Improved surgical outcome by modification of porcine dermal collagen implant in abdominal wall reconstruction in rats

AIM: We earlier showed in rats that fascial repair with Pelvicol, a porcine dermal collagen implant, was associated with a lesser inflammatory response but lower tensile strength in the early postoperative period as compared to Prolene. Herein we wanted to evaluate whether creation of pores in Pelvicol, facilitating ingrowth of fibrous tissue and vessels, would result in a higher tensile strength at d30 without compromising longer term results. METHODS: First tensile strength of Pelvicol modified with different pore sizes was evaluated ex vivo. In a second step, Pelvicol implants with pores were used to cover full-thickness abdominal wall defects in 36 rats. Implants were either Pelvicol (non-porous) or with pores of Phi : 0.7, 1.2, or 2.0 mm (n=6 each). Animals were sacrificed on d30 and 90 to evaluate the presence of herniation, infection, adhesions, change in thickness and tensile strength. Histopathology was performed to assess inflammatory response and collagen deposition. Data were compared to available data on Prolene implanted animals at same time points. RESULTS: Pelvicol with pore diameter of 2.5 mm was significantly weaker ex vivo. Animals repaired with non-porous material did develop seroma (2/6) or clinical infection (1/6) whereas none in the other groups did. There was a trend for increasing tensile strength at 30 d with increasing pore diameter, being significant in the 2.0-mm pore size group. This difference disappeared by 90 d, where all materials were equally strong as Prolene. The foreign body reaction was less intense in a pore-size dependent manner, with more abundant neo-vascularization and collagen deposition passing through the pores. CONCLUSION: Creation of pores in Pelvicol promotes neo-vascularization, collagen deposition, and fibrous tissue ingrowth, and at pore size 2.0 mm tensile strength was increased at d30 whereafter all materials had comparable strength.     

Diffusion-weighted MR imaging in monitoring the effect of a vascular targeting agent on rhabdomyosarcoma in rats

PURPOSE: To evaluate diffusion-weighted magnetic resonance (MR) imaging for monitoring tumor response in rats after administration of combretastatin A4 phosphate. MATERIALS AND METHODS: Study protocol was approved by local ethical committee for animal care and use. Rhabdomyosarcomas implanted subcutaneously in both flanks of 17 rats were evaluated with 1.5-T MR unit by using four-channel wrist coil. Transverse T2-weighted fast spin-echo sequences, T1-weighted spin-echo sequences before and after gadodiamide administration, and transverse echo-planar diffusion-weighted MR examinations were performed before, 1 and 6 hours, and 2 and 9 days after intraperitoneal injection of vascular targeting agent (combretastatin A4 phosphate, 25 mg/kg). Apparent diffusion coefficient (ADC) was automatically calculated from diffusion-weighted MR imaging findings. These findings were compared with histopathologic results at each time point. For statistical analysis, paired Student t tests with Bonferroni correction for multiple testing were used. RESULTS: T1-weighted images before combretastatin administration showed enhancement of solid tumor tissue but not of central necrosis. At 1 and 6 hours after combretastatin injection, enhancement of solid tissue disappeared almost completely, with exception of small peripheral rim. At 2 and 9 days after combretastatin injection, enhancement progressively reappeared in tumor periphery. ADC, however, showed decrease early after combretastatin injection ([1.26 +/- 0.16]x 10(-3) mm2/sec before, [1.18 +/- 0.17]x 10(-3) mm2/sec 1 hour after [P=.0005] and [1.08 +/- 0.14]x 10(-3) mm(2)/sec 6 hours after [P=.0007] combretastatin A4 phosphate injection), histologically corresponding to vessel congestion and vascular shutdown in periphery but no necrosis. An increase of ADC ([1.79 +/- 0.13]x 10(-3) mm2/sec) (P <.0001) 2 days after combretastatin A4 phosphate injection was paralleled by progressive histologic necrosis. A significant (P <.0001) decrease in ADC 9 days after treatment ([1.41 +/- 0.15]x 10(-3) mm2/sec) corresponded to tumor regrowth. CONCLUSION: In addition to basic relaxation-weighted MR imaging and postgadolinium T1-weighted MR imaging to enable prompt detection of vascular shutdown, diffusion-weighted MR imaging was used to discriminate between nonperfused but viable and necrotic tumor tissues for early monitoring of therapeutic effects of vascular targeting agent.     

Host response after reconstruction of abdominal wall defects with porcine dermal collagen in a rat model

OBJECTIVE: The purpose of this study was to compare the inflammatory response after implantation of Pelvicol with Prolene in a rat model. STUDY DESIGN: Full-thickness abdominal wall defects were created in 64 Wistar rats, and reconstructed with either Pelvicol or Prolene. Animals were sacrificed on days 7, 14, 30, and 90 to evaluate the presence of herniation, infection, adhesions, and changes in thickness and tensile strength of the implants. Histopathology and immunohistochemistry were performed to evaluate the collagen deposition and the inflammatory response. Statistics were done with unpaired t test and Mann-Whitney rank test. RESULTS: Pelvicol implantation induced infiltration of granulocytes, macrophages, and NK cells, which showed up-regulated expression of surface activation markers ICAM-1 and CD11b. This inflammatory response was significantly milder, and declined faster than in Prolene-implanted rats, and was also associated with fewer adhesions. Moreover, Pelvicol induced a slower, but more orderly collagen deposition, paralleling the surface of the implant. Pelvicol implants showed a slower increase in thickness and tensile strength early on, but this difference disappeared by day 90. CONCLUSION: Pelvicol induces a milder inflammatory response, less adhesion formation, more orderly collagen deposition than Prolene, and reaches a comparable tensile strength only after 90 days.     

Pulmonary effects of gastroschisis in a fetal rabbit model

Respiratory insufficiency is a significant cause of mortality and morbidity among infants with anterior abdominal wall defects (AWD). The aim of this study was to evaluate the pulmonary effects in a fetal rabbit model where gastroschisis was induced at midgestation. Gastroschisis (GAS) was created in 20 rabbit fetuses on day 22 or 23 of gestation (pseudoglandular phase; term = 31-32 days). The amniotic sacs of 13 fetuses were subjected to hysterotomy and amniotomy only (HYST), while 13 underwent a sham laparotomy which was immediately closed by sutures (SHAM). Eleven nonoperated littermates served as internal controls (CTR). Fetuses were harvested by cesarean section on day 31 of gestation prior to respiration. Pulmonary response was evaluated by left lung to body weight ratio (LWBWR), airway morphometry, and density of type II pneumocytes, as evaluated by the number of surfactant protein B-positive cells. Fetuses from the GAS group had significantly lower body weights than did CTR (P = 0.0129). Of these fetuses, 27% were growth-restricted, i.e., with a body weight under the 10th percentile of the CTR population. There were no differences in left lung weight and LWBWR among the GAS and CTR groups. Moreover, the GAS group had similar alveolar size, alveolar wall thickness, and type II cell density as CTR fetuses. Only mean terminal bronchiolar density (MTBD), which is inversely related to the alveolar space, was slightly increased in the GAS group, but without reaching significance (P = 0.0821). No effect on lung growth and maturation could be demonstrated in this study.     

Ischemic preconditioning reduces unloaded myocardial oxygen consumption in an in-vivo sheep model

OBJECTIVE: Ischemic preconditioning (IP) describes the adaptation of the myocardium to ischemic stress preceded by short periods of ischemia and reperfusion. However, its cardioprotective mechanisms are not completely understood. We assessed the effect of IP on ventricular energetics in an in-vivo sheep model. METHODS: IP was performed in six sheep by three 5 min aortic cross-clamping periods interspersed with 5 min of reperfusion during cardiopulmonary bypass and with six sheep as time-matched controls. Global myocardial ischemia was subsequently achieved by 30 min aortic cross-clamping with left ventricular unloading during normothermic cardiopulmonary bypass. Weaning from cardiopulmonary bypass was performed 40 min after reperfusion. At baseline, after treatment (IP or time-matched cardiopulmonary bypass), and up to 100 min after reperfusion, left ventricular pressure-volume loops were measured using a conductance catheter during a right heart bypass preparation. Contractility, diastolic function, and ventriculo-arterial coupling were evaluated. Ventricular energetics [the relation between myocardial oxygen consumption (MVO(2)) and systolic pressure-volume area (PVA)] was also evaluated. A right heart bypass was instituted to control the preload and to decompress the right ventricle completely, thereby eliminating parallel conductance variation and minimizing the contribution of the right ventricle to MVO(2). RESULTS: IP reduced unloaded MVO(2) (PVA-independent MVO(2)). Contractility, diastolic function, and ventriculo-arterial coupling in the IP group were better preserved than in the control group after ischemia-reperfusion. CONCLUSIONS: IP reduces unloaded MVO(2), and preserves contractility, diastolic function, and ventriculo-arterial coupling after 30 min global myocardial ischemia in an in-vivo sheep model.     

Secondary ciliary dyskinesia is absent after ciliogenesis in culture

Ultrastructural secondary ciliary dyskinesia (SCD) was measured using transmission electron microscopy in 301 biopsies and 439 samples after ciliogenesis in the sequential monolayer-suspension culture. Biopsies were taken in the context of exclusion of primary ciliary dyskinesia. SCD was frequently found in the biopsies: only 30% of the samples were normal (SCD < 5%), the mean percentage of SCD abnormalities was 11.9 +/- 12.9%. In 1/8 of the samples severe SCD (> 25%) was present. The most frequently encountered SCD abnormality was the membrane bleb, followed by the various peripheral microtubular abnormalities. With increasing total SCD the absence of the central pair became more important. After ciliogenesis in culture SCD was virtually absent: 1.0 +/- 1.8% for all 439 samples, 96% of the samples were within limits of normality (SCD < 5%). Moderate (15-25%) and severe SCD (> 25%) were never found. In more than 50% of the samples not one abnormality was found. There was no relation between the SCD in the biopsy and that after ciliogenesis. The absence of SCD after ciliogenesis is a major advantage for the diagnosis of PCD, specifically in cases with central pair abnormalities, peripheral microtubular pair abnormalities and those without a primary ultrastructural abnormality.     

Pulmonary toxicity of polyvinyl chloride particles after repeated intratracheal instillations in rats. Elevated CD4/CD8 lymphocyte ratio in bronchoalveolar lavage

Occupational exposure to polyvinyl chloride (PVC) particles has been associated with interstitial lung disease. Our previous study showed that a single intratracheal instillation of emulsion PVC particles, with or without residual additives, induces acute but transient alveolitis in a dose-dependent manner in rats. The aim of the present study was to investigate the pulmonary response after the administration of the same PVC particles (PVC-E3 and PVC-W3) given in the same cumulative doses (10 and 50 mg/kg BW), but fractionated as seven intratracheal instillations (7 x 1.4 and 7 x 7.1 mg/kg BW) in the course of 3 weeks (day 0 to day 21). Pulmonary response was characterized by analysis of lung weight, bronchoalveolar lavage (BAL) fluid for lactate dehydrogenase (LDH), total protein, and cell cytology, and a microscopic evaluation of lung tissue. BAL T lymphocyte phenotypes (CD3 + CD4 +, CD3 + CD8+) were analyzed by flow cytometry. On day 28, lung weights, BAL-LDH, cell numbers in BAL, and CD4/CD8 ratios in BAL T lymphocytes were higher in rats that had received the high dose of PVC-E3 or PVC-W3 than in rats that had received the low dose of PVC particles and control rats. On day 90, the pulmonary response had partially regressed towards control values, but there were still microscopically evident lesions in the lungs and greater CD4/CD8 ratio in the high dose groups. There were significant positive correlations between the CD4/CD8 ratio and a histopathology score of the lung (r = 0.36, P = 0.038 on day 28, and r = 0.46, P = 0.006 on day 90). In conclusion, repeated intratracheal instillations of PVC particles yielded similar results as single instillations. The examined PVC particles have the potential of inducing a limited and transient acute inflammatory reaction in the lung, and possibly a more persistent alteration of pulmonary T lymphocyte subsets towards a high CD4/CD8 ratio.     

Multi-modular bone healing assessment in a randomized controlled clinical trial of root-end surgery with the use of leukocyte- and platelet-rich fibrin and an occlusive membrane

Clinical Oral Investigations - The aim of this study was to assess in a multi-modular manner the bone healing 1&nbsp;year post root-end surgery (RES) with leukocyte- and platelet-rich fibrin...     

Growing bone cysts in long-term hemodialysis

All patients with chronic renal failure undergoing hemodialysis for more than 10 years in the university hospitals of Leuven were selected for this study. The medical records and radiographs of these 21 patients were studied retrospectively. Skeletal surveys were examined for the presence and location of subchondral cysts. The predialysis films and the films taken after 5, 10, 15 and 20 years of dialysis were reviewed. Subchondral cysts that grew in size and number were found in the wrist, humeral head, hip, and patella. Accurate measurements were made of cysts in the wrist and compared with a control group. In the dialysis group, cystic involvement of the wrist was more common and the size and number of the cysts were larger. Soft tissue swelling was seen in the dialysis group but not in controls. Soft tissue swelling was assessed on shoulder radiographs by measuring the acromiohumeral distance (ACD) and in the knees by ultrasonic measurement of synovial thickness [25]. In 11 patients synovial or bone biopsies or aspirated synovial fluid were available. All these patients had swollen joints and multiple subchondral periarticular cysts. Amyloid deposition was found in ten of these patients, and this proved to be composed of B2 microglobulins in seven (Table 1).     

Potential use of FDG-PET scan after induction chemotherapy in surgically staged IIIa-N2 non-small-cell lung cancer: A prospective pilot study

Background: Clearance of viable tumour cells in mediastinal lymph nodes (MLN) by induction chemotherapy (IC) – so-called MLN downstaging – is an important aspect of combined-modality treatment of N2-NSCLC. Reassessment of MLN after IC by CT is far from accurate, while re-mediastinoscopy is often technically difficult. Based on our previous results with FDG-PET in the initial staging of N2 disease, we investigated whether PET after IC could be helpful in predicting MLN downstaging and therapeutic outcome.Patients and methods: Patients underwent a first PET before IC. After three cycles of platinum-based IC, a second PET was performed before locoregional therapy, either surgery or radiotherapy. PET results were correlated with pathology of the MLN when available, and with survival.Results: Fifteen surgically staged N2-NSCLC patients were prospectively included. Locoregional therapy after IC consisted of surgery in nine and radiotherapy in six. Correlation with pathology of the nine resection specimens revealed that the accuracy of PET in predicting MLN downstaging was 100% (six true negatives; three true positives), whereas for CT it was only 67% (two false pos; one false neg). Reassessment with PET after IC was correlated with the outcome after the entire combined modality treatment. Survival was significantly better in patients with mediastinal clearance (P = 0.01) or with a greater than 50% decrease in the Standardised Uptake Value (SUV) of the primary tumour (P = 0.03) after IC.Conclusions: Mediastinal PET after IC accurately assesses pathologic MLN downstaging in N2-NSCLC. The data suggest a possible correlation of early survival with mediastinal clearance and an important decrease of SUV in the primary tumour. Confirmation of these preliminary findings would establish PET as a useful non-invasive tool to select patients for intensive locoregional treatment after IC.