Serum concentrations of collagen degrading enzymes and their inhibitors after downhill running

In the present study the release of proteins degrading extracellular matrix compounds to circulation was measured after damaging exercise in humans. Muscle damage was induced by downhill running; furthermore, the exercise was performed at both cold temperature (5 degrees C) and room temperature (22 degrees C) to study also the possible effect of environmental temperature on serum concentrations of matrix metalloproteinases MMP-2 and MMP-9, tissue inhibitors of metalloproteinases TIMP-1 and TIMP-2, and MMP-2/TIMP-2 complex, and muscle damage monitored by serum creatine kinase measurements. Results were compared with those obtained from patients having rhabdomyolysis, myositis and Becker muscular dystrophy. The present study demonstrates an acute increase in serum concentrations of MMP-9, TIMP-1, and MMP-2/TIMP-2 complex, but no changes in serum MMP-2 concentrations in response to eccentric exercise. Serum creatine kinase activity data suggest greater muscle damage after downhill running in a cold environment than at room temperature. The present observations about at most slight changes in serum MMP and TIMP concentrations and lack of their correlation to increased serum creatine kinase after exercise indicate that serum measurements of MMPs and TIMPs do not sensitively respond to exercise induced skeletal muscle damage and extracellular matrix regeneration. On the other hand, severe skeletal muscle damage, such as rhabdomyolysis, myositis and Becker muscular dystrophy, seemed to have an effect on serum MMP and TIMP concentrations.     

Evaluation of pleural disease using MR and CT. With special reference to malignant pleural mesothelioma

Purpose: To evaluate MR imaging and CT in differentiating malignant pleural mesothelioma from other malignancies or benign pleural disease.Material and Methods: Thirty-four patients (18 pleural mesotheliomas, 9 other malignancies, 7 benign pleural diseases) were examined using enhanced CT and MR. Two radiologists reviewed the CT and two others the MR images. Comparisons were made between the diagnostic groups and the imaging methods.Results: The abnormalities commonly found in malignant disease, but significantly less frequently in benign pleural disease, were focal thickening and enhancement of interlobar fissures. In mesothelioma, enhancement of interlobar fissures, tumour invasion of the diaphragm, mediastinal soft tissue or chest wall, were significantly more often observed than in other malignancies and MR was the most sensitive method. In other malignancies, invasion of bony structures was a more common finding and was also better shown by MR. The contrast-enhanced T1 fat-suppressed (CET1fs) sequence detected these features better than other MR sequences.Conclusion: MR, especially the CET1fs sequence in three planes, gave more information than enhanced CT. Focal thickening and enhancement of interlobar fissures were early abnormalities indicating malignant pleural disease. MR could be clinically useful for differentiating mesothelioma from other pleural diseases.     

Alarming wear of the first-generation polyethylene liner of the cementless porous-coated Biomet Universal cup: 107 hips followed for mean 6 years

Wear of the socket liner and resulting osteolysis are the major causes of failure in cementless hip arthroplasties. We report alarming wear of the first-generation polyethylene liner of the cementless porous-coated Biomet Universal cup. Radiographs of 107 primary hip arthroplasties were analyzed retrospectively. The mean follow-up time was 74 (47-91) months. The linear wear of the polyethylene liners was assessed using a modification of the Livermore method. The median linear wear was 1.0 (0-6.2) and the median linear wear rate was 0.17 mm/year. There was a statistically significant difference between the 28 mm and 32 mm femoral head groups both in the volumetric wear and in the volumetric wear rate. The median linear wear was 0.28 mm/year and 0.14 mm/year for the 32 mm and 28 mm heads, respectively. So far, 14 revisions have been performed or have been scheduled because of excessive wear of the polyethylene liner. In regression analysis, the factors related to the wear rate were the 32 mm size of the femoral head and screw fixation of acetabular shell. We found that the cases with calcar rounding were associated with significantly greater wear. Possible reasons for increased wear of the Hexloc liner may be the cylindrical design, thin polyethylene, and poor quality of the polyethylene. Regular clinical and radiographic follow-ups are recommended especially for hips with 32 mm femoral heads or with screw fixation. If progressive wear of the liner is observed, revision must be considered.     

Prefabricating bone in muscle by using free tibial periosteal grafts and self-reinforced polyglycolide and poly-L-lactide pins

To investigate the possibility of prefabricating bone of predetermined form in muscle using free tibial periosteal grafts and biodegradable pins, operations were performed on 12 growing rabbits. In each animal, (1) a graft around a self-reinforced polyglycolide (SR-PGA) pin, (2) a graft around a self-reinforced poly-L-lactide (SR-PLLA) pin, (3) a SR-PGA pin, and (4) a SR-PLLA pin were implanted in the dorsal muscles for 6 weeks. Histological and histomorphometric evaluations were performed. Bone formation from periosteal grafts was observed in all 12 animals. The shape of the newly-formed bone was grossly cylindrical in all specimens except one. Bone formation was stronger around the SR-PGA pins than around the SR-PLLA pins. The pins without grafts did not induce any bone formation, but fibrous tissue encapsulation instead. A mild foreign body reaction was elicited by SR-PGA pins, while it was almost absent with SR-PLLA pins. It is thus possible to prefabricate bone in a cylindrical form in growing rabbits using free tibial periosteal grafts and SR-PGA or SR-PLLA pins implanted in muscle.     

Heterogeneous expression of receptor mRNAs in parathyroid glands of secondary hyperparathyroidism.

BACKGROUND: Secondary hyperparathyroidism (HPT) is characterized by inappropriate control of parathyroid hormone (PTH) secretion and asymmetric hyperplasia of the parathyroid glands. Receptors for calcium and vitamin D are involved in the control of secretion, as well as parathyroid cell proliferation. Defective receptor mechanisms therefore may play a role in the pathogenensis of secondary HPT. Previous studies have shown that the expression of calcium receptor (CaR), calcium-sensing receptor (CAS) and vitamin D receptor (VDR) protein, and mRNA is decreased in hyperplastic parathyroid glands of secondary HPT when compared with normal parathyroid glands. METHODS: Thirty-six hyperplastic glands from 18 patients with secondary hyperparathyroidism were analyzed with in situ hybridization in order to investigate the expression of CaR, CAS, VDR, and PTH mRNAs in the same specimens. In nine nodular parathyroid glands, it was possible to make a comparison between the expression of these mRNAs in nodular and internodular areas. RESULTS: The level of CaR was in the same order of magnitude in the hyperplastic glands and in the biopsies of normal parathyroid, whereas the levels of CAS, VDR and PTH were clearly reduced in the hyperplastic glands. There was a positive correlation between the expression of CaR and CAS (P = 0.02). Otherwise, no correlations between CaR, CAS, VDR, and PTH mRNAs were found. The expression of all four genes was highly variable as well between different glands as within individual glands. CONCLUSION: The expression of mRNAs for receptors of importance in the control of PTH secretion and parathyroid cell proliferation is heterogeneously decreased in parathyroid glands of secondary HPT. The expression pattern corroborates earlier studies in which it has been assumed that each nodule in secondary HPT is of monoclonal origin, but that the monoclonal origin of each nodule is independent.     

Determinants of bone strength and fracture incidence in adult Finns: Cardiovascular Risk in Young Finns Study (the GENDI pQCT study)

Summary

Peripheral bone strength and fracture risk were studied in young adult Finns. Peripheral bone measures were associated with risk factors of osteoporosis in young adults and discriminated between those with and without low-energy fractures. In men, trabecular bone loss at peripheral bone sites starts before the age of 40 years.

Purpose

This is a cross-sectional study of the determinants of bone strength and fracture risk in young Finns using peripheral quantitative computed tomography (pQCT) and quantitative ultrasound (QUS).

Methods

pQCT scans were performed in 1,884 subjects at distal and shaft sites of non-dominant radius and left tibia, and QUS measures (n?=?1,415) at the left calcaneus. Lifestyle factors and medical conditions affecting bone health were assessed with questionnaires.

Results

In men, the youngest age cohort had the lowest trabecular volumetric bone mineral density (vBMD) at radius and tibia (difference between the youngest and the oldest, 4.4% and 5.6%, respectively, P?<?0.001) and lowest speed of ultrasound at the calcaneus (difference 0.5%, P?=?0.016). In women, bone traits did not differ by age groups. When sexes were pooled, underweight (relative risk (RR)?=?2.95, P?<?0.001), excess alcohol intake (1.52, P?=?0.036), smoking (1.29, P?=?0.025), Crohn’s disease or inflammatory bowel syndrome (2.43, P?=?0.016), epilepsy (2.54, P?=?0.011), use of corticosteroids (2.01, P?<?0.001) and inactivity (1.34, P?=?0.045) increased the risk of low trabecular vBMD. RRs for low-energy fractures were excess alcohol intake (2.58, P?=?<0.001), anorexia (3.74, P?=?0.041) and hypogonadism (2.08, P?=?0.015). Same risk factors predicted BMD and fractures in both sexes. Trabecular bone mineral content, vBMD and bone strength index showed greatest differences (4–9%; P?<?0.05) between those with and without low-energy fractures.

Conclusions

Peripheral QCT traits are associated with common risk factors of osteoporosis in young Finns and discriminate between those with and without low-energy fractures. In men, trabecular bone loss at peripheral bone sites starts before the age of 40 years.     

Cholesterol absorption and synthesis in pediatric kidney, liver, and heart transplant recipients

BACKGROUND: Hypercholesterolemia after organ transplantation is common. Previously, we observed higher serum total cholesterol (TC) concentrations in our pediatric kidney than liver or heart transplant recipients. To find an explanation to the observed difference, our kidney recipients' cholesterol synthesis and absorption efficiency was compared to those of liver and heart recipients. METHODS: Serum noncholesterol sterol ratios (10 x mmol to the mol of TC, surrogate estimates of hepatic cholesterol synthesis and intestinal absorption) were studied in 50 pediatric kidney, 25 liver and 12 heart transplant recipients without diabetes or cholestasis, and in 29 controls. RESULTS: The kidney recipients had lower Delta-cholesterol (P=0.031), similar lathosterol and higher desmosterol ratios (markers of cholesterol synthesis) (P=0.020), and similar campesterol and sitosterol ratios (markers of cholesterol absorption) when compared to the controls. The liver recipients had lower campesterol ratios than the kidney recipients and controls (P=0.002). Glomerular filtration rates were not associated with the ratios of noncholesterol sterols. Multivariate analysis showed markers of cholesterol synthesis to be lower and absorption to be higher in the kidney than the liver or the heart transplant recipients. Weight-adjusted dosages of immunosuppressive agents were associated with some ratios of noncholesterol sterols and cholestanol though these varied between the transplant recipient groups. CONCLUSIONS: Serum TC concentration in kidney recipients was not significantly associated with absorption efficiency or synthesis of cholesterol, though kidney transplantation was associated with low synthesis and high absorption efficiency of cholesterol. Immunosuppressive therapy with cyclosporine and methylprednisolone may modulate absorption efficiency and synthesis of cholesterol.     

Study of Nine Families with Haemoglobin-Lepore

The results of the clinical and haematological investigation of the members of nine families having a minor haemoglobin variant, designated Hb-Lepore, are presented. The abnormal haemoglobin has been found in the homozygous state (three cases) in combination with A₂ thalassaemia (four cases) and in the heterozygous state (56 cases).
In one homozygous individual very high concentrations of HbF and complete absence of HbA and HbA₂ were observed; Hb-Lepore was found in small quantity (8.6 per cent). The haemoglobin studies of the second homozygous individual were performed shortly after transfusion; they showed the presence of HbA and HbA₂. The third homozygote was not available for haemoglobin studies.
In the four double heterozygous individuals a high quantity of HbF and small amounts of the abnormal haemoglobin were found. In two of them the haemoglobin studies were performed 5 and 10 months after the last transfusion and the HbA and HbA₂ were present in the quantity of 36 and 29 per cent, and 0.9 and 1.4 per cent, respectively.
The clinical and haematological picture in both the homozygous and double heterozygous individuals were indistinguishable from thalassaemia major, but they were more severe in the three homozygous individuals than in three of the four double heterozygous patients. In the fourth heterozygous patient the severity was similar to that seen in the homozygous state. The heterozygous carriers showed the presence of low amounts of Hb-Lepore and HbF with an altered erythrocyte morphology resembling thalassaemia trait. The HbA₂ concentration was somewhat lower than normal (mean value, 1.86 per cent).     

Adenoviral gene transfer restores lysyl hydroxylase activity in type VI Ehlers-Danlos syndrome

Type VI Ehlers-Danlos syndrome is a disease characterized by disturbed lysine hydroxylation of collagen. The disease is caused by mutations in lysyl hydroxylase 1 gene and it affects several organs including the cardiovascular system, the joint and musculoskeletal system, and the skin. The skin of type VI Ehlers-Danlos syndrome patients is hyperelastic, scars easily, and heals slowly and poorly. We hypothesized that providing functional lysyl hydroxylase 1 gene to the fibroblasts in and around wounds in these patients would improve healing. In this study we tested the feasibility of transfer of the lysyl hydroxylase 1 gene into fibroblasts derived from rats and a type VI Ehlers-Danlos syndrome patient (in vitro) and into rat skin (in vivo). We first cloned human lysyl hydroxylase 1 cDNA into a recombinant adenoviral vector (Ad5RSV-LH). Transfection of human type VI Ehlers-Danlos syndrome fibroblasts (about 20% of normal lysyl hydroxylase 1 activity) with the vector increased lysyl hydroxylase 1 activity in these cells to near or greater levels than that of wild type, unaffected fibroblasts. The adenoviral vector successfully transfected rat fibroblasts producing both beta-galactosidase and lysyl hydroxylase 1 gene activity. We next expanded our studies to a rodent model. Intradermal injections of the vector to the abdominal skin of rats produced lysyl hydroxylase 1 mRNA and elevated lysyl hydroxylase 1 activity, in vivo. These data suggest the feasibility of gene replacement therapy to modify skin wound healing in type VI Ehlers-Danlos syndrome patients.     

Antiendomysial and antihuman recombinant tissue transglutaminase antibodies in the diagnosis of coeliac disease: a biopsy-proven European multicentre study

OBJECTIVE: To investigate the value of serum antitissue transglutaminase IgA antibodies (IgA-TTG) and IgA antiendomysial antibodies (IgA-EMA) in the diagnosis of coeliac disease in cohorts from different geographical areas in Europe. The setting allowed a further comparison between the antibody results and the conventional small-intestinal histology. METHODS: A total of 144 cases with coeliac disease [median age 19.5 years (range 0.9-81.4)], and 127 disease controls [median age 29.2 years (range 0.5-79.0)], were recruited, on the basis of biopsy, from 13 centres in nine countries. All biopsy specimens were re-evaluated and classified blindly a second time by two investigators. IgA-TTG were determined by ELISA with human recombinant antigen and IgA-EMA by an immunofluorescence test with human umbilical cord as antigen. RESULTS: The quality of the biopsy specimens was not acceptable in 29 (10.7%) of 271 cases and a reliable judgement could not be made, mainly due to poor orientation of the samples. The primary clinical diagnosis and the second classification of the biopsy specimens were divergent in nine cases, and one patient was initially enrolled in the wrong group. Thus, 126 coeliac patients and 106 controls, verified by biopsy, remained for final analysis. The sensitivity of IgA-TTG was 94% and IgA-EMA 89%, the specificity was 99% and 98%, respectively. CONCLUSIONS: Serum IgA-TTG measurement is effective and at least as good as IgA-EMA in the identification of coeliac disease. Due to a high percentage of poor histological specimens, the diagnosis of coeliac disease should not depend only on biopsy, but in addition the clinical picture and serology should be considered.