Functional outcome of thoracolumbar burst fractures managed with hyperextension casting or bracing and early mobilization.
Explore the source record for details and available documents.
Braces↗
Biomedical subjects
J R Chapman
Publications and source records attributed to J R Chapman.
Diabetic neuropathy after pancreas transplantation: determinants of recovery.
Although simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia and correction of uremia in type I diabetic patients with renal failure, little data are available on long-term outcome and clinical determinants of recovery of peripheral neuropathy. In this prospective study, 219 electrophysiological studies using a standardized protocol were performed before and up to 8 years after SPK in 44 patients. Nine control diabetic recipients with functioning kidney but nonfunctioning pancreas transplants were studied on 35 occasions. Patients were 38.5+/-7.9 years old (mean+/-SD) with pretransplant diabetes present for 25.2+/-7.6 years. Significant polyneuropathy (total nerve conduction scores [NCS] <-1.0) was present in 89% before transplantation, which correlated with body weight (r=0.628, P<0.001). Two distinct patterns of neurological recovery were observed after SPK. Conduction velocity (CV) improved in a biphasic pattern, with a rapid initial recovery followed by subsequent stabilization. In contrast, the recovery of nerve amplitude was monophasic, and continued to improve for up to 8 years. Initial improvement in NCS was primarily due to an increase in CV (P=0.002 vs. baseline), and was best in shorter and younger patients. Recovery of total NCS at 6 months after SPK, assessed by multivariate analysis, was least in obese recipients and when performed in patients who had started dialysis before SPK, and was associated with lower transplant kidney isotopic glomerular filtration rate and HLA mismatch (P<0.05 to 0.001). Subsequent improvement was associated with less severe initial neuropathy, smaller body weight, and longer duration of diabetes (P<0.01 to 0.001). Fasting hyperinsulinemia was associated with impairment of initial recovery and subsequent NCS after SPK, but was worse in the control group. Recovery of nerve action potential amplitudes was predicted by better initial amplitudes and HLA mismatch, lower body weight, and the use of nifedipine (P<0.05 to 0.001). Nifedipine was used for hypertension in 33% of SPK and was associated with better CV and amplitudes, particularly in the upper limbs, where there was less neuropathy. The use of angiotensin-converting enzyme inhibitors also appeared beneficial, but this was confined to the lower limbs. SPK resulted in a gradual, sustained, and late improvement in nerve action potential amplitudes, consistent with axonal regeneration and partial reversal of diabetic neuropathy. These data suggest that early transplantation of uremic diabetic patients before onset of severe neuropathy, minimizing obesity and optimizing renal transplant function, maximizes neurological recovery after SPK. Furthermore, the preliminary data support randomized clinical trials for evaluation of nifedipine and angiotensin-converting enzyme inhibitors in diabetic neuropathy.
Adult↗
The mechanism of cyclosporine toxicity induced by clarithromycin.
AIMS: Recently a number of case reports have described the interaction of clarithromycin with cyclosporine A, resulting in cyclosporine toxicity. This interaction is presumed to take place via the hepatic cytochrome P450 enzyme system. METHODS: Following a case of cyclosporine toxicity and acute renal failure in a transplant patient started on clarithromycin, we investigated the effect of oral clarithromycin on the hepatic P450 system in five healthy normal male volunteers, by means of the erythromycin breath test. RESULTS: Cytochrome P4503A (CYP3A) activity was reduced in all subjects by a mean level of 26% following clarithromycin treatment. This would result in a significant reduction in cyclosporine clearance in patients receiving clarithromycin. CONCLUSIONS: As clarithromycin was shown to inhibit CYP3A activity in all subjects tested, we recommend that a high degree of caution be exercised when clarithromycin is administered to patients receiving cyclosporine therapy or other drugs known to be eliminated by CYP3A-mediated metabolism.
Anti-Bacterial Agents↗
Experimental hyperacute rejection in pancreas allotransplants.
A model of sensitization by intraperitoneal lymph node inoculation was developed to test the hypothesis that hyperacute rejection (HAR) could occur in sensitized recipients of vascularized pancreas allografts. Ten pairs of outbred mongrel dogs that were lymphocytotoxic cross-match assay negative were inoculated with homogenized lymph nodes on either three or four occasions at fortnightly intervals before renal transplantation. A renal allograft from the same donor was used to test the HAR response and to further enhance sensitization by rejection of a vascularized organ. Pancreas transplants were performed 2 weeks later, with biopsies of the graft and blood samples taken at 0, 10, 20, and 30 min and then at 30-min intervals until the grafts were no longer viable. All renal and pancreas grafts were rejected in a classical hyperacute pattern. Within 4 min of revascularization of the pancreas, central lobular hemorrhage and vascular congestion appeared, followed by general edema. Histology demonstrated parallel changes of edema, vascular congestion, necrosis, hemorrhage, and leukocytic infiltrate, which all preceded graft infarction. A sharp decline in both arterial and venous white blood cell count and platelets occurred within 10 min of revascularization with initial sequestration and subsequent release of platelets from the graft (P=0.02). In summary, HAR of the allografted pancreas can be observed by the surgeon within minutes of revascularization, with predictable macroscopic and microscopic changes. This study supports the use of routine lymphocytotoxic cross-match tests for all recipients of pancreas transplants and implies that particular care is warranted in regraft pancreas allograft recipients.
Acute Disease↗
Reversal of cyclosporine malabsorption in diabetic recipients of simultaneous pancreas and kidney transplant using a microemulsion formulation.
In view of the known problems that diabetic recipients have with drug absorption and of the potential advantages of the microemulsion formulation of cyclosporine (Neoral), 17 previously diabetic recipients of simultaneous pancreas and kidney allografts were studied before and after conversion from Sandimmune (SIM) to Neoral (NEO) formulations of cyclosporine a mean of 4.75 +/- 2.0 years after transplantation. The aims of this study were to determine whether there were changes in the absorption profiles using the 2 formulations and to analyze the safety of conversion from SIM to NEO on a 1:1 ratio. Pharmacokinetic, clinical, and renal function parameters were measured 2 weeks before, and 2 and 4 weeks after conversion. Pharmacokinetics demonstrated that, when taking SIM, only 5 patients had "good absorption" (maximal concentration >500 ng/ml and time to maximal concentration < / = 2 hr), but after conversion to NEO, 14 at week +2, and 13 at week +4 were good absorbers (P<0.02 and <0.01, respectively). There was a 50% reduction in the time to maximal blood concentration (from 3.2 +/- 1.9 hr with SIM, to 1.8 +/- 1.3 hr on NEO [P<0.007]) and a 36% increase in trough and a 143% increase (P<0.01) in maximal blood concentrations, although the 9-hr cyclosporine AUC showed an 89% increase (P<0.01). There was an 18% mean reduction in dose per kilogram prescribed 4 weeks after conversion. Renal function, measured by serum creatinine and technecium-99m diethylenetriamine pentaacetic acid glomerular filtration rate, was not altered and no adverse events were attributed to NEO. This study confirmed that previously diabetic recipients of simultaneous renal pancreas allografts had variable and poor absorption of cyclosporine using conventional Sandimmune and that this absorption was improved by conversion to Neoral.
Absorption↗
Clinical determinants of glucose homeostasis after pancreas transplantation.
Although successful simultaneous pancreas and kidney transplantation (SPK) achieves normoglycemia in the majority of diabetic recipients with end-stage renal disease, little is known about the factors that influence long-term endocrine function. In this prospective study of 48 bladder-drained SPK patients, 209 oral glucose tolerance tests were performed between 3 months and 6 years after transplantation. Normal fasting glucose levels and systemic hyperinsulinemia were stable for up to 6 years after SPK. Multivariate analysis revealed that increased area-under-curve (AUC) levels of C-peptide 3 months after transplantation were predicted by short surgical pancreas anastomosis time, greater recipient body weight, and total HLA mismatch score. Episodes of acute pancreas rejection were not associated with reduced allograft insulin output in the long term. Insulin output, stimulated by oral glucose tolerance tests and assessed by the ratio of AUC insulin to AUC glucose, fell gradually after transplantation and was decreased by an elevated serum calcium level and high cyclosporine dose. The ratio of fasting insulin to glucose, which acts as a marker of peripheral insulin resistance, fell with time after transplantation and was increased by greater body weight, higher prednisolone dose, and lower cyclosporine dose. The inhibitory effect of cyclosporine on both fasting and postprandial insulin output was, however, minor when quantified by multivariate analysis. Endocrine function of the transplanted pancreas was not correlated with its exocrine function measured by urinary amylase excretion, nor was there a correlation with change in renal function measured by isotopic glomerular filtration rate. In summary, simultaneous pancreas and kidney transplantation leads to excellent long-term glucose homeostasis maintained at the expense of systemic hyperinsulinemia. The key factors adversely affecting peripheral resistance in SPK were corticosteroid therapy, body weight, and time after transplantation. The susceptibility of islets to ischemia-reperfusion injury, as quantitated by surgical anastomosis time, may have implications for islet transplantation programs, as may the relative resistance of islets to allograft rejection. Glucose homeostasis after SPK, while remaining abnormal, may be used as the standard against which islet transplantation must be measured.
Adult↗
Comparative biomechanical evaluation of different external fixation sidebars: stainless-steel tubes versus carbon fiber rods.
Carbon fiber rods were developed to provide radiolucent sidebars for external fixation. In the present study, a single-plane, half-pin, double-bar external fixator construct with either stainless-steel tubes or carbon fiber rods was applied on the anteromedial surface of an osteotomized synthetic human tibia and evaluated for fixation rigidity. Testing was performed with the bone fragments in cortical contact and with a 5-mm midshaft gap between the fragments. The sidebars then were loaded to failure in bending. The results of this study show (a) that the carbon fiber rods were 15% stiffer than the stainless-steel tubes (p = 0.009) and (b) that the external fixator with carbon fiber rods achieved approximately 85% of the fixation stiffness of the external fixator with stainless-steel tubes. The loss of stiffness of the external fixator with carbon fiber rods is most likely due to the clamps being less effective in connecting the carbon fiber rods rigidly to the Schanz screws.
Biomechanical Phenomena↗
A comparative biomechanical evaluation of a noncontacting plate and currently used devices for tibial fixation.
The appearance of porous bone under fixation plates during fracture healing, attributed to disturbance of blood supply by the plate, has led to new plate designs with reduced plate to bone contact. The fixation stability afforded by these devices, in comparison to implants commonly used for fixation, is not well known. Therefore, the construct stiffnesses of osteotomized synthetic tibiae fixed with dynamic compression plates, external fixators, or two configurations of noncontact plates were compared in axial compression, bending, and torsion with and without cortical contact at the osteotomy site. The results of this study show that (1) the noncontact plated constructs achieve comparable fixation rigidity to constructs using dynamic compression plates or external fixators, if applied at a distance no greater than 5 mm from the surface of the tibia, and (2) the fixation rigidity of the noncontact plate decreases as the distance between plate and bone surface increases.
Biomechanical Phenomena↗
Factors affecting the pullout strength of cancellous bone screws.
Screws placed into cancellous bone in orthopedic surgical applications, such as fixation of fractures of the femoral neck or the lumbar spine, can be subjected to high loads. Screw pullout is a possibility, especially if low density osteoporotic bone is encountered. The overall goal of this study was to determine how screw thread geometry, tapping, and cannulation affect the holding power of screws in cancellous bone and determine whether current designs achieve maximum purchase strength. Twelve types of commercially available cannulated and noncannulated cancellous bone screws were tested for pullout strength in rigid unicellular polyurethane foams of apparent densities and shear strengths within the range reported for human cancellous bone. The experimentally derived pullout strength was compared to a predicted shear failure force of the internal threads formed in the polyurethane foam. Screws embedded in porous materials pullout by shearing the internal threads in the porous material. Experimental pullout force was highly correlated to the predicted shear failure force (slope = 1.05, R2 = 0.947) demonstrating that it is controlled by the major diameter of the screw, the length of engagement of the thread, the shear strength of the material into which the screw is embedded, and a thread shape factor (TSF) which accounts for screw thread depth and pitch. The average TSF for cannulated screws was 17 percent lower than that of noncannulated cancellous screws, and the pullout force was correspondingly less. Increasing the TSF, a result of decreasing thread pitch or increasing thread depth, increases screw purchase strength in porous materials. Tapping was found to reduce pullout force by an average of 8 percent compared with nontapped holes (p = 0.0001). Tapping in porous materials decreases screw pullout strength because the removal of material by the tap enlarges hole volume by an average of 27 percent, in effect decreasing the depth and shear area of the internal threads in the porous material.
Animals↗
Mass spectrometry. Ionization methods and instrumentation.
Explore the source record for details and available documents.
Ions↗
Twin- versus single-bag disconnect systems: infection rates and cost of continuous ambulatory peritoneal dialysis.
Although twin-bag disconnect fluid-transfer systems for continuous ambulatory peritoneal dialysis (CAPD) have a lower rate of catheter-related infection than single-bag systems, their greater monetary purchase cost has prevented universal adoption. Therefore, a single-center randomized study was performed in 63 adult patients to compare the efficiency and total cost of Freeline Solo (FS, twin-bag) and Basic Y (BY, single-bag) systems. Patients were new to CAPD (N = 39), or had a new CAPD catheter, or had had no episodes of peritonitis or exit-site infection in the previous 12 months (N = 24). Total follow-up was 631 patient months (pt.mon), and 53 patients were still on the trial at its termination. Patients rated FS as easier to use than BY (P < 0.001). Peritonitis occurred on 23 occasions in 12 out of 30 patients using BY, and on seven occasions in five of 33 patients using FS. Time to first infection was less with BY than FS (hazard ratio, 2.4; 95% confidence interval (CI), 1.0 to 5.3; P < 0.04). Cumulative incidence of peritonitis was 1 per 14.0 pt.mon with BY and 1 per 46.5 pt.mon with FS (odds ratio, 3.6; 95% CI 1.5 to 8.5; P = 0.004). Length of hospitalization for peritonitis or exit-site infection was 98 days in six patients with BY, versus 17 days in two patients with FS. With BY, four catheters were removed because of infection, but none with FS (P < 0.05). With BY, the total cost of infection was $AUD127,079 ($5033 per pt.yr) versus $19,250 ($704 per pt.yr) with FS, which offset the higher purchase cost of FS. The total cost of CAPD was $AUD956 per pt.yr less with FS than BY. In conclusion, the higher purchase cost of the FS twin-bag system is more than offset by savings from its lower incidence of peritonitis.
Adolescent↗
Posterior instrumentation of the unstable cervicothoracic spine.
Fractures, tumors, and other causes of instability at the cervicothoracic junction pose diagnostic and treatment challenges. The authors report on 23 patients with instability of the cervicothoracic region, which was treated with posterior plate fixation and fusion between the lower cervical and upper thoracic spine. During operation AO reconstruction plates with 8- or 12-mm hole spacing were affixed to the spine using screws in the cervical lateral masses and the thoracic pedicles. Postoperative immobilization consisted of the patient's wearing a simple external brace for 2 months. The following parameters were analyzed during the pre- and postoperative treatment period: neurological status, spine anatomy and reconstruction, and complications. Follow up consisted of clinical and radiographic examinations (mean duration of follow up, 15.4 months; range, 6-41 months). No neurovascular or pulmonary complications arose from surgery. All patients achieved a solid arthrodesis based on flexion-extension radiographs. There was no significant change in angulation during the postoperative period, but one patient had an increase in translation that was not clinically significant. There were no hardware complications that required reoperation. One patient requested hardware removal in hopes of reducing postoperative pain in the cervicothoracic region. One postoperative wound infection required debridement but not hardware removal. The authors conclude that posterior plate fixation is a satisfactory method of treatment of cervicothoracic instability.
Adult↗
MRI in acute knee dislocation. A prospective study of clinical, MRI, and surgical findings.
We treated 17 knees in 15 patients with severe ligament derangement and dislocation by open repair and reconstruction. We assessed the competence of all structures thought to be important for stability by clinical examination, MRI interpretation, and surgery. Our findings showed that in these polytrauma patients clinical examination was not an accurate predictor of the extent or site of soft-tissue injury (53% to 82% correct) due mainly to the limitations of associated injuries. MRI was more accurate (85% to 100% correct) except for a negative result for the lateral collateral ligament and posterolateral capsule. The detail and reliability of MRI are invaluable in the preoperative planning of the surgical repair and reconstruction of dislocated knees.
Acute Disease↗
Conversion from Sandimmune to Neoral in stable renal and pancreas transplant recipients enhances cyclosporine absorption.
Explore the source record for details and available documents.
Administration, Oral↗
Renal dysfunction in acute rejection. Effect of HLA typing, therapy, and histology.
Acute rejection is a frequent cause of early graft dysfunction in renal transplantation, and serum creatinine is the most important measure of clinical response. However, there is little information on serum creatinine during rejection episodes. In this study, the determinants that might influence the clinical response of serum creatinine during acute rejection were evaluated in 96 renal transplant recipients with 100 episodes of biopsy-proven rejection, by univariate and multivariate analysis. The factors assessed for their influence on serum creatinine in acute rejection included: presence and severity of vascular or cellular rejection on biopsy, time taken to institute therapy, HLA mismatch, and the use of OKT3. The presence of vascular rejection on biopsy (n = 28) was a major determinant of impaired reciprocal area under the curve (AUC) of serum creatinine (P < 0.01), and was correlated with HLA-A and -B mismatch (r = 0.21, P < 0.05). Acute rejection associated with HLA-DR mismatch resulted in a more rapid increase of serum creatinine, a higher maximal creatinine, and a greater AUC creatinine (all P < 0.05). Treatment of acute rejection with OKT3 had a beneficial effect on AUC creatinine (P < 0.05) when compared with intravenous corticosteroids, by multivariate analysis. However, vascular rejection and HLA-DR mismatch had no effect on serum creatinine 1 year after transplantation. The biopsy cellular rejection score had no effect on AUC creatinine, although there was a modest effect on gradient of creatinine prior to biopsy. A minor adverse effect of delay in therapy of acute rejection could be demonstrated in the methylprednisolone-treated subgroup. In summary, HLA-DR mismatch and the presence of vascular rejection were the most important predictors of the severity of rejection assessed by the response of serum creatinine to treatment. Appropriate antirejection therapy should be instituted promptly to optimize clinical response during acute rejection.
Adult↗
Predicting glomerular filtration rate after kidney transplantation.
Serum creatinine is an important clinical measure of impairment of glomerular filtration rate (GFR) after kidney transplantation. The use of formulas that predict GFR (such as the Cockcroft-Gault) derived from patients with chronic renal failure and standardized against measured creatinine clearance may not be accurate when applied to kidney transplant recipients. The purpose of this study, was to investigate the level of inaccuracy and its causes and then to derive predictive GFR formulas that are appropriate to renal transplantation. Determinants of isotopic GFR, serum creatinine, and muscle mass were evaluated in consecutive kidney recipients (n = 146) using 99mTc DTPA GFR (n = 751) as a reference method. Factors that predicted GFR apart from serum creatinine included sex, height, body weight, serum urea, years on dialysis, numbers of rejections and infective episodes, and prednisolone dose. The relationship between serum creatinine and GFR was highly variable and dependent on factors that alter muscle mass and muscle catabolic rate. The relationship was further altered by ATN and chronic rejection when tubular secretion of creatinine was reduced. Three alternative GFR formulas (which can be applied to renal transplant patients according to the availability of clinical parameters) were derived and tested against six published methods of GFR estimation. Our derived formulas had the highest correlation, no overall bias, least scatter of sum of squares, and least error at low levels of GFR. They represent a better estimation of GFR in kidney transplantation than published formulas, and would allow a standardized approach to the study of long-term renal dysfunction.
Adult↗
Changing the regimen.
Explore the source record for details and available documents.
Adrenal Cortex Hormones↗
An overview of transplantation in Australia.
Organ donation in Australia has permitted transplantation of the kidneys, heart, lung, pancreas, liver and cornea. Each of these programs has successfully provided life and rehabilitation to Australians with end-stage failure of one or more organs. The programs are supported by an infrastructure of donor coordinators, matching and allocation procedures and national co-operative registries, which record and publish the outcome of each form of transplant. Four national organizations work to promote transplantation: the Transplantation Society of Australia and New Zealand; the Australasian Transplant Coordinators' Association; the Australian Kidney Foundation; and the Australian Co-ordinating Committee for Organ Registries and Donation. Australian donation rates are lower than in many, but not all, comparable developed democracies, however utilization of those donor offers is high, leading to 698 organ transplants being performed in 1993.
Australia↗