Selective nonoperative versus operative management of liver gunshot injuries: a retrospective cohort study.

INTRODUCTION: Experience accumulated over the last decades suggests nonoperative management (NOM) of civilian gunshot liver injuries can be safely applied in selected cases. This study aims to compare the outcomes of selective NOM versus operative management (OM) of patients sustaining gunshot wounds (GSW) to the liver. METHODS: A registry-based retrospective cohort analysis was performed for the period of 2008 to 2016 in a Brazilian trauma referral. Patients aged 16-80 years sustaining civilian GSW to right-sided abdominal quadrants and liver injury were included. Baseline data, vital signs, grade of liver injury, associated injuries, injury severity scores, blood transfusion requirements, liver- and non-liver-related complications, length-of-stay (LOS), and mortality were retrieved from individual registries. RESULTS: A total of 54 patients were eligible for analysis, of which 37 underwent NOM and 17 underwent OM. The median age was 25 years and all were male. No statistically significant differences were observed between groups regarding patients' demographics, injury scores, grade of liver injury and associated lesions. NOM patients tended to sustain higher-grade injuries (86.5% vs 64.7%; p = 0.08), and failure of conservative management was recorded in two (5.4%) cases. The rate of complications was 48% with no between-group statistically significant difference. Blood transfusion requirements were significantly higher in the OM group (58.8% vs 21.6%; p = 0.012). The median LOS was seven days. No deaths were recorded. CONCLUSION: Patients with liver GSW who are haemodynamically stable and without peritonitis are candidates for NOM. In this study, NOM was safe and effective even in high-grade injuries.

Tunable four-wave mixing enabled by a self-phase modulation of chirped pulses.

We experimentally demonstrate how a concatenation of the standard and microstructure fiber segments permits adjusting the four-wave mixing sideband position over a large spectral range by varying the chirp of an input pulsed pump at a fixed wavelength in the presence of a self-phase modulation. The blue- and redshifted sidebands can stand aside over ∼200 nm and ∼450 nm from the pump, respectively, which agrees well with the numerical simulations. We validate our approach by showing the feasibility of CARS imaging.

Recycling food waste to clean water: the use of a biodigester's residual liquid inoculum (RLI) to decolourise textile azo dyes.

A residual liquid inoculum (RLI) was used to decolourise solutions of Acid Yellow 25 (AY25) and Direct Violet 51 (DV51) azo dyes. The RLI was obtained through anaerobic digestion of food waste from a university restaurant. The concentration of bacteria in the RLI was 8.45 × 107 CFU mL-1. Dye solutions (50 µg mL-1) were inoculated with the RLI (20% v/v) and incubated at room temperature. The decolourisation studies took place at microaerophilic and in-batch conditions and at pH = 2.50. Initially, the dyes were taken up from solution by biosorption; maximum colour removal was achieved after 3 hours of incubation, with 88.66% for AY25 and 77.65% of DV51. At prolonged incubation times (3-96 hours) decolourisation was mainly attributed to biodegradation of the azo solutions, with breakage of the azo bond, as detected by UV-VIS spectroscopy and Fourier transform infrared (FT-IR) analysis. Analysis of UV-VIS absorption rates of dyes showed, however, that AY25 was more readily biodegradable whereas DV51 was more recalcitrant to the action of the RLI.

Multi-institutional competing risks analysis of distant brain failure and salvage patterns after upfront radiosurgery without whole brain radiotherapy for brain metastasis.

Background: In this study, we use a competing risks analysis to assess factors predictive of early-salvage whole brain radiotherapy (WBRT) and early death after upfront stereotactic radiosurgery (SRS) alone for brain metastases in an attempt to identify populations that benefit less from upfront SRS. Patients and methods: Patients from eight academic centers were treated with SRS for brain metastasis. Competing risks analysis was carried out for distant brain failure (DBF) versus death prior to DBF as well as for salvage SRS versus salvage WBRT versus death prior to salvage. Linear regression was used to determine predictors of the number of brain metastases at initial DBF (nDBF). Results: A total of 2657 patients were treated with upfront SRS alone. Multivariate analysis (MVA) identified an increased hazard of DBF associated with increasing number of brain metastases (P < 0.001), lowest SRS dose received (P < 0.001), and melanoma histology (P < 0.001), while there was a decreased hazard of DBF associated with increasing age (P < 0.001), KPS < 70 (P < 0.001), and progressive systemic disease (P = 0.004). MVA for first salvage SRS versus WBRT versus death prior to salvage revealed an increased hazard of first salvage WBRT seen with increasing number of brain metastases (P < 0.001) and a decreased hazard with widespread systemic disease (P = 0.002) and increasing age (P < 0.001). Variables associated with nDBF included age (P = 0.02), systemic disease status (P = 0.03), melanoma histology (P = 0.05), and initial number of brain metastases (P < 0.001). Conclusions: Patients with a higher initial number of brain metastases were more likely to experience DBF, have a higher nDBF, and receive early-salvage WBRT, while patients who were older, had lower KPS, or had more systemic disease were more likely to experience death prior to DBF or salvage WBRT.

The effect of microscopic margin status on survival in adult retroperitoneal soft tissue sarcomas.

INTRODUCTION: Resection is the primary treatment for retroperitoneal (RP) soft tissue sarcomas (STS). Whether obtaining microscopically negative margins (R0) improves overall survival (OS) over microscopically positive margins (R1) remains unclear. METHODS: Using the National Cancer Data Base, we identified adult patients diagnosed with RP STS after R0 or R1 resection from 1998 to 2011. We used a multivariable logistic regression model to identify clinicopathologic factors associated with margin status, including radiotherapy receipt. To assess differences in OS, the log-rank test, Cox proportional hazards regression, and propensity score matching were used. RESULTS: We identified 4015 patients; 2593 (64.6%) underwent R0 resection and 1422 (35.4%) underwent R1 resection. The most common histology was liposarcoma (2,371, 59.1%), median age was 60 years, and median follow up was 67 months. Median OS for R0 vs. R1 patients was 92 and 70 months, respectively (log-rank p < .001). Pre-operative RT was associated with increased probability of R0 resection (68.0% vs. 57.2%, p = .012). Multivariable regression showed R0 vs. R1 resection (HR 0.70, 95% CI 0.60-0.81, p < .001) was associated with improved survival, a finding confirmed on propensity score matching. Other significant predictors of OS included low tumor grade, younger age, smaller tumor size, liposarcoma histology, and receipt of RT (HR 0.81, 95% CI 0.70-0.93, p = .016). CONCLUSIONS: Patients who undergo R0 resection for RP STS appear to experience superior OS compared with patients who had R1 resections.

[Nutritional and Functional assessment of peritoneal dialysis patients in the clinical practice: Report from MITO-DP Group]. / Valutazione Nutrizionale e Funzionale dei pazienti in dialisi peritoneale nella pratica clinica: l'esperienza del Gruppo Medico-Infermieristico Toscano di Dialisi Peritoneale (M.I.TO.-DP).

Nutritional abnormalities and physical inactivity are risk factors of increased morbidity and mortality in patients with ESRD. Identify and define malnutrition, in particular protein-energy depletion (PEW), is an important task in the management of renal patients. The aim of this multicenter observational study was to implement the assessment of nutritional status and functional capacity in patients on peritoneal dialysis, including tests and validated methods which are relatively easy to apply in daily clinical practice. The study includes all the 133 prevalent patients (80 m, 53 f, age 65 14 years), in peritoneal dialysis treatment (vintage 26 19 months) in 9 centers in Tuscany. We performed anthropometry, bioimpedance (BIA), clinical biochemistry, evaluation of habitual physical activity (RAPA tests) and performance (Sit-To-Stand test), appetite-evaluation questionnaire, and indices including the Malnutrition Inflammation Score (MIS), Geriatric Nutrition Risk Index (GNRI), Charlson comorbidity index, Barthel and Karnowsky index. The latter showed a condition of dependence in 7.2% and 19.7% of cases, respectively. Poor appetite was recorded in 48.2%. The majority of patients fell within the overweight / obesity range (51%) with waist circumference values associated with increased cardiovascular risk in 51% of males and 60% of females. At the BIA analysis, a BCMI <8 kg/m2 was detected in 39% of patients; an estimated protein intake <1.0 g / kg/d was found in 59% of cases; 34% of patients had serum albumin <3.5 g / dl; control of acidosis was good (bicarbonate 25.4 3.8 mM) but hyperphosphatemia was present in 64.6% of patients. A condition of sedentary or light physical activity was reported by 65.1% of patients, vigorous activity only by 11.9%. The 86.5% of patients able to perform the Sit-to-stand test reported a lower than the reference values for age and sex. A diagnosis of PEW was possible in 8% of our series, while a MIS score> 11, indicative of PEW, took place in 12.7% of cases. The values of the MIS correlated directly with age and the degree of comorbidity and inversely with the sit-to-stand test, RAPA tests and appetite level. The data in this study show that single tests indicative of malnutrition disorders are frequent to be found in our series of peritoneal dialysis patients. However, a diagnosis of PEW is quite infrequent. A large percentage of patients are overweight with increased abdominal adiposity, and reduced cell mass and protein intake below recommended levels; the level of habitual physical activity is low, and the level of physical capability is scarce. Therefore it is conceivable a nutritional counseling intervention to increase the intake of proteins, limiting the phosphorus and (when indicated) energy intake and to stimulating spontaneous physical activity or arranging assisted programs for functional rehabilitation. Close monitoring of the nutritional status and implementation of programs of adapted physical activity should have a prominent role in the clinical management of patients on peritoneal dialysis.

Comparative study of toxicity of azo dye Procion Red MX-5B following biosorption and biodegradation treatments with the fungi Aspergillus niger and Aspergillus terreus.

Azo dyes are an important class of environmental contaminants and are characterized by the presence of one or more azo bonds (-N=N-) in their molecular structure. Effluents containing these compounds resist many types of treatments due to their molecular complexity. Therefore, alternative treatments, such as biosorption and biodegradation, have been widely studied to solve the problems caused by these substances, such as their harmful effects on the environment and organisms. The aim of the present study was to evaluate biosorption and biodegradation of the azo dye Procion Red MX-5B in solutions with the filamentous fungi Aspergillus niger and Aspergillus terreus. Decolorization tests were performed, followed by acute toxicity tests using Lactuca sativa seeds and Artemia salina larvae. Thirty percent dye removal of the solutions was achieved after 3 h of biosorption. UV-Vis spectroscopy revealed that removal of the dye molecules occurred without major molecular changes. The acute toxicity tests confirmed lack of molecular degradation following biosorption with A. niger, as toxicity to L. sativa seed reduced from 5% to 0%. For A. salina larvae, the solutions were nontoxic before and after treatment. In the biodegradation study with the fungus A. terreus, UV-Vis and FTIR spectroscopy revealed molecular degradation and the formation of secondary metabolites, such as primary and secondary amines. The biodegradation of the dye molecules was evaluated after 24, 240 and 336 h of treatment. The fungal biomass demonstrated considerable affinity for Procion Red MX-5B, achieving approximately 100% decolorization of the solutions by the end of treatment. However, the solutions resulting from this treatment exhibited a significant increase in toxicity, inhibiting the growth of L. sativa seeds by 43% and leading to a 100% mortality rate among the A. salina larvae. Based on the present findings, biodegradation was effective in the decolorization of the samples, but generated toxic metabolites, while biosorption was effective in both decolorization and reducing the toxicity of the solutions.

Total thyroidectomy versus hemithyroidectomy for patients with follicular neoplasm. A cost-utility analysis.

INTRODUCTION: Thyroid nodules are a common condition. Overall, 20% of the nodules assessed with FNAB correspond to the follicular pattern. A partial thyroidectomy is the minimal procedure that should be performed to determine the nature of these nodules. Some authors have suggested performing a total thyroidectomy based on the elimination of reoperation and ultrasound follow-up. The aim of this study was to evaluate the most cost-useful surgical strategy in a patient with an undetermined nodule, assessing complications, reoperation, recurrence and costs. MATERIAL AND METHODS: A cost-utility study was designed to compare hemithyroidectomy and total thyroidectomy. The outcomes were complications (definitive RLN palsy, permanent hypoparathyroidism, reoperation for cancer, and recurrence of the disease), direct costs and utility. We used the payer perspective at 5 years. A deterministic and probabilistic sensitivity analysis was completed. RESULTS: In a deterministic analysis, the cost, utility and cost-utility ratio was COP $12.981.801, 44.5 and COP $291.310 for total thyroidectomy and COP $14.309.889, 42.0 and $340.044 for partial thyroidectomy, respectively. The incremental cost-utility ratio was -$535.302 favoring total thyroidectomy. Partial thyroidectomy was more cost-effective when the risks of RLN injury and definitive hypoparathyroidism were greater than 8% and 9% in total thyroidectomy, respectively. In total, 46.8% of the simulations for partial thyroidectomy were located in the quadrant of more costly and less effective. CONCLUSION: Under a common range of complications, and considering the patient's preference and costs, total thyroidectomy should be selected as the most cost-effective treatment for patients with thyroid nodules and follicular patterns.

Acid Black 48 dye biosorption using Saccharomyces cerevisiae immobilized with treated sugarcane bagasse.

The textile industry consumes large quantities of water and chemicals, especially in dyeing and finishing processes. Textile dye adsorption can be accomplished with natural or synthetic compounds. Cell immobilization using biomaterials allows the reduction of toxicity and mechanical resistance and opens spaces within the matrix for cell growth. The use of natural materials, such as sugarcane bagasse, is promising due to the low costs involved. The aim of the present study was to evaluate the use of sugarcane bagasse treated with either polyethyleneimine (PEI), NaOH or distilled water in the cell immobilization of Saccharomyces cerevisiae for textile dye removal. Three different adsorption tests were conducted: treated sugarcane bagasse alone, free yeast cells and bagasse-immobilized yeast cells. Yeast immobilization was 31.34% with PEI-treated bagasse, 8.56% with distilled water and 22.54% with NaOH. PEI-treated bagasse exhibited the best removal rates of the dye at all pH values studied (2.50, 4.50 and 6.50). The best Acid Black 48 adsorption rates were obtained with use of free yeast cells. At pH 2.50, 1 mg of free yeast cells was able to remove 5488.49 g of the dye. The lowest adsorption capacity rates were obtained using treated bagasse alone. However, the use of bagasse-immobilized cells increased adsorption efficiency from 20 to 40%. The use of immobilized cells in textile dye removal is very attractive due to adsorbed dye precipitation, which eliminates the industrial need for centrifugation processes. Dye adsorption using only yeast cells or sugarcane bagasse requires separation methods.

Bioremediation of direct dyes in simulated textile effluents by a paramorphogenic form of Aspergillus oryzae.

Azo dyes are extensively used for coloring textiles, paper, food, leather, drinks, pharmaceutical products, cosmetics and inks. The textile industry consumes the largest amount of azo dyes, and it is estimated that approximately 10-15% of dyes used for coloring textiles may be lost in waste streams. Almost all azo dyes are synthetic and resist biodegradation, however, they can readily be reduced by a number of chemical and biological reducing systems. Biological treatment has advantages over physical and chemical methods due to lower costs and minimal environmental effect. This research focuses on the utilization of Aspergillus oryzae to remove some types of azo dyes from aqueous solutions. The fungus, physically induced in its paramorphogenic form (called 'pellets'), was used in the dye biosorption studies with both non-autoclaved and autoclaved hyphae, at different pH values. The goals were the removal of dyes by biosorption and the decrease of their toxicity. The dyes used were Direct Red 23 and Direct Violet 51. Their spectral stability (325-700 nm) was analyzed at different pH values (2.50, 4.50 and 6.50). The best biosorptive pH value and the toxicity limit, (which is given by the lethal concentration (LC(100)), were then determined. Each dye showed the same spectrum at different pH values. The best biosorptive pH was 2.50, for both non- autoclaved and autoclaved hyphae of A. oryzae. The toxicity level of the dyes was determined using the Trimmed Spearman-Karber Method, with Daphnia similis in all bioassays. The Direct Violet 51 (LC(100) 400 mg · mL(-1)) was found to be the most toxic dye, followed by the Direct Red 23 (LC(100) 900 mg · mL(-1)). The toxicity bioassays for each dye have shown that it is possible to decrease the toxicity level to zero by adding a small quantity of biomass from A. oryzae in its paramorphogenic form. The autoclaved biomass had a higher biosorptive capacity for the dye than the non-autoclaved biomass. The results show that bioremediation occurs with A. oryzae in its paramorphogenic form, and it can be used as a biosorptive substrate for treatment of industrial waste water containing azo dyes.

Perfusional evaluation of postesophagectomy gastroplasty with a radioisotopic study.

SUMMARY: Anastomotic fistula represents one of the frequent causes of postoperative morbidity and mortality following transhiatal esophageal resections. The main etiological factor is the ischemia of the gastric tube created for digestive transit reconstruction. Evidence suggests that per operative hypoperfusion can be maintained or even impaired after the surgery. Several methods have been employed in an attempt to assess the blood perfusion of the gastric flap, but they all pose limitations. However, there is a chronological relationship between perfusion assessments, which are almost exclusively performed per operatively, and the occurrence of a leak, which commonly appears several days after the surgery. The authors have developed a method of gastric perfusion evaluation by single photon emission computed tomography scintigraphy, which corrects that temporal matter, allowing the estimation of postoperative gastric perfusion. It is noninvasive, low cost, and may be applied by the time frame when most fistulas occur. High correlation between the event fistula and the low radiotracer uptake in the group of studied patients could be demonstrated. A role in the research of perfusion evaluation of different types of esophageal reconstruction is suggested.

[Dialysis and quality of life: identifying and managing critical aspects]. / Terapia dialitica e qualitá di vita: individuare le aree di criticitá per orientare alla metodica più idonea.

Living with a chronic disease is for the patient a ''disease experience'' that also affects the psychosocial sphere and has a negative impact on perceived quality of life. To estimate the effect of dialysis on the perceived quality of life and to identify by means of a specific questionnaire the aspects that are compromised most. From our results it emerged that the examined patients had a sufficiently good total perception of quality of life, even though about 30% of the patients reported critical aspects related to daily life and, in some age groups, also related to dialysis method. This study confirms the importance of developing educational and supportive predialysis programs in order to identify and reduce the critical aspects.

Retroesophageal right subclavian artery: a case report and a review of literature

We report a case of a rare anatomical anomalyof the retroesophageal right subclavian artery (RRSA) post-mortem. The subclavian arteries may vary in their origin, course or length. The right retroesophageal subclavian artery is a frequent defect of the embryological aortic arches. This variation is due to interruption of the fourth right aortic arch betweenthe notches for the common carotid artery andthe subclavian artery while the left fourth archremains intact. A regression of proximal portionof the right subclavian artery occurs and the retroesophageal aortic arch persists (AU)

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Gastric pH, sevelamer hydrochloride and omeprazole.

AIMS: Sevelamer hydrochloride is a polymer containing multiple amines (40% amine hydrochloride) separated by one carbon from the polymer backbone, and it is not absorbed by the intestine. These amines are partially protonated and interact with phosphate molecules through ionic and hydrogen bonding, therefore reducing phosphate absorption and lowering serum phosphate concentration. Alterations of gastric pH, in particular excessive alkalinization, could interfere with sevelamer phosphate binding capacity. CASE HISTORY: A 30-year-old dialysis patient affected by secondary hyperparathyroidism started sevelamer treatment, 4.8 g/day, with a basal serum phosphate of 6.9 mg/dl. The patient was also treated with omeprazole (20 mg/day) because of chronic gastritis. Phosphate levels normalized (4.2 mg/dl), but after four months of follow-up serum phosphate unexpectedly increased to 7.2 mg/dl. We found out that in the same period she had autonomously increased the dosage of omeprazole to 80 mg/day, due to worsening of dyspepsia. Gastric pH measurement showed a median level of 4.1, rather than the normal values of 1 - 2, indicating excessive pharmacological alkalinization. When omeprazole was reduced to the correct dose of 20 mg/day, we observed a rapid decrease of phosphate levels. CONCLUSION: This case report highlights the influence of gastric pH on sevelamer phosphate binding capacity. The high dose of omeprazole and the consequent excessive increase in gastric pH was probably responsible for a decreased phosphate binding capacity of sevelamer. When patients taking appropriate doses of sevelamer do not respond to treatment, a potential interaction with drugs determining an increase of gastric pH should be considered.

Molecular cytogenetic insights into the ageing syndrome Hutchinson-Gilford Progeria (HGPS).

Hutchinson-Gilford Progeria Syndrome (HGPS) is an extremely rare genetic disorder characterized by premature ageing in childhood and serves as a valuable model for the human ageing process in general. Most recently, point mutations in the lamin A (LMNA) gene on chromosome 1q have been associated with the disease, however how these mutations relate to the complex phenotype of HGPS remains to be established. It has been shown that fibroblasts from HGPS patients are frequently resistant to immortalization with telomerase (hTERT), consistent with the idea that the loss of a dominant acting HGPS gene is a pre-requisite for immortalization. In this study we report the first detailed cytogenetic analysis of hTERT-immortalised HGPS cell lines from three patients and one corresponding primary fibroblast culture. Our results provide evidence for a cytogenetic mosaicism in HGPS with a distinctive pattern of chromosome aberrations in all the HGP clones. Chromosome 11 alterations were observed at a high frequency in each immortalised HGPS cell line but were also present at a lower frequency in the corresponding primary cells. Moreover, we were able to identify the 11q13-->q23 region as a potential site of breakage. Our results are therefore consistent with a role of chromosome 11 alterations in the escape from senescence observed in HGPS cells. In addition to this defined rearrangement, we consistently observed complex chromosomal rearrangements, suggesting that HGPS displays features of chromosomal instability.

Oxidative stress, hepatocellular integrity, and hepatic function after initial reperfusion in human hepatic transplantation.

BACKGROUND: The mechanisms underlying liver graft dysfunction are not completely defined, although much of the injury derives from oxidative stress in organ reperfusion. The antioxidant glutathione in its reduced form (GSH) is an important agent to detoxify oxygen species after reperfusion. However, this effect might be limited by low concentrations at the end of cold storage. The objective of this study was to evaluate GSH and glutathione oxidized (GSSG) hepatic levels pre- and postreperfusion and correlate with hepatocellular injury and liver function in the 5 subsequent days after transplantation. METHODS: Liver biopsies were taken immediately before implant and 2 hours after venous reperfusion in 34 grafts, determining GSH, GSSG levels, and GSSG/GSH ratio. Aminotransferases (ALT, AST) and PT were measured for 5 days. RESULTS: There was a strong decrease in GSH concentration (P <.0001), increase of GSSG levels (P <.01), and increase of the GSSG/GSH ratio (P <.0001). No correlations were found between GSH, GSSG, or GSH/GSSH levels and AST, ALT, and PT. CONCLUSION: Glutathione levels showed significant changes after 2 hours of reperfusion, due to intense oxidative stress. Therapies to replenish GSH should be considered as a protective measure to avoid liver graft dysfunction after transplantation.

Detection and characterization of mechanisms of action of aneugenic chemicals.

A comprehensive evaluation of the genotoxic potential of chemicals requires the assessment of the ability to induce gene mutations and structural chromosome (clastogenic activity) and numerical chromosome (aneugenic activity) aberrations. Aneuploidy is a major cause of human reproductive failure and an important contributor to cancer and it is therefore important that any increase in its frequency due to chemical exposures should be recognized and controlled. The in vitro binucleate cell micronucleus assay provides a powerful tool to determine the ability of a chemical to induce chromosome damage. The application of an anti-kinetochore antibody to micronuclei allows their classification into kinetochore-positive and kinetochore-negative, indicating their origin by aneugenic or clastogenic mechanisms, respectively. The availability of chromosome-specific centromere probes allows the analysis of the segregation of chromosomes into the daughter nuclei of binucleate cells to evaluate chromosome non-disjunction. Quantitative relationships between the two major causes of aneuploidy, chromosome loss and non-disjunction, can be determined. The mechanisms leading to chromosome loss and non-disjunction can be investigated by the analysis of morphological and structural changes in the cell division apparatus by the application of specific stains and antibodies for various cell division components. We illustrate such analyses by the demonstration of the interaction of the monomer bisphenol-A with the centrosome of the mitotic spindle and the folic acid antagonist pyrimethamine with the centromeres of chromosomes. Both types of modifications lead to the induction of aneuploidy in exposed cells. Our studies also implicate the products of the p53 and XPD genes in the regulation of the fidelity of chromosome segregation at mitosis.

Role of hypotension in brain-death associated impairment of liver microcirculation and viability.

Hypotension in brain-dead organ donors is considered a determinant factor of graft viability. The aim of this study was to elucidate the role of hypotension in brain-death associated impairment of hepatic microcirculation and function. Male Sprague-Dawley rats with an intracranial balloon were used. Group I (n = 7) served as sham controls. In group II (n = 7) brain death was induced through inflation of an intracranial balloon. In group III (n = 7) hypotension without brain death was induced by means of pentobarbital. In group II, a steep rise of arterial pressure was followed by a fall to a lower level (P < 0.01, vs. group I). Also in group III arterial pressure was lower (P < 0.01, vs. group I). In group II, bile production was diminished (P < 0.05). Impaired sinusoidal perfusion (P < 0.01) and enhanced leukocyte endothelium interaction (P < 0.05) were documented in hepatic microvasculature. Electron microscopic analysis revealed vacuolization of hepatocytes; these changes were not observed in group III. Brain death induces specific changes of liver microcirculation, function and histomorphology. Independent of associated hypotension, brain death per se impairs donor liver graft quality.

Changes in hepatic microcirculation and histomorphology in brain-dead organ donors: an experimental study in rats.

OBJECTIVE: To assess the effect of brain death on hormonal homeostasis, hepatic microcirculation, and histomorphology in organ donors. DESIGN: Prospective randomised experimental study. SETTING: Institute for Surgical Research, Germany. SUBJECTS: 12 male Sprague-Dawley rats INTERVENTIONS: 6 rats acted as controls, and 6 had brain death induced by inflation of an intracranial balloon. MAIN OUTCOME MEASURES: Mean arterial pressure, serum concentration of antidiuretic hormone (ADH), thyroxine (T4), free-T4, triiodothyronine (T3) and free-T3, bile production, intravital fluorescence microscopy and electron microscopic appearances. RESULTS: After induction of brain death mean arterial pressure rose within 5 minutes followed by significant hypotension (p < 0.01). ADH concentration was reduced (p < 0.01), as was bile production (p < 0.05). There was impaired sinusoidal perfusion and increased interaction between leucocytes and endothelium in the hepatic microvasculature. The electron microscopic analysis showed vacuolisation of hepatocytes. CONCLUSION: Macrohaemodynamics, ADH homeostasis, and the hepatic microcirculation deteriorate after brain death, which leads to histomorphological damage of hepatocytes and compromised liver function.

The application of comparative genomic hybridization and fluorescence in situ hybridization to the characterization of genotoxicity screening tester strains AHH-1 and MCL-5.

AHH-1 TK+/- is a human B cell-derived lymphoblastoid cell line that constitutively expresses a high level of the cytochrome CYP1A1. The MCL-5 cell line was developed by transfection of AHH-1 with cDNAs encoding the human cytochrome P450s, CYP1A2, CYP2A6, CYP2E1, CYP3A4 and microsomal epoxide hydrolase carried in plasmids. The metabolic components of these cell lines make them a useful screening tool for use in mutagenicity studies. Although AHH-1 and MCL-5 are closely related, the two cell lines show differences which cannot be attributed to transfection. In the present study both cell lines were investigated for chromosome stability by comparative genomic hybridization (CGH) and fluorescence in situ hybridization (FISH) using whole chromosome probes and telomeric probes. Amplification in chromosomes 4q, 3q and 9p was observed in both cell lines. To compare the cell lines directly, AHH-1 and MCL-5 DNAs were co-hybridized on the same metaphases using a modified CGH technique. The only difference observed between AHH-1 and MCL-5 was the degree of amplification involving the subtelomeric region of chromosome 4; the additional telomeric region (4q) was translocated onto chromosome 11 and/or chromosome X. FISH was use to show the presence of isochromosomes 3q and 9p in both cell lines with a chromosome number of 48 or higher. These data demonstrate that CGH and FISH with chromosome-specific probes are able to resolve complex karyotypes and to highlight subchromosomal regions involved in rearrangements and potential chromosome fragile sites. Analyses such as those described here may be of considerable value in the determination of the stability of a variety of the cell lines used in the mutagenicity testing of chemicals.