Implementation of a standardized clinical test kit for diagnostics of periprosthetic infections in the clinical routine.

BACKGROUND: The number of primary arthroplasties is increasing and the proportion of revision arthroplasties is becoming increasingly more important. The need for standardized and guideline-based diagnostics for the safe detection of a periprosthetic joint infection (PJI) is becoming apparent. In the past 10 years various organizations have published definitions and diagnostic guidelines. The implementation of an inhouse standard test kit could help to simplify the process and could improve the diagnostic quality. METHOD: In 2016 a test kit was compiled in a monocentric prospective study, taking the International Consensus Meeting (ICM) criteria 2014 and the Infectious Diseases Society of America (IDSA) criteria into account, which also fulfils the definitions of the ICM criteria 2018 and criteria of the European Bone and Joint Infection Society 2021. The test kit was implemented in the clinical setting of a special department for aseptic and septic revision arthroplasty. The usability and accuracy of the test kit were examined. RESULTS: The test kit was implemented using blood samples (leukocyte count; C­reactive protein, CRP), samples for examining the synovial fluid (white blood cell count, PMN cell differentiation, microbiological culture for incubation over 14 days, alpha-defensin enzyme-linked immunosorbent assay, ELISA, leukocyte esterase test strips) together with information and request forms. Between April 2016 and February 2020 a total of 405 patients were investigated. Within 3 calendar years, the use of the test kit increased from 59% initially to 86%, and finally to 96% of cases in the third calendar year. The leukocyte esterase test strip was reliable in only 72%, due to undifferentiated readability or blood contamination. The costs increased by the only commercially available alpha-defensin ELISA test by approx. 52€ per puncture. The best individual test showed a sensitivity/specificity of 92.8%/95.2% with alpha-defensin. It was calculated which combinations showed a similar test quality and different combinations, such as CRP+ cell count+ microbiology showed a sensitivity/specificity both of around 90%. Metallosis is a challenge for preoperative PJI diagnostics. DISCUSSION: In a prospective study it was shown, that the implementation of the standardized test kit lead to a guideline based PJI diagnostic in all cases and thus to a significantly increase of the diagnostic quality. There is currently no single test that reliably excludes or proves an infection. The alpha-defensin laboratory ELISA test showed the best test accuracy, whereby the consideration of test combinations is obligatory and at the same time safe.

Exciton dynamics in perturbed vibronic molecular aggregates.

A site specific perturbation of a photo-excited molecular aggregate can lead to a localization of excitonic energy. We investigate this localization dynamics for laser-prepared excited states. Changing the parameters of the electric field significantly influences the exciton localization which offers the possibility for a selective control of this process. This is demonstrated for aggregates possessing a single vibrational degree of freedom per monomer unit. It is shown that the effects identified for the molecular dimer can be generalized to larger aggregates with a high density of vibronic states.

m-Trifluoromethyl-diphenyldiselenide as a pharmacological tool to treat preference symptoms related to AMPH-induced dependence in rats.

Amphetamine (AMPH) abuse is a world concern and a serious public health problem. Repeated administration of high doses of AMPH induces neuropsychiatric consequences, including addiction, reward and psychosis, whose pharmacological treatment has shown limited effectiveness. The m-trifluoromethyl-diphenyldiselenide [(m-CF3-PhSe)2] has been documented as a promising pharmacological agent in different animal models related to oxidative damage. In this study, we examined the influence of (m-CF3-PhSe)2 on withdrawal following re-exposure to AMPH. Wistar rats received d,l-AMPH or saline in the conditioned place preference (CPP) paradigm for 8days. Then, half of each initial (AMPH or saline) experimental group was treated with (m-CF3-PhSe)2 or vehicle, resulting in four final groups: i) Saline/vehicle; ii) (m-CF3-PhSe)2/saline; iii) AMPH/vehicle; and iv) AMPH/(m-CF3-PhSe)2. After fourteen days of (m-CF3-PhSe)2 treatment, animals were re-exposed to AMPH or vehicle in the CPP paradigm for three more days in order to assess drug re-conditioning and memory/locomotor activity, performed 24h after AMPH re-exposure in the CPP and the Y maze, respectively. Subsequently, ex-vivo assays were carried out in samples of the prefrontal cortex (PFC) of the animals. The (m-CF3-PhSe)2 treatment was able to prevent AMPH-induced re-conditioning symptoms in rats. Behavioral observations in the Y maze task showed no significant changes. AMPH exposure was able to increase 5-HT uptake as well as oxidative damage in the PFC, whereas (m-CF3-PhSe)2 treatment exerted a preventative effect against these alterations. The current findings suggest that (m-CF3-PhSe)2 might be considered a promising therapeutic tool for AMPH-induced addiction.

On the parameterization of vibronic Hamiltonians for molecular aggregates using absorption line-shapes as an input.

Absorption line-shapes of molecular aggregates are often calculated using a simple form for a vibronic Hamiltonian. Parameters which enter into the model are usually taken from measured spectra. Here, we address the question in how far different sets of input parameters used to calculate the spectra lead to similar spectral features. Therefore, we first present analytical expressions which illustrate the relation between the various parameters such as Huang-Rhys factors, electronic coupling elements, and aggregate size. Numerical calculations show that identical peak ratios and spectra can be obtained for different sets of parameters. This illustrates the basic difficulties in extracting reliable molecular information from a comparison of calculated and measured spectra.

[Osteoblasts : cellular and molecular regulatory mechanisms in fracture healing]. / Osteoblasten : Zelluläre und molekulare Regulationsmechanismen in der Frakturheilung.

Bone tissue possesses a unique regeneration ability, translating mechanical and metabolic stimuli into a biological response. The perpetual regeneration processes allow continuous self-renewal and adaptation to prevailing mechanical forces. The complex regulation of osteoblastic differentiation during fracture repair has not been completely defined. Two different transcription factors - RUNX2 and SP7 - are considered to be master genes of osteoblastic differentiation. Furthermore, the canonical WNT pathway plays an essential role in the activation of osteoblastic differentiation during both bone growth and fracture healing. Studies of fracture healing have revealed that downregulation of the WNT pathway causes a significant reduction in new bone formation. Moreover, correct WNT signalling is also required for BMP2-induced bone formation. There is increasing evidence that patients who develop recalcitrant fracture nonunions exhibit not only reduced numbers and differentiation capacity of osteogenic progenitors but also a significant downregulation of numerous factors in the WNT pathway. Therefore, better understanding of the WNT regulatory mechanisms could reveal new strategies for the treatment of delayed fracture healing and for the tissue engineering of bone.

Inhibition of osteosarcoma cell proliferation by the Hedgehog-inhibitor cyclopamine.

Osteosarcomas (OS) are the most frequent primary malignant bone tumors in humans. Even though OS are chemosensitive, about 30% of patients must be considered poor responders and consequently have a dismal long term prognosis. The Hedgehog (Hh) gene is crucial in the signalling pathways of proliferation and differentiation during embryonic development. There is evidence that uncontrolled activation of this pathway results in specific types of cancer and that inhibition of Hh signalling is able to suppress tumour growth and to induce apoptosis of neoplastic cells. This study investigates the impact of the steroidal alkaloid and Hh-inhibitor cyclopamine on osteosarcoma cells. Thus we demonstrate the drug's impact on cellular proliferation, cell cycle cell death as well as the cells' metabolism. We here demonstrate that cyclopamine exhibits a high efficacy against the osteosarcoma cell lines HOS, SaOS and OS-KA, a self-established primary osteosarcoma cell line. In particular, cyclopamine is able to inhibit proliferation and to promote cell death. Our results provide evidence for the potency of the Hh-inhibitor cyclopamine as a future treatment of osteosarcomas.

Immediate sexual rehabilitation by simultaneous placement of penile prosthesis in patients undergoing radical prostatectomy: initial results in 50 patients.

OBJECTIVES: To evaluate the results of simultaneous placement of a penile prosthesis with radical prostatectomy. METHODS: From June 1993 to June 1996, 50 men underwent a combination procedure of non-nerve sparing radical retropubic prostatectomy and placement of a penile prosthesis. We performed a retrospective chart review of these patients, examining patient age, preoperative prostate-specific antigen level, Gleason score, operative time, estimated blood loss, analgesic use, length of hospital stay, time until intercourse, and complications. This group was compared with a group of 72 men undergoing radical prostatectomy alone during the same time interval. RESULTS: No significant differences were noted in preoperative patient variables. The mean operative time for prosthesis insertion was 82 minutes, and the mean time to sexual intercourse was 12.7 weeks. No prosthesis infections have occurred, with a mean follow-up of 1.7 years. Four men (8%) have required revision of their inflatable penile prosthesis. There were no significant differences between the combination procedure and radical prostatectomy alone with regard to estimated blood loss, length of hospital stay, or analgesic use. CONCLUSIONS: Simultaneous placement of a penile prosthesis during radical prostatectomy provides early return to sexual function, with no apparent increase in morbidity. Further study will be required to determine the impact of combination surgery on psychosocial adjustment and quality of life.

Occult prostate cancer in men with low serum testosterone levels.

OBJECTIVE: To determine the prevalence of occult prostate cancer in men with low serum total testosterone or free testosterone levels. DESIGN: Retrospective analysis of a consecutive series of men. SETTING: Academic teaching hospital. PATIENTS: Seventy-seven men with low total testosterone or free testosterone levels, with normal results of digital rectal examination and prostate-specific antigen (PSA) levels of 4.0 ng/mL or less. The mean age was 58 years. INTERVENTIONS: Sextant prostate needle biopsies with ultrasound guidance. MAIN OUTCOME MEASURES: Results of prostate needle biopsies, transrectal ultrasound, prostate volume, PSA level, PSA density, total and free testosterone levels. RESULTS: Prostate cancer was identified in 14% (11/77) of the entire group and in 10 men (29%) aged 60 years or older. The median age for men with cancer was 64 years. Histologic examination showed Gleason scores of 6 or 7 for all cancers. No significant differences were noted between the cancer and benign groups with regard to PSA level, PSA density, prostate volume, total testosterone level, or free testosterone level. CONCLUSIONS: A high prevalence of biopsy-detectable prostate cancer was identified in men with low total or free testosterone levels despite normal PSA levels and results of digital rectal examination. These data suggest that (1) digital rectal examination and PSA levels are insensitive indicators of prostate cancer in men with low total or free testosterone levels, and (2) PSA levels may be altered by naturally occurring reductions in serum androgen levels.

Detached ciliary tufts in the epididymis: a lesson in applied anatomy.

We report a case of detached ciliary tufts (DCTs) discovered in the aspirate from an epididymal cyst in a 30-year-old man undergoing epididymal exploration for obstructive azoospermia. The specimen was initially misdiagnosed as a parasite due to its appearance and spontaneous motion on fresh smear. Since standard urology and histology texts identify ciliated cells only in the efferent duct of the male genital tract, the source of DCTs in this patient was mysterious. However, on further review, histologic studies have demonstrated that the first portion of the epididymis represents an extension of the efferent ducts and is lined with cilia. The fact that the caput epididymis is composed of branched efferent ducts has significant implications for our understanding of congenital absence of the vas, epididymal sperm aspiration, spermatoceles, and epididymal physiology.

Experience with the penile prosthesis and artificial urinary sphincter.

The therapy of two common urologic problems, erectile dysfunction and urinary stress incontinence, has been revolutionized over the last 20 years by the incorporation of principles of hydraulic mechanics into the field of silicone prosthesis implantation. The inflatable penile prosthesis is surgically implanted into men with impotence due to organic or psychogenic etiology. The artificial urinary sphincter has found widespread use in males and females in both the adult and pediatric populations with stress incontinence from a variety of causes. Associated with these popular devices are various complications relating to the anatomic site as well as the host's immunologic response. The use of these implants, as well as the technologic innovations resulting from various adverse effects, are reviewed herein.

Characteristics of live and killed brewer's yeast slurries and intoxication by intraruminal administration to cattle.

The physical and nutritional characteristics of live and killed brewer's yeast slurries and the possible toxicity of intraruminal administration of loading doses of these by-products were evaluated. Dry-matter (DM) percentages of live brewer's yeast slurry ranged from 10.5 to 29.0, and DM percentages of killed brewer's yeast slurry ranged from 14.6 to 18.5. Total crude protein (N X 6.25) percentages of live and killed yeast slurries (DM basis) were 44.1 and 43.1; ethanol percentages (wet basis) were 6.96 and 1.84, respectively. Phase contrast photomicrographs showed distinct differences in morphology between live and killed yeast cells. Intraruminal administration of loading doses (0, 2.3, 4.5 and 6.8 kg) of live and killed brewer's yeast slurries to bull calves induced clinical intoxication at the 4.5-kg and 6.9-kg dosages of live brewer's yeast slurry. No toxicity was induced either with the killed brewer's yeast or with the 0-kg or 2.3-kg dose levels of live brewer's yeast slurry. The clinical signs and plasma ethanol concentrations suggested ethanol intoxication. Ruminal NH3 concentrations increased to over 70 mg/dl with the 4.5-kg and 6.9-kg dosages of live brewer's yeast slurry, but they did not exceed 35 mg/dl with an equivalent dosage of killed brewer's yeast slurry.