A missense variant in the NSDHL gene in a Chihuahua with a congenital cornification disorder resembling inflammatory linear verrucous epidermal nevi.

Congenital hemidysplasia with ichthyosiform nevus and limb defects syndrome in humans is a genodermatosis characterized by inflammatory linear verrucous epidermal nevi (ILVEN), often showing a striking lateralization pattern. It is caused by variants in the NSDHL gene encoding a 3ß-hydroxysteroid dehydrogenase involved in the cholesterol biosynthesis pathway. In the present study, we investigated a female Chihuahua, which showed clinical and histological signs of ILVEN. We performed a candidate gene analysis in the affected animal. This analysis revealed a single missense variant in the NSDHL gene in the affected dog (XM_014111859.2:c.700G>A). The variant is predicted to cause a non-conservative amino acid change from glycine to arginine, XP_013967334.1:p.(Gly234Arg). The mutant allele was absent from WGS data of 594 genetically diverse dogs and eight wolves. Sanger sequencing confirmed that the variant was heterozygous in the affected dog and absent from 22 control Chihuahuas. Based on the knowledge about the functional impact of NSDHL variants in dogs and other species, c.700G>A is probably pathogenic and a convincing candidate causative variant for the observed skin lesions in the affected Chihuahua.

[Interactions between lung and kidney in the critically ill]. / Lunge-Nieren-Interaktionen bei kritisch Kranken.

Interactions between lung and kidney can significantly affect the course of acute diseases, a phenomenon that was first observed in the 1950s by describing pulmonary dysfunction in uremic patients. From animal experiments there is ample evidence for remote lung injury following acute kidney injury (AKI), with an increased risk for the development of pulmonary edema and acute respiratory distress syndrome (ARDS). Coincident ARDS and AKI are associated with higher rates of intubation and mechanical ventilation, significantly prolonged weaning from mechanical ventilation and increased mortality. On the other hand, acute lung diseases and mechanical ventilation can promote the development of AKI and are associated with increased mortality when AKI is also present. These bidirectional interactions may include hemodynamic adverse effects during mechanical ventilation or volume overload as well as the release or decreased clearance and metabolism of proinflammatory mediators (e.g., interleukin-6 and tumor necrosis factor-α), which may induce and aggravate distant organ injury. The aim of this work is to examine the interactions between lung and the kidney in critically ill patients, as well as discuss potential preventive approaches.

Do time of birth, unit volume, and staff seniority affect neonatal outcome in deliveries at ≥34+0 weeks of gestation?

OBJECTIVE: We investigated whether time of birth, unit volume, and staff seniority affect neonatal outcome in neonates born at ≥34+0 weeks of gestation. DESIGN: Population-based prospective cohort study. SETTING: Ten public hospitals in the Austrian province of Styria. SAMPLE: A total of 87 065 neonates delivered in the period 2004-2015. METHODS: Based on short-term outcome data, generalised linear mixed models were used to calculate the risk for adverse and severely adverse neonatal outcomes according to time of birth, unit volume, and staff seniority. MAIN OUTCOME MEASURES: Neonatal composite adverse and severely adverse outcome measures. RESULTS: The odds ratio for severely adverse events during the night-time (22:01-07:29 hours) compared with the daytime (07:30-15:00 hours) was 1.35 (95% confidence interval, 95% CI 1.13-1.61). There were no significant differences in neonatal outcome comparing weekdays and weekends, and comparing office hours and shifts. Units with 500-1000 deliveries per year had the lowest risk for adverse events. Adverse and severely adverse neonatal outcomes were least common for midwife-guided deliveries, and became more frequent with the level of experience of the doctors attending the delivery. With increasing pregnancy risks, senior staff attending delivery and delivering in a tertiary centre reduce the odds ratio for adverse events. CONCLUSIONS: Different times of delivery were associated with increased adverse neonatal outcomes. The management of uncomplicated deliveries by less experienced staff showed no negative impact on perinatal outcome. In contrast, riskier pregnancies delivered by senior staff in a tertiary centre favour a better outcome. Achieving a better balance in the total number of labour ward staff during the day and the night appears to be a greater priority than increasing the continuous presence of senior obstetrical staff on the labour ward during the out-of-hours period. TWEETABLE ABSTRACT: Deliveries during night time lead to a greater number of neonates experiencing severely adverse events.

Long-Term Follow-up of Recurrence and Patient Satisfaction After Surgical Treatment of Gynecomastia.

BACKGROUND: "Gynecomastia" is an enlargement of the male breast. Our study aims to assess patient satisfaction as well as evaluate differences in recurrence rates in lipomatous and glandular gynecomastia 10-19 years postoperatively. METHODS: Forty-one gynecomastia patients undergoing surgical treatment from 1997 to 2005 were invited for a follow-up examination 10-19 years postoperatively. Of these, 16 patients presented for a clinical examination. Patient satisfaction was measured with a validated questionnaire [consultation satisfaction questionnaire (CSQ)-9]. Furthermore, photo-material and patient charts were evaluated concerning preoperative macroscopical type of gynecomastia, BMI, and operative technique. RESULTS: Mean follow-up time was 13.8 years (range: 10.5-19 years). Eight patients (50%) had presented with lipomatous and eight patients (50%) with glandular gynecomastia prior to surgery. One of the patients with glandular gynecomastia (12.5%) presented with recurrence at the time of follow-up, while five of the eight patients showing lipomatous gynecomastia (62.5%) presented with recurrence. Interestingly, younger patient groups tend to be more satisfied with the operative treatment of gynecomastia than older patient groups, especially regarding the improvement of self-esteem. CONCLUSIONS: Long-term follow-up results showed that recurrence rates are significantly higher in patients with lipomatous gynecomastia than in patients with glandular gynecomastia, with BMI increase in patients with glandular and lipomatous gynecomastia showing no statistically significant differences. Furthermore, general patient satisfaction and improvement of self-esteem was higher in younger patient groups than older patient groups. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . CLINICAL TRIAL REGISTRATION NUMBER: DRKS00009630.

High-volume hemofiltration in critically ill patients: a systematic review and meta-analysis.

BACKGROUND: High volume hemofiltration (HVHF) has been proposed as method for blood purification, especially under the condition of systemic inflammatory syndromes. Our goal was to evaluate the effects of HVHF in critically ill patients. METHODS: A systematic review and meta-analysis was conducted of randomized controlled trials containing original data comparing HVHF defined by a dose of >50 mL/kg/h versus standard volume hemofiltration in critically ill patients. The primary outcome assessed was mortality. Additional endpoints assessed were renal recovery, vasopressor dependency, cytokine reduction and adverse events. RESULTS: Four studies investigating continuous HVHF and three studies examining pulse high volume hemofiltration (PHVHF) using prescribed doses between 62 and 85 mL/kg/h met the criteria for this systematic review and provided data eligible for meta-analysis on a total of 558 patients. Meta-analyses did not show an effect of continuous HVHF (odds ratio, OR: 0.85; 95% confidence interval [CI]: 0.50-1.45; 4 trials; N.=473) or PHVHF (OR: 0.62; 95% CI: 0.22-1.74; 3 trials; N.=85) on mortality (both combined: OR: 0.85; 95% CI: 0.60-1.22; 7 trials; N.=558). Continuous HVHF had no significant beneficial effect on renal recovery of survivors (OR: 0.62; 95% CI: 0.17-1.97; 3 trials; N.=445). Inconsistent reports of a more rapid hemodynamic stabilization or improved cytokine clearance were mainly restricted to PHVHF. CONCLUSION: No clear overall beneficial effect of HVHF or PHVHF compared to standard volume hemofiltration can be detected.

An analysis of the epidemiological and etiological factors of oral tumors of young adults in a Central-Eastern European population.

The etiology of tumors in young age is not precisely known yet, but studies on the topic generally agree that in this group of patients the traditionally known behavioural risk factors (tobacco and alcohol abuse) play no or a significantly less important role. Oral squamous cell carcinoma occurring at a young age is a topic of utmost importance that is extensively and intensively researched as, while the overall incidence of oral cancer is decreasing worldwide, that of squamous cell carcinoma diagnosed in young adults is steadily increasing. The present article aims at presenting the main questions and characteristics of tumors in young adults in Central-Eastern Europe and in developed West European countries as contrasted to tumors found in middle aged and elderly patients. Factors influencing the development of oral cancer include regulatory factors of the cell cycle, the inherited vulnerability of the genetic code of certain proteins and the presence of HPV infection with an oncogenic genotype. The connections of HPV infection and genetic damages are studied intensively. It is known that the prevalence of oral HPV infections is growing with a background of potentially changing sexual habits. It is debated, however, whether smoking and alcohol consumption could have a connection to HPV associated oral cancer and whether the spread of HPV in itself could be an explanation for the growing occurrence of young-age tumors. There is no consensus in the literature as to the prognostic significance of age. Some research groups have found a better life expectancy for young patients, while other authors found a worse prognosis for these patients. It is known that the prognosis of head and neck tumors, the prevalence of HPV infections as well as genetic mutations show regional and ethnic variations. This might be explained by differences in the degree of development of a preventive system, in the quality of care and in the attitudes of young patients towards visiting a doctor. The study is made difficult by incomparable patient selection criteria as well as by the question of the intraoral localisation of tumors as an independent risk factor.

[Monitoring of organ functions. Dysfunction of kidneys, liver, gastrointestinal tract, and coagulation]. / Monitoring von Organfunktionen. Dysfunktion von Niere, Leber, Gastrointestinaltrakt und Gerinnung.

Monitoring of organ function is one of the core tasks of intensive care medicine. Although various monitoring devices and parameters have already been established for some organs, there are no or only few conditionally useful parameters or scores available for the kidneys, liver, gastrointestinal tract, and blood coagulation. Therefore, specific biomarkers and scores as well as combinations of both are currently investigated for better monitoring of these organs. This article gives a critical overview of currently used as well as investigational biomarkers, tests and scores in general, and shows some examples of the implications for common diseases, clinical situations and constellations in the intensive care unit.

Reproducibility of ear cytology in dogs with otitis externa.

Eighty-three dogs with clinical signs of otitis externa and with ear cytology revealing microbial organisms were studied. Samples were collected from both ears of each dog by inserting two swabs successively into each ear canal, rotating each once through 360 degrees and then rolling it out in a line on to a glass slide. For each animal, four single parallel smears (SPS) were made on one slide, which was then appropriately labelled to identify the animal as well as the order of the samples. The slides, one representing each animal, were subsequently stained with modified Wright's stain. Six high-power fields of every SPS were counted. Golden retrievers and West Highland white terriers were found to be predisposed to developing otitis externa (P=0.0006 and P=0.0123, respectively). Otitis externa occurred significantly more frequently in dogs with pendulous pinnae than in dogs with erect pinnae (P=0.0009). There was no significant difference between the first and the second samples with respect to the number of microorganisms found (P>0.1 for cocci and P>0.5 for rods and yeasts), and there was a substantial agreement between the results of the two successive swabs for the presence of cocci (kappa=0.765) and rods (kappa=0.705). For yeasts, the agreement was only moderate (kappa=0.581).

Field studies on the photosynthesis of two desert Chilean plants: Prosopis chilensis and Prosopis tamarugo.

Photosynthetic parameters were investigated in relation to light intensity (PAR and UV-B) in two Chilean Prosopis sp., Prosopis chilensis and Prosopis tamarugo in their natural habitats. The objective of this work was to compare the photosynthetic responses and to determine the degree of adaptation of both species to visible- and UV-radiation stress. One of the study sites was Refresco in the Atacama Desert, where P. tamarugo is an endemic plant and P. chilensis was introduced, and the other was Peldehue in the valley of Central Chile where only P. chilensis is present. Due to latitude, light intensity (UV-B and PAR) is higher in Refresco than in Peldehue. The parameters investigated in both species were photosystem II fluorescence, CO(2) assimilation, stomatal conductance, photosynthetic pigment composition, flavonoid absorption patterns and composition of chlorophyll-protein complexes. Fluorescence studies, CO(2) assimilation and stomatal conductance studies demonstrated that photosynthetic activity is more efficient and stable throughout the day in P. tamarugo than in P. chilensis in Refresco. Chlorophyll-protein complexes also seemed to be more stable in P. tamarugo than in P. chilensis. Photosynthetic pigment analyses indicated possible photodamage in P. chilensis trees in Refresco, but not in Peldehue. Such photodamage was absent in P. tamarugo. There was a considerable change in the flavonoid pattern between noon and afternoon hours in both species at both study sites. The physiological implications of these changes indicate that P. tamarugo is more adapted to high solar radiation than P. chilensis.

High prevalence of K-ras-2 mutations in hepatocellular carcinomas in workers exposed to vinyl chloride.

OBJECTIVES: Vinyl chloride (VC) and its metabolites are human carcinogens associated with liver angiosarcomas (LAS) and also with hepatocellular carcinomas (HCCs). In VC associated LAS mutations of the K-ras-2 gene have been reported, however, no data about the prevalence of such mutations in VC-associated HCCs are available. The aim of the study was to evaluate possible specific K-ras-2 oncogene mutations in the case of HCCs due to VC. METHODS: The presence of K-ras-2 mutations was analysed in tissue from 12 patients with VC-associated HCCs. All patients had known long-term exposure to VC (average exposure amount: 9,942 ppm-years). Twenty patients with hepatocellular carcinoma due to hepatitis B (n = 7), hepatitis C (n = 5) and alcoholic liver cirrhosis (n= 8) served as a control group. The specific mutations were determined by direct sequencing of codons 12 and 13 of the K-ras-2 gene in carcinomatous and adjacent non-neoplastic liver tissue after microdissection. Immunohistochemical analysis was performed to detect p21ras protein. RESULTS: K-ras-2 mutations were found in five of 12 (42%) examined HCCs and in three cases of adjacent non-neoplastic liver tissue (25%). There were three guanine to adenine (G --> A) point mutations in the tumour tissue. All three mutations found in non-neoplastic liver from VC-exposed patients were also G --> A point mutations (codon 12- and codon 13-aspartate mutations). Within the control group, K-ras-2 mutations were found in three of 20 (15%) examined HCCs. CONCLUSIONS: Mutations of the K-ras-2 gene in hepatocellular carcinomas associated with VC exposure are frequent events. We observed a K-ras-2 mutation pattern characteristic of chloroethylene oxide, one of the carcinogenic metabolites of VC analysed in animal models. Our results suggest that VC had direct toxic effects not only on endothelial cells but also on hepatocytes, as it was previously only described in animal models.

Endothelialized biological heart valve prostheses in the non-human primate model.

OBJECTIVE: The main disadvantage of implanted cardiac valve bioprostheses remains primarily tissue failure due to calcification. Coating of bioprostheses with viable autologous endothelial cells may delay or even eliminate tissue calcification and subsequent cardiac dysfunction. METHODS: Glutaraldehyde-preserved Hancock bioprostheses (n = 5), pretreated with glutamic acid (8%) and cryopreserved allografts (n = 5) were lined, using endothelial cells harvested from the external jugular vein. Coated specimens were cultivated for 9 days in Medium 199 supplemented with 20% fetal calf serum and basic fibroblast growth factor. Endothelialized grafts were anastomosed into the descending thoracal aorta of adult Chacma baboons. Untreated valve bioprostheses (n = 4) served as controls. Forty days after implantation the prostheses were examined morphologically and immunohistochemically. RESULTS: After implantation endothelialized prostheses showed a positive Factor VIII related antigen reaction by immunohistochemistry on all valve surfaces. Scanning electron microscopy showed confluently lined leaflets with transplanted endothelial cells and displayed cobblestone morphology on all coated allografts. In contrast, the surface of pretreated xenograft valves revealed uncoated areas with platelet and leucocyte aggregates. No endothelium was observed on the leaflets of untreated controls 40 days after implantation. CONCLUSION: In vitro endothelialization of cardiac valve bioprostheses with autologous endothelial cells is possible. The newly created endothelium is shear stress resistant and the antithrombotic as well as the antiaggregatory capacity of the transplanted cells were retained. Lining with autologous endothelial cells could improve the durability and clinical outcome of biological valve prostheses.

[Endosonographic demonstration of extrapancreatic and extraintestinal gastrinoma]. / Endosonographischer Nachweis eines extrapankreatischen und extraintestinalen Gastrinoms.

HISTORY AND CLINICAL FINDINGS: No cause had been found for chronic diarrhoea in a 57-year-old man. Up to 15 watery stools daily had been without relation to food intake and without blood admixture. But muscular cramps had developed, especially in the legs. The patient had a history of recurrent peptic ulcers for which a selective proximal vagotomy had been performed 13 years ago. Physical examination was unremarkable. INVESTIGATIONS: Alkaline phosphatase activity (182 U/l) and C-reactive protein (9.3 mg/l) were slightly raised; serum iron was 42 micrograms/dl, while all other routine laboratory tests, including protein electrophoresis, blood picture and differential count were within normal limits. Gastroscopy revealed ulcerative duodenitis, gastritis with erosions and numerous ulcers and reflux oesophagitis, grade III-IV. Endosonography showed enlarged gastric mucosal relief as sign of foveolar hyperplasia and a ca. 4 x 3 cm tumour next to the duodenal bulb. Gastrin level was 7537 pg/ml (normal < 150 pg/ml). Computed tomography and somatostatin receptor scintigraphy confirmed the site and size of the gastrinoma. TREATMENT AND COURSE: Treatment with omeprazole (40 mg three times daily) slightly improved the symptoms. The tumour was excised a week after diagnosis. The patient has been symptom-free since then. CONCLUSION: Chronic diarrhoea of unknown aetiology can be caused by an endocrine tumour; endosonography can often provide information on the diagnosis and location of such a tumour.

Endothelialization of cardiac valve bioprostheses.

The main disadvantage of implanted xenograft valves used in cardiac surgery is their poor clinical long-term result, due to early tissue degeneration. In order to improve the performance of such glutaraldehyde fixed bioprostheses, a biological coating with viable endothelial cells was suggested. Therefore, glutaraldehyde preserved bovine pericard patches, as well as commercially available xenograft valves, were lined using human venous endothelial cells or microvascular cells from the subcutaneous fat tissue. Before cells were transplanted into their new environment, grafts were treated with an amino acid solution in order to neutralize the cytotoxic effect of free aldehydes, and precoated with fibronectin-heparin and basic fibroblast growth factor (bFGF) or endothelial cell growth supplement (ECGS) in order to enhance cell proliferation. Coated specimens were kept in culture conditions for a further seven days. Proliferation of transplanted cells was verified by an increase of activation following 3H-thymidine incorporation, while the maintained metabolic cell activity was demonstrated via Prostacycline (PGI2) measurement. Morphology was evaluated by means of scanning electron microscopy (SEM). As evaluated by the beta-Counter, 7 ng/ml bFGF (288,727 +/- 39,668 counts on day 4) substantially enhanced cell proliferation after seeding, opposed to the stimulation with 30,000 ng/ml ECGS (91,924 +/- 1129 counts on day 4), (p < 0.001). The PGI2 release of transplanted cells was stimulated with 25 microM Na arachidonic acid by the factor 2.6 +/- 0.3 and inhibited with 5 mM acetylsalicylic acid by the factor 0.7 +/- 0.2 on day 4 when compared with the basic level.(ABSTRACT TRUNCATED AT 250 WORDS)

[An unusual bone scintigram in osteomyelitis. A case report]. / Ungewöhnliches Knochenszintigramm bei Osteomyelitis. Kasuistischer Beitrag.

Despite hyperemia in the blood-pool phase of bone scintigraphy with 99mTc-MDP there was an decreased concentration of the nuclide in a 7-year-old boy with acute osteomyelitis of the femur. In addition to inflammatory destruction of the bone tissue, the other reason for this surprising scintigraphic finding might be a reduced blood flow because of thrombotic occlusion or compression of bone-supplying vessels.