Soluble receptor for AGE (RAGE) is a novel independent predictor of all-cause and cardiovascular mortality in type 1 diabetes

Aims/hypothesis  

Activation of the receptor for AGE (RAGE) is implicated in the development and progression of vascular complications of diabetes. In this study, we explore factors and mortality outcomes associated with soluble RAGE (sRAGE) in a multicentre nationwide cohort of Finnish adults with type 1 diabetes.     

Lack of association between the Gly40Ser polymorphism in the glucagon receptor gene and NIDDM in Finland

Summary A heterozygous polymorphism changing GGT⁴⁰ (Gly) to AGT⁴⁰ (Ser) (Gly40Ser) in the glucagon receptor gene was reported to be associated with non-insulin-dependent diabetes mellitus (NIDDM). A possible involvement of this polymorphism in impaired glucose tolerance was also suggested in a French population. To replicate this finding we screened 311 unrelated NIDDM patients, 101 unrelated individuals with impaired glucose tolerance and 306 control subjects for the presence of the Gly40Ser polymorphism by use of polymerase chain reaction-restriction fragment length polymorphism in a Finnish population. None of the NIDDM or impaired glucose tolerant patients had this polymorphism. Instead, four of the control subjects (1.3%) were heterozygous carriers of the polymorphism (NS). The age, body mass index, 2-h blood glucose level, 2-h insulin level, and incremental insulin area of the four subjects with this polymorphism were similar to those of the control subjects homozygous for the wild type. Taken together, the data do not support the suggested involvement of the Gly40Ser polymorphism in impaired glucose tolerance and the hypothesis of an association between NIDDM and the glucagon receptor gene in this population.Abbreviations GCG-R Glucagon receptor - IGT impaired glucose tolerance - NIDDM non-insulin-dependent diabetes mellitus - PCR-RFLP polymerase chain reaction-restriction fragment length polymorphism     

When does subluxation of the first carpometacarpal joint cause swan-neck deformity of the thumb in rheumatoid arthritis: A 20-year follow-up study

The aim of our study was to assess the incidence of subluxation of the first carpometacarpal joint (CMC I) and to evaluate which degree of subluxation produces swan-neck deformity of the thumb in rheumatoid arthritis (RA) occurring over 20 years. The hands of 83 rheumatoid factor (RF)-positive RA patients with recent (6 months) arthritis were evaluated radiographically at onset and at 1, 3, 8 and 15 years; 68 patients were evaluated at 20 years from entry. Subluxation was assessed in millimetres and compared with the MCP-I angle measurement to evaluate the thumb deformity. A statistical end-point analysis was performed between two different grades of subluxation. Subluxation of 2–3 mm was non-specific and only one third of these thumbs showed swan-neck deformity. At the end-point, subluxation of 4 mm was present in 17% of the thumbs, 81% of which had the swan-neck deformity; only five thumbs did not show this deformity, but presented deformed and unstable MCP I and interphalangeal joints. The frequency of swan-neck deformity was highly significantly (p<0.0001) increased in the thumbs with severe CMC I subluxation (4 mm) compared with lesser subluxation (<4 mm). When subluxation of the CMC I exceeds 4 mm, the swanneck deformity of the thumb is a common consequence. This deformity is often progressive, and the hand function of such patients should be followed up carefully, both clinically and radiographically.     

Valgus deformity and proximal subluxation of the rheumatoid elbow: a radiographic 15 year follow up study of 148 elbows

OBJECTIVE—To evaluate the nature of positional changes of humeroulnar (HU) and humeroradial (HR) joints in a cohort of 74 patients with seropositive and erosive rheumatoid arthritis (RA) followed up prospectively.
METHODS—At the 15 year follow up standard anteroposterior and lateral radiographs of 148 elbow joints were evaluated. The mediolateral HU angle of the elbow was measured from anteroposterior radiographs. The proximal subluxation of the HU joint was measured from lateral radiographs as the distance between the posterior aspect of the olecranon process and the posterior surface of the humerus. The anteroposterior subluxation of the HR joint was measured from lateral radiographs as the relation of the midpoint of head of the radius to the midpoint of the capitellum of the humerus. Destruction of the elbow joints was assessed with the Larsen method on a scale of 0 to 5 and compared with the measurements.
RESULTS—Mean HU angle in 148 elbows of patients with RA was 11.5° (SD 6.1), range −21° (varus) to 34° (valgus); 9.9° (SD 4.3) in men and 12.0° (SD 6.4) in women. The mean HU angle, 14.4° (SD 6.0) of the affected joints (Larsen grades 2-4), showed more valgus than the mean 9.8° (SD 2.5) of the non-affected (Larsen grades 0 to 1) joints; totally destroyed and unstable Larsen 5 joints were excluded. Mean HU and HR subluxations, 2.0 mm (SD 3.8) and 0.8 mm, of the affected joints (Larsen 2-5) were greater than the means, −1.1 mm (SD 1.5) and −0.4 mm (SD 0.9), of the non-affected joints. Both the HU proximal subluxation and the HR anterior subluxation correlated, r_s=0.64 (95% CI 0.53 to 0.73 ) and r_s=0.48 (95% CI 0.34 to 0.60), with the destruction of the elbow joint.
CONCLUSIONS—The elbow seems to turn into valgus during rheumatoid destruction and excision of the radial head may speed up this process. However, totally unstable Larsen grade 5 joints may also have varus deformity owing to mutilating bone destruction. The ulna subluxates proximally in relation to the humerus, whereas the radius moves slightly anteriorly as a consequence of elbow involvement.

     

Proteinuria and metabolic syndrome as predictors of cardiovascular death in non-diabetic and type 2 diabetic men and women

Aims/hypothesis Proteinuria predicts cardiovascular disease (CVD), but it is unclear whether this is explained by the association of the metabolic syndrome with proteinuria. Therefore, we investigated proteinuria and the metabolic syndrome as independent predictors of CVD death in men and women. Methods The cohort comprised 574 non-diabetic men, 707 non-diabetic women, 371 diabetic men and 349 diabetic women, all free of CVD at baseline. Modified World Health Organization criteria were used to define the metabolic syndrome, and a urinary protein concentration of ≥0.1 g/l (or ≥0.2 g/l) to define proteinuria. The endpoint was CVD mortality during the 18-year follow-up. Results Among non-diabetic men, CVD mortality per 1,000 person-years was as follows: no metabolic syndrome, no urinary protein group: 5.3; no metabolic syndrome, positive for urinary protein: 8.9; positive for metabolic syndrome, no urinary protein: 13.3; and positive for metabolic syndrome and urinary protein: 14.9. For non-diabetic women the corresponding values were: 0.9, 2.3, 4.9 and 7.9, respectively. Among diabetic men, CVD mortality per 1,000 person-years was 15.2, 32.5, 23.6 and 42.0 for the respective groups. Among diabetic women it was 25.3, 38.0, 26.3 and 40.3 (urinary protein in all cases defined as ≥0.1 g/l). In multivariate Cox models including both urinary protein and metabolic syndrome, the hazard ratios (HRs, 95% CI) of proteinuria for CVD mortality were 1.5 (0.9–2.4) in non-diabetic men, 1.8 (0.8–4.2) in non-diabetic women, 1.6 (1.0–2.6) in diabetic men and 1.6 (1.1–2.3) in diabetic women. Urinary protein as a continuous variable was associated with CVD mortality in all groups. The corresponding HRs for metabolic syndrome were: 1.6 (0.9–2.7), 4.0 (1.7–9.7), 1.5 (1.1–2.0) and 1.1 (0.8–1.5). Conclusions/interpretation Proteinuria predicted CVD mortality independently of the presence of metabolic syndrome in non-diabetic and diabetic subjects. Metabolic syndrome predicted CVD mortality in non-diabetic women and in diabetic men, independently of the presence of proteinuria.     

The multifidus muscle in patients with lumbar disc herniation. A histochemical and morphometric analysis of intraoperative biopsies

Structural changes in the multifidus muscle were analyzed in 41 patients operated on for herniated intervertebral disc. Twelve cadavers served as controls. The two main findings follow: Both in the patients and in the controls the Type 2 muscle fibers were markedly and selectively smaller than the Type 1 fibers, which were of normal size for striated muscles, and the internal structure of Type 1 fibers showed so-called core-targetoid and/or moth-eaten change. Group atrophy or fiber-type grouping (indicators of denervation and reinnervation) were observed only in a few patients. The selective small size of the Type 2 fibers may indicate atrophy due to relative inactivity of the multifidus muscle both in the patients and in the controls, ie, it does not need to be related to the herniated disc. Definite proof for denervation of the multifidus muscle was not observed, but neither the possibility be excluded. The cause of the core-targetoid and/or moth-eaten changes cannot yet be determined with certainty, because these changes are not specific for any single entity but may be due, for example, to denervation, ischemia, or altered use of the muscles because of pain. In any case, because the changes were significantly more common in the patients than in the controls, they signal for a pathologic condition, the character of which remains to be elucidated.     

Motor performance in physically well-recovered men with traumatic brain injury.

OBJECTIVE: The primary aim of this study was to compare the motor performance of physically well-recovered men with traumatic brain injury with that of healthy men. DESIGN: Cross-sectional study in a national rehabilitation centre. METHODS: Static and dynamic balance, agility and rhythm co-ordination of men with traumatic brain injury (n=34) and healthy controls (n=36) were assessed. Between-group differences in dynamic balance and agility were analysed by analysis of covariance and differences in static balance and rhythm co-ordination by logistic regression analysis. Cut-off points for clinical screening were determined by receiver operating characteristics analyses. RESULTS: Men with traumatic brain injury had impaired balance and agility compared with healthy men and in a rhythm co-ordination test they had difficulties in starting and sustaining simultaneous rhythmical movements of hands and feet. In receiver operating characteristics analyses a running figure-of-eight test (agility), tandem walking forwards (dynamic balance) and rhythm co-ordination test with fast tempo were found the most sensitive and specific for distinguishing between men with traumatic brain injury and the healthy men. CONCLUSIONS: The impairments in motor performance of physically well-recovered patients with traumatic brain injury were obvious. The results of this study extend the knowledge of problems in motor performance among patients with traumatic brain injury and provide further information for clinical rehabilitation.     

Long-term follow up of argon laser trabeculoplasty in pigmentary glaucoma.

Nine eyes in nine patients with pigmentary glaucoma were treated with argon laser trabeculoplasty (ALT). The mean age of the patients at the time of treatment was 35 years (range, 25 to 46 years); the mean follow up after treatment was 5.5 years. The initial pressure-lowering effect of ALT was 53% (15.3 mm Hg), ie, from a preoperative mean of 29.0 mm Hg to a postoperative mean of 13.7 mm Hg the day after ALT. However, the initial response to ALT wore off in 3 months, after which the intraocular pressure settled at a level 14% (4 mm Hg) lower than before treatment. The rate of failure (ie, unstable glaucoma after treatment) was 11%.     

Muscle injuries, their healing process and treatment

Muscle injuries represent one of the most common traumas in sports medicine. They have different clinical manifestations depending on the trauma mechanism: laceration, contusion and strain. The range of lesions varies from minor partial ruptures to complete ruptures of the muscle. The muscular tissue has a capacity to regenerate and the healing process consists of regeneration of muscle fibres and formation of a connective tissue scar. The healing is also greatly dependent on the ingrowth of vascularity and regeneration of intramuscular nerve branches. Immobilization and mobilization have a notable impact on the recovery, the former being of importance initially by reducing the size of injury and the latter later on by inducing greater granulation tissue production. Mobilization treatment is also a prerequisite for intensive muscle fibre regeneration and better preconditions to achieve the original tensile properties of the muscle. Surgical intervention is occasionally needed in complete ruptures to evacuate the haematoma or to suture the ruptured ends of the muscle to apposition.     

Skeletal muscle injury—molecular changes in the collagen during healing

Changes in the collagen types and cross-linking of granulation and scar tissue in the injured site of partially ruptured gastrocnemius muscle were studied after a reproducible contusion injury to the left calf of a rat. In normal i.m. collagen the proportion of Type I collagen was considerably higher than Type III. Following injury there was a rapid increase in the proportion of Type III collagen reaching a maximum at 5 days after injury. After a further 2 days the proportion of Type I had increased significantly resulting in a decrease of the Type III/I ratio to below that of the control. However, as healing progressed there was a gradual shift back to the Type III/I ratio for normal i.m. collagen. The collagen produced in response to an injury was initially stabilized by the stable keto-imine cross-link hydroxylysino-5-keto-norleucine, characteristic of embryonic collagenous tissues. The proportion of the stable keto-imine cross-link gradually decreased, and a reversion to the cross-link pattern of normal uninjured i.m. collagenous connective tissue occurred towards the end of the 42-day follow-up period. The present biochemical study demonstrates that during the early phases of the repair process there is a reversion to the collagens typically present in high proportions in embryonic dermal connective tissue. This suggests that the fibroblasts have the ability to modify their product expression under varying circumstances. The study also demonstrates the importance of collagen cross-linking in determining the tensile strength of collagen fibre during the repair process.