J. Urban Lindgren

Prediction of vertebral strength by dual photon absorptiometry and quantitative computed tomography

SummaryWe measured the lumbar bone mineral of 19 cadavers (10 women, 9 men) by dual photon absorptiometry (DPA) and quantitative computed tomography (QCT). In addition, we determined the ultimate load and stress of each vertebra, and finally ash content and volumetric ash density of the vertebral body. We found that single energy QCT was inferior to DPA and dual energy QCT in the prediction of the ultimate load or stress of vertebrae (P<0.001). The ultimate stress of predicted by using the dual energy QCT results (r=0.71; SEE=36.3 N/cm2) whereas the ultimate vertebral load was best predicted by using the DPA (BMC) results (r=0.80; SEE=740 N). If the QCT finding was multiplied with the surface area of the vertebral body it could be used to predict the ultimate load with good accuracy (r=0.74; SEE=841 N). All the above correlations were higher in women than in men. The frequency of vertebral compression fractures in the material was wel correlated with the bone mineral findings. A nonlinear (third degree) relationship between mineral content and mechanical characteristics is proposed but within the area of measurement used in clinical practice a linear (first degree) equation is preferred.

The critical role of IL-12p40 in initiating, enhancing, and perpetuating pathogenic events in murine experimental autoimmune neuritis

Interleukin 12 (IL‐12) is a proinflammatory cytokine with important immunoregulatory activities and is critical in determining the differentiation and generation of Th1 cells. For the present study, we investigated the role of endogenous IL‐12 in the pathogenesis of experimental autoimmune neuritis (EAN), which is a CD4+ T‐cell mediated autoimmune inflammatory disease of the peripheral nervous system. EAN is used as an animal model for Guillain‐Barré syndrome of humans. Here, EAN was established in IL‐12 p40 deficient mutant (IL‐12‐/‐) C57BL/6 mice by immunization with P0 peptide 180–199, a purified component of peripheral nerve myelin, and Freunds complete adjuvant. In these IL‐12‐/‐ mice the onset of clinical disease was delayed, and the incidence and severity of EAN were significantly reduced compared to that in wild‐type mice. The former groups clinical manifestations were associated with less P0‐peptide 180–199 induced secretion of interferon‐γ (IFN‐γ) by splenocytes in vitro and low production of anti‐P0‐peptide 180–199 IgG2b antibodies in serum. Fewer IFN‐γ and TNF‐α producing cells, but more cells secreting IL‐4, were found in sciatic nerve sections from IL‐12‐/‐ mice, consistent with impaired Th1 functions and response. However, the IL‐12 deficiency appeared not to affect P0 peptide 180–199‐specific T‐cell proliferation. These results indicate that IL‐12 has a major role in the initiation, enhancement and perpetuation of pathogenic events in EAN by promoting a Th1 cell‐mediated immune response and suppressing the Th2 response. This information augments consideration of IL‐12 as a therapeutic target in Guillain‐Barré syndrome and other T‐cell‐mediated autoimmune diseases.

Studies of the calcium accretion rate of bone during immobilization in intact and thyroparathyroidectomized adult rats

In order to study the role played by the thyroid and the parathyroid glands in the development of osteoporosis induced by immobilization, 153 male adult Sprague-Dawley rats allocated in two groups were used. The animals of one group were thyroparathyroidectomized; those of the other group were left intact. Each group was then divided into two subgroups; in one the right hind leg of the animals were immobilized by an elastic adhesive bandage. The animals were observed for varying periods of time up to 16 weeks. Studies of bone mass and45Ca accretion rate of the right and left femur and tibia were performed in all animals. The results indicate that disuse osteoporosis occurs in rats in the virtual absence of the thyroid and parathyroid glands. The bone loss of the immobilized femur and tibia was less pronounced in thyroparathyroidectomized rats compared to intact rats. The uptake of45Ca in bone treated by immobilization as compared to the non-immobilized bone was found to be increased to the same proportion in thyroparathyroidectomized and in intact rats. The calcium-accretion rate of non-immobilized bone was lower in thyroparathyroidectomized than in intact rats. The observations indicate that in the rat the parathyroid and thyroid hormones influence the rate of bone turnover and thereby the rate of development of disuse osteoporosis.

Exogenous soluble tumor necrosis factor receptor type I ameliorates murine experimental autoimmune neuritis

Tumor necrosis factor (TNF) and its receptor (TNFR) have been strongly implicated in the pathogenesis of autoimmune disease. Soluble cytokine receptors may be shed naturally from cell membranes to inhibit cytokine activity. Experimental autoimmune neuritis (EAN) is a CD4 Th1 cell-mediated animal model of Guillain-Barré syndrome (GBS) in humans. In the present study, we investigated the effects of soluble TNFR type I (sTNFR I) in EAN induced in mice by P0 peptide 180-199 and Freunds complete adjuvant. Our data from two different therapeutic regimens indicate that the administration of sTNFR I effectively ameliorated the clinical and pathological signs of EAN, i.e., decreased its severity, shortened its duration, and reduced inflammatory cell infiltration into the peripheral nervous system. The suppression of clinical EAN was accompanied in vitro by a marked reduction in antigen-specific T-cell proliferation and IFN-gamma synthesis by spleen cells from sTNFR I-treated mice, compared to control mice treated with PBS. These data directly demonstrate a pivotal role for TNF in the development of EAN and also suggest that sTNFR I may have therapeutic potential for alleviating GBS in humans.

The uncemented fully textured Lord hip prosthesis: a 10- to 15-year followup study.

One hundred fourteen total hip arthroplasties in 110 patients performed between 1979 and 1983 using the Lord femoral component were analyzed. Nine femoral revisions were performed within 13 years after surgery (two because of infection). Excluding infections there was a 94% 13-year survival according to a Kaplan-Meier analysis. Subsidence was seen in five hips (five patients), but only one needed revision surgery. Seventy-six hips (73 patients) had a radiographic followup of 10 years or more and were analyzed in detail. Changes in cortical thickness, density, and formation of spotwelds continued beyond 5 years after surgery, meaning the remodeling of periprosthetic bone continued beyond that time. Osteolysis on the femoral side was seen in seven hips, always in the proximal part of the femur, apparently as a continuation of the joint space. No remote focal osteolysis was seen. Elderly patients, women, and patients with a pedestal were overrepresented among individuals with many spotwelds. For the clinical outcome the Merle d’Aubigne and Postel score as modified by Charnley was used. Among 69 hips (66 patients) with a mean followup of 153 months 96% (66 hips) had a pain score equal to or greater than 4 and 74% (51 hips) had a score of 5 or 6. The Lord femoral component gave surprisingly good clinical long term results despite the bone remodeling (stress shielding), which in some cases was pronounced. The most obvious disadvantage with this design appears to be the difficulties associated with its removal when indicated.

Material and design in haematogenous implant-associated infections in a rabbit model

We used 111 rabbits to study the susceptibility to intravenously injected bacteria of conventional stainless steel plates, and titanium plates of either traditional design or of the PC-FIX concept, that is less traumatic to bone. After plating, the animals were given between 1 x 10(8) and 2 x 10(9) colony forming units of Staphylococcus aureus Wood 46 intravenously. Significant differences in infection rates (positive cultures) were found between conventional stainless steel plates (36-67% infected, depending on inoculum size) and titanium PC-FIX plates (6-7% infected). In fact, the infection rate at the PC-FIX plate did not differ from sham operated animals. Since conventionally designed titanium plates had an intermediate infection rate, it appears that design and material both are important for the risk of infection.

Combined treatment with calcitonin and 1,25-dihydroxyvitamin D3 for osteoporosis in women

SummaryTwenty-two middle-aged women with severe osteoporosis were treated for 2 years with either 0.5 mg of synthetic human calcitonin subcutaneously three times per week combined with 0.5 μg of calcitriol and 0.5 g of calcium per day orally or calcium only. The treatment with calcitonin plus calcitriol (12 patients) resulted in a significantly increased calcium absorption rate. The mean values for serum phosphate did not change during the treatment period and the mean values did not differ between the treatment groups, but the serum calcium and urinary Ca/Cr ratio increased somewhat in the group given the combined treatment. There was no evidence that the combined treatment improved the bone density in this study. It is possible that calcitriol, instead of increasing the effect of calcitonin by suppression of the parathyroid, might have counteracted its effect by increasing the bone resorption.

Intracerebroventricular administration of somatostatin prevents and attenuates adjuvant arthritis

The effects of somatostatin on the development of adjuvant arthritis induced by Mycobacterium butyricum were studied. Somatostatin was injected into the lateral cerebral ventricle every day for 14 days beginning on the first day of mycobacteria inoculation in the preventive group. In the treatment group, somatostatin was injected from day 17 until day 30 post-mycobacteria inoculation. Arthritis was evaluated by measuring ankle joint circumference and diameter as well as microscopic examination of ankle joint sections. Somatostatin profoundly inhibited the development of adjuvant arthritis and an anti-inflammatory action was observed in the treatment group. These results suggest that somatostatin has a central action that can prevent or attenuate symptoms associated with arthritis.

Effects of short- and long-term rat hind limb immobilization on spinal cord insulin-like growth factor-I and its receptor.

In this study we investigated changes in the spinal cord insulin-like growth factor-I peptide (IGF-I) and its receptors (IGF-IR) after hind limb immobilization for 5 days, 2, 4, and 8 weeks. Moreover, effects on IGF-I and nicotinic cholinergic receptors (nAChRs) in two types of skeletal muscle were also investigated. IGF-I levels were measured by radioimmunoassay (RIA) whereas IGF-IR and nAChRs were measured by quantitative receptor autoradiography. Spinal cord IGF-I levels decreased significantly after 5 days, 2 and 4 weeks of immobilization, whereas IGF-IR increased significantly after 4 and 8 weeks compared to controls. In skeletal muscles, nAChRs increased significantly after 5 days and 2 weeks in the soleus (SOL) and tibialis anterior (TIB) muscles, respectively, and continued up to 8 weeks in both muscles. IGF-I concentration decrease significantly after 4 and 8 weeks in the SOL and TIB muscles, respectively. Despite the normal levels of IGF-I in both muscles at the early time points (5 days and 2 weeks), low levels of IGF-I were observed concurrently in the spinal cord ipsilateral to the immobilized limb. Our findings suggest that the early decrease in the IGF-I level and the late upregulation in the IGF-IR in the spinal cord might represent a nervous system response to disuse.

Intracerebroventricular met-enkephalin administration modulates adjuvant arthritis.

The purpose of this study was to investigate the anti-inflammatory properties of intracerebroventricular met-enkephalin (met-enk) administration in an animal model of arthritis. Adjuvant arthritis was induced in rats by intradermal inoculation of mycobacterium butyricum and the effects of intraventricular met-enk+thiorphan (enkephalinase inhibitor) were studied. Treatment was initiated either simultaneously with the bacterial inoculation (preventive group) or on post-inoculation day 17 after the appearance of inflammation (treatment group). The degree of inflammation was evaluated by measuring the diameter and the circumference of the ankle joint immediately before the sacrifice (day 31) and by histologic examination of ankle joint sections. The results of this study revealed that combined intraventricular injections of met-enk+thiorphan reduced the arthritic-like inflammation in the preventive group as well as in the treatment group. These findings suggest that centrally applied met-enk+thiorphan may suppress the development adjuvant arthritis as well as the symptoms of manifest arthritis. Thus central met-enk may be involved in both hypothalamic pituitary adrenal axis and immune forms of stress-induced modulation.