Erythropoietin: clinical applications.

The last few years have seen an enormous increase in our knowledge on the haematopoietic growth factor erythropoietin (Epo), firstly with its purification and determination of its primary amino acid sequence, and more recently with the isolation of the Epo gene and its expression in mammalian cell lines. This review article summarizes the crucial biological features of Epo and critically examines the main results obtained in clinical trials on humans.     

Chemical synthesis and structure-activity relations for ANF analogues

Chemical synthesis of a new peptide hormone allows absolute confirmation of the peptide's structure, allows physiologic and pharmacologic evaluation of the hormone's properties in vivo and in vitro, and permits development of a radioimmunoassay for the hormone. The study of the effects of structure modification on the bioactivity of atrial natriuretic factor (ANF) is at the earliest stages of defining minimum molecular size, aspects of the bioactive conformation, and the contribution of each side chain to receptor binding. A particular problem in the evaluation of structure-function studies with ANF is the diversity of bioassays used by various laboratories.     

Electrogastrography. Evolution and clinical applications

Electrogastrography (EGG) is a non invasive technique of recording gastric myoelectrical activity by cutaneous electrodes. Although first reported about 70 years ago, the development of this methodology has been very slow, mainly because of several shortcomings in data acquisition, interpretation of EGG data and poor correlation with the antral contractile activity. Recently, EGG has received increasing interest and technical improvements. The better quality of the signal obtained and the applications with automated signal processing, have improved the interpretation of the EGG. For this reasons, the number of EGG applications, both experimental and clinical, has rapidly increased. However, the lack of invasivity of this methodology has suggested some clinical applications which probably exceeded the specific possibility of the EGG. We aimed in this study at analysing several parameters, whose clinical relevance is not clearly understood, obtained by the automatic analysis, to identify patients with gastric electrical abnormalities between 10 patients with abnormal gastric emptying and 10 healthy controls. The best separation between these two groups was obtained by combining both mean dominant frequency and power.     

Nuclear medicine in ARDS: clinical applications.

ARDS is still characterized by an exceedingly high mortality rate. Methods are then needed to detect ARDS at the earliest clinical stage. Over the last decade, radioisotopic techniques have developed, aimed at demonstrating an abnormal neutrophil sequestration in the lung or detecting functional alterations of the pulmonary alveolar-capillary barrier, which likely precede the onset of respiratory distress. Preliminary application of these techniques in patients with ARDS yielded conflicting results in terms of sensitivity and specificity. On the contrary, lung vascular abnormalities have been consistently observed in patients with ARDS studied by perfusion lung scanning. They consist of focal, non segmental perfusion defects, mostly peripheral and dorsal, with redistribution of blood flow to non-dependent lung regions. This scintigraphic pattern may be considered typical of ARDS since it is not observed in other acute lung disorders. Perfusion abnormalities on lung scans are detectable from the very early stage of ARDS and correlate with the severity of the syndrome as reflected by gas exchange, central hemodynamics, and chest radiography. Perfusion lung scanning may then be used in the early detection and evaluation of vascular injury in ARDS.     

Continuous flow peritoneal dialysis: clinical applications.

Continuous flow peritoneal dialysis (CFPD) can be considered a special form of hemodialysis, during which peritoneal effluent, rather than blood, is being dialyzed using standard hemodialysis technology. Preliminary clinical data have identified poor mixing of the dialysis solution, streaming and recirculation as a significant limitation in achieving maximal solute removal and ultrafiltration. Better catheter designs remain a research priority in this field. Although the clinical experience is limited to short-lasting experiments with CFPD, the preliminary data strongly support the superiority of CFPD as the most effective peritoneal dialysis modality in removing small solutes and providing high ultrafiltration rates. The levels of clearance attained are similar to quotidian hemodialysis. In addition, it is expected that the current methodology will provide a new standard of solution biocompatibility.     

Left atrial size: physiologic determinants and clinical applications.

Left atrial (LA) enlargement has been proposed as a barometer of diastolic burden and a predictor of common cardiovascular outcomes such as atrial fibrillation, stroke, congestive heart failure, and cardiovascular death. It has been shown that advancing age alone does not independently contribute to LA enlargement, and the impact of gender on LA volume can largely be accounted for by the differences in body surface area between men and women. Therefore, enlargement of the left atrium reflects remodeling associated with pathophysiologic processes. In this review, we discuss the normal size and phasic function of the left atrium. Further, we outline the clinically important aspects and pitfalls of evaluating LA size, and the methods for assessing LA function using echocardiography. Finally, we review the determinants of LA size and remodeling, and we describe the evidence regarding the prognostic value of LA size. The use of LA volume for risk stratification is an evolving science. More data are required with respect to the natural history of LA remodeling in disease, the degree of LA modifiability with therapy, and whether regression of LA size translates into improved cardiovascular outcomes.     

Three-dimensional Doppler. Techniques and clinical applications.

AIMS: Colour Doppler is the most widely used technique for assessing valve disease, but eccentric regurgitant jets cannot be visualized and measured by conventional 2D techniques. We have developed a new procedure for three-dimensional (3D) reconstruction of colour Doppler signals. METHODS AND RESULTS: Fifty patients with mitral regurgitation underwent transoesophageal echocardiography and 3D acquisition. The severity of mitral regurgitation was assessed by angiography and the regurgitant volumes were measured by pulsed Doppler. The jet areas were calculated by planimetry from conventional colour Doppler; the jet volumes were obtained by 3D Doppler. A higher degree of mitral regurgitation was found in the patients with eccentric jets. While jet areas showed poor correlation with regurgitant volumes (r = 0.61), jet volumes correlated significantly with regurgitant volumes (r = 0.93; P < 0.001). While jet areas failed to identify patients with different grades of regurgitation, jet volumes could so discriminate. CONCLUSIONS: 3D Doppler revealed new patterns of regurgitant flow and allowed a more accurate semiquantitative assessment of complex asymmetrical regurgitant jets. Three-dimensional colour Doppler has a great potential for becoming a reference method for the assessment of patients with heart valve disease.     

Transvenous atrial defibrillation--techniques and clinical applications.

Atrial fibrillation (AF) is the most common arrhythmia requiring treatment. The most desirable therapy may be restoration and maintenance of sinus rhythm. Limitations of the current methods for cardioversion of AF have prompted the development of transvenous atrial defibrillation (TADF) as an alternative and more effective technique for converting AF. Recent advances in the technique of TADF, particularly in the design and configuration of the electrodes, and the use of an optimal biphasic shock waveform have dramatically improved the efficacy of TADF for the termination of all types of AF. The reduction in voltage and energy requirements for cardioversion by TADF may allow the procedure to be performed with little or no sedation and the risk of general anesthesia may be avoided. Both experimental and clinical studies have demonstrated the feasibility, safety, and efficacy of using TADF as a new temporary or "permanent" mode of electrical therapy for AF. It has several potential applications, from acute termination of AF in the electrophysiology laboratory and in patients who have failed to respond to external cardioversion, to its use as an implantable device for treating recurrent AF. This article reviews the current technique and clinical applications of TADF for treatment of AF.     

Diuretics in the therapy of hypertension: current status.

Diuretics were the first effective oral agents for treating hypertension. They have proven to be safe and effective. Recently, they have been scrutinized as possibly being responsible for certain side effects that may increase risk for cardiovascular morbidity and mortality. A careful review of the literature suggests this class of agents warrants continued use as first-line therapy of hypertension, especially in certain demographic groups. However, monitoring of potential baleful effects and a general reduction in dosage are appropriate. Furthermore, selection of other (alternative) agents for monotherapy is advised in certain clinical circumstances.     

Signal-averaged electrocardiography: history, techniques, and clinical applications.

Signal averaging principles have been utilized since around 1875. Their application in medicine to enhance biologic signals was first made in 1947 for improved detection of electroencephalographic signals. The year 1963 marked the first application of this technique to cardiac signals. The more prevalent use in adult cardiology is in the detection of ventricular late potentials (VLPs) which correspond to areas of delayed ventricular activation as slowed conduction velocity. These VLPs have value in predicting the likelihood of malignant ventricular arrhythmias after myocardial infarction (MI). Negative predictive values on the order of 96-99% are convincing as to their ability to predict no arrhythmic event post-MI. Positive predictive values, on the other hand, are poor (10-29%) but improve (35-62%) in combination with other parameters such as depressed left ventricular function and frequent ventricular ectopy. Additional accepted uses for the signal-averaged electrocardiogram (SAECG) include prediction of successful ablative surgery for intractable ventricular tachycardia and facilitating evaluation of patients presenting with syncope of an unclear etiology. Potential future applications of the SAECG are (1) in following patients for rejection after cardiac transplant, (2) as a screening tool for the need for electrophysiologic study, (3) as a predictor of vessel patency after thrombolysis or percutaneous transluminal coronary angiography, and (4) as a tool to assess proarrhythmia. As the technique of signal averaging continues to evolve, its applications may become more diverse and its clinical effectiveness may improve.     

Ursodeoxycholic acid: Mechanism of action and novel clinical applications.

Ursodeoxycholic acid (UDCA) is used in the treatment of cholestatic liver diseases, gallstone dissolution, and for patients with hepatitis C virus infection to ameliorate elevated alanine aminotransferase levels. The efficacy of UDCA treatment has been debated and the mechanisms of action in humans have still not defined. Suggested mechanisms include the improvement of bile acid transport and/or detoxification, cytoprotection, and anti-apoptotic effects. In this review, we summarize the proposed molecular mechanisms for the action of UDCA, especially in hepatocytes, and also discuss the putative future clinical usage of this unique drug.     

Liver angioscintigraphy: clinical applications

Liver angioscintigraphy (LAS) is a radio-isotope method for the investigation of liver perfusion and its alteration in various hepatic diseases. It measures the arterial and portal venous fractions of total liver blood flow. The percentage of liver blood flow supplied by hepatic artery is estimated mathematically by the hepatic perfusion index (HPI), normally between 25 % and 40 %. The decrease of portal blood flow in liver cirrhosis is compensated ("buffer" mechanisms) by increased arterial supply, with higher HPI value. For a patient with chronic liver disease, HPI over 50% suggests arterialization of hepatic perfusion, guiding the diagnose to liver cirrhosis. Splenic curve is completing the diagnostic information of the hepatic curve. Corroborated with per rectal scintigraphy and liver SPECT, LAS offers a good hemodynamic staging of chronic inflammatory liver diseases. Malignant tumors (primitive or metastases) increase the arterial supply of the liver and decrease the portal flow, HPI being over 50% (currently 65 % - 90 %). Benign tumors do not change portal/arterial liver blood flow ratio. SPECT or non-scintigraphic morphological investigations increase the diagnostic value of LAS for primitive liver tumors. Liver cancer occurring on cirrhosis is a limitative factor for LAS. Hepatic metastases increase the arterial perfusion (and HPI value) very quickly, before their size allows morphologic imaging diagnosis. LAS is therefore an early method to diagnose liver metastases being especially used in colorectal cancer. Other clinical applications of LAS are: follow up of liver toxicity of drugs, evaluation of portal vein permeability, post surgery follow up of the liver tumor patients.