| 1. |
- Eklund, Anders, et al.
(författare)
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Infusion technique can be used to distinguish between dysfunction of a hydrocephalus shunt system and a progressive dementia
- 2004
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Ingår i: Medical and Biological Engineering and Computing. - : Springer. - 0140-0118 .- 1741-0444. ; 42:5, s. 644-649
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Tidskriftsartikel (refereegranskat)abstract
- In a deteriorating shunted patient with hydrocephalus, an investigation of shunt function is often performed to distinguish a dysfunctioning shunt from an aggravated condition of the disease. The paper illustrates how a lumbar cerebrospinal fluid (CSF) infusion method can be used to evaluate post-operative deterioration in a shunted patient in order to give the physician valuable support in the shunt revision decision. A 77-year-old man with hydrocephalus was treated operatively by the insertion of a CSF shunt. Owing to shunt failure, the shunt was revised twice during a 5 year period. Using a computerised infusion technique method, with two needles placed in the lumbar subarachnoid space, the CSF dynamic system was determined pre- and post-operatively with the functioning as well as the dysfunctioning shunts. The data were verified with a bench-test of the extirpated CSF shunt. There was a significant difference in conductance G between CSF systems with an open shunt and CSF systems with no shunt or an occluded shunt (ΔG=38mm3 s−1 kPa−1, p=0.014, n=7, ANOVA). CSF dynamics investigations, with and without a shunt, can give valuable clinical support in the management of a deteriorating hydrocephalus patient. With further development of the lumbar infusion method moving towards easy-to-use equipment, there is potential for widespread clinical use.
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| 2. |
- Johansson, M., et al.
(författare)
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Interleukin-2 and histamine in combination inhibit tumour growth and angiogenesis in malignant glioma
- 2000
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Ingår i: British Journal of Cancer. - : Cancer Research Campaign. - 0007-0920 .- 1532-1827. ; 83:6, s. 826-832
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Karlsson, Britt M., et al.
(författare)
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Nimodipine affects the microcirculation and modulates the vascular effects of acetylcholinesterase inhibition
- 2003
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Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; 108:2, s. 141-149
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 4. |
- Koskinen, Lars-Owe D., Professor, 1955-, et al.
(författare)
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Cerebrovascular effects of the TRH analogues pGlu-3-methyl-His-Pro amide and pGlu-Glu-Pro amide : a comparison with TRH.
- 2000
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Ingår i: Upsala Journal of Medical Sciences. - : Upsala Medical Society. - 0300-9734 .- 2000-1967. ; 105:1, s. 73-83
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 5. |
- Koskinen, Lars-Owe D., Professor, 1955-, et al.
(författare)
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Cigarette smoke and hypoxia induce acute changes in the testicular and cerebral microcirculation
- 2000
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Ingår i: Upsala Journal of Medical Sciences. - : Taylor & Francis. - 0300-9734 .- 2000-1967. ; 105:3, s. 215-226
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Tidskriftsartikel (refereegranskat)abstract
- 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.Our results indicate that short-term exposure to tobacco smoke induces marked acute vascular effects in both the brain and the testis. Apnea and moderate hypoxia elicited totyally different effects in the brain and testis, inicating different vascular control mechanisms.
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| 6. |
- Koskinen, Lars-Owe D., Professor, 1955-, et al.
(författare)
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Nitric oxide inhibition by L-NAME but not 7-NI induces a transient increase in cortical cerebral blood flow and affects the cerebrovasodilation induced by TRH
- 2003
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Ingår i: Peptides. - : Elsevier. - 0196-9781 .- 1873-5169. ; 24:4, s. 579-583
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Tidskriftsartikel (refereegranskat)abstract
- 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 microg 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.
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| 7. |
- Lundkvist, B., et al.
(författare)
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An adjustable CSF shunt : advices for clinical use
- 2003
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Ingår i: Acta Neurologica Scandinavica. - : Wiley-Blackwell. - 0001-6314 .- 1600-0404. ; 108:1, s. 38-42
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The opening pressure and the resistance of a CSF shunt are essential for clinical use in order to set the proper opening pressure and to determine the shunt function in vivo. We find it of vital importance to validate and supplement the product description given by the manufacturer. The in vitro properties of a newly introduced, adjustable differential pressure valve with a siphon-preventing device (Strata valve) was compared with its predecessor (Delta valve).METHODS: An automated, computerized experimental set-up based on regulation of pressure, built into an incubator at 37 degrees C, was used. Opening pressure, resistance and siphon preventing properties were determined. Six brand-new shunts of each type with catheters were tested. The Delta valves were at a performance level of 1.5.RESULTS: The hydrodynamic properties of the Strata and Delta valves were similar. The anti-siphoning device was functioning for all valves. The estimated mean resistance for Delta and Strata shunts was 2.6 +/- 0.4 and 2.2 +/- 1.0 mmHg/ml/min, respectively. The mean opening pressure for the five performance levels of the Strata shunt are: 3.3, 5.1, 7.7, 10.7 and 13.1 mmHg. There may however, be considerable variations between the shunts.CONCLUSIONS: The Strata shunt is a properly working adjustable valve with anti-siphoning device that showed good reproducibility concerning opening pressure and resistance. At performance level 1.5, the new Strata shunt was similar to its predecessor concerning opening pressure and resistance. The given values of the different opening pressures and resistance could be used for in vivo testing of the valve function with a standard lumbar CSF infusion test.
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| 8. |
- Magnusson, B. M., et al.
(författare)
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Biological effects after percutaneous absorption of thyrotropin-releasing hormone and its analogue M-TRH
- 2001
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Ingår i: Peptides. - : Elsevier. - 0196-9781 .- 1873-5169. ; 22:1, s. 73-79
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
- Magnusson, B.M., et al.
(författare)
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In vitro percutaneous penetration of topically applied capsaicin in relation to in vivo sensation responses
- 2000
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Ingår i: International Journal of Pharmaceutics. - : Elsevier BV. - 0378-5173 .- 1873-3476. ; 195:1-2, s. 55-62
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Tidskriftsartikel (refereegranskat)abstract
- Capsaicin, the primary pungent element in several spices, elicits a variety of physiological effects which are due to neurogenic responses. The aim of the study was to explore the in vivo sensation responses of capsaicin and to compare the results with the in vitro percutaneous absorption of the substance. The overall objectives were to determining an in vitro-in vivo correlation for capsaicin. Capsaicin was applied in a chamber on the volar forearm of twelve volunteers and in a flow-through diffusion chamber on excised human epidermal membranes. Topical administration of capsaicin produced a complex cutaneous sensation that changed in intensity and quality as a function of time and was characterized by sting, prick, burn and pain. Percutaneous steady-state penetrations of capsaicin with a receptor fluid consisting either of 4% bovine serum albumin in phosphate buffered saline or 50% ethanol in water were 28.2+/-2.7 and 29.6+/-2.9 microg/cm(2) per h, respectively. The corresponding cumulative penetrated amounts of capsaicin after 30 min were 14. 7+/-1.7 and 19.2+/-2.1 microg/cm(2), respectively. The present investigation indicates that there is a good correlation between in vivo physiological responses and in vitro percutaneous penetration of topically applied capsaicin.
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| 10. |
- Naredi, S., et al.
(författare)
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An outcome study of severe traumatic head injury using the "Lund therapy" with low-dose prostacyclin
- 2001
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Ingår i: Acta Anaesthesiologica Scandinavica. - : Wiley-Blackwell. - 0001-5172 .- 1399-6576. ; 45:4, s. 402-406
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Tidskriftsartikel (refereegranskat)abstract
- 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) ≤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.
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