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Biomedical subjects

K Knudsen

Publications and source records attributed to K Knudsen.

At least 73 records · Page 4Linked to original sources
PubMed1988

Effects of naloxone and verapamil in experimental amitriptyline poisoning in rats.

The effects of verapamil and naloxone as potential antidotes for amitriptyline-induced cardiotoxicity were investigated in an experimental rat model. Amitriptyline was infused continuously at a dose of 37.5 mg/kg/h. After 15 minutes, the animals were given either naloxone (2 mg/kg + 3 mg/kg/h), verapamil (0.08 mg/kg + 0.08 mg/kg/h), or physiological saline. In the group given naloxone, a significant decrease in heart rate was seen. Although MAP and max dP/dT increased, there was no significant difference from controls. Naloxone did not decrease mortality. When the bolus dose of verapamil was given, a significant decrease in MAP and max dP/dT was obtained. Although the mean blood pressure was significantly higher in those animals treated with verapamil who survived 60 minutes, verapamil did not change the course of the amitriptyline poisoning. In conclusion, our findings indicate that naloxone lacks significant positive effects and that verapamil has an additional negative inotropic effect. Neither drug can be recommended for the treatment of amitriptyline poisoning.

Amitriptyline↗
PubMed1988

Clonidine interaction in amitriptyline poisoning.

The effect of clonidine on amitriptyline-induced cardiotoxicity was investigated in an experimental rat mode. A continuous infusion of amitriptyline (30 mg/kg/h) was given until the animal died, usually within 2 hours. Fifteen minutes after starting the amitriptyline infusion, 50 micrograms/kg of clonidine was given intravenously over five minutes. This led to an increase in blood pressure and left ventricular end-diastolic pressure. There was no significant change in cardiac contractility. Heart rate decreased. These changes can be explained by an increase in afterload due to peripheral vasoconstriction. No signs of reduced sympathetic outflow were seen on the ECG. The peripheral effects of clonidine dominated over the central effects, which may be due to a competitive inhibition of amitriptyline at central noradrenergic sites. An increased afterload pushes the heart towards failure and increases mortality. In this model, clonidine did not reverse amitriptyline-induced cardiovascular toxicity. It may even be potentially harmful if used to treat tricyclic antidepressant poisoning.

Amitriptyline↗
PubMed1985

Cleavage of a 135 kD cell surface glycoprotein correlates with loss of fibroblast adhesion to fibronectin.

We have previously described a group of three plasma membrane glycoproteins that are recognized by an adhesion-disrupting antiserum and that are involved in fibronectin-mediated BHK cell adhesion. A peculiar property of these molecules is their resistance to tryptic digestion. We have now extended this study in the attempt to identify the active component within this group of molecules. SR/BALB mouse fibroblasts, used in this work, expose at their surface only two trypsin-resistant glycoproteins, gp1 (150 K) and gp2 (135 K), that are recognized by the adhesion-disrupting anti-BHK serum. Controlled proteolysis of the cell surface in the presence of a reducing agent results in the loss of cell adhesion to fibronectin-coated substratum. gp2 is selectively cleaved under these conditions. Moreover, cells treated with trypsin and reducing agent can no longer adsorb the adhesion-relevant antibodies from the anti-BHK serum. These data indicate that gp2 plays a critical role in the adhesion of SR/BALB fibroblasts to fibronectin-coated substratum, and that disulfide bonds are important in the conformation and function of this molecule.

Animals↗
PubMed1984

Effects of self poisoning with maprotiline.

Self poisoning with maprotiline was studied in 41 patients (43 episodes) consecutively admitted to an intensive care unit. Thirty five patients had taken more than one drug or alcohol. Fifteen patients were in coma grade III or IV; 17 patients were still not conscious after 24 hours in the intensive care unit. Among six patients given ventilation the mean duration of ventilation in the five who recovered was 36 hours. Three patients had a cardiorespiratory arrest, and one patient died. Twenty eight patients had a QRS interval of 100 ms or more, and 15 patients had seizures. In six patients seizures were precipitated by physostigmine. Cardiotoxicity after overdosage of maprotiline is equal to if not greater than that found after overdosage of conventional tricyclic antidepressants. Overdosage of maprotiline is more often associated with seizures than overdosage with tricyclic antidepressants. Physostigmine further increases the risk of seizures and should not be used in cases of overdosage of maprotiline.

Adult↗
PubMed1983

Identification and purification of a cell surface glycoprotein mediating intercellular adhesion in embryonic and adult tissue.

An antiserum against material shed into serum-free medium by MCF-7 human mammary carcinoma cells (anti-SFM II) disrupts cell-cell interactions in murine mammary tumor epithelial cells (MMTE). We now report purification of an 80 kd glycoprotein (GP80) from SFM of MCF-7 mammary carcinoma cells that blocks the activity of anti-SFM II. Anti-SFM II also inhibits compaction of eight-cell mouse embryos, and purified GP80 blocks this reaction. An antiserum against purified GP80 (anti-GP80) has all adhesion-disrupting activities displayed by anti-SFM II. It recognizes one band at 80 kd in SFM and a 120 kd band in detergent extracts of epithelial but not fibroblastic cells. In immunofluorescence studies it is restricted to sites of cell-cell interaction in cultured epithelial cells. Thus a cell surface glycoprotein of 120 kd, the medium form of which is approximately 80 kd, which is neither species nor tissue specific, is expressed at early stages of mammalian development and is found on epithelia.

Animals↗
PubMed1982

One year's treatment with propranolol after myocardial infarction: preliminary report of Norwegian multicentre trial.

A prospective, randomised, double-blind study was performed to compare the effects of propranolol and placebo on sudden cardiac death in a high-risk group of patients who survived acute myocardial infarction. Altogether 4929 patients with definite acute myocardial infarction were screened for inclusion: 574 (11.6%) died before randomisation, and 3795 (77%) were excluded. Five hundred and sixty patients aged 35 to 70 years were stratified into two risk groups and randomly assigned treatment with propranolol 40 mg four times a day or placebo. Treatment started four to six days after the infarction. By one year there had been 11 sudden deaths in the propranolol group and 23 in the placebo group (p less than 0.038, two-tailed test analysed according to the "intention-to-treat" principle). Altogether there were 25 deaths in the propranolol group and 37 in the placebo group (P less than 0.12), with 16 and 21 non-fatal reinfarctions respectively. A quarter of the patients were withdrawn from each group. Withdrawal because of heart failure during the first two weeks of treatment was significantly more common among propranolol-treated patients than among the controls, but thereafter the withdrawal rate was the same. The significant reduction in sudden death was comparable with that after alprenolol, practolol, and timolol, which suggests that the mechanism of prevention is beta-blockade rather than any other pharmacological property of the individual drugs.

Adult↗
PubMed1981

Acute, massive poisoning with digitoxin: report of seven cases and discussion of treatment.

Severe digitoxin poisoning in seven patients is reported. Doses taken varied from 2 to 20 mg, and maximal plasma concentrations of digitoxin from 50 to 237 nmol/L. One patient died from ventricular fibrillation, and the course in another was considerably protracted due to severe complications. The course in all patients was more dependent on underlying heart disease than on the plasma digitoxin concentration. Based on our own experiences and survey of the literature the following treatment is proposed: Gastric aspiration and lavage followed by instillation of activated charcoal should even be performed many hours after drug intake. In order to interrupt the enterohepatic circulation of digitoxin, repeated doses of charcoal should be given. Charcoal is preferable to cholestyramine because of its better tolerability. Ventricular arrhythmias should not be treated unless they are serious, because most antiarrhythmic drugs may further impede the AV-conduction. Phenytoin is the drug of choice, because the AV-conduction is less affected or even improved, and because the metabolism of digitoxin is accelerated. Conduction disturbances with bradycardia are frequently seen and may occur suddenly. Prophylactic introduction of a transvenous pacing catheter is therefore recommended as a routine procedure.

Adolescent↗
PubMed1975

Play therapy: preparing the young child for surgery.

A child is not a miniature adult. His thought processes are pre-conceptual, pre-logical, and characterized by many fantasies. The child needs concrete information about his impending surgery: (1) what will happen; (2) what is expected of him; (3) that he is not to blame for his illness or injury, and (4) where the organ to be removed or repaired is located and that no other body parts will be harmed. Play therapy is an effective method for providing tangible information about the surgical experience and simultaneously decreasing the child's fantasies and fears about the surgery.

Child↗
PubMedDate not supplied

Role of extracorporeal drug removal in acute theophylline poisoning. A review.

Theophylline, with its narrow therapeutic margin, is a common cause of iatrogenic and deliberate overdose. Most cases of self-poisoning are with sustained release preparations, with peak concentrations occurring up to 12 or more hours after overdose. Toxic symptoms are often seen at concentrations above 15 mg/L. Theophylline is metabolised within the cytochrome P-450 system, with an average total body clearance of 50 to 60 ml/min. Clearance is, however, affected by many factors such as other drugs or disease, and in overdose zero order kinetics may result in prolonged half-lives. Toxicity is characterised by agitation, tremor, nausea, vomiting, abdominal pains, seizures, and tachyarrhythmias. Hypokalaemia and metabolic acidosis are more profound in acute toxicity, and hypercalcaemia is usually present. Seizures occur at lower concentrations after chronic over-medication than after acute overdose. Gastric lavage should be performed in all patients presenting early, and an oral multiple dose charcoal regimen started with 50 to 100g charcoal, repeating with 50g doses and checking theophylline concentrations at 2- to 4-hour intervals. Multiple dose charcoal can be expected to double the clearance of theophylline, being as effective as a haemodialysis. Of the invasive techniques available, charcoal haemoperfusion is the most effective, increasing clearance 4- to 6-fold. Supportive care is particularly important. The aggressive supplementation of potassium, treatment of emesis with droperidol and ranitidine, and treatment of tachyarrhythmias and hypotension (possibly with propranolol), together with oral multiple dose charcoal may obviate the need for haemoperfusion. Seizures suggest increased morbidity and mortality. Charcoal haemoperfusion should be considered if plasma concentrations are greater than 100 mg/L in an acute intoxication or greater than 60 mg/L in a chronic intoxication. The decision to haemoperfuse should not be based on plasma concentrations alone, but an overall evaluation of the patient's laboratory and clinical status.

Blood Transfusion↗
PubMedDate not supplied

A community study of T lymphocyte subsets and malaria parasitaemia.

In a community survey of 312 children aged 3-6 years in urban Guinea-Bissau, we examined Plasmodium falciparum parasitaemia and T cell subsets. 183 children (59%) had parasites in their blood, 13 had fever > or = 37.5 degrees C, and 9 (3%) had fever and a parasite density > 5000/microL (clinical malaria). Compared with children with no parasitaemia or asymptomatic parasitaemia, children with acute malaria had lymphopenia and significantly lower total CD4 and CD8 cell counts, but there was no significant difference in white blood cell count percentages of CD4 and CD8 cells, or the CD4/CD8 ratio. Children with parasitaemia but without fever had a significantly lower percentage of CD4 cells than children without parasites (P = 0.031), but did not differ in any other haematological index. Controlling for other factors, the CD4 cell percentage was inversely correlated with the density of malaria parasites (P = 0.024), whereas there was no association with CD8 cell percentage or the CD4/CD8 ratio. Asymptomatic parasitaemia may be an important confounder in general community studies of T cell subsets in the tropics.

CD4-CD8 Ratio↗
PubMedDate not supplied

A comparison of vaccine efficacy and mortality during routine use of high-titre Edmonston-Zagreb and Schwarz standard measles vaccines in rural Senegal.

Vaccine efficacy and mortality in successive cohorts of children who routinely received either Edmonston-Zagreb high-titre (EZ-HT) or Schwarz standard (SW-STD) measles vaccines have been examined in a rural area of Senegal. The 2 vaccines were equally protective against measles infection (vaccination efficacy: EZ-HT 94%; SW-STD 93%). Children who did not attend a scheduled session to receive measles vaccine had a higher mortality rate between 9 months and 2 years of age than did children receiving either EZ-HT (mortality ratio [MR] = 1.81, 95% confidence interval [CI] 1.06-3.08) or SW-STD measles vaccine (MR = 1.74, 95% CI 0.95-3.21). Children of either sex vaccinated with EZ-HT had lower mortality than their equivalents who had not received any measles vaccine. There was no difference in overall mortality between recipients of EZ-HT and SW-STD (MR = 0.96, 95% CI 0.70-1.30). Using a Cox regression analysis to adjust for sex, age and significant background factors (season and death of mother), mortality rates tended to be lower for male recipients of EZ-HT than for boys receiving SW-STD (MR = 0.73, 95% CI 0.50-1.11) and higher for girls receiving EZ-HT than for girls receiving SW-STD (MR = 1.30, 95% CI 0.81-2.09) (test of interaction between sex and vaccine, P = 0.067). The tendency to reduced survival benefit for girls following receipt of high-titre measles vaccines substantiated observations from randomized trials in Guinea-Bissau, Senegal and Haiti. Existing data provide little support for the notion that high-titre vaccine is deleterious but it may not have the same beneficial effects as standard-titre measles vaccine.

Cohort Studies↗