Central odontogenic fibroma with amyloid: a diagnostically challenging case.

Odontogenic fibroma is a rare benign mesenchymal odontogenic tumor, with its histological diversity possibly posing diagnostic challenges. A case of the amyloid variant of central odontogenic fibroma, with epithelial cells in perineural and intraneural locations, is reported herein. The 46-year-old female patient had experienced discomfort related to her anterior right hard palate for approximately 25 years. Clinical examination revealed a depression in the anterior hard palate, and radiographic examination showed a well-defined radiolucent lesion with root resorption of the adjacent teeth. Histologically, the well-circumscribed tumor was composed of hypocellular collagenous connective tissue with small islands of odontogenic epithelium. In addition, the juxta-epithelial deposition of amyloid globules without calcification and epithelial cells in perineural and intraneural locations were observed, which posed a diagnostic challenge in differentiating the lesion from the non-calcifying variant of calcifying epithelial odontogenic tumor and sclerosing odontogenic carcinoma. However, on the basis of the clinical and radiographic findings, which were suggestive of a benign and slowly progressive process given the corticated, unilocular radiolucency, the considerable root resorption, and the long history of this finding in an otherwise healthy patient, the final diagnosis was amyloid variant of central odontogenic fibroma. Increased recognition of this variant of odontogenic fibroma and its differentiation from other more aggressive lesions could help the clinician to avoid overdiagnosis and overtreatment.

Gastrointestinal stromal tumour lacking mutations in the KIT and PDGFRA genes in a cat.

Molecular subtyping in gastrointestinal stromal tumours is a useful method for predicting the efficacy of treatment using tyrosine kinase inhibitors in humans. However, owing to the paucity of reports on mutational analyses, the association between genetic mutations and the therapeutic response to tyrosine kinase inhibitors remains unclear in feline gastrointestinal stromal tumours. In this report, we describe the case of a cat with a gastrointestinal stromal tumour which was unresponsive to tyrosine kinase inhibitors. A mutational analysis revealed that the cat lacked mutations in both the KIT and platelet-derived growth factor receptor-alpha (PDGFRA) genes. Our findings are consistent with the fact that KIT/PDGFRA wild-type gastrointestinal stromal tumours are less responsive to tyrosine kinase inhibitors in humans. This signifies the need for further evaluation and possibly individualised treatment for gastrointestinal stromal tumours in cats on the basis of mutational analyses.

Massive calcification around large joints in a patient subsequently diagnosed with adult-onset hypophosphatasia.

We report a 64-year-old Japanese woman with a history of progressive loss of motor function and painful swelling of large joints. At the age of 54, profound calcification appeared around the shoulder and hip joints, which did not heal after repeated surgical resections. Iliac bone biopsy revealed osteomalacic changes. Laboratory data showed low serum alkaline phosphatase (ALP) activity and a high urine phosphoethanolamine (PEA) concentration with normal serum calcium, phosphate, and fibroblast growth factor 23 (FGF23) levels. Subsequent genetic analysis of the ALPL gene confirmed the diagnosis of hypophosphatasia (HPP) with the identification of a heterozygous single nucleotide deletion, c.1559delT (p.Leu520ArgfsX86). We started a mineral-targeted enzyme replacement therapy, asfotase alfa (AA), to treat the patient's musculoskeletal symptoms. A follow-up bone biopsy after 12 months of AA treatment showed improvement of osteomalacia. Calcified deposits around the large joints were unchanged radiographically. To our knowledge, this is the first report of a patient with an adult-onset HPP who presented with profound calcification around multiple joints. Nonspecific clinical signs and symptoms in patients with adult-onset HPP often result in delayed diagnosis or misdiagnosis. We propose that bone biopsy and genetic analysis should be considered along with laboratory analysis for all patients with ectopic calcification around joints of unknown etiology for accurate diagnosis and better treatment.

Comparison of traditional two-injection dorsal digital block versus transthecal and subcutaneous single-injection digital block: A systematic review and meta-analysis.

Digital nerve block is a common procedure with several techniques, including the traditional digital nerve block, transthecal digital nerve block, and single subcutaneous palmar digital nerve block. This review aimed to evaluate the efficacy of these three methods. A systematic search was performed in the PubMed, Scopus, and Cochrane Library databases. The risk of bias of the studies was assessed using the Cochrane Collaboration's tool for assessing the risk of bias and the Risk of Bias Assessment Tool for Non-Randomized Studies. Fourteen prospective randomized controlled studies and one prospective comparative study were included. The three methods of digital block showed similar onset times, durations, injection pain and incidence of incomplete anesthesia. This review confirmed that all three methods of digital block are equally effective. Considering that patients prefer a single injection and the potential risk of complications, the single subcutaneous digital block could be more widely used.

Primary bone adult T cell lymphoma with multiple skeletal lesions and debilitating painful osteolysis: a case report.

There have been only a limited number of reports on primary adult T cell lymphoma/leukemia (ATL) in the bone. This is a case report of a 75-year-old patient initially reporting multiple bone pains that were attributed to osteolytic ATL. The patient developed spontaneous chest/back pain and visited a local hospital. Laboratory tests showed high levels of alkaline phosphatase (ALP), and computed tomography (CT) revealed skeletal lesions with osteolysis. Although multiple myeloma was initially suspected, the results of bone marrow aspiration and bone biopsy were inconsistent. After he was referred to our hospital, mild hypercalcemia (10.4 mg/dL) with low-normal intact parathyroid hormone (PTH) (27 pg/mL), low parathyroid hormone-related protein (PTHrP), and elevated 1,25-dihydroxy vitamin D (1,25OH2D) levels (136 pg/mL) narrowed the differential diagnosis down to lymphomatous and granulomatous diseases, and then, the high serum soluble IL-2 receptor (3,450 U/mL) and the flower cells recognized in the peripheral blood sample suggested the involvement of ATL. Finally, the reevaluation of the iliac bone biopsy sample led us to the histological diagnosis of ATL infiltration in the bone. The subsequent two courses of chemotherapy in addition to denosumab resulted in an objective partial metabolic response indicated in 18-fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Although very rare, the bone involvement of ATL could be used for the differential diagnosis for local osteolytic bone pain in addition to multiple myeloma and metastatic bone diseases.

MEASUREMENT OF INTERNAL RADIATION DOSE DISTRIBUTION IN CT EXAMINATIONS USING POLYETHYLENE TEREPHTHALATE RESIN.

This study proposes a new dosimetry method for the estimation of the internal radiation dose distribution of a subject undergoing computed tomography (CT) examinations. In this novel method, dose distribution of a subject by CT scans was estimated based on radiophotoluminance distribution with polyethylene terephthalate (PET) resin which was cut to the average head size of a Japanese 1-year-old child. The difference in dose distribution depending on the type of bowtie filter was visualized by imaging luminance distribution with the PET phantom using a charge-coupled device camera. Dose distribution images simulated from a water phantom of the same size as the PET phantom were compared with the luminance distribution images. The linear correlation was demonstrated between luminance of the PET phantom and the simulated water dose. In comparison with the simulated water doses and the converted water doses from luminance of the PET phantom, the relative differences were within 20%.

Endogenous viral gene ev21 is not responsible for the expression of late feathering in chickens.

The late-feathering (LF) gene K on the Z chromosome is an important gene in the chicken industry, which is frequently utilized for the feather sexing, a type of autosexing, of neonatal chicks. The K gene is closely associated with the endogenous ev21 gene from an avian leukosis virus and the incomplete duplication (ID) of prolactin receptor (PRLR) and sperm flagellar protein 2 (SPEF2) genes, and ev21 has been used as a molecular marker to detect LF birds. In the present study, a comprehensive survey for the presence or absence of ev21 and ID across 1,994 birds from 52 chicken breeds, three commercial hybrid groups, and the Red Jungle Fowl revealed that almost all LF breeds have both ev21 and ID. However, only one LF breed (Ingie) has only ID and no ev21. Moreover, this study revealed that almost all early (normal)-feathering (EF) breeds lack both ev21 and ID, but only one breed (White Plymouth Rock) included EF birds with ev21 but no ID. Therefore, regarding LF expression, the results indicated that ID is responsible, but ev21 is not required. Henceforth, ID should be used as a molecular marker to detect LF birds instead of ev21. Because ev21 contains the full genome of an avian leukosis virus, there is a risk of disease development in breeds with this gene. Therefore, the Ingie breed, which has no ev21 at the K locus, represents excellent material for the establishment of new LF stocks.

Photodynamic detection of canine mammary gland tumours after oral administration of 5-aminolevulinic acid.

5-Aminolevulinic acid (5-ALA) is widely used in photodynamic detection (PDD) and therapy. We evaluated the pharmacokinetics of 5-ALA-induced porphyrins and its effectiveness in PDD in dogs with mammary gland tumours (MGTs) following oral administration. Healthy dogs and those with MGTs (nine each) were orally administered 4 mg kg-1 5-ALA. Protoporphyrin IX (PpIX) was not detected in the plasma of healthy dogs but it peaked in dogs with MGT at 2 h after 5-ALA administration. In the PDD study, 16 dogs with MGT were orally administered 40 mg kg-1 5-ALA, and MGT but not normal tissue showed red fluorescence after 2-4 h. Photon counts were 6635-63 890 and 59-4011 (median, 19 943 and 919) for MGT and non-tumour tissues, respectively. Cell density strongly correlated with PpIX photon counts of MGT tissue of the dogs (R = 0.743, P = 0.0009). We suggest that 5-ALA-PDD might be an effective diagnostic tool for MGTs.

Enhancement of Satellite Cell Transplantation Efficiency by Leukemia Inhibitory Factor.

BACKGROUND AND OBJECTIVES: Cell transplantation is a promising therapy for several muscle diseases, including Duchenne muscular dystrophy. Satellite cells are stem cells in skeletal muscle that provide an important cell source for transplantation therapy. However, culture of satellite cells in vitro causes them to lose their undifferentiated state, associated with reduced transplantation efficiency. It is therefore necessary to develop optimal culture conditions for maintaining the undifferentiated state of satellite cells. METHODS: Primary satellite cells were cultured with or without leukemia inhibitory factor (LIF). The expression of undifferentiation and differentiation markers, and the transplantation efficiency were analyzed. RESULTS: LIF-treated satellite cells showed increased expression of Pax7, and enhanced transplantation efficiency in a mouse model of Duchenne muscular dystrophy. CONCLUSIONS: Our study showed that the treatment with LIF effectively maintained the undifferentiated state of satellite cells, and enhanced their transplantation efficiency. These results will contribute to the optimization of culture conditions for cell transplantation therapy.

Histological evaluation of skeletonized internal thoracic artery using ForceTriad™.

BACKGROUND: The internal thoracic artery (ITA) is a useful graft for coronary artery bypass grafting. Skeletonization, a technique that uses an ultrasonic scalpel, is increasingly used. However, the cost of an ultrasonic scalpel is extremely high. The purpose of this study was to determine whether a new electrosurgical cautery device (ForceTriad™) is as effective as an ultrasonic scalpel. METHODS: Bilateral ITAs were harvested from eight pigs using the skeletonizing technique. The ITA on one side was harvested with an ultrasonic scalpel and on the other side using the ForceTriad™. Macroscopic and histological examinations were performed in sixteen ITAs. RESULTS: No significant differences in the time required for harvesting were observed. The macroscopic findings revealed no significant change in any of the samples. The histological findings showed that the degree of thermal injury was similar. The normal structure was maintained in all samples. The ForceTriad™ costs US$ 226.82 less per patient than the ultrasonic scalpel. CONCLUSION: The new electrosurgical cautery device ForceTriad™ was less expensive, but it was equally effective. It appears that skeletonization performed with the new device is equivalent to that performed with an ultrasonic scalpel.

Multifocal granulomatous jejunitis associated with an argyrophilic gram-positive segmented filamentous bacterium in a Holstein cow.

Multifocal, raised, ulcerated firm nodules accompanied by an intussuscepted area were detected in the jejunum of an 8-year-old Holstein cow. The cut surfaces of the nodules were yellow-white. Microscopically, the lamina propria was expanded by an intense infiltration of epithelioid cells, multinucleate giant cells, macrophages, lymphocytes and neutrophils. Numerous bacteria were found within the granulomatous lesions. These were argyrophilic, gram-positive, periodic acid-Schiff-positive, segmented, rarely branched, elongate filamentous bacteria (2-28 µm in length, 0.2-0.35 µm in diameter). Ultrastructurally, a cell wall with an electron-transparent zone was detected. The present pathogen was clearly different from the argyrophilic, gram-negative, non-segmented, filamentous bacterium previously reported in a Holstein cow with jejunal granuloma. Comparative 16S rDNA gene sequencing analysis revealed that the organism was an unpublished species (GenBank accession number AB539875). This is the first report of bovine jejunal granuloma associated with an argyrophilic gram-positive segmented filamentous bacterium.

Serum factors that suppress cytotoxic effect of methotrexate.

AIM: To study the phenomenon that human erythroid leukemia K-562 cells are more sensitive to cytotoxic effect of antimetabolites when cultured in a serum-free medium than in a conventional medium containing fetal calf serum (FCS). METHODS: Cytotoxic effects of methotrexate, azaserine and 5-fluorouracil were estimated by accessing the lactate dehydrogenase (LDH) activity of viable tumor cells. Proteins of FCS were separated using two-dimensional electrophoresis followed by mass spectrometry analysis. RESULTS: Addition of 10% FCS attenuated anti-tumor activity of methotrexate and azaserine against K-562 cells compared with serum-free medium. Such an activity of FCS was different for each serum lot. Comparison of the proteins in active serum lot with those in not active one using two-dimensional electrophoresis showed that in the active serum there were proteins 150 kDa, which were absent in the not active serum lot. Mass spectrometry indicated that all those proteins had the amino acid sequence of albumin. Sera of one healthy volunteer and two patients with thyroid cancer also attenuated the activity of the agent. CONCLUSION: Several lots of FCS and human serum demonstrated the ability to attenuate the cytotoxic effect of methotrexate in vitro, possibly due to the formation of albumin dimers/MTX complexes.

In vivo anti-tumor activities of gelatin.

AIM: As reported previously, porcine skin gelatin exerted direct anti-tumor effect in vitro and induced anti-tumor peritoneal macrophages in vitro. The present study investigated whether or not the gelatin exerted anti-tumor effect in vivo. METHODS: In vitro anti-tumor activities of peritoneal macrophages and the gelatin were evaluated with tritium thymidine uptake by target tumor cells. In vivo anti-tumor activity was evaluated with the survival of tumor-bearing animals and the size of the tumor. RESULTS: Intraperitoneal daily administration of 12.5 mg of the gelatin prolonged the survival of mice which had been intraperitoneally inoculated with MH134 (hepatic cell carcinoma cell line) or Colon 26 (colon carcinoma cell line) tumor cells, and there were no tumors in case of MH134 cells inoculation. Intraperitoneal daily administration of 12.5 mg of the gelatin did not affect growth of subcutaneous MH134 tumor. The gelatin administered subcutaneously did not affect the survival of mice with intraperitoneal MH134 tumor. On the other hand, bovine skin gelatin administered subcutaneously achieved statistically significant prolongation of the survival. The contact of MH134 cells with porcine skin gelatin for 5 min was required for the gelatin to exert its anti-tumor activity in vitro. Porcine skin gelatin of 12.5 mg injected intraperitoneally was detected as protein in the peritoneal cavity 5 min after the injection. Peritoneal macrophages elicited by intraperitoneal injection with porcine skin gelatin suppressed tritium thymidine uptake by MH134 cells more strongly than those elicited by thioglycollate injection. CONCLUSION: Porcine skin gelatin administered intraperitoneally prolonged the survival of tumor-bearing mice via activation of peritoneal macrophages and involvement of direct anti-tumor activity of porcine skin gelatin. Key Words: porcine skin, gelatin, dissemination.

[Aprotinin reduces bleeding during off-pump coronary artery bypass grafting in a patient on ticlopidine; report of a case].

A 65-year-old man was admitted to a local hospital with symptoms of unstable angina pectoris. He was administered ticlopidine before drug eluting stent (DES) stenting for 2 weeks. Coronary angiography showed 3 vessel diseases. He was then admitted to our hospital due to a sudden onset of unstable angina following shock during the percutaneous coronary intervention (PCI) procedure, emergency off-pump coronary artery bypass grafting (OPCAB) was thus performed. He received aprotinin 5 hundred thousand KIU just at the start of surgery and 5 hundred thousand KIU after undergoing anastomosis of the coronary artery. Postoperatively, only some minor bleeding was observed. Aprotinin reduces bleeding, the transfusion requirements of packed red blood cells, platelets, and the total blood units in patients on ticlopidine who undergo emergency OPCAB.

Genetic analysis of multifocal superficial urothelial cancers by array-based comparative genomic hybridisation.

The purpose of this study was to investigate the accumulation of genetic alterations during metachronous and/or synchronous development of multifocal low-grade superficial urothelial tumours in the same patient, by using array-based comparative genomic hybridisation (array-CGH) and FGFR mutation analysis. We analysed 24 tumours (pTa-1 G1-2) from five patients. We had previously identified a clonal relationship among the tumours of each patient by microsatellite analysis. This time, unsupervised hierarchical cluster analysis revealed that the tumours from each patient were clustered together independently of the tumours from the other patients. All of the tumours from a single patient showed a set of 2-7 identical regional or whole-arm chromosomal changes. In addition, several individual alterations were also found. Cladistic diagrams revealed that the accumulation of genetic alterations could not be explained by a linear model, and the existence of a hypothetical precursor cell was assumed in four patients. In some cases, FGFR mutation seemed to occur later during multifocal tumour development. Taken together, these findings suggest that low-grade superficial urothelial tumours accumulate minor genetic alterations during multifocal development, although these tumours are genetically stable.

Primary oral KIT-positive tumour consistent with gastrointestinal stromal tumour.

Gastrointestinal stromal tumours are characteristically positive for KIT (reflective of the c-KIT gene). A case is reported of an apparent rapidly growing gastrointestinal stromal tumour, which arose in the floor of the mouth and metastasized to the left neck without evidence of disease elsewhere.