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.

[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.

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.

Interleukin-6 and transforming growth factor-beta 1 control expression of cathepsins B and L in human lung epithelial cells.

Cathepsins B and L are commonly expressed cysteine proteinases that play a major role in lysosomal bulk proteolysis, protein processing, matrix degradation, and tissue remodeling. Cathepsins are also implicated in tumor progression and metastasis, tissue injury, and inflammation. Cells at sites of inflammation often show upregulation and secretion of cathepsins. The regulation of cathepsin expression by inflammatory mediators is not well understood. The aims of this study were to investigate the effect of the cytokines interleukin-1 beta (IL-1 beta), IL-6, IL-10, transforming growth factor-beta 1 (TGF-beta 1), and hepatocyte growth factor (HGF) on expression of cathepsin B and cathepsin L mRNA (quantitative RT-PCR), on protein expression (ELISA, Western blot), and also on enzymatic activity of cathepsins B and L. Investigations were performed using the human lung epithelial cell line A-549. IL-6 was found to induce a concentration-dependent increase in mRNA expression, protein concentration, and enzymatic activity of cathepsin L. Cathepsin B mRNA and protein expression were not affected by IL-6. In contrast, TGF-beta 1 decreased the amount of cathepsin L mRNA and cathepsin B mRNA. At protein level, it was shown that TGF-beta 1 clearly reduced the concentration of cathepsin L but not cathepsin B. The cytokines IL-1 beta, IL-10, and HGF were found to exert no effect on cathepsin B and L expression. In conclusion, these results are the first to show that IL-6 and TGF-beta 1 have opposite effects on the regulation of expression of cathepsins B and L in A-549 human lung epithelial cells. The proinflammatory cytokine IL-6 induced an upregulation of cathepsin L, whereas TGF-beta 1 suppressed cathepsin B and L expression. Further studies are needed to clarify the mechanism that affects cathepsin B and L expression.

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.

Focal microsatellite mutations in relatives with prostatic adenocarcinoma.

Instability of short tandem repeat sequences, microsatellite instability (MI), has been reported to play an important role in the tumorigenesis of various adenocarcinomas, including prostatic adenocarcinoma. Although prostate cancer is not widely recognized as a heriditary cancer, familial clustering is well known. To investigate the frequency of microsatellite instability in familial prostatic adenocarcinomas we analyzed archival tumor tissue from seven paired first degree relatives with prostatic adenocarcinoma. Twelve dinucleotide, nine trinucleotide, six tetranucleotide repeats and the CAG repeat of the androgen receptor gene were screened for MI. Solitary mutations were observed in four separate cases (28.6%) and widespread somatic alterations were not identified. No statistical correlation to pathological characteristics was determined. Our data indicate that microsatellite instability is an uncommon phenomenon in prostatic adenocarcinoma within first degree relatives. Those changes present appear to manifest as focal mutations in contrast to the more global changes seen in MI.

[Radical prostatectomy in clinically localized prostate carcinoma. Pro laparoscopic approach]. / Die radikale Prostatektomie beim klinisch lokalisierten Prostatakarzinom. Pro laparoskopischer Zugangsweg.

Systematic development of laparoscopy during the last decade has led to establishing laparoscopic radical prostatectomy (LRP) as a surgical procedure. On the basis of extensive experience at our center, the advantages of the minimally invasive method are described as well as the problems still in existence. Reduced trauma caused by laparoscopic access in combination with clearly reduced blood loss has resulted in less morbidity after laparoscopic procedures. This is reflected in a shorter postoperative stay in hospital and faster convalescence. LRP as an ambitious and complex procedure has an average complication rate of 12%, which shows that the method has surpassed the stage of experimental surgery. By direct comparison, the costs of LRP are higher than for the open surgical procedure, but on the whole this is economically balanced by the lower morbidity, shorter hospital stay, and faster convalescence. The progress in technology to be expected in the field of laparoscopy will further increase quality, precision, and safety of LRP and thus contribute to the establishment of laparoscopic radical prostatectomy as a surgical method of choice.

[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.

[Renal carcinoma with invasion of the suprahepatic vena cava (Staehler stage III and IV): surgical treatment and results]. / Nierenzellkarzinom mit suprahepatischem V.-cava-Befall (Stadium III und IV nach Staehler). Operative Therapie und Ergebnisse.

The operative treatment of patients with renal cell carcinoma (RCC) and suprahepatic infradiaphragmatic or supradiaphragmatic vena cava invasion (Staehler stage III and IV) is still an interdisciplinary challenge. The potential high complication rate and the enormous operative-technical efforts have to be brought into line with the individual benefit for the patient. In this study, we have retrospectively analyzed the operative results of 24 patients. We have further compared the patients during follow-up and immunotherapy due to metastasis with a control group of 75 patients without vena cava invasion. Perioperative mortality in the 24 patients was 4%. Four patients had metastasis at presentation and 14 further patients developed metastatic disease during median follow-up of 23.5 months. Median survival was 45 months with a 1-, 3-, and 5-year survival rate of 92, 57, and 33%, respectively. In a multivariate analysis, only the presence of metastasis (p=0.002) and marginal immunotherapy (p=0.1), but not vena cava invasion (p=0.259) or a positive lymph node status (p=0.624) were significant predictors of a poor survival. For patients with RCC and suprahepatic infradiaphragmatic or supradiaphragmatic vena cava invasion (Staehler stage III and IV), the combination of an aggressive surgical treatment combined with subsequent immunotherapy in the presence of metastatic disease offers a realistic therapeutic option with reasonable survival rates.

[Voice dialogue--dialogue of voices]. / Voice Dialogue--Dialog der Stimmen.

Voice Dialogue is an integration of different therapeutic methods (Gestalttherapy, Psychodrama, Psychology of C.G. Jung, Transactional Analysis, Psychosynthesis). It is a therapeutic method, which allows in a rather humoristic way, without provoking lots of resistance, to contact the subpersonalities of a client. This will objectify and bring into awareness the different subpersonalities, as well as the disowned parts of the personality. Therefore we will have the chance to deal with these parts in a creative way without the Ego interfering critically. So a new balance can be found between the different subpersonalities and the Ego. Voice Dialogue can be applied very well in single, partner or family therapy and has worked successfully with grown-ups and especially with youngsters.

[Effects of the ashes of the Irazu volcano (Costa Rica) on various insects]. / Efecto de la ceniza del Volcán Irazú (Costa Rica) en algunos insectos

A study of the 1963-1965 eruptions of the Irazú volcano (Costa Rica) showed that the ashes altered the ecological conditions of a great number of insects. Experiments suggest a mechanical action of the abrasive particles on the epicuticle, making it permeable, and thus accelerating dehydration. Other insects, such as the honey bee (Apis mellifera), were not affected externally but through the ingestion of ash-contaminated nectar and by the massive destruction of the vegetation on which they depended. Great destruction of bee populations was observed during 1964 and 1965-66 in the San José area. On the other hand, the volcanic ash apparently favored other insects, especially those protected by a waxy secretion, and by the possible elimination of their natural enemies, to such proportions that they became pests of economic significance.

[Psychological military fitness--a catamnestic study]. / Die psychische Dienstfähigkeit--eine katamnestische Untersuchung.

1980 a psychiatric examination was made of a pre-selected collective (recruits of the tank-corps, ordinance-corps and highway police). Now, three years later, we have re-examined the 96 recruits regarding their psychic qualifications and military suitability and made a report. The methods and the results are illustrated and discussed in detail therein.