Depressant effect of digoxin on atrioventricular conduction in man.

We examined the effect of chronically administered digoxin on atrioventricular (A-V) conduction in nine cardiac transplant recipients. We assessed A-V conduction by measuring the duration from the pacing stimulus to the onset of the QRS complex (S'R interval) and by determining the occurrence of Wenckebach periodicity during rapid atrial pacing. We made measurements during a control period and during a period of digoxin administration of up to 37 days. During the digoxin period, the cycle length at which Wenckebach block occurred was prolonged by 14% of the control value and the S'R interval was significantly prolonged at paced rates of 110 beats per minute and faster. After digoxin was discontinued, the Wenckebach periodicity and S'R interval returned to control values. Atropine and propranolol did not alter digoxin's effect on A-V conduction. We conclude that digoxin exerts a direct (or non-neurally mediated) depressant effect upon A-V conduction in man, although the stress of tachycardia is necessary to demonstrate the effect.     

Autoimmune response in mothers of children with congenital and postnatally diagnosed isolated heart block: a population based study

OBJECTIVE: To study the autoimmune response in mothers of children with isolated congenital heart block (CHB) and heart block (HB) diagnosed postnatally. METHODS: We reviewed the Finnish hospital registries for patients born between 1950 and 2000 and diagnosed with isolated HB before the age of 16 years. Clinical data and sera for the determination of autoantibodies were available from 67 mothers of children with CHB and from 37 mothers of children with postnatally diagnosed HB 9.9 years and 22.6 years (mean) after the index delivery, respectively. Maternal antibodies to 52 kDa and 60 kDa SSA and 48 kDa SSB were determined by time-resolved fluoroimmunoassay (TR-FIA) and by immunoblotting. Other marker antibodies for connective tissue diseases (CTD) were determined by immunoblot and/or by immunofluorescence. The control group comprised 136 mothers with primary Sj?gren's syndrome (SS), systemic lupus erythematosus (SLE), or other CTD with healthy children. RESULTS: Sixty of our 67 mothers (90%) of children with CHB had antibodies to SSA or SSB by the methods initially used in this study. When retests and tests performed previously were taken into account, only 3 (4%) of the 67 mothers did not have any autoantibodies. Two (3%) of the 67 mothers had antibodies to dsDNA and one (1%) each to Jo-1/HRS, RNP-70 kDa, and histone proteins. Of 37 mothers of children with postnatally diagnosed HB, only 3 (8%) had any autoantibodies. Increased risk of having a child with CHB was indicated by maternal primary SS and high levels of anti-SSA and anti-SSB by all assays, whereas low risk was indicated by maternal SLE or other CTD and undetectable or low levels of the antibodies. No single anti-SSA or anti-SSB test was clearly superior to others, but in general, immunoblots were more specific than TR-FIA. CONCLUSION: Maternal autoimmune disorder is almost always associated with CHB but only rarely with postnatally diagnosed HB. Anti-SSA and anti-SSB are marker antibodies for mothers of children with CHB, and an increased risk of having an affected child is indicated by maternal primary SS and high titer antibodies to SSA and SSB.     

Reliable anticoagulation with enoxaparin in patients undergoing percutaneous coronary intervention: The pharmacokinetics of enoxaparin in PCI (PEPCI) study.

The objective of this study was to evaluate the pharmacokinetic response to intravenous (IV) enoxaparin given 8-12 hr after subcutaneous (SC) dosing in patients undergoing percutaneous coronary intervention (PCI). Fifty-five patients received SC enoxaparin (1 mg/kg every 12 hr) followed by an IV bolus (0.3 mg/kg) 8-12 hr after the last SC dose, at the start of PCI or during catheterization. Anti-Xa levels were within the target range in 98% of patients 2-8 hr after the last SC dose, in 96% of patients following the IV bolus, and in 91% of patients for a further 2 hr. Subcutaneous enoxaparin (1 mg/kg every 12 hr) provides sufficient anti-Xa levels for PCI 2-8 hr after the last dose. An additional 0.3 mg/kg enoxaparin dose given IV 8-12 hr after the last SC dose reliably maintains anti-Xa levels within the target for at least 2 additional hr.     

A novel approach to investigating the erythroid lineage, using both receptor analysis and haemoglobin detection

Progenitor cell failure in the erythroid lineage is a particular problem in bone marrow failure. To provide insight into early erythopoietic development we used sensitive techniques to examine the effects of SCF, IL-3 and MIP-1α on two developmentally arrested progenitor cell lines, HEL and K562. Quantitative flowcytometric analysis showed that both expressed receptors (SCF > MIP-1α >IL-3). Qualitative analysis revealed HEL cells expressed more receptors than K562 cells. Clonogenic assays with sensitive haemoglobin detection showed that SCF and IL-3 did not support HEL development and reduced haemoglobin production. MIP-1α reduced partially developed HEL colonies and haemoglobin in developed colonies. SCF increased development, but not haemoglobin in K562 cells, with IL-3 being more effective in both. MIP-1α increased the proportion of well-developed K562 colonies but not haemoglobin. This suggests SCF, IL-3 and MIP-1α all have a role to play in early erythroid cellular development, with differing actions depending on the stage of development.     

Use of adenosine-sensitive nondecremental accessory pathways in assessing the results of radiofrequency catheter ablation

Adenosine can cause conduction block in about 20% of nondecremental accessory pathways. Along with atrial activation mapping, adenosine may help differentiate retrograde AV node conduction versus residual accessory pathway conduction after radiofrequency catheter ablation; however, it is important to test the accessory pathway response to adenosine before ablation, particularly with a concealed accessory pathway.     

Concurrent use of intranasal and orally inhaled fluticasone propionate does not affect hypothalamic-pituitary-adrenal-axis function.

Two double-blind, randomized, placebo-controlled, parallel group safety and efficacy studies included evaluation of the hypothalamic-pituitary-adrenal (HPA)-axis effects of concurrent treatment with intranasal and orally inhaled fluticasone propionate (FP). In the first study, patients with asthma who were > or =12 years of age were assigned randomly to receive twice-daily doses (either 88 or 220 microg) of orally inhaled FP delivered from a metered-dose inhaler (MDI). In the second study, patients were assigned randomly to receive either orally inhaled FP 250 microg or orally inhaled FP 250 microg/salmeterol 50 microg delivered via the Diskus device. In both studies, patients with rhinitis were allowed to continue the use of intranasal FP at their usual dosing. Treatment periods were 26 weeks and 12 weeks for the MDI and Diskus studies, respectively. HPA-axis effects were assessed using response to short cosyntropin stimulation testing. The number and percentage of patients with an abnormal cortisol response, defined as a morning plasma cortisol of <5 microg/dL, a poststimulation peak of <18 microg/dL, or a poststimulation rise of <7 microg/dL, were summarized in two subgroups: patients who used intranasal FP and those who did not. The concurrent administration of intranasal FP and orally inhaled FP via an MDI or Diskus or via Diskus with salmeterol was not associated with HPA-axis effects compared with orally inhaled FP alone. The results of these two studies suggest that concurrent use of intranasal FP with orally inhaled FP administered via MDI or Diskus for treatment of comorbid rhinitis and asthma does not increase the risk of HPA-axis abnormalities.     

Alcohol consumption and prognosis in patients with left ventricular systolic dysfunction after a myocardial infarction

OBJECTIVES: We assessed the influence of alcohol intake on the development of symptomatic heart failure (HF) in patients with left ventricular (LV) dysfunction after a myocardial infarction (MI). BACKGROUND: In contrast to protection from coronary heart disease, alcohol consumption has been linked to cardiodepressant effects and has been considered contraindicated in patients with HF. METHODS: The Survival And Ventricular Enlargement (SAVE) trial randomized 2231 patients with a LV ejection fraction (EF) <40% following MI to an angiotensin-converting enzyme inhibitor or placebo. Patients were classified as nondrinkers, light-to-moderate drinkers (1 to 10 drinks/week), or heavy drinkers (>10 drinks/week) based on alcohol consumption reported at baseline. The primary outcome was hospitalization for HF or need for an open-label angiotensin-converting enzyme inhibitor. Analyses were repeated using alcohol consumption reported three months after MI. RESULTS: Nondrinkers were older and had more comorbidities than light-to-moderate and heavy drinkers. In univariate analyses, baseline light-to-moderate alcohol intake was associated with a lower incidence of HF compared with nondrinkers (hazard ratio [HR] 0.71; 95% confidence interval [CI] 0.57 to 0.87), whereas heavy drinking was not (HR 0.91; 95% CI 0.67 to 1.23). After adjustment for baseline differences, light-to-moderate baseline alcohol consumption no longer significantly influenced the development of HF (light-to-moderate drinkers HR 0.93; 95% CI 0.75 to 1.17; heavy drinkers HR 1.25; 95% CI 0.91 to 1.72). Alcohol consumption reported three months after the MI similarly did not modify the risk of adverse outcome. CONCLUSIONS: In patients with LV dysfunction after an MI, light-to-moderate alcohol intake either at baseline or following MI did not alter the risk for the development of HF requiring hospitalization or an open-label angiotensin-converting enzyme inhibitor.     

Obstructive sleep apnea, nasal congestion, and snoring: their systemic effects and impact on quality of life.

A literature review was conducted to evaluate the available published data on sleep-related breathing disorders with a focus on obstructive sleep apnea (OSA) syndrome, nasal congestion, and snoring. The MEDLINE database was used to obtain pertinent reviews and articles. The pathophysiology of snoring, a partial blockage of the airway, and of apnea or total airway obstruction, is described. Contributing factors to the etiology of the OSA syndrome as well as current methods of diagnosis are discussed. Adverse systemic sequelae of the OSA syndrome, especially those pertaining to the cardiovascular and respiratory systems, are detailed. Treatment options, both nonsurgical and surgical, which are used to improve the quality of life of patients with these disorders, are presented also.     

Effects of Gender and Comorbidity on Problem Drinking in a Community Sample

We investigated the influence of gender, comorbidity, drinking history, and age on the clinical manifestations of DSM-III alcohol abuse and/or dependence in men and women. The sample was drawn from the National Institute of Mental Health Epidemiologic Catchment Area study, a large-scale, multicenter survey to investigate psychiatric disorders in the community. The results showed that gender and comorbidity had independent effects on problem drinking after drinking history and age had been taken into account. Gender contributed to the age of onset of problem drinking and the rate of its development. Comorbidity, drinking history, and age contributed independently to its severity. The effects of these variables in this community sample paralleled those reported in treatment samples.