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Biomedical subjects

W B White

Publications and source records attributed to W B White.

At least 19 recordsLinked to original sources

Utilizing ambulatory blood pressure recordings to evaluate antihypertensive drug therapy.

Until recently, the efficacy and pharmacodynamics of antihypertensive agents were assessed by resting blood pressure measurements in the doctor's office or a research clinic. The limitations of the office or clinic blood pressure measurement include the lack of representation (from recording only 1 point of time in the dosing schedule), the effects of the doctor's office on the patient's blood pressure, and, perhaps more relevant, observer bias. Ambulatory monitoring of the blood pressure has gained worldwide acceptance as an alternative method to assess antihypertensive drug efficacy and the time-effect relation of a drug. The ambulatory monitoring devices have been refined and are smaller, more precise, and more reliable than earlier recording models. Although there are no reference standards for analysis of ambulatory blood pressure data, international consensus groups are presently addressing this problem. Key roles for ambulatory blood pressure recordings in clinical trials of antihypertensive agents now include determination of the entry criteria for patients, improving the assessment of peak/trough pharmacodynamics in the patient's own environment (including nocturnal/sleep readings), and evaluating efficacy through calculation of the hypertensive burden, or blood pressure load.

Ambulatory Care

Accuracy and analysis of ambulatory blood pressure monitoring data.

Two devices used to record blood pressure, the ambulatory blood pressure monitoring recorder and standard stethoscope and mercury column, were tested for accuracy against the direct intra-arterial blood pressure of patients at rest and during exercise. Recorders were found to be as accurate as mercury column measurement in patients at rest. A number of assessment techniques of ambulatory data are reviewed, including: calculation of mean or median pressures, assessment of blood pressure load, and integration of the area under the blood pressure curve over time. These have been applied during the daytime and nighttime hours. Blood pressure load and area under the blood pressure curve, using different threshold criteria for nighttime and daytime, are recommended because of their potentially closer relation to target-organ disease of hypertension than are office blood pressure readings.

Ambulatory Care

Diurnal blood pressure variability in mineralocorticoid excess syndrome.

Noninvasive 24-h blood pressure (BP) monitoring has demonstrated a diurnal blood pressure profile in most individuals that is characterized by higher arterial pressures during wakefulness and lower pressures at night during sleep. Recently, reports suggest that this typical diurnal variation is absent in syndromes of autonomic dysfunction and in some forms of secondary hypertension. We investigated the 24-h BP, BP variability, and adrenal steroid concentrations in a patient with deoxycorticosterone (DOC)-secreting adrenal adenoma prior to and following adrenalectomy. Preoperatively, when the patient had a ten-fold increase in serum concentrations of DOC, there was no fall in nocturnal BP despite a marked reduction in heart rate during sleep. Postoperatively, when the concentrations of DOC and other adrenal steroids returned to normal values, the 24-h BP profile normalized with restoration of the nocturnal reduction in pressure. These findings document the effects of mineralocorticoid overproduction on diurnal BP regulation. Intensive investigation of individuals with a well-defined etiology of hypertension and the absence of diurnal variation of BP may lead to further hypotheses that will define the role of both autonomic and nonautonomic factors in BP control.

Adenoma

Diurnal blood pressure and blood pressure variability in diabetic normotensive and hypertensive subjects.

PURPOSE: Ambulatory blood pressure monitoring has helped to identify different patterns of diurnal blood pressure variability in hypertensive patients. This review examines the available data, with special reference to diabetic hypertensives. DATA IDENTIFICATION: The diurnal rhythm is absent or abnormal in certain disease states, including diabetes mellitus, Cushing's syndrome, hyperaldosteronism and renal failure. Lack of a nocturnal decline in blood pressure is clinically significant, as it is associated with a greater prevalence of hypertensive target-organ disease. STUDY SELECTION: Clinical studies were assessed, in which casual and 24-h blood pressure measurements were available from normotensive and hypertensive patients with insulin-dependent or non-insulin-dependent diabetes mellitus. RESULTS OF DATA ANALYSIS: Studies comparing the diabetic with the non-diabetic normotensive (based on casual, or office blood pressure measurements) have shown that 24-h mean blood pressures are higher in diabetics. In insulin-dependent diabetics, the incidence of elevated nocturnal pressure appears to be greater than in non-insulin-dependent diabetics. Furthermore, recent reports have shown that ambulatory blood pressure is more closely correlated than casual blood pressure with urinary albumin excretion in type 1 diabetic hypertensives. CONCLUSIONS: Ambulatory blood pressure monitoring reveals certain characteristic blood pressure variability in the diabetic patient with hypertension and allows an assessment of the effects of antihypertensive drug therapy in order to ensure blood pressure control.

Antihypertensive Agents

Identification of formate dehydrogenase-specific mRNA species and nucleotide sequence of the fdhC gene of Methanobacterium formicicum.

The overlapping fdhA and fdhB genes of Methanobacterium formicicum, which encode the alpha and beta subunits, respectively, of formate dehydrogenase, were cotranscribed as part of an approximately 4.5-kb transcript. An additional gene (fdhC) upstream of fdhA was cotranscribed with fdhA and fdhB. The deduced amino acid sequence suggested that fdhC has the potential to encode a hydrophobic polypeptide with a calculated molecular weight of 29,417. A hydropathy plot of the hypothetical polypeptide indicated several potential membrane-spanning regions. The putative fdhC gene product had 28% identity with the deduced amino acid sequence of the nirC gene from Salmonella typhimurium. Northern (RNA) blot analyses and primer extension assays located a transcription start site 268 bp upstream of the initiation codon of fdhC. A sequence identical to the consensus promoter sequence for methanogenic organisms was situated between -35 and -25 bp from the proposed transcription start site. In addition to the 4.5-kb transcript, Northern blot analyses detected a 1.1-kb transcript with an fdhC-specific probe and a 3.4-kb transcript with either an fdhA- or fdhB-specific probe. The levels of all three transcripts were significantly greater in cells grown in media supplemented with molybdate.

Amino Acid Sequence

Impact of the daily blood pressure load on the development of hypertensive heart disease.

Blood pressure (BP) load is a method of data analysis for 24-hour BP recordings that calculates the percentage of elevated pressures above a defined threshold value. This paper reviews the relevance of BP load to indexes of hypertensive target organ disease and the usefulness of the load in assessing antihypertensive therapy. Studies that have assessed the range of BP load and the associations between the load and indexes of hypertensive target organ disease in untreated subjects were included in this review. Additional data from a therapeutic trial have been newly evaluated to assess the effects of lisinopril monotherapy on systolic and diastolic BP load in 30 mild-to-moderately hypertensive patients. BP load, whether taken as a percentage of elevated pressures over the day and night, or as integrated areas under the BP curve, predicts pathological indexes of hypertensive heart disease. In the therapeutic evaluation of BP load, lisinopril reduced systolic BP load from 75 to 44% (p < 0.001) and diastolic BP load from 56 to 29% (p < 0.001). The data have shown a close relationship between BP load and indexes of hypertensive disease. This finding and the ease of use in clinical therapeutic trials suggest that BP load reduction is a worthwhile parameter to follow in studies of antihypertensive drugs.

Adult

The role of ambulatory monitoring of the blood pressure for assessment of antihypertensive agents.

For many decades, the casual blood pressure (BP) has been the standard for assessing BP response to antihypertensive agents in clinical trials. Noninvasive ambulatory BP technology has improved vastly in the last 15 years and has been increasingly used in dose-response studies as well as efficacy trials. Through these studies we have learned that casual BP may not be representative of the average daily blood pressure, that it may be quite susceptible to observer bias, and that it may result in inaccurate calculation of the trough-to-peak ratio of an antihypertensive drug. Perhaps more importantly is that a large body of data now supports the superiority of average daily BP over that of the casual or clinic BP in predicting several indexes of hypertensive target organ damage. Thus, use of the ambulatory BP technique in antihypertensive trials yields BP data that are far less susceptible to improper diagnosis and are representative of the hypertensive burden that causes vascular disease.

Ambulatory Care

A multicenter evaluation of the A&D TM-2420 ambulatory blood pressure recorder.

The A&D TM-2420 (A&D Engineering, Milpitas, CA) is an automatic, portable, noninvasive blood pressure (BP) recorder which uses a dual microphone system for the detection of Korotkoff sounds. Its accuracy and clinical performance were assessed in a multicenter study that also addressed issues such as observer agreement and the effects of age, arm circumference, heart rate, posture, and blood pressure level on the observer-device differences. We compared 906 simultaneous, same-arm BP measurements in 151 subjects using the TM-2420 versus two skilled clinicians per site using a teaching stethoscope. The agreement between the TM-2420 and mercury column determinations were within 10 mm Hg for 86 to 91% of systolic readings and 91 to 94% of diastolic readings, depending on the posture; a level of agreement which would receive a 'B+' grade from the recent British Hypertension Society guidelines. The limits of agreement (2 standard deviations about the mean difference) for systolic BP between observers and the TM-2420 tended to be greater for the standing position (-20 to 15 mm Hg) compared to supine (-14 to 12 mm Hg) and seated (-13 to 8 mm Hg) positions. Limits of agreement between the observers and device were not dependent upon age, heart rate, arm size, or blood pressure level. Twenty-four-hour blood pressure monitoring in two of the four centers demonstrated an error code rate of 3.4%, excluding 'retries' that are one of the device's features. These data demonstrate an acceptable level of accuracy and performance of the sixth generation of the TM-2420 for use in clinical practice and research.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Ambulatory blood pressure monitoring during exercise and physical activity.

Ambulatory blood pressure recorders have two potential advantages over standard casual blood pressure measurements; they are able to take multiple recordings automatically throughout the day and night and also during the activities of normal daily living. At present, the general recommendations for validation of blood pressure recorders do not include assessment during motion. In order to obtain accurate information on an ambulatory blood pressure recorder's capabilities during exercise or physical activity, the blood pressure standard must use direct (intra-arterial) measurements. Data from some of the existing ambulatory blood pressure recorders suggest that many are accurate during resting measurements but lose their precision when the subjects are walking or during exercise. If ambulatory recorders are to be used in ambulant conditions with a moving arm, the device should be validated for accuracy and reliability during motion, using simultaneous direct measurements for comparison.

Activities of Daily Living

Blood pressure load and target organ effects in patients with essential hypertension.

The ambulatory blood pressure load has been defined as the elevated systolic and/or diastolic pressures over a 24-h period. This parameter, in a sense, represents the chronic pressure overload that induces myocardial and vascular damage associated with the hypertensive disease process. In recent years, blood pressure load has been arbitrarily defined as the percentage of blood pressures greater than 140/90 mmHg while awake and greater than 120/80 mmHg during sleeping hours or the integrated area under the blood pressure curve above the same values. Recent data presented here demonstrate that blood pressure load, expressed as a percentage value in mild hypertensives or as an integrated area under the curve in more moderate and severe hypertensives, is a better determinant of cardiac or vascular abnormalities than either casual or mean ambulatory blood pressure.

Blood Pressure

Assessment of ambulatory blood pressure recorders: accuracy and clinical performance.

There are now more than ten different manufacturers of non-invasive, portable blood pressure monitors in North America, Europe, and Japan. These ambulatory blood pressure recorders measure blood pressure by either auscultatory or oscillometric methodology. Technologic advances in the recorders have resulted in reduction in monitor size, reduction in or absence of motor noise during cuff inflation, ability to program the recorder without an external computer system, and enhanced precision. Recently, there has been concern that more structured validation protocols have not been implemented prior to the widespread marking of ambulatory blood pressure recorders. There is a need for proper assessment of recorders prior to use in clinical research or practice. Data on several existing recorders suggest that while most are reasonably accurate during resting measurements, many lose this accuracy during motion, and clinical performance may vary among the monitors. Validation studies of ambulatory recorders should include comparison with mercury column and intra-arterial determinations, resting and motion measurements, and assessment of clinical performance in hypertensive patients.

Blood Pressure

Ambulatory blood pressure and target organ involvement in hypertension.

Casual (or office) blood pressure values have been shown to be associated with cardiovascular morbidity or mortality in a variety of prospective trials assessing cardiovascular risk. In recent years, however, controversies have developed regarding the capacity of casual blood pressures to predict cardiovascular risk in an individual patient with high blood pressure. Prospective, cross-sectional studies have been performed in several centres that compare the capacity to predict hypertensive target organ involvement by casual vs 24-h mean, awake, or sleep blood pressures. Ambulatory blood pressure has been consistently superior to casual blood pressure in predicting target organ involvement in hypertension. As most of the data collected to date has involved cardiac studies, however, fewer conclusions can be drawn regarding renal and cerebrovascular disease. With regard to cardiac structure and/or function, ambulatory blood pressure is much more useful than casual blood pressure in determining the likelihood of an abnormal index in an individual patient with hypertension.

Blood Pressure Determination

Analysis of ambulatory blood pressure data in antihypertensive drug trials.

In recent years a number of different methods have been evolved to analyse ambulatory blood pressure monitoring data, particularly for evaluating the relationship between blood pressure and target-organ disease and for assessing the effects of antihypertensive drug therapy. The most commonly used methods include calculation of mean or median values during wakefulness and sleep, assessment of blood pressure variability and distribution, calculating blood pressure load, and, more recently, integrating the area under the blood pressure curve over time. Although all of these methods of data analysis have merit, none has been used exclusively in assessing the effects of antihypertensive therapy. The rationale for using a particular method of analysis should be based on the physiological or pharmacological modality under investigation, the reproducibility of the method, the ease of statistical manipulation and, most important, the relationship between the blood pressure determinant and indices of the hypertensive disease process (e.g. left ventricular enlargement, vascular compliance). Ambulatory blood pressure recordings are superior to clinic recordings in assessing the duration of activity of an antihypertensive drug, while Fourier transformation of individual blood pressure curves (in contrast to a group of curves) may aid the evaluation of peak and trough activity. As the blood pressure load and the area under the blood pressure curve are closely related to target-organ disease in hypertension, the use of these methods is advocated in assessing the efficacy of antihypertensive drugs.

Antihypertensive Agents

Assessment of four ambulatory blood pressure monitors and measurements by clinicians versus intraarterial blood pressure at rest and during exercise.

The accuracy of 4 different ambulatory blood pressure (BP) monitors was assessed by comparing them to simultaneous intraarterial BP (contralateral brachial artery) during rest, isometric and dynamic (bicycle) exercise in 48 hypertensive patients undergoing invasive hemodynamic evaluation. The differences between the intraarterially determined BP and values obtained by the various monitors were then compared to differences between BP measured directly and by 2 clinicians using a standard mercury column in 10 additional hypertensive patients. The monitors studied were the Accutracker II (auscultatory with mandatory electrocardiographic gating), Colin ABPM 630 (auscultatory or oscillometric), Del Mar Pressurometer IV (auscultatory with optional electrocardiographic gating) and SpaceLabs 90202 (oscillometric). During rest, the differences between intraarterially and clinician-determined systolic and diastolic BP were 4 +/- 8 and -4 +/- 6 mm Hg, respectively. The Accutracker II and Colin ABPM 630 using the auscultatory method showed less disparity and closer limits of agreement (2 standard deviations of the mean difference) with intraarterial BP than the clinicians' measurements, whereas the other units showed similar or greater limits of agreement. During both isometric and dynamic exercise, mean BP differences between intraarterial and clinician determinations were similar to those at rest but the limits of agreement increased. The limits of agreement between intraarterial and monitor-derived BP also increased during exercise compared to differences observed at rest. The Accutracker II and Colin ABPM 630 using the auscultatory method had limits of agreement with intraarterial BP that were either similar to or less than the clinician's, whereas the Colin monitor using the oscillometric method and the Del Mar Pressurometer IV showed greater disparity.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Pressure Determination

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

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