Pulmonary blood velocity profile variability in open-chest dogs: Influence of acutely altered hemodynamic states on profiles,and influence of profiles on the accuracy of techniques for cardiac output determination

Summary Clinical investigations focused on finding characteristics of noninvasively obtained measurements of pulmonary blood velocity that can be used to quantitate pulmonary blood flow and/or pulmonary pressure have often yielded results whose imprecision has been attributed to flow pattern variability. To determine flow pattern variability in an in vivo animal model in varying hemodynamic states, main pulmonary artery blood velocity waveforms were recorded in 17 dogs at 2-mm intervals along an anterior to posterior wall-oriented axis using a 20-MHz pulsed Doppler needle probe. Control data were obtained before the animals were subjected to altered flow (atrial level shunts) and pressure (10% O₂ inhalation) states. Instantaneous velocity profiles were computed throughout the cardiac cycle. Estimates of pulmonary blood flow were obtained assuming an elliptical model of the pulmonary artery which allowed computation of velocity at all points in the cross section, based on the measured values along the axis. Model-based estimates were compared to measured values and estimates obtained in the traditional fashion, i.e., the product of centerline velocity and cross-sectional area. Results clearly showed marked interanimal variability, even in control states. Reverse flow in the posterior half of the vessel, which tended to become more pronounced with increased pulmonary artery pressure, was observed during late systole and early diastole. Elevated pulmonary blood flow tended to increase the maximum velocities along the anterior wall relative to midline velocities. Neither estimate of cardiac output yielded consistently accurate results (r=0.77 for model-based method,r=0.80 for area times central velocity method). Findings of this study, which highlight the dependency of waveform characteristics on sampling site, the large degree of intersubject variability, and the need for large or multiple sample volumes for pulmonary blood flow determination, help clarify inconsistencies observed by clinicians and suggest that future work with animal models will facilitate a greater understanding of the determinants of human pulmonary velocity waveforms.Work supported in part by: NIH-R01-HL-35389     

Prolonged cardiac repolarisation during spontaneous nocturnal hypoglycaemia in children and adolescents with type 1 diabetes

Aims/hypothesis It has been postulated that hypoglycaemia-related cardiac dysrhythmia and, in particular, prolonged cardiac repolarisation, may contribute to increased mortality rates in children and adolescents with type 1 diabetes.Methods We examined the prevalence of prolonged QT interval on ECG during spontaneous hypoglycaemia in 44 type 1 diabetic subjects (aged 7–18 years), and explored the relationships between serial overnight measurements of QT interval corrected for heart rate (QTc) and serum glucose, potassium and epinephrine levels. Each subject underwent two overnight profiles; blood was sampled every 15 min for glucose measurements and hourly for potassium and epinephrine. Serial ECGs recorded half-hourly between 23.00 and 07.00 hours were available on 74 nights: 29 with spontaneous hypoglycaemia (defined as blood glucose <3.5 mmol/l) and 45 without hypoglycaemia.Results Mean overnight QTc was longer in females than in males (412 vs 400 ms, p=0.02), but was not related to age, diabetes duration or HbA₁c. Prolonged QTc (>440 ms) occurred on 20 out of 74 (27%) nights, with no significant differences between male and female subjects, and was more prevalent on nights with hypoglycaemia (13/29, 44%) than on nights without (7/45, 15%, p=0.0008). Potassium levels were lower on nights when hypoglycaemia occurred (minimum potassium 3.4 vs 3.7 mmol/l, p=0.0003) and were inversely correlated with maximum QTc (r=–0.40, p=0.03). In contrast, epinephrine levels were not higher on nights with hypoglycaemia and were not related to QTc.Conclusions/interpretation In young type 1 diabetic subjects, prolonged QTc occurred frequently with spontaneous overnight hypoglycaemia and may be related to insulin-induced hypokalaemia.     

Endogenous digoxin-immunoreactive substance in human pregnancies

We report the presence of an immunoreactive digoxin-like substance in blood from third trimester pregnant women. The sera from 51 women in the third trimester of pregnancy were analyzed by 4 commercially available digoxin RIAs. None of these patients was receiving digoxin. Digoxin immunoreactivity was detected in all patients by 3 of 4 assays. The measured values, in nanograms per ml digoxin equivalent, were (mean +/- SD): method A, 0.27 +/- 0.05; method B, 0.28 +/- 0.07; method C, 0.01 +/- 0.01; and method D, 0.15 +/- 0.06. Method B measured values greater than 0.50 ng/ml in sera from 5 patients. Digoxin immunoactivity was not detectable 24 h postpartum, suggesting a half-life in serum of 6 h or less. Exogenous digoxin added to these serum samples resulted in quantitatively additive increments above the endogenous measured levels. Three of 4 digoxin RIAs did not distinguish between true digoxin and the endogenous substance present in the sera of third-trimester pregnant patients. Preliminary evidence suggests that the endogenous digoxin immunoactivity is not due to elevation of levels of major known steroids in the blood of these women. Clinical management of women requiring digoxin therapy during pregnancy, therefore, is complicated by the inability to assume the same therapeutic range of digoxin in serum during the third trimester of pregnancy as in adult nonpregnant individuals.     

Experimenter-defined quit dates for smoking cessation: adherence improves outcomes for women but not for men

Aims Smoking cessation treatment trials often require that smokers quit on or before a protocol‐defined date. The goals of this paper were to: (1) identify factors associated with adherence to a protocol‐defined quit date and (2) determine whether such adherence predicts cessation outcome (relapse). Design A quasi‐experimental secondary analysis of data collected from a randomized placebo‐controlled trial of fluoxetine (60 mg or 30 mg) versus placebo for smoking cessation. Setting and participants Clinic‐based smoking cessation treatment program comprising 989 non‐depressed smokers. Intervention Participants received cognitive behavioral therapy for smoking cessation and either study medication or placebo for 10 weeks. They were required to set a quit date within 2 weeks of their second study visit (by visit 4). Findings Significant predictors of quit date adherence were low nicotine dependence and active drug treatment. High‐dose fluoxetine (60 mg) and male gender were protective against relapse. Adherence to quit date was not an independent predictor of relapse; instead there was a significant interaction between quit date adherence and gender. Among non‐adherers to the quit date, women were more than 2.5 times as likely as men to relapse; among adherers to the quit date, women were only 1.3 times as likely as men to relapse. Conclusions Although women were more likely than men to relapse regardless of quit date adherence, adherence was strongly protective against relapse for women.     

Comparison of endocardial activation times at effective and ineffective ablation sites within the pulmonary veins

INTRODUCTION: Recent studies demonstrated that atrial arrhythmias may be generated within pulmonary veins. The purpose of this study was to compare the endocardial activation times at effective and ineffective ablation sites during radiofrequency catheter ablation of arrhythmias initiated or generated within pulmonary veins. METHODS AND RESULTS: Twenty-one of 28 patients without structural heart disease underwent successful ablation of 23 arrhythmogenic foci within a pulmonary vein. Electrograms were recorded at 75 pulmonary venous sites and categorized into three groups: 23 successful ablation sites; 28 unsuccessful target sites within an arrhythmogenic pulmonary vein; and 24 sites within nonarrhythmogenic pulmonary veins. The endocardial activation time of premature depolarizations arising at successful target sites was significantly earlier than at other sites. During premature depolarizations, an endocardial activation time of -75 msec or earlier had a sensitivity of 83% and a specificity of 79% for identification of a successful ablation site. Endocardial activation times earlier than -100 msec were recorded only at successful ablation sites, and endocardial activation times later than -30 msec were recorded only at sites within nonarrhythmogenic pulmonary veins. The presence of a split potential during sinus rhythm or premature depolarizations was not a specific indicator of a successful ablation site. CONCLUSION: The endocardial activation times of premature depolarizations that arise within pulmonary veins and initiate atrial tachycardia/fibrillation are useful in identifying successful ablation sites.     

The Labelling Index of Primitive Plasma Cells Determines the Clinical Behaviour of Patients with Myelomatosis

For patients with multiple myeloma the most important laboratory correlate of prognosis and disease activity is the bromodeoxyuridine (BrdUrd) plasma cell labelling index (LI). However, the traditional immunofluorescent microscope LI technique, like other manual enumeration assays, can suffer from poor precision and accuracy. In this study the LI of different subpopulations of plasma cells (CD38⁺⁺) as determined by flow cytometry was correlated with disease state. The mean LI of the total CD38⁺⁺ population was significantly higher (2.7±0.4%) than the LI determined by the traditional slide technique (0.6±0.1%) for 65 samples tested. Primitive plasma cells (CD38⁺⁺, CD45⁺⁺) had a higher labelling index than mature plasma cells (CD38⁺⁺, CD45⁻) (7.0±1.3% v 1.8%±0.3%) and in one patient the LI of the primitive plasma cells was 46%. In addition, the LI of the mature plasma cells was lower than the total plasma cell population. As expected, there was a significant difference between the LI of patients in plateau phase and progressive disease but this difference was greatest when the LI of the primitive plasma cells was studied (9.2±2.9% v 2.2±0.7%; z =19.9, P <0.001). This study has raised some concerns about the sensitivity and accuracy of the traditional labelling index and has shown that the increased LI associated with progressive disease is almost entirely attributable to an increase in the LI of the primitive plasma cell subpopulation and that the LI of primitive plasma cells provides a more clinically significant correlation with disease status than the traditional assay.     

Effects of an antiserum to rat growth hormone on lactation in the rat

A highly specific antiserum to rat GH (anti-rGH) was used to assess the role of GH in lactation in the rat. When administered alone, anti-rGH had no effect on litter weight gain, whereas bromocriptine reduced serum prolactin concentrations and litter weight gain for up to 7 days when given on day 4 of lactation. When bromocriptine and anti-rGH were given in combination, however, litter weight gain declined even more dramatically so that pups were receiving virtually no milk 2-3 days after treatment. Daily litter exchange failed to prevent this effect. Concurrent injections of highly purified GH (prolactin contamination undetectable) prevented the dramatic decline in litter weight gain induced by combined bromocriptine and anti-rGH treatment, so that these litters grew as well as those receiving bromocriptine alone. Growth hormone did not act by influencing serum prolactin concentrations, which remained low during GH therapy. Direct effects of anti-rGH or GH on the pups (transferred through the milk) were ruled out since virtually identical results were obtained when milk yield was estimated during a 30-min suckling period after a 3-h separation of mother and pups. Lactation had virtually ceased 3 days after treatment with both bromocriptine and anti-rGH, but it could be reinitiated by a single injection of prolactin or GH, and subsequent recovery was virtually complete. The results of this study show that prolactin can maintain a full milk yield in the absence of GH, milk yield is reduced by approximately 50% in the absence of prolactin and milk yield is totally stopped in the absence of prolactin and GH.(ABSTRACT TRUNCATED AT 250 WORDS)     

Guidelines for microplate techniques in liquid-phase blood grouping and antibody screening

Summary. This document is an introduction to microplate serology prepared at a time of very active research and development. Antibody detection techniques are expected to improve during the lifetime of this document. Approximately 25% of hospital blood banks are ABO and D grouping by microplate techniques. Antibody screening by microplate techniques is only being carried out by a small percentage of hospital blood banks but there is likely to be a change to antiglobulin tests by microplate procedures as soon as the methods have been thoroughly tested and approved. There are one or two weak links in these procedures which could give rise to serious errors:— (1) Antiglobulin reagents standardized for spin-tube tests may be subject to prozones in liquid phase microplate tests. Each new batch of antiglobulin reagent must be standardized by the microplate procedure in use to show that the reagent is at its optimum anti-IgG dilution for use. However dilutions greater than 1:2 may seriously compromise the anti-complement activity of the reagent. (2) Automated cell washers for microplates are currently under development and should be evaluated by replicate tests with weak anti-D sensitized cells. (3) The combination of diluted anti-IgG and poor washing procedures may lead to neutralization of anti-IgG and cause false negative errors. Future development for improved antiglobulin tests in microplates by a solid phase system is now well advanced and workers proposing to change to antibody screening by microplates are advised to bear this in mind. It is hoped that microplate methodology will move towards standardization based on national guidelines using standard antibody reagents for the validation of new microplate procedures.