Pre-eclampsia: a lifelong disorder.
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Cardiovascular Diseases↗
Biomedical subjects
Mark A Brown
Publications and source records attributed to Mark A Brown.
A comparison of outcomes with angiotensin-converting--enzyme inhibitors and diuretics for hypertension in the elderly.
BACKGROUND: Treatment of hypertension with diuretics, beta-blockers, or both leads to improved outcomes. It has been postulated that agents that inhibit the renin-angiotensin system confer benefit beyond the reduction of blood pressure alone. We compared the outcomes in older subjects with hypertension who were treated with angiotensin-converting-enzyme (ACE) inhibitors with the outcomes in those treated with diuretic agents. METHODS: We conducted a prospective, randomized, open-label study with blinded assessment of end points in 6083 subjects with hypertension who were 65 to 84 years of age and received health care at 1594 family practices. Subjects were followed for a median of 4.1 years, and the total numbers of cardiovascular events in the two treatment groups were compared with the use of multivariate proportional-hazards models. RESULTS: At base line, the treatment groups were well matched in terms of age, sex, and blood pressure. By the end of the study, blood pressure had decreased to a similar extent in both groups (a decrease of 26/12 mm Hg). There were 695 cardiovascular events or deaths from any cause in the ACE-inhibitor group (56.1 per 1000 patient-years) and 736 cardiovascular events or deaths from any cause in the diuretic group (59.8 per 1000 patient-years; the hazard ratio for a cardiovascular event or death with ACE-inhibitor treatment was 0.89 [95 percent confidence interval, 0.79 to 1.00]; P=0.05). Among male subjects, the hazard ratio was 0.83 (95 percent confidence interval, 0.71 to 0.97; P=0.02); among female subjects, the hazard ratio was 1.00 (95 percent confidence interval, 0.83 to 1.21; P=0.98); the P value for the interaction between sex and treatment-group assignment was 0.15. The rates of nonfatal cardiovascular events and myocardial infarctions decreased with ACE-inhibitor treatment, whereas a similar number of strokes occurred in each group (although there were more fatal strokes in the ACE-inhibitor group). CONCLUSIONS: Initiation of antihypertensive treatment involving ACE inhibitors in older subjects, particularly men, appears to lead to better outcomes than treatment with diuretic agents, despite similar reductions of blood pressure.
Aged↗
Method of birth alters interferon-gamma and interleukin-12 production by cord blood mononuclear cells.
Many uncertainties exist regarding the capability of cord blood mononuclear cells (CBMC) to produce cytokines. A number of conflicting reports led us to examine the effects of method of birth on CBMC production of interferon-gamma (IFN-gamma), interleukin-4 (IL-4) and interleukin-12 (IL-12). While constitutive production of IL-4 was found in both vaginally and cesarean-delivered infants, constitutive IFN-gamma or IL-12 production was found in neither. CBMC from vaginally delivered infants responded to stimulation with concanavalin A/phorbol 12-myristate 13-acetate (Con A/PMA), phytohemagglutinin (PHA), and lipopolysaccharide (LPS) with significantly higher levels of IFN-gamma than CBMC from unlabored cesarean section (CS) infants. Production of IL-12 was increased in the vaginally delivered group in response to LPS and PHA but not to ConA/PMA. In contrast, mode of delivery was not associated with differences in IL-4 production. These results indicate that mode of delivery significantly alters the capability of CBMC to produce some cytokines and therefore should be taken into account in interpreting fetal/neonatal mononuclear cell function studies.
Delivery, Obstetric↗
Forearm blood flow in pre-eclampsia.
UNLABELLED: OBJECTIVE 1. To characterise the forearm vascular reactivity of women with pre-eclampsia in the third trimester of pregnancy and compare it with that in normal or gestational hypertensive pregnancies. 2. To document female sex steroid (oestradiol, progesterone, oestriol and betahCG) levels in the three groups of women. DESIGN: Forearm blood flow was measured by venous occlusion plethysmography during intra-arterial infusion of saline and vasoactive substances: angiotensin II, sodium nitroprusside, acetylcholine and N(G)-monomethyl-L-arginine (L-NMMA). SETTING: Research laboratory at St George Hospital, Kogarah, Sydney, Australia. SAMPLE: Fifteen non-pregnant women in the follicular phase of the menstrual cycle, 15 third trimester normal pregnant women, 13 women in the third trimester with gestational hypertension and 15 women with pre-eclampsia. MAIN OUTCOME MEASURES: Changes in forearm blood flow in response to vasoactive substances. RESULTS: Normal pregnant women had higher baseline forearm blood flow than non-pregnant women, decreased vasodilator responses to sodium nitroprusside and reduced vasoconstrictor responses to angiotensin II. No difference in response to angiotensin II, sodium nitroprusside or L-NMMA was found among normal pregnant, pre-eclampsia or gestational hypertension women, but vasodilatory responses of pre-eclamptic women to acetylcholine were reduced compared with normal pregnant women. Higher serum progesterone levels were found in women with pre-eclampsia and gestational hypertension than in normal pregnancy. CONCLUSION: The hyperdynamic circulation of normal pregnancy is characterised by refractoriness to angiotensin II but this is not altered in pre-eclampsia. Pre-eclamptic women demonstrate a reduced vasodilator response to acetylcholine which, in the absence of any alteration in response to L-NMMA, implies that factors other than nitric oxide deficiency mediate the vasoconstriction of pre-eclampsia.
Acetylcholine↗
The clinical utility of routine urinalysis in pregnancy: a prospective study.
OBJECTIVES: To determine whether routine urinalysis in the antenatal period facilitates diagnosis of pre-eclampsia. Can routine urinalysis during pregnancy be discontinued in women with normal results of dipstick urinalysis and microscopy at the first antenatal visit? DESIGN: Prospective observational study. SETTING: A metropolitan public hospital and a private hospital in Sydney (NSW). PARTICIPANTS: One thousand women were enrolled at their first antenatal visit (March to November 1999), and 913 completed the study. OUTCOME MEASURES: The primary outcome was a diagnosis of de novo hypertension (gestational hypertension, pre-eclampsia, or pre-eclampsia superimposed on chronic hypertension). RESULTS: Thirty-five women had dipstick proteinuria at their first antenatal visit. In 25 (71%) of these women, further dipstick proteinuria was detected during pregnancy, and two (6%) were diagnosed with pre-eclampsia. Of the 867 without dipstick proteinuria at the first visit, 338 (39%) had dipstick proteinuria (> 1+) at some time during pregnancy. There were no statistically significant differences in the proportion of women with and without dipstick proteinuria at their first visit who developed hypertension during pregnancy. Only six women developed proteinuria before the onset of hypertension. Women who had an abnormal result of a midstream urine test at their first visit, compared with women with a normal result, were more likely to have a urinary tract infection diagnosed during pregnancy; however, the numbers were small. CONCLUSION: In the absence of hypertension, routine urinalysis during pregnancy is a poor predictor of pre-eclampsia. Therefore, after an initial screening urinalysis, routine urinalysis could be eliminated from antenatal care without adverse outcomes for women.
Adolescent↗
Post-translational processing of Drosophila nucleoside diphosphate kinase.
Nucleoside diphosphate kinase (NDPK) was purified from Drosophila melanogaster by a combination of anion-exchange, hydroxyapatite, and reversed-phase chromatography. The identity of the purified enzyme was confirmed by sequencing internal peptides (the N-terminus appeared to be blocked). Post-translational modifications were investigated by using protein chemical and mass spectrometric methods. Analysis by nanoelectrospray ionization-mass spectrometry revealed that the mass of the enzyme was considerably smaller than that predicted from its amino acid sequence. Although its open-reading frame predicts a 153-residue polypeptide, the mature enzyme was found to comprise 152 amino acids, being modified by proteolytic removal of the initiator Met and N-acetylation of Ala2. This explains why the observed pI of the Drosophila enzyme is more acidic than that predicted from its amino acid sequence. No additional post-translational modifications such as glycosylation or O-phosphorylation, which have been identified on homologous NDPKs from other organisms, were detected on the Drosophila enzyme.
Animals↗
Identification of catalytically important amino acids in human ceruloplasmin by site-directed mutagenesis.
The involvement of amino acid residues previously proposed on the basis of structural data to have roles in the ferroxidase and diamine oxidase activities of human ceruloplasmin was investigated. Variants of human ceruloplasmin, in which residues proposed to be involved in electron transfer and/or iron-binding had been altered by site-directed mutagenesis, were expressed in HEK293 cells. E633A and E597A/H602A variants exhibited reduction in both activities by 50-60% compared to recombinant wild-type ceruloplasmin. The variant E935A/H940A had reduced ferroxidase activity (50%) but unaltered diamine oxidase activity, whereas the variant E971A exhibited enhanced diamine oxidase activity. For the L329M variant, both activities were identical to those of wild-type ceruloplasmin.
Amino Acid Substitution↗
Magnetic resonance imaging of pulmonary parenchymal disease using a modified breath-hold 3D gradient-echo technique: initial observations.
PURPOSE: To determine the potential of a modified breath-hold 3D gradient-echo technique for visualizing pulmonary parenchymal diseases. MATERIALS AND METHODS: Twenty-one magnetic resonance imaging (MRI) studies of the lungs were performed in 20 patients (15 male and 5 female; age range, 7.7-86.1 years) with pulmonary diseases comprising non-small-cell, small-cell, and bronchioalveolar carcinomas, endobronchial mucoepidermoid carcinoma, metastases, pneumonia, Wegener's granulomatosis, chronic obstructive pulmonary disease, arterio-venous malformation, and bronchogenic cyst. Confirmation of diagnoses was obtained via histopathology (14 patients) and follow-up (6 patients). MRI studies were performed at 1.5 T before and after administration of gadolinium using a modified volumetric interpolated breath-hold examination (VIBE) sequence. All images were evaluated prospectively regarding lesion detection and characterization. MR findings were correlated with final diagnoses. Retrospective grading (scores, 1-4) was performed for general image quality (rated "poor" to "excellent"); presence of artifacts ("negligible" to "severe"); and imaging quality of pulmonary lesions (conspicuity and contrast on pre- and postgadolinium images). RESULTS: Twenty-three solid pulmonary lesions, 25 infiltrates and segmental atelectases, and 1 cyst were detected and prospectively correctly diagnosed. Sizes ranged from 0.3-10 cm. The mean scores for image quality and presence of artifacts were 3.3 (SD, 0.7) and 1.8 (SD, 0.7), respectively. Conspicuity and contrast of pulmonary lesions received mean scores between 3.0 and 3.8 (SD, 0.4-0.7). CONCLUSION: This MRI technique allows imaging of a wide spectrum of solid and nonsolid pulmonary parenchymal diseases with reproducible high image quality, effective suppression of artifacts, high resolution, and visualization of gadolinium enhancement.
Adolescent↗
Platelet activation in the hypertensive disorders of pregnancy.
OBJECTIVE: The purpose of this study was to determine whether platelet activation occurs only in preeclampsia or also in normal pregnancy. STUDY DESIGN: Thirty women with preeclampsia, 30 women with gestational hypertension, 20 women with essential hypertension, 30 pregnant women with normotension, and 30 nonpregnant women were recruited at St George Hospital, Sydney, Australia. Platelet activation was determined by flow cytometry on whole blood samples. RESULTS: Platelet activation was similar in all groups, except the group with preeclampsia. Compared with normal pregnant women, women with preeclampsia had significantly greater CD62 expression (1.35% vs 0.61%; P =.002), CD63 expression (1.73% vs 0.95%; P <.0001) and annexin V binding (1.03% vs 0.66%;P =.03) and significantly fewer circulating platelet microparticles (33 vs 49 x10(9)/L; P =.001). This was unrelated to other parameters that included platelet counts. Women with gestational hypertension in whom preeclampsia developed did not have enhanced platelet activation profiles. CONCLUSION: Platelet activation is increased in preeclampsia but not in other hypertensive disorders or in normal pregnancy. This may be part of the pathophysiologic factors of preeclampsia complications but is not predictable by the platelet count and is not apparent in all women with preeclampsia.
Adult↗
Efficacy and safety of nifedipine tablets for the acute treatment of severe hypertension in pregnancy.
OBJECTIVE: The purpose of this study was to determine whether the slower- and longer-acting nifedipine tablets were as effective and safe as the rapid onset and short-acting nifedipine capsules for the treatment of acute severe hypertension in pregnancy. STUDY DESIGN: Sixty-four women in the second half of pregnancy who were not in labor randomly received 10 mg nifedipine tablets (n = 55 studies) or 10 mg nifedipine capsules (n = 74 studies) if blood pressure was > or =170/110 mm Hg. Blood pressure, heart rate, and cardiotocography were monitored over the subsequent 90 minutes. Successful treatment was a target blood pressure of 110 to 169/80 to 109 mm Hg after 90 minutes; unsuccessful treatment included fetal distress at any stage, the requirement for additional treatment (intravenous hydralazine), or the development of hypotension by 90 minutes after treatment. RESULTS: Nifedipine capsules lowered blood pressure further (28/19 vs 21/13 mm Hg; P =.03) than nifedipine tablets, but more than three quarters of each group had a successful treatment. Twice as many women (28%) who received nifedipine tablets required a second dose to achieve successful treatment (P =.05), but fewer women had hypotensive episodes (P =.001). Fetal distress was uncommon in both groups (3%-4%), and both groups were delivered an average of 4 days after the study. CONCLUSION: Nifedipine tablets, although of slower onset, are as effective as nifedipine capsules for the rapid treatment of severe hypertension in pregnancy.
Acute Disease↗
'Reverse white-coat hypertension' in older hypertensives.
OBJECTIVES: The role of ambulatory blood pressure monitoring (ABPM) in the elderly is unclear. This study has examined differences between clinic and ambulatory blood pressure (BP) in a large cohort of older hypertensives, with particular respect to the factors influencing the direction and magnitude of this difference. DESIGN: The Second Australian National Blood Pressure Study (ANBP2) is a general practice-based randomized-outcome trial in 6083 older hypertensives treated with an angiotensin-converting enzyme (ACE) inhibitor or diuretic-based regimen. Before starting treatment a subset of 713 patients (age range 65-83 years) had a 'successful' 26-hour ambulatory blood pressure recording with a SpaceLabs 90207 recorder. RESULTS: Average clinic BP (+/- SD) was 167 +/- 12/90 +/- 8 mmHg. Average daytime ambulatory BP was 157 +/- 15*/89 +/- 10* mmHg and night ambulatory BP was 137 +/- 16+/74 +/- 10+ mmHg (different from clinic BP: *P < 0.01;from daytime ambulatory BP: +P < 0.001). Twenty-one to 45% of all patients had higher daytime systolic or diastolic ambulatory BP than clinic readings, with smoking, previous treatment for hypertension and lower clinic BP being the main predictors of this 'reverse white-coat effect'. CONCLUSIONS: Although mean daytime ambulatory blood pressures were lower than clinic readings in this large cohort of untreated older hypertensives, a substantial proportion showed the reverse of the so-called 'white-coat effect'. These findings identify the important role for ABPM in the elderly, not only for avoiding overtreatment in those with typical 'white-coat hypertension' but also for ensuring adequate treatment is given to those with the reverse of this phenomenon.
Age Factors↗
Hypertension in pregnancy: do consensus statements make a difference?
OBJECTIVES: (i) To document variation in management of hypertension in pregnancy; (ii) to determine whether this variation falls within current management guidelines; and (iii) to make recommendations for developing future guidelines. DESIGN: Questionnaire-based survey. SETTING: Australia and New Zealand. POPULATION: All specialist obstetricians. METHODS: Questionnaires were sent to 1198 obstetricians in Australia and New Zealand. Those returned by respondents currently in obstetric practice were analysed. Information was obtained on their current clinical practices relating to the diagnosis and management of hypertension in pregnancy. RESULTS: Of 1198 obstetricians surveyed, 973 (81%) replied. Of these, 686 (71%) were responsible for obstetric care. Considerable variation in practice was found, particularly in relation to the measurement of blood pressure, the determination of hypertension and significant proteinuria, and the decision to institute antihypertensive drug treatment. The recommendations of the Australasian 1993 Consensus Statement appeared to have had little influence on practice. There has been a striking increase in the use of magnesium sulphate for the prevention of convulsions in preeclampsia. CONCLUSIONS: There is significant variation in management of hypertensive pregnancies that differs from current guidelines. It is not known whether this diversity adversely affects clinical outcomes. Until further outcome evidence is available, consensus statements may be better confined to basic aspects of management for which there is high level evidence.
Adult↗
Innovation in veterans' health care and assistance: the Department of Veterans Affairs 10 years after the Gulf War.
The Department of Veterans Affairs (VA) has responded to significant challenges in treating and compensating Persian Gulf War veterans by adapting existing programs and developing new ones. The VA established a Gulf War health examination registry and expanded existing "Vet Centers" to provide assistance to Gulf War veterans. Health care eligibility income limitations were eliminated. Outreach efforts included a national newsletter, veterans' organization briefings, and other products. The VA is developing targeted training programs and continuing medical education for health care providers. Numerous major research initiatives have begun. Innovations include the establishment of environmental hazards research centers, clinical demonstration projects, and centers for the study of war-related illness. These efforts required increased coordination among federal agencies and collaboration with other countries. In a precedent-setting development, Congress gave the VA authority to compensate certain veterans with undiagnosed illnesses. Veterans from future conflicts and peacekeeping missions can expect improved services from the VA as a result of these initiatives.
Humans↗
Platelets: a new target for gene therapy of haemophilia B.
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Blood Platelets↗