Ventricular septal defect and subaortic stenosis: An analysis of 41 patients

Forty-one patients with subaortic stenosis (SAS) and ventricular septal defect (VSD) were identified from the cardiac records of the Hospital for Sick Children, Toronto, Ontario. The diagnosis of an associated SAS was made clinically in only 1 patient, who had findings of left ventricular (LV) hypertrophy with strain on the electrocardiogram. There was a delay of 3.1 years between initial presentation and detection of SAS. The SAS was not diagnosed at initial catheterization in 17 patients and was confirmed at subsequent catheter studies in 8 patients, surgery in 5 and autopsy in 4. Associated defects included coarctation of the aorta in 12 patients, mitral valve abnormalities in 4, and right-sided obstructions, including anomalous right ventricular muscle bundles in 6 patients, tetralogy in 4 and pulmonic stenosis in 1 patient.

The mean gradient across the LV outflow tract was 25 mm Hg. Nineteen patients had serial catheters without intervening surgery, and the outflow gradient increased from a mean of 9 to 36 mm Hg. The mechanism of SAS consisted of fibrous diaphragm and fibromuscular obstruction in 31 cases, muscular narrowing in 4, protruding tricuspid valve leaflet in 2, hypertrophic cardiomyopathy in 2, anterolateral twist in 1 patient and redundant tissue tag in 1. Thirty-eight patients had a perimembranous VSD, 19 of whom had an associated so-called aneurysm of the membranous septum; 2 had an infundibular VSD and 1 patient had a central muscular defect. Although the SAS was located below the VSD in 30 cases, the associated heart failure and reduced cardiac output can mask the presence or severity of associated SAS. Cross-sectional echocardiography and axial angiography have greatly improved recognition of associated SAS.     

Room temperature ADP induced first stage hyperaggregation of human blood platelets: a previously undescribed phenomenon and its relationship to spontaneous cold induced platelet aggregation

ADP induced human platelet aggregation was shown to be accentuated when tested at 20-30 degrees C as increased sensitivity and as a greater change of optical density although second stage aggregation and the release reaction did not occur. This previously undescribed phenomenon is defined as room temperature ADP induced first stage hyperaggregation. Aggregation, which occurs under the above mentioned conditions with a quantity of ADP insufficient to maintain the aggregation (usually less than 1.5 micron), is reversible when the temperature is raised to 37 degrees C. After rewarming to these temperatures, second stage aggregation appeared in the presence of larger quantities of ADP (usually more than 2 microns) and could be blocked by aspirin. The absence of the release reaction was demonstrated with a lumi-aggregometer. Spontaneous cold induced platelet aggregation seen after chilling platelets to 0-4 degrees C is shown to be a distinct phenomenon.     

Impact of high‐dose interferon induction and ribavirin therapy in patients with chronic hepatitis C relapsing after or not responding to interferon monotherapy

Background/aims: Initial high‐dose interferon‐α induction therapy in combination with ribavirin improves sustained response rates in treatment‐naïve patients. This prospective, randomized, controlled study tested whether non‐responders or relapsers to interferon monotherapy also benefit from induction therapy. Methods: Patients with chronic hepatitis C who had not responded to (n=75) or relapsed (n=80) after previous interferon therapy were randomized to receive three different interferon doses during the first 14 weeks of therapy (A: 10 MU IntronA®/day for 2 weeks, followed by 10 MU/2 days for 12 weeks; B:5 MU/d for 14 weeks; C: 5 MU/2 days for 14 weeks) followed in all by 5 MU/2 days for 24 weeks. All patients received 1–1.2 g ribavirin/day throughout the whole study. Results: The rates of viral clearance at any time on treatment were similar in all groups. Sustained response rates were also not different among the groups in interferon nonresponders (A 32%, B 29%, C 31%) and relapsers (A 64%, B 68%, C 71%), respectively, as well as in patients with different genotypes. As expected, sustained response rates were higher in patients with genotype non‐1 than in those with genotype 1. Conclusion: High‐dose induction therapy does not improve the outcome of interferon/ribavirin therapy in interferon nonresponders or relapsers.     

Extracellular KIT receptor mutants, commonly found in core binding factor AML, are constitutively active and respond to imatinib mesylate

Multiple genetic alterations are required to induce acute myelogenous leukemia (AML). Mutations in the extracellular domain of the KIT receptor are almost exclusively found in patients with AML carrying translocations or inversions affecting members of the core binding factor (CBF) gene family and correlate with a high risk of relapse. We demonstrate that these complex insertion and deletion mutations lead to constitutive activation of the KIT receptor, which induces factor-independent growth of interleukin-3 (IL-3)-dependent cells. Mutation of the evolutionary conserved amino acid D419 within the extracellular domain was sufficient to constitutively activate the KIT receptor, although high expression levels were required. Dose-dependent growth inhibition and apoptosis were observed using either the protein tyrosine kinase inhibitor imatinib mesylate (STI571, Gleevec) or by blocking the phosphoinositide-3-kinase (PI3K)-AKT pathway. Our data show that the addition of kinase inhibitors to conventional chemotherapy might be a new therapeutic option for CBF-AML expressing mutant KIT.     

Clinical aspects and endoscopic management of gastrointestinal bleeding from Dieulafoy's lesion]

OBJECTIVE: the aim of the study was to assess the incidence, clinical presentation, location, and response to endoscopic therapy of gastrointestinal bleeding from Dieulafoy's lesion. MATERIAL AND METHOD: ALL consecutive episodes of gastrointestinal bleeding due to Dieulafoy's lesion seen between 2000 and 2006 were retrospectively reviewed. All main clinical and endoscopic data were collected: type and effectiveness of endoscopic therapy, rebleeding, complications, and mortality during hospitalization. RESULTS: WE found 41 patients, 26 males and 15 females, median age of 71.19 years. Dieulafoy's lesion accounted for 1.55% of all gastrointestinal bleeding episodes during the study period. The incidence of Dieulafoy's lesion was 2.2 cases/100.000 inhabitants/year. Active bleeding at endoscopy was present in 85.36%, and comorbidity in 92.68%. The stomach was the most frequent location (60.97%), followed by duodenum (29.26%). Endoscopic therapy achieved initial hemostasis in all cases. Three patients (7.31%) initially treated with epinephrine injection showed rebleeding and properly responded to a second session of endoscopic therapy. No surgery was needed. The mortality rate during hospitalization was 4.87%. CONCLUSIONS: Dieulafoy's lesion is an uncommon, but potentially severe cause of gastrointestinal bleeding. It may be found in any location within the gastrointestinal tract. Endoscopic therapy is effective and safe. Injected epinephrine alone is associated with a higher risk of rebleeding.     

Leukemia inhibitory factor suppresses proliferation, alkaline phosphatase activity, and type I collagen messenger ribonucleic acid level and enhances osteopontin mRNA level in murine osteoblast-like (MC3T3E1) cells

The effect of leukemia inhibitory factor (LIF) on proliferation and phenotypic expression in murine osteoblast-like (MC3T3E1) cells was examined. LIF inhibited the proliferation of these cells by up to 20% and DNA synthesis was inhibited in a dose-dependent manner with an ED50 of about 0.2 ng/ml. The effect of LIF relative to matched controls increased with decreasing serum concentration, reaching 30% inhibition at 0.2% serum. LIF also reduced the stimulatory effects of platelet-derived growth factor and insulin-like growth factor I on DNA synthesis. The inhibition of the DNA synthesis by saturating concentration of transforming growth factor beta was further enhanced by the addition of LIF, suggesting independent pathways for the action of the two growth inhibitors. In addition, LIF reduced alkaline phosphatase activity and the abundance of type I collagen messenger RNA, but increased the level of osteopontin messenger RNA. These findings suggest that LIF may play a role in regulating the function of osteoblasts.     

Arrhythmias in patients with surgically treated atrial septal defects

Atrial arrhythmias complicate the clinical course of adult patients with an atrial septal defect. Atrial flutter is more prevalent in younger patients, and frequently regresses after surgical defect closure. Atrial fibrillation however, which results from a chronic underlying disease, rarely reverts to sinus rhythm after surgical repair. While younger patients with atrial flutter clearly benefit from defect closure alone, this is not evident in older patients with fibrillation, who may need an additional anti-arrhythmic procedure concomitant to defect closure.     

Prognosis and life expectancy in chronic liver disease

The aim of the present study was to define prognosis and life expectancy in patients with chronic liver disease of different etiologies and to relate them to an age- and sex-matched normal population. After a follow-up of 15 years, life expectancy of 620 patients with chronic liver disease was retrospectively calculated and compared with an age- and sex-matched normal population. Among patients with cirrhosis, prognosis was dependent upon the Child classification (P=0.001). Patients with alcoholic cirrhosis and fatty liver disease were younger (P=0.01) and had a lower life expectancy than patients with other causes of chronic liver disease (P=0.004). Patients with hepatitis B and hepatitis C cirrhosis showed a comparable prognosis and a significantly lower life expectancy than the age- and sex-matched population. Cryptogenic and autoimmune liver diseases showed a comparable life expectancy but a significantly shorter life expectancy than the normal population. In patients with ₁-antitrypsin deficiency-associated cirrhosis, a high viral coinfection rate was found (P=0.01). For patients with noncirrhotic hemochromatosis, prognosis was poorer than that for the age- and sex-matched population. In patients with asymptomatic primary biliary cirrhosis, chronic persistent hepatitis B, and ₁-antitrypsin deficiency without cirrhosis, life expectancy was equal to that of the normal population. Prognosis and life expectancy in chronic liver disease depend on stage, cause, and symptoms of chronic liver disease; age; and possibilities of treatment. In patients with hereditary liver disease, additional viral infection or alcohol abuse lead to a significant deterioration of life expectancy. Patients with alcoholic chronic liver disease have the poorest prognosis.     

In vivo regulation of virulence in Pseudomonas aeruginosa associated with genetic rearrangement.

A chronic pulmonary infection model was used to induce conversion to the mucoid phenotype by Pseudomonas aeruginosa PAO. At 6 months after initial inoculation, organisms isolated from infected lungs demonstrated the mucoid phenotype. Significant decreases (P less than .01) were seen in the levels of exotoxin A, exoenzyme S, phospholipase C, and pyochelin produced by the mucoid P. aeruginosa PAO rat lung isolates that returned to parental levels after reversion to the nonmucoid phenotype. In addition, lipopolysaccharide of the mucoid PAO lung isolates failed to react with serotype B-specific antibody in contrast to the original PAO and the revertant PAO organisms. Digestion of chromosomal DNA and hybridization with P. aeruginosa virulence factor-specific probes demonstrated that conversion to the mucoid phenotype was associated with rearrangement of chromosomal DNA upstream of the exotoxin A gene. Analysis of DNA from revertant organisms revealed hybridization patterns identical to the original PAO organism.