A precise and simple isodose-volume-based verification method for HDR and LDR brachytherapy plans.

PURPOSE: The American Association of Physicists in Medicine (AAPM) code of practice for brachytherapy physics recommends performing an independent treatment time calculation. For this we implemented an easy to use isodose-based verification method for HDR (high-dose-rate) and LDR (low-dose-rate) brachytherapy plans. MATERIAL AND METHODS: Dose-volume-based methods have been developed for Ir-192-based high-dose-rate (HDR) and I-125 prostate low-dose-rate (LDR) brachytherapy. They allow checking the integral dwell time or activity when the volume of a suitable isodose is known. The verification method was validated for 55 clinical HDR and 243 clinical LDR plans. RESULTS: For HDR brachytherapy, the mean absolute difference between the estimated and calculated integral dwell time was 0.8% ± 1.0% (n = 30) with a single-source path and 2.7% ± 1.1% (n = 25) for multiple source paths. The corresponding value for LDR brachytherapy was 1.8% ± 2.0% (n = 243). In HDR brachytherapy, the verification method depends slightly on the plan class when considering one or more than one source paths. Good agreement between the estimated and calculated integral dwell times was obtained based on the 2 Gy isodose. Unlike HDR brachytherapy, the parameters used in the verification method for LDR brachytherapy plan verification strongly depend on the type of seed distribution. So, we recommend using an isodose at the prescribed dose for prostate HDR therapy. CONCLUSIONS: Isodose-based verification methods are precise, do not presuppose dedicated tools, and are simple to implement in clinical practice.

Outcome of antibiotic therapy with ciprofloxacin in chronic bacterial prostatitis.

Chronic bacterial prostatitis (CBP) is a rare infection of the prostate with Escherichia coli being the predominant causative pathogen. Appropriate antimicrobial therapy is mandatory for cure. We report on our experience with a 4-week regimen of ciprofloxacin in 40 men suffering from CBP due to E. coli. Follow-up was conducted over a period of 12 to 24 months. The microbiological work-up included an analysis of expressed prostatic secretions (EPS) and semen. Eradication of the pathogen in EPS was achieved in 92% of patients 3 months after therapy and in about 70 to 80% of patients evaluated 12 and 24 months after treatment, respectively. Treatment failure was not associated with the presence of prostatic calculi, as assessed by transrectal ultrasonography. After successful therapy, mean EPS pH decreased significantly from 7.95 to 7.35. Significant bacteriospermia with E. coli was detected in 21/22 (95.5%) patients before treatment and in 6/22 (27.3%) patients 6 months after therapy. Our data reconfirm ciprofloxacin as an excellent antimicrobial agent in the therapy of CBP. However, eradication of the pathogen is unpredictable and cannot be achieved in every case. Further studies should correlate microbiological treatment success with symptomatic relief, as assessed by standardised questionnaires.

Impairment of bacterial clearance induced by norepinephrine infusion in rabbits.

OBJECTIVE: Purpose of the study was to investigate the potential influence of norepinephrine (NE) on immune functions in terms of systemic and organ-specific bacterial clearance in rabbits. DESIGN: To enable quantification of the clearance process, defined numbers of exogenous Escherichia coli (1.3 x 10(8) CFU) were injected intravenously 60 min after starting the NE infusion at a low dose (1 microgram/kg per min, n = 6), causing an increase (30 mmHg) in mean arterial pressure without affecting the oxygen uptake, and at a higher dose (7.5 micrograms/kg per min, n = 6), resulting in a marked decrease (20%) in oxygen uptake, after infusion of NaCl solution (control, n = 6). In additional experiments (n = 6) NE (1 microgram/kg per min) was tested in endotoxemia induced by simultaneous infusion of endotoxin (40 micrograms/kg per h). Parameters monitored were arterial pressure, oxygen uptake, and rates of bacterial elimination from the blood. At 180 min after E. coli injection, the animals were sacrificed, and tissue samples of liver, kidney, spleen, and lung were collected for bacterial counts. RESULTS: NE infusion resulted in a dose-dependent prolonged elimination of the injected E. coli from the blood and in significantly higher (p < 0.05) numbers of CFU in liver and lung compared to the controls. Significant impairment of bacterial clearance was found after shock-producing endotoxemia, whereas simultaneous infusion of NE and endotoxin caused only a slightly delayed blood clearance of the injected bacteria. CONCLUSION: NE dose dependently affected bacterial clearance, which might be due to ischemia-derived hypoxic impairment of the phagocytosis and lysis function of the reticuloendothelial system, whereas NE improved elimination of bacteria in a state of endotoxic shock.

Comparative efficacies of ofloxacin, cefotaxime, and doxycycline for treatment of experimental epididymitis due to Escherichia coli in rats.

The in vivo efficacy of ofloxacin was compared with those of cefotaxime and doxycycline in a rat model of epididymitis due to Escherichia coli. Treatment was started 24 h after infection and was continued for 7 days. Ofloxacin reduced the numbers of E. coli organisms in the epididymides significantly more than the other therapeutic regimens and cured the infection more frequently. Histopathological changes in the epididymides of ofloxacin-treated animals were significantly less severe than those observed in untreated animals. Doxycycline was less effective than ofloxacin but significantly reduced the titers of organisms in rat epididymides. In contrast, despite excellent in vitro activity, cefotaxime failed to reduce the magnitude of infection. The results of this study suggest that ofloxacin may be a very effective antimicrobial agent for the treatment of epididymitis due to E. coli.

Quality assessment of external data: a further means of reducing animal use for toxicity testing--a case study.

One overlooked area of quality assurance (QA) is the critical, in-depth reassessment of toxicity data from secondary compilations. Such retrospective QA may play a role in avoiding needless additional or repeated animal testing, as this case study shows. Initially, the task was simply to carry out toxicity testing of a chemical for LD50 determination for regulatory purposes. The impetus for this proposed (re-)testing was the erroneously calculated low LD50 value for just one species and one route of administration. Examination of the original literature cited as the source of the seemingly anomalous LD50 value revealed that a combination of conceptual and transcriptional errors had been made when the results were translated from the original German research paper and were put into two widely used secondary compilations: RTECS and HSDB. Correcting these errors rendered the true value for LD50, which was no longer out of step with values for other species, nor was it sufficiently low to cause any concern in the work place. The critical reassessment removed the need to use any further animal studies to assess the situation. It is concluded that, in some cases, "reassessing" existing data can be added to the established list of "refining, reducing, and replacing" as a means of decreasing animal use in toxicological evaluation.

Refractory chronic bacterial prostatitis: a re-evaluation of ciprofloxacin treatment after a median followup of 30 months.

A total of 16 men suffering from refractory chronic bacterial prostatitis caused by Escherichia coli was treated with ciprofloxacin for 4 weeks. After a median followup of 30 months (range 21 to 36 months) 10 of the 16 patients were considered cured as judged by bacteriological results and clinical symptoms. In 2 men a second ciprofloxacin regimen obviously showed success also. In 2 patients ciprofloxacin therapy failed and in 2 therapy had to be discontinued due to side effects of the central nervous system.

Chronic bacterial prostatitis: therapeutic experience with ciprofloxacin.

Ciprofloxacin was used for the treatment of refractory chronic bacterial prostatis. 17 men with symptoms of prostatitis for more than one year who had not responded to treatment courses of six weeks trimethoprim-sulfamethoxazole or trimethoprim alone received 500 mg ciprofloxacin twice daily per os for two weeks. Up to one year follow-up proved eradication of Escherichia coli in seven of ten and of other pathogens in two of five cases. In a second study, 16 patients with proven chronic bacterial prostatitis who had failed on pretreatment with co-trimoxazole, trimethoprim or norfloxacin, respectively, received 500 mg ciprofloxacin twice daily for four weeks. E. coli was the causative organism for all cases. After a median follow-up of 30 (21-36) months, ten out of 16 patients are clinically cured with permanent eradication of the causative organism. In two men a second treatment course with ciprofloxacin is considered successful. Two patients stopped treatment for central nervous system complaints.

Chronic copper toxicity in a dairy herd.

The addition of excessive copper to a commercially prepared dairy ration caused chronic copper toxicity in a dairy herd. A formulation error by a feed company resulted in copper levels of 800 to 1,000 mg/kg in the "as fed concentrate," amounting to about 400-500 mg copper/kg of the whole ration. Five animals died with typical signs of acute copper toxicity, including intravascular hemolysis and methemoglobinemia. A further 39 cows died on the farm from a combination of debilitation and secondary infectious causes, and 215 were sent to slaughter because of debilitation and poor milk production. The mortality of calves born to dams that had been fed the toxic concentrate was approximately 50%.We postulate that dairy cows, particularly pregnant cows, may be more susceptible to copper toxicity than other cattle, and suggest reexamination of the presently allowable maximum levels of copper supplementation of diets for dairy cattle.

Treatment of chronic bacterial prostatitis with ciprofloxacin. Results of a one-year follow-up study.

In a one-year follow-up study, short-term therapy with ciprofloxacin proved to be beneficial in the treatment of chronic bacterial prostatitis, particularly in cases of Escherichia coli prostatitis. Ciprofloxacin therapy of E. coli prostatitis was a complete success in five of 12 patients, a probable success in two, and in one patient the outcome cannot be judged. Ciprofloxacin treatment failed in three men, and therapy was discontinued in one patient because of side effects. Enterobacter aerogenes prostatitis was cured. Ciprofloxacin treatment was insufficient in three patients with Streptococcus faecalis prostatitis and in one patient with Pseudomonas aeruginosa prostatitis.

Chronic copper toxicity in a dairy cow.

A three year old Holstein dairy cow fed a ration containing a copper supplement died of chronic copper poisoning. The concentration of copper in the liver was 331 ppm (wet weight). The typical lesions of chronic copper toxicity including icterus, hepatic fibrosis and hemoglobinemic nephrosis were found at necropsy. The chronic copper toxicity was not considered to be a herd problem since the liver copper concentration in a slaughtered cull animal and blood samples taken from five animals in the same herd were within normal limits.