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Biomedical subjects

T Hedner

Publications and source records attributed to T Hedner.

At least 145 records · Page 8Linked to original sources
PubMed1995

Functional explanation for increased atrial natriuretic peptide in systemic sclerosis.

We related atrial natriuretic peptide (ANP) among 30 consecutive patients with systemic sclerosis (SScl) and 48 gender- and age-matched controls to the measurements of left ventricular (LV) function as evaluated by echocardiography and external pulse curves to determine possible causative factors for an increased level of plasma ANP. The patients had a markedly elevated plasma ANP level (239.4 +/- 59 vs. 178.2 +/- 36 pmol/l, p < 0.0005), which was not related to LV systolic function, heart rate, or blood pressure. Patients had LV hypertrophy and plasma ANP correlated directly to interventricular septal thickness (r = 0.41, p < 0.005), LV posterior wall thickness (r = 0.32, p < 0.01), and wall thickness to cavity dimension (r = 0.44, p < 0.0005), LV mass index (r = 0.40, p < 0.005). LV early filling properties were impaired, with reduction of atrial emptying index (p < 0.0005) and increased contribution of atrial contraction to LV filling. Plasma ANP correlated to atrial emptying index (r = 0.41, p < 0.0005) and to apex-cardiographic a wave (r = 0.28, p < 0.05). Plasma ANP was also related to left atrial dimension index (r = 0.27, p < 0.05), and was still related to atrial emptying index, but not to left atrial dimension, when considering the degree of LV hypertrophy in multivariate analysis. We conclude that ANP is elevated in patients with SScl. Reduced LV compliance, probably due to increased fibrosis, may cause changes in atrial pressure sufficient to stimulate ANP production without systolic dysfunction as a prerequisite.

Adult↗
PubMed1995

Postoperative analgesic effects of intra-articular bupivacaine and morphine after arthroscopic cruciate ligament surgery.

Intra-articular administration of local anaesthetics such as bupivacaine can produce short-term postoperative analgesia in patients undergoing diagnostic arthroscopy or arthroscopic meniscectomy. A peripheral anti-nociceptive effect may also be induced by the administration of intra-articular opiates interacting with local opioid receptors in inflamed peripheral tissue. In the present study we aimed to study the analgesic effects of intra-articularly given bupivacaine and morphine sulphate (as well as the combination of both drugs) on postoperative pain. In a prospective, randomized, double-blind manner 40 patients received one of the following: (a) morphine (1 mg in 20 ml NaCl), (b) bupivacaine (20 ml, 0.375%), (c) combination of both or (d) saline (20 ml, control group) intra-articularly at the end of arthroscopic anterior cruciate ligament (ACL) reconstruction. The postoperative pain was assessed via a visual analogue scale (VAS) during the first 48 h after surgery, and supplemental analgesic requirements were noted. All comparisons were made versus the control group receiving saline. The pain scores were significantly lower in the morphine group at 24 and 48 h, and in the bupivacaine group at 2, 4 and 6 h after surgery. In the group that received a combination of both bupivacaine and morphine, the pain scores were significantly reduced throughout the whole postoperative observation period. No side-effects or complications from therapy were seen in any of the groups. The conclusion of this study is that intra-articular morphine is effective in the postoperative period after arthroscopic ACL reconstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Cardiovascular and renal effects of alpha-trinositol in ischemic heart failure rats.

Previous studies have demonstrated that alpha-trinositol (D-myo-inositol-1.2.6-trisphosphate; PP56) may act as a functional neuropeptide Y (NPY) inhibitor. Because NPY is known to be a potent vasoconstrictor, the effects of alpha-trinositol on renal function, vascular responses and the potentiating effects of NPY were investigated in rats with congestive heart failure (CHF) induced by ligation of the left coronary artery. Incremental doses of alpha-trinositol were given to conscious rats (bolus 2, 4 or 10 mg/kg i.v. followed by a 15-minute infusion 20, 40 and 100 mg/kg/h, respectively). Urinary volume, sodium and potassium excretions were significantly increased in both CHF and sham-operated control animals after alpha-trinositol administration compared with saline. Diuresis and natriuresis were observed also during co-administration of alpha-trinositol with NPY but not with norepinephrine (NE). In the pithed CHF rats, threshold doses of NPY potentiated the pressor effects of endothelin-1 (ET-1) and angiotensin II (AII), but not preganglionic nerve stimulation or phenylephrine administration. Alpha-trinositol antagonized both the pressor response to NPY and the potentiation by NPY of pressor responses to effects of ET-1 and AII. Our data show that alpha-trinositol exhibis diuretic and natriuretic effects as well as vascular antagonistic effects on NPY in normal and CHF rats. These effects of alpha-trinositol may be due to an interaction with NPY mediated antidiuresis and antinatriuresis.

Animals↗
PubMed1995

Outcomes of epidural morphine treatment in cancer pain: nine years of clinical experience.

The outcome of epidural morphine therapy is described in 146 consecutive cancer patients who were treated by a community hospital-based pain service. The routine procedure used a standard epidural catheter that was tunneled subcutaneously. One hundred and twenty-one patients improved and stayed on lifelong or chronic epidural opioids. Mean treatment time was 92 days (median, 47; range, 2-2040); 49% of the time was spent as outpatients. Twenty-five patients failed to respond to the treatment. The oral daily morphine-equivalent dose prior to inclusion was 164 mg. The mean daily epidural start dose of morphine was 18 mg (range, 6-120), and the mean daily dose at termination was 69 mg (range, 2-540). The dose escalations, described as the ratio of the maximum dose to the minimum maintenance start dose, were moderate, with a mean of 4.1 (median, 2.5), which corresponded to a percent increase of 5.1 (median, 2.7) per patient per day. Lack of effect due to the character of the original symptoms or progression of pain was the main reason for withdrawal from epidural opioid therapy (N = 27), followed by catheter-related problems (N = 9) and drug-related complications (N = 5). Also due to drug-related complications, epidural morphine therapy was changed to buprenorphine or methadone in 19 patients. Adjuvant systemic opioids were given to ten patients and epidural local anesthetics were administered to 17 of the subjects. Neuropathic pain, certain visceral pain types, incident pain on movement, and pain from cutaneous ulcerations were characteristics of poor responders.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Effects of vagus nerve stimulation on amino acids and other metabolites in the CSF of patients with partial seizures.

Electrical stimulation of the vagus nerve (VNS) is a new method for the treatment of patients with medically intractable epilepsy. Sixteen patients, ten of whom participated in a larger multicenter double-blind trial on the efficacy of VNS in epilepsy, and six who participated in pilot studies, consented to participate in the present study. Ten patients received HIGH stimulation and six patients LOW stimulation for the 3-month trial. Cerebrospinal fluid (CSF) samples (16 ml) were collected both before and after 3 months of VNS. Amino acid and neurotransmitter metabolites were analyzed. Four patients responded to VS with more than a 25% seizure reduction after 3 months. Mean and median concentrations of phosphoethanolamine (PEA) increased in responders and decreased in nonresponders. Free GABA increased in both groups but more so in the nonresponders. After 9 months of VS (6-9 months on HIGH stimulation) 4 of 15 patients had more than 40% seizure reduction. There were significant correlations between seizure reduction and increases in asparagine, phenylalanine, PEA, alanine and tryptophan concentrations. Comparison between patients with HIGH or LOW stimulation showed a significant increase in ethanolamine (EA) in the HIGH group and a decrease in glutamine in the LOW group. All patients regardless of response or stimulation intensity showed significantly increased total and free GABA levels. A decrease in CSF aspartate was marginally significant. Other trends were decreases in glutamate and increases in 5-hydroxyindoleacetic acid. Chronic VNS appears to have an effect on various amino acids pools in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Seizure frequency and CSF parameters in a double-blind placebo controlled trial of gabapentin in patients with intractable complex partial seizures.

Gabapentin (GBP) is a non-protein-bound gamma amino acid which is not subjected to metabolic degradation in man. As part of a placebo-controlled double-blind study, patients suffering from intractable complex partial seizures with or without secondary generalization were followed with lumbar punctures at baseline and after three months of GBP treatment (900 mg/day or 1200 mg/day). Cerebrospinal fluid (CSF) was analyzed for concentrations of GBP, amino acids including GABA, homovanillic acid (HVA), and 5 hydroxyindoleacetic acid (5-HIAA). The results indicate that there were no changes in the selected amino acids, HVA, or 5-HIAA after GBP treatment. At steady state the CSF/plasma ratios of GBP ranged from 0.056 to 0.34, indicating that there may be some type of active out-transport of GBP across the blood-brain barrier. No linear relationship was observed between plasma and CSF levels in these patients.

Acetates↗
PubMed1995

Effects of prostaglandin E2 and capsaicin on behavior and cerebrospinal fluid amino acid concentrations of unanesthetized rats: a microdialysis study.

Prostaglandin E2 (PGE2) delivered to the spinal cord produces an increased sensitivity to noxious (hyperalgesia) and innocuous (allodynia) stimuli. The mechanisms that underlie this effect remain unknown, but a PGE2-evoked enhancement of spinal neurotransmitter release may be involved. To address this hypothesis, we examined the effect of PGE2 on CSF concentrations of amino acids and also the modulatory effect of PGE2 on capsaicin-evoked changes of spinal amino acid concentrations using a microdialysis probe placed in the lumbar subarachnoid space. Amino acids were quantified using HPLC with fluorescence detection. Addition of 1 mM, but not 10 or 100 microM, PGE2 to the perfusate for a 10-min period (flow rate, 5 microliters/min) evoked an immediate increase (80-100%) in glutamate (Glu), aspartate (Asp), taurine (Tau), glycine (Gly), and gamma-aminobutyric acid (GABA) concentrations. Similarly, capsaicin infusion (0.1-10 microM) induced a dose-dependent increase in Glu, Asp, Tau, Gly, GABA, and ethanolamine levels. Significant increases in amino acid levels evoked by PGE2 or capsaicin were associated with a touch-evoked allodynia. The combination of PGE2 (10 microM) and capsaicin (0.1 or 1.0 microM) at concentrations that individually had no effect together evoked a significant increase (60-100%) in Glu, Asp, Tau, Gly, and GABA concentrations and produced tactile allodynia. These data demonstrate that spinally delivered PGE2 or capsaicin substantially elevates CSF concentrations of both excitatory and inhibitory amino acids. The capacity of PGE2 to enhance and prolong capsaicin-evoked amino acid concentrations may be one of the mechanisms by which spinal PGE2 produces hyperalgesia and allodynia.

Amino Acids↗
PubMed1995

Effects of some novel D-myo-inositol-phosphate derivatives on binding and sympathetic transmission.

The vascular effects of myo-inositol and a series of D-myo-inositol phosphate derivatives: D-myo inositol-1-monophosphate (Ins[1]P1), D-myo-inositol-2-monophosphate (Ins[2]P1), D-myo-inositol-1, 2-biphosphate (Ins[1,2,6]P2), D-myo-inositol-1,2,6-trisphosphate (Ins[1,2,6]P3, alpha-trinositol; PP56), D-myo-inositol-1,2,5,6-tetraphosphate (Ins[1,2,5,6]P4), and D-myo-inositol-1,2,3,4,5,6-hexa-phosphate (InsP6, phytic acid) were studied in binding assays in rat heart membranes, in vitro in isolated guinea pig basilar artery, and in vivo in pithed rats. In binding assays in rat heart membranes, Ins[1,2,6]P3, Ins[1,2,5,6]P4, and InsP6 displaced the binding of [3H] alpha-trinositol [3H]Ins[1,2,6]P3). In the isolated guinea pig basilar artery, Ins[1,2]P2 and Ins[1,2,6]P3 inhibited the contractile effects of exogenous neuropeptide Y (NPY) in the concentration range of 10(-8)-10(-6) M. In pithed Sprague-Dawley rats, Ins[1,2,6]P3 inhibited the NPY-induced pressor response in the dose range [2 mg/kg (3.8 mumol/kg) combined with an infusion of 20 mg/kg/h (38 mumol/kg/h) for 30 min] in which no inhibitory effects on the pressor responses were elicited by preganglionic nerve stimulation (PNS) or a bolus injection of phenylephrine (Phe). Ins[1,2]P2 had only slight NPY inhibitory effects in vivo. We conclude that selected inositol derivatives may inhibit the vasopressor effects to NPY in vitro and in vivo. In particular, Ins[1,2,6]P3, which most readily inhibited the NPY-induced pressor response in vivo, may represent a new class of synthetic nonpeptide drugs, which may inhibit the vascular effects of NPY without binding to the NPY receptor itself.

Analysis of Variance↗
PubMed1995

The cost-effectiveness of a cardiovascular multiple-risk-factor intervention programme in treated hypertensive men.

OBJECTIVES: The aim of this study was to carry out a cost-effectiveness analysis of a multifactorial intervention programme in treated hypertensive patients. DESIGN: A cost-effectiveness analysis based on 3 years of follow-up in an open, randomized, parallel-group study with allocation either to a comprehensive, multiple-risk factor modification programme or to conventional treatment. SETTING: An outpatient clinic of a city hospital. SUBJECTS: Inclusion criteria were: male sex, age 50-72 (mean 66.4) years, treated hypertension and at least one of the following: serum cholesterol > or = 6.5 mmol L-1, and/or smoking and/or diabetes mellitus. A total of 508 patients were included in the study. INTERVENTIONS: Advice given to individuals, and group meetings based on nutritional advice and behavioural treatment principles. If necessary, drug therapy could be instituted to achieve the treatment goals in the intervention group: serum total cholesterol of < 6.0 mmol L-1, no smoking, HbAlc < 6.0% and diastolic blood pressure < 90 mmHg in both groups. MAIN OUTCOME MEASURE: Incremental cost per life-year gained of the intervention programme. RESULTS: The cost per life-year gained was SEK 4000 in an estimation based on the observed risk reduction and ranged between SEK 62,000 and SEK 163,000 in three estimations based on the risk factor changes. CONCLUSIONS: The analysis indicates that the intervention programme is cost-effective in the studied patient population.

Aged↗
PubMed1995

Modulation of vascular contractile responses to alpha 1- and alpha 2-adrenergic and neuropeptide Y receptor stimulation in rats with ischaemic heart failure.

In order to evaluate adaptational changes in vascular function in congestive heart failure (CHF), we studied the contractile responses of isolated arterial and venous blood vessels from rats suffering from CHF induced by coronary artery ligature, resulting in a myocardial infarction. The contractile responses of the basilar, femoral and renal arteries and of the iliac vein were examined in relation to adrenergic and neuropeptide Y (NPY) receptor function by the action of the alpha 1 agonist phenylephrine, the alpha 2 agonist clonidine and NPY. The contractile force was measured (in mN) and in % of K(+)-induced contraction as well as pD2 to each agonist. When stimulated by a 60 mM K(+)-buffer solution, the femoral and renal arteries from CHF rats responded with a stronger contraction (Emax; 9.4 +/- 0.6 and 9.8 +/- 0.6 mN) than the corresponding Sham vessels (Emax; 6.2 +/- 0.7 and 5.6 +/- 0.4 mN respectively, P < 0.001). On the contrary, the iliac vein of CHF responded less to K+ than the Sham iliac vein (Emax 2.5 +/- 0.2 and 3.7 +/- 0.5 mN, P < 0.01). The CHF iliac vein responded with a weaker contraction when stimulated with phenylephrine (Emax 1.9 +/- 0.4 mN) and showed a lower sensitivity (pD2 5.6 +/- 0.1) than the corresponding sham vessel (Emax 5.7 +/- 2.3 mN and pD2 6.3 +/- 0.5, P < 0.05). The CHF renal artery was less sensitive to clonidine (pD2 6.4 +/- 0.6) than the Sham renal artery (pD2 7.2 +/- 0.1, P < 0.05). The results indicate differences between CHF and Sham vessel segments according to both contractile capacity induced by K(+)-depolarization and to agonist induced contractile capacity and sensitivity. The differences are not of general nature but vary according to the vascular bed examined.

Animals↗
PubMed1995

Enhanced pressor responses to experimental and daily-life stress in borderline hypertension.

OBJECTIVE: It has been suggested that the blood pressure elevation in borderline hypertension is caused by hyperreactivity to stress. We addressed the questions: are subjects with borderline hypertension hyperreactive to mental stress, and, if so, is this reflected in greater blood pressure responses during daily-life activities, and does non-specific pressor amplification by structural vascular changes contribute to reactivity changes? METHODS: Standardized mental stress was performed during invasive monitoring in 54 borderline hypertensive subjects [systolic blood pressure (SBP) 140-160 or diastolic blood pressure (DBP) 84-95 mmHg, or both] and 20 normotensive control subjects (110-130/60-80 mmHg). Sixteen borderline hypertensive subjects had a cardiac index greater than the mean + 1SD of the normotensive control group (hyperkinetic subgroup) and 38 borderline hypertensive subjects had a cardiac index below that level (normokinetic subgroup). Minimal vascular resistance in the forearm and calf was assessed by plethysmography. Ambulatory 24-h blood pressure was recorded. RESULTS: Subjects with hyperkinetic borderline hypertension had similar intra-arterial blood pressure levels to normokinetic borderline hypertensive subjects. Total peripheral resistance was lower in hyperkinetic borderline hypertensive than in normokinetic borderline hypertensive or normotensive control subjects. Hyperkinetic borderline hypertensive subjects had a significantly lower forearm minimal vascular resistance than normokinetic borderline hypertensive subjects. SBP and mean arterial blood pressure responses to stress were augmented in both borderline hypertensive subgroups. Hyperkinetic borderline hypertensive subjects also showed diastolic hyperreactivity in response to mental stress, in comparison both with normokinetic borderline hypertensive and with normotensive control subjects. During ambulatory blood pressure recording, hyperkinetic borderline hypertensive subjects had greater DBP and mean blood pressure increases from night to day than normotensive control and normokinetic borderline hypertensive subjects. CONCLUSION: Borderline hypertension is characterized by pressor hyperreactivity to mental stress. In hyperkinetic borderline hypertensive subjects, stress hyperresponsiveness is also reflected by greater night-to-day blood pressure gradients during 24-h monitoring. Pressor hyperreactivity in hyperkinetic borderline hypertension is not explained by structural changes in the calf or forearm vasculature.

Adolescent↗
PubMed1995

Blood platelet activation and membrane glycoprotein changes during extracorporeal life support (ECLS). In vitro studies.

The aim of this study was to evaluate an in vitro model for investigation of platelet function parameters in an extracorporeal system. Two different perfusion pumps were compared, a roller pump (Polystan) and a centrifugal pump (Biomedicus). A continuous increase in glycoprotein (GP)1b-negative platelets was observed in both circuits. A marked increase of plasma beta-thromboglobulin thromboglobulin concentration and a decrease of the intracellular pool of serotonin was observed, indicating a marked release of alpha as well as of dense granules. The plasma concentration of glycocalicin increased in parallel with a reduced platelet surface expression of GP1b, suggesting that the loss of GP1b is caused by proteolysis rather than by a downregulation of this receptor protein. It is concluded that ECLS results in a pronounced platelet degranulation and causes changes of important membrane receptors which might explain some of the bleeding problems observed in patients treated with ECLS. No significant difference was noted between the roller pump and the centrifugal pump. Trial of strategies, e.g., protease inhibitors and nitric oxide to revert this untoward effect of ECLS are highly warranted.

Artificial Organs↗