A three-dimensional laminated paper model of the scaphoid from computed tomography.

PURPOSE: To describe a method of producing a life-sized three-dimensional (3D) solid model of a scaphoid bone by combining multidetector-row computed tomography (MDCT) volume data and rapid prototyping technique using thin paper as material, and to evaluate the dimensional accuracy of the experimental model. MATERIAL AND METHODS: We experimentally produced life-sized 3D solid models of 14 cadavers' scaphoid bones using high-resolution MDCT volume data, and evaluated the dimensional accuracy of the 3D solid models. RESULTS: The 3D solid model was almost perfectly produced in both size and shape (length, height, width, dorsal cortical angle, and landmarks of the scaphoid bone) compared to the real cadaver's scaphoid bone. In addition to accuracy, the cost and time for creating the model might be reasonable. CONCLUSION: This technique may be useful in assisting repair of scaphoid bone fracture.

Application of boron-entrapped stealth liposomes to inhibition of growth of tumour cells in the in vivo boron neutron-capture therapy model.

Tumour cell destruction in boron neutron-capture therapy (BNCT) is due to the nuclear reaction between (10)B and thermal neutrons. It is necessary for effective BNCT therapy to accumulate (10)B atoms in the tumour cells. The delivery system consisted of polyethylene-glycol (PEG) binding liposomes (DPPC/cholesterol/DSPC-PEG2000) with an entrapped (10)B-compound and we evaluated the cytotoxic effects of intravenously injected (10)B-PEG-liposomes on human pancreatic carcinoma xenografts in nude mice with thermal neutron irradiation. After thermal neutron irradiation of mice injected with (10)B-PEG-liposomes, growth of AsPC-1 tumours was suppressed relative to controls. Injection of (10)B-PEG-liposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. These results suggest that intravenous injection of (10)B-PEG-liposomes can increase the retention of (10)B atoms by tumour cells, causing suppression of tumour growth in vivo, after thermal neutron irradiation.

Analysis of Tsuge's procedure for the treatment of radial nerve paralysis.

Radial deviation and limited flexion of the wrist joint and a lack of abduction of the thumb have been noticed after the Riordan's procedure. Therefore, Tsuge et al. modified the Riordan's procedure, and their procedure includes transfer of the pronator teres to the extensor carpi radialis brevis, the flexor carpi radialis (FCR) to the extensor digitorum communis (EDC), and the palmaris longus to the extensor pollicis longus, along with tenodesis of the abductor pollicis longus. We reviewed the charts of 21 patients with isolated radial nerve paralysis who were treated with the Tsuge's procedure. Mean follow-up period was 11.3 years. Postoperatively, patients showed good extension of the metacarpophalangeal joint measured at the middle finger, useful flexion of the wrist joint, and decreased radial deviation of the wrist. The FCR transfer to the EDC is an excellent procedure for extension of the fingers. However, reconstruction of active abduction of the thumb remains controversial.

Treatment of subungual glomus tumour.

We reviewed 30 patients with subungual glomus tumours of the hand operated on between 1964 and 1997. Seven patients were male and 23 were female. Their age ranged from 16 to 78 years. A transungual approach was selected in 27 patients, and a periungual approach in three. Pre-operative pain subsided in all of the patients, but recurrence of the pain was observed in nine. Nail deformities were observed in nine patients before surgery. After surgery, it disappeared in three patients, persisted in six, and new deformities developed in five. To avoid recurrence of pain, it is important that the accurate pre-operative localisation of the tumour and a complete extirpation should be performed. To avoid nail deformity, it is better to apply a periungual approach for tumours developing in the peripheral region, and a transungual approach followed by meticulous repair of the nail bed for tumours developing in the central region.

Liposomes bearing polyethyleneglycol-coupled transferrin with intracellular targeting property to the solid tumors in vivo.

PURPOSE: The purpose of this study was to determine the usefulness of transferrin (TF)-pendant-type polyethyleneglycol (PEG)-liposomes (TF-PEG-liposomes), in which TF was covalently linked to the distal terminal of PEG chains on the external surface of PEG-liposomes as a carrier for in vivo cytoplasmic targeting to tumor cells. METHODS: Small unilamellar TF-PEG-liposomes (100-140 nm in diameter) were prepared from DSPC, CH, DSPE-PEG, and DSPE-PEG-COOH (2:1:0.11:0.021, molar ratio), and were conjugated to TF via the carboxyl residue of DSPE-PEG-COOH. The intracellular targeting ability of TF-PEG-liposomes to tumor cells was examined in vitro and in Colon 26 tumor-bearing mice. RESULTS: TF-PEG-liposomes, bearing approximately 25 TF molecules per liposome, readily bound to mouse Colon 26 cells in vitro and were internalized by receptor-mediated endocytosis. TF-PEG-liposomes showed a prolonged residence time in the circulation and low RES uptake in Colon 26 tumor-bearing mice, resulting in enhanced extravasation of the liposomes into the solid tumor tissue. Electron microscopic studies in Colon 26 tumor-bearing mice revealed that the extravasated TF-PEG-liposomes were internalized into tumor cells by receptor-mediated endocytosis. CONCLUSION: TF-PEG-liposomes had the capabilities of specific receptor binding and receptor-mediated endocytosis to target cells after extravasation into solid tumors in vivo. Such liposomes should be useful for in vivo cytoplasmic targeting of chemotherapeutic agents or plasmid DNAs to target cells.

Three-dimensional morphological analysis of antigen-antibody reaction in hepatic sinusoids preserved in hypothermic UW solution.

ICAM-1 antigen-antibody reaction was visualized by three-dimensional immunoscanning electron microscopy of hepatic sinusoids in rat liver treated with hypothermic University of Wisconsin (UW) organ preservation solution. The results were compared with similar antigen-antibody reactions carried out with immunoliposomes injected in vivo. Morphologically, the hepatic sinusoids were preserved well during the hypothermic procedure. Endothelial cells had a large number of fenestrations, which partly aggregated and formed sieve plates. ICAM-1 expression was induced by injection of LPS and detected by monoclonal antibody in the UW solution followed by gold-labeled secondary antibody. ICAM-1 was restricted mostly to the unique areas of sieve plates with immature, small fenestrations. A similar distribution of ICAM-1 was present when detected by in vivo injection of immunoliposomes containing the monoclonal ICAM-1 antibody. The results showed that antigen-antibody reactions can take place in livers preserved in hypothermic UW solution. Further, the reaction is similar to that which could occur in vivo during transplantation. This suggests that it may be possible to block potentially harmful antigen-antibody reactions by addition of appropriate antibodies to hypothermic UW solution prior to transplantation.

Free vascularized toe joint transfer to the hand. A technique for simultaneous reconstruction of the soft tissue.

Twelve patients underwent reconstruction of injured finger joints using our technique of a vascularized transfer of the second toe proximal interphalangeal joint. The age of the patients at operation ranged from 7 to 47 years and the postoperative follow-up was 9 to 48 months. All the joint transfers survived and united with resolution of the preoperative joint pain, deformity and instability. The average range of motion of the reconstructed joints was 59 degrees in the proximal interphalangeal and 54 degrees in the metacarpophalangeal joints. No patient complained of pain or functional deficits in the donor foot.

Cell proliferation and death of growth plate chondrocyte caused by ischemia and reperfusion.

The aim of this study was to assess the short-term response of cell kinetics of growth plate chondrocytes under conditions of warm ischemia and reperfusion. To understand the time-course changes that occur after reperfusion, 0 and 6 h of warm ischemia was produced in the right hindlimb of 35-day-old Wistar rats by isolating the vascular pedicle occlusion. The animals were killed at 12, 24, 48, or 96 h postoperatively after reperfusion, and proximal tibia growth plates were investigated. To investigate the effect of the ischemia period on the kinetics of growth plate chondrocytes, 0, 2, 4, 6, and 8 h of ischemia was induced, and the animals were killed for evaluation 24 h after reperfusion. For evaluation of cell kinetics, BrdU was used to observe the changes in cell proliferation of growth plate chondrocytes, and TUNEL was used to estimate the changes in rate of cell death. In the time-course study, both 0 and 6 h of ischemia increased cell proliferation at 12 and 24 h after reperfusion; however, at 48 and 96 h, the proliferation rate was not further increased. At 12 and 24 h postoperatively, 6 h of ischemia increased chondrocyte proliferation more than 0 h of ischemia with significant differences; 6 h of ischemia led to an increased cell death rate at 12, 24, and 48 h postoperatively, whereas 0 h of ischemia did not affect the cell death rate. In the ischemia time-dependent study, the cell proliferation rate induced by 4 h of ischemia was highest in all controlled periods of ischemia. Cell death rate increased gradually with increases in ischemia time 24 h after reperfusion. This experiment showed that ischemic damage causes short-term postoperative changes in the kinetics of growth plate chondrocytes.

Carpal tunnel syndrome in radial dysplasia.

We treated three patients for carpal tunnel syndrome which developed more than 10 years after reconstructive surgery for radial dysplasia. All responded to decompressive surgery. The radial carpal bones were hypoplastic in all cases, and in two we measured the carpal tunnel with computed tomography (CT). This showed that the anteroposterior diameter and cross-sectional area of the carpal tunnel were small because of the hypoplasia of the carpal bones. We believe carpal tunnel syndrome occurs with radial dysplasia because of the narrow anteroposterior diameter and small cross-sectional area of the carpal tunnel.

Clinical assessment of long-term safety and efficacy of a widely implanted polyacrylic intraocular lens material.

PURPOSE: To evaluate the long-term safety and efficacy, in a large series of patients, of polyacrylic intraocular lens implants 1 and 3 years after surgery, compared with polymethylmethacrylate intraocular lens implants. METHODS: This was a randomized, prospective study of 1,514 eyes of 1,202 patients that were examined for a 1-year follow-up study and 1,264 eyes of 990 patients that were examined for a 3-year follow-up study. All the patients were prospectively randomized to receive a polyacrylic or polymethylmethacrylate intraocular lens implant. A standardized surgical protocol was performed using a phacoemulsification technique and capsulorhexis. Any surgical complications were excluded, and all patients had standard postoperative medication and follow-up. Postoperative measurements included spectacle-corrected visual acuity, occurrence of postoperative sight-threatening or lens-related complications, and adverse reactions. Results were compared between the polyacrylic intraocular lens and polymethylmethacrylate intraocular lens groups. Results were also compared with standards for polymethylmethacrylate intraocular lens that were established by the US Food and Drug Administration and a previous study for silicone lens. RESULTS: The overall complete follow-up rates were 79.9% for 1-year follow-up and 69.5% for 3-year follow-up. At 1 year, the mean logarithm of the minimum angle of resolution (logMAR) of visual acuity was 0.037 +/- 0.150 and 0.042 +/- 0.154 in best case patients of the polyacrylic intraocular lens group and polymethylmethacrylate intraocular lens group, respectively. At 3 years, the mean logMAR visual acuity was 0.038 +/- 0.155 and 0.054 +/- 0.181 in best case patients in the polyacrylic intraocular lens group and polymethylmethacrylate intraocular lens group. There was no significant difference between groups at 1 and 3 years. At 1 year, 96.8% of best case patients in the polyacrylic intraocular lens group and 95.8% of those in the polymethylmethacrylate intraocular lens group achieved corrected visual acuity of 0.5 or better. At 3 years, 96.4% of best case patients in the polyacrylic intraocular lens group and 94.9% of those in the polymethylmethacrylate group achieved a corrected visual acuity of 0.5 or better; no significant difference was found at 1 and 3 years. The rate of sight-threatening complications was 1. 2% for the polyacrylic intraocular lens group of all patients and 1. 5% for the polymethylmethacrylate intraocular lens group at 1 year, and 1.6% for the polyacrylic intraocular lens group and 1.4% for the polymethylmethacrylate intraocular lens group at 3 years. No significant difference was found between the groups. The cumulative rate of Nd:YAG capsulotomy for the polyacrylic intraocular lens group (7.1%) was significantly lower than that for the polymethylmethacrylate intraocular lens group (38.1%) through 3 years (P <.0001). CONCLUSIONS: Polyacrylic intraocular lenses demonstrated safe and effective performance through long-term follow-up at a level equal to or better than polymethylmethacrylate intraocular lenses. Patients undergoing polyacrylic intraocular lens implantation achieved excellent postoperative visual acuity and experienced a low rate of postoperative complications, adverse reactions, and Nd:YAG capsulotomy. These long-term clinical results are an important outcome database for the ongoing use of this foldable optic material.

Trapeziometacarpal joint arthrodesis for the treatment of arthrosis.

We undertook a retrospective follow-up study of arthrodesis of 21 trapeziometacarpal joints in 19 patients. Internal fixation was by two or three Kirschner wires and a bone graft. No joint failed to unite. Painless joints and stable grasping were achieved. Subjective estimations of improvement were excellent for 16 joints. However, some patients complained of clumsiness after the procedure. Instability was seen in six metacarpophalangeal (MP) joints of the thumb. The most common indication for trapeziometacarpal joint arthrodesis was painful arthritis in vigorous, young male labourers. However, preoperative evaluation of the function of the MP joint is necessary to determine suitability for surgery.

Double-toe transplantation following temporary insertion of a block of silicone for reconstruction of a traumatic metacarpal defect.

The treatment of the mutilated hand with more than one digit missing and a metacarpal defect is challenging. We used double-toe transfer after temporary insertion of a block of silicone to fill the bony defect.

Surgical treatment of the cleft foot.

Between 1970 and 1997, we treated a total of 32 cleft feet in 21 patients (11 male and 10 female). We classified cases of cleft foot on the basis of the number of central ray deficiencies. Fourteen patients with 22 cleft feet were followed up for more than 1 year postoperatively (9 feet had no or one central ray deficiency, and 13 feet had two or three central ray deficiencies). The mean follow-up period was 8.8 years. The objective of this study was to evaluate the results of operative treatment of cleft foot. We evaluated the results of three methods: simple closure of the cleft, application of a double-pedicled flap, and insertion of a silicone block. Cosmetic complications, including widening of the foot, hypertrophic scarring, pigmentation of the grafted skin, and overlapping of the toes, were observed in patients with two or three central ray deficiencies. Few functional complications were observed: None of the patients experienced gait disturbances, although one patient complained of pain following walking. Roentgenography showed that the distance between the first and fifth metatarsals was 86 percent of that of the contralateral foot. When treating patients with no or one central ray deficiency, satisfactory results can be expected with simple closure of the cleft. However, in patients with two or three central ray deficiencies, it is difficult to obtain satisfactory results with simple closure of the cleft or application of a double-pedicled flap. Therefore, silicone block insertion to correct the defect is recommended when there is more than one central ray deficiency.

Targeting chemotherapy to solid tumors with long-circulating thermosensitive liposomes and local hyperthermia.

The effectiveness of the combination of long-circulating, thermosensitive liposomes and hyperthermia is described. Small-sized, thermosensitive liposomes that encapsulate doxorubicin (DXR-PEG-TSL (SUV)) have a prolonged circulation time and are extravasated to targeted solid tumors in vivo, where they preferentially release the agent in an anatomical site subjected to local hyperthermia. Liposomes were prepared by the incorporation of amphipathic polyethyleneglycol (PEG) to prolong their circulation time. DXR-PEG-TSL (SUV) was retained longest and was accumulated most efficiently in solid tumors in Balb/c mice. The combination of DXR-PEG-TSL (SUV) and hyperthermia at the tumor sites 3 h after injection, gave high concentrations of doxorubicin in tumor tissue and resulted in more effective tumor retardation and increased survival time. A large amount of DXR-PEG-TSL (SUV) was extravasated into the tumors during circulation for 3 h after injection, suggesting that the encapsulated drug was released into the interstitial spaces of the lesions by local hyperthermia. This system is expected to be clinically valuable for the delivery of a wide range of chemotherapeutic agents in the treatment of solid tumors.

Long-term results of fractionated strontium-90 radiation therapy for pterygia.

PURPOSE: The long-term safety and effectiveness of fractionated strontium-90 radiation therapy (RT) for pterygium were reviewed retrospectively. METHODS AND MATERIALS: Between 1984 and 1996, 399 patients with 490 pterygia were treated with a strontium-90 eye applicator following surgical removal of the pterygium. The median follow-up period was 61 months (range 2-178). Of the 490 pterygia, 452 were fresh, 17 were recurrences after surgical removal alone, and 21 were recurrences after surgical removal plus postoperative RT. Fractionated RT of 31-42 Gy/4-5 fractions/22-29 days was given for 95.1% of the pterygia. RESULTS: In total, 58 (11.8%) local recurrences of pterygia were noted. The median time of local recurrences was 10 months, ranging from 2 to 93 months, and 16 recurrences (28%) were noted later than 24 months after treatment. The interval between surgery and the start of RT (1-3 days vs. >3 days) and recurrent pterygia were significant variables for local control in the multivariate analysis, while total RT dose (7-29 Gy vs. 31-50 Gy) was a marginally significant variable. Late toxicities that may be associated with strontium-90 RT were scleromalacia (scleral thinning) in 4 eyes, adhesion of eyelids in 3 eyes, and scleral ulcer in 2 eyes. CONCLUSION: Fractionated strontium-90 RT of approximately 40 Gy/4-5 fractions was safe and effective for preventing recurrence of pterygia, when RT was started within 3 days of surgery.

Thyrocyte proliferation by cellular adhesion to infiltrating lymphocytes through the intercellular adhesion molecule-1/lymphocyte function-associated antigen-1 pathway in Graves' disease.

Graves' disease (GD) is an autoimmune thyroid disease characterized by infiltration of lymphocytes into the thyroid, and intrathyroid lymphocytes are known to play an important role in the pathogenesis of GD. However, it remains to be understood how lymphocytes adhere to thyrocytes and regulate the thyrocyte function through cellular adhesion. We studied the mechanisms of T cell adhesion to thyrocytes using intrathyroid mononuclear cells (ITMC) and thyrocytes purified from the thyroids of patients with GD. The following novel features of cellular adhesion of ITMC to thyrocytes in the regulation of the thyrocyte function in GD were observed: 1) GD-ITMC expressed lymphocyte function-associated antigen (LFA)-1, which became an active adhesive configuration much higher than peripheral blood mononuclear cells (PBMC) from normal volunteers and GD patients; 2) GD-thyrocytes expressed a high quantity of intercellular adhesion molecule (ICAM)-1; 3) GD-ITMC adhered to GD-thyrocytes, whereas normal PBMC required activation stimuli by phorbol myriacetate, a pharmacological integrin-trigger, to adhere to GD- thyrocytes; 4) monoclonal antibody-blocking studies showed that the adhesion of the activated PBMC and ITMC to thyrocytes was mainly mediated by the LFA-1/ICAM-1 pathway; 5) the adhesion of GD-thyrocytes to the activated-PBMC or ITMC induced the proliferation of the thyrocytes, which was blocked by the addition of ICAM-1 and/or LFA-1 monoclonal antibodies; and 6) in GD thyrocytes of early cultures, ICAM-1 expression on GD-thyrocytes and its adhesion to LFA-1 on phorbol myriacetate-activated PBMC or ITMC were not modulated by the addition of interleukin-1beta or interferon-gamma, and proliferation of thyrocytes by the cellular adhesion via the ICAM-1/LFA-1 pathway was independent of the proliferative response of these cytokines. Taken together, these results suggest that lymphocytes infiltrating GD thyroid induce proliferation of GD-thyrocyte by the cellular adhesion to thyrocytes via ICAM-1/LFA-1, which may lead to the development of a goiter.

Rejection and regeneration in peripheral nerve homografts in rats after withdrawal of cyclosporin: morphological and immunohistochemical assessment.

Peripheral nerve homografts 35 mm long were inserted in rats to study rejection and regeneration of nerves after suspension of an immunosuppressant (cyclosporin), and the correlation between the Schwann cells of the host and the donor during the course of regeneration. Sciatic nerve homografts from 36 ACI-RT1a rats were transplanted into Lewis-RT1(1) rats. Isografts were taken from 24 Lewis rats. Cyclosporin 5 mg/kg/day was given subcutaneously for 12 weeks. In the homograft group the myelinated axons that regenerated while the immunosuppressant was being given were covered mainly with Schwann cells from the donor, and after the immunosuppressant was withdrawn both Schwann cells of the donor and axons were rejected. However, while the cyclosporin was being given the Schwann cells of the host migrated into the nerve graft together with a few myelinated axons that escaped rejection, and unmyelinated axons that regenerated after rejection were myelinated by the Schwann cells of host.

Size-dependent extravasation and interstitial localization of polyethyleneglycol liposomes in solid tumor-bearing mice.

We have examined the size dependence of extravasation and interstitial localization of polyethyleneglycol-coated liposomes (PEG-liposomes) in the solid tumor tissue by means of electron microscopic observation. Liposomes composed of distearoyl phosphatidylcholine, cholesterol and distearoylphosphatidylethanolamine derivative of polyethyleneglycol (PEG) were prepared in various size ranges. PEG-liposomes with an average diameter of 100-200 nm showed the most prolonged circulation time and the greatest tumor accumulation in all the solid tumors employed in this experiment. Although large PEG-liposomes with a diameter of 400 nm showed a short circulation time in normal mice, the results in splenectomized mice indicated that they do have an intrinsic prolonged circulation character in vivo. However, large PEG-liposomes could not extravasate into solid tumor tissue. These results indicate that the size of liposomes is critical for extravasation. The electron microscopic observations revealed the almost exclusive engulfment of extravasated liposomes by tumor-associated macrophages; very few were taken up by tumor cells.