Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass.

OBJECTIVE: The objective of this study was to quantify hormones that regulate energy and glucose homeostasis to establish possible mechanisms for the greater efficacy of Roux-en-Y gastric bypass (RYGB) compared with laparoscopic adjustable gastric banding (LAGB) in achieving weight loss and improved insulin sensitivity. DESIGN: Longitudinal study of patients undergoing LAGB (n=15) and RYGB (n=28) who were studied before surgery and at 2, 12, 26 and 52 weeks afterwards. MEASUREMENTS: Fasting blood samples were drawn at each visit. Postprandial blood samples were also obtained before surgery and at 26 and 52 weeks. Samples were assayed for peptide YY (PYY), ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, leptin, thyrotropic hormone, free T(4) and free T(3). RESULTS: At 1 year there was greater weight loss in RYGB compared with LAGB patients (30 vs 15%), but final body mass index was similar (34 vs 33 kg m(-2)). At week 52, area under the curve (AUC) for PYY in RYGB subjects was greater than LAGB (P<0.01). GLP-1 levels at 30 min after meal were threefold greater after RYGB compared with LAGB (P<0.001). Conversely, ghrelin AUC increased after LAGB at week 52 (P<0.05) but tended to decrease after RYGB. Fasting glucose, insulin, and leptin and homeostasis model of assessment (HOMA-IR) decreased in both groups over time but were significantly lower at week 52 after RYGB compared with LAGB. The change in leptin correlated significantly with weight loss in LAGB (r=0.86) and RYGB (r=0.77), however, HOMA-IR correlated significantly with weight loss only in LAGB (r=0.78), and not RYGB (r=0.15). There was a significant decrease in free T(3) (P<0.01) after RYGB. CONCLUSIONS: Differences in levels of gut hormones may play a role in promoting greater weight loss and insulin sensitivity after RYGB compared with LAGB, however, weight loss may be limited by decreases in free T(3) and leptin.

Sex differences in visceral adipose tissue post-bariatric surgery compared to matched non-surgical controls.

OBJECTIVE AND METHODS: Given the profound weight loss after gastric banding and bypass we compared fat compartmentalization by whole body magnetic resonance imaging in women and men after these procedures to two groups of non-surgical controls who were either matched for age, weight and height or were of lower body mass index (BMI). RESULT: In women post-surgery (n=17; BMI 31.7 kg/m(2)) there was lower visceral adipose tissue (VAT) (1.4 vs 2.5 kg; P<0.01) compared with matched controls (n=59; BMI 32.1 kg/m(2)). In contrast, VAT (5.3 vs 5.4 kg) was nearly identical in men post-surgery (n=10; BMI 34.1 kg/m(2)) compared with matched controls (n=10; BMI 32.1 kg/m(2)) even though the degree of weight reduction was not significantly different from women (27.4 vs 32.6%). Furthermore, VAT when adjusted for total adipose tissue (TAT) was 43% less in women post-surgery (1.2 vs 2.1 kg; P=0.03) than in controls with lower BMI (25.1 kg/m(2)). After adjustment for TAT, subcutaneous adipose tissue in women post-surgery was significantly greater than matched controls (35.1 vs 34.2 kg; P=0.03). There was a significant negative correlation of VAT and the degree of weight loss in women (r=-0.57; P=0.018) but this relationship was not significant in men (r=-0.39; P=0.27). Skeletal muscle was lower in both sexes compared with matched controls (women, 21.8 vs 23.1 kg; men, 32.5 vs 35.5 kg). CONCLUSION: Prospective studies are necessary to confirm if there is a sexual dimorphism in the effects of bariatric surgery on body composition.

Genetic deletion of JNK1 and JNK2 aggravates the DSS-induced colitis in mice.

The c-Jun N-terminal kinases (JNKs) are considered as novel targets for therapy of inflammatory bowel diseases (IBD). However, the relevant JNK isoforms have to be elucidated. Here, we analyze the individual contribution of the JNK1 and JNK2 isoforms in a dextran sulfate sodium (DSS) model of experimental colitis. JNK1 and JNK2 knockout mice (JNK1 ko, JNK2 ko) and their wild-type controls (WT1, WT2) received three cycles of DSS treatment, each consisting of 1.7% DSS for 5 days, followed by 5 days with water. Animals were daily evaluated by a disease activity index (DAI) comprising measurement of body weight, estimation of stool consistency, and test for occult blood/gross rectal bleeding. After 30 days all animals were sacrificed, and the inflamed intestine was histologically evaluated by a crypt damage score. Unexpectedly, neither JNK1 ko nor JNK2 ko prevented mice from developing a chronic colitis when compared to wild-type controls WT1 and WT2, respectively. On the contrary, DAI and mortality were aggravated in JNK2 ko compared to WT2. DAI and mortality did not differ between JNK1 ko and WT1, but the histological crypt damage score was significantly enhanced in the cecum of JNK1 ko mice. Genetic deletion of JNK2 worsens the disease outcome in an experimental model of murine colitis. We hypothesize that the functional deletion of the otherwise proapoptotic JNK2 prolongs the activity of proinflammatory immune cells with deterioration of disease activity.

The influence of bone allograft processing on osteoblast attachment and function.

In order to assess the influence of eight different sterilisation and disinfection methods for bone allografts on adhesion, proliferation, and differentiation of human bone marrow stromal cells (BMSC), cells were grown in culture and then plated onto pieces of human bone allografts. Following processing methods were tested: autoclavation (AUT), low-temperature-plasma sterilisation of demineralised allografts (D-LTP), ethylene oxide sterilisation (EtO), fresh frozen bone (FFB), 80 degrees C-thermodisinfection (80 degrees C), gamma-irradiation (Gamma), chemical solvent disinfection (CSD), and Barrycidal-disinfection (BAR). The seeding efficiency was determined after one hour to detect the number of attached cells before mitosis started. The cell viability was determined after 3, 7, and 21 days. Tests to confirm the osteoblastic differentiation included histochemical alkaline phosphatase staining and RT-PCR for osteocalcin. Human BMSC showed greatest attachment affinities for D-LTP-, 80 degrees C-, and CSD-allografts, whereas less cells were found attached to AUT-, EtO-, FFB-, Gamma-, and BAR-probes. Cell viability assays at day 3 revealed highest proliferation rates within the FFB- and 80 degrees C-groups, whereas after 21 days most viable cells were found in D-LTP-, 80 degrees C-, CSD-, and Gamma-groups. BAR-treatment showed a considerably toxic effect and therefore was excluded from all further experiments. Highest AP-activity and gene expression of osteocalcin were detected in the D-LTP-group in comparison with all other groups. In summary, our results demonstrate that cell adhesion, final population, and function of BMSC are influenced by different disinfection and sterilisation methods. Therefore, processing-related alterations of BMSC-function may be important for the success of bone grafting. The experimental setup used in the present work may be useful for further optimisation of bone allograft processing.

[Monteggia injuries in adults: Critical analysis of injury pattern, management, and results]. / Monteggia-Verletzungen im ErwachsenenalterEine kritische Analyse von Verletzungsmuster, Management und Ergebnissen.

BACKGROUND: Complications, revision surgery, and unsatisfactory functional results after operative management of Monteggia fractures are frequent. Moreover, hardly any studies exist that deal exclusively with the therapeutic concept for adults. PATIENTS AND METHODS: Between January 1988 and December 2001, 68 patients with Monteggia fractures or equivalent injury were surgically treated. A total of 49 patients could be followed up after 83 months (25-176). Fracture type was assessed according to Bado's classification, functional results according to the Mayo elbow performance score, and the extent of osteoarthritis based on the criteria of Baird and Johnson. RESULTS: The median age of the follow-up patients was 38 years (18-89, 31 men, 18 women). Corresponding to Bado's classification the following injuries were observed: 18 cases of type 1, 22 of type 2, 5 of type 3, and 4 cases of type 4. After surgical intervention, 14 patients achieved "very good", 21 "good", 9 "satisfactory", and 5 "poor" results. Of the 14 patients with either "satisfactory" or "poor" results, 9 manifested a type 2 injury. Complications requiring revision surgery occurred in 14 patients and complications not requiring revision in another 14. Severe osteoarthritic changes in the humeral or radioulnar joint were observed in 4 cases. CONCLUSIONS: Monteggia fractures in adults are fraught with complications despite good functional results in the majority of cases. The patient should be made aware early on of the risk of residual functional deficits and the need for further surgical intervention.

Effects of agouti-related protein on metabolism and hypothalamic neuropeptide gene expression.

The hypothalamic melanocortin system regulates feeding in part through interaction of the appetite stimulating peptide, agouti-related protein (AGRP), and the anorectic peptide, alpha-melanocyte stimulating hormone, a peptide derived from the pro-opiomelanocortin (POMC) polyprotein. Central administration of AGRP induces hyperphagia and increased gain in body weight in rodents, but may also exert metabolic effects even when hyperphagia is prevented. In the present studies, the effects of AGRP on hypothalamic neuropeptide gene expression and metabolism were examined in the rat. Central administration of AGRP for 3- and 7-day periods resulted in hyperphagia, increased body weight and increased plasma leptin and insulin concentrations compared to saline-injected controls. Hypothalamic concentrations of Pomc mRNA were also increased by 27% and 44% (in 3- and 7-day experiments, respectively). The hypothalamic concentration of Agrp mRNA was unchanged after 3 days, but was significantly decreased by 33% after 7 days of AGRP infusion. To determine if these changes were dependent upon AGRP-induced hyperphagia, pair-fed rats with restricted food intake receiving central administration of AGRP were also studied. In the absence of hyperphagia, intracerebralventricular administration of AGRP caused significant increases in plasma leptin and insulin concentrations (two-fold and 1.5-fold, respectively) and fat pad mass. A significant increase in hypothalamic Pomc mRNA concentrations was not detected in pair-fed rats. In contrast, Agrp mRNA concentrations remained suppressed by 45% in the pair-fed group after 7 days of AGRP infusion despite equal body weight compared to saline controls. The ratio of hypothalamic Pomc to Agrp mRNA was elevated two-fold in ad libitum and pair-fed AGRP-injected rats, which is consistent with increased stimulation of central melanocortin signalling pathways. Thus, central administration of AGRP exerts changes in hypothalamic neuropeptide gene expression and metabolic effects that are independent of the effects on food intake and body weight.

Proximal humeral fractures: how stiff should an implant be? A comparative mechanical study with new implants in human specimens.

BACKGROUND: The objective of this study was to determine the in vitro characteristics of the clinically used and newly developed implants for the stabilization of proximal humeral fractures under static and cyclic loading. The goal was to optimize implant stiffness for fracture stabilization even in weak bone stock. METHODS: In a laboratory study using 35 fresh human humeri, the specimens were randomized into 5 groups, which included the clinically used humerus T-plate (HTP), the cross-screw osteosynthesis (CSO), the unreamed proximal humerus nail with spiral blade (UHN), the recently developed Synclaw Proximal Humerus Nail (Synclaw PHN) and the angle-stable Locking Compression Plate Proximal Humerus (LCP-PH). The implant stiffness was determined for three clinically relevant load cases: axial compression, torsion and varus bending. In addition, a cyclic varus-bending test was performed to determine the implant properties under cyclic loading. RESULTS: In contrast to a rather elastic and minimally invasive implant(LCP-PH), the conventionally designed ones (Synclaw PHN, CSO, HTP, UHN) showed rather high stiffness values under static loading. In cyclic loading, a strong decrease in stiffness ( p<0.05) was found for the rigid implants HTP and UHN. In comparison with the other implants, only the elastic implant (LCP-PH) showed a significantly lower load reduction in a weak bone stock (17+/-6.2%). CONCLUSION: The high initial stiffness of rigid implants led to an early loosening and failure of the implant-bone interface under cyclic loading. Implants with low stiffness and elastic characteristics, however, appear to minimize the peak stresses at the bone-implant interface, making them particularly suitable for fracture fixation in osteoporotic bone.

[Isolated rupture of the subscapularis tendon in the overhead athlete - the result of chronical overuse?]. / Die isolierte Ruptur der Subskapularissehne beim jungen Uberkopfsportler - Folge chronischer Uberbeanspruchung?

The case of a 27-year-old overhead athlete with chronic shoulder pain because of an isolated subscapularis tear without trauma is described. Arthroscopy has proven to be the appropriate method for detailed visualisation of the injury and facilitates the operative planning. Furthermore, arthroscopy closes the problem of a "diagnostic gap". In the presented case, the results at the two year follow-up are excellent. The authors conclude that an operative approach is also justified in non-traumatic isolated ruptures of the subscapularis muscle.

Arthroscopic-assisted simultaneous reconstruction of the posterior cruciate ligament and the lateral collateral ligament using hamstrings and absorbable screws.

Arthroscopic-assisted simultaneous reconstruction of the posterior cruciate ligament (PCL) and the lateral collateral ligament (LCL) using hamstring tendon grafts is described. The femoral tunnel is drilled through an incision over the medial femoral condyle and the tibial tunnel through the same skin incision used for harvesting the tendon graft. PCL reconstruction is performed using a 4-strand hamstring tendon graft and absorbable screw fixation. The tendon of the semitendinosus muscle of the uninvolved knee is used as a lateral loop for LCL reconstruction. After pulling the transplant through the fibular head, femoral fixation of the loop is made with an absorbable screw.

[Crossed screw osteosynthesis of proximal humerus fractures]. / Die gekreuzte Schraubenosteosynthese proximaler Humerusfrakturen.

Between March 1997 and October 1999 thirty-one patients with displaced proximal humeral fractures were treated with crossed screw osteosynthesis. Insertion of the screws was realized by using a deltoideo-pectoral approach placing the screws anteriorly and posteriorly in a crossed manner from the distal fragment into the humeral head. Additionally, in all two-part-fractures a tension band was applied. In all three-part-fractures, the greater tuberosity was reattached by additional screws. In 21 patients (14 female, 7 male, median age 62 years, 18-86) a clinical and radiological follow-up (median 18 months, 10-29) was obtained. Fractures were classified as two-part-fractures in 10 patients and as three-part-fractures in 11 patients. According to the Constant-Score, "excellent" and "good" results were achieved in 15 patients, "moderate" results were found in 3 patients. However, in 3 patients results were only "poor" (1 two-part-, 2 three-part-fractures). The complication rate was 29% (premature hardware removal due to head perforation in 3 cases; humeral head necrosis necessitating prosthetic replacement in 2 patients; secondary displacement in 1 case). Crossed screw osteosynthesis represents an justified alternative in the surgical treatment of displaced proximal humeral fractures permitting early functional therapy.

Fracture-dislocations of the elbow joint--strategy for treatment and results.

Between January 1993 and December 1996, 41 patients with fracture dislocation of the elbow joint were treated in our department. In 28 patients (median age 46 years, range 15-77 years; 16 male, 12 female), a clinical and radiological follow-up was obtained after median 34 months (range 12-59 months). In addition to the humero-ulnar dislocation, isolated fractures were present in 13 patients and combined fractures in 15 (all with involvement of the radial head). Primary neurological deficits were found in 7 and open fractures in 3 patients. In 7 patients, primary definitive surgical therapy was carried out by open reduction and internal fixation. A two-step surgical management (initial closed reduction and immobilization, 5 patients with external fixator, 7 with plaster; secondary open surgical procedure) was performed in 12 and conservative treatment in 9 patients. According to the Leipzig Elbow Score, taking subjective, clinical and radiological criteria into consideration, 4 patients achieved 'excellent' and 5 patients a 'good' result. Ten patients were scored 'moderate' and 9 'poor'. The rate of secondary complications necessitating revision was 36%. Poor results were primarily caused by extensive initial soft-tissue damage, delayed definitive surgical therapy, and ectopic heterotopic ossification. In contrast, fracture localization and degree of arthrosis were not of significant importance for the final outcome. In fracture dislocations, the goal is a primary definitive surgical treatment aiming for early postoperative physiotherapy.

[Perioperative local instillation of ropivacaine for postoperative pain relief after surgery on extremities]. / Perioperative lokale Instillation von Ropivacain zur postoperativen Schmerzreduktion in der Extremitätenchirurgie. Eine prospektiv randomisierte Doppelblindstudie.

INTRODUCTION: The relief of postoperative pain remains one of the most important goals for adequate surgical patient care. METHODS: Prospective, randomised, double-blinded study, including 118 patients (67 M;/ 51 F; median age 43 years, min. 18, max. 74). Two groups were formed. In the verum group a wound instillation with ropivacaine was performed, in the control group not. Intensity of pain, demand for analgesics and satisfaction of the patient were evaluated postoperatively. In 10 patients ropivacaine plasma levels were measured. RESULTS: Significant postoperative pain relief and a decrease in analgesic consumption were found on instillation of ropivacaine. Compared to the control group, patients receiving ropivacaine were significantly more satisfied with the postoperative pain management. Potential toxic plasma levels were not found. CONCLUSION: By the presented method, the surgeon actively contributes to a significant reduction in postoperative pain and analgesic consumption. Furthermore, the patient's benefit is reflected by higher satisfaction with the pain management. Complications due to toxic plasma levels are not seen.

[Pemphigus chronicus benignus familiaris (Hailey-Hailey disease) and bipolar affective disease in 3 members of a family]. / Pemphigus chronicus benignus familiaris (Morbus Hailey-Hailey) und bipolare affektive Erkrankung bei drei Mitgliedern einer Familie.

We report on three family members suffering from both autosomal dominant Hailey-Hailey disease and bipolar affective disorder. As molecular biology techniques have made the localization of genes causing simple Mendelian traits possible as a routine task, the gene for Hailey-Hailey disease will presumably be localized in the foreseeable future. The Hailey-Hailey gene and its chromosomal surrounding will then be a region of interest for linkage studies in bipolar affective disorder.

The function and differential sorting of a family of aplysia prohormone processing enzymes.

We have cloned four members of the family of subtilisin-like endoproteases expressed in the bag cell neurons of Aplysia and have demonstrated that two of these enzymes are capable of correctly cleaving the egg-laying hormone precursor. The egg-laying hormone precursor undergoes an ordered series of cleavages, such that different peptides are differentially sorted into distinct secretory vesicles. We have used electron microscopic chemistry to demonstrate that at least one processing enzyme is differentially segregated into a class of secretory vesicles containing the bag cell peptides. The segregation of specific endoproteases, along with specific neuropeptides within a given cell type, may ensure appropriate cleavage and prevent inappropriate cleavage of the polyprotein precursors.

Prohormone processing in Xenopus oocytes: characterization of cleavage signals and cleavage enzymes.

In this study, we characterize the sequences required for the cleavage of prohormones in Xenopus oocytes. We demonstrate that the yeast alpha-factor and the Aplysia egg-laying hormone (ELH) precursors are not cleaved in oocytes following simple pairs of basic residues, such as Lys-Arg, but that the ELH precursor is cleaved following the consensus sequence Arg-Xaa-(Lys/Arg)-Arg. This motif is conserved among precursors that are cleaved in virtually all mammalian cell types. Mutations that generate this sequence in the alpha-factor prohormone also result in efficient processing within oocytes. Cleavage at this consensus sequence may be due to the action of the Xenopus homologues of mammalian furin.

Isolation and functional expression of a mammalian prohormone processing enzyme, murine prohormone convertase 1.

We have combined gene cloning with an assay for prohormone biosynthesis and processing in Xenopus oocytes to identify the genes that encode mammalian prohormone processing enzymes. The coinjection of RNA encoding murine prohormone convertase 1 (mPC1), a mammalian endoprotease, along with proopiomelanocortin RNA into an oocyte results in the appropriate cleavage after paired basic residues in the proopiomelanocortin polyprotein necessary to generate corticotropin. The ability of mPC1 to generate corticotropin, along with the observation that mPC1 is specifically expressed in endocrine and neuronal cells, suggests that the mPC1 gene encodes the endopeptidase responsible for the pathway of proopiomelanocortin cleavage observed in the anterior pituitary.

Carcinoma of the colon. Cancer specific long-term survival. A series of 615 patients treated by one surgeon.

The cancer specific survival in 615 patients undergoing resection for carcinoma of the colon is presented. The patients were operated on and managed by one surgeon between 1950--1977. Computer analysis has been made of the prospectively collected data. Results are presented as median survival in months and as percentage survivors at 5, 10, 15 and 20 years. Curative resection gave a cancer specific survival at the seventy-fifth percentile of 66 months, corresponding to 76% survival at five years and 67% at 20 years. Age and sex were not significant prognostic factors. Dukes' Stages A, B and C had five-year survivals of 88%, 78% and 60% respectively, after curative resection. The median survival after palliative resection was 14 months. Site of the primary tumor within the colon was of significant prognostic importance only when the poor survival in tumors of the transverse colon was compared with the favorable survival in those of the splenic flexure, ascending, descending and sigmoid colon.

I. Carcinoma of the rectum and rectosigmoid: cancer specific long-term survival. A series of 1061 cases treated by one surgeon.

The long-term cancer specific survival based on individual follow-up and analysis of prospectively collected data from 1061 patients undergoing resection for carcinoma of the rectum is presented. All patients were operated on and managed by one surgeon. Survival data for 978 cases were analyzed according to the methods of Kaplan and Meier, and Gehan. Results have been presented as cancer specific survival times in months and as percentage survivor rates at five-year intervals. The median overall cancer specific survival time was 96 months. Five, ten, 15, and 20-year survival rates were 56, 49, 47, and 46%, respectively. After a potentially curative resection of the tumor, the corresponding percentages were 69, 60, 57, and 56%. Age and sex were not significant prognostic factors. A death rate from recurrent cancer of nil was seen after 15.4 years. At this point, the cancer specific survival rates were 77% for patients in Stage A, 59% in Stage B, 37% in Stage C, and 9% for patients with tumors invading adjacent organs (D1), while no patient with macroscopic metastases to distant organs (Stage D2) survived beyond four and a half years (median, 11 months).