A Systematic Review of Job Loss Prevention Interventions for Persons with Inflammatory Arthritis

Journal of Occupational Rehabilitation - Purpose To present an overview of the evidence of the effect of job loss prevention interventions, aiming to improve work ability and decrease absenteeism...     

Lengthening extraocular muscle with autologous muscle transplants

Increasing extraocular muscle length by regenerative growth has been proposed as a potentially useful means of treating patients with paralytic or multiple re-operation strabismus. This study evaluates the viability and pattern of regeneration of fresh, autologous extraocular muscle and temporalis muscle transplants in the canine orbit. Bilateral grafts of either inferior oblique or temporalis muscle were sewn between host lateral rectus muscles and the globe. Grafts were biopsied and examined by light and electron microscopy at survival times to 56 days. Functional responses to abducens nucleus stimulation were examined in one extraocular muscle and one temporalis muscle graft at 15 weeks post-operatively. During the first week, both graft types were characterized by loss of pre-terminal nerve from neuromuscular junctions, muscle fiber necrosis that spared the central fibers, and inflammatory cell infiltrate. Myoblasts migrated into and fused within the existing basal laminae of degenerating fibers. By 14 days, grafts were populated by immature myofibers. Neuromuscular junctions were seen by 56 days, coinciding with muscle fiber differentiation as seen by enzyme histochemistry. Only two grafts failed to show regeneration. At 15 weeks survival, both types of grafts contracted in response to abducens nucleus stimulation. Free skeletal muscle grafts to extraocular muscle survive and mature with clear evidence of contractility by 15 weeks. These data suggest that muscle graft procedures could be useful in the management of certain types of strabismus where greater muscle length is needed.     

Noise in the signal-averaged electrocardiogram and accuracy for identification of patients with sustained monomorphic ventricular tachycardia after myocardial infarction

Late potentials are detected at various noise levels in clinicalstudies. The aim of this study was, in a case-control design,to assess the effect of residual noise level on the identificationof patients with sustained monomorphic ventncular tachycardiaafter myocardial infarction. Electrocardiograms from 16 patientswith prior myocardial infarction and documented sustained monomorphicventricular tachycardia and 41 patients with prior myocardialinfarction and without ventncular tachycardia, were analysedby two signal averaging procedures to noise level 0·2and 0·4 µV Standard time domain parameters weremeasured. Two definitions of late potential were analysed: (1)if any two of the following criteria were present (signal-averagedQRS duration >120 ms, late potential duration >40 ms,and root-mean-square voltage of the terminal 40 ms of the filteredQRS <25µV); or (2) if the signal-averaged QRS duration120 ms. Overall the signal-averaged electrocardiogram performedbetter at noise level 0·4µV compared to noise level0·2µV with respect to identification of patientswith or without ventricular tachycardia after myocordial infarction.Reducing noise level from 0·4 to 0·2 µVincreased the sensitivity, but the consequence was a substantialdecrease in specificity. Our data indicate that when a highsensitivity is the goal, the definition based only on signal-averagedQRS duration 120 ms should be applied; sensitivity was 88% andspecificity 59% at noise level 0·4 µV. If a highspecificity is the goal, the definition should be based on thedefinition with two abnormal parameters; sensitivity was 69%and specificity 68% at noise level 0·4µV.     

Steady-state kinetics of imipramine in patients

Steady-state plasma level kinetics were studied in 76 patients given imipramine (IP) 150 to 225 mg/day for 2–5 weeks. IP was given in three divided doses at 8.00 a.m., 1.00 p.m. and 5.00 p.m. Plasma concentrations of IP and its active metabolite desipramine (DMI) were determined by quantitative in situ thin-layer chromatography. The plasma levels of IP and DMI showed pronounced flucutations throughout the day with a ratio of about 2 between highest and lowest level. Patients with steady-state levels of IP and/or DMI below 50 g/l reached this within 1 week of treatment. Patients with higher steady-state levels reached steady-state concentrations within 2–3 weeks. There were some intraindividual fluctuations in plasma levels from week to week after steady state had been reached (coefficient of variation: 10–20%). Interindividually, the steady-state levels corrected to a dose of 3.5 mg/kg per day varied considerably: IP: 6–356 g/l, DMI: 24–659 g/l and IP+DMI: 58–809 g/l. The steady-state plasma levels showed a skew distribution that became normal by logarithmic transformation. The IP/DMI ratio ranged from 0.07 to 5.5 with a median value of 0.47. Compared to data from amitriptyline treated patients the IP/DMI ratios had significantly lower median value and larger variation than the corresponding plasma level ratios of amitriptyline/nortriptyline. Several statistically significant differences in steady-state levels between age groups were found. For IP: Women aged 30–39 had lower levels than women aged 20–29, 40–49, and 50–59, and men aged 50–59 and 60–65; men aged 30–39 had lower levels than men aged 60–65. For DMI: Women aged 30–39 had lower levels than women aged 50–59.     

Muscular Performance and Fatigue in Primary Hyperparathyroidism

The purpose of this study was to evaluate changes in muscular strength and endurance, work capacity, and subjective fatigue following surgical treatment of primary hyperparathyroidism (pHPT), and to assess whether changes in muscular function were due to changes in activation of the muscles. A prospective consecutive study design was used, and patients surgically treated for nontoxic goiter served as controls. Nineteen female patients with mild to moderate pHPT and 20 controls were included. Maximal isometric handgrip and quadriceps strength, quadriceps endurance (intermittent stimulation), and quadriceps activation (superimposed twitch technique) were used for evaluation of muscular function. All patients were operated on successfully. Knee extension strength increased by 17 ± 17% (mean ± SD; p= 0.0004) in the patients, whereas no change was observed in the controls. The relative strength increase correlated positively to patient age at operation (r= 0.52, p= 0.02). Handgrip strength, quadriceps endurance, and general work capacity did not change in any group after operation. Subjective fatigue was preoperatively higher in patients than in controls (p= 0.01), and decreased postoperatively to the level of controls. In conclusion, women with pHPT increase knee extension force after parathyroidectomy as a result of increased force generation capacity of the muscle. If change in physical performance is a determinant for change in subjective fatigue in pHPT after operation, then change in strength of the quadriceps muscle seems to be of primary importance, whereas handgrip strength, muscular endurance, and work capacity do not seem to be important. The cause of the increasing strength benefit with increasing age at operation as found in this study needs further investigation.     

Inhibition of hyperacute transplant rejection by soluble proteins with the functional domains of CD46 and FcgammaRII

BACKGROUND: Recombinant soluble forms of complement regulatory molecules, including the human complement regulatory protein CD46 (rsCD46), have been shown to inhibit hyperacute transplant rejection (HAR) and protect against complement-mediated inflammatory tissue damage. Similarly, recombinant soluble forms of the immunoglobulin receptor FcgammaRII (rsFcgammaRII) can attenuate antibody-mediated inflammatory responses. We have produced and tested the function of novel recombinant chimeric proteins that incorporate the functional domains of both CD46 (membrane cofactor protein, MCP) and the low affinity human IgG receptor FcgammaRII (CD32). METHODS: Two recombinant soluble chimeric proteins (CD46:FcR and FcR:CD46) were designed and produced using a human cell expression system. Their ability to protect cells against complement-mediated lysis (through the CD46 domain) and bind human IgG (through the Fc receptor domain) was assessed in vitro. They were also tested in vivo in the rat reverse passive Arthus reaction and a murine model of hyperacute cardiac transplant rejection. RESULTS: In vitro, the functional domains of the chimeric proteins each retained their activity. In vivo, the serum half-life of the recombinant chimeric proteins in mice was more than either rsCD46 or rsFcgammaRII. In the rat reverse passive Arthus reaction, intradermal injection of each recombinant protein substantially reduced inflammatory skin edema (>50%) and polymorphonuclear neutrophil infiltration (>90%). In the hyperacute rejection model, i.v. treatment with FcR:CD46 prevented complement-mediated rejection, macroscopic bruising, edema, and thrombosis more effectively than rsCD46. CONCLUSIONS: CD46/FcgammaRII bifunctional proteins have an improved ability to control complement-mediated hyperacute graft rejection and have therapeutic potential in other conditions involving antibody-mediated inflammation.     

Safety and efficacy of drospirenone used in a continuous combination with 17beta-estradiol for prevention of postmenopausal osteoporosis.

OBJECTIVE: To evaluate the combination of 17beta-estradiol and continuous drospirenone for the prevention of postmenopausal osteoporosis. METHODS: A total of 180 (75%) healthy postmenopausal women aged 45-65 years completed a 2-year prospective study. Bone mineral density (BMD) at lumbar spine, hip and total body as well as endometrial thickness, markers of bone turnover and serum lipids were measured regularly. Treatment groups were given placebo or 1 mg 17beta-estradiol combined with 1, 2 or 3 mg drospirenone daily. RESULTS: BMD at the lumbar spine, hip and total body increased by 7, 4 and 3%, respectively, in all hormone groups versus placebo (all p < 0.001). Bone markers all decreased accordingly (serum osteocalcin 52%, serum bone specific alkaline phosphatase 36%, serum CrossLaps 67% and urinary CrossLaps 75% from baseline; all p < 0.001). Total cholesterol and low-density lipoprotein cholesterol decreased by 8% and 13%, respectively (both p < 0.001). High-density lipoprotein cholesterol and triglycerides remained unchanged. No significant dose-related effects were found. Endometrial thickness increased by 1.2 mm only in the 1-mg drospirenone group (p < 0.01 versus placebo). CONCLUSION: The combination of 17beta-estradiol and drospirenone has a positive effect on BMD and a potentially beneficial effect on lipids. Although endometrial thickness increased slightly, the safety of the endometrium was assured, as no cases of hyperplasia or cancer occurred.     

The long-term impact of 2-3 years of hormone replacement therapy on cardiovascular mortality and atherosclerosis in healthy women.

OBJECTIVE: The effect of hormone replacement therapy (HRT) on cardiovascular risk is intensely debated. The aim of this study was to investigate the long-term effects of HRT given for a few years on all-cause and cardiovascular mortality and the severity of atherosclerosis. METHODS: This analysis was based on a cohort of 1,458 postmenopausal women (55.8 +/- 6.1 years old) who previously participated in a number of randomized, placebo-controlled, clinical trials assessing the efficacy of 2-3 years of therapy with various estrogen plus progestin combinations for preventing bone loss. Women were followed on average for 9.8 years and came for a follow-up visit. Outcome variables were all-cause and cardiovascular mortality and the severity of atherosclerosis, as estimated by semi-quantitative scoring of vascular calcification in the lumbar aorta on lateral radiographs. RESULTS: A total of 174 women died during the observation period. All-cause mortality was decreased by 30% in the HRT+ group compared with the HRT- group (hazard ratio (HR) 0.70; 95% confidence interval (CI) 0.50-0.97) after adjusting for age, body mass index and smoking. Under the same conditions, similar results characterized mortality from cardiovascular disease (n = 61 deaths; 35.1% of all deaths) and coronary heart disease (n = 39 deaths; 22.4% of all deaths), which were decreased by 46% (HR 0.54, 95% CI 0.29-0.98, p = 0.045) and 53% (HR 0.47, 95% CI 0.21-1.03, p = 0.062), respectively. Furthermore, the mean severity score of aortic calcification at follow-up was significantly lower in hormone-treated compared to non-treated women (p < 0.0001). CONCLUSION: Women who receive 2-3 years of HRT after menopause do not have increased all-cause mortality, and results of the present study suggest relative cardiovascular benefits compared to those who had not used hormones.