Genotypic and phenotypic characterization of Staphylococcus aureus causing persistent and nonpersistent subclinical bovine intramammary infections during lactation or the dry period.

Staphylococcus aureus is a significant pathogen frequently causing persistent intramammary infections (IMI) in dairy cows. We compared some genotypic and phenotypic characteristics of 285 strains collected from quarter milk samples from cows with persistent and nonpersistent subclinical IMI across Canada. Variable number of tandem repeats typing was used to infer the persistence of the same S. aureus strain in 3 consecutive quarter milk samples collected at intervals of 3 wk during lactation or before and after dry-off. All first isolates of the series were used as the representative strains from persistent IMI and were compared with nonpersistent strains for the presence of genes seg, sen, sec, and tst as well as by spa typing. Biofilm production in vitro and hld-RNAIII expression levels were also quantified. The gene seg was associated with a reduction in the likelihood of the bacteria to cause a persistent IMI during lactation. Strains persisting through the dry period produced significantly more biofilm in vitro than strains that do not persist after calving. Also, we showed that strains expressing more hld were more likely to be nonpersistent during either lactation or through the dry period. Three spa types were predominant (t529, t267, and a novel type: t13401). In the strains studied, the spa type tbl 2645 was the most frequent, and 97.0% of the strains of this spa type carried both sen and seg. Strains from the spa type tbl 2645 were less likely to cause a persistent IMI in the dry period. Most (86.7%) of the strains of the novel spa type (t13401) were negative for seg, sen, or both and produced significantly more biofilm in vitro than tbl 2645 and t267. The present study expanded our current knowledge on the genotypic and phenotypic traits of S. aureus strains recovered from persistent and nonpersistent IMI in Canada.

Immunorelevant proteins for the diagnosis of bovine staphylococcal mastitis.

Staphylococcus aureus is a leading cause of bovine mastitis, a condition in which the udder of the cow is inflamed, reducing the quality and quantity of milk produced. Staphylococcal mastitis is a common infection that can develop into a chronic form. The segregation of infected animals is an important preventive practice but relies on an effective diagnostic method. For this purpose, we constructed a genomic library of S. aureus, and a screening step was conducted with antiserum produced using the total protein extract of the pathogen. The nucleotide sequences of the immunoselected clones were aligned with the genome of bovine S. aureus RF122, which enabled the identification of 65 different loci, including proteins related to metabolism, adhesion and cell wall production, toxins, regulatory proteins, and hypothetical proteins. The subcellular location of the immunoreactive polypeptides was also determined. Fifty-two percent were cytoplasmic, 34 % were located in areas exposed to the host's immune system, and for 14 %, the location could not be determined. In silico analysis of the presence of these proteins in mastitis pathogens showed that Fib, ClfA, and the hypothetical protein SAB0166 were the only proteins specific for S. aureus. Therefore, these proteins are promising candidates for the serodiagnosis of staphylococcal mastitis.

Use of electrophysiologic testing in patients with nonsustained ventricular tachycardia: prognostic and therapeutic implications.

Forty patients with coronary artery disease and nonsustained ventricular tachycardia on ambulatory electrocardiographic monitoring underwent programmed electrical stimulation. In 22 patients, monomorphic ventricular tachycardia was induced at baseline drug-free electrophysiologic testing; 9 of these patients subsequently developed a clinical sustained ventricular tachyarrhythmia. In 18 patients, no tachycardia could be induced, and none of these 18 had subsequent tachycardia. In 25 of the 40 patients, arrhythmia management was guided by the results of electrophysiologic testing; this group included 11 patients who received antiarrhythmic therapy for induced ventricular tachycardia and 14 patients without inducible ventricular tachycardia who did not receive antiarrhythmic therapy. In the remaining 15 patients, arrhythmia management was not based on the results of electrophysiologic testing. Only two episodes of clinical sustained tachyarrhythmia occurred in the group receiving electrophysiologically guided therapy compared with seven episodes in the group treated without electrophysiologic guidance (p less than 0.01). Thus, in patients with coronary artery disease with nonsustained ventricular tachycardia on ambulatory electrocardiography, electrophysiologic testing can identify those at high and low risk for subsequent clinical tachycardia events. Furthermore, results of such testing can be used to optimize arrhythmia management in these patients.

Posttranscriptional regulation of the c-myb proto-oncogene in estrogen receptor-positive breast cancer cells.

We have determined that expression of the c-myb proto-oncogene is associated with estrogen receptor (ER) status and not with tumor progression in human breast epithelial cells. Analysis of normal, immortalized, nontumorigenic, and tumorigenic mammary epithelial cells showed that only ER+ tumor cell lines expressed readily detectable levels of c-myb mRNA and a Mr 75,000 protein that was the same size as the c-myb transcripts and protein products present in hematopoietic cells. In this report we show that c-myb mRNA and protein levels are down-regulated during estrogen withdrawal. A 20-fold increase in c-myb mRNA and protein expression was observed upon addition of beta-estradiol to the culture medium. Nuclear run-on transcription analyses showed that c-myb was transcribed at the same rate in the presence and absence of estrogen, suggesting that c-myb mRNA accumulation was regulated at a posttranscriptional level. To provide additional evidence that c-myb mRNA was dependent on ER expression, we examined c-myb mRNA levels in MCF-7 cells selected for resistance to antineoplastic drugs. c-myb expression was decreased only in cell lines that showed concomitant loss of ER expression. Moreover, c-myb mRNA was expressed and modulated by estrogen in ER-, MDA-MB-231 cells stably transfected with a human ER gene. When considered together, these data indicate that c-myb mRNA levels are regulated by estrogens and further suggest that this proto-oncogene plays a role in the biology of ER+ breast tumor cells.

Differential expression of multiple MDM2 messenger RNAs and proteins in normal and tumorigenic breast epithelial cells.

The MDM2 gene is a nuclear phosphoprotein that is regulated by p53 and functions, in one capacity, to inhibit the transcriptional activity of the wild-type p53 protein. Multiple MDM2 transcripts were detected in human breast epithelial cells. In estrogen receptor-negative normal, immortal, and tumorigenic breast epithelial cells, we found a good correlation between MDM2 mRNA levels and expression of wild-type p53. When wild-type p53 was overexpressed in estrogen receptor-negative tumor cells containing a mutant or no endogenous p53, MDM2 mRNA levels increased significantly, indicating that wild-type p53 positively influences MDM2 mRNA levels in these tumor cells. Because all estrogen receptor-positive breast tumor cells had high MDM2 mRNA levels regardless of the status of their endogenous p53 protein, other factors likely influence MDM2 expression in these cells. Distinct MDM2 proteins (range, Mr 54,000-68,000 and 90,000-100,000, respectively) were differentially expressed in human breast epithelial cells. The lower molecular weight MDM2 proteins were most abundant in the normal mammary cells but present at varying levels in many of the tumor cells examined. MDM2 was a nuclear protein; however, nuclear staining intensity did not always correlate with the amount of MDM2-immunoreactive protein as determined by Western blot analysis. This discrepancy suggests that MDM2 interacts with novel cellular proteins in different kinds of breast epithelial cells.

Treatment Planning and Delivery of Whole Brain Irradiation with Hippocampal Avoidance in Rats.

BACKGROUND: Despite the clinical benefit of whole brain radiotherapy (WBRT), patients and physicians are concerned by the long-term impact on cognitive functioning. Many studies investigating the molecular and cellular impact of WBRT have used rodent models. However, there has not been a rodent protocol comparable to the recently reported Radiation Therapy Oncology Group (RTOG) protocol for WBRT with hippocampal avoidance (HA) which is intended to spare cognitive function. The aim of this study was to develop a hippocampal-sparing WBRT protocol in Wistar rats. METHODS: The technical and clinical challenges encountered in hippocampal sparing during rat WBRT are substantial. Three key challenges were identified: hippocampal localization, treatment planning, and treatment localization. Hippocampal localization was achieved with sophisticated imaging techniques requiring deformable registration of a rat MRI atlas with a high resolution MRI followed by fusion via rigid registration to a CBCT. Treatment planning employed a Monte Carlo dose calculation in SmART-Plan and creation of 0.5 cm thick lead blocks custom-shaped to match DRR projections. Treatment localization necessitated the on-board image-guidance capability of the XRAD C225Cx micro-CT/micro-irradiator (Precision X-Ray). Treatment was accomplished with opposed lateral fields with 225 KVp X-rays at a current of 13 mA filtered through 0.3 mm of copper using a 40x40 mm square collimator and the lead blocks. A single fraction of 4 Gy was delivered (2 Gy per lateral field) with a 41 second beam on time per field at a dose rate of 304.5 cGy/min. Dosimetric verification of hippocampal sparing was performed using radiochromic film. In vivo verification of HA was performed after delivery of a single 4 Gy fraction either with or without HA using γ-H2Ax staining of tissue sections from the brain to quantify the amount of DNA damage in rats treated with HA, WBRT, or sham-irradiated (negative controls). RESULTS: The mean dose delivered to radiochromic film beneath the hippocampal block was 0.52 Gy compared to 3.93 Gy without the block, indicating an 87% reduction in the dose delivered to the hippocampus. This difference was consistent with doses predicted by Monte Carlo dose calculation. The Dose Volume Histogram (DVH) generated via Monte Carlo simulation showed an underdose of the target volume (brain minus hippocampus) with 50% of the target volume receiving 100% of the prescription isodose as a result of the lateral blocking techniques sparing some midline thalamic and subcortical tissue. Staining of brain sections with anti-phospho-Histone H2A.X (reflecting double-strand DNA breaks) demonstrated that this treatment protocol limited radiation dose to the hippocampus in vivo. The mean signal intensity from γ-H2Ax staining in the cortex was not significantly different from the signal intensity in the cortex of rats treated with WBRT (5.40 v. 5.75, P = 0.32). In contrast, the signal intensity in the hippocampus of rats treated with HA was significantly lower than rats treated with WBRT (4.55 v. 6.93, P = 0.012). CONCLUSION: Despite the challenges of planning conformal treatments for small volumes in rodents, our dosimetric and in vivo data show that WBRT with HA is feasible in rats. This study provides a useful platform for further application and refinement of the technique.

Recent advances in programmable pacemakers. Consideration of advantages, longevity and future expectations.

The important electrical characteristics of conventional ventricular demand pacemakers currently widely employed are unable to be altered by noninvasive means after their implantation. However, a number of domestic pacemaker manufacturers have started to introduce a new modality for atraumatic modulation of these devices, the fully programmable pacemaker system, whereby the several variables regulating pacemaker operation may be optimized on an individual basis according to need. Such programmable pacemaker functions which can be varied include rate, energy output, refractory period and sensing threshold. The indications, significance and mechanisms for control of the various function programming are delineated for physician understanding at the present time.

Effect of antihypertensive therapy on the circadian blood pressure pattern.

This study employed 24-hour automated ambulatory blood pressure monitoring to evaluate whole-day patterns of blood pressure in age-matched groups of normotensive volunteers, untreated hypertensive patients, and hypertensive patients treated with prazosin. As would be expected, overall systolic and diastolic blood pressures were found to be lowest in the normotensive subjects and highest in the untreated hypertensive patients. The systolic and diastolic blood pressure values for patients receiving prazosin twice daily were significantly lower than in the untreated patients; they were slightly, but not significantly, higher than the values recorded for the normotensive volunteers. The data from 24-hour monitoring revealed no between-group differences in the actual circadian rhythm of the blood pressure. This finding established that the blood pressure pattern for hypertensive patients treated with prazosin was parallel to that for normal individuals. Thus, prazosin administered twice daily reduces blood pressure throughout a full 24-hour period in a fashion that maintains the normal circadian pattern of the blood pressure.

Activators and inhibitors of the ion channel of the NMDA receptor.

The involvement of the glutamate-glycine activated ion channels of the NMDA receptor in various neurophysiological processes has made this ion channel the focus of intense research. The excessive release of glutamate in a variety of neuronal hypoxic conditions implicates the NMDA receptor in a number of neuropatholological states, such as stroke, chronic pain, Parkinson's disease, Alzheimer's disease, ALS, and epilepsy, among others, thus making this receptor a prime drug target candidate. A variety of agents are known to be effective in opening and closing of the ion channels of this receptor, among the latter group of agents is the peptidic conantokins. Through the use of electrophysiological measurements with a number of cell types containing natural and recombinant subunits of the NMDA receptor, much knowledge is evolving regarding the mechanism of action of activators and inhibitors of the NMDA receptor ion channels. In addition, structure-function studies of the conantokins in these systems have been revealing in terms of their complimentary sites on the NMDA receptor. These relationships serve as the main focus of this review.

Inhibition of NMDA-induced currents by conantokin-G and conantokin-T in cultured embryonic murine hippocampal neurons.

Conantokin-G (con-G) and conantokin-T (con-T) are small (17 and 21 amino acids, respectively) gamma-carboxyglutamate (Gla) containing peptides derived from the venoms of marine cone snails that are potent and selective inhibitors of N-methyl-D-aspartate (NMDA) receptors. In this study, the effects of con-G and con-T on NMDA-evoked responses were evaluated in mouse primary hippocampal neuronal cultures using the whole-cell patch-clamp technique. Under equilibrium conditions, NMDA-induced currents were inhibited by con-G and con-T (10 nM-100 microM) in a dose-dependent manner while maintaining a holding potential of -70 mV. In the presence of saturating amounts of NMDA (100 microM) and glycine (1 microM), the IC50 values obtained were 487 +/- 85 nM for con-G and 1030 +/- 130 nM for con-T. NMDA (10 microM-1 mM) dose-response curves produced in the presence of con-G or con-T (1 or 3 microM) resulted in a downward shift of the current response at saturation with NMDA, without affecting the EC50. The maximum response obtainable in the absence of peptide could not be achieved by increasing concentrations of NMDA. The same effect was also observed for conantokin inhibition of spermine-potentiated responses. Association rate constants (k(on)) for the peptides were determined in the presence of NMDA and glycine, with and without the addition of spermine. Using a single binding site bimolecular model, k(on) values were 3.1 +/- 0.2 x 10(3) M(-1) s(-1) for con-G and 3.2 +/- 0.1 x 10(3) M(-1) s(-1) for con-T in the absence of spermine. The added presence of a saturating amount of spermine (300 microM) resulted in an approximate 60% increase in the k(on) values for both con-G and con-T. These results demonstrate that con-T and con-G inhibit NMDA-evoked currents, as well as the potentiation by spermine, in what appears to be a noncompetitive manner, and that spermine increases the rate of conantokin inhibition.

Kinetic and mechanistic characterization of NMDA receptor antagonism by replacement and truncation variants of the conantokin peptides.

The characterization of conantokin-T (con-T), conantokin-R (con-R), and variants thereof, using the whole-cell patch clamp technique, was undertaken to evaluate the contribution of various residues towards the onset and recovery of N-methyl-D-aspartate (NMDA) receptor inhibition in cultured embryonic murine hippocampal neurons. The results obtained indicate that the two most C-terminal gamma-carboxyglutamic acid (Gla) residues of the conantokins, while not essential for activity, provided for more tenacious binding to the receptor. Specifically, con-T[gamma10K/gamma14K] and con-R[gamma11A/gamma15A] displayed 5.6- and 8.4-fold decreases in tau(off), respectively, compared to the parent peptides. For the truncated con-T variants, con-T[1-9/Q6G], and a sarcosine (Src)-containing species, con-T[1-9/G1Src/Q6G], the tau(off) was over 80- and 40-fold faster, respectively, compared to con-T. For the latter peptide, the coapplication of 300 microM spermine enhanced the onset rate constant from 3.1x10(3)M(-1) x s(-1) to 12.6x10(3)M(-1) x s(-1). From analysis of equilibrium dose-inhibition curves using the Cheng-Prusoff equation, a K(i) value of 1.1 microM for the peptide was obtained. Con-T[1-9/G1Src/Q6G] demonstrated an apparent competitive mode of inhibition relative to NMDA. Schild analysis of the data yielded an equilibrium dissociation constant of 2.4 microM for the interaction of con-T[1-9/G1Src/Q6G] with the receptor.

Inhibition of nicotinic acetylcholine receptors by apolipoprotein E-derived peptides in rat hippocampal slices.

Apolipoprotein E (ApoE) is a well-known genetic risk factor for Alzheimer's disease (AD). Dysfunctions in cholinergic signaling, and in particular in the function of neuronal nicotinic acetylcholine receptors (nAChRs), have also been linked with AD and cognition. To address whether there is a link between ApoE and nAChR function, we used electrophysiological techniques to test the effects of synthetic ApoE-mimetic peptides derived from the low-density lipoprotein receptor (LDLR) binding domain for the ability to modulate nAChR activity in hippocampal interneurons. ApoE(133-149) completely inhibited ACh-evoked responses in a dose-dependent manner, yielding an IC(50) value of 720+/-70 nM. A shorter peptide spanning residues 141-148 mimicked this effect while a second peptide spanning residues 133-140 was without effect, indicating that the arginine-rich domain is responsible for nAChR interaction. Inhibition of ACh-evoked responses was voltage-independent, and displayed partial receptor specificity as no effect on glycine- or GABA-evoked responses occurred. These results demonstrate that peptides derived from the LDLR binding domain of ApoE block the function of nAChRs in hippocampal slices, an interaction that may have implications for AD.

Virus penetration of examination gloves.

Examination gloves worn for protection from biohazards were sampled and evaluated for their ability to exclude virus particles. We found that thin gloves manufactured from polyethylene or polyvinyl chloride are ineffective barriers while gloves of thin latex are superior but not without failure. Polyethylene and polyvinyl chloride gloves had failure rates of 40% and 22%, respectively. Following exposure to the common disinfectant, 70% ethanol, these failure rates increased to 94% and 56% for polyethylene and polyvinyl chloride gloves, respectively. Latex, although permeable to ethanol, was penetrated by virus less than 1% of the time regardless of whether the latex had been pre-exposed to disinfectant or not. This study highlights the need for caution on the part of those who rely upon examination gloves for protection from infectious agents as well as the need for establishing more adequate standards and testing procedures for their manufacture.

Ventricular arrhythmias in aortic valve disease: analysis of 102 patients.

Frequency and grade of ventricular arrhythmias in patients with isolated aortic stenosis (AS) or regurgitation (AR) were determined by 24-hour ambulatory electrocardiographic monitoring. The occurrence of ventricular arrhythmias in patients with aortic valve disease was compared with that in matched control subjects without aortic valve disease. Complex arrhythmias were significantly more prevalent in patients with valve disease than in control subjects (40 of 102 vs 19 of 102); the significant difference occurred in patients without concomitant coronary artery disease (CAD). In patients with valve disease without CAD, complex arrhythmias were significantly more common than in normal control subjects (22 of 65 vs 4 of 64); in the presence of CAD, complex arrhythmias were as prevalent in those with aortic valve disease as in those without it (18 of 37 vs 15 of 37, respectively). Among patients with AS or AR, arrhythmia occurrence and grade of ventricular ectopic activity were not related to the degree of AS or AR, ventricular hemodynamics or the presence or absence of concomitant CAD.

Efficacy and safety of oral cibenzoline for ventricular arrhythmias.

This study evaluates acute and chronic therapy with cibenzoline, a new class I antiarrhythmic drug, in 49 patients with ventricular arrhythmias. Acute therapy with 260 to 330 mg/day of cibenzoline resulted in a significant reduction in the number of hourly ventricular premature complexes (VPCs) (from 377 +/- 60 to 116 +/- 33, p less than 0.001), total paired VPCs in 24 hours (from 531 +/- 196 to 101 +/- 66, p less than 0.02), and total episodes of ventricular tachycardia in 24 hours (from 31 +/- 10 to 4 +/- 3, p less than 0.01). Among this group, acute therapy resulted in more than 75% suppression of VPC frequency in 29 of 49 patients, more than 90% suppression of paired VPCs in 31 of 42 patients, and complete suppression of ventricular tachycardia in 21 of 27 patients. Radionuclide evaluation of ventricular function revealed no deleterious effect of cibenzoline on ventricular function. Significant suppression of VPC frequency was maintained during 6 months of therapy in 16 of 19 patients and during 12 months of therapy in 9 of 10 patients. Trough plasma cibenzoline levels were measured during the acute dosing period. These levels did not differ among the group of responders (326 +/- 140 ng/ml) compared with nonresponders (354 +/- 282 mg/ml). Cibenzoline therapy resulted in adverse effects 18 patients and necessitated discontinuing therapy in 12. No patient had a proarrhythmic effect. In conclusion, cibenzoline appears to be as efficacious as the available antiarrhythmic drugs in treating chronic complex ventricular arrhythmias. Drug-related adverse effects occur with a frequency similar to that of other antiarrhythmic drugs.

Influence of patient characteristics in the selection of patients for defibrillator implantation (the AVID Registry). Antiarrhythmics Versus Implantable Defibrillators.

The Antiarrhythmics Versus Implantable Defibrillators (AVID) trial is a prospective, randomized study of treatment for life-threatening ventricular arrhythmias. Patients who are eligible for the main trial but who are not enrolled for any reason are followed in a registry. The objective of the present study was to determine whether there are identifiable patient characteristics among these registry patients that may influence whether a patient is treated with an implantable defibrillator. The 914 patients in the registry were divided into 2 groups according to whether the primary treatment was an implantable defibrillator. The mean age of defibrillator patients was 60 years, compared with 65 years in the nondefibrillator group (p <0.001). Only 11.2% of defibrillator recipients were minorities, whereas the percentage of minorities in the nondefibrillator group was 18.7% (p <0.003). A history of recurrent ventricular fibrillation was more likely in the group treated with defibrillators (8.9% vs 4.4%, p <0.01), whereas a history of atrial fibrillation or diabetes mellitus were both significantly more likely in the nondefibrillator group. Among defibrillator patients, a higher proportion had ventricular fibrillation as the index arrhythmia; patients with ventricular tachycardia were significantly more likely to be treated without devices. In this prospective but nonrandomized cohort of patients treated for life-threatening ventricular arrhythmias, older age, minority status, and comorbidity reduced the chances that a patient would be treated with a defibrillator.

Comparison of antihypertensive therapies by noninvasive techniques.

We compared the antihypertensive effects of the beta-blocker atenolol and the converting enzyme inhibitor lisinopril during 12 weeks of treatment in patients with mild to moderate essential hypertension. Atenolol (n = 10) significantly decreased conventionally measured blood pressure from 144/103 to 135/93 mm Hg and lisinopril (n = 9) from 150/104 to 130/92 mm Hg. Based on data derived from automated 24-h ambulatory blood pressure monitoring, atenolol decreased the average whole-day systolic pressure by 18 +/- 6 mm Hg (p less than 0.02) and the diastolic pressure by 11 +/- 2 mm Hg (p less than 0.01). Lisinopril produced decreases of 27 +/- 5 mm Hg (p less than 0.01) and 13 +/- 2 mm Hg (p less than 0.001). Examination of the 24-h blood pressure patterns showed that the efficacies of the two drugs were similar. Each appeared to be effective throughout the whole-day monitoring period, although only lisinopril significantly decreased blood pressure during the final four-h period (4 AM to 8 AM) preceding the next day's dose. Neither drug produced significant echocardiographic changes in left ventricular wall thickness or muscle mass during the short-term treatment. Lisinopril and atenolol effectively decrease blood pressure during a 24-h period. Moreover, we found that automated whole-day blood pressure monitoring is a useful tool for comparing the efficacy and duration of action of differing antihypertensive agents.

Pentazocine abuse. Report of a case with pulmonary arterial cellulose granulomas and pulmonary hypertension.

We report a patient who developed pulmonary hypertension following repeated intravenous injection of dissolved pentazocine tablets. Through analysis of lung biopsy material, this was shown to be due to embolization of the cellulose filler in the tablet and the tissue reaction it produced. Administration of prednisone appeared to improve the patient's clinical state.

Salt restriction lowers resting blood pressure but not 24-h ambulatory blood pressure.

Dietary salt restriction is the most common therapeutic recommendation given to hypertensives, but past studies have assessed the effect of salt restriction using resting blood pressure (BP) measurements not with the newer technique of 24-h ambulatory BP monitoring. We compared the effect of high (250 mEq Na/day) and low (10 mEq Na/day) salt diets on resting versus ambulatory BP in 12 normal and 15 hypertensive subjects. Each diet was given for 7 days. Ambulatory BP was monitored from day 6 to day 7 of each diet; resting supine BP was measured on the morning of day 8. In normal subjects, neither resting nor ambulatory BP changed with sodium restriction. In hypertensives, resting BP fell 14 +/- 3/6 +/- 2 mm Hg (systolic/diastolic; P less than .01 for both) with sodium restriction while ambulatory BP fell only 4 +/- 2/2 +/- 2 (P = NS). The resting BP fall was significantly greater than the ambulatory BP fall (P less than .05) for both systolic and diastolic pressure. Ambulatory heart rates were also significantly greater during sodium restriction, suggesting that the low salt diet activated the sympathetic nervous system. This may, in turn, have partially offset the hypotensive effect of sodium restriction. We conclude that using resting BP to assess the effect of sodium restriction may overestimate the efficacy of this therapy. Ambulatory BP monitoring should be employed in future studies of sodium restriction.

Diastolic blood pressure and left ventricular filling.

Many factors appear to influence diastolic left ventricular (LV) filling, including age, hypertension, and myocardial and coronary disease. Doppler-echocardiography was used to asses the influences of blood pressure (BP) on LV filling in 43 normotensive volunteers aged 12 +/- 0.98 years with heart rates less than or equal to 90 beats/min. Doppler peak diastolic transmitral flow velocities, diastolic flow integrals, and early diastolic deceleration were measured. An interesting difference was noted between the influence of systolic and diastolic BP. Systolic BP was related to LV mass (r = 0.43; P less than 0.005), but was unrelated to any of the Doppler filling indices. Diastolic BP was unrelated to LV mass, but was inversely related to peak early diastolic flow velocity (r = -0.37; P less than 0.05), early diastolic flow velocity integral (r = -0.34; P less than 0.05). The ratio of late-to-early filling (A/E) was directly related to diastolic BP (r = 0.42; P less than 0.005). The relationship between A/E and diastolic BP was strong in subjects (n = 21) with bimodal P waves in electrocardiogram (ECG) lead V1 (r = 0.61; P less than 0.005), but absent in those (n = 15) with unimodal P waves (r = 0.18; P = NS). Thus, the pattern of LV filling is related to the level of diastolic BP in normal adolescents, especially in those with bimodal P waves on ECG. These diastolic BP related changes are independent of heart rate and LV hypertrophy and may represent very early pre-hypertensive alterations in LV diastolic function.