The use of ileocecal pouch with appendix as an urethral substitute in patients who are willing to have a orthotopic bladder replacement - point of technique.

INTRODUCTION: The authors describe the technique of orthotopic bladder replacement with an ileocecal pouch and unaltered appendix used as an orthotopic urethral substitute. Additional procedures with regard to the bothersome voiding symptoms will be described. MATERIAL AND METHODS: In a small cohort of 5 patients with muscle invasive bladder cancer with tumor involvement of the bladder neck or proximal urethra (2 males/3 females) we performed the following reconstruction. A low pressure reservoir was achieved by antimesenteric longitudinal transection of terminal ileum and cecum/colon ascendens and formation of a pouch. To develop the neourethra, the appendix together with it is accompanying mesentery was drawn through the pelvic floor and sutured to the bulbar urethra in males or formed as a complete neourethra in female patients respectively. RESULTS: There were no intraoperative nor early postoperative unwanted sequelae. Both male patients experienced recurrent anastomotic urethral stricture, consequently a Memokath stent and artificial urinary sphincter was implanted resulting in normal voluntary micturition. All female patients remained socially continent during the follow up period, one of them performing (clean intermittent catheterization) CIC. CONCLUSION: The technique described offers the possibility of orthotopic bladder replacement even in traditionally unsuitable, but highly motivated patients, who are requesting orthotopic bladder replacement for improved body image. It allows extension of urethral resection and provides additional continence support. However, additional measures such as urethral stenting, CIC or artificial urinary sphincter implantation may be necessary for long lasting success. Although, not being a routine method for urinary diversion this technique may be used in select patients.

Bolsa ileocecal con utilización del apéndice como neouretra en pacientes dispuestos a sustitución vesical ortotópica: descripción de la técnica / The use of ileocecal pouch with appendix as an urethral substitute in patients who are willing to have a orthotopic bladder replacement - point of technique

Introducción: Los autores describen la técnica de sustitución vesical ortotópica mediante bolsa ileocecal y apéndice inalterado como sustituto ortotópico de la uretra. Se describirán procedimientos adicionales con respecto a las molestias por síntomas de vaciado.Material y métodosEn una pequeña cohorte de 5 pacientes con cáncer de vejiga musculoinvasivo con afectación tumoral del cuello vesical o de la uretra proximal (2 hombres/3 mujeres) realizamos la siguiente reconstrucción. Se obtuvo un reservorio de baja presión mediante la incisión longitudinal antimesentérica del íleon terminal y el ciego/colon ascendente y la formación de una bolsa. Para desarrollar la neouretra, el apéndice y su mesenterio se extrajeron a través del suelo pélvico y se suturó a la uretra bulbar en los hombres o se formó como una neouretra completa en las mujeres, respectivamente.ResultadosNo hubo secuelas indeseables intraoperatorias ni postoperatorias tempranas. Ambos pacientes masculinos experimentaron una estenosis de la anastomosis uretral recurrente, por lo que se realizó un implante de stent Memokath y un esfínter urinario artificial, resultando en una micción voluntaria normal. Todas las pacientes femeninas permanecieron socialmente continentes durante el período de seguimiento, una de ellas realizando cateterismo intermitente limpio (CIL).ConclusiónLa técnica descrita ofrece la posibilidad de la sustitución vesical ortotópica incluso en pacientes tradicionalmente considerados como no aptos, pero muy motivados, que lo solicitan para mejorar su imagen corporal. Permite ampliar la resección uretral y proporciona un apoyo adicional a la continencia. Sin embargo, pueden ser necesarias medidas adicionales como la colocación de un stent uretral, el CIL o el implante de un esfínter urinario artificial para obtener un éxito duradero. Aunque no es un método rutinario de derivación urinaria, esta técnica puede utilizarse en pacientes seleccionados. (AU)

Introduction: The authors describe the technique of orthotopic bladder replacement with an ileocecal pouch and unaltered appendix used as an orthotopic urethral substitute. Additional procedures with regard to the bothersome voiding symptoms will be described.Material and methodsIn a small cohort of 5 patients with muscle invasive bladder cancer with tumor involvement of the bladder neck or proximal urethra (2 males/3 females) we performed the following reconstruction. A low pressure reservoir was achieved by antimesenteric longitudinal transection of terminal ileum and cecum/colon ascendens and formation of a pouch. To develop the neourethra, the appendix together with its accompanying mesentery was drawn through the pelvic floor and sutured to the bulbar urethra in males or formed as a complete neourethra in female patients respectively.ResultsThere were no intraoperative nor early postoperative unwanted sequelae. Both male patients experienced recurrent anastomotic urethral stricture, consequently a Memokath stent and artificial urinary sphincter was implanted resulting in normal voluntary micturition. All female patients remained socially continent during the follow up period, one of them performing clean intermittent catheterization (CIC).ConclusionThe technique described offers the possibility of orthotopic bladder replacement even in traditionally unsuitable, but highly motivated patients, who are requesting orthotopic bladder replacement for improved body image. It allows extension of urethral resection and provides additional continence support. However, additional measures such as urethral stenting, CIC or artificial urinary sphincter implantation may be necessary for long lasting success. Although, not being a routine method for urinary diversion this technique may be used in select patients. (AU)

Effects of ropivacaine, bupivacaine and sufentanil in colon and pancreatic cancer cells in vitro.

The perioperative period is supposed to be a vulnerable period for cancer progression. Results of clinical studies indicate that the use of regional anesthesia can influence and improve oncological outcome of cancer patients. Uncontrolled cell proliferation and resistance to apoptotic cell death are important characteristics of solid tumors. The aim of this study was to investigate the effects of the clinically used local anesthetics ropivacaine or bupivacaine and the opioid analgesic sufentanil on cell proliferation, cell cycle distribution and apoptosis of colon (HT 29 and SW 480) and pancreatic (PaTu 8988t and PANC 1) cancer cell lines in vitro. Cell proliferation was measured by Cell Proliferation ELISA BrdU Assay. Apoptosis was analyzed by annexin V staining and cell cycle distribution was detected by flow cytometry. Ropivacaine, bupivacaine and sufentanil did not change apoptosis rate and cell cycle distribution in clinically concentration. Only high concentrations of ropivacaine or bupivacaine revealed antiproliferative potency. Protective effects of epidural anesthesia observed in clinical studies seem not to be based on direct effects of these drugs on cancer cells.

Effect of a novel nonviral gene delivery of BMP-2 on bone healing.

BACKGROUND: Gene therapeutic drug delivery approaches have been introduced to improve the efficiency of growth factors at the site of interest. This study investigated the efficacy and safety of a new nonviral copolymer-protected gene vector (COPROG) for the stimulation of bone healing. METHODS: In vitro, rat osteoblasts were transfected with COPROG + luciferase plasmid or COPROG + hBMP-2 plasmid. In vivo, rat tibial fractures were intramedullary stabilized with uncoated versus COPROG+hBMP-2-plasmid-coated titanium K-wires. The tibiae were prepared for biomechanical and histological analyses at days 28 and 42 and for transfection/safety study at days 2, 4, 7, 28, and 42. RESULTS: In vitro results showed luciferase expression until day 21, and hBMP-2-protein was measured from day 2 - day 10. In vivo, the local application of hBMP-2-plasmid showed a significantly higher maximum load after 42 days compared to that in the control. The histomorphometric analysis revealed a significantly less mineralized periosteal callus area in the BMP-2 group compared to the control at day 28. The rt-PCR showed no systemic biodistribution of luciferase RNA. CONCLUSION: A positive effect on fracture healing by nonviral BMP-2 plasmid application from COPROG-coated implants could be shown in this study; however, the effect of the vector may be improved with higher plasmid concentrations. Transfection showed no biodistribution to distant organs and was considered to be safe.

Future of local bone regeneration - Protein versus gene therapy.

The most promising attempts to achieve bone regeneration artificially are based on the application of mediators such as bone morphogenetic proteins (BMPs) directly to the deficient tissue site. BMPs, as promoters of the regenerative process, have the ability to induce de novo bone formation in various tissues, and many animal models have demonstrated their high potential for ectopic and orthotopic bone formation. However, the biological activity of the soluble factors that promote bone formation in vivo is limited by diffusion and degradation, leading to a short half-life. Local delivery remains a problem in clinical applications. Several materials, including hydroxyapatite, tricalcium phosphate, demineralised bone matrices, poly-lactic acid homo- and heterodimers, and collagen have been tested as carriers and delivery systems for these factors in a sustained and appropriate manner. Unfortunately these delivery vehicles often have limitations in terms of biodegradability, inflammatory and immunological rejection, disease transmission, and most importantly, an inability to provide a sustained, continuous release of these factors at the region of interest. In coping with these problems, new approaches have been established: genes encoding these growth factor proteins can be delivered to the target cells. In this way the transfected cells serve as local "bioreactors", as they express the exogenous genes and secrete the synthesised proteins into their vicinity. The purpose of this review is to present the different methods of gene versus growth factor delivery in tissue engineering. Our review focuses on these promising and innovative methods that are defined as regional gene therapy and provide an alternative to the direct application of growth factors. Various advantages and disadvantages of non-viral and viral vectors are discussed. This review identifies potential candidate genes and target cells, and in vivo as well as ex vivo approaches for cell transduction and transfection. In explaining the biological basis, this paper also refers to current experimental and clinical applications.

Early weight gain and outcome in Henoch-Schönlein nephritis.

BACKGROUND: Intrauterine growth restriction seems to be a risk factor for an aggravated course of secondary renal diseases in children. Catch-up growth after birth may play a critical role. We tested if there is an association between an aggravated course of nephritis in Henoch-Schönlein Purpura (PSHN) and low birth weight or early weight gain during infancy. PATIENTS: We retrospectively analysed the clinical course of 34 children with PSHN. METHODS: Patients were sorted according their birth weight standard deviation score (SDS) in tertiles. Early weight gain was defined as gain of weight standard deviation score >0.67 between birth and 2 years of age. RESULTS: Patients with higher birth weight needed Cyclophosphamide in a higher rate than low birth weight children. In the high weight gain group (SDS gain >0.67) 9 of the 11 patients compared to 7 of 22 patients in the low weight gain group (SDS gain <0.67) presented with arterial hypertension during the initial manifestation of PSH nephritis (p=0.01). Median systolic blood pressure SDS in the high weight gain group was 1.54 (-1.39-4.71) versus 0.29 (0.52-4.05) in the low weight gain group (p=0.008). Nevertheless, other clinical parameters during first manifestation and follow-up were not relevantly different. CONCLUSION: In contrast to the data of children with idiopathic nephrotic syndrome or IgA nephropathy, this study does neither provide evidence for an association between low birth weight nor early weight gain and the later course of PSHN. Interestingly, early weight gain was associated with a higher systolic blood pressure during the initial manifestation of PSHN.

[Benefits and risks of tube feeding via gastrostoma in infants and children with peritoneal dialysis]. / Nutzen und Risiko eines Gastrostomas bei Säuglingen und Kleinkindern mit chronischer Peritonealdialyse.

BACKGROUND: Nutrition of children with end-stage renal disease and peritoneal dialysis (PD) is often difficult. Tube feeding via a gastrostoma is discussed controversially, and some authors consider this as a contraindication because of the risk of peritonitis. METHODS: In our centre 16 infants and children with end-stage renal disease were treated with PD and tube feeding over a gastrostoma in the last 12 years. The patients showed dystrophy (mean BMI -1.73 SDS) and were too small (mean body length -4.56 SDS). Seven of them (median age 11 months) received a gastrostoma before insertion of a Tenkhoff-catheter and start of PD. Nine children (median age 5 months) had PD primarily before insertion of the gastrostoma and start of tube feeding. RESULTS: Patients with start of PD while a gastrostoma was already inserted had 15 events with peritonitis in the observation time of 91 months (1.98 per patient year). Patients with primary start of PD had 12 events with peritonitis in a total time of 43 month (3.34 per patient year), after insertion while PD was already running the number of events fell significantly to 25 peritonitis events in a total of 271 months (1.11 per patient year, p < 0.01). The children had a benefit from tube feeding via a gastrostoma in regard of body weight (BMI + 1.61 SDS, p < 0.01) as well as growth (body height + 2.29 SDS, p < 0.05). CONCLUSION: Tube feeding via a gastrostoma is a good and safe option for alimentation, even under peritoneal dialysis. A decrease of PD-associated peritonitis under tube feeding was observed while physical development was positively influenced.

Dynamics of magnetic lipoplexes studied by single particle tracking in living cells.

Magnetofection, gene delivery under the influence of a magnetic field, is a technique to increase transfection efficiency by enforcing gene vector contact with a target cell. Mechanisms of magnetic lipoplex internalization and intracellular details of magnetofection are still unknown. In this study, cellular dynamics of magnetic lipoplexes were examined in real time by means of highly sensitive dual-color fluorescence microscopy. Single particle tracking of magnetic lipoplexes provided trajectories representing the movement of the lipoplexes during internalization and subsequent intracellular processes. Magnetic lipoplexes show a three-phase behavior similar to polyplexes. During phase I lipoplexes are attached to the cell surface and show slow cooperative transport behavior. Phase II takes place inside the cell and was characterized by anomalous and confined diffusion. Phase III represented active transport along microtubules inside the cell. The majority of lipoplexes were internalized via endocytosis during phase I. On later time scales the formation of a perinuclear ring was observed. Persisting colocalization of fluid phase marker and lipoplexes after 24 h indicated slow endosomal release. In short, the internalization characteristics of magnetic lipoplexes are very similar to that of polyplexes. Furthermore our results suggest that the magnetic field induces an increased concentration of magnetic complexes on the cell surface resulting in higher transfection efficiency.

Photoactivated release of cargo from the cavity of polyelectrolyte capsules to the cytosol of cells.

Polyelectrolyte capsules with metal nanoparticles in their walls and fluorescently labeled polymers as cargo inside their cavity were prepared. Capsules were ingested by living cells with no uncontrolled release of the cargo upon the incorporation process. Photoinduced heating of the metal nanoparticles in the capsule walls lead to rupture of the capsule walls, and the polymeric cargo was released to the whole cytosol. Viability tests demonstrate that opening of capsules at moderate light intensities does not impair the cellular metabolism, whereas capsule opening at high light intensities ultimately leads to cell death.

Intra-tumoral gene delivery of feIL-2, feIFN-gamma and feGM-CSF using magnetofection as a neoadjuvant treatment option for feline fibrosarcomas: a phase-I study.

Despite aggressive pre- or postoperative treatment, feline fibrosarcomas have a high relapse rate. In this study, a new treatment option based on immune stimulation by intra-tumoral delivery of three feline cytokine genes was performed. The objective of this phase-I dose-escalation study was to determine a safe dose for further evaluation in a subsequent phase-II trial. Twenty-five client-owned cats with clinical diagnosis of fibrosarcoma - primary tumours as well as recurrences - entered the study. Four increasing doses of plasmids coding for feIL-2, feIFN-gamma or feGM-CSF, respectively, were previously defined. In groups I, II, III and IV these doses were 15, 50, 150 and 450 microg per plasmid and a corresponding amount of magnetic nanoparticles. Two preoperative intra-tumoral injections of the magnetic DNA solution were followed by magnetofection. A group of four control cats received only surgical treatment. Side effects were registered and graded according to the VCOG-CTCAE scale and correlated to treatment. Statistical analyses included one-way anova, post hoc and Kruskal-Wallis tests. ELISA tests detecting plasma feIFN-gamma and plasma feGM-CSF were performed. One cat out of group IV (450 microg per plasmid) showed adverse events probably related to gene delivery. As these side effects were self-limiting and occurred only in one of eight cats in group IV, this dose was determined to be well tolerable. Altogether six cats developed local recurrences during a 1-year observation period. Four of these cats had been treated with dose IV. Regarding these observations, a subsequent phase-II trial including a representative amount of cats should be tested for the efficacy of dose IV as well as dose III.

Size of surgical margin does not influence recurrence rates after curative liver resection for colorectal cancer liver metastases.

BACKGROUND: The aim of this study was to examine the relationship between surgical margin status and site of recurrence after potentially curative liver resection for colorectal metastases using an ultrasonic dissection technique. METHODS: Between January 2000 and December 2003, 176 patients underwent liver resection with curative intent for colorectal metastases at a single institution. Demographics, operative data, pathological margin status, site of recurrence and long-term survival data were collected prospectively and analysed. RESULTS: On pathological analysis, resection margins were positive in 43 patients, negative by 1-9 mm in 110, and clear by more than 9 mm in 23 patients. At a median follow-up of 33 months, 133 of 176 patients had developed a recurrence, only five of whom had recurrence at the surgical margin. Recurrence at the surgical margin was not significantly related to the size of the margin. Overall, the median time to recurrence was 12.6 months, which was independent of surgical margin size, although there was a significantly higher proportion of patients with multiple metastases in the group with a positive margin (P = 0.008). Margin status did not correlate significantly with either recurrence-free or overall survival. CONCLUSION: The rate of recurrence at the surgical margin was low and a positive margin was not associated with an increased risk of recurrence either at the surgical margin or elsewhere.

[Pancreas. Congenital changes, acute and chronic pancreatitis]. / Pankreas. Angeborene Veränderungen, akute und chronische Pankreatitis.

The pancreas develops from ventral and dorsal buds, which undergo fusion. Failure to fuse results in pancreas divisum, which is defined by separate pancreatic ductal systems draining into the duodenum. Risk of developing pancreatitis is increased in pancreas divisum. MR cholangiopancreatography (MRCP) is the technique of choice for detecting it non-invasively. Annular pancreas is the result of incomplete rotation of the pancreatic bud around the duodenum with the persistence of parenchyma or a fibrous band encircling (stenosing) the duodenum. Acute pancreatitis is usually caused by bile duct stones or alcohol abuse. Contrast-enhanced multi-detector row CT is the method of choice to assess the extent of this disease. In acute pancreatitis, the role of MRCP is mainly limited to finding bile duct stones in patients with suspected biliary pancreatitis. Chronic pancreatitis results in relentless and irreversible loss of exocrine (and sometimes endocrine) function of the pancreas. MDCT even shows subtle calcifications. MRCP is the method of choice for non-invasive assessment of the duct. Inflammatory pseudotumor in chronic pancreatitis and groove pancreatitis are difficult to differentiate from pancreatic cancer. In these cases, multiple imaging methods such as MDCT, MRI and endosonography including biopsy may be used to make a diagnosis.

Intrauterine growth retardation aggravates the course of acute mesangioproliferative glomerulonephritis in the rat.

Intrauterine growth retardation (IUGR) aggravates the course of acute mesangioproliferative glomerulonephritis (GN) in the rat. Observational studies in children suggest that IUGR may be associated with a severe course of kidney diseases such as IgA nephropathy. We tested the hypothesis that IUGR leads to aggravation of acute mesangioproliferative GN in former IUGR rats. IUGR was induced in Wistar rats by isocaloric protein restriction in pregnant dams. Litter size was reduced to six male neonates in low protein animals (LP) and normal protein animals (NP). At 8 weeks GN was induced by injection of an anti-Thy-1.1 antibody. Rats were killed on days 4 and 14 after induction of GN and kidneys were investigated for inflammation and sclerosis using real-time polymerase chain reaction and histological methods. On day 4 after induction of GN, LP animals showed more glomerulosclerosis and tubulointerstitial lesions. On day 14, inflammatory markers (expression of monocyte chemoattractant protein 1, osteopontin, tumor necrosis factor and interleukin-6), extracellular matrix accumulation and markers of sclerosis (plasminogen activator inhibitor-1 expression, transforming growth factor-beta1 expression, score for glomerulosclerosis, glomerular deposition of collagen I and collagen IV) were more severe in LP animals. Some degree of induction of inflammatory and profibrotic markers was also present in non-nephritic LP animals. However, these rats did not display marked glomerulosclerosis or interstitial fibrosis. We conclude that after IUGR inflammatory damage is aggravated and the reparation of the kidney is impaired during the course of acute mesangioproliferative GN, leading to more sclerotic lesions.

Using magnetic forces to enhance non-viral gene transfer to airway epithelium in vivo.

We have assessed whether magnetic forces (magnetofection) can enhance non-viral gene transfer to the airways. TransMAG(PEI), a superparamagnetic particle was coupled to Lipofectamine 2000 or cationic lipid 67 (GL67)/plasmid DNA (pDNA) liposome complexes. In vitro transfection with these formulations resulted in approximately 300- and 30-fold increase in reporter gene expression, respectively, after exposure to a magnetic field, but only at suboptimal pDNA concentrations. Because GL67 has been formulated for in vivo use, we next assessed TransMAG(PEI) in the murine nasal epithelium in vivo, and compared this to naked pDNA. At the concentrations required for in vivo experiments, precipitation of magnetic complexes was seen. After extensive optimization, addition of non-precipitated magnetic particles resulted in approximately seven- and 90-fold decrease in gene expression for naked pDNA and GL67/pDNA liposome complexes, respectively, compared to non-magnetic particles. Thus, whereas exposure to a magnetic field improved in vitro transfection efficiency, translation to the in vivo setting remains difficult.

[Pancreas. Part II: Tumors]. / Pankreas. Teil II: Tumoren.

Adenocarcinoma is the most common malignant pancreatic tumor, affecting the head in 60-70% of cases. By the time of diagnosis, approximately 80% of tumors are unresectable. Helical CT is very effective in detection and staging of adenocarcinoma, with a sensitivity of 76-92% for detection and an accuracy of 80-90% for staging, but it has limitations in the detection of small cancers (< or =2 cm). Multidetector CT (MDCT) has brought substantial improvements with its inherent 3D imaging capability. Mangafodipir-enhanced MRI is a problem-solving tool in the depiction of small cancers following an equivocal CT imaging result. Gadolinium-enhanced 3D gradient-echo MRI is helpful in the assessment of vascular invasion of cancer and in determining the etiology of cystic lesions. Serous cystadenoma is benign, has a lobulated contour and contains innumerable small cysts of 0.1-2 cm in diameter. Mucinous cystic neoplasms are unilocular or multilocular (fewer than six cysts), and the cyst diameter exceeds 2 cm. The presence of solid nodular components should alert the radiologist to suspect cystadenocarcinoma. Neuroendocrine tumors are mostly hypervascular. Diagnosis of insulinoma is a challenge: they are <2 cm in 90% of cases and mostly hypervascular at CT or MRI. A combination of contrast-enhanced MDCT, MRI, endosonography, and/or somatostatin receptor scintigraphy is used to detect these small tumors. This review summarizes the imaging features of the most common pancreatic tumors and discusses the limitations of CT, MRI and endosonography.

No effect of homocysteine-lowering therapy on vascular inflammation and haemostasis in peripheral arterial occlusive disease.

BACKGROUND: Although peripheral arterial occlusive disease (PAOD) is significantly associated with elevated homocysteine levels, the clinical relevance of hyperhomocysteinaemia for the prevention and progression of PAOD is still unknown. MATERIALS AND METHODS: A total of 65 patients suffering from symptomatic PAOD with elevated homocysteine levels were randomized onto placebo or B-vitamins (50 mg thiaminhydrochlorid, 50 mg pyridoxine, and 0.05 mg cyanocobalamin), plus 5 mg folic acid daily for 6 weeks. Serum levels of folic acid, vitamin B12, creatinine, ultra-sensitive C-reactive protein (usCRP), interleukin (IL)-6, IL-8, IL-18, monocyte-chemo-attractant-protein-1 (MCP-1) and plasma levels of homocysteine, tissue factor (TF) and tissue factor pathway inhibitor (TFPI) were determined on the 1st day and 42nd day. Primary outcome was reduction of homocysteine, secondary outcomes were reduction of usCRP, IL-6, IL-8, Il-18, MCP-1, TF and TFPI. RESULTS: The mean reduction of homocysteine concentration was 33% (95%CI 33.36-55.76, or 18.9+/-5.4 micromol L-1-12.6+/-2.8 micromol L-1, P=0) in the B-vitamin group compared with 1% in the placebo group. Folic acid (P=0) and vitamin B12 (P=0) increased significantly in the verum group, but both remained unchanged in the control group. No treatment effect of lowering of homocysteine on any markers of haemostasis (TF, TFPI) or inflammation (usCRP, IL-6, IL-8, IL-18 and MCP-1) was observed. CONCLUSION: Although homocysteine is associated with vascular disease risk in the general population and in particular with PAOD, marked lowering of homocysteine concentrations by folic acid and B-vitamin supplementation does not influence inflammatory responses involving usCRP, IL-6, IL-8, IL-18 and MCP-1, nor tissue factor. These results provide evidence against a major effect of hyperhomocysteinaemia on vascular chronic inflammation or coagulation in patients with symptomatic peripheral arterial occlusive disease.

[Pancreas. Part I: congenital changes, acute and chronic pancreatitis]. / Pankreas. Teil I: Angeborene Veränderungen, akute und chronische Pankreatitis.

The pancreas develops from ventral and the dorsal buds, which undergo fusion. Failure to fuse results in pancreas divisum, which is defined by separate pancreatic ductal systems draining into the duodenum. Risk of developing pancreatitis is increased in pancreas divisum because of insufficient drainage. MR cholangiopancreatography (MRCP) is the technique of choice for detecting pancreas divisum non-invasively. Annular pancreas is the result of incomplete rotation of the pancreatic bud around the duodenum with the persistence of parenchyma or a fibrous band encircling (and sometimes stenosing) the duodenum. Acute pancreatitis is usually caused by bile duct stones or alcohol abuse. The Atlanta classification differentiates between mild acute and severe acute pancreatitis associated with organ failure and/or local complications such as necrosis, abscess or pseudocyst. Contrast-enhanced multi-detector row CT is the method of choice to assess the extent of disease. Balthazar et al.'s CT severity index assesses the risk of mortality and morbidity. In acute pancreatitis, the role of MRCP is mainly limited to finding bile duct stones in patients with suspected biliary pancreatitis. Chronic pancreatitis results in relentless and irreversible loss of exocrine (and sometimes endocrine) function of the pancreas. MDCT even shows subtle calcifications. MRCP is the method of choice for non-invasive assessment of the duct. Inflammatory pseudotumor in chronic pancreatitis and groove pancreatitis are difficult to differentiate from pancreatic cancer. In these cases, multiple imaging methods such as MDCT, MRI and endosonography including biopsy may be used to make a diagnosis.

Fibrillin-1 regulates mesangial cell attachment, spreading, migration and proliferation.

The microfibrillar protein fibrillin-1 is present in many organs, including the vasculature, eye, and dermis, and is thought to convey structural anchorage and elastic strength. Fibrillin-1 is also a component of the mesangial matrix. To assess the functional relevance of fibrillin-1 for cell-matrix interactions in the glomerulus, we studied the attachment, spreading, migration and proliferation of mesangial cells on fibrillin-1 and the regulation of fibrillin-1 in experimental anti-Thy1.1 nephritis displaying mesangial cell migration and proliferation in vivo. During the acute phase of experimental Thy1.1 nephritis, glomerular fibrillin-1 messenger ribonucleic acid expression and protein immunoreactivity were significantly induced as compared to controls. In a hexosaminidase-based adhesion assay, mesangial cells showed concentration-dependent attachment to fibrillin-1, similar to what was observed for fibronectin. The cell attachment was Arg-Gly-Asp dependent. Further, fibrillin-1 significantly promoted spreading and focal contact formation detected by immunostaining for vinculin. Mesangial cell migration, assessed by a transmigration assay, and proliferation, measured by a 5-bromo-2'-deoxy-uridine incorporation assay, were augmented by fibrillin-1. In diabetic mice underexpressing fibrillin-1, glomerular cell proliferation, determined by counting proliferating cell nuclear antigen-positive cells in renal sections, was significantly lower than in diabetic control mice. We conclude that fibrillin-1 promotes mesangial cell attachment, spreading, migration, and proliferation. We speculate that fibrillin-1 may thus contribute to mesangial hypercellularity during glomerular disease.

Matrix-based autologous chondrocyte implantation for cartilage repair with HyalograftC: two-year follow-up by magnetic resonance imaging.

OBJECTIVE: Monitoring of articular cartilage repair after matrix-associated autologous chondrocyte implantation with HyalograftC by a new grading system based on non-invasive high-resolution magnetic resonance imaging. PATIENTS AND METHODS: In 23 patients, postoperative magnetic resonance imaging (MRI) was performed between 76 and 120 weeks. In nine of these patients, five MRI examinations were performed at 4, 12, 24, 52 and 104 weeks after HyalograftC implant. The repair tissue was described with separate variables: degree of defect repair in width and length, signal intensity of the repair tissue and status of the subchondral bone. For these variables a grading system with point scale evaluation was applied. CONCLUSION: High-resolution MRI provides a non-invasive tool for monitoring the development of cartilage repair tissue following HyalograftC technology, shows a good correlation with clinical outcome and may help to differentiate abnormal repair tissue from a normal maturation process.

A randomized clinical trial of valacyclovir in multiple sclerosis.

OBJECTIVE: The human Herpesvirus type-6 (HHV-6) has been implicated in multiple sclerosis (MS). Valacyclovir is an antiviral agent with an excellent safety profile. A two-year placebo-controlled, double-blind study was conducted to (1) ascertain if high-dose, prolonged treatment with valacyclovir would be safe and (2) observe if valacyclovir would delay the progression of MS clinically or by magnetic resonance imaging (MRI). DESIGN/METHODS: Fifty-eight patients were stratified as to severity and randomly assigned to receive valacyclovir (3000 mg/day) or placebo for a period of two years. Patients were followed clinically over the two-year period by means of the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI) and brain MRI scans. Patients underwent routine lab studies every three months. Patients continued on the medication for two years unless they had a sustained progression or repeated exacerbations. RESULTS: No patient discontinued the study due to side effects or toxicity. In Relative Ranking of Progression, time to first attack, attack rate, and time to withdrawal there were trends (but not statistically significant) toward drug effect over placebo in the Severe clinical category. MRI evaluation showed no significant drug effect. CONCLUSIONS: Although not statistically significant, positive trends were detected for acyclovir by clinical measures, but not by MRI.