Effects on the buoyant density of rabbit platelets of ADP and agents that increase the concentration of cyclic AMP

Rabbit platelets were aggregated by adenosine diphosphate (ADP), allowed to deaggregate and then separated into density subpopulations by centrifugation through discontinuous Stractan density gradients. Although ADP causes little or no release of the contents of the amine storage granules of rabbit platelets, ADP caused a decrease in platelet density as compared with control platelets subjected to the same procedures except for exposure to ADP. The density change persisted for at least four hours. The apparent size of platelets stimulated with ADP increased initially, but returned to control values during a one-hour period. A similar decrease in platelet density was observed with an albumin density gradient. Under conditions in which aggregation did not occur in response to ADP with ethylenediaminetetraacetic acid (EDTA) in the medium, little or no decrease in platelet density was observed. Agglutination with polylysine did not change platelet density. Thus, not only agents such as thrombin and plasmin that cause the release of the contents of the platelet granules decrease platelet density, but ADP also has this effect. Platelets would be exposed to all of these stimuli during thromboembolic processes, and their effect on platelets may account for the decrease in platelet density observed previously in experiments with rabbits with indwelling aortic catheters. Agents that increase the concentration of cyclic AMP (cAMP) in platelets (PGE1, adenosine, dibutyryl cAMP, forskolin, and papaverine) also decreased platelet density. This effect persisted when the platelets were washed and resuspended in fresh medium and was also demonstrable in plasma. Platelet size was gradually increased by prostaglandin E1 (PGE1) which maintains platelets in a disc shape and does not cause the release of granule contents, indicating that the decrease in platelet density caused by PGE1 may be attributable to platelet swelling.     

Half the burden of fragility fractures in the community occur in women without osteoporosis. When is fracture prevention cost-effective?

To determine the age- and BMD-specific burden of fractures in the community and the cost-effectiveness of targeted drug therapy, we studied a demographically well-categorized population with a single main health provider. Of 1224 women over 50 years of age sustaining fractures during 2 years, the distribution of all fractures was 11%, 20%, 33%, and 36% in those aged 50-59, 60-69, 70-79, and 80+ years, respectively. Osteoporosis (T score < -2.5) was present in 20%, 46%, 59%, and 69% in the respective age groups. Based on this sample and census data for the whole country, treating all women over 50 years of age in Australia with a drug that halves fracture risk in osteoporotic women and reduces fractures in those without osteoporosis by 20%, was estimated to prevent 18,000 or 36% of the 50,000 fractures per year at a total cost of $573 million (AUD). Screening using a bone mineral density of T score of -2.5 as a cutoff, misses 80%, 54%, 41%, and 31% of fractures in women in the respective age groups. An analysis of cost per averted fracture by age group suggests that treating women in the 50- to 59-year age group with osteoporosis alone costs $156,400 per averted fracture. However, in women aged over 80 years, the cost per averted fracture is $28,500. We infer that treating all women over 50 years of age is not feasible. Using osteoporosis and age (>60 years) as criteria for intervention reduces the population burden of fractures by 28% and is cost-effective but solutions to the prevention of the remaining 72% of fragility fractures remain unavailable.     

Intra-lesional injections of collagenase are ineffective in the treatment of keloid and hypertrophic scars.

The treatment of keloid and hypertrophic scars remains difficult. Enzymatic digestion of keloid scars has been previously proposed as an effective treatment strategy for reducing the volume of keloid scars. To test this, we administered intra-lesional injections of pure collagenase (between 600 and 4500 units for each scar) into the keloid and hypertrophic scars of seven human volunteers (five keloid and two hypertrophic scars). Five patients (three keloid and two hypertrophic) received more than one injection of collagenase. The treatment resulted in a temporary reduction in scar volume for three of the patients with keloid scars. However, scar volumes for these three patients returned to the same (or greater) levels after 6 months of follow-up. Treatment with collagenase produced no change in scar volume for the two patients with hypertrophic scar. Side effects were numerous and severe including; pain, swelling, blistering, ulceration and ecchymosis at the site of injection. One patient required admission to hospital for 48 h after the first injection. Maximum length of follow-up was 6 months. None of the seven patients completed the study and returned for final follow-up at 2 years. This pilot study suggests that treatment of keloid and hypertrophic scars with intra-lesional injections of collagenase is ineffective.     

Early Conversion to Prednisolone/Everolimus as an Alternative Weaning Regimen Associates With Beneficial Renal Transplant Histology and Function: The Randomized‐Controlled MECANO Trial

In renal transplantation, use of calcineurin inhibitors (CNIs) is associated with nephrotoxicity and immunosuppression with malignancies and infections. This trial aimed to minimize CNI exposure and total immunosuppression while maintaining efficacy. We performed a randomized controlled, open‐label multicenter trial with early cyclosporine A (CsA) elimination. Patients started with basiliximab, prednisolone (P), mycophenolate sodium (MPS), and CsA. At 6 months, immunosuppression was tapered to P/CsA, P/MPS, or P/everolimus (EVL). Primary outcomes were renal fibrosis and inflammation. Secondary outcomes were estimated glomerular filtration rate (eGFR) and incidence of rejection at 24 months. The P/MPS arm was prematurely halted. The trial continued with P/CsA (N = 89) and P/EVL (N = 96). Interstitial fibrosis and inflammation were significantly decreased and the eGFR was significantly higher in the P/EVL arm. Cumulative rejection rates were 13% (P/EVL) and 19% (P/CsA), (p = 0.08). A post hoc analysis of HLA and donor‐specific antibodies at 1 year after transplantation revealed no differences. An individualized immunosuppressive strategy of early CNI elimination to dual therapy with everolimus was associated with decreased allograft fibrosis, preserved allograft function, and good efficacy, but also with more serious adverse events and discontinuation. This can be a valuable alternative regimen in patients suffering from CNI toxicity.     

Results of four-corner arthrodesis using dorsal circular plate fixation

PURPOSE: Four-corner arthrodesis with scaphoid excision has been used to reduce pain and preserve functional range of motion for patients with radioscaphoid arthritis. Early results of 4-corner arthrodesis with scaphoid excision using dorsal circular plate fixation are compared with reported results in the literature. METHODS: We reviewed retrospectively the first 18 four-corner arthrodeses performed with this system by 4 hand surgeons. Two patients had revision surgery for nonunions before the study that were considered failures. Eight patients returned for final radiographs, objective examination, and functional questionnaire. The average follow-up period was 20 months (range, 13-33 mo). These results were compared with reported results in the literature using alternate fixation methods. RESULTS: Radiographic union was achieved in only 3 wrists. Range of motion was 46% that of the opposite normal wrist and grip strength compared with the opposite wrist was 56%. Five patients would have the procedure again and 6 of 8 have returned to their original employment. CONCLUSIONS: Four-corner arthrodesis with scaphoid excision using a circular internal fixation plate produced a high number of nonunions. Grip strength and range of motion results also were inferior to those reported in the literature.     

Functional outcome and persistent disability after isolated fracture of the femur

Background

The purpose of this study was to assess the functional outcome and causes of persistent disability in patients with isolated femoral shaft fractures treated at an academic level-1 trauma centre.

Methods

We prospectively enrolled 40 consecutive skeletally mature patients with isolated, nonpathologic diaphyseal femur fractures. All patients underwent fracture reduction and fixation using an antegrade locked intramedullary nail. We measured functional outcome using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index and the Short Musculoskeletal Functional Assessment (SMFA). We obtained visual analog scores for pain in the groin, buttock, thigh and knee 6 months after the injury.

Results

Joint-related and musculoskeletal outcome scores improved gradually from the baseline assessment to the 6-month review. Mean scores (and standard deviations [SDs]) on the WOMAC index improved gradually from 57 (23) to 24 (22) for pain, from 57 (25) to 30 (20) for stiffness and from 70 (21) to 21 (23) for function (p < 0.001). The mean SMFA score (and SD) improved from 64 (13) to 25 (20) (p = 0.024). We noted no further improvements in functional outcome measures from the 6-month to the 12-month assessment (p > 0.21). Patients reported more pain in the knee than in other anatomic locations; the mean pain scores (and SDs) were 3.7 (3.1) in the knee, 2.5 (2.7) in the thigh, 1.7 (2.7) in the buttock and 1.0 (1.7) in the groin (p = 0.003). We noted correlations between knee pain and WOMAC pain (ρ = 0.748, p < 0.001), function (ρ = 0.701, p < 0.001) and SMFA (ρ = 0.733, p < 0.001). We noted weaker correlations between thigh, groin and buttock pain and functional outcomes, with ρ scores ranging from 0.2 to 0.55.

Conclusion

Recovery from femur fractures occurs most rapidly in the first 6 months after injury. Residual deficits in functional outcome were still measurable 12 months after injury. Knee pain was the most common and most severe source of patient discomfort 12 months after isolated femur fractures, and demonstrated moderate to good correlation with general and joint-specific functional outcome measures.     

Clinical and familial study of arrhythmogenic right ventricular cardiomyopathy

Objective　To explore the characteristics of arrhythmogenic right ventricular cardiomyopathy (ARVC). Methods　Seven patients with arrhythmogenic right ventricular cardiomyopathy and 34 members of three families were studied. All patients and family members underwent history collection, clinical examination, electrocardiogram (ECG), two-dimensional echocardiography (2-DE) and a signal averaging electrocardiogram. Programmed ventricular stimulation was performed in five patients. Results　All patients and family members had normal morphologic characteristics and normal function of the left ventricular by 2-DE. Fourteen persons had abnormal findings indicating ARVC. Five had enlargement of the right ventricular with diffused hypocontractility, eight had thin and systolic bulging in the focal anterior wall with hypokinesia and one had bulging of the inferior wall. Twenty-five persons (seven patients and 18 family members) had abnormal findings in ECG. Positive ventricular late potential was recorded in 13 persons (six patients). Two to three monomorphic ventricular tachycardia (VT) with left bundle branch block (LBBB) configurations were induced in five patients. Ventricular fibrillation was induced in two patients during the electrophysiologic study (EPS). Five patients had very high pacing threshold and/or ineffective pacing in one or many regions of the right ventricle. Two members of one family died suddenly. One member was a dwarf with ARVC. Spontaneous VT with a left bundle branch block (LBBB) configuration was recorded in five patients, polymorphic VT with extremely short coupling interval in one, and premature ventricular complexes with LBBB configuration in 12 (six patients). Conclusion　Our familial study strongly suggests that ARVC may be a hereditary disease and it is helpful in the diagnosis and detection of ARVC. The most common manifestations were abnormal structure and function of the right ventricle and abnormal ECG of repolarization and ventricular arrhythmia which originates from the right ventricle.     

Otolith function tests--a differentiated, quality-assured screening system

INTRODUCTION: More than 30% of all otogenic vestibular disorders are related to isolated macular dysfunction. Videooculographic examination techniques for the otolith-ocular reflex, e. g. by means of eccentric rotation tests, are not widely used in clinical routine as these put a considerable strain on technical and staff resources. Thus, there is a considerable risk of "false negative" classification of vertigo disorders being labelled as "non-otogenic". By means of vestibular-evoked myogenic potentials (VEMPs) and caloric irrigation in prone and supine position, several examination techniques for a side-related investigation of macula-induced vestibulo-ocular reflexes are available. The objective of this study is to compare and evaluate these techniques as screening tests. METHODS: In 32 patients with vestibular disorders we performed investigations for VEMPs, eccentric rotation tests, as well as caloric irrigation for macular reaction in prone and supine position. In addition, we performed other audiologic and vestibular function tests which were complemented by the clinical course in order to differentiate each case between otogenic and non-otogenic vertigo with or without macular affection. RESULTS: The technical feasibility as well as patients' acceptance for VEMP testing is better than for eccentric rotation tests. The sensitivity index for VEMPs (89%) as well as for caloric irrigation in prone and supine position for macular examination (71%) is satisfactory. However, the specificity of VEMPs is inferior (53%) to eccentric rotation (100%). DISCUSSION: Both the examination for VEMPs as well as caloric macular testing in prone and supine position carry features which make them feasible for screening, even though these two procedures test for two different parts of the otolith system. However, to confirm a diagnosis and to set up a therapeutic concept for macular function disorders, eccentric rotation should be added.     

In-111-labeled leukocyte scintigraphy in suspected orthopedic prosthesis infection: comparison with other imaging modalities

When infection of prosthetic orthopedic implants is suspected, optimal management requires accurate confirmation or exclusion of infection. The authors retrospectively studied 98 patients with possible infection who underwent scanning with indium-111-labeled white blood cells (WBCs) and subsequently underwent surgery within 14 days. At surgery, 50 patients had infections, as determined by means of culture or histologic results. The diagnostic accuracy of In-111 scanning was compared with that of plain radiography, arthrography, three-phase bone scanning, and various clinical and laboratory findings classically associated with infection. Positive findings on In-111 WBC scans and elevated erythrocyte sedimentation rates were found to be the most predictive variables in the diagnosis of septic prostheses (P less than or equal to .001 and P less than or equal to .002, respectively). Likelihood ratio analysis more clearly demonstrated the superiority of In-111 WBC scanning, with positive and negative scans yielding likelihood ratios of 5.0 and 0.16, respectively.