Force distribution through the wrist joint in patients with different stages of Kienböck's disease: using computed tomography osteoabsorptiometry

The pattern of subchondral bone density has been considered to reflect the stress distribution that occurs under physiologic loading conditions. To determine the force distribution through the wrist joint with Kienb?ck's disease in living subjects, we applied a computed tomography osteoabsorptiometry and investigated the subchondral bone density pattern across the radio-carpal joint of 6 normal subjects and 10 patients suffering from Kienb?ck's disease (Lichtman's stage IIIA, 5 patients; stage IIIB, 5 patients). A single density maximum was found in each scaphoid and lunate fossa in all normal subjects. Among the subjects with Kienb?ck's disease, the current analysis demonstrated that the density maximum area significantly increased in the scaphoid fossa and decreased in the lunate fossa from stage IIIA to IIIB group. These findings indicate that the load is shifted away from the lunate to the scaphoid with the progression of Kienb?ck's disease in living subjects.     

Vertebral decancellation for severe scoliosis

STUDY DESIGN: The results of staged surgery including vertebral decancellation were reviewed retrospectively for 21 patients with severe scoliosis. OBJECTIVES: To evaluate the benefits and limitations of vertebral decancellation as new anterior surgical procedure. SUMMARY OF BACKGROUND DATA: The curvatures of severe scoliosis are often very rigid, and surgical correction using the anterior or posterior approach may not achieve the desired correction. Some studies reported neurologic complications might appear due to the aggressive approach or excessive correction force. METHODS: Twenty-one patients (average age, 17.0 years) with severe scoliosis, in whom Cobb angle was over 80 degrees (average angle, 107 degrees), underwent staged anterior and posterior spinal reconstruction. Vertebral decancellation was performed as anterior procedure, and until posterior instrumentation, halo traction was carried out. The transition of curvatures in coronal and sagittal planes was assessed in this series. RESULTS: The average correction rate of lateral curvature at the final follow-up was 46%. The average loss of correction was 2.5 degrees. Kyphosis, measured between T5 and T12, changed from 41 degrees to 36 degrees. Lordosis, measured between L1 and S1, changed from 56 degrees to 45 degrees. Transient neurologic deficit was seen in one case after vertebral decancellation. CONCLUSIONS: Staged surgery including vertebral decancellation is an effective surgical method for patients with severe scoliosis, where an inflexible rigid curve or the risk of occurrence of neurologic complications due to temporary correction may exist.     

Coracoacromial arch decompression in rotator cuff surgery

In rotator cuff surgery it is important to obtain adequate decompression of the coracoacromial arch. However, it is difficult to localize the impingement site preoperatively. Based on histological and morphological studies and the clinical findings in 45 patients and 15 cadavers, we have tried to determine the impingement site. In addition, as a part of these investigations, we assessed the clinical outcome for 100 patients. Soft tissue decompression was indicated in 12 shoulders, anterior acromioplasty in 67 and anterior acromioplasty with coracoplasty in 21. According to Neer’s criteria there were 92 satisfactory and 8 unsatisfactory results. The mean postoperative UCLA score was 33.4 points and the results were rated excellent in 78, good in 18 and fair in 4.

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Résumé  Dans la chirurgie de la coiffe des rotateurs, il est important d’obtenir une décompression adéquate sous-acromiale, mais il est difficile de localiser la zone de conflit avant l’opération. A partir d’études histologiques, morphologiques et des conclusions cliniques chez 45 malades et 15 cadavres, nous avons essayé de déterminer l’emplacement du conflit. De plus, nous avons évalué le résultat clinique de 100 cas. La décompression des parties molles était indiquée dans 12 épaules, l’acromioplastie antérieure dans 67 et l’acromioplastie antérieure avec coracoplastie dans 21 cas. D’après les critères de NEER, il y avait 92 résultats satisfaisants et 8 médiocres. Le score UCLA moyen postopératoire était à 33,4 points avec 78 résultats jugés excellents, 18 jugés bons, et 4 médiocres.

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Accepted: 19 March 2000     

Vascularised fibular grafts. An experience of 102 patients

The results and complications of 104 vascularised fibular grafts in 102 patients are presented. Bony union was ultimately achieved in 97 patients, with primary union in 84 (84%). The mean time to union was 15.5 weeks (8 to 40). In 13 patients, primary union was achieved at one end of the fibula and secondary union at the other end. In these patients, the mean time to union was 31.1 weeks (24 to 40). Five patients failed to achieve union, with a resultant pseudarthrosis (3 patients) or amputation (2 patients). There were various complications. Immediate thrombosis occurred in 14 cases. In two of 23 patients with osteomyelitis, infection recurred at two and six months after surgery, respectively. Both patients had active osteomyelitis less than one month before the operation. Bony infection occurred in a patient with a synovial sarcoma of the forearm one year after surgery. In 15 patients, 19 fractures of the fibular graft occurred after bony union, all except one within one year after union. In patients in whom an external fixator had been used, fracture occurred soon after its removal. Union was difficult to achieve in cases of congenital pseudarthrosis of the tibia. Appropriate alignment of the fibular graft is an important factor in preventing stress fracture. The vascularised fibula should be protected during the first year after union. Postoperative complications at the donor site included transient palsy of the superficial peroneal nerve in three patients, contracture of flexor hallucis longus in two and valgus deformity of the ankle in three. Vascularised fibular grafts are useful in the reconstruction of massive bony defects. We believe that meticulous preoperative planning, including choosing which vessels to select in the recipient and the type of fixation devices to use, and care in the introduction of the vascularised fibula, can improve the results and prevent complications.     

In vivo efficacy of a novel double liposome as an oral dosage form of salmon calcitonin

A simple method for the preparation of the inner liposomes for double liposomes (DL) was developed. The encapsulation efficiency of erythrosine in liposomes prepared by this new method is superior to that of the previous method because of the concentration of the drug in the lipid membrane. To evaluate the usefulness of DL prepared by the glass‐filter method modified in this study as an oral dosage form of salmon calcitonin (SCT), a suspension of liposomes containing SCT was administered to rats at a dose of 10 μg SCT/kg. Each type of DL showed better efficacy than its inner liposomes alone. The decrease in plasma calcium level was dependent on the electrical charge and particle size of the inner liposomes. The hypocalcemic efficacy of DL encapsulating SCT‐loading cationic liposomes relative to that after subcutaneous administration of SCT at a dose of 1 μg/kg was 6.47%, which was the largest value obtained. These results indicated that not only the particle size but also the electrical charge of inner liposomes affect intestinal absorption. This study verified that the efficacy was increased because of the decrease in diameter of the inner liposomes and the use of lipid with a positive charge. These findings concluded that DL might be useful as an oral dosage form of SCT. Drug Dev. Res. 58:253–257, 2003. © 2003 Wiley‐Liss, Inc.     

Experimental study of vascularized bone grafts: hypertrophy of the grafted bone

The mechanism underlying hypertrophy of experimentally vascularized bone grafts was studied in 15-week-old rats. The segmental ulna was grafted to the tibial defect with an external fixator. In experiment 1, 24 rats were classified into four groups to evaluate conventional (non-vascularized), cuff (periosteum-encased, non-vascularized), and vascularized bone grafts, and vascularized segmental grafts with fracture. In experiment 2, 12 rats were classified into two groups according to the presence of mechanical loading. This involved vascularized bone grafts with external fixators, and vascularized bone grafts with external fixators removed after bone union. The bone dynamics of the grafts were investigated by several methods, including roentgenographic analysis, histologic studies, and fluorochrome labeling. In experiment 1, a slight bone formation was recognized in the conventional bone graft, while irregular bone formation with creeping substitution was observed in the cuff graft. The vascularized bone graft showed significant hypertrophy; hypertrophy of the vascularized bone with fracture was greater than that without fracture. In experiment 2, markedly circumferential bone formation was observed after removal of the external fixator, while slight new bone formation was observed during the late postoperative period in bone with an external fixator. These results suggest that hypertrophy can be promoted by artificial fracture of the grafted bone, and that mechanical loading is an important factor for remodeling of grafted bone.     

Dysadherin overexpression in pancreatic ductal adenocarcinoma reflects tumor aggressiveness: relationship to e-cadherin expression.

PURPOSE: The E-cadherin-mediated cell adhesion system is frequently inactivated by multiple mechanisms and is involved in tumor progression in many types of cancer. Recently, we reported the cloning and characterization of dysadherin and showed that it downregulated E-cadherin and promoted metastasis. The aim of this study was to investigate the clinical significance of dysadherin expression and the relationship between dysadherin expression and E-cadherin expression in pancreatic ductal adenocarcinoma. PATIENTS AND METHODS: We examined dysadherin and E-cadherin expression in 125 surgically resected pancreatic ductal adenocarcinoma patients using immunohistochemistry. RESULTS: Dysadherin was expressed at the cell membrane of cancer cells, but not in nontumor duct and acinar cells. Its expression was stronger in infiltrative and poorly differentiated nests compared with well-differentiated nests. Although the correlation between the expression of dysadherin and E-cadherin was not significant, a group of patients showed reduced E-cadherin expression with dysadherin overexpression. Increased dysadherin expression was significantly correlated with distant metastasis (P =.047), high tumor grade (P =.006), positive tumor margins (P =.024), and infiltrative type of growth pattern (P =.014). A survival advantage was observed in patients with 0% to 20% dysadherin-positive cells compared with patients with 51% to 100% dysadherin-positive cells, independent of tumor-node-metastasis classification, and World Health Organization tumor grade (P =.019). A combination of increased dysadherin expression and reduced E-cadherin expression (< 90%) further worsened the prognosis. CONCLUSION: In pancreatic ductal adenocarcinoma, dysadherin expression seems to reflect tumor aggressiveness and to be a positive marker of poor prognosis when considered both alone and in combination with downregulation of E-cadherin.     

Cytotoxic Mechanisms of FK317, a New Class of Bioreductive Agent with Potent Antitumor Activity

FK317 is a member of a new class of bioreductive agents that exhibit strong cytotoxicity against various human cancer cells. The effect of FK317 was found to be stronger than that of mitomycin C (MMC), adriamycin (ADR) or cisplatin (CDDP). Alkaline elution analysis indicated that FK317 formed interstrand DNA-DNA and DNA-protein cross-links in cells. On the other hand, no DNA single-strand breaks were observed in the cells treated with FK317. In a cell-free system the deacetylated metabolites produced cross-linked DNA under reductive conditions, though FK317 itself did not form DNA-DNA cross-links. In order to elucidate the metabolic activation mechanisms, we established an FK317-resistant subline from human non-small cell lung cancer cells (Lu99) by stepwise and brief exposure (1 h) to FK317. The resistant subline (Lu99/317) showed cross-resistance to MMC and carboquone (CQ), but not to ADR or CDDP. DT-diaphorase, which is one of the activation enzymes of MMC and CQ, was deficient in Lu99/317 cells as determined by enzyme activity assay. However, the levels of NADPH:cytochrome P450 reductase, which is another activation enzyme for MMC and CQ, were comparable in resistant and parent cell lines. Treatment of the cells with dicumarol, an inhibitor of DT-diaphorase, reduced the cytotoxicity of FK317 to Lu99 cells, but not to Lu99/317 cells. These results indicate that deacetylation of FK317 is necessary for its reductive activation, and deacetylated FK317 is reduced by DT-diaphorase to form an active metabolite, which produces DNA-DNA interstrand and DNA-protein cross-links that lead to cell death.     

Response of quiescent and total tumor cells in solid tumors to neutrons with various cadmium ratios

Purpose: Response of quiescent (Q) and total tumor cells in solid tumors to neutron irradiation with three different cadmium (Cd) ratios was examined. The role of Q cells in tumor control was also discussed.Methods and Materials: C3H/He mice bearing SCC VII tumors received continuous administration of 5-bromo-2′-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Thirty minutes after intraperitoneal injection of sodium borocaptate-¹⁰B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-¹⁰B (BPA), the tumors were irradiated with neutrons, or those without ¹⁰B-compounds were irradiated with gamma rays. This neutron irradiation was performed using neutrons with three different cadmium (Cd) ratios. The tumors were then excised, minced, and trypsinized. The tumor cell suspensions were incubated with cytochalasin-B (a cytokinesis-blocker), and the micronucleus (MN) frequency in cells without BrdU labeling (Q cells) was determined using immunofluorescence staining for BrdU. The MN frequency in total (P + Q) tumor cells was determined from tumors that were not pretreated with BrdU. The sensitivity to neutrons was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency).Results: Without ¹⁰B-compounds, the MN frequency in Q cells was lower than that in the total cell population. The sensitivity difference between total and Q cells was reduced by neutron irradiation. Relative biological effectiveness (RBE) of neutrons compared with gamma rays was larger in Q cells than in total cells, and the RBE values for low-Cd-ratio neutrons tended to be larger than those for high-Cd-ratio neutrons. With ¹⁰B-compounds, MN frequency for each cell population was increased, especially for total cells. This increase in MN frequency was marked when high-Cd-ratio neutrons were used. BPA increased the MN frequency for total tumor cells more than BSH. Nevertheless, the sensitivity of Q cells treated with BPA was lower than that in BSH-treated Q cells. This tendency was clearly observed in high-Cd-ratio neutrons.Conclusion: From the viewpoint of enhancing the Q-cell sensitivity, tumors should be irradiated with high-Cd-ratio neutrons after BSH administration. However, normal tissue reaction remains to be examined because of its low tumor-to-normal tissue and tumor-to-blood biodistribution ratios.