Biomedical subjects

C Nordin

Publications and source records attributed to C Nordin.

At least 55 records · Page 3Linked to original sources

PubMed1996

Stillbirth is no longer managed as a nonevent: a nationwide study in Sweden.

BACKGROUND: Giving birth to a stillborn child is a tragedy. The aim of this study is to investigate the meeting of mothers with their stillborn children and the women's experiences of support during and after the delivery. METHODS: In a nationwide study in Sweden, data from 636 women who gave birth to a stillborn or live baby were collected by means of an anonymous postal questionnaire in 1994. RESULTS: Among the 314 women who gave birth to a stillborn child, nearly every mother had seen her child, and 80 percent had carressed her baby. More than 90 percent of the mothers stated that the medical staff showed respect, and about 80 percent of the mothers stated that staff exhibited tenderness toward their dead children. The mother's assessment of respect and tenderness to her child by medical staff was almost identical between stillbirths and live births. Nearly 70 percent of the women reported that the hospital had good routines to support mothers of stillborn children. Feelings of sadness and having been deeply hurt or angered by the medical staff's behavior were reported by 37 percent of the women. A difficult balance is still to be achieved between women being forced to encounter the baby when not yet ready versus others who wish the staff had given more encouragement. The value of properly taken photographs is described. CONCLUSIONS: Treating stillbirth as a nonevent has been largely, if not entirely, abandoned in Sweden. Most mothers of a stillborn child experience that the medical staff treat their dead children appropriately.

Adult↗

PubMed1996

Response of Ca(2+)-loaded, depolarized guinea pig myocytes to critically timed premature stimulations.

Single premature stimulations during trains of nondriven action potentials induced by depolarization normally cause a transient hyperpolarization of diastolic membrane potential before the subsequent spontaneous upstroke. However, rare, marked transient depolarizations have also been reported. This paper presents experimental data and computer simulations that characterize transient depolarization following premature stimulations and investigate the role of intracellular [Ca2+] in generating this unusual response. In isolated guinea pig myocytes, transient depolarizations (range 4-58 mV) consistently occurred following stimulations 100-160 ms after the upstroke of spontaneous action potentials during exposure to K(+)-free Tyrode solution, which raises intracellular [Ca2+]. In contrast, no transient depolarizations developed when stimulations were delivered during injection of constant inward current or brief exposure to very low dose of Ba2+ (250-500 microM). The experimental response to K(+)-free Tyrode solution was reproduced by a computer model of the transmembrane current and intracellular Ca2+ flux of an isolated guinea pig ventricular myocyte (24) following reduction of extracellular [K+] below 1 mM. Transient depolarization was generated primarily by Na/Ca exchange. Simulations using only those equations governing intracellular Ca2+ cycling revealed that bursts of Ca2+ into the myoplasm after Ca2+ loading caused a transient increase in trough myoplasmic [Ca2+] when the coupling interval following the upstroke of a myoplasmic [Ca2+] oscillation was nearly identical to those coupling intervals that caused pacing-induced transient depolarization of membrane potential after the upstroke of an action potential. These results suggest that transient depolarizations following nondriven action potentials arise from critically timed, stimulus-induced perturbation of intracellular [Ca2+] oscillations associated with Ca2+ overload. Simulations using a multicellular model suggest that critically timed premature stimulations can initiate trains of depolarized, nondriven action potentials in otherwise quiescent, Ca(2+)-overloaded heterogeneous syncytia by a similar mechanism.

Action Potentials↗

PubMed1996

Antidepressant and anxiolytic profiles of E-10-hydroxynortriptyline on electrocorticograms of rats.

Electrocorticograms of rats were recorded after administration of increasing doses of the major metabolite of nortriptyline (NT), E-10-hydroxynortriptyline (E-10-OH-NT). The results were compared with those of NT administration. In visual as well as computerized evaluations, E-10-OH-NT demonstrated clear antidepressant properties, thus confirming previous experiments in depressed patients. There is some evidence that E-10-OH-NT also has an anxiolytic profile. The results with the parent drug NT were not so pronounced. Since E-10-OH-NT has been shown to be devoid of side effects when previously administered to humans, this substance is clearly to be considered of interest for potential development into a new antidepressant. Whether or not the anxiolytic profile is of clinical interest needs to be investigated further.

Animals↗

PubMed1996

Psychic and social consequences of women in relation to memories of a stillborn child: a pilot study.

Prevalence and determinants of long-term psychosocial morbidity among women giving birth to a stillborn child are largely unknown. Few, if any, systematic epidemiologic studies are available. In this pilot study we investigated one alternative way to collect data from relevant patient populations and formulated some hypotheses. Moreover, questions found unhelpful in this context were identified, e.g., whether the mother had bathed her dead child or not. Fruitful hypotheses found worthwhile testing were, among others: the risk of long-term anxiety-related symptoms is reduced if (1) the woman has seen her stillborn child, (2) she has an ultrasonic or photographic picture of the child, and (3) she has gone through a ritual, primarily burial of the child; moreover, (4) divorce may be a social consequence of the intrauterine loss of a child.

Adult↗

PubMed1995

CSF and serum concentrations of clozapine and its demethyl metabolite: a pilot study.

With the aim of exploring putative correlations between serum and CSF levels of clozapine and its demethyl metabolite, lumbar puncture was performed on four male and five female schizophrenic patients during long-term treatment with clozapine. Three consecutive 6-ml fractions were collected after at least 8 h of bedrest and fasting. On comparing serum and CSF levels, a correlation was found for norclozapine in the third (13-18 ml) CSF fraction. Norclozapine in the first (0-6 ml) CSF correlated significantly with height. The CSF/serum ratio of clozapine in the first fraction was correlated significantly with body weight. No correlations were found between serum levels of clozapine and norclozapine, or between the serum and CSF levels of clozapine. The study suffers from a small number of patients (for ethical reasons), but the present results might be explicable if the first (0-6 ml) CSF fraction represents a cul-du-sac of the CSF, mirroring the previous day's drug levels. The second fraction, then, will represent the CSF level in the steady state during the night.

Adult↗

PubMed1995

Terfenadine blocks time-dependent Ca2+, Na+, and K+ channels in guinea pig ventricular myocytes.

Terfenadine, which blocks delayed rectifier K+ channels (Ik), is structurally related to diphenylalkylamine L-type Ca2+ channel (ICa) blockers and has been reported to render Purkinje fibers inexcitable. We used standard whole-cell patch clamp techniques in isolated guinea pig ventricular myocytes to investigate the direct effect of terfenadine on ICa after discovering that the upstrokes of early afterdepolarizations in guinea pig myocytes were inhibited by the drug at concentrations > or = 10(-6)M. Some data analyzing the effect of terfenadine on time-dependent Na+ channels (INa) and IK also were obtained. All experiments were controlled for time of intracellular dialysis. Terfenadine (3 x 10(-6)M) reduced peak ICa (measured in either K+-containing or Cs+-substituted intracellular solutions from holding potentials of -40 mV) after 10 min exposure [peak at 0 mV in K+-deficient dialysis solution -4.2 +/- 2.3 pA/pF (mean +/- SD, n = 5) versus -13.02 +/- 4.33 pA/pF in control solution (n = 5), p < 0.01], and ICa was almost completely blocked after 15 min drug exposure. Ten minutes of exposure to terfenadine (3 x 10-6M) also caused near-complete blockade of peak INa when INa was measured at -40 mV after 300 ms conditioning pulses from a holding potential of -40 to potentials between -60 and -90 mV. The effect was much less pronounced when INa was measured from a holding potential of -90 mV. After exposure to terfenadine 3 x 10 (-6)M, IK density, measured as peak tail current at -40 mV after 300-ms depolarizations, was also reduced but not eliminated at membrane potentials between -20 and +60 mV. In contrast, exposure to terfenadine caused no significant change in the current-voltage relationship after 300-ms steps from -90 to +60 mV. Terfenadine had no effect on time constants of decay of IK or ICa. These results suggest that terfenadine blocks several time- and voltage-dependent channels, possibly by binding to a common protein structure, not related to ion selectivity, that is primarily associated with time-dependent activation of channel conductance.

Animals↗

PubMed1995

Attempted suicide predicts suicide risk in mood disorders.

Suicide risk was studied in a sample of 346 mood disorder inpatients, 92 of whom were admitted after a current suicide attempt. The overall suicide mortality after a mean observation period of 6 years was 8%. The potential of attempted suicide to predict suicide risk in hospitalized patients with mood disorders was studied by survival analysis after subgrouping on the basis of whether a current suicide attempt had occurred or not. The suicide risk the first year after attempting suicide was 12% (11/92), compared with 2% (4/254) in the mood disorder subgroup with no current suicide attempt. The long-range suicide risk after a current suicide attempt in depression was 15% (14/92) as compared with 5% (13/254) among those without a current suicide attempt. It is concluded that a current suicide attempt in mood disorder inpatients predicts suicide risk particularly within the first year and should be taken very seriously.

Adult↗

PubMed1995

Computer model of current-induced early afterdepolarizations in guinea pig ventricular myocytes.

We tested the ability of a computer model of transmembrane current and intracellular Ca2+ flux in the isolated guinea pig myocyte (Nordin, C., Am. J. Physiol. 265 (Heart Circ. Physiol. 34): H2117-H2136, 1993) to reproduce data from prior experimental studies and new data presented in this study regarding the behavior of early afterdepolarizations induced by constant inward current, a response closely related to the effect of localized injury currents in damaged myocardial syncytia. The goals of the study were to confirm the model's capacity to reproduce relevant experimental responses for which it was not originally designed and to analyze the mechanisms underlying the experimental phenomena. Under normal conditions, current-induced early afterdepolarizations in the model developed only from membrane potentials associated with L-type Ca2+ channel window current, and the magnitude of upstrokes was unaffected by blockade of either delayed rectifier K+ current or sarcoplasmic reticulum Ca2+ release. After Ca2+ loading secondary to either reduced extracellular [K+] or inhibition of Na(+)-K(+)-adenosinetriphosphatase activity, the threshold potential for current-induced early afterdepolarizations in the model, as with experimental myocytes, shifted to membrane potentials negative to the threshold potential for Ca2+ channel activation. Upstrokes were initiated by inward currents generated by electrogenic Na/Ca exchange following oscillatory Ca2+ release from the sarcoplasmic reticulum. New experiments presented in this study demonstrate that bursts of rapid depolarizing stimulations terminate current-induced early afterdepolarizations. Termination is caused by transient hyperpolarizations, which increase as a function of number or duration of stimulations, and if strong enough, cross the all-or-none threshold and lead to full repolarization. This experimental response was accurately simulated by the model through interactions that led to activation of delayed rectifier current, inactivation of Ca2+ channel current, and a reduction in inward Na/Ca exchange current secondary to altered intracellular Ca2+ cycling. We confirm that the model accurately simulates a wide range of responses beyond its original experimental constraints and suggest that current-induced early afterdepolarizations are initiated and terminated by complex processes that vary with specific experimental conditions and involve multiple currents.

Animals↗

PubMed1995

The influence of gender, education and experience on moral sensitivity in psychiatric nursing: a pilot study.

The purpose of this study was to investigate some factors which may influence moral decision-making in psychiatric nursing practice. The Moral Sensitivity Questionnaire, a 30-item, seven-point Likert scale, measures six dimensions that are assumed to be related to moral sensitivity. In scoring, the test is divided into six categories: interpersonal orientation, structuring moral meaning, expressing benevolence, modifying autonomy, experiencing conflict, and reliance on medical authority. Seventy-nine nurses, employed in the same psychiatric district, were included in the sample. Significant differences were found for some items in five of the six categories regarding gender, post-basic nursing education, experience as a mental care worker and type of clinical setting.

Adult↗

PubMed1995

Active hydroxymetabolites of antidepressants. Emphasis on E-10-hydroxy-nortriptyline.

Hydroxymetabolites of the antidepressants nortriptyline and desipramine, like the parent drugs, inhibit neuronal uptake of noradrenaline (norepinephrine). In both plasma and cerebrospinal fluid (CSF), the concentrations of the 10-hydroxymetabolites of nortriptyline (10-OH-NT) are usually higher than those of the parent drugs, but there is a pronounced interindividual variation in the plasma concentrations. This shows that during treatment with nortriptyline, hydroxymetabolites exert, at least in some patients, major effects on brain noradrenaline neurons. Hydroxymetabolites of antidepressants are formed by the polymorphic cytochrome P450 enzyme CYP2D6. Nortriptyline is hydroxylated by this enzyme in a highly stereospecific way to the (-)-enantiomer of E-10-OH-NT. Among Caucasians, 7% are poor metabolisers of the CYP2D6 probe drug debrisoquine. These patients will form very little hydroxymetabolite. The affinity of E-10-OH-NT for muscarinic acetylcholine receptors in vitro was only one-eighteenth of the affinity of nortriptyline for these receptors. In healthy individuals, nortriptyline decreased saliva flow to a significantly greater extent than either E-10-OH-NT or placebo. In an ultrarapid hydroxylator of nortriptyline treated with very high doses of nortriptyline, the plasma concentration of unconjugated 10-OH-NT was very high without any sign of anticholinergic adverse effects. These results show that hydroxymetabolites of nortriptyline have much less anticholinergic effect than the parent drug. When racemic E-10-OH-NT per se was given to healthy individuals, the plasma concentration of the (-)-enantiomer was 5-fold higher than that of (+)-E-10-OH-NT. The 2 enantiomers were eliminated in parallel with an elimination half-life of 8 to 10 hours. A combined in vitro and in vivo investigation showed that a mean of 64% of (+)-E-10-OH-NT was glucuronidated in the liver and subsequently eliminated in urine. Of the administered (-)-enantiomer, a mean of 36% was eliminated as glucuronide formed in the intestine and 35% was actively secreted as unchanged form in urine. Plasma protein binding, determined by ultrafiltration, of the (+)- and (-)-enantiomers of E-10-OH-NT was 54 and 69%, respectively, which is less than that of nortriptyline (92%). The concentration of E-10-OH-NT in CSF was 50% of the concentration of unbound in plasma. There seems to be a stereoselective active transport of E-10-OH-NT from the CSF to blood. We administered racemic E-10-OH-NT to 5 patients during a major depressive episode.(ABSTRACT TRUNCATED AT 400 WORDS)

Blood Proteins↗

PubMed1995

An analysis of some dimensions of the concept of moral sensing exemplified in psychiatric care.

There are few studies that focus on the interpersonal aspect of everyday ethical conflicts. Conceptual frameworks for research into ethical decision making in the health care system are mainly based on an ethic in which objectivity and principle-based thinking is emphasized, leaving the experience of concrete moral conflicts relatively unexplored. The aim of this paper is to analyze the dimensions of "moral sensing," a concept identified in an earlier grounded theory study of psychiatric nursing. Four dimensions of the concept of moral sensing, i.e., feeling, intuition, benevolence and genuineness, were synthesized by reviewing the works of past and contemporary philosophers. The analysis of moral sensing and its dimensions is exemplified by actual nurse-patient encounters in psychiatric nursing practice.

Decision Making↗

PubMed1994

Quantitation of N-terminally extended tachykinins in cerebrospinal fluid from healthy subjects.

N-terminally extended substance P (SP) and neuropeptide K (NPK), an N-terminally extended form of neurokinin A (NKA), were determined in cerebrospinal fluid (CSF) from healthy human subjects by combined high performance liquid chromatography and radioimmunoassay. The concentrations of the peptides were similar in fresh CSF and in CSF which had been kept frozen for up to 5 months. SP and NKA were not present in measurable amounts in neither fresh CSF nor in CSF that had been frozen. On the other hand, when synthetic SP and NKA were added to approx. 2 pM concentration to fresh CSF samples, both peptides were recovered to 85 and 98%, respectively. There were no significant concentration gradients of the peptides in the first 18 ml (three consecutive 6 ml fractions) of CSF (n = 10). In contrast, we confirmed previous findings, that there are gradients of the amine metabolites 5-HIAA (P < 0.01) and HVA (P < 0.001) (n = 5). The concentrations of extended SP (expressed in SP equivalents) and NPK in the first 6 ml of CSF were 1.5 +/- 0.7 pM and 14.2 +/- 6.4 pM (mean +/- S.D., n = 10), respectively. The present results thus show that the levels of N-terminally extended SP and NKA are stable in frozen CSF samples for up to 5 months. The virtual lack of SP and NKA in CSF does not seem to be due to losses during sample preparation or storage.

Adult↗

PubMed1994

Reduced calcium current density in single myocytes isolated from hypertrophied failing guinea pig hearts.

The present study explored the possibility that an alteration in the transmembrane calcium current (ICa), through its ability to modulate Ca2+ release from the sarcoplasmic reticulum, could contribute to the depressed peak [Ca2+]i we previously observed in hypertrophied failing myocardium. Whole-cell patch clamp was used to measure ICa in single guinea pig ventricular myocytes isolated from hearts of normal guinea pigs and from guinea pig hearts in which hypertrophy and failure were induced by gradually developing left ventricular pressure overload subsequent to ascending aortic banding of young animals. Membrane capacitance (Cm) was significantly greater. and ICa, normalized for Cm, was significantly lower in myocytes from hypertrophied failing hearts. Myocytes from hypertrophied failing hearts did not differ significantly from normal myocytes in terms of the voltage-dependence of the activation variable (d) of ICa (except at -30 mV), the time course of removal of inactivation of ICa, and the time constant of decay of ICa. Measurement of the voltage dependence of the inactivation variable (f) of ICa showed that significantly more steady-state inactivation was present at 0, -10, and -20 mV in myocytes from hypertrophied failing hearts. Multiple regression analysis of all data indicated that ICa density decreased with increasing myocyte membrane area (as reflected by Cm) irrespective of any specific effects of hypertrophy and heart failure. We conclude that ICa, normalized for Cm, is significantly reduced in myocytes isolated from hypertrophied failing hearts, probably by a process associated with increased cell size, per se.

Animals↗

PubMed1994

Role of L-type calcium channel window current in generating current-induced early afterdepolarizations.

INTRODUCTION: Early afterdepolarizations (EADs) can give rise to triggered activity and thereby produce cardiac arrhythmias. We used the whole-cell patch clamp technique to examine the relationship between L-type Ca2+ channel window current and the generation of EADs in single ventricular myocytes isolated from guinea pig hearts. METHODS AND RESULTS: With a high concentration of EGTA in the internal solution and Na(+)-containing physiologic external solution, EADs were induced in unclamped cells by injecting intracellular depolarizing current pulses. During voltage clamp protocols designed to simulate action potentials interrupted by EADs, we recorded an inward shift in total current up to 0.7 pA/pF over 400 msec at test steps in the range of the take-off potential for EADs. Cd2+ (0.2 mM) blocked most of the inward shift of current during the test steps and abolished EADs. When the same voltage clamp protocol was used following perfusion with an Na(+)-free, K(+)-free external solution, the Cd(2+)-sensitive inward currents recorded during the test steps were similar to those obtained in physiologic external solution. The overlapping range of potentials for partial activation of the d and f variables of L-type Ca2+ current ("window" region) measured in Na(+)-free, K(+)-free external solution was virtually the same as the voltage range of the Cd(2+)-sensitive inward currents. CONCLUSION: Our experiments suggest that: (1) EADs can arise under conditions of high EGTA buffering of intracellular [Ca2+]; and (2) under these conditions, L-type Ca2+ channel window current plays a major role in the initiation of EADs.

Action Potentials↗

PubMed1994

Modifying autonomy--a concept grounded in nurses' experiences of moral decision-making in psychiatric practice.

Fourteen experienced psychiatric nurses participated in a pilot study aimed at describing the experiential aspect of making decisions for the patient. In-depth interviews focused on conflicts, were transcribed, coded, and categorized according to the Grounded Theory method. The theoretical construct, 'modifying autonomy' and its dimensions, such as being aware of the patient's vulnerability, caring for and caring about the patient, were identified. The findings in this study make clear the need for further research into the experiential aspect of ethical decision-making in psychiatric practice.

Beneficence↗

PubMed1994

Mechanism of current-induced early afterdepolarizations in guinea pig ventricular myocytes.

We investigated possible ionic mechanisms that cause early afterdepolarizations (EADs) following the injection of constant inward current in guinea pig ventricular myocytes by several interventions that affect failure of action potential repolarization. The amount of constant current was adjusted to measure the threshold potential (Vth) associated with the minimum inward current required for inducing EADs [threshold current (Ith)] and also the magnitude of EADs at Vth and following adjustment of current to generate takeoff potentials of -30 and -20 mV. Interventions associated with either inhibition of Ca2+ release from the sarcoplasmic reticulum (ryanodine 5 x 10(-6) M) or L-type membrane Ca2+ channel current (verapamil 1.1 x 10(-5) M and nisoldipine 5 x 10(-7) M) reduced or abolished EADs arising from -30 or -20 mV. Cells that generated delayed afterdepolarizations (DADs) in the absence of depolarizing current after 20 stimulations at 5 Hz either in control solution or following interventions associated with Ca2+ loading (reduced extracellular [K+] or increased extracellular [Ca2+]) also developed a marked shift in Vth of current-induced EADs at 1-Hz stimulation to more negative potentials [60.3 +/- 10.7 mV (mean +/- SD, n = 17) vs. -41.7 +/- 6.4 mV in cells without DADs in control solution (n = 25), P < 0.001]. Ca2+ loading also increased the magnitude of EADs arising from Vth and -20 mV. Exposure to quinidine (1.23 x 10(-5) M), which blocks both Na+ and delayed rectifier K+ channels, significantly reduced Ith but had only minimal effect on the magnitude of EADs. Our results suggest that L-type Ca2+ channel current and [Ca2+]-sensitive inward current associated with release of Ca2+ from the sarcoplasmic reticulum are the major currents that cause this form of EADs, and that Ca2+ loading promotes the development of large EADs likely to propagate to normal tissue.

Action Potentials↗

PubMed1994

CSF 5-HIAA predicts suicide risk after attempted suicide.

Suicide risk after attempted suicide, as predicted by cerebrospinal fluid (CSF) monoamine metabolite concentrations, was studied in a sample of 92 psychiatric mood disorder inpatients admitted shortly after attempting suicide. The potential of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the CSF to predict suicide risk within the first year after attempted suicide was studied by means of survival analysis after after median split subgrouping. Eleven patients (12%) committed suicide within 1 year after attempted suicide. Eight of these belonged to the below-the-median (< 87 nM) CSF 5-HIAA subgroup, that is, the suicide risk was 17% as compared with 7% among those with above-the-median CSF 5-HIAA. The cumulative number of survived patient-months during the first year after attempted suicide was significantly lower in the low CSF 5-HIAA subgroup. It was concluded that low CSF 5-HIAA predicts short-range suicide risk after attempted suicide in mood disorder psychiatric inpatients. These findings lend further support to the serotonin hypothesis of suicide risk.

Adult↗

PubMed1993

CSF/plasma ratio of 10-hydroxynortriptyline is influenced by sex and body height.

The CSF/plasma ratios of nortriptyline (NT) and its major metabolite 10-hydroxy-NT (10-OH-NT) were investigated retrospectively in 25 depressed patients. For 10-OH-NT (but not NT), a significant influence of sex and body height was found, most conspicuously in males, in whom the ratio related to body height curvilinearly (N = 8; R = 0.93; P < 0.01). In males, the NT/10-OH-NT ratio in plasma correlated with body height (N = 8; r = 0.80; P < 0.05). Hypothetically, CSF circulation is partly influenced by body height, which accounts for a steeper gradient of 10-OH-NT across the blood-brain barrier in taller persons. From the lumbar site, the more polar 10-OH-NT is assumed to be eliminated by bulk flow via the villi, while the less polar NT exits by diffusion in the choroid plexus. Prospective studies are urgently needed to further evaluate the distribution of antidepressants in the CSF.

Adult↗