Effect of rosiglitazone on capillary density and angiogenesis in adipose tissue of normoglycaemic humans in a randomised controlled trial.

AIMS/HYPOTHESIS: Recent reports of decreased capillary density in the adipose tissue of obese individuals suggest that an imbalance of angiogenesis and adipogenesis may, in part, underlie insulin resistance. This study aimed to determine whether the insulin-sensitising peroxisome proliferator-activated receptor γ (PPARγ) activator rosiglitazone affects adipose tissue vascularisation in normal humans. METHODS: A randomised, parallel-group, investigator-blinded placebo-controlled trial was conducted with normoglycaemic volunteers with BMI 27-43, recruited from the community at the University of Massachusetts Medical School, Worcester, MA, USA. Peri-umbilical adipose tissue biopsies were obtained before and after treatment for 6 weeks with rosiglitazone (8 mg once daily) or placebo, which were randomly allocated from a sequentially numbered list. The primary outcomes were adipocyte size and capillary density measured by immunohistochemistry, and angiogenic potential assessed by capillary sprout formation in Matrigel. Secondary outcomes were serum adiponectin, glycaemic, lipid and liver function variables. RESULTS: A total of 35 individuals fulfilling the inclusion criteria were randomised, and complete before-vs-after analyses were achieved in 30 participants (13 and 17, placebo and rosiglitazone, respectively). Significant differences, assessed by paired two-tailed Student t tests, were seen in response to rosiglitazone for adipocyte size (3,458 ± 202 vs 2,693 ± 223 µm(2), p = 0.0049), capillary density (5.6 ± 0.5 vs 7.5 ± 0.5 lumens/field, p = 0.0098), serum adiponectin (14.3 ± 1.5 vs 28.6 ± 3.0 ng/ml, p < 0.0001) and alkaline phosphatase (1.04 ± 0.07 vs 0.87 ± 0.05 µkat/l, p = 0.001). A difference in angiogenic potential before and after treatment between the placebo and rosiglitazone groups was also seen (-23.88 ± 14 vs 13.42 ± 13, p = 0.029, two-tailed Mann-Whitney test). CONCLUSIONS/INTERPRETATION: Significant effects on adipose tissue vascular architecture occur after a short period of treatment with rosiglitazone in individuals with normal glucose tolerance. Improved adipose tissue vascularisation may, in part, mediate the therapeutic actions of this class of drugs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01150981 FUNDING: The study was funded by National Institutes of Health grant DK089101 to S. Corvera, and by pilot funding from the University of Massachusetts (UMASS) Center for Clinical Translational Sciences (M. Thompson, S. Malkani and S. Corvera). Morphology core services were supported by UMASS Diabetes Endocrine Research Center (DERC) grant DK32520.

Case report: MR imaging features of endometriosis at the umbilicus.

The radiological features of extrapelvic endometriosis at the umbilicus with large ovarian endometriomas are described. In this patient, the umbilical lesion appears as hypointense on T(1) weighted and T(2) weighted MR images. The MR characteristics of endometriosis at the umbilicus are compared with those found within the pelvis.

Long-term exercise adherence after intensive rehabilitation for chronic low back pain.

PURPOSE: The purpose of this study was to examine exercise compliance in patients with chronic low back pain (CLBP) after participation in an intensive spine rehabilitation program. METHODS: Exercise behaviors in 122 consecutive subjects with CLBP who completed a program of quota based exercise were examined. Frequency per week of performance of four exercise activities, Oswestry disability scores, and visual analog scale (VAS) scores were assessed at evaluation, 3-month, and 12-month follow-up by patient-completed questionnaires. RESULTS: Percentage of patients responding to initial, 3-month, and 12-month questionnaires were 100%, 86%, and 71%, respectively. Frequencies of exercise behaviors were compared by Wilcoxon signed-rank test and were found to increase significantly between evaluation and 3 months (P < 0.000), and evaluation and 12-month follow-up (P < 0.000). The percentages of patients reporting three or more times weekly performance of the following activities at evaluation and at three month follow-up, respectively, were: 1) stretching for the back and legs, 35% and 93%; 2) aerobic exercise, 44% and 87%; 3) back-strengthening exercises, 15% and 82%; and, 4) weight training, 6% and 71%. Evaluation and follow-up Oswestry disability and visual analog scale (VAS) scores for back pain were compared using Student's t-test. Significant improvements (P < 0.000) were noted for each of these scales at 3-month follow-up that were maintained at 12-month follow-up. CONCLUSION: It is concluded that exercise behaviors can be increased and maintained in CLBP patients without adversely affecting pain or function.

Long-term clinical outcome following coronary artery bypass grafting for isolated stenosis of the left anterior descending coronary artery.

AIMS: To detail the clinical and angiographic profile, and long-term outcome in consecutive patients with isolated stenosis of the left anterior descending coronary artery undergoing bypass surgery. METHODS: A retrospective study of all patients (n = 301) (January 1984-December 1990) and undergoing coronary artery bypass grafting for isolated left anterior descending disease, in the Irish Republic, was performed. Survival was compared with that of an exact age- and gender-matched cohort. RESULTS: Mean age was 53 (+/- 9.3) years. There were 238 (79%) males. In 241 (80%) patients an internal thoracic arterial bypass graft was used. Operative mortality was 1.3%. Of the 280 (93%) patients alive (16 cardiac deaths) at 7.1 (+/- 1.9) years, 105 (35%) had angina, 26 (9%) suffered an interval myocardial infarction, and repeat revascularization was required on 29 (10%). Female gender (P = 0.002), pre-operative myocardial infarction (P = 0.02), significant diagonal disease (P = 0.04) and postoperative myocardial infarction (P = 0.0001) were independently associated with survival. Females were more likely to develop congestive cardiac failure (P = 0.01) or postoperative angina (P = 0.03) than their male counterparts. CONCLUSIONS: Survivorship (97%) and event-free survival (96%) at 5 years following coronary artery bypass grafting for isolated left anterior descending coronary artery disease is excellent and equivalent to an age-matched and gender-matched cohort.

Decreasing disability in chronic back pain through aggressive spine rehabilitation.

This paper discusses specific techniques for rehabilitation of chronic low back pain through aggressive physical therapy with behavioral support. The rationale for approaching the outcome dimensions of impairments in back function and pain-related disability as opposed to chronic pain symptoms is explained. This approach requires that impairments in back function are systematically identified through the quantification of trunk flexibility, straight leg raising, back extensor strength, lifting ability, and endurance. The described treatment approach focuses on eliminating those impairments through aggressive, quota-based exercise and is usually completed within 8 weeks. It requires only a modest amount of space and equipment. Useful behavioral techniques for extinguishing pain behaviors, lessening pain beliefs, and for promoting wellness are described. Results from a treatment program using these techniques demonstrate normal back function and reduced disability for a majority of treated persons. Applying such a program to the VA population is an important challenge.

The effect of compensation involvement on the reporting of pain and disability by patients referred for rehabilitation of chronic low back pain.

STUDY DESIGN: In this prospective, observational, cohort study of 192 individuals with chronic low back pain, the group of individuals was divided based on compensation involvement, and their presentation pain and disability, treatment recommendations, and compliance were compared. For 85 of these individuals who completed a spine rehabilitation program, their pain and disability at 3 and 12 months were compared. OBJECTIVES: To test the theory that individuals with compensation involvement presented with greater pain and disability and would report less change of pain and disability after rehabilitation efforts. BACKGROUND: Previous studies have produced conflicting results concerning this issue. METHODS: Individuals were recruited as consecutive patients referred for consultation at a spine rehabilitation center. Pain, depression, and disability were assessed using self-report questionnaires at evaluation and at 3 and 12 months. Rehabilitation services consisted of aggressive, quota-based exercises aimed at correcting impairments in flexibility, strength, endurance, and lifting capacity, identified through quantification of back function. Multifactoral analysis of variance models were used to control for baseline differences between compensation and noncompensation patients during analysis of target variables. RESULTS: The compensation group included 96 patients; these patients reported more pain, depression, and disability than the 96 patients without compensation involvement. These differences persisted when baseline differences were controlled for with multifactoral analysis of variance models. Treatment recommendations and compliance were not affected by compensation. For patients completing the spine rehabilitation program, length of treatment, flexibility, strength, lifting ability, and lower extremity work performance before and after treatment and patient satisfaction ratings were similar for the compensation and noncompensation groups. At 3 and 12 months, improvements in depression and disability were noted for both groups, but were statistically and clinically less substantial for the compensation group. At the 12 month follow-up visit, pain scores improved for the noncompensation group, but not for the compensation group. CONCLUSIONS: In chronic low back pain, compensation involvement may have an adverse effect on self-reported pain, depression, and disability before and after rehabilitation interventions.

Rehabilitation of acute and subacute low back and neck pain in the work-injured patient.

In spite of the favorable natural history and the nonserious nature of the problem of much work-related low back and neck pain, conventional rehabilitation methods have failed to reduce work disability. Recently, rehabilitation goals have shifted from exclusively reducing or eradicating pain to improving patients' work and activity tolerance, avoiding illness behaviors, and preventing deconditioning and chronicity. Rehabilitation programs must incorporate strategies that have been proved to improve outcome in randomized, controlled trials. Treatment should be based on duration of symptoms, severity of impairment, and patient response. Consideration must be given to physical and psychological therapeutic milieu. Acute patients should be educated that pain is a normal part of recovery, and that activity maintenance improves outcome. Therapy should focus on restoring or maintaining flexibility, strength, and level of fitness while maintaining maximum productivity. Some acute patients may wish to change health habits and may undergo several sessions of general and low back conditioning training with the development of a health-club or home maintenance regimen. Patients failing to respond favorably to acute treatment and other subacute patients should participate in quota-based graded exercise regimens, with behavioral management. Quantification of function for flexibility, trunk strength, lifting capacity, and cardiovascular fitness is recommended to document progress and guide treatment. "Wellness" is stressed. Incorporating direct return-to-work advice into the treatment plan is important, as is direct communication with the employer throughout treatment. Patients should be cleared for full-duty return to work at treatment end in most circumstances. Successfully managed patients will feel confident about abilities for work and general activities. Intensive management of subacute patients may require 4 to 6 weeks and 12 to 18 comprehensive rehabilitation sessions. Once such comprehensive treatment has been provided, patients may be deemed at a medical endpoint, and further "chronic" rehabilitation treatment should not be necessary. The rehabilitation principles discussed here for work-injured low back and neck pain patients may be used to treat other industrial injuries as long as medical clearance is given for applying the treatment model. Specific time frames for recovery and expected performance for specific diagnoses need to be developed.

Portable hyperbaric oxygen therapy in the emergency department with the modified Gamow bag.

STUDY OBJECTIVE: To compare oxygen administration by means of an inflatable portable hyperbaric chamber with that through a nonrebreather mask for the elimination of carboxyhemoglobin (COHb). DESIGN: Double-crossover prospective analysis. SETTING: University emergency department, Level I trauma center. PARTICIPANTS: Twelve healthy paid adult volunteers, all smokers. INTERVENTIONS: Each subject smoked five cigarettes within 60 minutes. COHb levels were measured before and after smoking by means of cooximetry. Subjects then breathed hyperbaric and normobaric oxygen in separate trials for 40 minutes. Normobaric oxygen was administered through a nonrebreather face mask at 15 L/minute outside the Gamow bag. Hyperbaric oxygen was delivered inside the Gamow bag with a demand valve regulator mask at a pressure of 1.58 atmospheres absolute pressure (8.5 psi). Venous blood (.5 mL) was sampled every 5 minutes. The specimens were iced and assayed for COHb in triplicate. RESULTS: A significant increase in the elimination of COHb was observed for each subject in the Gamow bag (P < .05, repeated-measures ANOVA). The average half-life for COHb elimination was 27.5 +/- 1.08 minutes (mean +/- SE) (n = 10). IV access failure occurred in two patients, with incomplete data as a result. CONCLUSION: The modified Gamow bag eliminated COHb more quickly than did nonrebreather mask oxygen and proved simple to operate and maintain. No complications were noted for any of the subjects. One subject experienced claustrophobia, but it abated after the bag was inflated.

Comparison of total lumbosacral flexion and true lumbar flexion measured by a dual inclinometer technique.

STUDY DESIGN: This study investigated the interrelationship between total lumbosacral flexion and true lumbar flexion in a population of chronic low back pain sufferers, measured with a dual inclinometer technique. Correlations with self-reported disability also were assessed. Self-reported disability was measured with the Million Visual Analog Scale. OBJECTIVES: To assess whether total lumbosacral flexion could be substituted for true lumbar flexion in the clinical evaluation of trunk mobility. To determine which measure of flexion is a better predictor of self-reported disability after an intensive rehabilitation program for chronic spinal disorders. SUMMARY OF BACKGROUND DATA: Eighty-nine consecutive patients with chronic low back pain were evaluated. Fourteen subjects were excluded because of previous surgery. Seventy-five meet inclusion criteria and underwent quantification of lumbar mobility. Sixty-four met literacy criteria and were administered the Million Visual Analog Scale. Thirty-six patients completed rehabilitation and were re-evaluated at program completion for lumbar mobility. Thirty-three were re-evaluated with the Million Visual Analog Scale. RESULTS: Pearson's correlation coefficients for lumbar versus total flexion were r = 0.88 for initial evaluation and r = 0.84 after treatment. Correlation coefficients also were calculated for lumbar flexion and total flexion with disability scores. Before treatment, both measurements accounted for similar amounts of the variance in disability scores. However, after treatment, total flexion correlated higher with self-reported disability (r = -0.62 versus r = -0.43). CONCLUSIONS: Our results suggest that total lumbosacral flexion may be as equally relevant as true lumbar flexion in the measurement of trunk mobility in the clinical examination of patients with chronic low back pain. Regarding their relationship to self-reported disability, total flexion seems to be more relevant to outcome after intensive rehabilitation.

An overview of muscle strengthening.

This article gives an overview of muscle strengthening. In this review, we explore the underlying rationale, the process, and the physiologic adjustments that occur as muscles are trained to become stronger. Although controversy surrounds methods used to strengthen muscles, most agree that regular strength training exercises, regardless of the type, can be beneficial.

Computerized analysis of isokinetic torque curves for muscle strengthening.

Isokinetic exercise measurements are widely used in rehabilitation medicine for evaluation and treatment planning. Computerized peak torque, work, and power measurements in isokinetic exercise can be obtained reliably when testing muscles that cross the knee and elbow joints. Important technical considerations in torque curve analysis are axis alignment, instrument calibration, and damp and gravity correction factors. The usefulness of these measurements has been limited by the small number of accurate scientific studies providing valid normative data on healthy individuals.

Influence of gender and age on the behind-the-back reach test.

The behind-the-back reach test is a reproducible and reliable physical fitness test for musculoskeletal extensibility of the upper extremities, shoulder girdles, and upper back. Requiring only a rigid ruler and marking pen, administration of this test can be learned easily both by medical and nonmedical personnel. Normative data derived from a study of healthy subjects of different ages demonstrated that extensibility decreases with age. Moreover, musculoskeletal extensibility for women was significantly greater than that for men. The test results were not influenced significantly by anthropometric measurements.

Talotibial exostoses with entrapment of the deep peroneal nerve.

An athlete with talotibial exostoses with entrapment of the deep peroneal nerve is presented. This diagnosis was made by history, physical and roentgenographic examinations, bone scan, and isokinetic exercising. Treatment of this condition involved surgical excision of the boney exostoses.