meropenem and gentamicin (100%). Multivariate logistic regression analysis showed orthotopic Hautmann neobladder to be associated with increased infections complications: odds ratio 4.1 (95% confidence interval 1.6-10.5), p = 0.03. CONCLUSIONS: The incidence of infections after radical cystectomy is high and particularly ureteral stent removal was associated with both bacteremia and complicated urinary tract infections. Based on the results of this study, antibiotic prophylaxis might need to be broadened for patients undergoing radical cystectomy. Further research is required to investigate whether current guidelines need to be altered concerning administration of antibiotic prophylaxis just before stent removal.

Gastric erosions induced by analgesic drug mixtures in the rat.

Gastric erosions after oral administration of analgesics separately and in admixture have been examined in adult rats. After administration of acetylsalicylic acid (aspirin), phenacetin, paracetamol and caffeine as single drugs, gastric erosions were only observed with aspirin. The combination of aspirin with phenacetin did not change, that of aspirin with caffeine significantly increased, and aspirin with paracetamol significantly decreased the incidence of gastric lesions compared with aspirin alone. The results for aspirin with paracetamol did not differ from those for the vehicle. Addition of caffeine to the combination of aspirin and phenacetin caused a significant increase in erosions, but when given with aspirin and paracetamol no erosions occurred. The mechanisms underlying the effects of these drugs on aspirin-induced erosions are discussed.

Reduction of animal use for toxicological evaluation: the Netherlands Health Council report on the LD50.

In 1981 the Health Council of the Netherlands installed a committee to report on the scientific value of the LD50 and on ways of obtaining the information needed for the toxicological evaluation of chemical products at the expense of less experimental animals and of less suffering. This was done at the request of the Minister of Public Health and Environmental Hygiene. The first four reports have been published. The first one discusses the different methods for estimating the median lethal dose, and stresses that a high precision is seldom needed. A limit test would suffice in many cases. The test for abnormal toxicity of the European Pharmacopoeia (General method) has a power of discrimination of 0.96 when the dose injected in fact is equal to the LD50; the power of the version of this test intended for immunosera and vaccines is even higher. The second report deals with pharmaceutical preparations, immunosera and vaccines. The types of toxicity data and the precision required differ in the successive stages of screening, selection, development up to registration and quality control. Determination of an LD50 with a high precision is required only for preparations with a narrow therapeutic margin, and in very exceptional cases for quality control.

Effects of intravenous verapamil on left ventricular systolic function and diastolic filling dynamics in patients with coronary artery disease: analysis of intramyocardial markers.

Left ventricular (LV) intramyocardial markers (MM) were used to study the effects of intravenous verapamil on LV pump function and diastolic filling dynamics. Verapamil (0.1 mg/kg bolus followed by 0.005 mg/kg/min) was administered to 10 patients with severe coronary artery disease 4 years after coronary bypass grafting and implantation of 7 tantalum markers into the LV. MM were filmed at 100 frames/sec (biplane 30 degrees RAO/60 degrees LAO). The digitized biplane MM coordinates were transformed into 3-dimensional coordinates and maximal projection area was defined. LV volumes were calculated frame-by-frame and ejection fraction and peak filling rate derived. Pressure-volume relations were calculated in early-, mid-, and end-diastole. Verapamil caused a slight rise in end-diastolic pressure (12 to 14 mmHg, p less than 0.001) and end-diastolic volume (142 to 152 ml; p less than 0.005) and a fall in max dP/dt (1732 to 1570 mmHg/s; p less than 0.01) reflecting the drug's negative inotropic action. Verapamil reduced LV systolic pressure (136 to 126 mmHg; p less than 0.01), diastolic aortic pressure (74 to 68 mmHg; p less than 0.001) and peripheral resistance (1496 to 1348 dynes.s.cm-5; p less than 0.025); cardiac index was increased (2.7 to 2.9 l/min/m2; p less than 0.05), as were ejection fraction (47 to 49%; p less than 0.02) and stroke volume (67 to 75 ml; p less than 0.001). Great cardiac vein flow increased as well (88 to 102 ml/min; p less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

The anti-inflammatory, analgesic and antipyretic activities of non-narcotic analgesic drug mixtures in rats.

The effects of non-narcotic analgesics have been examined, separately and in admixture, on carrageenan-induced hind paw oedema and on yeast-induced hyperalgesia and hyperthermia in adult rats. The efficacy of the drugs was evaluated using the kinetics of drug-receptor interaction. In addition, the hypothesis was tested that the anti-inflammatory, analgesic and antipyretic activities of the drug mixtures used equal the addition of the activities of the individual drugs and could be predicted from their intrinsic activities and affinities. Dose-dependent inhibition of paw oedema, hyperalgesia and hyperthermia was observed after oral administration of acetylsalicylic acid (aspirin), paracetamol, phenacetin (60, 125, 250 and 500 mg.kg--1), and caffeine (12.5, 25, 50 and 100 mg.kf--1). Over the dose-ranges used, the anti-inflammatory activities of paracetamol, phenacetin and caffeine tended to be smaller than that of aspirin. The dose producing a semi-maximal effect for caffeine was lower than that for aspirin which in turn was comparable to that for paracetamol or phenacetin. The analgesic activities of phenacetin and caffeine were classified as stronger than that of aspirin, whereas the efficacy of paracetamol was similar. Paracetamol and aspirin were comparable as antipyretics. The antipyretic activity of phenacetin was higher but that of caffeine was lower than that of aspirin. For caffeine the dose producing a semi-maximal effect was lower than that of aspirin. Within the dose-ranges used, low doses of mixtures of aspirin with either paracetamol, phenacetin or caffeine exhibited anti-inflammatory, analgesic and antipyretic activities which were not different from the activities expected on the basis of addition. Incidentally, at some of the higher dose levels potentiation of the activity of the drugs was found. Low doses of the triple combinations: aspirin + paracetamol + caffeine and aspirin + phenacetin + caffeine showed anti-inflammatory and antipyretic activities which were not different from those expected on the basis of addition, but the activities observed with higher doses of these combinations indicated potentiation. It is concluded that, in the rat, the anti-inflammatory, analgesic and antipyretic activities of dual and triple combinations of aspirin, paracetamol, phenacetin and caffeine at least equal the activities expected on the basis of addition.

Diastolic dysfunction during acute cardiac allograft rejection.

Left ventricular diastolic function was evaluated in 41 heart transplant patients during acute rejection by an analysis of echocardiograms and surgically implanted intramyocardial tantalum markers. In 35 patients, isovolumic relaxation time was calculated from M-mode tracings selected from two-dimensional echocardiographic recordings. A total of 84 biopsy findings of no rejection, moderate rejection, and severe acute rejection after treatment were correlated with measurements of isovolumic relaxation time. In six patients, end-diastolic volume, end-systolic volume, stroke volume, ejection fraction, and peak filling rate were obtained from biplanar cineradiographic images of intramyocardial markers. Data from 11 prerejection periods were compared with those of moderate acute rejection. All echocardiograms and marker images were analyzed without previous knowledge of biopsy findings. At times of acute rejection, isovolumic relaxation time decreased from 107 to 65 msec (p less than 0.01) and returned to 98 msec after immunosuppressive therapy. Ejection fraction and end-systolic volume did not change significantly with acute rejection, whereas stroke volume decreased from 76 to 67 ml (p less than 0.05). In contrast to the effects on systolic function, episodes of acute rejection were accompanied by a decrease in end-diastolic volume from 166 to 153 ml (p less than 0.01) and a reduction in peak filling rate from 514 to 460 ml/sec (p less than 0.05). These data suggest that acute cardiac rejection is associated with relative preservation of left ventricular systolic performance but with alterations in diastolic dynamics similar to those seen in "restrictive" cardiomyopathy.