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We have designed and constructed an inexpensive imaging system based on charge-coupled device (CCD) technology and utilized it to demonstrate the sensitivity and rapid detection possible with Lumigen chemiluminescent reagents. We also report the development of two new chemiluminescent reagents, Lumi-Phos Plus and Lumigen PS. Lumi-Phos Plus is an enhanced formulation for the rapid detection of alkaline phosphatase on membranes and in solution. It provides excellent images in blotting applications with exposures of under a minute. Lumigen PS represents a new generation of peroxidase detection reagents. The wide dynamic range with excellent linearity, higher signal and lower background than other chemiluminescent reagents make Lumigen PS of unsurpassed value in enzyme-linked immunoassays and nucleic acid probe assays using HRP conjugates.

The etiology of spontaneous hemarthrosis of the knee in elderly patients with osteoarthritis is still unknown. This report discusses six cases, one that was managed with conservative measures and five in which arthroscopic evaluation and treatment were performed. These patients were elderly individuals whose chief complaint was knee pain and swelling about the joint, without an obvious history of trauma. Each of the five operative patients underwent arthroscopic surgery after repeated hemorrhage into the joint that did not respond to serial aspirations of large amounts of blood and immobilization, using a knee immobilizer. The roentgenograms of each involved knee demonstrated lateral compartment osteoarthritis. Arthroscopic examination revealed a degenerative flap tear of the posterior horn of the lateral meniscus in the five operative cases. These patients underwent arthroscopic resection of the injured lateral meniscus and did not experience a recurrence of the hemarthrosis. The origin of the bleeding was most likely from the peripheral arteries of the posterior horn of the lateral meniscus.

Objective: To investigate the effect of T cell depletion on established collagen-induced arthritis (CIA) in mice, using monoclonal antibodies (MAb) to T cell receptor alpha/beta (TCR alpha/beta). In addition, experiments using anti-CD3 MAb were performed for comparison., Methods: CIA was induced in male DBA/1 mice by immunizing them twice with bovine type II collagen (CII). The arthritis score and anti-CII antibody titers were examined serially. Proportions of T cells were determined by fluorescence-activated cell sorter (FACS) analysis on spleen cells or peripheral blood cells., Results: When anti-TCR alpha/beta MAb was injected on the day of CII priming, no arthritis was detected in association with depressed anti-CII antibody titers. Unexpectedly, however, when MAb was given after arthritis was established, a rapid exacerbation of arthritis was observed, which resulted in ankylosis of most joints. Anti-CII antibody titers were not affected. The addition of anti-TCR gamma/delta MAb had no effect on the augmented arthritis. T cell depletion by anti-CD3 MAb during established CIA also caused an enhancement of arthritis, which was, however, weak and only transient. FACS analysis revealed that the early improvement of arthritis after the transient augmentation seen in the mice treated with anti-CD3 MAb paralleled the early recovery of alpha/beta T cells in the periphery., Conclusion: The present results support the concept that alpha/beta T cells, in general, may play a regulatory role in the clinical course of murine CIA after disease onset. Therefore, caution is recommended when using intensive T cell-targeted therapy in patients with rheumatoid arthritis.

In vitro data support the view that T cells in adjuvant-induced arthritis (AIA) respond to the proteoglycan (PG) component of articular cartilage; however, an in vivo role for PG in AIA has yet to be shown. To do so, we examined the effects of pretreatment with bovine cartilage high density PG (HDPG) on AIA induced by heat-killed Mycobacterium butyricum in Lewis rats. Purified bovine cartilage HDPG emulsified in Freund's incomplete adjuvant (FIA) was injected intradermally into rats 7 days before challenge with Myco. butyricum. The severity of arthritis was significantly suppressed in rats pretreated with as little as 0.75 mg of HDPG, and the arthritis was completely suppressed in rats pretreated with 3.0 mg of HDPG. This suppression was specific, as the same treatment did not protect against type II collagen-induced arthritis. Suppression of AIA is primarily a property of the HDPG, as suppression of the arthritis was significantly less with pretreatment with 3.0 mg of middle density fractions of PG, and no suppression was observed with pretreatment with the lowest density fraction of PG. Thus we report that pretreatment with cartilage HDPG, but not lower density PG, can induce specific suppression of AIA. These in vivo results support the view that immunity to cartilage HDPG plays a major role in the pathogenesis of AIA, and can induce specific tolerance to this type of arthritis.

12 anemic and 10 non-anemic patients with rheumatoid arthritis were treated with recombinant human erythropoietin (rHuEPO) before arthroplasty. The patients received 400-800 units/kg of rHuEPO subcutaneously once a week. Autologous blood was collected after the hemoglobin concentration was increased by 5 percent or more. All but one of the patients responded to the treatment. They were given 1-3 units of autologous blood, and underwent the operation without homologous blood transfusion. The mean duration of the treatment was 1 month. In 1 patient with severe anemia, additional transfusion with 2 units of blood was necessary during the operation. In all patients, there was a tendency for the hemoglobin response ratio to rHuEPO to correlate negatively with the initial CRP levels. The treatment did not affect the patients' clinical rheumatologic condition and there were no adverse effects. These results demonstrated that the treatment with subcutaneous rHuEPO is both effective and non-toxic and can therefore eliminate the need for homologous blood transfusion in anemic patients undergoing arthroplasty for rheumatoid arthritis.

Perthes' disease was seen in two boys, aged 6 1/2, with the Russell-Silver Syndrome. Both presented with groin or thigh pain in their shortened side together with a progressive limp. They were treated conservatively, and when reviewed 6 1/2 years after diagnosis the lesions of the hip had improved clinically and radiographically. The leg length discrepancy did not increase.

The newly developed 99mTc-labeled renal imaging agent, mercaptoacetyltriglycine (MAG3), is a tubular secreted compound. It is expected the most suitable agent to measure renal function and image urinary tract because of the excellent imaging properties and availability of 99mTc and preferred biological qualities of radiohippurates. We examined 15 patients (8 males, 7 females, mean age 55 years old) with renal and urinary tract disease. After drinking 400 ml of water, 185, 370 or 555 MBq of 99mTc-MAG3 was injected with the supine position. Dynamic scans were acquired for 20 minutes on a large field of view gamma camera (ZLC-7500 Siemens Medical Inc.) linked to a computer system (Scintipac-2400 Shimadzu Co.) in a 64 x 64 matrix. Regions of interest (ROI) were placed around each kidney. Curves of 12 seconds frame rate were generated from all two ROIs over the 20 minutes study. The time to peak count (Tmax) and time from peak count to a half count (T1/2) were calculated from the curve data. 99mTc-DTPA renal imaging was examined to the same patients with the same method like 99mTc-MAG3. The renogram of 131I-orthoiodohippurate (OIH) was performed with probe method. The excellent quality of the renal image was obtained with 185-555 MBq of 99mTc-MAG3 compared with the same dose of 99mTc-DTPA respectively. The diagnostic value of 99mTc-MAG3 renal imaging was as well as 99mTc-DMSA renal imaging. The Tmax of 99mTc-MAG3 renogram was same value of that of both 99mTc-DTPA and 131I-OIH renogram. The T1/2 of 99mTc-MAG3 renogram was significantly lower than that of 99mTc-DTPA renogram. The T1/2 of 99mTc-MAG3 renogram was slightly higher that of 131I-OIH renogram. We conclude that the renal imaging of 99mTc-MAG3 was able to acquire the most excellent image and the proper renogram pattern as same as 131I-OIH renogram.

We have used reconstituted basement membrane molecules which have formed into barriers in order to investigate the invasive potential of malignant bone and soft tissue tumour cells in vitro. A number of cell lines established from human malignant tumours demonstrated a high degree of invasiveness, although fibroblasts showed no ability to penetrate the basement membrane barrier. H-ras oncogene transfected cells into the fibroblasts were much more invasive than the parent lines. Primary cultures of malignant tumour cells demonstrated invasiveness, while those of nonmetastatic cells and fibroblasts did not. The binding of tumour cells to laminin in the basement membranes was found to induce secretion of collagenase and motility which are crucial factors for invasion. A synthetic peptide, Tyr-Ile-Gly-Ser-Arg, was able to suppress the invasiveness of HT1080 human fibrosarcoma cells, and also reduced lung colonisation in vitro. The results suggest that the in vitro assay was useful, firstly to determine the invasive potential, secondly to investigate the mechanism of invasion, and finally to development treatment against invasion and metastases.

The affinity of the tibia bone for cylinders of hydroxyapatite (HA) and Ti-6Al-4V was investigated in three experimental animal models: intact rat tibiae, ovariectomized rat tibiae and ovariectomized plus neurectomized rat tibiae. The affinity index (the length of bone directly apposed to the implant/the total length of the bone-implant interface x 100%) was calculated. In intact and ovariectomized tibiae, no significant difference existed between the affinity index of HA and Ti-6Al-4V. In ovariectomized plus neurectomized tibiae, the affinity index of HA was greater than for Ti-6Al-4V from 8 to 24 wk after implantation (8 wk, P < 0.05; 12 wk, P < 0.005; 24 wk, P < 0.05). The affinity index of Ti-6Al-4V in normal tibiae was greater than that in ovariectomized or ovariectomized plus neurectomized tibiae. There was no significant difference of the affinity index of HA between normal, ovariectomized or ovariectomized plus neurectomized tibiae. Osteoporotic bone demonstrated a greater affinity to HA than Ti-6Al-4V in an experimental animal model.

The effect of simple cold storage in Euro-Collins solution on prolonging successful preservation time was examined on an established rat limb transplant model. Limbs amputated at mid-thigh level were simply immersed in the solution and stored in a refrigerator at 4 degrees C. After varying periods of cold storage, the limb was orthotopically grafted to another isogeneic rat using microsurgical techniques. The survival rates for 12, 24, 48 and 72 hours' storage were 100%, 90%, 67% and 50% respectively, and the longest time of successful preservation achieved was 78 hours. Survival rates were greatly decreased when amputated limbs were initially perfused with Euro-Collins solution and immersed in the same solution. In a third set of experiments, the limbs were preserved by a conventional method of cold storage in air, and the survival rates were decreased even further. Evaluation by measuring postoperative paw swelling and microscopic examination of the grafts further confirmed the effectiveness of the simple immersion method without perfusion.

We have previously demonstrated that there was no significant difference between the affinity of bone to bio-inert ceramics and stainless steel in a histological study. In this study, the bone-implant interface shear strength of alumina ceramics (Al2O3), zirconia ceramics (ZrO2), stainless steel (SUS316L) and sintered hydroxyapatite (HA) were compared in 19 dogs using a transcortical push-out model of the femur 4 and 12 wk after implantation. The interface shear strength of HA was significantly greater than that of alumina ceramics, zirconia ceramics and stainless steel (P < 0.001). There was no significant difference between bio-inert ceramics and stainless steel.

Herniation of the calcified nucleus pulposus is a rare complication of intervertebral disc calcification in children. Surgical intervention is rarely indicated in the majority of such cases. This paper reports a 12-year-old boy with a calcified nucleus pulposus at C7-T1 which had ruptured into the spinal canal, causing dissociated motor loss. Anterior discectomy and fusion were performed and the patient's muscle weakness markedly improved after surgery.

Type II collagen-induced arthritis (CIA) is a pathologic process mediated, in part, by humoral immune mechanisms. Because many antibody-mediated reactions are neutrophil-dependent, the role of this cell population was examined in passive CIA transferred with anti-type II collagen (CII) antibody. In cyclophosphamide (CY)-induced leukocytopenic rats, swelling and inflammation associated with the arthritic response were significantly reduced. Concomitant administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF) to leukocytopenic rats for 7 consecutive days from the day of CY injection resulted in the recovery of peripheral blood neutrophils count and the abrogation of the suppression of arthritis with an optimal dose of anti-CII antibody. Further study demonstrated that a prior administration of rhG-CSF to naive rats for five consecutive days resulted in the significant and specific increase of peripheral blood neutrophils count and enhancement of passive arthritis with a suboptimal dose of anti-CII antibody. It was suggested that neutrophils played an important role in the development of passive CIA.

The risk of persistence and recurrence of infection in posterior spinal instrumentation surgery for spinal tuberculosis was studied clinically and microbiologically. Eleven patients with thoracic, thoracolumbar, and lumbar spinal tuberculosis treated by debridement, anterior fusion, and combined posterior instrumentation surgery were analyzed. Seven patients had tuberculosis in both anterior and posterior spinal elements. There were no cases of persistence or recurrence of infection after surgery, and instrumentation provided immediate stability and protected against development of kyphotic deformity. The adherence properties of Mycobacterium tuberculosis to stainless steel (SUS 316) was evaluated experimentally. The results showed that posterior instrumentation surgery was not a hazard to spinal tuberculosis infection when combined with radical debridement and intensive anti-tuberculosis chemotherapy.

Preoperative blood reservation for autologous blood transfusion generally causes anemia. We performed a double blind controlled study to determine the optimal dose of subcutaneous rHuEPO (recombinant human erythropoietin, KRN5702) for preventing preoperative anemia due to blood reservation. Patients received KRN5702 subcutaneously once a week in a doses of 12000, 24000 or 36000 IU by a double blind technique. After storage of 1200 ml of their own blood right before surgery, their hemoglobin (Hb) averaged about 1 and was about 0.5 g/dl lower than the level before administration of KRN5702 in doses of 12000 and 24000 IU, respectively. This fall was significant. In patients receiving KRN5702 in a dose of 36000 IU, the level of Hb rose instead of a fall; Hb immediately before surgery was 1.1% higher than that before administration which, however, was not significant. This elevation indicates a possibility of abnormal elevation of Hb at this dose. The mean Hb value right before surgery was significantly lower in patients receiving 12000 IU KRN5702 than in patients of the other two groups. The recovery rate of Hb was an indicator to reflect improvement of anemic conditions, and increased as the dose increased after the blood reservation. The rate in the 12000 IU group was significantly lower than that in the other two groups; there was not much difference between the other two rates. We estimated that to reserve 1200 ml of autologous blood, 24000 IU of KRN5702 is adequate but not excessive. One patient receiving 24000 IU showed side effects including an elevation of body temperature, rash, and edema.

A Multi-gated SPECT was acquired commonly in 64 x 64 matrix and 8 frames per cardiac cycle (64 x 64/8F). But it was not established that 64 x 64 matrix and 8 frames per cardiac cycle were the most suitable in multi-gated SPECT. Five normal volunteers were examined multi-gated 201Tl SPECT with 5 acquisition modes of 128 x 128 matrix/16 frames, 128 x 128/8F, 64 x 64/32F, 64 x 64/8F using multi-detector SPECT system (GCA-9300). And we calculated percent wall thickening (%WT) [%WT = (ES counts - ED counts)/ED counts] in 9 cases with 64 x 64/8F. The images quality of both 128 x 128/16F and 128 x 128/8F was not clear in compared with images of both 64 x 64/16F and 64 x 64/8F, because the end-diastolic phase of 128 x 128/16F images showed a decreased uptake of 201Tl in the antero-apical region. Although 64 x 64 (8) images had only 8 frames per cardiac cycle, we could observe systolic and diastolic phase and we could calculate %WT. The %WT (M +/- SD) of horizontal long axis images were 48 +/- 15 (sept. basal), 48 +/- 19 (sept. apical), 65 +/- 29 (apex), 49 +/- 22 (lat. apical) and 40 +/- 15 (lat. basal).(ABSTRACT TRUNCATED AT 250 WORDS)

In the electrodiagnosis of cubital tunnel syndrome, the abductor digiti minimi (ADM) muscle is frequently used to evoke compound muscle action potentials (CMAP) in order to measure the motor nerve conduction velocity (MNCV) in the ulnar nerve. Slowing of the MNCV across the elbow is a major criteria in the electrodiagnosis of cubital tunnel syndrome. However, in advanced cases, slowing of the MNCV is also seen in the forearm segment, thus, localization of the nerve palsy is sometimes difficult. We evoked CMAP from the flexor carpi ulnaris (FCU) muscle to assess the value of electrophysiological examination of this muscle in the diagnosis of cubital tunnel syndrome. CMAP from the FCU muscle could be evoked in many cases when CMAP from the ADM muscle could not. Also, the motor terminal latency (MTL) of the FCU was prolonged in proportion to the slowing of the MNCV across the elbow. Therefore, electrophysiological examination of the FCU muscle is useful in the diagnosis of cubital tunnel syndrome, especially when intrinsic muscle atrophy is severe and the CMAP from these muscles cannot be evoked.

Spinal evoked potentials, sciatic neurogenic motor evoked potentials, and somatosensory evoked potentials were recorded before and after overdistraction of the spinal cord, and compared with the clinical status of 14 pigs. The sciatic neurogenic motor evoked potential consisted of two components: fast and slow. The fast component was more sensitive and associated to a greater degree with motor function in wake-up tests than the slow component somatosensory evoked potential and spinal evoked potential. Furthermore, the loss of only the fast component in the initial status allowed the possibility of improvement of motor activity in the final wake-up test. The peripheral neurogenic motor evoked potentials recording yielded more information about spinal cord function: motor and sensory. The current study suggests that a peripheral response is a better index to the onset of overdistraction and to the efficiency of intervention, when the neurologic deficit after overdistraction of the spine is reversible.

Although we could acquire a detailed 512 x 2048 matrix whole body scintigraphy, the 512 x 2048 matrix whole body scintigraphy was divided to the upper and lower half of the body, because a many of CRT system displayed only 1024 x 1024 matrix with non interlace mode. We made 12 dots of normal vertical image distance to 0 dot with laser imaging system (Li-10 Konica medical inc.), and we printed these divided whole body images in the four partition of the film. The lead bar phantom (interval from 6 mm to 3 mm) filled with 99mTcO4- was studied by both 512 x 2048 matrix whole body scanning mode and 256 x 1024 whole body scanning mode in the basic study. And the distance between the lead bar phantom and the gamma camera was changed from 10 mm to 100 mm. We studied 41 patients with metastatic bone tumor (14 breast cancer, 7 lung cancer, 7 prostate cancer, 5 others, 6 unknown origin) clinically. However the 512 x 2048 matrix whole body scan was better quality of images than 256 x 1024 matrix whole body scan at 100 mm distance in the basic study. The abnormal uptake of metastatic sites was shown equally in both 512 x 2048 and 256 x 1024 matrix whole body scintigraphy. The 512 x 2048 matrix whole body scan was better quality of images than 256 x 1024 matrix whole body scan in 26 out of 41 patients, equal in 10 out of 41 patients and worse in 3 out of 41 patients. The matrix size of 512 x 2048 matrix whole body scintigraphy (0.98 mm2) was smaller than that of 256 x 1024 matrix whole body scintigraphy (1.95 mm2).(ABSTRACT TRUNCATED AT 250 WORDS)

The therapeutic efficacy on intra-arterial (IA) and intravenous (IV) cisplatin on both foot tumors and lung metastases of transitional cell carcinoma RBT-1 in rats was compared. 5 mg/kg of either IA or IV cisplatin was administered to rats bearing both a foot tumor and pulmonary metastases. The antitumor effects on foot tumors were evaluated by changes in paw volume, foot weight and tumor area, and on lung metastases by a prolongation in life span after the amputation of the affected limb. IA cisplatin had remarkable therapeutic efficacy on the foot tumor as compared with IV cisplatin. Life span prolongation was obtained by both the IA and IV infusion. However, there was no significant difference between the survival of the rats given IV and those given IA cisplatin. These results indicate that IA cisplatin is more effective than IV cisplatin on primary tumors, and the effects of IA and IV cisplatin on lung metastases and survival are similar.

Somatosensory evoked potentials (SEPs) were recorded at the lumbar spine following stimulation of the tibial nerve (mixed-nerve SEP; MSEP), the sural nerve (specific nerve SEP; SSEP), and the skin corresponding to the L6 and S1 dermatomes (dermatomal field SEP; DSEP-L and DSEP-S) in the hog. To determine the sensitivity of these three SEPs to the single nerve root (S1 root) function, the effects of nerve roots lesioning were investigated. Cutting S1 nerve root reduced the peak-to-peak amplitude of MSEP by only 28% in comparison with baseline values. The relative amplitudes of SSEP, DSEP-L, and DSEP-S were decreased by 46%, 11% and 51%, respectively. When S1 nerve root was left intact and L5, L6, and S2 nerve roots were cut, the relative amplitudes of MSEP, SSEP, DSEP-L, and DSEP-S were decreased to 68%, 73%, 31%, and 74%, respectively. These results indicate that DSEP-S is as sensitive to the function of S1 nerve root as SSEP but the sensitivities of DSEP-S and SSEP are low in the hog. MSEP is shown unsuitable to monitor the single nerve root dysfunction.

A case of Proteus syndrome in a 13-year-old boy with macrodactyly, hemihypertrophy, exostosis of the skull, epidermal naevi, palmar and plantar masses, and scoliosis is reported. Macrodactyly involving the left thumb was treated surgically. The usual findings in macrodactyly, hypertrophy of the digital nerves and proliferation of subcutaneous fat, were not observed in this case. Macrodactyly associated with Proteus syndrome should be distinguished from other forms of macrodactyly because of its poor prognosis and high rate of recurrence.

In vitro, bioinert stainless steel and titanium alloy, and bioactive sintered hydroxyapatite and hydroxyapatite-coated titanium materials were exposed to Staphylococcus epidermidis to study bacterial adhesion. Scanning electron microscopy showed that fibrous strands interconnected the adherent bacteria, and that background matrix enclosed bacterial colonies. This adherent mode of growth may reduce the susceptibility of the bacteria to host clearance mechanisms and antibiotic therapy. Adherence assays revealed that bacterial adherence to sintered hydroxyapatite was higher than to the other 3 materials.

The interface shear strength of uncoated Ti-6Al-4V, dense sintered hydroxyapatite (HA), and HA-coated Ti-6Al-4V were compared. Interface shear strength was determined using a transcortical push-out model in dogs 4 and 12 weeks after implantation. The interface shear strength of dense sintered HA and HA-coated Ti-6Al-4V was significantly higher than that of uncoated Ti-6Al-4V (P < .001). There was no significant difference between the interface shear strength of dense sintered HA and HA-coated Ti-6Al-4V. After the push-out test for HA-coated implants, the regions fractured at the bone-coating interface and at the coating-titanium interface coexisted at 4 weeks after implantation. At 12 weeks, the fracture site was, in all cases, the HA coating-titanium interface, and, in a few samples, fractures inside the coating layer also were visible.

99mTc-tetrofosmin is a lipophilic, cationic diphosphine which has been developed for myocardial imaging. We examined 9 patients with ischemic heart disease including 3 angina pectoris (AP), 4 old myocardial infarction (OMI), 1 AP with OMI and 1 syndrome X. One patient was examined before and after operation. 370 MBq of 99mTc-tetrofosmin was injected during exercise and 740 MBq at rest. And 74 MBq of 201Tl myocardial exercise and redistribution scintigraphy was also performed to compare with 99mTc-tetrofosmin myocardial scintigraphy. SPECT, multiple gated SPECT and anterior planar images were obtained in all cases. We calculated percent wall thickening (%WT) using multiple gated SPECT images. There was a decreased lung uptake in 99mTc-tetrofosmin planar images compared to 201Tl myocardial scintigraphy. Liver and Biliary system uptake in 99mTc-tetrofosmin images was decreased with intake of milk. Segmental comparison of SPECT images showed an agreement in 9/10 of the segment between 201Tl and 99mTc-tetrofosmin. We could obtain excellent quality of multiple gated SPECT images in all patients. We could calculate percent wall thickening (%WT) in all patients. We conclude that 99mTc-tetrofosmin myocardial scintigraphy should provide usefulness for detection of ischemic myocardium as same as 201Tl myocardial scintigraphy, although the biologic characteristics of two agents were different. These data and excellent quality of multiple gated SPECT images suggest that 99mTc-tetrofosmin is a new 99mTc agent for evaluation of patients with ischemic heart disease.

This is the first report of the process of formulation of a cervical osteophyte causing dysphagia. The patient had ankylosing spinal hyperostosis and OPLL and was followed radiographically for a long time before the onset of dysphagia. The radiological observation suggested that dysphagia was produced when the immobile part of the esophagus was compressed by the anterior projecting cervical osteophyte. The immobility of the esophagus is an important factor in determining whether dysphagia occurs. Another possible contributing factor to dysphagia in this patient was the ossification of the cervical anterior and posterior longitudinal ligaments. The OPLL affected intervertebral segmental motion and induced the formation of anterior projecting cervical osteophytes.

To investigate the association of alcohol intake, cigarette smoking, occupation, and other factors with the development of idiopathic osteonecrosis of the femoral head, a nationwide multicenter case-control study was conducted in Japan during 1988-1990, comparing 118 cases with no history of systemic corticosteroid use with 236 controls matched for sex, age, ethnicity, clinic, and date of initial examination. The risks of developing femoral head necrosis associated with potential risk factors were estimated by adjusted relative odds obtained by a conditional logistic regression model. The elevated relative odds were observed for occasional drinkers (relative odds = 3.2, 95% confidence interval 1.1-9.2) and regular drinkers (relative odds = 13.1, 95% confidence interval 4.1-42.5) with a significant dose-response relation (p < 0.001). For current drinkers, the relative odds were 2.8, 9.4, and 14.8 for < 320, 320-799, and > or = 800 g/week of ethanol intake, respectively. An increased risk was found for current smokers (relative odds = 4.7, 95% confidence interval 1.5-14.5), but a linear increasing trend in the cumulative effect of smoking was not evident at 20 pack-years or over. A weak but significant dose-response relation was observed for daily occupational energy consumption (p < 0.05). The present study confirmed the strong association of alcohol intake and positive association of cigarette smoking and suggested the role of heavy physical work.

Arthrograms and operative findings of 19 patients with 26 congenital dislocations of the knee (CDK) were reviewed to clarify the pathologic features, methods of treatment, and the optimum treatment for the patient with multiple joint deformities. The fundamental pathologic features in CDK involved a shortening of the quadriceps femoris tendon, a tight anterior articular capsule, and hypoplasia of the suprapatellar bursa. Valgus deformity of the knee, which was observed in half of the patients, was caused by the fragility of the medial components of the knee. This fragility was attributable to the forward displacement of the tibial insertion of the medial components. Arthrograms served as effective indicators when evaluating the pathologic features and determining the applicability of surgical therapy. There were limits to conservative therapy that were dependent on the extent of the pathologic changes. In extremely refractory patients with arthrogryposis multiplex congenita (AMC), an elimination of genu recurvatum and an improved range of movement could be obtained by the use of surgery. The valgus deformity was significantly reduced by invasive treatment that reinforced the fragile inner components. Experience with nine patients with multiple lower-limb joint deformities indicates that the knee dislocation should be treated before any of the other deformities.

Primary rhabdomyosarcoma of bone is exceedingly rare. We present a case of rhabdomyosarcoma of the iliac bone in a 32-year-old male. Histologically, the tumour consisted mainly of a uniform proliferation of elongated spindle cells arranged in a herring bone pattern, simulating fibrosarcoma. Focally there was a conventional embryonal pattern with scattered rhabdomyoblasts possessing an eosinophilic cytoplasm. Immunohistochemical studies disclosed expression of muscle markers such as desmin and muscle-specific actin, in both the embryonal and spindle-cell areas and myoglobin only in the embryonal areas. Such histological features are unusual for classical embryonal rhabdomyosarcoma. The anatomical site and age of the patient are also atypical.

Primary bone tumours and metastases of the patella are rare. We report two cases of metastases, one from a carcinoma of the salivary gland which was bilateral and the other from extramammary Paget's disease with invasive carcinoma.

We reviewed 106 consecutive patients who had undergone anterior cervical fusion with the Caspar instrumentation system between 1984 and 1989. Preoperative diagnoses were cervical spondylosis in 73 patients, a traumatic lesion in 12, ossification of the posterior longitudinal ligament in 9, cervical disc herniation in 6, and tumour or miscellaneous lesions in 6. In the 106 patients, 56 had two levels fused and 27 had three levels fused. At an average duration of follow-up of 4 years and 7 months, nonunion occurred in 3 of the 83 patients with multiple level fusions. Screw loosening occurred in 8 of the 106 patients, but there was no oesophageal perforation.

Congenital triggering of a digit other than the thumb is a rare. A nine year old boy has been treated for congenital, multiple trigger digits in addition to the thumb. The operative findings were only slight thickening of the flexor pulley and noticeable fusiform swelling of the flexor tendons.

We measured evoked mixed nerve action potentials (EMNAP) in the forearm segment of 108 hands as an indicator of retrograde degeneration in the carpal tunnel syndrome (CTS). This was made by recording at the elbow and stimulating the median nerve 4 cm proximal to the wrist crease. The amplitude of this EMNAP decreased in proportion to the prolongation of the motor terminal latency (MTL) or the decrease in the amplitude of the compound muscle action potential (CMAP) from the abductor pollicis brevis (APB) muscle. This suggests that retrograde degeneration progresses as the severity of CTS increases. This decrease was also in proportion to the decrease in the motor nerve conduction velocity (MNCV) in the forearm. Both MNCV in the forearm and EMNAP can indicate retrograde degeneration in CTS, but the MNCV cannot be measured when muscle atrophy is severe and the CMAP cannot be elicited. Therefore, we believe that EMNAP is a more useful measure of the retrograde changes in CTS.

The pathobiology of total joint prosthesis infection was investigated in vitro. Discs of polymethylmethacrylate (PMMA) were exposed to a suspension containing cells of 10(8) per mL Staphylococcus epidermidis E-46. After 12 hours, exposed discs were rinsed with phosphate-buffered saline and placed in brain heart infusion broth containing antibiotics (2.5 mg per mL of Cephaloridine). After gentle shaking for 24 hours at 37 degrees C, the bacteria on the PMMA surface were detached and washed with phosphate-buffered saline to remove the antibiotics. Compared with the free bacteria which were detached from the PMMA by sonication immediately after exposure to the antibiotic solution, those allowed to remain adhered to the PMMA surface were more resistant to antibiotics. Scanning electron microscopy showed accumulation of bacteria surrounded by slime on PMMA discs exposed for 12 hours. Our results indicate that resistance of bacteria to antibiotics is increased after adherence to the biomaterial and formation of a slime layer.

Blood flow rates of the canine femoral head were experimentally determined during traction, compression, and hip joint tamponade using the hydrogen washout technique. In puppies, blood flow rate of the femoral head was significantly decreased with either traction or compression applied at one half body weight. Either maneuver, when combined with hip joint tamponade, reduced blood flow rate of the femoral head an average of more than 70% as compared with the initial control rate. In adult dogs, combinations of either traction or compression, at one-half body weight, with hip joint tamponade did not significantly decrease blood flow rate of the femoral head as compared with control values. Perfusion defect of blue silicone could be observed only in puppies around the hip during combinations of traction or compression with hip joint tamponade and involved the posterior superior capital branches of the medial circumflex artery and the arteries in the ligamentum teres. These experimental data may have important implications for the pathogenesis of iatrogenic avascular necrosis in the treatment of congenitally dislocated hip, Legg-Perthes disease, and avascular necrosis following nondisplaced femoral neck fracture.

Histological and electron microscopic studies were performed to demonstrate the changes in the morphology of the growth plate that occur in allografts obtained from the limbs of growing rats. A genetically defined model was used in which the right hindlimbs of Lewis rats were orthotopically transplanted into Fischer-344 recipient rats. These strains are matched for major histocompatibility antigens but mismatched for minor histocompatibility antigens. The disparity at the minor histocompatibility complex between the Lewis donors and the Fischer recipients creates a weak histocompatibility barrier to transplantation. Lewis-to-Lewis syngeneic limb grafts were used as controls. The proximal parts of the transplanted tibiae were excised during acute rejection of the allograft on days 1, 5, 8, 11, 14, and 28 postoperatively. During rejection, a widened zone of calcified cartilage in the growth plate was observed at eleven days; this zone increased progressively thereafter. The number of chondroclasts in the primary spongiosa of the metaphysis had decreased significantly at eleven days, and chondroclasts had disappeared completely at fourteen days, in association with mononuclear cell infiltration. Electron microscopic examination revealed inactive morphology in some chondroclasts at eight days, and the number of inactive chondroclasts had increased significantly on day 11. At fourteen days, there were no viable chondroclasts in the primary spongiosa, and only remnants of degenerated chondroclasts were present. These findings suggest that the chondroclasts were early targets of rejection and their loss resulted in the cessation of resorption of the calcified cartilage. However, the proliferation and maturation of chondrocytes in the growth plate and the calcification of the matrix continued, despite progression of rejection in the metaphysis. Thus, survival of the chondrocytes and rejection of the chondroclasts apparently led to the formation of a widened calcifying zone in the growth plate.

The authors determined the effects of distraction of the spine on physiologic integrity of the spinal cord using neurogenic motor evoked potentials (NMEPs), somatosensory evoked potentials (SEPs), spinal cord blood flow measurements, and clinical status in nine hogs. Spinal cord blood flow was measured after each level of distraction using the hydrogen washout technique. The results indicated that blood flow of at least 65% of baseline was required to maintain physiologic integrity of the spinal cord, and that a decrease of blood flow to 12% of baseline was associated with paraplegia. Neurogenic motor evoked potentials always correlated with the animal's postsurgical clinical status, whereas the SEP was falsely negative in one animal.

We reviewed 29 patients who had developed destructive arthropathy of the spine during long-term haemodialysis. Their mean age when haemodialysis began was 43.8 years; at diagnosis they had been dialysed for an average of 8.6 years. In 26 patients, the lesions were between C4 and C7; in six they were between L4 and S1, three having lesions in both regions. Sixteen patients had had previous surgery for carpal tunnel syndrome. Spinal surgery was performed in nine patients with satisfactory results in only five. We demonstrated beta-2 microglobulin amyloid deposits in the discs and surrounding ligaments in all biopsied cases. The natural history and management of this condition are not yet clear.

The authors investigated the effects of focal compression on physiologic integrity; somatosensory evoked potentials, neurogenic motor evoked potentials and spine-to-spine potentials, on spinal cord circulation and clinical status in four different type of compression; posterior, anterior, circumferential, and lateral in 31 pigs. Spine-to-spine potentials degraded earlier in amplitude than somatosensory evoked and motor evoked potentials regardless of direction of compression. The first lost potential was the somatosensory evoked one during posterior, circumferential, and lateral compression and motor evoked potentials during anterior compression. Somatosensory evoked potential was the only wave to detect the side of lateral compression. Following release of compression somatosensory evoked potentials and motor evoked potentials returned almost to 100% in amplitude, whereas spine-to-spine potentials recovered to approximately 50%. At that time all animals showed grossly normal motion in hind-limb, therefore spine-to-spine potentials might be too sensitive to motor function. Spine-to-spine potentials should contain more tracts than either somatosensory evoked potentials or motor evoked potentials. Somatosensory evoked potentials probably show more posterior part, whereas motor evoked potentials do more of the anterior part of the spinal cord. The spinal cord revealed a complete ischemia regardless of direction of compression when at least one potential was gone, however it regained the shape and perfusion following release of compression although there were some hemorrhagic contusions remaining. These suggest that ischemic changes may play some part in degradation of potentials, however it does not influence much the recovery following release of compression because it regains quickly. The final recovery depends on the complication.

We investigated the effect of tobramycin-impregnated polymethylmethacrylate (PMMA) bone cement on the adhesion and colonization of Staphylococcus epidermidis. The pattern of colonization was quantitated using plate count techniques and electron microscopy. Colonization of the tobramycin-impregnated disc surface by adhesive bacteria was demonstrated but it was less than in the control disc. This finding suggests that tobramycin may reduce bacterial adherence and proliferation on the PMMA surface.

Tumor cells must attach themselves to basement membranes, through which they degrade and migrate, in order to spread to distant sites. If vascular endothelial cells are damaged by pretreatment with anticancer drugs and the subendothelial basement membranes are exposed, the attachment of malignant cells to basement membranes and subsequent metastasis formation in some tissues may be enhanced. In this study, the pretreatment of endothelial cell monolayers and mice with cyclophosphamide (CPA) was respectively shown to promote the adhesion of HT1080 human fibrosarcoma cells to endothelial cell monolayers in vitro and lung colonization in vivo. YIGSR, a synthetic laminin pentapeptide, inhibited the enhancement of lung colonization by CPA when it was co-injected intravenously with tumor cells. This inhibitory effect of YIGSR may be due to a reduction in the adhesion of HT1080 cells to injured blood vessel walls since YIGSR inhibited both the adhesion of HT1080 cells to CPA-treated endothelial cell monolayers and the invasion through basement membranes in vitro.

From 1972 until 1988, transtrochanteric rotational osteotomy was used to treat 474 hips in 378 patients with idiopathic and steroid-induced osteonecrosis of the femoral head. Two hundred twenty-nine of 295 hips with anterior rotation and follow-up periods ranging from three to 16 years had excellent surgical results (success rate, 78%). Outcome was chiefly dependent on the ratio of transposed intact posterior articular surface to the acetabular weight-bearing area after osteotomy. This relationship suggested that the transposed intact area should occupy more than 36% of the acetabular weight-bearing area by adequate rotation and intentional varus position in addition to rotation, especially for extensive lesions. Salvage operations, such as total hip arthroplasty, were performed on 18 hips, of which ten hips were cases of either relative indication for extensive lesions in young patients or other misindications for rotational osteotomy. Four hips sustained neck fracture, including three hips after 180 degrees of posterior rotation; two hips were complicated with avascular necrosis, and another two hips developed osteoarthrosis. Histologically, femoral heads with osteoarthrosis removed at the time of salvage operation showed complete healing of the necrotic lesion. The overall findings indicate that healing of the necrotic lesion of the femoral head may be brought about by rotational osteotomy if it spares the vulnerable site from the brunt of mechanical stress.

We propose new criteria for the electrodiagnosis of Martin-Gruber connection. Forty-seven patients with cubital tunnel syndrome were studied, and 8 (17%) were found to have a Martin-Gruber connection. Eighty-seven patients without cubital tunnel syndrome were also studied, and 14 (16%) had a Martin-Gruber connection. The rate of occurrence of the anastomosis in these two groups was approximately the same. No sensory communication was demonstrated, and the lateral intrinsic muscles received more innervation from the communicating branch than the hypothenar muscles. The entry point of the crossing fiber from the median nerve to the ulnar nerve was 3 to 10 cm distal to the medial humeral epicondyle, and there may be a significant risk of injury in ulnar nerve transposition.

We have used an extract of basement membranes which can be reconstituted into a biologically active gel matrix composed predominantly of collagen IV, laminin, nidogen, and heparin sulfate proteoglycan, in order to study the mechanisms involved in tumor cell invasion. When layered onto a porous filter in a Boyden chamber, the gel forms a barrier to the passage of normal cells. Malignant cells are able to cross this layer when the conditioned medium of NIH 3T3 cells is used as a chemoattractant to stimulate cell migration. A variety of human tumor cells have thus been studied in this system and we find a high correlation between their invasiveness in vitro and their malignant behavior as exhibited in vivo. We have used this in vitro invasion assay to test for factors which might inhibit tumor cell invasion. Collagenase IV is produced by malignant cells and is thought to be required for invasion. Indeed, inhibitors of this enzyme have demonstrated reduced tumor cell invasiveness. One site of five amino acids, on the B1 chain, which has been shown to promote cell adhesion, migration and binding to laminin receptor, was found to inhibit the invasion of tumor cells. In addition, factors which elevated cAMP levels were also able to suppress the invasiveness of tumor cells. These data suggest that the assay system described herein can be successfully utilized to study the invasive activity of tumor cells and those factors that may inhibit the spread of malignant cells.

The affinity of bone for bioinert ceramics and stainless steel was compared using calcified bone specimens. We implanted cylinders of alumina ceramics (Al2O3), zirconia ceramics (ZrO2) and SUS-316 L stainless steel into the distal femoral epiphyses of dogs and then made observations from 4 to 96 wk post-operatively. Irregularities in the histological specimens suggested the presence of artefacts due to the insertion technique. We subsequently used screws inserted into holes tapped with a tap that had a diameter identical to the screws, and observed these implants from 4 to 96 wk after insertion. There was no detectable difference in the affinity index for all three materials from 4 to 96 wk after implantation. The affinity index was calculated as the ratio of the new bone directly adjoining the implant without any intervening fibrous membrane or bone marrow to the total length of the bone-implant interface x 100%.

We have operated on 42 patients with bone metastasis from various primary tumors over the past fourteen years. The number of operated cases of metastasis secondary to thyroid and breast carcinoma was especially high, since patients with such types of cancer have prolonged life expectancies in general. The sites of these operation were as follows: 27 in the spine, 12 in the femur, 2 in the tibia, and 1 in the humerus.

Tobramycin sulfate powder (1.2 g) was mixed with Palacos polymethylmethacrylate (PMMA) bone cement (40 g) to produce 100 discs containing 5.9 mg tobramycin per disc. These discs were used to evaluate the inhibition of bacterial adhesion to an antibiotic-laden biomaterial. Tobramycin-impregnated PMMA discs and control discs containing no tobramycin were exposed in vitro to Staphylococcus epidermidis. Colonization was quantitated using plate count techniques and electron microscopy. Tobramycin-impregnated surfaces reduced adhesive bacteria colonization by 1 log relative to control discs. These observations suggest that tobramycin-impregnated PMMA may not be significantly effective in preventing colonization of the biomaterial substratum and PMMA may be a poor choice as a drug delivery vehicle in biomaterial and compromised tissue-centered infections.

The use of standing radiographs to determine correction angles for high tibial osteotomy is not appropriate because the relative angle of the articular surfaces (condylar-plateau angle) in the weight-bearing knee changes after the osteotomy. This may give unpredictable results postoperatively. We found that the condylar-plateau angle in postoperative standing films is very similar to that seen in non-weight-bearing supine views, and suggest that these latter radiographs be used for pre-operative planning. We describe our early results, using a special osteotomy jig, in 140 knees.