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Biomedical subjects

N E Larsen

Publications and source records attributed to N E Larsen.

At least 19 recordsLinked to original sources
PubMed1992

Effect of hylan on cartilage and chondrocyte cultures.

The protective role of hylan, a hyaluronan [hyaluronic acid (HA)] derivative, was studied in explanted bovine cartilage and isolated chondrocytes. Cartilage and chondrocytes were exposed to degradative enzymes (lysate from activated polymorphonuclear leukocytes), oxygen-derived free radicals (ODFR), conditioned media from mononuclear cells (MCCM), and interleukin-1 (IL-1), in the presence and absence of hylan. The effect of HA was also studied. In cartilage explants susceptibility to pertubation was evaluated in terms of 35S release and proteoglycan depletion and was compared to control cultures; high viscosity hylan was found to reduce 35S release in cartilage explants caused by degradative enzymes, ODFR, MCCM, and IL-1. The hylan effect was reversible and viscosity-dependent. In chondrocyte cultures, high viscosity hylan was effective in reducing cell injury caused by degradative enzymes and ODFR. The data suggest that the glycosaminoglycan hylan, as well as native HA, may mediate exposure to and/or response to stimuli associated with initiation of degenerative processes in cartilage tissues.

Animals↗
PubMed1992

Computer-assisted alignment of standard serial sections without use of artificial landmarks. A practical approach to the utilization of incomplete information in 3-D reconstruction of the hippocampal region.

An algorithm for the alignment of stained serial sections without the support of artificial landmarks is described. Four-hundred-thirty serial sections of the rabbit hippocampal region were digitized, and computer-based alignment was performed without use of artificial markers, resulting in a consistent matrix. Following proper filtration, artificial sections were cut through the matrix. In a second experiment every second image was deleted and reconstructed by interpolation with a minor loss of biological information. In a third experiment every second image was deleted and the rest of the images were 'disordered', realigned and the missing planes reconstructed by interpolation. Under these circumstances the matrix was reconstructed with some loss of information. These results may widen the limits of 3-dimensional (3-D) reconstruction, as routine histological preparations normally include only every second or every third section without artificial landmarks.

Algorithms↗
PubMed1991

[Therapy control of perphenazine. 2. Clinical aspects].

Rational use of serum concentration monitoring of the neuroleptic, perphenazine, was evaluated in a prospective investigation. A total of 141 hospitalized patients with paranoid symptoms (excluding mania) requiring treatment were included during the investigation period (one year). Perphenazine was administered (fixed doses) orally (92 patients) and parenterally (depot, decanoate, 45 patients) in a six-week treatment period. Serum concentrations of perphenazine were monitored after 10-14 days oral treatment, on the 14th and 21st days after the commencement of depot treatment. The patients were steered on to the recommended therapeutic range for perphenazine (1.5-6 nmol), according to the serum level measured. Global clinical assessment was carried out by the departmental physicians. Therapy control of perphenazine by serum monitoring was an important supplement to the clinical evaluation of therapeutic effect. Fifteen (65%) out of 23 patients who were treated orally with insufficient therapeutic effect, showed non-compliance or elevated metabolism. On the basis of a single serum concentration measurements (12 hours values), it proved possible to steer the majority of patients onto the recommended therapeutic level. In this way, the individual patient reached optimal therapeutic effect with a minimum of side-effects.

Adult↗
PubMed1991

Hylan gel composition for percutaneous embolization.

Viscoelastic, pseudoplastic, radiopaque injectable hylan gel for percutaneous embolization was developed and evaluated by in vitro and in vivo tests. The embolization gel is composed of cross-linked hylan (hyaluronan, hyaluronate), tantalum, microcrystalline cellulose, hexamethonium chloride, and thrombin. Upon delivery through small-lumen catheters to the appropriate vascular site, the gel induces formation of a solid blood/gel coagulum. Results from animal studies (rat aorta, rabbit auricular artery) demonstrate that formation of complete and long-lasting arterial blockage is readily achievable without complications due to blood flow, partial vessel obstruction, uncontrolled polymerization, or movement of the gel or its components (specifically thrombin and hexamethonium chloride) into the circulation. Microscopic evaluation indicates that arterial occlusion initially occurs as a result of the injected gel and formed fibrin; at 7 weeks and beyond, arteries are occluded by injected gel, inflammatory cells and fibrosis (scar tissue).

Animals↗
PubMed1991

Perphenazine decanoate and cis(z)-flupentixol decanoate in maintenance treatment of schizophrenic outpatients. Serum levels at the minimum effective dose.

Two groups of schizophrenic outpatients were treated with perphenazine decanoate (N = 20) and cis(z)-flupentixol decanoate (N = 24) respectively. Every 3 months the dose was gradually reduced until symptoms appeared that were suggestive of a prodromal phase of a psychotic episode. A slightly higher dose was then promptly reinstituted (the minimum effective dose). At each dose level, two blood samples were drawn for determination of serum concentration. The mean minimum effective dose of perphenazine decanoate was 99.3 mg/2 weeks (range 21.6-270.5), while the mean minimum effective dose of cis(z)-flupentixol decanoate was 60 mg/2 weeks (range 20-250). The corresponding mean serum level of perphenazine decanoate was 7.3 nmol/l (range 2.0-18.1) and of cis(z)-flupentixol decanoate 7.8 nmol/l (range 1.2-37.0). There was a significant correlation between the administered doses and the corresponding serum levels for both drugs (r = 0.87, P less than 0.01). A weak positive correlation was found between serum levels at the minimum effective dose and symptom intensity (BPRS total score) (r = 0.53, P less than 0.02) for perphenazine, but not cis(z)-flupentixol. No correlation was found between serum levels and side effects or length of neuroleptic treatment. It is concluded that the serum drug concentrations corresponding to the lowest effective dose are so variable that routine serum level monitoring may be of limited value in the long-term maintenance treatment of schizophrenia.

Adult↗
PubMed1991

Matrix engineering.

Matrix engineering is a technology that utilizes hyaluronan (HA, hyaluronic acid) based matrices to control, direct or augment tissue regenerative processes. Hyaluronan and the concept of matrix engineering have become established tools in ophthalmic and orthopaedic medicine. The clinical indications for HA are limited by the physical properties and short residence time of the natural HA molecule. To expand and improve upon its current medical applications, a family of HA derivatives was prepared by chemical modification and cross-linking. Relative to the non-modified HA molecule, the hylan family of polymers provides more versatile physical forms, improved mechanical properties and an extended residence time. Hylan can also be used as a surface coating to improve blood compatibility. The chemical, physical and biological properties of hylans will be reviewed, focusing on the specific therapeutic indications they enable.

Animals↗
PubMed1991

Scintigraphic determination of gastrointestinal transit times. A comparison with breath hydrogen and radiologic methods.

A scintigraphic method for determination of gastrointestinal transit times was compared with the breath hydrogen test and a multiple-bolus, single-radiograph technique. A close temporal association was found between the caecal appearance of radioactivity and the onset of breath hydrogen excretion in eight healthy subjects. Neither mean small-intestinal nor mean orocaecal transit times of the radiolabelled marker were correlated with the magnitude of hydrogen peak, hydrogen peak time, or the area under hydrogen curve. No correlation was noted between whole-gut transit time of the radiolabelled marker and mean whole-gut transit time calculated from a 6-day administration of the radiopaque marker in 16 healthy subjects. The stool weight was inversely correlated with the mean colonic (r = -0.46, p = 0.009) and the mean whole-gut (r = -0.45, p = 0.011) transit times of the radiolabelled marker. In conclusion, inadequate delineation of the caecal region seems to be an unimportant drawback of the scintigraphic measurements, whereas day-to-day variation in gastrointestinal transit rates may influence the reliability of the assessments. Probably, quantitative transit data cannot be obtained from the breath hydrogen concentration profiles.

Adult↗
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↗
PubMed1979

Determination of bromocriptine in plasma: comparison of gas chromatography, mass fragmentography and liquid chromatography.

Gas chromatographic, mass fragmentographic and liquid chromatographic techniques for the determinations of bromocriptine (2-bromo-alpha-ergocriptine; Parlodel) in human plasma are described. These methods were found to be suitable for determining concentrations of bromocriptine down to 0.5, 1.0 and 10.0 microgram/l, respectively. Accuracy, specificity and analytical capacity were satisfactory for all three methods. Gas chromatography was compared with liquid chromatography, and the two methods were demonstrated to give identical results in patients treated with bromocriptine for Parkinson's disease. Gas chromatography was also compared with mass fragmentography, and the results from these two assays were also in agreement.

Bromocriptine↗
PubMed1979

Pharmacokinetics of bromocriptine during continuous oral treatment of Parkinson's disease.

The plasma kinetics of bromocriptine (BCT), a long-acting dopamine agonist, was studied in twelve patients with Parkinson's disease, using a newly developed gas chromatographic method of analysis. Each patient received BCT for at least three weeks in a constant but different dose regimen. Concomitant treatment with 1-DOPA was not allowed. During a 6-day hospitalization period, a blood sample was taken immediately before the afternoon dose at 14.00 h (Cmin) to determine the steady-state level. On the 6th day blood samples were collected every hour during two 8 h dose intervals. The results showed a significant correlation between the mean values of the AUC and the Cmin. First order elimination kinetics appeared to be followed by BCT, at least for the plasma concentrations commonly found. Considerable inter-individual variation was demonstrated both for the dose/plasma concentration ratio and for calculated plasma clearances. No serious side-effects were observed during the investigation.

Aged↗
PubMed1979

Cimetidine assay in human plasma by liquid chromatography.

An assay for the determination of cimetidine in human plasma is described. Cimetidine was extracted from alkalized plasma with ethyl acetate, washed once over hydrochloric acid, re-extracted into ethyl acetate, and the organic phase was evaporated to dryness. The residue was dissolved in ethanol and injected into a liquid chromatograph. In vitro sulphoxidation was found to occur in whole blood, for which reason the assay was performed in plasma. The accuracy of the method was found to be within 3% and the lower limit for sensitivity was demonstrated to be 0.1 mg/l using 750 microliters plasma. Five volunteers received 1 g cimetidine perorally per day given in four doses with various intervals. Blood samples were drawn hourly, five dose intervals over two days. The average minimum concentration of plasma cimetidine was found to correlate significantly with the mean value of the area under the time/concentration curve over a period of three dose intervals (r = 0.96).

Adolescent↗
PubMed1979

Plasma levels of perphenazine and its major metabolites during simultaneous treatment with anticholinergic drugs.

1. A gas chromatographic method was applied to study plasma levels of perphenazine (PPZ) and its major metabolites in man before and during simultaneous antiparkinson treatment. Twenty-six psychotic patients received various forms of PPZ administration as well as antiparkinson drugs. 2. Biperidine (5 mg) was administered intravenously to each of five patients, who 5 days earlier had had a single dose of PPZ-enanthate i.m. No significant alterations in plasma concentrations of PPZ were observed. 3. In fourteen patients receiving oral PPZ treatment the plasma levels of PPZ and its metabolites did not deviate significantly from controls after addition of biperidine or orphenadine given for 3 weeks in fixed oral doses. 4. The ratio between PPZ plasma concentration measured 4 and 7 h after the morning dose was not affected by concomitant antiparkinson therapy. 5. It is concluded that no clinically relevant pharmacokinetic interaction takes place between PPZ and two generally used antiparkinson drugs during steady-state conditions in psychotic patients.

Administration, Oral↗
PubMed1979

Saliva secretion following long-term antidepressant treatment with nortriptyline controlled by plasma levels.

Eight patients undergoing antidepressant therapy with nortriptyline for 1--4 years were investigated. The period of the investigation was 7 weeks and included a 2-week placebo period, blind for the patients. Total saliva secretion measurement, the nortriptyline plasma level, and signs and symptoms of depression and side effects were obtained once a week during the study. The results of the investigation were: (1) long-term treatment with nortriptyline is followed by hyposecretion or xerostomia, (2) the reduction of the secretion is reversible, (3) re-establishment of treatment with dosage leading to the same serum level of nortriptyline is immediately followed by a drop in saliva secretion, and (4) the changes in salivary secretion are useful as an indicator of side effects. The practical importance of the investigation is discussed.

Aged↗