Lars-Owe Koskinen - Academia.edu (original) (raw)

Papers by Lars-Owe Koskinen

Journal of Pharmacy and Pharmacology, 1981

Administration of thyroliberin (TRH) to reserpinized mice causes tremor and counteracts the hypot... more Administration of thyroliberin (TRH) to reserpinized mice causes tremor and counteracts the hypothermia in a dose-dependent fashion. The thyroliberin response is inhibited by gamma-hydroxybutyric acid (GHB) and baclofen, but not by other, more specific GABA-ergic agents, such as THIP, gamma-acetylenic GABA, and sodium valproate. Picrotoxin neither potentiates nor inhibits the thyroliberin actions. Nor are the thyroliberin effects dependent on cholinergic, monoaminergic or histaminergic mechanisms. The results repudiate a current hypothesis, that the peptide actions may be mediated by GABA-ergic pathways in the brain.

Journal of Pharmacy and Pharmacology, 1997

The effect of nimodipine, a vasoactive calcium antagonist, on the disappearance of soman from blo... more The effect of nimodipine, a vasoactive calcium antagonist, on the disappearance of soman from blood was studied in anaesthetized rabbits intoxicated with soman (10.8 μg kg -1 iv). Blood samples from the left heart ventricle and femoral artery were used to investigate soman ...

Journal of Clinical Monitoring and Computing, 2016

Measurement of intracranial pressure (ICP) is necessary in many neurological and neurosurgical di... more Measurement of intracranial pressure (ICP) is necessary in many neurological and neurosurgical diseases. To avoid lumbar puncture or intracranial ICP probes, non-invasive ICP techniques are becoming popular. A recently developed technology uses two-depth Doppler to compare arterial pulsations in the intra- and extra-cranial segments of the ophthalmic artery for non-invasive estimation of ICP. The aim of this study was to investigate how well non-invasively-measured ICP and invasively-measured cerebrospinal fluid (CSF) pressure correlate. We performed multiple measurements over a wide ICP span in eighteen elderly patients with communicating hydrocephalus. As a reference, an automatic CSF infusion apparatus was connected to the lumbar space. Ringer&amp;amp;amp;#39;s solution was used to create elevation to pre-defined ICP levels. Bench tests of the infusion apparatus showed a random error (95 % CI) of less than ±0.9 mmHg and a systematic error of less than ±0.5 mmHg. Reliable Doppler signals were obtained in 13 (72 %) patients. An infusion test could not be performed in one patient. Thus, twelve patients and a total of 61 paired data points were studied. The correlation between invasive and non-invasive ICP measurements was good (R = 0.74), and the 95 % limits of agreements were -1.4 ± 8.8 mmHg. The within-patient correlation varied between 0.47 and 1.00. This non-invasive technique is promising, and these results encourage further development and evaluation before the method can be recommended for use in clinical practice.

Neurosurgery, 2012

ABSTRACT The ventrolateral thalamus (ventral intermediate nucleus [Vim]) is the traditional targe... more ABSTRACT The ventrolateral thalamus (ventral intermediate nucleus [Vim]) is the traditional target for neurosurgical treatment of essential tremor. The target, however, has varied substantially among different neurosurgeons. To evaluate the effect of deep brain stimulation in the thalamus and posterior subthalamic area (PSA) in relation to electrode location. Thirty-six (17 Vim/19 PSA) patients with 44 deep brain stimulation electrodes were included in this retrospective study. The effect of stimulation was evaluated with standardized settings for each contact using items from the Essential Tremor Rating Scale. When each contact was evaluated in terms of the treated hand with standardized stimulation, the electrode contact providing the best effect in the individual patient was located in the zona incerta or radiation prelemniscalis in 54% and the Vim in 12%. Forty contacts provided a tremor reduction of > 90%. Of these, 43% were located in the PSA and 18% in the Vim according to the Schaltenbrand atlas. Of these 40 contacts, 37 were found in the PSA group. More contacts yielding an optimal effect were found in the PSA group than in the Vim. Many patients operated on in the Vim got the best effect from a contact located in the PSA. This might suggest that the PSA is a more efficient target than the Vim.

Neurocritical care, Jan 23, 2014

This prospective consecutive double-blinded randomized study investigated the effect of prostacyc... more This prospective consecutive double-blinded randomized study investigated the effect of prostacyclin on pressure reactivity (PR) in severe traumatic brain injured patients. Other aims were to describe PR over time and its relation to outcome. Blunt head trauma patients, Glasgow coma scale ≤8, age 15-70 years were included and randomized to prostacyclin treatment (n = 23) or placebo (n = 25). Outcome was assessed using the extended Glasgow outcome scale (GOSE) at 3 months. PR was calculated as the regression coefficient between the hourly mean values of ICP versus MAP. Pressure active/stable was defined as PR ≤0. Mean PR over 96 h (PRtot) was 0.077 ± 0.168, in the prostacyclin group 0.030 ± 0.153 and in the placebo group 0.120 ± 0.173 (p < 0.02). There was a larger portion of pressure-active/stable patients in the prostacyclin group than in the placebo group (p < 0.05). Intra-individual changes over time were common. PRtot correlated negatively with GOSE score (p < 0.04). PR...

Peptides, 1998

The neuropeptide thyrotropin-releasing hormone (TRH) elicits a variety of physiological effects o... more The neuropeptide thyrotropin-releasing hormone (TRH) elicits a variety of physiological effects of which some are due to cholinergic mechanisms. TRH modulates in vivo the effects of compounds affecting acetylcholinesterase (AChE). In the present study the in vitro effects of TRH on the activity of AChE were explored. TRH has no effect at physiologically relevant concentrations. At unphysiologically high concentrations (>5 mM) a slight inhibition was found. This was noticed also when the enzyme was exposed to the amide-free tripeptide analog p-Glu-His-Pro. We conclude that any cholinergic effect of TRH observed in vivo is unlikely to be due to a direct interaction of the peptide with AChE.

The new Certas™ shunt for the treatment of hydrocephalus has seven standard pressure settings tha... more The new Certas™ shunt for the treatment of hydrocephalus has seven standard pressure settings that according to the manufacturer range from 36 to 238 mmH 2 O, and an additional "Virtual Off" setting with an opening pressure >400 mmH 2 O. Information on actual pressure response and reliability of shunt performance is important in clinical application, especially the "Virtual Off" setting as a non-surgical replacement for shunt ligation. The objective of this study was to evaluate the in-vitro hydrodynamic performance of the Certas™ shunt.

Journal of neurosurgical anesthesiology, 2015

Postoperative nausea and vomiting (PONV) is a multifactorial problem after general anesthesia. De... more Postoperative nausea and vomiting (PONV) is a multifactorial problem after general anesthesia. Despite antiemetic prophylaxis and improved anesthetic techniques, PONV still occurs frequently after craniotomies. P6 stimulation is described as an alternative method for preventing PONV. The primary aim of this study was to determine whether P6 acupressure with Sea-Band could reduce postoperative nausea after elective craniotomy. Secondary aims were to investigate whether the frequency of vomiting and the need for antiemetics could be reduced. In this randomized, double-blinded, placebo-controlled study, patients were randomized into either a P6 acupressure group (n=43) or a sham group (n=52). Bands were applied unilaterally at the end of surgery, and all patients were administered prophylactic ondansetron. Postoperative nausea was evaluated with a Numerical Rating Scale, 0 to10, and the frequency of vomiting was recorded for 48 hours. We found no significant effect from P6 acupressure ...

SpringerPlus, 2014

A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centr... more A prospective, randomised, double-blinded, clinical trial was performed at a level 1 trauma centre to determine if a prostacyclin analogue, epoprostenol (Flolan®), could attenuate systemic inflammatory response in patients with severe traumatic brain injury (TBI). 46 patients with severe TBI, randomised to epoprostenol (n = 23) or placebo (n = 23). Epoprostenol, 0.5 ng · kg(-1) · min(-1), or placebo (saline) was given intravenously for 72 hours and then tapered off over the next 24 hours. Interleukin-6 (IL-6), interleukin-8 (IL-8), soluble intracellular adhesion molecule-1 (sICAM-1), C-reactive protein (CRP), and asymmetric dimethylarginine (ADMA) levels were measured over five days. Measurements were made at 24 h intervals ≤24 h after TBI to 97-120 h after TBI. A significantly lower CRP level was detected in the epoprostenol group compared to the placebo group within 73-96 h (p = 0.04) and within 97-120 h (p = 0.008) after trauma. IL-6 within 73-96 h after TBI was significantly low...

Case reports in neurology, 2013

Cerebral venous sinus thrombosis (CVST) may occur following head trauma and contribute to intracr... more Cerebral venous sinus thrombosis (CVST) may occur following head trauma and contribute to intracranial hypertension that mandates immediate action. Anticoagulant therapy is the first line of treatment in CVST but may not be applicable in patients with head trauma. Here, we report on the treatment of 2 patients with CVST. In 1 patient, there was an attempt to perform thrombectomy and thrombolysis, and eventually a decompressive craniectomy was performed. In this patient, there was an excellent outcome. In the other patient, an immediate decompressive craniectomy was performed that did not improve the outcome.

Management of Severe Traumatic Brain Injury, 2012

Upsala Journal of Medical Sciences, 1987

The effects of bilateral electrical stimulation (SS) of the cervical sympathetic chain on intra- ... more The effects of bilateral electrical stimulation (SS) of the cervical sympathetic chain on intra- and extra cerebral blood flows were studied with the labelled microsphere method in the rabbit. Control blood flow was determined before the SS was started. The stimulation frequency was 7 Hz, the impulse duration 2 ms, the intensity 7 V and the stimulation time varied between 1 to 5 minutes before the second blood flow determination. Arterial blood gas values and blood pressure were unaffected by the stimulation. Due to the SS there were blood flow decrements in the extracranial tissues between 60-96%. The blood flow in the eyes, the dura, pineal gland and choroid plexa was markedly reduced during the SS. No obvious effect was elicited by the SS in the regional or total cerebral blood flow. The stimulation to control blood flow ratio ranged between 0.92 +/- 0.08 to 1.13 +/- 0.09 in different parts of the brain. The conclusions are that SS elicits vasoconstriction in several extra- and intracranial nonneuronal tissues and in the eye. Cerebral blood flow is not influenced by the SS.

Upsala Journal of Medical Sciences, 2000

Upsala Journal of Medical Sciences, 2003

The present investigation was undertaken in order to study whether microvascular effects of the c... more The present investigation was undertaken in order to study whether microvascular effects of the calcium antagonist nimodipine induces changes that can explain an increased detoxification of the highly toxic cholinesterase inhibitor soman. Anaesthetised, tracheotomised and artificially ventilated rats were treated intra-peritoneally (ip) with nimodipine, 10 mg kg(-1) or vehicle followed one hour later by the exposure to 45 microg kg(-1) soman (iv). Nimodipine per se induced a vasodilation in the intestine, myocardium and other muscles. In the abdominal skin soman elicited a significant vasoconstriction that was turned into an increased blood flow after nimodipine pre-treatment. A slight vasoconstriction in diaphragm of soman intoxicated rats was turned into a significant vasodilation by nimodipine pre-treatment. In the intestinal parts no effect of soman was detected. However, in nimodipine pretreated animals soman induced a significant vasoconstriction. The capacity of soman detoxifying processes, i.e. enzymatic hydrolysis and covalent binding to different esterases, is unequally distributed throughout the body. Together with the knowledge of the detoxifying processes of cholinesterase inhibition the results support our theory, that nimodipine alters the peripheral blood flow in a beneficial way resulting in improved detoxification ability.

Scandinavian Journal of Clinical & Laboratory Investigation, 2012

Subarachnoid haemorrhage (SAH) is associated with an inflammatory systemic response and cardiovas... more Subarachnoid haemorrhage (SAH) is associated with an inflammatory systemic response and cardiovascular complications. Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, mediates vasoconstriction and might contribute to cerebral vasoconstriction and cardiovascular complications after SAH. ADMA is also involved in inflammation and induces endothelial dysfunction. The aim of this study was to evaluate whether and how CRP (marker for systemic inflammation) and ADMA increased in patients during the acute phase (first week) after SAH. The ADMA level was also assessed in the patients in a non-acute phase (three months), and in healthy controls. A prospective study of 20 patients with aneurysmal SAH. ADMA and CRP were followed daily during the first week after SAH and a follow up sample for ADMA was obtained 3 months later. A single blood sample for ADMA was collected from age- and sex-matched healthy controls (n = 40, two for each case). CRP increased significantly from day 2; 16 (Confidence interval (CI) 10-23) mg/L to day 4; 84 (CI 47-120) mg/L, (p &amp;amp;amp;lt; 0.01). ADMA increased significantly from day 2; 0.22 (CI 0.17-0.27) μmol/L, to day 7; 0.37 (CI 0.21-0.54) μmol/L, p &amp;amp;amp;lt; 0.01. ADMA remained elevated at a 3-month follow-up: 0.36 (CI 0.31-0.42) μmol/L. ADMA in the first sample from the patients (day 1-3); 0.25 (CI 0.19-0.30) μmol/L, was not different from ADMA in matched healthy controls; 0.25 (CI 0.20-0.31), p &amp;amp;amp;gt; 0.05. After SAH, CRP and ADMA in serum increased significantly during the first week and ADMA remained elevated 3 months later.

Peptides, 1991

The cardiovascular effects of IV naloxone and a subsequent administration of TRH IV were studied ... more The cardiovascular effects of IV naloxone and a subsequent administration of TRH IV were studied in the rabbit. Naloxone caused a vasodilation in the myocardium and adrenal glands. Naloxone elicited an increment in cerebral blood flow in several regions which attenuated the cerebrovasodilating effect of TRH in a few regions. The blockade of endogenous opioids with naloxone did not modify the peripheral vasoconstricting effect of TRH or affect the vascular effects of TRH mediated by the peripheral sympathetic nerves. The results indicate that naloxone has a vasodilating effect in the myocardium and CNS in anesthetized rabbits. The major part of the cardiovascular effect of TRH is not dependent on mechanisms sensitive to naloxone.

Peptides, 1989

peripheral blood flow effects of TRH in the rat--A role of vagal nerves. PEPTIDES 10(5) [933][934... more peripheral blood flow effects of TRH in the rat--A role of vagal nerves. PEPTIDES 10(5) [933][934][935][936][937][938] 1989.--The cardiovascular effects of the IV infusion of TRH were studied in the rat. TRH tended to increase the MAP and markedly increased the CBFto t in the control group, in vagotomized animals and in methylatropine-pretreated rats. A marked vasodilation was noted in the pancreas, gastric mucosa, duodenum and cardiac muscle. This effect was turned to vasoconstriction, the heart excluded, in vagotomized animals. Muscarinic blockade attenuated the vasodilating effect of TRH in the duodenum and gastric mucosa. The results indicate that TRH elicits cerebral vasodilation and a partly nonmuscafinic parasympathetically mediated vasodilation in several gastrointestinal organs in parallel with a vasoconstriction which is unmasked by vagotomy.

Peptides, 2003

The tripeptide thyrotropin releasing hormone (TRH) has multiple interesting and complex physiolog... more The tripeptide thyrotropin releasing hormone (TRH) has multiple interesting and complex physiological effects. One of these is the cerebrovasodilating effect, which has been described under several different conditions. The final mechanism for this effect is unknown. In the present study, we found an initial atropine-resistant cerebral vasodilation (24%) elicited by the NOS inhibitor L-NAME in the rat. D-NAME and 7-NI did not produce this effect. TRH (300 g kg −1 , i.v.) induced an increase in cerebral blood flow by 62%. L-NAME reduced this effect significantly. The cerebrovasodilating mechanism of TRH, at least in part, is endothelial NO dependent as the neuronal 7-NI NOS inhibitor does not affect the TRH response.