Tunnelling of thoracic epidural catheters is associated with fewer catheter-related infections: a retrospective registry analysis.

BACKGROUND: Catheter-related infections are a serious complication of continuous thoracic epidural analgesia. Tunnelling catheters subcutaneously may reduce infection risk. We thus tested the hypothesis that tunnelling of thoracic epidural catheters is associated with a lower risk of catheter-related infections. METHODS: Twenty-two thousand, four hundred and eleven surgical patients with continuous thoracic epidural analgesia included in the German Network for Regional Anaesthesia registry between 2007 and 2014 were grouped by whether their catheters were tunnelled (n=12 870) or not (n=9541). Catheter-related infections in each group were compared with Student's unpaired t and χ(2) tests. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated with logistic regression, adjusting for potential confounding factors, including age, ASA physical status score, use of catheter for ≥4 days, multiple skin puncture, hospital, and surgical department. RESULTS: There were fewer catheter-related infections in patients with tunnelled catheters (4.5 vs 5.5%, P<0.001). Mild infections were also less common (4.0 vs 4.6%, P=0.009), as were moderate infections (0.4 vs 0.8%, P<0.001). After adjustment for potential confounding factors, tunnelling remained an independent prevention for any grade of infection (adjusted OR 0.51, 95% CI 0.42-0.61, P<0.001) and for mild infections (adjusted OR 0.54, 95% CI 0.43-0.66, P<0.001) and moderate and severe infections (adjusted OR 0.44, 95% CI 0.28-0.70, P=0.001). CONCLUSION: Tunnelling was associated with a lower risk of thoracic epidural catheter-related infections.

Snap-fits and upper limb functional limitations in German automotive workers.

BACKGROUND: The use of snap-fit fasteners in automotive assembly has increased in the last 10 years. Their impact on musculoskeletal function of the upper limbs in assembly workers is not well described. AIMS: To investigate the association between snap-fit assembly and upper limb functional limitations (ULFLs) in workers after a large-scale expansion of snap-fit assembly by a German automotive company. METHODS: Cross-sectional data on blue-collar production workers' exposure to snap-fit assembly and ULFLs were collected from medical check-ups and company registers. The association between duration of snap-fit assembly and ULFLs, and the dose-response relationship between the two were analysed using logistic regression, adjusted for body mass index, gender and employment duration before snap-fit exposure. RESULTS: The study group included 10722 workers. Within the company, 8.4, 6.9 and 10.3% were exposed to snap-fit 1-12, 13-24 and ≥25 months, respectively. After adjusting for confounders, snap-fit exposure for 1-12 months [odds ratio (OR) = 1.59, 95% confidence interval (CI) 0.88-2.88] and 13-24 months (OR = 1.48, 95% CI 0.76-2.88) was not statistically significantly associated with ULFLs compared with an unexposed group. However, exposure to ≥25 months of snap-fit assembly was statistically significant associated with ULFLs showing >2-fold risk (OR = 2.44, 95% CI 1.52-3.92). No clear dose-response relationship was found. CONCLUSIONS: Our study suggests a negative long-term impact from snap-fit assembly on workers' upper limb function. Company physicians should be vigilant for signs of upper limb musculoskeletal disorders among workers exposed to snap-fit assembly.

Obesity in regional anesthesia--a risk factor for peripheral catheter-related infections.

BACKGROUND: Obesity is believed to increase the risk of surgical site infections and possibly increase the risk of catheter-related infections in regional anesthesia. We, therefore, analyzed the influence of obesity on catheter-related infections defined within a national registry for regional anesthesia. METHODS: The German Network for Regional Anesthesia database with 25 participating clinical centers was analyzed between 2007 and 2012. Exactly, 28,249 cases (13,239 peripheral nerve and 15,010 neuraxial blocks) of patients ≥ 14 years were grouped in I: underweight (BMI 13.2-18.49 kg/m(2) , n = 597), II: normal weight (BMI 18.5-24.9 kg/m(2) , n = 9272), III: overweight (BMI 25.0-29.9 kg/m(2) , n = 10,632), and IV: obese (BMI 30.0-70.3 kg/m(2) , n = 7,744). The analysis focused on peripheral and neuraxial catheter-related infections. Differences between the groups were tested with non-parametric ANOVA and chi-square (P < 0.05). Binary logistic regression was used to compare obese, overweight, or underweight patients with normal weight patients. Odds ratios (OR and 95% confidence interval) were calculated and adjusted for potential confounders. RESULTS: Confounders with significant influence on the risk for catheter-related infections were gender, age, ASA score, diabetes, preoperative infection, multiple skin puncture, and prolonged catheter use. The incidence (normal weight: 2.1%, obese: 3.6%; P < 0.001) and the risk of peripheral catheter-related infection was increased in obese compared to normal weight patients [adjusted OR: 1.69 (1.25-2.28); P < 0.001]. In neuraxial sites, the incidence of catheter-related infections differed significantly between normal weight and obese patients (normal weight: 3.2%, obese: 2.3%; P = 0.01), whereas the risk was comparable [adjusted OR: 0.95 (0.71-1.28); P = 0.92]. CONCLUSION: This retrospective cohort study suggests that obesity is an independent risk factor for peripheral, but not neuraxial, catheter-related infections.

[Anakinra treatment in Schnitzler syndrome -  results of the first retrospective multicenter study in six patients from the Czech Republic]. / Lécba anakinrou u Schnitzler syndromu -  výsledky první retrospektivní multicentrické studie sesti pacientu z Ceské republiky.

BACKGROUND: Schnitzler syndrome is a very rare, acquired, autoinflammatory disease of mostly adult onset with characteristic combination of chronic recurrent urticaria and monoclonal immunoglobulin M or G gammopathy predisposing the patients to malignant lymphoproliferation. In this work, we analyzed the results of bio-logical therapy with anakinra on a national level aiming to supply data for effective pharmaco-economic estimates, lay the grounds of nationwide patient registry, raise awareness among professional public and optimize provided health care. PATIENTS AND METHODS: The retrospective study (10/ 2006- 9/ 2013) included six males with definite Schnitzler syndrome verified by the new Strasbourg criteria. All patients were pretreated with antihistamines, nonsteroidal antiinflammatory drugs and glucocorticoids. Four patients underwent two or more treatment lines including intravenous bisphosphonates, 2- chlorodeoxyadenosine (cladribine), interferonα, PUVA photochemotherapy, cyclosporine A, thalidomide, bortezomib, chlorambucil, cyclophosphamide, colchicine and methotrexate. Anakinra monotherapy was initiated in standard dosing (100 mg subcutaneously daily). RESULTS: Complete and partial remissions were achieved in five (83%) and one patients (17%), respectively. Complete remission was characterized by urticaria and pain regression (within hours), normalization of inflammatory markers (with--in days) and bone metabolism improvement assessed by the markers of osteoblastic osteoformation and osteoclastic osteoresorption in one case (within weeks). With normalized inflammatory markers (including interleukin6 and interleukin18), arthralgia and sporadic exacerbations of urticaria and fevers persist in the patient in partial remission with proven Q703K polymorphism in NLRP3 gene. The median treatment followup was 30.5 months (37.2 ± 31.2 (n = 6)). The dosing interval was prolonged in one case of complete remission to 48 hours. No serious adverse reactions occurred during anakinra application. CONCLUSION: In Schnitzler syndrome, anakinra represents an effective, verified and safe medication with potentionally longterm administration not compromising its original efficacy and subjective tolerance. Anakinra, blocking autonomous inflammatory reaction of the organism via interleukin1 pathway, is a generally accepted first line treatment that should be made available in standard dosing for all Schnitzler patients.

"Alice in Wonderland syndrome" associated with topiramate for migraine prevention.

Various visual and sensory phenomena have been described in migraine with aura. Among those, the 'Alice in Wonderland' syndrome is defined as a distortion of the body image with the patient being aware of its unreal nature. Here, the case of a 17-year-old girl with migraine without aura who developed an 'Alice in Wonderland' syndrome repeatedly on topiramate treatment was presented and potential pathophysiological concepts were discussed.

Mycobacterium marinum epididymoorchitis: case report and literature review.

Mycobacterium marinum is the most frequent non-tuberculous Mycobacterium in humans. We report the first ever described case of epididymoorchitis resulting from hematogenous spread of M. marinum from hand oligoarthritis. This was initially mistaken for rheumatoid disease and methylprednisolone-induced immunosuppression led to hematogenous spread of infection to the testis and epididymis.

Immunohistochemical fingerprinting of the network of seven adhesion/growth-regulatory lectins in human skin and detection of distinct tumour-associated alterations.

Glycans of natural glycoconjugates are considered as a source of biological information relevant to cell adhesion or growth. Sugar-based messages are decoded and translated into responses by endogenous lectins. This mechanism assigns a functional dimension to tumour-associated changes of glycosylation. Consequently, it calls for mapping the lectin presence in tumours. Such an analysis has so far commonly been performed with the scope to determine expression of a few distinct proteins, e.g. from the effector family of galectins with focus on galectins-1 and -3. Due to the emerging evidence for functional divergence among galectins it is timely to address the challenge to evaluate their presence beyond these few family members. Having raised a panel of non-cross- -reactive antibodies against seven human galectins covering all three subfamilies, we de scribe their expression profiles in human skin. Comparison of normal and malignant tissues enabled us to define galectin-type-dependent alterations, arguing in favour of distinct functionalities. It is concluded that comprehensive monitoring performed to define the different aspects of the galectin network, as documented in this pilot study, is advisable for future histopathologic studies aimed at delineating clinical correlations.

Targeted enzyme therapy of experimental glomerulonephritis in rats.

We sought to determine whether systemic administration of proteases ameliorates membranous nephritis induced in rats by immunization and challenge with cationic bovine gamma globulin, and whether targeting of protease to glomerular capillaries increases efficacy. Proteases substituted with biotin were targeted via the cationic protein avidin A, which by virtue of its charge has affinity for the glomerular basement membrane. Despite identical pretreatment proteinuria, rats given untargeted protease (biotin-conjugated without avidin, or unconjugated plus avidin) had significantly less proteinuria than saline-treated controls and nephrotic rats given avidin plus biotin-conjugated (targeted) protease had even less proteinuria and reduced glomerular rat IgG and C3. Among more severely nephrotic rats, targeted protease was again more effective than untargeted protease at reducing proteinuria, and also decreased the size of electron-dense glomerular deposits, hypercholesterolemia, and creatininemia. Inactivated targeted proteases had no effect on proteinuria, hypercholesterolemia, or azotemia. Finally, active targeted protease did not affect proteinuria in the nonimmune mediated nephrosis induced by puromycin aminonucleoside. We conclude that systemic protease can specifically diminish glomerular immune deposits, proteinuria, hyperlipidemia, and creatininemia associated with experimental immune complex glomerulonephritis but not toxic nephrosis, and that targeted protease is more effective than untargeted protease.

Collagen degradation products and proinflammatory cytokines in systemic and localized scleroderma.

The aim of this study was to assess the degradation of collagen type I and proinflammatory cytokines in systemic and localized scleroderma compared with psoriasis and healthy controls. Total 99 individuals were examined - 24 with SSc, 22 with LSc, 39 patients with PsV and 14 healthy controls. U-PD and U-DPD were measured using a sensitive isocratic HPLC method. Serum levels of IL-6 and soluble IL-2R were assayed using commercial ELISA kits. In the SSc group U-PD and U-DPD levels (nmol/mmol creatinine) were increased compared with controls (P = 0.001) and with PsV (P = 0.006). IL-6 levels were increased compared with controls (P = 0.004) and with PsV (P = 0.002). IL-2R concentrations were insignificantly increased in comparison with controls and were lower than in PsV, but the difference was not significant. In the LSc group excretion of U-PD and U-DPD did not differ from controls, but was insignificantly decreased compared with PsV. IL-6 levels were increased compared with controls (P = 0.001) and also with PsV (P = 0.03). IL-2R concentrations were significantly increased in comparison with controls only (P = 0.03). In patients with SSc our data have shown the most intensive collagen degradation and simultaneously an active inflammation, as documented by IL-6, which reflects the pathological processes in the skin and visceral organs compared with PsV patients and healthy individuals. In the LSc group collagen degradation was similar to that in control groups, but a certain inflammatory activity was observed.

Glycophenotype of psoriatic skin.

Psoriasis is considered an auto-immune disease with consequential keratinocyte hyperproliferation resulting in specific architecture of psoriatic skin. This process is associated with phenotypical keratinocyte changes including an altered carbohydrate expression pattern studied by labelled plant lectins. Expression of endogenous lectins and their reactive glycoligands are differentiation-dependent in squamous epithelia including epidermis. However, no data are available on psoriatic skin, although this disease represents an important medical problem. We investigated the expression of galectin-1, -3, -7 and the presence of their glycoligands in the psoriatic skin and compared the results with the normal skin samples. The results were correlated to expression patterns of cytokeratin 10 and cytokeratin peptide 37 as markers of keratinocyte differentiation as well as to the expression of proliferation marker Ki67. Contrary to normal epidermis, the psoriatic epithelium expressed no galectin-3 and no glycoligands for galectin-1. Strong expression of galectin-3/galectin-3-reactive glycoligands in capillaries of psoriatic dermis represents one of the most important findings demonstrating the activation of endothelium in the course of the disease. The keratin expression pattern was not affected in psoriatic skin compared with normal epidermis. In conclusion, the altered galectin expression and binding pattern in psoriatic skin indicates the modified process of keratinocyte maturation in hyperactivated psoriatic epithelium. The enhanced expression of galectin-3/galectin-3-reactive glycoligands in dermal capillaries of psoriatic skin can be important for rearrangement of the capillary network and migration of inflammatory cells to psoriatic skin.

[New trends in diagnosis and treatment of systemic sclerosis]. / Nové trendy v diagnostice a lécbe systémové sklerodermie.

Systemic sclerosis (SSc) is a generalised connective tissue disease of unknown origin, which clinically shows by skin thickening and sclerosis of different extent (scleroderma) and by typical involvement of visceral organs. At the same time fibrotic and sclerotic changes occur in the blood vesel walls. SSc usually involves females at young and middle age. Myalgias, arthralgias and arthritis are nonspecific, tendon friction rubs in fingers are more typical for this diagnosis. Gastrointestinal involvement starts early in the oropharyngeal part, esophagus and proceeds into the distal parts. Fibrotic changes lead to slow transit dysmotility and pseudoobstruction and/or dilation of the bowels. The main symptoms are dysphagia, pyrosis, malabsorption and constipation. SSc produces two major patterns of abnormality within the lungs a fibrosing alveolitis or a primary pulmonary vascular disease. More frequently an insterstitial process develops which can be followed by pulmonary arterial hypertension. Cardiac involvement can also have different forms. Myocardial fibrosis usually appears at first in the conduction system by arrhythmias and various conduction blocks while pericarditis is mostly asymptomatic. Renal manifestation of SSc is observed in 8-10% patients. The most severe form--scleroderma renal crisis is characterised by the new onset of accelerated hypertension and rapidly progressive oliguric renal failure. No therapies have been proven to modify the course of SSc. Some of the drugs can affect only the skin changes. Majority of the currently applied agents have only a symptomatic effect.

Clinical correlations of potential activity markers in systemic sclerosis.

The objectives of the project were the following: (1) to establish a group of patients with a confirmed diagnosis of systemic sclerosis (Ssc), (2) to perform a detailed entrance examination of each patient, (3) to determine concentrations of potential activity markers, and (4) to make a comprehensive examination of each patient 1 year after inclusion into the study. A total of 49 patients were examined, 36 with a limited form of SSc, 9 with diffuse SSc, and 4 with other forms of SSc. We determined plasma or serum levels of the N-terminal propeptide of procollagen type III (NPIIIP), interleukin-6 (IL-6), soluble receptor for interleukin-2 (sIL-2r), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular adhesion molecule-1 (sVCAM-1), von Willebrand factor antigen (vWFAg), and big endothelin-1 (BET-1) using commercial kits, and urinary excretion of pyridinoline (PYR) and deoxypyridinoline (D-PYR) using high-performance liquid chromatography. Correlations of these markers with selected clinical data were calculated. The mean levels of all potential activity markers were increased compared with normal values, but differences were not significant. The levels of NPIIIP, D-PYR, and IL-6 were normal. The measured values after 1 year did not differ from the entry values. At entry, NPIIIP concentrations correlated with the finger-to-palm distance, and D-PYR corresponded with findings on a simplified health assessment questionnaire (FQ). IL-6 levels correlated with the leukocyte count, sIL-2r with the FQ, and ET-1 with the diffuse lung capacity for carbon monoxide. In general, we found only a few clinical correlates of potential activity markers. Our data confirmed the correlations of collagen metabolism markers with skin involvement and FQ, as was reported previously. Larger studies in this field are needed.

Detection of new diagnostic markers in pathology by focus on growth-regulatory endogenous lectins. The case study of galectin-7 in squamous epithelia.

Lectins represent one of pivotal regulators of the cell proliferation The potential of galectin-7 as a new prognostic marker was studied in normal and transformed squamous epithelia of both ectodermal (epidermis, cornea vs. trichoepithelioma, basal and squamous cell carcinoma) and endodermal (vocal fold epithelium vs. carcinoma) origin. Studies on the cultured cells were also performed. Expression of galectin-7 seems to be connected to the process of stratification, no matter of origin of epithelium. Its expression is significantly reduced in malignant cells, thus galectin-7 might be a differentiation marker of epithelial malignancies.

Eicosanoids in experimental and human renal disease.

The renal prostaglandins and thromboxanes are powerful autacoids with potential effects on renal hemodynamics, salt and water metabolism, and the immune system. The possibility of adverse effects on renal function in certain patients with renal disease due to cyclooxygenase inhibition with nonsteroidal anti-inflammatory drugs has long been appreciated. Experimental evidence indicates that renal prostaglandin and thromboxane production is increased in several models of renal disease and that similar decrements in renal function occur with cyclooxygenase inhibition and may be due to inhibition of vasodilator prostaglandins. Additionally, several investigators have shown that administration of prostaglandins may be therapeutic in some forms of renal disease, particularly immunologically mediated diseases. Dietary modification to affect prostaglandin production has also been promising in certain experimental models. In contrast to vasodilator prostaglandins, thromboxane is a potent vasoconstrictor and would be expected to have adverse effects on renal function. Despite demonstration of elevated glomerular thromboxane, studies using inhibitors of thromboxane synthesis in immunologically mediated glomerular disease have been disappointing. There is some evidence, however, that these drugs may be of benefit in ureteric obstruction and renal transplant rejection.

Diuretic therapeutics in the pediatric patient.

Careful management of fluid and electrolytes has long been an intrinsic part of pediatric practice. However, the augmentation of these manipulations through the rational use of diuretic agents requires considerable skill. In pediatric medicine, the regulation of pharmacokinetic processes and their interface with pharmacodynamic processes show dramatic age-related changes. These ontogenetic processes and their modification by various disease states must be considered carefully before selection and application of diuretic agents. The available data concerning the ontogeny of renal function and the attempts to apply diuretic therapy to pediatric disease are reviewed. It is concluded that results obtained to date suffer from the absence of a rigorous attempt to answer the fundamental therapeutic questions: What drug? What dose? What duration of therapy? A rational "target-effect" strategy is proposed for the application of diuretic agents to pediatric medicine.

The roles of eicosanoids in experimental glomerulonephritis.

There is accumulating evidence showing alterations of renal eicosanoid synthesis in glomerular disease. Despite the complexity of their role in glomerulonephritis, these compounds appear to play a major part in the inflammatory response and in control of renal hemodynamics. The role of eicosanoids in the filtration of macromolecules has not been established, but there is indirect evidence of their involvement in mediating proteinuria. Dietary manipulation, either by high EPA, high linoleic acid, or EFA-deficient diet, in experimental glomerulonephritis have shown promising results as summarized in Table 1. The therapeutic potential of alterations in dietary fatty acid to modulate the inflammatory response appears to be of great value. Table 2 summarizes the effects of different dietary fatty acid alterations on eicosanoid synthesis. Nonetheless, we should point out that most of the studies of alterations in dietary fatty acids did not document changes in glomerular synthesis of prostaglandin, thromboxane, or HETES. Further studies examining the effects of different fatty acid regimens on glomerular eicosanoid synthesis and the role of these eicosanoids in the development of glomerulonephritis will provide valuable information. These findings could determine the specific type of dietary manipulation to inhibit or stimulate the production of selected eicosanoids.

Quantitative histochemical measurement of GABA-transaminase: method for evaluation of intracerebral lesions produced by excitotoxic agents.

GABA-transaminase (GABA-T) activity of fresh frozen coronal sections through rat striatum was evaluated 4-6 weeks after intrastriatal application of kainic or ibotenic acid. 16 micrograms sections were processed for GABA-T histochemistry and were evaluated quantitatively by computerized densitometry using image analysis. Alternate sections (200 micrograms) were assayed for GABA-T activity in vitro. Gross examination of sections stained for GABA-T revealed obvious lack of staining in the vicinity of lesions produced by either kainate (0.5-1.0 micrograms) or ibotenate (10-20 micrograms); the extent of each lesion was clearly delineated by the stain. Quantitative analysis of stained sections revealed that the lesioned tissue contained 80-90% less GABA-T activity than control tissue. This loss of GABA-T was in agreement with values obtained in adjacent sections assayed in vitro. Similar studies in substantia nigra clearly and quantitatively demonstrated damage induced by ibotenate or kainate in this nucleus as well as in tissue in the overlying reticular formation. Moreover, two compartments of GABA-T were discriminated in substantia nigra: one associated with neural perikarya, which was sensitive to kainic and ibotenic acids (80% of total GABA-T), and a second associated with afferent terminals arising from forebrain projections (20%). Thus, after destruction of neurons with kainic or ibotenic acid, GABA-T activity is largely eliminated. Under these conditions, it appears that glia contribute relatively little to the GABA-T activity measured either histochemically or by direct chemical assay in homogenates.

Eosinophilic fasciitis in an adolescent girl with lymphadenopathy and vitiligo-like and linear scleroderma-like changes. A case report.

The patient, a 14-year-old girl, suffered from arthralgias which occurred after tonsillitis. Two months later she developed edema of the left lower extremity, finger flexion contractures and induration of the skin of the left leg, associated with hypergammaglobulinemia, peripheral hypereosinophilia, elevated ESR and a positivity of ANA and anti ds-DNA antibodies. A biopsy of the inguinal lymph node, performed because of left inguinal and retroperitoneal lymphadenopathy, showed only slight inflammatory activation and a granulomatous reaction after lymphography. A few days after the lymphography linear erythema evolving later into hyperpigmentation and corresponding to the superficial lymphatics developed on the left side of the body, very probably as a reaction to the patent-blue dye. Deep en-block skin biopsy confirmed the diagnosis of eosinophilic fasciitis (EF). After two years of therapy with prednisone and d-penicillamine the patient felt well, and her flexion contractures resolved, ANA were positive, while anti ds-DNA were negative. Linear hyperpigmentation persisted, and linear scleroderma-like changes developed on the left lower limb. A vitiligo-like lesion on the right foot which occurred after one year of therapy persisted. The possible risk of developing systemic connective tissue disease necessitates the long term follow up of this patient.

Comparison of the expression of Langerin and 175 kD mannose receptor in antigen-presenting cells in normal human skin and basal cell carcinoma.

The presence of professional antigen-presenting cells in tumours can influence their further spreading. Location of cells exhibiting a specific marker of Langerhans cells--Langerin, and the 175 kD mannose receptor as a marker of dendritic cells of non-Langerhans type and macrophages, was studied using double staining in the normal human epidermis and in basal cell carcinomas. The Langerin-positive cells strictly colonized the epidermis and no cells were found in the dermis, where 175 kD mannose receptor-exhibiting cells were present. Very rare elements in the epidermal/dermal interface were positive for both markers. A low incidence of Langerin-positive cells was found in tumours and 1/3 of studied carcinomas were even Langerhans cell-free. The extraepithelial presence of Langerin-positive cells forming contacts with dendrite-like protrusions of 175 kD mannose receptor-exhibiting cells was found in connective tissue surrounding the tumour epithelium and indicates possible cooperation of both elements.

The chromatographic and GC/MS analysis of organic priority pollutants in water.

This article is an overview of the proposed EPA methods for the analysis of priority pollutants in water by chromatography and gas chromatography/mass spectrometry (GC/MS). It discusses sampling, storage, apparatus, sample preparation, chromatographic and GC/MS analysis, quality control and quality assurance, and data handling as they apply to the proposed methods. Comments on the legal implications are included to underline the importance of understanding the NPDES permit granting and effluent monitoring system, as it applies to the proposed methods.