Assessment of myocardial fibrosis with T1 mapping MRI.

Myocardial fibrosis can arise from a range of pathological processes and its presence correlates with adverse clinical outcomes. Cardiac magnetic resonance (CMR) can provide a non-invasive assessment of cardiac structure, function, and tissue characteristics, which includes late gadolinium enhancement (LGE) techniques to identify focal irreversible replacement fibrosis with a high degree of accuracy and reproducibility. Importantly the presence of LGE is consistently associated with adverse outcomes in a range of common cardiac conditions; however, LGE techniques are qualitative and unable to detect diffuse myocardial fibrosis, which is an earlier form of fibrosis preceding replacement fibrosis that may be reversible. Novel T1 mapping techniques allow quantitative CMR assessment of diffuse myocardial fibrosis with the two most common measures being native T1 and extracellular volume (ECV) fraction. Native T1 differentiates normal from infarcted myocardium, is abnormal in hypertrophic cardiomyopathy, and may be particularly useful in the diagnosis of Anderson-Fabry disease and amyloidosis. ECV is a surrogate measure of the extracellular space and is equivalent to the myocardial volume of distribution of the gadolinium-based contrast medium. It is reproducible and correlates well with fibrosis on histology. ECV is abnormal in patients with cardiac failure and aortic stenosis, and is associated with functional impairment in these groups. T1 mapping techniques promise to allow earlier detection of disease, monitor disease progression, and inform prognosis; however, limitations remain. In particular, reference ranges are lacking for T1 mapping values as these are influenced by specific CMR techniques and magnetic field strength. In addition, there is significant overlap between T1 mapping values in healthy controls and most disease states, particularly using native T1, limiting the clinical application of these techniques at present.

Perioperative elafin for ischaemia-reperfusion injury during coronary artery bypass graft surgery: a randomised-controlled trial.

BACKGROUND: Elafin is a potent endogenous neutrophil elastase inhibitor that protects against myocardial inflammation and injury in preclinical models of ischaemic-reperfusion injury. We investigated whether elafin could inhibit myocardial ischaemia-reperfusion injury induced during coronary artery bypass graft (CABG) surgery. METHODS AND RESULTS: In a randomised double-blind placebo-controlled parallel group clinical trial, 87 patients undergoing CABG surgery were randomised 1:1 to intravenous elafin 200 mg or saline placebo administered after induction of anaesthesia and prior to sternotomy. Myocardial injury was measured as cardiac troponin I release over 48 h (area under the curve (AUC)) and myocardial infarction identified with MRI. Postischaemic inflammation was measured by plasma markers including AUC high-sensitive C reactive protein (hs-CRP) and myeloperoxidase (MPO). Elafin infusion was safe and resulted in >3000-fold increase in plasma elafin concentrations and >50% inhibition of elastase activity in the first 24 h. This did not reduce myocardial injury over 48 h (ratio of geometric means (elafin/placebo) of AUC troponin I 0.74 (95% CI 0.47 to 1.15, p=0.18)) although post hoc analysis of the high-sensitive assay revealed lower troponin I concentrations at 6 h in elafin-treated patients (median 2.4 vs 4.1 µg/L, p=0.035). Elafin had no effect on myocardial infarction (elafin, 7/34 vs placebo, 5/35 patients) or on markers of inflammation: mean differences for AUC hs-CRP of 499 mg/L/48 h (95% CI -207 to 1205, p=0.16), and AUC MPO of 238 ng/mL/48 h (95% CI -235 to 711, p=0.320). CONCLUSIONS: There was no strong evidence that neutrophil elastase inhibition with a single-dose elafin treatment reduced myocardial injury and inflammation following CABG-induced ischaemia-reperfusion injury. TRIAL REGISTRATION NUMBER: (EudraCT 2010-019527-58, ISRCTN82061264).

Nanoparticle enhanced MRI scanning to detect cellular inflammation in experimental chronic renal allograft rejection.

Objectives. We investigated whether ultrasmall paramagnetic particles of iron oxide- (USPIO-) enhanced magnetic resonance imaging (MRI) can detect experimental chronic allograft damage in a murine renal allograft model. Materials and Methods. Two cohorts of mice underwent renal transplantation with either a syngeneic isograft or allograft kidney. MRI scanning was performed prior to and 48 hours after USPIO infusion using T2(∗)-weighted protocols. R2(∗) values were calculated to indicate the degree of USPIO uptake. Native kidneys and skeletal muscle were imaged as reference tissues and renal explants analysed by histology and electron microscopy. Results. R2(∗) values in the allograft group were higher compared to the isograft group when indexed to native kidney (median 1.24 (interquartile range: 1.12 to 1.36) versus 0.96 (0.92 to 1.04), P < 0.01). R2(∗) values were also higher in the allograft transplant when indexed to skeletal muscle (6.24 (5.63 to 13.51)) compared to native kidney (2.91 (1.11 to 6.46) P < 0.05). Increased R2(∗) signal in kidney allograft was associated with macrophage and iron staining on histology. USPIO were identified within tissue resident macrophages on electron microscopy. Conclusion. USPIO-enhanced MRI identifies macrophage.

Metacarpophalangeal joints in rheumatoid arthritis of the hand.

Treatment of the MP joint in the patient with rheumatoid arthritis can lead to very satisfying results. Decision making is based on the degree of compromise in the hand and the knowledge of anticipated outcomes with surgery. In patients in whom pain is an overriding feature, implant surgery is highly successful. The timing for implant surgery in regard to deformity is less clear. Soft tissue correction procedures without implants appear to have value in the treatment of moderate to late disease and further documentation of the long-term outcomes will prove helpful in determining the roles of such procedures. If silicone rubber MCP arthroplasty is performed, one can anticipate an arc of motion in the 50-degree range, with improvement of extensor lag. There also is improvement of ulnar deviation, although recurrence into the 10 to 15 degree range is not unexpected. Complications such as deep infection, recurrent deformity, and implant breakage all play a role in making the decision to undertake surgery. Younger patients obviously have more risk for future prosthetic problems. The development of silicone implant arthroplasty of the MP joint has given the hand surgeon a valuable way of improving hand function in patients with severe rheumatoid involvement. It is a procedure the outcome of which may be anticipated and patients may be reassured with some degree of confidence that the hand surgeon can provide them with improved hand function.

A self-administered hand symptom diagram for the diagnosis and epidemiologic study of carpal tunnel syndrome.

Noninvasive tests for carpal tunnel syndrome (CTS) are of limited diagnostic value. A self-administered hand symptom diagram has been developed for use in the diagnosis and epidemiologic study of CTS. Diagrams are rated classic CTS, probable, possible or unlikely. Diagram ratings were compared with nerve conduction diagnoses in 110 patients with upper extremity complaints. A hand diagram rating of classic or probable CTS had sensitivity of 0.64, specificity of 0.73 and positive predictive value of 0.58. The negative predictive value of an unlikely diagram was 0.91. We conclude that the diagram is a useful diagnostic tool and may be valuable for occupational and population screening.

The carpal tunnel syndrome: diagnostic utility of the history and physical examination findings.

STUDY OBJECTIVE: To assess the value of a history and physical examination findings in diagnosing the carpal tunnel syndrome, and to determine whether constellations of clinical findings identify patients at high or low risk for the carpal tunnel syndrome. DESIGN: Comparison of diagnostic tests with neurophysiologic testing. SETTING: Patients with upper extremity complaints of diverse causes referred to a neurophysiology laboratory for diagnostic studies. METHODS: Before nerve conduction testing, a history, demographic and physical examination data, and a hand pain diagram were obtained from each patient. Diagrams were categorized as indicating the classic carpal tunnel syndrome, or as probable, possible, or unlikely to indicate the carpal tunnel syndrome. Associations between clinical data and nerve conduction results were examined in univariate and multivariate analyses. RESULTS: Of 110 patients in the study, 44 (40%) had the carpal tunnel syndrome. Individually, the best predictors were hand pain diagram rating (positive predictive value, 0.59; 95% CI, 0.48 to 0.68) and Tinel sign (positive predictive value, 0.55, CI, 0.45 to 0.65). The combination of a positive Tinel sign and a probable or classic diagram rating had a positive predictive value of 0.71; CI, 0.53 to 0.85. Other findings from physical examination and the history were less useful. Just 9% of patients under 40 years of age with possible or unlikely diagram ratings had the carpal tunnel syndrome. CONCLUSIONS: With the exceptions of age, Tinel sign, and hand pain diagram rating, findings from the physical examination and the history had limited diagnostic utility. Patients under 40 years of age with possible or unlikely diagram ratings were at low risk for the carpal tunnel syndrome. This finding, which should be confirmed in an independent population, suggests that subsets of patients may be managed without nerve conduction studies.

A self-administered hand diagram for the diagnosis of carpal tunnel syndrome.

A self-administered hand diagram has been developed to assist in the evaluation of upper extremity paresthesias. A rating system was devised to classify diagrams into four categories: classic, probable, possible, or unlikely carpal tunnel syndrome. Diagram ratings of 63 patients (85 hands) evaluated in a hand clinic were compared with diagnoses established independent of diagram results by objective clinical criteria. The sensitivity of diagrams rated classic or probable was 80% and specificity was 90%. We conclude that the hand diagram is valuable in the diagnosis of carpal tunnel syndrome among patients with upper extremity paresthesias.

Treatment of tenosynovitis in rheumatoid arthritis.

Tenosynovitis in the hand of a patient with rheumatoid arthritis will occur in common sites. If the tenosynovitis cannot be controlled by nonsurgical means, there are surgical approaches to the disease. Tenosynovectomy can give successful, long-term relief from the synovitis, and can also prevent tendon ruptures.

Treatment of traumatic arthritis in children.

Although alternatives do exist for the treatment of traumatic arthritis in children, all efforts should be directed to treat the initial condition to avoid its progression to arthritis. Once arthritis is established, then follow the axiom, "treat patients, not x-rays." If despite all attempts at conservative treatment, a surgical option is necessary, then attention must be given to potential future growth, joint stability, and alignment, pain relief, and anticipated postoperative range of motion. All cases must be individualized because, unfortunately, none of the alternatives available is capable of guaranteeing a "normal" end result.

Removable thermocouple probe microvascular patency monitor: an experimental and clinical study.

Based upon experimental animal evaluation and a preliminary clinical experience in 18 patients with 3 recognized failing flaps, the implantable thermocouple probe microvascular method of vessel patency assessment would appear to be a promising new technique worthy of further clinical investigation.

Extremity replantation.

Replantation surgery has progressed in 20 years from a laboratory curiosity to a common and useful clinical procedure. All patients with partial or complete amputations should be considered for replantation of the part. However, only a number of these patients are appropriate for replantation. The indications for replantation should not be based only on the potential viability of the limb, but, more important, should be based on the potential function of the replanted part. The function is related to the level of the amputation, to the mechanism of the amputation, and to the age and motivation of the patient. Replantation surgery requires technical competence and clinical acumen. Surgeons performing replantations should maintain their microvascular technique in laboratory work and elective microsurgical procedures. Because the operations are quite arduous and require teams of surgeons relieving each other and because assessment of the appropriateness of replantation requires considerable clinical experience, replantation operations are best performed by teams in large medical centers.

Breaking force of the rabbit growth plate and its application to epiphyseal distraction.

The in vitro breaking forces of the distal femoral growth plates of young rabbits were measured as a background to the design of a bone lengthening method, using epiphyseal distraction. The mean breaking force in 16 femora was 12.98 +/- 3.48 kg and the mean strain was 0.91 +/- 0.33 mm. The mean stress in 10 femora was 14.51 +/- 3.88 kg/cm2. The procedure was repeated, after applying a 1.0 kg dead weight to 6 femora for 24 hours and the breaking force was then 15.01 +/- 4.70 kg, with a mean strain of 0.85 +/- 0.62 mm. A further 8 rabbits then underwent epiphyseal distraction for 2 days in vivo, with 1 or 2 kg forces delivered to two parallel K wires by a pair of spring devices, whereupon the femora were removed and tested as before. The breaking force on the distracted side was now only 8.91 +/- 3.71 kg, compared with 13.99 +/- 3.40 kg on the control side. Although not fractured, these plates had obviously been weakened. The clinical implication of this is discussed.

A tissue-culture model of cartilage breakdown in rheumatoid arthritis. Quantitative aspects of proteoglycan release.

1. The destruction of articular cartilage in human rheumatoid and other arthritides is the result of diverse mechanical, inflammatory and local cellular factors. A tissue-culture model for studying cartilage-synovial interactions that may be involved in the final common pathway of joint destruction is described. 2. Matrix breakdown was studied in vitro by using bovine nasal-cartilage discs cultivated in contact with synovium. Synovia were obtained from human and animal sources. Human tissue came from patients with ;classical' rheumatoid arthritis, and animal tissue from rabbits with antigen-induced arthritis. 3. Cartilage discs increased their proteoglycan content 2-3-fold during 8 days in culture. Proteoglycan was also released into culture medium, approx. 70% arising from cartilage breakdown. 4. Synovial explants from human rheumatoid and rabbit antigen-induced arthritis produced equivalent stimulation of proteoglycan release. After an initial lag phase, the breakdown rate rose abruptly to a maximum, resulting in a 2-fold increase of proteoglycan accumulation in culture medium after 8-10 days. 5. High-molecular-weight products shed into culture media were characterized chromatographically and by differential enzymic digestion. Proteoglycan-chondroitin sulphate accounted for 90% of the released polyanion, and its partial degradation in the presence of synovial explants was consistent with limited proteolytic cleavage. 6. Rheumatoid synovium applied to dead cartilage increased the basal rate of proteoglycan release. Living cartilage was capable of more extensive autolysis, even in the absence of synovium. However, optimal proteoglycan release required the interaction of living synovium with live cartilage. These findings support the view that a significant component of cartilage breakdown may be chondrocyte-mediated.

Temperature monitoring in digital replantation.

Postoperative monitoring of replanted and revascularized digits with skin temperature probes was performed on the 20 patients admitted to the Duke University Medical Center Orthopaedic Replantation Service from April to July, 1977. Using multiple probes, temperatures were recorded for the replanted digit, a control digit on the same hand, and the dressing which represented the ambient temperature. In addition, the following simultaneous clinical inspections were performed on the digits: capillary refill, skin color, turgor, audibility of arterial Doppler tones, and amplitude of pulp pressure tracing. Temperatures of the replanted digits were in the range of 26.0 degrees to 35.0 degrees C. Control temperatures remained relatively stable, in the range of 33.0 degrees to 35.0 degrees C. From the authors' experience the patterns of temperature change which signaled changes in perfusion of the replanted digit and possible poor prognosis were (1) the temperature of the replanted digit dropping more than 2.5 degrees C while the control temperature stayed constant; (2) the temperature of the replanted digit dropping below 30.0 degrees C for longer than 1 hour; and (3) the control temperature dropping below 30.0 degrees C with no correctable cause found.