Regional myocardial dysfunction: evaluation of patients with prior myocardial infarction with fast CT

A prototype ultrafast cine computed tomographic (CT) scanner, designed specifically for cardiac imaging, was used to evaluate a preliminary series of patients with prior myocardial infarction (n = 21) and a control group without coronary artery disease (n = 5). Multilevel 50-msec CT scan exposures were obtained during peripheral intravenous bolus injections of contrast medium. A comparison was made between cine-CT scans and standard left ventriculographic images in assessing segmental left ventricular motion. Results indicate that cine CT, performed at sufficiently rapid speeds (20 scans per second) to allow useful analysis of regional ventricular wall motion, can provide adequate image quality. Analysis of 110 segments revealed a good correlation (90.9%) between the two techniques in characterizing normal from abnormal regional wall motion. Cine CT, based on this initial study, demonstrates considerable potential for evaluating not only cardiac chamber dimensions but also segmental wall dynamics.     

Fabry disease: diagnosis and management, with emphasis on the renal manifestations

PURPOSE OF REVIEW: Interest in the diagnosis and treatment of Fabry disease has been greatly stimulated by the availability of Food and Drug Administration-approved, effective enzyme-replacement therapy. This review will update the progress in this area over the last 18 months that effective enzyme-replacement therapy has become available. RECENT FINDINGS: Fabry disease is often associated with proteinuric chronic kidney disease, and it appears that the treatment paradigms that have proven to be so effective in diabetes mellitus and other forms of proteinuric renal disease are also effective, in conjunction with enzyme-replacement therapy for treating the renal manifestations of Fabry disease. As such, Fabry disease represents an interesting example of progressive proteinuric renal disease in which the usual blood pressure is lower than in other renal diseases. This makes the use of effective anti-proteinuric therapy challenging, especially considering the autonomic dysfunction that appears to be part of the disease. Recent advances are considered in this review, with emphasis on the role of kidney biopsy, effective dosing and maximal comprehensive therapy of Fabry disease. SUMMARY: Maximal, comprehensive therapy for Fabry disease includes effective enzyme-replacement therapy and all of the adjunctive therapies that are currently used to treat all forms of proteinuric chronic kidney disease. It is anticipated that this approach will preserve kidney function and also benefit the cardiac and cerebrovascular systems in patients with Fabry disease.     

Oxidative stress in hypertension and chronic kidney disease: role of angiotensin II

Angiotensin II, via the type 1 (AT1) receptor, stimulates oxidative stress. The vasculature, interstitium, juxtaglomerular apparatus, and the distal nephron in the kidney express nicotinamide adenine dinucleotide phosphate (NADPH) oxidase that generates superoxide anion, which is an important component of angiotensin II-induced oxidative stress. The angiotensinogen gene is stimulated by NF-kappaB activation, which is sensitive to the redox ratio, providing a positive feedback loop that can upregulate angiotensin II production. Oxidative stress can accompany hypertension in many models, including the spontaneously hypertensive rat (SHR), angiotensin II-infused rats, renovascular hypertension, and the deoxycorticosterone acetate (DOCA) salt model of hypertension. AT1 receptor antagonists can abrogate the effects of angiotensin II on oxidative stress, thus providing an important mechanistic insight onto the renal protective effects of these agents in conditions associated with angiotensin II excess.     

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.     

Bupropion sustained release for the treatment of hypoactive sexual desire disorder in premenopausal women

Premenopausal women meeting operational criteria for idiopathic, acquired, global hypoactive sexual desire disorder were studied in a randomized, double-blind, placebo-controlled, multiple-site escalating dose 112-day trial of bupropion sustained release. Outcome was measured by investigator-rating and self-administered questionnaires. All measures indicated greater sexual responsiveness in women receiving bupropion. The Changes in Sexual Functioning Questionnaire indicated that bupropion had significant effects on increasing measures of sexual arousal, orgasm completion, and sexual satisfaction.     

Restoration of wild-type conformation to full-length and truncated p53 proteins: specific effects of ATP and ADP

Mutations in the core domain of the tumour suppressor p53 gene occur in over 50% of human cancers and are not present in normal cells hence p53 protein is a prime target for anti-cancer therapy. In full-length p53 protein, mutations have been shown to destabilize protein structure from wild-type to mutant conformation resulting in differential exposure of conformational epitopes PAb1620, PAb240 and PAb246 in murine p53 protein. In recent studies, putative anti-cancer agents have been designed for rescuing wild-type p53 conformation and function. Using full-length and truncated murine p53 proteins derived from the baculoviral system, we analyzed the recovery of PAb246 and PAb1620 epitopes and have identified regions of p53 required for optimal renaturation in vitro to wild-type. The influence of ATP and ADP on the process was also determined. We demonstrate a difference in the dose-dependent effect of ATP and ADP on renaturation of full-length wild-type and monomeric p53 proteins. Putative ATP binding sites were identified at residues 1-67 and 98-303 in conjunction with a putative ADP binding site at residues 98-303 and negative regulation of ATP/ADP binding by the proline-rich region. Improved efficacy and reduced toxicity of anti-cancer therapy may depend upon compounds engineered to rescue hot-spot core mutations in the context of full-length p53.     

Persistence of oropharyngeal Candida albicans strains with reduced susceptibilities to fluconazole among human immunodeficiency virus-seropositive children and adults in a long-term care facility

Nineteen oropharyngeal Candida albicans isolates from six children and seven adults living with AIDS at the Russia AIDS Centre, Moscow, from 1990 to 1998 were selected for molecular typing. Two fluconazole-resistant C. albicans genotypes were identified from a child who contracted human immunodeficiency virus infection during the Elista Hospital outbreak in the Kalmyk Republic in 1989. Highly related strains were observed 4 years later in the oral lesions and colonization of two patients and a health care worker. There may be a tendency for persons who are living with AIDS in a long-term care facility and who receive fluconazole therapy for oropharyngeal candidiasis to harbor and spread fluconazole-resistant C. albicans strains.