Biomedical subjects

L O Koskinen

Publications and source records attributed to L O Koskinen.

At least 19 recordsLinked to original sources

PubMed2001

Biological effects after percutaneous absorption of thyrotropin-releasing hormone and its analogue M-TRH.

Besides its well known endocrinological effects, thyrotropin-releasing hormone (TRH) has potential clinical value in the treatment of neurotrauma and various neurologic and psychiatric disorders. The aim of this study was to assess if transdermal delivery of TRH and its analogue, M-TRH, in the presence of enhancers, is an effective means for administration of the peptides. Using the in vitro diffusion cell method, the effect of ethanol and a terpene on the transdermal penetration of the peptides across full-thickness rat skin were studied. Steady-state permeability values for TRH and M-TRH were 8.7 +/- 2.2 and 6.7 +/- 1.4 microg/cm(2) h, respectively. The addition of 3 % terpene in combination with 47 % ethanol increased the penetration of TRH and M-TRH to 16.2 +/- 1.7 and 14.6 +/- 2.1 microg/cm(2) h, respectively. Rats were studied in vivo for release of thyroid-stimulating hormone (TSH) as a biologic effect after transdermally delivered peptide. Topical application of TRH and M-TRH induced an increase in TSH serum concentration from 0.32 +/- 0.09 ng/ml to 32.6 +/- 5.0 and 22.9 +/- 7.6 ng/ml, respectively, after 30 min. The addition of terpene and ethanol in combination with TRH or M-TRH, increased the TSH release to 43.0 +/- 3.8 and 48.4 +/- 4.0 ng/ml, respectively. It is concluded that, in the rat, peptides can be absorbed through the skin with retained biologic activity, and in amounts sufficient to elicit a physiological response.

Animals↗

PubMed2001

An outcome study of severe traumatic head injury using the "Lund therapy" with low-dose prostacyclin.

BACKGROUND: There are two independent head injury outcome studies using the "Lund concept", and both showed a mortality rate of about 10%, and a favourable outcome (Glasgow outcome scale, GOS 4 and 5) of about 70%. The Lund concept aims at controlling intracranial pressure, and improving microcirculation around contusions. Intracranial pressure is controlled by maintaining a normal colloid osmotic pressure and reducing the hydrostatic capillary pressure. Microcirculation is improved by ensuring strict normovolaemia and reducing sympathetic discharge. The endogenous substance prostacyclin with its antiaggregatory/antiadhesive effects may further improve microcirculation, which finds support from a microdialysis-based clinical study and an experimental brain trauma study. The present clinical outcome study aims at evaluating whether the previously obtained good outcome with the Lund therapy can be reproduced, and whether the addition of prostacyclin has any adverse side-effects. METHODS: All 31 consecutive patients with severe head injury, Glasgow coma scale (GCS) < or = 8, admitted to the University Hospital of Umeå during 1998 were included. The Lund therapy including prostacyclin infusion for the first three days at a dose of 0.5 ng kg(-1) min(-1). Outcome was evaluated according to the GOS >10 months after the injury. RESULTS: One patient died, another suffered vegetative state and 7 severe disability. Of the 22 patients with favourable outcome, 19 showed good recovery and 3 moderate disability. No adverse side-effects of prostacyclin were observed. CONCLUSION: The outcome results from previous studies using the Lund therapy were reproduced, and no adverse side-effects of low-dose prostacyclin were observed.

Adolescent↗

PubMed2001

Antithrombin treatment in patients with traumatic brain injury: a pilot study.

This study will determine if early administration of antithrombin concentrate to patients with traumatic brain injury (TBI) can inhibit or significantly shorten the time of coagulopathy. The progress of brain injury monitored by computed tomographic scan (CT) was also assessed, as was the time needed for intensive care and outcome related to Glasgow outcome scale (GOS). Twenty-eight patients with isolated brain trauma verified with CT were included in either of two parallel groups. The Glasgow coma score (GCS) was mean 7.5, and median 7.0; signifying a moderate to severe traumatic brain injury but with a mortality of only 3.5%. The patients randomized to antithrombin treatment received a total of 100 U/kg BW during 24 hours. To measure hypercoagulability, soluble fibrin (SF), D-dimer (D-d), and thrombin-antithrombin complex (TAT) were assessed together with antithrombin (AT) and routine coagulation tests. Before treatment, SF, D-d, and TAT were markedly increased in both groups. Soluble fibrin and D-dimer (measured after treatment began) appeared to decrease faster in the AT group, and there was a statistically significant difference between the groups at 36 hours for SF and at 36 hours, 48 hours, and at Day 3 for D-d. Thrombin-antithrombin complex levels were very high in both groups but, surprisingly, showed no significant difference between the groups. The authors conclude that antithrombin concentrate administered to patients with severe TBI resulted in a marginal reduction of hypercoagulation. We could not detect any obvious influence by antithrombin on brain injury progress, on CT, or on outcome or time needed for intensive care.

Adolescent↗

PubMed2001

Two computerized methods used to analyze intracranial pressure B waves: comparison with traditional visual interpretation.

OBJECT: Slow and rhythmic oscillations in intracranial pressure (ICP), also known as B waves, have been claimed to be one of the best preoperative predictive factors in idiopathic adult hydrocephalus syndrome (IAHS). Definitions of B waves vary widely, and previously reported results must be treated with caution. The aims of the present study were to develop a definition of B waves, to develop a method to estimate the B-wave content in an ICP recording by using computer algorithms, and to validate these procedures by comparison with the traditional visual interpretation. METHODS: In eight patients with IAHS, ICP was continuously monitored for approximately 20 hours. The ICP B-wave activity as a percentage of total monitoring time (B%) was estimated by using visual estimation according to the definition given by Lundberg, and also by using two computer algorithms (Methods I and II). In Method I each individual wave was classified as a B wave or not, whereas Method II was used to estimate the B-wave content by evaluating the B-wave power in 10-minute blocks of ICP recordings. CONCLUSIONS: The two computerized algorithms produced similar results. However, with the amplitude set to 1 mm Hg, Method I yielded the highest correlation with the visual analysis (r = 0.74). At least 5 hours of monitoring time was needed for an acceptable approximation of the B% in an overnight ICP recording. The advantages of using modern technology in the analysis of B-wave content of ICP are obvious and these methods should be used in future studies.

Aged↗

PubMed2001

Cerebrospinal fluid hydrodynamics after placement of a shunt with an antisiphon device: a long-term study.

OBJECT: Few studies have been performed to investigate the cerebrospinal fluid (CSF) hydrodynamic profile in patients with idiopathic adult hydrocephalus syndrome (IAHS) before and after shunt implantation. The authors compared the in vivo CSF hydrodynamic properties, including the degree of gravity-induced CSF flow, of a shunt with an antisiphon device with a standard shunt. METHODS: Twelve patients with IAHS underwent insertion of shunts with Delta valves. Clinical testing, magnetic resonance imaging, and CSF hydrodynamic investigations were conducted with intracranial pressure (ICP), gravity effect, and pressure-flow curve of the shunt estimated at baseline and at 3 and 12 months postoperatively. No shunt was revised. Despite postoperative clinical improvement in all patients who received Delta valves, the mean ICP was only moderately reduced (mean decrease at 3 months 0.3 kPa [p = 0.02], at 12 months 0.2 kPa [not significant]). Patients with the greatest increase in ICP preoperatively had the most pronounced decrease postoperatively. The hydrostatic effect of the Delta valves was significantly lower than with the Hakim shunts (0.1-0.2 kPa compared with 0.6 kPa). The increased conductance (that is, lowered resistance) was up to 14 times higher with the Delta valves compared with preoperative levels. CONCLUSIONS: The function of a CSF shunt may be more complicated than previously thought; the subcutaneous pressure acting on the antisiphon device can modify the shunt characteristics. A compensatory increase in CSF production may counteract the increased outflow through the shunt. The improved CSF outflow conductance may increase the intracranial compliance and thereby dampen a pathological ICP waveform.

Aged↗

PubMed2000

Three-year survival and functional outcome of patients with idiopathic adult hydrocephalus syndrome.

The functional outcome of 42 patients with idiopathic adult hydrocephalus syndrome (IAHS) was followed over a 3-year period after shunting. Survival curves were compared with those of age-matched healthy elderly subjects and patients with first-ever ischemic stroke. Twenty-seven patients with IAHS were improved 3 months after the operation and 11 remained improved at the 3-year follow-up. The case fatality in patients with stroke and those with IAHS was similar (32% versus 28%), but the relative risk of death among IAHS patients compared to a general elderly population was 3.3.

Aged↗

PubMed2000

Endoscopic transthoracic sympathicotomy affects the autonomic modulation of heart rate in patients with palmar hyperhidrosis.

BACKGROUND: Palmar hyperhidrosis has been associated with an increased activity of the sympathetic nervous system. The objective of this study was to assess the immediate and long-term effects of endoscopic transthoracic sympathicotomy on the autonomic modulation of the heart rate in patients with palmar hyperhidrosis. METHODS: Power spectrum analysis of heart rate variability in the lying position and after passive tilt to the upright position was performed in thirteen patients the day before and after sympathicotomy. A follow-up recording was performed in ten patients approximately six months later. Recordings from 26 healthy subjects were used as a reference group. FINDINGS: The patients had a tendency to higher power of the low-frequency (LF: 0.04-0.15 Hz) and high-frequency (HF; above 0.15 Hz) components than controls in the upright position. After sympathicotomy LF power was reduced, but HF power was unchanged. At follow-up LF power remained at a lower level, but now HF power was reduced. INTERPRETATION: Patients with palmar hyperhidrosis have a sympathetic overactivity but also a compensatory high parasympathetic activity. Sympathicotomy results in an initial sympathovagal imbalance with a parasympathetic predominance, which is restored on a long-term basis.

Adult↗

PubMed2000

Cutaneous sympathetic vasoconstrictor reflexes for the evaluation of interscalene brachial plexus block.

BACKGROUND: Although signs of sympathetic blockade following interscalene brachial plexus block include Horner's syndrome, increased skin temperature and vasodilatation, the degree of sympathetic blockade is not easily determined. The aim of this study was, therefore, to use activation of cutaneous finger pad vasoconstrictor reflexes for description and quantification of the degree of sympathetic blockade following unilateral interscalene brachial plexus block. METHODS: Eight patients scheduled for acromioplasty under general anesthesia were studied. An interscalene plexus catheter was inserted preoperatively on the side to be operated upon and used postoperatively for administration of bupivacaine, given as a bolus (1.25 mg kg(-1)) followed by a continuous infusion (0.25 mg kg(-1) h(-1)). Skin blood flow (SBF) in the pad of the index finger was assessed by the laser Doppler technique, and regional skin vascular resistance (RVR) was calculated. The inspiratory gasp test (apnea at end-inspiration) or a local heat provocation were used as provocations of the cutaneous microcirculation. RESULTS: Interscalene brachial plexus block increased SBF and decreased RVR at rest, and produced satisfactory sensory and motor block. The inspiratory gasp test decreased SBF and increased RVR in the unblocked arm, while the opposite, increased SBF and decreased RVR, were observed during local heat provocation. In the blocked arm, these gasp-induced cutaneous vasoconstrictor and heat-induced vasodilator responses were attenuated. CONCLUSIONS: Interscalene brachial plexus block reduces regional sympathetic nervous activity, illustrated by increases in skin blood flow, skin temperature and attenuated vasoconstrictor responses to an inspiratory gasp. The inspiratory gasp vasoconstrictive response is a powerful and sensitive indicator for monitoring the sympathetic blockade following interscalene brachial plexus block.

Adult↗

PubMed2000

Interleukin-2 and histamine in combination inhibit tumour growth and angiogenesis in malignant glioma.

Biotherapy including interleukin-2 (IL-2) treatment seems to be more effective outside the central nervous system when compared to the effects obtained when the same tumour is located intracerebrally. Recently published studies suggest that reduced activity of NK cells in tumour tissue can be increased by histamine. The present study was designed to determine whether IL-2 and histamine, alone or in combination, can induce anti-tumour effects in an orthotopic rat glioma model. One group of rats was treated with histamine alone (4 mg kg(-1)s.c. as daily injections from day 6 after intracranial tumour implantation), another group with IL-2 alone as a continuous subcutaneous infusion and a third group with both histamine and IL-2. The animals were sacrificed at day 24 after tumour implantation. IL-2 and histamine in combination significantly reduced tumour growth. The microvessel density was significantly reduced, an effect mainly affecting the small vessels. No obvious alteration in the pattern of VEGF mRNA expression was evident and no significant changes in apoptosis were observed. Neither IL-2 nor histamine alone caused any detectable effects on tumour growth. Histamine caused an early and pronounced decline in tumour blood flow compared to normal brain. The results indicate that the novel combination of IL-2 and histamine can be of value in reducing intracerebral tumour growth and, thus, it might be of interest to re-evaluate the therapeutic potential of biotherapy in malignant glioma.

Animals↗

PubMed2000

Brain abscess caused by methicillin-resistant Staphylococcus aureus.

A Swedish tourist was admitted to a Cuban hospital due to epileptic seizures caused by brain tumors. Upon return to Sweden and admission to our hospital, methicillin-resistant Staphylococcus aureus (MRSA) was isolated. He was later considered to be free of MRSA but then developed a brain abscess from which MRSA was isolated.

Brain Abscess↗

PubMed2000

Cerebrovascular effects of the TRH analogues pGlu-3-methyl-His-Pro amide and pGlu-Glu-Pro amide: a comparison with TRH.

The goal of the study was to assess whether TRH analogues possess cerebrovascular effects similar to the native peptide. The neuropeptide thyrotropin releasing hormone (TRH) elicits cerebrovasodilation in several species under various conditions. The laser-Doppler method was employed to study the effects of TRH and the analogues pGlu-3-methyl-His-Pro amid (M-TRH) and pGlu-Glu-Pro amide. Intravenous (i.v.) injection of 300 microg kg(-1) of TRH elicited cerebrovasodilation and a 62% increase in blood flow within 1 minute. M-TRH, in a dose of 300 microg kg(-1) i.v., elicited a 80% increase in cerebral blood flow. Even a minute dose of M-TRH (625 ng kg(-1)) caused an increase in cerebral blood flow. No clear difference in effects on the cerebral blood flow was observed between spontaneously and mechanically ventilated animals, pGlu-Glu-Pro amide had no cerebrovascular effect.

Animals↗

PubMed2000

Cigarette smoke and hypoxia induce acute changes in the testicular and cerebral microcirculation.

The acute effects of cigarette smoking and hypoxia on the cerebral and testicular microcirculation were studied in anestethised adult rats. Smoking for 2 min did not influence arterial pO2, pCO2 or pH but it induced an increase in cerebral blood flow by 34% and inhibited vasomotion in the testis for about 1 h. One hour after smoke exposure apnea induced a slight increase in arterial pCO2, a significant decrease in pO2, and an increase in cerebral blood flow (CBF) by 54%. In animals not previously exposed to cigarette smoke apnea increased CBF by 121%, demonstrating that a short-term exposure to tobacco smoke influences the cerebrovascular reactivity for more than one hour. In the testis, apnea resulted in a decreased blood flow by 39% and a complete depression of vasomotion. Breathing 10% O2/90% N2 resulted in moderate hypoxia, a total disappearance of the vasomotion in the testis, a 24% decrease in testicular blood flow, but a 23% increase in CBF.

Animals↗

PubMed1999

Continuous interscalene brachial plexus block for postoperative analgesia following shoulder surgery.

BACKGROUND: Severe postoperative pain is a well-known problem following shoulder surgery. This study evaluates the clinical efficacy of continuous interscalene brachial plexus block, patient-controlled analgesia, and morphine (i.v. and i.m.) for postoperative analgesia in this setting. METHODS: Thirty patients, scheduled for acromioplasty during general anesthesia, were randomly allocated to one of three different postoperative pain management groups. Group MO received morphine (5 mg i.m. and 2 mg i.v.) when visual analogue pain score (VAS) > 3, group PL received a continuous interscalene brachial plexus block with bupivacaine (1.25 mg kg-1 + 0.25 mg kg-1 h-1) and group PCA received patient-controlled analgesia with morphine (bolus 1 mg). Postoperative pain relief was assessed (24 h) by VAS, circulatory and respiratory stress parameters (heart rate, systemic arterial pressure and respiratory rate) and stress metabolites (glucose, lactate, glycerol by abdominal subcutaneous microdialysis). RESULTS: Pain relief in the PL group was effective (VAS < 3) and significantly more potent than in groups MO and PCA, except at 16 and 20 h. Lactate was significantly increased in the PL group, glucose was significantly increased in all groups, while glycerol showed a variable pattern. There were no significant stress metabolite differences among groups. VAS showed no statistical correlation with microdialysate, respiratory or circulatory data. CONCLUSION: Successful continuous interscalene brachial plexus block provides very good pain relief following shoulder surgery and is superior to the other methods studied. However, we were unable to demonstrate a correlation between VAS pain scores and stress indicators in metabolic, circulatory and respiratory parameters.

Adolescent↗

PubMed1998

The neuropeptide TRH has a minor effect on the enzymatic activity of acetylcholinesterase in vitro.

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.

Acetylcholinesterase↗

PubMed1997

Tumor blood flow and the cytotoxic effects of estramustine and its constituents in a rat glioma model.

OBJECTIVE: Estramustine (EaM) is a conjugate of nor-nitrogen mustard (NNM) and 17 beta-estradiol (E2) that has cytotoxic and radiosensitizing effects on experimental malignant glioma. Its mechanism of action is only partly understood. To further investigate the mechanism in vivo, the effects on tumor blood flow (TBF) and tumor growth were analyzed. METHODS: TBF was measured by radioactive microspheres, and tumor growth was measured by weight. Apoptosis was evaluated by in situ end labeling and gel electrophoresis. The effects of the constituents NNM and E2 were also evaluated. RESULTS: EaM increased TBF to 153.8 ml/100 g/min after 3 days and to 153.9 ml/100 g/min after 10 days of treatment, compared with 94.0 ml/100 g/min in untreated controls. Cerebral blood flow did not change after EaM treatment. NNM increased TBF but also showed a tendency to increase cerebral blood flow. E2 increased TBF, whereas cerebral blood flow was unchanged. EaM resulted in a rapid reduction in tumor weight from 230 mg in untreated animals to 146 mg after 3 days of treatment. EaM induced an early transient fragmentation of deoxyribonucleic acid in glioma but not in the normal brain. Neither NNM nor E2 affected tumor weight. CONCLUSION: EaM increases TBF in the BT4C rat glioma model with a concomitant rapid antitumoral effect. The increase in TBF could partially be induced by an estrogen-like action of EaM, but the rapid cytotoxic effect of the drug is obviously attributed to the intact EaM compound. This cytotoxic effect might be attributable to the induction of programmed cell death.

Animals↗

PubMed1997

The effect of the calcium antagonist nimodipine on the detoxification of soman in anaesthetized rabbits.

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 micrograms kg-1 i.v.). Blood samples from the left heart ventricle and femoral artery were used to investigate soman detoxification. The concentrations of the soman isomers C+P- and C-P- in blood samples were determined by gas chromatography coupled with high-resolution mass spectrometry. During the sampling, 15-300 s after soman injection, the soman concentration in control animals decreased from 50 to 0.029 ng mL-1; in animals pre-treated with nimodipine (10 mg kg-1) it decreased from 15 to 0.033 ng mL-1. In animals pre-treated with nimodipine the soman concentration was significantly reduced during the first minute of sampling. No differences were detected between soman concentrations in samples from the heart and femoral artery. Acetylcholinesterase inhibition was also used as an indicator of soman activity; there was no difference between the activity of this enzyme in different peripheral organs of control and nimodipine-treated animals. Nimodipine reduces the initial concentration of soman in the blood, which might be of significance in the treatment of soman intoxication.

Acetylcholinesterase↗

PubMed1997

Terpene-enhanced transdermal permeation of water and ethanol in human epidermis.

The study was performed to investigate the effect of penetration enhancers on the stratum corneum barrier. Epidermal membranes were prepared from freeze-stored (-70 degrees C) Caucasian breast skin and mounted in a flow-through diffusion cell. The validity of the freeze storage procedure was verified by measurement of [3H]-water penetration. The effect of the cyclic terpene, carveol, on the transdermal penetration of water and ethanol was studied in vitro. Control ethanol and water penetration measured with a donor solution of 50% ethanol/PBS (w/w) was 1.9+/-0.2 and 3.6+/-0.5 x 10(-3) cm/h. The addition of 3% carveol to the donor solution increased the permeation of ethanol and water after 4 h to 8.3+/-1.1 and 12.5+/-1.9 x 10(-3) cm/h, respectively. In a separate experiment, terpinen-4-ol and alpha-terpineol were also tested, in addition to carveol, for effect on tritium flux. No significant difference in maximum tritium flux was obtained between the three terpenes studied. The maximum increase in permeability coefficients of carveol, terpinen-4-ol and alpha-terpineol was 10.6, 8.7 and 10.9, respectively.

Cyclohexane Monoterpenes↗

PubMed1996

Effects of TRH and atropine on induction and duration of anesthesia with propofol in rats.

The effects of IV TRH pretreatment on induction of anesthesia with propofol or pentobarbital were investigated in rats. The effects of IV TRH, administered after induction, on duration of propofol anesthesia and the interaction with atropine were also studied. The doses of propofol or pentobarbital were not influenced by TRH. TRH reduced duration of anesthesia after propofol, with higher brain concentrations of propofol at recovery. Atropine did not block this effect, but given alone prolonged duration of anesthesia. It is concluded that TRH shortens the duration of propofol anesthesia, probably due to a pharmacodynamic effect and not to a pharmacokinetic interaction.

Anesthesia↗