Socio-economic status influences blood pressure control despite equal access to care.

OBJECTIVE: Denmark has a health care system with free and equal access to care irrespective of age and socio-economic status (SES). We conducted a cross-sectional study to investigate a possible association between SES and blood pressure (BP) control of hypertensive patients treated in general practice. METHODS: We enrolled 184 general practices and 5260 hypertensive patients. The general practitioners reported information about BP and diagnosis of diabetes. Information about education, income, antihypertensive drug treatment and other co-morbidity was retrieved from relevant registers from Statistics Denmark. The outcome measure was BP control defined as BP <140/90 mmHg in general and <130/80 mmHg in diabetics. RESULTS: Patients <65 years and with an educational level of 10-12 years had increased odds ratio (OR) of BP control compared to patients with an educational level <10 years. Patients ≥65 years had increased OR of BP control if they were married/cohabiting as compared to being single, whereas education and income had no impact in this age group. Diabetics had significantly reduced odds of BP control irrespective of age, educational or income level. CONCLUSIONS: Despite equal access to care for all patients, SES had significant impact on BP control in this survey. Diabetes and cardiovascular disease also had a substantial influence irrespective of age, educational and income level.

Treatment of 5413 hypertensive patients: a cross-sectional study.

BACKGROUND: Most hypertensive patients are managed in primary care in Denmark, but previous studies have shown that only 21-43% of hypertensive patients achieve optimal blood pressure (BP) control. Antihypertensive drug treatment, risk factors and cardiovascular disease (CVD) are some of the important factors to consider when optimizing the individual treatment strategy in hypertensive patients. OBJECTIVE: To examine treatment of BP according to Danish guidelines (BP < 140/90 mmHg generally and <130/80 mmHg for diabetics) in a population from general practice in relation to risk factors, CVD and diagnosis of diabetes. METHODS: A cross-sectional study comprising 184 practices and 5413 hypertensive patients was carried out in Denmark. The general practitioners filled in information on each patient's risk factors, CVD and antihypertensive drug treatment. Patients filled in a questionnaire on risk factors. The outcome measures were optimal BP control according to Danish guidelines and antihypertensive drug treatment. RESULTS: Mean patient age was 65.9 years [95% confidence interval (CI): 65.6-66.1]. Optimal BP control was achieved in 29.1% (95% CI: 27.9-30.3) of the study population. Among 842 diabetics with or without CVD, optimal BP control was achieved in 10.9% (95% CI: 8.8-10.3), while 38.7% (35.5-41.9) of patients with CVD achieved optimal BP control. The majority of all patients were treated with 1 (32.5%, 95% CI: 32.5 (31.3-33.8)) or two antihypertensive drugs (39.0%, 95% CI: 38.2-40.8). In hypertensive diabetics, 17.7% were not treated with an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker. CONCLUSION: In general practice, the proportion of hypertensive patients achieving optimal BP control is inadequate. The majority of hypertensive patients are treated with only one or two antihypertensive drugs.

Low-dose spironolactone reduces plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension.

Diabetic patients with hypertension are at particularly high risk of vascular damage and consequently cardiovascular and renal disease. Fibulin-1, an extracellular matrix glycoprotein, is increased in arterial tissue and plasma from individuals with type 2 diabetes. This study aimed to evaluate whether antihypertensive treatment with spironolactone changes plasma fibulin-1 levels. In a multicenter, double-blind, randomized, placebo-controlled study, 119 patients with type 2 diabetes and resistant hypertension were included. A dose of spironolactone 25 mg or matching placebo was added to previous treatment at randomization. Blood pressure (BP) and plasma fibulin-1 were measured at baseline and at 16 weeks follow-up. Overall, 112 patients completed the study. All measures of BP were reduced in the spironolactone group at follow-up. Plasma fibulin-1 was significantly reduced after spironolactone treatment (P=0.009), but increased after placebo (P=0.017). Baseline plasma fibulin-1 correlated with BP and estimated glomerular filtration rate. Increased levels of plasma fibulin-1 (P=0.004) were observed in diabetic participants reporting erectile dysfunction as compared with participants who did not. Treatment with low-dose spironolactone reduced plasma fibulin-1 levels in patients with type 2 diabetes and resistant hypertension. This supports the hypothesis that the antihypertensive effect of the mineralocorticoid receptor blocker in part may be due to regression of vascular remodeling.

Hypothermic perfusion of rabbit kidneys with solutions containing gelatin polypeptides.

Rabbit kidneys were perfused with a solution of extracellular electrolyte composition, made hypertonic with glucose and containing the gelatin polypeptide preparation Haemaccel (Hoechst) as the only colloid. Perfusions were carried out at 5 and 10 C for 19 hr, and function was tested by autografting. All of the kidneys perfused at the higher temperature showed immediate life-sustaining function after transplantation and contralateral nephrectomy, whereas only one graft of five perfused at the lower temperature showed any function. The suitability of the Haemaccel solution as a vehicle for introducing the cryoprotective agent glycerol was tested by perfusing kidneys for 4 hr with a solutiont containing 2% glycerol; the function of these organs was similar to that of kidneys transplanted without perfusion. Ultrastructural examination of kidneys perfused for 24 hr at 10 C showed excellent structural preservation, but measurements of water and ion contents and the penetration of marker molecules in nonmetabolizing kidneys showed 2.8% Haemaccel to be somewhat less effective than 6% bovine serum albumin in stabilizing these values. The Haemaccel perfusate is considered to be highly suitable for the introduction and removal of cryoprotective agents, and the results of hypothermic preservation by continuous perfusion are encouraging.

Preservation of rabbit kidneys using a solution containing hydrolyzed starch.

An organ preservation solution has been developed by combining some features of the hypertonic citrate formulation of Ross, Marshall, and Escott (RME) with some features of UW solution. Specifically the solution (HP16) contains a balance of cations similar to that in RME and the same concentration of citrate, but sulfate is replaced by chloride and mannitol by a starch hydrolysis product (SHP). A gelatin-derived polypeptide (Haemaccel) is included to provide colloid osmotic pressure. The objective was to increase the effectiveness of RME by using a higher-molecular-weight osmoticum than mannitol, but avoiding the expense of raffinose; reducing the osmolality to a more physiological level; and including a colloid to make the solution suitable for continuous perfusion. The effectiveness of the solution was tested by 48-hr hypothermic preservation of rabbit kidneys. The results were compared with those obtained using RME or UW. It was shown that simple hypothermic storage was more effective than continuous perfusion, and that HP16 was more effective than RME and as effective as UW. The improvement over RME was ascribed to the isotonic osmolality and the inclusion of a higher-molecular-weight osmoticum (the SHP), possibly supplemented by the colloid (Haemaccel). Two SHP preparations, both with dextrose-equivalent values of approximately 35, were equally effective. These materials contain a standardized mixture of dextrose, maltose, and tri- and oligosaccharides, and have the osmotic properties of a trisaccharide. The results provide a new, inexpensive preservation solution that is as effective as any so far tested with this model, and they support the importance of appropriate osmotic properties for solutions to be used in organ preservation.

Tracking and factors predicting rising in 'tracking quartile' in blood pressure from childhood to adulthood: Odense Schoolchild Study.

This prospective study determines the degree of tracking and investigates factors predicting a rise in blood pressure (BP) quartile in a cohort of 1369 subjects who were followed for 11 years from childhood into young adulthood. In 900 of these subjects BP, height, weight, physical fitness and BP responses to a maximal exercise testing were measured both at baseline and at follow-up. BP, weight, height and body mass index (BMI) were divided into sex-specific quartiles at both examinations. Tracking was evaluated by examining the tendency of remaining in the same quartile from baseline to follow-up and by measuring product-moment correlation coefficients. Tracking in the upper and lower quartile for BP, weight, height and BMI were significant. Odds ratios for staying in the upper or lower quartile through the follow-up period ranged from 1.6 to 2.4 for diastolic BP and from 2.1 to 3.1 for systolic BP. The range of correlation coefficients for the anthropometric measurements were 0.57-0.75, for diastolic BP 0.12-0.22 and for systolic BP 0.34-0.36 respectively. Changes in weight or relative weight as well as BP response to an exercise test were the factors which predicted a rise in quartile through the 11 years of follow-up. The existence of the inevitable regression to the mean problem in large longitudinal studies of BP was demonstrated by the finding of baseline BP being a significant factor in the prediction of rising in systolic, diastolic or both systolic and diastolic BP quartiles.

Ambulatory blood pressure in 570 Danes aged 19-21 years: the Odense Schoolchild Study.

Ambulatory blood pressure (ABP) measurements were performed in a Danish population of 295 males and 275 females aged 19-21 years. Individualised day and night periods were defined from the subjects own recording of bedtime and rising on the day of their ABP measurements. During these individualised periods the ABP values for daytime, night-time and for the whole 24-h period were measured. The mean +/- s.d. values for systolic/diastolic ABP for the whole population were (124+/-11)/(70+/-7) mm Hg in the daytime, (106+/-12)/(60+/-9) mm Hg in the night-time, and (120+/-11)/(68+/-7) mm Hg in the whole 24-h period. Males had a mean systolic ABP of 9 mm Hg and mean diastolic ABP of 5 mm Hg higher than females. In males mean +/- s.d. systolic/diastolic ABP values in the daytime were (129+/-10)/(73+/-7) mm Hg, in the night-time (111+/-12)/(63+/-8) mm Hg, and in the whole 24-h period (125+/-10)/(71+/-7) mm Hg. The corresponding values in females were (119+/-10)/(68+/-6) mm Hg, (103+/-11)/(57+/-8) mmHg, and (115+/-10)/(66+/-6) mm Hg, respectively. In conclusion this study provides sex-specific normal values for ABP in a 19 to 21-year-old age group based on individualised daytime and night-time periods.

Crossover comparison of the pharmacokinetics of amlodipine and felodipine ER in hypertensive patients.

The pharmacokinetics of amlodipine 5 mg and felodipine ER (extended release) 5 mg o.d. after single and 2 weeks of repeated oral doses, were compared in 28 essential hypertensive patients using a crossover design. As a secondary parameter the effects of the drugs on blood pressure were assessed. Significant differences were found between all principal pharmacokinetic variables, when comparing the 2 treatments after both single and repeated dosing. The coefficients of variation of maximal drug concentration and AUC after single dosing and at steady-state were significantly higher for felodipine ER than for amlodipine. After repeated dosing the peak-to-trough plasma concentration ratio were 1.58 and 4.43 (p < 0.001) for amlodipine and felodipine ER, respectively. Both drugs lowered systolic and diastolic blood pressure to the same extent after 2 weeks of repeated dosing. No significant differences between the blood pressure lowering vs time profile of the 2 drugs were encountered. In conclusion, the interpatient drug concentration variability and the peak-to-trough plasma concentration ratio were more favorable for amlodipine compared to felodipine ER. It remains to be established whether these characteristics are also reflected in a more smooth and consistent blood pressure control.

Renal transplantation in the rabbit: a model for preservation studies.

Transplantation is necessary for evaluation of kidney preservation procedures, and a model using a small laboratory animal is desirable. The rabbit was found to be a suitable animal for this purpose. Even long periods of anaesthesia without artificial respiration were safely achieved. Hydration and serum electrolytes could be maintained within normal ranges with intravenous injections of isotonic saline and dextrose during and after the operation. The kidneys were implanted by anastomosing the artery and vein end-to-side to the abdominal aorta and the posterior vena cava respectively. The ureter was implanted into the bladder over a nylon stent. In a recent 100 transplantations the incidence of vascular thrombosis was low (4%), but rather more (10%) mainly late ureteral complications were encountered. Transplanted kidneys showed good function with mean peak serum creatinines of 285 mumol/l and normal macroscopic and histological appearance at autopsy.

[Treatment of chronic occupational lead poisoning with dimercaptosuccinic acid (DMSA)]. / Behandling af erhvervsbetinget kronisk blyforgiftning med dimerkaptoravsyre (DMSA).

2,3-dimercaptosuccinic acid (DMSA) mobilizes lead from superficial depots. In comparison with other chelating agents, DMSA has a high therapeutic index and has the additional advantage that it can be administered orally. We have used DMSA for treatment of chronic occupational lead poisoning in a 54-year old male with signs of neurotoxic effects. The treatment resulted in a rapid decrease in the blood-lead concentration, followed by a slow increase after the treatment and subsequent stabilization at a blood-lead level lower than prior to treatment. During the first course of treatment, almost 100 mumols lead was excreted in the urine. As a result of successive courses of treatments, the patient's condition was improved. However, during the third course of treatment, he developed a mucocutaneous rash which faded again after withdrawal of DMSA; this reaction was subsequently provoked by sub-therapeutic doses, and continued treatment was therefore cancelled. Only minor, reversible side effects of DMSA have hitherto been reported, and DMSA must therefore be regarded a promising agent for long-term, out-patient chelation treatment of chronic lead poisoning.

[Treatment of acute chloroquine poisoning]. / Behandling af akut klorokinforgiftning.

Acute chloroquine poisoning is life threatening with risk of death from apnoea and cardiac arrhythmia within a few hours of ingestion. Mechanical ventilation, infusion of pressor agents and large doses of diazepam seem to provide effective treatment. This treatment was introduced by Riou et alii (N Engl J Med 1988; 318; 1-6), and we used it successfully in a case of severe chloroquine poisoning. Intensive treatment was given during the first two days of intoxication, when the whole blood chloroquine phosphate concentration was high (more than 10 mumol/kg), corresponding to absorption from the gut and distribution to the organs. Hereafter the whole blood chloroquine phosphate concentration decreased increasingly slowly, probably due to equilibrium with tissue stores.

[Continuing medical education via questionnaire studies. Three pilot projects for anesthesiology, cardiology and neurology]. / Efteruddannelse af laeger via spørgeskemaundersøgelser. Tre pilotprojekter inden for anaestesiologi, kardiologi og neurologi.

The Danish Medical Association and the scientific societies have initiated three studies to evaluate the use of questionnaires for continuous medical education. One study was a questionnaire in anaesthesiology with 30 questions with answers yes/no/no answer, which was sent to 600 specialists in anaesthesiology. One study was in cardiology with a multiple choice questionnaire, sent to 300 general practitioners and 75 specialists in internal medicine outside cardiology. One study concerned the educational value of State-of-the-Art articles about neurology in Ugeskrift for Laeger (Journal of the Danish Medical Association) sent to 500 doctors outside neurology. All questionnaires were sent anonymously, with one general reminder. For the anaesthesiology study 234 questionnaires were returned (40.5%). In the cardiology study 195 questionnaires were returned (52%). For the study on neurology 278 answered (56%). Only about half of the questionnaires were returned for the three studies, and a lot of effort and resources were put into the studies. An extension from these small pilot studies to a general systematic continuous methodology with updated questionnaires in the postgraduate medical education seems troublesome. An optional self-registration for medical education such as The Canadian "Mocomp concept" might be a more realistic suggestion.

The effect of cooling rate during perfusion on function and morphology of rabbit kidney grafts.

The effect of cooling of rabbit kidneys during the initial flush with Collins' solution for simple hypothermic storage was studied. After cooling at an average rate of 3.7 degrees C/min. graft function was found to be immediately life-sustaining, and renal morphology after perfusion as well as 30 min. and 24 hours posttransplant was found to be normal. Posttransplant function after cooling at a rate of 7.2 degrees C/min. was significantly lower, permitting survival of only 30% of recipient animals, and damage was seen in proximal tubular cells.

Selective renal vasoconstriction, exaggerated natriuresis and excretion rates of exosomic proteins in essential hypertension.

AIM: In essential hypertension (EH), the regulation of renal sodium excretion is aberrant. We hypothesized that in mild EH, (i) abnormal dynamics of plasma renin concentration (PRC) and atrial natriuretic peptide (ANP) are responsible for the exaggerated natriuresis, and (ii) exosomic protein patterns reflect the renal tubular abnormality involved in the dysregulation of sodium excretion. METHODS: After 2-week drug washout and 4-day diet, systemic and renal hemodynamics, cardio-renal hormones, glomerular filtration and renal excretion were studied in male patients during saline loading (SL). Excretion rates of exosome-related urinary proteins including apical membrane transporters were determined by proteomics-based methods. RESULTS: In patients, baseline renal vascular conductance was reduced (-44%, P < 0.001), but non-renal vascular conductances were normal while PRC was reduced and ANP elevated (both P < 0.01). SL induced exaggerated natriuresis and reduced PRC (P < 0.01), at normal suppression rate. SL increased arterial pressure in patients (+11 mmHg, P < 0.001), but not in controls; however, during time control, patients showed identical increases (+10 mmHg, P < 0.005) apparently dissociating arterial pressure from natriuresis. At baseline, excretion rates of 438 proteins ranged from 0.07 to 49.8 pmol (mmol creatinine)(-1); 12 proteins were found in all subjects, and 21 proteins were found in two or more patients, but not in controls. In patients, the excretion rate of retinoic acid-induced gene 2 protein was reduced, and excretion rates of other proteins showed increased variances compatible with pathophysiological and clinical applicability. CONCLUSION: Essential hypertension patients exhibit selective renal vasoconstriction and individually varying excretion rates of several exosome-related proteins. Hormonal changes, rather than arterial pressure, seem to cause exaggeration of natriuresis.