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Biomedical subjects

S Skjeldal

Publications and source records attributed to S Skjeldal.

At least 19 recordsLinked to original sources

The Scandinavian Sarcoma Group Skeletal Metastasis Register. Survival after surgery for bone metastases in the pelvis and extremities.

INTRODUCTION: The assessment of the prognosis for the individual patient is important for the choice of surgical treatment of skeletal metastases. In 1999 the Scandinavian Sarcoma Group (SSG) initiated the Skeletal Metastasis Register as a multicentric, prospective study to provide a scientific basis for treatment recommendations. To improve prognostication we analyzed the survival of patients with skeletal metastases surgically treated at 9 SSG centres. PATIENTS AND METHODS: 460 patients with an average age of 64 years underwent 501 operations for non-spinal skeletal metastases. 7% were operated for more than one metastasis. Carcinoma of the breast, prostate, kidney and lung were the dominating primary tumors. RESULTS: The survival rate was 0.4 at 1 year, 0.3 at 2 years and 0.2 at 3 years. Univariate analysis showed that survival was related to bone localization, skeletal metastatic load, presence of visceral metastases, Karnofsky performance score, primary tumor type, presence of a complete pathological fracture and preoperative hemoglobin content. Multivariate regression analysis showed that pathological fracture, visceral metastases, haemoglobin content < 7 mmol/L and lung cancer were negative prognostic factors for survival. Myeloma was the sole positive prognostic factor for survival.

Bone Neoplasms↗

Carvedilol reduces ischaemic skeletal muscle necrosis.

Carvedilol is an alpha1 and nonselective beta-adrenergic receptor antagonist with antioxidative properties known to protect against reperfusion injury in the heart, brain, and kidneys. The aim of this study was to test the hypothesis that carvedilol improves postischaemic reperfusion and tissue survival in skeletal muscle. Sixteen Wistar rats underwent tourniquet ischaemia of the left hindlimb for 3 hours and 15 minutes at 27 degrees C. Single-fiber laser Doppler probes were inserted in the left and right anterior tibial muscles, and microvascular perfusion was measured until 2 hours after removal of the tourniquet. Perfusion indices for each 15-minute interval were calculated for the left hindlimb (tourniquet ischaemia) by dividing the postischaemic by the pre-ischaemic laser Doppler flowmetry values, and the geometrical areas under the curves representing a plot of perfusion index relative to time, measured in arbitrary units, were compared. Laser Doppler flowmetry values for the right anterior tibial muscle were compared. Tissue damage was measured by histomorphometry of necrotic areas and no-reflow zones in cross sections from the anterior tibial muscle 72 hours after ischaemia. Neutrophils were counted in the same sections. The treatment group received 1 mg carvedilol/kg body weight before ischaemia and 1 mg/kg immediately before removal of the tourniquets. The areas under the curves representing the plot of perfusion index relative to time were larger for the rats treated with carvedilol: 9.5 compared with 3.0 arbitrary units (p = 0.0003). Treatment did not change the laser Doppler flowmetry values for the right hindlimbs. The histomorphometric areas of necrosis in cross sections from the muscles were reduced from 88% (38-96%) in the control animals to 41% (7-85%) in those treated with carvedilol (p = 0.01), and the area of no-reflow was reduced from 20% (2-52%) to 0% (0-7%) (p = 0.006). The number of neutrophils did not differ between groups. The study supports the hypothesis that carvedilol improves early reperfusion and protects skeletal muscle subjected to 3 hours and 15 minutes of ischaemia.

Adrenergic beta-Antagonists↗

Protective effect of the endothelin antagonist Bosentan against ischemic skeletal muscle necrosis.

We tested the hypothesis that blocking of the endothelin system by Bosentan, a combined endothelin-A and -B receptor antagonist (Hoffmann La Roche, Basel, Switzerland), improves postischemic skeletal muscle reperfusion and reduces tissue damage. 16 Wistar rats were subjected to 3 h and 15 min hindlimb tourniquet ischemia at 27 degrees C. Perfusion was continuously measured with Laser Doppler Flowmetry (LDF) in the anterior tibial muscle during ischemia and the first 2 h of reperfusion. Perfusion indices were calculated for each 15 min, by dividing each LDF value by the preischemic LDF value of the leg. The areas under the perfusion index curves were compared. 72 h after ischemia, histomorphometry of necrosis and no-reflow zones, and counting of neutrophils were done in cross-sections of the muscles. The animals were randomized into two groups. The treatment group received an injection of Bosentan 15 mg/kg 10 min before ischemia, and this dose was repeated 5 min before reperfusion of the hindlimbs. The treatment group obtained an improved reperfusion (4.48 vs. 1.72, p = 0.02). The median cross-sectional area of necrosis was smaller in the treatment group, 70% vs. 93% (p = 0.02), while neither the areas of no-reflow nor the neutrophil counts in reperfused necrotic areas were different. This study supports the hypothesis that Bosentan seems to improve reperfusion and reduces postischemic skeletal muscle damage.

Animals↗

Endothelin-1 is upregulated during skeletal muscle ischemia and reperfusion.

The aim of the present study was to test the hypothesis that the vasoconstrictive peptide endothelin-1 is upregulated in ischemia and reperfusion in skeletal muscle. Sixty-eight Wistar rats were included in the series: 12 served as controls that did not undergo the procedure, 16 underwent sham operations, and 40 were subjected to a modified tourniquet ischemia for 3 hours and 20 minutes. Of the 40 rats, 16 were killed at the end of the ischemic period, 16 underwent reperfusion for 2 hours, and eight underwent reperfusion for 72 hours. Areas of necrosis were measured by morphometry in hematoxylin and eosin-stained cross sections of the anterior tibial muscles that had been reperfused for 72 hours. Sections from the controls, the muscles that had not been reperfused, and the reperfused muscles were immunostained for endothelin-1. Serum endothelin-1 levels in blood samples from the aorta were determined with a commercial enzyme immunoassay kit. The anterior tibial muscle was harvested for preproendothelin-1 mRNA analysis with RNase protection assay. The hematoxylin and eosin-stained sections showed extensive necrosis with an acellular core of no reperfusion. The muscular core demonstrated weak immunostaining for endothelin-1 in all sections, a subfascial narrow brim of fibers showed enhanced immunoreactivity at the end of ischemia, and all fibers outside the core stained by 2 hours after the start of reperfusion. After 72 hours of reperfusion, the fibers outside the core stained positive in a checkerboard-like pattern. There were no differences in serum endothelin-1 levels between the groups. Preproendothelin-1 mRNA analysis with RNase protection assay showed 2-fold upregulation at the end of ischemia and 4-fold upregulation after 2 hours of reperfusion (p = 0.001). This study supports the hypothesis that both ischemia and reperfusion upregulate endothelin-1 in skeletal muscle.

Animals↗

Healing of tibial fractures is not impaired after acute hindlimb ischemia in rats.

The influence of transient circulatory arrest on the healing of closed tibial fractures was investigated in rats by the use of a hindlimb tourniquet technique. Twenty-four animals were randomly divided into three groups. In all animals, the left lower leg was fractured and fixed with an intramedullary nail system. In the ischemic group, complete acute transient ischemia for 4.5 h and neurapraxia of the sciatic and femoral nerves were induced prior to fracture. In the neurapraxia group, the sciatic and femoral nerves were crushed with forceps before fracture. In the control group, no other intervention than fracture was made. The rats of the control group ambulated normally 3-4 days after the operation. The animals of the ischemic and neurapraxia groups resumed normal weight-bearing after about 3 weeks. After 6 weeks, all animals were killed, and mechanical strength and bone mineral turnover of the healing tibia as well as blood flow of the bone and musculature were evaluated. The weight of the tibia and the corresponding anterior tibial muscle in the ischemic and neurapraxia animals were reduced compared with the control rats. Bone mineral turnover was found to be lower in the ischemic group. There were no differences between the groups in mechanical strength nor in blood circulation of bone and muscle. In conclusion, complete, acute hindlimb ischemia for 4.5 h in rats did not cause delayed healing of closed tibial fractures.

Animals↗

Compartment pressure in nailed tibial fractures. A threshold of 30 mmHg for decompression gives 29% fasciotomies.

During the past few years we have monitored tissue pressure in patients treated with intramedullary nailing of tibial shaft fractures. A value of 30 mmHg has been used as the threshold for fasciotomy. The purpose of this study was to evaluate this practice. Sixty-three patients were included in the series. Forty-three fractures were closed, 18 grade I (Gustilo) and two grade II. Tissue pressure measurements were performed in 43 patients. Eighteen legs were treated with decompressive fasciotomy, three on clinical findings alone, and 15 after measurement of a pressure higher than 30 mmHg. This gives a fasciotomy rate of 29%. At follow-up two patients were dead. All fractures were healed, and there were no major complications such as deep infection, extensive muscle necrosis, paresis or short-foot syndrome. Three fasciotomized patients had significantly reduced muscle strength compared with the contralateral leg.

Adolescent↗

Anterior cruciate ligament strength. Can it be estimated by non-destructive testing?

For structural and material bone strength, non-destructive tests exist, while no such tests have been developed for ligaments. In the present study we compared the geometry and bone mineral content (BMC) of the rat tibia with the tensile strength of the anterior cruciate ligament (ACL). A significant correlation was found between the mediolateral diameter of the tibial condyle and ACL load to failure (r=0.83). Calculating the area of the condyle as an ellipse increased this correlation to r=0.93. No significant correlation was found to BMC. If this correlation is also found in humans, the mediolateral tibial head diameter may be used to estimate the strength of the ACL non-destructively.

Absorptiometry, Photon↗

Severe hindlimb ischemia causes periosteal proliferation in the rat tibia.

In this rat study, we found tibial periosteal hyperplasia and hypertrophy, and appositional new bone formation 3 days after transient hindlimb ischemia. This response was positively correlated to the extent of muscle necrosis, which was increased either by raising the environmental temperature during ischemia or by prolonging the period of ischemia. By changing the temperature from 21 degrees C to 34 degrees C, the area periost in percent of the total tibial area was increased from 5 to 17, and by changing the duration of ischemia from 3 to 5 hours, it increased from 8 to 18.

Animals↗

[Transiliacal screw fixation of the sacrum in unstable pelvic ring fractures].

This article presents our experiences from fixation of the sacrum by transiliacal screw in 13 patients with unstable fractures of the pelvic ring. Early mobilization, with no secondary dislocation or postoperative complications, was achieved in all patients. Sagittal instability in unstable pelvic ring fractures must be acknowledged. The transiliac screw offers the possibility of early mobilization of patients with this fracture. The procedure is demanding and patients selected for this treatment should be referred to hospitals with experience in the treatment of pelvic fractures.

Adult↗

No increasing injury during early reperfusion of skeletal muscle.

Early reperfusion is thought to contribute to the final parenchymal and microvascular injury after transient ischaemia of skeletal muscle. Albumin, a large molecule which is not found in intact cells, can be used as an early marker of extensive membrane injury. In the present study, staining of intracellular albumin was used to test the hypothesis that muscle cell injury increases during early reperfusion. Complete ischaemia was induced for 3 h 15 min in rat hindlimbs. A total of 16 animals were randomized into two groups. The anterior tibial muscles were dissected and fixed in formaldehyde without reperfusion in one group, while circulation was re-established in the hindlimbs for 3 h in the other group. Cross-sections from the muscles were stained with antisera against rat albumin, using fast red as chromogen. This immunostaining showed a central zone of injured cells in each cross-section. The albumin-positive areas, calculated as a percentage of the total cross-sectional areas were 76 and 77% in the two groups respectively. This difference was not significant, suggesting that ischaemia and not reperfusion was the major trauma.

Albumins↗

[Compartment pressure after intramedullary fracture nailing].

Acute compartment syndrome is a serious complication to tibial fractures. The reported incidence is 1-10%. The present series includes 60 patients treated with intramedullary nailing of fractures in the tibial diaphysis. Tissue pressure was measured in 31 patients. Decompressive fasciotomy was performed if the pressure exceeded 30 mm Hg for more than 30 minutes. Follow-up showed no patients with clinical sequelae from a compartment syndrome, but the incidence of fasciotomy was as high as 18%.

Compartment Syndromes↗

Hamstrings and gastrocnemius co-contraction protects the anterior cruciate ligament against failure: an in vivo study in the rat.

An anesthetized rat model was used to study the effects of muscle contraction on the ultimate tensile load and the energy absorption at failure of the anterior cruciate ligament. In both knees, the joint capsule and ligaments, except for the anterior cruciate ligament, were divided, and the menisci were removed with the aid of a stereomicroscope. The cruciate ligament of the right knee was tested in tension until failure by femorotibial distraction during contraction of the hamstrings and calf muscles induced by electrical stimulation of the ischiatic nerve. The cruciate ligament of the left knee, which was loaded to failure with nonstimulated (relaxed) muscles, served as the control. The mean ultimate tensile load during muscle contraction was 86 N compared with 53 N when tested with relaxed muscles (p < 0.001). The energy absorption at failure was 0.41 and 0.19 J during contraction and relaxation, respectively (p < 0.05). This study suggests that previous investigations evaluating the force and energy necessary to rupture the anterior cruciate ligament (with use of a femur-anterior cruciate ligament-tibia complex stripped of all soft tissues and without gastrocnemius-hamstring muscle contractions) are incomplete and probably not representative of the in vivo situation.

Animals↗

Cerebral blood flow measured with intracerebral laser-Dopplerflow probes and radioactive microspheres.

We have measured cerebral blood flow with intracerebral laser-Doppler microprobes in pentobarbital-anesthetized pigs. We compared the results with measurements from laser-Doppler probes placed on the surface of the brain and with blood flow estimation by the radioactive microsphere method. The cerebral blood flow was varied by alterations in inspired carbon dioxide, hemorrhagic hypotension, and high cerebrospinal fluid pressure. The intracerebral probes and the surface probes showed parallel responses to variations in cerebral blood flow. The correlation was closest between surface probes and the intracerebral probes measuring from the cerebral cortex (r = 0.46; P < 0.005). The r value between laser-Doppler flowmetry and radioactive microspheres was 0.41 (P < 0.0005) for all measurements. The correlation to microspheres was best for the probes located 3 or 10 mm into the brain and poorest for the surface probe. In conclusion, intracerebral laser-Doppler flow measurements reflect changes in blood flow, and the technique appears useful for continuous estimates of cerebral blood flow.

Animals↗

Periosteal response to transient ischemia. Histological studies on the rat tibia.

Complete arrest of blood flow was induced for 4.5 hours in the left hindlimb of Wistar rats by a tourniquet applied proximally to the thigh. Histologically the periost of the tibial bone after 3 days showed marked hypertrophy and hyperplasia of the periosteal cells with an osteogen differentiation. This response is similar to the initial formation of external callus during fracture healing. Transient ischemia may be an important factor in initiating fracture healing.

Animals↗

Cardiovascular response to blood loss during high intracranial pressure.

The authors hypothesized that the combination of hemorrhage and increased intracranial pressure (ICP) has deleterious effects on cardiovascular function. The effect of blood loss during normal and increased ICP was studied in eight pigs. The mean arterial pressure (MAP), pulmonary arterial pressure, pulmonary capillary wedge pressure, cardiac output, and cerebrospinal fluid (CSF) pressure were measured. The regional tissue blood flow was determined with radioactive microspheres labeled with four different nuclides. High ICP (80% of MAP) was induced by infusion of artificial CSF into the cisterna magna. The response to rapid arterial bleeding of 25% of blood volume was measured. The decrease in blood flow to the intestine, skeletal muscle, and the kidneys after blood loss was significantly greater during high ICP. The decrease in blood flow to the spleen and pancreas tended to be greater during high ICP, whereas the changes in blood flow to the liver, adrenal glands, and heart muscle showed no such tendency. The fall in cardiac output and heart stroke volume after blood loss were more pronounced when the ICP was high, and the increase in systemic vascular resistance was considerably greater. These observations suggest that during high ICP the physiological protective mechanisms against blood loss are impaired in the systemic circulation, and a loss of 25% of the blood volume, normally well compensated for, may induce a state of shock.

Animals↗

The repair of a ruptured deltoid ligament is not necessary in ankle fractures.

We randomised 50 patients with ankle fractures of Weber types B and C and a ruptured deltoid ligament treated by open reduction and internal fixation to two treatment groups to examine the influence of the repair of a ruptured deltoid ligament. No differences were found except for a longer duration of surgery in the repair group. Our findings suggest that a ruptured deltoid ligament can be left unexplored without any effect either on early mobilisation or on the long-term result.

Adolescent↗

Aneuploidy in benign tumors and nonneoplastic lesions of musculoskeletal tissues.

BACKGROUND: Aneuploidy in DNA flow cytometry (FCM) of musculoskeletal tumors is generally considered to be a sign of malignancy. Previously, giant cell tumor of the bone has been reported to contain aneuploid (near-diploid) DNA stemlines. Otherwise, only spordic cases have been reported. The authors wanted to study the relationships among DNA FCM, histology, and clinical course of nonmalignant musculoskeletal lesions. METHODS: Twenty-eight histologically benign tumors and seven nonneoplastic lesions were subjected to DNA FCM: After tissue preparation mechanically and with ribonuclease and trypsin, the isolated nuclei were stained with propidium iodine using chicken and rainbow trout erythrocytes as controls. In the DNA FCM histograms, ploidy and cell cycle fractions were determined using a computerized mathematical model. The histologic diagnoses were made without knowledge of the DNA FCM results. RESULTS: Aneuploidy was found in eight lesions. A shoulder in the diploid peak, suggesting a diploid and a near-diploid population, was found in DNA histograms of a condensing osteitis of the clavicle (a benign inflammatory process) and of a giant cell tumor of bone. The latter lesion also had a tetraploid population. Six benign tumors--two enchondromas, one osteochondroma, one subcutaneous and one intramuscular lipoma, and a calcifying aponeurotic fibroma--showed clear aneuploidy with separate peaks. The S-phase fraction was less than 10% in all cases. The highest aneuploid population, DNA index = 1.70, in a subcutaneous lipoma, was small, with an undetectable S phase. Despite nonradical operations in seven lesions, no recurrences were observed during a median follow-up of 49 months (range, 28-73 months). CONCLUSIONS: Small aneuploid populations with low DNA synthetic activity may be compatible with a benign histologic picture and uneventful clinical course of the musculoskeletal lesion.

Adolescent↗