Left ventricular systolic and diastolic function assessed with two-dimensional and doppler echocardiography in "white coat" hypertension.

OBJECTIVES: The aim of this study was to investigate left ventricular function in subjects with "white coat" hypertension, defined as office arterial diastolic pressure > or = 90 and ambulatory daytime pressures < 140/90 mm Hg. BACKGROUND: The white coat arterial pressure response may, by influencing left ventricular function, have a confounding effect in studies of heart disease. METHODS: Two-dimensional and Doppler echocardiography combined with the calibrated subclavian arterial pulse tracing, were used to assess variables of left ventricular function in 26 subjects with white coat hypertension (office arterial diastolic pressure > or = 90 and < 115 mm Hg and ambulatory daytime diastolic pressure > or = 90 mm Hg) and 32 normotensive subjects. RESULTS: In subjects with white coat hypertension, systolic arterial pressure during the echocardiographic examination was significantly higher than ambulatory daytime systolic pressure. This pressure response was positively related to the ratio of the systolic to diastolic pulmonary venous flow peak velocities and to the peak velocity of flow reversion during atrial systole; it was inversely related to the ratio of early to late mitral flow peak velocities. Left ventricular stroke volume, ejection fraction and velocity of circumferential fiber shortening did not differ in the study groups, but left ventricular external work and end-systolic wall stress were increased in the white coat group. CONCLUSIONS: The arterial pressure response in subjects with white coat hypertension is associated with increased left ventricular external work, increased end-systolic wall stress and alterations of left ventricular filling but normal ejection fraction and velocity of circumferential fiber shortening.

Hemodynamics in white coat hypertension compared to ambulatory hypertension and normotension.

Hemodynamic alterations associated with the blood pressure response in subjects with white coat hypertension may provide insight into the pathophysiologic mechanisms of this condition. Systemic arterial hemodynamics were investigated with a recently validated method based on noninvasive estimates of aortic root pressure and flow in 28 subjects with white coat hypertension (diastolic pressure > or = 90 mm Hg measured by the general practitioner [GP arterial pressure] and ambulatory daytime pressures < 140/90 mm Hg), in 23 subjects with previously untreated, ambulatory hypertension (GP diastolic pressure > or = 90 and < 115 mm Hg and ambulatory daytime diastolic pressure > or = 90 mm Hg), and in 32 normotensive subjects. The groups did not differ significantly concerning age, gender, body surface area, heart rate, stroke index and cardiac index, but total peripheral resistance index was increased and total arterial compliance reduced in the white coat group and the hypertensive group compared to the normotensive group. The subjects in the white coat group with a systolic arterial pressure during echocardiography that was > 5 mm Hg higher than the ambulatory daytime systolic pressure (n = 19) had increased cardiac index, increased total peripheral resistance, and decreased total arterial compliance compared to the normotensive group. The subjects in this group with a hemodynamic pattern characterized by a high ratio of cardiac index/peripheral vascular resistance were significantly younger than the subjects with the opposite pattern. Thus, the blood pressure increase in subjects with white coat hypertension is associated with increased cardiac output, increased peripheral vascular resistance, and reduced total arterial compliance, but the hemodynamic pattern may be influenced by age.

Erythropoietin and uremic toxicity during continuous ambulatory peritoneal dialysis.

This study examined the effect of continuous ambulatory peritoneal dialysis (CAPD) on erythropoiesis and macrophage function. The parameters evaluated were hemoglobin, erythropoiesis-stimulating factor(s) (ESF), and the inhibitory effect of patients' plasma and peritoneal dialysate on erythropoiesis in vitro and on the function of macrophages from normal humans cultured in vitro. ESF was determined by a cell culture assay using hepatic erythroid colony forming cells (CFUE) from newborn mice. The uremic inhibitory effect on macrophages cultured in vitro was expressed as macrophage survival in percentage of controls. Five patients were studied, one of whom was anephric. Hemoglobin increased, without blood transfusions during CAPD treatment, suggesting improved erythropoiesis. Plasma ESF increased in all patients; dialysate ESF increased in all but one patient. Survival of macrophage in vitro, incubated with plasma or dialysate, also improved. In two patients, the inhibitory effect of plasma samples on erythropoiesis in vitro decreased during CAPD treatment. These observations indicate that CAPD removes inhibitors of erythropoiesis and human macrophage function in vitro, and are consistent with transport of inhibitory substances of high molecular weight into the peritoneal cavity. The anephric patient showed improvement of erythropoiesis similar to that of the nephric patients, indicating that the kidney may not be the main producer of erythropoietin (Ep) in patients undergoing CAPD. Peritoneal macrophages may be a site of extrarenal Ep production in this situation. With regard to the parameters studied, CAPD treatment is superior to conventional hemodialysis.

Removal of uremic toxins and regeneration of hemofiltrate by a selective dual hemofiltration artificial kidney (SEDUFARK) system.

A new system for the treatment of patients with end-stage renal failure has been developed. The SElective DUal Filtration ARtificial Kidney (SEDUFARK) is based on a dual filtration technique combined with low flow dialysis. Primary hemofiltrate containing large molecular weight substances is regenerated through a second filter followed by dialysis before the fluid containing essential substances of low molecular weight is returned to the patient. The ability of SEDUFARK to purify blood from uremic patients has been evaluated using a human macrophage assay system. Uremic plasma post SEDUFARK treatment was significantly less toxic than matched pre treatment plasma and the SEDUFARK regeneration system was found superior to conventional hemofiltration treatment.

Transport of uremic toxins through conventional hemodialysis membranes.

Human mononuclear phagocytes cultured in vitro were tested after preincubation with uremic plasma dialyzed in vitro and the effects of pre and post hemodialysis plasma were compared with the effect of dialyzates equilibrated with uremic plasma in vivo. Factors in uremic blood plasma inhibiting phagocytosis of Candida albicans could not be removed by means of conventional hemodialysis with cuprophan (CPN) or polyacrylonitrile (PAN) membranes. Hemofiltrates of uremic blood plasma produced by PAN membranes caused a significant inhibition of phagocytes in our test system while CPN hemofiltrates did not.

Propranolol in the treatment of migraine.

Beta-blocking drugs that prevent cranial vasodilatation are potentially valuable in the prophylaxis of migraine. Forty-nine patients with either classic or common migraine were treated with propranolol 160 mg/day for an average of six months. The first 30 of the patients to respond well to this treatment then participated in a double-blind cross-over trial with a placebo and propranolol. The mean frequency of headache attacks was significantly reduced by propranolol. None of the patients expressed a preference for placebo. Propranolol seems to be an effective prophylactic for common and classic migraine but the antimigraine properties of the various beta-blocking agents probably differ.

[Mild hypertension]. / Mild hypertensjon.

The Norwegian Report on Evaluation and Treatment of Mild Hypertension and The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure were both published at the end of 1997. The prevalence of hypertension and the proportion of the total adult population on antihypertensive medication is about 20% and 10% respectively in both countries. In both reports patients are assessed and graded according to various risk factors for developing cardiovascular disease. However, in the American recommendations it seems that this will only have marginal impact on the number of persons with uncomplicated mild hypertension who will be recommended drug therapy. The Norwegian guidelines recommend drug therapy only where there is a minimum of 20% absolute risk (30% for the age group 60-69 years) of developing cardiovascular disease or of death within ten years. Drug therapy is not recommended for persons over 70 years with uncomplicated mild hypertension, whereas treatment is advised in cases of complicated mild hypertension. It is therefore estimated that drug therapy will be recommended for less than 50% of patients with uncomplicated mild hypertension, as opposed to almost 100% according to the American guidelines.

Hyperlipidaemia in renal transplant patients.

OBJECTIVES: The aim of study was to assess the prevalence and severity of hyperlipidaemia in renal transplant patients in a Nordic country. DESIGN: Multicentre, cross-sectional study. SETTING: Outpatients and ward inpatients registered from 23 hospitals covering all regions of the country. SUBJECTS: Renal transplant patients with a functioning graft were registered: 406 patients in all; that is, 43% of the national renal transplant population. All patients used prednisolone, 71% used cyclosporine, either with (51%) or without (20%) azathioprine. Total cholesterol values from general population were obtained from a national survey. MAIN OUTCOME MEASURES: Blood lipids and their relation to clinical parameters. RESULTS: Total cholesterol was significantly higher in transplant patients than in the general population for both genders and all age groups (P < 0.01). Female patients had higher total cholesterol (mean +/- SD: 7.49 +/- 1.61 mmol L(-1)) than males (7.01 +/- 1.55 mmol L(-1); P < 0.001), and also higher HDL cholesterol (1.55 +/- 0.43 vs. males: 1.32 +/- 0.46 mmol L(-1); P < 0.001). Triglycerides were equally elevated in both genders, and 33% had values above 2.2 mmol L(-1). Reduced creatinine clearance, a high body-mass index, female gender, hypertension, and coronary artery disease were independently associated with higher total cholesterol. Beta blockers were associated with lower HDL cholesterol and higher triglycerides, and diuretics with higher triglycerides. Blood lipid levels were not associated with cyclosporine immunosuppression. CONCLUSION: Hyperlipidaemia is prevalent after renal transplantation, and is associated with impaired graft function, hypertension, and with the use of beta blockers and diuretics, but not with the use of cyclosporine.

A comparison of solute clearance and ultrafiltration volume in peritoneal dialysis with total or fractional (50%) intraperitoneal volume exchange with the same dialysate flow rate.

BACKGROUND: The most efficient way to perform automated peritoneal dialysis (APD) has not yet been defined. Tidal peritoneal dialysis (TPD) has been claimed to be more efficient than traditional intermittent peritoneal dialysis (IPD), but few comparative studies have been done keeping dialysate flow the same in the two treatment techniques. METHODS: Six patients were treated with 10, 14 and 24 litres total dialysis fluid volume during 9 h (flow rate 18.5, 25.9 and 44.4 ml/min), receiving the treatments both as IPD and TPD. Glucose concentration in the fluid was held constant during all treatments. Transperitoneal clearances (ml/min) for urea, creatinine and uric acid and ultrafiltration volume was calculated, and comparisons made between TPD and IPD. The total intraperitoneal dwell time was calculated for each treatment session. A peritoneal equilibration test was also done for each patient. RESULTS: The ratio of the creatinine concentration in dialysate to the concentration in plasma at 4 h obtained with the peritoneal equilibration test (PET) averaged 0.77 (range 0.69-0.82). Urea clearance was higher for IPD than for TPD with 10 litres: 14.3 +/- 2.4 and 13.3 +/- 2.7 (P = 0.0092). For 14 and 24 litres urea clearance for IPD and TPD was 16.9 +/- 2.3 and 15.9 +/- 3.5 (n.s.) and 20.9 +/- 3.6 and 19.9 +/- 5.6 (n.s.) respectively. Creatinine clearance was higher for IPD than for TPD with 10 litres: 9.6 +/- 1.3 and 8.9 +/- 1.3 (P = 0.0002). For 14 and 24 litres creatinine clearance for IPD and TPD was 11.0 +/- 0.7 and 9.9 +/- 2.0 (n.s.) and 12.3 +/- 1.2 and 12.4 +/- 2.2 (n.s.) respectively. Uric acid clearance was higher for IPD than for TPD with 10 litres: 8.4 +/- 1.3 and 7.7 +/- 1.0 (P = 0.0054). For 14 and 24 litres uric acid clearance for IPD and TPD was 9.3 +/- 1.7 and 8.9 +/- 2.2 (n.s.) and 11.3 +/- 2.9 and 10.6 +/- 2.6 (n.s.) respectively. IPD gave significantly higher ultrafiltration volume (ml) than IPD for both 10 and 14 litres: 944 +/- 278 and 783 +/- 200 (P = 0.0313) and 1147 +/- 202 and 937 +/- 211 (P = 0.0478). For 24 litres there was no significant difference between IPD and TPD: 1220 +/- 224 and 1253 +/- 256. CONCLUSION: With the lowest dialysate flow rate (18.5 ml/min), solute clearance and ultrafiltration volume was higher on IPD than on TPD. With the intermediate flow rate (25.9 ml/min) the ultrafiltration volume was higher on IPD, but no difference was found for solute clearance. With the highest flow rate (44.4 ml/min) there was no difference neither for ultrafiltration nor for solute clearances.

Quality of life after cerebrovascular stroke: a systematic study of patients' preferences for different functional outcomes.

OBJECTIVES: To elicit valid quality of life estimates and the highest acceptable treatment risk of different outcomes after stroke. This is a prerequisite for rational medical decision-making, especially when considering treatments like thrombolysis. SUBJECTS: Healthy people, non-stroke medical patients and stroke survivors aged 20-84 years (n = 158) INTERVENTIONS: Subjects were interviewed by a physician using three different methods ('standard gamble', 'time trade-off' and 'direct scaling') supported by an interactive computer program. MAIN OUTCOME MEASURES: We measured utility, a numerical value ranging from 0.00 (death) to 1.00 (perfect health), representing the strength of the patient's preference for an outcome. When using the standard gamble method, risk is also introduced into the measurement. RESULTS: People's preferences for stroke outcomes varied widely, and the estimates were influenced by assessment method. We found that previous stroke, marital status and age were the only independent variables influencing the utility given. Subjects in our population over the age of 45 were very comparable to the real population at risk for acute stroke regarding these three variables, and they assigned a median utility of 0.91 (10th percentile, 0.65; 90th percentile, 0.99) to a minor stroke and 0.61 (10th percentile, 0.08; 90th percentile, 0.95) to a major stroke using the standard gamble method. CONCLUSIONS: Most people do not feel that suffering from stroke is an overwhelming catastrophe and they do not accept treatment options with very high risks.

Cardiovascular morbidity and risk factors in renal transplant patients.

BACKGROUND: Cardiovascular disease is now the major cause of death in renal transplant patients. This study aimed to assess the prevalence of cardiovascular disease in stable renal transplant patients as compared with the general background population, and to assess risk factors for cardiovascular disease in this patient group. METHODS: A cross-sectional multicentre study comprising 406 stable renal transplant patients (age 47+/-16 years, 60% males, 71% taking cyclosporin A) were assessed clinically and biochemically 48 months (median) after transplantation and compared with the general population. Multivariate analysis was used to assess the relation between cardiovascular disease and risk factors. RESULTS: Hypertension was present in 55% of males and 34% of females (P<0.001), in 51% with cyclosporin A and in 33% without (P<0.001). Ischaemic heart disease (i.e. angina pectoris and/or previous myocardial infarction) was present in 14% (males: 18%, females: 10%, P<0.05) and in 24% of diabetics vs 12% of non-diabetics (P<0.01). Cerebro- and peripheral vascular disease was found in 3% and 4%, respectively. Odds ratio for angina pectoris (patients vs general population) was: in age group 40-49 years (males/females), 12/16; 50-59 years, 6/4; 60-69 years, 3/4. Ischaemic heart disease was, besides age and gender, independently associated with total cholesterol (P<0.01), and peripheral vascular disease to systolic blood pressure (P<0.01). CONCLUSIONS: Cardiovascular disease is highly prevalent in renal transplant patients, and is independently associated with age, gender, total cholesterol and systolic blood pressure.

Diuretic action of bumetanide in advanced chronic renal insufficiency.

The effect of bumetanide, a new potent diuretic, was studied in twelve patients with severe chronic renal failure (GFR 2.7 - 10.7 ml/min). Bumetanide 8 mg i.v. caused increased excretion of water and sodium in all patients. In some patients sodium excretion was greater than 50% of filtered load indicating an effect on proximal tubules. Bumetanide 2 mg i.v. was significantly less effective than 8 mg and a greater diuretic effect was produced by bumetanide 16 mg. In a comparative study bumetanide 8 mg was less potent than furosemide 250 mg, a finding in contrast to the potency rate ratio of 1/40 in other conditions. Side effects consisted of mild to moderate muscle pain and stiffness, especially localized in the neck, shoulders and calves. These side effects occurred only in patients with a GFR less than 5.3 ml/min. They were noted in all patients receiving 16 mg and in 3 out of 12 patients who took bumetanide 8 mg. There was no relationship between the occurrence of side effects and plasma bumetanide levels, electrolyte levels or the renal excretion of bumetanide and electrolytes.

Plasma concentrations and transperitoneal transport of native insulin and C-peptide in patients on continuous ambulatory peritoneal dialysis.

The insulin and C-peptide response to glucose (50 g), given intraperitoneally or enterally, and the elimination rate of these compounds has been studied in five nondiabetic patients on continuous ambulatory peritoneal dialysis (CAPD). The fasting C-peptide concentrations were three to ten times the normal values, whereas the fasting plasma insulin concentrations were within normal limits. After intraperitoneal glucose administration, a more marked hyperglycemia (P less than 0.05) and a more long lasting hyperinsulinemia (P less than 0.05) were found than after the enteral glucose load. The relative change in plasma C-peptide was slower and less pronounced in both experiments. Estimated total body clearance (Kt) for insulin was higher than for C-peptide (P less than 0.01), but dialysis clearance (Kd) for C-peptide was higher than for insulin in both experiments (P less than 0.01). The markedly elevated fasting C-peptide concentrations in plasma can be explained only partly by the absence of normal kidney function and suggests a continuously increased production of C-peptide during CAPD treatment. This was not reflected by the fasting plasma insulin concentrations. C-peptide measurements in plasma and dialysate during CAPD could be helpful in evaluating the beta-cell function in patients in need of exogenous insulin.

Toxicity of middle molecules: clinical evaluation using a selective filtration artificial kidney.

The effect of four uremic patients, treated 4-6 months with a new artificial kidney system aimed to remove molecules between 10,000-40,000 daltons returning substances with mol wt 200-10,000 back to the patients, was compared with the effect of conventional hemodialysis. The patients treated with this system obtained a more stable hemoglobin concentration without blood transfusions. They got an increased mean nerve conduction velocity and their plasma increased in quality as culture medium on human mononuclear phagocytes grown in vitro.

[White coat hypertension]. / Kontorhypertensjon.

The prevalence of white coat hypertension, which is defined by hypertension in the physician's office, and normotension at other times, may be as high as 30% in a hypertensive population. Since white coat hypertension is associated with a low degree of end-organ damage and, accordingly, a potential favourable prognosis, the use of ambulatory blood pressure recordings has increased with the aim of identifying hypertensive subjects who may not need medical treatment. White coat hypertension is, however, not yet clearly defined, and there seems to be evidence that such subjects may have reduced vasodilator capacity. Low arterial compliance, a feature associated with hypertension in the elderly, seems to be another characteristic. Hence, although the prognostic significance of white coat hypertension has not yet been completely defined, there is accumulating evidence that ambulatory blood pressure recordings may serve as an important tool in the risk assessment of subjects with arterial hypertension.

A decision analysis of thrombolytic therapy compared with standard therapy in acute ischaemic stroke.

OBJECTIVES: Experts draw different conclusions on whether thrombolysis can be recommended or not for acute ischaemic stroke. A major problem is weighing the improvement in functional ability against the risk of increased mortality. We wanted to examine this uncertainty regarding thrombolysis using a systematic approach and with a strong emphasis on the patient's point of view. METHODS: We performed a decision analysis where the base case focused on an average stroke patient. We used published probabilities for different functional outcomes after standard supportive care and after adding tissue plasminogen activator (tPA), and we tried to estimate corresponding long-term survival. We interviewed 158 subjects with the standard gamble method to elicit their preference values (utility) for these outcomes. RESULTS: When using the baseline data for an average stroke patient, thrombolysis with tPA was the better choice, with 48 extra quality-adjusted living days; tPA was also superior in 117 individual decision analyses, giving from 10 to 173 extra days. However, sensitivity analysis showed that these results were highly susceptible to changes in utility for major disability, probability of early death, and long-term survival after thrombolysis. To increase the gain as well as the margin of safety regarding the treatment choice, thrombolysis should be restricted to patients who assign low utility values < 0.6-0.7 to major poststroke disability (death = 0.0, good health = 1.0). CONCLUSION: Evaluated by decision analysis, thrombolysis with tPA is on average superior to standard therapy for the few patients fulfilling the strict medical inclusion criteria. Individual incorporation of the patient's point of view narrows the indication even further.

The effect of peritonitis on the transperitoneal transport of cefuroxime in patients on CAPD treatment.

The pharmacokinetics and transperitoneal transport of cefuroxime were investigated in CAPD patients without peritonitis (n = 6), receiving 500 mg of the drug intravenously (i.v.) and intraperitoneally (i.p.) on separate occasions. CAPD patients with peritonitis were also investigated after i.p. administration of an initial dose of 500 mg cefuroxime followed by repeated doses of 250 mg. Routine hospital CAPD procedures and dwell-time schedules were followed during the study, and frequent blood and dialysate samples were collected. Cefuroxime was analysed by HPLC methods, and pharmacokinetic parameters were calculated. In the patients without peritonitis, the following pharmacokinetic parameters after i.v. and i.p. administration did not differ significantly (mean +/- SD): elimination half-life, 15.1 +/- 1.9 h; apparent volume of distribution 27.9 +/- 2.91; and total clearance, 21.5 +/- 1.2 ml/min. In contrast, the transperitoneal transport of cefuroxime differed significantly in the three studies. After i.v. administration the apparent transperitoneal clearance was low and time dependent, ranging from 4.2 +/- 1.2 to 1.4 +/- 0.4 ml/min. After i.p. administration the apparent transperitoneal clearance increased to 10.9 +/- 2.4 ml/min, whereas in the peritonitis patients a further increase to 21.5 +/- 3.5 ml/min was observed. In all patients we found cefuroxime concentrations in serum and dialysate, greatly exceeding MIC values of most pathogens involved in CAPD peritonitis and other systemic bacterial infections.

[Diagnosis and treatment of high blood pressure. How to invest?]. / Diagnostikk og behandling av høyt blodtrykk. Hvordan investere?

High blood pressure is a major risk factor for development of cardiovascular diseases. During 1992 and 1993, several national consensus reports about treatment of arterial hypertension have been published. There are discrepancies between the recommendations contained in the reports, which has caused uncertainty among physicians. We discuss the basic problems connected to evaluation and recommendation, and the demand for standardization and organization of the health service programme for patients with high blood pressure. It is possible to learn from, and thereby achieve better quality of medical practice, through a continuous registration of our routines and results. The Trondheim model is designed to depict specific information from the primary health services in a follow-up programme. This information is sampled in a data base from which primary physicians can obtain feedback on statistical evaluations twice a year. This is defined as a quality assurance programme to secure and improve the quality of the medical service to patients with high blood pressure.