Comparative assay of fluorescent antibody test results among twelve European National Reference Laboratories using various anti-rabies conjugates.

Twelve National Reference Laboratories (NRLs) for rabies have undertaken a comparative assay to assess the comparison of fluorescent antibody test (FAT) results using five coded commercial anti-rabies conjugates (Biorad, Bioveta, Fujirebio, Millipore, and SIFIN conjugates). Homogenized positive brain tissues infected with various lyssavirus species as well as negative samples were analyzed blindly using a standardized FAT procedure. Conjugates B, C, D, and E were found to be significantly more effective than conjugate A for GS7 (French RABV) diluted samples (1/8 and 1/100) while the frequency of concordant results of conjugates C and D differ significantly from conjugates A, B and E for CVS 27. For detection of EBLV-1 strains, conjugates C and D also presented a significantly lower frequency of discordant results compared to conjugates A, B and E. Conjugates B, C and D were found to be significantly more effective than conjugates E and A for EBLV-2 and ABLV samples. In view of these results, conjugates C and D set themselves apart from the others and appeared as the most effective of this 5-panel conjugates. This study clearly demonstrates that the variability of conjugates used by National Reference Laboratories can potentially lead to discordant results and influence assay sensitivity. In case of false negative results this could have a dramatic impact if the animal under investigation is responsible for human exposure. To avoid such situations, confirmatory tests should be implemented.

Analysis of vaccine-virus-associated rabies cases in red foxes (Vulpes vulpes) after oral rabies vaccination campaigns in Germany and Austria.

To eradicate rabies in foxes, almost 97 million oral rabies vaccine baits have been distributed in Germany and Austria since 1983 and 1986, respectively. Since 2007, no terrestrial cases have been reported in either country. The most widely used oral rabies vaccine viruses in these countries were SAD (Street Alabama Dufferin) strains, e.g. SAD B19 (53.2%) and SAD P5/88 (44.5%). In this paper, we describe six possible vaccine-virus-associated rabies cases in red foxes (Vulpes vulpes) detected during post-vaccination surveillance from 2001 to 2006, involving two different vaccines and different batches. Compared to prototypic vaccine strains, full-genome sequencing revealed between 1 and 5 single nucleotide alterations in the L gene in 5 of 6 SAD isolates, resulting in up to two amino acid substitutions. However, experimental infection of juvenile foxes showed that those mutations had no influence on pathogenicity. The cases described here, coming from geographically widely separated regions, do not represent a spatial cluster. More importantly, enhanced surveillance showed that the vaccine viruses involved did not become established in the red fox population. It seems that the number of reported vaccine virus-associated rabies cases is determined predominantly by the intensity of surveillance after the oral rabies vaccination campaign and not by the selection of strains.

Molecular epidemiology of rabies viruses in Europe.

Several different strains of classical rabies virus co-circulate in Europe. In order to investigate the roles of the host species and topography on the molecular epidemiology of these viruses, a 400 bp region of the nucleoprotein gene was sequenced and compared with more than 500 European virus isolates. Viruses from 21 European countries were represented including some unique panels of archived isolates from the former Republic of Yugoslavia, Estonia, the Czech Republic, Poland and Austria. Phylogenetic analysis of 198 unique sequences demonstrated numerous groups of viruses clustered at both geographical and host-species levels.

Job sharing as an employment alternative in group medical practice.

Although physicians discuss quality-of-life and employment issues with their patients, they often fail to consider flexible scheduling and reduced employment options to lessen their own job stress. We examined one of these options by surveying two community-based, private practice groups with a combined 13-year experience with job sharing. We found that a majority of respondents rated job sharing as successful, and most wanted it to continue. Job sharers derived considerable personal benefit from the arrangement and had significantly more positive attitudes toward work than full-time physicians. Job sharing appeared to have little impact on practice parameters. Dependability, flexibility and willingness to cooperate were the most important attributes in choosing a job-sharing partner. Job sharing is an employment alternative worth exploring to retain physicians in medical group practice.

[Relevant problems of persistent bacterial infections]. / Aktuelle Probleme persistierender bakterieller Infektionen.

The persistance of human bacterial infections is influenced by different factors and varies in duration. Besides genetical defects of the immune system the persistance of bacteria may also be enfavored by underlying diseases also. Regarding the duration of the persistance the long or even life long lasting infections are of special clinical, epidemiological and public health interest. The topic deals with present problems only, the tuberculosis is excluded and discussed in another presentation.

Human pancreatic tissue concentration of bactericidal antibiotics.

Pancreatic infection represents the most important cause of fatal outcome in human acute pancreatitis. In a comparative analysis, human pancreatic tissue concentrations of 10 different bactericidal antibiotics were determined in 89 patients undergoing pancreatic surgery. Concentrations of the antibiotics were determined in the blood and pancreatic tissue using high-pressure liquid chromatography. Pancreatic tissue concentrations 120 minutes after intravenous administration were as follows: mezlocillin, 19.0 mg/kg; piperacillin, 20.3 mg/kg; cefotaxime, 9.1 mg/kg; ceftizoxime, 7.9 mg/kg; netilmicin, 0.4 mg/kg; tobramycin, 0.4 mg/kg; ofloxacin, 1.7 mg/kg; ciprofloxacin, 0.9 mg/kg; imipenem, 6.0 mg/kg; metronidazole, 3.5 mg/kg. Three groups of antibiotics were established: group A, substances with low tissue concentrations (netilmicin, tobramycin), which were below the minimal inhibitory concentrations of most bacteria found in pancreatic infection; group B, antibiotics with pancreatic tissue concentrations which were sufficient to inhibit some but not all bacteria in pancreatic infection (mezlocillin, piperacillin, ceftizoxime, cefotaxime); group C, substances with high pancreatic tissue levels as well as high bactericidal activity against most of the germs present in pancreatic infection (ciprofloxacin, ofloxacin, imipenem). These data could serve as the basis for adequate antibiotic prophylaxis or treatment of pancreatic infection.

Introducing quality improvement thinking to medical students: the Cleveland asthma project.

This article describes a medical school's effort to introduce quality improvement (QI) concepts and methods through experiential learning to students as part of a required eight-week primary care clerkship. Each student describes a patient with asthma, investigates the cost of care, and assesses the outcome through an interview with the patient. These patients are considered together as recipients of an areawide process of care. The statistical tools of QI were adapted in a workbook to help students understand care as a process and their role as physicians in improving it.

Resin versus standard blood culture media used with the new BACTEC automated infrared system: an evaluation in febrile granulocytopenic patients.

Resin-containing aerobic and anaerobic blood culture media (NR 16A and NR 17A) for use with the new BACTEC infrared blood cultures system were compared with standard BACTEC media (NR 6A and NR 7A) in their efficacy to detect bacteremia in febrile granulocytopenic patients receiving antimicrobial treatment. A total of 1185 sets of blood cultures obtained from 341 patients during a 12-month period were evaluated. There were 109 positive cultures (9.2%) with 128 pathogenic organisms isolated from 52 patients (15.2%). Statistically significant differences were found between aerobic media, but not between anaerobic media. Aerobic resin bottles (NR 16A) were more often positive (90 versus 78, p less than 0.05) than standard aerobic bottles (NR 6A). They yielded a higher number of microorganismS (98 versus 80, p less than 0.05) per culture and per culture-positive patient (53 versus 42, p less than 0.01). NR 16A cultures also were more often positive after 1-day incubation (44% versus 21%, p less than 0.01) than NR 6A cultures and allowed earlier subcultivation. The use of NR 16A medium instead of resin-free aerobic NR 6A medium may enhance the detection of bacteremia in selected groups of patients receiving antimicrobial treatment, and can shorten the time until detection of bacteremia.

[Fish breeder granuloma: infection caused by Mycobacterium marinum and other atypical mycobacteria in the human. Analysis of 8 cases and review of the literature]. / Fischzüchtergranulom: Infektion durch Mycobacterium marinum und andere atypische Mykobakterien beim Menschen. Analyse von acht Fällen und Literaturübersicht.

Granulomatous lesions of the skin and tendon sheaths after exposure to fish tank or aquarium water are frequently caused by non-tuberculous so-called atypical mycobacteria. Mycobacterium marinum is the species most often isolated from such lesions. Rarely, other non-tuberculous species of mycobacteria may be isolated. In contrast to swimming-pool granuloma as the epidemic form of Mycobacterium marinum infection of man, fish tank granuloma seems to be a rare sporadic human disease that is often misdiagnosed. We report eight cases of fish tank granuloma. Five patients had sporotrichoid lesions, and one patient had a singular lesion. Three patients presented with tenosynovitis. Culture-proven Mycobacterium marinum infection was found in four patients, in one patient the causative organism isolated from the biopsy specimen was identified as Mycobacterium kansasii. In three patients with typical appearance of the lesions and exposure to fish tank water, biopsy specimens for culture were not available, and the diagnosis was histopathologically confirmed. Surgical treatment had an unfavourable outcome in two of three patients. Conservative antimicrobial therapy was evaluated in six patients. Similar to published reports, the treatment with rifampicin in combination with other agents seemed to be a useful therapy. Complete remission was, however, also achieved with doxycycline monotherapy. Microbiological diagnosis should be attempted in suspected cases of fish tank granuloma, and, if therapy is indicated, we strongly suggest primary medical treatment.

A survey of Cleveland Clinic training-program alumni. Implications for evaluation of graduate medical education.

The graduate of a medical training program is in a unique position to evaluate that program in comparison with the realities of medical practice. A survey of alumni of the Cleveland Clinic's graduate training programs was conducted in September 1986. The alumni's perceptions of the quality of their programs and the educational services provided by the Division of Education are discussed in relation to the educational administrative structure and evaluation process at The Cleveland Clinic Foundation. The need for such evaluation methods, as well as additional techniques to provide a comprehensive evaluation system in graduate medical education, is emphasized.

The penetration of antibiotics into human pancreas.

In order to analyse the penetration of two antibiotics (mezlocillin and metronidazole) which cover the spectrum of microorganisms involved in pancreatic infection, we determined their concentration in pancreatic tissue, juice and cyst fluid in 16 patients undergoing pancreatic surgery. In addition, the external pancreatic fistula fluid of one patient was analysed for antibiotic concentration and bacterial counts during a seven-day treatment with mezlocillin, metronidazole and netilmicin (i.v.). Antibiotic concentrations were determined by HPLC between 16 and 210 (median 74) min after i.v. administration of 4 g mezlocillin and 500 mg metronidazole, respectively. The median concentration of mezlocillin was 23.2 (range: 3.1-37.4) mg/kg, 15.9 (range: 4.2-55.0) mg/l and 9.9 (range: 5.2-14.8) mg/l in pancreatic tissue, juice and cyst fluid, respectively. The median concentration of metronidazole was 5.1 (range: 1.8-13.0) mg/kg, 8.5 (range: 3.6-16.2) mg/l and 1.2 (0.9-1.4) mg/l in pancreatic tissue, juice and cyst fluid, respectively. From the fistula patient, seven different bacteria were cultured (five aerobic and two anaerobic isolates); their concentration in fistula fluid ranged from 10(5) to 10(7) CFU/ml. The bacteria sensitive for mezlocillin and metronidazole disappeared after four days of i.v. treatment, whereas the two isolates sensitive for netilmicin showed continuous growth seven days after i.v. treatment. The peak concentrations for mezlocillin, metronidazole and netilmicin in the fistula fluid were 6.8 mg/l, 5.6 mg/l and less than 0.1 mg/l, respectively.

[Bismuth subsalicylate treatment in chronic Campylobacter pylori-associated erosive gastritis]. / Wismutsubsalicylat-Behandlung bei Campylobacter-pylori-assoziierter chronischer erosiver Gastritis.

In a prospective open study 21 patients with upper abdominal complaints and chronic active gastritis as well as endoscopically proven erosions were treated with bismuth subsalicylate (4 X 30 ml/day, corresponding to 4 X 314 mg Bi3+) for three weeks. In 20 patients (95%) Campylobacter pylori (CP) was found in at least two of three examinations (culture, CLO quick-test, special histology). After the treatment 17 of 21 patients (81%) were CP negative, and the clinical symptoms had gradually disappeared. The histologically demonstrated degree of activity had regressed significantly after the three-week treatment; in 90% of patients the inflammatory process had completely abated. These results demonstrate that bismuth subsalicylate is highly effective in the acute treatment of CP-associated chronic erosive gastritis.

A peer review process to assess the quality of graduate medical education.

Accreditation standards for graduate medical education require the internal evaluation of programs. In this paper, the authors describe a system of peer review instituted to meet these requirements and report on the supporting administrative structure and outcome of the peer review process. Although time-consuming and in some cases causing apprehension among staff members and residents, the experience of a peer review process was useful for staff members, residents, and administrators. Peer review was found to be effective in identifying program strengths and weaknesses and in increasing communication among staff members and between administrators and staff members about the teaching programs.

In vitro antibacterial activity of imipenem in combination with newer quinolone derivatives.

The antibacterial activity of imipenem combined with norfloxacin, ciprofloxacin, or ofloxacin against 43 gram-positive cocci and 53 aerobic gram-negative rods compared to results obtained with the combination of imipenem with amikacin. Synergistic antibacterial action (defined as FIC index less than or equal to 0.5) was found for 28% of strains with imipenem/amikacin and imipenem/norfloxacin, in 23% with imipenem/ofloxacin, and in 18% with imipenem/ciprofloxacin. Antagonistic activity (FIC index greater than 1.0) was found in 21, 21, 32, and 23% respectively. These rates were not statistically different for gram-positive and gram-negative isolates. Antagonistic activity seemed to occur more frequently with Pseudomonas spp. and enterococci than with staphylococci or Enterobacteriaceae. A tendency for increased rates of antagonism was noted in strains with higher MIC values. Clinically significant and meaningful positive interactions (defined as a decrease of imipenem MICs to below 2.0 micrograms/ml) were found with imipenem/amikacin against several Pseudomonas spp., with imipenem/ofloxacin or ciprofloxacin against Streptococcus faecium and with all combinations against Proteus spp. We conclude that continuous treatment with newer quinolone derivatives for selective decontamination in neutropenic patients receiving imipenem antibacterial therapy for treatment of infection should not be regarded as effective combination therapy.

Marketing issues in continuing medical education.

Marketing is an important component of continuing medical education (CME). However, marketing is more than the identification of methods to recover costs of delivering programming. It focuses on meeting the needs and desires of physician participants, identifying an appropriate location, satisfying the goals of a sponsoring institution, and making an effect on the quality of care given by receivers and deliverers of CME. This paper discusses these issues as well as describes results of a survey designed to gather opinions on CME activities from alumni of training programs of a large, referral-based, multispecialty group practice. The data suggest that CME programs should be targeted to certain specialty groups as determined by field of training rather than practice specialty. Physicians' preferences for CME activities held at resort settings should be considered. Finally, participation in CME may itself be a marketing tool for a sponsoring institution to increase referrals.