bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence for the involvement of CaMKII and AMPK in Ca2+-dependent signaling pathways regulating FA uptake and oxidation in contracting rodent muscle
Authors: Raney Marcella A. , Turcotte Lorraine P.
Published: February 2008

Calcium-calmodulin/dependent protein kinase II (CaMKII), AMP-activated protein kinase (AMPK), and extracellular signal-regulated kinase (ERK1/2) have each been implicated in the regulation of substrate metabolism during exercise. The purpose of this study was to determine whether CaMKII is involved in the regulation of FA uptake and oxidation and, if it is involved, whether it does so independently of AMPK and ERK1/2. Rat hindquarters were perfused at rest with ( n = 16) or without ( n = 10) 3 mM caffeine, or during electrical stimulation ( n = 14). For each condition, rats were subdivided and treated with 10 μM of either KN92 or KN93, inactive and active CaMKII inhibitors, respectively. Both caffeine treatment and electrical stimulation significantly increased FA uptake and oxidation. KN93 abolished caffeine-induced FA uptake, decreased contraction-induced FA uptake by 33%, and abolished both caffeine- and contraction-induced FA oxidation ( P < 0.05). Caffeine had no effect on ERK1/2 phosphorylation ( P > 0.05) and increased α2-AMPK activity by 68% ( P < 0.05). Electrical stimulation increased ERK1/2 phosphorylation and α2-AMPK activity by 51% and 3.4-fold, respectively ( P < 0.05). KN93 had no effect on caffeine-induced α2-AMPK activity, ERK1/2 phosphorylation, or contraction-induced ERK1/2 phosphorylation ( P > 0.05). Alternatively, it decreased contraction-induced α2-AMPK activity by 51% ( P < 0.05), suggesting that CaMKII lies upstream of AMPK. These results demonstrate that regulation of contraction-induced FA uptake and oxidation occurs in part via Ca2+-independent activation of ERK1/2 as well as Ca2+-dependent activation of CaMKII and AMPK.
Evaluation of the Antiangiogenic Potential of AQ4N
Authors: O'Rourke Martin , Ward Claire , Worthington Jenny , McKenna Julie , Valentine Andrea , Robson Tracy , Hirst David G. , McKeown Stephanie R.
Published: March 2008

Purpose: A number of cytotoxic chemotherapy agents tested at low concentrations show antiangiogenic properties with limited cytotoxicity, e.g., cyclophosphamide, tirapazamine, and mitoxantrone. AQ4N is a bioreductive alkylaminoanthraquinone that is cytotoxic when reduced to AQ4; hence, it can be used to target hypoxic tumor cells. AQ4N is structurally similar to mitoxantrone and was evaluated for antiangiogenic properties without the need for bioreduction.

Experimental Design: The effect of AQ4N and fumagillin on human microvascular endothelial cells (HMEC-1) was measured using a variety of in vitro assays, i.e., 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound scrape, tubule formation, rat aortic ring, and invasion assays. Low-dose AQ4N (20 mg/kg) was also given in vivo to mice bearing a tumor in a dorsal skin flap.

Results: AQ4N (10−11 to 10−5 mol/L) had no effect on HMEC-1 viability. AQ4N (10−9 to 10−5mol/L) caused a sigmoidal dose-dependent inhibition of endothelial cell migration in the wound scrape model. Fumagillin showed a similar response over a lower dose range (10−13 to 10−9 mol/L); however, the maximal inhibition was less (25% versus 43% for AQ4N). AQ4N inhibited HMEC-1 cell contacts on Matrigel (10−8 to 10−5 mol/L), HMEC-1 cell invasion, and sprouting in rat aorta explants. Immunofluorescence staining with tubulin, vimentim, dynein, and phalloidin revealed that AQ4N caused disruption to the cell cytoskeleton. When AQ4N (20 mg/kg) was given in vivo for 5 days, microvessels disappeared in LNCaP tumors grown in a dorsal skin flap.

Conclusions: This combination of assays has shown that AQ4N possesses antiangiogenic effects in normoxic conditions, which could potentially contribute to antitumor activity.
Lack of Skeletal Effect of Soy Isoflavones in Intact Growing, Female Rats May Be Explained by Constant Serum Estrogenic Activity despite Reduced Serum Estradiol
Authors: Peterson Catherine A. , Kubas Karen L. , Hartman Stephanie J. , Rottinghaus George E. , Taylor Julia A. , Welshons Wade V.
Published: February 2008

Background/Aims: Scarce data exist on the effects of soy isoflavones (IF) on bone during peripuberty, a known ‘window of opportunity’ for bone consolidation. Our aim was to determine the skeletal, reproductive, and serum estradiol (E2)/estrogenic activity response of consuming naturally-occurring soy protein-associated IF during peripuberty. Methods: Weanling (∼3 weeks old), female rats were placed on one of four nutritionally-complete dietary regimens in which protein (200 g/kg diet) was provided as casein or soy protein isolates containing either 0.11 (Low IF), 2.16 (Med IF), or 3.95 (High IF) mg total aglycone isoflavones/g protein for 8 weeks, during which body weights and estrus cycling were recorded. Results: Bone growth and density were unaffected by soy intake while the reproductive tissues showed a slight response (greater uterine weights of the Med and High IF groups). Despite suppression of E2 concentrations in the High IF group, total circulating estrogenic activity was unaltered. Moreover, in the High IF group, E2 was significantly depressed compared with bioassayable estrogenic activity, suggesting negative feedback inhibition of E2 by the elevated circulating levels of IF. Conclusions: This suppression in E2 with maintenance of total serum estrogenicity in the High IF group may explain the lack of effect observed in the skeletal tissues.
Artificial Neural Network Model Is Superior to Logistic Regression Model in Predicting Treatment Outcomes of Interferon-Based Combination Therapy in Patients with Chronic Hepatitis C
Authors: Wang Chun-Hsiang , Mo Lein-Ray , Lin Ruey-Chang , Kuo Jen-Juan , Chang Kuo-Kuan , Wu Jieh-Jen
Published: February 2008

Background/Aims: Patients with chronic hepatitis C (CHC) can achieve a sustained virologic response if they received pegylated interferon plus ribavirin therapy; however, some of them do not respond or relapse after treatment. The aim of this study was to compare the ability of two statistical models to predict treatment outcomes. Methods: Clinical data, biochemical values, and liver histological features of 107 patients with CHC were collected and assessed using a logistic regression (LR) model and an artificial neural network (ANN) model. Both the LR and ANN models were compared by receiver-operating characteristics curves. Results: Aspartate aminotransferase (p = 0.017), prothrombin time (p = 0.002), body mass index (BMI; p = 0.003), and fibrosis score of liver histology (p = 0.002) were found to be significant predictive factors by univariate analysis. The independent significant predicting factor was BMI by multivariate LR analysis (p = 0.0095). The area under receiver-operating characteristics of the ANN model was larger than that of the LR model (85 vs. 58.4%). Conclusions: It was found that BMI is an independent factor for identifying patients with favorable treatment response. A useful ANN model in predicting outcomes of standard treatment for CHC infection was developed and showed greater accuracy than the LR model.
Prevalence of Hepatitis E Virus IgG Antibody in Japanese Patients with Hemophilia
Authors: Toyoda Hidenori , Honda Takashi , Hayashi Kazuhiko , Katano Yoshiaki , Goto Hidemi , Kumada Takashi , Takahashi Kazuaki , Abe Natsumi , Mishiro Shunji , Takamatsu Junki
Published: February 2008

Objective: We investigated the prevalence of antibody against hepatitis E virus (HEV) in Japanese patients with hemophilia. Methods: IgG antibody against HEV was measured in serum of 80 Japanese patients with hemophilia by enzyme-linked immunosorbent assay. The prevalence of HEV antibody was compared with the reported prevalence of HEV antibody in Japanese patients undergoing hemodialysis and in Japanese healthy blood donors. Characteristics of patients and coinfection with other transfusion-transmissible viruses were compared in patients with and without HEV antibody. Results: Anti-HEV IgG antibody was detected in 13 of 80 patients (16.3%). The prevalence was far higher than that reported in Japanese blood donors (3.7%) and was higher than that in Japanese patients undergoing hemodialysis (9.4%). The patients with HEV antibody were significantly older than those without. HEV antibody was not detected in patients <20 years of age and in patients who had received only virus-inactivated coagulation factors. No association was observed between positivity for anti-HEV antibody and severity of hemophilia or coinfection with other parenterally transmissible viruses. Conclusion: Our results suggest that the parenteral transmission of HEV may have occurred in Japanese patients with hemophilia via non-virus-inactivated coagulation factors.
Comparison of Two Dialysers (AN69ST vs. FX100) for Heparin-Free Dialysis in Patients with Oral Anticoagulation
Authors: Kodras Katharina , Benesch Thomas , Neumann Irmgard , Haas Martin
Published: February 2008

Background: Heparin-free dialysis (HFD), i.e. only priming of the dialyser and no systemic heparinization, might reduce the risk of bleeding in dialysis patients receiving oral anticoagulation. The efficacy of HFD with two different membranes [polyacrylonitrile (AN69ST) vs. polysulphone (FX100)] was therefore investigated. Methods: In a crossover design, 10 patients were treated with either membrane for 1 week (total 30 sessions). Weekly Kt/V and urea reduction rate (URR) were measured and thrombus formation evaluated by measurement of D-dimer and inspection of the air traps and dialyser. Results: Change of clotting markers was similar with both membranes. Complete thrombosis occurred in 3/30 patients with the AN69ST and in 1/30 patients with the FX100 membrane. Kt/V did not differ between the groups, but the URR was slightly higher with the FX100. Conclusion: HFD prevents dialyser occlusion in the majority of patients treated with oral anticoagulants. Both polysulphone and polyacrylonitrile membranes seem to be equally effective.
Mineral Metabolism and Mortality in Dialysis Patients: A Reassessment of the K/DOQI Guideline
Authors: Noordzij Marlies , Korevaar Johanna C. , Dekker Friedo W. , Boeschoten Elisabeth W. , Bos Willem J. , Krediet Raymond T. , Bossuyt Patrick M. , Geskus Ronald B.
Published: February 2008

Background: Several studies found associations between higher plasma calcium and phosphorus and mortality in dialysis patients. However, different predefined categories and reference values were applied and the precise shape of these relationships remains unclear. Methods: We evaluated 1,621 patients from NECOSAD, a prospective multicenter cohort study of incident dialysis patients (60 ± 15 years, 61% male, 64% hemodialysis). We used multivariate Cox regression and restricted cubic spline regression to study the effects of time-updated plasma concentrations on mortality in a flexible manner. Results: 486 patients (30%) died during follow-up. Elevated phosphorus concentration was associated with higher mortality (p = 0.0009). The association of high calcium with mortality was borderline significant (p = 0.07). Within the studied ranges, we could not identify a threshold where an appreciable change in mortality risk occurred. Conclusions: Mortality risk started to increase at a relatively low phosphorus concentration (4.5 mg/dl). Low-normal calcium combined with low-normal phosphorus concentration was associated with the lowest mortality.
Brain Tumors of Early Infants
Authors: Sato Osamu , Tamura Akira , Sano Keiji
Published: February 2008

The authors describe their experience with ten cases of brain tumors in children in whom the onset of symptoms occurred within the first year of life, but who were operated on when they were 2 months to 4 years of age. The series includes 5 gliomas (4 supratentorial, 1 cerebellar; 3 astrocytomas, 1 spongioblastoma, 1 ependymoblastoma), 2 teratomas of the lateral ventricle, and 3 single cases of third ventricle choroid plexus papilloma, temporal lobe sarcoma, and a parasellar craniopharyngioma. Six cases were partially removed, one of them was shunted. Only biopsy was carried out in two, one of which was shunted. The only case of radical removal was a lateral ventricle teratoma; this patient died at operation. Nine patients survived at surgery, three of whom are alive on the 3rd, 4th, and 7th postoperative year. There were two late deaths: one at 2 years (lateral ventricle astrocytoma, which was only biopsied) and one at 7 years and 3 months (spongioblastoma) following surgery. This series from a 40-year period (1933–1973) represents 0.4% of 2,832 brain tumors and 1.9% of 528 brain tumors in the pediatric age. The authors emphasize the need to treat brain tumors in early infancy and insist on the use of radiotherapy and chemotherapy when the lesions are not radically removed at surgery.
Adjuvant Immunotherapy for Malignant Brain Tumors in Infants and Children
Authors: Takakura Kintomo , Miki Yoshimasa , Kubo Osami
Published: February 2008

Immune deficiency of immunocompetent cells or of humoral factors are essential causes of tumor growth. The authors have investigated the transfer of immunocompetent cells – allogeneic bone marrow cell transfusion and white blood cell intracranial infusion – for the treatment of 11 malignant gliomas in infants and children as an adjuvant to surgery, radiation and/or chemotherapy. Ten cases, from 3 months to 11 years, received bone marrow cell transfusion. Two medulloblastomas and 3 pontine gliomas are dead. Five cases are alive and well 37–65 months following surgery. Among these two posterior fossa neoplasms, a medulloblastoma and a glioblastoma have survived 46 and 65 months, respectively. One cerebral glioblastoma received allogeneic white blood cells infused locally into the tumor bed: it recurred 1 year following surgery, chemotherapy, and immunotherapy. Cytolysis of the tumor cells by sensitized lymphoid cells were demonstrated in this case. The role of immunotherapy should be limited at the present time to adjuvant therapy until its effect on tumor growth is statistically confirmed. The results so far are promising, and improvement of the immunological approach in treating malignant brain tumors is under way.
A New Device for Long-Term Intracranial Pressure Measurement
Authors: Meyer Glenn A. , Lyon Warren C. , Bustard Thomas S.
Published: February 2008

This paper describes the authors’ approach to the problem of long-term intracranial pressure measurement. Several prior devices have not proven useful for clinical studies of more than a few days duration. Study of 22 of the authors’ devices in primates has established the validity of both engineering and medical design assumptions. Useful pressure data has been collected for up to 2 months. Redesign to decrease tambour permeability should allow a useful life of months or years.
Comparative Study of Various Models of Experimental Hydrocephalus
Authors: Matsumoto Satoshi , Hirayama Akihiko , Yamasaki Shun , Shirataki Kunio , Fujiwara Kiyoshi
Published: February 2008

The authors present morphological findings in the brains of rabbits, dogs, cats, rats, and mice that have been used as experimental hydrocephalic models. The methods used were as follows: (1) silicone oil injection into the cisterna magna and the neighboring basal cisterns in rabbits by the method of Wisniewski; (2) kaolin administration into the cisterna magna in rabbits and dogs (Dixon); (3) ballooning method with Foley’s catheter into the 4th ventricle in rabbits (Milhorat); (4) plug formation with small pieces of laminalia into the cisterna magna in rabbits by our method; (5) Hy-3 hereditary hydrocephalic mouse bred by Gruenberg; (6) ligation of the placental vessels of the pregnant rat at 13 days of gestation by our method, and (7) transplacental intraperitoneal administration of ethylnitrosourea in a pregnant rat at 9.5 days of gestation. The models with silicone oil, kaolin, laminalia, and ballooning methods produced obstructive hydrocephalus with various grades of ventricular dilatation. The models with the ethylnitrosourea-induced method, ligation of placental vessels, and Hy-3 mouse produced prenatal hydrocephalus. Dilatation of the ventricular system and histological abnormalities do not occur as a uniform process.
Cystic Cavum veli interpositi Associated with Normal or Low Pressure Hydrocephalus
Authors: Raimondi Anthony J. , Gutierrez Francisco A. , Jones Ronald R. , Winston Stuart R.
Published: February 2008

A new clinical syndrome, characterized by progressive increase in head size (without intracranial hypertension), variable delay in milestones, moderate ventricular dilation, and the presence of a cavum veli interpositi is herein described. The arteriographic and venographic signs are suggestive, but not diagnostic, of the presence of a cavum veli interpositi. Pneumoencephalography, with adequate filling of the subarachnoid spaces and ventricles, is essential to confirming the diagnosis. Cerebrospinal fluid shunting appears to result in an improvement, but the results cannot as yet be considered definitive since only 10 of our 29 patients were shunted.
Treatment of Infected Ventricular Shunts
Authors: McLaurin Robert L.
Published: February 2008

25 shunt infections following 23 vascular and 2 peritoneal shunts are reviewed, thus enlarging a previous review. Intraventricular administration of antibiotics are essential to reach the CSF beyond the blood-SF barrier, the tubing and the valve. Methicillin in dosages of 25–50 mg/day, intraventricularly combined with systemic therapy, have been used most often in this series. The only death in this series occurred when the infection was cured. The remaining 24 have no evidence of residual infection following 6 months to 5 years. Only 14 have had shunt removal. The results indicate that shunt removal should not be the initial means of treating infected shunts.
Ventriculovenous Shunt to the Proximal Segment of a Ligated Neck Vein
Authors: El Shafei Ismail L.
Published: February 2008

The author proposes ventriculovenous shunts to a ligated neck vein (external jugular or facial) for the treatment of hydrocephalus. He postulates that the ligated neck vein is filled with CSF and becomes an extension of the shunt tube, which prevents venous thrombosis. The pressure of the shunt at the venous tube was shown to be about 90 mm H2O avoiding excessive ventricular decompression. Reflux of blood to the ventricle can occur if the infant’s cranium is compressible and must be prevented by protecting the cranium from external pressure with a bandage or helmet or by incorporating a one-way valve into the shunt. 31 cases of advanced hydrocephalus were thus treated during a 4-year period. Ages ranged from 15 days to 55 years, the cranium was rigid in 13 and compressible in 18. A valve was used in only two cases. Shunts were patent 7–10 days after surgery, as shown at autopsies in two early postoperative deaths. In two cases meningitis occurred, one of them died. The shunt was removed in one case on account of meningitis and in 4 cases due to cervical CSF leakage. The former and three of the latter were reoperated with success. Three cases had distal shunt obstruction, two due to kinking of the tube, and one due to reflux of blood. One of the former died. 23 patients benefited from the operation, 5 of which were operated on twice. The follow-up period was from 0.5–44 months (average 11.5 months). The last two cases were operated on using a one-way valve and a spiral wire in the venous segment of the tube. They are well 2 and 3 months, respectively, following surgery.
Schizencephaly: a Clinical Study and Review
Authors: Page Larry K. , Brown Stuart B. , Gargano Fredie P. , Shortz Roger W.
Published: February 2008

Schizencephaly is a rare malformation in which symmetrical portions of the cerebral mantle fail to develop. It should be differentiated by angiography and pneumography from the porencephalies that follow destructive lesions and from the prognostically more favorable subdural hematomas and effusions. If the diagnosis of this anomaly can be firmly established short of surgical exploration, operation or further treatment of any kind is not, in the authors opinion, warranted.
Intracranial Abscess: Treatment by Continuous Catheter Drainage
Authors: Selker Robert G.
Published: February 2008

15 children with brain abscesses were subjected to continuous catheter drainage as the procedure of choice for a solitary encapsulated abscess. Although many still advocate craniotomy and total excision, this series, coupled with the experience of others in the literature, leaves little doubt that catheter drainage alone is sufficient. The simplicity of creating a burr hole under local anesthesia, the ability to irrigate with antibiotics and then outline the cavity with contrast agents are but a few of the advantages of this method.
α-Fetoprotein and the Prenatal Diagnosis of Central Nervous System Disorders
Authors: Brock D.J.H.
Published: February 2008

The use of amniotic fluid α-fetoprotein measurements in the early prenatal diagnosis of central nervous system disorders is reviewed. The method is sensitive and specific and has had a pronounced effect on the counselling of mothers who have already had a child with spina bifida or anencephaly. Measurement of other amniotic fluid components, such as fetal macrophages, β-trace protein, α2-macroglobulin or fibrinogen-degradation products, is less reliable and these should not be used in making primary diagnoses. The assay of α-fetoprotein in maternal serum shows signs of being a useful preliminary screening process, and may identify pregnancies where amniocentesis and confirmatory amniotic fluid determinations should be offered.
Midline Commissurotomy for the Treatment of Some Cases of Intractable Epilepsy
Authors: Amacher Loren
Published: February 2008

When epilepsy is localized, limited excisions can be very effective for control of seizures without increased neurological deficit. Van Wagenen found that a seizure discharge confined to one hemisphere would not produce an unconscious state, so he treated his patients with partial or complete sections of the corpus callosum with more success with complete sectioning. Erickson showed that total callosal section was necessary to stop the spread of cortically induced seizures from one hemisphere to the other. Luessenhop reported on four patients treated by divisions of the corpus callosum.
Ependymomas of Childhood
Authors: Liu Mei , Boggs Joseph , Kidd James
Published: February 2008

We have conducted a correlative histological and clinical study on 34 cases of childhood ependymomas encountered at the Children’s Memorial Hospital from1953 to 1974. The cases were classified into grades A, B and C according to the extent of cytological differentiation and the correlation between the histological grades and the clinical outcome was obtained. It is concluded that the biological behavior of an ependymoma could be predicted to a large extent by the degree of cytological differentiation and by its anatomical location. A large share of the infratentorial ependymomas are well differentiated (grade A) and prognosis in this group is good when complete surgical removal could be accomplished. Most of the supratentorial ependymomas belong to the intermediate grade B and the malignant grade C; prognosis in these two grades is less predictable, approximately two thirds of these patients died within 3 years. The most malignant form is the ependymoblastoma. This is a highly primitive neoplasm histologically similar to medulloblastoma but shows evidence of ependymal differentiation. Most of the ependymoblastomas are located in the supratentorial region and the average length of survival is 20 months.
The Tethered Spinal Cord: Its Protean Manifestations, Diagnosis and Surgical Correction
Authors: Hoffman Harold J. , Hendrick Bruce , Humphreys Robin P.
Published: February 2008

31 children with spina bifida occulta who have presented with back pain, scoliosis, a progressive neurological deficit involving lower limbs or a neurogenic bladder have been found to have a tethered spinal cord. Release of the tethered spinal cord has always relieved pain, frequently corrected a progressive scoliosis, and arrested or improved neurogenic foot deformities as well as neurogenic bladder.
Headache in Classical Hemophilia
Authors: Curless Richard G. , Corrigan, jr. James J.
Published: February 2008

Headache in a hemophiliac poses a major problem. The fact that at least half of hemophiliacs with proven intracranial hemorrhage present with a headache but no preexisting injury, requires an aggressive approach to the management of these patients. Recent articles point out successful instances of craniotomy in hemophilia, but relatively few hemophiliacs with headaches progress to that stage. We have reviewed the literature and added three cases in an attempt to establish the risk of spinal puncture and cerebral angiography in the evaluation of these patients. The data presented suggests that with replacement therapy and attention to angio-graphic technique, both procedures may be performed with minimal risk.
Medical Treatment for Spasticity in Children with Cerebral Palsy
Authors: Nogen Alan G.
Published: February 2008

Dantrium® and Valium® were compared in 22 children manifesting various degrees of spasticity. Treatment brought definite improvement in spasticity and in activities of daily living in 20 of the 22 patients. The two-part double-blind study showed that Dantrium was most effective in nine and Valium in seven cases. In four cases the drugs appeared to be equally beneficial. The combination of Dantrium and Valium appeared to be more effective in eight patients than either medication alone, the greatest effect being seen in the upper extremities and about the hip joints. Patients on placebo showed no significant change. Side effects of lethargy and drowsiness on the combination were not bothersome after a short period of acclimation. The results indicate that the spasticity of cerebral palsy can be relieved significantly, and that the combination of peripherally and centrally acting agents is more beneficial than either medication alone.
Multiple Arteriovenous Malformations of Spinal Cord and Brain in a Child
Authors: Hoffman H.J. , Mohr G. , Kusunoki T.
Published: February 2008

A case of extensive spinal cord arteriovenous malformation (AVM) associated with a small AVM of the right temporal lobe in a child is presented. Direct surgical approach with successful treatment in several stages was achieved and an excellent result was obtained.
Meningocoele manqué
Authors: Lassman L.P. , James Michael
Published: February 2008

Meningocoele manqué is a congenital anomaly relating to the spinal cord, cauda equina and the filum terminale commonly found on exploration of the spinal cord in cases of spina bifida occulta. The anomalies consist of fibrous bands, aberrant nerve roots and adhesions within the theca which may tether or press on the neural structures so interfering with nerve conduction and causing increasing neurological deficit. Treatment is to free the neural structures from these bands and adhesions surgically. An account is given of 45 cases with a discussion of their similarity to cases of meningocoele, thus justifying the naming of a previously undescribed clinical entity. Meningocoele manque demonstrates the relation of spina bifida occulta to spina bifida cystica as having a similar origin differing only in degree of severity. All the cases discussed are drawn from a personal series of 200 cases of spina bifida occulta which have had surgical exploration of the spinal cord.
Angiographic Characteristics of Certain Subdural Collections of Fluid
Authors: Gutierrez Francisco A.
Published: February 2008

The presence of abnormal amounts of fluid in the subdural space has been referred to as subdural hematoma, subdural effusion and subdural hygroma. These are supposed to be differentiated by the appearance of the fluid and the presence of membranes in the subdural space. Although both hygroma and chronic subdural hematoma are liquid, space-occupying lesions which cause pressure in the underlying brain, we have found that there are definite angiographic, clinical and prognostic differences between them. These differences are described.
Intracranial Tumors of Children
Authors: Heiskanen O.
Published: February 2008

A report is made on 323 intracranial tumors of children reported to the Cancer Registry in Finland in 1958–1967. The most common sites were the cerebellum, cerebral hemispheres and brain stem. 54% of the tumors were in the posterior fossa. The most common histological types were medulloblastoma, cerebellar astrocytoma and ependymoma. The incidence on the basis of this series was 2.4/105/y. The general outlook for intracranial tumors in childhood was not very good. After a follow-up time of from 5 to 16 years, 31% of the patients were alive. The best prognosis was in cerebellar astrocytomas and cerebral spongioblastomas. In some tumors of the thalamus and third ventricle remissions for over 10 years were achieved by shunt and radiotherapy alone.
Subdural Effusion: Results After Treatment with Subdural-Pleural Shunts
Authors: Arsalo A. , Louhimo I. , Santavuori P. , Valtonen S.
Published: February 2008

In an unselected material of 22 consecutive patients subdural effusion, which did not respond to repeated taps, was treated with subdural-pleural shunt operation using nonvalve silicone catheters. After a mean follow-up time of 3 years 4 months, 17 patients (77%) were mentally and 15 patients (69°/o) neurologically normal. The results are certainly not worse than results achieved with craniotomies and membranectomies. A shunt operation is more simple and less hazardous than membranectomy and we agree with the opinion that the latter is an obsolete procedure in the treatment of persistent subdural effusions.
Fatty Acid in Cerebrospinal Fluid of Congenital Hydrocephalus
Authors: Onodera Yoshihisa , Ito Hiroshi
Published: February 2008

In this presentation the analysis of fatty acid composition in cerebrospinal fluid (CSF), by gas-chromatography, in 40 cases of congenital hydrocephalus before and after shunting operation is discussed. Each fatty acid content was determined by the method which uses arachidic acid as an indicator. The total fatty acid value was found to be significantly higher than normal in the preoperative period in hydrocephalus. The concentration of the total and of the short chain fatty acids (less than C16) in the CSF was higher in the high ventricular CSF pressure group of hydrocephalic patients (above 150 mm H2O) than in the low pressure group. The concentration level of all these fatty acids in the CSF was higher in the cases showing poor prognosis than in those with good prognosis 3 weeks after operation.
Electro-Clinical Follow-up of Shunted Hydrocephalic Children
Authors: Varfis Georges , Berney Jean , Beaumanoir Anne
Published: February 2008

In a survey of 29 hydrocephalic children treated by ventriculoatrial shunt (Holter valve) with a follow-up of 4 years, EEG records before the operation and at least once a year thereafter, the authors can support the view that an epileptogenic focus has developed around the place of insertion of the ventricular catheter in 19 cases, leading to epileptic seizures in 17 up to now. Thus the incidence of convulsions in this particular group of patients is 0.59 (17/29), the limits of confidence 95% being 0.39–0.76. The irritative abnormalities occur usually during the second year after the operation and the delay for the onset of clinical seizures is variable. The age at operation seems to influence the occurrence of the epileptogenic scar. The type of hydrocephalus and especially the presence of an associated cerebral focal lesion can be of importance in the development of clinical seizures.
Spontaneous Occlusion of an Intracranial Arteriovenous Malformation
Authors: Pascual-Castroviejo I. , Pascual-Pascual J.I. , Blazquez M.G. , Lopez-Martin V.
Published: February 2008

The case of a 2-month-old girl is described in whom an arteriovenous malformation (AVM) was observed in the paramedial region of the right cerebral hemisphere associated with an arachnoid cyst in the right fronto-parieto-temporo-occipital region. The only treatment was evacuation of the arachnoid cyst by trephination. When the child was 3 years old, images of the AVM were not found although all the intracranial vessels were angiographically explored. It is considered that the reduced pressure in the right cranial cavity due to the drainage of the arachnoid cyst may contribute to the occlusion of the AVM by causing a slight displacement of the intracranial structures towards the side of the drained cyst.
Disc Space Infections in Children
Authors: Rubin Robert C. , Jacobs George B. , Cooper Paul R. , Wille Rosanne L.
Published: February 2008

Intractable low back pain in children is often due to disc space infections. The clinical presentation, diagnostic workup, and treatment of four cases are presented. Symptoms often occur well before radiographic findings are evident. The diagnosis can only be made by a high degree of suspicion and repeated X-rays. Antecedent causes, such as urinary infection or intravenous administration of narcotics were lacking in this group. Fever or a preceding febrile illness was often, but not invariably, present. Percutaneous biopsies were not usually helpful. Myelography in each instance was normal. Bed rest reduced but did not alleviate the back pain. The institution of appropriate antibiotic therapy resulted in a prompt diminution of pain.
Group B Streptococcal Meningitis: Delayed Response to Treatment
Authors: Edwards Kathryn , Ferrieri Patricia , Thompson Theodore R. , Davis Todd
Published: February 2008

Four infants with group B streptococcal meningitis had a delayed response to antibiotic therapy. Resolution of cerebrospinal fluid infection and/or pleocytosis occurred only after prolonged and intensive antimicrobial management. In this respect, these infants were similar to infants with gram-negative enteric meningitis. It is suggested that infants with group B streptococcal meningitis be closely monitored to insure adequate response to therapy.
Local Delivery of the K
Ca
3.1 Blocker, TRAM-34, Prevents Acute Angioplasty-Induced Coronary Smooth Muscle Phenotypic Modulation and Limits Stenosis
Authors: Tharp D.L. , Wamhoff B.R. , Wulff H. , Raman G. , Cheong A. , Bowles D.K.
Published: February 2008

Objective—

We previously demonstrated that upregulation of intermediate-conductance Ca
2+
-activated K
+
channels (K
Ca
3.1) is necessary for mitogen-induced phenotypic modulation in isolated porcine coronary smooth muscle cells (SMCs). The objective of the present study was to determine the role of K
Ca
3.1 in the regulation of coronary SMC phenotypic modulation in vivo using a swine model of postangioplasty restenosis.

Methods and Results—

Balloon angioplasty was performed on coronary arteries of swine using either noncoated or balloons coated with the specific K
Ca
3.1 blocker TRAM-34. Expression of K
Ca
3.1, c-jun, c-fos, repressor element-1 silencing transcription factor (REST), smooth muscle myosin heavy chain (SMMHC), and myocardin was measured using qRT-PCR in isolated medial cells 2 hours and 2 days postangioplasty. K
Ca
3.1, c-jun, and c-fos mRNA levels were increased 2 hours postangioplasty, whereas REST expression decreased. SMMHC expression was unchanged at 2 hours, but decreased 2 days postangioplasty. Use of TRAM-34 coated balloons prevented K
Ca
3.1 upregulation and REST downregulation at 2 hours, SMMHC and myocardin downregulation at 2 days, and attenuated subsequent restenosis 14 and 28 days postangioplasty. Immunohistochemical analysis demonstrated corresponding changes at the protein level.

Conclusion—

Blockade of K
Ca
3.1 by delivery of TRAM-34 via balloon catheter prevented smooth muscle phenotypic modulation and limited subsequent restenosis.
Human Stanniocalcin-1 Blocks TNF-α–Induced Monolayer Permeability in Human Coronary Artery Endothelial Cells
Authors: Chen Changyi , Jamaluddin Md Saha , Yan Shaoyu , Sheikh-Hamad David , Yao Qizhi
Published: February 2008

Objective—

Our previous studies revealed upregulation of stanniocalcin-1 (STC1) in cardiac vessels in dilated cardiomyopathy. However, the functional significance of STC1 is unknown. The objective of this study was to determine the effects of STC1 on TNF-α–induced monolayer permeability of human coronary artery endothelial cells (HCAECs).

Methods and Results—

Cells were pretreated with STC1 for 30 minutes followed by treatment with TNF-α (2 ng/mL) for 24 hours. Monolayer permeability was studied using a transwell system. STC1 pretreatment significantly blocked TNF-α–induced monolayer permeability in a concentration- and time-dependent manner. STC1 effectively blocked TNF-α–induced downregulation of endothelial tight junction proteins zonula occluden-1 and claudin-1 at both mRNA and protein levels. STC1 also significantly decreased TNF-α–induced superoxide anion production. The inhibitory effect of STC1 was specific to TNF-α, as it failed to inhibit VEGF-induced endothelial permeability. Furthermore, STC1 partially blocked NF-κB and JNK activation in TNF-α–treated endothelial cells. JNK inhibitor and antioxidant also effectively blocked TNF-α–induced NF-κB activation and monolayer permeability in HCAECs.

Conclusions—

STC1 maintains endothelial permeability in TNF-α–treated HCAECs through preservation of tight junction protein expression, suppression of superoxide anion production, and inhibition of the activation of NFκB and JNK, suggesting an important role for STC1 in regulating endothelial functions during cardiovascular inflammation.
Simvastatin Reduces
Chlamydophila pneumoniae
–Mediated Histone Modifications and Gene Expression in Cultured Human Endothelial Cells
Authors: Schmeck Bernd , Beermann Wiebke , N’Guessan Philippe Dje , Hocke Andreas C. , Opitz Bastian , Eitel Julia , Dinh Quoc Thai , Witzenrath Martin , Krüll Matthias , Suttorp Norbert , Hippenstiel Stefan
Published: February 2008

Inflammatory activation of the endothelium by
Chlamydophila pneumoniae
infection has been implicated in the development of chronic vascular lesions and coronary heart disease by seroepidemiological and animal studies. We tested the hypothesis that
C pneumoniae
induced inflammatory gene expression is regulated by Rho-GTPase–related histone modifications.
C pneumoniae
infection induced the liberation of proinflammatory interleukin-6, interleukin-8, granulocyte colony-stimulating factor, macrophage inflammatory protein-1β, granulocyte/macrophage colony-stimulating factor, and interferon-γ by human endothelial cells. Cytokine secretion was reduced by simvastatin and the specific Rac1 inhibitor NSC23766 but was synergistically enhanced by inhibitors of histone deacetylases trichostatin A and suberoylanilide hydroxamic acid. Infection of endothelial cells with viable
C pneumoniae
, but not exposure to heat-inactivated
C pneumoniae
or infection with
C trachomatis
, induced acetylation of histone H4 and phosphorylation and acetylation of histone H3. Pretreatment of
C pneumoniae
–infected cells with simvastatin or NSC23766 reduced global histone modifications as well as specific modifications at the
il8
gene promoter, as shown by chromatin immunoprecipitation. Reduced recruitment of nuclear factor κB p65/RelA as well as of RNA polymerase II was observed in statin-treated cells. Taken together, Rac1-mediated histone modifications seem to play an important role in
C pneumoniae
–induced cytokine production by human endothelial cells.
Is the Impact of Job Control on Stroke Independent From Socioeconomic Status?
Authors: Toivanen Susanna , Hemström Örjan
Published: February 2008

Background and Purpose—

The main purpose of this study was to test whether the impact of job control on stroke mortality is independent of socioeconomic factors.

Methods—

This was a register-based cohort study of nearly 3.5 million working people (25 to 64 years of age in the 1990 Swedish Census) with a 5-year follow-up for stroke mortality. Job control was aggregated to the data from a secondary data source (job exposure matrix). Gender-specific Poisson regressions were performed.

Results—

Compared with high job control occupations, low job control was significantly related to hemorrhagic (relative risk, 1.54; 95% CI, 1.10 to 2.17) and all-stroke mortality (relative risk, 1.50; 95% CI, 1.11 to 2.03) in women but not in men. The significance of job control in women was independent of all confounders included (marital status, education level, and occupational class). Class-specific analyses indicated a consistent effect of job control for most classes (significant for female lower nonmanuals). However, low job control did not increase the risk of stroke mortality in upper nonmanuals.

Conclusions—

Job control was significantly related to hemorrhagic and all-stroke mortality in women but not in men.
Retinal Signs and Stroke
Authors: Baker Michelle L. , Hand Peter J. , Wang Jie Jin , Wong Tien Y.
Published: February 2008

Background and Purpose—

The retinal and cerebral vasculature share similar anatomic, physiological, and embryological characteristics. We reviewed the literature, focusing particularly on recent population-based studies, to examine the relationship between retinal signs and stroke.

Summary of Review—

Hypertensive retinopathy signs (eg, focal retinal arteriolar narrowing, arterio-venous nicking) were associated with prevalent stroke, incident stroke, and stroke mortality, independent of blood pressure and other cerebrovascular risk factors. Diabetic retinopathy signs (eg, microaneurysms, hard exudates) were similarly associated with incident stroke and stroke mortality. Retinal arteriolar emboli were associated with stroke mortality but not incident stroke. There were fewer studies on the association of other retinal signs such as retinal vein occlusion and age-related macular degeneration with stroke, and the results were less consistent.

Conclusion—

Many retinal conditions are associated with stroke, reflecting possible concomitant pathophysiological processes affecting both the eye and the brain. However, the incremental value of a retinal examination for prediction of future stroke risk remains to be determined.
Mechanical Thrombectomy for Acute Ischemic Stroke
Authors: Smith Wade S. , Sung Gene , Saver Jeffrey , Budzik Ronald , Duckwiler Gary , Liebeskind David S. , Lutsep Helmi L. , Rymer Marilyn M. , Higashida Randall T. , Starkman Sidney , Gobin Y. Pierre
Published: February 2008

Background and Purpose—

Endovascular mechanical thrombectomy may be used during acute ischemic stroke due to large vessel intracranial occlusion. First-generation MERCI devices achieved recanalization rates of 48% and, when coupled with intraarterial thrombolytic drugs, recanalization rates of 60% have been reported. Enhancements in embolectomy device design may improve recanalization rates.

Methods—

Multi MERCI was an international, multicenter, prospective, single-arm trial of thrombectomy in patients with large vessel stroke treated within 8 hours of symptom onset. Patients with persistent large vessel occlusion after IV tissue plasminogen activator treatment were included. Once the newer generation (L5 Retriever) device became available, investigators were instructed to use the L5 Retriever to open vessels and could subsequently use older generation devices and/or intraarterial tissue plasminogen activator. Primary outcome was recanalization of the target vessel.

Results—

One hundred sixty-four patients received thrombectomy and 131 were initially treated with the L5 Retriever. Mean age±SD was 68±16 years, and baseline median (interquartile range) National Institutes of Health Stroke Scale score was 19 (15 to 23). Treatment with the L5 Retriever resulted in successful recanalization in 75 of 131 (57.3%) treatable vessels and in 91 of 131 (69.5%) after adjunctive therapy (intraarterial tissue plasminogen activator, mechanical). Overall, favorable clinical outcomes (modified Rankin Scale 0 to 2) occurred in 36% and mortality was 34%; both outcomes were significantly related to vascular recanalization. Symptomatic intracerebral hemorrhage occurred in 16 patients (9.8%); 4 (2.4%) of these were parenchymal hematoma type II. Clinically significant procedural complications occurred in 9 (5.5%) patients.

Conclusions—

Higher rates of recanalization were associated with a newer generation thrombectomy device compared with first-generation devices, but these differences did not achieve statistical significance. Mortality trended lower and the proportion of good clinical outcomes trended higher, consistent with better recanalization.
Toll-Like Receptor 4 Is Involved in Subacute Stress–Induced Neuroinflammation and in the Worsening of Experimental Stroke
Authors: Caso Javier R. , Pradillo Jesus M. , Hurtado Olivia , Leza Juan C. , Moro Maria A. , Lizasoain Ignacio
Published: February 2008

Background and Purpose—

Psychological stress causes an inflammatory response in the brain and is able to exacerbate brain damage caused by experimental stroke. We previously reported that subacute immobilization stress in mice worsens stroke outcome through mechanisms that involve inflammatory mechanisms, such as accumulation of oxidative/nitrosative mediators and expression of inducible nitric oxide synthase and cyclooxygenase-2 in the brain. Some of these inflammatory mediators could be regulated by innate immunity, the activation of which takes place in the brain and produces an inflammatory response mediated by toll-like receptors (TLRs). Recently, we described the implications of TLR4 in ischemic injury, but the role of TLR4 in stress has not yet been examined. We therefore investigated whether inflammation produced by immobilization stress differs in mice that lack a functional TLR4 signaling pathway.

Methods—

We used an experimental paradigm consisting of the exposure of mice to repeated immobilization sessions (1 hour daily for 7 days) before permanent middle cerebral artery occlusion.

Results—

We found that TLR4-deficient mice subjected to subacute stress had a better behavioral condition compared with normal mice (C3H/HeN) and that this effect was associated with a minor inflammatory response (cyclooxygenase-2 and inducible nitric oxide synthase expression) and lipid peroxidation (malondialdehyde levels) in brain tissue. Furthermore, previous exposure to stress was followed by a smaller infarct volume after permanent middle cerebral artery occlusion in TLR4-deficient mice than in mice that express TLR4 normally.

Conclusions—

Our results indicate that TLR4 is involved in the inflammatory response after subacute stress and its exacerbating effect on stroke. These data implicate the effects of innate immunity on inflammation and damage in the brain after stroke.