Detection of circulating crosslinked fibrin derivatives by a heat extraction-SDS gradient gel electrophoretic technique

A technique has been developed to identify and quantitate unique plasmic degradation products of crosslinked fibrin in plasma. In this method, fibrin derivatives are extracted by heat precipitation and dissolved with disulfide bond reduction, after which the crosslinked gamma-gamma chain remnants are identified by SDS-polyacrylamide gradient gel electrophoresis and quantitated by densitometric analysis. A heterogenous group of gamma-gamma chains with molecular weights between 100,000 and 76,000 daltons was identified in lysates of crosslinked fibrin during plasmic degradation in vitro. Three stages of crosslinked fibrin degradation have been arbitrarily defined based primarily on the extent of degradation of these gamma-gamma polypeptide chains. As little as 20 microgram of crosslinked fibrin digests added to 1 ml of normal plasma could be detected by the heat-extraction--gel- electrophoresis technique, identifying the gamma-gamma derivatives with molecular weights of 96,000, 86,000, 82,000, and 76,000 daltons. Plasmic derivatives of gamma-gamma chains were not found in normal plasma, but they were identified in the plasma of patients with disseminated intravascular coagulation and deep-vein thrombosis, both before and in increased quantity during successful thrombolytic therapy.     

Molecular markers to guide primary radical treatment selection in localized prostate cancer

Localized prostate cancer can be effectively treated by surgical or radiotherapy approaches. In selected cases, active surveillance may also be appropriate. The choice of therapy for an individual is dependent on a number of factors but it is well recognized that different therapies may work equally well. Conversely, many patients will fail a particular treatment despite apparently favorable disease characteristics. A priori knowledge of how a tumor will respond to a treatment would be a powerful tool toward tailored therapy. Very little attention has been paid to the role of biomarkers in predicting therapy-specific responses. In this article, the current evidence for the use of tissue biomarkers to guide radical therapy selection in localized prostate cancer is discussed. Treatment failure mechanisms and the future design of research are also considered with regard to how they might inform biomarker discovery and validation in this important area of clinical need.     

The bottom line: Outcomes after conservation treatment in anal cancer

At the Department of Radiation Oncology, Westmead Hospital, between 1980 and 2000, 60 patients with squamous cell carcinoma of anal canal or margin (including 15 with Stage IIIA or IIIB) were treated radically; 55 received chemoradiation (89% were prescribed mitomycin C and 5‐fluorouracil). Five‐year overall survival was 64% (95% confidence interval (CI): 48–79%), with a median survival of 9.75 years (median follow up 5.6 years, range 5 months to 22.5 years). Ten patients have died of disease. At 2 years the local control rate was 86%, and colostomy‐free survival was 83%. Relapse after 2 years was uncommon. Tumour size was the main factor driving outcomes, especially survival. Patients with larger tumours (T > 4 cm) had a hazard ratio for survival of 5.7 (95% CI: 1.8–17). Fourteen (24%) patients experienced treatment interruptions as a result of acute toxicity, including one death from neutropoenic sepsis. Seven (12%) patients, in total, experienced one or more late toxicities, grade 3 or above, including four women (all postmenopausal) who developed a radiation‐induced bone injury. Most patients with anal cancer can expect to retain a functional sphincter after chemoradiation/radiation. Further studies are in progress to determine the optimal chemoradiation protocol.     

Doppler flow characteristics in the assessment of pulmonary artery pressure in ductus arteriosus

The Doppler spectral pattern of flow through the ductus arteriosus was studied in 117 patients. In 37 who underwent catheterisation, Doppler records and aortic and pulmonary artery pressure were available (21 simultaneously with two catheters) for review while the others had surgical ligation of the duct on the basis of the results of non-invasive tests. Four flow patterns were obtained: (a) continuous flow, maximum velocity in late systole with gradual fall throughout diastole; (b) continuous flow, high systolic flow with rapid fall to a very low early diastolic velocity maintained throughout diastole; (c) continuous low velocity, maximum in late diastole; and (d) bidirectional flow. Flow pattern (a) was associated with normal or slightly raised pulmonary artery pressure; (b) with raised pulmonary artery pressure; and (c) and (d) with pulmonary artery pressure at systemic values. Comparison of the Doppler and measured pressure differences between the great arteries was reasonably good for peak values but poor for the trough readings. Doppler ultrasound clearly showed ductal flow; the flow pattern gave an indication of the pulmonary artery pressure, but pressure measurement by application of the Bernoulli equation to the flow velocities cannot yet be regarded as reliable.     

Intrauterine spermatic cord torsion in the newborn: sonographic and pathologic correlation

In five newborn patients with spermatic cord torsion, sonography demonstrated an enlarged and globular testis, hydrocele, and skin thickening. In four of these patients the testicular parenchyma was heterogeneous. Peripheral hypoechoic areas were seen in two of the four patients; the other two had a central hypoechoic region and a peripheral echogenic rim. The testis in the fifth patient was diffusely hyperechoic. Duplex Doppler sonography performed in two patients failed to demonstrate any signal in the spermatic cord in either the abnormal or contralateral hemiscrotum. Scintigraphic findings were positive for testicular torsion in two patients and equivocal in three patients. Surgery was performed 2-12 days after sonography and established the diagnosis of spermatic cord torsion. Pathologic examination demonstrated hemorrhagic infarction of the entire testis as well as scattered calcifications. The authors conclude that a solid globular testicular mass seen during the neonatal period is suggestive of intrauterine spermatic cord torsion.     

Influence of colour Doppler echocardiography on the ultrasonic assessment of congenital heart disease: a prospective study.

OBJECTIVE--To evaluate the additional information provided by colour Doppler in the ultrasonic assessment of congenital heart disease. PATIENTS AND METHODS--A prospective study of 215 children (age range 1 day-16 years) presenting with clinical signs of congenital heart disease. RESULTS--Colour Doppler was essential for the diagnosis of an anomalous left coronary artery and altered the management of a patient initially diagnosed as having cardiomyopathy. Colour Doppler provided extra information, but without major impact on management, in the following: the diagnosis of ventricular septal defects associated with other defects, of multiple ventricular septal defects, of anomalous pulmonary venous drainage, and of mild mitral regurgitation; the demonstration of site of coarctation, of stenotic or hypoplastic pulmonary artery branches, of unobstructed flow through a right atrial membrane, and of left ventricle to right atrium regurgitation; the assessment of the width of the duct and of flow through the patent foramen ovale in transposition and tricuspid atresia; the differentiation of pulmonary atresia from critical pulmonary stenosis and the measurement of maximum velocity of tricuspid regurgitation. CONCLUSIONS--Ideally all patients should undergo colour Doppler studies before cardiac surgery to ensure a more accurate diagnosis. However, since the additional information provided does not affect the management in most patients, machines without colour Doppler can provide a satisfactory service in paediatric cardiology centres in countries where resources are limited.