Regional differences in responses of rabbit detrusor to electrical and adrenergic stimulation: influence of outlet obstruction

OBJECTIVE: To examine regional responses of control and obstructed rabbit detrusor strips to electrical and adrenergic stimulation, and determine whether outlet obstruction causes regional variations in blood flow throughout the detrusor, as the detrusor smooth muscle of the bladder body has previously been considered homogeneous in its pharmacological properties. MATERIALS AND METHODS: Fourteen male rabbits had the bladder outlet surgically obstructed for 2 weeks and were compared with 10 unoperated control rabbits. Blood flow was measured with the bladder empty and at capacity, using fluorescent microspheres. Paired dorsal and ventral strips were harvested from the midline equatorial detrusor and electrically and adrenergically stimulated. RESULTS: Obstructed rabbits had significantly higher bladder capacities and bladder weights than control rabbits. Dorsal strips from both control and obstructed rabbits contracted in response to noradrenaline, whereas ventral strips relaxed. The addition of prazosin, a nonselective alpha1-adrenergic-receptor blocker, completely blocked the contraction in dorsal strips, but had no effect on responses of ventral strips. There was also a regional difference in response to electrical stimulation, with ventral strips generating significantly more tension than dorsal strips in both control and obstructed rabbits. There were no regional differences in detrusor blood flow. Obstruction resulted in significantly lower responses to all forms of stimulation, and significantly less blood flow throughout the detrusor. CONCLUSION: There are regional differences in adrenergic receptor function and response to electrical-field stimulation throughout control and obstructed rabbit detrusor, a region that was previously thought to be functionally homogeneous. These differences must be recognized and acknowledged to obtain accurate and reproducible data from in vitro studies of the bladder.     

Revisional eyelid surgery: treatment of severe postblepharoplasty lower eyelid retraction

A common and challenging complication of lower blepharoplasty is severe lower eyelid retraction. This complication is esthetically displeasing and can result in ocular discomfort, blurred vision, and exposure keratopathy. The hard palate graft and cheek-lift procedures can eliminate the lower lid retraction without creating disfiguring facial scars. The authors discuss their approach to the treatment of severe lower eyelid retraction after cosmetic blepharoplasty.     

Assessing the minimum number of lymph nodes needed at radical cystectomy in patients with bladder cancer

OBJECTIVE

To identify the likelihood of finding one or more positive lymph nodes (LNs) according to the number of LNs removed at radical cystectomy (RC), as the number of LNs removed affects disease progression and survival after RC.

PATIENTS AND METHODS

Between 1984 and 2003, 731 assessable patients had RC and bilateral pelvic lymphadenectomy at three different institutions. ROC curve coordinates were used to determine the probability of identifying one or more positive LNs according to the total number of removed LNs.

RESULTS

Of the 731 patients, 174 (23.8%) had LNs metastases. The mean (median, range) number of LNs removed was 18.7 (17, 1–80). The ROC coordinate‐based plots of the number of removed LNs and the probability of finding one or more LNs metastases indicated that removing 45 LNs yielded a 90% probability. Conversely, removing either 15 or 25 LNs indicated, respectively, 50% and 75% probability of detecting one or more LNs metastases.

CONCLUSIONS

These data indicate that removing 25 LNs might represent the lowest threshold for the extent of lymphadenectomy at RC. Our findings confirm the importance of an extended lymph node dissection.     

Analysis of Factors Associated with Outcome in Patients Undergoing Isolated Hepatic Perfusion for Unresectable Liver Metastases from Colorectal Center

Aim  To define the indications for hyperthermic isolated hepatic perfusion (IHP) in patients with unresectable liver metastases (LM) from colorectal cancer (CRC) with particular focus on IHP’s utility as a second-line option for patients whose tumors have progressed following combination systemic chemotherapy treatment. Methods  From June 1994 through July 2005, 120 patients with unresectable CRC LM underwent IHP with melphalan (n = 69), tumor necrosis factor (TNF) (n = 10) or both (n = 41). Hepatic arterial infusion (HAI) with floxuridine started 6–8 weeks post IHP in 46 (38%). Patients were followed for toxicity, radiographic response, and overall survival (OS). Wilcoxon rank-sum and Fisher’s exact tests were used to compare parameters by response category; survival and hepatic progression-free survival were calculated by the Kaplan–Meier method. Results  Of 79 males and 41 females, 96 (80%) received prior chemotherapy. There were five (4%) operative/treatment mortalities. There were 69 responses in 114 evaluable patients (61%). Total melphalan dose and combination melphalan/TNF were each associated with response; age, preoperative carcinoembryonic antigen (CEA), prior chemotherapy for established LM, tumor burden, and post-IHP HAI therapy were not. Median overall survival was 17.4 months and 2-year survival was 34%. Factors found to be independently related to survival were preoperative CEA <30 ng/mL and use of post-IHP HAI (P < 0.015). Conclusions  IHP results in marked tumor regression and prolonged survival in patients with CRC LM. Continued development of IHP in this clinical setting is warranted.     

Amide proton transfer imaging of the breast at 3 T: Establishing reproducibility and possible feasibility assessing chemotherapy response

Chemical exchange saturation transfer imaging can generate contrast that is sensitive to amide protons associated with proteins and peptides (termed amide proton transfer, APT). In breast cancer, APT contrast may report on underlying changes in microstructural tissue composition. However, to date, there have been no developments or applications of APT chemical exchange saturation transfer to breast cancer. As a result, the aims of this study were to (i) experimentally explore optimal scan parameters for breast chemical exchange saturation transfer near the amide resonance at 3 T, (ii) establish the reliability of APT imaging of healthy fibroglandular tissue, and (iii) demonstrate preliminary results on APT changes in locally advanced breast cancer observed during the course of neoadjuvant chemotherapy. Chemical exchange saturation transfer measurements were experimentally optimized on cross‐linked bovine serum albumin phantoms, and the reliability of APT imaging was assessed in 10 women with no history of breast disease. The mean difference between test–retest APT values was not significantly different from zero, and the individual difference values were not dependent on the average APT value. The 95% confidence interval limits were ±0.70% (α = 0.05), and the repeatability was 1.91. APT measurements were also performed in three women before and after one cycle of chemotherapy. Following therapy, APT increased in the one patient with progressive disease and decreased in the two patients with a partial or complete response. Together, these results suggest that APT imaging may report on treatment response in these patients. Magn Reson Med, 2013. © 2012 Wiley Periodicals, Inc.     

Axial 3D gradient-echo imaging for improved multiple sclerosis lesion detection in the cervical spinal cord at 3T

Introduction

In multiple sclerosis (MS), spinal cord imaging can help in diagnosis and follow-up evaluation. However, spinal cord magnetic resonance imaging (MRI) is technically challenging, and image quality, particularly in the axial plane, is typically poor compared to brain MRI. Because gradient-recalled echo (GRE) images might offer improved contrast resolution within the spinal cord at high magnetic field strength, both without and with a magnetization transfer prepulse, we compared them to T2-weighted fast-spin-echo (T2-FSE) images for the detection of MS lesions in the cervical cord at 3T.

Methods

On a clinical 3T MRI scanner, we studied 62 MS cases and 19 healthy volunteers. Axial 3D GRE sequences were performed without and with off-resonance radiofrequency irradiation. To mimic clinical practice, all images were evaluated in conjunction with linked images from a sagittal short tau inversion recovery scan, which is considered the gold standard for lesion detection in MS. Two experienced observers recorded image quality, location and size of focal lesions, atrophy, swelling, and diffuse signal abnormality independently at first and then in consensus.

Results

The number and volume of lesions detected with high confidence was more than three times as high on both GRE sequences compared to T2-FSE (p?<?0.0001). Approximately 5 % of GRE scans were affected by artifacts that interfered with image interpretation, not significantly different from T2W-FSE.

Conclusions

Axial 3D GRE sequences are useful for MS lesion detection when compared to 2D T2-FSE sequences in the cervical spinal cord at 3T and should be considered when examining intramedullary spinal cord lesions.     

Preoperative FLAC/Granulocyte-Colony-Stimulating Factor Chemotherapy for Stage II Breast Cancer: A Prospective Randomized Trial

Background: Preoperative chemotherapy for stage II breast cancer may reduce locoregional tumors and provides initial treatment for systemic micrometastases. We conducted a prospective, randomized trial to evaluate the ability of intensive preoperative chemotherapy to enhance the outcome of this approach.Methods: Patients with clinical stage II breast cancer (T2N0, T1N1, and T2N1) were prospectively randomized to receive either preoperative or postoperative chemotherapy with five 21-day cycles of fluorouracil, leucovorin calcium, doxorubicin, and cyclophosphamide (FLAC)/granulocyte-colony-stimulating factor. Local therapy consisted of modified radical mastectomy or segmentectomy/axillary dissection/breast radiotherapy, according to patient preference.Results: Fifty-three women were randomized (26 preoperative chemotherapy and 27 postoperative chemotherapy). The objective clinical response rate of the primary tumor to preoperative chemotherapy was 80%, and the pathologic complete response rate was 20%. Preoperative chemotherapy reduced the overall incidence and number of axillary lymph node metastases. There was no difference in the use of breast-conserving local therapy between the two treatment arms. There were 20 local/regional or distant recurrences (9 preoperative and 11 postoperative). There was no difference in the overall or disease-free survival between the preoperative and postoperative chemotherapy arms.Conclusions: Preoperative FLAC/granulocyte-colony-stimulating factor chemotherapy was effective against local/regional tumors in stage II breast cancer but was otherwise comparable to postoperative chemotherapy.     

Cortical brain mapping of peripheral nerves using functional magnetic resonance imaging in a rodent model

The regions of the body have cortical and subcortical representation in proportion to their degree of innervation. The rat forepaw has been studied extensively in recent years using functional magnetic resonance imaging (fMRI), typically by stimulation using electrodes directly inserted into the skin of the forepaw. Here we stimulate the nerve directly using surgically implanted electrodes. A major distinction is that stimulation of the skin of the forepaw is mostly sensory, whereas direct nerve stimulation reveals not only the sensory system but also deep brain structures associated with motor activity. In this article, we seek to define both the motor and sensory cortical and subcortical representations associated with the four major nerves of the rodent upper extremity. We electrically stimulated each nerve (median, ulnar, radial, and musculocutaneous) during fMRI acquisition using a 9.4-T Bruker scanner (Bruker BioSpin, Billerica, MA). A current level of 0.5 to 1.0 mA and a frequency of 5 Hz were used while keeping the duration constant. A distinct pattern of cortical activation was found for each nerve that can be correlated with known sensorimotor afferent and efferent pathways to the rat forepaw. This direct nerve stimulation rat model can provide insight into peripheral nerve injury.     

Autocystectomy following extensive genitourinary tuberculosis: Presentation and management

Genitourinary tuberculosis is an important cause of morbidity in developing and developed countries. We describe a case of extensive genitourinary tuberculosis in which there was complete destruction of the right kidney, stricture of the entire left ureter and an autocystectomized bladder. He presented in azotemia with urinary incontinence and was managed by right nephroureterectomy, ileal replacement of left ureter and ileal neobladder after a preliminary nephrostomy and antituberculous chemotherapy.     

Age affects outcomes in chronic kidney disease

Chronic kidney disease (CKD) is common among the elderly. However, little is known about how the clinical implications of CKD vary with age. We examined the age-specific incidence of death, treated end-stage renal disease (ESRD), and change in estimated glomerular filtration rate (eGFR) among 209,622 US veterans with CKD stages 3 to 5 followed for a mean of 3.2 years. Patients aged 75 years or older at baseline comprised 47% of the overall cohort and accounted for 28% of the 9227 cases of ESRD that occurred during follow-up. Among patients of all ages, rates of both death and ESRD were inversely related to eGFR at baseline. However, among those with comparable levels of eGFR, older patients had higher rates of death and lower rates of ESRD than younger patients. Consequently, the level of eGFR below which the risk of ESRD exceeded the risk of death varied by age, ranging from 45 ml/min per 1.73 m(2) for 18 to 44 year old patients to 15 ml/min per 1.73 m(2) for 65 to 84 year old patients. Among those 85 years or older, the risk of death always exceeded the risk of ESRD in this cohort. Among patients with eGFR levels <45 ml/min per 1.73 m(2) at baseline, older patients were less likely than their younger counterparts to experience an annual decline in eGFR of >3 ml/min per 1.73 m(2). In conclusion, age is a major effect modifier among patients with an eGFR of <60 ml/min per 1.73 m(2), challenging us to move beyond a uniform stage-based approach to managing CKD.