Interface pressure, perceptual, and mean arterial pressure responses to different blood flow restriction systems.

This study examined the cuff to limb interface pressure during blood flow restriction (BFR), and the perceptual and mean arterial pressure responses, in different BFR systems. Eighteen participants attended three experimental sessions in a randomised, crossover, counterbalanced design. Participants underwent inflations at 40% and 80% limb occlusive pressure (LOP) at rest and completed 4 sets of unilateral leg press exercise at 30% of one repetition maximum with BFR at 80% LOP. Different BFR systems were used each session: an automatic rapid-inflation (RI), automatic personalized tourniquet (PT) and manual handheld pump and sphygmomanometer (HS) system. Interface pressure was measured using a universal interface device with pressure sensors. Perceived exertion and pain were measured after each set, mean arterial pressure (MAP) was measured pre-, 1-minute post- and 5-minutes post-exercise. Interface pressure was lower than the set pressure in all BFR systems at rest (P < .05). Interface pressure was, on average, 10 ± 8 and 48 ± 36 mm Hg higher than the set pressure in the RI and HS system (P < .01), with no differences observed in the PT system (P > .05), during exercise. Pain and exertion were greater in sets 3 and 4 in the RI and HS system compared to the PT system (P < .05). MAP was higher in the RI and HS system compared to the PT system at 1-minute and 5-minutes post-exercise (P < .05). BFR systems applying higher pressures amplify mean arterial pressure and perceptual responses. Automatic BFR systems appear to regulate pressure effectively within an acceptable range during BFR exercise.

The influence of pain, kinesiophobia and psychological comorbidities on the accuracy of rating of perceived exertion in UK military spinal rehabilitation.

INTRODUCTION: Chronic low back pain (CLBP) is a leading cause of disability in the UK Military. Pain and psychological comorbidities have been reported to influence the rating of perceived exertion (RPE). Exercise rehabilitation can be monitored using RPE; however, the accuracy of RPE in inpatient CLBP rehabilitation is unknown. METHODS: A prospective cohort correlation study of 40 UK Military inpatients with CLBP was completed. Disability (ODI), kinesiophobia (TSK), anxiety (GAD-7) and depression (PHQ-9) were subjectively reported at the beginning and end of a 3 week intervention. Pain (VAS) and HR were recorded in the first aerobic exercise (AE) session (T1) and the final aerobic exercise session (T2). RPE was reported for each AE session. RESULTS: At T1, a positive correlation was observed between RPE accuracy (-7.2±20.9), and pre-exercise pain (2.7 mm ±1.6 mm) (p>0.001) and ODI (31.0±16.9) (p>0.05), and a negative relationship between RPE accuracy and average HR (135 bpm ±22 bpm) (p>0.001) was observed. At T2, there was no significant correlation between RPE accuracy (-4.4±22.6) and pre-exercise pain (2.8 mm ±1.6 mm) or ODI (34.0±16.5) (p>0.05). The strong negative relationship between RPE accuracy and average HR (137 bpm ±20 bpm) remained at T2. Improved RPE accuracy over the 3-week rehabilitation programme was correlated to the change in average HR (r=-0.314, p<0.05). CONCLUSIONS: Comorbidities may negatively affect RPE accuracy in CLBP, but the magnitude of the influence reduces over intensive rehabilitation.

Does the serum peptidome reveal hemostatic dysregulation?

There is a significant need for markers that are diagnostic of disease, particularly cancer. For these biomarkers to be useful they would need to be able to detect disease early in its progression with high sensitivity and specificity. Many approaches are being undertaken to attempt to find such biomarkers using the tools of systems biology, i.e., parallel measurement techniques including proteomics (parallel protein measurements). Often the premise behind such an approach was to cast a wide net and then design an assay for specific elements that were found to be diagnostic. One such approach has utilized matrix-assisted laser desorption/ionization-mass spectrometry to interrogate the low-molecular-weight component of serum (the fluid component of blood following clotting), the serum peptidome. This approach has the appealing characteristic of speed of analysis but has a number of shortcomings mostly due to signal:noise and mass resolution in some instruments, making peak analysis difficult. Of course, experimental design and statistical analysis have to be conducted with the system limitations in mind. These points have been addressed by others, but few have focused on a potentially larger issue with serum peptidome analysis - are the signals being measured informing us about the disease state directly or indirectly through measurement of another physiological process such as hemostatic dysregulation? This article will present evidence that points to careful measures of the serum peptidome revealing differences in clotting time in disease states and not direct measures of tumor proteolytic activity on blood proteins.

Identification and characterization of proSAAS, a granin-like neuroendocrine peptide precursor that inhibits prohormone processing.

Five novel peptides were identified in the brains of mice lacking active carboxypeptidase E, a neuropeptide-processing enzyme. These peptides are produced from a single precursor, termed proSAAS, which is present in human, mouse, and rat. ProSAAS mRNA is expressed primarily in brain and other neuroendocrine tissues (pituitary, adrenal, pancreas); within brain, the mRNA is broadly distributed among neurons. When expressed in AtT-20 cells, proSAAS is secreted via the regulated pathway and is also processed at paired-basic cleavage sites into smaller peptides. Overexpression of proSAAS in the AtT-20 cells substantially reduces the rate of processing of the endogenous prohormone proopiomelanocortin. Purified proSAAS inhibits prohormone convertase 1 activity with an IC(50) of 590 nM but does not inhibit prohormone convertase 2. Taken together, proSAAS may represent an endogenous inhibitor of prohormone convertase 1.

On the complexities of ceramide changes in cells undergoing apoptosis: lack of evidence for a second messenger function in apoptotic induction.

The generation of cellular ceramides as a second messenger has been implicated as a regulatory and required step for the induction of apoptosis. In this study, we have applied a recently developed mass spectrometric technique to the determination of changes in physiological ceramide levels during apoptosis induced by tumor necrosis factor plus cycloheximide in U937 cells and the chemical agents anisomycin or geranylgeraniol in HL-60 cells. The mass spectrometric method has significant advantages over traditional methods for ceramide quantitation in that it determines the relative abundance of all ceramide species present in complex biological lipid mixtures individually and simultaneously. We quantitiated ceramides ranging from C14 to C26, finding that their basal levels and relative distribution varied significantly, both within and between different cell types. However, we were not able to detect any significant changes in either total ceramide content or species distribution until 1 h or more post-stimulation with any of these treatments, by which time the cells were in an advanced stage of apoptosis. Differences were also seen between all three treatments in the ceramide species distribution observed in these late stages of apoptosis. These data indicate that in vivo ceramide generation occurs as a consequence of apoptosis rather than as an essential second messenger involved in its induction. They also pose new questions about the potential roles that certain ceramide species may play in the late stages of apoptosis, and demonstrate a clear need to utilize the resolving power of mass spectrometry-based assays in any future investigations into the biological function of ceramides.

Mass spectrometric identification of proteins released from mitochondria undergoing permeability transition.

Mitochondrial membrane permeabilization is a rate-limiting step of cell death. This process is, at least in part, mediated by opening of the permeability transition pore complex (PTPC) Several soluble proteins from the mitochondrial intermembrane space and matrix are involved in the activation of catabolic hydrolases including caspases and nucleases. We therefore investigated the composition of a mixture of proteins released from purified mitochondria upon PTPC opening. This mixture was subjected to a novel proteomics/mass spectrometric approach designed to identify a maximum of peptides. Peptides from a total of 79 known proteins or genes were identified. In addition, 21 matches with expressed sequence tags (EST) were obtained. Among the known proteins, several may have indirect or direct pro-apoptotic properties. Thus endozepine, a ligand of the peripheral benzodiazepin receptor (whose occupation may facilitate mitochondrial membrane permeabilization), was found among the released proteins. Several proteins involved in protein import were also released, namely the so-called X-linked deafness dystonia protein (DDP) and the glucose regulated protein 75 (grb75), meaning that protein import may become irreversibly disrupted in mitochondria of apoptotic cells. In addition, a number of catabolic enzymes are detected: arginase 1 (which degrades arginine), sulfite oxidase (which degrades sulfur amino acids), and epoxide hydrolase. Although the functional impact of each of these proteins on apoptosis remains elusive, the present data bank of mitochondrial proteins released upon PTPC opening should help further elucidation of the death process.

Proteomics: the industrialization of protein chemistry.

Establishing a proteomics platform in the industrial setting initially required implementation of a series of robotic systems to allow a high-throughput approach to analysis and identification of differences observed on 2-D electrophoresis gels. Now, a simpler alternative approach employing chromatography-based systems is emerging for identification of many components of complex mixtures, which can also provide quantitative comparisons through the use of a new labeling methodology.

The detection of loose bodies in the elbow: the value of MRI and CT arthrography.

Our aim was to determine the clinical value of MRI and CT arthrography in predicting the presence of loose bodies in the elbow. A series of 26 patients with mechanical symptoms in the elbow had plain radiography, MRI and CT arthrography, followed by routine arthroscopy of the elbow. The location and number of loose bodies determined by MRI and CT arthrography were recorded. Pre-operative plain radiography, MRI and CT arthrography were compared with arthroscopy. Both MRI and CT arthrography had excellent sensitivity (92% to 100%) but low to moderate specificity (15% to 77%) in identifying posteriorly-based loose bodies. Neither MRI nor CT arthrography was consistently sensitive (46% to 91%) or specific (13% to 73%) in predicting the presence or absence of loose bodies anteriorly. The overall sensitivity for the detection of loose bodies in either compartment was 88% to 100% and the specificity 20% to 70%. Pre-operative radiography had a similar sensitivity and specificity of 84% and 71%, respectively. Our results suggest that neither CT arthrography nor MRI is reliable or accurate enough to be any more effective than plain radiography alone in patients presenting with mechanical symptoms in the elbow.

Urinary excretion of 6 beta-hydroxycortisol as an in vivo marker for CYP3A induction: applications and recommendations.

OBJECTIVE: To evaluate the usefulness of 6 beta-hydroxycortisol as a screen for CYP3A induction in early-phase drug development. METHODS: Five groups of 12 healthy elderly men were randomized to one of five treatment regimens: (1) 600 mg rifampin (INN, rifampicin) once daily, (2) placebo once daily, (3) 40 mg SB 216469 twice a day, (4) 60 mg SB 216469 twice a day, or (5) 40 mg SB 216469 three times a day. All medications were taken orally and administered for 7 consecutive days. Urine was collected over a 24-hour period for each subject before administration and on the last day of administration for each respective regimen for measurement of 6 beta-hydroxycortisol and 17-hydroxycorticosteroid concentrations. RESULTS: Subjects in the rifampin group had a significant increase from predose value in the 24-hour urinary excretion of 6 beta-hydroxycortisol and the ratio of 6 beta-hydroxycortisol to 17-hydroxycorticosteroid. All 12 subjects in the rifampin group had increases in 6 beta-hydroxycortisol excretion, whereas 11 of 12 had an increase in the ratio. The placebo and three active treatment groups did not show significant changes in either parameter. CONCLUSIONS: Urinary excretion of 6 beta-hydroxycortisol may be useful as a screening tool in early-phase development to assess the potential for an investigational drug to induce CYP3A.

Triple "E" syndrome: bilateral locked posterior fracture dislocation of the shoulders.

Bilateral locked posterior fracture dislocation of the shoulders is one of the least common injuries of the shoulder, and this injury has been suggested to be pathognomonic of seizures when diagnosed in the absence of trauma. The authors present a case of idiopathic bilateral locked posterior fracture dislocations of the shoulder, along with a review of the medical literature. The authors also present the "triple E syndrome," describing the possible etiologies of this injury: epilepsy (or any convulsive seizure), electrocution, or extreme trauma.

The pathology of Yersinia enterocolitica ileocolitis.

The terminal ileum and proximal colon were resected in two children presenting with fever and right lower quadrant abdominal pain. The pathological findings were characteristic; elongated ulcerations with underlying lymphoid hyperplasia involved the distal ileum and smaller punctate aphthoid ulcers involved the distal ileum and colon. Transmural inflammation was seen in both cases and resulted in thickened, erythematous distal ileum mistaken at surgery for Crohn's disease. Yersinia enterocolitica was recovered from operative cultures of both the specimens. One of the two patients had a 1:1280 serological titer for Yersinia enterocolitica 1 week after surgery. The pathologic findings of Yersinia enterocolitica ileocolitis are distinctive and easily differentiated from Crohn's disease and other pathologic processes in this region. Operative diagnosis can be difficult but if the possibility of Yersinia infection is considered, the correct diagnosis can usually be made without unnecessary surgical resection.

Evaluation of storage phosphor imaging for quantitative analysis of 2-D gels using the Quest II system.

The advent of storage phosphor technology has been of considerable benefit to the imaging of gel-separated radiolabeled proteins due to the rapid and quantitative nature of the data acquisition process. Previously, times over one month were required to obtain fluorographs of the same gel to yield data of sufficient dynamic range for quantitative analysis of high-resolution two-dimensional (2-D) gels. As we are in the process of building a human 2-D gel protein database, and therefore have a high throughput of 2-D gels both to image and quantitate using the Quest II software, we undertook an evaluation of a storage phosphor imager, including an evaluation of signal fade. The results of this evaluation demonstrate the feasibility of using such a system, and we describe the procedures that allow us to use this technique for quantitative analysis of many complex 2-D gel patterns. These procedures include a useful batch printing program that allows printing of many images in a non-interactive mode. Examples will be presented of how autoradiography, using storage phosphor plates and the Quest II system, have enabled us to begin building a human 2-D gel protein database including posttranslational modification information, without the previous time constraints associated with such a project.

Population and individual bioequivalence: lessons from real data and simulation studies.

The Food and Drug Administration (FDA) has proposed replacing the 1992 average bioequivalence (ABE) with population and individual bioequivalence (PBE & IBE), as outlined in the preliminary draft guidance of December 1997, which was subsequently replaced by the draft guidances of August 1999 and resolved in the final guidance of October 2000. This has led to considerable public debate among regulatory, academic, and industry experts at numerous conferences (e.g., FDA/AAPS March 1998, FDA/AAPS August-September 1999, FDA Pharmaceutical Sciences Advisory Committee September 1999) and in the literature. The final guidance calls for ABE to remain as the primary criterion by which new formulations may be judged ready for access to the marketplace. In addition, the FDA recommends the use of replicate study designs for the specific drug classes of controlled-release formulations and highly variable drugs. The final guidance also alludes to the possibility of a sponsor requesting alternative criteria such as PBE and IBE following consultation with the FDA. This procedure amounts to a data collection period during which data suitable to evaluate the operating characteristics of PBE and IBE would be generated, analyzed, and discussed among interested parties. A comprehensive review of currently available databases is useful in determining the ultimate value of this data collection period. This report provides an update to the previous publication by the authors. In all, 28 data sets from 20 replicate cross-over bioequivalence studies have been analyzed (n = 12-96) using the statistical methodology in the most recent FDA draft guidance. The results are presented below. ABE Pass: ABE Fail: Total: AUC/Cmax AUC/Cmax AUC/Cmax AUC/Cmax Pass PBE & IBE 20/14 1/3 21/17 Pass IBE only 1/0 0/0 1/0 Fail PBE and IBE 0/2 0/1 0/3 Fail IBE only 2/3 4/5 6/8 Total 23/19 5/9 28/28 Review of the database reveals many interesting features, most notably the lack of consistent results within a given data set across all three criteria. The sensitivity of subject-by-formulation interaction to sample size and inherent variability of the compounds is further explored through simulation studies. It is concluded that additional simulation assessments must be considered when evaluating the value of a data collection period for PBE and IBE assessment. It will be shown that definitive conclusions regarding some of the operating characteristics of PBE and IBE can be achieved through a combination of data-driven hypotheses followed by simulation studies to further evaluate the hypotheses. Some recommendations for further data collection will be made.

Lack of effect of rosiglitazone on the pharmacokinetics of oral contraceptives in healthy female volunteers.

The effect of rosiglitazone (Avandia [BRL 49653C]) on the pharmacokinetics of ethinylestradiol and norethindrone was evaluated after repeat dosing of rosiglitazone with an oral contraceptive (OC; Ortho-Novum 1/35 containing norethindrone 1 mg and ethinylestradiol 0.035 mg) in a randomized, double-blind, placebo-controlled crossover study. Thirty-four healthy female volunteers received oral rosiglitazone (RSG) 8 mg + OC or matched placebo (P) + OC daily on days 1 to 14 of a 28-day OC dosing cycle; the alternate regimen was administered during a second cycle. Ethinylestradiol and norethindrone pharmacokinetics were determined from plasma concentrations on day 14. Lack of pharmacokinetic effect was prospectively defined as 90% CI for the point estimate (PE) of the ratio (RSG + OC):(P + OC) contained within a 20% equivalence range for both ethinylestradiol and norethindrone (analyzed by ANOVA). For RSG + OC and P + OC, respectively, mean ethinylestradiol AUC(0-24) was 1126 and 1208 pg.h/mL (PE: 0.92; 90% CI: 0.88-0.97), and mean norethindrone AUC(0-24) was 178 and 171 ng.h/mL (PE: 1.04; 90% CI: 1.00-1.07). Thus, rosiglitazone had no significant effects on the pharmacokinetics of ethinylestradiol or norethindrone. Coadministration of rosiglitazone with OCs does not induce metabolism of these synthetic sex steroids and is not expected to impair the efficacy of OCs or hormone replacement therapy.

PhRMA perspective on population and individual bioequivalence.

The Food and Drug Administration (FDA) issued a second-draft guidance in August 1999 on the subject of in vivo bioequivalence, which is based on the concepts of individual and population bioequivalence (IBE and PBE, respectively). The intention of this guidance is to replace the 1992 guidance that requires that in vivo bioequivalence be demonstrated by average bioequivalence (ABE). Although the concepts of population and individual bioequivalence are intuitively reasonable, a detailed review of the literature has not uncovered clinical evidence to justify the additional burden to the innovator and generic companies as well as the consumer that the new guidelines would impose. The criteria for bioequivalence described in the draft guidance employ aggregate statistics that combine information about differences in bioavailability between formulation means and differences in bioavailability variation of formulations between and within subjects. The purely technical aspects of the statistical approach are reasonably sound. However, PhRMA believes that important operational issues remain that need to be resolved before any changes to current practice are implemented. PhRMA believes that the ideals of prescribability and switchability are intuitively reasonable, but it is uncertain of the extent to which the proposed guidance can achieve these goals. It is not clear whether the attainment of such goals is necessary in the evaluation of bioequivalence given the role this plays in drug development, and the lack of clinical evidence argues against a pressing need to change current practice. PhRMA is concerned that the trade-off offered by the aggregate criteria may ultimately represent more harm than good to the public interest. PhRMA recommends more rigorous evaluation of methods based on two-way crossover designs before moving to methods that require more complex designs. One such method is identified herein and contains procedures for estimating prescribability and switchability. The possibility of a phase-in or trial period to collect replicate crossover data to further evaluate IBE and PBE and possibly allow market access based on these criteria as they are being evaluated has been proposed. PhRMA believes this is unprecedented and will offer little additional information beyond that which can be obtained by simulation or has already been collected by the FDA. Simulation studies have the advantage of allowing evaluation of the sensitivity of various procedures to represent the data patterns as created within the simulation. Operating characteristics by which proposed criteria can be adequately judged have not yet been defined. The limitations of ABE for highly variable drugs and narrow therapeutic drugs are well appreciated and may be addressed by means other than a wholesale change in the current criteria.

Cutaneous T-cell lymphoma. Evaluation of pretreatment skin biopsy specimens by a panel of pathologists.

BACKGROUND AND DESIGN: Cutaneous T-cell lymphoma (CTCL) frequently presents a difficult diagnostic challenge for the clinician and pathologist. To assess the diagnostic validity of conventional histopathologic findings in CTCL, pretreatment skin biopsy specimens were scored prospectively and independently by a panel of five to seven dermatopathologists and pathologists. Scores were compared with disease outcome. Repeatability of these scores was examined among observers and for the same observer. The study population consisted of 165 subjects, initially referred for suspected mycosis fungoides or Sézary syndrome. Ninety-two patients determined to have CTCL have been followed up for 6.3 +/- 3.5 years (mean +/- SD) and are categorized according to disease outcome: 22 are in complete remission, 35 are in partial remission, three have progressive lymphoma, 15 died of disease, 13 died of other causes, and four were unavailable for follow-up. Seventy-three patients determined not to have CTCL have been followed up for 5.3 +/- 3.2 years without subsequent clinicopathologic evidence of CTCL. These longitudinal data allowed comparisons of the clinical course with the original histologic interpretations. RESULTS: Data showed that the histologic scores rendered by the pathology panel did not correlate with stage of disease and were not an accurate predictor of clinical outcome, because the histologic ratings did not discriminate between patients who eventually had complete remission and those with either progressive lymphoma or who have died of disease. The results also substantiate the low inherent reliability of histopathologic findings in CTCL. Large differences existed among pathologists in scoring the study populations and repeated reading of selected cases by the same panel member resulted in a change of diagnosis 15% of the time. Among the histologic features evaluated, only the presence of mitoses in the infiltrating cells showed a trend toward an unfavorable outcome. CONCLUSION: Pathologic diagnosis in the CTCL disease spectrum should be interpreted with caution and then only in conjunction with the clinical evaluation. As expected, the use of an average value from a panel of readers added a component of stability to the histologic interpretation.

Ligamentous stabilizers against posterolateral rotatory instability of the elbow.

BACKGROUND: The lateral ulnar collateral ligament, the entire lateral collateral ligament complex, and the overlying extensor muscles have all been suggested as key stabilizers against posterolateral rotatory instability of the elbow. The purpose of this investigation was to determine whether either an intact radial collateral ligament alone or an intact lateral ulnar collateral ligament alone is sufficient to prevent posterolateral rotatory instability when the annular ligament is intact. METHODS: Sequential sectioning of the radial collateral and lateral ulnar collateral ligaments was performed in twelve fresh-frozen cadaveric upper extremities. At each stage of the sectioning protocol, a pivot shift test was performed with the arm in a vertical position. Passive elbow flexion was performed with the forearm maintained in either pronation or supination and the arm in the varus and valgus gravity-loaded orientations. An electromagnetic tracking device was used to quantify the internal-external rotation and varus-valgus angulation of the ulna with respect to the humerus. RESULTS: Compared with the intact elbow, no differences in the magnitude of internal-external rotation or maximum varus-valgus laxity of the ulna were detected with only the radial collateral or lateral ulnar collateral ligament intact (p > 0.05). However, once the entire lateral collateral ligament was transected, significant increases in internal-external rotation (p = 0.0007) and maximum varus-valgus laxity (p < 0.0001) were measured. None of the pivot shift tests had a clinically positive result until the entire lateral collateral ligament was sectioned. CONCLUSIONS: This study suggests that, when the annular ligament is intact, either the radial collateral ligament or the lateral ulnar collateral ligament can be transected without inducing posterolateral rotatory instability of the elbow.

Arthroplasty with a metal radial head for unreconstructible fractures of the radial head.

BACKGROUND: Treatment of unreconstructible comminuted fractures of the radial head remains controversial. There is limited information on the outcome of management of these injuries with arthroplasty with a metal radial head implant. METHODS: The functional outcomes of arthroplasties with a metal radial head implant for the treatment of twenty-five displaced, unreconstructible fractures of the radial head in twenty-four consecutive patients (mean age, fifty-four years) were evaluated at a mean of thirty-nine months (minimum, two years). There were ten Mason type-III and fifteen Mason-Johnston type-IV injuries. Two of these injuries were isolated, and twenty-three were associated with other elbow fractures and/or ligamentous injuries. RESULTS: At the time of follow-up, Short Form-36 (SF-36) summary scores suggested that overall health-related quality of life was within the normal range (physical component = 47 +/- 10, and mental component = 49 +/- 13). Other outcome scales indicated mild disability of the upper extremity (Disabilities of the Arm, Shoulder and Hand score = 17 +/- 19), wrist (Patient-Rated Wrist Evaluation score = 17 +/- 21 and Wrist Outcome Score = 60 +/- 10), and elbow (Mayo Elbow Performance Index = 80 +/- 16). According to the Mayo Elbow Performance Index, three results were graded as poor; five, as fair; and seventeen, as good or excellent. The poor and fair outcomes were associated with concomitant injury in two patients, a history of a psychiatric disorder in three, comorbidity in two, a Workers' Compensation claim in two, and litigation in one. Subjective patient satisfaction averaged 9.2 on a scale of 1 to 10. Elbow flexion of the injured extremity averaged 140 degrees +/- 9 degrees; extension, -8 degrees +/- 7 degrees; pronation, 78 degrees +/- 9 degrees; and supination, 68 degrees +/- 10 degrees. A significant loss of elbow flexion and extension and of forearm supination occurred in the affected extremity, which also had significantly less strength of isometric forearm pronation (17%) and supination (18%) as well as significantly less grip strength (p < 0.05). Asymptomatic bone lucencies surrounded the stem of the implant in seventeen of the twenty-five elbows. Valgus stability was restored, and proximal radial migration did not occur. Complications, all of which resolved, included one complex regional pain syndrome, one ulnar neuropathy, one posterior interosseous nerve palsy, one episode of elbow stiffness, and one wound infection. CONCLUSIONS: Patients treated with a metal radial head implant for a severely comminuted radial head fracture will have mild-to-moderate impairment of the physical capability of the elbow and wrist. At the time of short-term follow-up, arthroplasty with a metal radial head implant was found to have been a safe and effective treatment option for patients with an unreconstructible radial head fracture; however, long-term follow-up is still needed.

Functional outcome of semiconstrained total elbow arthroplasty.

BACKGROUND: The objective of the present study was to review the results of primary total elbow arthroplasty with use of the Coonrad-Morrey prosthesis. Two hypotheses were tested: (1) the results in patients with inflammatory arthritis would be superior to those in patients with a traumatic or posttraumatic condition, and (2) the isometric extensor torque after total elbow arthroplasty would be significantly less than that of the contralateral elbow. METHODS: Forty-seven consecutive patients (fifty-one elbows) had the operation performed by one of three surgeons between November 1, 1989, and June 30, 1996. Thirty-six surviving patients (thirty-nine elbows) were available for follow-up. The mean duration (and standard deviation) of follow-up was 50 +/- 11 months (range, twenty-four to ninety-seven months). The mean age at the time of the operation was 64 +/- 11 years (range, twenty-seven to eighty-seven years). Eighteen patients (twenty-one elbows) had inflammatory arthritis. Eighteen patients (eighteen elbows) had an acute fracture or posttraumatic condition (posttraumatic osteoarthritis in eight, an acute fracture of the humerus in seven, nonunion of the distal aspect of the humerus in two, and primary osteoarthritis in one). The patients were evaluated with use of questionnaires (the Mayo elbow performance index, the Short Form-36 [SF-36], and the Disabilities of the Arm, Shoulder and Hand [DASH] Questionnaire); clinical examination by an orthopaedic surgeon who was not involved with the pre-operative, operative, postoperative, or follow-up care; radiographs; and elbow strength-testing with an isokinetic dynamometer. RESULTS: The mean score (and standard deviation) on the Mayo elbow performance index for the group that had inflammatory arthritis (90 +/- 11 points) was significantly higher than that for the group with a traumatic or posttraumatic condition (78 +/- 18 points) at the time of the latest follow-up (p < 0.05). In both groups, the mean extensor torque of the involved elbow was significantly less than that of the contralateral elbow (p < 0.05). No significant difference between the groups was found with respect to the flexion-extension arc of motion. Ten elbows (26 percent) had ulnar nerve dysfunction (a transient deficit in six and a permanent deficit in four); nine (23 percent), an intraoperative fracture (of the humeral diaphysis in four, of the ulnar diaphysis in four, and of the olecranon in one); three (8 percent), a periprosthetic infection; three, a triceps disruption; and one (3 percent), a revision because of a fracture of the ulnar component. There were no other revisions. Of the thirty-four elbows with complete radiographic follow-up, twenty-three had no change in the bone-cement interface. Progressive radiolucency was noted around the ulnar prosthesis in eight elbows, around the humeral prosthesis in one elbow, and around both components in two elbows. CONCLUSIONS: Patients who had a total elbow arthroplasty with use of a semiconstrained Coonrad-Morrey prosthesis were generally satisfied; the mean level of patient satisfaction was 9.2 of a possible 10 points for those who had inflammatory arthritis and 8.6 points for those who had a fracture or posttraumatic condition. The rates of complications involving the ulnar nerve, intraoperative fracture, triceps disruption, deep infection, and periprosthetic radiolucency are of concern.

Distal biceps brachii tendon repair. An in vitro biomechanical study of tendon reattachment.

Clinical reports suggest that suture anchors can simplify repair of distal biceps tendon avulsions. In this study, fixation strengths of Mitek and Statak suture anchors were compared with strength of reattachment using transosseous suture tunnels in eight cadaveric radii. Cyclic loading and load-to-failure testing were performed: No specimen failed during testing to 50 N for 3600 cycles: however, four of the Mitek anchors and one of the Statak anchors protruded out of the medullary canal. The mean load to failure of the Mitek suture anchor complexes was 220 +/- 54 N, that of the Statak suture anchor complexes was 187 +/- 64 N, and that of the transosseous sutures was 307 +/- 142 N. There was no significant difference in the failure load or mechanism of failure between the Statak and Mitek anchors. Transosseous sutures failed at significantly greater loads on static testing than the suture anchors. Cyclic loading results suggest that the bony fixation achieved using these three techniques should be sufficient to allow immediate passive mobilization of the elbow after surgery. Protrusion of the suture anchors out of the tuberosity during cyclic loading is a concern because of potential development of a gap at the repair site and interference with forearm rotation.