Does the neutral zone quantification method matter? Efficacy of evaluating neutral zone during destabilization and restabilization in human spine implant testing.

Neutral zone (NZ) is an important biomechanical parameter when evaluating spinal instability following destabilizing and restabilizing events, with particular relevance for implant efficacy testing. It remains unclear what NZ calculation methods are most sensitive at capturing NZ changes across treatment conditions and a direct comparison is needed. The purpose of this study was to determine the most sensitive method at quantifying instability in human spines. Six cadaveric lumbar motion segments were subjected to a repeated measures implant testing schema of four sequential conditions: (1) Intact, (2) injury by herniation, (3) device implantation, (4) long-term cyclic fatigue loading. NZ was expected to increase after destabilization (steps 2 & 4) and decrease after restabilization (step 3). NZ methods compared in this study were: trilinear (TL), double sigmoid (DS), zero load (ZL), stiffness threshold (ST), and extrapolated elastic zone (EEZ). TL, ZL, and EEZ identified statistically significant NZ differences after each condition in flexion/extension and lateral bending. The ZL method also captured differences in axial rotation. All methods identified expected NZ changes after destabilization and restabilization, except DS in axial rotation. The TL, ZL, and EEZ methods were the most sensitive methods with this human cadaveric dataset. Future investigations comparing methods with additional datasets will clarify outcome generalizability and determine what curve profiles are most suitable for DS and ST methods. Understanding the applicability of NZ methods can enhance rigor and reliability of spinal instability measurements when quantifying the efficacy of novel implants and permits insight into clinically relevant biomechanical changes.

Males Have Higher Rates of Peri-operative Mortality Following Surgery for Osteoporotic Vertebral Compression Fracture.

In this study, we evaluated the association between sex and the incidence of postoperative mortality in the peri-operative period following surgical intervention for OVCF. We found no statistical association between surgical complications and patient sex. However, males exhibited higher rates of mortality and 30-day readmissions relative to females. INTRODUCTION: Osteoporotic vertebral compression fractures (OVCF) contribute substantially to the financial burden of the US healthcare system. As the size of the elderly population grows, the number of fractures attributed to osteoporosis is expected to increase. Studies have shown that osteoporotic patients are at an increased risk for medical and surgical complications. The purpose of this study was to evaluate the association between sex and the incidence of postoperative mortality in the peri-operative period following surgical intervention for OVCF. METHODS: A retrospective analysis of the American College of Surgeons National Surgery Quality Improvement Project (ACS-NSQIP) database from 2007 to 2014 identified 1979 patients. Patients were grouped as male or female. Mortality within 30 days of surgery due to any cause, incidence of surgical complications, and 30-day readmission rates following surgery were tabulated. A multivariate logistic regression analysis was conducted to calculate odds ratios (OR) with corresponding p values and 95% confidence intervals. RESULTS: In total, 1979 patients met inclusion and exclusion criteria. Mortality within the 30 days following surgery for OVCF was statistically greater in men than in women (OR = 1.58; p = 0.050). The 30-day readmission rate was also statistically higher in men (OR = 1.41; p = 0.017). Neither minor (OR = 0.90; p = 0.560) nor major (OR = 1.14; p = 0.569) complications were statistically correlated with sex. On average, men underwent surgery for OVCF at a younger age than women. CONCLUSIONS: Male patients undergoing surgery for OVCF have higher rates of peri-operative mortality and 30-day readmissions following surgery. Sex was not found to be associated with postoperative complications. LEVEL OF EVIDENCE: III.

[Smell impairment in COVID-19 patients: mechanisms and clinical significance]. / Narushenie obonyaniya u bol'nykh COVID-19: mekhanizmy i klinicheskoe znachenie.

Numerous studies have shown that loss of smell is a serious symptom that requires careful differential diagnosis. There is convincing evidence that a violation of the sense of smell is not so much a sign of the pathology of the nasal cavity and paranasal sinuses, but it can be a manifestation of neurodegenerative diseases. Some patients with the identified SARS-CoV-2 virus have neurological symptoms. Most of them are not specific - headache, dizziness, fatigue, myalgia. A small percentage of patients with COVID-19 infection have convulsions, impaired consciousness, and the presence of 2019-NCoV RNA was found in the cerebrospinal fluid. Data on the development of new symptoms of the disease, in the form of anosmia and dysgeusia, are presented.

Thermoresponsive, redox-polymerized cellulosic hydrogels undergo in situ gelation and restore intervertebral disc biomechanics post discectomy.

Back and neck pain are commonly associated with intervertebral disc (IVD) degeneration. Structural augmentation of diseased nucleus pulposus (NP) tissue with biomaterials could restore degeneration-related IVD height loss and degraded biomechanical behaviors; however, effective NP replacement biomaterials are not commercially available. This study developed a novel, crosslinked, dual-polymer network (DPN) hydrogel comprised of methacrylated carboxymethylcellulose (CMC) and methylcellulose (MC), and used in vitro, in situ and in vivo testing to assess its efficacy as an injectable, in situ gelling, biocompatible material that matches native NP properties and restores IVD biomechanical behaviors. Thermogelling MC was required to enable consistent and timely gelation of CMC in situ within whole IVDs. The CMC-MC hydrogel was tuned to match compressive and swelling NP tissue properties. When injected into whole IVDs after discectomy injury, CMC-MC restored IVD height and compressive biomechanical behaviors, including range of motion and neutral zone stiffness, to intact levels. Subcutaneous implantation of the hydrogels in rats further demonstrated good biocompatibility of CMC-MC with a relatively thin fibrous capsule, similar to comparable biomaterials. In conclusion, CMC-MC is an injectable, tunable and biocompatible hydrogel with strong potential to be used as an NP replacement biomaterial since it can gel in situ, match NP properties, and restore IVD height and biomechanical function. Future investigations will evaluate herniation risk under severe loading conditions and assess long-term in vivo performance.

Study of worker's exposure to Tantalum-bearing particles in a mining and metallurgical plant.

The objective of this study was to assess worker exposure to mineral dust particles, and a metabolic model, based on the model adopted by ICRP, was applied to assess human exposure to Ta, and predicted values of Ta concentrations in excreta. The occupational exposure to Th, U, Nb, and Ta-bearing particles during routine tasks to obtain Fe-Nb alloys was estimated using air samplers and excreta samples. Ta concentrations in food samples and in drinking water were also determined. The results support that workers were occupationally exposed to Ta-bearing particles, and also indicate that a source of Ta exposure for both workers and the control group was the ingestion of drinking water containing soluble compounds of Ta. Therefore, some Ta compounds should be considered soluble compounds in gastrointestinal tract. Consequently, the metabolic model based on ICRP metabolic model and/or the transfer factor f 1 for Ta should be reviewed and the solubility of Ta compounds in gastrointestinal should be determined.

Comparative study between a spectral domain and a high-speed single-beam swept source OCTA system for identifying choroidal neovascularization in AMD.

This comparative study between a SD- and SS-OCTA system for visualizing neovascular patterns in AMD, also assessed the influence of cataract on OCTA imaging. 25 eyes with active CNV (AMD) were documented by FA, ICGA and SD-OCT. Two OCTA devices were used: A custom built SS-OCTA (1050 nm, 400,000 A-scans/s, 5 × 5 mm, no image segmentation); AngioVue (OptoVue, CA, USA) SD-OCTA (840 nm, 70.000 A-scans/s, 3 × 3 mm, SSADA technology). Two retina experts graded CNV types and vascular patterns. Cataract influence on OCTA image quality was reported for the superficial retinal plexus (6 eyes). The SS-OCTA prototype showed more CNV lesions compared to the SD-OCTA system (p = 0.01). Overall sensitivity of SD- and SS-OCTA systems to detect CNV lesions was.32 and.68, respectively. The SS-OCTA system was able to detect discrete lesion characteristics better than the SD-OCTA. No significant difference was found in the ability to identify CNV in treatment-naïve eyes. There was no significant influence of cataract. The SS-OCTA prototype detected CNV-associated vascular patterns more reliably than the SD-OCTA system. This is attributed to the SS-OCTA system's longer center wavelength and higher A-scan rate yielding higher definition and contrast of small neovascular structures. The SS-OCTA system used showed no advantage regarding cataract influence.

Reduced tissue osmolarity increases TRPV4 expression and pro-inflammatory cytokines in intervertebral disc cells.

The mechanical behaviour and cellular metabolism of intervertebral discs (IVDs) and articular cartilage are strongly influenced by their proteoglycan content and associated osmotic properties. This osmotic environment is a biophysical signal that changes with disease and may contribute to the elevated matrix breakdown and altered biologic response to loading observed in IVD degeneration and osteoarthritis. This study tested the hypothesis that changes in osmo-sensation by the transient receptor potential vallinoid-4 (TRPV4) ion channel occur with disease and contribute to the inflammatory environment found during degeneration. Immunohistochemistry on bovine IVDs from an inflammatory organ culture model were used to investigate if TRPV4 is expressed in the IVD and how expression changes with degeneration. Western blot, live-cell calcium imaging, and qRT-PCR were used to investigate whether osmolarity changes or tumour necrosis factor α (TNFα) regulate TRPV4 expression, and how altered TRPV4 expression influences calcium signalling and pro-inflammatory cytokine expression. TRPV4 expression correlated with TNFα expression, and was increased when cultured in reduced medium osmolarity and unaltered with TNFα-stimulation. Increased TRPV4 expression increased the calcium flux following TRPV4 activation and increased interleukin-1ß (IL-1ß) and IL-6 gene expression in IVD cells. TRPV4 expression was qualitatively elevated in regions of aggrecan depletion in degenerated human IVDs. Collectively, results suggest that reduced tissue osmolarity, likely following proteoglycan degradation, can increase TRPV4 signalling and enhance pro-inflammatory cytokine production, suggesting changes in TRPV4 mediated osmo-sensation may contribute to the progressive matrix breakdown in disease.

[Geriatric Proximal Femoral Fracture and Urinary Tract Infection - Considerations for Perioperative Infection Prophylaxis]. / Geriatrische proximale Femurfraktur und Harnwegsinfekt ­ Überlegungen zur perioperativen Infektionsprophylaxe.

Background: Perioperative infection prophylaxis with cephalosporins is standard in surgical treatment of proximal femoral fractures (PFF). Geriatric patients (pat.) are at risk of chronic infections and the bacteria from these can lead to unknown hygienic problems in an early operation. We therefore characterised the colonisation of the urinary tract in pat. (≥ 65 years) with PFF and observed bacterial development in deep wound infections over a period of 10 years. The aim was to discover gaps in perioperative infection prophylaxis. Patients and Methods: Between September 2013 and November 2015, colonisation of the urinary tract and microbial resistance were investigated on admission of all pat. (≥ 65 years) with the diagnosis of PFF (n = 351; f/m 263/88; median age [∅] 83.57 [65-100] years). Between 2005 and 2014, 2161 pat. with a PFF were operated in our clinic (f/m 1623/538; ∅ 82.35 [65-101] years). 991 pat. (∅ 81.84 [65-101] years) with femoral neck fracture [FNF] were treated with endoprosthesis/osteosynthesis, 1170 pat. (∅ 82,78 [65-101] years) with per-/subtrochanteric fracture [PTF] were treated with osteosynthesis. In a retrospective data analysis, deep wound infections, microbiological composition and changes in microbial resistances over time were identified. Results: Bacteriuria (BU) was detected in the urine sediment of 35.61 % (n = 125) of our pat. In 47.2 % of these pat., BU was accompanied by laboratory signs of manifest urinary tract infection. In 10.4 % of these pat., colonisation of the urinary tract with multi-resistant pathogens was detected; 26.4 % were resistant to cefuroxime. The rate of deep infections in pat. with endoprosthesis/osteosynthesis in FNF was 2.8 % (n = 28; f/m 19/9; ∅ 81.35 [67-92] years), with osteosynthesis in PTF 1,1 % (n = 14; f/m 10/4; ∅ 81.0 [70-91] years). A comparison of the periods 2005-2009 and 2010-2014 showed a shift in the spectrum of pathogens from cephalosporin-sensitive to cephalosporin-resistant enterococci. Resistance of pathogens against cephalosporins increased from 43 to 81 %. Conclusion: We found an increasing risk in geriatric pat. from multiresistant pathogens in the urinary tract and from an increase in the cephalosporin resistance of pathogens in urinary tract infections and in deep wound infections. This indicates that perioperative infection prophylaxis with a cephalosporin is not effective. Especially in nursing homes, development of resistance to antibiotics is an increasing problem. Thus, concepts of perioperative infection prophylaxis in geriatric patients should be reconsidered.

[Intramedullary Stabilisation of Displaced Midshaft Clavicular Fractures in Heavy Workers and Complex Fracture Pattern]. / Intramedulläre Stabilisation von dislozierten Klavikulaschaftfrakturen bei Schwerarbeitern und komplexen Frakturen.

BACKGROUND: The medical literature recommends plate osteosynthesis (PO) for complex displaced midshaft clavicular fractures (DMCF) OTA type 15B3 and for heavy workers with displaced clavicular fractures. Recovery of DMCF treated with intramedullary stabilisation (IMS) will be examined and compared to published data for duration of inability to work (DIW) after conservative treatment as well as after PO, with respect to the DIW. PATIENTS AND METHODS: Between 09/2009 and 07/2015, the DIW of 58 patients (8 f, 50 m, mean age 38.4 [20-59] years) with DMCF treated with open reduction and IMS (Titanium Elastic Nail [TEN], Synthes, Umkirch, Germany) was determined. Inclusion criteria were the presence of closed unilateral DMCF and presence of a job with national insurance at the time of accident. DIW was counted in days, starting with the accident, and ending on the last day before resumption of full work. All patients were functionally treated for 6 weeks postoperatively without weights for the shoulder and with a maximum of 90° abduction/flexion. The workload was classified in accordance with REFA criteria: group 0-1 (low physical workload) and group 2-4 (high physical workload). Fracture patterns (simple vs. complex) and postoperative physiotherapy (yes vs. no) were investigated for both REFA groups, as these factors may influence DIW. Fracture classification was performed in accordance with the OTA classification, as simple fractures (OTA type 15B1 and 15B2), and complex fractures (OTA type 15B3). Effects were concerned significant if p ≤ 0.05. RESULTS: Median DIW was independent of physical workload, with 39.86 (3-150) days (n = 58). Patients with low physical workload (REFA 0-1; n = 33) had shorter duration of DIW, with an average of 32.48 (3-136) days than patients with higher physical workload (REFA 2-4; n = 25), with 49.6 (14-150) days (p = 0.02). The fracture type did not influence this significantly (simple fractures [n = 35]: average 40.54 [3-150] days; complex fractures [n = 23]: average 38.82 [14-136] days, p = 0.85). Within each REFA group, differences in DIW for each fracture type were greater, but did not attain statistical significance. Patients without postoperative PT (n = 30) had a shorter DIW, with an average of 30.5 (3-84) days, than patients with postoperative PT (n = 28), with an average of 49.89 (14-150) days (p = 0.021). Within both REFA groups, DIW changed similarly with postoperative PT, in some cases with statistical significance. CONCLUSION: DIW after IMS of DMCF does not depend on the complexity of the fracture. For heavy workers, DIW after IMS is significantly longer than for light physical workers. IMS of DMCF permits immediate pain-adapted movement of the shoulder, with a maximal abduction/flexion up to 90°, no matter what the fracture type. Patients given additional professional PT showed longer DIW than those without such treatment.

Form and function of the intervertebral disc in health and disease: a morphological and stain comparison study.

Multiple histologic measurements are commonly used to assess degenerative changes in intervertebral disc (IVD) structure; however, there is no consensus on which stains offer the clearest visualization of specific areas within the IVD. The objective of this study was to compare multiple tinctorial stains, evaluate their ability to highlight structural features within the IVD, and investigate how they influence the capacity to implement a degeneration scoring system. Lumbar IVDs from seven human autopsy specimens were stained using six commonly used stains (Hematoxylin/Eosin, Toluidine Blue, Safranin-O/Fast Green, Extended FAST, modified Gomori's Trichrome, and Picrosirius Red Alcian Blue). All IVDs were evaluated by three separate graders to independently determine which stains (i) were most effective at discerning different structural features within different regions of the IVDs and (ii) allowed for the most reproducible assessment of degeneration grade, as assessed via the Rutges histological scoring system (Rutges et al. A validated new histological classification for intervertebral disc degeneration. Osteoarthritis Cartilage, 21, 2039-47). Although Trichrome, XFAST and PR/AB stains were all effective at highlighting different regions of whole IVDs, we recommend the use of PR/AB because it had the highest degree of rater agreement on assigned degeneration grade, allowed greater resolution of degeneration grade, has an inferential relationship between color and composition, and allowed clear differentiation of the different regions and structural disruptions within the IVD. The use of a standard set of stains together with a histological grading scheme can aid in the characterization of structural changes in different regions of the IVD and may simplify comparisons across the field. This collection of human IVD histological images highlights how IVD degeneration is not a single disease but a composite of multiple processes such as aging, injury, repair, and disease, each of which are unique to the individual.

Fibrin-genipin adhesive hydrogel for annulus fibrosus repair: performance evaluation with large animal organ culture, in situ biomechanics, and in vivo degradation tests.

Annulus fibrosus (AF) defects from annular tears, herniation, and discectomy procedures are associated with painful conditions and accelerated intervertebral disc (IVD) degeneration. Currently, no effective treatments exist to repair AF damage, restore IVD biomechanics and promote tissue regeneration. An injectable fibrin-genipin adhesive hydrogel (Fib-Gen) was evaluated for its performance repairing large AF defects in a bovine caudal IVD model using ex vivo organ culture and biomechanical testing of motion segments, and for its in vivo longevity and biocompatibility in a rat model by subcutaneous implantation. Fib-Gen sealed AF defects, prevented IVD height loss, and remained well-integrated with native AF tissue following approximately 14,000 cycles of compression in 6-day organ culture experiments. Fib-Gen repair also retained high viability of native AF cells near the repair site, reduced nitric oxide released to the media, and showed evidence of AF cell migration into the gel. Biomechanically, Fib-Gen fully restored compressive stiffness to intact levels validating organ culture findings. However, only partial restoration of tensile and torsional stiffness was obtained, suggesting opportunities to enhance this formulation. Subcutaneous implantation results, when compared with the literature, suggested Fib-Gen exhibited similar biocompatibility behaviour to fibrin alone but degraded much more slowly. We conclude that injectable Fib-Gen successfully sealed large AF defects, promoted functional restoration with improved motion segment biomechanics, and served as a biocompatible adhesive biomaterial that had greatly enhanced in vivo longevity compared to fibrin. Fib-Gen offers promise for AF repairs that may prevent painful conditions and accelerated degeneration of the IVD, and warrants further material development and evaluation.

C5 nerve root palsy following decompression of the cervical spine: a systematic evaluation of the literature.

C5 nerve root palsy is a rare and potentially debilitating complication of cervical spine surgery. Currently, however, there are no guidelines to help surgeons to prevent or treat this complication. We carried out a systematic review of the literature to identify the causes of this complication and options for its prevention and treatment. Searches of PubMed, Embase and Medline yielded 60 articles for inclusion, most of which addressed C5 palsy as a complication of surgery. Although many possible causes were given, most authors supported posterior migration of the spinal cord with tethering of the nerve root as being the most likely. Early detection and prevention of a C5 nerve root palsy using neurophysiological monitoring and variations in surgical technique show promise by allowing surgeons to minimise or prevent the incidence of C5 palsy. Conservative treatment is the current treatment of choice; most patients make a full recovery within two years.

Development and validation of a bioreactor system for dynamic loading and mechanical characterization of whole human intervertebral discs in organ culture.

Intervertebral disc (IVD) degeneration is a common cause of back pain, and attempts to develop therapies are frustrated by lack of model systems that mimic the human condition. Human IVD organ culture models can address this gap, yet current models are limited since vertebral endplates are removed to maintain cell viability, physiological loading is not applied, and mechanical behaviors are not measured. This study aimed to (i) establish a method for isolating human IVDs from autopsy with intact vertebral endplates, and (ii) develop and validate an organ culture loading system for human or bovine IVDs. Human IVDs with intact endplates were isolated from cadavers within 48h of death and cultured for up to 21 days. IVDs remained viable with ~80% cell viability in nucleus and annulus regions. A dynamic loading system was designed and built with the capacity to culture 9 bovine or 6 human IVDs simultaneously while applying simulated physiologic loads (maximum force: 4kN) and measuring IVD mechanical behaviors. The loading system accurately applied dynamic loading regimes (RMS error <2.5N and total harmonic distortion <2.45%), and precisely evaluated mechanical behavior of rubber and bovine IVDs. Bovine IVDs maintained their mechanical behavior and retained >85% viable cells throughout the 3 week culture period. This organ culture loading system can closely mimic physiological conditions and be used to investigate response of living human and bovine IVDs to mechanical and chemical challenges and to screen therapeutic repair techniques.

A role for TNFα in intervertebral disc degeneration: a non-recoverable catabolic shift.

This study examines the effect of TNFα on whole bovine intervertebral discs in organ culture and its association with changes characteristic of intervertebral disc degeneration (IDD) in order to inform future treatments to mitigate the chronic inflammatory state commonly found with painful IDD. Pro-inflammatory cytokines such as TNFα contribute to disc pathology and are implicated in the catabolic phenotype associated with painful IDD. Whole bovine discs were cultured to examine cellular (anabolic/catabolic gene expression, cell viability and senescence using ß-galactosidase) and structural (histology and aggrecan degradation) changes in response to TNFα treatment. Control or TNFα cultures were assessed at 7 and 21 days; the 21 day group also included a recovery group with 7 days TNFα followed by 14 days in basal media. TNFα induced catabolic and anti-anabolic shifts in the nucleus pulposus (NP) and annulus fibrosus (AF) at 7 days and this persisted until 21 days however cell viability was not affected. Data indicates that TNFα increased aggrecan degradation products and suggests increased ß-galactosidase staining at 21 days without any recovery. TNFα treatment of whole bovine discs for 7 days induced changes similar to the degeneration processes that occur in human IDD: aggrecan degradation, increased catabolism, pro-inflammatory cytokines and nerve growth factor expression. TNFα significantly reduced anabolism in cultured IVDs and a possible mechanism may be associated with cell senescence. Results therefore suggest that successful treatments must promote anabolism and cell proliferation in addition to limiting inflammation.

Radon in indoor concentrations and indoor concentrations of metal dust particles in museums and other public buildings.

The aim of this study was to evaluate the public and occupational exposure to radon and metal-bearing particles in museums and public buildings located in the city of Rio de Janeiro, Brazil. For this study, four buildings were selected: two historic buildings, which currently house an art gallery and an art museum; and two modern buildings, a chapel and a club. Integrated radon concentration measurements were performed using passive radon detectors with solid state nuclear track detector-type Lexan used as nuclear track detector. Air samplers with a cyclone were used to collect the airborne particle samples that were analyzed by the particle-induced X-ray emission technique. The average unattached-radon concentrations in indoor air in the buildings were above 40 Bq/m(3), with the exception of Building D as measured in 2009. The average radon concentrations in indoor air in the four buildings in 2009 were below the recommended reference level by World Health Organization (100 Bq/m(3)); however, in 2011, the average concentrations of radon in Buildings A and C were above this level, though lower than 300 Bq/m(3). The average concentrations of unattached radon were lower than 148 Bq/m(3) (4pCi/L), the USEPA level recommended to take action to reduce the concentrations of radon in indoor air. The unattached-radon average concentrations were also lower than the value recommended by the European Union for new houses. As the unattached-radon concentrations were below the international level recommended to take action to reduce the radon concentration in air, it was concluded that during the period of sampling, there was low risk to human health due to the inhalation of unattached radon in these four buildings.

Notochordal cell-derived therapeutic strategies for discogenic back pain.

An understanding of the processes that occur during development of the intervertebral disk can help inform therapeutic strategies for discogenic pain. This article reviews the literature to identify candidates that are found in or derived from the notochord or notochordal cells and evaluates the theory that such factors could be isolated and used as biologics to target the structural disruption, inflammation, and neurovascular ingrowth often associated with discogenic back pain. A systematic review using PubMed was performed with a primary search using keywords "(notochordal OR notochord) And (nerves OR blood vessels OR SHH OR chondroitin sulfate OR notch OR CTGF) NOT chordoma." Secondary searches involved keywords associated with the intervertebral disk and pain. Several potential therapeutic candidates from the notochord and their possible targets were identified. Studies are needed to further identify candidates, explore mechanisms for effect, and to validate the theory that these candidates can promote structural restoration and limit or inhibit neurovascular ingrowth using in vivo studies.

International round-robin study on the Ames fluctuation test.

An international round-robin study on the Ames fluctuation test [ISO 11350, 2012], a microplate version of the classic plate-incorporation method for the detection of mutagenicity in water, wastewater and chemicals was performed by 18 laboratories from seven countries. Such a round-robin study is a precondition for both the finalization of the ISO standardization process and a possible regulatory implementation in water legislation. The laboratories tested four water samples (spiked/nonspiked) and two chemical mixtures with and without supplementation of a S9-mix. Validity criteria (acceptable spontaneous and positive control-induced mutation counts) were fulfilled by 92-100%, depending on the test conditions. A two-step method for statistical evaluation of the test results is proposed and assessed in terms of specificity and sensitivity. The data were first subjected to powerful analysis of variance (ANOVA) after an arcsine-square-root transformation to detect significant differences between the test samples and the negative control (NC). A threshold (TH) value based on a pooled NC was then calculated to exclude false positive test results. Statistically, positive effects observed by the William's test were considered negative, if the mean of all replicates of a sample did not exceed the calculated TH. By making use of this approach, the overall test sensitivity was 100%, and the test specificity ranged from 80 to 100%.

[Gastroenteritis with fever, headache and rash after travelling in India]. / Gastroenteritis mit Fieber, Zephalgie und Exanthem nach Indienreise.

A 63-year-old patient presented to our emergency unit two days after returning from India suffering from watery diarrhea, nausea, fever and headache. On admission we found a maculopapular rash on his trunk and forehead. Laboratory findings revealed a leuko-thrombopenia and elevated levels of CRP and procalcitonin. We started treatment with ciprofloxacin. After 48 hours of treatment the diarrhea subsided, whereas the rush on his trunk increased. Under the suspicion of rickettsial fever we started doxycycline 200 mg/d. Because of an incipient pneumonia we added ceftriaxon. The patient improved rapidly and the laboratory abnormalities resolved. Serological investigations revealed a significant increase of specific antibodies against Rickettsia typhi. In conclusion, headache with fever and maculopapular rash after traveling to endemic countries should rise suspicion for murine typhus.

Scaling behaviour of hyaluronic acid in solution with mono- and divalent ions.

The effect of the simultaneous presence of mono- and divalent cations on the thermodynamics of polyelectrolyte solutions is not fully understood. In physiological conditions, combinations of these ions affect structure formation in biopolymer systems. It is known that divalent counterions form a tight sheath around the polymer backbone, while monovalent ions are distributed in a diffuse cloud. Dynamic light scattering measurements of the collective diffusion coefficient D and the osmotic compressibility of semi-dilute hyaluronan solutions containing different ratios of sodium and calcium ions are compared with simple polyelectrolyte models. Scaling relationships are derived in terms of polymer concentration and ionic strength J of the added salt. Differences in the effects of sodium and calcium ions are expressed only through J.

[Pancytopenia, hepatosplenomegaly and dry cough after breast cancer]. / Panzytopenie, Hepatosplenomegalie und Reizhusten nach Mamma-Karzinom.

HISTORY AND CLINICAL FINDINGS: A 71-year-old woman had suffered for 6 weeks from fatigue, dry cough and fever. Five years previously breast cancer had been diagnosed and had been successfully treated with subtotal mastectomy and postoperative radiotherapy, as well as aromatase inhibitor until shortly before the present admission. There was no history of travel to tropical countries, but during the last summer she had spent two weeks in Northern Italy. [corrected] INVESTIGATIONS: On admission the body temperature was 38,5 C with a mild tachycardia (108/min). Laboratory findings revealed a pancytopenia and slightly elevated liver enzymes. The ultrasound showed a hepatosplenomegaly. The investigation of the bone marrow showed a great amount of parasitic forms due to visceral leishmaniasis [corrected] TREATMENT, COURSE AND DIAGNOSIS: Treatment with liposomal amphotericin B brought about rapid improvement, the dry cough subsided and the laboratory results became normal. CONCLUSION: Pancytopenia, fever, dry cough and hepatosplenomegaly after travelling to Mediterranean countries should raise suspicion of visceral leishmaniasis. This diagnosis is confirmed by direct detection of the parasite in the bone marrow. Administration of liposomal amphotericin B is efficacious and safe, bringing about full recovery in up to 90% of cases.