Achilles tendon biomechanics in psoriatic arthritis patients with ultrasound proven enthesitis.

OBJECTIVE: To investigate Achilles tendon (AT) biomechanics in psoriatic arthritis (PsA) patients with ultrasound confirmed features of enthesitis. METHOD: PsA patients and healthy control subjects underwent three-dimensional (3D) gait analysis to measure walking speed, rotational joint motion and the moments, power, and AT force at the ankle-subtalar joint complex. The Glasgow Ultrasound Enthesitis Scoring System (GUESS) was used to score the presence of enthesophytes, erosions, retrocalcaneal bursitis, and tendon thickening. Power Doppler ultrasound signal (PDUS) was used to detect active disease. Peripheral joint arthritis, acute-phase reactants, global health, disability, and foot impairments were recorded. A core set of biomechanical variables that influence the insertion of the AT and indirect estimates of tendon loading were compared between PsA patients and control subjects with and without enthesitis. RESULTS: Forty-two PsA patients with a mean disease duration of 10.6 (SD 9.4) years and 29 control subjects were studied. Seventeen (40%) PsA patients had clinically detectable AT entheseal pain. Twenty-eight (67%) PsA patients and nine (31%) control subjects had one or more GUESS enthesitis features, predominantly enthesophytes. PsA patients with enthesitis walked significantly more slowly than control subjects (p = 0.019) and generated lower peak ankle joint moments (p = 0.006), power (p = 0.001), and AT force (p = 0.003). Ankle-subtalar joint complex motion was comparable and no between-group differences were found for peak dorsiflexion (p = 0.59), eversion (p = 0.05), and internal rotation (p = 0.19). CONCLUSIONS: In this group of PsA patients, the AT insertional angle was not influenced by ankle-subtalar joint motion in those with and without enthesitis. Moreover, the PsA patients with enthesitis had significantly lower AT loading.

Biomechanics of the foot in rheumatoid arthritis: identifying abnormal function and the factors associated with localised disease 'impact'.

BACKGROUND: Rheumatoid arthritis is a chronic inflammatory joint disease which affects the joints and soft-tissues of the foot and ankle. The aim of this study was to evaluate biomechanical foot function and determine factors associated with localised disease burden in patients with this disease. METHODS: Seventy-four rheumatoid arthritis patients (mean (standard deviation) age, 56 years (12); median (interquartile range) disease duration, 13 (5,19)) and 54 able-bodied adults (mean (standard deviation) age, 55 years (12)) completed the Leeds foot impact scale. Biomechanical foot function was measured using three-dimensional instrumented gait analysis. Disease activity score, the number of swollen and tender foot joints, and rearfoot and forefoot deformity were recorded. Sequential multiple linear regression was undertaken to identify independent predictors of foot disease burden. FINDINGS: The median (interquartile range) Leeds foot impact scale scores in the impairment and activity/participation subscales were 13 (10,14) and 17 (12,22) for the rheumatoid arthritis and 1 (0,3) and 0 (0,1) for the able-bodied adults, P<0.0001 both subscales. The patients had significantly higher numbers of swollen (P<0.0001) and tender foot joints (P<0.0001) and greater rearfoot (P<0.0001) and forefoot (P<0.0001) deformity. Rheumatoid arthritis patients walked slower (P<0.0001) and had altered biomechanical foot function. Sequential regression analysis revealed that when the effects of global disease activity and disease duration were statistically controlled for, foot pain, the number of swollen foot joints and walking speed, and foot pain and walking speed were able to predict disease burden on the Leeds foot impact scale impairment (P<0.0005) and Leeds foot impact scale activity/participation (P<0.0005) subscales, respectively. INTERPRETATION: In this cohort of rheumatoid arthritis patients, foot pain, swollen foot joint count and walking speed were identified as independent predictors of impairment and activity limitation and participation restriction. The foot disease burden model comprises important elements of pain, inflammatory and functional (biomechanical) factors.

The relationship between passive range of motion and range of motion during gait and plantar pressure measurements.

AIMS: To investigate the relationship between limited joint mobility (LJM; measured both passively and during gait) and plantar pressure measurements. METHODS: A cross-sectional study involving 28 diabetic patients with peripheral neuropathy but no plantar ulceration (DN), 25 diabetic patients with ulceration (DU), 25 diabetic control patients with no ulceration or peripheral neuropathy (DC), and 25 non-diabetic reference subjects (NDR). Movements of the ankle joint complex (AJC) and 1st metatarsophalangeal (MTP) joint were recorded, together with plantar pressures. RESULTS: The passive range of motion at the AJC was significantly reduced in all the diabetes groups, but the gait range of motion was comparable with non-diabetic subjects. At the AJC, no correlation was found between the passive and gait range of motion (ROM) and these were not correlated with plantar pressure variables. At the 1st MTP, a correlation was found between the passive and gait dorsiflexion ROM and a significant correlation existed between gait dorsiflexion ROM at the 1st MTP joint and peak forefoot pressures in the DU group. CONCLUSIONS: Despite a significant reduction in the passive ROM at the AJC in the diabetic groups, the gait ROM was indistinguishable from reference subjects and was not correlated with plantar pressure variables. At the 1st MTP joint, a correlation was found between the passive and gait ROM and furthermore the gait ROM was correlated with peak forefoot pressures, suggesting ROM measures at the 1st MTP joint may be preferable to ROM measures at the AJC.

Debridement of plantar callosities in rheumatoid arthritis: a randomized controlled trial.

OBJECTIVE: To compare forefoot pain, pressure and function before and after normal and sham callus treatment in rheumatoid arthritis (RA). PATIENTS AND METHODS: Thirty-eight RA patients were randomly assigned to normal (NCT group) or sham (SCT) scalpel debridement. The sham procedure comprised blunt-edged scalpel paring of the callus which delivered a physical stimulus but left the hyperkeratotic tissue intact, the procedure being partially obscured from the patient. Forefoot pain was assessed using a 100 mm visual analogue scale (VAS), pressure using a high-resolution foot pressure scanner and function using the spatial-temporal gait parameters measured on an instrumented walkway. Radiographic scores of joint erosion were obtained for metatarsophalangeal (MTP) joints with and without overlying callosities. The trial consisted of a randomized sham-controlled phase evaluating the immediate same-day treatment effect and an unblinded 4-week follow-up phase. RESULTS: During the sham-controlled phase, forefoot pain improved in both groups by only 3 points on a VAS and no statistically significant between-group difference was found (P = 0.48). When data were pooled during the unblinded phase, the improvement in forefoot pain reached a peak after 2 days and gradually lessened over the next 28 days. Following debridement, peak pressures at the callus sites decreased in the NCT group and increased in the SCT group, but there was no statistically significant between-group difference (P = 0.16). The area of and duration of contact of the callus site on the ground remained unchanged following treatment in both groups. Following debridement, walking speed was increased, the stride-length was longer and the double-support time shorter in both groups; however, between-group differences did not reach levels of statistical significance. MTP joints with overlying callus were significantly more eroded than those without (P = 0.02). CONCLUSIONS: Treatment of painful plantar callosities in RA using scalpel debridement lessened forefoot pain but the effect was no greater than sham treatment. Localized pressure or gait function was not significantly improved following treatment.

Remote adenoviral gene delivery to the spinal cord: contralateral delivery and reinjection.

OBJECTIVE: This study characterizes the distribution of adenoviral genes in the spinal cord after viral vector injection into the sciatic nerve. It also evaluates the ability of repeated adenoviral sciatic nerve injections to prolong gene expression in the spinal cord. METHODS: Rat sciatic nerves were unilaterally coinjected with the retrograde tracer Fluoro-Gold (Fluorochrome, Inc., Denver, CO) and the adenoviral vector Ad5RSVntLacZ. The distribution of adenoviral gene expression in the spinal cord was compared with that of Fluoro-Gold. Next, levels of gene expression in the sciatic nerve and spinal cord were compared after single and repeated injections of Ad5RSVntLacZ. Finally, remote spinal cord gene expression in naive animals was compared with expression in animals that had been pretreated with subcutaneous Ad5RSVntLacZ inoculation. RESULTS: Viral gene expression was detected in all quadrants of the spinal cord gray matter, whereas Fluoro-Gold was detected only in the ipsilateral ventral horn (n = 5). This remote delivery was blocked by sciatic nerve transection (n = 10). Viral gene expression occurred in the sciatic nerve after both initial and repeated injections, whereas remote gene expression in the spinal cord was observed only after primary sciatic nerve injection (n = 24; P < 0.003). As with repeated sciatic nerve injections, subcutaneous inoculation with Ad5RSVntLacZ blocked subsequent remote spinal cord gene delivery (n = 8; P < 0.05). CONCLUSION: Remote viral gene delivery occurs in neurons without direct sciatic nerve projections but is dependent on intact peripheral nerves. Repeated injections fail to boost spinal cord gene expression, because of immune recognition of reinjected virus.

Intracerebral hemorrhage-induced neuronal death.

OBJECTIVE: The mechanisms underlying neural injury in intracerebral hemorrhage (ICH) remain uncertain. The present two-part study investigated cell death in the region of ICH and its association with caspase-3 activation. METHODS: ICH was produced in adult rats by injection of 100 microl of autologous blood or saline into the right basal ganglia. The animals' brains were removed at 6 hours or at 1, 3, 7, or 14 days after hemorrhage. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin in situ nick end-labeling (TUNEL) was used to detect deoxyribonucleic acid (DNA) fragmentation. TUNEL-positive cells were quantified. Caspase-3 activation was measured by Western blotting and immunohistochemistry. Double labeling was used to compare TUNEL with caspase-3 distribution and to identify the cell types affected. TUNEL-positive cells were also quantified at 6 hours, 1 day, and 3 days after injection of 5 U of thrombin into the right basal ganglion. RESULTS: At 6 hours, TUNEL-positive cells appeared in the ICH model (but not in the saline control brains) and were present for more than 2 weeks after ICH, peaking at 3 days. Western blot analysis revealed that the increase in immunoreactivity for the activated caspase-3 precedes that of DNA fragmentation, peaking at 1 day after ICH and declining thereafter. Immunohistochemistry analysis showed nucleus translocation of caspase-3 after ICH. Double-labeling studies demonstrated that both neurons and astrocytes surrounding the clot were TUNEL-positive. In addition, TUNEL and caspase-3 were colocalized in the same cells. Intracerebral thrombin injection elicited DNA fragmentation similar to that observed after the injection of blood. CONCLUSION: Double-strand breaks in genomic DNA and induction of caspase-3 were demonstrated adjacent to parenchymal hematoma in the animals' brains. These results provide evidence that cell loss after ICH is associated with activation of caspase-3.

A preliminary study determining the feasibility of electromagnetic tracking for kinematics at the ankle joint complex.

OBJECTIVE: To determine the feasibility of using electromagnetic tracking (EMT) for quantifying three-dimensional kinematics at the ankle joint complex (AJC). METHODS: AJC kinematics were recorded in 10 normal healthy adults, and 10 rheumatoid arthritis patients presenting with AJC instability and deformity who were undergoing footwear and orthotic intervention. RESULTS: Kinematics in normal subjects had strong face validity, curve shape showing moderate (n=9), good (n=8) or excellent (n=4) agreement with data from seven published studies. The range of motion about the x-axis (15.2 degrees ) was similar to reference values (17.0 degrees ), but our technique underestimated rotations about the y- (8.1 degrees vs 14.0 degrees ) and z-axes (7.7 degrees vs 12.2 degrees ). In the rheumatoid arthritis pronated foot group, eversion and internal rotation during the stance phase of gait were between 2 and 5 times greater than for normal subjects. The use of a corrective foot orthosis in this group restored normal kinematics, reducing maximum eversion and internal rotation by 57 and 68%, respectively. CONCLUSION: A new technique for measuring kinematics at the AJC is described. Based upon the findings of this pilot study, EMT may be useful for diagnosing AJC dysfunction and quantifying the mechanical efficacy of footwear and orthosis interventions.

TCL1 oncogene expression in AIDS-related lymphomas and lymphoid tissues.

AIDS-related non-Hodgkin's lymphoma (AIDS NHL) comprises a diverse and heterogeneous group of high-grade B cell tumors. Certain classes of AIDS NHL are associated with alterations in oncogenes or tumor-suppressor genes or infections by oncogenic herpesviruses. However, the clinically significant class of AIDS NHL designated immunoblastic lymphoma plasmacytoid (AIDS IBLP) lacks any consistent genetic alterations. We identified the TCL1 oncogene from a set of AIDS IBLP-associated cDNA fragments generated by subtractive hybridization with non-AIDS IBLP. Aberrant TCL1 expression has been implicated in T cell leukemia/lymphoma development, and its expression also has been seen in many established B cell tumor lines. However, TCL1 expression has not been reported in AIDS NHL. We find that TCL1 is expressed in the majority of AIDS IBLP tumors examined. TCL1 protein expression is restricted to tumor cells in AIDS IBLP tissue samples analyzed with immunohistochemical staining. Hyperplastic lymph node and tonsil also exhibit strong TCL1 protein expression in mantle zone B cells and in rare interfollicular zone cells, whereas follicle-center B cells (centroblasts and centrocytes) show weaker expression. These results establish TCL1 as the most prevalent of all of the surveyed oncogenes associated with AIDS IBLP. They also indicate that abundant TCL1 expression in quiescent mantle zone B cells is down-regulated in activated germinal center follicular B cells in parallel to the known expression pattern of BCL-2. High-level expression in nonproliferating B cells suggests that TCL1 may function in protecting naïve preactivated B cells from apoptosis.

Characterization of adenoviral gene expression in spinal cord after remote vector delivery.

OBJECTIVES: Recent work has established that the remote injection of attenuated adenoviral vectors may result in central nervous system (CNS) gene expression. These studies suggest that virus passes through peripheral nerves into the CNS. The present experiment attempts to characterize this phenomenon systematically. METHODS: Spinal cord cells staining for the reporter gene beta-galactosidase were histologically quantified after microinjection of the viral vector Ad5RSVntLacZ into rat footpad, muscle, or sciatic nerve. The effects of injection location, titer, and time, as well as nerve crush and dexamethasone, were examined. RESULTS: Sciatic nerve viral vector injection results in significantly higher CNS uptake than intramuscular and subcutaneous injections (P < 0.05). Nerve crush injury caused a time-dependent reduction in spinal cord gene uptake after sciatic nerve adenoviral injection (P < 0.05). Neuronal staining reaches its peak at 6 days after injection (P < 0.002). Peripheral nerve delivery to the CNS increases with augmented titers (P < 0.03). Finally, gene expression is augmented by administration of dexamethasone (P < 0.0001). CONCLUSION: Remote adenoviral vector injection represents a potential method for spinal cord gene therapy that avoids any manipulation of CNS tissue.

Quality determinants and hospital satisfaction. Perceptions of the facility and staff might be key influencing factors.

Perceptions of service quality ultimately affect consumer satisfaction, but objective measures of quality can be hard to come by when evaluating the quality of clinical care in a hospital. To determine if dimensions other than those found in models such as SERVQUAL were at play, the authors undertook a survey of 472 consumers, who were divided into two groups: those who had been hospital patients within the last three years (users) and those who were visitors (observers). The results suggest that facilities-related and human-factor related considerations helped shape the quality assessments of both groups, with observers generally giving higher marks to the hospitals with which they were familiar on the dimension of facilities-related quality and users expressing a less critical view of the human-factor dimension.

The effects of demographics on determinants of perceived health-care service quality. The case of users and observers.

Notes that previous research suggests the components of perceived service quality are industry specific, and that calls have been made for academics to integrate their theory into practice. Investigates the effects of demographic factors on users and observers of perceived hospital quality. Reports results suggesting perceived quality is industry specific, users and observers differ in their perceptions of hospital quality and demographic factors do make a difference in perceived hospital quality.

Reassessing retiree benefits: the new challenge.

For most employers, uncertainty about the future shape of the U.S. health care system, rising health care costs and FAS 106 accounting rules mean it is important to manage retiree medical costs. Survey data shows many employers are taking steps to manage their future retiree health care costs. These steps include reducing benefit levels, introducing service-related contributions and introducing managed care elements to retiree medical plans.

Development and evaluation of the revised Alcohol Evaluation Instrument.

This study reports on the development of a revised version of the Alcohol Evaluation Instrument (ALCEVAL-R). Items in the four major areas of the ALCEVAL-R were factor analyzed separately and relationships among factors were examined. Results suggest that the ALCEVAL-R measures clinically meaningful aspects of the alcoholic patient's occupational and social status, and reveals important dimensions of alcohol consumption and of the personal and social consequences of alcohol abuse.

Plasma levels of norepinephrine during the periovulatory period in normal women. Further studies.

Eleven normally cycling women in whom laparotomy was indicated for benign gynecologic pathology were studied. Surgery was performed on day 0 (expected day of ovulation). Blood samples were drawn daily from day -8 to day -4, and every 8 hours from day -3 to day +2; estradiol (E2), progesterone (P), norepinephrine (NE), and LH were determined by RIA. Ovulation was certified by ovarian visualization and biopsy during laparotomy. In nine ovulatory patients mean E2 peak was found 48 hours before LH peak. Mean NE levels showed minimal variations until 48 hours before LH peak; 8 hours after E2 peak mean NE values increased significantly, fell 8 hours later, and rose immediately again, reaching maximal levels 24 hours after E2 peak. These values remained high until 16 hours before the LH peak and decreased gradually, thereafter reaching basal levels 32 hours after LH peak. Two anovulatory patients showed an atypical pattern of ovarian steroids and LH secretion and NE showed large variations without any correlation with estradiol or LH levels. This study confirms previous findings in women and experimental work in animals regarding the existence of a noradrenergic trigger mechanism to the LH ovulatory discharge.