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Biomedical subjects

U Lindgren

Publications and source records attributed to U Lindgren.

At least 19 recordsLinked to original sources

Systemic immune response in whiplash injury and ankle sprain: elevated IL-6 and IL-10.

Whiplash injury and whiplash-associated disorders (WAD) are significant problems of modern society. Numerous attempts have been made to characterize the nature of whiplash injury. Whether the immune system is involved during the disease process is not known. In a prospective study, using enzyme-linked immunospot (ELISPOT) assays, we examined numbers of blood mononuclear cells (MNC) secreting pro- (IFN-gamma, TNF-alpha, IL-6) and anti-inflammatory (IL-10) cytokines in patients with WAD and, for reference, patients with ankle sprain and multiple sclerosis and healthy subjects. An immune response reflected by elevated numbers of TNF-alpha- and IL-10-secreting blood MNC was observed in patients with WAD examined within 3 days compared to 14 days after the whiplash injury. The patients with WAD examined within 3 days after the injury had also higher numbers of IL-6 and IL-10 secreting blood MNC compared to healthy subjects. The alterations of cytokine profiles observed in WAD were also observed in patients with ankle sprain when examined within 3 days after trauma. In contrast, there were no differences for cytokine profiles between patients with WAD examined 14 days after the whiplash injury and healthy subjects. Relatively minor trauma like WAD and ankle sprain are associated with a systemic dysregulation in numbers of cells secreting pro- as well as anti-inflammatory cytokines.

Adolescent↗

Chemokines and their receptors in whiplash injury: elevated RANTES and CCR-5.

The human sufferings and socioeconomic burden due to whip-lash-associated disorders (WAD) are obvious but the pathogenesis of WAD is obscure. The possible involvement of the immune system during the disease process in WAD is not known. Effector molecules including chemokines and their receptors could play a role in WAD. In a prospective study using flow cytometry, we examined percentages of blood mononuclear cells (MNC) expressing the chemokines RANTES, MCP-1, MIP-1alpha, MIP-1beta, and IL-8, the chemokine receptor CCR-5, the T cell activation marker CD25, and the T cell chemoattractant IL-16 in patients with WAD and, for reference, in healthy controls. Higher percentages of RANTES-expressing blood MNC and T cells were observed in patients with WAD examined within 3 days compared to 14 days after the whiplash injury and, likewise, compared with healthy controls. The patients with WAD examined within 3 days after the accident also had higher percentages of CCR-5-expressing blood MNC, T cells, and CD45RO+ T cells compared to healthy controls. In contrast, there were no differences for any of these variables between patients with WAD examined 14 days after injury and healthy controls. In conclusion, WAD is associated with a systemic but transient dysregulation in percentages of RANTES and CCR-5 expressing MNC and T cells.

Adult↗

Growth hormone-regulated intracellular signaling in UMR 106 osteosarcoma cells.

Growth hormone (GH) and insulin-like growth factor 1 (IGF-1) are important growth factors for postnatal longitudinal bone growth. Although many effects of GH on bone growth are mediated by IGF-1, GH can directly influence bone cells. Limited knowledge exists regarding specific intracellular signaling pathways and genes activated by GH in bone cells. GH is known to activate several intracellular signaling pathways, among them the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway. GH mainly activates JAK2 and both isoforms of STAT5, A and B. STAT5 gene deletion experiments have shown the importance of these transcription factors for growth. To understand the molecular mechanism(s) behind this, different experimental models are needed. The UMR 106 cell line is a rat clonal osteosarcoma cell line with osteoblast-like phenotypic properties, one is the endogenous expression of GH receptor (GHR). The present study focused on whether these cells express a functional GH-responsive JAK2/STAT5 pathway. Analysis of cell extracts by immunoprecipitation and Western blot showed that physiological concentrations of GH activated JAK2. Western blot analysis of nuclear extracts from GH-stimulated UMR 106 cells showed that physiological concentrations of GH induced nuclear translocation of both STAT5 isoforms, but with STAT5A being predominant. Both isoforms displayed similar nuclear turnover after GH stimulation of cells. Gel electrophoretic mobility shift assay (GEMSA) of nuclear extract revealed that both STAT5A and STAT5B obtained DNA-binding capacity after GH stimulation. Thus, we have shown, for the first time, the expression and GH-induced activation of JAK2 and STAT5A/B in UMR 106 osteoblast-like cells. This study also shows that this cell line is a suitable experimental model to study unique GH effects in osteoblasts mediated by STAT5.

Animals↗

Postoperative mental impairment in hip fracture patients. A randomized study of reorientation measures in 223 patients.

Mental impairment is a common and serious complication in geriatric surgery. We studied 223 hip fracture patients. They were over 64 years of age (mean 81), with no history of mental deterioration and acutely admitted to hospital from independent living conditions. They were randomized into two groups. One of these was subjected to reorientation measures during the perioperative phase, i.e., presurgery admission to the orthopedic ward, accompanied home visits during the hospital stay and access to reorientation devices--they received a large clock, calendar, radio, TV-set, telephone and were encouraged to wear their own clothing. Otherwise, there were no differences in the treatment given to the two groups. We used monitoring of cognitive function with the Short Portable Mental Status Questionnaire (SPMSQ) and a feedback program for evaluation of the treatment results. There was a low incidence of postoperative cognitive deterioration in both groups, compared with historical controls. However, no difference in mental status was noted when we compared the two groups. The conclusion is that attributes were less important than the psychological environment for postoperative mental deterioration. The mean total continuous hospitalization (transfers between departments and hospitals included) in the reorientation group was 22 (95% CI: 17-43) days, the corresponding figures for the controls were 30 (14-29) days.

Aftercare↗

Continuity, assessment and feedback in orthopaedic nursing care practice is cost-effective.

Hip fracture treatment and rehabilitation are often considered as separate issues and generally performed in different locations. The rapidly increasing proportion of patients that is old and very old now calls for a new approach. This is a prospective study of 909 consecutive hip fracture patients, over 64 years old, admitted to hospital from an independent living situation. In a specialized hip fracture unit, 256 patients were given an early and intense rehabilitation program. It focused on continuity, feedback, reorientation and continuous monitoring of cognitive function and activities of daily living (ADL). Eighty-five percent of the patients could return directly to their own home after the initial treatment period. The mean total utilization of health care resources during the first 4 months after the injury was lower (28 institutional days) than in 286 historical controls given conventional rehabilitation (39 days, p < 0.05). At 4 months, 81% of the patients still lived in their own home vs. 72% of the controls and the 1-year mortality was 14% (21% in the controls, p < 0.05). After the project had been completed 297 patients formed an additional control group. In this group the proportion discharged to their own home decreased to 44% and the number of bed-days during the first 4 months returned to the pre-study level (39 days). It thus appears to be cost-effective to allocate sufficient rehabilitation resources early in the treatment of elderly patients with hip fractures. Annual savings in the catchment area due to the intervention were calculated to approximately 5,000,000 SEK. Continuous assessment and adequate continuity gives the staff emotional feedback, which promotes their personal commitment.

Activities of Daily Living↗

Rib-vertebral angle asymmetry in idiopathic, neuromuscular and experimentally induced scoliosis.

The concave and convex rib-vertebral angle (RVA) at levels T2-T12 was measured on AP radiographs of 19 patients with right convex idiopathic thoracic scoliosis and 10 patients with major thoracic right convex neuromuscular scoliosis. The difference between the angles on the concave and the convex sides, the RVAD, was calculated. The RVAs were also measured on radiographs from three animal groups in which spinal curves had been induced experimentally in a variety of ways. Group 1 comprised 16 rabbits that had been subjected to selective electrostimulation of the latissimus dorsi, the erector spinae and the intercostal muscles. Group 2 comprised four dead rabbits whose spines had been subjected to manual bending. Group 3 comprised eight rabbits that had undergone mechanical elongation of one rib. In both the idiopathic and the neuromuscular group, the convex RVA was smaller than the concave RVA between levels T2 and T8, with a maximal difference between T4 to T5. From T9 to T12 the concave RVA was smaller than the convex. The RVA in relation to the scoliotic segment, i.e. the apex level of the curve and the two neighbouring vertebrae above and below this level, showed similar results. With increasing Cobb angle the RVADs increased linearly with the greatest difference at the second vertebra above the apex. In the three experimental groups the pattern of the RVADs between T6 to T12 was basically similar to the findings of the clinical study. From the results of these clinical and experimental studies, it is concluded that the typical pattern of the RVAs on the concave and convex sides seems to be independent of the underlying cause of the spinal curvature. It is likely that the RVADs result from a passive mechanical adaptation of the ribs to the lateral curvature of the spine.

Adolescent↗

The appearance and disappearance of cognitive impairment in elderly patients during treatment for hip fracture.

We studied the natural course of cognitive state in 256 consecutive hip fracture patients who were admitted from an independent living situation. We employed a treatment programme that focused on preventing postoperative cognitive impairment. Cognitive function was assessed with the SPSMQ screening test. The incidence of postoperative cognitive impairment among those lucid on admission was 13%, which generally was reversed before discharge. Thirty-seven percent were cognitively impaired on admission; of those, 51% reached normal test scores while in hospital. Those who recovered within the first week had as good a prognosis during the first year as those who remained lucid throughout the hospital stay. Cognitive impairment was associated with an increased complication rate, e.g. a three-fold increase of early fracture displacement and a four-fold increase of wound infection. This increased risk was present even in patients with mild/moderate cognitive impairment and could not entirely be explained by age. Our results suggest that it is possible to decrease postoperative cognitive impairment by routine monitoring of cognitive status, a high level of continuity and a reorientation programme. The routine assessment of the cognitive function is recommended in geriatric patients who are admitted for surgery.

Activities of Daily Living↗

Prediction of the outcome after hip fracture in elderly patients.

We report a prospective study of 232 consecutive patients with hip fractures. All were over 64 years of age and living independently before admission to a geriatric orthopaedic ward. We assessed the value, at admission, of predicting factors for independent living at one year after injury. The most important factors were: (1) preinjury function in activities of daily living (grade A or B on the Katz et al (1963) scale); (2) absence of other medical conditions which would impair rehabilitation; and (3) cognitive function better than 7 on the Pfeiffer (1975) mental questionnaire. The odds ratios (95% CI) for these three predictors were 3.5 (1.3 to 9.1), 2.9 (1.3 to 6.1) and 2.4 (1.9 to 4.9), respectively. When all predictors were positive at admission, 92% were living independently at one year; with one, two or three negative predictors, the percentages living independently were 76, 61 and 27, respectively. The median values of the total number of days in hospital, irrespective of diagnosis, during the first year were 12, 24, 29 and 149 days for the four groups. The mortality at one year was predictable on admission only by the number of medical conditions: with no other diagnosis than the fracture the mortality was 0%; with one or two additional conditions the mortality was 14%; and with three or more additional diagnoses it was 24%. These simple and robust predictors can be used to optimise resources for rehabilitation.

Activities of Daily Living↗

Prolactin binding sites in rat brain and liver: effects of long-term ovariectomy and ovarian steroids.

The effects of long-term ovariectomy on the levels of brain and liver lactogenic binding sites as well as plasma and liver prolactin (PRL) have been investigated in sham-operated and ovariectomized rats receiving either 17 beta estradiol (OVX-E), progesterone (OVX-P), or vehicle (OVX-V). The levels of lactogenic binding sites in the parietal and piriform cortices, amygdala, thalamus, hypothalamus, as well as in the liver were significantly decreased after long-term ovariectomy. Moreover, the levels of plasma and liver PRL were also significantly decreased. Exogenous estradiol and progesterone replacement restored the levels of lactogenic binding sites in the parietal cortex and hypothalamus as well as in the liver. However, plasma and liver PRL levels were significantly increased by estradiol but only restored by progesterone. These results suggest that ovarian steroids influence the levels of lactogenic binding sites and prolactin.

Animals↗

A qualitative and quantitative study of retrieved femoral heads in three different types of resurface hip arthroplasties.

Tissue reactions and percentage of mineralized bone in three different types of retrieved femoral head hip resurface prostheses were studied in undecalcified ground sections without removing the metal. All of the prostheses demonstrated soft tissue between the cement-implant and bone. There were some areas without soft tissue between bone and cement. This bone was often not normally stained, indicating a disturbed mineralization. The soft tissue layer in the cemented prostheses was observed in different stages of necrosis, while the uncemented prostheses demonstrated a thick collagen membrane. One of the cemented groups demonstrated a gradual decrease of mineralized bone towards the cement. The uncemented implants revealed normal bone qualitatively and quantitatively when the bone bordering the prosthesis was excluded. Too high interfacial stresses were probably a major failure mechanism, especially in the rapidly failed noncemented prostheses. Negative long-term effects of the cement on the bone may have contributed to failure in the cemented resurface arthroplasties.

Adult↗

Heterotopic bone after hip arthroplasty. Defining the patient at risk.

Periarticular heterotopic bone (HB) formation after hip arthroplasty can be prevented by indomethacin or radiation. It is therefore important to identify patients at risk. The authors analyzed 124 consecutive cases of primary total hip arthroplasty (THA) performed by the same trans-trochanteric operative approach in 124 patients. Heterotopic bone occurred more often in men (84%) than in women (67%), and greater amounts of bone were formed in men. On anteroposterior (AP) roentgenographs, the median area of projected HB in men was 24.7 cm2 and 0.69 cm2 in women. Heterotopic bone was less common in patients with polyarthritis compared with patients with osteoarthrosis. In women with osteoarthrosis, old age was associated with the occurrence of HB; women older than 65 years of age had 0.70 cm2 of HB on AP roentgenographs (mean), whereas those younger than 65 years had 0.18 cm2. Hypertrophic osteoarthrosis was more common in men, but associated with HB only in women. Women with hypertrophic osteoarthrosis developed the same amount of HB as men with osteoarthrosis. Men with osteoarthrosis or sequelae after fractures, older women with osteoarthrosis, and women with hypertrophic osteoarthrosis should be considered for prophylactic treatment against HB formation after a THA.

Age Factors↗

Surgical treatment of forefoot deformity with special reference to polyarthritis.

Among 523 patients consecutively treated for forefoot pain and deformity, 64 had inflammatory arthritis. Most patients no longer had difficulties finding shoes that fit after the deformities were surgically corrected. Although about one half of the patients had some residual symptoms after treatment, 57 (89%) were satisfied with the operation. If the deformities are corrected early, joint resections can be avoided and toe function preserved.

Adolescent↗

The influence of mediolateral deformity, tibial torsion, and foot position on femorotibial load. Prediction of a musculoskeletal computer model.

The influence of mediolateral deformity, tibial torsion, and different centers of foot support was studied with a three-dimensional computer model that incorporates the significant muscles of the lower extremities needed for quasi-static walking. This theoretical method avoids the variability in gait pattern from the pain and discomfort associated with deformity in patients. The study illustrates the possible importance of the muscle force on the load across the knee and ankle. High strains in the medial gastrocnemius and the medial hamstring created particularly high loads in the medial compartment of the knee. Internal torsion and varus deformity were associated with the highest loads in the medial compartment of the knee, although the peak load for each deformity occurred in different phases of the gait cycle. Both external torsion and valgus deformity generally decreased the load in the medial compartment, but early in the gait cycle external torsion increased the loads on the medial side. In addition, when the center of support of the body was in the forefoot, the loads through the knee were lower than when foot support was at the heel. As expected, if the center of support was on the lateral foot line, the lateral compartment was subjected to more load and, conversely, when the center of support was on the medial part of the foot the medial compartment of the knee was more loaded. Although the predicted forces agree well with those found with other methods, we think that the model is best used to measure the direction of influence of specific factors.

Biomechanical Phenomena↗

Functional significance of heterotopic bone formation after total hip arthroplasty.

The effects of heterotopic bone formation on hip function after arthroplasty was studied in 145 cases of total hip arthroplasty. Hip muscle strength was determined 1.8-2.9 years after the operation, using a Cybex II dynamometer. Heterotopic bone formation was seen after 75% of the operations, and in 21% significant amounts developed (Brooker's classes III and IV). The gain in range of motion after surgery was significantly less in the groups with class III or IV heterotopic bone than in those without heterotopic bone formation. Heterotopic bone did not cause pain or Trendelenburg's limp after surgery; in fact, patients with trochanteric pain had less heterotopic bone than those without this pain. Hip flexion strength was greater in men with heterotopic bone than in those without heterotopic bone. Also, men with heterotopic bone formation had a higher mean maximum strength in extension but lower mean strength in abduction than did men without heterotopic bone (NS). When only patients with unilateral hip disease were considered, the same differences were found around the healthy hip; men with heterotopic bone formation had greater strength in flexion and extension than men without heterotopic bone formation and the same tendencies were seen in women. Accordingly, heterotopic bone had no serious impact on hip muscle strength in this study.

Adult↗

A new transtrochanteric approach to the hip.

This transtrochanteric approach to the hip maintains continuity between the greater trochanter and the vastus lateralis muscle, thereby preventing the gross displacement of the greater trochanter and preserving the branches of the lateral circumflex vessels to it. The procedure offers the advantages of easy exposure and a high rate of bony union between trochanter and femur. We have used the procedure in 189 consecutive operations; in only four cases did union between the bones not occur. The trochanter was never cranially displaced more than three cm, and even in the cases of non-union abductor power was good. Although we do not recommend trochanteric osteotomy for every case of total hip replacement, we suggest that the approach be used for cases where technical problems are anticipated.

Bone Wires↗

Comparative study of the effects of radiation, indomethacin, prednisolone, and ethane-1-hydroxy-1,1-diphosphonate (EHDP) in the prevention of ectopic bone formation.

Forty male New Zealand white rabbits were treated with immobilization and forcible manipulation of the right knee known to cause ectopic bone formation in the quadriceps muscle. The animals were also treated with either: A) A total radiation dose of 1840 rad (18.4 Gy); B) A 0.5 mg/kg/day oral dose of prednisolone; C) 10 mg/kg/day of indomethacin, given in two oral doses; D) Ethane-1-hydroxy-1,1-diphosphonate (EHDP) given in a 20-mg/kg/day oral dose; or E) with the vehicle given alone as a control. The experimental period was four weeks, and the amount of ectopic bone was determined by planimetry of serial transverse sections of the femur. The degree of knee stiffness was recorded during the experiment. The amount (mean +/- SEM) of ectopic bone was 1.412 +/- 0.264 cm3 in controls; it was insignificantly higher in the EHDP-treated group, but significantly lower (p less than 0.01) in rabbits treated with radiation (0.390 +/- 0.094 cm3), prednisolone (0.181 +/- 0.076 cm3), and indomethacin (0.314 +/- 0.112 cm3). In control animals and those given EHDP, the treatment invariably led to almost complete stiffness of the right knee. The rabbits treated with prednisolone and indomethacin offered the least resistance to the manipulations, and the group treated with radiation showed intermediate stiffness. Semiquantitative histologic evaluation demonstrated less inflammation in the group treated with prednisolone than in the control group.

Animals↗