Deficiency of insulin receptor substrate-1 impairs skeletal growth through early closure of epiphyseal cartilage.

Morphological analyses in and around the epiphyseal cartilage of mice deficient in insulin receptor substrate-1 (IRS-1) showed IRS-1 signaling to be important for skeletal growth by preventing early closure of the epiphyseal cartilage and maintaining the subsequent bone turnover at the primary spongiosa. Introduction: IRS-1 is an essential molecule for intracellular signaling by IGF-I and insulin, both of which are potent anabolic regulators of cartilage and bone metabolism. To clarify the role of IRS-1 signaling in the skeletal growth, morphological analyses were performed in and around the epiphyseal cartilage of mice deficient in IRS-1 (IRS-1(-/-)), whose limbs and trunk were 20-30% shorter than wildtype (WT) mice. MATERIALS AND METHODS: The epiphyseal cartilage and the primary spongiosa at proximal tibias of homozygous IRS-1(-/-) and WT male littermates were compared using histological, immunohistochemical, enzyme cytohistochemical, ultrastructural, and bone histomorphometrical analyses. RESULTS: In and around the WT epiphyseal cartilage, IRS-1 and insulin-like growth factor (IGF)-1 receptors were widely expressed, whereas IRS-2 was weakly localized in bone cells. Chronological observation revealed that height of the proliferative zone and the size of hypertrophic chondrocytes were decreased in WT mice as a function of age, and these decreases were accelerated in the IRS-1 (-/-) cartilage, whose findings at 12 weeks were similar to those of WT at 24 weeks. In the IRS-1(-/-) cartilage, proliferating chondrocytes with positive proliferating cell nuclear antigen (PCNA) or parathyroid hormone (PTH)/PTH-related peptide (PTHrP) receptor immunostaining had almost disappeared by 12 weeks. Contrarily, TUNEL+ apoptotic cells were increased in the hypertrophic zone, at the bottom of which most of the chondrocytes were surrounded by the calcified matrix, suggesting the closure of the cartilage. In the primary spongiosa, bone volume, alkaline phosphatase (ALP)+ osteoblasts, TRACP+ osteoclasts, and the osteopontin-positive cement line were markedly decreased. Bone histomorphometrical parameters for both bone formation and resorption were significantly lower in IRS-1(-/-) mice, indicating the suppression of bone turnover. CONCLUSION: The IRS-1(-/-) epiphyseal cartilage exhibited insufficient proliferation of chondrocytes, calcification of hypertrophic chondrocytes, acceleration of apoptosis, and early closure of the growth plate. Thus, the data strongly suggest that IRS-1 signaling is important for the skeletal growth by preventing early closure of the epiphyseal cartilage and by maintaining the subsequent bone turnover at the primary spongiosa.     

Adamantinoma of the proximal femur: a case report

Adamantinoma is a rare low-grade malignant bone tumor with an indolent course. The tibia is involved in 85%–90% of long-bone cases. We encountered a patient with primary adamantinoma of the proximal femur. A 60-year-old woman fell and fractured her proximal left femur in the area of a cystic lesion. She underwent an osteosynthesis procedure, and bone union was obtained. After 3 years she developed pain in the left thigh, and a radiographic abnormality was found at the fracture site. A metastatic bone tumor was suspected, and curettage and cementing were carried out. Histologically, we found an epithelial component but failed to detect any primary cancer. Local recurrence became evident after another 6 years. A marginal excision was performed and a bipolar femoral prosthesis was implanted. We finally diagnosed the patient with adamantinoma. In this report we describe the characteristics of this tumor and discuss the reasoning concerning the differential diagnosis and therapeutic plan.     

Effects of dominant and nondominant eyes in binocular rivalry.

PURPOSE: To investigate the relation between sighting and sensory eye dominance and attempt to quantitatively examine eye dominance using a balance technique based on binocular rivalry. METHODS: The durations of exclusive visibility of the dominant and nondominant eye target in binocular rivalry were measured in 14 subjects. The dominant eye was determined by using the hole-in-card test (sighting dominance). In study 1, contrast of the target in one eye was fixed at 100% and contrast of the target in the other eye was varied from 100% to 80% to 60% to 40% to 20%, when using rectangular gratings of 1, 2, and 4 cycles per degree (cpd) at 2 degrees, 4 degrees , and 8 degrees in size. In study 2, contrast of the target in the nondominant eye was fixed at 100% and contrast of the target in the dominant eye was varied from 100% to 80% to 60% to 40% to 20%, when using a rectangular grating of 2 cpd at 4 degrees in size. RESULTS: In study 1, the total duration of exclusive visibilities of the dominant eye target; that is, the target seen by the eye that had sighting dominance was longer compared with that of the nondominant eye target. When using rectangular gratings of 4 cpd, mean total duration of exclusive visibility of the dominant eye target was statistically longer than that of the nondominant eye target (p < 0.05). In study 2, reversals (in which duration of exclusive visibility of the nondominant eye becomes longer than the dominant eye when the contrast of the dominant eye target is decreased) were observed for all contrasts except for 100%. CONCLUSIONS: The dominant sighting eye identified by the hole-in-card test coincided with the dominant eye as determined by binocular rivalry. The contrast at which reversal occurs indicates the balance point of dominance and seems to be a useful quantitative indicator of eye dominance to clinical applications.     

ENDOSCOPIC PANCREATIC STENTING IN CHRONIC PANCREATITIS WITH DUCTAL DILATION PROXIMAL TO A STRICTURE: A SAFE and EFFECTIVE PROTOCOL

After removal of intraductal stones, a 10‐Fr or 7‐Fr pancreatic stent was placed in 16 patients with upstream ductal dilation proximal to a stricture of the main pancreatic duct. Stents were removed after a mean duration of 52.5 days. Nine patients underwent repeated stenting. About one year after removal of the initial stent, when the remaining upstream ductal dilation was found on follow‐up pancreatograms, the next stent was replaced. Repeated stenting improved outflow of pancreatic juice more effectively than one‐time stenting. Correlation between long‐term pain relief without recurrence of intraductal stones and reduction of duct diameter was also shown. Stent occlusion was observed in 14 of 30 stents. Stent occlusion was frequently associated with recurrence of pancreatitis and intraductal stones, and was also associated with morphologic changes in the pancreatic ductal system. Although there were no significant differences between stent patency of the initial stents and that of the next stents, stent patency of 10‐Fr stents was superior to that of 7‐Fr stents. 10‐Fr stents should be removed within 8 weeks and 7‐Fr stents should be removed within 4 weeks for the prevention of stent occlusion. Repeated stenting with short‐term stenting is therefore considered a safe and effective protocol of endoscopic pancreatic stenting.     

Normal stomach wall and gastric cancer: evaluation with high-resolution operative US

Operative ultrasound examinations were performed using a 7.5-MHz transducer during nine operations for advanced gastric cancers and during six for early cancers. Normal stomach wall showed five layers that corresponded to histologic structures. Fourteen of 15 tumors, including nonpalpable early cancers, were localized with ultrasonography. In addition, both depth of penetration and lateral wall extension of the gastric cancers were precisely determined with this technique. Our preliminary results indicate that high-resolution operative ultrasonography may become a diagnostic aid during gastric cancer operations.     

Clinical experience with cefodizime in bacterial infection of children

Clinical studies were performed on cefodizime (THR-221, CDZM), a new cephem antibiotic as described below. CDZM was administered to 13 patients in dose levels ranging from 55 to 96 mg/kg/day t.i.d. for 3-7 days (5.5 days on average). These patients included 8 with pneumonia, 2 with tonsillitis, 1 each with bronchitis, phlegmon and urinary tract infection. The overall efficacy rate was 92.3%, i.e., efficacy was excellent in 8, good in 4 and poor in 1. Bacteriological efficacy was 83.3%, i.e., 5 strains of bacteria (Streptococcus pneumoniae 1, Haemophilus influenzae 3, Haemophilus parainfluenzae 1) were eradicated and 1 was unchanged (Enterobacter cloacae, MIC greater than 100 micrograms/ml). Clinical side effect was not observed during the treatment. Laboratory abnormalities were observed in 2 cases, i.e., a slight elevation of GPT and a mild eosinophilia. The above results suggest that CDZM is a useful antibiotic for treating pediatric bacterial infections.     

Induction chemoradiotherapy prior to surgery for non-small cell lung cancer invading the left atrium.

We present a case of a 58-year-old man with diagnosis of lung adenocarcinoma invading the left atrium. He was treated with induction chemoradiotherapy for T4N1M0 disease, showing objective response. Then, a left upper lobectomy with a partial resection of the left atrium was performed without cardiopulmonary bypass. No residual tumor cells existed in the resected specimens, showing pathological complete response. Our case suggests that induction chemoradiotherapy prior to surgery can be an appropriate strategy among carefully selected patients with non-small cell lung cancer invading the left atrium.