Differential effects of aquatic anaesthetics on the pharmacokinetics of antibiotics: Examples using florfenicol in Nile tilapia (Oreochromis niloticus).

Anaesthetics are commonly applied in pharmacokinetic (PK) studies to assure smooth handling of experimental procedures or to promote animal welfare. However, the influence of anaesthetics on the PK of co-administered drug is generally unknown but assumes ignorable. The goal of the study was to investigate the effect of tricaine methanesulfonate (MS-222), 2-phenoxyethanol (2-PE) and eugenol (EUG) on the PK of florfenicol (FF) in Nile tilapia. Twenty-eight fish were repeatedly exposed to 90 ppm EUG, 300 ppm MS-222 or 900 ppm 2-PE before FF oral administration (15 mg/kg) and each successive blood sampling. The serum concentration-time profiles were analysed by a 2-compartmental model, and the generated parameters in the control (without anaesthetic) and anaesthetic groups were statistically compared. The results demonstrated that the serum concentrations of each anaesthetic were similar at every FF sampling times (70 µg/ml for MS-222; 277 µg/ml for 2-PE; and 61 µg/ml for EUG). In comparison with the control group, the repeated use of MS-222 did not result in a statistical difference in most of the PK parameters. In contrast, the elimination half-lives of the 2-PE and EUG groups were significantly longer whereas the absorption and distribution half-lives of the 2-PE group were significantly shorter than the control, resulting in altered optimal dosages in the simulation modelling. Whether or not the numbers and extent of PK parameters change mitigate subsequent estimations of other PK-derived secondary values such as dosing regimen and withdrawal time remains to be elucidated, but the auxiliary use of anaesthetics in PK studies should not assume uninfluential.

Carfilzomib combined with ex vivo-expanded patient autologous natural killer cells for myeloma immunotherapy.

Natural killer (NK) cell-based immunotherapy is promising, as NK cells are in the first line of defense against cancer and capital of lysing tumor cells without pre-stimulation. However, NK cells from multiple myeloma (MM) patients are always deficient in numbers and the expression of certain activating receptors, disabling them in cytotoxicity against the cancer. Therefore, effective strategies to expand NK cells and increase NK cell-mediated cytotoxicity against MM are significant. Here, NK cells were efficiently expanded from peripheral blood mononuclear cells (PBMCs) of newly diagnosed MM patients after co-culture with irradiated K562 cells transfected with 41BBL and membrane-bound interleukin (IL)-15 (K562-mb15-41BBL) in the presence of 200 IU/ml human IL-2. The ex vivo-expanded NK cells were demonstrated to vigorously kill both MM cells and autologous primary MM cells without significant lysis of patient normal cells. Further exploration revealed a significant increase in cell surface expression of most activating receptors of NK cells and indicated that expanded NK (exp-NK) cell killing of MM cells was mediated by perforin/granzyme. NK cells are capital of lysing human leukocyte antigen (HLA) I-deficient tumor cells and carfizomib, a selective proteasome inhibitor approved for the treatment of relapsed/refractory MM patient, down-regulates the expression of HLA class I, thus enhancing NK cell-mediated lysis in MM. Here, we found for the first time that carfizomib dramatically augmented ex vivo exp-NK cell cytotoxicity against patient autologous MM cells, suggesting the use of exp-NK alone or in combination with the drug to treat MM patient.

Plasma pharmacokinetics and tissue depletion of cyromazine and its metabolite melamine following oral administration in laying chickens.

The study was designed to characterize the plasma pharmacokinetics and tissue depletion profiles (including eggs) of cyromazine (CYR) in chickens following oral administration alone or in combination with melamine (MEL). In order to assess the pharmacokinetic profile of CYR, chickens were administered 1 or 10 mg/kg (single oral doses), whereas residue studies were conducted in chickens fed CYR alone (5 or 10 mg/kg) or CYR (5 mg/kg) and MEL (5 mg/kg) for a period of 14 days. Estimates for the apparent volume of distribution (1.66 L/kg), clearance (7.17 mL/kg/min), and elimination half-life (2.82 h) were derived by noncompartmental analyses. The highest concentration of CYR occurred in liver but fell below detectable limits within 3 days following drug withdrawal from feed. Combined feeding of MEL with CYR did not significantly alter CYR tissue levels. CYR residues were detected only in egg white and were undetectable at the 2nd day postadministration. No MEL was found in eggs unless it had been added to the feed, and when present, it almost exclusively restricted to the egg white. Based upon the results of this initial study of CYR pharmacokinetics and residue depletion, it appears that use of CYR as a feed additive either alone (5 or 10 mg/kg) or in combination with MEL (both agents at 5 mg/kg) does not produce unsafe residue levels in edible products as long as appropriate withdrawal periods are followed for tissues (3 days) and eggs (2 days). However, our results indicate that adoption of a zero-day withdrawal period should be reconsidered in light of these results.

Stage IE/IIE extranodal NK/T-cell lymphoma arising in the nasal cavity: analysis of CT findings and their prognostic value.

AIM: To investigate the computed tomography (CT) findings in patients with stage IE/IIE extranodal natural killer/T-cell lymphoma (ENKTL) arising in the nasal cavity and to evaluate whether imaging findings revealed by CT have prognostic value. MATERIALS AND METHODS: The CT findings of 62 patients diagnosed with IE/IIE ENKTL arising in the nasal cavity were retrospectively reviewed. Imaging findings were investigated, and evaluated imaging findings were analysed for the prognostic value of overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 62 patients, 21 (34%) presented with a superficial infiltrative, 38 (61%) with a mass forming, and three (5%) with a combined pattern. Of all imaging findings, local invasiveness (n = 26, 42%), including bony destruction, erosion, or soft-tissue involvement, was the only independent prognostic factor for OS [p = 0.008; hazard ratio (HR): 3.85; 95% confidence intervals (CI): 1.42-10.44] and DFS (p = 0.001; HR: 4.25; 95% CI: 1.72-10.47). In a subgroup analysis of 36 cases with no local invasiveness, a superficial infiltrative pattern in one nasal cavity was a positive prognostic factor for OS (p = 0.028) and DFS (p = 0.008). CONCLUSION: Imaging findings at CT provided clinically useful predictions for treatment outcomes. Local invasiveness revealed by CT findings was a strong prognostic factor for poor OS and DFS. In addition, in patients with no local invasiveness, a superficial infiltrative pattern in one nasal cavity predicted favourable OS and DFS.

Comparison of extracts from cooked and raw lentil in antagonizing angiotensin II-induced hypertension and cardiac hypertrophy.

AIM: The objective of this study is to examine effects of extracts from cooked lentils on angiotensin II (Ang II)-induced hypertension, cardiac hypertrophy and fibrosis in normotensive rats. MATERIALS AND METHODS: Animals were divided into four groups (n=5 each group): control group, Ang II group, Ang II plus cooked lentil extract (Ang II+CLE) group, and Ang II plus raw lentil extract (Ang II+RLE) group. The telemetry blood pressure transducers were implanted into all rats. A telemetry BP probe was positioned intra-abdominally and secured to the ventral abdominal muscle with the catheter inserted into the lower abdominal aorta. Heart wall thickness, cross-sectional area of cardiomyocytes, diameter of the arterial cross-sections, and perivascular fibrosis in heart and kidney were measured. The surface area of positive-staining cardiomyocytes was analyzed using image analysis software. Reactive oxygen species (ROS) generation was determined using an oxidant-sensitive fluorogenic probe. RESULTS: Rats that received cooked or raw lentil extracts (oral administration, 8 weeks) show significantly attenuated Ang II-induced elevation in blood pressure, cardiac hypertrophy, perivascular fibrosis. Results demonstrated that pretreatment of cardiomyocytes with cooked or raw lentil extract significantly attenuated the Ang II-induced increase in the size of cells (16.0±1.7% and 21.2±2.9%, respectively, n=5, p < 0.05), and cooked or raw lentil extracts also attenuated the Ang II-induced increase in the reactive oxygen species levels in cardiomyocytes (19.8±2.2% & 26.6±3.1%, respectively, n=5, p < 0.05). CONCLUSIONS: This study showed that extracts from cooked lentils could prevent Ang II-induced elevation in blood pressure, cardiac hypertrophy, small arterial remodeling and perivascular fibrosis, and heating process does not have any significant affect on these protective effects.

Self-assembled growth of GaAs anti quantum dots in InAs matrix by migration enhanced molecular beam epitaxy.

Self-assembled GaAs anti quantum dots (AQDs) were grown in an InAs matrix via migration enhanced molecular beam epitaxy. The transmission electron microscopy image showed that the 2D to 3D transition thickness is below 1.5 monolayers (MLs) of GaAs coverage. The average diameter and height of the GaAs AQDs for 1.5 ML GaAs coverage taken from the atomic force microscopy image were approximately 29.0 nm and 1.4 nm, respectively. The density was approximately 6.0 x 10(10) cm(-2). The size of the AQDs was enlarged in the InAs matrix compared with that on the surface. These results indicate that the GaAs AQDs in the InAs matrix under tensile strain can be effectively formed with the assistance of the migration enhanced epitaxy method.

Pharmacokinetics and tissue depletion of florfenicol in Leghorn and Taiwan Native chickens.

Florfenicol (Ff) is a synthetic antibiotic with a broad antibacterial spectrum and high therapeutic effectiveness that was specifically developed for veterinary use. In the present study, tissue residual levels and the pharmacokinetics of Ff after oral administration of 30 mg/kg to Leghorn and Taiwan Native chicken were studied. Furthermore, differential pharmacokinetics between leg and breast muscles were compared using samples collected from an optimized microdialysis model designed for avian species. Significant differences in C(max) were detected between the plasma and muscle microdialysates, and between the breast and leg microdialysates of the Leghorn chickens by noncompartmental pharmacokinetic analysis. After a single oral dose of Ff at 30 mg/kg, the drug was quickly absorbed and widely distributed with tissue penetration factors significantly different between leg and breast muscles. The serum protein binding of Ff was estimated to be 16.8 ± 1.2%. Significant breed differences in tissue depletion were noted and characterized by higher Ff concentration in the brain, lung, kidney and at least 12 h longer resident times in kidney, heart and spleen for Taiwan Native chicken. Results from this investigation demonstrate the practicality of using in vivo microdialysis in chickens for pharmacokinetic studies and reveal significant time-dependent differences in the free concentrations of Ff in leg and breast muscles. The tissue depletion study signified breed differences in tissue residue concentration and detection times between Leghorn and Taiwan Native chickens. Therefore, currently used withdrawal times for Ff in chickens can not be assumed safe for Taiwan Native chickens.

Texture evolution in grain-oriented electrical steel during hot band annealing and cold rolling.

The optimization of magnetic and physical properties of electrical steel is imperative for many engineering applications. The key factors to improve magnetic properties are the steel composition as well as control of the crystallographic orientation and microstructure of the steel during processing. However, this requires careful control of processing at all stages of production. Under certain conditions of deformation and annealing, electrical steel can be produced to have favourable texture components. For grain-oriented (GO) electrical steels that are used in most transformer cores, a pronounced {110} <001> Goss texture plays a vital role to achieve low power losses and high permeability. Essentially, Goss texture develops during secondary re-crystallization in GO electrical steels; however, the mechanism of the abnormal Goss grain growth is still disputed in the literature. In the current study, the influence of the annealing conditions on the development of annealing, cold rolling and re-crystallization textures of hot-rolled GO electrical steel were investigated in detail following each processing step. Furthermore, the orientation data from electron backscatter diffraction were used to evaluate the orientation-dependent stored energy of deformed grains after hot rolling. In the light of new findings in the present study, annealing and deformation texture development mechanisms were critically reviewed.

Caffeine-induced hyperactivity in the horse: comparisons of drug and metabolite concentrations in blood and cerebrospinal fluid.

The goals of this study were to elucidate the temporal and quantitative relationships between caffeine and its major bioactive metabolites in blood and cerebrospinal fluid (CSF) and to characterize the pharmacokinetic-pharmacodynamic relationship for caffeine-induced changes in spontaneous locomotor activity in the horse. We hypothesized that caffeine and its metabolites distribute efficiently into the CSF to antagonize adenosine A1 and A2a receptors and that spontaneous locomotor activity correlates well with caffeine and/or metabolite concentrations in CSF and blood. A microdialysis system was developed to allow simultaneous monitoring of locomotor activity and collection of CSF and blood samples for pharmacokinetic analysis. CSF concentrations of caffeine and its metabolites were evaluated to determine the percentage of central adenosine receptor blockade by the established standard inhibition curves. Caffeine increased the spontaneous locomotor activity for up to 4 h in a dose-dependent manner. After 3 mg/kg caffeine administration, blood caffeine concentration as well as locomotor activity increased sharply to near peak level while CSF caffeine concentrations exhibited a slow rise to a steady-state 75 min later. High correlation coefficient was found between locomotor activity and caffeine concentrations in blood (R(2 )=0.95) and in CSF (R(2) = 0.93). At 3 mg/kg dosage, theophylline was the only detectable caffeine metabolite in the CSF. The concentrations reached in the CSF were sufficient to partially block central adenosine A1 (14% blockade) and A2a (11% blockade) receptors. There were no statistically significant differences between the pharmacokinetics of caffeine in the blood and CSF. This study provides novel evidence that locomotor stimulation in horses is closely correlated with caffeine concentrations in the blood and CSF and, furthermore, is consistent with blockade of central adenosine receptors.

Detection and characterization of intracranial aneurysms with 16-channel multidetector row CT angiography: a prospective comparison of volume-rendered images and digital subtraction angiography.

BACKGROUND AND PURPOSE: The aim of our study was to compare multidetector row CT angiography (MDCTA) with digital subtraction angiography (DSA) in the detection and characterization of intracranial aneurysms. MATERIALS AND METHODS: In our blinded prospective study, 85 patients with suspected intracranial aneurysm (47 women, 38 men; age range, 19-83 years) underwent both 16-channel MDCTA and DSA. The MDCT angiograms were interpreted for the presence, location, size, ratio of the neck to the dome (N/D ratio), and lobularity of the aneurysms and relationship of the aneurysm with the adjacent arterial branches, by using volume-rendering techniques. MDCTA and DSA images (reference standard) were interpreted by 2 independent readers, and the results were compared. RESULTS: A total of 93 aneurysms were detected at DSA in 71 patients, whereas no aneurysms were detected in 14 patients. Compared with DSA, the overall sensitivity, specificity, and accuracy of MDCTA on a per-aneurysm basis were 92.5%, 93.3%, and 92.6%, respectively, for both independent readers. For aneurysms of <3 mm, however, MDCTA had a sensitivity of 74.1% for reader 1 and 77.8% for reader 2. There was excellent agreement between readers in the detection of aneurysms (kappa = 0.822). In addition, MDCTA was also accurate in determining N/D ratio of aneurysms, aneurysm lobularity, and adjacent arterial branches. CONCLUSION: MDCTA is accurate in the detection and characterization of intracranial aneurysms and can be used as a reliable alternative imaging technique to DSA in selected cases.

Characterization of bacterial susceptibility isolates in sixteen dairy farms in Taiwan.

Bacteria were isolated from dairy cows, dairy farm environments, and dairy workers in 2 geographically different areas of eastern and northern Taiwan. Isolates were evaluated for antimicrobial susceptibility and the phylogenetics of isolated Escherichia coli O157:H7 were characterized. A total of 1,346 bacteria were identified, including 226 E. coli, 30 Pseudomonas spp. (7 Pseudomonas aeruginosa), 259 other gram-negative bacteria, 271 Enterococcus spp., 314 Staphylococcus spp., 195 Streptococcus spp., and 51 other gram-positive bacteria. Among them, 88% (1,184/1,346) of the isolates were resistant to sulfadimethoxine. The percentages of gram-negative bacteria resistant to oxy-tetracycline and streptomycin were 48% (249/515) and 78% (404/515), respectively. Gram-positive bacteria isolated from eastern Taiwan, the least polluted region of Taiwan, were found to have greater antimicrobial resistance than those isolated from northern Taiwan. Two E. coli O157:H7 from 2 different geographical areas were isolated. Both were vt2-positive but vt1-negative and had phylogenetic similarities of 82 and 67%, respectively, compared with previous isolates. Information on antimicrobial susceptibility revealed from this dairy farm survey may serve as a baseline for future studies and may also highlight the need to formulate better regulation strategies for the safe use of antimicrobials on food-producing farms.

Inhibition of dimethylnitrosamine-induced strand breaks in liver DNA and liver cell necrosis by diethyldithiocarbamate.

Diethyldithiocarbamate (DEDTC) prevented dimethylnitrosamine (DMN)-induced strand breaks in liver DNA and liver cell necrosis in male Wistar rats. In contrast, DEDTC did not inhibit the fragmentation of liver DNA caused by several other chemical carcinogens (N-hydroxy-2-acetylaminofluorene, 3-hydroxyxanthine, aflatoxin B1, N-acetoxy-2-acetylaminofluorene, methyl methanesulfonate, methylnitrosourea, and methylazoxy-methanol acetate), whether or not they required metabolic activation. Aminoacetonitrile exerted an action similar to that of DEDTC. The inhibitory effect was transitory, lasting at least for 4 hours, and protection for longer than 4 hours required multiple administrations of DEDTC. DEDTC also inhibited the serum clearance of DMN, methylation of liver DNA, and oxidative demethylation of DMN in the in vitro hepatic microsomal system prepared from either male Wistar rats or from hamsters. Interference of the metabolism of DMN appeared to be the mechanism by which DEDTC arrested DMN-induced biochemical and biologic effects.

Accelerating effect of ascorbic acid on N-nitrosamine formation and nitrosation by oxyhyponitrite.

The reaction of nitrite ion with ascorbic acid and its effect on the rate of nitrosation of secondary amines have been investigated by differential pulse polarography in aqueous acidic solution. Ascorbic acid shows nonuniform behavior: it accelerates the nitrosation of N-methylaniline between pH 1.00 and 1.95, allows the nitrosation of diphenylamine and iminodiacetonitrile, but inhibits the nitrosation of secondary amines, such as dimethylamine, diethylamine, proline, hydroxyproline, N-methylaminoacetonitrile, N-methylaminopropionitrile, and sarcosine. The nitrosating agent generated by the reaction between ascorbic acid and nitrite ion appears to be oxyhyponitrite ion (N2O3-2).

Nonuniform alteration of cis-diamminedichloroplatinum(II) tissue distribution in dogs with whole body hyperthermia.

The purpose of this study was to investigate the pharmacokinetics and tissue disposition of cisplatin (CDDP) in euthermic and hyperthermic dogs to determine if hyperthermic alteration of tissue CDDP concentration is uniform. Eighteen female beagle dogs received 20, 50, or 80 mg/m2 CDDP by constant infusion for 60 min under normothermic or hyperthermic conditions (n = 3/subgroup). Blood, plasma, and ultrafiltered plasma samples were collected during the infusion. At termination of infusion, animals were immediately sacrificed, all major tissues were collected, and platinum levels were determined by atomic absorption spectroscopy. Platinum concentrations in all blood fractions of hyperthermic dogs tended to be lower than those of normothermic dogs. The correlation between dose and blood area under the concentration-time curve was linear at both temperatures. Each tissue concentration was normalized for that individual dog's blood area under the curve. The ratio of relative extraction at 42 degrees C to that at 37 degrees C were compared for each tissue. Values of 1.0 were interpreted as indicating uniform relative tissue extraction at each temperature. Values of greater than 2.0 were obtained in lung and ileum, while values of greater than 1.5 were obtained in liver, adrenal, stomach, colon, duodenum, spleen, and pancreas. Values of less than 1.0 were obtained in skin and superficial lymph nodes. These results indicate that hyperthermia significantly alters the pattern of CDDP tissue disposition in a nonuniform manner and that pharmacokinetic data obtained at one temperature, e.g., areas under the curve, cannot be used to directly predict tissue concentrations at another temperature.

Synergism between two amphenicol of antibiotics, florfenicol and thiamphenicol, against Staphylococcus aureus.

Synergistic effects between the same class of antibiotics are rarely reported. In the current study, two amphenicols, namely florfenicol and thiamphenicol, exhibited both in vitro and in vivo synergism against clinical isolates ofStaphylococcus aureusfrom chickens, cattle and pigs. Checkerboard assays on 21S. aureusisolates showed that in 80 per cent of methicillin-susceptibleS. aureus(MSSA) and 82 per cent of methicillin-resistantS. aureus(MRSA) isolates tested, the minimal inhibitory concentration (MIC) of florfenicol could be reduced by 75 per cent (1/4 MIC) or more (up to 1/16 MIC) when combined with 1/2 MIC of thiamphenicol to exhibit antimicrobial activity comparable to the respective drugs at original strength (1×MIC). A synergistic effect (fractional inhibitory concentration index ≤0.5 or ≥2-log10decrease in colony-forming unit/ml in time-kill study) was evident against 30 per cent of MSSA and 45 per cent of MRSA strains tested. A study in mice revealed that the florfenicol/thiamphenicol combination at reduced dosages provided sufficient protection againstS. aureuschallenge. The possible mechanism warrants further study but likely includes the facilitated uptake of thiamphenicol via florfenicol action, and this facilitation was not limited to amphenicol class. The present study may offer new strategy for combination therapy and provide potential alternatives for effective treatment againstS. aureusinfections.

Impact of paraaortic lymphadenectomy for endometrial cancer with positive pelvic lymph nodes: A Korean Radiation Oncology Group study (KROG 13-17).

AIM: We investigated the role of paraaortic lymph node dissection (PALND) in patients with stage IIIC1 endometrial carcinoma after surgery followed by adjuvant radiotherapy (RT) alone or chemoradiotherapy (CTRT). METHODS: We performed a subgroup analysis in 151 patients treated with adjuvant pelvic RT. Paraaortic-recurrence free survival, disease-free survival (DFS) and overall survival (OS) were analyzed. RESULTS: In adjuvant RT alone, PALND was significantly related to reduced risk of paraaortic recurrence (0% vs. 17.1%) and distant metastasis (4.5% vs. 19.5%) compared with the no PALND group. PALND affected 5-year DFS (90.2% vs. 58.9%, p = 0.016) and OS (100% vs. 83.1%, p = 0.022). For the CTRT group, the paraaortic recurrence rate was 19.5% for the no PALND group and 12.8% for the PALND group (p = 0.682). Of patients who underwent PALND in the CTRT group, less extensive PALND was significantly related to increased paraaortic recurrence (≤10 vs. >10 dissected LNs, 17.1% vs. 0%). In the no PALND group (n = 82), 5-year paraaortic-recurrence free survival was 79.4% for the CTRT group and 76.2% for the RT alone group (p = 0.941). In multivariate analysis, PALND was significantly associated with reduced risk of disease-specific death (HR, 0.50; 95% CI, 0.26-0.96; p = 0.037). CONCLUSION: PALND provided excellent paraaortic control and improved outcome in stage IIIC1 endometrial cancer with favorable tumor features treated with adjuvant RT alone. Less extensive PALND was associated with significantly increased paraaortic recurrence in patients with advanced tumor features treated with adjuvant CTRT. Combined CTRT did not affect disease control in the paraaortic region compared with RT alone.

Genotoxicity evaluation of electromagnetic fields generated by 835-MHz mobile phone frequency band.

It is still unclear whether the exposure to electromagnetic fields (EMFs) generated by mobile phone radiation is directly linked to cancer. We examined the biological effects of an EMF at 835 MHz, the most widely used communication frequency band in Korean CDMA mobile phone networks, on bacterial reverse mutation (Ames assay) and DNA stability (in vitro DNA degradation). In the Ames assay, tester strains alone or combined with positive mutagen were applied in an artificial mobile phone frequency EMF generator with continuous waveform at a specific absorption rate (SAR) of 4 W/kg for 48 h. In the presence of the 835-MHz EMF radiation, incubation with positive mutagen 4-nitroquinoline-1-oxide and cumene hydroxide further increased the mutation rate in Escherichia coli WP2 and TA102, respectively, while the contrary results in Salmonella typhimurium TA98 and TA1535 treated with 4-nitroquinoline-1-oxide and sodium azide, respectively, were shown as antimutagenic. However, these mutagenic or co-mutagenic effects of 835-MHz radiation were not significantly repeated in other relevant strains with same mutation type. In the DNA degradation test, the exposure to 835-MHz EMF did not change the rate of degradation observed using plasmid pBluescript SK(+) as an indicator. Thus, we suggest that 835-MHz EMF under the conditions of our study neither affected the reverse mutation frequency nor accelerated DNA degradation in vitro.

Focal nodular hyperplasia presenting as acute abdomen.

Focal nodular hyperplasia (FNH) is a benign liver tumour with an asymptomatic course, rarely causing complications. When the diagnosis is certain, only watchful observation is necessary. We highlight an interesting case of a 42-year-old woman with a FNH that ruptured and became haemorrhagic, thus presenting as an acute surgical abdomen. The diagnosis was only established after surgical resection with histopathological confirmation. Although haemorrhage of hepatic FNH is extremely rare, this case highlights the small risk of rupture in large lesions.

Depletion of plasma factor XIII prevents disseminated intravascular coagulation-induced organ damage.

The impact of clot stability affecting the vasculopathy and tissue necrosis in Shwartzman reaction was investigated using plasma Factor XIII A2-depleted rabbit (FXIII-DR). Plasma Factor XIIIA2 (FXIIIA2) was depleted by infusion of the mono-specific goat anti-rabbit FXIIIA2 IgG. Generalized Shwartzman reaction (GSR) was induced by priming and challenged by i.v. injection of LPS and local Shwartzman reaction (LSR) was primed by intradermal injection of LPS and challenged by i.v. injection of LPS. Histological examination of the GSR animals showed, extensive thrombi accumulation in renal tubules and bilateral cortical necrosis of kidney in 8 out of 10 rabbits but none in the FXIII-DR. Fibrinogen levels were elevated to 3 approximately 4 fold at 24 h and lowered at 48 h whereas a steady rise was seen in the FXIII-DR. FDP levels in GSR animals were significantly elevated at 24 h and further increased at 48 h but only slightly elevated in the FXIII-DR. Examination of the LSR tissues after 48 h showed an acute onset of progressive cutaneous vascular thrombosis, purpura, and secondary hemorrhagic necrosis whereas neither fibrin deposit nor necrosis of tissue were detected in FXIII-DR despite of an early edema formation. Fibrinogen levels were also increased two fold at 24 h but returned to basal levels at 48 h in control LSR animals but not affected at all in FXIII-DR. These results suggest that during the severe inflammatory conditions such as sepsis, the fibrinolytic system is functionally sufficient to dissipate the pathogenic accumulation of disseminated intravascular clots and exudated fibrin clots if those clots were prevented from getting crosslinked in plasma.

Combined chemotherapy and radiation versus radiation alone in the management of localized angiocentric lymphoma of the head and neck.

BACKGROUND AND PURPOSE: To clarify the clinical benefit derived from the combined modality therapy (CMT) comprised of chemotherapy and involved-field radiotherapy (XRT) for stage I and II angiocentric lymphomas of the head and neck. MATERIAL AND METHODS: Of 143 patients with angiocentric lymphoma of the head and neck treated at the Yonsei Cancer Center between 1976 and 1995, 104 patients (XRT group) received involved-field XRT alone with a median dose of 50.4 Gy (range: 20-70 Gy), while 39 patients (CMT group) received a median three cycles (range: 1-6 cycles) of chemotherapy before starting involved-field XRT. The response rate, patterns of failure, complications, and survival data of the XRT group were compared with those of the CMT group. RESULTS: Despite a higher response rate, local failure was the most common pattern of failure in patients of the both groups. The patterns of failure, including the systemic relapse rate were not influenced by the addition of combination chemotherapy. Although both modalities were well tolerated by the majority of patients, aberrant immunologic disorders or medical illnesses, such as a hemophagocytic syndrome, sepsis, intractable hemorrhage, or the evolution of second primary malignancies were more frequently observed in patients of the CMT group. The prognosis of patients in the XRT group was relatively poor, with a 5-year overall actuarial survival rate of 38% and disease-free survival rate of 32%, respectively. However, their clinical outcome was not altered by the addition of systemic chemotherapy. Achieving complete remission was the most important prognostic factor on univariate and multivariate analyses, but treatment modality was not found to be a prognostic variable influencing survival. CONCLUSIONS: Involved-field XRT alone for angiocentric lymphoma of the head and neck was insufficient to achieve an improved survival rate, but the combination of chemotherapy and involved-field XRT failed to demonstrate any therapeutic advantage over involved-field XRT alone.