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P Bucher

Publications and source records attributed to P Bucher.

At least 19 recordsLinked to original sources

Results from percutaneous drainage of Hinchey stage II diverticulitis guided by computed tomography scan.

BACKGROUND: Percutaneous abscess drainage guided by computed tomography scan is considered the initial step in the management of patients presenting with Hinchey II diverticulitis. The rationale behind this approach is to manage the septic complication conservatively and to follow this later using elective sigmoidectomy with primary anastomosis. METHODS: The clinical outcomes for Hinchey II patients who underwent percutaneous abscess drainage in our institution were reviewed. Drainage was considered a failure when signs of continuing sepsis developed, abscess or fistula recurred within 4 weeks of drainage, and emergency surgical resection with or without a colostomy had to be performed. RESULTS: A total of 34 patients (17 men and 17 women; median age, 71 years; range, 34-90 years) were considered for analysis. The median abscess size was 6 cm (range, 3-18 cm), and the median duration of drainage was 8 days (range, 1-18 days). Drainage was considered successful for 23 patients (67%). The causes of failure for the remaining 11 patients included continuing sepsis (n = 5), abscess recurrence (n = 5), and fistula formation (n = 1). Ten patients who failed percutaneous abscess drainage underwent an emergency Hartmann procedure, with a median delay of 14 days (range, 1-65 days) between drainage and surgery. Three patients in this group (33%) died in the immediate postoperative period. Among the 23 patients successfully drained, 12 underwent elective sigmoid resection with a primary anastomosis. The median delay between drainage and surgery was 101 days (range, 40-420 days). In this group, there were no anastomotic leaks and no mortality. CONCLUSION: Drainage of Hinchey II diverticulitis guided by computed scan was successful in two-thirds of the cases, and 35% of the patients eventually underwent a safe elective sigmoid resection with primary anastomosis. By contrast, failure of percutaneous abscess drainage to control sepsis is associated with a high mortality rate when an emergency resection is performed. The current results demonstrate that percutaneous abscess drainage is an effective initial therapeutic approach for patients with Hinchey II diverticulitis, and that emergency surgery should be avoided whenever possible.

Abdominal Abscess↗

Laparoscopic versus open resection for appendix carcinoid.

BACKGROUND: Since an increasing number of appendectomies are performed via laparoscopy, it is crucial to determine the impact of this approach on appendix carcinoid (AC) outcome. The goal of this study was to compare results of laparoscopic (LAP) versus open (OP) appendectomy for AC according to intend to treat approach. METHODS: A retrospective review (1991-2003) identified 39 patients (median age, 36 years; range, 12-83) treated by laparoscopy (LAP) or laparotomy (OP) for AC in a single institution. Follow-up was complete for all patients (median, 67 months; range, 4-132). RESULTS: Most cases had associated acute appendicitis (64%). Median carcinoid size was 1.1 cm (range, 0.3-5) and 0.4 cm (range, 0.2-3) in the LAP and OP groups, respectively. LAP and OP were performed in 21 (54%) and 18 (46%) patients, respectively. Surgical margins were positive in two patients in the LAP group and one patient in the OP group (p = 0.6). Right colectomies were performed for AC >2 cm in five patients after LAP and in four patients after OP (p = 0.9). Actuarial 5-year survival rates were 100 and 94% in the LAP and OP groups, respectively (p = 0.2). Two patients died in the OP group, one due to metastatic carcinoid and the other due to metachronous colorectal cancer. Synchronous or metachronous colorectal carcinomas developed in six patients (15%). CONCLUSION: Laparoscopic appendectomy is a safe procedure for AC, with carcinologic and long-term results similar to those of conventional appendectomy. Thus, pre- or per-operative suspicion of AC is not a contraindication to LAP. Prognosis of AC appears more dependent on carcinoid malignant potential or associated tumors. Risk for developing colorectal adenocarcinoma is high in AC patients and warrants follow-up of all patients with colonoscopic screening.

Adolescent↗

An audit of surgical management of gastrointestinal stromal tumours (GIST).

AIM: To analyze GIST outcome after primary resection and to determine if a new grading system could adequately predict there prognosis. METHODS: A retrospective review (1993-2002) identified 80 patients who underwent primary surgical resection for, c-KIT positive, GIST. Follow-up was complete for all patients (median follow-up 42, range 1-132, months). GIST were classified as low or high grade according to the following parameters: size, mitotic rate, mitotic index (MiB1), presence of necrosis, invasion of adjacent structure and presence of metastasis. RESULTS: GIST originated from the stomach (46), small bowel (30), colon and rectum two and mesentery two. At surgery, 94% of cases presented with localized disease and 6% blood born metastasis with or without lymph node invasion. Resections were complete (R0) in 72 cases. R0 resection correlated with prognosis (p<0.01). Sixty GIST were classified as low grade (median follow-up 60 months) and 20 as high grade (median follow-up 27 months). Five-year actuarial survival of patients with low or high grade GIST were of 95 and 21%, respectively, (p<0.001). CONCLUSION: Prognosis of GIST after surgical treatment is influenced by completeness of primary resection and tumour malignant potential. Low grade GIST have an excellent prognosis after surgery alone, while high grade GIST have a high rate of recurrence after primary resection. Adjuvant treatment should be advocated for patient with either high grade GIST or after incomplete primary resection. The presented grading system can reliably predict GIST outcome after primary surgical treatment. Complete surgical resection offers good chance of cure for low grade GIST, while for high grade GIST surgery alone is not sufficient. The presented grading system could be used to identify patients who may benefit of adjuvant treatment with imatinib mesylate after GIST resection.

Adult↗

Randomized clinical trial of mechanical bowel preparation versus no preparation before elective left-sided colorectal surgery.

BACKGROUND: Mechanical bowel preparation (MBP) is performed routinely before colorectal surgery to reduce the risk of postoperative infectious complications. The aim of this randomized clinical trial was to compare the outcome of patients who underwent elective left-sided colorectal surgery with or without MBP. METHODS: Patients scheduled for elective left-sided colorectal resection with primary anastomosis were randomized to preoperative MBP (3 litres of polyethylene glycol) (group 1) or surgery without MBP (group 2). Postoperative abdominal infectious complications and extra-abdominal morbidity were recorded prospectively. RESULTS: One hundred and fifty-three patients were included in the study, 78 in group 1 and 75 in group 2. Demographic, clinical and treatment characteristics did not differ significantly between the two groups. The overall rate of abdominal infectious complications (anastomotic leak, intra-abdominal abscess, peritonitis and wound infection) was 22 per cent in group 1 and 8 per cent in group 2 (P = 0.028). Anastomotic leak occurred in five patients (6 per cent) in group 1 and one (1 per cent) in group 2 (P = 0.210) [corrected] Extra-abdominal morbidity rates were 24 and 11 per cent respectively (P = 0.034). Hospital stay was longer for patients who had MBP (mean(s.d.) 14.9(13.1) versus 9.9(3.8) days; P = 0.024). CONCLUSION: Elective left-sided colorectal surgery without MBP is safe and is associated with reduced postoperative morbidity.

Adult↗

Impact of a sirolimus/tacrolimus-based immunosuppressive regimen on kidney function after islet transplantation.

AIM: Islet transplantation is gaining recognition as a therapeutic option for selected diabetic patients. The immunosuppressive regimen based on sirolimus/low-dose tacrolimus is considered a major breakthrough that allowed considerable improvement in graft survival. A high incidence of side effects associated with such a regimen has been reported in the literature, but this immunosuppressive protocol is generally considered safe or even protective to the kidney. Herein, we analyze the impact of the sirolimus/low-dose tacrolimus-based protocol on kidney function. PATIENTS AND METHODS: Five islet-after-kidney and 5 islet-transplant-alone patients were enrolled and followed up. Renal function was assessed by the periodic measurement of serum creatinine and by the presence of albuminuria. Metabolic control markers and graft function were followed, as well as immunosuppressive whole blood trough levels. RESULTS: Kidney function significantly decreased in 6 of 10 patients. Neither metabolic markers nor immunosuppressive drugs levels were significantly associated with the decreased kidney function. CONCLUSION: Although a specific etiology was not identified, subsets of patients presented a higher risk for decrease of kidney function. The presence of low creatinine clearance, albuminuria, and long-established kidney graft were associated with poorer outcomes.

Creatinine↗

Appendix tumors in the era of laparoscopic appendectomy.

BACKGROUND: The safety of laparoscopic appendectomy for the management of incidentally discovered appendiceal tumors has not yet been established. METHODS: Appendiceal tumor cases managed by laparoscopy or laparotomy over a 10-year period were reviewed. RESULTS: The pathological diagnoses were 23 carcinoid and 20 cancerous lesions. The median patient ages were 36 and 69 years, respectively, for carcinoid and other tumors (p < 0.05). Acute appendicitis was present in 70% of carcinoid cases and 35% of other tumors (p < 0.05). Eight patients with carcinoid tumors were operated on by laparoscopy, whereas 15 underwent laparotomy. Laparoscopic and open procedures were performed in three and 17 patients with cancerous lesions, respectively. Invaded surgical margins were seen after laparoscopy in 20% of patients and open surgery in 6%. Synchronous colon carcinoma was detected in 14% of the patients with an appendix neoplasm. The 5-year survival rates were similar after both laparoscopic and open appendectomy for either carcinoid or other tumors. CONCLUSION: Laparoscopic appendectomy for appendiceal tumors seems to have a slightly higher rate of inadequate resection. However, it is not associated with a significantly worse patient prognosis than open appendectomy.

Adenocarcinoma↗

Short-term immunosuppression reduces fibrotic cellular infiltration around barium-M-alginate microbeads injected intraportally.

INTRODUCTION: One of the major barriers affecting the viability of encapsulated islets is pericapsular fibrotic infiltration (PFI). This study aimed to design strategies to reduce PFI around intraportally injected alginate microbeads. METHODS: Empty, highly purified, barium-M-alginate microbeads (400 microm) were injected intraportally into Lewis rats (3000 beads/rat). Rats (n = 9/group) were treated daily with either rapamycine (RAPA; 1 mg/kg/d p.o.), tacrolimus (TAC; 2 mg/kg/d p.o.), a combination of both, or gadolinium-chloride (GdC13, 20 mg/kg/d i.v., at day -1 and day +4). Treatment was discontinued at 10 days. Three rats/group were sacrificed at 3, 7, and 42 days after transplantation. Cellular composition of PFI was evaluated by immunohistochemistry. Severity of the reaction to the beads was determined by measuring the thickness of PFI on histology. RESULTS: The main cellular components of PFI in the liver were macrophages and myofibroblasts. There was a significant (P <.05) reduction in the thickness of PFI in all treated groups, even 6 weeks after transplantation. Encapsulated rat islets showed excellent insulin response to glucose in vitro, with a stimulation index of 3.6 +/- 2.0. CONCLUSION: Combination of highly purified alginate with short-term immunosuppression reduces fibrotic overgrowth around microbeads injected intraportally.

Alginates↗

Morbidity associated with intraportal islet transplantation.

INTRODUCTION: Complications associated with intraportal islet infusion have been reported. In this study, we analyzed the relationship between occurrence of complications and islet preparation characteristics/infusion technique. METHODS: We reviewed all intraportal islet infusions from 1992 to 2003. RESULTS: Sixteen islet autotransplantations were performed without infusion-related complications. The tissue volume injected was 13 +/- 11 mL with basal and peak portal pressures of 13 +/- 6 and 21 +/- 6 mm Hg. Seventy-seven intraportal islet allotransplantations were performed in 51 patients. Fifteen islet infusions were done by laparotomy during simultaneous islet/kidney transplantation without complication. Among 62 percutaneous transhepatic injections, nine complications (two portal branch thrombosis and seven intra-abdominal hemorrhages) were recorded. Rise in portal pressure was related to tissue volume injected (P <.05). Basal and peak portal pressures were 14 +/- 5 and 18 +/- 6 mm Hg in uncomplicated infusions, 14 +/- 9 and 18 +/- 9 mm Hg in the thrombosis group, and 13 +/- 7 and 18 +/- 5 mm Hg in the hemorrhage group (P >.05). Complications occurred only after percutaneous islet infusion (P <.03). CONCLUSIONS: Procedure-related morbidity of intraportal islet infusion is low. Changes in portal pressure are related to volume of tissue injected but do not seem to be associated with the occurrence of complications. Percutaneous infusion is a minimally invasive procedure, but this advantage must be balanced by the higher rate of complications.

Hemorrhage↗

Serva collagenase NB1: a new enzyme preparation for human islet isolation.

INTRODUCTION: Advances in the rate of success of human islet isolation are due in part to the availability of new purified enzyme blends. In this study we evaluated a new enzyme preparation composed of a highly purified collagenase that can be reproducibly blended with predetermined amounts of separately packaged neutral protease. METHODS: Nine human islet isolations were performed with collagenase NB1 supplemented with neutral protease (Serva Electrophoresis GMbH, group I). Yields, purity, morphology, in vitro function and islet cell apoptosis were assessed. The results were compared to those of nine human islet isolations performed with Liberase (Roche, group II) and matched for donor age, BMI, and circumstances of death. RESULTS: Islet yields were similar in both groups. However, islet equivalents (IE) per gram of pancreas and IE number to islet number were higher in group I (P <.05). Stimulation indices after insulin response to glucose (static incubation) were similar in both groups. Islet cell apoptosis rate was statistically significantly lower in group I. Islet morphology was significantly improved in group I with a higher proportion of intact islets. CONCLUSION: This new enzyme preparation (collagenase NB1 with neutral protease adjunct) was as effective as Liberase in terms of islet yields and function. Islet morphology was improved and rate of islet cell apoptosis was lower with this new collagenase. The absence of lot-to-lot variability in terms of neutral protease to collagenase ratio makes collagenase NB1 a promising enzyme for human islet isolation.

Body Mass Index↗

Optimization of neutral protease to collagenase activity ratio for islet of Langerhans isolation.

AIM: The optimal neutral protease to collagenase activity ratio has not been determined for islet isolation. We evaluated a new highly purified collagenase that can be blended with predetermined amounts of neutral protease (NP). METHODS: Islets were isolated from 7 groups of Sprague-Dawley rats. In group I, collagenase type XI (Sigma) at 2 mg/mL, and, in group II, Liberase at 0.6 mg/mL (2.4 PZ- U/mL; Roche) were used as controls. In groups III to VII, collagenase NB1 0.6 mg/mL (2.4 PZ-U/mL; Serva Electrophoresis) was used with increasing amounts of added NP. The NP to collagenase activity ratio (DMC-U/PZ-U) increased from 0.5% in group III to 2.0% in group VII. RESULTS: Mean islet equivalent (IE) yields per rat were 1367, 1755, 597, 895, 1712, 1043, and 905 in groups I to VII. IE yields were maximal at DMC-U/PZ-U = 1.2%. Islet morphology was influenced by NP concentration with decreasing numbers of trapped islets and increasing numbers of fragmented islets as NP contents increased. Cytokine release, islet cell apoptosis, and in vitro function were significantly better in groups III to VII as compared with groups I and II. CONCLUSION: NP is a crucial additive to collagenase for islet isolation. Optimization of the NP to collagenase activity ratio (1.2% in this model) improves yields and morphology after islet isolation.

Animals↗

Microbial surveillance during human pancreatic islet isolation.

OBJECTIVES: The study aim was to investigate the microbiological safety of islet isolation and transplantation. MATERIALS AND METHODS: Between 1996 and 2002, prospective microbiological screening was performed on all pancreata procured for islet transplantation. Pancreas transport media and postpurification preparations were screened for microbiological contamination. Prior to isolation, pancreata were washed with either Hanks solution (group I, n = 170) or decontaminated with antiseptic and antimicrobial drugs (group II, n = 45). RESULTS: Microbiological contamination of the pancreas preservation media was shown in 62%. Analysis of the contaminants showed 74% gram-positive, 21% gram-negative organisms, and 5% fungi. The donor condition or procurement center did not influence the contamination rate. Longer pancreas transport duration was significantly associated with bacterial contamination (P <.05). In group I, 16 (9.4%) of 170 islet preparations presented microbial contamination at the end of the isolation procedures. Gram-positive organisms were present in 10 (6%), gram-negative organisms in 4 (2.4%), and fungi in 2 (1.2%) preparations. Four islet preparations (2.4%) from pancreata with noninfected transport medium were positive on postpurification cultures, all with gram-positive organisms. In group II, only 2 of 45 islet preparations (4.4%) presented microbial contamination at the end of the isolation process. CONCLUSIONS: The rate of microbial contamination during pancreas procurement and transport is high. Significant contaminants present when beginning islet isolation become undetectable by the conclusion of isolation. Diminishing the bio-burden by pancreas decontamination reduces the risk of contamination of the final islet preparation.

Animals↗

Islet autotransplantation for the prevention of surgical diabetes after extended pancreatectomy for the resection of benign tumors of the pancreas.

OBJECTIVE: The objective of this article is to report a single-center experience with islet autotransplantation after extensive pancreatic resection for benign tumors of the pancreas. MATERIALS AND METHODS: Seven patients underwent extensive left pancreatectomy for benign lesions located at the neck of the pancreas. Once an unequivocal diagnosis of a benign nature was ascertained, the rest of the specimen was processed and the unpurified pancreatic digest was infused into the portal vein. The results were compared with those of 8 autotransplantations performed for chronic pancreatitis over the same period. RESULTS: Tumors were 4 cystadenomas, 2 insulinomas and 1 neuroendocrine tumor. Mean islet yields were 275,000 islet equivalents (IEQ) versus 129,000 in chronic pancreatitis (P =.04) or 6700 IEQ/g of tissue versus 1900 (P =.002), resulting in transplantation of 4200 IEQ/kg body weight vs 2150 in chronic pancreatitis (P =.03), respectively at 4-month to 7.5-year follow-up, all patients are alive and 6 of 7 are off insulin. All patients off insulin after at least 1 year currently have a normal IVGTT, with K values ranging between -1.19 and -2.36 (normal < -1.00). All patients, including 1 on insulin, display positive basal and glucagon-stimulated C-peptide levels. CONCLUSIONS: Compared with chronic pancreatitis tissue resected for benign tumors is more likely to achieve good islet yields, and thus insulin independence after autotransplantation. Islet autotransplantation should be considered when extensive pancreatectomy is required for resection of a benign tumor, and only if the benign nature of the lesion is demonstrated unequivocally.

Aged↗

Islet of Langerhans allogeneic transplantation at the University of Geneva in the steroid free era in islet after kidney and simultaneous islet-kidney transplantations.

AIMS: We report a single-center experience of islet allogeneic transplantation in islet after kidney (IAK) and simultaneous islet-kidney (SIK) type 1 diabetic recipients using a steroid-free immunosuppressive regimen. METHODS: Eight patients received 12 islet infusions in 5 IAK and 3 SIK procedures. Median age was 51 years (range, 30-58 years) with a male:female ratio of 2:6. IAK was considered only for patients with a stable kidney function and a creatinine clearance level >60 mL/min. SIK was considered for patients with a counterindication for simultaneous kidney-pancreas transplantation. Immunosuppression was based on sirolimus/tacrolimus combined with daclizumab induction. Two consecutive infusions of >5000 islet equivalents (IEQ)/kg were planned. RESULTS: Five patients completed the transplantation course, whereas 3 patients received only 1 islet infusion. All patients have functional grafts (C-peptide >166 pmol/L) at 6-month median follow-up. Of 5 patients who completed their transplantation course 4 became insulin independent. HbA1c and fructosamine decreased over time, showing improved metabolic control. Severe adverse events were observed in 4 patients. One SIK patient died after OKT-3 treatment of severe kidney rejection. CONCLUSIONS: The Edmonton immunosuppressive protocol can be applied for patients undergoing either IAK or SIK procedures, with a high rate of graft function and insulin independence. Morbidity is higher than among patients undergoing solitary islet transplantation for type 1 brittle diabetes.

Adult↗

Retransplantation of discordant xenogeneic islets with costimulatory blockade.

BACKGROUND: The aim of the study was to analyze the possibility of xenogeneic islet retransplantation using costimulatory blockade. METHODS: Streptozotocin-induced diabetic mice were transplanted under the kidney capsule with human islets. Mice were nephrectomized and retransplanted with 1000 human islets under the contralateral kidney capsule 14 days later. Four groups were performed group I, first and second Tx without MR1; group II, first Tx without MR1, second Tx with MR1; group III, first Tx with MR1, second Tx without MR1; group IV, first and second Tx with MR1. A control group was transplanted only once without MR1 with human islets. After second Tx, cross-matches between recipient, serum and human lymphocyte were done for detection of antidonor antibodies. RESULTS: In the control group, mean graft survival was 13 (+/-7) days. In group I, mean graft survival was 5 +/- 3 days. In group II, mean graft survival was 16 +/- 13 days. In group III, mean graft survival was 81 +/- 22 days. In group IV, no rejection were recorded and all graft survived more than 120 days. Pretransplant cross-matches were negative. In groups I and II all cross-matches were positive, while none were positive in group IV. CONCLUSION: Retransplantation of xenogeneic islets was associated with accelerated rejection. After presensitization, MR1 was unable to induce tolerance to a second Tx. MR1 given at the first Tx only allowed prolonged survival of the second Tx, but rejection still occurred. MR1 given at first and second Tx allowed long-term survival of retransplanted xenoislets and prevented occurrence of antidonor antibodies.

Animals↗

Successful islet after kidney transplantations in a distance over 1000 kilometres: Preliminary results of the Budapest-Geneva collaboration.

To overcome critical islet processing and to ensure patient safety and quality care, we have established an international collaboration between two geographically distant transplant centers for islet transplantation. Four pancreata were harvested and immediately preserved by the two-layer method (oxygenated perfluorocarbon+University of Wisconsin) and subsequently transported for the automated method isolation to Geneva. After purification, the islets were cultured overnight and transported the next day back to Budapest. Three consecutive kidney transplant patients with type 1 diabetes mellitus underwent islet transplantation via percutaneous transhepatic portal embolization using the bag-method. The immunosuppression consisted of daclizumab, sirolimus, and low-dose tacrolimus. Mean donor age was 43.7 years, mean body mass index: 26.5. The islet isolation process began within 8 hours from the donor aorta cross-clamp in all cases. The isolation success rate was 80% (4 of 5). In Budapest, the islets were assessed for viability. No complications occurred during the transplantation, and the portal pressure remained within the normal range. The first patient received 12,000 IU/BW from two donors and the insulin requirement decreased from 40 U/d to 10 U/d. The second patient received 7200 IU/BW from a single donor and became immediately insulin free. The third patient was given 7100 IU/BW; the insulin requirement decreased from 39 U/d to 14 U/d. Posttransplant follow-up for the three patients are 7 months, 4 months, and 2 weeks, respectively. All patients achieved metabolic stability. These preliminary results demonstrate the feasibility of an international collaborative islet transplantation program at a distance over 1000 km.

Adult↗

Paraganglioma of the ampulla of Vater: a potentially malignant neoplasm.

Paragangliomas are rare tumours originating from neuroectodermic remnants and are usually considered as benign. We present two cases of paraganglioma of the ampulla of Vater that were treated surgically by pancreaticoduodenectomy. In one case, histopathology revealed malignant characteristics of the tumour with invasion of the pancreas and simultaneous duodenal lymph-node metastases. Both patients had a favourable outcome without disease recurrence at 40 and 44 months postoperatively. Only 21 cases of ampullary paraganglioma have been reported in the literature, 7 of them with malignant characteristics. In conclusion, paragangliomas of the ampulla of Vater have malignant potential. Surgical therapy of these tumours should not be limited to local resection, as disease recurrence and lymph node involvement have been reported. We propose that paragangliomas of the ampulla of Vater should be operated by cephalic pancreaticoduodenectomy, which allows long-term and disease-free survival.

Adult↗

The implementation of the 'International Classification of Functioning, Disability and Health' (ICF) in daily practice of neurorehabilitation: an interdisciplinary project at the Kantonsspital of Lucerne, Switzerland.

PURPOSE: The current paper describes the implementation of ICF as a standard language and framework for description of human functioning and disability for common use in every day work by the multiprofessional team. METHOD: An interdisciplinary project team involving all rehabilitation specialities was constituted. The extensive original document of ICF was broken down to a simplified raster for body functions and structures, activities and participation, as well as for contextual factors. These rasters had to cover the most important aspects concerning the patients treated on our unit. Checklists on the basis of these rasters were worked out for use by the different specialized teams. Using these checklists, rehabilitation conferences, form and language of interdisciplinary communication, goal setting and documentation were introduced newly in every day work for the interdisciplinary rehabilitation team, structured strictly based on the ICF-criteria. RESULTS: Since April 2002 the ICF-based processes are implemented in routine work for all members of the rehabilitation staff. First experiences show good acceptance by the team members, improvements in communication and documentation as well as substantial gains in content and handling of rehabilitation conferences. As a result of the implementation we observed, that participation, context and domiciliary interventions gained quite more influence in every day work at the unit. CONCLUSION: Implementation improved considerably the quality of interdisciplinary work processes and contributed to a more systematic approach to rehabilitation tasks by the team members.

Activities of Daily Living↗

HLA-DR2 dose effect on susceptibility to multiple sclerosis and influence on disease course.

Models of disease susceptibility in multiple sclerosis (MS) often assume a dominant action for the HLA-DRB1*1501 allele and its associated haplotype (DRB1*1501-DQB1*0602 or DR2). A robust and phenotypically well-characterized MS data set was used to explore this model in more detail. A dose effect of HLA-DR2 haplotypes on MS susceptibility was revealed. This observation suggests that, in addition to the role of HLA-DR2 in MS, two copies of a susceptibility haplotype further increase disease risk. Second, we report that DR2 haplotypes modify disease expression. There is a paucity of benign MS and an increase of severe MS in individuals homozygous for DR2. Concepts of the molecular mechanisms that underlie linkage and association of the human leukocyte antigen (HLA) region to MS need to be revised to accommodate these data.

Disease Progression↗