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Biomedical subjects

S Eriksen

Publications and source records attributed to S Eriksen.

At least 19 recordsLinked to original sources

Blood-brain barrier disruption for the treatment of malignant brain tumors: The National Program.

Chemotherapy delivery for the treatment of malignant brain tumors is markedly enhanced when given in conjunction with osmotic opening of the blood-brain barrier. Osmotic opening or disruption of the blood-brain barrier is achieved while the patient is under general anesthesia, by the infusion of mannitol into the internal carotid or vertebral artery circulation. The mannitol infusion is followed by administration of intraarterial chemotherapy. A National Blood-Brain Barrier Program now exists and includes six universities. Within the National Program over 4200 blood-brain barrier disruption procedures have been performed in over 400 patients. Patients with primary central nervous system (CNS) lymphoma, glioma, primitive neuroectodermal tumor (PNET), germ cell and metastatic cancer are eligible for treatment. Results in patients with primary CNS lymphoma, recently reported in the Cancer Journal, include the first example of a durable response in a primary brain tumor without loss of cognitive function and without use of radiotherapy. Results with PNET and germ cell tumors are also very encouraging. Advanced practice nurses coordinate the care of blood-brain barrier disruption patients. Care includes patients selection, education, close neurological observation, maintenance of fluid and electrolyte balance and managing effects of high-dose chemotherapy. Both acute and long-term medical and psychological follow-up are an essential component of the program, as well as patient and family support.

Antineoplastic Agents↗

Toxin of the marine alga Prymnesium patelliferum enhances voltage dependent Ca(2+)-currents, elevates the cytosolic Ca(2+)-concentration and facilitates hormone release in clonal rat pituitary cells.

The marine flagellate Prymnesium patelliferum produces toxins lethal to fish. The toxin extracted from the alga has haemolytic, cytotoxic and neurotoxic effects, but the action mechanisms of the toxin are not known in detail. We have examined the toxin effects on the voltage sensitive Ca(2+)-currents, the cytosolic Ca(2+)-level ([Ca2+]i) and the prolactin release in clonal rat anterior pituitary GH4C1 cells, which possess T- and L-type Ca(2+)-channels. The trans-membrane Ca(2+)-current was recorded using whole-cell voltage clamp. After 5-15 min exposure to the algal toxin at a final concentration of 50,000-100,000 cells mL-1, the Ca(2+)-currents through both the T- and L-channels showed a 2-3-fold enhancement. The voltage sensitivity of the Ca(2+)-currents was not affected by the algal toxin, and the toxin-induced currents were inhibited by 100 microM of the Ca(2+)-channel blocker D-600. In toxin-exposed cells microfluorometric measurements based on fura-2 revealed an increase of [Ca2+]i from 100-150 to 300-500 nM. This elevation was delayed and partially inhibited by 100 microM D-600. The algal toxin induced prolactin release in a dose-dependent manner, and this effect was inhibited by the Ca(2+)-channel blocker verapamil. We therefore conclude that the toxin of P. patelliferum affects the Ca2+ homeostasis of the pituitary cells by increasing the leak through voltage sensitive Ca(2+)-channels, resulting in increased [Ca2+]i and secretion of prolactin.

Animals↗

Diphtheria toxin at low pH depolarizes the membrane, increases the membrane conductance and induces a new type of ion channel in Vero cells.

Receptor-dependent translocation of diphtheria toxin across the surface membrane of Vero cells was studied using patch clamp techniques. Translocation was induced by exposing cells with surface-bound toxin to low pH. Whole cell current and voltage clamp recordings showed that toxin translocation was associated with membrane depolarization and increased membrane conductance. The conductance increase was voltage independent, with a reversal potential of approximately 15 mV. This value was unaffected by changing the Cl- gradient across the membrane and microfluorometric measurements showed that the cytosolic Ca2+ concentration was only marginally elevated by the translocation. The conductance increase is thus mainly due to monovalent cations. Exposing outside-out and cell-attached patches with bound toxin to low pH induced a new type of ion channel in the membrane. The channel current was inward at negative membrane potentials and the single channel conductance was approximately 30 pS. This value is about three times larger than for receptor-independent channels induced by diphtheria toxin or toxin fragments in artificial lipid membranes.

Animals↗

Dose-dependent effects of perindopril on blood pressure and small-artery structure.

Long-term treatment of young spontaneously hypertensive rats (SHR) with angiotensin-converting enzyme (ACE) inhibitors has a persistent effect on blood pressure when treatment is withdrawn. The aim of the present study was to determine whether this effect could be mediated by the effect of treatment on resistance-artery structure. We determined the dose dependence of ACE-inhibitor therapy on blood pressure and small-artery structure during treatment and on the recovery of blood pressure when treatment was withdrawn. SHR (40 per group) were treated from age 4 to 24 weeks with one of three doses of perindopril (0.4, 0.8, or 1.5 mg/kg per day). Control groups were untreated SHR and Wistar-Kyoto rats. At 24 weeks, treatment was stopped and small arteries were taken from half of the rats from the mesenteric, femoral, cerebral, and coronary vascular beds for morphological and functional measurements. The blood pressure of the other half of the rats was followed until 36 weeks of age. During treatment, perindopril caused a dose-dependent reduction in blood pressure and in the media-lumen ratio and media area of the small arteries, whereas there was a dose-dependent increase in lumen diameter. The effect of treatment on the structure of arteries from the different vascular beds was homogeneous. Compared with values from Wistar-Kyoto rats, blood pressure normalization in SHR was not associated with full normalization of structure. After withdrawal of treatment, there was an inverse relation between perindopril dose and the persistent effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Particulate contamination in spinal analgesia.

A microscopic investigation was undertaken to quantify the amount of particulate contamination in the injectates of bupivacaine 0.5% in spinal analgesia. No differences were found between samples prepared with either a glass syringe or a disposable plastic syringe, nor could differences be documented between groups where atraumatic opening of vials, perforation of vial stoppers or opening of glass ampoules was performed. The use of commercially available bacterial filters was followed by a significant increase in the amount of particulate contamination, probably filter debris. The clinical use of such filters in spinal analgesia is therefore questionable.

Anesthesia, Spinal↗

Sore throat after operation: influence of tracheal intubation, intracuff pressure and type of cuff.

One hundred and eighty-four patients were studied to elucidate the contribution of intracuff pressure and cuff type to the occurrence of sore throat and hoarseness after operation. The patients were allocated to one of the following groups: A = mask only; B = reusable Rüsch tube with intermittent cuff volume adjustment; C = reusable Rüsch tube without cuff volume adjustment; D = disposable Portex Blue Line tube with intermittent cuff volume adjustment; E = disposable Shiley Low Pressure tube with intermittent cuff volume adjustment. Nitrous oxide was a component of anaesthesia in all patients. Moderate or severe symptoms were recorded in 30-33% of the patients in groups C, D and E, contrasting with group B, in which these sequelae were seen in only 10% of patients (P less than 0.025). All sequelae occurred less frequently in group A than in any of the other groups (P less than 0.025). Women were more likely to develop sore throat after intubation than were men (P less than 0.01). A possible relationship between differences in cuff-trachea contact area is postulated.

Adolescent↗

Effects of nitrous oxide on systolic time intervals.

The effects of inhalation of oxygen, nitrous oxide/oxygen and nitrous oxide/nitrogen/oxygen on systolic time intervals (PEP (pre-ejection period) and LVET (left ventricular ejection time) were investigated in eight healthy persons. Nitrous oxide 40%, administered with oxygen or oxygen/nitrogen, prolonged PEP significantly by 25% and 22%, respectively. Inhalation of oxygen also prolonged PEP but to a significantly minor degree. LVET, heart rate and MAP were unchanged during the experiments. Derivatives from the systolic time intervals, i.e. PEP/LVET, I/PEP2 and ejection fraction changed significantly in the nitrous oxide groups. It is concluded that nitrous oxide depresses cardiac performance, to some degree, even when administered at a rather low concentration.

Adult↗

Thiopental-nitrous oxide- halothane anesthesia and repeated succinylcholine: comparison of preoperative glycopyrrolate and atropine administration.

The effects of glycopyrrolate and atropine given prior to thiopental-N2O-halothane anesthesia on bradyarrhythmias associated with the administration of succinylcholine were studied and compared. Sixty healthy adult patients were allocated at random to one of three groups. Three minutes before induction of anesthesia with thiopental (4 to 5 mg/kg) one group received glycopyrrolate, 0.0045 mg/kg IV, the second group, glycopyrrolate, 0.008 mg/kg IV, and the third group, atropine, 0.009 mg/kg IV. Succinylcholine, 1 mg/kg of body weight, was given 1 minute and 6 minutes after the conclusion of the thiopental injection. ECG monitoring was continuous, and serum K+ levels as well as PaO2 and paCO2 were repeatedly measured. In all three groups patients were adequately and equally protected against serious bradyarrhythmias following the second dose of succinylcholine by atropine and glycopyrrolate in the doses used.

Adult↗

Effects on muscarinic receptors of various agents in reversal of neuro-muscular blockade: a study evaluating atropine, glycopyrron, neostigmine and pyridostigmine.

The effects were studied of various drug combinations, recommended for use in reversal of neuromuscular blockade, on heart rate and salivary secretions in 80 healthy patients anaesthetized with nitrous oxide-oxygen-halothane and relaxed with d-tubocurarine. The drug combinations were mixtures of atropine 1 mg--neostigmine 2.5 mg, atropine 1 mg--pyridostigmine 15 mg, glycopyrron 0.5 mg--neostigmine 2.5 mg, and glycopyrron 0.5 mg--pyridostigmine 15 mg, respectively. It was found that administration of the atropine-containing mixtures induced more pronounced initial increases and delayed decreases in heart rate than the mixtures containing glycopyrron. Pyridostigmine-containing mixtures elicited a somewhat more pronounced initial increase in heart rate than neostigmine-containing mixtures, but a less pronounced and delayed decrease in heart rate. Supraventricular arrhythmias occurred less frequently in the pyridostigmine groups than in the neostigmine groups. No such difference was found between the atropine and glycopyrron groups. Glycopyrron caused a more intense dryness of the mouth than atropine. A differential attitude towards the use of drugs for reversal of neuromuscular blockade, based on the cardiovascular state of the particular patient, might be recommendable.

Adolescent↗

Changes in myocardial performance induced by pancuronium and gallamine in hypercapnic and hypocapnic dogs.

Changes in myocardial performance after administration of gallamine 1.5 mg kg-1 and pancuronium 0.1 mg kg-1 were investigated in hypercapnic (PaCO2 = 7.08 kPa) and hypocapnic (PaCO2 = 2.74 kPa) dogs anaesthetized with thiopentone, nitrous oxide and halothane. Administration of pancuronium during hypocapnia caused a decrease of 25% in dP/dt max (corrected for changes in preload, afterload and heart rate). This change was not seen during hypercapnia, probably because of the associated sympathetic stimulation. By contrast, gallamine was without effect on dP/dt max in both groups. The increase in heart rate and cardiac output caused by the atropine-like action of both groups. The increase in heart rate and cardiac output caused by the atropine-like action of these relaxant drugs differed in the hypercapnic and hypocapnic group of dogs, with the more pronounced response in the latter group. The duration of the chronotropic changes was the same in both groups.

Animals↗

Some aspects of ocular function after precurarization.

Small doses of nondepolarizing relaxants are often recommended as prior medication to suxamethonium in order to avoid or attenuate the side effects elicited by the latter drug. After D-tubocurarine (0.05 mg/kg b.w. and 0.075 mg/kg b.w.) in unmedicated volunteers, a dose-dependent recession of the monocular near point of accomodation was recorded. This recession, which parallelled the decrease in grip strength, was 4 cm and 9 cm, respectively. The same doses evoked an exophoria of 14 and 17 prism diopters, respectively. Intraocular pressure was significantly lowered by D-tubocurarine 0.05 mg/kg b.w., from 2.01 kPa (15.1 mmHg) to 1.64 kPa (12.3 mmHg), and by pancuronium 0.015 mg/kg b.w. from 1.90 kPa (14.3 mmHg) to 1.44 kPa (10.8 mmHg). The decreases lasted for 7 min. Gallamine 0.3 mg/kg b.w. also decreased intraocular pressure, but to a lesser degree, and with statistical significance only during the fourth minute after administration. Relaxation of extraocular muscles may change the slightly ovoid shape of the eyeball into a more spherical one, thereby inducing a fall in intraocular pressure and a recession of the near point of accommodation.

Accommodation, Ocular↗