Effects of mycophenolate mofetil and lisinopril on collagen deposition in unilateral ureteral obstruction in rats

BACKGROUND/AIMS: Unilateral ureteral obstruction (UUO) in rats has been used as a model of renal interstitial fibrosis, in which therapeutic trials can be of important clinical relevance. In this study, we investigated the effects of mycophenolate mofetil (MMF), the angiotensin-converting enzyme (ACE) inhibitor lisinopril (L), and the combination of both drugs, given daily for 14 days to UUO rats, on the renal fibrogenic process triggered by UUO. METHODS: Rats underwent surgical UUO, followed by treatment with daily doses of either MMF, lisinopril, or both, and were then sacrificed after 14 days. Kidney fragments were fixed for histopathological examination (hematoxylin-eosin and periodic acid-Schiff reactive) and immunohistochemistry for myofibroblasts (alpha-smooth muscle actin; alpha-SMA) and macrophages (ED-1). Histomorphometrical analysis of collagen was performed with Sirius red staining, and collagen content was assessed by the amount of hydroxyproline. Cortex and medulla were analyzed separately. RESULTS: MMF, lisinopril and MMF+L reduced the density of alpha-SMA- and ED-1-positive cells (p < 0.05), interstitial volume (p < 0.05) and decreased Sirius-red-stained areas by 54.6, 35.6 and 58.0%, and hydroxyproline content by 60.1, 49.7 and 62.7%, respectively. No differences were observed among treated groups. CONCLUSION: MMF and the ACE inhibitor lisinopril attenuated the progression of the fibrogenic process of UUO in an equivalent manner. The combination of both drugs did not add any further improvement in the collagen content.     

Effect of 4- and 8-wk intensive Tai Chi Training on balance control in the elderly

PURPOSE: The objective of this study was to examine whether 4 and/or 8 wk of intensive Tai Chi practice could improve balance control in the healthy elderly subjects. METHODS: Forty-nine community-dwelling elderly subjects (aged 69.1 +/- SD 5.8 yr) voluntarily participated in an intervention program of either supervised Tai Chi or general education for 1.5 h, 6x wk for 8 wk. Two balance tests were administered using computerized dynamic posturography before, at 4 and 8 wk during training, and at 4 wk after training ended: 1) the sensory organization test measured subjects' abilities to use somatosensory, visual, and vestibular information to control their body sway during stance under six sensory conditions; and 2) the limits of stability test measured subjects' abilities to voluntarily weight shift to eight spatial positions within their base of support. These outcome measures were compared between the two intervention groups, and with those of experienced Tai Chi practitioners having means of 7.2 and 10.1 yr of practice from two previous studies. RESULTS: Statistical analysis demonstrated that, after 4 and 8 wk of intensive Tai Chi training, the elderly subjects achieved significantly better 1) vestibular ratio in the sensory organization test (P = 0.006) and 2) directional control of their leaning trajectory in the limits of stability test (P = 0.018), when compared with those of the control group. These improvements were maintained even at follow-up 4 wk afterward. Furthermore, the improved balance performance from week 4 on was comparable to that of experienced Tai Chi practitioners. CONCLUSIONS: The above findings indicated that even 4 wk of intensive Tai Chi training are sufficient to improve balance control in the elderly subjects.     

Interim results from a national multicenter phase II trial of combination bacillus Calmette-Guerin plus interferon alfa-2b for superficial bladder cancer

PURPOSE: Interim results are provided from a large multicenter trial of combination bacillus Calmette-Guerin (BCG) plus interferon (IFN) alfa-2b for BCG naive (BCG-N) and previous BCG failure (BCG-F) cases of superficial bladder cancer. MATERIALS AND METHODS: A total of 490 patients enrolled from May 1999 to May 2000 with a median of 24 months of followup were analyzed. The BCG-N group (259) was treated with a 6-week induction course of standard dose BCG plus 50 million units of IFN followed by 3, 3-week maintenance cycles of reduced dose BCG (1/3 to 1/10) plus 50 million units IFN at 3, 9 and 15 months after induction. The BCG-F group (231) was treated similarly except induction therapy began at a decreased (1/3 to 1/10) BCG dose. RESULTS: The simple tumor recurrence rates for BCG-N and BCG-F groups were 40% and 52%, and the Kaplan-Meier estimates for disease freedom at 24 months were 57% and 42%, respectively. Progression to muscle invasion occurred in 5% and 4.3% while metastasis occurred in 2.3% and 2.6%, respectively. In each group 3.9% of patients underwent cystectomy and 2 patients in each group died of bladder cancer. Serious adverse events occurred in 5.5% with infection related serious adverse events being less prevalent in the BCG-F group (2.6% vs 5.4%). Toxicity related dropout, treatment delay and/or further BCG dose reduction, and need for symptomatic drugs were similar. Moderate to severe local side effects during induction were higher in the BCG-F group (6.2% vs 16.9%) but equilibrated during maintenance therapy. Systemic reactions were rare. CONCLUSIONS: This multicenter trial provides a benchmark for the efficacy and safety of combination BCG and IFN as up front and salvage therapy. The incremental value of IFN cannot be determined from this study.     

Daily vs twice daily enoxaparin in the prevention of venous thromboembolic disorders during rehabilitation following acute spinal cord injury

BACKGROUND: Subcutaneous administration of low molecular weight heparin (eg, enoxaparin) has been shown to be safe and effective in the prevention of acute venous thromboembolic (TE) disease following acute spinal cord injury (SCI) in the rehabilitation setting. However, emerging evidence suggests that different dosing strategies may be equivalent. OBJECTIVE: To determine whether subcutaneous enoxaparin, 40 mg once daily, when compared with subcutaneous enoxaparin, 30 mg twice daily, is equally safe and effective in the prevention of venous TE disease in patients with SCI. DESIGN: Retrospective chart review. SETTING: A freestanding, inpatient, acute, rehabilitation hospital. PATIENTS: One hundred and twenty-nine patients admitted from June 2000 through June 2002 for inpatient rehabilitation following an acute SCI who received either enoxaparin, 40 mg once daily, or enoxaparin, 30 mg twice daily, for prophylaxis for TE disease. RESULTS: Equivalent prophylaxis efficacy was seen in both enoxaparin groups. Symptomatic venous thromboembolism did not differ, with deep vein thromboses occurring in 1 of 49 (2.0%) patients receiving twice-daily enoxaparin, and 1 of 80 (1.25%) patients receiving once-daily enoxaparin (chi2 = 0.125, NS). Pulmonary embolism was seen in 1 of 49 (2.0%) patients treated with twice-daily enoxaparin and in none of the patients in the once-daily group (chi2 = 1.64, NS). Bleeding complications also did not differ between the 2 treatment groups; these were observed in 2 of 49 (4.1%) patients receiving twice-daily enoxaparin and in 5 of 80 (6.3%) patients receiving once-daily enoxaparin (chi2 = 0.228, NS). CONCLUSION: Subcutaneous enoxaparin administered once or twice daily is equally effective for the prevention of venous TE disease. Both dosing strategies are associated with a low incidence of bleeding in patients with SCI who are undergoing rehabilitation.     

Effect of magnetic resonance imaging on internal magnet strength in Med-El Combi 40+ cochlear implants

OBJECTIVE: Magnetic resonance imaging (MRI) has been contraindicated when cochlear implants containing an internal magnet are in place because of concerns regarding torque, force, demagnetization, artifacts, induced voltages, and heating. The objective was to determine the magnetic field strength of Med-El Combi 40+ cochlear implant internal magnets after MRI studies. STUDY DESIGN/METHODS: Two fresh cadavers were used to study demagnetization using a repeated measures design and a magnetometer. Pre- and postMRI measurement of magnetic field strength was completed. Five sets of sagittal T1-weighted, axial T1-weighted, and axial T2-weighted sequences were performed on a cadaver at 0.2 Tesla in the device-up and device-down positions. In the other cadaver, 15 sets of sagittal T1-weighted, axial T1-weighted, and axial T2-weighted sequences were performed on a cadaver at 1.5 Tesla were conducted, 5 each with the head oriented at 80, 90, and 100 degrees rotated around the yaw plane (rotated around the z-axis). Subsequently, three cochlear implant patients completed 0.2 Tesla MRIs. For these patients, subjective and objective assessment of cochlear implant performance was performed. SETTING: Academic medical center. RESULTS: In the cadaver studies, analysis of variance showed no significant difference in the magnetic field strength after the 0.2 or 1.5 Tesla scans. There was no significant difference in the magnetic field strength for the three patients undergoing 0.2 Tesla MRIs and no adverse consequences, including no changes in telemetry, auditory sensations, nonauditory sensations, and sound quality. CONCLUSIONS: No significant demagnetization of the internal magnet occurred during repeated 1.5 Tesla MRI scans with the head orientations used in this study. In the cochlear implant patients, no significant demagnetization of the internal magnet occurred after a 0.2 Tesla MRI.     

Laryngeal embryonal rhabdomyosarcoma: a case of cervical metastases 13 years after treatment and a 25-year review of existing literature

Rhabdomyosarcoma is the most common soft tissue sarcoma in childhood, the majority of which are of the embryonal rhabdomyosarcoma (ER) variety. Present day treatment protocols involve a combination of aggressive surgery, chemotherapy, and radiation therapy. Embryonal rhabdomyosarcoma of the larynx is rare and unlike ER of other regions exhibits excellent response to multimodality treatment without the need for extensive surgery. We report a case of cervical metastases in a 29-year-old man 13 years after treatment of his laryngeal ER. To our knowledge, this is the first reported case of late neck metastases in ER of the larynx and the second reported case of delayed presentation of recurrent disease. A 25-year review of all published reports of ER of the larynx was conducted that highlights the move toward organ preservation with the multimodality treatment protocols. Embryonal rhabdomyosarcoma of the larynx is highly responsive to combination chemoradiotherapy, allowing for excellent cure rates without the need for extensive surgery. Late relapses warrant long-term follow-up.     

Mental imagery for promoting relearning for people after stroke: a randomized controlled trial

OBJECTIVE: To study the efficacy of mental imagery at promoting relearning for people after a stroke. DESIGN: Prospective, randomized controlled trial. SETTING: An inpatient rehabilitation stroke unit in Hong Kong. PARTICIPANTS: Forty-six inpatients, 60 years of age or older, after a cerebral infarction. INTERVENTIONS: Patients were randomized to receive 15 sessions (1 h/d for 3 wk) of either the mental imagery program or the conventional functional training intervention on the relearning of daily living tasks. MAIN OUTCOME MEASURES: Performance of 15 trained and 5 untrained tasks, including household, cooking, and shopping tasks; and the Fugl-Meyer Assessment and Color Trails Test (CTT). RESULTS: Patients engaged in mental imagery-based intervention showed better relearning of both trained and untrained tasks compared with the control group (trained tasks: P<.005; untrained tasks: P<.001). They also demonstrated a greater ability to retain the trained tasks after 1 month and transfer the skills relearned to other untrained tasks (P<.001). However, among the various ability measures, the mental imagery group showed a significant increase in the CTT scores only after the intervention (P<.005). CONCLUSIONS: Mental imagery can be used as a training strategy to promote the relearning of daily tasks for people after an acute stroke. The imagery process is likely to improve the planning and execution of both the trained and the untrained (novel) tasks. The effect of its relearning appears to help patients to retain and generalize the skills and tasks learned in the rehabilitation program.     

Direct visualization of cystic fibrosis transmembrane regulator mutations in the clinical laboratory setting

BACKGROUND: The recommendation for population- based cystic fibrosis (CF) carrier screening by the American College of Medical Genetics for the 25 most prevalent mutations and 6 polymorphisms in the CF transmembrane regulatory gene has greatly increased clinical laboratory test volumes. We describe the development and technical validation of a DNA chip in a 96-well format to allow for high-throughput genotype analysis. METHODS: The CF Portrait chip contains an 8 x 8 array of capture probes and controls to detect all requisite alleles. Single-tube multiplex PCR with 15 biotin-labeled primer pairs was used to amplify sequences containing all single-nucleotide polymorphisms to be interrogated. Detection of a thin-film signal created by hybridization of multiplex PCR-amplified DNA to complementary capture probes was performed with an automated image analysis instrument, NucleoSight. Allele classification, data formatting, and uploading to a laboratory information system were fully automated. RESULTS: The described platform correctly classified all mutations and polymorphisms and can screen approximately 1300 patient samples in a 10-h shift. Final validation was performed by two separate 1000-sample comparisons with Roche CF Gold line probe strips and the Applera CF OLA, Ver 3.0. The CF Portrait Biochip made no errors during this validation, whereas the Applera assay made seven miscalls of the IVS-8 5T/7T/9T polymorphism CONCLUSIONS: The CF Portrait platform is an automated, high-throughput, DNA chip-based assay capable of accurately classifying all CF mutations in the recommended screening panel, including the IVS-8 5T/7T/9T polymorphism.