Intrathecal granulocyte colony-stimulating factor modulate glial cell line-derived neurotrophic factor and vascular endothelial growth factor A expression in glial cells after experimental spinal cord ischemia.

The hematopoietic growth factor, granulocyte colony-stimulating factor (G-CSF), has become one of the few growth factors approved for clinical use. It has therapeutic potential for numerous neurodegenerative diseases; however, at present the cellular effects of G-CSF on the central nervous system remain unclear and in need of investigation. In the present study, we used spinal cord ischemia, a neurodegenerative model, to examine the effects of intrathecal (i.t.) G-CSF on glial cell (microglia and astrocyte) activation and neuroprotective factor expression, including glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor A (VEGF-A) protein expression. Our results indicate that i.t. G-CSF could enhance ischemia-induced microglial activation and inhibit ischemia-induced astrocyte activation. Both GDNF and VEGF-A are upregulated after injury, and i.t. G-CSF could enhance GDNF and VEGF-A expressions after injury. Interestingly, our results indicate that performing i.t. G-CSF alone on normal animals could have the effect of microglial and astrocyte activation and enhanced GDNF and VEGF-A expressions. Furthermore, through laser scanning confocal microscopy, we found that astrocytes may contribute to the majority of GDNF and VEGF-A expressions of G-CSF after spinal cord ischemia. Overall, this G-CSF-induced upregulation suggests that activation of endogenous neuroprotective mechanisms could resist neurodegenerative insults. These observations demonstrate the cellular mechanism of i.t. G-CSF after spinal cord ischemia and confirm the neuroprotective effect of G-CSF after spinal cord ischemia injury.

Suppressive effects of intrathecal granulocyte colony-stimulating factor on excessive release of excitatory amino acids in the spinal cerebrospinal fluid of rats with cord ischemia: role of glutamate transporters.

Recently, the hematopoietic factor, granulocyte colony-stimulating factor (G-CSF), has been shown to exhibit neuroprotective effects in CNS injuries. Our previous study demonstrated that intrathecal (i.t.) G-CSF significantly improved neurological defects in spinal cord ischemic rats. Considerable evidence indicates that the release of excessive amounts of excitatory amino acids (EAAs) plays a critical role in neuron injury induced by ischemic insult. In the present study, we used a spinal cord ischemia-microdialysis model to examine whether i.t. G-CSF exerted antiexcitotoxicity effects in a rat model of spinal cord ischemia. I.t. catheters and a microdialysis probe were implanted in male Wistar rats. The results revealed that spinal cord ischemia-induced neurological defects were accompanied by a significant increase in the concentration of EAAs (aspartate and glutamate) in the spinal dialysates from 30 min to 2 days after reperfusion. I.t administration of G-CSF immediately after the performance of surgery designed to induce ischemia led to a significant reduction in ischemia-induced increases in the levels of spinal EAAs. Moreover, i.t. G-CSF also brought about a significant reduction in the elevation of spinal EAA concentrations induced by exogenous i.t. administration of glutamate (10 microl of 500 mM). I.t. G-CSF attenuated spinal cord ischemia-induced downregulation of expression of three glutamate transporters (GTs), glial transporter Glu-Asp transporter (GLAST), Glu transporter-1 (GLT-1), and excitatory amino acid carrier 1 (EAAC1) protein 48 h after spinal cord ischemic surgery. Immunohistofluorescent staining showed that i.t. G-CSF significantly upregulated expression of the three GTs in the gray matter of the lumbar spinal cord from 3 to 24 h after injection. We propose that i.t. G-CSF possesses an ability to reduce the extent of spinal cord ischemia-induced excitotoxicity by inducing the expression of glutamate transporters.

Long-term visual outcomes of laser-treated threshold retinopathy of prematurity: a study of refractive status at 7 years.

PURPOSE: To assess the long-term visual outcomes and refractive status in patients with diode laser-treated threshold retinopathy of prematurity (ROP), and to investigate the causes of impaired visual function. METHOD: A total of 60 eyes of 30 consecutive patients with diode laser-treated threshold ROP were recalled for assessment at the age of 7 years or more. RESULTS: There were 38 eyes (65.5%) achieving 6/12 or better vision, however, an unfavourable visual outcome (6/60 or worse) occurred in four eyes (6.9%). One eye (1.7%) had unfavourable structural outcome. Of these 60 laser-treated eyes, 46 eyes (77.0%) were myopic, the overall mean spherical equivalent was -3.87 D. Anisometropia (>or=1.5 D) was also noted in 14 patients (46.7%). Strabismus was present in nine patients (30.0%). Perinatal neurological events of intraventricular haemorrhage (IVH) were identified in eight children (26.7%), periventricular leucomalacia (PVL) in eight children (26.7%), and cerebral palsy (CP) in four children (13.3%). There was a statistically significant association of the presence of strabismus with PVL (P=0.002). The presence of anisometropia was a significant risk factor associated with poor visual outcome of 6/15 or worse in laser-treated ROP (P=0.002). CONCLUSION: The majority of patients with diode laser-treated threshold ROP had favourable anatomical and visual outcomes. However, anisometropia, advanced refractive error, strabismus, and perinatal neurological events remain important causes of impaired visual function. Long-term follow-up is very important for early detection and timely treatment of these ocular morbidities.

Isoflurane attenuates dynorphin-induced cytotoxicity and downregulation of Bcl-2 expression in differentiated neuroblastoma SH-SY5Y cells.

BACKGROUND: It has been proposed that the volatile anesthetic isoflurane induces neuroprotection and that the endogenous opioid peptide dynorphin induces neurocytotoxicity in cells. The levels of dynorphin are often significantly elevated in neuropathophysiological conditions, and dynorphin can directly induce toxicity. However, the neuroprotective effects of isoflurane on dynorphin-induced cytotoxicity are still unclear. METHODS: In order to determine the effect of isoflurane on dynorphin-induced cytotoxicity in neuronal cells, we have designed a device wherein cultured human neuroblastoma SH-SY5Y cells can be exposed to isoflurane. Fully differentiated SH-SY5Y cells were obtained by treating the cells with retinoic acid for 6 days. We examined SH-SY5Y cell survival, apoptosis, and antiapoptotic protein expression by cell viability, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling stain, and Western blot analysis, respectively. RESULTS: After 16 h of dynorphin (10 microM) treatment, the SH-SY5Y cells showed significant cytotoxicity, apoptosis, and downregulation of the antiapoptotic Bcl-2 protein expression. These effects of dynorphin were significantly inhibited by isoflurane exposure for 32 h [pretreatment for 16 h and posttreatment (after dynorphin treatment) for 16 h]. CONCLUSION: Thus, our results suggest that isoflurane exerts neuroprotective effects in the case of dynorphin-induced pathophysiological disruption.

Intrathecally injected granulocyte colony-stimulating factor produced neuroprotective effects in spinal cord ischemia via the mitogen-activated protein kinase and Akt pathways.

Granulocyte colony-stimulating factor (G-CSF) is a potent hematopoietic factor. Recently, this factor has been shown to exhibit neuroprotective effects on many CNS injuries. Spinal cord ischemic injury that frequently results in paraplegia is a major cause of morbidity after thoracic aorta operations. In the present study, we examined the neuroprotective role of G-CSF on spinal cord ischemia-induced neurological dysfunctions and changes in the mitogen-activated protein kinase (MAPK) and Akt signaling pathways in the spinal cord. Spinal cord ischemia was induced in male Wistar rats by occluding the descending aorta with a 2F Fogarty catheter for 12 min 30 s. Immediately after ischemia surgery, the rats were administered G-CSF (10 mug) or saline by intrathecal (i.t.) injection. The rats were divided into four groups: control, ischemia plus saline, ischemia plus G-CSF and G-CSF alone. The neurological dysfunctions were assessed by calculating the motor deficit index after ischemia surgery. The expressions of MAPK and Akt were studied using Western blotting and double immunohistochemistry. First, we observed that ischemia plus i.t. G-CSF can significantly reduce the motor function defects and downregulate phospho-p38 and phospho-c-Jun N-terminal kinase protein expressions-this can be compared with the ischemia plus saline group. In addition, G-CSF inhibited the ischemia-induced activation of p38 in the astrocytes. Furthermore, we concluded that i.t. G-CSF produced a significant increase in phospho-Akt and phospho-ERK in the motor neurons and exhibited beneficial effects on the spinal cord ischemia-induced neurological defects.

Preventive effects of intrathecal methylprednisolone administration on spinal cord ischemia in rats: the role of excitatory amino acid metabolizing systems.

Spinal cord ischemic injury usually results in paraplegia, which is a major cause of morbidity after thoracic aorta operations. Ample evidence indicates that massive release of excitatory amino acids (EAAs; glutamate) plays an important role in the development of neuronal ischemic injuries. However, there is a lack of direct evidence to indicate the involvement of EAAs in the glutamate metabolizing system (including the glutamate transporter isoforms, i.e. the Glu-Asp transporter (GLAST), Glu transporter-1 (GLT-1), and excitatory amino acid carrier one (EAAC1); glutamine synthetase (GS); and glutamate dehydrogenase (GDH)) in spinal cord ischemia. In the present results, we found that methylprednisolone (MP; intrathecal (i.t.) injection, 200 mug twice daily administered for 3 days before ischemia), a synthetic glucocorticoid, is the therapeutic agent for the treatment of spinal injuries in humans, can significantly reduce the ischemia-induced motor function defect and down-regulate the glutamate metabolizing system (including GLAST, GLT-1, GS, and GDH) in male Wistar rats. The spinal cord ischemia-induced down-regulation of EAAC1 protein expression in the ventral portion of the lumbar spinal cord was partly inhibited by pretreatment with i.t. MP. However, MP did not affect the down-regulation of EAAC1 in the dorsal portion of the lumbar spinal cord after spinal cord ischemia. The i.t. injection of MP alone did not change the neurological functions and the expression of proteins of the glutamate metabolizing system in the spinal cord. Our results indicate that spinal cord ischemia-induced neurological deficits accompany the decrease in the expression of proteins of the glutamate metabolizing system in the lumbar portion of the spinal cord. The i.t. MP pretreatment significantly prevented these symptoms. These results support the observation that MP delivery through an i.t. injection, is beneficial for the treatment of spinal cord ischemic injuries.

Abdominal vascular injury during lumbar disc surgery.

Major vascular injury is an unusual but well-recognized complication of vertebral disc surgery. Isolated arterial laceration is the most common type of this vessel injury in lumbar spine surgery, with early manifestation due to retroperitoneal hemorrhage. Two cases are described that illustrate the full spectrum of acute manifestation of such injuries. Two cases of acute hemorrhage due to arterial trauma were seen; one mortality case was recognized during the operation and one salvaged in the recovery room. In both cases unstable perioperative hemodynamics and postoperative distended abdomen were observed. It is the purpose of this paper to report two cases and to discuss the morbid anatomy, diagnosis of such vascular injuries and anesthetic handling of retroperitoneal hemorrhage. For anesthesiologists who are also drill workers while doing lumbar spinal or epidural anesthesia, these rare catastrophes remind us to pay special attention to the vertebral vascular (not only skeletal) anatomy.

Effect of oral clonidine premedication on perioperative hemodynamic response and postoperative analgesic requirement for patients undergoing laparoscopic cholecystectomy.

BACKGROUND: To investigate the clinical efficacy of oral clonidine premedication in anesthesia and analgesia in patients undergoing laparoscopic cholecystectomy (LC). METHODS: One hundred and ten patients, scheduled for elective laparoscopic cholecystectomy, were recruited for the prospective, randomized, single-blind, comparative study. They were randomly allotted to either of the placebo or clonidine group. Patients of the placebo group (n = 65) were premedicated with oral antacid (alugel hydroxide 300 mg), while those in the clonidine group (n = 45) were premedicated with oral clonidine 150 micrograms prior to anesthesia. The premedication was given 60 to 90 min before the anticipated time of induction of anesthesia. Normocapnia was maintained throughout the perioperative period. Mass spectrometer was used to assess the inspired and expiratory concentrations of isoflurane, the anesthetic used for maintenance of anesthesia. Postoperative pain intensity, sedation scores, adverse events, time to the first dose of postoperative analgesic and cumulative analgesic requirement in 24 hours were recorded. Data were expressed as mean +/- SD. RESULTS: Patients in the clonidine group displayed greater hemodynamic stability perioperatively and the isoflurane requirement was also reduced (30% less). The postoperative analgesic requirement was less (1.5 +/- 1.3 vs. 2.2 +/- 1.3 dose, P < 0.05) and the time for the first dose of analgesic was prolonged (411 +/- 565 vs. 264 +/- 441 min) in comparison with the placebo group but no statistic difference was found. CONCLUSIONS: Oral clonidine premedication helped to provide perioperative hemodynamic stability, spared the use of isoflurane and reduced the requirement of postoperative analgesia so as to smoother the way to recovery in patients undergoing LC.

Fatal pulmonary embolism in a child undergoing extra-ventricular drainage surgery--a case report.

Thromboembolism is rather common in neurological patients and patients with brain tumor, who are bed-ridden or with partial immobile limb. In serious instances morbidity and mortality are inevitable. We present a case report on a fatal pulmonary embolism in a 2-year-old girl who underwent extra-ventricular drainage procedure under general anesthesia for occipital subdural effusion, a sequela of the former surgery undertaken to remove the choroid plexus papilloma 13 days ago. Sudden cardiac arrest occurred during induction of anesthesia and she finally succumbed in spite of vigorous cardiopulmonary resuscitation. Transthoracic and transesophageal echocardiography performed in the course of resuscitation disclosed thrombi of various sizes scattering in right atrium, the right ventricle, main pulmonary trunk, and the left pulmonary artery. The cause of death was thought to be severe obstruction of right ventricular outflow tract by large thrombi. The etiological factors which possibly led to the thrombosis were discussed, and the methods of diagnosis and treatment were also explored.

Anesthetic management of a parturient with Eisenmenger's syndrome and preeclampsia during cesarean section--a case report.

It has been recommended that women with Eisenmenger's syndrome (ES) are better not to become pregnant and pregnancy may justifiably be terminated by artificial abortion to avoid high maternal mortality and coherent fetal mortality. We present a case report about a parturient with ventricular septal defect (VSD) and ES who received general anesthesia for Cesarean section (C/S) because of preeclampsia, as a result of which she finally succumbed to an episode of intraoperative hypotension in spite of vigorous cardiopulmonary resuscitation. The death was thought to be precipitated by continuous deterioration of maternal health during the 3rd trimester of gestation. The anesthetic management of pregnant ES patients in confinement was reviewed and discussed, and the possible etiological factors relevant to the tragic outcome were also explored.

Anesthetic management in a parturient with progressive systemic sclerosis during cesarean section--a case report.

This case report concerns a successful Cesarean section (C/S) delivery in an expectant woman affected with progressive systemic sclerosis (PSS) with clinical manifestations of severe pulmonary hypertension (PH), cor pulmonale, severely restrictive ventilatory impairment, pregnancy-induced hypertension (PIH), and esophageal dysfunction under general anesthesia (GA). This is an extremely rare condition in obstetrics and the victim is usually in a great peril of conception, delivery, surgery and anesthesia because of poor pulmonary and cardiac reserves. We herewith reported our experience in two GAs given uniquely to the same patient who was affected with the disorder and discuss the problem.

Incidence and risk factors of guidewire-induced arrhythmia during internal jugular venous catheterization: comparison of marked and plain J-wires.

STUDY OBJECTIVES: To compare the incidence and risk factors of guidewire-induced arrhythmia (GIA) during internal jugular venous catheterization (IJV). DESIGN: Prospective study. SETTING: Operating rooms at a medical center. PATIENTS: 303 ASA physical status I, II, III, and IV patients undergoing elective surgery. INTERVENTIONS: All patients were cannulated with the central venous catheters placed via the right internal jugular vein after induction of anesthesia. They were randomly divided into two groups. In one group, we used a marked J-wire and inverted up to, but not beyond 20 cm (Group M, n = 127). In the other group, a plain unmarked J-wire was used and inserted at will (Group UM, n = 176). All IJV catheterizations were performed by residents, and the length of J-wire inserted was then measured. MEASUREMENTS AND MAIN RESULTS: Types of arrhythmia [eg, premature atrial contraction (PAC) or premature ventricular contraction (PVC)] were interpreted by attending anesthesiologists on lead II ECG. Patients in Group UM had a significantly greater incidence of GIA than those in Group M (28.4% vs. 3.9%; p < .005). However, in both groups, PAC occurred more frequently than PVC. Factors such as the inserted length of guidewire longer than 20 cm, body height less than 170 cm, and female gender were significantly associated with GIA (p < 0.005). CONCLUSIONS: Limiting the length of the guidewire insertion to less than or equal to 20 cm for right IJV catheterization by using a marked J-wire will reduce the incidence of GIA. We recommend the use of a marked J-wire for IJV catheterization.

Transesophageal indirect atrial pacing for open-heart surgery in children.

BACKGROUND: Transesophageal atrial pacing (TAP) has been successfully applied for clinical use for more than 30 years. Not only for cardiac pacing, or diagnosis and treatment of rhythmic disturbance but also for assessing the presence and severity of coronary artery disease and maintaining adequate heart rate can TAP provide satisfactory effect. In this study we applied TAP on children undergoing the cardiac surgery to evaluate its efficacy and side effects during such major surgery. METHODS: Twenty-four children (15 M and 9 F) undergoing open-heart surgery with informed consents were included in this study. After induction of anesthesia the bipolar pacing electrode (Tapcath, Arzco Medical Electronics) was inserted into esophagus through the nose until the ideal site for atrial pacing was found by monitoring the esophageal ECG lead (lead I), and then initiation of atrial pacing was performed by applying the transesophageal cardiac stimulator (Arzco Medical Electronics). Continuous ECG, arterial blood pressure and central venous pressure (CVP) were simultaneously monitored and recorded. Patient's height, inserted length of the pacing electrode, current and pulse duration for effective atrial pacing were also recorded. RESULTS: The effective rate for initiating sinus tachycardia (atrial capture) by applying TAP was 79.2% (19/24) in our study. For effective atrial pacing the average current was 11.6 +/- 2.4 mA, the average stimulus pulse duration was 4.8 +/- 1.0 ms, and the average inserted length of bipolar electrode was 19.1 +/- 2.2 cm. CONCLUSIONS: TAP method can be applied satisfactorily in children undergoing cardiac surgery. If urgent cardiac pacing must be applied in these patients TAP would be a choice.

Is postextrasystolic potentiation dependent on Starling's law? Biplane angiographic studies in normal subjects.

The cineangiograms of 26 normal subjects were analyzed to study the effect of Starling's mechanism on postextrasystolic potentiation. The end-diastolic volumes (single plane and biplane) of the left ventricle were similar in the regular sinus beat before an extrasystole and sequential sinus beats after an extrasystole. However, the ejection fraction, mean normalized systolic ejection rate, mean velocity of fiber shortening and long-axis shortening were consistently larger in the first sinus beat after an extrasystole. We conclude that postextrasystolic potentiation is independent of left ventricular end-diastolic volume in normal human hearts and the compensatory pause after an extrasystole does not result in increased end-diastolic volume.

ESCA studies of surface chemical composition of segmented polyurethanes.

Surface chemical analysis of two commercially available polyurethanes, i.e., Avcothane and Biomer was carried out by electron spectroscopy for chemical analysis (ESCA). The depth which is subject to analysis is in the range of 50-100 A. The variables studied in this study are the difference in exposure to air or to the mold substrate during the solvent casting process. Model compounds such as a pure polydimethylsiloxane, polyether soft segment and hard segment copolymer were used to identify and assign various ESCA peaks. The air facing surface of Avcothane which is the blood contacting surface is found to be covered mostly with polydimethylsiloxane polymer, with a small amount of polyether soft segment mixed with silicone. Therefore, the hard segment of the polyurethanes is hidden beneath the blood contact surface in Avcothane. In Biomer films, the air facing surface contains a greater concentration of polyether soft segment than the substrate surface. These results are consistent with our previous results obtained by Fourier transform IR internal reflection and Auger electron spectroscopy.

Application of Auger electron spectroscopy for surface chemical analysis of Avcothane.

The effect of the exposure to air or to the substrate during the solvent casting process on the surface chemical composition of Avcothane, a blood compatible biomaterial, was studied by employing Auger electron spectroscopy. The surface layer of 10-15A thickness was analyzed without sputtering, but for the studies probing a deeper layer, argon ion sputtering at a low enough voltage to prevent artifacts was utilized. It is found that the air facing surface which is the blood contact surface contains a greater amount of silicone polymer and a much lower amount of the urethane hard segment in the first 10-15A-deep layer than in the comparably thick layer of the substrate surface. However, the depth-composition profile obtained by sputtering indicate that, probably at a deeper depth, the chemical compositions in terms of silicone polymer and hard segment is comparable both in the air side and the substrate side.

Surface chemical analysis of Avcothane and Biomer by Fourier transform IR internal reflection spectroscopy.

During the solvent casting process, one side of the polymer film is exposed to air while the other side is in contact with a substrate, used as a mold. We have studied the effect of this difference in exposure during casting on the chemical composition of two types of segmented polyurethane, Biomer and Avcothane, by using Fourier transform IR internal reflection spectroscopy. Also, a depth-composition profile was obtained by placing a thin barrier film between the reflection plate and the polymer film. In Avcothane, the air side, which is the blood-contact side, contains a greater amount of the soft segment than the substrate side, and this is more pronounced in the layer closer to the surface. The anisotropy in composition is more drastic when the silicone content is compared. In a layer about 1.5 mu thick, one can detect a greater amount of silicone in the substrate side than in the air side. However, when one averages the concentration in a layer of about 0.8 microns the trend in reversed; i.e., the greater amount of silicone is now present in the air side than in the substrate side. In Biomer films, the anisotropy in chemical composition is less pronounced. Only a modest increase in the relative content of the soft segment/hard segment is observed in the air side when a depth-composition profile is obtained.