A double-blind dose-ranging study of risedronate in Japanese patients with osteoporosis (a study by the Risedronate Late Phase II Research Group)

To determine the clinical recommended dosage regimen of risedronate for the treatment of involutional osteoporosis in Japanese patients, dose-response relationships for the efficacy and safety of this drug were investigated using a multi-center, randomized, double-blind, parallel group comparative design with four dose levels of risedronate (placebo, 1 mg, 2.5 mg and 5 mg per day). A total of 211 patients diagnosed with involutional osteoporosis according to the criteria proposed by the Japanese Society for Bone and Mineral Research were randomized and received one of the four doses once daily for 36 weeks. All patients were supplemented with 200 mg of calcium daily in the form of calcium lactate. The primary efficacy endpoint was the percent change in bone mineral density of the lumbar spine (L2-L4 BMD) determined by dual-energy X-ray absorptiometry (DXA) from baseline to the time of final evaluation. Changes in biochemical markers of bone turnover and safety profile were also compared. Percent changes in L2-L4 BMD at final evaluation in the placebo, and 1-, 2.5-, and 5-mg risedronate groups were 0.79+/-5.30, 2.71+/-4.93, 5.29+/-3.96, and 5.15+/-4.25% (mean+/-SD), respectively. A linear dose-response relationship was obtained up to a dose of 2.5 mg, whereas no further increase in BMD was observed at 5 mg. The decrease in bone turnover markers, including N-terminal osteocalcin, phosphorus, and urinary deoxypyridinoline, also showed a linear dose-response relationship up to a dose of 2.5 mg. Alkaline phosphatase level decreased linearly up to a dose of 5 mg. Risedronate was well tolerated in this 36-week study with 1- to 5-mg doses. Neither the overall incidence of adverse events nor the percentage of patients without problem in overall safety assessment differed significantly among the dose groups including the placebo group. Based on these results, a once-daily dose of 2.5 mg of risedronate, which is half that used in Caucasians, is recommended for the treatment of involutional osteoporosis in Japanese patients.     

Effect of epidermal growth factor on cadherin-mediated adhesion in a human oesophageal cancer cell line.

Epidermal growth factor (EGF) mediates many pleiotrophic biological effects, one of which is alteration of cellular morphology. In the present study, we examine the possibility that this alteration in cell morphology is caused in part by the dysfunction of cadherin-mediated cell-cell adhesion using the human oesophageal cancer cell line TE-2R, which expresses E-cadherin and EGF receptor. In the presence of EGF, TE-2R changed its shape from round to fibroblastic and its colony formation from compact to sparse. Vanadate, a tyrosine phosphatase inhibitor, further potentiated the EGF response, whereas herbimycin A, a tyrosine kinase inhibitor, interfered with it. Moreover, EGF enabled the cells to invade in organotypic raft culture. These phenomena were accompanied not by decreased expression of the E-cadherin molecule but by a change in its localisation from the lateral adhesion site to the whole cell surface. Both alpha- and beta-catenin, cadherin-binding proteins, were also expressed at the same level throughout these morphological changes. Finally, we examined tyrosine phosphorylation of E-cadherin and alpha- and beta-catenin, and observed tyrosine phosphorylation of beta-catenin induced by EGF. These results suggest that EGF counteracts E-cadherin-mediated junctional assembly through phosphorylation of beta-catenin and modulates tumour cell behaviour to a more aggressive phenotype.     

Antiinflammatory properties of the new antirheumatic agent 4-acetylaminophenylacetic acid

The antiinflammatory activity of 4-acetylaminophenylacetic acid (MS-932) was investigated. MS-932 did not suppress the acute inflammation of carrageenin-induced paw edema in rats or of primary swelling in adjuvant arthritic rats. However, prophylactic treatment with MS-932 inhibited secondary inflammation in adjuvant arthritic rats. MS-932 also restored to normal the weight of the spleen and the serum albumin/globulin ratio of adjuvant arthritic rats. In addition to its prophylactic effect, MS-932 had a therapeutic effect on adjuvant arthritis. In in vitro tests, MS-932 did not inhibit prostaglandin E2 biosynthesis from arachidonic acid by sheep seminal vesicle microsomal enzyme or superoxide generation by guinea pig neutrophils stimulated with opsonized zymosan. MS-932 had no analgesic effect in mice and no antipyretic effect in rats. These results indicate that MS-932 suppresses adjuvant arthritis through modulation of the immune system.     

Associations of brachial-ankle pulse wave velocity and carotid atherosclerotic lesions with silent cerebral lesions.

Silent cerebral lesions are increasingly found in mass screenings using MRI and magnetic resonance angiography (MRA). The purpose of this paper is to assess the usefulness of two non-invasive clinical tests-carotid ultrasound examination and brachial-ankle pulse wave velocity (baPWV) measurement-for predicting silent cerebral infarction (SCI) and silent intracranial arterial stenosis. Data were collected on 480 asymptomatic adult subjects who participated in a brain screening program at a single hospital between April 2003 and March 2006. All participants underwent baPWV measurement, B-mode ultrasonography of carotid arteries, MRI, and MRA. Data on 476 (99.1%) subjects were included in the analysis. Among these, 273 (57.4%) were male and the mean age was 51.5 years; 161 (33.8%) had carotid plaque; 33 (6.9%) had increased intima-media thickness (IMT); 99 (20.8%) had SCI; and 7 (1.5%) had intracranial arterial stenosis. The multivariate analysis showed that age (odds ratio [OR]: 1.12; 95% confidence interval [CI]: 1.08-1.17), carotid plaque (OR: 2.69; 1.59-4.56), increased IMT (OR: 2.40; 1.02-5.65), and a history of hypertension treatment (OR 2.22; 1.11-4.43) were significantly associated with SCI. Also, increased IMT (OR 9.70: 1.48-63.71) was related to intracranial arterial stenosis. Brachial-ankle PWV was related to SCI (p<0.01) and intracranial stenosis (p=0.01) in univariate analysis but not in multivariate analysis. The presence of carotid plaque and that of increased IMT on ultrasound examination are useful for assessing the risk of SIC. Increased IMT is also predictive of intracranial arterial stenosis.     

The long-term results of meniscus transplantation for articular cartilage defects in the knee joint

The purpose of this study was to examine the long-term clinical results of meniscus transplantation for articular cartilage defects in the knee joint. The type of study was case series. From October 1990 to June 1995, eight cases underwent allogenic or autogenic meniscus transplantations for articular cartilage defects, and seven cases were available for follow-up evaluations. The age at surgery ranged from 14 to 42 years of age (average 22.5). In one case, transplantation of tissue-engineered cartilage was performed due to pain 5 years after surgery. The other six cases were followed up for 8–13 years (average 10.1). The size of the cartilage defect ranged from 1.0 to 6.3 cm² (average 2.8 cm²). Patients were evaluated with the Lysholm score and MR images. We also performed arthroscopic examinations in three cases at the final evaluation. This study leads to the conclusion that meniscus transplantation for articular cartilage damage is not comparable to autologous chondrocyte transplantation. Two cases showed a good clinical outcome but the tissue remained as fibrocartilage tissue in the long-term.     

Results of low- and high-dose-rate interstitial brachytherapy for T3 mobile tongue cancer.

PURPOSE: To evaluate the treatment results of low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy (ISBT) for T3 mobile tongue cancer. MATERIAL AND METHODS: Between 1974 and 1992, 61 patients with T3 mobile tongue cancer were treated with LDR ISBT using (192)Ir hairpins with or without single pins. In addition, between 1991 and 1999, 14 patients were treated with HDR ISBT. For nine patients treated with ISBT alone, the total dose was 59-94 Gy (median 72 Gy) within one week in LDR ISBT and 60 Gy/10 fractions/5 days in HDR ISBT. For 66 patients treated with a combination therapy of external beam radiotherapy (EBRT) and ISBT, the total dose was 12.5-60 Gy (median 30 Gy) of EBRT and 50-112 Gy (median 68 Gy) within 1 week in LDR ISBT or 32-60 Gy (median 48 Gy)/8-10 fractions/5-7 days in HDR ISBT. RESULTS: The 2- and 3-year local control rates of all patients were both 68%. The 2- and 3-year local control rates of patients treated with LDR ISBT were both 67%, and those with HDR ISBT were both 71%. The local control rate of patients treated with HDR ISBT was similar to those with LDR ISBT. CONCLUSIONS: ISBT for T3 mobile tongue cancer is effective and acceptable. The treatment result of HDR ISBT is almost similar to that of LDR ISBT for T3 mobile tongue cancer.     

Impaired cardiovascular autonomic function in Parkinson's disease with visual hallucinations.

We assessed the relations of visual hallucinations (VH) to cardiovascular autonomic dysfunction in patients with Parkinson's disease (PD). The subjects were 37 patients without VH (VH(-)) and 31 with VH (VH(+)). Autonomic function was evaluated on the basis of cardiac 123-radioiodinated metaiodobenzylguanidine (123I-MIBG) uptake and hemodynamic testing with Valsalva maneuver. Systolic blood pressure (SBP) and plasma norepinephrine concentrations (NE) were measured by tilt-table testing. 123I-MIBG uptake was lower in VH(+) than VH(-). Hemodynamic studies showed that VH(-) had only cardiac sympathetic and parasympathetic dysfunction, while VH(+) additionally had reduced vasomotor sympathetic functions. The fall in SBP during tilt-table testing was greater in VH(+) than VH(-). NE and its difference in the supine and upright positions were decreased in VH(+). We conclude that cardiac and vasomotor sympathetic dysfunction is more severe in VH(+) than in VH(-). Severe dysfunction in PD with VH is probably attributed to Lewy-body lesions or neuronal loss in sympathetic ganglia, the central autonomic system, or both.     

Bilateral symmetric tonic posturing suggesting propagation to the supplementary motor area in a patient with precuneate cortical dysplasia.

We report a patient manifesting seizures with bilateral symmetric tonic posturing, which were markedly reduced after resection of the left precuneus. A 16-year-old man had sudden onset, complex partial seizures with bilateral symmetric tonic posturing since the age of eight years. Magnetic resonance fluid-attenuated inversion-recovery imaging revealed a hyperintense lesion in left precuneus. In almost all focal seizures recorded during an invasive EEG evaluation, ictal onset was detected from the inferomesial aspect of the lesion, but fast paroxysmal discharges from the ipsilateral supplementary motor area (SMA) were observed just before the clinical onset. After surgical excision of the EEG onset zone, including the lesion, seizure frequency was markedly (> 95%) reduced. By the 20th month after surgery, there were only brief nocturnal seizures involving slight elevation of both shoulders and slight abduction of both arms, with preservation of consciousness occurring once every few days. Invasive EEG findings and surgical outcome suggested that the epileptic activity originating from the epileptogenic zone may have propagated to the symptomatogenic zone including mainly the ipsilateral SMA. In summary, we report an interesting case of bilateral symmetric tonic posturing suggesting propagation to the SMA. MRI and invasive EEG confirmed the epileptogenic focus as a precuneate cortical dysplasia lesion.[Published with video sequences].     

STANDARD IMAGING TECHNIQUES OF ENDOSCOPIC ULTRASOUND‐GUIDED FINE‐NEEDLE ASPIRATION USING A CURVED LINEAR ARRAY ECHOENDOSCOPE

Standard imaging techniques using a curved linear array echoendocope are summarized to facilitate the attainment of expertise in endoscopic ultrasonography and endoscopic ultrasound‐guided fine needle aspiration, and to promote the widespread use of this diagnostic and therapeutic tool. Typical images of the mediastinal organs, the bilio‐pancreatic systems and neighboring organs by scanning from the esophagus, stomach, duodenal bulb, and descending portion of the duodenum, are shown in a sequential manner. The basic techniques of endoscopic ultrasound‐guided fine needle aspiration are also presented.     

Metastatic penile tumor from lower pharynx: a case report

Metastatic tumor of the penis is uncommon and only 95 cases have been reported in Japan. A 70-year-old man, who had squamous cell carcinoma of the lower pharynx, complained of urethral induration. Biopsy was performed and pathological diagnosis was metastatic tumor of penis originating from the lower pharynx. Although partial response in tumor size was noted by irradiation therapy, the patient died of multiple metastases in the 4th month after the diagnosis. This case is the first report of metastatic penile tumor originating from the lower pharynx.