The relationships among ischaemic GABA efflux from brain tissue and extracellular and intracellul... more The relationships among ischaemic GABA efflux from brain tissue and extracellular and intracellular concentrations of sodium, chloride and potassium ions were investigated by means of 1) transverse hippocampal slices from rat and 2) functional expression of a high affinity GABA transporter inXenopus oocytes. Brain slices were incubated for 20 min in medium where extracellular sodium and chloride were substituted with impermeant ions. Isethionate (Iseth) substitution for chloride generated a 7-fold increase in GABA efflux. Choline (Chol) but not N-methyl-D-glucamine (NMDG) substitution for sodium likewise increased GABA efflux. Reducing the osmolarity of the medium by decreasing both sodium and chloride concentrations (Hyp) increased GABA efflux 3-fold. This release was blocked by mannitol (Man). Blocking sodium channels with 1 μM of tetrodotoxin (TTX) also increased the release 3-fold. Energy deprivation (ED) increased the GABA release 50-fold. ED/Iseth left the release unchanged, ED/Chol increased the GABA efflux by 23%, whereas ED/NMDG reduced the release by 41%. Adding mannitol did not block the ED-evoked release, whereas TTX reduced it by 52%. Release of preloaded [3H]-GABA from oocytes expressing the GAT-1 GABA transporter was then examined. Depolarisation by current injection or 100 mM extracellular K+ did not increase GABA release. Sodium chloride injection, however, caused membrane depolarisation and a 100-fold increased GABA efflux from the oocytes. This release was blocked when the osmolarity was increased extracellularly by adding mannitol. These results show that 1) TTX releases GABA from brain tissue but blocks release during ED, 2) the high affinity GABA carrier must be altered in order to reverse, 3) ischaemic GABA release is sodium independent, and is modulated by large cations, 4) mannitoi blocks the reversal of high affinity carriers in oocytes, but the release from brain slices during ED is unaffected. Taken together, the results suggest that ischaemic release of GABA from brain tissue does not occur by means of reversed high affinity carriers alone, but rather that it is controlled by more complex mechanisms.
American Journal of Obstetrics and Gynecology, 2006
The etiology of chronic pelvic pain is disputed and multifactorial. We studied the effect of Mens... more The etiology of chronic pelvic pain is disputed and multifactorial. We studied the effect of Mensendieck somatocognitive therapy aimed at reducing physical pain by changing posture, movement and respiration patterns combined with standard gynecological treatment.Women with chronic pelvic pain unexplained by pelvic pathology were randomized into 2 groups: (1) standard gynecological treatment and (2) gynecological treatment plus somatocognitive therapy. A Mensendieck test of motor function (posture, movement, gait, sitting posture, respiration) and a visual analogue score of pain were obtained before and after the 90-day treatment period.The test results of patients treated by standard gynecological measures were unchanged (nonsignificant). By contrast, the patients receiving somatocognitive therapy in addition improved scores by 25% to 60% for all motor functions (P < .01, largest improvement for respiration, up from average 2.98 [SEM 0.30] to 4.72 [0.37]), and pain scores reduced by 50% (down from 5.60 [0.40] to 2.89 [0.40], P < .01).Mensendieck somatocognitive therapy combined with standard gynecological care improved pain experience and motor functions of women with chronic pelvic pain better than gynecological treatment alone.
The release of 10 amino acids from rat hippocampal slices during exposure to hyposmotic stress or... more The release of 10 amino acids from rat hippocampal slices during exposure to hyposmotic stress or energy deprivation was measured by high-performance liquid chromatography. Exposing the slices to hyposmotic stress by lowering extracellular NaCl caused a 10-fold release of taurine (p &lt; 0.01) and over a twofold increase of gamma-aminobutyric acid (GABA) and glutamate (p &lt; 0.01). These changes were reversed by mannitol. Exposure to combined glucose and oxygen deprivation (energy deprivation) caused a 50-fold increase in the release of GABA, a 40-fold increase in glutamate release (p &lt; 0.01), and a twofold to sixfold increase in taurine, aspartate, glycine, asparagine, serine, and alanine release (p &lt; 0.05) but no change in glutamine. Energy deprivation increased the water content by 21%. Mannitol blocked this increase and further enhanced the release of glutamate and aspartate (p &lt; 0.01) but not of GABA. The permissivity of the amino acids was plotted against the pI (pH at isoelectric point) and hydropathy indexes. Energy deprivation increased the permissivity in the following order: acidic &gt; neutral &gt; basic. Among neutral amino acids, permissivity increased with increasing hydrophobicity. These results indicate that the mechanisms of amino acid release are different during cerebral ischemia and hyposmotic stress.
Historic background and development of our somatocognitive approach: Mensendieck physiotherapy of... more Historic background and development of our somatocognitive approach: Mensendieck physiotherapy of the Oslo School is a tradition of physiotherapy founded by the American physician Bess Mensendieck, a contemporary and fellow student of Sigmund Freud at the Paris School of Neurology. It builds on the principles of functional anatomy and the theories of motor learning. We have further developed the theory and practice from this physiotherapy tradition, challenged by the enormous load of patients with longstanding, incapacitating pain on western health care systems, by seeking to incorporate inspirational ideas from body oriented dynamic psychotherapy and cognitive psychotherapy. We developed somatocognitive therapy as a hybrid of physiotherapy and cognitive psychotherapy by focusing on the present cognitive content of the mind of the patient, contrary to a focus on analysis of the subconscious and interpretation of dreams, and acknowledging the important role of the body in pain-eliciting defense mechanisms against mental stress and negative emotions. The core of this somatocognitive therapy: (1) To promote awareness of own body, (2) graded task assignment related to the motor patterns utilized in daily activities, (3) combined with an empathic attitude built on dialogue and mutual understanding, and emotional containment and support. The goal is for the patient to develop coping strategies and mastery of own life. In addition, (4) manual release of tensed muscles and applied relaxation techniques are important. Methods and results of an illustrative study: One area in particular need of development and research is sexual pain disorders. We have applied this somatocognitive therapy in a randomized, controlled intervention study of women with chronic pelvic pain (CPP). We summarize methods and results of this study. Methods: 40 patients with CPP were included in a randomized, controlled intervention study. The patients were randomized into (1) a control group, receiving treatment as usual (Standard Gynecological Treatment, STGT) and (2) a group receiving STGT + Mensendieck Somatocognitive Therapy (MSCT). The patients were assessed by means of Visual Analogue Scale of Pain (VASP), Standardized Mensendieck Test (SMT) for analysis of motor patterns (posture, movement, gait, sitting posture and respiration), and General Health Questionnaire (GHQ-30) assessing psychological distress, at baseline (inclusion into study), after three months of out-patient therapy and at 1 year follow-up. Results: The women averaged 31 years, pain duration 6.1 years, average number of previous surgical procedures 1.8 per women. In the STGT group, no significant change was found, neither in pain scores, motor patterns or psychological distress during the observation period. In the group receiving STGT + MSCT, significant reduction in pain score and improvement in motor function were found at the end of therapy, and the significant improvement continued through the follow-up (64% reduction of pain scores, and 80% increase in the average score for respiration, as an example of motor pattern improvement). GHQ scores were significantly improved for anxiety and coping (p < 0.01). Conclusions: Somatocognitive therapy is a new approach that appears to be very promising in the management of chronic gynecological pain. Short-term out-patient treatment significantly reduces pain scores and improves motor function. Implications: Chronic pelvic pain in women is a major health care problem with no specific therapies and poor prognosis. A novel, somatocognitive approach has documented positive effects. It is now studied by other clinical researchers in order to reinforce its evidence base.
Most heart transplant (HTx) recipients develop hypertension, characterized by increased periphera... more Most heart transplant (HTx) recipients develop hypertension, characterized by increased peripheral vascular tone and endothelial dysfunction. Reduced levels of nitric oxide (NO) have been found in essential hypertension, and herein we investigated the possible role of altered concentrations of NO in posttransplant hypertension. Plasma levels of the NO-derived end products NO2(-) + NO3(-), the endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA), and the inflammatory cytokine tumor necrosis factor (TNF)-alpha were examined in 65 stable hypertensive long-term (6 years [range 1-13]) survivors of HTx. HTx recipients were compared with 39 individuals with essential hypertension and 25 normotensive controls. RESULTS Hypertensive HTx recipients had raised NO2(-) + NO3(-) levels in plasma, positively correlated with 24-hour mean blood pressure (BP). In contrast, individuals with essential hypertension had decreased NO2(-) + NO3(-) concentration comparing controls, inversely correlated with 24-hour mean BP. Moreover, although TNF-alpha levels were significantly raised in HTx recipients compared with both healthy controls and individuals with essential hypertension, it was positively correlated to 24-hour BP and NO2(-) + NO3(-). Although only a slight increase was found in essential hypertension, no correlations were found in these nontransplant individuals. Finally, although asymmetric dimethylarginine (ADMA) tended to be raised in essential hypertension, this endogenous nitric oxide synthase (NOS) inhibitor was significantly decreased in HTx recipients compared with normotensive controls. Our findings suggest that different mechanisms may be operating in the pathogenesis of posttransplant compared with essential hypertension, with persistent inflammation, raised NO2(-) + NO3(-), and decreased ADMA levels characterizing the former group.
This article describes the effect of isoflurane on amino acid release and tissue content induced ... more This article describes the effect of isoflurane on amino acid release and tissue content induced by energy deprivation in slices of rat hippocampus. Energy deprivation (95% N2 / 5% CO2 and glucose free medium) (ED) induced an increase in the release of all amino acids measured, with the exception of glutamine. The tissue content of all amino acids except gamma-aminobutyric acid (GABA) and arginine was concomitantly reduced. Isoflurane (1.5% and 3.0%) reduced glutamate release during ED by 27% and 28% (p &lt; 0.05 as compared with release without isoflurane), respectively, whereas the tissue content was slightly increased. Similarly, GABA release was reduced by 25% and 25% (p &lt; 0.05 as compared with release without isoflurane) accompanied by an insignificant enhancement in tissue content as compared with ED without isoflurane. Isoflurane reduced the release of taurine and most of the other amino acids. The total amount of all amino acids (both released and retained) was not significantly altered by the anesthetic. These observations demonstrate that isoflurane can modify the changes in amino acid handling induced by energy deprivation.
Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, has been suggested to... more Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, has been suggested to be a novel risk factor for endothelial dysfunction. It has previously been reported that hyperhomocysteinaemia may be associated with impaired endothelium-dependent vasodilation and reduced plasma level of NO-derived endproducts (NOx). In the present study, plasma levels of arginine and ADMA were measured in twenty-one healthy control subjects, and in twenty-one hyperhomocysteinaemic subjects before and after 6 weeks and 12 months of folic acid supplementation, and compared with previously measured plasma NOx values in the hyperhomocysteinaemic subjects. Compared with control subjects, hyperhomocysteinaemic subjects had higher plasma levels of arginine and ADMA. More importantly, folic acid therapy significantly reduced plasma levels of arginine and ADMA. Furthermore, plasma levels of arginine and ADMA were positively correlated with plasma homocysteine levels and negatively correlated with plasma folate, as well as negatively correlated with plasma NOx. Our results suggest that ADMA may be a mediator of the atherogenic effects of homocysteine. * Corresponding author: Dr Kirsten B. Holven, fax +47 2307 3630, email [email protected]
Historic background and development of our somatocognitive approach: Mensendieck physiotherapy of... more Historic background and development of our somatocognitive approach: Mensendieck physiotherapy of the Oslo School is a tradition of physiotherapy founded by the American physician Bess Mensendieck, a contemporary and fellow student of Sigmund Freud at the Paris School of Neurology. It builds on the principles of functional anatomy and the theories of motor learning. We have further developed the theory and practice from this physiotherapy tradition, challenged by the enormous load of patients with longstanding, incapacitating pain on western health care systems, by seeking to incorporate inspirational ideas from body oriented dynamic psychotherapy and cognitive psychotherapy. We developed somatocognitive therapy as a hybrid of physiotherapy and cognitive psychotherapy by focusing on the present cognitive content of the mind of the patient, contrary to a focus on analysis of the subconscious and interpretation of dreams, and acknowledging the important role of the body in pain-eliciting defense mechanisms against mental stress and negative emotions. The core of this somatocognitive therapy: (1) To promote awareness of own body, (2) graded task assignment related to the motor patterns utilized in daily activities, (3) combined with an empathic attitude built on dialogue and mutual understanding, and emotional containment and support. The goal is for the patient to develop coping strategies and mastery of own life. In addition, (4) manual release of tensed muscles and applied relaxation techniques are important. Methods and results of an illustrative study: One area in particular need of development and research is sexual pain disorders. We have applied this somatocognitive therapy in a randomized, controlled intervention study of women with chronic pelvic pain (CPP). We summarize methods and results of this study. Methods: 40 patients with CPP were included in a randomized, controlled intervention study. The patients were randomized into (1) a control group, receiving treatment as usual (Standard Gynecological Treatment, STGT) and (2) a group receiving STGT + Mensendieck Somatocognitive Therapy (MSCT). The patients were assessed by means of Visual Analogue Scale of Pain (VASP), Standardized Mensendieck Test (SMT) for analysis of motor patterns (posture, movement, gait, sitting posture and respiration), and General Health Questionnaire (GHQ-30) assessing psychological distress, at baseline (inclusion into study), after three months of out-patient therapy and at 1 year follow-up. Results: The women averaged 31 years, pain duration 6.1 years, average number of previous surgical procedures 1.8 per women. In the STGT group, no significant change was found, neither in pain scores, motor patterns or psychological distress during the observation period. In the group receiving STGT + MSCT, significant reduction in pain score and improvement in motor function were found at the end of therapy, and the significant improvement continued through the follow-up (64% reduction of pain scores, and 80% increase in the average score for respiration, as an example of motor pattern improvement). GHQ scores were significantly improved for anxiety and coping (p < 0.01). Conclusions: Somatocognitive therapy is a new approach that appears to be very promising in the management of chronic gynecological pain. Short-term out-patient treatment significantly reduces pain scores and improves motor function. Implications: Chronic pelvic pain in women is a major health care problem with no specific therapies and poor prognosis. A novel, somatocognitive approach has documented positive effects. It is now studied by other clinical researchers in order to reinforce its evidence base.
American Journal of Obstetrics and Gynecology, 2008
Chronic pelvic pain is a common source of disability among women in the western world. Here we re... more Chronic pelvic pain is a common source of disability among women in the western world. Here we report that 3 months of Mensendieck somatocognitive intervention in chronic pelvic pain patients was followed by continued improvements of outcomes at 1-year follow-up in a randomized, controlled study design. Forty women with chronic pelvic pain unexplained by pelvic pathology were randomly assigned to 2 groups: (1) standard gynecologic treatment and (2) gynecologic treatment plus somatocognitive therapy aimed at reducing physical pain by changing posture, movement, and respiration patterns. A standardized Mensendieck test (SMT) of motor function (assessing posture, movement, gait, sitting posture, and respiration), a self-rating questionnaire assessing psychologic distress and general well-being (GHQ-30) and a visual analog score of pain (VAS) were obtained before, after 90 days of treatment and 1 year after inclusion. Patients treated by standard gynecologic treatment/supervision did not improve significantly at 1-year follow-up in any of the test modalities. By contrast, those who in addition received somatocognitive therapy had improved scores for all motor functions and pain, as well as GHQ-30 scores for coping, and anxiety-insomnia-distress. Mensendieck somatocognitive therapy combined with standard gynecologic care improves psychologic distress, pain experience, and motor functions of women with chronic pelvic pain better than gynecologic treatment alone. The effect lasted and even further improvement occurred 9 months after treatment.
Objective: Chronic pelvic pain (CPP) is a common cause of infirmity but is still poorly understoo... more Objective: Chronic pelvic pain (CPP) is a common cause of infirmity but is still poorly understood. We studied the clinical characteristics, including body awareness, of 60 women with this diagnosis compared to those of healthy controls in an effort to understand its pathophysiology and to develop a more efficient treatment protocol. Methods: After prior gynecologic and psychometric evaluation, the women were examined with the Standardized Mensendieck Test to evaluate posture and movement patterns. Pain history and pain score were obtained, and patterns of muscular density, elasticity, and tenderness were determined by palpation. The body awareness of patients was assessed through clinical evaluation.
A standardized test was developed to evaluate posture, movement, gait, sitting posture, and respi... more A standardized test was developed to evaluate posture, movement, gait, sitting posture, and respiration of patients with psychosomatic disorders, based on the Mensendieck principles of observation and analysis of motor function. To validate the test and to make a comprehensive body examination of a defined group of patients, it was applied in a study of women with chronic pelvic pain (CPP, ICD10 F45.4). Fifteen women with CPP and 15 matched, healthy controls were examined. Test subjects were video recorded and scored by three experienced Mensendieck physical therapists, blinded with respect to the selection of subjects. Scores from 0 (for least functional movement) to 7 (optimal function) were assigned to each test person according to a test manual. High intraclass correlations (Chronbach's alpha ranging from 0.82 to 0.97) were found among the testers. The standardized Mensendieck test (SMT) discriminated well between women with CPP and the controls (sensitivity 0.9, specificity 0.7, mean values). The CPP patients scored significantly lower than the controls in all subtests (p < 0.01). The largest difference in scores were found for gait (patients 2.70 AE 0.11, vs. control, 5.60 AE 0.09) and respiration (patients 2.88 AE 0.14, vs. control, 5.63 AE 0.10). The results indicate that, in the hands of experienced Mensendieck therapists, the SMT is a reliable tool, demonstrating a good discriminative validity. Furthermore, it may turn out to be a useful instrument in the evaluation of patients with somatoform disorders. It may also point toward a possible therapeutic treatment approach to patients with CPP.
The aim of the present study was to investigate the release of amino-acids in human cerebral cort... more The aim of the present study was to investigate the release of amino-acids in human cerebral cortex during membrane depolarization and simulated ischaemia (energy deprivation). Superfluous tissue from temporal lobe resections for epilepsy was cut into 500 μm thick slices and incubated in vitro. Membrane depolarization with 50 mM K+ caused a release of glutamate, aspartate, GABA and glycine, but not glutamine or leucine. The release of glutamate and GABA was Ca++-dependent. Slices were exposed to simulated ischaemia (energy deprivation; ED) by combined glucose/oxygen deprivation. This caused a Ca++-indepedent release of glutamate, aspartate, GABA, glycine, and taurine which started after 8 min, peaked at the end or shortly after the 27 min period of ED, and returned to control levels within 11 min following termination of ED. Preloaded D-[3H]aspartate was released both during K+-stimulation and ED. Release of D-[3H]aspartate during ED was delayed compared to glutamate supporting an initial phase of synaptic glutamate release. Uptake of L-[3H]glutamate was increased during the period of glutamate release, suggesting passive diffusion across the cell membrane or enhanced transport efficacy in cellular elements with functioning uptake mechanisms.
A standardized test was developed to evaluate posture, movement, gait, sitting posture, and respi... more A standardized test was developed to evaluate posture, movement, gait, sitting posture, and respiration of patients with psychosomatic disorders, based on the Mensendieck principles of observation and analysis of motor function. To validate the test and to make a comprehensive body examination of a defined group of patients, it was applied in a study of women with chronic pelvic pain (CPP, ICD10 F45.4). Fifteen women with CPP and 15 matched, healthy controls were examined. Test subjects were video recorded and scored by three experienced Mensendieck physical therapists, blinded with respect to the selection of subjects. Scores from 0 (for least functional movement) to 7 (optimal function) were assigned to each test person according to a test manual. High intraclass correlations (Chronbach's alpha ranging from 0.82 to 0.97) were found among the testers. The standardized Mensendieck test (SMT) discriminated well between women with CPP and the controls (sensitivity 0.9, specificity 0.7, mean values). The CPP patients scored significantly lower than the controls in all subtests (p < 0.01). The largest difference in scores were found for gait (patients 2.70 AE 0.11, vs. control, 5.60 AE 0.09) and respiration (patients 2.88 AE 0.14, vs. control, 5.63 AE 0.10). The results indicate that, in the hands of experienced Mensendieck therapists, the SMT is a reliable tool, demonstrating a good discriminative validity. Furthermore, it may turn out to be a useful instrument in the evaluation of patients with somatoform disorders. It may also point toward a possible therapeutic treatment approach to patients with CPP.
Plasma c o n c e n t r a t i o n s of f i v e AA ( a s p a r a t e ASP, g l u t a m a t e GLU, g ... more Plasma c o n c e n t r a t i o n s of f i v e AA ( a s p a r a t e ASP, g l u t a m a t e GLU, g l y c i n e GLY, t a u r i n e TAU, and gamma-aminob u t y r i c a c i d GABA were measured i n a r t e r i a l ( a ) and s a g i t t a l s i n u s ( v ) plasma samples i n n i n e p i g l e t s exposed t o H0(10% 0,) and k N ( b l e e d i n g 2 0 % ) . Samples were t a k e n a t b a s e l i n e (BL), d u r i n g HO, a f t e r HV, and 30 ( 3 0 ' ) and 60 min ( 6 0 ' ) a f t e r HO. B e s u l t s I ; ( p e r c e n t change from BL, a samples, m e a n i s m ) .
The release of the amino acids GABA, taurine, glycine, glutamine and leucine from human neocortex... more The release of the amino acids GABA, taurine, glycine, glutamine and leucine from human neocortex was investigated in vitro by utilizing brain tissue removed during 8 standard temporal lobectomies for epilepsy or tumor. Slices (0.5 mm thick) were cut from each biopsy and randomly placed in three different chambers. After 90 min preincubation, the three sets of slices were incubated for 60 s in wells containing, respectively, (A) regular ACSF (control), (B) ACSF with 50 mM K + (to depolarize the cell membrane) and (C) ACSF with 50 mM K +, 0 mM Ca 2. and 4 mM Mg 2÷ (depolarization during blocked synaptic transmission). The content of amino acids in the wells was determined by high-performance liquid chromatography after pre-column derivatization of the amino acids with o-phthalaldehyde. Membrane depolarization (well B) increased the GABA release to 650% (620 pmol/mg) of control (well A, 95 pmol/mg). Blocking synaptic transmission (well C) reduced the evoked release by 50% (360 pmol/mg). The release of glycine, taurine, glutamine and leucine during membrane depolarization was not significantly different from the control values. The data provide evidence for a Ca2+-dependent release of GABA, supporting a possible role of this amino acid as a neurotransmitter in human neocortex.
The relationships among ischaemic GABA efflux from brain tissue and extracellular and intracellul... more The relationships among ischaemic GABA efflux from brain tissue and extracellular and intracellular concentrations of sodium, chloride and potassium ions were investigated by means of 1) transverse hippocampal slices from rat and 2) functional expression of a high affinity GABA transporter inXenopus oocytes. Brain slices were incubated for 20 min in medium where extracellular sodium and chloride were substituted with impermeant ions. Isethionate (Iseth) substitution for chloride generated a 7-fold increase in GABA efflux. Choline (Chol) but not N-methyl-D-glucamine (NMDG) substitution for sodium likewise increased GABA efflux. Reducing the osmolarity of the medium by decreasing both sodium and chloride concentrations (Hyp) increased GABA efflux 3-fold. This release was blocked by mannitol (Man). Blocking sodium channels with 1 μM of tetrodotoxin (TTX) also increased the release 3-fold. Energy deprivation (ED) increased the GABA release 50-fold. ED/Iseth left the release unchanged, ED/Chol increased the GABA efflux by 23%, whereas ED/NMDG reduced the release by 41%. Adding mannitol did not block the ED-evoked release, whereas TTX reduced it by 52%. Release of preloaded [3H]-GABA from oocytes expressing the GAT-1 GABA transporter was then examined. Depolarisation by current injection or 100 mM extracellular K+ did not increase GABA release. Sodium chloride injection, however, caused membrane depolarisation and a 100-fold increased GABA efflux from the oocytes. This release was blocked when the osmolarity was increased extracellularly by adding mannitol. These results show that 1) TTX releases GABA from brain tissue but blocks release during ED, 2) the high affinity GABA carrier must be altered in order to reverse, 3) ischaemic GABA release is sodium independent, and is modulated by large cations, 4) mannitoi blocks the reversal of high affinity carriers in oocytes, but the release from brain slices during ED is unaffected. Taken together, the results suggest that ischaemic release of GABA from brain tissue does not occur by means of reversed high affinity carriers alone, but rather that it is controlled by more complex mechanisms.
American Journal of Obstetrics and Gynecology, 2006
The etiology of chronic pelvic pain is disputed and multifactorial. We studied the effect of Mens... more The etiology of chronic pelvic pain is disputed and multifactorial. We studied the effect of Mensendieck somatocognitive therapy aimed at reducing physical pain by changing posture, movement and respiration patterns combined with standard gynecological treatment.Women with chronic pelvic pain unexplained by pelvic pathology were randomized into 2 groups: (1) standard gynecological treatment and (2) gynecological treatment plus somatocognitive therapy. A Mensendieck test of motor function (posture, movement, gait, sitting posture, respiration) and a visual analogue score of pain were obtained before and after the 90-day treatment period.The test results of patients treated by standard gynecological measures were unchanged (nonsignificant). By contrast, the patients receiving somatocognitive therapy in addition improved scores by 25% to 60% for all motor functions (P < .01, largest improvement for respiration, up from average 2.98 [SEM 0.30] to 4.72 [0.37]), and pain scores reduced by 50% (down from 5.60 [0.40] to 2.89 [0.40], P < .01).Mensendieck somatocognitive therapy combined with standard gynecological care improved pain experience and motor functions of women with chronic pelvic pain better than gynecological treatment alone.
The release of 10 amino acids from rat hippocampal slices during exposure to hyposmotic stress or... more The release of 10 amino acids from rat hippocampal slices during exposure to hyposmotic stress or energy deprivation was measured by high-performance liquid chromatography. Exposing the slices to hyposmotic stress by lowering extracellular NaCl caused a 10-fold release of taurine (p &lt; 0.01) and over a twofold increase of gamma-aminobutyric acid (GABA) and glutamate (p &lt; 0.01). These changes were reversed by mannitol. Exposure to combined glucose and oxygen deprivation (energy deprivation) caused a 50-fold increase in the release of GABA, a 40-fold increase in glutamate release (p &lt; 0.01), and a twofold to sixfold increase in taurine, aspartate, glycine, asparagine, serine, and alanine release (p &lt; 0.05) but no change in glutamine. Energy deprivation increased the water content by 21%. Mannitol blocked this increase and further enhanced the release of glutamate and aspartate (p &lt; 0.01) but not of GABA. The permissivity of the amino acids was plotted against the pI (pH at isoelectric point) and hydropathy indexes. Energy deprivation increased the permissivity in the following order: acidic &gt; neutral &gt; basic. Among neutral amino acids, permissivity increased with increasing hydrophobicity. These results indicate that the mechanisms of amino acid release are different during cerebral ischemia and hyposmotic stress.
Historic background and development of our somatocognitive approach: Mensendieck physiotherapy of... more Historic background and development of our somatocognitive approach: Mensendieck physiotherapy of the Oslo School is a tradition of physiotherapy founded by the American physician Bess Mensendieck, a contemporary and fellow student of Sigmund Freud at the Paris School of Neurology. It builds on the principles of functional anatomy and the theories of motor learning. We have further developed the theory and practice from this physiotherapy tradition, challenged by the enormous load of patients with longstanding, incapacitating pain on western health care systems, by seeking to incorporate inspirational ideas from body oriented dynamic psychotherapy and cognitive psychotherapy. We developed somatocognitive therapy as a hybrid of physiotherapy and cognitive psychotherapy by focusing on the present cognitive content of the mind of the patient, contrary to a focus on analysis of the subconscious and interpretation of dreams, and acknowledging the important role of the body in pain-eliciting defense mechanisms against mental stress and negative emotions. The core of this somatocognitive therapy: (1) To promote awareness of own body, (2) graded task assignment related to the motor patterns utilized in daily activities, (3) combined with an empathic attitude built on dialogue and mutual understanding, and emotional containment and support. The goal is for the patient to develop coping strategies and mastery of own life. In addition, (4) manual release of tensed muscles and applied relaxation techniques are important. Methods and results of an illustrative study: One area in particular need of development and research is sexual pain disorders. We have applied this somatocognitive therapy in a randomized, controlled intervention study of women with chronic pelvic pain (CPP). We summarize methods and results of this study. Methods: 40 patients with CPP were included in a randomized, controlled intervention study. The patients were randomized into (1) a control group, receiving treatment as usual (Standard Gynecological Treatment, STGT) and (2) a group receiving STGT + Mensendieck Somatocognitive Therapy (MSCT). The patients were assessed by means of Visual Analogue Scale of Pain (VASP), Standardized Mensendieck Test (SMT) for analysis of motor patterns (posture, movement, gait, sitting posture and respiration), and General Health Questionnaire (GHQ-30) assessing psychological distress, at baseline (inclusion into study), after three months of out-patient therapy and at 1 year follow-up. Results: The women averaged 31 years, pain duration 6.1 years, average number of previous surgical procedures 1.8 per women. In the STGT group, no significant change was found, neither in pain scores, motor patterns or psychological distress during the observation period. In the group receiving STGT + MSCT, significant reduction in pain score and improvement in motor function were found at the end of therapy, and the significant improvement continued through the follow-up (64% reduction of pain scores, and 80% increase in the average score for respiration, as an example of motor pattern improvement). GHQ scores were significantly improved for anxiety and coping (p < 0.01). Conclusions: Somatocognitive therapy is a new approach that appears to be very promising in the management of chronic gynecological pain. Short-term out-patient treatment significantly reduces pain scores and improves motor function. Implications: Chronic pelvic pain in women is a major health care problem with no specific therapies and poor prognosis. A novel, somatocognitive approach has documented positive effects. It is now studied by other clinical researchers in order to reinforce its evidence base.
Most heart transplant (HTx) recipients develop hypertension, characterized by increased periphera... more Most heart transplant (HTx) recipients develop hypertension, characterized by increased peripheral vascular tone and endothelial dysfunction. Reduced levels of nitric oxide (NO) have been found in essential hypertension, and herein we investigated the possible role of altered concentrations of NO in posttransplant hypertension. Plasma levels of the NO-derived end products NO2(-) + NO3(-), the endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA), and the inflammatory cytokine tumor necrosis factor (TNF)-alpha were examined in 65 stable hypertensive long-term (6 years [range 1-13]) survivors of HTx. HTx recipients were compared with 39 individuals with essential hypertension and 25 normotensive controls. RESULTS Hypertensive HTx recipients had raised NO2(-) + NO3(-) levels in plasma, positively correlated with 24-hour mean blood pressure (BP). In contrast, individuals with essential hypertension had decreased NO2(-) + NO3(-) concentration comparing controls, inversely correlated with 24-hour mean BP. Moreover, although TNF-alpha levels were significantly raised in HTx recipients compared with both healthy controls and individuals with essential hypertension, it was positively correlated to 24-hour BP and NO2(-) + NO3(-). Although only a slight increase was found in essential hypertension, no correlations were found in these nontransplant individuals. Finally, although asymmetric dimethylarginine (ADMA) tended to be raised in essential hypertension, this endogenous nitric oxide synthase (NOS) inhibitor was significantly decreased in HTx recipients compared with normotensive controls. Our findings suggest that different mechanisms may be operating in the pathogenesis of posttransplant compared with essential hypertension, with persistent inflammation, raised NO2(-) + NO3(-), and decreased ADMA levels characterizing the former group.
This article describes the effect of isoflurane on amino acid release and tissue content induced ... more This article describes the effect of isoflurane on amino acid release and tissue content induced by energy deprivation in slices of rat hippocampus. Energy deprivation (95% N2 / 5% CO2 and glucose free medium) (ED) induced an increase in the release of all amino acids measured, with the exception of glutamine. The tissue content of all amino acids except gamma-aminobutyric acid (GABA) and arginine was concomitantly reduced. Isoflurane (1.5% and 3.0%) reduced glutamate release during ED by 27% and 28% (p &lt; 0.05 as compared with release without isoflurane), respectively, whereas the tissue content was slightly increased. Similarly, GABA release was reduced by 25% and 25% (p &lt; 0.05 as compared with release without isoflurane) accompanied by an insignificant enhancement in tissue content as compared with ED without isoflurane. Isoflurane reduced the release of taurine and most of the other amino acids. The total amount of all amino acids (both released and retained) was not significantly altered by the anesthetic. These observations demonstrate that isoflurane can modify the changes in amino acid handling induced by energy deprivation.
Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, has been suggested to... more Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthase, has been suggested to be a novel risk factor for endothelial dysfunction. It has previously been reported that hyperhomocysteinaemia may be associated with impaired endothelium-dependent vasodilation and reduced plasma level of NO-derived endproducts (NOx). In the present study, plasma levels of arginine and ADMA were measured in twenty-one healthy control subjects, and in twenty-one hyperhomocysteinaemic subjects before and after 6 weeks and 12 months of folic acid supplementation, and compared with previously measured plasma NOx values in the hyperhomocysteinaemic subjects. Compared with control subjects, hyperhomocysteinaemic subjects had higher plasma levels of arginine and ADMA. More importantly, folic acid therapy significantly reduced plasma levels of arginine and ADMA. Furthermore, plasma levels of arginine and ADMA were positively correlated with plasma homocysteine levels and negatively correlated with plasma folate, as well as negatively correlated with plasma NOx. Our results suggest that ADMA may be a mediator of the atherogenic effects of homocysteine. * Corresponding author: Dr Kirsten B. Holven, fax +47 2307 3630, email [email protected]
Historic background and development of our somatocognitive approach: Mensendieck physiotherapy of... more Historic background and development of our somatocognitive approach: Mensendieck physiotherapy of the Oslo School is a tradition of physiotherapy founded by the American physician Bess Mensendieck, a contemporary and fellow student of Sigmund Freud at the Paris School of Neurology. It builds on the principles of functional anatomy and the theories of motor learning. We have further developed the theory and practice from this physiotherapy tradition, challenged by the enormous load of patients with longstanding, incapacitating pain on western health care systems, by seeking to incorporate inspirational ideas from body oriented dynamic psychotherapy and cognitive psychotherapy. We developed somatocognitive therapy as a hybrid of physiotherapy and cognitive psychotherapy by focusing on the present cognitive content of the mind of the patient, contrary to a focus on analysis of the subconscious and interpretation of dreams, and acknowledging the important role of the body in pain-eliciting defense mechanisms against mental stress and negative emotions. The core of this somatocognitive therapy: (1) To promote awareness of own body, (2) graded task assignment related to the motor patterns utilized in daily activities, (3) combined with an empathic attitude built on dialogue and mutual understanding, and emotional containment and support. The goal is for the patient to develop coping strategies and mastery of own life. In addition, (4) manual release of tensed muscles and applied relaxation techniques are important. Methods and results of an illustrative study: One area in particular need of development and research is sexual pain disorders. We have applied this somatocognitive therapy in a randomized, controlled intervention study of women with chronic pelvic pain (CPP). We summarize methods and results of this study. Methods: 40 patients with CPP were included in a randomized, controlled intervention study. The patients were randomized into (1) a control group, receiving treatment as usual (Standard Gynecological Treatment, STGT) and (2) a group receiving STGT + Mensendieck Somatocognitive Therapy (MSCT). The patients were assessed by means of Visual Analogue Scale of Pain (VASP), Standardized Mensendieck Test (SMT) for analysis of motor patterns (posture, movement, gait, sitting posture and respiration), and General Health Questionnaire (GHQ-30) assessing psychological distress, at baseline (inclusion into study), after three months of out-patient therapy and at 1 year follow-up. Results: The women averaged 31 years, pain duration 6.1 years, average number of previous surgical procedures 1.8 per women. In the STGT group, no significant change was found, neither in pain scores, motor patterns or psychological distress during the observation period. In the group receiving STGT + MSCT, significant reduction in pain score and improvement in motor function were found at the end of therapy, and the significant improvement continued through the follow-up (64% reduction of pain scores, and 80% increase in the average score for respiration, as an example of motor pattern improvement). GHQ scores were significantly improved for anxiety and coping (p < 0.01). Conclusions: Somatocognitive therapy is a new approach that appears to be very promising in the management of chronic gynecological pain. Short-term out-patient treatment significantly reduces pain scores and improves motor function. Implications: Chronic pelvic pain in women is a major health care problem with no specific therapies and poor prognosis. A novel, somatocognitive approach has documented positive effects. It is now studied by other clinical researchers in order to reinforce its evidence base.
American Journal of Obstetrics and Gynecology, 2008
Chronic pelvic pain is a common source of disability among women in the western world. Here we re... more Chronic pelvic pain is a common source of disability among women in the western world. Here we report that 3 months of Mensendieck somatocognitive intervention in chronic pelvic pain patients was followed by continued improvements of outcomes at 1-year follow-up in a randomized, controlled study design. Forty women with chronic pelvic pain unexplained by pelvic pathology were randomly assigned to 2 groups: (1) standard gynecologic treatment and (2) gynecologic treatment plus somatocognitive therapy aimed at reducing physical pain by changing posture, movement, and respiration patterns. A standardized Mensendieck test (SMT) of motor function (assessing posture, movement, gait, sitting posture, and respiration), a self-rating questionnaire assessing psychologic distress and general well-being (GHQ-30) and a visual analog score of pain (VAS) were obtained before, after 90 days of treatment and 1 year after inclusion. Patients treated by standard gynecologic treatment/supervision did not improve significantly at 1-year follow-up in any of the test modalities. By contrast, those who in addition received somatocognitive therapy had improved scores for all motor functions and pain, as well as GHQ-30 scores for coping, and anxiety-insomnia-distress. Mensendieck somatocognitive therapy combined with standard gynecologic care improves psychologic distress, pain experience, and motor functions of women with chronic pelvic pain better than gynecologic treatment alone. The effect lasted and even further improvement occurred 9 months after treatment.
Objective: Chronic pelvic pain (CPP) is a common cause of infirmity but is still poorly understoo... more Objective: Chronic pelvic pain (CPP) is a common cause of infirmity but is still poorly understood. We studied the clinical characteristics, including body awareness, of 60 women with this diagnosis compared to those of healthy controls in an effort to understand its pathophysiology and to develop a more efficient treatment protocol. Methods: After prior gynecologic and psychometric evaluation, the women were examined with the Standardized Mensendieck Test to evaluate posture and movement patterns. Pain history and pain score were obtained, and patterns of muscular density, elasticity, and tenderness were determined by palpation. The body awareness of patients was assessed through clinical evaluation.
A standardized test was developed to evaluate posture, movement, gait, sitting posture, and respi... more A standardized test was developed to evaluate posture, movement, gait, sitting posture, and respiration of patients with psychosomatic disorders, based on the Mensendieck principles of observation and analysis of motor function. To validate the test and to make a comprehensive body examination of a defined group of patients, it was applied in a study of women with chronic pelvic pain (CPP, ICD10 F45.4). Fifteen women with CPP and 15 matched, healthy controls were examined. Test subjects were video recorded and scored by three experienced Mensendieck physical therapists, blinded with respect to the selection of subjects. Scores from 0 (for least functional movement) to 7 (optimal function) were assigned to each test person according to a test manual. High intraclass correlations (Chronbach's alpha ranging from 0.82 to 0.97) were found among the testers. The standardized Mensendieck test (SMT) discriminated well between women with CPP and the controls (sensitivity 0.9, specificity 0.7, mean values). The CPP patients scored significantly lower than the controls in all subtests (p < 0.01). The largest difference in scores were found for gait (patients 2.70 AE 0.11, vs. control, 5.60 AE 0.09) and respiration (patients 2.88 AE 0.14, vs. control, 5.63 AE 0.10). The results indicate that, in the hands of experienced Mensendieck therapists, the SMT is a reliable tool, demonstrating a good discriminative validity. Furthermore, it may turn out to be a useful instrument in the evaluation of patients with somatoform disorders. It may also point toward a possible therapeutic treatment approach to patients with CPP.
The aim of the present study was to investigate the release of amino-acids in human cerebral cort... more The aim of the present study was to investigate the release of amino-acids in human cerebral cortex during membrane depolarization and simulated ischaemia (energy deprivation). Superfluous tissue from temporal lobe resections for epilepsy was cut into 500 μm thick slices and incubated in vitro. Membrane depolarization with 50 mM K+ caused a release of glutamate, aspartate, GABA and glycine, but not glutamine or leucine. The release of glutamate and GABA was Ca++-dependent. Slices were exposed to simulated ischaemia (energy deprivation; ED) by combined glucose/oxygen deprivation. This caused a Ca++-indepedent release of glutamate, aspartate, GABA, glycine, and taurine which started after 8 min, peaked at the end or shortly after the 27 min period of ED, and returned to control levels within 11 min following termination of ED. Preloaded D-[3H]aspartate was released both during K+-stimulation and ED. Release of D-[3H]aspartate during ED was delayed compared to glutamate supporting an initial phase of synaptic glutamate release. Uptake of L-[3H]glutamate was increased during the period of glutamate release, suggesting passive diffusion across the cell membrane or enhanced transport efficacy in cellular elements with functioning uptake mechanisms.
A standardized test was developed to evaluate posture, movement, gait, sitting posture, and respi... more A standardized test was developed to evaluate posture, movement, gait, sitting posture, and respiration of patients with psychosomatic disorders, based on the Mensendieck principles of observation and analysis of motor function. To validate the test and to make a comprehensive body examination of a defined group of patients, it was applied in a study of women with chronic pelvic pain (CPP, ICD10 F45.4). Fifteen women with CPP and 15 matched, healthy controls were examined. Test subjects were video recorded and scored by three experienced Mensendieck physical therapists, blinded with respect to the selection of subjects. Scores from 0 (for least functional movement) to 7 (optimal function) were assigned to each test person according to a test manual. High intraclass correlations (Chronbach's alpha ranging from 0.82 to 0.97) were found among the testers. The standardized Mensendieck test (SMT) discriminated well between women with CPP and the controls (sensitivity 0.9, specificity 0.7, mean values). The CPP patients scored significantly lower than the controls in all subtests (p < 0.01). The largest difference in scores were found for gait (patients 2.70 AE 0.11, vs. control, 5.60 AE 0.09) and respiration (patients 2.88 AE 0.14, vs. control, 5.63 AE 0.10). The results indicate that, in the hands of experienced Mensendieck therapists, the SMT is a reliable tool, demonstrating a good discriminative validity. Furthermore, it may turn out to be a useful instrument in the evaluation of patients with somatoform disorders. It may also point toward a possible therapeutic treatment approach to patients with CPP.
Plasma c o n c e n t r a t i o n s of f i v e AA ( a s p a r a t e ASP, g l u t a m a t e GLU, g ... more Plasma c o n c e n t r a t i o n s of f i v e AA ( a s p a r a t e ASP, g l u t a m a t e GLU, g l y c i n e GLY, t a u r i n e TAU, and gamma-aminob u t y r i c a c i d GABA were measured i n a r t e r i a l ( a ) and s a g i t t a l s i n u s ( v ) plasma samples i n n i n e p i g l e t s exposed t o H0(10% 0,) and k N ( b l e e d i n g 2 0 % ) . Samples were t a k e n a t b a s e l i n e (BL), d u r i n g HO, a f t e r HV, and 30 ( 3 0 ' ) and 60 min ( 6 0 ' ) a f t e r HO. B e s u l t s I ; ( p e r c e n t change from BL, a samples, m e a n i s m ) .
The release of the amino acids GABA, taurine, glycine, glutamine and leucine from human neocortex... more The release of the amino acids GABA, taurine, glycine, glutamine and leucine from human neocortex was investigated in vitro by utilizing brain tissue removed during 8 standard temporal lobectomies for epilepsy or tumor. Slices (0.5 mm thick) were cut from each biopsy and randomly placed in three different chambers. After 90 min preincubation, the three sets of slices were incubated for 60 s in wells containing, respectively, (A) regular ACSF (control), (B) ACSF with 50 mM K + (to depolarize the cell membrane) and (C) ACSF with 50 mM K +, 0 mM Ca 2. and 4 mM Mg 2÷ (depolarization during blocked synaptic transmission). The content of amino acids in the wells was determined by high-performance liquid chromatography after pre-column derivatization of the amino acids with o-phthalaldehyde. Membrane depolarization (well B) increased the GABA release to 650% (620 pmol/mg) of control (well A, 95 pmol/mg). Blocking synaptic transmission (well C) reduced the evoked release by 50% (360 pmol/mg). The release of glycine, taurine, glutamine and leucine during membrane depolarization was not significantly different from the control values. The data provide evidence for a Ca2+-dependent release of GABA, supporting a possible role of this amino acid as a neurotransmitter in human neocortex.
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