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Biomedical subjects

H Herlitz

Publications and source records attributed to H Herlitz.

At least 19 recordsLinked to original sources
PubMed1996

Relationship between sodium-lithium countertransport and insulin sensitivity in mild hypertension.

OBJECTIVES: To study the relationship between insulin sensitivity and sodium-lithium countertransport (Na(+)-Li+ CT) in mild, essential hypertension, and to investigate the effect of metformin and metoprolol, respectively. DESIGN: A double-blind, triple cross-over, placebo-controlled study over a total period of 18 weeks. SETTING. A hypertension out-patient clinic and research laboratory at Sahlgrenska University Hospital. SUBJECTS: Seventeen non-obese men with mild essential -hypertension and 17 weight-matched, healthy controls. INTERVENTIONS: Metformin 850 mg b.i.d., metoprolol CR 100 mg once daily and placebo were given during 18 weeks. Each treatment period was 6 weeks. A euglycaemic clamp was performed and erythrocyte Na(+)-Li+ CT measured after each 6-week treatment period. MAIN OUTCOME MEASURES: Insulin sensitivity, erythrocyte Na(+)-Li+ CT, their interrelation, and the effect of metformin and metoprolol CR on both variables, respectively. RESULTS: The hypertensive men tended to have an elevated Na(+)-Li+ CT compared with the control subjects (0.34 +/- 0.03 versus 0.26 +/- 0.02 mmol L-1 h-1, P < 0.1). Glucose disposal rate was similar, but plasma insulin levels higher (P < 0.05) among the hypertensives than the controls. Na(+)-Li+ CT exhibited a positive relationship to BMI (r = 0.53, P = 0.03) and a negative correlation to glucose disposal rate (r = -0.66, P = 0.008) in the hypertensive subjects. In multiple regression analysis, Na(+)-Li+ CT showed a significant correlation to glucose disposal rate only. In the control subjects, there was no relation between glucose metabolism and Na(+)-Li+ CT. Neither metformin nor metoprolol influenced Na(+)-Li+ CT, glucose disposal rate or plasma insulin. CONCLUSION: Erythrocyte Na(+)-Li+ CT seemed to be closely related to insulin-glucose metabolism in mild hypertension, but was not influenced by metformin or metoprolol.

Antihypertensive Agents↗
PubMed1996

Bone mineral and related biochemical variables in patients with Kock ileal reservoir or Bricker conduit for urinary diversion.

PURPOSE: Bone material content was studied with single photon absorptiometry and dual energy x-ray absorptiometry , and the various biochemical parameters related to bone metabolism in patients with Kock reservoirs or Bricker conduits for urinary diversion. MATERIALS AND METHODS: We examined 34 patients with Kock ileal reservoirs to the skin (29) or urethra (5) and 14 with Bricker conduits 2 to 17 years after urinary diversion. Bone mineral density was measured in the radius with single photon absorptiometry, and in th femur, lumbar spine and whole body with dual x-ray absorptiometry. Serum concentrations of 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, osteocalcin, parathyroid hormone, bone specific alkaline phosphatase and ionized calcium were determined. Arterial blood gases were analyzed. RESULTS: The mean values for bone mineral density did not differ from age-matched controls in either group and no signs of decrease were observed with followup. Vitamin D serum concentration values remained within normal limits in all patients. Most patients had normal blood gas values. Mean values for osteocalcin, parathyroid hormone, bone specific alkaline phosphatase and ionized calcium also were within normal limits, although a few patients had elevated osteocalcin values indicating increased bone turnover. CONCLUSION: Urinary diversion with a Kock reservoir or Bricker conduit did not cause bone demineralization of significant changes in different markers of bone metabolism in patients examined 2 to 17 years after urinary diversion.

Absorptiometry, Photon↗
PubMed1996

Stimulatory effect of insulin on tubular sodium reabsorption in normotensive subjects with a positive family history of hypertension.

BACKGROUND: Insulin resistance and hyperinsulinaemia has been suggested as a pathogenetic mechanism in hypertension. METHODS: In this investigation the renal response to insulin was studied in normotensive subjects with a positive family history of hypertension in two generations (n = 14), in one weight-matched (n = 11) and one lean (n = 13) control group. During hyperinsulinaemia (euglycaemic hyperinsulinaemic clamp technique) we determined renal haemodynamics (clearances of 51Cr-EDTA and PAH) and urinary sodium excretion. Lithium clearance was used to estimate the segmental tubular reabsorption of sodium. RESULTS: In subjects with a positive family history of hypertension, hyperinsulinaemia did not influence renal plasma flow (RPF) or glomerular filtration rate (GFR) but urinary sodium excretion decreased by 50%. Estimated proximal tubular sodium reabsorption was unaffected by insulin while estimated distal fractional sodium reabsorption increased, P < 0.01. At the end of the clamp a low-dose infusion of angiotensin II (0.1 ng/kg per min) was superimposed. GFR and RPF then decreased significantly concomitant with urinary excretion of sodium. In control subjects hyperinsulinaemia caused an unchanged GFR in both groups, increased RPF in the lean control group and 15-25% reduction in sodium excretion. No alteration was seen in estimated proximal tubular sodium reabsorption, but estimated distal tubular sodium reabsorption increased (P < 0.05) in the lean control group. Angiotensin II elicited a further increase in distal fractional tubular sodium reabsorption in both groups (P < 0.05). CONCLUSION: In normotensive subjects with a positive family history of hypertension, in contrast to control subjects without such history, hyperinsulinaemia caused a marked decrease in urinary sodium excretion in presence of unchanged RPF and GFR indicating a renal tubular effect of insulin located at distal site of the renal tubules. Angiotensin II caused further sodium retention, probably due to an effect on renal haemodynamics.

Adult↗
PubMed1995

Does microalbuminuria predict cardiovascular events in nondiabetic men with treated hypertension? Risk Factor Intervention Study Group.

The aim of this study was to investigate the predictive value of microalbuminuria (overnight urinary albumin excretion rate 17 to 100 mg/12 h) as a risk factor for future major cardiovascular events in nondiabetic patients with treated hypertension in a prospective study with follow-up time of 3.3 years. Overnight urinary albumin excretion was measured in 345 nondiabetic treated hypertensive men, aged 50 to 72 years, either with a serum cholesterol of > or = 6.5 mmol/L or smokers, or both. Cardiovascular morbidity was closely recorded during the follow-up period. At entry, microalbuminuria was found in 84 patients (24.3%) and 12 patients had macroalbuminuria (3.5%). During the follow-up period there were no differences in new cardiovascular events between patients with microalbuminuria and those with normoalbuminuria. However, an increase in the risk of future major cardiovascular events occurred in patients with urinary albumin excretion above 100 mg/12 h (macroalbuminuria). In a Cox regression analysis urinary albumin excretion was not associated with the incidence of future major cardiovascular events unless a more detailed approach was used, showing that this was the case for urinary albumin excretion above 100 mg/12 h (macroalbuminuria). Calculations with an alternative definition of microalbuminuria and mortality as end-point did not change the principal result. In conclusion, microalbuminuria does not seem to be a predictor of future mortality and cardiovascular morbidity in nondiabetic men with treated hypertension and at high risk of coronary heart disease. However, macroalbuminuria was associated with future major cardiovascular events in this group of patients.

Aged↗
PubMed1994

Functional autoimmune epitope on alpha 1-adrenergic receptors in patients with malignant hypertension.

Because of the growing evidence that hypertensive disease is accompanied by immunological dysfunction, we have investigated autoimmunity in patients with malignant hypertension. Peptides corresponding to the sequence of the second extracellular loops of the human alpha 1-adrenergic receptor and the M2-muscarinic receptor were used as antigens in an ELISA. Serum from 4 (12%) of 33 healthy controls, 3 (20%) of 15 patients with malignant essential hypertension, and 7 (64%) of 11 with secondary hypertension showed positive responses in the ELISA for the alpha 1-adrenergic receptor peptide. Positive responses were significantly more common among the patients with secondary hypertension than in the other two groups (p < 0.01). By contrast, no autoantibodies against the M2-muscarinic receptor peptide were detected in either hypertensive group. Autoantibodies against the alpha 1-adrenergic receptor, affinity-purified from patients with positive responses, specifically recognised bands with molecular masses of 68, 40, and 37 kDa on immunoblotted membrane proteins of rat ventricles. The patients' autoantibodies caused a decrease in tritiated prazosin binding sites and an increase in heart beating frequency of neonatal cultured rat cardiomyocytes; antibodies purified from the controls had no effect. Circulating autoantibodies against the alpha 1-adrenergic receptor are present in a subgroup of patients with malignant hypertension. These autoantibodies have pharmacological activity in vitro, which suggests that they may be involved in the pathogenesis of malignant hypertension.

Adult↗
PubMed1994

Autoantibodies against cardiac G-protein-coupled receptors define different populations with cardiomyopathies but not with hypertension.

It was previously shown that the second extracellular loop of cardiovascular G-protein-coupled receptors is an antigenic target for pharmacologically active autoantibodies in patients with idiopathic dilated cardiomyopathy. To extend these observations to cover patients with the same disease from different geographical origins or to patients with other cardiac diseases, peptides corresponding to the sequences of the second extracellular loops of the human M2 muscarinic receptors and beta adrenoceptors were used as antigens in an enzyme immunoassay. Sera from patients from Sweden and Japan with idiopathic dilated cardiomyopathy (DCM, n = 32), hypertrophic cardiomyopathy (HCM, n = 23), malignant essential hypertension (MEH, n = 11), malignant secondary hypertension (MSH, n = 10), and sera from healthy blood donors (HBD, n = 49) were tested. Sera from patients with DCM recognized the muscarinic receptor peptide in 38% of cases and the beta 1 adrenoceptor peptide in 31% of cases. In 50% of the positive patients, autoantibodies against both peptides coexisted as shown by competition experiments using both peptides as inhibitors. In HCM patients, there was a lower frequency of autoantibodies but with a higher but not significant predominance against the M2 peptide. No autoantibodies were detected in sera from patients with MEH or MSH. Autoantibodies against the M2 muscarinic receptors, affinity-purified from positive patients, displayed pharmacological activity as demonstrated by changes in the affinity and number of radioligand binding sites. In contrast, antibodies purified from positive HBD had no effect. These results confirm that autoantibodies displaying pharmacological activity against G-protein-coupled cardiovascular receptors are mainly restricted to patients with idiopathic dilated cardiomyopathy and that different autoantibody populations are responsible for the recognition of the different receptors.

Adult↗
PubMed1994

Effect of recombinant human growth hormone on cellular sodium metabolism.

1. The effect of treatment with recombinant human growth hormone on urinary sodium excretion, total body water, the renin-angiotensin system and erythrocyte sodium metabolism was investigated in 16 adults with growth hormone deficiency. 2. Total body water was determined by isotopic dilution, and erythrocyte electrolyte contents were analysed using flame photometry. The rate of sodium influx and the efflux rate constant of sodium were calculated from values of 22Na in erythrocytes in vitro. 3. One week of treatment with recombinant human growth hormone caused a decrease in urinary sodium excretion in 9/10 patients and an increase in erythrocyte sodium content. Total body water, plasma renin activity, angiotensin II concentration and transmembrane sodium transport were unaltered. 4. Six months of treatment with recombinant human growth hormone caused significant increases in total body water, erythrocyte sodium content and sodium transmembrane influx. Plasma renin activity tended to increase, whereas blood pressure and serum sodium and potassium concentrations remained unchanged. After 6 months on recombinant human growth hormone total body water showed a significant negative correlation with plasma renin activity. 5. The enhanced erythrocyte sodium transport, if this reflects what happens in the renal tubular cell, combined with a decrease in urinary sodium excretion, during treatment with recombinant human growth hormone could indicate an increase in tubular sodium reabsorption induced by the hormone. An increased plasma renin activity associated with the lack of blood pressure rise would reinforce sodium and water retention.

Adult↗
PubMed1994

Abnormalities in the renin-angiotensin-aldosterone system in normotensive subjects with a positive family history of hypertension.

Non-hypertensive men with a positive family history of hypertension in two generations (N = 16) were compared with weight-matched (N = 13) and lean (N = 12) control groups with a negative family history of hypertension with respect to the activity of the renin-angiotensin-aldosterone system at baseline and during an oral glucose tolerance test. Blood pressure was measured phonographically after 30 min of semirecumbent rest and the oral glucose tolerance test was performed after a 10-h overnight fast with 100 g of glucose given orally. Blood samples were drawn from a peripheral catheter at baseline, 30 and 120 min after the glucose challenge. Systolic and diastolic blood pressures did not differ between subjects with a positive or a negative family history of hypertension. At baseline, blood glucose and plasma insulin were similar in the three groups while the group with a positive family history of hypertension had a significantly lower plasma renin activity (PRA) (0.85 +/- 0.09 compared with the weight-matched but not with the lean control group (1.36 +/- 0.13 and 1.06 +/- 0.15 ng AI.ml-1.h-1; p < 0.01 and NS, respectively). The PRA increased significantly after the glucose challenge in all groups (p < 0.01), while the plasma aldosterone concentration decreased after 30 min and then showed an increase at 120 min. The PRA response was less pronounced in the group with a positive family history of hypertension compared with the weight-matched and lean control groups (p < 0.05 and p < 0.01, respectively). Serum potassium did not change significantly in either group after the glucose challenge. Urinary sodium excretion was similar in the three groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Early renal graft function in recipients treated with the calcium channel blocker felodipine.

Calcium channel blocking agents (CCB) differ in molecular structure and effects. Each must therefore be evaluated separately. Out of 139 patients who received cadaveric kidney transplants between March 1990 and December 1991 22 were treated with the CCB agent felodipine as antihypertensive therapy on admission and post transplant. The early function of their grafts was compared with that of grafts to patients not treated with any CCB agent pre or post transplant (n = 38). There were no other significant differences in patient or donor characteristics. In the felodipine treated group, 18/22 showed immediate onset of graft function vs 20/38 in the non CCB group (p = 0.02). Dialysis post transplant was required by one felodipine-treated patient vs 12 in the non CCB group. Serum creatinine on day 7 was lower in felodipine treated patients, median 155 vs 259 mumol/l. Felodipine treatment did not seem to cause any significant interaction with cyclosporin A (CyA). The frequency and severity of acute rejection did not differ between the groups.

Adolescent↗
PubMed1994

Superselective transarterial embolization of renal arteriovenous malformations of cryptogenic origin.

Renal arteriovenous (AV) shunts of unknown origin are rare clinical findings. When symptomatic they can as other renal AV shunts and malformations cause hypertension, congestive heart failure and hematuria. During the last few years the treatment has tended to go from surgery to the more gentle and renal parenchyma sparing but yet effective endovacular embolization techniques. Two cases of renal vascular malformations with severe clinical symptoms necessitating treatment are presented. Treatment was successfully performed with tissue adhesive and coils.

Adult↗
PubMed1994

Influence of pH on reservoir mucosal absorption/-secretion and tubular and glomerular function. Studies in patients with a continent ileal reservoir for urinary diversion.

Ten patients with a continent ileal reservoir for urinary diversion were studied regarding transmucosal fluxes of water and electrolytes at different pH. The urine was by-passed the reservoir via a Foley catheter. The experiment set-up was designed to exclude urine from reservoir mucosa exposition during the study. Test solutions of pH 4 and pH 7 with electrolytes and a non-absorbable volume marker (PEG MW 4000) were instilled into the empty reservoir. The influence of altered pH on the flow of water and Na,+K+ and Cl- across the reservoir mucosa was analysed. The maximal concentration ability after intranasal desmopressin (Minirin), the creatinine and Na-clearance as well as the fractional Na-excretion were calculated from measurements on the by-passed urine. The results showed a secretion of water, Na+ and Cl- into the reservoir while the K+ content was constant. The mucosal flows of water and electrolytes were not affected by alterations in reservoir pH. Maximal concentration ability appeared to be reduced compared to normals. Fractional Na excretion was within normal limits.

Adult↗
PubMed1994

Relationship between change in erythrocyte sodium and antihypertensive response to enalapril.

To investigate the effects of enalapril and hydrochlorothiazide on erythrocyte sodium and potassium in relation to their effects on BP, 28 men (mean age 46 years, range 22-64 years) with previously untreated essential hypertension (casual DBP > or = 95 mmHg) were randomised to enalapril (n = 14) or hydrochlorothiazide (n = 14) treatment. BP was also measured intraarterially (brachial artery) and the mean arterial pressure (MAP) recorded. Intraerythrocyte sodium and potassium were measured by flame photometry at baseline and after 26 weeks of active treatment in the hypertensive patients and also in 28 age- and sex-matched normotensive control subjects. There was a significant positive relationship between intra-arterial BP and intraerythrocyte sodium in untreated hypertensives, but there was no significant difference in mean intraerythrocyte sodium or potassium content between hypertensive and normotensive subjects at baseline. The distribution of values of intraerythrocyte sodium, however, differed between hypertensive and normotensive subjects. Supine MAP was lowered from 113 +/- 4 to 97 +/- 3 mmHg and from 110 +/- 3 to 102 +/- 2 mmHg on enalapril and hydrochlorothiazide treatment, respectively. BP reduction with enalapril was associated with a significant decrease in intraerythrocyte sodium (P = 0.02), while hydrochlorothiazide had no effect. There was no significant correlation between delta MAP and delta intraerythrocyte sodium after 26 weeks in any of the groups. Intraerythrocyte potassium did not change on treatment with either drug. In conclusion, there wa a significant relationship between intra-arterial BP and intraerythrocyte sodium in untreated hypertensives. Both enalapril and hydrochlorothiazide reduced BP effectively while enalapril only reduced intraerythrocyte sodium.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Renal and systemic sympathetic counterregulation in response to vasodilators in renovascular hypertension.

1. Twenty-two patients with renovascular hypertension and significant lateralization of renin secretion were investigated with respect to arterial and renal venous plasma noradrenaline and dopamine concentrations before and 30 min after two different blood pressure-lowering procedures (enalaprilat or dihydralazine intravenously). 2. In one group of patients (n = 10) blood pressure reduction by 7.5 mg of dihydralazine caused stimulation of the renin-angiotensin system and increased heart rate (P < 0.01) as well as arterial and renal venous plasma noradrenaline and dopamine concentrations (P < 0.01 for both). The elevation of the plasma dopamine concentration was more pronounced than that of noradrenaline, yielding increased dopamine/noradrenaline ratios both peripherally (P < 0.05) and in the renal veins (P < 0.05). 3. In the second group of patients (n = 12) a comparable reduction in blood pressure elicited by 1.25 mg of enalaprilat was not accompanied by alterations in heart rate or in noradrenaline or dopamine levels in arterial plasma or renal venous plasma from either kidney. 4. Thus, inhibition of angiotensin-converting enzyme does not elicit the expected sympathetic counter-regulatory response to blood pressure reduction; the mechanism(s) involved remains to be clarified.

Adolescent↗
PubMed1993

Microalbuminuria in treated hypertensive men at high risk of coronary disease. The Risk Factor Intervention Study Group.

OBJECTIVE: To examine whether microalbuminuria is a marker of cardiovascular disease in treated hypertensive men without diabetes mellitus at high coronary risk and to examine the associations between microalbuminuria and recognized cardiovascular risk factors. DESIGN: Cross-sectional study. SETTING: Outpatient clinic in city hospital. PATIENTS: Three hundred and thirty-three treated hypertensive men, aged 50-72 years, either with a serum cholesterol of > or = 6.5 mmol/l or smokers, or both. The patients were recruited mainly from a population-based sample of hypertensive men. Patients with diabetes mellitus or overnight urinary albumin excretion of > 100 mg/12 h were excluded from the analyses. MAIN OUTCOME MEASURES: Overnight urinary albumin excretion, prevalence of microalbuminuria (defined as 17-100 mg/12 h) and organ damage (cardiovascular events or major electrocardiogram changes, or both), various well-established risk factor levels, blood glucose and plasma insulin responses to an oral glucose tolerance test. RESULTS: Microalbuminuria was found in 25% of the cohort. Among microalbuminuric patients, organ damage was significantly more common (47.6%) than in the normoalbuminuric group (30.9%). However, the sensitivity and specificity of microalbuminuria as a marker of organ damage were only 34 and 80%, respectively. Microalbuminuria was significantly related to body mass index and waist:hip ratio, age and plasma insulin during oral glucose tolerance testing. These relationships also persisted after adjustment for treatment with thiazides or beta-blockers. CONCLUSIONS: In treated hypertensive men without diabetes mellitus, microalbuminuria was associated with factors known to be related to insulin resistance. It had a low sensitivity as a marker of concomitant cardiovascular disease.

Aged↗
PubMed1993

Abnormal immune function in malignant hypertension.

OBJECTIVE: To investigate the extent to which the immune system is influenced in patients with previous malignant hypertension. DESIGN: Twenty-three patients with malignant hypertension (fundus hypertonicus grades III or IV) in the Gothenburg area were studied over a 3-year period. After treatment had been instituted they were investigated to establish the function of the cellular immune system (number of T lymphocytes and the proliferative response to T-cell mitogens), human leucocyte antigens A, B and C and frequency of autoantibodies. METHODS: The numbers of T lymphocytes were quantified as erythrocyte rosettes. Lymphocyte-stimulation tests were carried out using the T-cell mitogens phytohaemagglutinin and concanavalin-A. Autoantibodies were determined with immunoassay techniques and leucocyte A, B and C antigens with a lymphocytotoxicity test. RESULTS: The frequency of T lymphocytes and their baseline thymidine incorporation were significantly depressed in patients with previously malignant hypertension compared with control subjects. The group with malignant hypertension also had a decreased proliferative response to concanavalin-A but not to phytohaemagglutinin, and they had an increased frequency of antinuclear antibodies. Human leucocyte antigen B15 tended to occur more frequently in patients with malignant and non-malignant hypertension than in control subjects, especially if a family history of hypertension was taken into consideration. CONCLUSION: The results from the present study indicate that immune mechanisms are involved in malignant hypertension, either secondary to the vascular damage or as a primary abnormality.

Antibody Formation↗
PubMed1993

Altered erythrocyte transmembrane transport of sodium and potassium in patients with conventional or reservoir ileostomy.

After proctocolectomy, the loss of the colonic absorptive capacity of sodium is compensated for by increased small intestine sodium absorption and renal conservation of Na by enhanced tubular reabsorption. These processes entail increased cellular sodium transport in the enterocytes and in the renal tubular cells. In order to evaluate if there is a general increase in cellular transport of Na after proctocolectomy for inflammatory bowel diseases erythrocyte Na and K contents and the transmembrane Na fluxes were determined in 35 patients with conventional ileostomy, 23 of which were reinvestigated after conversion to continent reservoir ileostomy. A selected group of another 12 patients having high output from their reservoir ileostomy and low urinary Na were studied concomitantly and 33 healthy subjects served as controls. The intracellular Na content did not differ between the groups while the intracellular K levels were higher in patients with conventional or continent ileostomy compared to controls. In addition, the Na influx and the efflux rate constant of Na were both increased after conversion to reservoir ileostomy. Na influx correlated positively with intake and urinary excretion of Na in conventional ileostomy patients. The results suggest that patients with ileostomy have an increased cellular K uptake and that construction of a reservoir ileostomy further alters cell cation transport by increasing the transmembrane Na turnover.

Adult↗