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Biomedical subjects

C Nordin

Publications and source records attributed to C Nordin.

At least 19 recordsLinked to original sources
PubMed2001

Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia.

Kynurenic acid is an endogenous glutamate antagonist with a preferential action at the glycine-site of the N-methyl D-aspartate-receptor. Mounting evidence indicate that the compound is significantly involved in basal neurophysiological processes in the brain. In the present investigation, cerebrospinal fluid (CSF) level of kynurenic acid was analyzed in 28 male schizophrenic patients and 17 male healthy controls by means of high pressure liquid chromatography and fluorescence detection. Schizophrenic patients showed elevated CSF levels of kynurenic acid (1.67+/-0.27 nM) compared to the control group (0.97+/-0.07 nM). Furthermore, CSF levels of kynurenic acid in schizophrenic patients were also found to correlate with age. The present finding is indicative of a contribution of kynurenic acid in the pathogenesis of schizophrenia.

Adolescent↗
PubMed2001

Prevalence of depressive symptoms in late pregnancy and postpartum.

BACKGROUND: Postnatal depression refers to a non-psychotic depressive episode that begins in or extends into the postpartum period. The aims of this study were to examine the prevalence of depressive symptoms in a pregnant and later postnatal population, to determine the natural course of these symptoms and whether there is an association between antenatal and postnatal depressive symptomatology. METHODS: A longitudinal study with a total population of 1,558 consecutively registered pregnant women in the southeast region of Sweden. Presence of depressive symptoms was measured with the Edinburgh Postnatal Depression Scale on four occasions namely in gestational week 35-36, in the maternity ward, 6-8 weeks and 6 months postpartum. RESULTS: The prevalence of depressive symptoms during late pregnancy was 17%; in the maternity ward 18%; 6-8 weeks postnatally 13%; and 6 months postnatally, 13%. A correlation between antenatal and postnatal depressive symptoms was found (r=0.50, p<0.0001). CONCLUSION: Detection of women at risk for developing postnatal depressive symptoms can be done during late pregnancy. Antenatal care clinics constitute a natural and useful environment for recognition of women with depressive symptoms.

Adolescent↗
PubMed2001

Enantioselective analysis of citalopram and metabolites in adolescents.

Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent despite its increasing use in these age groups. The aim of this study was to investigate a group of adolescents treated for depression, with respect to the steady-state plasma concentrations of the enantiomers of citalopram and its demethylated metabolites desmethylcitalopram and didesmethylcitalopram. Moreover, the authors studied the genotypes for the polymorphic cytochrome P450 enzymes CYP2D6 and CYP2C19 in relation to the different enantiomers. The S/R ratios of citalopram and desmethylcitalopram found in this study of 19 adolescents were similar to studies involving older patients. The concentrations of the R-(-)- and S-(+)-enantiomers of citalopram and desmethylcitalopram were also in agreement with values from earlier studies, the R-(-)-enantiomer (distomer) being the major enantiomer. The results indicate that the use of oral contraceptives may have some influence on the metabolism of citalopram. This might be because of an interaction of the contraceptive hormones with the CYP2C19 enzyme.

Adolescent↗
PubMed2001

Monoamine compounds in cerebrospinal fluid of healthy subjects punctured without preceding strict bed rest: a pilot study.

The interpretation of data on compounds in the lumbar cerebrospinal fluid (CSF) is limited by several confounding factors, e.g. motor activity for which strict bed rest prior to lumbar puncture is recommended for standardisation. Now we report data from 14 healthy males employing the standardised procedure except for the requirement of strict bed rest. The levels of serotonin, noradrenaline, 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid and 4-hydroxy-3-methoxyphenylglycol in the second CSF fraction (7-12 ml) were significantly higher than those in the first fraction (0-6 ml), indicating the presence of concentration gradients. 5-HIAA was negatively influenced by age and the neuraxis distance in the lying position and positively by atmospheric pressure. Storage time and atmospheric pressure contributed to the variance in dopamine. Both tyrosine, tryptophan and dopamine were linearly correlated with storage time. We also found a significant curvilinear correlation between tapping time and atmospheric pressure. On comparing with previous studies, the results support the notion that the issue of strict bed rest or not prior to lumbar puncture might have to be taken into consideration when interpreting lumbar monoamine CSF data.

3,4-Dihydroxyphenylacetic Acid↗
PubMed2001

CSF collection time at lumbar puncture is influenced by plasma cholesterol and triglycerides.

It is a fairly well-known fact that the CSF collection time (tapping time) at lumbar puncture may influence CSF levels of monoamine compounds (e.g. the serotonin metabolite 5-hydroxyindoleacetic acid, 5-HIAA) and some neuropeptides. Since serum levels of cholesterol and triglycerides and low CSF levels of 5-HIAA have been linked to violent behaviour and impulsivity, we investigated retrospectively whether serum cholesterol and triglycerides affect CSF collection time. The series consists of 14 healthy males lumbar punctured at the L(4-5) level. We found that both serum cholesterol and serum triglycerides influenced the CSF collection time for 12 ml of CSF (R = 0.77; p = 0.0067). There was no correlation between cholesterol in serum and CSF, nor between cholesterol in the CSF and collection time. However, we accidentally found a correlation between cholesterol in the CSF and age. The proposed hypothesis tries to explain why cholesterol- and triglyceride-rich lipoprotein particles modify the CSF collection time and influence endothelial function with a subsequent effect on CSF production and/or intraspinal pressure. Thus, it may be of interest to pay attention to serum cholesterol and triglycerides, their effect on CSF collection time and, in the next step, their putative impact on levels of various compounds in the CSF.

Adult↗
PubMed2001

Depressive symptoms in hypothyroid disorder with some observations on biochemical correlates.

Lumbar punctures and ratings of depressive symptoms were done in hypothyroid patients before and during L-thyroxine therapy. Before treatment, the most prominent symptoms were concentration difficulties, lassitude, and reduced sexual interest. All patients suffered from sleep disturbances. Suicidal thoughts did not occur at all. Inner tension was negatively correlated with the anxiogenic cholecystokinin tetrapeptide (CCK-4) in the cerebrospinal fluid (CSF), while reduced sexual interest was negatively correlated with CSF tryptophan. Furthermore, failing memory correlated negatively with T3 as well as T4 in serum. A positive correlation was found between failing memory and serum TSH. All patients improved significantly during treatment. No biochemical correlates were found. In conclusion, hypothyroidism is associated with major depressive symptoms. CSF CCK-4 and tryptophan, as well as serum thyroid hormones, may constitute biochemical correlates for some of these symptoms.

Adult↗
PubMed2001

Intraspinal pressure influences CSF disposition of tryptophan and 5-HIAA.

Cerebrospinal fluid (CSF) concentrations of monoamine compounds are influenced by factors such as age, gender, height, body weight, tapping time, and atmospheric pressure. We have now examined the role of intraspinal pressure. Thirteen male volunteers underwent lumbar puncture in the right decubitus position without preceding strict bed rest. The intraspinal pressure was recorded, and monoamine precursors, transmitters, and metabolites were analyzed in two consecutively collected CSF fractions. Tryptophan in 12 ml of CSF and the 5-hydroxyindoleacetic acid concentration ratio [fraction II (7--12 ml CSF)/fraction I (0--6 ml CSF)] correlated with the intraspinal pressure. Hypothetically, the intraspinal pressure may be a confounding factor for a correct interpretation of CSF tryptophan and 5-hydroxyindoleacetic acid concentrations, and this is an issue that has to be addressed in future CSF studies.

Adult↗
PubMed2001

Quantitative pharmacogenetics of nortriptyline: a novel approach.

OBJECTIVE: To quantitatively model nortriptyline clearance as a function of the cytochrome P450 (CYP) 2D6 genotype and to estimate the contribution of genotype to the interindividual variability in steady-state plasma concentration and metabolic clearance. DESIGN: Modelling study using data from two previously published studies. PARTICIPANTS: 20 healthy volunteers receiving single oral doses of nortriptyline and 20 patients with depression on steady-state oral treatment. METHODS: A total of 275 nortriptyline plasma concentrations were analysed by standard nonlinear regression and nonlinear mixed effect models. The pharmacokinetic model was a 1-compartment model with first order absorption and elimination. All participants had previously been genotyped with respect to the CYP2D6 polymorphism. RESULTS: A model in which the intrinsic clearance is a linear function of the number of functional CYP2D6 genes and hepatic blood flow is fixed to 60 L/h gave the closest fit of the pharmacokinetic model to the data. Stable estimates were obtained for population pharmacokinetic parameters and interindividual variances. Assuming 100% absorption, the model allows systemic clearance and bioavailability to be estimated. Bioavailability was found to vary between 0.17 and 0.71, depending on the genotype. Using the frequency distribution of CYP2D6 genotype with the above results we estimate that, in compliant Swedish individuals on nortriptyline monotherapy, the number of functional CYP2D6 genes could explain 21% of the total interindividual variance in oral clearance of nortriptyline and 34% of that in steady-state plasma concentrations. CONCLUSION: Nonlinear mixed-effects modelling can be used to quantify the influence of the number of functional CYP2D6 genes on the metabolic clearance and plasma concentration of drugs metabolised by this enzyme. Gene dose has a significant impact on drug pharmacokinetics and prior knowledge of it may aid in predicting plasma concentration of the drug and thus tailoring patient-specific dosage regimens.

Adolescent↗
PubMed2000

Therapeutic drug monitoring of selective serotonin reuptake inhibitors influences clinical dosing strategies and reduces drug costs in depressed elderly patients.

OBJECTIVE: This study was initiated in order to describe and evaluate the effects of a therapeutic drug monitoring (TDM) routine of selective serotonin reuptake inhibitors (SSRIs) on treatment strategies and drug costs in depressed elderly patients. METHOD: Blood samples were drawn from elderly depressed patients and analysed for steady-state trough serum concentrations of citalopram (n = 48), paroxetine (n = 48) or sertraline (n = 39). A global efficacy evaluation was made at baseline and after 6-9 months. Antidepressant drug costs before and after TDM were estimated. RESULTS: Eight samples were excluded due to technical problems or noncompliance. In 65 of the 127 (51.2%) remaining cases, the treatment strategy was changed according to the TDM outcome, in most a reduction of the prescribed dose. Bioanalytical TDM costs included the antidepressant drug costs after TDM were reduced by 10.2%. CONCLUSION: The results support the utility of TDM in the search for the individual minimum effective SSRI dose in the elderly.

Aged↗
PubMed2000

Cerebrospinal fluid levels of monoamine compounds and cholecystokinin peptides after exposure to standardized barometric pressure.

BACKGROUND: Connections between mood changes and weather have been described throughout the ages, and in more recent years, there have been reports on a relationship between atmospheric pressure and neurotransmitter levels in cerebrospinal fluid. METHODS: To further investigate this issue under strictly standardized conditions, we have lumbar-punctured 8 healthy males under low (963 hPa) and high (1064 hPa) barometric pressure, using a pressure chamber. RESULTS: Under high pressure, the tyrosine concentrations in the cerebrospinal fluid (CSF) were lower, while the cholecystokinin tetrapeptide (CCK-4) levels were higher. No differences between low and high pressure were found for tryptophan, 5-hydroxyindolacetic acid (5-HIAA), dopamine (DA), and sulphated cholecystokinin octapeptide (CCK-8S). The serum level of CCK-8S was higher under high pressure. On comparing concentration ratios between the second and the first CSF fraction, we found significantly increased ratios for homovanillic acid (HVA) and 4-hydroxy-3-methoxyphenylglycol (HMPG), but a decreased ratio for tyrosine under high pressure. The difference in the concentration ratios of HVA between low and high pressure correlated negatively with age. Intraspinal pressure correlated negatively with tapping time at low pressure. CONCLUSION: Our results are in line with the hypothesis that atmospheric pressure influences CSF levels of monoamine compounds and cholecystokinin peptides.

Adult↗
PubMed1999

Cholecystokinin peptides in cerebrospinal fluid: a study in healthy male subjects lumbar-punctured without preceding strict bed-rest.

In a recent study we analysed the concentrations of two forms of cholecystokinin (CCK), CCK-8S (sulphated) and CCK-4 in cerebrospinal fluid (CSF) obtained from 14 healthy male volunteers lumbar-punctured after a minimum of eight hours of strict bed-rest. We have now lumbar-punctured another group of 14 healthy males, using the same procedure except for the requirement of strict bed-rest prior to puncture. In contrast to our previous study, the concentration of CCK-4 (but not CCK-8S) was significantly higher in the second CSF fraction (7-12 ml) than in the first one (0-6 ml). On using the concentration ratio between the second and first fraction, CCK-8S (but not CCK-4) correlated positively with the atmospheric pressure, which is in contrast to our previous study in which a significant negative correlation was found. When the lumbar CSF concentrations were expressed as the concentration per minute of tapping-time (an estimate of the mass flow), atmospheric pressure, age and the neuraxis distance in the lying position made significant contributions to the variance in CCK-8S. A significant positive correlation with atmospheric pressure was found for CCK-4. In conclusion, the results indicate that the question of strict bed-rest or not prior to lumbar puncture may have to be considered when interpreting data on lumbar CSF concentrations of CCK. A controlled study is warranted.

Adult↗
PubMed1999

Serum and cerebrospinal fluid concentrations of melatonin: a pilot study in healthy male volunteers.

Melatonin was determined in serum and cerebrospinal fluid (CSF) obtained from 13 healthy males lumbar-punctured in the sitting position without preceding bed rest. There was a significant correlation between the levels of melatonin in serum and the CSF. The serum concentration was lower than that in the CSF, a finding that calls in question the theory that melatonin is mainly released from the pineal gland into the bloodstream. In conclusion, serum levels of melatonin in healthy male volunteers, mirror the CSF concentrations when lumbar puncture is carried out using the described technique.

Adult↗
PubMed1999

Could discontinuing smoking be hazardous for patients administered clozapine medication? A case report.

A 35-year-old man with schizophrenia was successfully treated with clozapine at a daily oral dose of 700-725 mg for more than 7 consecutive years. Two weeks after abrupt cessation of chronic heavy cigarette smoking, he suddenly developed tonic clonic seizures followed by stupor and coma. After 2 days of intensive care, the patient recovered completely but could not recall the episode. Clozapine therapy was reinstituted and could be carried out successfully at 425 mg daily, i.e., at an approximately 40% reduction of the daily dose before he stopped smoking. The sudden cessation of smoking most likely caused a rise in plasma concentrations of clozapine and/or clozapine metabolites resulting in the seizure episode. A likely mechanism is that the heavy smoking had induced cytochrome P450-1A2, the main enzyme involved in the metabolism of clozapine.

Adult↗
PubMed1999

Postoperative mental impairment in hip fracture patients. A randomized study of reorientation measures in 223 patients.

Mental impairment is a common and serious complication in geriatric surgery. We studied 223 hip fracture patients. They were over 64 years of age (mean 81), with no history of mental deterioration and acutely admitted to hospital from independent living conditions. They were randomized into two groups. One of these was subjected to reorientation measures during the perioperative phase, i.e., presurgery admission to the orthopedic ward, accompanied home visits during the hospital stay and access to reorientation devices--they received a large clock, calendar, radio, TV-set, telephone and were encouraged to wear their own clothing. Otherwise, there were no differences in the treatment given to the two groups. We used monitoring of cognitive function with the Short Portable Mental Status Questionnaire (SPMSQ) and a feedback program for evaluation of the treatment results. There was a low incidence of postoperative cognitive deterioration in both groups, compared with historical controls. However, no difference in mental status was noted when we compared the two groups. The conclusion is that attributes were less important than the psychological environment for postoperative mental deterioration. The mean total continuous hospitalization (transfers between departments and hospitals included) in the reorientation group was 22 (95% CI: 17-43) days, the corresponding figures for the controls were 30 (14-29) days.

Aftercare↗
PubMed1998

A comparison of women's memories of care during pregnancy, labour and delivery after stillbirth or live birth.

OBJECTIVE: To compare women's reports of aspects of their care during pregnancy, labour and delivery following stillbirth and live birth. DESIGN: Data were collected by postal questionnaire in 1994. SETTING: A Swedish nation-wide population-based study of cohorts defined in 1991. PARTICIPANTS: Three hundred and fourteen women with stillbirth (subjects) and 322 women with live birth (controls). MEASUREMENTS AND FINDINGS: Labour and delivery were assessed as physically 'insufferably hard' by 52 (17%) of the subjects and 33 (10%) of the controls. The corresponding figures for emotional strains were 144 (47%) and 21 (7%). Obstetric analgesia was more frequently used during labour for stillbirth. One hundred and thirty-eight (44%) subjects, as compared to 44 (2%) of the controls, left hospital within 24 hours of birth. Almost all the women with stillbirth 296 (95%) stated that it was important to have an explanation of the baby's death. Adverse events related to bromocriptine given to inhibit postpartum lactation, were reported by 60 (22%) of the subjects. KEY CONCLUSIONS: It is possible to ease the distress of labour and delivery for stillbirth. Discussion of the aetiology of the baby's death with the mother should be a priority. The optimal length of stay in hospital after stillbirth remains to be defined. Non-pharmacological inhibition of lactation may be presented as an alternative to bromocriptine, breast binding is a concrete 'reality confrontation' for the woman and may aid her in her grieving process. Further studies concerning breast binding vs pharmacological inhibition of lactation and long-term psychological outcome are warranted.

Adult↗