Effect of long-term β2-agonist dosing on human cardiac β-adrenoceptor expression in vivo: Comparison with changes in lung and mononuclear leukocyte β-receptors

Background. Tachyphylaxis to the cardiac effects of β-adrenoceptor stimulation after long-term β₂-agonist administration is well recognized, but the influence on global cardiac β-adrenoceptor density has not been previously investigated in vivo. Positron emission tomography (PET) has made possible the noninvasive quantification of regional receptor density. This study assesses the effect of long-term β₂-agonist dosing on cardiac β-adrenoceptors.Methods and Results. β-Adrenoceptors in the hearts of 29 healthy male subjects aged 35 ± 8 years were imaged and quantified in vivo by means of PET and compared with the receptor density in the same subjects' lung tissue. Mononuclear leukocyte (MNL) β-receptor density was determined in vitro by means of a radioligand binding assay. β-Receptor density was 8.41 ± 2.03 pmol/gm tissue in heart, 10.81 ± 1.91 pmol/gm tissue in lung, and 38.0 ± 17.5 fmol/mg protein on MNLs. There was a weak relationship between cardiac and pulmonary β-receptor densities (r = 0.45, p < 0.02) but not between cardiac and MNL receptor density. In seven subjects, the measurements were repeated after 2 weeks of albuterol treatment (4 mg orally twice daily and 200 μg inhaled four times daily in the first week, with doubling of the dose during the second week). After the albuterol treatment, β-receptor density fell on average by 19% (p < 0.05) in the heart compared with 22% (p < 0.05) in the lung and 42% (p < 0.05) in MNLs. Correlations were found between the percentage changes in receptor density in heart and lung (r = 0.98, p < 0.001) and in heart and MNLs (r = 0.99, p < 0.002).Conclusions. Two weeks of high-dose albuterol results in equivalent downregulation of β-receptors in vivo, both in the lung and in the heart.     

Uniform analysis of dose distribution in interstitial brachytherapy dosimetry systems

In brachytherapy, articles are published with dose and homogeneity specifications using different systems which are hard to compare. For the same "stated dose", the dose delivered, volume treated and activity chosen are not the same in different systems, due to the fact that the source placement rules are different. In this article, the authors have circumvented this problem by the use of an approach not applied hitherto, viz. by determining the value of the Uniformity index (UI) of an implant using different systems. This value takes into account the integral dose within the treatment volume and is compared with an idealized implant, where the dose is uniform and the target and treatment volumes are the same. This method of evaluation has been applied for single plane, multiple plane and cylindrical volume implants using the Manchester, Quimby and Paris systems. Although the results obtained are different, the degree of closeness of these values are striking, with some minor exceptions. Thus, it is possible to combine all the brachytherapy parameters, such as: dose, homogeneity, treatment volume within a single value to determine the quality of an implant.     

Pulsed dye laser treatment of capillary malformations in infants at 2‐weekly versus 3‐monthly intervals,reducing the need for general anaesthesia

Capillary malformations (CM) cause significant psychosocial complications. Pulsed dye laser (PDL) treatment at 6–12‐weekly intervals under general anaesthesia (GA) commencing in infants at 6 months of age remains the standard of care in order to achieve maximal improvement prior to school age. The safety of repeated GA in children is controversial. Shortening the time between treatments increases the number that can be delivered prior to 6 months of age, thus reducing the number of subsequent treatments needed under GA. We investigated the safety and effectiveness of more frequent PDL treatment of CM in infancy via a pilot, prospective patient‐controlled study of 10 patients. Using 595 nm (Vbeam) PDL, the entire CM was treated initially, then half the CM randomly allocated to 2‐weekly and half to 3‐monthly intervals for two further treatments. Photographs of the CM taken 3 months after treatment completion were evaluated by an independent, blinded dermatologist. Nine infants completed the study. Three infants (33%) had more improvement on the 2‐weekly treated side and four (44%) had more improvement on the 3‐monthly treated side. Two patients (22%) showed no difference between sides. Treatments were well tolerated without complications. We conclude that 2‐weekly PDL treatments of CM in infants aged under 6 months is effective and well tolerated without adverse effects. Our preliminary data suggest a possible superior efficacy with 3‐monthly treatment intervals; however, larger studies are warranted for stronger evidence. More frequent non‐GA treatment of CM in infants should be further investigated to decrease the risk of repeated GA exposure in young children.     

Challenges in Pulmonary Risk Assessment and Perioperative Management in Bariatric Surgery Patients

Bariatric surgery has serious associated medical comorbidity and procedure-related risks and is, thus, considered an intermediate-to-high-risk non-cardiac surgery. Altered respiratory mechanics, obstructive sleep apnea (OSA), and less often, pulmonary hypertension and postoperative pulmonary embolism are the major contributors to poor pulmonary outcomes in obese patients. Attention to posture and positioning is critical in patients with OSA. Suspected OSA patients requiring intravenous narcotics should be kept in a monitored setting with frequent assessments and naloxone kept at the bedside. Use of reverse Tredelenburg position, preinduction, maintenance of positive end-expiratory pressure, and use of continuous positive airway pressure can help improve oxygenation in the perioperative period.     

Consideration of appropriate clinical applications for cardiac xenotransplantation

The field of cardiac xenotransplantation has entered an exciting era due to recent advances in the field. Although several hurdles remain, the use of rapidly evolving transgenic technology has the potential to address current allogeneic donor pool constraints and mechanical circulatory system device limitations. The success of xenotransplantation will undoubtedly be dependent on specific patient selection criteria. Defining these particular indications for xenotransplantation is important as we approach the possibility of clinical applications.     

Endoscopic Diagnosis of a Clinically Silent Aortoesophageal Fistula: Case Report and Review of the Literature

We report a rare case of a secondary aortoesophageal fistula discovered incidentally during elective upper endoscopy. The patient had previously undergone repair of a descending thoracic aortic aneurysm with a Dacron interposition graft. Esophagoscopy 2 months after the aneurysm repair demonstrated a large mid-esophageal erosion with visualization of the aortic graft at the base. The aortoesophageal fistula had been clinically silent to this point. During preparation for surgery the patient developed large-volume esophageal hemorrhage and died following attempted endovascular repair of the fistula. A review of the literature on the diagnosis and surgical management of aortoesophageal fistula is presented.Presented at the 30th Annual Meeting of the Military Society for Vascular Surgery, Bethesda, MD, December 5, 2002.     

Outcome profiles of locoregional disease after radical prostatectomy and radiotherapy

The purpose of the present study was to examine the outcome profiles of a large number of patients with locally advanced adenocarcinoma of the prostate following radical perineal prostatectomy (RPP) for clinically organ-confined disease. Of 1662 men who underwent RPP performed by a single surgeon between January 1972 and January 1999, 692 patients (41.6%) aged a median of 66.1 years were found to have extracapsular disease on pathological evaluation. The extent of disease was categorized as either specimen-confined (n=355) or margin-positive (n=337). The histological grade of the cancer was characterized using the Gleason score. Time to biochemical failure, defined as a prostate-specific antigen (PSA) level of ≥0.5 ng/ml, and cancer-associated survival were the end points of our outcome analysis using the Kaplan-Meier product-limit method. The median time to cancer-associated death for patients with specimen- confined and margin-positive disease was 18.5 and 13.1 years, respectively. After 5 years, 37% and 54% of the patients with specimen-confined and margin-positive disease, respectively, had PSA failure. Prostate cancer patients with a Gleason score of 5–6, 7, and 8–10 experienced a median time to cancer-associated death of 19.9, 19.2, and 10.5 years, respectively. A subset of patients undergoing adjunctive radiation therapy (XRT) relapsed biochemically after a median period of approximately 18 months. RPP provides a substantial disease-control benefit in patients with specimen-confined cancer. The time to biochemical failure and the time to cancer-associated death are significantly influenced by the biology of the underlying disease, necessitating long-term follow-up in the outcome analysis of any modality of treatment for prostate cancer. A benefit of early adjunctive XRT for local failure remains to be determined.     

Lymph node metastasis in T1 adenocarcinoma of the colon and rectum

The biology of colorectal cancer differs according to location within the large intestine. To evaluate the clinical significance of tumor location as a risk factor for lymph node metastasis (LNM), we performed a detailed pathological review of T1 adenocarcinomas of the colon and rectum. T1 adenocarcinomas of the colon and rectum treated by radical resection (n = 428) were identified from prospective clinical databases at two institutions. Tumor location was assigned as right colon (cecum to transverse), left colon (splenic flexure to sigmoid), or rectum (0–18 cm from AV). Pathology slides were reviewed, extent of submucosal invasion (sm width, sm depth) was quantified using an optical micrometer, and morphologic features of the cancer and its infiltrating margin were recorded. The overall rate of LNM was 10%. On univariate analysis, LNM was significantly more common in the rectum (27/176, 15%) compared to the left colon (13/160, 8%, p = .04) or right colon (3/92, 3%, p = .003). However, on multivariate analysis, deep submucosal invasion and lymphovascular invasion were independent and significant risk factors, whereas tumor location was not. T1 colorectal cancers have a progressively higher risk of LNM as their location becomes more distal. However, the increasing rate of LNM observed in cancers of the left colon and rectum is explained by a higher prevalence of high-risk pathologic features. In early colorectal cancers, tumor morphology is the strongest clinical predictor of metastatic behavior. Presented at the Forty-Fifth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004 Presented at the Forty-Fifth Annual Meeting of The Society for Surgery of the Alimentary Tract, New Orleans, Louisiana, May 15–19, 2004