Randomised trial of management of hypertensive pregnancies by Korotkoff phase IV or phase V

BACKGROUND: There is debate about whether diastolic blood pressure should be recorded as the fourth (muffling, K4) or fifth (disappearance, K5) Korotkoff sound in pregnancy. We compared maternal and fetal outcomes and the likelihood that episodes of severe hypertension would be recorded when hypertensive pregnancies were managed according to either K4 or K5. METHODS: 220 pregnant women with diastolic hypertension (K4 > or =90 mm Hg) after the 20th week of gestation were enrolled in a prospective randomised study at two obstetric units in Australia; they were randomly assigned management with K4 (n=103) or K5 (n=117) for the remainder of the pregnancy. Clinical management was according to a uniform department protocol. Analysis was by intention to treat. All the women completed the trial. FINDINGS: An episode of severe hypertension (systolic > or =170 mm Hg, diastolic > or =110 mm Hg, or both) was more likely to be recorded with use of K4 than with use of K5 (39 [38%] vs 30 [26%] women, p=0.051), mainly because of a greater likelihood that severe diastolic hypertension would be recorded (34 [33%] vs 20 [17%], p=0.006). The frequency of severe systolic hypertension and simultaneous severe systolic and diastolic hypertension did not differ between groups. Pregnancy was prolonged by an average of 2 weeks in both groups, and there were no significant differences between the groups in laboratory data, requirements for antihypertensive treatment, birthweight, fetal growth retardation, or perinatal mortality. There was no eclampsia or significant maternal morbidity in either group. INTERPRETATION: A change from use of K4 to K5 would mean that one fewer case of severe diastolic hypertension would be recorded for every six hypertensive pregnancies, but all other episodes of severe hypertension would be recorded with similar frequency. Since the K4/K5 difference is smaller in hypertensive than in normotensive pregnant women and since K5 is closer to the actual intra-arterial pressure and more reliably detected, universal adoption of K5 to record diastolic blood pressure in hypertensive pregnancy should be considered.     

Report of the Canadian Hypertension Society Consensus Conference: 2. Nonpharmacologic management and prevention of hypertensive disorders in pregnancy

OBJECTIVE: To provide Canadian physicians with comprehensive, evidence-based guidelines for the nonpharmacologic management and prevention of gestational hypertension and pre-existing hypertension during pregnancy. OPTIONS: Lifestyle modifications, dietary or nutrient interventions, plasma volume expansion and use of prostaglandin precursors or inhibitors. OUTCOMES: In gestational hypertension, prevention of complications and death related to either its occurrence (primary or secondary prevention) or its severity (tertiary prevention). In pre-existing hypertension, prevention of superimposed gestational hypertension and intrauterine growth retardation. EVIDENCE: Articles retrieved from the pregnancy and childbirth module of the Cochrane Database of Systematic Reviews; pertinent articles published from 1966 to 1996, retrieved through a MEDLINE search; and review of original randomized trials from 1942 to 1996. If evidence was unavailable, consensus was reached by the members of the consensus panel set up by the Canadian Hypertension Society. VALUES: High priority was given to prevention of adverse maternal and neonatal outcomes in pregnancies with established hypertension and in those at high risk of gestational hypertension through the provision of effective nonpharmacologic management. BENEFITS, HARMS AND COSTS: Reduction in rate of long-term hospital admissions among women with gestational hypertension, with establishment of safe home-care blood pressure monitoring and appropriate rest. Targeting prophylactic interventions in selected high-risk groups may avoid ineffective use in the general population. Cost was not considered. RECOMMENDATION: Nonpharmacologic management should be considered for pregnant women with a systolic blood pressure of 140-150 mm Hg or a diastolic pressure of 90-99 mm Hg, or both, measured in a clinical setting. A short-term hospital stay may be required for diagnosis and for ruling out severe gestational hypertension (preeclampsia). In the latter case, the only effective treatment is delivery. Palliative management, dependent on blood pressure, gestational age and presence of associated maternal and fetal risk factors, includes close supervision, limitation of activities and some bed rest. A normal diet without salt restriction is advised. Promising preventive interventions that may reduce the incidence of gestational hypertension, especially with proteinuria, include calcium supplementation (2 g/d), fish oil supplementation and low-dose acetylsalicylic acid therapy, particularly in women at high risk for early-onset gestational hypertension. Pre-existing hypertension should be managed the same way as before pregnancy. However, additional concerns are the effects on fetal well-being and the worsening of hypertension during the second half of pregnancy. There is, as yet, no treatment that will prevent exacerbation of the condition. VALIDATION: The guidelines share the principles in consensus reports from the US and Australia on the nonpharmacologic management of hypertension in pregnancy.     

Managing hypertension: the postgraduate medicine lecture

Managing hypertension effectively requires careful evaluation of the patient, in particular for the presence of target-organ damage and of other risk factors for atherosclerosis. Dietary management has proved to be unsatisfactory in most hypertensive patients, as patients resist dietary restrictions or any other changes in life-style. Drug treatment has been shown to significantly reduce morbidity and mortality in patients with diastolic blood pressures above 104 mm Hg. Evidence suggests that drug treatment is also effective in those with diastolic pressures between 90 and 104 mm Hg. Selection of drugs is still an empirical decision--treatment with an oral diuretic usually is effective for mild hypertension (diastolic pressures 90 to 115 mm Hg). A sympathetic depressant, often propranolol, may be added to the regimen next, and if this is ineffective, a vasodilator (usually hydralazine) is included. Common side effects of antihypertensive drugs are seldom serious but can be annoying. Patients should be forewarned about them, and about the effects of untreated hypertension in an effort to improve compliance.     

Pregnancy in the chronically hypertensive patient

The majority of patients with mild chronic hypertension have successful pregnancy outcomes. Most perinatal morbidity is secondary to superimposed preeclampsia. Antihypertensive therapy does not appear to significantly affect pregnancy outcome, nor the incidence of superimposed preeclampsia in mild chronic hypertensives. The maternal and fetal risks are considerably higher for severe chronic hypertension and for those patients with target organ disease. These patients ideally should be counseled regarding their risks prior to pregnancy. Antihypertensive therapy should be instituted at diastolic pressures greater than or equal to 100 mm Hg.     

Chronic administration of dexamethasone results in Fc receptor up-regulation and inhibition of class I antigen expression on macrophages from MRL/lpr autoimmune mice

OBJECTIVE: To assess the influence of hypertensive disorders in pregnancy on the subsequent risk of placental abruption and uterine bleeding of unknown aetiology, and to examine the combined effects of hypertensive disorders and cigarette smoking during pregnancy on the risk of uteroplacental bleeding disorders. DESIGN: Retrospective cohort study. SETTING: Data for this study were derived from the Nova Scotia Atlee Perinatal database, Canada, comprising of women who were delivered in the province between 1980 and 1993. POPULATION: 120,666 pregnancies resulting in singleton births, of which 13,360 pregnancies were complicated by pre-eclampsia and/or chronic hypertension. MAIN OUTCOME MEASURES: Risks and relative risks of placental abruption and uterine bleeding of unknown aetiology in pregnancies complicated by chronic hypertension, mild and severe pre-eclampsia, and chronic hypertension with superimposed pre-eclampsia, each compared with normotensive patients. Adjusted relative risks were obtained through the fit of multivariable logistic regression models based on the method of generalised estimating equations. RESULTS: Chronically hypertensive women had no increased risk of abruption (RR 1.4; 95% CI 0.5-3.6), while women whose pregnancies were complicated by severe pre-eclampsia (RR 3.8; 95% CI 2.1-6.9), and chronic hypertension with superimposed pre-eclampsia (RR 2.8; 95% CI 1.2-6.3) showed strong associations with placental abruption. However, none of the hypertensive disorders were associated with uterine bleeding of unknown aetiology. The association between placental abruption and hypertensive disorders varied by parity. Parous women with chronic hypertension and superimposed pre-eclampsia were at greater risk of placental abruption (aRR 3.8; 95% CI 1.9-7.8) than nulliparous women with chronic hypertension and superimposed pre-eclampsia (aRR 1.6; 95% CI 0.5-4.9). The joint effects of smoking and hypertension had a greater effect on the risk of placental abruption than would have been expected based on their individual effects. CONCLUSIONS: The pattern of association between placental abruption and hypertension varied in relation to the specific type of hypertensive disorder. However, uterine bleeding of unknown aetiology was not associated with hypertension. Findings from this study suggest that placental abruption and uterine bleeding of unknown origin are aetiologically distinct obstetric complications with respect to hypertensive disorders during pregnancy.     

Maternal renal artery blood flow velocimetry in normal and hypertensive pregnancies

OBJECTIVE: To investigate the effect of normal pregnancy and hypertensive disorders of pregnancy on the maternal renal artery Doppler blood flow velocity indices. METHODS: The patient material consisted of 30 normal pregnant women, 29 women with pregnancy induced hypertension, 43 women with preeclampsia and 22 pregnant women with chronic hypertension. Blood flow velocities in the segmental renal arteries from the right kidney were analysed by pulsed and color Doppler. The systolic/diastolic (s.d.) ratio, resistance index (RI) and pulsatility index (PI) were used for Doppler waveform analysis. RESULTS: In all of the groups of hypertensive pregnant women renal artery Doppler indices were significantly lower compared to the normal pregnant women group. There was a significant negative relationship between renal artery PI and mean arterial pressure in the preeclampsia group and in the chronic hypertension group. CONCLUSION: The present results demonstrate that the mechanism of renal autoregulation in preeclampsia might be altered, leaving glomerulus unprotected from increased blood pressure. It seems that the concept of renal vasoconstriction in preeclampsia might be disputed and needs further investigation.     

Effect of reduced dietary sodium on blood pressure: a meta-analysis of randomized controlled trials

OBJECTIVE:- To ascertain whether restriction of dietary sodium lowers blood pressure in hypertensive and normotensive individuals. DATA SOURCES:- An English-language computerized literature search, restricted to human studies with Medical Subject Heading terms, "hypertension," "blood pressure," "vascular resistance," "sodium and dietary," "diet and sodium restricted," "sodium chloride," "clinical trial," "randomized controlled trial," and "prospective studies," was conducted. Bibliographies of review articles and personal files were also searched. TRIAL SELECTION:- Trials that had randomized allocation to control and dietary sodium intervention groups, monitored by timed sodium excretion, with outcome measures of both systolic and diastolic blood pressure were selected by blinded review of the methods section. DATA EXTRACTION:- Two observers extracted data independently, using purpose-designed forms, and discrepancies were resolved by discussion. DATA SYNTHESIS:- The 56 trials that met our inclusion criteria showed significant heterogeneity. Publication bias was also evident. The mean reduction (95% confidence interval) in daily urinary sodium excretion, a proxy measure of dietary sodium intake, was 95 mmol/d (71-119 mmol/d) in 28 trials with 1131 hypertensive subjects and 125 mmol/d (95-156 mmol/d) in 28 trials with 2374 normotensive subjects. After adjustment for measurement error of urinary sodium excretion, the decrease in blood pressure for a 100-mmol/d reduction in daily sodium excretion was 3.7 mm Hg (2.35-5.05 mm Hg) for systolic (P<.001) and 0.9 mm Hg (-0.13 to 1.85 mm Hg) for diastolic (P=.09) in the hypertensive trials, and 1.0 mm Hg (0.51-1.56 mm Hg) for systolic (P<.001) and 0.1 mm Hg (-0.32 to 0.51 mm Hg) for diastolic (P=.64) in the normotensive trials. Decreases in blood pressure were larger in trials of older hypertensive individuals and small and nonsignificant in trials of normotensive individuals whose meals were prepared and who lived outside the institutional setting. CONCLUSION:- Dietary sodium restriction for older hypertensive individuals might be considered, but the evidence in the normotensive population does not support current recommendations for universal dietary sodium restriction.     

Pregnancy induced hypertension

Hypertension remains a leading cause of perinatal morbidity and mortality. Classification of the hypertensive disorders of pregnancy is 1) preeclampsia-eclampsia, 2) chronic hypertension, 3) chronic hypertension with superimposed preeclampsia-eclampsia. Preeclampsia is characterized by the triad of hypertension, proteinuria, and edema but these findings are not specific. Although the etiology and pathogenesis of preeclampsia remain unknown, several factors such as abnormalities in prostaglandin systems, in coagulation process, derangements of the endothelium and so on. Management of preeclampsia is bed rest, aspirin administration, antihypertensive agents (beta-blockers, hydralazine, alpha-methyldopa) would be used for reduction of blood pressure.     

Risk factors associated with preeclampsia in healthy nulliparous women. The Calcium for Preeclampsia Prevention (CPEP) Study Group

OBJECTIVE: Our goal was to identify risk factors for the development of preeclampsia in nulliparous women enrolled in a multicenter trial comparing calcium supplementation to a placebo. STUDY DESIGN: A total of 4589 women from five centers was studied. Analysis of risk factors for preeclampsia was performed in 4314 who carried the pregnancy to > 20 weeks. Baseline systolic and diastolic blood pressure, demographic characteristics, and findings after randomization were examined for the prediction of preeclampsia. Preeclampsia was defined as hypertension (diastolic blood pressure > or = 90 mm Hg on two occasions 4 hours to 1 week apart) and proteinuria (> or = 300 mg/24 hours, a protein/creatinine ratio > or = 0.35, one dipstick measurement > or = 2+ or two dipstick measurements > or = 1+ at an interval as specified for diastolic blood pressure). RESULTS: Preeclampsia developed in 326 women (7.6%). The first analysis treated each risk factor as a categoric variable in a univariate regression. Maternal age, blood group and Rh factor, alcohol use, previous abortion or miscarriage, private insurance, and calcium supplementation were not statistically significant. Risk factors initially found to be significant were body mass index, systolic blood pressure, diastolic blood pressure, non-white race (African-American and other), clinical center, and smoking. Adjusted odds ratios computed with a logistic regression model revealed that body mass index (odds ratio 3.22 for > or = 35 kg/m2 vs < 19.8 kg/m2), systolic blood pressure (odds ratio 2.66 for > or = 120 vs < 101 mm Hg), diastolic blood pressure (odds ratio 1.72 for > or = 61 mm Hg vs < 60 mm Hg), and clinical center (odds ratio 1.85 for Memphis vs the other clinical centers) were statistically significant predictors of preeclampsia. Results of the final model fit revealed that preeclampsia risk increases significantly (p < 0.0001) with increased body mass index at randomization, as well as with increased systolic and diastolic blood pressure at randomization. Calcium supplementation had no effect on the risks posed by body mass index and blood pressure. Among risk factors developing after randomization, an abnormal results of a glucose screen (plasma glucose > or = 140 mg/dl 1 hour after a 50 gm glucose challenge) was not found to be associated with a significant risk of preeclampsia. CONCLUSION: These risk factors should be of value in counseling women regarding preeclampsia and should aid in understanding the pathophysiologic characteristics of this syndrome.     

Changes in left ventricular structure and function in patients with white coat hypertension: cross sectional survey

OBJECTIVES: To assess the relation between white coat hypertension and alterations of left ventricular structure and function. DESIGN: Cross sectional survey. SETTING: Augsburg, Germany. SUBJECTS: 1677 subjects, aged 25 to 74 years, who participated in an echocardiographic substudy of the monitoring of trends and determinants in cardiovascular disease Augsburg study during 1994-5. OUTCOME MEASURES: Blood pressure measurements and M mode, two dimensional, and Doppler echocardiography. After at least 30 minutes' rest blood pressure was measured three times by a technician, and once by a physician after echocardiography. Subjects were classified as normotensive (technician <140/90 mm Hg, physician <160/95 mm Hg; n=849), white coat hypertensive (technician <140/90 mm Hg, physician >=160/95 mm Hg; n=160), mildly hypertensive (technician >=140/90 mm Hg, physician <160/95 mm Hg; n=129), and sustained hypertensive (taking antihypertensive drugs or blood pressure measured by a technician >=140/90 mm Hg, and physician >=160/95 mm Hg; n=538). RESULTS: White coat hypertension was more common in men than women (10.9% versus 8.2% respectively) and positively related to age and body mass index. After adjustment for these variables, white coat hypertension was associated with an increase in left ventricular mass and an increased prevalence of left ventricular hypertrophy (odds ratio 1.9, 95% confidence interval 1.2 to 3.2; P=0.009) compared with normotensive patients. The increase in left ventricular mass was secondary to significantly increased septal and posterior wall thicknesses whereas end diastolic diameters were similar in both groups with white coat hypertension or normotension. Additionally, the systolic white coat effect (difference between blood pressures recorded by a technician and physician) was associated with increased left ventricular mass and increased prevalence of left ventricular hypertrophy (P<0.05 each). Values for systolic left ventricular function (M mode fractional shortening) were above normal in subjects with white coat hypertension whereas diastolic filling and left atrial size were similar to those in normotension. CONCLUSION: About 10% of the general population show exaggerated inotropic and blood pressure responses when mildly stressed. This is associated with an increased risk of left ventricular hypertrophy.     

Felodipine use in pregnancy. Report of three cases

BACKGROUND: Calcium channel blockers are effective agents for the management of chronic hypertension and are being used with increasing frequency. If their safety and efficacy during pregnancy can be documented, women can be counseled to continue their antihypertensive agent during pregnancy. To our knowledge, the use of felodipine, a calcium channel blocker of the dihydropyridine group, during pregnancy has not been described. CASES: We report three cases of felodipine use in pregnancy by women with chronic hypertension. CONCLUSION: In women with severe hypertension (diastolic blood pressure > 100 mm Hg) who require pharmacologic treatment of it during pregnancy, felodipine appears to be an acceptable option.     

Paradoxical hypertension after reversal of heart failure in patients treated with intensive vasodilator therapy

Hypertension is a major cause of heart failure, evolving from left ventricular hypertrophy to systolic and diastolic dysfunction. Although effective heart failure therapy has been associated with a lowering or no change in systemic arterial blood pressure in long-term follow-up, this study describes the symptomatic, clinical, and left ventricular functional response of a subgroup of heart failure patients with a prior history of hypertension who demonstrated a paradoxical hypertensive response despite high-dose vasodilator therapy. We prospectively identified 45 patients with a past history of hypertension who had become normotensive with symptomatic heart failure. Of these 45 heart failure patients, 12 became hypertensive while receiving therapy in follow-up, with systolic blood pressure > or = 140 mm Hg (Group A). The remaining 33 patients did not have a hypertensive response to therapy (Group B). In the 12 Group A patients, 60+/-10 years old, with symptomatic heart failure for 6.3+/-4.3 years, vasodilator therapy was intensified in the 2.0+/-0.5 years of follow-up, achieving final doses of enalapril 78+/-19 mg and isosorbide dinitrate 293 +/-106 mg per day. New York Heart Association classification improved from 2.9+/-0.8 to 1.3+/-0.5 (P < or = .0001), with a reduction in heart-failure-related hospitalizations. Left ventricular ejection fraction increased from 17+/-6% to 40+/-10% (P < .0001). Follow-up blood pressure at 1 to 3 months was unchanged. However, both systolic and diastolic blood pressure increased at final follow-up, rising from 116+/-14 to 154+/-13 mm Hg (P = .0001) and from 71+/-9 to 85+/-14 mm Hg (P = .004), respectively. Renal function remained unchanged. Although both groups had similar clinical responses, there were more blacks and women in the hypertensive Group A. Effectively, 12 of 45 (27%) heart failure patients with an antecedent history of hypertension demonstrated a paradoxical hypertensive response to vasodilator therapy. The recurrence of hypertension in a significant portion of patients successfully treated for heart failure has important clinical implications.     

Proteinuria, other selected urinary abnormalities and hypertension among teenage secondary school students in Nairobi, Kenya

Four hundred and three teenage secondary school students (50.6% males) from two girls' and two boys' Nairobi City Schools, selected by stratified sampling, were screened to determine the prevalence of proteinuria, haematuria, nitrituria and hypertension. Nine students (2.2%) had significant proteinuria while 14 (3.5%) had microscopic haematuria. Two students had combined proteinuria and haematuria. There was no statistically significant difference in the prevalence of proteinuria and/or haematuria between the sexes. Other urinary abnormalities detected were leucocyturia in 14(3.5%) and nitrites in four (1%). Leucocyturia was commonner in females (p = 0.001). Cloudy urinary appearance was significantly associated with the presence of leucocyturia (p = 0.0028) and proteinuria (p = 0.0276). Neither personal history of recurrent sore throat and skin infections nor family history of hypertension, diabetes mellitus or kidney disease was significantly associated with proteinuria or haematuria. Blood pressure tended to increase with age. Mean systolic and diastolic blood pressures were significantly higher in boys than girls in the age group 15-18 years (P < 0.001). Of the 397 students whose blood pressures were measured, four (1%) were found to be hypertensive. Weight and body mass index were strong positive correlates of blood pressure. The prevalence of proteinuria, haematuria, other urinary abnormalities and hypertension ranges between 1% and 3.5% among teenage secondary school children. The majority are asymptomatic and have no significant associations. It is recommended that routine urinalysis and blood pressure measurements should be part of the school health service so as to identify asymptomatic students who require close monitoring and/or intervention.     

Racial differences in perceptions concerning hypertension and its consequences

To investigate racial differences in hypertensive patients' understanding of their disorder, we administered a questionnaire to 83 black and 260 white outpatients with the diagnosis of hypertension designated in their medical chart. No racial differences in systolic or diastolic blood pressure, age, or male/female ratio were observed. However, blacks were more likely than whites to identify renal failure as a consequence of hypertension, whereas whites were more likely to identify atherosclerosis. Blacks also were more likely than whites to accept higher diastolic blood pressures as normal (90 to 100 mm Hg versus 80 to 90 mm Hg). There was no correlation between knowledge and blood pressure. Our observations show that both racial groups are well educated about antihypertensive therapy as well as the consequences and complications of hypertension. Comprehensive treatment of hypertension should include educational strategies that are population-specific and that address ways to change disease-relevant behaviors, rather than merely identifying which behaviors to change.     

Characteristics of 9194 patients with left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint Reduction in Hypertension

-Losartan was the first available orally administered selective antagonist of the angiotensin II type 1 receptor developed for the treatment of hypertension. The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality. Patients with essential hypertension, aged between 55 and 80 years, and ECG-documented left ventricular hypertrophy (LVH) were included. Altogether, 9223 patients in Scandinavia, the United Kingdom, and the United States were randomized from June 1995 through April 1997, and 9194 remain after exclusion of a study center at which irregularities were discovered. This population of hypertensives (mean systolic/diastolic blood pressure, 174.4/97.8 mm Hg) with LVH comprises women (54.1%) and men, mostly retired from active work (mean age, 66.9 years), with a high prevalence of overweight (mean body mass index, 28.0 kg/m2), diabetes mellitus (12.3%), lipid disorders (18.0%), and symptoms or signs of coronary heart disease (15.1%). There were fewer current smokers (<17%) than in the general population, and approximately 7% were nonwhite. Almost 30% of participants had been untreated for at least 6 months when screened for the study. Only 1557 persons who entered the placebo run-in period of 14 days were excluded, predominantly because of sitting blood pressures above or below the predetermined range of 160-200/95-115 mm Hg and ECG-LVH criteria not met. By application of simple 12-lead ECG criteria for LVH (Cornell voltage QRS duration product formula plus Sokolow-Lyon voltage read by a core laboratory), hypertensive patients with LVH with an average 5-year coronary heart disease risk of 22.3% according to the Framingham score were identified. This population is now being treated (goal, <140/90 mm Hg) in adherence with the protocol for at least 4 years after final enrollment (ie, through April 2001) and until at least 1040 patients suffer myocardial infarction, stroke, or cardiovascular death.     

Hypertensive and normal pregnancy: a longitudinal study of blood pressure, distensibility of dorsal hand veins and the ratio of the stable metabolites of thromboxane A2 and prostacyclin in plasma

OBJECTIVE: By combining serial measurements of the circulating concentrations of thromboxane A2 and prostacyclin with measurements of venous distensibility (taken during the pregnancies of both normal women and those with pregnancy induced hypertension or pre-eclampsia), to test the following hypotheses: 1. that changes in the venous plasma ratio of thromboxane (TXB2) and 6-keto-PGF1 alpha would correlate with changes in the blood pressure of women developing and recovering from pregnancy induced hypertension or pre-eclampsia and 2. that changes in venous distensibility would correlate with changes in arterial blood pressure in pregnancy induced hypertension or pre-eclampsia. DESIGN: Prospective, longitudinal cohort study. SETTING: John Hunter Hospital clinic, Newcastle, Australia. SUBJECTS: One hundred and sixty primiparous women, recruited when presenting for their first routine antenatal visit, were investigated at, or close to, 19, 28 and 37 weeks of gestation; a subgroup was also studied in the postnatal period. The measurements of the patients who developed pregnancy induced hypertension or pre-eclampsia were compared with those of controls selected from the cohort. MAIN OUTCOME MEASURES: Serial measurements of the circulating concentrations of the stable metabolites of thromboxane A2 and prostacyclin (TXB2 and 6-keto-PGF1 alpha, respectively), venous distensibility and immediate (no rest) and resting (for at least 30 min) blood pressures. RESULTS: There was no significant difference between the subject and control groups at any time during or after the pregnancy in the concentrations of prostaglandin metabolites, their ratio or venous distensibility. In contrast, there was a significant difference between the groups at 19 weeks for immediate and resting readings of diastolic pressure (6 mmHg (95% CI 1.5 to 10.5) and 4 mmHg (95% CI 0.1 to 7.9), respectively). These differences increased through the pregnancy but mean postnatal readings for the groups were almost identical suggesting that the subjects were not intrinsically hypertensive compared with controls. Blood pressures for the subject group, both immediate and resting, were significantly different from the 19 week readings at 28 weeks (diastolic) and at 37 weeks (systolic and diastolic). The only significant change from first readings among controls was in postnatal systolic pressure which was significantly higher than 19 week values, probably reflecting the vasodilatation, with accompanying hypotension, of early, normal pregnancy. This difference was not observed in those who subsequently developed pregnancy induced hypertension or pre-eclampsia. CONCLUSIONS: Our study was unable to demonstrate differences in circulating metabolites or venous distensibility between normotensive women and those with pregnancy induced hypertension or pre-eclampsia. If pregnancy induced hypertension or pre-eclampsia in humans represents not so much the presence of abnormal constrictor influences as a process initiated by failure of normal vasodilatation in early pregnancy, studies carried out later may detect mainly adaptive and secondary changes.     

Proteinuria, hypertension and chronic renal failure in X-linked Kallmann's syndrome, a defined genetic cause of solitary functioning kidney

BACKGROUND: Anosmia and hypogonadotrophic hypogonadism are the classic features of X-linked Kallmann's syndrome, a disorder caused by mutations of KAL, a gene expressed during kidney and brain development. About a third of patients have a solitary functioning kidney, but little is known about their renal morbidity. METHODS: We studied seven patients aged 22-35 years with X-linked Kallmann's syndrome and a solitary functioning kidney. RESULTS: Two patients developed significant proteinuria associated with mild to moderate arterial hypertension in the second to third decades of life. In one, proteinuria and renal impairment preceded the appearance of hypertension, and the disorder progressed to chronic renal failure. The remaining five patients had normal plasma creatinine concentrations and no significant proteinuria although four had borderline systolic and/or diastolic hypertension. In two sets of patients from the same kindreds, there was a striking discordance for the occurrence of renal morbidity. CONCLUSIONS: All patients with X-linked Kallmann's syndrome should be screened for renal malformations, and those with solitary kidneys require life-long follow-up to detect hypertension, proteinuria and renal failure.     

Impaired tumorigenicity of IL-4-producing murine neuroblastoma cells in immunodeficient nude mice

OBJECTIVE: Our purpose was to evaluate the clinical utility of serum uric acid measurements in the hypertensive diseases of pregnancy. STUDY DESIGN: We performed a nested case-control study to assess the clinical utility of serum uric acid measurements in women with hypertensive diseases of pregnancy. We identified 344 women who had serum uric acid measurements at term and categorized them into five diagnostic groups according to definitions of hypertensive diseases in pregnancy published by the National Working Group on Hypertension in Pregnancy: transient hypertension of pregnancy (n = 69), preeclampsia (n = 130), chronic hypertension (n = 23), chronic hypertension with superimposed preeclampsia (n = 29), and normal (n = 93). We compared the mean uric acid concentration for each group with use of a one-way analysis of variance and Scheffe's post hoc test and calculated the sensitivities and specificities in diagnosing preeclampsia as well as the likelihood ratios for serum uric acid values of 5.5, 6.0, and 6.5 mg/dl. We also examined the correlation between serum uric acid levels and several clinical outcome measures in women with hypertensive diseases of pregnancy. RESULTS: The mean serum uric acid values for women with preeclampsia (6.2 +/- 1.4 mg/dl) and transient hypertension (5.6 +/- 1.7 mg/dl) were significantly higher than those of controls (4.3 +/- 0.8 mg/dl, p < 0.05). The difference in mean serum uric acid values between women with chronic hypertension (4.9 +/- 1.0 mg/dl) and superimposed preeclampsia (5.8 +/- 1.4 mg/dl) were not statistically significant. The likelihood ratio of having preeclampsia with a serum uric acid value of 5.5 mg/dl was 1.41 in gestational hypertension of pregnancy and 2.5 in chronic hypertension. With use of a receiver-operator characteristic curve, we were unable to identify a serum uric acid value that could be used to differentiate various hypertensive diseases of pregnancy. There was a weak correlation between serum uric acid values and several clinical outcome measures of preeclampsia (r = 0.06 to 0.26). CONCLUSION: Although mean serum uric acid values are elevated in women with preeclampsia, the clinical utility of serum uric acid values in differentiating various hypertensive diseases of pregnancy appears to be limited. In the setting of chronic hypertension, however, a serum uric acid level of > or = 5.5 mg/dl could identify women with an increased likelihood of having superimposed preeclampsia.     

Modern trends in the treatment of hypertension

The main problem of treatment of hypertension in this country as well as abroad is the fact that only less than one quarter of hypertensive patients are treated effectively and have thus normal blood pressure readings. More effective treatment of hypertension is thus one of the main tasks of health care systems in different countries. The objective of treatment of hypertension is to achieve a normal blood pressure. Evidence has been provided that diuretics and beta-blockers markedly reduce cerebrovascular and cardiovascular mortality, in particular in the elderly. ACE inhibitors are the drugs of choice in patients with heart failure or asymptomatic left ventricular dysfunction and in patients with diabetic nephropathy. Unsuitable for treatment of hypertension are short acting calcium channel blockers, in particular nifedipine. On the other hand, long-acting calcium channel blockers reduce the cerebrovascular mortality in elderly hypertensive patients. A number of questions still remain the subject of research: a) should diastolic pressure be reduced to values lower than 90 mm Hg; so far it is necessary only in hypertensive subjects with diabetes mellitus and in juvenile hypertensives; b) is the influence of new groups of antihypertensive drugs, in particular calcium channel blockers, similar, better or worse than that of diuretics and beta-blockers in the prevention of cardiovascular and cerebrovascular morbidity and mortality?; c) is it wise to recommend acetylsalicylic acid also to hypertensive patients without clinical signs of IHD or atherosclerotic affection of other vessels?; d) what is the value of combined antihypertensive and hypolipidaemic pharmacological treatment? Will this combination be not much more valuable in the prevention of IHD?; e) is the prognosis of hypertensive subjects with left ventricular hypertrophy better when ACE inhibitors are used as compared with other antihypertensive drugs?; f) do ACE inhibitors influence the prognosis of diabetic patients more favourably than beta-blockers?     

Surgical repair of fecal incontinence. Correlation of sonographic anal sphincter integrity with subjective cure

We examined the relationship between left ventricular hypertrophy (LVH) and renal and retinal damage in 174 untreated patients with essential hypertension. As an index of renal and retinal damage, we examined proteinuria and retinal vascular change. LVH was diagnosed according to left ventricular mass obtained from echocardiography. Of the hypertensive patients, 111 patients (64%) had LVH. The incidences of proteinuria and advanced retinal vascular change were higher in patients with LVH than in those without LVH. In a multiple regression model, there was a significant positive correlation between left ventricular mass and proteinuria, as well as diastolic blood pressure, sex, age and body mass index. In conclusion, proteinuria is related to elevated left ventricular mass in patients with essential hypertension.