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N E Larsen

Publications and source records attributed to N E Larsen.

At least 37 records · Page 2Linked to original sources
PubMed1990

ALMA, an editor for large sequence alignments.

A dedicated sequence editor, ALMA, was developed for aligning many sequences of proteins or RNA molecules or longer DNA fragments. Like previously published editors, ALMA is menu directed, screen oriented, and offers similarity and consensus display. ALMA has the additional features of collective movement of sequences, acceptance of input from many sources including structure files and databases, secondary structure display, and easy merging of alignments. In order to maintain sequence integrity and save disk space, gaps and sequences are stored separately. Automatic recovery of a session is possible. Finally, the program allows interaction between manual and automatic alignment.

Amino Acid Sequence↗
PubMed1989

The relationship between perphenazine plasma levels and clinical response in acute schizophrenia.

1. Twelve patients with schizophrenia according to RDC participated in a double-blind study, comparing two dose levels of perphenazine, 16 or 32 mg, during four weeks. 2. The patients were assessed with a subscale to CPRS and global scores, measuring improvement of regular intervals during four weeks. 3. Blood samples for assay of plasma perphenazine were collected once a week. 4. These results are in many respects in accordance with earlier published data with perphenazine, that is a good clinical response is achieved with a plasma concentration of perphenazine between 1-5 nmol/L. 5. No incidence of severe adverse symptoms were observed.

Adult↗
PubMed1989

Prediction of the optimal perphenazine decanoate dose based on blood samples drawn within the first three weeks.

During a 3-month period, 52 paranoid psychotic inpatients were treated with perphenazine decanoate (Trilafon decanoate) in order to determine a treatment schedule ensuring perphenazine serum levels within the optimal range (2-6 nmol/L). All patients received 1 ml (108 mg) perphenazine decanoate on days 0, 7 and 21, after which the doses and intervals were individually adjusted according to the clinical condition. It was shown that the sum of 2 measurements of perphenazine concentration early during treatment, viz., on days 14 and 21, correlates strongly (r = 0.96) with the steady-state level obtained after 3 months. Consequently, a nomogram for dose and length of interval could be elaborated giving steady-state serum levels of perphenazine of about 4 nmol/L, i.e., in the middle of the optimal concentration range.

Adolescent↗
PubMed1986

Hydroxyproline/creatinine ratios as estimates of bone resorption in early postmenopausal women. Fasting and 24-h urine samples compared.

Ratio of urinary hydroxyproline/creatinine excretion is often used as an index of bone resorption. To establish the difference between the fasting urinary content (FU-HPR/CR) and the 24-h urinary excretion (24 h-U-HPR/CR) we determined hydroxyproline and creatinine in specimens from a group of early postmenopausal women. One hundred and eighty-six early postmenopausal women were randomized into 10 groups receiving various doses of sequential female sex hormones and/or 1,25(OH)2D3, 0.25 microgram per day, or placebo. In all groups there were parallel changes of FU-HPR/CR and 24 h-U-HPR/CR, and in all groups treated with oestrogens the values decreased significantly. The changes in FU-HPR/CR were more pronounced than in the 24-h-U-HPR/CR, which indicates that FU-HPR/CR is a more sensitive marker of changes in bone resorption. The strong correlation between the mean values of 24-h-U-HPR/CR and those of FU-HPR/CR suggests that both methods are convenient for evaluating changes during long-term studies in groups of patients. The correlation on an individual basis is weak. The substantial intraindividual variation in 24-h-U-HPR/CR, (34.6%) indicates that FU-HPR/CR (CV = 17.0%) is the more valid variable for individual patients.

Bone Resorption↗
PubMed1985

Effect of bacterial endotoxin on the transmembrane electrical potential and plasma membrane fluidity of human monocytes.

In order to gain insight into the physical interaction between bacterial endotoxins and the surface of human monocytes, we investigated the effects of Salmonella typhi endotoxin and lipid A on two functional properties of the plasma membrane of these cells: (1) the transmembrane electrical potential and (2) the fluidity of the lipid bilayer. Using the fluorescent lipophilic cationic probe 3,3'-dipropylthiodicarbocyanine (di-S-C3(5] to monitor the transmembrane electrical potential, we found that neither endotoxin nor lipid A induced depolarization of the monocyte's plasma membrane or impeded its ability to undergo depolarization in response to phorbol myristate acetate. When the resting transmembrane potential of the monocyte was analyzed by exposing di-S-C3(5)-labeled cells suspended in media containing incremental concentrations of potassium ion (K+) to valinomycin, no difference between the response of control cells and cells pretreated with endotoxin was noted. We next examined the effect of endotoxin and lipid A on the fluidity of the monocyte's plasma membrane by monitoring the intensity of the fluorescence of 1,6-diphenyl-1,3,5-hexatriene. By quantifying the intensity of parallel and perpendicular polarized light emitted by this membrane-embedded probe between 8 and 56 degrees C, measurements of molecular anisotropy were used to identify temperature-dependent phase transitions within the hydrocarbon region of the plasma membrane and to estimate the relative microviscosity of the lipid bilayer before and after exposing the cells to endotoxin or lipid A. Although the temperature at which phase transitions occurred was the same in all experimental groups of cells, preincubation of monocytes with either endotoxin or lipid A appeared to increase both the apparent microviscosity of the cell membrane and the order of the lipid bilayer as reflected by a decrease in its flow-activation energy. Our data indicate that when endotoxin molecules contact the surface of the monocyte, the lipid A moiety appears to become incorporated into the plasma membrane, increasing the microviscosity of the lipid bilayer without significantly altering its ionic permeability. We therefore conclude that the metabolic activation of monocytes by endotoxin is not coupled to, or initiated by, membrane depolarization.

Endotoxins↗
PubMed1985

Therapeutic advantages of monitoring plasma concentrations of perphenazine in clinical practice.

Two hundred and twenty-eight acute paranoid psychotic in-patients received continuous treatment with perphenazine for a period of at least 5 weeks, before blood samples were taken to determine perphenazine plasma levels and conclusions regarding therapeutic efficacy and motor side effects. Patients with plasma concentrations within the range of 2-6 nmol/l showed an excellent antipsychotic response, concomitantly with a low incidence of extrapyramidal side effects. However, patients with plasma levels below or above this range either demonstrated a poor therapeutic response or a high degree of side effects respectively. The results indicate that with increasing age significantly lower doses of perphenazine are required to ensure an optimal clinical response. No difference, however, was seen between sexes with regard to dose response.

Adolescent↗
PubMed1985

Dextropropoxyphene kinetics after single and repeated oral doses in man.

The kinetics of dextropropoxyphene (DP) and its main metabolite norpropoxyphene (NP) were studied in 6 healthy male subjects after a single oral dose of 195 mg DP HCl, and during and after 12 daily single oral doses of 195 mg DP HCl. The kinetics varied up to five-fold between individuals after the single dose, the apparent mean elimination half-life (t1/2) was 16 h for DP and 29 h for NP. The mean apparent overall plasma clearance (CL) for DP was 2.61/min. There was no systematic difference in DP clearance between the single and multiple doses, but the accuracy of individual predictions from single to multiple doses was poor, probably because of imprecise determinations of the AUC and t1/2 in the single dose experiments. The individual correlation between single and multiple dose kinetics was good for NP, although the predicted plasma levels during steady state were significantly higher than the observed levels (mean AUCss/AUCsd: 0.81). There was no sign of saturation kinetics on repeated administration. In fact, autoinduction, resulting in significantly lower plasma concentrations after treatment for 1 week was found for NP and was indicated for DP. On discontinuing DP after 12 days of treatment, the apparent mean t1/2 of DP was 23 h and of NP 25 h.

Administration, Oral↗
PubMed1985

Pharmacokinetic implications of different oil vehicles used in depot neuroleptic treatment.

On separate occasions two male schizophrenic inpatients were given intramuscular injections of equal amounts of perphenazine decanoate dissolved in sesame oil and Viscoleo, respectively. Substantially more even, but also lower perphenazine plasma concentrations were found within the dose intervals following the injections of perphenazine decanoate dissolved in sesame oil compared to the intervals following the Viscoleo-preparation. The occurrence of extrapyramidal side effects were consistent with the magnitude of the perphenazine plasma concentrations. The results support the importance of selecting an appropriate oil vehicle in a depot neuroleptic.

Adult↗
PubMed1985

Perphenazine decanoate in sesame oil vs. perphenazine enanthate in sesame oil: a comparative study of pharmacokinetic properties and some clinical implications.

Ten schizophrenic inpatients were each treated with perphenazine enanthate (PE) and perphenazine decanoate (PD). Following a cross-over study design it was possible to evaluate differences in plasma profiles between the two preparations, and to relate these to encountered side effects. All patients had previously been receiving neuroleptic treatment and had been diagnosed according to DSM-III. The dosage and intervals between injections were on an individual basis. The results indicate that at all dosage levels, the decanoate preparation showed significantly lower peak plasma concentrations of perphenazine. Extrapyramidal side effects and sedation were also less pronounced after the administration of PD. The more even and flat plasma concentrations obtained with PD, may facilitate plasma monitored therapy by using minimum concentration values.

Adult↗
PubMed1985

Development of cimetidine resistance in the Zollinger-Ellison syndrome.

A patient with the Zollinger-Ellison syndrome was followed with multiple gastric secretion tests and serum gastrin analyses for six years. During this period cimetidine requirement increased to a daily dose of 8 g, but it reversed spontaneously after two years. The altered cimetidine effectiveness was not associated with reduced oral bioavailability and serum calcium was unchanged. Total serum gastrin was very high at all times, and fractionation of gastrins in serum by gel filtration showed varying proportion of big to small gastrins, but not in a mode which explained the parietal cell resistance to cimetidine.

Adult↗
PubMed1985

The kinetics of the production of granulocyte-monocyte colony stimulating activity (GM-CSA) by isolated human monocytes: response to bacterial endotoxin.

When mononuclear phagocytes are stimulated by bacterial endotoxins, they produce Granulocyte-Monocyte Colony-Stimulating Activity (GM-CSA). In order to study the kinetics of the production of GM-CSA by human monocytes, we prepared suspensions of these cells and studied their response to Salmonella typhi endotoxin. We found that when human monocytes were exposed to this preparation of endotoxin, they synthesized GM-CSA de novo and subsequently secreted it into the extracellular environment; however, within hours, the cells became highly refractory to further stimulation by endotoxin. The resistance to endotoxin which these cells rapidly acquired in vitro could not be accounted for by cell attrition, the accumulation of toxic metabolites in the cultures, negative feedback inhibition by newly synthesized GM-CSA, depolarization of the plasma membrane of the cells, or by degradation of endotoxin. When we studied the binding of tritium-labeled endotoxin to viable monocytes, we found that after monocytes were initially exposed to endotoxin, their subsequent ability to bind lipopolysaccharide molecules onto the surface of the plasma membrane was reduced. When we subjected concentrated supernates from endotoxin-stimulated monocyte cultures to gel filtration and isoelectric focusing, we noted that GM-CSA derived from human monocytes had an apparent molecular weight of approximately 42,000 daltons. Our results indicate that resistance to bacterial endotoxins acquired by mononuclear phagocytes may play a role in the immunologic phenomenon of immediate endotoxin tolerance observed in vivo and may in part be due to down-regulation of endotoxin binding to the outer surface of the cell.

Cells, Cultured↗
PubMed1985

Perphenazine decanoate vs. perphenazine enanthate: efficacy and side effects in a 6 week double-blind, comparative study of 50 drug monitored psychotic patients.

In a six-week randomized, double-blind study the efficacy and side effects of perphenazine decanoate (PD) and perphenazine enanthate (PE) were evaluated and compared in 26 and 24 acute psychotic patients respectively. Of either formulation 100 mg were administered intramuscularly every two weeks. Maximum and minimum plasma concentrations of perphenazine were measured for each injection period using gas liquid chromatography. There was no statistically significant difference between PD and PE in terms of overall antipsychotic efficacy, assessed by means of the Brief Psychiatric Rating Scale (BPRS). However, when an 'Amelioration Score' (AMS) of at least 50% of the totally obtainable scores was defined as individual response criterion it was revealed that the PD group only one patient (4%) did not meet this criterion, compared with six patients (25%) in the PE group. Extrapyramidal side effects were significantly more pronounced in the PE-treated patients, who also required significantly higher amounts of antiparkinson medication. The mean maximum concentration of perphenazine in plasma was 5.0 nmol/l in the PD, and 10.6 nmol/l in the PE-treated patients. The ratio of the mean maximum to the mean minimum concentration was 1.41 and 4.02 in the decanoate and enanthate groups respectively. In the patients treated with PD there were signs of accumulation indicating the possibility of prolonging dosage intervals. The present study yielded further support to previous findings demonstrating that intramuscular administration of PD dissolved in sesame oil, in contrast to PE, results in even and flat plasma perphenazine concentration curves, which not only provides a stable antipsychotic effect but also most likely carry the responsibility for the low incidence of extrapyramidal side effects observed.

Adult↗
PubMed1985

Long-term depot neuroleptic treatment with perphenazine decanoate. I. Efficacy and side effects in a 12 month study of 42 drug monitored psychotic patients.

In an open, prospective 12 month study of perphenazine decanoate (PD), 42 psychotic patients diagnosed according to DSM-III were treated with a fixed depot interval and an individual dose, guided by gas chromatographic perphenazine plasma concentration monitoring combined with clinical evaluation. Degree of illness was rated using a social-psychiatric CGI-scale and extrapyramidal side effects were evaluated by means of a modified Simpson and Angus rating scale. After six months of treatment, a statistically significant improvement was found (p less than 0.001). During the last six months a further slight reduction in mean CGI-scores was observed. Mild to moderate extrapyramidal side effects occurred in 9 patients (21%) principally during the initial phase of therapy. No other side effects or changes in blood chemistry were found during the study. Plasma concentrations of perphenazine increased during the initial 3 months and stabilized hereafter. There were however, large intra- and inter-individual variations in the perphenazine plasma concentration/dose ratio. In addition, it was observed that plasma concentrations of perphenazine were significantly higher in patients who had been treated with neuroleptics for more than 10 years compared to those who had been treated 5 years or less. This observation indicates gradual development of tolerance to neuroleptic treatment. This study demonstrates that PD is a safe and effective remedy for maintenance therapy in psychotic patients.

Adult↗
PubMed1985

Long-term depot neuroleptic treatment with perphenazine decanoate. II. Different depot intervals in the last 6 months of a 12 month study of 42 drug monitored psychotic patients.

In order to investigate the feasibility of administering perphenazine decanoate (PD) at three week intervals the 42 patients participating in the previously reported open, prospective 12 month study were, after six months, treated according to the following scheme: 21 patients continued to receive injections every two weeks (group I), whereas in the remaining 21 patients the intervals between injections were extended to 3 weeks (group II). Both groups continued to respond equally well to therapy. Moreover it was observed that the mean daily dose of perphenazine was significantly reduced when using 3 weeks intervals. This study demonstrates that PD administered every 3 weeks is a safe and effective remedy for maintenance therapy in psychotic patients.

Adult↗
PubMed1984

Interaction of radiolabeled endotoxin molecules with human monocyte membranes.

Radiolabeled and biologically active endotoxin molecules were prepared, and their binding to monocyte plasma membranes was studied. The binding of 3H-endotoxin and 51Cr-lipid A to isolated membranes was found to be less specific and of lower apparent affinity than that observed using whole cells. Plasma membranes isolated from intact, viable 51Cr-lipid A-pretreated monocytes were found to contain a significant portion of the cell-associated 51Cr-lipid A following Percoll density gradient fractionation of post-nuclear homogenates. When monocytes were pretreated with 3H-endotoxin under the same experimental conditions, all of the label was recovered in the extracellular medium, and subcellular fractionation revealed no fractions which contained tritium. Taken together, our results suggest that specific and high affinity interactions between monocyte membranes and endotoxin molecules are likely to depend on plasma membrane structures which are assembled in intact monocytes but which are disrupted when plasma membranes are isolated from these cells.

Cell Fractionation↗
PubMed1984

Interaction between endotoxin and human monocytes: characteristics of the binding of 3H-labeled lipopolysaccharide and 51Cr-labeled lipid A before and after the induction of endotoxin tolerance.

Salmonella typhi endotoxin (lipopolysaccharide, LPS) was labeled with tritium and purified by gel filtration. Using this preparation, we found that binding of 3H-labeled LPS (3H-LPS) to isolated human monocytes consisted of a rapid (t1/2 less than 5 min), reversible, temperature-independent phase of surface adsorption that was followed by a slower (t1/2 greater than 20 min) period of binding that was irreversible and temperature-dependent. The interactions between 3H-LPS and monocytes that we measured were dependent both on the concentration of LPS and the cell number. We observed an apparent decrease in 3H-LPS surface binding after initial treatment of the cells with LPS, which was most likely due to an acquired reduction in the number of sites on the monocyte membrane available for the binding of LPS. Estimates of the parameters of the binding of 3H-LPS were calculated from a double-reciprocal plot (1/bound vs. 1/free) of the surface binding data and suggest that the relative binding affinity (Kd) for 3H-LPS was unchanged after pretreatment of the monocytes with LPS; however, the total number of LPS binding sites appeared to be reduced by this manipulation. The results of competition binding experiments also suggest that the binding affinity for 3H-LPS was the same before and after incubation of the cells with LPS. Lipid A, which we extracted from LPS and labeled with chromium-51, exhibited a binding affinity similar to that of 3H-LPS and, like 3H-LPS, could be displaced from the cells by competing concentrations of unfractionated LPS; however, the kinetics of binding of the two labeled ligands differed considerably. Our results suggest that exposure of monocytes to LPS may alter the ability of these cells to interact with, and consequently respond to, LPS.

Biological Transport↗