Anti-beta(1)-adrenergic receptor antibodies and heart failure: causation, not just correlation

Antibodies specific for the beta(1)-adrenergic receptor are found in patients with chronic heart failure of various etiologies. From work presented in this issue of the JCI, we can now infer that these antibodies actually contribute to the pathogenesis of chronic heart failure. This commentary discusses mechanisms by which these antibodies may engender cardiomyopathy.     

Should patients with a pre-operative prostatespecific antigen greater than 15ng/ml be offered radical prostatectomy?

Background Patients with prostate cancer with a pre-operative prostate-specific antigen (PSA) τ;15ng/ml who undergo radical retropubic prostatectomy (RRP) generally do not have a good outcome, yet may have organ-confined cancer and should be offered the option of surgery. Aim To assess the outcome of patients who underwent RRP with a pre-operative PSA ≥ 15ng/ml. Methods Thirty-four patients, mean pre-operative PSA: 25.46ng/ml (15.03–76.6) and mean Gleason score: 6.4 (5–9) were assessed. Results Two groups were identified. Group I: 41% (14/34) have no biochemical recurrence to mean follow up of 58 months (30–106). Mean PSA: 18.8ng/ml (15.03–25.84). Mean Gleason score: 6.1 (5–7). Clinical stage: T1c in 80%. No patient had seminal vesicle or lymph node involvement. Group II: 59% (20/34) have biochemical recurrence or died (3) from their disease to mean follow up of 66 months (36–98). Mean PSA: 28.9ng/ml (15.28–76.6). Mean Gleason score: 6.7 (5–9). Clinical stage: T1c in 25%. Eleven patients had seminal vesicle (8) involvement or positive lymph nodes (3) or both (2). Conclusion RRP seems feasible in patients whose pre-operative PSA is between 15 and 25ng/ml with stage T1c, Gleason score ≤ 7 and negative lymph node frozen section.     

Rationale and design of the avoiding cardiovascular events through combination therapy in patients living with systolic hypertension (ACCOMPLISH) trial: the first randomized controlled trial to compare the clinical outcome effects of first-line combination therapies in hypertension

Reducing blood pressure (BP) to target levels is a major priority in preventing clinical events in hypertension. Typically this requires more than one drug, and recent guidelines on hypertension management therefore recommend starting with combination treatment in many patients. Diuretics have often been part of such therapy, usually paired with angiotensin converting enzyme (ACE) inhibitors or similar agents; but calcium channel blockers are also highly efficacious in reducing BP when combined with ACE inhibitors. In addition, these drug classes, separately and in combination, appear to have vasculoprotective properties. Because the primary goal of treating hypertension is to enhance survival and reduce cardiovascular outcomes, the Rationale and Design of Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) trial is designed as the first blinded and randomized study to prospectively compare the effects on these endpoints of two antihypertensive combinations, benazapril/hydrochlorothiazide (force titrated to 40/12.5 mg) and amlodipine besylate/benazapril (force titrated to 5/40 mg). The doses can be further titrated to 40/25 mg or 10/40 mg, and other classes of drugs can be added as needed for optimal BP control. The primary study endpoint is a composite of cardiovascular mortality and morbidity. The study will be performed in hypertensive patients (systolic BP > or = 160 mm Hg or currently on antihypertensive therapy) with risk factors for cardiovascular events (prior events, target organ damage, kidney disease, or diabetes). A total of 6300 subjects will be randomized to each group with the expectation that a total of 1642 primary endpoints will occur during a 5-year period, providing 90% power to detect the 15% relative reduction in events (alpha = 0.05) hypothesized to favor the amlodipine besylate/benazapril group. The ACCOMPLISH study will be performed in the United States and Europe. The first patient was randomizedduring 2003, and the trial should conclude in 2008.     

Breath-hold magnetic resonance cholangiopancreatography in the evaluation of malignant pancreaticobiliary obstruction

OBJECTIVE: This study was designed to determine the effectiveness of magnetic resonance cholangiopancreatography (MRCP) using a breath-hold single-shot fast spin echo (SSFSE) technique in imaging patients with malignant biliary and/or pancreatic duct obstruction. METHODS: One hundred thirty-one breath-hold MRCP studies in patients with malignant pancreatic and/or biliary obstruction were evaluated. Pathologic diagnoses included pancreatic cancer, biliary malignancy, gallbladder carcinoma, hepatic neoplasms, malignant lymphadenopathy, and ampullary carcinoma. Two observers independently reviewed the images in a blinded fashion to assess the level of obstruction and the site of underlying tumor. RESULTS: The level of obstruction was correctly identified in 104 of 131 cases (79%) by observer 1 and in 107 of 131 cases (82%) by observer 2. The site of underlying tumor was correctly identified in 113 of 131 cases (86%) by observer 1 and in 110 of 131 cases (84%) by observer 2. CONCLUSION: Magnetic resonance cholangiopancreatography utilizing the SSFSE technique can accurately assess the level of obstruction and the site of underlying tumor in patients with malignant pancreaticobiliary obstruction, without the risks of cholangiography. This MRCP technique allows for visualization of intra- and extraductal anatomy and pathology.     

Appendicitis During Pregnancy

Acute appendicitis is the most common extra-uterine surgical emergency requiring immediate surgical intervention during pregnancy [1]. Six young female patients presented with appendicitis during May 1996 to May 2001 in different service hospitals. Five patients underwent emergency appendectomy successfully. Gestational age at presentation included first trimester in 4 patients, second trimester in 2 patients and none in third trimester. 84% had pathologically proven acute appendicitis. One patient presented with appendicular lump in first trimester, proved on ultra sonography examination, which was treated by Oshner Sherren regime and subsequently interval appendectomy was done in second trimester. No long term adverse maternal morbidity or mortality was reported. One patient had premature onset of labour and delivered. Natural history of acute appendicitis is not changed during pregnancy while gestational physiological changes obscure the accurate diagnosis of acute appendicitis.Key Words: Acute appendicitis, Appendectomy, Pregnancy     

Prospects for cardiovascular research

Cardiovascular disease is the greatest threat to human life and health. The past decade has seen remarkable progress in clinical and basic cardiovascular research, and many areas of opportunity are promising. The pace of current progress in clinical and basic research is such that remarkable improvement in the quality and length of life for those at risk for cardiovascular disease is likely.     

Overexpression of the cardiac beta(2)-adrenergic receptor and expression of a beta-adrenergic receptor kinase-1 (betaARK1) inhibitor both increase myocardial contractility but have differential effects on susceptibility to ischemic injury

Cardiac beta(2)-adrenergic receptor (beta(2)AR) overexpression is a potential contractile therapy for heart failure. Cardiac contractility was elevated in mice overexpressing beta(2)ARs (TG4s) with no adverse effects under normal conditions. To assess the consequences of beta(2)AR overexpression during ischemia, perfused hearts from TG4 and wild-type mice were subjected to 20-minute ischemia and 40-minute reperfusion. During ischemia, ATP and pH fell lower in TG4 hearts than wild type. Ischemic injury was greater in TG4 hearts, as indicated by lower postischemic recoveries of contractile function, ATP, and phosphocreatine. Because beta(2)ARs, unlike beta(1)ARs, couple to G(i) as well as G(s), we pretreated mice with the G(i) inhibitor pertussis toxin (PTX). PTX treatment increased basal contractility in TG4 hearts and abolished the contractile resistance to isoproterenol. During ischemia, ATP fell lower in TG4+PTX than in TG4 hearts. Recoveries of contractile function and ATP were lower in TG4+PTX than in TG4 hearts. We also studied mice that overexpressed either betaARK1 (TGbetaARK1) or a betaARK1 inhibitor (TGbetaARKct). Recoveries of function, ATP, and phosphocreatine were higher in TGbetaARK1 hearts than in wild-type hearts. Despite basal contractility being elevated in TGbetaARKct hearts to the same level as that of TG4s, ischemic injury was not increased. In summary, beta(2)AR overexpression increased ischemic injury, whereas betaARK1 overexpression was protective. Ischemic injury in the beta(2)AR overexpressors was exacerbated by PTX treatment, implying that it was G(s) not G(i) activity that enhanced injury. Unlike beta(2)AR overexpression, basal contractility was increased by betaARK1 inhibitor expression without increasing ischemic injury, thus implicating a safer potential therapy for heart failure.     

Solitary bronchioloalveolar carcinoma: CT criteria

The computed tomographic (CT) scans of 30 patients with solitary bronchioloalveolar carcinoma were reviewed. Common features at CT included the peripheral or subpleural location of a pulmonary mass (25 cases), pseudocavitation (18 cases), heterogeneous attenuation (17 cases), irregular margins forming a star pattern (22 cases), and pleural tags (21 cases). Using these CT criteria, four independent observers attempted to identify cases of bronchioloalveolar carcinoma from a larger sample of lung cancers and benign lesions by categorizing a series of test cases into four probability categories. Although the bronchioloalveolar carcinomas were correctly ranked in the two highest probability categories 75% of the time (in 45 of 60 cases), there was considerable overlap with other lung lesions, particularly with adenocarcinoma and large cell undifferentiated carcinoma. However, even though the typical features of bronchioloalveolar carcinoma are not invariable or highly specific, they are characteristic enough to suggest the diagnosis.     

Transdermal fentanyl for chronic pain in AIDS: a pilot study

This prospective, open-label, before-after trial was designed to compare the efficacy of oral opioids with that of transdermal fentanyl in severe AIDS-related chronic pain, as well as assess barriers, patient satisfaction, and side effects. Thirty-five sequentially selected male and female outpatients with AIDS who were at least 18 years old were enrolled. All had chronic pain requiring continuous treatment with > or = 45 mg/day oral morphine or an equivalent. Eighteen of the patients had a history of chemical dependency. Baseline data were collected while patients received their previously prescribed opioid; assessments were made again after a stable transdermal fentanyl dose (25--300 microg/h) had been maintained for 15 days. Patients completed the International Association for the Study of Pain Classification of Chronic Pain Syndromes questionnaire, the Brief Pain Inventory, and a Satisfaction With Pain Medication questionnaire for assessing pain intensity, relief, and interference with normal functioning. With transdermal fentanyl, pain severity scores decreased significantly, mean pain relief scores increased, and daily functioning measures improved significantly. Most adverse events were mild and unrelated to fentanyl use. Transdermal fentanyl was effective for chronic pain in both chemically dependent and non-chemically dependent patients with AIDS.