Concomitant Tissue Research Articles

Optimizing Normal Tissue Sparing in Ion Therapy Using Calculated Isoeffective Dose for Ion Selection

To investigate how the selection of ion type affects the calculated isoeffective dose to the surrounding normal tissue as a function of both normal tissue and target tissue α/β ratios. A microdosimetric biologic dose model was incorporated into a Geant4 simulation of parallel opposed beams of protons, helium, lithium, beryllium, carbon, and neon ions. The beams were constructed to give a homogeneous isoeffective dose to a volume in the center of a water phantom for target tissues covering a range of cobalt equivalent α/β ratios of 1-20 Gy. Concomitant normal tissue isoeffective doses in the plateau of the ion beam were then compared for different ions across the range of normal tissue and target tissue radiosensitivities for a fixed isoeffective dose to the target tissue. The ion type yielding the optimal normal tissue sparing was highly dependent on the α/β ratio of both the normal and the target tissue. For carbon ions, the calculated isoeffective dose to normal tissue at a 5-cm depth varied by almost a factor of 5, depending on the α/β ratios of the normal and target tissue. This ranges from a factor of 2 less than the isoeffective dose of a similar proton treatment to a factor of 2 greater. No single ion is optimal for all treatment scenarios. The heavier ions are superior in cases in which the α/β ratio of the target tissue is low and the α/β ratio of normal tissue is high, and protons are superior in the opposite circumstances. Lithium and beryllium appear to offer dose advantages similar to carbon, with a considerably lower normal tissue dose when the α/β ratio in the target tissue is high and the α/β ratio in the normal tissue is low.

Associated risk factors and management of chronic diabetic foot ulcers exceeding 6 months’ duration

BackgroundThe management of chronic diabetic foot ulcers (DFU) poses a great challenge to the treating physician and surgeon. The aim of this study was to identify the risk factors, clinical presentation, and outcomes associated with chronic DFU>6 months’ duration.MethodsThis prospective study was performed in Jabir Abu Eliz Diabetic Centre (JADC), Khartoum, Sudan. A total of 108 patients who had DFU for >6 months were included. Recorded data included patient's demographics, DFU presentation, associated comorbidities, and outcomes. DFU description included size, depth, protective sensation, perfusion, and presence of infection. Comorbidities assessed included eye impairment, renal and heart disease. All patients received necessary local wound care with sharp debridement of any concomitant necrotic and infected tissues and off-loading with appropriate shoe gear and therapeutic devices.ResultsThe mean age of the studied patients was 56+SD 9 years with a male to female ratio of 3:3.3. The mean duration of DFU was 18±SD 17 months (ranging from 6 to 84 months). Ulcer healing was significantly associated with off-loading, mainly the use of total contact cast (TCC) (p=0.013). Non-healing ulcerations were significantly associated with longer duration of the chronic DFU>12 months (p=0.002), smoking (p=0.000), poor glycemic control as evidenced by an elevated HbA1c (>7%), large size (mean SD 8+4 cm), increased depth (p<0.001), presence of skin callus (p<0.000), impaired limb perfusion (p=0.001), impaired protective sensation as measured by 10 g monofilament (p=0.002), neuroischemia (p=0.002), and Charcot neuroarthropathy (p=0.017).DiscussionRisk factors associated with chronic DFU of>6 months’ duration included the presentation of an ulcer with increased size and depth, with associated skin callus and neuroischemia, in a diabetic patient with a history of smoking and increased HbA1c >7%. Off-loading mainly with the use of TCC is an effective method of managing long-standing DFU.

Intraoperative Fluorescence Vascular Angiography: During Tibial Bypass

Preventing amputations in persons with lower extremity complications of diabetes is a complex endeavor, particularly in those with concomitant ischemia and tissue loss. Fluorescence angiography (Novadaq SPY system) may provide a tool for objective evaluations of tissue viability in the diabetic foot, which is an important indicator of the ability of the diabetic ulcer to heal adequately. The SPY system uses a low-power laser coupled with a charge-coupled device camera and indocyanine green (ICG) to sequence perfusion at the surface of the skin. We present an illustrated example of the potential utility of ICG fluorescence angiography (ICGFA) before and after vascular intervention in a high-risk limb. ICGFA appeared to reveal demarcation between viable and nonviable tissue and real-time perfusion, specifically capillary fill. ICGFA clarified the extent of necessary debridement and provided an immediate indication of improvement in regional perfusion status following revascularization. Future studies involving ICGFA may include pre- and postdebridement and closure perfusion, comparison of tissue perfusion pre- and post-endovascular therapy, and lower extremity flap viability. Future works will also address the consistency of results with ICGFA by analyzing a larger cohort of patients being treated by our unit.

Concomitant Face and Hand Transplantation

Face and hand composite tissue allotransplantations have evolved into a promising subset of reconstructive transplant surgery due to recent advances in immunotherapy. Concomitant composite tissue allotransplantation, which involves a variable combination of facial (myocutaneous versus osteomyocutaneous) and upper extremity (ie, various levels) composite subtypes, has been performed infrequently at this time. In this review, we will describe many reasons as to why this field remains unexplored. Undoubtedly, future investigation is warranted to investigate the potential advantages and disadvantages of using this approach versus a staged manner for alloreconstruction and to identify the complexities of cortical reorganization and rehabilitation in this setting.

Micropapillary Thyroid Carcinoma and Concomitant Ectopic Thyroid Tissue in the Adrenal Gland: Metastasis or Metaplasia?

Ectopic thyroid tissue is a rare finding but has been reported in many thoracic and abdominal locations. It is usually an incidental pathologic finding after an unrelated surgical intervention. When thyroid tissue is found outside the thyroid bed, it is important to rule out thyroid cancer metastasis. We present a case of a 61-year-old African American woman who was incidentally found to have concomitant ectopic thyroid tissue in the adrenal gland and a papillary thyroid microcarcinoma (PTMC) in the right lobe of the thyroid. The concurrent finding of ectopic thyroid tissue and PTMC posed the diagnostic dilemma of whether the extrathyroidal tissue was metastasis or metaplasia, with very different treatment implications. Although many of these incidental micropapillary cancers are indolent, some patients do experience local or distant metastasis. Therefore, it is important to delineate which of these microtumors are likely to metastasize. Some tumor markers and gene mutations have been proposed to help differentiate the more benign tumors from the more aggressive tumors, but there is currently no standard method for determination of metastatic potential. Here we present the seventh known case of ectopic thyroid tissue in the adrenal gland and the first case of concomitant incidental PTMC in the setting of this ectopic tissue finding. Using this case, we discuss the diagnostic and therapeutic challenges faced and propose the use of biomarkers to help determine the metastatic potential of these tumors.

Selective elimination of pathogenic synovial fluid T-cells from Rheumatoid Arthritis and Juvenile Idiopathic Arthritis by targeted activation of Fas-apoptotic signaling

In Rheumatoid Arthritis (RA) and Juvenile Idiopathic Arthritis (JIA) elimination of autoreactive T-cells by FasL/Fas-mediated Activation-Induced Cell Death (AICD) appears to be inhibited resulting in the perpetuation of the inflammatory response and concomitant progressive tissue destruction. Here, we report on a novel strategy that aims to overcome the local inhibition of AICD by using rationally designed recombinant fusion proteins in which sFasL is genetically fused to a T-cell selective targeting domain. The series included sFasL fusion proteins with engineered binding specificity for various T-cell surface-expressed proteins including CD7, CD28, RANKL and CD40L. The proposed mode of action is that selective binding of a given sFasL fusion protein results in its accretion at the cell surface of T-cells only, displaying a surplus of sFasL that is available to reactivate AICD in pathogenic synovial T-cells. Of the series of T-cell targeting FasL fusion proteins a CD7-targeted fusion protein, designated scFvCD7:sFasL, proved to be the most potent, with significant pro-apoptotic activity towards synovial fluid T-cells in all patient samples tested (RA; n=22: JIA; n=6). Treatment with scFvCD7:sFasL induced up to 80% apoptosis in CD3-positive synovial T-cells. Importantly, scFvCD7:sFasL potently activated Fas-signaling in synovial TH1-cells as well as synovial Treg cells, but not in synovial TH2 cells. These findings indicate that scFvCD7:sFasL may be of therapeutic value for the selective elimination of pathogenic synovial T-cells of the TH1 subtype in both RA and JIA.

Effects of dietary starch concentration on the performance of lactating primiparous rabbit does

During the first reproductive cycle rabbit does have a negative energy balance caused by foetal development and the concomitant maternal tissue growth. Many authors suggested to reduce the weight’s loss of the does and the reproductive performance through various feeding strategies (Xiccato, 1996). In particular, the addition of fat to the diet does not improve the energy balance of the does; high levels of starch seem to involve serious risks of diarrhoea in pups...

Incidental Papillary Thyroid Carcinoma in a Patient Presenting With Graves' Hyperthyroidism and Concomitant Obstructive Sequestered Intrathoracic Multinodular Goiter

A previously healthy 27-year-old woman presented with a thyroid goiter, symptoms of thyrotoxicosis, and mild respiratory obstruction. The serum thyroid stimulating hormone (TSH) was suppressed, serum T4 was elevated, and 24-hour radioiodine uptake was elevated at 59%. Thyroid scintigraphy showed intense uptake in an enlarged gland, with a cold nodule on the right, and a large isolated mass in the mediastinum, with very mild uptake. Total thyroidectomy and excision of the mediastinal mass revealed multiple pathologies: Graves disease in the thyroid gland with an incidental papillary thyroid carcinoma, and a benign sequestered intrathoracic multinodular goiter. Thyroid carcinoma can develop in a gland affected by Graves disease, however, the presence of concomitant sequestered intrathoracic thyroid tissue unaffected by Graves disease is highly unusual and has not been previously described. We present the scintigraphic findings, and several theories that could help explain these findings.

Dental implants in patients with rheumatoid arthritis: clinical outcome and peri‐implant findings

Implant prosthodontic treatment outcomes for patients suffering from autoimmune rheumatoid arthritis (RA) with or without concomitant connective tissue diseases (CTD) were evaluated. Thirty-four female patients' (25 isolated RA; nine RA+CTD) implant survival/success rate, peri-implant conditions (marginal bone loss, pocket depth, plaque index, gingiva index and bleeding index) and incidence of prosthodontic maintenance were retrospectively evaluated. Implants evaluated presented a high implant survival (100%) and a 3.5-year success (93.8%) rate during the follow-up programme (mean 47.6 month) without difference between isolated RA (94.6%) and RA and concomitant CTD (92.3%), respectively. In isolated RA, acceptable marginal bone resorption (mean: 2.1 mm; SD: 0.5 mm), pocket depth (mean: 2.8 mm; SD:3.2 mm) and healthy soft-tissue conditions (plaque/bleeding/gingiva index Grade 0 in 80%) were noticed. However, patients with RA+CTD presented increased bone resorption (mean: 3.1 mm; SD: 0.7 mm) and more vulnerable soft-tissue conditions (higher bleeding index) differing significantly to patients with isolated RA (p<0.01). Peri-implant parameters were significantly influenced by the patients' underlying disease (RA, RA+CTD; Kruskal-Wallis test, Jonckheere-Terpstra test). In contrast to isolated RA, in RA patients with concomitant CTD, differences in the peri-implant parameters such as pronounced marginal bone resorption and bleeding may be anticipated and appear to be significantly influenced by the patients' underlying disease.

Face, Upper Extremity, and Concomitant Transplantation: Potential Concerns and Challenges Ahead

From its origination involving successful rat hind-limb allograft studies using cyclosporine, face and upper extremity composite tissue allotransplantation has since developed into an exciting and promising subset of reconstructive transplant surgery. Current surgical technique involving composite tissue allotransplantation has allowed optimal outcomes in patients with massive facial and/or upper extremity defects; however, with its coexisting immunologic barrier, obligatory lifelong immunosuppression commits each patient to a daily risk of transplant-related complications with many unanswered questions. Since 1998, nearly 50 hand transplantations in 40 patients have been performed around the world at various levels ranging from wrist level to shoulder level. However, the risk-to-benefit ratio remains controversial in bilateral versus unilateral transplantation and has yet to be determined. From recent experience, the two most important determinants of the success of each patient's upper extremity transplant are patient compliance and intense rehabilitation. A total of nine face transplants have been performed since 2005. Multiple aesthetic subunits (i.e., nose, lips, eyelids) with or without underlying craniofacial skeletal defects (i.e., maxilla, mandible) have been successfully restored, thereby providing restoration of vital facial functions (i.e., smiling) in an unprecedented manner. As of today, face transplantation carries an estimated 2-year mortality of 20 percent. Concomitant composite tissue allotransplantation, which involves a variable combination of allograft subtypes, has been performed in two of the nine face transplant patients. These have included simultaneous bilateral hand transplants and tongue with mandible. Future study is warranted to investigate the potential advantages and disadvantages of using this approach versus a staged approach for reconstruction.

Concomitant Endothelin‐1 Overexpression in Lung Transplant Donors and Recipients Predicts Primary Graft Dysfunction

Primary graft dysfunction (PGD) causes significant morbidity following lung transplantation (LTX). Mortality is high in PGD and therapeutic strategies are limited. To investigate whether endothelin-1 (ET-1) that mediates increased vascular permeability and edema formation in lung grafts can predict PGD, ET-1 mRNA expression was examined in lung tissue biopsies of 105 donors and recipients obtained shortly before LTX. Serum ET-1 concentration was assessed by ELISA. PGD grade was diagnosed and scored by oxygenation and radiological characteristics according to ISHLT guidelines. PGD grade 3 developed in 11% of patients. ET-1 mRNA expression was significantly increased in both donor (p < 0.0001) and recipient (p = 0.01) developing PGD as compared to no PGD group. Pretransplant ET-1 serum concentrations were elevated in recipients with PGD as compared to no PGD group (p < 0.0001), although serum ET-1 was not different between donors whose grafts developed PGD grades 0-3. In regression analysis, concomitant elevated donor tissue ET-1 and recipient serum ET-1 predicted PGD grade 3. This study indicates that pretransplant ET-1 mRNA overexpression in donors associated with elevated pretransplant serum ET-1 in recipients contribute to PGD development and that their assessment might be beneficial to predict PGD and to identify recipients who could benefit from a targeted ET-1 blockade.

Intravascular tissue reactions induced by various types of bioabsorbable polymeric materials: correlation between the degradation profiles and corresponding tissue reactions

IntroductionSeveral different bioabsorbable polymeric coil materials are currently used with the goal of improving treatment outcomes of endovascular embolization of intracranial aneurysms. However, little is known about the correlation between polymer degradation profiles and concomitant tissue responses in a blood vessel. The authors describe in vitro degradation characteristics of nine different polymeric materials and their corresponding tissue responses induced in rabbit carotid arteries.Methods Mass loss and molecular weight loss of nine commercially available bioabsorbable sutures were evaluated in vitro up to16 weeks. The same nine materials, as well as platinum coils, were implanted into blind-end carotid arteries (n = 44) in rabbits, and their tissue reactions were evaluated histologically 14 days after the implantation.ResultsFive of the nine polymers elicited moderate to strong tissue reactions relative to the remaining materials. While polymer mass loss did not correlate with their histologic findings, polymers that showed a faster rate of molecular weight loss had a tendency to present more active tissue reactions such as strong fibrocellular response around the implanted material with a moderate inflammatory cell infiltration. Maxon exhibited the fastest rate of molecular weight loss and poly-l-lactic acid the slowest.ConclusionsThe rate of molecular weight loss may be an important factor that is associated with the degree of bioactivity when bioabsorbable polymers are implanted into blood vessels. For further quantitative analysis, additional experiments utilizing established aneurysm models need to be conducted.

A nonlinear biphasic model of flow-controlled infusion in brain: Fluid transport and tissue deformation analyses

A biphasic nonlinear mathematical model is proposed for the concomitant fluid transport and tissue deformation that occurs during constant flow rate infusions into brain tissue. The model takes into account material and geometrical nonlinearities, a hydraulic conductivity dependent on strain, and nonlinear boundary conditions at the infusion cavity. The biphasic equations were implemented in a custom written code assuming spherical symmetry and using an updated Lagrangian finite element algorithm. Results of the model showed that both, geometric and material nonlinearities play an important role in the physics of infusions, yielding important differences from infinitesimal analyses. Geometrical nonlinearities were mainly due to the significant enlargement of the infusion cavity, while variations of the parameters that describe the degree of nonlinearity of the stress–strain curve yielded significant differences in all distributions. For example, a parameter set showing stiffening under tension yielded maximum values of radial displacement and porosity not localized at the infusion cavity. On the other hand, a parameter set showing softening under tension yielded a slight decrease in the fluid velocity for a three-fold increase in the flow rate, which can be explained by the substantial increase of the infusion cavity, not considered in linear analyses. This study strongly suggests that significant enlargement of the infusion cavity is a real phenomenon during infusions that may produce collateral damage to brain tissue. Our results indicate that more experimental tests have to be undertaken in order to determine material nonlinearities of brain tissue over a range of strains. With better understanding of these nonlinear effects, clinicians may be able to develop protocols that can minimize the damage to surrounding tissue.

Penis covering and simultaneous urethral replacement by scrotal skin for severe penile and urethral necrosis

Penile strangulation with severe necrosis and concomitant significant tissue loss is a challenging problem for reconstructive surgery. Final reconstruction and tissue augmentation of the resected penis often require multi-step plastic reconstruction. Severe damage of the phallus with gangrene and septic complication caused by a bronze ring were first conservatively treated to achieve dry gangrene. The glans of the penis, the whole penile skin, and distal third of the corpus spongiosum with the urethra were lost to necrosis, resulting in a missing urethral segment on the penis. Surgery was performed 3 months after removing the metal ring; a one-step skin and urethral reconstruction was done. Good functional and esthetic results could be achieved by mid-term follow-up. In long-lasting penile strangulation with damaged blood supply, further surgery and treatment are needed in addition to immediate decompression. Most commonly in these situations, amputation seems to be the best and easiest action to be taken. However, our case shows that even in a most severe situation, careful conservative treatment allows preserving the phallus, and subsequently reconstruction enables reaching the best functional and esthetic results.

Intracorporeal electrokinetic lithotripsy: an advancement in minimally invasive management of parotid duct calculus

Symptomatic salivary stones in the middle or proximal parotid duct have previously been treated by gland excision, which is associated with a 3-7 per cent risk to the facial nerve. Minimally invasive approaches to the management of salivary duct calculi have been devised over the past decade. Fluoroscopically guided basket retrieval, lithotripsy and intra-oral stone removal under general anaesthesia have found favour with most surgeons. Endoscopically controlled intracorporeal shock wave lithotripsy using the pneumoblastic lithotripter has been replaced by electrohydraulic lithotripsy (used in sialolith treatment). The electrokinetic lithotripter is normally used for the treatment of lower ureteric stones, and has the benefit of minimal concomitant tissue damage. We have extended its use to the treatment of parotid duct calculi. We present initial results for its use in the treatment of a proximal parotid duct stone. Application of the shock wave to the stone under direct vision avoided injury to the duct or to any local structure. The patient made an uneventful recovery and was asymptomatic after 18 months' follow up. Continuous, endoscopically monitored electrokinetic lithotripsy with good irrigation gives a well illuminated field and absolute delivery of energy to the target. It avoids the side effects caused by impact of the shock wave on the parotid duct and adjacent anatomical structures, thereby making it a safer procedure.

Combined Single-Stage Osseous and Soft Tissue Reconstruction of the Tibia With the Ilizarov Method and Tissue Transfer

To determine the outcome of single-stage soft tissue and osseous reconstruction using the Ilizarov method and soft-tissue transfer. A retrospective review. : A university-affiliated, tertiary-care center. We identified 11 patients from a retrospective review from January 1994 to July 1999 who underwent single-stage soft tissue and osseous reconstruction using the Ilizarov method. All 11 patients had an initial traumatic mechanism to their tibia and had previous operative intervention before the combined procedure. The Ilizarov procedure was performed for infected tibial nonunion (8 cases), or complex fracture with soft-tissue loss (3 cases). Soft tissue transplant survival, union, range of motion, leg length discrepancy, the Association for the Study and Application of the Method of Ilizarov (ASAMI) score, radiographic parameters. There were 8 concomitant free tissue flaps and 3 local pedicled flaps. Two patients had primary bone grafting, and 5 others had addition of an antibiotic impregnated bone substitute. There were 8 cases of elective reconstructive surgery and 3 cases of acute traumatic fracture. The mean duration of Ilizarov application was 26 weeks (range, 7 to 42). Eight tibiae united primarily, and 3 healed after delayed bone grafting. There were 2 major flap complications. Both were successfully managed with repeat surgery. One patient sustained a repeat open fracture and subsequently received an amputation. According to the ASAMI score, there were 9 excellent results, 1 good result, and 1 poor result. Our study suggests that concomitant osseous and soft-tissue reconstruction with the Ilizarov technique and free or pedicled flaps is a viable option for patients with composite tissue defects.

Mortality in Patients With Pelvic Fractures: Results From the German Pelvic Injury Register

Pelvic and acetabular fractures are rare injuries and account for approximately 3% to 8% of all fractures. Often the result of high energy blunt trauma, most of the patients sustaining pelvic injuries are at high risk of associated injuries strongly influencing outcome and survival rates. Because of anatomic differences it has been suggested that pediatric pelvic fractures are different injuries as compared with that of adults. However, this has been controversially discussed. Aim of this multicenter register study was to identify similarities and differences between pediatric and adult pelvic trauma and evaluate the influence of changes in medical treatment by comparison of two treatment periods. In this multicenter register study, data of 4,291 patients treated from 1991 to 1993 (n = 1,723) or 1998 to 2000 (n = 2,568) for pelvic fractures in one of the 23 participating hospitals were evaluated for age, gender, Injury Severity Score (ISS), Hannover Polytrauma Score (PTS), fracture type (using Tile's classification), peripelvic soft tissue injury, need for emergency measures, mortality, cause of death, and need for operative stabilization. We compared the patients' characteristics of the two treatment periods and pediatric with adult pelvic injuries. Statistical analysis was performed using SAS software. There was no difference in terms of ISS, PTS, and presence of peripelvic soft tissue injuries between the two observation periods. Mortality rate dropped significantly from 7.9% to 5% (p < 0.0001) in the latter treatment period. Death was directly attributed to the pelvic injury in 11% from 1991 to 1993. This rate dropped significantly to 7% in the period from 1998 to 2000 (p = 0.020). A type fractures decreased from 61.1% (1991-1993) to 57.1% (1998-2000) of patients (p = 0.028) and except for these simple fractures there was a significant overall trend toward surgical treatment. Multivariate analysis revealed ISS, PTS, concomitant soft tissue injuries, and need for emergency measures as independent risk factors for death whereas surgical stabilization and treatment in the latter treatment period were associated with an increased survival rate. We found no difference between the adult and the pediatric group in terms of ISS and concomitant peripelvic soft tissue injuries. Children were less likely to receive surgical treatment (19.4% vs. 34.5%, p < 0.0001) but requirement for emergency measures was higher in the pediatric group (17.9% vs. 11.1%, p = 0.033). Moreover, we found no significant differences in mortality between both groups (6.1% vs. 8.2%, p = 0.28). Multivariate analysis showed age </=15 years was not an independent risk factor for death. The survival rate of patients sustaining pelvic fracture has improved significantly within the last decade. Most deaths in patients with pelvic fractures are not caused by the pelvic fracture itself but are linked to associated injuries. Despite anatomic and epidemiologic differences there are significant similarities between pediatric and adult patients with pelvic injuries and the mortality rate of children is not different from that of adults.

Physiology-Based Simulations of a Pathological Condition

Liver cirrhosis is a progressive disease characterized by loss of functional hepatocytes with concomitant connective tissue and nodule formation in the liver. The morphological and physiological changes associated with the disease substantially affect drug pharmacokinetics. Whole-body physiologically based pharmacokinetic (WB-PBPK) modelling is a predictive technique that quantitatively relates the pharmacokinetic parameters of a drug to such (patho-)physiological conditions. To extend an existing WB-PBPK model, based on the physiological changes associated with liver cirrhosis, which allows for prediction of drug pharmacokinetics in patients with liver cirrhosis. The literature was searched for quantitative measures of the physiological changes associated with the presence of Child-Pugh class A through C liver cirrhosis. The parameters that were included were the organ blood flows, cardiac index, plasma binding protein concentrations, haematocrit, functional liver volume, hepatic enzymatic activity and glomerular filtration rate. Predictions of pharmacokinetic profiles and parameters were compared with literature data for the model compounds alfentanil, lidocaine (lignocaine), theophylline and levetiracetam. The predicted versus observed plasma concentration-time profiles for alfentanil and lidocaine were similar, such that the pharmacokinetic changes associated with Child-Pugh class A, B and C liver cirrhosis were adequately described. The theophylline elimination half-life was greatly increased in Child-Pugh class B and C patients compared with controls, as predicted by the model. Levetiracetam urinary excretion was consistently reduced with disease progression and very closely resembled observed values. Consideration of the physiological differences between healthy individuals and patients with liver cirrhosis was important for the simulation of drug pharmacokinetics in this compromised group. The WB-PBPK model was altered to incorporate these physiological differences with the result of adequate simulation of drug pharmacokinetics. The information provided in this study will allow other researchers to further validate this liver cirrhosis model within a WB-PBPK model.

Laparoscopic Repair of Rectourethral Fistulas After Prostate Surgery

To present our experience with laparoscopic rectourinary fistula (RUF) repair. RUF is a rare entity that can develop after ablative or extirpative prostate surgery. Successful management often requires an aggressive approach. Several techniques have been described for surgical correction. From October 2004 to October 2005, 3 patients were treated for RUF. The mean age was 63 years (range 58 to 68). RUF developed after open simple prostatectomy, open radical prostatectomy, and transurethral prostate resection. The operative steps were dependent on the location of the fistulous tract (bladder-prostate-urethra). When the fistula involved the prostatic capsule, the technique included capsulectomy and urethrovesical anastomosis. When the bladder was involved, a transvesical approach was used, involving dissection of the fistulous tract, closure of the rectum, tissue interposition, and bladder closure. The mean operative time was 247 minutes (range 230 to 270). The mean hospital stay was 2.6 days (range 2 to 3). No complications occurred. At a mean follow-up of 12 months (range 7 to 19), all patients were free of fistula recurrence. Laparoscopic repair of RUF is feasible and represents an attractive alternative to the standard approaches. The laparoscopic technique facilitates concomitant colostomy and tissue interposition without the need for patient repositioning or an additional incision.

Radial nerve repair using an autologous denatured muscle graft: comparison with outcomes of nerve graft repair

The efficiency of denatured muscle grafting in nerve repair has been confirmed in experimental models and animals. The first clinical trials to repair digital nerves and mixed sensory-motor nerves were encouraging regarding sensory recovery but motor recovery was poor, probably because of delayed repair. We present the functional outcome of repair of motor nerves using denatured muscle graft and compare the results with those using standard nerve graft techniques. This prospective study included 9 radial nerve defects repaired with denatured muscle grafts and 23 radial nerve defects repaired using nerve grafts. Missile induced nerve injury, mid-arm level of lesion, a nerve gap smaller than 6 cm, and a preoperative interval of less than 5 months were characteristics shared by all patients. None of the patients had concomitant vascular injury, severe scarring, or significant soft tissue damage in the region of nerve repair. Motor recovery was estimated with 0-5 points, at least 4.7 years after surgery, according to the BMRC scale. A successful outcome (>or=M3) was achieved in 7 out of the 9 patients treated using a muscle graft and in 21 out of the 23 patients treated using nerve grafts (P > 0.05). Excellent recovery and the clinically significant re-establishment of thumb extension (M5 grade) were never achieved in the patients treated using muscle grafts. The average motor score was significantly better in patients treated with nerve grafts than in those who received muscle grafts (3.8 +/- 0.9 and 3.2 +/- 0.8; P = 0.035). With the patients who received muscle grafts, an inverse correlation existed between motor recovery and the length of the nerve gap (P = 0.017). Denatured muscle grafts can be useful for bridging short radial nerve defects, but the quality of recovery is significantly worse than after nerve graft repair. Even if relatively short nerve defects are bridged with denatured muscle grafts, the outcomes correlate inversely with the length of the gap.