Plasma phylloquinone, menaquinone-4 and menaquinone-7 levels and coronary artery calcification.

Vitamin K is considered to be involved in the pathological mechanisms of coronary artery calcification (CAC). Correlation between CAC and plasma vitamin K levels was studied. A total of 103 patients, with at least one coronary risk factor, were studied. CAC was measured using 64-slice multislice computed tomography (MSCT) and divided into three groups: none (CAC score = 0; n 25), mild to moderate (0 < CAC score < 400; n 52) and severe (CAC score > 400; n 26). Phylloquinone (PK) and menaquinone (MK)-4 and MK-7 were measured by HPLC-tandem MS. Mean age of patients was 64 (sd 13) years, of which 57 % were male. Median CAC score was 57·2. Median levels of PK, MK-4 and MK-7 were 1·33, 0 and 6·99 ng/ml, showing that MK-7 was the dominant vitamin K in this population. MK-7 showed a significant inverse correlation with uncarboxylated osteocalcin (ucOC, P = 0·014), protein induced by vitamin K absence of antagonist-2 (PIVKA-2, P = 0·013), intact parathyroid hormone (P = 0·007) and bone-specific alkaline phosphatase (P = 0·018). CAC showed an inverse correlation with total circulating uncarboxylated matrix Gla protein (t-ucMGP, P = 0·018) and Hb (P = 0·05), and a positive correlation with age (P < 0·001), creatinine, collagen type 1 cross-linked N-terminal telopeptide (NTX, P = 0·03), pulse wave velocity (P < 0·001) and osteoprotegerin (P < 0·001). However, CAC did not have a significant correlation with plasma levels of PK, MK-4 or MK-7. In conclusion, plasma MK-7, MK-4 or PK level did not show significant correlation with CAC despite the association between plasma vitamin K levels and vitamin K-dependent proteins such as ucOC or PIVKA-2.

Zygoma implant-supported prosthetic rehabilitation of a patient with a maxillary defect.

This clinical report describes the successful management of a patient who underwent extensive resection of a maxillary cancer, by introduction of a maxillary obturator prosthesis using zygoma implants. The patient was a 57-year-old man with cancer of the upper anterior gingiva. The maxillary bone in the affected region had been extensively excised by radical surgery. Owing to loss of teeth retaining the denture, the existing prosthesis was unstable, and the patient experienced severe speech and mastication disorders. Four zygoma implants (two on each side), and two conventional dental implants (one each at both maxillary tuberosities) were used as denture retainers. The obturator prosthesis was stabilized by the implants, and the patient's oral function improved. High-level compatibility between the implant and surrounding tissue was obtained by mucosal regeneration around the implant. The results suggest that the combination of zygoma and conventional dental implants improves postoperative oral function by facilitating retention of the obturator prostheses.

Friend leukaemia insertion (Fli)-1 is a prediction marker candidate for radiotherapy resistant oral squamous cell carcinoma.

Radiotherapy is commonly used to treat oral squamous cell carcinoma (OSCC), but its therapeutic effects are unpredictable. To determine which genes correlate with radiation resistance in oral cancer, the authors evaluated radiation sensitivity using a standard colony formation assay with a gene microarray system for seven OSCC cell lines. They found significant associations between dozens of gene-expression levels and radiation resistance of OSCC cell lines. Following analysis of the different radiosensitive cancer cell lines, the friend leukaemia insertion (Fli)-1 gene was selected as a prediction marker gene for OSCC radiotherapy resistance. Fli-1 expression was associated with radiation resistance in OSCC patients. These data help to predict the effects radiation therapy has on OSCC, in turn contributing to the development of alternative radiation therapies.

Identification of a truncated cystatin SA-I as a saliva biomarker for oral squamous cell carcinoma using the SELDI ProteinChip platform.

New and more consistent biomarkers of oral squamous cell carcinoma (OSCC) are needed to improve early detection of the disease and to monitor patient management. The aim of this study was to detect new OSCC tumor markers in saliva. Unstimulated saliva, collected from patients with primary stage I OSCC as matched pre-and post-treatment samples, was used in the analysis. A surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF) ProteinChip system was used to screen for differentially expressed proteins in the saliva samples. This analysis revealed 26 proteins with significantly different expression levels in the pre-and post-treatment samples (P<0.05). A 14 kDa protein detected in pre-treatment saliva from the OSCC patients was identified as a truncated cystatin SA-I, with deletion of three amino acids from the N-terminus. The authors propose that ProteinChip analysis may provide a reliable screening test for early diagnosis of OSCC and that truncated cystatin SA-I might be a useful tumor biomarker for OSCC.

Radiological and histological features of tumoral calcinosis of the dorsum of the foot.

Tumoral calcinosis is a rare condition characterized by large calcific masses occurring predominantly in the juxta-articular regions of the extremities. To our knowledge, occurrences in the foot, particularly in association with bone erosion, have been very rare. A 52-year-old Japanese man presented with a mass in the foot, the size of which increased over a period of 27 years. CT scan and MRI demonstrated a 6 cm x 3 cm x 2.5 cm sized mass. There was bone erosion of the dorsal side of the third metatarsal head. Marginal excision was made. Histopathologically, the mass was composed of amorphous calcification with inflammatory cell infiltration. X-ray diffraction method revealed that the pattern of the mass coincided with hydroxyapatite. The patients had no local recurrence at 5 years after operation.

Comparison of methods to stimulate ovarian follicular growth in cynomolgus and African green monkeys for collection of mature oocytes.

The objective was to compare various gonadotropin-based methods to stimulate ovarian follicular growth in female cynomolgus (n=16) and African green monkeys (n=8) for collection of mature oocytes. On the 1st day of menstruation, the monkeys were treated with 3.75 mg leuprorelin acetate (a GnRH agonist). Starting 2-3 weeks later, ovarian follicular growth was stimulated as follows: (a) 25 IU/kg of human FSH (hFSH) in a glycerol solution given once daily for 9 d; (b) 200 IU of eCG given six times during a 9-d interval; (c) 75 IU/kg hFSH in a glycerol solution given three times (72 h intervals) during a 6-d interval. In addition, the monkeys were given 1200 or 4000 IU of hCG 36 h (Methods A and B) or 60 h (Method C) after the last gonadotropin treatment, and oocyte collection was attempted 36-38 h after hCG. Although there were no significant differences among methods in the number of oocytes collected, in cynomolgus monkeys, hFSH (Methods A and C) was better than eCG (Method B; 12 and 10 versus 7 mature oocytes, respectively), whereas in African green monkeys, eCG (Method B) was more effective than hFSH (Method A; 12 versus 7 mature oocytes). Furthermore, in cynomolgus monkeys, Method C was nearly as effective as Method A; using a glycerol solution as a solvent decreased the frequency of hFSH administration from nine to three times. In conclusion, in cynomolgus and African green monkeys, ovarian response depended on the species and on the individual, and in cynomolgus monkeys, hFSH in a glycerol solvent was effective.

Inguinal endometriosis attaching to the round ligament.

We report a case of endometriosis in the right inguinal region, attached to the right round ligament in a 28-year-old woman. At the age of 20, laparoscopic left ovarian cystectomy and pelvic adhesiolysis for endometriosis was carried out. She noticed a right tender groin mass 7 months previously, and the tumour size fluctuated with the menstrual cycle. A poorly circumscribed elastic hard mass, measuring 3 cm in diameter, was palpated in her right inguinal region. Magnetic resonance imaging showed a 2.5 cm x 2.5 cm mass in the right inguinal canal and a 5.4 cm x 6.8 cm mass was seen in the left ovary. The mass enlarged during menstruation. The groin mass was removed, in addition to carrying out laparoscopic ovarian cystectomy. At operation, the groin mass was found to be in continuity with the round ligament of extraperitoneal portion. Histological diagnosis of endometriosis was made in both ovarian and inguinal tumours. After surgery, the pain disappeared completely. Worth mentioning is that MRI clearly showed the change of tumour size depending on the menstrual cycle, which aided in arriving at the correct diagnosis of endometriosis in an unusual location.

Ossification of the Achilles tendon--a case report.

Ossification of the Achilles tendon is a very unusual condition. We report a case with bilateral Achilles tendon ossification followed up for twelve years, treated twice surgically on the left side and conservatively on the right side. At the age of 51, the patient's plain radiogram showed bilateral ossifications of the Achilles tendon (right 55 mm, left 15 mm in length). The left side small mass was removed. The right side mass was decided to be followed up because of its large size. At the age of 61, ossification recurred on the left side. Conservative treatment with etidronate disodium for two years failed to prevent ossification from progressing. At the age of 63, the mass on the right and left sides increased to 70 mm and 45 mm in length, respectively. The mass of the left side was excised again, and dull pain disappeared postoperatively on the left side.

Pilot study of the optimum hematocrit for patients in the predialysis stage after renal transplantation.

Anemia is a common complication in patients with chronic kidney diseases including posttransplant patients. Guidelines for the treatment of anemia in chronic kidney disease published by NHF-K/DOQI recommend the target hemoglobin and hematocrit (Hb and Ht) levels to be in the 11 to 12 g/dL and 33% to 36% ranges, respectively, which are somewhat higher than those recommended in Japan (Ht = 30%). However, these guidelines were established mainly from the data on hemodialysis patients with only limited information available as to the impact of anemia control in posttransplant patients. The aim of the present study was to evaluate cardiac function and quality of life (QOL) when the Ht was raised to about 36% by administration of recombinant-human-erythropoietin (rHuEPO) to patients with mild impairment of renal function (s-Cre < 2.0 mg/dL) after renal transplantation. Twenty-five patients were analyzed for cardiac function, blood data, and QOL in a prospective study encompassing 8 months of rHuEPO treatment. Using a once weekly subcutaneous dose of 6000 IU of Epoetin-beta, the Ht became 33% to 36% and Hb was 11 to 12 g/dL. Among the cardiac function tests, left ventricular end-diastolic diameter and left ventricular mass index decreased significantly. QOL did not show any significant changes after administration of rHuEPO. In conclusion, we demonstrated a potential benefit of using rHuEPO to maintain the Hb between 11 and 12 g/dL and the Ht between 33% and 36% in posttransplant patients with regard to the prevention of cardiovascular complications. Further study is required to establish the benefits of correcting anemia by rHuEPO on the outcome of posttransplant patients.

A case of inguinal endometriosis with difficulty in preoperative diagnosis.

An unusual case of endometriosis involving the right round ligament in a 40-year-old woman is presented. After giving birth to two children, she first noticed a tender mass in the right groin at the age of 36. It didn't change in size but pain appeared at the age of 38, disturbing her daily life. A poorly circumscribed elastic hard mass, measuring 3 cm in diameter, was palpable in her right inguinal region. Magnetic resonance imaging demonstrated a 2x3 cm mass in the right inguinal canal. At operation, a mass was found to be in continuity with the round ligament at the inguinal canal. Histological diagnosis was endometriosis. After operation, she was completely relieved of pain. It is important to include endometriosis in the differential diagnosis for painful inguinal masses in women of childbearing age.

Glomus tumors with cystic changes around the ankle.

Sizable glomus tumors with cystic changes in the ankle are extremely uncommon. This paper describes painless glomus tumors with cystic changes arising in the ankle of a 22-year-old woman. At the age of 14, a painless mass was noticed on the lateral side of the left ankle, and at age 21, another mass appeared on the medial side of the same ankle. Magnetic resonance imaging (MRI) and computed tomography (CT) scanning revealed 4.5 x 4.0 cm and 2.0 x 2.0 cm sized masses on the medial side and a 3.0 x 4.0 cm sized cystic mass on the lateral side of the ankle. The tumors were removed en bloc. Microscopically, the tumor consisted of perivascularly arranged cells with punched-out, round, and regular nuclei. Immunohistochemically, the tumor cells expressed SMA and HHF-35, indicating smooth muscle cell characters. The patient had no recurrence at 2 years after surgery.

Primary leiomyosarcoma with the invasion into the intertrabecular space of bone: a case report and the review of the literatures.

Primary leiomyosarcoma of bone is very rare. Most of reported cases were osteolytic. We report a primary leiomyosarcoma arising from the neck of the femur of a 43-year-old woman who had no remarkable abnormalities on plain radiographs. Magnetic resonance imaging (MRI) clearly depicted the lesion. Biopsy revealed it leiomyosarcoma. Gynecological and gastrointestinal examinations ruled out metastatic leiomyosarcoma. Wide excision of the tumor was performed and followed by endoprosthetic replacement of the proximal femur. Microscopic examination revealed tumor cells infiltrating into the intertrabecular space.

Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine or tacrolimus.

Hyperlipidemia is frequently developed following renal transplantation and results in worsening of the patient's prognosis. In study 1, the effects of immunosuppressants, cyclosporine (CsA) and tacrolimus on serum lipids were compared in-patients undergoing renal transplantation. The study included 32 cases of renal transplantation recipients who randomized to the CsA treatment group (15 patients) and the tacrolimus group (17 patients). Before and 1 month after the transplantation, we assessed the serum lipid levels, apolipoprotein levels, the concentrations of cholesterol in the respective lipoprotein fractions and the enzyme activities related to lipid-metabolism. The serum lipid levels in both groups were significantly increased at 1 month after renal transplantation. In the CsA group, there were significant increases in cholesterol contents in very-low-density lipoprotein (VLDL), LDL2 and HDL2 fractions, whereas, in the tacrolimus group, cholesterol content was increased in VLDL and HDL2 fractions. In study 2, 1 month after renal transplantation, 19 patients with hypercholesterolemia (total cholesterol (TC) >200 mg/dl) and hypertriglyceridemia (triglyceride (TG) >150 mg/dl) were treated with simvastatin 5-10 mg/day for 6 months. Simvastatin treatment significantly decreased serum TC (240+/-29-200+/-22 mg/dl, P<0.001), low-density lipoprotein cholesterol (LDL-C; 114+/-20-99+/-17 mg/dl, P<0.05) and TG levels (217+/-103-130+/-38 mg/dl, P<0.01). In addition, there were significant decreases in very-low-density lipoprotein cholesterol (VLDL-C; 53+/-20-34+/-15 mg/dl, P<0.001). The Cmax and AUC of simvastatin were increased about eight-fold, when simvastatin was given in combination with CsA. In contrast, no significant changes in simvastatin levels were observed when combination with tacrolimus. Although simvastatin levels were increased with CsA, there were no abnormal changes in renal and liver functions, creatinine phosphokinase (CPK) levels or in incidence of adverse effects.

Imaging features of intraosseous lipomas of the calcaneus.

We report two cases of intraosseous lipoma arising in the calcaneus of a 36-year-old and a 22-year-old women complaining of heel pain. Plain radiographs and computed tomography scans revealed cystic lesions in the calcaneus triangle. On magnetic resonance images, the lesions had high signal intensities on both T1-weighted and T2-weighted images, corresponding to adipose tissue. Histological examination revealed mature fat cells with small bone fragments. Curettage and bone grafting were performed. There was no recurrence identified on plain radiographs 2 years following the surgery.

Inhibitors of cyclooxygenase-2 (COX-2) suppressed the proliferation and differentiation of human leukaemia cell lines.

Prostaglandins (PG) are known to play important roles in the proliferation and differentiation of leukaemia cells. The effect of the inhibitors of cyclooxygenase-2 (COX-2), a rate-limiting enzyme for the synthesis of PG, on the proliferation and differentiation of leukaemia cell lines was investigated. COX-2 inhibitors, NS-398 and nabumetone, suppressed the proliferation of U-937 and ML-1 cells by inducing a G0/G1 cell-cycle arrest. Cell-cycle arrest induced by these COX-2 inhibitors was not associated with an upregulation of the cyclin-dependent kinase inhibitors. COX-2 inhibitors also inhibited the differentiation of these cells induced by interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha) and retinoic acid (RA). Treatment with NS-398 did not suppress the levels of PGs produced by these cells. Although COX-2 antisense oligonucleotide showed a similar inhibitory effect on these cells, its inhibitory effect was smaller than that of NS-398. These results suggest that COX-2 inhibitors may suppress the proliferation and differentiation of leukaemia cells both via COX-2-dependent and -independent pathways.

Specific inhibition of cyclooxygenase-2 results in inhibition of proliferation of oral cancer cell lines via suppression of prostaglandin E2 production.

Prostaglandins (PGs) are known to play important roles in the proliferation of various types of cancer cells. PGs are produced by the action of cyclooxygenase (COX) enzymes, and two forms of COX, COX-1 and COX-2, have been described. Previous studies have demonstrated that overexpression of COX-2 is associated with colon carcinogenesis, tumor invasion and metastatic potential of colon cancer. In this study, the role of COX-2 on proliferation of squamous cell carcinoma cell lines was investigated. NS-398, a selective COX-2 inhibitor, inhibited proliferation of NA cells, a squamous cell caricinoma cell line that constitutively expresses COX-2 mRNA. NS-398 suppressed the spontaneous production of PGE2 by NA cells, and the antiproliferative effect of NS-398 was abolished by addition of PGE2. Similar results were obtained from experiments using COX-2 antisense oligonucleotide. These results suggest that specific inhibition of COX-2 inhibits proliferation of cancer cells expressing COX-2 mRNA via suppression of PGE2 production.

Extraskeletal osteosarcoma arising in the buttock.

Extraskeletal osteosarcoma is a rare sarcoma that accounts for about 1% of malignant soft tissue tumours. We report an very unusual case of a small-size extraskeletal osteosarcoma arising in the superficial subcutaneous region of the buttock. The patient was a 55 year-old female. She incidentally noticed a small nodule in the right trochanteric region. It was removed under local anesthesia at a private clinic. An additional wide excision was performed at our hospital. There was an 8 mm? 10 mm mass in the subcutaneous tissue. No invasion of the underlying fascia was observed. Microscopic examination of the removed tumour showed bizarre-looking spindle and giant cells with lace-like osteoid. The tumour was diagnosed as extraskeletal osteosarcoma. Chemotherapy with Rosen T-20 was administered to the patient. The patient has survived without recurrence or metastasis for 4 years since the primary surgery. Its superficial location, very small size, wide excision, and chemotherapy were thought to contribute to her long survival.

Periosteal Ewing's sarcoma: radiological imaging and histological features.

Periosteal Ewing's sarcoma is very rare. In this report, we describe three cases of periosteal Ewing's sarcoma, illustrating the principal clinical, radiographic, and histologic features. The patients were aged 15, 16, and 20 years old, with an average of 17 years. The tumor occurred in the humerus in two and in the femur in one. Plain radiography showed a laminated periosteal reaction with a Codman's triangle over a subperiosteal soft-tissue mass or saucerization. The unusual site of Ewing's sarcoma was clearly visualized by computed tomography (CT) and magnetic resonance imaging (MRI) and confirmed by histological examination. Chemotherapy and/or irradiation was employed before and after wide excision. The patients have survived an average of 6 years after the primary surgery.

Twenty-six-years' survival with multiple bone metastasis of malignant pheochromocytoma.

The prognosis of metastatic pheochromocytoma is poor in general. There have been few instances of long-term survival reported. We report a case of a 44-year-old woman who has survived for 26 years after bone metastasis. She was diagnosed as having pheochromocytoma arising in the left adrenal medulla in 1974. Metastasis of pheochromocytoma in the first and third lumbar vertebrae and the right ilium was observed at the same time. The primary lesion was removed, and posterior lumbar spinal fusion was performed for immobilization. The metastatic lesion in the ilium was left untouched. After 26 years, she is well despite a recurrence of the tumors in the skull and a new metastasis in the left abdomen.