Metastatic diagnosis of canine sternal lymph nodes using computed tomography characteristics: A retrospective cross-sectional study.

The accurate evaluation of sternal lymph nodes (StLNs) is critical for the staging of canine thoraco-abdominal tumours. Computed tomography (CT) provides a non-invasive means of assessing StLNs, but its diagnostic accuracy for identifying metastases is unclear. In this retrospective cross-sectional study, we assessed the diagnostic power of various CT measurements. Fifty-seven dogs that underwent concurrent CT and cytological examination of the StLNs were enrolled retrospectively. The size, shape, X-ray attenuation and uniformity of the StLNs were assessed. The dogs were divided into metastasis-negative (n = 21) and metastasis-positive (n = 36) groups. Logistic regression analysis showed that the size (StLN-to-second sternebra ratio [ratio-size]) and precontrast attenuation were significantly different between groups. Combining these parameters achieved a specificity and positive predictive value of 100% (cut-off values: 1.0, 37.5 Hounsfield units, respectively). This suggests that the combination of ratio-size and precontrast attenuation is effective for differentiating metastasis to the StLNs on CT.

Clinicopathologic Impact of Early Medullary Ray Injury in Patients Following Kidney Transplantation.

BACKGROUND: Previously, we explored the histopathologic characteristics of medullary ray injury (MRI) inducing interstitial fibrosis and tubular atrophy (IF/TA) to determine its etiologies, which include calcineurin inhibitor (CNI) toxicity and urologic complications. However, we did not examine the effects of these etiologies on long-term kidney allograft prognosis, because biopsy timing differed among cases. AIM: We examined the influence of early MRI on kidney allograft prognosis using protocol biopsies taken within a 3-month time frame. METHODS: We defined early MRI as tubular degeneration with interstitial edema or mild fibrosis localized to the medullary ray. We divided 53 protocol biopsies into 2 groups, with and without early MRI. Early MRI+ cases with isometric vacuolization were classified as CNI toxicity; those with Tamm-Horsfall protein in the interstitium and a thyroidlike appearance were classified as urinary tract system abnormalities; remaining cases were classified as "others." We compared changes in serum levels of creatinine (sCr) over 3 years and fibrosis extent at 1 year. RESULTS: The sCr levels were significantly higher in the MRI+ group than the MRI- group at 3 years (P = .024). Examining the 3 MRI+ subgroups, only the MRI+ urinary tract system abnormalities group had significantly high sCr levels compared to the MRI- group (P = .019). The MRI+ group showed significant signs of IF/TA at 1 year. CONCLUSIONS: Early MRI after kidney transplantation was significantly more likely to develop IF/TA at 1 year and had higher sCr levels at 3 years. In such cases, intervention might preserve graft function over the long term.

Three-dimensional conformal radiation therapy for inoperable massive hepatocellular carcinoma in six dogs.

OBJECTIVES: To evaluate the activity and tolerability of three-dimensional conformal radiation therapy (3D-CRT) in dogs with massive hepatocellular carcinoma. MATERIALS AND METHODS: Six dogs with massive hepatocellular carcinoma that were ineligible for surgical resection or with owners who declined surgical resection, and underwent 3D-CRT were retrospectively reviewed. 6 to 10 Gy per fraction was prescribed at isocentre of planning target volume to a total dose of 18 to 42 Gy with 1 to 2 fractions per week for a total of 3 to 7 fractions. Follow-up examinations included physical examination, contrast-enhanced CT scan and blood analysis (complete blood count, electrolytes and serum biochemical panel). RESULTS: The median follow-up time after 3D-CRT was 534 (range, 281 to 1057) days. An objective response was observed in five of six cases. Radiation-induced liver disease developed in one dog but was asymptomatic and reversible. Toxicity was not noted in any other dog. CLINICAL SIGNIFICANCE: 3D-CRT appears to be a viable treatment option for dogs with inoperable massive hepatocellular carcinoma.

Tumor promotion by 12-O-tetradecanoylphorbol-13-acetate in an ultra-short-term skin carcinogenesis bioassay using rasH2 mice.

Assessment of the skin tumor-promoting potential of 12-O-tetradecanoylphorbol-13-acetate (TPA) after initiation with 7,12-dimethylbenz[a]anthracene (DMBA) was conducted using rasH2 transgenic (Tg) mice and their nontransgenic (non-Tg) littermates. Mice were treated with DMBA (50 µg/100 µL acetone) on clipped back skin at the commencement of the study, and 1 week thereafter, TPA was applied at 8 µg/200 µL or 4 µg/200 µL acetone, once or twice weekly, for 7 weeks. Skin nodules were observed in the rasH2 Tg mice from week 4, and the incidence reached 100% at weeks 5 and 6. The number of skin nodules (multiplicity) in the 8-µg twice-weekly, 8-µg once-weekly, 4-µg twice-weekly, and 4-µg once-weekly groups was 62.4, 46.2, 62.6, and 36.9, respectively. The non-Tg mice also developed skin nodules, but the sensitivity to induction in the rasH2 Tg mice was higher. No nodules were observed in the acetone groups, but single nodules were apparent in the no-treatment rasH2 Tg and non-Tg groups. In conclusion, skin promotion effects could be detected within only 8 weeks in the rasH2 mice, and the concentration of 4 µg TPA once weekly was sufficient as a positive control. This short-term skin carcinogenesis bioassay using rasH2 mice could represent a useful tool for the assessment of drug and chemical safety with cutaneous treatment.

[Massive hemoptysis after lobectomy for bronchiectasis].

A 67-years-old female, who was suffered from hemoptysis for about 50 years and was diagnosed as bronchiectasis of left lower lobe, was admitted to our hospital to receive elective surgical treatment. Left lower lobectomy was performed, and on the 10th postoperative day, massive hemoptysis occurred and intratracheal hemorrhage caused occlusion of the respiratory tract. Selective bronchial arteriogram revealed that bronchial artery of the left upper lobe developed remarkably, compared with the findings 1 year ago, and the bleeding site was located in the left upper lobe, which seemed to be almost normal before the operation. After embolization of this artery the hemoptysis stopped. If bronchial artery, which develop well and distribute to the bleeding lobe of the lung, have branches to adjacent another lobe, change of blood stream of bronchial artery by operation may cause early postoperative recurrence of hemoptysis.

[Ganglioneuroma derived from inferior trunk of the brachial plexus and first intercostal nerve].

A 62-years-old Japanese male, who had mediastinal tumor at the left thoracic inlet, was admitted to our hospital to receive surgical treatment. The tumor behind the left subclavian artery was guessed to be neurogenic benign tumor, though the involvement of the brachial plexus was unclear. We approached the tumor by means of left hemi-collar skin incision, resulting in performing safe operation with directly looking at the tumor that communicated with 1st intercostal nerve and inferior trunk of the left brachial plexus. Pathological diagnosis of the resected tumor was ganglioneuroma. Cervical approach by means of hemi-collar skin incision is thought to be available for surgical treatment of tumors at the thoracic inlet because of easy accessibility and less invasiveness than other approach with dividing bones, such as clavicle, sternum, or ribs.

Conditional interleukin-12 gene therapy promotes safe and effective antitumor immunity.

We and others have previously demonstrated that (chronic) interleukin (IL)-12 gene therapy delivered intratumorally through ex vivo gene-engineered dendritic cell (DC) is competent to promote the regression of established murine tumors. In this report, we have developed a conditional expression system (rAd.RheoIL12) to determine the temporal requirements of transgenic IL-12p70 production by administered DC on therapeutic outcome in a subcutaneous B16 melanoma model. DCs infected with rAd.RheoIL12 (DC.RheoIL12) secreted IL-12p70 in a tightly regulated fashion in response to a synthetic diacylhydrazine small molecule ligand in vitro, and the treatment benefit of DC.RheoIL12 delivered into B16 lesions was strictly ligand dependent in vivo. Indeed, DC.RheoIL12-based therapy promoted the regression of established day 7 B16 tumor lesions after intratumoral injection, provided that ligand administration occurred within 24 h of DC injection and was sustained for approximately 5 or more days. Treatment efficacy was correlated to the magnitude of systemic anti-B16 CD8(+) T cells cross-primed in vivo, which in turn, appeared dependent on the early enhanced in vivo survival of adoptively transferred DC.RheoIL12 in tumor and tumor-draining lymph nodes. The unique safety feature of DC.RheoIL12 application was emphasized in a combined treatment model with rIL-2, where profound TNF-alpha-associated toxicity could be ameliorated upon discontinuation of activating ligand administration.

90-Day repeated-dose toxicity study of licorice flavonoid oil (LFO) in rats.

Licorice flavonoid oil (LFO) is a new functional food ingredient consisting of licorice hydrophobic polyphenols in medium-chain triglycerides (MCT). As part of a safety evaluation, a 90-day oral toxicity study in rats was conducted using an LFO concentrate solution (2.90% glabridin). Male and female animals were assigned to one of 12 groups (10 males or females per group) and received corn oil (negative control), MCT (vehicle control), or 400, 600, 800 or 1600 mg/kg of the LFO concentrate solution. In conclusion, LFO concentrate solution induced an anticoagulation effect in both sexes, although there was a clear sex difference. Based on these findings, it is concluded that the no-observed-adverse-effect level (NOAEL) for the LFO concentrate solution is estimated to be 800 mg/kg/day for female rats, and approximately 400 mg/kg/day for male rats.

[Yolk sac tumor of the anterior mediastinum and pulmonary metastases; report of a case].

A 31-year-old female was clinically diagnosed as having a anterior mediastinal yolk sac tumor because of the elevation of the AFP (17,500 ng/ml), a large mass lesion (9 x 5 cm) in the anterior mediastinum and bilateral lung metastases. After 4 courses of chemotherapy with cisplatin (CDDP), etoposide (VP-16) and bleomycin hydrochloride (BLM), the mediastinal mass reduced in size significantly and the serum AFP level reached within normal range. Fluorodeoxyglucose-positron emission tomography (FDG-PET) showed a weak uptake in the mediastinum, accordingly the operation was performed. The tumor was completely removed and there were no viable foci of the tumor in part of the tumor. After the operation, 4 courses of chemotherapy with carboplatin (CBDCA), VP-16 and ifosfamide (IFM) were performed. She is alive without evidence of recurrence in 5 months after operation. It was noticed that the serum AFP is a useful indicator for determing the chance of operation after chemotherapy.

Thirteen-week feeding study of thaumatin (a natural proteinaceous sweetener), sterilized by electron beam irradiation, in Sprague-Dawley rats.

This study was designed to evaluate and characterize any subchronic toxicity of thaumatin sterilized by electron beam irradiation (5.0 kGy) when administered at dietary levels of 0% (control), 0.3%, 1.0% and 3.0% to groups of 10 male and 10 female Crj: CD (SD) IGS rats for 13 weeks. Separate groups of both sexes received 3.0% non-irradiated thaumatin. There were no treatment-related clinical signs or adverse effects on the survival rate, body weight, food consumption, water consumption and urinalysis, ophthalmology, haematology, or blood biochemistry data. No treatment-related alterations in gross pathology or organ weights were found in any group. On histopathological examination, sporadic spontaneous lesions known to occur in this strain of rats were the only findings, with no specific relation to the test substance. Thus, the no-observed-adverse-effect-level (NOAEL) was judged to be a dietary level of at least 3.0% (2502 mg/kg body weight/day for males, 2889 mg/kg body weight/day for females) for electron beam irradiated thaumatin under the present experimental conditions. It was concluded that electron beam-irradiation of thaumatin does not cause changes of any toxicological significance.

28-Day repeated dose toxicity study of dried microorganism in rats.

Ubidecarenone, also known as CoQ(10), is currently sold as a dietary supplement in the United States, with a majority of these products derived from the fermentation of carbohydrates or tobacco leaf extracts. In addition to its availability in dietary supplements, CoQ(10) is now being considered for use in foods. Accordingly, as part of the process for attaining "Generally Recognized as Safe" status, and to supplement information already available regarding the safety of CoQ(10) per se, a 28-day oral toxicity study in rats was conducted to evaluate the subacute safety of a microorganism biomass used as a new source in CoQ(10) production. Groups of Crj:CD(SD) rats (SPF) (6 males or females per group, 4 groups per sex) received dried microorganism at doses of 0, 500, 1000 or 2000 mg/kg/day via intragastric intubation. Clinical observations were recorded, and body weight, and food and water consumptions measured throughout the study. At the end of the study, aortic blood samples were collected from all animals for analysis of hematological and clinical chemistry parameters, and gross pathologic examination was performed. Histopathologic examination was performed on select tissues from the control and high-dose groups. There were no treatment-related changes that were considered to be of toxicological significance. Since rats treated with 2000 mg/kg of dried microorganism did not demonstrate any treatment-related changes, the no-observable-adverse-effect level (NOAEL) for dried microorganism was estimated to be greater than 2000 mg/kg/day under the present study conditions.

Oesophageal hypersensitivity in Japanese patients with non-erosive gastro-oesophageal reflux diseases.

BACKGROUND: Visceral hypersensitivity plays a major role in the pathogenesis of non-erosive oesophageal reflux disease (NERD). Prevalence of NERD differs according to the population and geographical region. Oesophageal hypersensitivity in NERD has not been well studied, especially in Japanese patients. AIM: To investigate oesophageal hypersensitivity in Japanese NERD patients. PATIENTS AND METHODS: We performed upper GI endoscopy and the modified acid perfusion test on 14 control subjects and 68 GERD patients, including 26 with NERD, 34 with erosive GERD, and six with Barrett's oesophagus. The stimulus-response function to acid was quantified by three parameters (lag time, intensity rating and the acid perfusion sensory score) and compared among four groups. RESULTS: The mean value of the lag time, intensity rating, and acid perfusion scores in NERD patients (4.6 +/- 3.4, 4.4 +/- 3.4, 27.8 +/- 26.7, respectively) were higher than in erosive GERD (3.2 +/- 3.3, 3.0 +/- 3.2, 18.2 +/- 24.8) and Barrett patients (2.5 +/- 4.0, 1.8 +/- 3.3, 15.0 +/- 28.8), and significantly higher than in the control group (1.7 +/- 2.7, 1.1 +/- 2.0, 5.4 +/- 11.8). The ratio of patients with higher sensory scores was also greater in the NERD group (57.7%) than in erosive GERD (32.3%) and Barrett group (16.7%), and significantly greater than in control group (6.7%). CONCLUSION: Our findings suggest that oesophageal sensitivity is likely to be enhanced especially in NERD patients also in Japanese population in comparison with erosive GERD, Barrett's oesophagus and controls.

Review of combination of peritoneal dialysis and hemodialysis as a modality of treatment for end-stage renal disease.

Because the contribution of residual renal function (RRF) to total solute clearance is often significant in continuous ambulatory peritoneal dialysis (CAPD), loss of RRF over time can lead to inadequate dialysis if appropriate prescription management strategies are not pursued. Additionally, declines in ultrafiltration caused by increases in peritoneal permeability may limit continuation of CAPD therapy. Peritoneal dialysis and hemodialysis (PD + HD) combination therapy (complementary dialysis therapy) is an alternative method. This therapy allows the patient to maintain daily activities, as with CAPD, while undergoing once-a-week HD supplements for the insufficient removal of solutes and water. This therapy allows for the continuation of PD without shifting to total HD in PD patients who continue to have uremic symptoms even after individualization of the PD prescription. This treatment option is psychologically more acceptable to patients and may be expected to provide such accompanying beneficial effects as peritoneal resting, improvement of QOL and reduction in medical cost.

Western blotting analysis of the beta-hexosaminidase alpha- and beta-subunits in cultured fibroblasts from cases of various forms of GM2 gangliosidosis.

OBJECTIVES: The GM2 gangliosidoses are a group of genetic disorders caused by the accumulation of ganglioside GM2 in neuronal cells. We examined the alpha- and beta-subunits of beta-hexosaminidases by a non-radioisotopes detecting system to evaluate whether it was a useful method for understanding of the pathophysiologies of GM2 gangliosidoses. MATERIALS AND METHODS: We investigated the alpha- and beta-subunits of beta-hexosaminidases in cultured fibroblasts from cases of various forms of GM2 gangliosidosis by means of Western blotting and a chemiluminescence detection system. RESULTS: In a patient with infantile Tay-Sachs disease [HEXA genotype, Int5-SA(g-1-->t)/Int5-SA(g-1-->t)], the mature alpha-subunit was undetectable. In a patient with infantile Sandhoff disease (HEXB genotype, C534Y/C534Y), the mature beta-subunit was deficient. However, a small amount of the mature beta-subunit was detected in a patient with adult Sandhoff disease (HEXB genotype, R505Q(+I207V)/R505Q(+I207V)), which may have resulted in the residual enzyme activity and mild clinical course. Normal amounts of alpha- and beta-subunits were detected in a patient with GM2 activator deficiency. CONCLUSION: This method is easy and sensitive for detecting target proteins, and is useful for clarification of the pathophysiologies of GM2 gangliosidoses.

Epoprostenol sodium, a prostaglandin I2, lacks tumor promoting effects in a medium-term liver carcinogenesis bioassay in rats.

Potential modifying effects of epoprostenol sodium administration on liver carcinogenesis were investigated in male F344/DuCrj rats initially treated with N-nitrosodiethylamine (DEN). Two weeks after a single dose of DEN (200 mg/kg, intraperitoneally), rats daily received subcutaneously epoprostenol sodium at doses of 0, 1, 10 and 100 microg/kg, or were fed phenobarbital sodium (PB) at a dietary level of 500 parts per million (ppm) as positive control for 6 weeks. All animals were subjected to partial hepatectomy at week 3, and were killed at week 8. Prominent flushing of extremis and signs of behavioural depression occurred after injection and lasted for 1 h in rats given 100 microg/kg epoprostenol sodium. Such clinical signs were slight in rats treated with 10 microg/kg, but not observed with 1 microg/kg. Marked decrease in body weight gain was noted in rats given 100 microg/kg. Statistically significant changes in relative liver weights were not found in any group given the test chemical. Epoprostenol sodium did not significantly increase the quantitative values for glutathione S-transferase placental form (GST-P) positive liver cell foci observed after DEN initiation, in clear contrast to the positive control. The results thus demonstrate that epoprostenol sodium lacks modifying potential for liver carcinogenesis in our medium-term bioassay system.

The incidence of reflux oesophagitis after cure of Helicobacter pylori in a Japanese population.

AIM: To investigate the incidence of reflux oesophagitis after antibacterial therapy for Helicobacter pylori infection in our patient population. METHODS: Subjects were 451 H. pylori-infected patients (primary symptom: peptic ulcer disease in 347, nonulcer dyspepsia in 100, and reflux oesophagitis in four): 11 of these patients had reflux oesophagitis on study entry. H. pylori infection was treated by a proton pump inhibitor/amoxycillin-clarithromycin regimen for either 7 or 14 days. Each patient was examined by endoscopy before treatment and more than 6 months after treatment to compare oesophageal findings. In addition, 227 patients were interviewed regarding reflux symptoms, using symptom questionnaires, before and more than 6 months after treatment. RESULTS: Among 440 patients who did not have reflux oesophagitis prior to antibacterial treatment (340 peptic ulcer patients and 100 nonulcer dyspepsia patients), 23 patients whose infection was eradicated developed reflux oesophagitis (5.4%). The 11 patients who had reflux oesophagitis prior to treatment were all successfully cured of infection. Six of these patients showed no change in their oesophagitis, while the condition improved in three and worsened in two. Symptom scores improved in 34 of the 36 patients who reported reflux symptoms. Among 19 patients who showed persistent infection, only one developed reflux oesophagitis (5.2%), while none complained of newly developed symptoms following treatment. CONCLUSIONS: Development of reflux oesophagitis after treatment of H. pylori infection was observed in a Japanese population. However, the incidence of this condition was comparable between those with persistent H. pylori infection and those in whom the infection was eradicated.