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Biomedical subjects

W B White

Publications and source records attributed to W B White.

At least 109 records · Page 6Linked to original sources
PubMed1990

Cloning and sequencing of a bile acid-inducible operon from Eubacterium sp. strain VPI 12708.

Two bile acid-inducible polypeptides from Eubacterium sp. strain VPI 12708 with molecular weights of 27,000 and approximately 45,000 have previously been shown to be encoded by genes residing on a 2.9-kb EcoRI fragment. We now report the cloning and sequencing of three additional overlapping DNA fragments upstream from this EcoRI fragment. Together, these four fragments contain a large segment of a bile acid-inducible operon which encodes the 27,000- and 45,000-Mr (now shown to be 47,500-Mr) polypeptides and open reading frames potentially coding for four additional polypeptides with molecular weights of 59,500, 58,000, 19,500, and 9,000 to 11,500. A bile acid-inducible polypeptide with an apparent Mr of 23,500, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, was purified to homogeneity, and the N-terminal amino acid sequence that was obtained matched the sequence deduced from the open reading frame coding for the 19,500-Mr polypeptide. A short DNA segment containing the 3' downstream end of the gene coding for the 47,500-Mr polypeptide was not successfully cloned but was directly sequenced from DNA fragments synthesized by polymerase chain reaction. The mRNA initiation site for the bile acid-inducible operon was shown by primer extension to be immediately upstream from the gene encoding the 58,000-Mr polypeptide. A potential promoter region upstream from the mRNA initiation site displayed significant homology with the promoter regions of previously identified bile acid-inducible genes from Eubacterium sp. strain VPI 12708. We hypothesize that this bile acid-inducible operon codes for most of the enzymes involved in the bile acid 7 alpha-dehydroxylation pathway in this bacterium.

Amino Acid Sequence↗
PubMed1990

Multiple copies of a bile acid-inducible gene in Eubacterium sp. strain VPI 12708.

Eubacterium sp. strain VPI 12708 is an anaerobic intestinal bacterium which possesses inducible bile acid 7-dehydroxylation activity. Several new polypeptides are produced in this strain following induction with cholic acid. Genes coding for two copies of a bile acid-inducible 27,000-dalton polypeptide (baiA1 and baiA2) have been previously cloned and sequenced. We now report on a gene coding for a third copy of this 27,000-dalton polypeptide (baiA3). The baiA3 gene has been cloned in lambda DASH on an 11.2-kilobase DNA fragment from a partial Sau3A digest of the Eubacterium DNA. DNA sequence analysis of the baiA3 gene revealed 100% homology with the baiA1 gene within the coding region of the 27,000-dalton polypeptides. The baiA2 gene shares 81% sequence identity with the other two genes at the nucleotide level. The flanking nucleotide sequences associated with the baiA1 and baiA3 genes are identical for 930 bases in the 5' direction from the initiation codon and for at least 325 bases in the 3' direction from the stop codon, including the putative promoter regions for the genes. An additional open reading frame (occupying from 621 to 648 bases, depending on the correct start codon) was found in the identical 5' regions associated with the baiA1 and baiA3 clones. The 5' sequence 930 bases upstream from the baiA1 and baiA3 genes was totally divergent. The baiA2 gene, which is part of a large bile acid-inducible operon, showed no homology with the other two genes either in the 5' or 3' direction from the polypeptide coding region, except for a 15-base-pair presumed ribosome-binding site in the 5' region. These studies strongly suggest that a gene duplication (baiA1 and baiA3) has occurred and is stably maintained in this bacterium.

Amino Acid Sequence↗
PubMed1990

Predicting hypertensive heart disease via non-invasive methodology: relationship between ambulatory blood pressure and cardiac indices derived by echocardiography and radionuclide ventriculography.

The sensitivity of echocardiographically derived left ventricular mass in predicting morbidity in essential hypertension has led to widespread use of this measurement in cross-sectional studies to assess the pathophysiology of hypertensive heart disease. Over the past decade, a variety of studies in hypertensives have evaluated the blood pressure determinants of both the structural and the functional aspects of left ventricular hypertrophy. Recent data presented here demonstrate that average daily blood pressure derived from non-invasive ambulatory blood pressure monitoring is superior to casual blood pressure in predicting an increased left ventricular mass index and left atrial dimension, and altered left ventricular systolic and diastolic function. Further data analysis in previously untreated mildly hypertensive subjects (diastolic blood pressure less than 140/90 mmHg) showed that the average daily pressure load (defined as the percentage of blood pressure values greater than 140/90 mmHg while awake and greater than 120/80 mmHg during sleep) delineates groups at high and low risk of developing hypertensive heart disease.

Blood Pressure↗
PubMed1989

Effects of age and 24-hour ambulatory blood pressure on rapid left ventricular filling.

To determine the associations of age, blood pressure (BP) and cardiac structure with left ventricular (LV) diastolic performance, 47 subjects (21 normotensives and 26 age-matched, previously untreated hypertensives) were studied by 24-hour ambulatory BP monitoring, radionuclide ventriculography and sector-guided M-mode echocardiography. Normotension was defined as an awake ambulatory BP less than 130/80 mm Hg and hypertension as an awake ambulatory BP greater than 135/85 mm Hg. Univariate analyses revealed strong negative correlations of LV filling rate with age (r = -0.67, p less than 0.001), 24-hour systolic or diastolic BP (r = -0.59 for systolic BP and -0.57 for diastolic BP, p less than 0.001 for both) and a modest positive correlation with LV ejection fraction (r = 0.42, p less than 0.05). After multivariate analysis, significant dependencies of both the left atrial index and LV mass index on ambulatory BP were found, which negated the significance of the relation of these 2 cardiac structural variables with LV filling rate. The final regression equation predicted LV filling rate from age, BP and LV ejection fraction. Age was the most important single correlate of LV filling, as evidenced by the 14 of 16 subjects (88%) over the age of 53 years (8 hypertensives, 6 normotensives) who had reduced LV filling rates compared with only 9 of the remaining 31 subjects (29%, all hypertensives) under the age of 53 years with reduced LV filling rates. These data demonstrate that LV filling rate is more dependent upon age and BP than left atrial or LV size.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Average daily blood pressure, not office blood pressure, determines cardiac function in patients with hypertension.

To determine the presence of cardiac disease in hypertensive patients with disparities between physician and out-of-office blood pressures, we prospectively studied three groups of age-matched patients identified by both casual (office) and ambulatory blood pressures: (1) office blood pressure greater than 140/90 mm Hg and awake ambulatory blood pressure of 130/80 mm Hg or less ("office" hypertensives); (2) office blood pressure less than 135/85 mm Hg and awake ambulatory blood pressure of 130/80 mm Hg or less (normotensives); and (3) office blood pressure greater than 140/90 mm Hg and awake ambulatory blood pressure of 140/90 mm Hg or greater ("daytime" hypertensives). In the patients with office hypertension, both the left atrial index and left ventricular mass index were significantly less than in patients with daytime hypertension and not statistically different from those of the normotensive subjects. Left ventricular filling rate at rest and ejection fraction at peak exercise were significantly greater in the office hypertensive group than in the daytime hypertensive group but were no different from those of the normotensive subjects. These findings demonstrate that patients with blood pressure elevation only in the physician's office have cardiac size and function similar to those of normotensive individuals. Thus, the average daily blood pressure best predicts cardiac end-organ damage.

Adult↗
PubMed1989

Nitrendipine in human plasma and breast milk.

To assess the disposition of the dihydropyridine calcium antagonist, nitrendipine, in lactating mothers, we studied three breast-feeding women to determine simultaneous plasma and breast milk concentrations of nitrendipine and its inactive pyridine analog metabolite after both a single 10 mg oral dose and 5 days of continuous therapy (20 mg per day). Nitrendipine was excreted in breast milk at peak concentrations ranging from 4.3 to 6.5 ng/ml 1-2 h after acute dosing while its inactive pyridine metabolite ranged from 6.9 to 11.9 ng.ml-1. After 5 days of dosing, Cmax remained in the same range and the breast milk/whole plasma concentration ratio for nitrendipine was 0.2 to 0.5. On the fourth day of continuous dosing, average concentrations of nitrendipine from 24-h collections of the milk were 1.1 to 3.8 ng.ml-1. Thus, nitrendipine and its metabolite are excreted in very low concentrations in human breast milk. Based on a maternal dose of 20 mg daily, a newborn infant would ingest an average of 1.7 micrograms of nitrendipine per day, or a relative dose of 0.095%.

Adult↗
PubMed1989

Assessment of the daily blood pressure load as a determinant of cardiac function in patients with mild-to-moderate hypertension.

The distribution of blood pressure (BP) values over the day and night was assessed in a group of 30 never previously treated patients with mild-to-moderate essential hypertension via 24-hour ambulatory BP monitoring. Elevated BP values during the awake hours (greater than 140/90 mm Hg) and sleeping hours (greater than 120/80 mm Hg) were used to calculate the total percentage of abnormal BP values (load) in each patient. The relationship between BP load and several indexes of hypertensive cardiac target organ involvement was compared to the relationships among office (casual), 24-hour average BP values, and cardiac indexes. Casual systolic and diastolic BP values did not correlate with left ventricular mass index, left atrial index, or peak left ventricular filling rate. Both 24-hour average BP and systolic and diastolic BP loads correlated with all indexes of cardiac target organ involvement. The BP loads were related to left ventricular mass index and left atrial index more strongly than were the mean 24-hour BP values; however, they were equally correlated for peak left ventricular filling rate. If greater than 40% of the ambulatory BP values were elevated, the likelihood of increased mass or decreased filling was greater than 61%, whereas if less than 40% of the BP values were elevated, the incidence of an abnormal cardiac test result decreased to less than 17%. These data show that the percentage of elevated BP values that includes both the awake and asleep periods is predictive of cardiac target organ involvement in patients with mild-to-moderate hypertension. Patients with mild hypertension who have more than 40% abnormal BP values should strongly be considered for antihypertensive therapy.

Adult↗
PubMed1989

Regression of left ventricular mass is accompanied by improvement in rapid left ventricular filling following antihypertensive therapy with metoprolol.

Left ventricular hypertrophy is associated with abnormal left ventricular diastolic filling in patients with hypertension. To assess the effects of antihypertensive therapy on the heart in nine previously untreated patients with echocardiographically-detected left ventricular hypertrophy, left ventricular mass and rapid left ventricular filling rate were compared before and after 6 months of treatment with metoprolol monotherapy. Metoprolol was given in doses of 100 to 400 mg/day (average dose, 167 mg/day in two divided doses) and significantly reduced both casual, office blood pressure (150/101 to 130/86 mm Hg, p less than 0.01) and 24-hour ambulatory blood pressure (139/91 to 126/79 mm Hg, p less than 0.05 for systolic, p less than 0.01 for diastolic). Following treatment with metoprolol, left ventricular mass index decreased from 135 +/- 20 to 120 +/- 13 gm/m2 (p less than 0.05), while rapid left ventricular filling rate increased from 1.89 +/- 0.24 to 2.09 +/- 0.27 end-diastolic volumes/sec (p less than 0.01). The reduction in left ventricular mass index was secondary to decreased posterior and septal wall thicknesses (13% and 11%, respectively, p less than 0.05 for both), as there were no changes in the left ventricular internal dimensions. Neither resting nor exercise left ventricular ejection fraction changed on metoprolol therapy compared to the baseline values. These data demonstrate that regression of left ventricular hypertrophy in never-previously-treated hypertensive patients is accompanied by improved diastolic performance following beta-adrenergic blocker monotherapy.

Adult↗
PubMed1989

Rapid left ventricular filling is more dependent on age and twenty-four-hour blood pressure than on cardiac size.

The associations of age, blood pressure and cardiac structure with rapid left ventricular filling were assessed in 47 subjects (21 normotensives and 26 age-matched untreated hypertensives) by 24-h ambulatory blood pressure monitoring, sector-guided M-mode echocardiography and radionuclide ventriculography. Univariate analyses revealed strong negative correlations of the left ventricular filling rate with age, and 24-h systolic and diastolic blood pressure, and a moderate positive correlation with the left ventricular ejection fraction at rest. Multiple regression analysis was performed with these variables, left atrial size and left ventricular mass index. Left atrial size and the left ventricular mass index were dependent on 24-h blood pressure, indicating that these two cardiac structural variables were less important than left ventricular filling. Age was undoubtedly the most important correlate of left ventricular filling, since 88% of the subjects over 53 years of age had reduced left ventricular filling rates regardless of the blood pressure status. However, under the age of 53 years, only the hypertensives had reduced filling rates. Thus, our study shows that the left ventricular filling rate is more dependent on age and 24-h blood pressure than on the left ventricular mass index. Furthermore, in patients over 53 years of age, it is not possible to separate the effects of hypertension on the diastolic function of the heart from the physiological alterations associated with ageing.

Aging↗
PubMed1989

Clinical evaluation of the Colin ABPM 630 at rest and during exercise: an ambulatory blood pressure monitor with gas-powered cuff inflation.

The Colin ABPM 630 is a silent, gas-powered (CO2) ambulatory blood pressure monitor which uses both ausculatory and/or oscillometric methods to measure blood pressure. We compared simultaneous, same-arm blood pressures obtained with the monitor with those made by two blinded, skilled clinicians using a mercury column and teaching stethoscope. In a second study, the monitor readings were also compared with opposite-arm intra-arterial recordings of blood pressure. The group mean systolic blood pressures obtained by the Colin monitor via the Korotkoff mode were almost identical to the mercury column readings (127.8 +/- 19.4 versus 128.1 +/- 19.3 mmHg, P = NS) and the limit of agreement (2 standard deviations) for the differences in the two methods was +/- 9 mmHg. The diastolic blood pressure obtained by the Colin monitor was significantly lower than the clinician's readings (-6.0 +/- 5.9 mmHg, P less than 0.0001). Similar findings were obtained with the oscillometric mode, however, the mean systolic blood pressure given by the monitor was slightly higher than that given by the mercury column (1.9 +/- 4.5 mmHg, P less than 0.001). In contrast to the mercury column comparisons, the mean diastolic blood pressure obtained with the monitor was nearly the same as the mean intra-arterial diastolic blood pressure for both the Korotkoff (0.1 +/- 5.6 mmHg) and the oscillometric modes (1.2 +/- 6.3 mmHg). During 100-watt bicycle exercise, there was a considerably greater scatter in the individual comparisons of the monitor and intra-arterial blood pressure than that seen in the measurements at rest, but the group means were again similar.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Clinical evaluation of the Accutracker II ambulatory blood pressure monitor: assessment of performance in two countries and comparison with sphygmomanometry and intra-arterial blood pressure at rest and during exercise.

In order to assess the Accutracker II (Suntech Medical Instruments, Raleigh, North Carolina, USA), a relatively new ambulatory blood pressure (BP) monitor, versus standard forms of BP measurement, we compared same- and contralateral-arm measurements made, via a t-tube connected to a mercury column sphygmomanometer, by two clinicians using a teaching stethoscope and by intra-arterial recordings. Average systolic BP values obtained using the Accutracker II were similar to both the mercury column and intra-arterial determinations, but average diastolic BP values were lower than both the average mercury column (2.8 +/- 4.2 mmHg, P less than 0.001) and intra-arterial measurements (2.0 +/- 4.7 mmHg, P less than 0.02). During isometric exercise and 100-watt bicycle exercise, there were greater limits of agreement for the differences in BP between the Accutracker II and the intra-arterial transducer than were observed for the resting measurements, but these differences were no greater than those observed between intra-arterial and clinician-determined BP measurements. The clinical performance of the Accutracker II was assessed using 119 hypertensive subjects (84 in Norway and 35 in the USA) who wore the monitor for 24 h. While there was good-to-excellent data return in both countries, there were significantly less error codes secondary to excessive arm motion observed in Norway. Our data demonstrate that the Accutracker II is quite accurate compared with both the mercury column and intra-arterial methods of measuring BP, and performs well during 24 h outpatient activities. Our findings also indicate certain geographical differences which may be important in the performance of ambulatory BP-monitoring studies.

Adolescent↗
PubMed1989

Comparative renal effects of intravenous administration of fenoldopam mesylate and sodium nitroprusside in patients with severe hypertension.

We studied the renal effects of intravenous administration of fenoldopam mesylate, a dopamine-1 agonist, vs sodium nitroprusside following acute reduction of blood pressure (BP) in 11 patients with severe hypertension (supine BP, 168/124 to 252/135 mm Hg). Following randomization (open-label), timed urinary and plasma samples for clearance of urea and creatinine and excretion of sodium, potassium, and calcium were obtained as well as plasma renin activity for a two-hour collection prior to infusion, during a two-hour period of BP control (supine diastolic BP, 95 to 110 mm Hg), and following two hours off the drugs. Mean arterial pressure was lowered similarly with the two drugs (-22% on fenoldopam vs -20% on nitroprusside; P = NS), and neither plasma renin activity nor plasma aldosterone concentration were changed by either drug. However, patients receiving fenoldopam had significant increases in urinary flow and excretion of sodium, potassium, and calcium, whereas patients receiving nitroprusside had no changes in these parameters. Patients receiving fenoldopam had a net fluid balance of -334 mL from the end of baseline to the end of the treatment period, while the nitroprusside group had a positive balance of 382 mL. Thus, these findings show that acute BP reduction with fenoldopam is associated with both a diuresis and natriuresis in severely hypertensive patients while lowering BP with nitroprusside does not predictably alter renal function and causes a moderate expansion in volume.

Adult↗
PubMed1988

Ejaculatory failure and urinary dysfunction secondary to labetalol.

We describe 3 men with moderate to severe essential hypertension in whom ejaculatory failure developed after therapy with labetalol, an antihypertensive drug with alpha-1 and beta-adrenergic blocking properties. No decrease in libido or erectile dysfunction was reported by any of the patients. Previous and subsequent antihypertensive therapy with either alpha or beta-adrenergic blocking agents failed to cause similar symptoms. These findings reveal a unique spectrum of genitourinary dysfunction associated with the multireceptor blocking properties of labetalol.

Adult↗
PubMed1988

Selective dopamine-1 agonist therapy in severe hypertension: effects of intravenous fenoldopam.

To determine the effects of dopamine-1 agonist therapy in severe hypertension, blood pressure, heart rate, catecholamines and left ventricular function were studied in 18 patients (10 with renal disease) with diastolic blood pressure greater than 120 mm Hg (range 124 to 160) after intravenous fenoldopam therapy. Constant infusions of fenoldopam were titrated upward every 10 to 20 min from an initial dose of 0.1 microgram/kg per min to a maximal dose of 0.9 microgram/kg per min. The therapeutic goal of a supine diastolic blood pressure of less than 110 mm Hg was achieved in every patient within 1 h at an average dose of 0.34 +/- 0.22 microgram/kg per min. Blood pressure decreased from 214/134 +/- 33/10 mm Hg at baseline to 170/96 +/- 29/7 mm Hg (p less than 0.0001) at 3 h, whereas heart rate increased from 77 +/- 23 to 88 +/- 21 beats/min (p less than 0.01). Plasma norepinephrine increased during the fenoldopam infusion; epinephrine and dopamine levels did not change. Two indexes of left ventricular function (end-systolic dimension and isovolumic relaxation time) improved during the fenoldopam infusion, but mitral flow velocities during ventricular filling were unchanged. Side effects of intravenous fenoldopam were mild, transient and associated with the marked vasodilatory properties of the drug. Thus, fenoldopam is safe and effective as a parenteral monotherapy in patients with severe essential and renovascular hypertension. Preliminary data suggest that blood pressure reduction with selective dopamine-1 agonist therapy is accompanied by improved left ventricular function.

Adult↗
PubMed1988

The effects of the long-acting angiotensin-converting enzyme inhibitor cilazapril on casual, exercise, and ambulatory blood pressure.

We assessed blood pressure (BP) and heart rate (HR) responses in a double-blind, randomized study comparing cilazapril, a long-acting, nonsulfhydryl-group converting enzyme inhibitor, with placebo in 18 patients with mild to moderate (sitting diastolic BP, 95 to 114 mm Hg) essential hypertension. The BP and HR parameters were evaluated at rest (casual, 24 hours after administration), during treadmill exercise testing (Bruce protocol), and with 24-hour noninvasive ambulatory BP monitoring. These assessments were made after a 4-week drug washout period and after 8 to 12 weeks of therapy. After 8 weeks of therapy with cilazapril (mean dose 3.6 +/- 0.9 mg/day), casual BP decreased 19/11 mm Hg (p less than 0.01), whereas placebo lowered BP by 4/5 mm Hg (difference not significant) compared with the baseline period. The casual HR was modestly (7 beats/min) but significantly (p less than 0.05) lowered by cilazapril monotherapy. Exercise BP was reduced by cilazapril (reduction at peak HR, 23/11 +/- 10/5 mm Hg; p less than 0.05), and exercise HR was unchanged. Compared with baseline, the duration of exercise was improved with cilazapril but not with placebo (1.0 minute vs -0.2 minute; p less than 0.05). Twenty-four-hour mean, awake, and sleep BPs were reduced with cilazapril with the most impressive reduction occurring during the awake period (19/12 mm Hg; p less than 0.01). These data demonstrate that cilazapril lowers casual, exercise, and ambulatory BP with a modest but significant improvement in exercise time. Thus cilazapril may be particularly effective in the physically active hypertensive patient.

Adult↗