Monocular chromatic contrast threshold and achromatic contrast sensitivity in children born prematurely

PURPOSE: To study the effect of prematurity on monocular chromatic contrast thresholds (CCT) and achromatic contrast sensitivity (ACS). DESIGN: Case-control study. METHODS: A prospective study of 59 children born at less than 33 weeks' gestation was undertaken. Subjects were identified during routine neonatal screening for retinopathy of prematurity and recalled for testing at age 7 to 13 years. Five had stage 1 retinopathy of prematurity, seven had stage 2, and three had stage 3. Sixty-eight full-term children were recruited as controls. Those with major cerebral or eye disease were excluded. The CCT and ACS were measured monocularly in the eye with better visual acuity using static, computer-generated, sinusoidal gratings, displayed on a high-resolution monitor. The CCT and ACS were determined using a randomized double-staircase reversal algorithm. The ACS was measured at five spatial frequencies (0.22, 0.44, 0.88, 1.75, and 3.50 cycles/degree), and the CCT was measured along red-green and tritan confusion axes. RESULTS: Red-green (P =.326) and tritan (P =.910) contrast thresholds and ACS (P >.394 for all spatial frequencies) were similar to the control group. CONCLUSIONS: Previous research suggests that prematurity adversely affects color vision and ACS. This study used a computerized psychophysical test that minimized the test errors inherent in many previous studies. Unexpectedly, CCT and ACS were found to be similar to full-term children.     

Selection of an HEL-derived cell line expressing high levels of platelet factor 4

A platelet factor 4 (PF4)-expressing cell line, HELNeo, was derived from the human erythroleukemia cell line, HEL. This was achieved by stable transfection of HEL cells with a construct containing the rat PF4 promoter driving the gene coding for resistance to neomycin, followed by selection of neomycin-resistant clones. HELNeo cells were all nonadhering and about 5% of the cells had polyploid nuclei (> or = 8N), as compared with 1% in HEL cells. Immunohistochemistry showed that about 90% of the HELNeo cells contained PF4, whereas only approximately 5% of the HEL cells contained PF4. No significant parallel enrichment was observed for other megakaryocytic markers, such as the glycoprotein complex IIb/IIIa, von Willebrand factor, and platelet activation- dependent granule to external membrane glycoprotein (PADGEM), which were present to a similar extent in both HEL and HELNeo lines. The increased expression of PF4 in HELNeo cells was confirmed by transient expression assays and was associated with a fivefold increase in trans- acting factors binding to the PF4 promoter. These cells should be a rich source for purifying trans-acting factors binding to the PF4 gene. Moreover, our study shows how a lineage-specific promoter may be used to generate lineage-specific cell lines from a multilineage hematopoietic cell line.     

Valsartan in chronic heart failure

OBJECTIVE: To evaluate the evidence for valsartan in the treatment of heart failure and determine its need for formulary inclusion. DATA SOURCES: OVID and PubMed databases were searched (1983-June 2004) using the key words angiotensin-receptor blocker, heart failure, valsartan, Diovan, and angiotensin-converting enzyme inhibitor. Only English-language literature was selected. STUDY SELECTION AND DATA EXTRACTION: Pharmacology and pharmacokinetic evaluations for valsartan were selected. Prospective, randomized clinical trials investigating the use of valsartan and other angiotensin-receptor blockers (ARBs) in chronic heart failure were evaluated. DATA SYNTHESIS: Valsartan, a selective antagonist for angiotensin receptor subtype 1, is the first ARB to be approved for use in chronic heart failure. Clinical trial data support valsartan as an alternative to angiotensin-converting enzyme (ACE) inhibitors in ACE inhibitor-intolerant patients with chronic heart failure. Valsartan is generally well tolerated, with renal impairment, elevated serum creatinine and potassium levels, and dizziness being the most common adverse effects; consequently, patients experiencing those adverse events while taking ACE inhibitors are likely to experience them with valsartan. Although further study is needed, differences in effectiveness among races may exist with use of valsartan; however, at this time, valsartan is recommended as an alternative to ACE inhibitors regardless of race. Candesartan and losartan have been studied in similar settings. Candesartan's data support its use in heart failure; however, losartan's data have been less consistent. CONCLUSIONS: Valsartan is a safe and effective alternative for heart failure patients intolerant of ACE inhibitors. Valsartan has not been shown to be safe and effective when used in combination with ACE inhibitors.     

The distribution and prognosis of anomalous coronary arteries identified by cardiovascular magnetic resonance: 15?year experience from two tertiary centres

Background

Aberrant coronary arteries represent a diverse group of congenital disorders. Post-mortem studies reveal a high risk of exercise-related sudden cardiac death in those with an anomalous coronary artery originating from the opposite sinus of Valsalva (ACAOS) with an inter-arterial course. There is little documentation of lifetime history and long-term follow-up of patients with coronary artery anomalies.

Methods

Patients with anomalous coronary arteries undergoing cardiovascular magnetic resonance over a 15-year period were identified and classified by anatomy and course. Medical records were reviewed for major adverse cardiovascular events (MACE). Revascularisation or myocardial infarction counted only if occurring in the distribution of the anomalous artery.

Results

Consecutive patients with coronary artery anomalies were retrospectively identified (n = 172). Median follow-up time was 4.3 years (IQR 2.5–7.8, maximum 15.6). 116 patients had ACAOS of which 64 (55%) had an inter-arterial course (IAC) and 52 (45%) did not. During follow up 110 ACAOS patients were alive, 5 died and 1 lost to follow-up.ACAOS patients experienced 58 MACE events (5 cardiovascular deaths, 5 PCI, 24 CABG and 24 had myocardial infarction). 47 MACE events occurred in ACAOS with IAC and 11 in those without (p < 0.0001), the statistical difference driven by surgical revascularisation and myocardial infarction.

Conclusions

In life, patients with an anomalous coronary artery originating from the opposite sinus of Valsalva taking an IAC have higher rates of both myocardial infarction and surgical revascularisation during long-term follow up, compared to those without IAC.     

Cytogenetic studies in patients with secondary leukemia/dysmyelopoietic syndrome after different treatment modalities

Cytogenetic studies of 68 patients who developed secondary leukemia (SL)/dysmyelopoietic syndrome (DMS) after extensive chemotherapy and/or radiation therapy as well as patients who developed SL/DMS without such treatment showed that those patients who received radiation alone or with chemotherapy had more extensive numerical and structural abnormalities than those who received only chemotherapy. In terms of the specific chromosomal abnormalities, there are no differences between the various treatment groups. Hypodiploidy is the most common form of aneuploidy in these patients, with the most common numerical abnormality being the loss of chromosome 7. The most common structural abnormalities involved chromosomes 3 and 5. When compared with patients with de novo leukemia and DMS, the chromosomal abnormalities in these patients are more complex and extensive. Serial studies revealed that cytogenetic abnormalities do not precede the development of hematologic changes by significant time periods.     

Human platelet fibrinogen: purification and hemostatic properties

Conditions were developed in which 80% to 90% of platelet fibrinogen could be routinely purified in nondegraded form from the fluid phase of platelet suspensions stimulated with the calcium ionophore, A23187, in the presence of calcium, leupeptin, and prostaglandin E1. Fibrinogen was separated from other released proteins by chromatography on diethylaminoethanol (DEAE)-cellulose using a continuous pH and ionic strength gradient. Purified platelet fibrinogen, greater than 98% homogeneous by immunoelectrophoresis and sodium-dodecyl sulfate- polyacrylamide gel electrophoresis (SDS-PAGE), consisted of intact A alpha, B beta and gamma A chains, but not gamma' chains, and was 95% to 96% clottable. Platelet fibrinogen was shown to compete for the binding of radiolabeled plasma fibrinogen to ADP-activated platelets in a manner identical to that of unlabeled plasma fibrinogen itself. Also, at equivalent protein concentrations, platelet and plasma fibrinogens supported platelet aggregation to an equivalent extent. Based upon these results, we conclude that there is no significant difference between platelet and plasma fibrinogen with respect to their size, their clottability, their affinity for the activated platelet fibrinogen receptor, or their capacity to support subsequent platelet aggregation.