Reflux nach bariatrischen Operationen

Obesity and gastro-esophageal reflux disease (GERD) are two of the major health problems of the industrialized world. Both condition have increased prevalence, pathophysiological and endoscopic studies identified obesity a major risk factor in the development of GERD. Conversely, successful weight reduction improves GERD symptoms and diminishes the use of acid suppressive medication. Bariatric interventions are not all equal when it comes to controlling GERD symptoms, lesions and use of medication. Gastric banding has a variable influence on GERD, while most patients report improved reflux symptoms, up to 20% of patient can develop "de novo" reflux symptoms following gastric banding. Gastric sleeve resection increases reflux symptoms, in particular in patients with an ideal, tubular gastroplasty and those with proximal (fundic) pouch. Roux-en-Y gastric bypass has a positive effect of GERD, reducing symptoms and use of acid suppressive medications. From an esophageal perspective, gastric bypass is the preferred bariatric procedure to treat and prevent GERD in morbidly obese patients.

Genetics of upper and lower airway diseases in the horse.

Genetic predispositions for guttural pouch tympany, recurrent laryngeal neuropathy and recurrent airway obstruction (RAO) are well documented. There is also evidence that exercise-induced pulmonary haemorrhage and infectious diseases of the respiratory tract in horses have a genetic component. The clinical expression of equine respiratory diseases with a genetic basis results from complex interactions between the environment and the genetic make-up of each individual horse. The genetic effects are likely to be due to variations in several genes, i.e. they are polygenic. It is therefore unlikely that single gene tests will be diagnostically useful in these disorders. Genetic profiling panels, combining several genetic factors with an assessment of environmental risk factors, may have greater value, but much work is still needed to uncover diagnostically useful genetic markers or even causative variants for equine respiratory diseases. Nonetheless, chromosomal regions associated with guttural pouch tympany, recurrent laryngeal neuropathy and RAO have been identified. The association of RAO with other hypersensitivities and with resistance to intestinal parasites requires further study. This review aims to provide an overview of the available data and current thoughts on the genetics of equine airway diseases.

Apoptotic enteropathy caused by antimetabolites and TNF-α antagonists.

AIMS To investigate whether drugs others than mycophenolic acid and ipilimumab might cause graft-versus-host-like apoptotic enteropathy, the clinicopathological findings in four patients were examined who had developed watery diarrhoea and apoptotic enteropathy (three cases from colon and one case from ileal pouch) after intake of antimetabolites (methotrexate and capecitabine) and/or tumour necrosis factor-α inhibitors (etanercept and infliximab). METHODS The clinical charts, endoscopy reports and intestinal biopsies from all endoscopies were reviewed for all patients. Biopsies were evaluated semiquantitatively for apoptosis of basal crypts, dilated damaged crypts, defined as cystically dilated crypts with flattened degenerated epithelium containing apoptotic debris and few neutrophils, and mucosal architecture. Further, the presence of intraepithelial lymphocytes, chronic inflammatory cells in the lamina propria and mucosal ulcerations was recorded and immunohistochemical analysis for human cytomegalovirus and herpes simplex virus was performed. RESULTS Endoscopic examination revealed normal mucosa in two patients, whereas the other two showed focal ulcerations. Histological changes included increased apoptosis of basal crypts, the presence of dilated damaged crypts and architecture distortion. In all cases, a temporal association between drug intake and/or dose increase, and onset of diarrhoea, was observed, and no convincing evidence of other potentially underlying causes of colitis/enteritis was found, including infections. CONCLUSIONS Pathologists should be aware of the expanding spectrum of drugs that can cause apoptotic enteropathy, including antimetabolites and tumour necrosis factor-α inhibitors.

Steroidogenesis of the testis - new genes and pathways

Defects of androgen biosynthesis cause 46,XY disorder of sexual development (DSD). All steroids are produced from cholesterol and the early steps of steroidogenesis are common to mineralocorticoid, glucocorticoid and sex steroid production. Genetic mutations in enzymes and proteins supporting the early biosynthesis pathways cause adrenal insufficiency (AI), DSD and gonadal insufficiency. The classic androgen biosynthesis defects with AI are lipoid CAH, CYP11A1 and HSD3B2 deficiencies. Deficiency of CYP17A1 rarely causes AI, and HSD17B3 or SRD5A2 deficiencies only cause 46,XY DSD and gonadal insufficiency. All androgen biosynthesis depends on 17,20 lyase activity of CYP17A1 which is supported by P450 oxidoreductase (POR) and cytochrome b5 (CYB5). Therefore 46,XY DSD with apparent 17,20 lyase deficiency may be due to mutations in CYP17A1, POR or CYB5. Illustrated by patients harboring mutations in SRD5A2, normal development of the male external genitalia depends largely on dihydrotestosterone (DHT) which is converted from circulating testicular testosterone (T) through SRD5A2 in the genital skin. In the classic androgen biosynthetic pathway, T is produced from DHEA and androstenedione/-diol in the testis. However, recently found mutations in AKR1C2/4 genes in undervirilized 46,XY individuals have established a role for a novel, alternative, backdoor pathway for fetal testicular DHT synthesis. In this pathway, which has been first elucidated for the tammar wallaby pouch young, 17-hydroxyprogesterone is converted directly to DHT by 5α-3α reductive steps without going through the androgens of the classic pathway. Enzymes AKR1C2/4 catalyse the critical 3αHSD reductive reaction which feeds 17OH-DHP into the backdoor pathway. In conclusion, androgen production in the fetal testis seems to utilize two pathways but their exact interplay remains to be elucidated.

First evidence for differential and sequential efferent effects of stimulus relevance and goal conduciveness appraisal.

In the context of a memory task, participants were presented with pictures displaying biological and cultural threat stimuli or neutral stimuli (stimulus relevance manipulation) with superimposed symbols signaling monetary gains or losses (goal conduciveness manipulation). Results for heart rate and facial electromyogram show differential efferent effects of the respective appraisal outcomes and provide first evidence for sequential processing, as postulated by Scherer's component process model of emotion. Specifically, as predicted, muscle activity over the brow and cheek regions marking the process of relevance appraisal occurred significantly earlier than facial muscle activity markers of goal conduciveness appraisal. Heart rate, in contrast, was influenced by the stimulus relevance manipulation only.

The Sensitivity of Physiological Measures to Phobic and Nonphobic Fear Intensity

We investigated whether amygdala activation, autonomic responses, respiratory responses, and facial muscle activity (measured over the brow and cheek [fear grin] regions) are all sensitive to phobic versus nonphobic fear and, more importantly, whether effects in these variables vary as a function of both phobic and nonphobic fear intensity. Spider-phobic and comparably low spider-fearful control participants imagined encountering different animals and rated their subjective fear while their central and peripheral nervous system activity was measured. All measures included in our study were sensitive to variations in subjective fear, but were related to different ranges and positions on the subjective fear level continuum. Left amygdala activation, heart rate, and facial muscle activity over the cheek region captured fear intensity variations even within narrowly described regions on the fear level continuum (here within extremely low levels of fear and within considerable phobic fear). Skin conductance and facial muscle activity over the brow region did not capture fear intensity variations within low levels of fear: skin conductance mirrored only extreme levels of fear, and activity over the brow region distinguished phobic from nonphobic fear but also low-to-moderate and high phobic fear. Finally, respiratory measures distinguished phobic from nonphobic fear with no further differentiation within phobic and nonphobic fear. We conclude that a careful consideration of the measures to be used in an investigation and the population to be examined can be critical in order to obtain significant results.

Urinary diversion in elderly patients

BACKGROUND Bladder cancer represents one of the ten most prevalent cancers worldwide. More than 400,000 people worldwide are newly diagnosed every year. Within 2 years after diagnosis, 80 % of patients with muscle invasive bladder cancer without treatment die. METHODS The aggressive local surgical approach with a cystectomy is the therapy of choice. The median age of patients with de novo bladder cancer is 70 years. Thus bladder cancer is a cancer of the elderly. For demographical reasons, the number of eldery patients undergoing radical cystectomy will rise in the next few years. The type of urinary diversion is a major factor influencing perioperative morbidity and quality of life in these patients. Incontinent urinary diversions are preferentially used in daily practice. CONCLUSIONS There are only a few contraindications for orthotopic neobladder; however, age alone is not a contraindication. Patient selection and a nerve sparing approach are crucial in men and women to achieve excellent functional results with orthotopic neobladder in elderly patients.

Regional facial asymmetries in unilateral orofacial clefts

OBJECTIVES Assess facial asymmetry in subjects with unilateral cleft lip (UCL), unilateral cleft lip and alveolus (UCLA), and unilateral cleft lip, alveolus, and palate (UCLP), and to evaluate which area of the face is most asymmetrical. METHODS Standardized three-dimensional facial images of 58 patients (9 UCL, 21 UCLA, and 28 UCLP; age range: 8.6-12.3 years) and 121 controls (age range 9-12 years) were mirrored and distance maps were created. Absolute mean asymmetry values were calculated for the whole face, cheek, nose, lips, and chin. One-way analysis of variance, Kruskal-Wallis, and t-test were used to assess the differences between clefts and controls for the whole face and separate areas. RESULTS Clefts and controls differ significantly for the whole face as well as in all areas. Asymmetry is distributed differently over the face for all groups. In UCLA, the nose was significantly more asymmetric compared with chin and cheek (P = 0.038 and 0.024, respectively). For UCL, significant differences in asymmetry between nose and chin and chin and cheek were present (P = 0.038 and 0.046, respectively). In the control group, the chin was the most asymmetric area compared to lip and nose (P = 0.002 and P = 0.001, respectively) followed by the nose (P = 0.004). In UCLP, the nose, followed by the lips, was the most asymmetric area compared to chin, cheek (P < 0.001 and P = 0.016, respectively). LIMITATIONS Despite division into regional areas, the method may still exclude or underrate smaller local areas in the face, which are better visualized in a facial colour coded distance map than quantified by distance numbers. The UCL subsample is small. CONCLUSION Each type of cleft has its own distinct asymmetry pattern. Children with unilateral clefts show more facial asymmetry than children without clefts.