Effects of rapamycin on cerebral oxygen supply and consumption during reperfusion after cerebral ischemia.

Activation of the mammalian target of rapamycin (mTOR) leads to cell growth and survival. We tested the hypothesis that inhibition of mTOR would increase infarct size and decrease microregional O2 supply/consumption balance after cerebral ischemia-reperfusion. This was tested in isoflurane-anesthetized rats with middle cerebral artery blockade for 1h and reperfusion for 2h with and without rapamycin (20mg/kg once daily for two days prior to ischemia). Regional cerebral blood flow was determined using a C(14)-iodoantipyrine autoradiographic technique. Regional small-vessel arterial and venous oxygen saturations were determined microspectrophotometrically. The control ischemic-reperfused cortex had a similar blood flow and O2 consumption to the contralateral cortex. However, microregional O2 supply/consumption balance was significantly reduced in the ischemic-reperfused cortex. Rapamycin significantly increased cerebral O2 consumption and further reduced O2 supply/consumption balance in the reperfused area. This was associated with an increased cortical infarct size (13.5±0.8% control vs. 21.5±0.9% rapamycin). We also found that ischemia-reperfusion increased AKT and S6K1 phosphorylation, while rapamycin decreased this phosphorylation in both the control and ischemic-reperfused cortex. This suggests that mTOR is important for not only cell survival, but also for the control of oxygen balance after cerebral ischemia-reperfusion.

Congenital Scoliosis.

Congenital scoliosis is a lateral deformity of the spine with a disturbance of the sagittal profile caused by malformations of vertebra and ribs. Typically, early surgical intervention is the suggested treatment (before three-years-old) for young patients with congenital scoliosis. While a previous study was conducted in 2011 to investigate long-term studies supporting the necessity for this recommendation and no evidence was found , this current review, is an updated search for evidence published from 2011 through March 2015. This also failed to find any prospective or randomized controlled studies to support the hypothesis that spinal fusion surgery in patients with congenital scoliosis should be considered as evidence-based treatment. Contradictory results exist on the safety of hemivertebra resection and segmental fusion using pedicle screw fixation. When using the VEPTR (vertical expandable prosthetic titanium rib) device, studies show a high rate of complications exist. It is difficult to predict the final outcome for patients with congenital scoliosis. However, it is possible that many patients with congenital scoliosis may be able to avoid spinal surgery with the application of advanced bracing technology [5]. Therefore, it is only prudent to advocate for conservative management first before spinal surgery is considered.

Bracing Scoliosis - State of the Art.

Spinal bracing is indicated in moderate to severe curves during growth. Brace effectiveness in halting progression of adolescent idiopathic scolisosis has been shown in a Cochrane review and in a randomized controlled trial (RCT). The outcome of brace treatment is dependent on the extent of in-brace correction and compliance. We have reviewed the literature on bracing to determine the types of brace that offer the best in-brace correction. MATERIALS AND METHODS: The literature has been searched for papers on bracing with documented in-brace corrections and long-term results . RESULTS: The in-brace percentage of correction of asymmetric braces is generally higher than that of the symmetric braces. According to the literature found in our search, long-term corrections are possible when starting treatment early, at an immature stage and with asymmetric braces of recent standards. CONCLUSIONS: Bracing today is supported by high quality evidence (Level I). Asymmetric braces have led to better corrections than that described for symmetric braces . An improvement of the average corrective effect has been described due to the latest CAD / CAM development. Long-term corrections are possible when starting brace treatment early, at an immature stage and with asymmetric braces of recent standards.

Inclusion criteria for physical therapy intervention studies on scoliosis - a review of the literature.

UNLABELLED: There is a wide variation of the inclusion criteria found in studies investigating the outcome of conservative scoliosis treatment. While the application of the SRS criteria for studies on bracing seem useful, there are no inclusion criteria for the investigation of physiotherapy alone. This study has been performed to investigate the possibility to find useful inclusion criteria for future prospective studies on physiotherapy (PT). MATERIALS AND METHODS: A PubMed and (incomplete) hand search for outcome papers on PT has been performed in order to detect study designs and inclusion criteria used. RESULTS: Real outcome papers (start of treatment in immature samples / end results after the end of growth) have not been found. Some papers investigated mid-term effects of exercises, most were retrospective, few prospective and many included patient samples with questionable treatment indications. DISCUSSION: No paper has been found with patients of risk for being progressive followed from premenarchial status until skeletal maturity under physiotherapy treatment alone. Claims made to regard physiotherapy as an evidence based method of treatment are not justified scientifically. An agreement of the scientific community on common inclusion criteria for future studies on PT is necessary. We would suggest the following: (1) girls only, (2) age 10 to 13 with the first signs of maturation (Tanner II), (3) Risser 0-2, (4) risk for progression 40 - 60% according to Lonstein and Carlson. CONCLUSION: There is no outcome paper on PT in scoliosis with a patient sample at risk for being progressive followed from premenarchial status until skeletal maturity. Therefore, only bracing can be regarded as being evidence based in the management of scoliosis patients during growth.

SpineCor vs. natural history - explanation of the results obtained using a simple biomechanical model.

In the recent peer reviewed literature the SpineCor is described as an effective method of treatment for patients with scoliosis. However until recently no prospective controlled end-result study is presented comparing the results obtained with this soft brace to natural history. The objective was to determine whether the results obtained by the use of the SpineCor are better than natural history during pubertal growth spurt. The method employed prospective comparison of the survival rates of SpineCor treatment vs. natural history with respect to curve progression during pubertal growth spurt. 12 Patients with Cobb angles between 16 and 32 degrees (at average 21 degrees) during pubertal growth spurt are presented as a case series treated with the SpineCor. Survival rate of this sample is described and compared to natural history (SRS brace study 1995). All girls treated in both studies were at risk for being progressive with the first clinical signs of maturation (Tanner 2-3). During the pubertal growth spurt most of the patients (11/12) with SpineCor progressed clinically and radiologically as well (at least 5 degrees). Progression could be stopped changing SpineCor to the Chêneau brace in most of the sample described (7/10). The avarage Cobb angle at the start of treatment with the SpineCor was 21.3 degrees, after an average observation time of 21.5 months 31 degrees. At 24 months of treatment time 33% of the patients with the SpineCor where still under treatment with their original bracing concept, at 72 months follow-up time 8 % of the patients with the SpineCor survived with respect to curvature progression. Survival proportion in the SpineCor sample, though was 0.08, while in the natural history cohort it was 0.34. The SpineCor treatment during pubertal growth spurt seems to lead to a worse outcome than observation only. The use of a simple biomechanical model explains that in the brace the compression forces exceed the lateral forces used for the corrective movement. Therefore SpineCor does not seem to be indicated as a treatment during pubertal growth spurt.

Comparison of the kyphosis angle evaluated by video rasterstereography (VRS) with x-ray measurements.

UNLABELLED: Surface topography evaluations are prone to technical errors due to postural sway of the patients measured. The technical error of lateral deviation (rms) and surface rotation (rms) may vary between 15 and 20%, while the kyphosis angle (IP-ITL) has a technical error of only 5% (2,5 degrees), which is comparable to the x-ray measurement. Purpose of this study was to investigate the hypothesis that video rasterstereography can be used for prognostication of a kyphosis patient. MATERIALS AND METHODS: 53 Patients (23 females, 30 males, average age 17 years with a range from 11 to 56 years) undergoing in-patient rehabilitation have been measured with the help of video rasterstereography (VRS) before starting the treatment program and the values for kyphosis angle have been correlated to the kyphosis angle measured on a lateral x-ray (XR) not older than 6 weeks before VRS measurement. 26 had a thoracic Scheuermann, 3 a thoracolumbar, 15 an Idiopathic Kyphosis and 9 a kyphosis of other origin. RESULTS: Average Kyphosis angle XR was 49 degrees (SD 17) and VRS 63 degrees (SD 13). There was a high significant Pearson correlation of 0.78 and a high significant difference of 14 degrees in the t-test (t -9,6, p<0,001). CONCLUSIONS: The kyphosis angle VRS (Vertebra prominens - lower neutral zone of inclination) seems to allow a follow-up of individual kyphosis patients. The XR kyphosis angle according to Stagnara is measured from T4 to the lower end vertebra and therefore is lower than the VRS kyphosis angle measured from T1. The difference found between XR and VRS kyphosis angles may be explained by the angle between T1 (VRS) and T4 (XR) differently used as the upper end vertebra. Therefore the prognostication of an individual patient seems possible within certain limits.

Postural changes in patients with scoliosis in different postural positions revealed by surface topography.

UNLABELLED: Claims have been made that surface topography is an objective tool, however there are significant postural influences (relatively large technical error due to postural sway) those measurements are prone to. Purpose of this study was to help estimate these influences by measuring patients with scoliosis in three standardized postural positions. MATERIAL AND METHODS: We studied the surface-topography measurement in 100 in-patients with idiopathic scoliosis divided into different age-groups. First group: 7 to 12 years (n=12), second group: 13 to 16 years (n=51), the third 17 to 20 years (n=15) and the fourth >21 years (n=22) (7 males and 93 females). The thoracic Cobb angle was 26.4 degrees, lumbar Cobb angle 25.7 degrees. We investigated the average lateral deviation (rms) and average surface rotation (rms). Measurements were taken one day before the patients left the clinic, after a 3 or 4 week in-patient intensive rehabilitation program (SIR), in three different postures:Normal posture: no specific instructions: standing with feet in an standardized way. Conscious posture: The patients acquired this posture during intensive daily exercising. Corrected posture: The most corrected posture the patients are able to achieve by using specific muscle tension and specific breathing techniques. We compared the results between the different postures. Then we calculated the results for the different age groups. RESULTS: There are significant differences in both parameters tested, some of them more than 40% to 67% greater than the measurement error calculated. The best results were achieved in the second and the third group with the conscious posture, the adult group had the best valued in most corrected posture. For the youngest patients there were no significant changes with the different postures. CONCLUSIONS: Surface measurements can be influenced by artificial postures and therefore cannot be attributed as objective. This is why the surface measurements should be made by someone independent from the treatment process in order to exclude any bias as far as possible. Surface topography may be used for postural monitoring in the rehabilitation process of patients with scoliosis.

Congenital scoliosis - presentation of three severe cases treated conservatively.

UNLABELLED: In view of the very limited data about conservative treatment of patients with congenital scoliosis (CS) available, early surgery is suggested already in mild cases with formation failures in the first three years of life. It is common sense that patients with failures of segmentation will not benefit from conservative treatment at all and the same applies to failures of formation with curves of >50 degrees in infancy. MATERIALS AND METHODS: Two patients with rib synostosis denied surgery before entering the pubertal growth spurt. These patients have been treated conservatively with braces and Scoliosis In-Patient Rehabilitation (SIR) and now are beyond the pubertal growth spurt. One patient with a formation failure and a curve of >50 degrees lumbar has been treated with the help of braces and physiotherapy from 1.6 years on and is still under treatment now at the age of 15 years. RESULTS: Severe decompensation was prevented in the two patients with failure of segmentation, however a severe thoracic deformity is evident with underdeveloped lung function and severe restrictive ventilation disorder. The patient with failure of formation is well developed, now without cosmetic or physical complaints although his curve progressed at the end of the growth spurt due to final mal-compliance. CONCLUSIONS: Failures of segmentation should be advised to have surgery before entering the pubertal growth spurt. In case they deny, conservative treatment can at least in part be beneficial. For patients with failures of formation conservative treatment should be suggested in the first place because long-term outcomes of early surgery beyond pubertal growth spurt are not yet revealed.

Conservative scoliosis treatment in patients with Prader-Willi syndrome.

UNLABELLED: Patients with Prader-Willi syndrome often suffer from scoliosis of major degrees. Due to current literature surgical intervention seems the gold standard of treatment although the rate of complications in this condition are reported to be significantly higher than in patients with Adolescent Idiopathic Scoliosis. Purpose of this study was to reveal the effects of conservative treatment in this rare patient population. MATERIALS AND METHODS: A case series of patients with this condition has been investigated to estimate as to whether Prader-Willi patients with scoliosis may benefit from conservative scoliosis management. 9 Patients with this condition have been found in our out-patient database. 5 of these retarded patients (3 girls, two boys) today are 19 years and older and therefore are without any significant residual growth. Average Cobb angle was 47 degrees (34 - 66 degrees) at 12 years, average observation time was 6.4 years. RESULTS: Two of the five patients progressed. Average Cobb angle after follow-up was 52 degrees. No progression beyond 70 degrees has been found after cessation of growth. In one patient the curve deteriorated clearly after reducing brace wearing time and therefore was due to non-compliance. CONCLUSIONS: Stabilisation of scoliosis due to Prader-Willi syndrome is possible by means of conservative management. To expose this patient population to the risks of surgical management seems not to be justified.

Silencing Jnk1 and Jnk2 accelerates basal lipolysis and promotes fatty acid re-esterification in mouse adipocytes.

AIMS/HYPOTHESIS: Elevated plasma levels of NEFA impair insulin action. Given the positive linear correlation between NEFA released by adipocytes and plasma NEFA levels, identification of mechanisms controlling adipocyte lipolysis and NEFA release could provide a guide to new therapies for insulin resistance and type 2 diabetes. METHODS: Short hairpin RNA-mediated gene ablation was used to determine the functions of c-Jun N-terminal kinase (JNK)1 and JNK2 in adipocytes. RESULTS: Combined JNK1/JNK2 deficiency drastically increased basal glycerol release, whereas individual JNK1- or JNK2-deficiency had no effect, indicating that JNK1/JNK2-deficiency enhances basal lipolysis, whereas the alternate subtype compensates for a single JNK subtype deficiency in the regulation of basal lipolysis. The profoundly increased glycerol release associated with JNK1/JNK2-deficiency was not accompanied by a concomitant increase in NEFA release over time. In addition, JNK1-deficiency, but not JNK2-deficiency, drastically decreased NEFA release as compared with that in JNK-intact cells, a result of increased NEFA re-esterification. In microarray, quantitative RT-PCR and western blotting, JNK1-, JNK2- and JNK1/JNK2-deficiencies selectively upregulated many genes involved in NEFA management, without affecting the expression of genes involved in insulin signalling. Assays using reporter genes driven by peroxisome proliferator-activated receptor gamma (PPAR-gamma)-responsive promoters indicate distinct roles for JNK1 and JNK2 in regulating the transcriptional effects of PPAR-gamma. CONCLUSIONS/INTERPRETATION: While JNK1 and JNK2 have shared roles in the regulation of basal lipolysis, JNK1 has a more profound role in supporting baseline NEFA release. Inhibition of JNK1 activity in adipocytes has potential therapeutic uses for management of elevated circulating NEFA levels at the onset of insulin resistance.

The treatment of adolescent idiopathic scoliosis (AIS) according to present evidence. A systematic review.

Traditionally, the treatment options for adolescent idiopathic scoliosis (AIS), the most common form of scoliosis, are exercises; in-patient rehabilitation; braces and surgery. The outcomes of treatments are usually compared with the natural history or observation (non-intervention). The aim of this paper was to provide a synopsis of all treatment options in the light of evidence based practice (EBP). A systematic review was carried out using the most encompassing databases available. Literature has been searched for the outcome parameter ''rate of progression'' and only prospective controlled studies that have considered the treatment versus the natural history have been included. The search strategy included the following terms: ''adolescent idiopathic scoliosis''; ''idiopathic scoliosis''; ''natural history''; ''observation''; ''physiotherapy''; ''physical therapy''; ''rehabilitation''; ''bracing''; ''orthotics'' and ''surgery''. Prospective short-term studies have been found to support outpatient physiotherapy. One prospective controlled study was found to support scoliosis in-patient rehabilitation (SIR). One prospective multi-centre study, a long-term prospective controlled study and a meta-analysis have been found to support bracing. No controlled study, neither short, mid nor long-term, was found to reveal any substantial evidence to support surgery as a treatment for this condition. There is some evidence supporting the conservative treatment for AIS. No substantial evidence has been found in terms of prospective controlled studies to support surgical intervention. In light of the unknown long-term effects of surgery, a randomised controlled trial (RCT) seems necessary. Due to the presence of evidence to support conservative treatments, a plan to compose a RCT for conservative treatment options seems unethical. But it is also important to conclude that the evidence for conservative treatments is weak in number and length.

Improving excellence in scoliosis rehabilitation: a controlled study of matched pairs.

OBJECTIVES: Physiotherapy programmes so far mainly address the lateral deformity of scoliosis, a few aim at the correction of rotation and only very few address the sagittal profile. Meanwhile, there is evidence that correction forces applied in the sagittal plane are also able to correct the scoliotic deformity in the coronal and frontal planes. So it should be possible to improve excellence in scoliosis rehabilitation by the implementation of exercises to correct the sagittal deformity in scoliosis patients. An exercise programme (physio-logic exercises) aiming at a physiologic sagittal profile was developed to add to the programme applied at the centre or to replace certain exercises or exercising positions. MATERIAL AND METHODS: To test the hypothesis that physio-logic exercises improve the outcome of Scoliosis Intensive Rehabilitation (SIR), the following study design was chosen: Prospective controlled trial of pairs of patients with idiopathic scoliosis matched by sex, age, Cobb angle and curve pattern. There were 18 patients in the treatment group (SIR + physio-logic exercises) and 18 patients in the control group (SIR only), all in matched pairs. Average Cobb angle in the treatment group was 34.5 degrees (SD 7.8) Cobb angle in the control group was 31.6 degrees (SD 5.8). Age in the treatment group was at average 15.3 years (SD 1.1) and in the control group 14.7 years (SD 1.3). Thirteen of the 18 patients in either group had a brace. Outcome parameter: average lateral deviation (mm), average surface rotation ( degrees ) and maximum Kyphosis angle ( degrees ) as evaluated with the help of surface topography (Formetric-system). RESULTS: Lateral deviation (mm) decreased significantly after the performance of the physio-logic programme and highly significantly in the physio-logic ADL posture; however, it was not significant after completion of the whole rehabilitation programme (2.3 vs 0.3 mm in the controls). Surface rotation improved at average 1.2 degrees in the treatment group and 0.8 degrees in the controls while Kyphosis angle did not improve in both groups. DISCUSSION: The physio-logic programme has to be regarded as a useful 'add on' to Scoliosis Rehabilitation with regards to the lateral deviation of the scoliotic trunk. A longitudinal controlled study is necessary to evaluate the long-term effect of the the physio-logic programme also with the help of X-rays.

'SOSORT consensus paper on brace action: TLSO biomechanics of correction (investigating the rationale for force vector selection)'.

BACKGROUND: The effectiveness of orthotic treatment continues to be controversial in international medical literature due to differences in the reported results and conclusions of various studies. Heterogeneity of the samples has been suggested as a reason for conflicting results. Besides the obvious theoretical differences between the brace concepts, the variability in the technical factors can also explain the contradictory results between same brace types. This paper will investigate the degree of variability among responses of scoliosis specialists from the Brace Study Ground of the International Society on Scoliosis Orthopedic and Rehabilitation Treatment SOSORT. Ultimately, this information could be a foundation for establishing a consensus and framework for future prospective controlled studies. METHODS: A preliminary questionnaire on the topic of 'brace action' relative to the theory of three-dimensional scoliosis correction and brace treatment was developed and circulated to specialists interested in the conservative treatment of adolescent idiopathic scoliosis. A particular case was presented (main thoracic curve with minor lumbar). Several key points emerged and were used to develop a second questionnaire which was discussed and full filed after the SOSORT consensus meeting (Milano, Italy, January 2005). RESULTS: Twenty-one questionnaires were completed. The Chêneau brace was the most frequently recommended. The importance of the three point system mechanism was stressed. Options about proper pad placement on the thoracic convexity were divided 50% for the pad reaching or involving the apical vertebra and 50% for the pad acting caudal to the apical vertebra. There was agreement about the direction of the vector force, 85% selecting a 'dorso lateral to ventro medial' direction but about the shape of the pad to produce such a force. Principles related to three-dimensional correction achieved high consensus (80%-85%), but suggested methods of correction were quite diverse. CONCLUSION: This study reveals that among participating SOSORT specialists there continues to be a strongly held and conflicting if not a contentious opinion regarding brace design and treatment. If the goal of a 'treatment consensus' is realistic and achievable, significantly more effort will be required to reconcile these differences.

Effects of 17beta-estradiol on blood-brain barrier disruption during focal cerebral ischemia in younger and older rats.

This study was performed to compare the effects of 17beta-estradiol on blood-brain barrier disruption in focal cerebral ischemia between younger and older rats. Younger (three-month-old) and older (24-month-old) ovariectomized female Fischer 344 rats were studied. In one half of each age group, a 500 microg 17beta-estradiol 21-day release pellet and in another half, a vehicle pellet was implanted 21 days before the experiments. One hour after middle cerebral artery occlusion, the transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid and the volume of 3H-dextran distribution were determined to examine the degree of blood-brain barrier disruption. In all four groups, the Ki in the ischemic cortex was higher than in the corresponding contralateral cortex. There was no significant difference in the Ki in both cortices among the groups. The volume of dextran distribution of the ischemic cortex was only greater than in the corresponding contralateral cortex in the older 17beta-estradiol-treated group, and the volume of that group was greater than the younger 17beta-estradiol-treated group (4.00 +/- 1.29 VS. 2.13 +/- 0.88 ml/100 g). After analyzing the difference in Ki between the ischemic cortex and the contralateral cortex in each animal, the difference was significantly greater in the older 17beta-estradiol-treated rats than the older vehicle-treated rats (3.40 +/- 2.10 VS. 1.26 +/- 1.44 microl/g/min). In the younger rats, however, 17beta-estradiol did not significantly affect the difference. Our data showed that 17beta-estradiol treatment failed to attenuate the BBB disruption in the cerebral ischemic cortex in the older or younger Fischer 344 rats. However, our data also suggest the possibility that 17beta-estradiol could aggravate the BBB disruption in older rats.

Sagittal counter forces (SCF) in the treatment of idiopathic scoliosis: a preliminary report.

BACKGROUND: In patients with idiopathic scoliosis (IS), reduced thoracic kyphosis and reduced lumbar lordosis frequently occur in correlation with the lateral spinal curvature. Normalization of the sagittal profile and hyper-correction of the deviation in frontal and coronal plane are the main issues of the latest concept of bracing. The purpose of this study was to investigate the influence of of sagittal counter forces (SCF) on the scoliotic deformity. STUDY DESIGN: A case series of four patients with IS treated with two braces designed to improve the sagittal profile (Rigo-System-Chêneau-brace and with a sagittal counter force brace, SCF-brace). METHODS: The short-term effect (30 min) of both braces was evaluated using surface topography (Formetric surface topography system, Diers International, Wiesbaden). RESULTS: One patient (Cobb angle 92 degrees ) showed no short-term correction in the frontal and coronal planes; others (Cobb angles between 39 and 48 degrees ) exhibited valuable correction in frontal and coronal planes. There was no short-term correction in the sagittal plane for either brace. CONCLUSION: The application of sagittal counter forces (SCF) seems to have similar short-term effects as 3D correction and should be addressed more in future concepts of scoliosis bracing.

Effects of 17beta-estradiol on blood-brain barrier disruption in focal ischemia during GABA(A) receptor inhibition.

We performed this study to determine whether gamma-aminobutyric acid (GABA(A)) receptor inhibition could reverse the effect of 17beta-estradiol on blood-brain barrier (BBB) disruption in focal cerebral ischemia. Young ovariectomized rats were implanted with a 500 microg 17beta-estradiol 21-day release pellet or with a vehicle pellet 21 days before the experiments. Forty-five minutes after middle cerebral artery (MCA) occlusion, half of each group was infused with bicuculline (a GABA(A) receptor antagonist) 1 mg/kg/min for 2 min followed by 0.1 mg/kg/min up to the end of experiments. The other half was infused with the same volume of normal saline. The transfer coefficient (Ki) of 14C-alpha-aminoisobutyric acid and the volume of 3H-dextran distribution (70,000 Daltons) were determined to measure the degree of BBB disruption one hour after MCA occlusion. In the control vehicle-treated animals, the Ki in the ischemic cortex (7.2 +/- 2.6 microl/g/min) was higher than in the contralateral cortex (2.5 +/- 1.4 microl/g/min). After bicuculline infusion, the Ki in the ischemic cortex increased (10.6 +/- 5.4 microl/g/min) although the increase was not statistically significant. In the 17beta-estradiol treated animals, the Ki in the ischemic cortex (3.8 +/- 1.6 microl/g/min) was lower than control vehicle-treated rats. With bicuculline infusion, the Ki in the ischemic cortex (14.5 +/- 6.8 microl/g/min) was markedly increased. In the non-ischemic cortex, there was no significant difference in Ki among the experimental groups. The volume of dextran distribution was not significantly different between the experimental groups in the ischemic or non-ischemic cortex. Our data suggests that part of the reason for the decreased BBB disruption in the focal ischemic area after 17beta-estradiol treatment could be due to the interaction between GABA(A) receptors and 17beta-estradiol.

17beta-estradiol prevents blood-brain barrier disruption induced by VEGF.

We performed this study to determine how pretreatment of the ovariectomized rats with 17beta-estradiol could affect blood-brain barrier disruption caused by the vascular endothelial growth factor (VEGF), an important mediator of vascular permeability. Ovariectomized female rats aged twelve to fourteen weeks were used in the study. A 500 micro g 17beta-estradiol 21-day release pellet was implanted in the 17beta-estradiol group, and a vehicle pellet was implanted in the control group 21 days before the experiments. We performed three craniotomies under isoflurane anesthesia to expose cerebral cortices. Normal saline, 10 (- 10)M and 10 (- 9)M VEGF patches were applied on each hole for 30 min. The transfer coefficient (Ki) of (14)C-alpha-amino isobutyric acid and volume of (3)H-dextran (70,000 dalton) distribution were determined to measure the degree of BBB disruption. Ki was increased by 108 % and 138 % with 10 (- 10)M and 10 (- 9)M VEGF respectively after VEGF application in the control group (p < 0.01). However, there was no significant increase in the Ki with the VEGF application in the 17beta-estradiol group, and their values were significantly lower than the corresponding data of the control group (10 (- 10)M: - 55 %, 10 (- 9)M: - 52 %, p <0.05). The volume of dextran distribution in the control group increased by 47 % with VEGF 10 (- 9)M (p < 0.05), whereas there was no significant change in the volume of dextran distribution with VEGF application in the 17beta-estradiol group and the volume was lower than the corresponding volume of the vehicle-treated control group (10 (- 10)M: - 34 %, 10 (- 9)M: -32 %, p < 0.05). In conclusion, our study demonstrated that chronic 17beta-estradiol treatment prevented BBB disruption induced by the VEGF in the ovariectomized rats.

[Conservative treatment of idiopathic scoliosis with physical therapy and orthoses]. / Die konservative Behandlung der idiopathischen Skoliose durch Krankengymnastik und Orthesen.

Opinions differ in the international literature about the efficacy of conservative approaches to scoliosis treatment. Because this divergence of opinion corresponds to a great discrepancy in the standards applied to conservative treatment methods, it is not astonishing that the results of conservative treatment as described in the literature also differ. Scoliosis normally does not have such dramatic effects that immediate surgery would be indicated.Moreover, it is clear from the published literature that it is the functional and physiological impairments of scoliosis patients--including pain, torso deformity, psychological disturbance, and pulmonary dysfunction--which require therapeutic intervention. In Germany the triad of outpatient physiotherapy, intensive inpatient rehabilitation, and bracing has proven effective in conservative scoliosis treatment.Indication, content, and results of the individual treatment procedures are described and discussed. The positive outcomes of this practice validate a policy of offering conservative scoliosis treatment as an alternative to patients, including those for whom surgery is indicated.

Effect of conservative management on the prevalence of surgery in patients with adolescent idiopathic scoliosis.

STUDY DESIGN: Retrospective analysis of outcome in terms of prevalence of surgery for adolescent idiopathic scoliosis in patients receiving conservative management. OBJECTIVES: To determine whether a centre with an active policy of conservative management has fewer patients who eventually undergo surgery for adolescent idiopathic scoliosis than a centre where the practice is non-intervention. BACKGROUND DATA: The efficacy of orthoses for the treatment of idiopathic scoliosis was called into question in a recent publication. Because the prevalence of surgery in an untreated group of patients (28.1%) was not significantly different from that in a braced group (22.4%), the authors concluded that bracing appears to make no difference. Based on prior experience, this conclusion is questioned. METHODS: Since 1991, bracing and physical therapy have been recommended for children with adolescent idiopathic scoliosis at a centre in Barcelona, Spain. The scoliosis database was searched for patients with adolescent idiopathic scoliosis who were at least 15 years of age at last review and who had adequate documentation of the Cobb angle. The prevalence of surgery was compared with that of published data from a centre where the practice is non-intervention. RESULTS: From a total of 106 braced cases out of which 97 were followed up, six cases (5.6%) ultimately underwent spinal fusion. A worst case analysis, which assumes that all nine cases that were lost to follow-up had operations, brings the uppermost number of cases that could have undergone spinal fusion to 15 (14.1%). Either percentage is significant statistically when compared to the 28.1% reported surgeries from the centre with the policy of non-intervention. CONCLUSIONS: If conservative management does reduce the proportion of children with adolescent idiopathic scoliosis that require surgery, it can be said to provide a real and meaningful advantage to both the patients and the community. It is contended that conservative methods of treatment should never be ruled out from scoliosis management, because they can and do offer a viable alternative to those patients who cannot or will not opt for surgical treatment.