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Biomedical subjects

P Friberg

Publications and source records attributed to P Friberg.

At least 19 recordsLinked to original sources
PubMed2005

Long-term outcome of a large series of patients surgically treated for pheochromocytoma.

OBJECTIVE: To analyse the morbidity, mortality and long-term outcome in a consecutive series of surgically treated patients with pheochromocytoma (PC), or paraganglioma (PG), from the western region of Sweden between 1950 and 1997. PATIENTS: All patients (n = 121) who had been hospitalized and treated for PC/PG over 47 years. DESIGN: Retrospective review of patients with PC/PG regarding presenting symptoms, tumour characteristics, clinical management and long-term outcome after treatment. SETTING: One referral centre for all patients from the western region of Sweden. RESULTS: During an observation of 15 +/- 6 years, 42 patients died vs. 23.6 expected in the general population (P < 0.001). There was no intra- or post-operative mortality. Four patients with sporadic disease died of malignant PC and six with hereditary disease of associated neuroectodermal tumours. Five patients died of other malignancies, 20 of cardiovascular disease and seven of other causes. Besides older age at primary surgery, elevated urinary excretion of methoxy-catecholamines was the only observed risk factor for death (P = 0.02). At diagnosis 85% of the patients were hypertensive; one year after surgery more than half were still hypertensive. However, pre- and post-operative hypertension did not influence the risk for death versus controls. CONCLUSION: Pheochromocytoma/PG can be safely treated by surgery. Death of malignant PC/PG was unusual, but the patients as a group had an increased risk of death. We recommend life-long follow-up of patients treated for PC/PG with screening for recurrent tumour in sporadic cases and for associated tumours in hereditary cases. This strategy would also be helpful in diagnosing cardiovascular disease at an early stage.

Adrenal Gland Neoplasms↗
PubMed2004

Increased left ventricular mass in obese adolescents.

AIMS: An increase of left ventricular mass (LVM) has been reported in obese adolescents in previous studies using echocardiography. The aim of our study was to determine the extent of the increase in LVM and correlation to other risk factors using cardiac magnetic resonance imaging in obese and lean adolescents. METHODS AND RESULTS: Nineteen obese and 20 lean adolescents were recruited. Following resting blood pressure measurements and blood sampling for insulin, triglycerides, and cholesterol levels, all subjects underwent cardiac magnetic resonance examination to assess LVM. LVM adjusted for body height was 16% greater in obese compared to lean adolescents (median 66 g/m, p = 0.0042). Obese subjects had higher resting systolic blood pressures than controls (median 115 vs. 110 mmHg, p = 0.0077) and higher fasting triglyceride and insulin levels. HDL-cholesterol levels were lower in the obese group compared with the lean group. CONCLUSIONS: Obese adolescents had a higher LVM than age-matched lean subjects, which correlated mainly with body mass index and systolic blood pressure. These findings add to the established cardiovascular risk profile of obese adolescents.

Adolescent↗
PubMed2004

The renin-angiotensin system in kidney development.

All components of the renin-angiotensin system (RAS) are highly expressed in the developing kidney in a pattern suggesting a role for angiotensin II in renal development. In support of this notion, pharmacological interruption of angiotensin II type-1 (AT(1)) receptor signalling in animals with an ongoing nephrogenesis produces specific renal abnormalities characterized by papillary atrophy, abnormal wall thickening of intrarenal arterioles, tubular atrophy associated with expansion of the interstitium, and a marked impairment in urinary concentrating ability. Similar changes in renal morphology and function develop also in mice with targeted inactivation of genes encoding renin, angiotensinogen, angiotensin-converting enzyme, or both AT(1) receptor isoforms simultaneously. Taken together, these results clearly indicate that an intact signalling through AT(1) receptors is a prerequisite for normal renal development. The present report mainly reviews the renal abnormalities induced by blocking the RAS pharmacologically in experimental animal models. In addition, pathogenetic mechanisms are discussed.

Animals↗
PubMed2002

Sympathetic nervous activation following subarachnoid hemorrhage: Influence of intravenous clonidine.

BACKGROUND: Subarachnoid hemorrhage is often accompanied by systemic complications and cerebral vasospasm. Elevated levels of circulating catecholamines may be involved in the pathophysiology behind these events. The alpha-2-agonist clonidine inhibits sympathetic outflow by a central mechanism. Unrestricted sympathoexcitation may be detrimental and administration of clonidine may be beneficial in these patients. METHODS: Using isotope dilution methodology, norepinephrine kinetic determinations, comprising determination of arterial norepinephrine concentration and rates of norepinephrine spillover to and removal, or clearance, from plasma, were performed on three occasions during the first week after subarachnoid hemorrhage in 25 patients. Eleven of these patients received clonidine (continuous i.v. infusion 5.8 +/- 0.7 microg x kg(-1) x 24 h(-1)) and the remainder, standard therapy. Initial results were compared with 17 healthy age-matched subjects and eight patients suffering from severe traumatic brain injury without traumatic subarachnoid hemorrhage. RESULTS: Subarachnoid hemorrhage patients exhibited markedly elevated arterial plasma norepinephrine concentrations [3.74 +/- 0.48, P < 0.001 vs. healthy subjects (1.59 +/- 0.11 nmol/L) and P < 0.05 vs. head trauma patients (1.94 +/- 0.29 nmol/L)]. The rate of clearance of norepinephrine from plasma in the subarachnoid patients was also significantly greater than that observed in the healthy subjects (2.66 +/- 0.15 vs. 2.14 +/- 0.15 L/min, P < 0.05) and the head trauma patients (2.00 +/- 0.12 L/min, P < 0.05). Compared with both control groups, on admission the rate of spillover of norepinephrine to plasma following subarachnoid hemorrhage was markedly elevated (9.11 +/- 1.12, P < 0.001). Clonidine treatment (continuous i.v. infusion 5.8 +/- 0.7 microg x kg(-1) x 24 h(-1)) did not reduce the increased rate of spillover of norepinephrine to plasma following subarachnoid hemorrhage. CONCLUSION: Sympathetic nervous activity is markedly elevated following subarachnoid bleeding. Clonidine had no effect on the rate of norepinephrine spillover to, or clearance from, plasma in these patients. Clearly, further studies are required to elucidate the mechanisms responsible for generating sympathetic nervous activation following subarachnoid hemorrhage.

Adrenergic alpha-Agonists↗
PubMed2001

Acute and chronic alterations in blood pressure variability following experimental subarachnoid haemorrhage.

This study examined the role of the renin-angiotensin and vasopressin systems on systolic blood pressure (SBP) variability following subarachnoid haemorrhage (SAH) in conscious rats. Animals received no treatment, the angiotensin II AT1 receptor antagonist, losartan, or the vascular vasopressin receptor antagonist, AVPX. SAH resulted in a transient sympathetic activation as estimated from the increase in the mid-frequency oscillations of SBP (3.2 +/- 0.8 mm Hg2, 3 hours after the injury vs. 1.3 +/- 0.3 mm Hg2 in control conditions, p < 0.01). On the second and fourth day following SAH, a marked elevation in the low-frequency component of SBP was observed (7.1 +/- 1.0 mm Hg2 on day 2 vs. 2.6 +/- 0.3 mm Hg2 in control conditions, p < 0.001 and 6.3 +/- 1.1 mm Hg2 on day 4 vs. 2.6 +/- 0.3 mm Hg2 in control conditions, p < 0.01). Pre-treatment with losartan prevented the acute rise in the mid-frequency oscillations in SBP and partially reduced the low-frequency component observed at 2 and 4 days. Administration of AVPX on the second and fourth day following SAH normalised the elevated low-frequency oscillations in SBP. This study indicates that the modifications in SBP variability observed in the early and delayed stage after subarachnoid haemorrhage involve angiotensin II. Vasopressin seems to be implicated in the delayed development of low-frequency fluctuations of SBP.

Animals↗
PubMed2001

Renal cortical accumulation of hyaluronan in adult rats exposed neonatally to angiotensin-converting enzyme inhibition.

Neonatal inhibition of the renin-angiotensin system [angiotensin-converting enzyme (ACE) inhibition] in the rat results in long-term abnormal renal morphology and function, including interstitial inflammation and fibrosis. Hyaluronan (hyaluronic acid, HA) has pathological implications in inflammatory diseases and renal ischaemia-reperfusion injury. The present study aimed at determining if renal cortical HA in the adult rat is correlated to the abnormal morphology and function in rats treated neonatally with the ACE inhibitor enalapril. In adult control rats (23 weeks old), the cortical HA content was very low [about 5 microg g(-1) dry weight (d.w.)] and about 1% of the papillary HA content. In rats treated neonatally with enalapril (days 3-13), the cortical HA level was 15 times that in control rats already at 21 days after birth, and it persisted at this level during adulthood (at 23 weeks). At 13 weeks the enalapril-treated animals showed markedly reduced ability (-53%) to concentrate urine during 24-h thirst provocation. At 21 days as well as at 23 weeks the enalapril-treated kidneys displayed morphological changes, such as papillary atrophy, dilation of the tubules and cellular infiltration of the cortical tissue. Histochemical staining confirmed the HA quantification assay and revealed a patchy staining for HA located in the same regions as the infiltrating cells. In conclusion, neonatal treatment with the ACE inhibitor enalapril results in renal morphological and functional abnormalities during adulthood. Cortical HA levels are already seriously elevated at day 21 and coexist with infiltrating cells. Besides the known effects of angiotensin II in development, the accumulation of HA in these kidneys may be involved in the genesis of at least the cortical abnormalities in enalapril-treated animals because of the proinflammatory effects and water-binding properties of HA.

Age Factors↗
PubMed2001

Treatment of abdominally obese men with a serotonin reuptake inhibitor: a pilot study.

OBJECTIVE: To investigate the effects of a selective serotonin reuptake inhibitor (SSRI) on the neuroendocrine and autonomic nervous system perturbations found in abdominal obesity. DESIGN: Treatment for 6 months with citalopram and for 6 months with placebo using a double-blind, cross-over design, with a 2-month wash-out period between treatment periods. SUBJECTS: Sixteen healthy men, 45-60 years, moderately obese and with an abdominal fat distribution. MEASUREMENTS: Anthropometry, three different depression rating scales, serum lipids, testosterone, IGF-I, oral glucose tolerance test (OGTT), pituitary stimulation with corticotropin releasing hormone (CRH), arithmetic stress test, and excretion of cortisol and metoxycatecholamines in urine, collected during 24 h. RESULTS: Cortisol concentrations in the morning were low before treatment, indicating a perturbed function of the hypothalamic-pituitary-adrenal (HPA) axis. After treatment with citalopram morning cortisol concentrations rose to normal. Cortisol concentrations after stimulation with CRH or stress were elevated by citalopram treatment, but urinary cortisol excretion was unchanged. The glucose concentrations after OGTT (120 min) tended to be reduced, with unchanged insulin concentrations, whilst other metabolic values did not change during treatment. Heart rate after administration of CRH, and during laboratory stress test, decreased by treatment with citalopram. Diurnal urinary excretion of metoxycatecholamines tended to decrease. Neither body mass index nor waist/hip circumference ratio decreased. Depression scores were within normal limits before treatment and did not change. CONCLUSION: The results of this pilot study indicate improvements in the regulation of neuroendocrine-autonomic systems as well as metabolism in abdominal obesity during treatment with an SSRI.

Body Constitution↗
PubMed2001

Subarachnoid haemorrhage-induced sympathoexcitation in rats is reversed by bosentan or sodium nitroprusside.

1. The roles played by nitric oxide (NO) and endothelin (ET) in the genesis of sympathetic nervous activation following experimental subarachnoid haemorrhage was investigated using spectral analysis of blood pressure rhythms. 2. Subarachnoid haemorrhage was induced in conscious rats by injecting 0.3 mL homologous blood via a catheter placed along the surface of the brain and directed towards the circle of Willis. Three hours after the insult and after sympathetic activation was evident, animals received either an acute injection of the ET antagonist bosentan (5 mg/kg, i.v.; n = 7), an infusion of the NO donor sodium nitroprusside (SNP; 18 microg/h; n = 7) or no treatment (n = 7). 3. Three hours following the induction of subarachnoid haemorrhage, the mid-frequency components of systolic blood pressure were markedly elevated, indicating a pronounced sympathoexcitation. However, blood pressure and heart rate levels remained unchanged at this time. In the absence of treatment, the mid-frequency components of blood pressure remained elevated for a subsequent 2 h. Treatment with a non-hypotensive dose of SNP reversed the sympathoexcitation within 1 h. Treatment with bosentan was also effective in reducing the mid-frequency oscillations in blood pressure associated with subarachnoid haemorrhage. 4. Our results indicate that subarachnoid haemorrhage is associated with an acute activation of the sympathetic nervous system. The degree of sympathoexcitation can be reversed by the use of either bosentan or SNP.

Animals↗
PubMed2000

Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: evidence in support of the catecholamine hypothesis of mood disorders.

BACKGROUND: The etiology of depressive illness has been linked with brain monoaminergic neuronal dysfunction, yet the development of sensitive markers of endogenous depression has proven difficult. METHODS: Using catheters placed in an internal jugular vein, we estimated the release of brain monoamine neurotransmitters in 19 healthy volunteers and in 9 patients with nonbipolar depressive illness refractory to medication at rest and following intravenous desipramine hydrochloride. Venoarterial plasma concentration gradients were used to quantify the amount of neurotransmitters stemming from the brain. Cerebral oxidative metabolism was assessed concurrently from measurements of oxygen and carbon dioxide gas exchange via the process of regional indirect calorimetry. RESULTS: The brains of these patients exhibited reduced venoarterial norepinephrine (4.0 +/- 2.7 nmol/L vs 0.7 +/- 1.3 nmol/L) and homovanillic acid concentration gradients (8.3 +/- 7.8 nmol/L vs 3.1 +/- 1.9 nmol/L), and used an energy source other than glucose. Internal jugular 5-hydroxyindoleacetic acid concentration gradients were not reduced in the patients with depressive illness. While both the reduction in norepinephrine turnover and the defect in cerebral metabolism were normalized following pharmacological blockade of the norepinephrine transporter with desipramine, paradoxically it was the brain's turnover of dopamine that bore a significant relation to the patients' clinical status (r(s) = 0.79, P =.02). The positive nature of this relationship remains difficult to reconcile. CONCLUSIONS: In accordance with the monoamine hypothesis, a deficit in brain norepinephrine and dopamine exists in patients with depressive illness. Moreover, the brains of these patients use an energy source other than glucose, a situation that is normalized following the acute pharmacological blockade of the norepinephrine transporter with the tricyclic antidepressant, desipramine.

Adult↗
PubMed2000

Acute renal responses to angiotensin-converting enzyme inhibition in the neonatal pig.

Pharmacological interruption or genetic disruption of the renin-angiotensin system before completion of nephrogenesis produces papillary atrophy and an impaired urinary concentrating ability. The mechanisms involved are yet to be elucidated, but renal hypoperfusion and subsequent ischemia, particularly to the immature renal medulla, may be hypothesized. The acute intrarenal responses to angiotensin-converting enzyme (ACE) inhibition in the newborn piglet were thus investigated by means of regional blood flow distribution, renal interstitial hydrostatic pressure (RIHP), and medullary oxygen tension (PO2) in the anesthetised 4- to 5-day-old piglet. Moreover, the calcium antagonist nifedipine and the nitric oxide synthesis inhibitor L-NAME were also given in order to reduce renal blood flow by other means. The drugs were given intravenously in equipotent pressor doses, mimicking intraperitoneal injections in neonatal rats. Enalaprilat (200 microg/kg) reduced mean arterial pressure (MAP) by 14+/-10% (mean+/-SD, P=0.006) and RIHP by 18+/-18% (P=0.001), whereas total renal blood flow and medullary PO2 remained unchanged. In contrast, nifedipine (0.5 mg/kg) reduced MAP and RIHP by 39+/-8% and 38+/-14%, respectively, total and regional blood flows by 30%-60%, and medullary PO, by 46+/-29% (P=0.001). Acute administration of L-NAME (15 mg/kg) increased MAP by 27+/-10% (P=0.0005), whereas RIHP and renal blood flow decreased by 20%-50%, resulting in a reduction of the medullary PO2 by 10+/-12% (P=0.05). We conclude that the renal abnormalities observed after neonatal ACE inhibition are not likely to be caused by renal ischemia.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2000

Role of the sympathetic nervous system in human renovascular hypertension.

The findings in humans as to whether elevated sympathetic nerve activity contributes to renovascular hypertension have been less consistent compared with the results obtained in experimental models of renovascular hypertension. Collectively, there are several lines of evidence to support the view that sympathetic nerve activity is elevated in patients with renovascular hypertension. It is uncertain, however, whether this adrenergic overactivity is specific for renovascular hypertension per se, or the cause of severe hypertension with target organ damage. Central or peripheral stimulation of sympathetic nerve activity by angiotensin II, or stimulation of central sympathetic outflow via afferent renal nerves of ischemic kidneys, are possible mechanisms to explain the elevated sympathetic nerve activity in renovascular hypertension. Therapy that diminishes the activity of the sympathetic nervous system and the renin-angiotensin system seems rational and could perhaps also improve the poor prognosis for these patients.

Adrenergic Fibers↗
PubMed2000

Subarachnoid hemorrhage induced sympathoexcitation arises due to changes in endothelin and/or nitric oxide activity.

OBJECTIVE: The demonstration of the effectiveness of endothelin antagonists and nitric oxide donors in managing vasospasm following subarachnoid hemorrhage is encouraging. Whether such drugs can modify the sympathoexcitation that accompanies this condition remains unknown and was the basis for the present report. METHODS: Subarachnoid hemorrhage was induced in conscious rats by injecting blood via a catheter placed along the surface of the brain and directed towards the circle of Willis. We combined measurements of arterial plasma catecholamines with the spectral analysis of blood pressure variability in order to examine sympathetic nervous activation following subarachnoid hemorrhage. Experiments were performed in untreated animals and in rats following pretreatment with either bosentan or sodium nitroprusside. RESULTS: Indicative of a pronounced sympathoexcitation, the 0.2-0.6 Hz frequency components of blood pressure were markedly elevated following subarachnoid hemorrhage (2.5 +/- 0.5 vs. 8.9 +/- 2.6 mmHg2, P < 0.01). Parallel changes in plasma norepinephrine concentration were observed (1.0 +/- 0.2 vs. 2.4 +/- 0.4 nmol/l, P < 0.01). The subarachnoid injection of saline did not modify blood pressure variability or plasma norepinephrine concentrations. Pretreatment with either bosentan or sodium nitroprusside completely prevented the subarachnoid hemorrhage induced sympathoexcitation. CONCLUSIONS: Experimental subarachnoid hemorrhage is associated with a pronounced activation of the sympathetic nervous system. It would appear that this sympathoexcitation has its roots ensconced in either the release of endothelin or an impairment in nitric oxide mediated vasodilation.

Animals↗
PubMed2000

Candesartan cilexetil and renal hemodynamics in hypertensive patients.

This randomized, double-blind, placebo-controlled crossover study evaluated the effects of the angiotensin II type 1 (AT1)-receptor blocker candesartan cilexetil on renal blood perfusion and glomerular filtration in patients with primary hypertension with diastolic blood pressure of 100 to 114 mm Hg. After a 4-week placebo run-in period, patients were randomized to receive either 16 mg candesartan cilexetil or placebo once daily for 6 weeks, after which they were switched to the alternative treatment. At the end of each period, 24 h after the last dose, renal assessments were made and the plasma renin activity, plasma concentrations of angiotensin II, aldosterone, and catecholamines were measured. Compared with placebo, candesartan cilexetil significantly reduced mean arterial pressure, by 8 mm Hg (95% confidence interval [CI], 3;12). Renal vascular resistance was significantly reduced by 0.03 mm Hg/mL min(-1) (95% CI, 0.01; 0.06). There was a small nonsignificant increase in renal plasma flow. The filtration fraction fell slightly from 0.24 to 0.22 (95% CI, -0.00, 0.04). As expected, angiotensin II concentrations and plasma renin activity were increased and the aldosterone concentrations were reduced. Catecholamine concentrations were unaffected. In conclusion, 6 weeks' treatment with 16 mg candesartan cilexetil once daily induced a reduction of renal vascular resistance and a trend toward increased renal plasma flow despite a reduction in mean arterial pressure. Because the glomerular filtration rate was maintained the filtration fraction was reduced, indicating a decreased glomerular capillary pressure.

Adult↗
PubMed2000

Renal effects of amino acid infusion in cardiac surgery.

OBJECTIVE: To evaluate effects of amino acids on renal function and oxygen consumption and the role of individual amino acids on renal blood flow (RBF) changes. DESIGN: Prospective, randomized, controlled study. SETTING: Operating room in cardiothoracic surgery department, university hospital. PARTICIPANTS: Twenty-two male patients submitted to elective first-time coronary artery bypass surgery. INTERVENTIONS: A catheter was placed in the left renal vein for thermodilution RBF measurements and blood sampling. In 11 patients, a balanced mixed amino acid infusion was infused (200 mL/hr) for 30 minutes immediately after the operation. MEASUREMENTS AND MAIN RESULTS: RBF and glomerular filtration rate increased during amino acid infusion compared with the control group. Renal oxygen consumption increased in the amino acid group and correlated with the increase in RBF (r = 0.70, p<0.001). Amino acid infusion induced two- to fourfold increases in plasma concentrations of individual amino acid concentrations and promoted renal extraction of aspartate, glutamate, glycine, and histidine. No correlation was observed between arterial concentration or uptake of individual amino acids and RBF. CONCLUSIONS: The increase in RBF from a mixed amino acid infusion was associated with increased glomerular filtration rate and renal consumption of oxygen. Changes in RBF of a mixed amino acid infusion could not be linked to plasma level or renal uptake of any individual amino acids.

Adult↗
PubMed2000

The activity of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system in relation to waist/hip circumference ratio in men.

OBJECTIVE: To investigate possible differences, between generally and abdominally obese men, in activity and regulation of the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system. RESEARCH METHODS AND PROCEDURES: Fifty non-diabetic, middle-aged men were selected to obtain two groups with similar body mass index (BMI) but different waist/hip circumference ratio (WHR). Measurements were performed of the activity of the HPA axis and the sympathetic nervous system, as well as metabolic and endocrine variables. RESULTS: Men with a high WHR, in comparisons with men with a low WHR, had higher insulin, glucose, and triglyceride values in the basal state and higher glucose and insulin after an oral glucose tolerance test. Men with high WHR had elevated diurnal adrenocorticotropic hormone (ACTH) values but similar cortisol values, except lower cortisol values in the morning. Diurnal growth hormone concentrations showed reduced peak size. Stimulation of the HPA axis with corticotropin-releasing hormone (CRH) and laboratory stress showed no difference in ACTH values between groups, but cortisol values were lower in men with high WHR. In comparison with men with a low WHR, men with a high WHR had elevated pulse pressure and heart rate in the basal state and after challenges by CRH and laboratory stress. They also had increased urinary excretion of catecholamine metabolites. DISCUSSION: These results suggest a mild dysregulation of the HPA axis, occurring with elevated WHR independent of the BMI. The results also indicate a central activation of the sympathetic nervous system, such as in the early phases of hypertension, correlating with insulin resistance.

Adipose Tissue↗