The use of oclacitinib compared to azathioprine in the management of canine pemphigus foliaceus: A retrospective analysis.

BACKGROUND: Oclacitinib (Apoquel; Zoetis) has been reported to be beneficial for treating immune-mediated disorders. HYPOTHESIS/OBJECTIVES: This retrospective study evaluates in which group of dogs [oclacitinib (OC) or azathioprine (AZ)] remission of pemphigus foliaceus (PF) was more effectively achieved with matched induction dosing of glucocorticoids; it further evaluates which group had a higher glucocorticoid-sparing effect. ANIMALS: Review of 30 medical records of dogs diagnosed with PF presented to a private practice dermatological service. MATERIALS AND METHODS: Retrospective analysis of dogs diagnosed with PF and treated with OC or AZ in combination with glucocorticoids. RESULTS: There was no significant difference in the ability to induce remission between AZ and OC groups. In the AZ group, 13 of 15 dogs went into some type of remission (partial or complete), compared with 11 of 15 in the OC group. There was no significant difference between the two groups for the glucocorticoid-sparing effect. The AZ group had an average reduction of 77.9% from the induction glucocorticoid dose, and OC group had an average reduction of 64.4%. One of 15 patients in the AZ group and three of 15 patients in the OC group had a 100% reduction of the glucocorticoid dose. CONCLUSIONS AND CLINICAL RELEVANCE: These results indicate that OC can be considered as a treatment option for canine PF.

Loop-mediated isothermal amplification for paratyphoid fever - a proof-of-principle analysis.

In-house loop-mediated isothermal amplification (LAMP) procedures for the detection of paratyphoid fever-associated bacteria on serovar level were evaluated. Therefore, LAMP primers for Salmonella genus, for two LAMP schemes for S. Paratyphi A, for S. Paratyphi B and for S. Paratyphi C were tested with DNA from culture isolates from strain collections and spiked blood cultures against published PCR protocols targeting the same micro-organisms. Sensitivity and specificity for DNA from culture isolates verified by LAMP ranged from 80·0 to 100·0% and 96·1 to 100·0% vs 65 to 100% and 98·7 to 100% for the PCR approaches. For the spiked blood culture materials, sensitivity and specificity for LAMP ranged from 87·5 to 100·0% and 96·7 to 100·0% vs from 60 to 100% and 98·2 to 100% for PCR. In conclusion, LAMP for paratyphoid fever shows comparable performance characteristics as PCR. Due to its easy application, the procedure is well suited for surveillance purposes in resource-limited settings. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of easy-to-apply, point-of-care-testing-like loop-mediated isothermal amplification (LAMP) for the diagnosis of paratyphoid fever is evaluated. This approach can contribute to low-threshold availability of surveillance options for resource limited settings. Easy-to-teach and easy-to-apply LAMP schemes with similar performance characteristics as PCR are provided. The described test evaluation is of particular use for surveillance and public health experts.

Energy loss via urine and faeces--a combustive analysis in diabetic rats and the impact of antidiabetic treatment on body weight.

AIMS: Intensive glycaemic control in type 2 diabetes achieved by insulin is generally accompanied by body weight gain. This study was performed to emphasize the meaning of caloric analysis of urine and faeces for energy balance. METHODS: We measured energetic loss via urine and faeces during antihyperglycaemic treatment in male obese Zucker diabetic fatty (ZDF) rats. Rats were treated for 10 days with the sodium-glucose-linked transporter-2 (SGLT2) inhibitor AVE2268, with insulin glargine, with the GLP-1 receptor agonist lixisenatide and with the combination of insulin glargine and lixisenatide. Each study was accompanied by one lean (Fa/?) and one obese (fa/fa) untreated non-diabetic and diabetic control group, respectively. Blood glucose, body weight alterations and food assimilation efficiency were monitored. RESULTS: In control ZDF rats, more than 12 g/day of pure glucose was urinarily excreted. In total, the energetic loss via urine exceeded 30% from total energy uptake. Insulin glargine treatment decreased urinary energetic loss, leading to a body weight gain of approximately 3 g/day. An almost body weight-neutral antihyperglycaemic treatment could be achieved with AVE2268 and lixisenatide. While lixisenatide reduced body weight gain via reduction of energy uptake, the SGLT2 inhibitor even increased urinary glucose and thus energy excretion. Combining insulin glargine with lixisenatide attenuated the anabolic effect of insulin resulting in weight neutrality. CONCLUSIONS: Our data clearly show renal contribution to the body's energy control by urinary glucose excretion (UGE) during antidiabetic treatment. The undesired retained energy could be reduced via additional UGE or via simultaneous reduction of energy uptake and/or energy retention.

Description of measles D4-Hamburg outbreak in Hamburg, Germany, December 2008 to June 2009, which disproportionally affected a local Roma community.

From December 2008 to June 2009 a measles outbreak occurred in the Federal State of Hamburg, Germany. The outbreak affected 216 persons and was caused by a new measles strain termed D4-Hamburg which led to consecutive outbreaks between 2009 and 2011 in at least 12 European countries. Here, we describe epidemiological characteristics of the outbreak and evaluate the control measures taken in Hamburg. In one of the seven boroughs of Hamburg a local Roma community comprised more than 50% of the notified cases.We compared in a stratified analysis the age distribution of these cases with cases of fellow citizens who did not belong to the Roma community. The age group of infants (0-11 months) comprised 33% among the non-Roma measles cases, while in the Roma community only 4% belonged to this stratum. In the stratum of 5-17 year-olds only 8% were affected among the non-Roma cases, whereas in the Roma community 50% belonged to this age group. We discuss the influencing factors that might have led to this difference in age distribution between the two groups.

[New developments in minimally invasive urology: NOTES (Natural Orifice Transluminal Endoscopic Surgery) and LESS (Laparo-Endoscopic Single-Site Surgery) in urology]. / Neue Entwicklungen in der minimalinvasiven Urologie: NOTES (Natural Orifice Transluminal Endoscopic Surgery) und LESS (Laparoendoscopic Single-Site Surgery) in der Urologie.

Laparoscopic surgery in urology has undergone a rapid development in the last decade. In general, many studies have underlined the benefits of laparoscopy in urology. The latest innovations in the field of minimally invasive urology are aimed at a further reduction of the morbidity associated with minimally invasive surgery. Two novel innovations are currently being developed, natural orifice transluminal endoscopic surgery (NOTES), whereby intraperitoneal access is gained through natural orifices and laparo-endoscopic single-site surgery (LESS), wherein one surgical access is used both for introducing instruments and for retrieving the specimen. Many case reports and small patient series have been published rapidly in the past two years. However, comparative randomised studies to conventional laparoscopy or open surgery do not yet exist. LESS and NOTES are two new innovative approaches, whereby feasibility studies not only for simple nephrectomy but also for complex procedures like partial nephrectomy, radical prostatectomy, ureterocystoneostomy have been published. In the next few years, comparative studies between these techniques and conventional laparoscopy can be expected.

Nephrotoxicity caused by brown spider venom phospholipase-D (dermonecrotic toxin) depends on catalytic activity.

Bites from brown spiders (Loxosceles genus) have clinical manifestations including skin necrosis with gravitational spreading, and systemic involvement that may include renal failure, hemolysis, and thrombocytopenia. Mice were exposed to recombinant wild-type phospholipase-D, or to an isoform with a mutation in the catalytic domain resulting in no phospholipasic activity. Renal biopsies from mice treated with the wild-type toxin showed glomerular edema, erythrocytes and collapse of Bowman's space, edema and deposition of proteinaceous material within the tubular lumen. Ultrastructural analyses confirmed cytotoxicity by demonstrating disorders of glomerulus at foot processes and at fenestrated endothelium. Tubule alterations include deposits of amorphous material and edema, as well as an increase of epithelial cytoplasmic multivesicular bodies and electron-dense structures. There was an absence of nephrotoxicity in mice treated with the mutated toxin. Analyses of urine and blood showed that wild type toxin induced hematuria and elevation of blood urea, while treatment with mutated toxin caused no changes. Mouse lethality experiments also showed oliguria and mortality after treatment with wild-type toxin, but not following exposure to the mutated toxin. Immunofluorescence using antibodies to phospholipase-D toxin showed deposition of both toxins along the renal tubular structures as detected by confocal microscopy. Immunoblots of urine showed a 30 kDa band in samples from animals treated with wild-type toxin, but no band from mice exposed to mutated toxin. Wild-type toxin treatment caused cytoplasmic vacuolization, impaired spreading, reduction of cellular viability, and cell-cell and cell-substratum detachment in MDCK cells, while treatment with mutated isoform had no effect. Finally, there is a direct correlation between toxin activity on cell membrane phospholipids generating choline and cytotoxicity. We have defined for the first time a molecular mechanism for Loxosceles venom nephrotoxicity that is dependent on the catalytic activity of phospholipase-D toxin.

Fast-track surgery in laparoscopic radical prostatectomy: basic principles.

Fast-track surgery describes innovative treatment concepts ensuring a faster convalescence phase. The aim of this study was to allow hospital discharge 3 days after surgery without additional complications in patients receiving LRPE for localized prostate cancer. Twenty-five patients each were randomized in the study groups to verify if a fast-track regimen could be transferred into clinical routine. The perioperative data, early complications, hospital stay as well as readmission rate were analyzed. The mean postoperative stay was 3.6 days in the fast-track group versus 6.7 days in the conventional group. The overall complications were significantly less in the fast-track procedure. The readmission rate was low and not significant. Patients receiving an LRPE benefit from a suitable fast-track concept. The postoperative hospital stay could be shortened nearly by half with a significantly decreased overall complication rate. Thus, fast-track concepts might contribute to saving resources in the long term. However, more evidence based on larger prospective trials is needed to achieve optimal quality of life for patients perioperatively.

[Management of trauma to the male external genitalia]. / Externes Genitaltrauma beim Mann.

Male genital injury, although rarely life-threatening, demands prompt, appropriate management to prevent long-term sexual and psychological damage. However, because of the rarity and disparity of severe genital injuries, there is still no universal therapeutic strategy. Urethral injury, although rare, may be associated with substantial long-term morbidity such as fistulas and strictures. Injuries to the scrotum and its contents may cause impaired fertility, chronic pain, hypogonadism, and altered self-image. Penile injury may lead to pain, curvature, and erectile dysfunction. This article concentrates on reviewing the major etiologies and mechanisms of urethral and genital injuries in men and summarizes principles and strategies of treatment based on the guidelines of the European Association of Urology.

[Coincidence of testicular germ cell tumor and sarcoidosis: A diagnostic challenge]. / Testikulärer Keimzelltumor und Sarkoidose: Eine diagnostische Herausforderung.

Several case reports and small case series have described a total of 66 patients with sarcoidosis and testicular cancer so far. This report describes three additional cases. We highlight the association of sarcoidosis and testicular cancer and comment on the potential impact of this connection on the interpretation of the radiological and pathological findings in suspected cancer relapse. Sarcoidosis, a condition that can be combined with testicular cancer, should always be considered in the differential diagnosis.

[Kidney transplantation in childhood and adolescence]. / Nierentransplantation im Kindes- und Jugendalter.

The reasons for end-stage renal disease in pediatric patients differ from adults. The therapy of choice is renal transplantation. A total of 117 children and adolescents were treated with renal transplantation in 2003 in Germany. Immunosuppressive therapy and related comorbidities are the main problems in pediatric patients. The following article provides a summary of transplantation in children, preparation, and follow-up.

Circadian variation of the cell proliferation in the jejunal epithelium of rats at weaning phase.

Circadian variation in cell proliferation of the jejunal epithelium of 18-day-old rats was studied using the 2-h arrested metaphase score and crypt isolation method. A continuous decrease in the arrested metaphases occurred from 07.00 h to 13.00 h. From 17.00 h arrested metaphase values increased and were maintained at the higher level during the dark period as showed by Cosinor analyses (P < 0.05). These results indicate that in the young rat there is already a circadian variation in jejunal epithelial cell proliferation as early as 18 days. We can even suggest that the presence of a circadian rhythm at weaning contributes to the steady state of cell proliferation in the intestinal epithelium observed in adult life.

Laparoscopic donor nephrectomy.

Laparoscopic live donor nephrectomy (LDN) has removed disincentives of potential donors and may bear the potential to increase kidney donation. Multiple modifications have been made to abbreviate the learning curve while at the same time guarantee the highest possible level of medical quality for donor and recipient. We reviewed the literature for the evolution of the different LDN techniques and their impact on donor, graft and operating surgeon, including the subtleties of different surgical accesses, vessel handling and organ extraction. We performed a literature search (PubMed, DIMDI, medline) to evaluate the development of the LDN techniques from 1995 to 2003. Today more than 200 centres worldwide perform LDN. Hand-assistance has led to a spread of LDN. Studies comparing open and hand-assisted LDN show a reduction of operating and warm ischaemia times for the hand-assisted LDN. Different surgical access sites (trans- or retroperitoneal), different vessel dissection approaches, donor organ delivery techniques, delivery sites and variations of hand-assistance techniques reflect the evolution of LDN. Proper techniques and their combination for the consecutive surgical steps minimize both warm ischaemia time and operating time while offering the donor a safe minimally invasive laparoscopic procedure. LDN has breathed new life into the moribund field of living kidney donation. Within a few years LDN could become the standard approach in living kidney donation. Surgeons working in this field must be trained thoroughly and well acquainted with the subtleties of the different LDN techniques and their respective advantages and disadvantages.

Proteasome inhibitors modulate chemokine production in lung epithelial and monocytic cells.

Proteasome inhibition has become a target for antitumour and anti-inflammatory therapy. The present study investigated the influence of cysteine proteinase and proteasome inhibitors on chemokine production in lung epithelial cells and monocytic cells. The lung carcinoma cell lines A549, SK-MES, NCI-H727, virus-transformed bronchial epithelial cell line BEAS-2B, primary lung epithelial cells, and the acute monocytic leukaemia cell lines Mono-Mac-6 and THP-1 were incubated with proteasome (N-acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN), beta-lactone) or cysteine proteinase inhibitor (L-trans-Epoxysuccinyl-Leu-3-methylbutylamide-ethyl ester) and the influence on chemokine production (interleukin-8: IL-8, monocyte chemoattractant protein-1, RANTES) was quantified at protein and mRNA levels. Inhibition of proteasome activity by ALLN and beta-lactone resulted in significantly increased IL-8 secretion (5- to 22-fold). Cysteine proteinase inhibitors did not influence chemokine production. The simultaneous rise in IL-8 mRNA was caused by an increased half-life of mRNA and increased RNA synthesis. Moreover, analysis of transcription factor activation revealed induction of activator protein-1 (c-Jun) activity by proteasome inhibition, whereas nuclear factor-kappaB (p50 and p65) was not activated. The significant increase in IL-8 production after proteasome inhibition was also observed in primary lung epithelial cells and in monocytic cells. In addition, the secreted IL-8 was biologically active as shown by the neutrophil chemotaxis assay. In conclusion, it was shown that proteasome inhibitors stimulate interleukin-8 secretion in lung epithelial cells and monocytic cells, thus recruiting neutrophils.

Nonmyeloablative stem cell transplantation in metastatic renal cell carcinoma: delayed graft-versus-tumor effect is associated with chimerism conversion but transplantation has high toxicity.

Seven out of 29 patients with metastatic renal cell carcinoma (RCC) considered eligible for allogeneic stem cell transplantation underwent nonmyeloablative stem cell transplantation (NST) from HLA-identical donors. Conditioning comprised cyclophosphamide, fludarabine and antithymocyte globulin. Prolonged mixed chimerism (MC) after engraftment converted to complete donor chimerism (CC) after infusion of donor lymphocytes and/or graft-versus-host disease (GvHD) in six patients. Five patients developed severe GvHD. Two of seven patients had a delayed tumor response after conversion to CC. After a median follow-up of 10 months (4-24 months), 5/7 patients are alive, one in very good partial remission (PR), one with stable and three with progressive disease. One of the seven patients died from sepsis in PR and 1/7 died from rapid tumor progression after sustained MC. None of the 22 nontransplanted patients responded to further therapies. Survival after 1 year was 59% in transplanted and 66% in nontransplanted patients (n.s.). A pooled data analysis from the literature suggests a graft-versus-tumor effect after transplant in patients with metastatic RCC, which becomes effective after chimerism conversion. Available data demonstrate high nonrelapse mortality in these patients. NST in RCC still has to be regarded as an investigational approach requiring careful patients' selection and longer follow-up within clinical studies.

Cell cycle time and rate of entry of cells into mitosis in the small intestine of young rats.

Cell cycle time (T(C)) and the rate of entry of cells into mitosis (r(M)) in the jejunum and duodenum of young rats were investigated using the stathmokinetic method. The cell cycle times in the jejunum were 24.3 and 28.3 h in light and dark periods, respectively. Cell cycle times in the duodenum were 17.1 and 21.5 h in light and dark periods, respectively. Rates of entry of cells into mitosis in the jejunum were 1.2 and 1.1 cells/cell/h in light and dark periods and rates of entry of cells into mitosis in the duodenum were 1.4 and 1.8 cells/cell/h in light and dark periods, respectively. Although these changes to cell cycle time values are not statistically significant, the variation between the two periods should be considered in relation to its possible biological effects.

Tumor type M2 pyruvate kinase expression in metastatic renal cell carcinoma.

The M2 isoenzyme of pyruvate kinase (M2-PK) is specifically expressed in tumor cells (TuM2-PK) and has been detected in the peripheral blood of patients with renal cell carcinoma (RCC). TuM2-PK is not useful as a biological marker in localized RCC. We analysed TuM2-PK in 68 patients with metastatic RCC after initial surgery and prior to or during chemoimmunotherapy of metastases. In 50 patients, the levels of TuM2-PK were measured during chemoimmunotherapy with interleukin-2, interferon-alpha2a and 5-fluorouracil for up to 8 months and were correlated to response as assessed by radiological imaging techniques. TuM2-PK was quantified with a commercially available enzyme linked immunosorbent assay kit using a cut off of 15 kU/l. In 48 of 68 patients (71%), TuM2-PK was elevated above the cut-off. TuM2-PK was significantly higher in G3 tumors than in G2 tumors. In 34 of 50 patients (68%) undergoing chemoimmunotherapy, a positive correlation between TuM2-PK values and response to treatment was observed. Based on these data, we would not recommend the routine clinical use of TuM2-PK in metastatic RCC at this point.

Elastic properties of 2D colloidal crystals from video microscopy.

Elastic constants of two-dimensional (2D) colloidal crystals are determined by measuring strain fluctuations induced by Brownian motion of particles. Paramagnetic colloids confined to an air-water interface of a pendant drop are crystallized under the action of a magnetic field, which is applied perpendicular to the 2D layer. Using video microscopy and digital image processing we measure fluctuations of the microscopic strain obtained from random displacements of the colloidal particles from their mean (reference) positions. From these we calculate system-size dependent elastic constants, which are extrapolated using finite-size scaling to obtain their values in the thermodynamic limit. The data are found to agree rather well with zero-temperature calculations.

[Improvement of hemostasis in laparoscopic and open partial nephrectomy with gelatin thrombin matrix (FloSeal)]. / Verbesserung der Hämostase bei laparoskopischen und offenen Teilnephrektomien durch Gelatine-Thrombin-Matrix (FloSeal).

Long-term follow-up studies have demonstrated that effective local tumor control and long-term tumor-free progression rates can be achieved by nephron-sparing surgery. However, hemostasis is a major issue and the lack of effective means of hemostasis has limited a wider use of the laparoscopic approach to nephron-sparing surgery. Between January 2001 and August 2002, a total of 36 patients with renal cell carcinomas were treated by partial nephrectomies using a two-component tissue sealant (FloSeal). The median age was 55.2 years (range: 34-71 years). Follow-up time was 1-18 months (median: 5.5 months). The tumor diameter ranged from 2 to 5 cm (median: 2.9 cm). Open retroperitoneal surgery was performed in 17 cases and laparoscopic partial nephrectomy in 19 cases. The two-component tissue sealant (consisting of a gelatin matrix with granular and thrombin components) was applied after resection of the tumor and before perfusion of the kidney. The following parameters were recorded: (1) time until complete hemostasis was achieved, (2) decrease in postoperative hemoglobin level, (3) postoperative bleeding, and (4) presence or absence of a perirenal hematoma 24 h and 10 days postoperatively by ultrasound. After application of the tissue sealant for 1-2 min to the moist resection site, hemostasis was immediate in all cases. During the laparoscopic partial nephrectomies, a laparoscopic applicator was used that avoided wasting the tissue sealant within the dead space of the instrument. When reperfusion of the kidney was established, hemostasis was maintained. The decrease in postoperative hemoglobin level ranged from 0.3 to 1.2 points (median: 0.8 points). None of the patients required blood transfusions. There were no cases of postoperative bleeding. An ultrasound examination 24 h and 10 days postoperatively demonstrated the absence of a significant perirenal hematoma. The two-component tissue sealant FloSeal provided immediate and durable hemostasis in open and laparoscopic partial nephrectomies. The tissue sealant may provide a tool to expand the possibilities of laparoscopic nephron-sparing surgery.

[Laparoscopic dismembered pyeloplasty with Anderson-Hynes technique]. / Die laparoskopische Nierenbeckenplastik mit Kontinuitätstrennung nach Anderson-Hynes.

Because of the minimal invasiveness of the laparoscopic approach, we introduced the laparoscopic dismembered pyeloplasty in our treatment modalities for patients with primary UPJ obstruction. We report on our technique and the results after a median follow-up of more than 2 years. Between August 1997 and September 2002, 52 patients underwent a laparoscopic dismembered pyeloplasty at our institution. All patients had a symptomatic primary PJ obstruction. We prefer the transperitoneal route with laterocolic exposure of the kidney. After preparation and exposure of the ureter and the renal pelvis, we performed in each case the dismembered Anderson-Hynes pyeloplasty with resection of the pelvis and reanastomosis between the ureter and renal pelvis. Intracorporeal suturing and knotting techniques were used exclusively. All procedures could be performed successfully. In no case was conversion to open surgery necessary. The mean operative time was 180 min. Crossing vessels were present in 57% of patients. The mean postoperative hospital stay was 4 days. The first patient had an anastomosis insufficiency, which required laparoscopic repair. The same patient failed in the follow-up. He developed a late recurrence of the stenosis and needed an open repair. In all other patients the obstruction was resolved or significantly improved. The long-term success rate is 98% with a follow-up of 25 months. Our results with laparoscopic dismembered pyeloplasties compare favorably with those achieved by open pyeloplasties with less perioperative morbidity and discomfort. We do believe that laparoscopic dismembered pyeloplasty will be the method of choice in the treatment of UPJ obstruction.

[Laparoscopic radical nephrectomy: indications, techniques, and oncological outcome]. / Die laparoskopische transperitoneale Tumornephrektomie. Indikation, Technik und onkologisches Outcome.

Renal cell carcinoma is likely to become one of the most important indications for laparoscopic surgery worldwide. The laparoscopic technique combines the benefits of the minimally invasive approach with established surgical principles. In our institution the laparoscopic transperitoneal approach with intact specimen extraction has become the standard technique for radical nephrectomies. We report the indications, techniques, and oncological outcome in a single center experience in 100 cases. The mean tumor size was 5.9 cm (range: 2-11 cm), the blood loss was 220 ml, and the mean surgical time was 211 min, including the learning curves of five surgeons. Histological findings were pT1 in 66 (66%), pT2 in 11 (11%), and pT3 in 19 (19%) patients with an increasing tumor size according to the experience of the surgeons. In four cases (4%) histology did not prove malignant disease. Positive lymph nodes were detected in three cases (3%) and surgical margins were negative for tumor in all patients. To date 61 patients were available for follow-up; patients with primary metastatic disease were excluded from this analysis. Follow-up was between 1 and 30 months with an average of 12.9 months. Progressive disease occurred in two cases in patients with pT3G3 tumors. No cases of local recurrence or port metastasis occurred during observation. Laparoscopic radical nephrectomy is a routine, effective treatment for patients with renal cell carcinoma. Our follow-up data up to 30 months confirm the effectiveness of laparoscopic radical nephrectomy in terms of surgical principles and oncological outcome.