Hemolysis parameters of St. Jude Medical: Hemodynamic Plus and Regent valves in aortic position

BACKGROUND: Elevated plasma lactate dehydrogenase (LDH) concentration may reflect hemolysis due to mechanical heart valve dysfunction. Thus, knowledge of LDH levels in patients with properly working prostheses is required. Because hemolysis parameters for the SJM Hemodynamic Plus (HP) and Regent series are currently not available, the purpose of our study was to determine these data. METHODS: At 12-19 months follow-up after isolated aortic valve replacement with SJM HP(R) or Regent prostheses, we examined 102 patients by transthoracic echocardiography and determined plasma LDH, haptoglobin, bilirubin and hemoglobin. RESULTS: Five patients with properly working prostheses were excluded because of increased LDH due to non-cardiac reasons. In four patients with paravalvular leakage, LDH was 244, 307, 446 and 628 U/l, respectively. In patients with properly working prostheses, LDH was 287+/-52 (range: 163-374) U/l for HP(R) (n=33) and 274+/-48 (151-386) U/l for Regent valves (n=60, p=0.2). Haptoglobin was <1g/l in all patients; in 91% of HP and 75% of Regent valves, haptoglobin was below detection limit. Bilirubin and hemoglobin as well as red blood cell count (RBC) were normal in all patients except for five patients with renal anemia, two patients with paravalvular leakage and four patients with macrocytosis due to alcohol abuse. There was no correlation between LDH and transvalvular gradient (r=-0.02) or valve size (r=0.25). CONCLUSIONS: In patients with SJM HP(R) or Regent valves in aortic position, LDH values > 400 U/l indicate valvular dysfunction or leakage if non-cardiac causes for hemolysis are excluded. However, paravalvular leakage can be present without substantially increased LDH. Haptoglobin has no diagnostic value as it is almost always markedly reduced. Hemolysis does not correlate with transvalvular gradient or prosthesis size.     

Growth requirements,growth factor responsiveness,and growth factor secretion of three human embryonal carcinoma cell lines

Summary The in vitro growth requirements of three human embryonal carcinoma cell lines (H 12.7, 2102 EP, 1428 A) were investigated. The basal medium DME/F12 supplemented with insulin, transferrin, and low-density and high-density lipoproteins was sufficient to support substantial multiplication of all three lines. The most efficient attachment factor was either fibronectin (for 2102 EP and 1428 A) or collagen type I (H 12.7). In a serum-free system the influence of epidermal growth factor (EGF), insulin-like growth factor I, multiplication stimulating activity (MSA), a platelet extract, and the glucocorticoids dexamethasone and hydrocortisone, as determined by the DNA synthesis rate of the cells, was generally minimal. However, the DNA synthesis rate of cell lines H 12.7 and 2102 EP was increased by MSA, and the line with the highest potential to differentiate (H 12.7) was stimulated by EGF. All three cell lines secreted growth factors in a heterologous stimulation assay. Insulin-like growth factors I and II were not part of the growth promoting activity. The inhibitory effect of a monoclonal anti-EGF antibody on the ³H-thymidine incorporation of cell line 2102 EP might indicate autocrine secretion of EGF or an EGF-like factor by this cell line.     

Long-term clearance from small airways in patients with cystic fibrosis.

Impaired mucociliary clearance is a hallmark of cystic fibrosis (CF). Early morphological changes first appear in the small airways. Lung clearance was investigated in 11 young CF adults with mild-to-moderate lung disease using a method depositing particles mainly in the small airways. Radiolabelled Teflon particles (6 microm) were inhaled with an extremely slow inhalation flow, 0.05 L x s(-1). Lung retention was measured immediately following inhalations and, on four occasions up to 21 days. The results were compared with data from healthy subjects. The lung retention at 24 h in % of deposition was 67% (95% confidence interval 58-76) in the CF patients, compared to 48% (42-53) in the healthy subjects. Clearance on days 1-7 was larger in the CF patients, 22% (15-29) compared to the healthy subjects, 14% (12-16). No difference was observed between the CF patients and the healthy subjects in the slow clearance phase at day 7 to day 21, representing small airway clearance. Impaired mucociliary clearance in CF patients results in increased 24-h retention and a prolonged rapid clearance phase. The results of the study do not support the current authors' hypothesis that clearance from small airways is slower in cystic fibrosis patients compared to healthy subjects. Furthermore, the data suggest that mucociliary transport is not the dominant clearance mechanism in small airways.     

Hypercholesterolemia in pregnant mice does not affect atherosclerosis in adult offspring

In humans, maternal hypercholesterolemia during pregnancy promotes microscopical fatty streaks in the children. The mechanism is unknown. Fatty streaks are clinically silent, and many of them regress and never develop into advanced atherosclerosis. The aim of this study was to investigate whether hypercholesterolemia in pregnant mice induced more advanced atherosclerosis in their adult progeny. Hypercholesterolemic (HC) apolipoprotein E knockout (apoE(-/-)) female mice were mated with normocholesterolemic (NC) wild-type (apoE(+/+)) males and vice versa. All parents were almost identical genetically except for apoE. Therefore, all progeny became genetically identical and heterozygous apoE(+/-). They were born of either HC (i.e. apoE(-/-)) or NC (i.e. apoE(+/+)) mothers. The progeny were killed 6 months after birth and the amount of atherosclerosis in the aortic root was assessed. Females developed more atherosclerosis than males (P<0.001) but, regardless of sex, maternal hypercholesterolemia during pregnancy had no influence on the amount of atherosclerosis in adult progeny. Males of HC mothers had lower plasma cholesterol levels than males of NC mothers. Thus, in mice, maternal hypercholesterolemia during pregnancy does not promote the development of advanced atherosclerosis in their adult progeny.     

Helicobacter pylori infection, not gastroesophageal reflux, is the major cause of inflammation and intestinal metaplasia of gastric cardiac mucosa

OBJECTIVE: The etiology of inflammation below the normal Z-line is an area of intense debate. Some suggest this is the earliest change of chronic gastroesophageal reflux disease (GERD), whereas others indict Helicobacter pylori (H. pylori) as the main cause. The aim of this study was to evaluate the relationship among inflammation of gastric cardiac mucosa (carditis), H. pylori infection, and intestinal metaplasia in patients with GERD and Barrett's esophagus compared with age-matched controls. METHODS: Patients with GERD and Barrett's esophagus were compared with controls undergoing endoscopy for a variety of other conditions. Endoscopic biopsy specimens from the gastric cardia (obtained on retroflexed view), fundus, and antrum were evaluated for inflammation, H. pylori infection, and intestinal metaplasia. RESULTS: The prevalence of H. pylori infection did not significantly differ among the study populations: controls (42%), GERD (33%), and Barrett's esophagus (27%) (p = 0.20). However, the prevalence of carditis significantly decreased from the control group (30%) to those with GERD (23%) and Barrett's esophagus (11%) (p = 0.03). Overall, 42 of 51 (82%) patients with carditis had H. pylori; all had pangastritis. The prevalence of cardia intestinal metaplasia also significantly decreased from the control group (15%) to those with GERD (4%) and Barrett's esophagus (0%) (p = 0.003). Of 13 patients with cardia intestinal metaplasia, 12 had carditis, 10 had H. pylori infection, and seven had intestinal metaplasia elsewhere in the stomach. CONCLUSIONS: Inflammation of gastric cardiac mucosa decreases in prevalence from controls to patients with GERD and Barrett's esophagus and correlates strongly with H. pylori infection. Cardia intestinal metaplasia is associated with H. pylori-related cardiac inflammation and intestinal metaplasia elsewhere in the stomach.     

Comparison of sotalol versus amiodarone in maintaining stability of sinus rhythm in patients with atrial fibrillation (Sotalol-Amiodarone Fibrillation Efficacy Trial [Safe-T])

The Sotalol-Amiodarone Fibrillation Efficacy Trial (SAFE-T) is a randomized, double-blind, multicenter, placebo-controlled trial in which the effects of sotalol and amiodarone in maintaining stability of sinus rhythm are being examined in patients with persistent atrial fibrillation at 20 Veterans Affairs medical centers. The time to the occurrence of atrial fibrillation or flutter in patients with atrial fibrillation converted to sinus rhythm is the primary outcome measure, with a number of parameters as secondary end points. SAFE-T had randomized 665 patients when enrollment terminated on October 31, 2001. Follow-up of patients continued until October 31, 2002, for a maximum period of 54 months and a minimum period of 12 months for all patients.     

Identification and modulation of a naturally processed T cell epitope from the diabetes-associated autoantigen human glutamic acid decarboxylase 65 (hGAD65)

T cell recognition of autoantigens is critical to progressive immune-mediated destruction of islet cells, which leads to autoimmune diabetes. We identified a naturally presented autoantigen from the human islet antigen glutamic acid decarboxylase, 65-kDa isoform (GAD65), by using a combination of chromatography and mass spectrometry of peptides bound by the type I diabetes (insulin-dependent diabetes mellitus, IDDM)-associated HLA-DR4 molecule. Peptides encompassing this epitope-stimulated GAD65-specific T cells from diabetic patients and a DR4-positive individual at high risk for developing IDDM. T cell responses were antagonized by altered peptide ligands containing single amino acid modifications. This direct identification and manipulation of GAD65 epitope recognition provides an approach toward dissection of the complex CD4(+) T cell response in IDDM.