Variable tibiofemoral articular contact stress in fixed-bearing total knee arthroplasties.

BACKGROUND: Rotational allowance at the tibiofemoral joint would be required during deep flexion. However, the amount of flexion and rotation has not been investigated in modern total knee arthroplasty (TKA) designs. The present study aimed to determine the contact stress in five posterior-stabilized fixed-bearing TKA designs. HYPOTHESIS: We hypothesized that the contact area and stresses at the tibiofemoral articular surfaces vary according to the type of implant design and tested condition. MATERIALS AND METHODS: The contact area and mean and peak contact stresses at the tibiofemoral articular surfaces were determined when a compressive load of 1200N was applied to a NexGen LPS Flex, Scorpio NRG, Genesis II, PFC Sigma, and Foundation implant. Measurements were performed at 0° and 45° flexion with 0°, 5°, 10°, and 15° rotation, and at 90° and 135° flexion with 0, 5°, 10°, 15°, and 20° rotation. RESULTS: The LPS Flex showed that the femoral component could not achieve 20° rotation at 135° flexion. The Scorpio NRG showed less than 20MPa of contact stress at all conditions. The Genesis II showed higher contact stress than 20MPa at 135° flexion with 20° rotation. The PFC Sigma showed that the femoral component could not achieve >10° rotation at any flexion angle. The Foundation showed more than 20MPa of contact stress at 90° flexion with 20° rotation and at 135° flexion with 10°, 15°, and 20° rotation. DISCUSSION: Surgeons should be more aware of the variable contact conditions of the tibiofemoral articular surfaces in individual TKA designs. LEVEL OF EVIDENCE: Level IV, basic science study.

Biomechanical properties of heat-treated bone grafts.

INTRODUCTION: A possible critical complication associated with banking bone is human immunodeficiency virus (HIV) infection. Recently, since the report of HIV infection in bone allografts from an HIV-seronegative donor, a more reliable method of sterilization for preserved bone graft has become necessary. Heat treatment of banking bone is one of the simple sterilization methods. This method is especially safe and practical for the prevention of HIV infection. MATERIALS AND METHODS: We previously reported a biological study on heat-treated bone graft. In that study, we showed that revascularization and new bone formation of bone graft after heat treatment at 60 degrees C was nearly the same as that of non-heat-treated bone graft, while at 100 degrees C, revascularization and new bone formation showed a significant delay. This time, we examined the change of mechanical strength of heat-treated bone grafts after transplantation in an experiment. To eliminate the problem of antigenicity of grafted bone, we used autografts, not allografts. Two types of heat-treated autografts were employed: heat-treated at 60 degrees C for 30 min and heat-treated at 100 degrees C for 5 min; as a control, fresh autografts were replaced in the left femur of rabbits. A strength test was performed for both the transplanted bone and the untreated intact right femur with time after transplantation. The strength test consisted of a compression test and torsional test, and the strength was compared between transplanted bone and the untreated intact right femur. RESULTS: In the compression test, the grafts heat-treated at 60 degrees C showed a strength ratio before transplantation of 97.3%. The strength ratio decreased to 63.5% at 18 weeks after transplantation. Then the strength ratio increased and recovered to 94.5% at 48 weeks after transplantation. However, the grafts heat-treated at 100 degrees C showed unsatisfactory mechanical strength, at 48 weeks the strength ratio was 60.1%, which was significantly lower compared with controls. In the torsional test, the grafts heat-treated at 60 degrees C showed almost the same strength observed in the compression test. However, the grafts heat-treated at 100 degrees C showed unsatisfactory mechanical strength: at 48 weeks, the strength ratio was 57.3%. CONCLUSION: Therefore, heat treatment at 60 degrees C is a useful sterilization method, not only in biological but also mechanical terms.

[Atypical Fisher syndrome with optic nerve involvement].

We report a 38-year-old woman who developed what appeared to be Fisher syndrome associated with optic nerve involvement. One week after a common cold, she developed double vision and left facial palsy. Four days after the onset, she developed bilateral blurred vision, painful total ophthalmoplegia, and ataxic gait. Brain CT and MRI findings were normal. Her vision worsened but the optic fundi were normal. Serum anti-GQ 1 b antibody was elevated. She received steroid therapy at another hospital, and her vision, facial palsy and ocular pain improved. She was transferred to our hospital and we treated her by plasma exchange. She showed near complete recovery. Human optic and ocular nerves contain high amount of GQ 1 b. This may be a underlying mechanism for optic nerve involvement in Fisher syndrome. We thought that she had an atypical Fisher syndrome associated with optic nerve involvement.

[An 84-year-old woman with progressive mental deterioration and abnormal behavior].

We report an 84-year-old woman with progressive mental deterioration. She was well until January 1994, when she was 80 years of the age. At that time she developed a delusional ideation, in that she stated that she would be killed by her fellow members of the society for elderly, in which she was belonging. At times, she closed the shutter of her house saying that a stranger was wandering outside of her house. In 1995, she could not identify the face of her son's wife. When she went out for shopping, she lost her way to the home. She prowled about in and out of her home. In 1996, she had to be admitted to a nursing home, where quarrelled with other patients and behaved violently. She was admitted to the neurology service of Hatsuishi Hospital on November 20th, 1997. Family history revealed that her mother was said to be demented. On admission, she was alert and behaved in a good manner. She was disoriented to the time and unable to do serial 7. Her memory was very poor. She did not show aphasia or apraxia. Cranial nerves appeared to be intact. She showed no weakness or muscle atrophy. Gait was normal for her age. Plastic rigidity was noted in four limbs more on the right side. No ataxia was noted. Deep tendon reflexes were exaggerated, however, no Babinski sign was noted. Sensory examination was intact. Her hospital course was characterized by the development of progressive gait disturbance, violent behaviour, and prowling around. On November 30th, 1998, she fell down and suffered from a fracture in the neck of her femur. Although replacement of the femur head was performed, she became unable to walk after this episode. Her mental functions deteriorated further. She developed pneumonia and expired on February 2, 1999. She was discussed in a neurological CPC and the chief discussant arrived at a conclusion that the patient probably had diffuse Lewy body disease, because of the combination of dementia and parkinsonism. Other possibilities discussed in the CPC included Pick's disease, frontotemporal dementia and parkinsonism, and Alzheimer's disease. Post-mortem examination revealed moderate atrophy in the frontal and temporal cortices. Microscopic examination showed atrophy and gliosis in the hippocampus. Many diffuse plaque and neuritic plaques were seen in the frontal cortex by methenamine silver staining. Neurofibrillary tangles were also found. The Meynert nucleus was preserved. The putamen and the substantia nigra were also intact. Pathologic diagnosis was consistent with Alzheimer's disease.

[A 64-year-old man with parkinsonism as an initial symptom followed by dementia associated with marked abnormal behaviours].

We report a 64-year-old man with parkinsonism as an initial symptom, which was followed by dementia and abnormal behaviours. He was well until 1985, when he was 49 years old, when he noted rest tremor in his right hand. Soon tremor appeared in his left hand as well. He was seen in our clinic and levodopa was prescribed. He was doing well with this medication, however, in 1993, he started to suffer from on-off phenomenon. He also noted visual hallucination. In 1994, he stole a watermelon and ate it in the shop. He repeated such abnormal behaviours. In 1995, he was admitted to the neurology service of Hatsuishi Hospital. On admission, he was alert and oriented. He did not seem to be demented; however, he admitted stealing and hypersexual behaviours. No aphasia, apraxia, or agnosia was noted. In the cranial nerves, downward gaze was markedly restricted. He showed masked and seborrhoic face, and small voice. No motor palsy was noted, but he walked in small steps with freezing and start hesitation. Marked neck and axial rigidity was noted. Tremor was absent except for in the tongue. No cerebellar ataxia was noted. Deep tendon reflexes were diminished. Plantar response was extensor bilaterally. Forced grasp was noted also bilaterally. He was treated with levodopa and pergolide, but he continued to show on-off phenomenon. His balance problem and akinesia became progressively worse; still he showed hypersexual behaviour problems. He also showed progressive decline in cognitive functions. In 1997, he started to show dysphagia. He developed aspiration pneumonia in July of 1998. In 1999, he developed emotional incontinence and became unable to walk. He also developed repeated aspiration pneumonia. He died on March 1, 2000. He was discussed in a neurological CPC and the chief discussant arrived at a conclusion that the patient had corticobasal degeneration. Other diagnoses entertained included dementia with Lewy bodies, diffuse Lewy body disease, and frontotemporal dementia. Majority of the participants thought that diffuse Lewy body disease was most likely. Post-mortem examination revealed marked nigral neuronal loss, gliosis and Lewy bodies in the remaining neurons. Abundant Lewy bodies of cortical type were seen wide spread in the cortical areas, but particularly many in the amygdaloid nucleus. Lewy bodies were also seen in the subcortical structures such as the dorsal motor nucleus, oculomotor nucleus, Meynert nucleus, putamen, and thalamus. What was interesting was marked neuronal loss of the pontine nuclei, demyelination of the pontocerebellar fiber, and moderate neuronal loss of the cerebellar Purkinje neurons, a reminiscent of pontocerebellar atrophy. However, the inferior olivary nucleus was intact.

[A 77-year-old man with gait and gaze disturbance].

We report a 77-year-old Japanese man with progressive gait disturbance. He was well until his 71 years of the age (1992), when he noted an onset of disturbance in his speech, which was followed by difficulty in using his left hand. He did not attempt to use his left hand afterwards. He started to fall down in the spring of 1994. He was admitted to our service on October 6, 1994. Neurologic examination revealed an alert and oriented man. He showed limb-kinetic apraxia in his left hand with anosognosia for his apraxia. Vertical gaze was impaired. He walked in small steps. He had moderate axial and limb rigidity. He had no weakness, ataxia, or tremor. Deep tendon reflexes were normal. Plantar response was flexor. Sensation was intact. His gait had progressively become worse and he was admitted to another hospital in April of 1996. At that time he was disoriented to time. He was only able to walk a few steps with support. He continued to show limb-kinetic apraxia in his left hand. He developed dementia and dysphagia and he expired on October 27, 1998. He was discussed in a neurological CPC, and the chief discussant arrived at the conclusion that the patient had corticobasal degeneration. Most of the participants agreed with this diagnosis, but a few of them thought that progressive supranuclear palsy would be more likely. Post-mortem examination revealed no gross cortical atrophy. The right hemisphere was kept frozen for future biochemical analysis. The left precentral gyrus showed spongy changes, neuronal loss and gliosis. The pallidum, putamen, and the subthalamic nucleus were unremarkable, however, neurofibrillary tangles were seen in the subthalamic nucleus. The substantia nigra showed only slight neuronal loss; neuronal pigments were well retained. A few neurofibrillary tangles were seen in the remaining neurons. The cerebellar dentate nucleus showed grumose degeneration. Gallyas-Braak staining revealed many tuft-shaped astrocytes in the precentral gyrus. Pathologic diagnosis was progressive supranuclear palsy. Some participants thought that this diagnosis was unacceptable, because the pathologic changes in the substantia nigra, globus pallidus, and the subthalamic nucleus, which were usually severely involved in PSP, did not show typical changes of PSP. In addition, the predominant clinical feature was limb-kinetic apraxia, although he showed vertical gaze paresis and parkinsonian gait, which could also be seen in corticobasal degeneration. There was a big discussion among participants with regard to the diagnosis.

Revascularization and new bone formation in heat-treated bone grafts.

Human imnmunodeficiency virus (HIV) infection is one of the possible serious complications associated with bone allografts. In order to prevent infection, grafted bone is sterilized by various treatments. Heat treatment has attracted attention as a simple and practical method. We carried out a histological study of the influence of heat treatment on autogenic bone grafts. To eliminate the problem of antigenicity of grafted bone, we used autografts, not allografts. Three types of heat-treated autografts were employed: heat-treated at 60 degrees C for 30 min, at 80 degrees C for 10 min, and at 100 degrees C for 5 min; as a control, fresh autografts were replaced in the rabbits' ilium. One, 2, 4 and 8 weeks after grafting, we performed microangiography and prepared two types of samples: transparent and haematoxylin-eosin (H&E) stained. Then, using an image analyzer, we quantitatively measured revascularization and new bone formation in the grafted bone. The grafts heat-treated at 60 degrees C showed early and good revascularization and new bone formation, from 1 to 8 weeks. The grafts heat-treated at 80 degrees C showed relatively good revascularization and new bone formation. However, the grafts heat-treated at 100 degrees C showed unsatisfactory revascularization and bone formation, less than 40% of control 8 weeks after grafting. Therefore, heat treatment at 60-80 degrees C does not seriously affect revascularization and new bone formation.

Mitochondrial dysfunction in Parkinson's disease.

This review discusses the etiology and pathogenesis of Parkinson's disease (PD). Mitochondrial respiratory failure and oxidative stress appear to be two major contributors to nigral neuronal death in PD. Complex I deficiency has been reported by several groups and appears to be one of the basic abnormalities responsible for mitochondrial failure. The principal question is whether or not complex I deficiency is primary or secondary. The second question is whether or not complex I deficiency is localized in the nigrostriatal system or is systemically present. It is our impression that complex I deficiency is not the primary cause but that its deficiency appears to be systemic. The primary cause may be the combination of genetic background and potential nigral neurotoxins. Exposure of nigral neurons to a high risk for oxidative damage because of its high dopamine content may be the reason for more pronounced nigral complex I deficiency compared to systemic organs. Oxidative stress and mitochondrial failure produce a vicious cycle in nigral neurons. To explore the genetic risk factors of sporadic PD, studies on familial PD and parkinsonism are important. Recently, an autosomal dominant form of familial PD was found to be caused by point mutations of the alpha-synuclein gene, and an autosomal recessive familial parkinsonism was mapped to the long arm of chromosome 6 near the Mn-SOD gene locus. Information obtained in these familial cases will contribute to the research on sporadic PD.

Fragile mitochondrial DNA: the missing link in the apoptotic neuronal cell death in Parkinson's disease.

The oxidative stress theory, the mitochondrial (mt) hypothesis, and the apoptosis hypothesis are proposed as the cause of neuronal cell death in Parkinson's disease (PD). However, the direct link between them has remained unknown. Recently, the mt control of nuclear apoptosis is documented that collapse of mt transmembrane potential due to energy crisis leads to release of apoptotic protease activating-factors into cytosol and subsequently nuclear DNA fragmentation. However, an endogenous factor responsible for the energy crisis under physiological conditions is missing. Here we report the missing factor as that mtDNA in the striatum of a parkinsonian patient fragments into 134 types of deleted pieces, being detected by the total detection system for mtDNA deletion. The system has documented that the mtDNA is extremely susceptible to hydroxyl radical damage, hence to oxidative stress, enough to cause the cellular energy crisis. The extensive fragility of mtDNA in brain stem could link the oxidative stress up with the apoptotic neuronal cell-death of PD.

Immunosuppressive effect of tacrolimus (FK-506). Bone xenografts in rabbits.

We examined the immunomodulatory effect of the macrolide antibiotic FK-506 (tacrolimus) in bone xenograft transplantation. Full-thickness pieces of iliac bone from mongrel dogs were transplanted into the iliac bone of Japanese white rabbits. FK-506 at a dose of 1.6 mg/kg/day was injected into the rabbits for 10 days after transplantation. In the animals treated with FK-506, inflammatory cell infiltration was remarkably reduced and revascularization accompanied by new bone formation occurred in the grafts. At 4 months after the transplantation, the formation of new bone and of mature new bone marrow were observed. In a control group, inflammatory cell infiltration was marked around the graft from 2 weeks after the transplantation. Revascularization from the recipient site to the graft in the control group was poor and only a small amount of new bone had formed at 4 months. Our findings suggest that short-term administration of FK-506 has a beneficial effect on experimental xenograft bone transplantation.

[The relationship between visual agnosia and visual pathway for perception].

We report a patient with a unique visual agnosia, who was thought to have lost visual functions except for the primary visual function. The patient was a 71-year-old woman with progressive memory loss and cerebro-cortical atrophy in MRI; her clinical diagnosis was senile dementia of Alzheimer's type. A battery of tests to detect higher visual dysfunctions was performed. First of all, we presented small dots and lines in front of the patient; the patient was able to recognize them. When a triangle, a tetragon, a cube, pieces of paper of different colors and lines of different length were presented, she was unable to recognize those objects. When pictures of her family members or filled circles of different size including small dots and lines were presented, the patient could only detect those small dots and any of lines; she could not recognize the members of her family. The cerebral blood flow was severely reduced in the occipital lobe except for the striate cortex. These data suggested that the visual function of striate cortex was preserved in this patient; the disturbance of higher visual functions was thought to be caused by the dysfunction of extra striate cortex.

Osteogenesis in xenogeneic bone transplantation, using an immunosuppressant. Rabbit-rat experiments.

We investigated osteogenesis and lymphocyte subsets in xenogeneic bone transplantation, using the immunosuppressant FK506 (FK). Iliac bones of rabbits were transplanted as fresh and frozen xenogeneic bone grafts into an intramuscular pouch of rats. FK was injected intramuscularly in half of the rats in a dose of 3 mg/kg/day for 14 days after transplantation. At 2, 4, and 8 weeks, transplanted grafts and the lymphocyte subsets of these rats were examined. In the group not given FK, the grafted bone became necrotic and infiltrated with small round cells around the trabeculae. In the FK group, at 2 and 4 weeks, new bone was formed in the fresh xenografts without infiltration of lymphocytes. At 8 weeks, the new bone became necrotic and lymphocytes were present. The percentage of T cells (CD 5), B cells and the ratio of CD 4 cells/CD 8 cells were smaller in the FK group. Using an immunosuppressant we concluded that xenogeneic bone has an osteogeneic potency.

Role of mitochondria in the etiology and pathogenesis of Parkinson's disease.

We discuss the etiology and pathogenesis of Parkinson's disease (PD). Our group and others have found a decrease in complex I of the mitochondrial electron transfer complex in the substantia nigra of patients with PD; in addition, we reported loss of the alpha-ketoglutarate dehydrogenase complex (KGDHC) in the substantia nigra. Dual loss of complex I and the KGDHC will deleteriously affect the electron transport and ATP synthesis; we believe that energy crisis is the most important mechanism of nigral cell death in PD. Oxidative stress has also been implicated as an important contributor to nigral cell death in PD, but we believe that oxidative stress is a secondary phenomenon to respiratory failure, because respiratory failure will increase oxygen free-radical formation and consume glutathione. The primary cause of mitochondrial respiratory failure has not been elucidated yet, but additive effect of environmental neurotoxins in genetically predisposed persons appears to be the most likely possibility.

Point mutations of mitochondrial genome in Parkinson's disease.

Oxidative stress and subsequent energy crisis have been proposed as the cause of nigral neuronal cell death in Parkinson's disease. We have reported defects in the mitochondrial respiratory chain and increased amount of deleted mitochondrial genome in the nigrostriatal system of patients with Parkinson's disease. Deletion in mitochondrial DNA could be ascribed to somatically acquired premature aging leading to cell death. To elucidate the contribution of maternally transmitted point mutations in mitochondrial DNA to the premature DNA damages, we employed a direct sequencing system and analyzed the total nucleotide sequences of mitochondrial DNA in the brains of five patients with idiopathic Parkinson's disease. There were no predominant point mutations among the patients in contrast to some neuromuscular diseases. However, each patient had several point mutations that would result in a significant change in the gene products. Some of these mutations may be involved either in the increased production of oxygen radicals from the mitochondrial respiratory chain or in the increased susceptibility of the respiratory chain components to oxidative damage. We propose that some of these mutations can be regarded as one of the risk factors accelerating degeneration of nigrostriatal pathway in Parkinson's disease.

Studies on the pathogenesis of Parkinson's disease in Japan.

Studies on the pathogenesis of nigral cell death in Parkinson's disease (PD) are reviewed. Discussions are focused mainly on studies performed by Japanese investigators because of the purpose of this issue. We and other groups found a decrease in complex I of the mitochondrial electron transfer complex in the substantia nigra of patients with PD, and in addition to complex I deficiency, we reported loss of alpha-ketoglutarate dehydrogenase complex of the tricarboxylic acid cycle (TCA cycle) by immunohistochemistry. Thus mitochondrial respiratory failure and resultant energy crisis appear to be one of the most important mechanisms that lead nigral neurons to cell death. The primary cause of mitochondrial respiratory failure has not been elucidated yet; however, environmental neurotoxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) may be responsible for nigral cell death in PD; in this respect a number of candidate toxins including tetrahydroisoquinolines and beta-carbolines have extensively been studied for nigral as well as mitochondrial toxicity. Recent progress in this field is also reviewed. Even if an environmental neurotoxin is involved in PD, exposure to such a neurotoxin alone may not account for its pathogenesis, as most of us are probably being exposed to the same toxin. Therefore, genetic predisposition appears to be essential for the development of PD. The genetic predisposition may involve hepatic detoxifying enzymes for such neurotoxins, the transport mechanism of those toxins to the brain, bioactivation of those toxins in the brain, the uptake mechanism to the nigral neurons, and the activity levels of target enzymes or proteins; all of these factors are being extensively studied in many laboratories at a molecular level.

An immunohistochemical study on alpha-ketoglutarate dehydrogenase complex in Parkinson's disease.

We report an immunohistochemical study of the mitochondrial alpha-ketoglutarate dehydrogenase complex (KGDHC) in the substantia nigra in Parkinson's disease. The KGDHC, the three enzyme complex catalyzing the oxidation of alpha-ketoglutarate to succinate through succinic semialdehyde, is the rate-regulating enzyme of the TCA cycle. The mitochondrial toxin, MPP+, inhibits not only complex I but also the KGDHC. Therefore, we investigated this enzyme complex in Parkinson's disease. In the control patients (n = 6), the immunostaining of the melanized nigral neurons was generally uniform; most of the melanized neurons showed good immunostaining with some neurons showing somewhat reduced staining. In Parkinson's disease (n = 9), many melanized neurons showed reduced immunostaining for the KGDHC, and those neurons were more frequently seen in the lateral one-third of substantia nigra. The decrease in the immunostaining for the KGDHC correlated roughly with the severity of degeneration. The KGDHC is more vulnerable to degeneration than complex II, III, and IV as noted in our previous immunohistochemical study. Even if secondary, the loss may play a role in the progression of the disease.

[A 66-year-old man with backache and progressive difficulty of gait].

We report a 66-year-old man with progressive spinal paraplegia. He was well until June of 1991 when he had an onset of backache and right chest pain. On August 25, he lost sensation to void and he became unable to urinate. On the same day, he noted weakness in his legs which became progressively worse, and he was admitted to our hospital. Past medical history included diabetes mellitus which was found 3 years previously. He had upper gastrointestinal series 2 months before, which revealed a normal study. On admission, he was alert and general physical examination was unremarkable. Neurological examination revealed a mentally sound man with normal higher cerebral functions. Cranial nerves were also intact. He was unable to walk. No muscle atrophy was noted, but he had moderate to marked (2/5) weakness in both legs. No ataxia was noted in the upper extremities. Jaw jerk was normal, however, deep reflexes in the upper extremities were decreased, and absent in the lower extremities Babinski sign was present bilaterally. All sensory modalities were diminished below the Th 6 dermatome. No meningeal sign was present. Emergency myelography was performed on the day of admission, which revealed complete block from the Th4 to Th8 segments. CSF taken at that time was xanthochromic, positive Queckenstedt test containing 1,133 mg/dl of protein, 54 mg/dl of sugar and 1/3 microliters of lymphocyte. On August 31, laminectomy was performed from Th5 to Th7. The spinal bones in this area was very fragile and hemorrhagic. A soft yellowish vascular-rich tissue was surrounding the spinal cord in the epidural space. Despite surgery his weakness in legs worsened, and he became paraplegic by September 10th. He became somnolent with disorientation to time. In the subsequent course, he developed metabolic acidosis on September 26. On September 28, he became anuric and hypotensive. He expired later on that day.(ABSTRACT TRUNCATED AT 400 WORDS)

Quantitative analysis of revascularisation and new bone formation in experimental bone grafts. The use of an image input and processing system.

Revascularisation and new bone formation in bone grafts has been extensively studied by histological techniques, but the images obtained are very complex and consequently difficult to evaluate quantitatively. We report similar analyses in experimental bone grafts using newer computerised digital techniques. Fresh autografts and fresh and frozen allografts were used. The histological analogue images from them were input digitally into an image processor. The amount of revascularisation and new bone formation could then be quantified in the different grafts. This system has proved to be a useful method of evaluation which could be applied to the quantitative analysis of other histological images.