Achieving stomal continence with an ileal pouch and a percutaneous implant.

In this study, a soft-tissue-anchored, percutaneous port used as a mechanical continence-preserving valve in reservoir ileo- and urostomies was functionally and morphologically evaluated in eight dogs. During follow-up, the skin failed to attach to the implant, but the intestine inside the stoma port appeared to be attached to the mesh. After reaching adequate reservoir volume, the urostomies were rendered continent by attaching a lid to the implant. The experiments were ended at different time intervals due to implant-related adverse events. In only one case did the histological evaluation reveal integration at both the implant-intestine and implant-skin interfaces, with a low degree of inflammation and the absence of bacterial colonisation. In the remaining cases, integration was not obtained and instead mucosal downgrowth and biofilm formation were observed. The skin-implant junction was characterised by the absence of direct contact between the epidermis and the implant. Varying degrees of epidermal downgrowth, granulation tissue formation, inflammatory cell infiltration and bacterial growth and biofilm formation were prominent findings. In contrast, the subcutaneously located anchor part of the titanium port was well integrated and encapsulated by fibrous tissue. These results demonstrate the opportunity to achieve integration between a soft-tissue-anchored titanium port, skin and intestine. However, predictable long-term function could not be achieved in these animal models due to implant- and non-implant-related adverse events. Unless barriers at both the implant-skin and implant-intestine junctions are created, epidermal and mucosal downward migration and biofilm formation will jeopardise implant performance.

Mix-and-diffuse serial synchrotron crystallography.

Unravelling the interaction of biological macromolecules with ligands and substrates at high spatial and temporal resolution remains a major challenge in structural biology. The development of serial crystallography methods at X-ray free-electron lasers and subsequently at synchrotron light sources allows new approaches to tackle this challenge. Here, a new polyimide tape drive designed for mix-and-diffuse serial crystallography experiments is reported. The structure of lysozyme bound by the competitive inhibitor chitotriose was determined using this device in combination with microfluidic mixers. The electron densities obtained from mixing times of 2 and 50 s show clear binding of chitotriose to the enzyme at a high level of detail. The success of this approach shows the potential for high-throughput drug screening and even structural enzymology on short timescales at bright synchrotron light sources.

Single-shot diffraction data from the Mimivirus particle using an X-ray free-electron laser.

Free-electron lasers (FEL) hold the potential to revolutionize structural biology by producing X-ray pules short enough to outrun radiation damage, thus allowing imaging of biological samples without the limitation from radiation damage. Thus, a major part of the scientific case for the first FELs was three-dimensional (3D) reconstruction of non-crystalline biological objects. In a recent publication we demonstrated the first 3D reconstruction of a biological object from an X-ray FEL using this technique. The sample was the giant Mimivirus, which is one of the largest known viruses with a diameter of 450 nm. Here we present the dataset used for this successful reconstruction. Data-analysis methods for single-particle imaging at FELs are undergoing heavy development but data collection relies on very limited time available through a highly competitive proposal process. This dataset provides experimental data to the entire community and could boost algorithm development and provide a benchmark dataset for new algorithms.

Three-dimensional reconstruction of the giant mimivirus particle with an x-ray free-electron laser.

We present a proof-of-concept three-dimensional reconstruction of the giant mimivirus particle from experimentally measured diffraction patterns from an x-ray free-electron laser. Three-dimensional imaging requires the assembly of many two-dimensional patterns into an internally consistent Fourier volume. Since each particle is randomly oriented when exposed to the x-ray pulse, relative orientations have to be retrieved from the diffraction data alone. We achieve this with a modified version of the expand, maximize and compress algorithm and validate our result using new methods.

Urostomy and health-related quality of life in patients with lower urinary tract dysfunction.

OBJECTIVE: Urinary diversion may be an option in patients with disabling lower urinary tract dysfunction (DLUTD), refractory to conservative and minor invasive treatment. The aim of this study was to evaluate whether urostomy improves quality of life and cost of surgery, in terms of complications, loss of kidney function and hospital stay, in these patients. MATERIAL AND METHODS: This prospective study included 52 consecutive patients (nine men and 43 women) with various benign disorders. Twenty-six patients received an ileal conduit and 26 a continent cutaneous diversion. The patients completed the general health-related quality of life instrument WHOQOL-BREF and a urinary problem-specific quality of life instrument preoperatively and 6 and 12 months after surgery. Length of hospital stay and complications were registered. Intravenous urography and determination of glomerular filtration rate (GFR) were performed preoperatively and 12 months postoperatively. RESULTS: Disease-specific and health-related quality of life improved significantly (p < 0.0005 and p < 0.05) in all domains except for social relationship, from preoperative to 12 months after surgery. There was no difference in improvement between patients with continent and those with incontinent diversion. Mean hospital stay was 14 days. Early and late complications required open surgery in 12 patients (23%). GFR was unchanged postoperatively. CONCLUSIONS: Urinary diversion improves health-related and disease-specific quality of life in patients with DLUTD refractory to conservative and minor invasive treatments. The burden of surgery is acceptable. Urinary diversion could be recommended more often in such patients.

Functional results after orthotopic bladder substitution: a prospective multicentre study comparing four types of neobladder.

OBJECTIVE: The aim of this study was to evaluate enterocystometry, voiding pattern and urine leakage of four types of orthotopic bladder substitute. MATERIAL AND METHODS: At eight urological departments, 78 consecutive men were studied: 66 with an ileal neobladder [30 Studer pouches (S), 24 Hautmann pouches (H) and 12 T-pouches (T)] and 12 with a right colonic [Goldwasser type (G)] neobladder. Enterocystometry, determination of residual urine, micturition protocol and 24 h pad weight test were performed 6 and 12 months postoperatively. RESULTS: Colonic neobladders had higher pouch pressure at first desire, normal desire and strong desire than ileal neobladders (except at first and normal desire at 12 months) (p < 0.02) and contraction was present more often at both 6 and 12 months (p < 0.01 and p < 0.01). Compliance was good in all types of pouch. Intermittent self-catheterization was more common in H patients at 6 months (p = 0.033). All patients with colonic neobladders used pads during the day and night. In patients with ileal pouches 32% used pads during the day and 70% during the night at 12 months. Urine leakage was higher in patients with colonic bladders at 6 and 12 months during the day (mean/median of 98/31 ml and 82/16 ml versus 10/0 ml and 4/0 ml, p < 0.001). T-pouches had excellent day-time continence, but nocturnal leakage was high. CONCLUSIONS: The Hautmann pouch and the Studer pouch behaved similarly at enterocystometry and clinically, and continence was good in the majority of patients. The low number of patients with the other two types of pouch precludes definitive statements.

Half century of followup after ureterosigmoidostomy performed in early childhood.

PURPOSE: We studied clinical outcomes, especially regarding colorectal adenocarcinoma, in patients who underwent ureterosigmoidostomy in early childhood between 1944 and 1961. MATERIALS AND METHODS: A total of 25 consecutive patients underwent ureterosigmoidostomy at a mean age of 3.1 years. The most common indication for ureterosigmoidostomy was bladder exstrophy-epispadias complex. The study period ended in 2010. Patient files were retrospectively evaluated, personal telephone interviews were performed and colorectal histology was reevaluated. One girl who died 4 days postoperatively was excluded. RESULTS: Of the 24 patients 17 were alive in 2010 with a mean age of 59 years (range 48 to 67), and 2 still had a functioning ureterosigmoidostomy. A total of 20 patients with a mean age of 33 years had undergone re-diversion at a mean of 30 years postoperatively. Invasive colorectal adenocarcinoma developed in 7 patients and colorectal adenocarcinoma in situ in 1. Five patients died due to generalized colorectal adenocarcinoma. Mean time from ureterosigmoidostomy to diagnosis of invasive colorectal adenocarcinoma was 38 years (range 23 to 55). Three cases were diagnosed at 1, 21 and 25 years after re-diversion. One patient with colorectal adenocarcinoma in situ was 22 years old at polyp resection, which was 20 years after re-diversion. A carcinoid tumor developed in 1 patient. Of the 7 cases of invasive colorectal adenocarcinoma 6 were low differentiated. CONCLUSIONS: After a half century of followup in 25 individuals undergoing ureterosigmoidostomy during childhood 17 were still alive and 20 had undergone re-diversion. Compared to the general Swedish population, the risk of colorectal adenocarcinoma was increased 42 times and the incidence of low differentiation was extremely high.

Femtosecond free-electron laser x-ray diffraction data sets for algorithm development.

We describe femtosecond X-ray diffraction data sets of viruses and nanoparticles collected at the Linac Coherent Light Source. The data establish the first large benchmark data sets for coherent diffraction methods freely available to the public, to bolster the development of algorithms that are essential for developing this novel approach as a useful imaging technique. Applications are 2D reconstructions, orientation classification and finally 3D imaging by assembling 2D patterns into a 3D diffraction volume.

Single mimivirus particles intercepted and imaged with an X-ray laser.

X-ray lasers offer new capabilities in understanding the structure of biological systems, complex materials and matter under extreme conditions. Very short and extremely bright, coherent X-ray pulses can be used to outrun key damage processes and obtain a single diffraction pattern from a large macromolecule, a virus or a cell before the sample explodes and turns into plasma. The continuous diffraction pattern of non-crystalline objects permits oversampling and direct phase retrieval. Here we show that high-quality diffraction data can be obtained with a single X-ray pulse from a non-crystalline biological sample, a single mimivirus particle, which was injected into the pulsed beam of a hard-X-ray free-electron laser, the Linac Coherent Light Source. Calculations indicate that the energy deposited into the virus by the pulse heated the particle to over 100,000 K after the pulse had left the sample. The reconstructed exit wavefront (image) yielded 32-nm full-period resolution in a single exposure and showed no measurable damage. The reconstruction indicates inhomogeneous arrangement of dense material inside the virion. We expect that significantly higher resolutions will be achieved in such experiments with shorter and brighter photon pulses focused to a smaller area. The resolution in such experiments can be further extended for samples available in multiple identical copies.

Impaired renal function in newly spinal cord injured patients improves in the chronic state--effect of clean intermittent catheterization?

PURPOSE: We investigated renal function in spinal cord injured subjects in relation to the level and completeness of injury and bladder emptying regimen in the acute and chronic stages. MATERIALS AND METHODS: A retrospective chart review was performed of 169 spinal cord injured subjects treated at the Spinal Cord Injury Unit, Sahlgrenska Hospital between 1985 and 2002. Renal function based on glomerular filtration rate was evaluated by chromium ethylenediaminetetraacetic acid clearance 3 to 4 months after injury and at followup 3 to 5 years after injury. RESULTS: The glomerular filtration rate was lower than expected in the first investigation in the whole group (82% of the expected value). When divided according to level of lesion the figure was lower in the cervical (81%) and thoracic (88%) levels of the lesion and in the American Spinal Injury Association A group compared to the American Spinal Injury Association B-E group. In the second investigation we found a significant improvement in the whole group of 6%. When dividing the group according to bladder emptying regimen we found that in the group that emptied the bladder by clean intermittent catheterization glomerular filtration rate improved significantly (+7%). CONCLUSIONS: Spinal cord injury affects renal function and has a deteriorating effect on glomerular filtration rate. The reduction is seen on the cervical and thoracic levels of injury and in complete injuries. Renal function improves with time after injury and improvement is seen most clearly in the group that uses clean intermittent catheterization as a bladder emptying method.

Long-term results of reconstructive surgery in patients with bladder pain syndrome/interstitial cystitis: subtyping is imperative.

OBJECTIVES: To evaluate the long-term outcome after reconstructive surgery in patients with bladder pain syndrome/interstitial cystitis subdivided into subtypes. METHODS: A total of 47 patients, fulfilling the National Institutes of Health/National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases criteria, were evaluated retrospectively. They all had undergone reconstructive surgery during the 25-year period of 1978 to 2003. The surgical procedures included noncontinent ureteroenterocutaneostomy (12 patients), supratrigonal cystectomy and ileocystoplasty (23 patients), continent urinary diversion (Kock pouch; 10 patients), continent orthotopic diversion (1 patient), and cecocystoplasty (1 patient). The series comprised 34 patients with classic Hunner type disease and 13 patients with nonulcer bladder pain syndrome/interstitial cystitis. The patients were preoperatively assessed by interview, visual analog pain scale, micturition diaries, urinalysis, intravenous urography, urethrocystoscopy, and bladder distension during anesthesia, including biopsy and, in selected cases, urodynamic evaluation. The data were obtained by surveying the clinical records. RESULTS: For 28 of the 34 patients with classic Hunner-type disease, the initial surgical procedure resulted in complete symptom resolution. Of the remaining 6 patients, 4 were successfully treated with a supplementary diversion procedure, cystectomy, or transurethral ulcer resection in the trigonal remnant. In contrast, only 3 of the 13 patients with nonulcer disease experienced symptom resolution after reconstructive surgery, and 2 of these required a supravesical diversion procedure. CONCLUSIONS: Reconstructive surgery for refractory bladder pain syndrome/interstitial cystitis is an appropriate last resort only for patients with end-stage Hunner's disease. The decision to embark on major reconstructive surgery in patients with bladder pain syndrome/interstitial cystitis should be preceded by a thorough preoperative evaluation, with emphasis on assessment to determine the relevant subtype (ie, classic or nonulcer disease).

Relationships between free radical levels during carotid endarterectomy and markers of arteriosclerotic disease.

BACKGROUND: Free radical production is elevated in jugular venous blood emerging from the brain in conjunction with carotid endarterectomy. This study explores the relationships between markers for lesion progression in arteriosclerosis, production of radicals and clinical characteristics. METHODS: The radical production during carotid endarterectomy was studied in 13 patients with an ex vivo spin trap method using OXANOH as a spin trap. MCP-1, ICAM-1, MMP-9 and oxLDL were determined in venous blood samples before, during and after clamping of the carotid artery. Principal component analysis (PCA) as well as partial least square regression analysis (PLS) was applied to interpret the data. RESULTS: PCA and PLS analysis revealed that high values of MMP-9 and low values of ICAM-1 were associated with high radical production whereas MCP-1 and oxLDL were not correlated to radical production. MMP-9 was elevated at diabetes, high haemoglobin, high leucocyte counts and thrombocyte counts as well as at contralateral stenosis, whereas ICAM-1 showed reversed relationships to these clinical variables. MCP-1 increased during surgery. CONCLUSIONS: The main finding in our study is that MMP-9 in plasma is asscociated with radical production during carotid endarterectomy, suggesting that this enzyme might be involved in the pathogenesis of brain damage in conjunction with ischaemia-reperfusion.

Afferent intussuscepted antireflux nipple valve complications in the Kock pouch for continent urinary diversion Early results with a modified technique.

OBJECTIVES: To analyse the risk of afferent nipple valve stenosis and its consequences and management in patients with a Kock pouch for continent urinary diversion and to study the early results after using an alternative antireflux technique. MATERIAL AND METHODS: Sixty patients consecutively operated on with a conventional Kock reservoir for continent cutaneous urinary diversion between 1988 and 2001 were analysed with regard to the occurrence of afferent nipple valve stenosis and its clinical characteristics. Sixteen patients operated on for continent urinary diversion during the period 2002-04 had the antireflux valve constructed according to the serous-lined extramural ileal valve technique. RESULTS: Eight patients with a conventional Kock pouch developed true afferent nipple valve stenosis and the risk approached 30% after 15 years. Dilatation and stenting were usually successful. CONCLUSIONS: The high risk of afferent nipple valve stenosis when using the intussuscepted nipple valve in the construction of a Kock reservoir for continent cutaneous urinary diversion calls for an alternative method for anastomosing the ureters to the reservoir. Our early results with the combined Kock/T-pouch are promising.

Normal or increased bile acid uptake in isolated mucosa from patients with bile acid malabsorption.

INTRODUCTION: Bile acid malabsorption as reflected by an abnormal Se-labelled homocholic acid-taurine (SeHCAT) test is associated with diarrhoea, but the mechanisms and cause-and-effect relations are unclear. OBJECTIVES: Primarily, to determine whether there is a reduced active bile acid uptake in the terminal ileum in patients with bile acid malabsorption. Secondarily, to study the linkage between bile acid malabsorption and hepatic bile acid synthesis. METHODS: Ileal biopsies were taken from patients with diarrhoea and from controls with normal bowel habits. Maximal active bile acid uptake was assessed in ileal biopsies using a previously validated technique based on uptake of C-labelled taurocholate. To monitor the hepatic synthesis, 7alpha-hydroxy-4-cholesten-3-one, a bile acid precursor, was assayed in blood. The SeHCAT-retention test was used to diagnose bile acid malabsorption. RESULTS: The taurocholate uptake in specimens from diarrhoea patients was higher compared with the controls [median, 7.7 (n=53) vs 6.1 micromol/g per min (n=17)] (P<0.01) but no difference was seen between those with bile acid malabsorption (n=18) versus diarrhoea with a normal SeHCAT test (n=23). The SeHCAT values and 7alpha-hydroxy-4-cholesten-3-one were inversely correlated. CONCLUSIONS: The data do not support bile acid malabsorption being due to a reduced active bile acid uptake capacity in the terminal ileum.

Osteoporosis in adults with meningomyelocele: an unrecognized problem at rehabilitation clinics.

OBJECTIVES: To assess the prevalence of osteoporosis and osteopenia in adults with meningomyelocele and to explore whether neurologic level, ambulatory status, and other medical problems are associated with bone mineral density (BMD). DESIGN: A cross-sectional study, including a self-administered questionnaire and clinical assessment. SETTING: Outpatient referral clinic in Sweden. PARTICIPANTS: Twenty-one adults (mean age, 30 y) with meningomyelocele admitted to the Young Adult Teams in Göteborg and Boras, Sweden. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: BMD in the lumbar spine and hip and forearm measured with dual x-ray absorptiometry. RESULTS: Seven (33%) subjects had osteoporosis in at least 1 of the measured sites. Three patients had osteopenia and 2 had osteoporosis in the lumbar spine. Among the 15 subjects whose BMD of the hip region could be reliably measured, 7 (47%) had osteoporosis in the femoral neck or trochanteric region of the hip. Subjects with other medical problems commonly occurring in meningomyelocele had lower BMD in the femoral neck and trochanteric region of the hip than subjects without such factors. Ambulation alone showed only a tendency to be associated with BMD of the femoral neck, whereas the effect of other medical risk factors on BMD of the femoral neck was stronger among the nonambulators than the ambulators. CONCLUSIONS: Our results show that osteoporosis is a medical problem to be considered when treating and rehabilitating patients with meningomyelocele.

Continent cutaneous urinary diversion is still a valid alternative after cystectomy for bladder carcinoma.

OBJECTIVE: We compared patient opinions concerning reservoir/bladder function as well as quality of life (QOL) after cystectomy for bladder carcinoma and continent cutaneous urinary diversion or orthotopic bladder reconstruction. MATERIAL AND METHODS: Fifteen patients with Kock reservoirs (11 females, 4 males) and 11 men with orthotopic bladders answered the European Organization for Research and Treatment of Cancer quality-of-life questionnaire-C30 as well as specially constructed questions concerning reservoir/bladder function. The glomerular filtration rate (GFR) was determined using Cr-EDTA or iohexol clearance. RESULTS: Functioning and global health/QOL scales did not differ between the two groups of operated patients or between diverted patients and gender- and age-matched groups from the general population. The majority of the patients were satisfied/very satisfied with their diversion but more patients were troubled by leakage in the orthotopic bladder group than in the Kock reservoir group. The GFR was similar in the two groups. CONCLUSION: Continent cutaneous urinary diversion is associated with fewer leakage problems than orthotopic bladder reconstruction after cystectomy for bladder carcinoma.

Prophylaxis against bone loss in Kock reservoir patients with reduced glomerular filtration rate.

OBJECTIVE: We investigated whether treatment with calcium carbonate and vitamin D3 can improve the bone mineral content of patients with ileal reservoirs for continent urinary diversion and a reduced glomerular filtration rate (GFR). MATERIAL AND METHODS: Twenty-six patients with Kock reservoirs were included in the study. Bone mineralization was determined using dual-energy X-ray absorptiometry. Kidney function was estimated from Cr-EDTA clearance and serum cystatin C concentration. Osteocalcin and parathyroid hormone in serum were also measured. Patients with reduced GFR were treated with calcium carbonate and vitamin D3 perorally. RESULTS: Bone mineral density in the femur neck and hip increased in the treatment group, as reflected by an improved T score. CONCLUSION: Patients with ileal reservoirs for continent urinary diversion and reduced kidney function should be supplemented with calcium carbonate and vitamin D3 in order to reduce the long-term risk of osteoporosis.

Luminal nitric oxide in ileal reservoirs for continent cutaneous diversion or orthotopic bladder reconstruction.

OBJECTIVES: To measure mucosal inflammation as reflected in nitric oxide (NO) production in ileal reservoirs for the storage of urine and to correlate it with the growth of bacteria as well as CRP. METHODS: Intraluminal gas NO concentrations were determined using the chemoluminescence technique in 25 patients with continent cutaneous ileal reservoirs (Kock pouch) and 12 patients with orthotopic bladders (hemi-Kock or T-pouch). NO concentrations were determined in both intestinal reservoir gas and silicon catheter balloon gas. Urinary culture and blood CRP determinations were performed. RESULTS: NO concentrations in reservoir gas were higher than in silicon catheter balloons. Bacteriuria was associated with approximately 20 times higher NO concentrations than sterile urine. NO concentrations did not differ between continent cutaneous reservoirs or orthotopic bladders when due attention was paid to variance in the rate of bacteriuria. Elevated CRP was associated with higher NO concentrations. Bacteriuria with acinetobacter, enterococci and pseudomonas appeared to cause comparatively lower NO concentrations. The inflammatory response of reservoir walls to bacteriuria did not decrease with time. CONCLUSIONS: Urine in itself causes much less intestinal wall inflammation than bacteriuria, as reflected in NO production. High CRP values are associated with high NO concentrations. The inflammatory response varies with the bacterial specimens.

Effects of pretreatment with a xanthine oxidase inhibitor on free radical levels during carotid endarterectomy.

OBJECTIVE: Free radicals contribute to the tissue damage caused by ischaemia-reperfusion. The aim of the present study was to investigate whether preoperative antioxidant therapy (allopurinol) affects free radical levels in cerebral venous blood in connection with surgery for carotid artery stenosis. MATERIALS AND METHODS: Twenty-five patients were randomised into the study. Thirteen were controls and 12 were pretreated with allopurinol the day before surgery. Before, during and after surgery, blood samples were drawn from the ipsilateral jugular vein. Radical levels were measured using the spin trap technique ex vivo using OXANOH as the spin trap. Multivariate statistics were used with Principal Component Analysis and Partial Least Square regression analysis. RESULTS: Radical levels increased with diabetes, high leukocyte count, high creatinine and a high degree of contralateral stenosis. Radical levels decreased with high age, blood pressure, collateral circulation as well as operation for left-side carotid artery stenosis. After pretreatment with allopurinol, several of the relationships noted in the control group were eliminated, i.e. leukocyte count, side of operation, Betapred pretreatment and collateral circulation. CONCLUSIONS: Radical levels can be determined in connection with surgery for carotid artery stenosis using an ex vivo spin trap method. With preoperative antioxidant therapy the relationships between enhanced radical levels and clinical data, as seen in control subjects, disappeared. This might indicate a beneficial effect of preoperative pretreatment with antioxidants.