Changes in microstructure and gene expression of articular chondrocytes cultured in a tube under mechanical stress

OBJECTIVE: The objective of this study was to clarify the effects of mechanical stress on chondrocytes cultured in a tube. Centrifugal pressure was applied to chondrocytes cultured in a tube for 28 days, and the effect of this stress was evaluated using a molecular biological method. DESIGN: Articular cartilage was harvested from a rabbit. A cell suspension was then prepared, and transferred in 1 ml aliquots to polypropylene tubes. After 48 h of incubation, centrifugal pressure (6.9 MPa) was applied every 24 h. Changes in morphology, expression of messenger RNA (mRNA) for insulin-like growth factor-I (IGF-I) and type II collagen, cell number, wet weight and protein concentration were evaluated. RESULTS: Microscopically, formation of chondrocyte clusters was seen in the cultures subjected to stress. Ultrastructurally, collagen fibers were seen to run parallel to the cytoplasmic surface of the stressed chondrocytes. The peak of IGF-I mRNA expression was seen on day 5, whereas type II collagen mRNA expression peaked on day 14. Cell number, wet weight and protein concentration were significantly increased in the stressed cultures. CONCLUSIONS: These results suggest that mechanical stress might affect the arrangement of collagen fibers and the IGF-I activity of chondrocytes cultured in a tube, thus influencing chondrocyte proliferation and increasing the volume of the extracellular matrix. Furthermore, mechanical stress may also affect the metabolism of articular cartilage in vitro.     

Homocysteine as a predictive factor for hip fracture in stroke patients

Risk of hip fractures in stroke patients is higher than that in a reference population. Hyperhomocysteinemia is regarded as a risk factor for ischemic stroke. The high prevalence of osteoporosis among patients with homocystinuria suggests that hyperhomocysteine may also increase the risk of fractures. To determine the association between homocysteine concentration and the risk of hip fractures, we studied a cohort of stroke patients with hemiplegia. Age-adjusted incidence rates of a hip fracture were calculated for quartiles of homocysteine concentrations. Cox proportional-hazard regression was used to calculate hazard ratios for quartiles of homocysteine levels. The initial enrolment of 433 hemiplegic patients with ischemic stroke, older than 65 years old, were followed for up to 10 years. The mean plasma homocysteine concentration at the enrolment was 14.1 +/- 5.2 micromol/L. There were 33 hip fractures among men and 46 among women during the mean follow-up period of 9.0 years. The age-adjusted incidence rates per 1000 person-years for hip fractures increased almost linearly from 2.89 in the lowest to 27.87 in the highest quartiles of homocysteine levels. We conclude that hyperhomocysteinemia is one of the risk factors for hip fractures in stroke patients.     

Effect of folate and mecobalamin on hip fractures in patients with stroke: a randomized controlled trial

Context  Stroke increases the risk of subsequent hip fracture by 2 to 4 times. Hyperhomocysteinemia is a risk factor for both ischemic stroke and osteoporotic fractures in elderly men and women. Treatment with folate and mecobalamin (vitamin B₁₂) may improve hyperhomocysteinemia. Objective  To investigate whether treatment with folate and vitamin B₁₂ reduces the incidence of hip fractures in patients with hemiplegia following stroke. Design, Setting, and Patients  A double-blind, randomized controlled study of 628 consecutive patients aged 65 years or older with residual hemiplegia at least 1 year following first ischemic stroke, who were recruited from a single Japanese hospital from April 1, 2000, to May 31, 2001. Patients were assigned to daily oral treatment with 5 mg of folate and 1500 µg of mecobalamin, or double placebo; 559 completed the 2-year follow-up. Main Outcome Measure  Incidence of hip fractures in the 2 patient groups during the 2-year follow-up. Results  At baseline, patients in both groups had high levels of plasma homocysteine and low levels of serum cobalamin and serum folate. After 2 years, plasma homocysteine levels decreased by 38% in the treatment group and increased by 31% in the placebo group (P<.001). The number of hip fractures per 1000 patient-years was 10 and 43 for the treatment and placebo groups, respectively (P<.001). The adjusted relative risk, absolute risk reduction, and the number needed to treat for hip fractures in the treatment vs placebo groups were 0.20 (95% confidence interval [CI], 0.08-0.50), 7.1% (95% CI, 3.6%-10.8%), and 14 (95% CI, 9-28), respectively. No significant adverse effects were reported. Conclusion  In this Japanese population with a high baseline fracture risk, combined treatment with folate and vitamin B₁₂ is safe and effective in reducing the risk of a hip fracture in elderly patients following stroke.      

Measurement of articular cartilage volumes in the normal knee by magnetic resonance imaging: can cartilage volumes be estimated from physical characteristics?

In recent times several studies have been performed on magnetic resonance imaging (MRI) sequences for imaging cartilage. A fat-suppressed three-dimensional sequence is one such noteworthy example. More recent studies have reported that the total volume of cartilage in a knee joint can be elucidated using this sequence. Based on these studies, we hypothesized that the total volume of cartilage in the knee joint may reflect certain other physical characteristics. The purpose of the current study was to clarify the articular cartilage volumes of the patella and femur in the human knee joints of healthy adults using MRI and to analyze the correlation of these volumes with other physical characteristics. The material comprised 68 knees of 68 Japanese healthy volunteers, aged from their twenties to their forties (37 men and 31 women) who had no past history of joint disease or trauma in the legs. The knees were imaged by MRI with a fat-suppressed three-dimensional sequence, and the cartilage volumes were calculated by computer processing. The factors analyzed were age, body weight, height, leg length, foot size, circumferences of the thigh and lower leg, the distance between medial and lateral femoral condyles, the diameter of the tibial head, body mass index, general joint laxity, quadriceps angle, and leg-heel alignment. The mean cartilage volume was 7.6 ± 1.6cm³ (8.3 ± 1.6cm³ in men, 6.7 ± 0.9cm³ in women). It was significantly larger in men than in women. However, the volume positively correlated with body weight, height, leg length, and foot size, without distinction of gender or age. Based on these data, a multiple regression analysis was developed: cartilage volume = 0.113 × height – 11.053. We concluded that the cartilage volume depends on physical size regardless of gender, and it can be estimated from factors of physical size.     

In vivo PET measurements with [11C]PE2I to evaluate fetal mesencephalic transplantations to unilateral 6-OHDA-lesioned rats

Positron emission tomography (PET) is a useful tool to assess and visualize neurotransmissions in vivo. In this study, we performed repeated PET scans with [11C]PE2I, a tracer of the dopamine transporter, to evaluate the alteration of the expression of dopamine (DA) transmission component after a fetal mesencephalic transplantation. The fetal mesencephalic cells were transplanted into the striatum of unilateral 6-OHDA-lesioned rats. PET scans with [11C]PE2I were performed to evaluate the DA transporter before and 2 and 4 weeks after the transplantation. Rotation behavior tests, in vitro autoradiography, measurements of DA contents in the striatum by high-performance liquid chromatography (HPLC), and tyrosine hydroxylase (TH) immunohistological examinations were performed at the same time points and examined for their relationship to changes in the dopamine transporter. The number of ipsilateral rotations induced by methamphetamine injections decreased. DA contents in the striatum measured with HPLC significantly increased. In the PET study, the binding potential of [11C]PE2I increased at 4 weeks. The results of the in vitro autoradiography study corresponded with those of the PET study. The degrees of the change in the binding potentials correlated with those of the numbers of rotations in the behavioral study and the DA contents in the striatum. In the histological examination, TH-positive cells with axons were observed at 2 and 4 weeks after the transplantation. As the dopamine transporter exists only in the axon terminal of DA neurons, these results suggested that PET measurements of [11C]PE2I binding indicated not only survival, but maturity and functioning of the transplanted cells. Repeated PET measurements of DA transporters are a useful tool in assessing the effectiveness of neural transplantations.     

Intradural jugular tuberclectomy in a case of inadequate extradural removal

BACKGROUND: The jugular tubercles are paired protuberances that arise from the inferolateral margins of the clivus and project posterosuperiorly over the hypoglossal canal. These bony structures sometimes obscure and hinder surgical manipulation of lesions situated in the lateral and premedullary cisterns during extended far lateral suboccipital approaches. The application of intradural jugular tuberclectomy is described to remove this bony eminence. METHODS: A case of ruptured dissecting aneurysm in the vertebral artery was treated through the transcondylar approach. Extradural removal of the posterior portion of the jugular tubercle was performed. The dura over the jugular tubercle was then removed, and the anterior part of the jugular tubercle was drilled away between the intradural hypoglossal canal foramen and jugular foramen under the lower cranial nerves. RESULTS: Great care was required during the intradural drilling procedure to prevent damage to the lower cranial nerves, brain stem, and jugular bulb. Intradural jugular tuberclectomy provided an adequate microscopic view of the midline anterior lower clival region. CONCLUSIONS: Intradural jugular tuberclectomy is a useful technique to remove the anterior part of this bony eminence after the transcondylar approach.     

Blood ionized calcium fraction in various serum albumin levels surveyed in non-dialysis patients

Blood ionized calcium (iCa) fraction is affected by the serum albumin(Alb) level, even though this effect might not be appropriately estimated by the formulae proposed previously. To clarify a reasonable regimen for predicting iCa from serum total Ca (tCa), we investigated the relationship of blood iCa, tCa, and serum Alb levels through 124 samples from 116 non-dialysis patients requiring iCa measurement at the Nephrology Section of Toride Kyodo General Hospital. The patients comprised 61 males and 55 females with the mean age of 66.9 +/- 1.4 years, including 9 cases of hypercalcemia, 110 of normocalcemia, and 5 of hypocalcemia based on their iCa levels. Their background diseases were 25 cases of chronic glomerulonephritis, 17 of nephrotic syndrome, 40 of diabetes mellitus, 4 of collagen diseases, and 30 of others. Their mean serum Cr was 2.44 +/- 0.21 mg/dl, and 77 patients showed elevated Cr levels. Four adjustment formulae: one derived from Payne's, two from the proposal of K/DOQI Clinical Practice Guidelines, and a theoretical one based on the previous in vitro experiments, were compared with the non-adjusted value (tCa itself) with respect to their suitability for estimating iCa. The correlation coefficient of tCa with iCa was higher than the values adjusted by the above four formulae. The difference of iCa from tCa divided by eight, which concisely predicted iCa based on the assumption that half the serum Ca is bound to protein, was less than 1/8th of the other adjusted Ca levels. Hence none of the adjusted Ca by the above formulae was superior to nonadjusted tCa from the point of estimating the iCa level. Moreover, the sensitivity for predicting hypocalcemia was the highest in tCa, even though its specificity was lower than the other adjusted values. In conclusion, no adjustment formula is required to predict ionized Ca from tCa, and to screen hypo- or hypercalcemia.     

Platypnea-orthodeoxia syndrome combined with multiple congenital heart anomalies

A 71-year-old woman was admitted for paralysis on the left side of her body. She developed dyspnea and hypoxemia after admission. Although pulmonary embolism was suspected, hypoxemia and dyspnea occurred repeatedly in spite of anticoagulation therapy. Transesophageal echocardiography revealed a patent foramen ovale (PFO), an atrial septal aneurysm (ASA), and a right-to-left shunt that appeared in an upright position. She was diagnosed with platypnea-orthodeoxia syndrome. Moreover, cardiac catheterization showed congenital anomalies, such as unroofed coronary sinus, partial anomalous pulmonary venous return and persistent left superior vena cava. Simple surgical closure of the ASA and PFO improved all of her symptoms.