Magnetic resonance imaging in the canine double-haemorrhage subarachnoid haemorrhage model.

In this study, we investigated T2 weighted imaging (T2WI) and T2 values of the cortex, thalamus and cerebrospinal fluid (CSF) of the ventricles in the canine double-haemorrhage subarachnoid haemorrhage (DHSAH) model. T2 values in the cortex increased compared to prescan values from 123.07 +/- 18.72 msec on day 2 to 89.43 +/- 1.98 msec on day 7 (p < 0.05). A trend toward a temporal increase in T2 values was observed in the thalamus, but did not reach significance. The T2 values of the ventricular CSF increased by 102.2% on day 2 and 159.6% on day 7 compared to prescan values. These changes reached significance (p < 0.05) on day 7. Additionally, the ventricular size increased over the study period. Our data suggest that we can use this model to investigate acute brain injury and normal pressure hydrocephalus (NPH) after SAH.

Exercise-induced systolic dysfunction in patients with non-obstructive hypertrophic cardiomyopathy and mutations in the cardiac troponin genes.

OBJECTIVES: The aim of this study was to investigate left ventricular (LV) function reserve in hypertrophic cardiomyopathy (HCM) patients with and without cardiac troponin gene mutations before transition to the dilated phase. METHODS: LV ejection fraction (EF) was continuously evaluated in 52 patients with non-obstructive HCM during supine ergometer exercise using radionuclide ventricular function monitoring with a cadmium telluride detector (VEST). On the basis of genetic analysis, patients were divided into two groups: 10 with cardiac troponin gene mutations (group A) and 42 without these gene mutations (group B). RESULTS: Exercise duration, peak exercise load, and heart rate during exercise did not differ between the two groups. The differences from baseline to peak exercise ofthe LV end-diastolic volume decreased similarly in the twogroups. In contrast, the difference of the LV end-systolicvolume in group A increased significantly compared withgroup B (17.7% (SD 12.7%) vs 3.4% (SD 13.2%);p=0.0031). Consequently, the difference of LVEF ingroup A decreased significantly in contrast with group B(-14.1% (SD 11.1%) vs -1.2% (SD 11.7%); p=0.0025).Additionally, the changes in LVEF and stroke volumedecreased significantly more in group A than in group B(-22.2% (SD 18.6%) vs -1.1% (SD 17.8%); p=0.0017and -12.9% (SD 21.7%) vs 12.3% (SD 24.4%);p=0.0042, respectively). CONCLUSIONS: These results suggest that HCM patientswith cardiac troponin gene mutations may displayexercise-induced LV systolic dysfunction more frequentlythan HCM patients without this abnormality

Anti-apoptotic effect of granulocyte-colony stimulating factor after focal cerebral ischemia in the rat.

We investigated the molecular mechanisms of the anti-apoptotic properties of granulocyte-colony stimulating factor (G-CSF) on neurons and whether G-CSF affects glial cell survival following focal cerebral ischemia in rats. Sprague-Dawley rats were subjected to a transient 90 min middle cerebral artery occlusion (MCAO) by the intraluminal occlusion technique. Rats were treated with either a single dose of G-CSF (50 microg/kg, s.c.) at the onset of reperfusion or G-CSF (50 microg/kg body weight, s.c.) was administered starting at the onset of reperfusion and followed by the administration of the same dose per day for an additional 2 days. Brains were harvested either 24 h, 72 h or 2 weeks after reperfusion for assays of infarct volume, immunohistological studies and Western blot analysis for phosphorylated signal transducer and activator of transcription 3 (pSTAT3), Pim-1, bcl-2, Bax, cytochrome c, cellular inhibitor of apoptosis protein 2 (cIAP2), and cleaved caspase-3 levels. G-CSF significantly reduced infarct volume and ameliorated the early neurological outcome. G-CSF treatment significantly up-regulated pSTAT3, Pim-1, bcl-2 expression, and down-regulated cytochrome c release to the cytosol, Bax translocation to the mitochondria, and cleaved caspase-3 levels in neurons. The activation of the STAT3 pathway was accompanied by increased cIAP2 expression in glial cells. After MCAO, G-CSF treatment increased both neuronal and glial survival by effecting different anti-apoptotic pathways which reflects the multifactorial actions of this drug. These changes were associated with remarkable improvement in tissue preservation and behavioral outcome.

Comparison of propofol/remifentanil and sevoflurane/remifentanil for maintenance of anaesthesia for elective intracranial surgery.

BACKGROUND: Propofol and sevoflurane are suitable agents for maintenance of anaesthesia during neurosurgical procedures. We have prospectively compared these agents in combination with the short-acting opioid, remifentanil. METHODS: Fifty unpremedicated patients undergoing elective craniotomy received remifentanil 1 microg kg(-1) followed by an infusion commencing at 0.5 microg kg(-1) min(-1) reducing to 0.25 microg kg(-1) min(-1) after craniotomy. Anaesthesia was induced with propofol, and maintained with either a target-controlled infusion of propofol, minimum target 2 microg ml(-1) or sevoflurane, initial concentration 2%(ET). Episodes of mean arterial pressure (MAP) more than 100 mm Hg or less than 60 mm Hg for more than 1 min were defined as hypertensive or hypotensive events, respectively. A surgical assessment of operating conditions and times to spontaneous respiration, extubation, obey commands and eye opening were recorded. Drug acquisition costs were calculated. RESULTS: Twenty-four and twenty-six patients were assigned to propofol (Group P) and sevoflurane anaesthesia (Group S), respectively. The number of hypertensive events was comparable, whilst more hypotensive events were observed in Group S than in Group P (P=0.053, chi-squared test). As rescue therapy, more labetolol [45 (33) vs 76 (58) mg, P=0.073] and ephedrine [4.80 (2.21) vs 9.78 (5.59) mg, P=0.020] were used in Group S. Between group differences in recovery times were small and clinically unimportant. The combined hourly acquisition costs of hypnotic, analgesic, and vasoactive drugs appeared to be lower in patients maintained with sevoflurane than with propofol. CONCLUSION: Propofol/remifentanil and sevoflurane/remifentanil both provided satisfactory anaesthesia for intracranial surgery.

Effective doses of vecuronium in a patient with myotonic dystrophy.

Of the forms of muscular dystrophy, myotonic dystrophy has the greatest systemic involvement. Although most patients with myotonic dystrophy show normal sensitivity to non-depolarising neuromuscular blocking drugs, some have been reported to show greatly increased sensitivity to these drugs, and little is known about the sensitivity of different muscles. We compared effective doses of vecuronium in a patient with myotonic dystrophy at the orbicularis oculi, adductor pollicis and flexor hallucis brevis muscles during total intravenous anaesthesia. The calculated ED50 for the orbicularis oculi (7.77 microg x kg(-1) (95% CI 3.10-16.8 microg x kg(-1))) was lower than for the adductor pollicis (25.3 microg x kg(-1) (95% CI 20.7-43.3 microg x kg(-1))) and flexor hallucis brevis muscles (29.5 microg x kg(-1) (95% CI 11.0-85.6 microg x kg(-1); p < 0.01)). The ED90 was also lower for the orbicularis oculi (35.7 microg x kg(-1) (95% CI 14.8-66.5 microg x kg(-1))) than for the other muscles (51.8 microg x kg(-1) (95% CI 29.3-145.0 microg x kg(-1)) and 50.6 microg x kg(-1) (95% CI 5.29-642.0 microg x kg(-1)), respectively) (p < 0.01)).

Propofol pharmacokinetics in a dwarfism patient.

Pharmacokinetic information is important to control anesthetic depth. However, there are few available pharmacokinetic data of propofol in dwarfism patients. We anesthetized a dwarfism patient who underwent spinal decompression, and investigated the pharmacokinetics of propofol. The patient was a 40-year-old man suffering from muscle weakness and numbness in the arms. The operation consisted of two stages; anterior approach in the supine position and posterior approach in the prone position. We also obtained arterial blood for pharmacokinetic analysis. Distribution volume at steady-state and clearance in the supine position was 180 and 0.92 l min- 1, respectively, and in the prone position 127 and 0.74 l min- 1, respectively, in spite of a continuous infusion of dopamine. The data in the supine position were well predicted by Gepts' parameters (used in Diprifusor Zeneca Ltd, Cheshire, UK), which means the target-controlled infusion (TCI) technique can be available in the supine position, while attention is necessary to avoid overdosing when a patient is placed in the prone position.

Mechanisms of the mass effect of cerebral contusion: ICP monitoring and diffusion MRI study.

OBJECTIVE: Cerebral contusion is sometimes associated with a non-hemorrhagic mass effect which progresses rapidly within 12-48 hours post-trauma. In order to determine the mechanisms underlying such a mass effect, we analyzed data obtained from ICP monitoring and diffusion MRI in a total of 38 patients with cerebral contusion. METHODS: Diffusion imaging and ADC mapping were performed employing 1.5 T echo planar MRI. ADC values were expressed as a ratio relative to the values of intact brain areas. RESULTS: In 6 patients, ICP became uncontrollable medically and surgical resection of the contused brain tissue was eventually performed. Within 24 hours post-trauma, diffusion images revealed a low intensity core and a high intensity rim in the contusion. The ADC ratio increased in the central area (1.13 +/- 0.21) and decreased in the peripheral area (0.67 +/- 0.14). A crescent-shaped zone of very high ADC ratio (1.45 +/- 0.14) was observed at the border between these two areas during the period of 24-48 hours. CONCLUSIONS: It appears that the capacitance of edema fluid accumulation is elevated by cellular disintegration in the central area, whereas the resistance to edema fluid propagation is elevated by cellular swelling in the peripheral area. We suggest that such events facilitate extracellular edema fluid accumulation within contused brain tissue and contribute, together with cellular swelling itself, to the non-hemorrhagic mass effect of cerebral contusion.

Deep brain stimulation therapy for a persistent vegetative state.

Twenty cases of a persistent vegetative state (PVS) caused by various kinds of brain damage were neurologically and electrophysiologically evaluated at 3 months after persistence of the PVS, and were treated by deep brain stimulation (DBS) therapy. The stimulation sites were the mesencephalic reticular formation (2 cases) and CM-pf complex (18 cases). Seven of the patients emerged from the PVS, and became able to obey verbal commands. However, they remained in a bedridden state. These 7 cases revealed a desynchronization or slight desynchronization pattern on continuous EEG frequency analysis. The Vth wave of ABR and N20 of SEP could be recorded even with a prolonged latency, and the pain-related P250 was recorded with an amplitude of over 7 microV. We conclude that chronic DBS therapy may be useful for allowing the patient to emerge from a PVS, if the candidates are selected according to the neurophysiological criteria. In view of the severely disabled state of the patients who emerged from the PVS, a special rehabilitation program which includes neurostimulation therapy may be necessary for treatment of the PVS.

[Propofol pharmacokinetics in a patient with TSH producing pituitary adenoma].

We investigated propofol pharmacokinetics in a patient with secondary hyperthyroidism caused by thyroid stimulating hormone (TSH) producing pituitary adenoma. Laboratory data indicated thyrotoxic state with elevated TSH, FT3 and FT4 levels. General anesthesia was maintained with a doubled propofol infusion rate (8-10 mg.kg-1.hr-1) compared to our standard procedure. During 370 min of infusion, propofol concentrations in arterial blood were kept within optimal ranges (2-4 micrograms.ml-1). Although the clearance of propofol was high (2.8 l.min-1) because of the thyrotoxic state, the patient showed delayed recovery from anesthesia. The half-life of blood propofol after the termination of infusion exceeded 30 minutes (normal: 10-15 minutes). We conclude that the delayed recovery was due to the accumulation of propofol in the adipose tissue during long-term infusion in spite of the increased propofol clearance.

Left-molar approach improves the laryngeal view in patients with difficult laryngoscopy.

BACKGROUND: The molar approach of laryngoscopy is reported to improve glottic view in sporadic cases of difficult laryngoscopy. The authors studied the effect of molar approaches and optimal external laryngeal manipulation (OELM) using the Macintosh blade. METHODS: A series of 1,015 adult patients who underwent general anesthesia and tracheal intubation was studied. Laryngoscopy was carried out using a Macintosh no. 3 or 4 standard blade. Three consecutive trials of direct laryngoscopy using the midline and left- and right-molar approaches were carried out under full muscle relaxation with optimal head and neck positioning. The best glottic views were recorded for each approach with and without OELM. RESULTS: Difficult laryngoscopy with a midline approach accounted for 6.5% (66 cases) before OELM and 1.97% (20 cases) after OELM. A left-molar approach with OELM further reduced difficult laryngoscopy to seven cases (P < 0.001 vs. midline approach with OELM); a right-molar approach with OELM reduced difficult laryngoscopy to 18 cases (P = 0.48). CONCLUSIONS: The left-molar approach with OELM improves the laryngeal view in patients with difficult laryngoscopy.

The influence of hypoxia and hyperoxia on the kinetics of propofol emulsion.

PURPOSE: To study the effect of hypoxia and hyperoxia on the pharmacokinetics of propofol emulsion, hepatic blood flow and arterial ketone body ratio in the rabbit. METHODS: Twenty four male rabbits were anesthetized with isoflurane (1.5-2%) in oxygen. After the surgical procedure, isoflurane administration was discontinued and intravenous propofol infusion (30 mg x kg(-1) x hr(-1)) was started. The infusion rate of propofol was maintained throughout the study. After an initial 90 min period of propofol infusion, rabbits were randomly allocated to one of three groups: hypoxia (F(I)O2 = 0.1), normoxia (F(I)O2 = 0.21), and hyperoxia (F(I)O2 = 1.0). Propofol infusion was continued under the allocated F(I)O2 for 60 min. Propofol concentrations in arterial blood, total body clearance of propofol, hepatic blood flow and arterial ketone body ratio were measured. RESULTS: The mean arterial propofol concentration at the end of infusion was higher in the hypoxia group (15.2 +/- 2.8 microg x mL(-1), mean +/- SD) than in the normoxia (7.4 +/- 1.7) and hyperoxia (8.0 +/- 1.9) groups (P < 0.05). Total body clearance of propofol, hepatic blood flow and arterial ketone body ratio were all reduced in the hypoxia group (P < 0.05). Total ketone body concentration in arterial blood increased in the hyperoxia group (P < 0.01). CONCLUSION: Hypoxia produced an accumulation of propofol in blood and reduced propofol clearance. These changes could result from decreased hepatic blood flow and low cellular energy charge in the liver. Hyperoxia, on the other hand, increased total ketone body in arterial blood.

Lesion-making surgery versus brain stimulation for treatment of Parkinson's disease.

With the resurgence of interest in neurosurgical intervention for the treatment of drug-resistant Parkinson's disease, posteroventral pallidotomy (internal globus pallidus) has become a procedure widely applied by neurosurgeons. In chronic deep brain stimulation, the stimulation target is the same area as the above lesion-making point: the ventralis intermedius thalamic nucleus, subthalamic nucleus, and internal globus pallidus, since deep brain stimulation does not induce brain damage, and it is possible to control the stimulation (frequency and strength). There is also no recurrence. This procedure has the reversibility, selectivity, and adjustability that is ideal for functional neurosurgery. Such chronic stimulation therapy has thus now become an alternative to lesion-making stereotactic surgery. However, stimulation therapy directed at a particular target has more specific effects on particular symptoms of Parkinson's disease, so that an effective stimulation target needs to be selected depending on the nature of the syndrome to be improved. This article presents a review of the most recent reports on how to perform safer and more effective pallidotomy, and of recent basic and clinical reports concerning pallidal stimulation. Some answers to the question of whether or not stimulation therapy is an alternative to lesion-making surgery at the internal globus pallidus to improve parkinsonian syndrome and levodopa-induced dyskinesias are discussed.

[Use of personal computers by diplomats of anesthesiology in Japan].

Use of personal computers by diplomats of the Japanese Board of Anesthesiology working in Japanese university hospitals was investigated. Unsigned questionnaires were returned from 232 diplomats of 18 anesthesia departments. The age of responders ranged from twenties to sixties. Personal computer systems are used by 223 diplomats (96.1%), while nine (3.9%) do not use them. The computer systems used are: Apple Macintosh 77%, IBM compatible PC 21% and UNIX 2%. Although 197 diplomats have e-mail addresses, only 162 of them actually send and receive e-mails. Diplomats in fifties use e-mail most actively and those in sixties come second.

The effects of arm position on central spread of local anesthetics and on quality of the block with axillary brachial plexus block.

BACKGROUND AND OBJECTIVES: Spread of local anesthetic solution in axillary brachial plexus block is thought to be influenced by the position of the arm and the use of compression maneuvers. We investigated how these two factors affected central local anesthetic spread and block quality. METHODS: Radiographic spread of local anesthetic was studied in 80 adult patients. They received mepivacaine mixed with contrast agent through an indwelling catheter with the arm abducted to either 0 or 90 degrees , and with or without local digital compression. Central and peripheral spread of the contrast agent was evaluated with anteroposterior radiographs of the axilla. Block quality was studied in a separate series of 70 adult patients. They received mepivacaine with the arm abducted 0 degrees or 90 degrees . The degree of sensory and motor block was assessed 20 minutes after the injection. RESULTS: Arm position at 0 degrees abduction promoted central spread of the contrast agent. Although digital compression suppressed peripheral spread effectively, it did not improve the central spread of the solution. Sensory block was comparable in all terminal nerves of the arm in both arm positions, whereas motor block of the radial nerve was promoted with no abduction. CONCLUSIONS: The central spread of local anesthetics is facilitated by injection without abduction of the arm but not by the use of compression at the injection site. This, however, did not alter the quality of the block.

Propofol clearance and distribution volume increase in patients with hyperthyroidism.

UNLABELLED: We investigated propofol pharmacokinetics in seven hyperthyroid (Group H) and eight euthyroid (Group E) patients undergoing elective subtotal thyroidectomy. Anesthesia was induced with an i.v. injection of 2 mg/kg propofol and maintained with a continuous propofol infusion while ventilation was controlled with 60% nitrous oxide in oxygen. The propofol infusion rate was adjusted in the range of 4-10 mg.kg-1.h-1 based on physiological signs such as heart rate and blood pressure. Arterial blood was sampled to measure the propofol concentration. The mean propofol infusion rates were higher in hyperthyroid than in patients with euthyroidism (median values Group H 10.0 mg.kg-1.h-1, Group E 6.5 mg.kg-1.h-1; P < 0.05), although the reverse was true for average propofol concentrations (Group H 1.8 micrograms/mL, Group E 3.3 micrograms/mL; P < 0.05). Group H also had higher values for propofol clearance (5.1 L/min versus 2.5 L/min; P < 0.05) and distribution volume at steady state (10.0 L/kg versus 2.8 L/kg; P < 0.05). Because distribution volume and clearance in patients with hyperthyroidism were increased, propofol concentrations could not reach anesthetic levels. IMPLICATIONS: Propofol decreases heart rate and blood pressure, which are desirable properties for anesthesia in patients with hyperthyroidism. However, because clearance and distribution volume of propofol are increased, propofol infusion rates had to be increased to reach anesthetic blood concentrations.

Effects of inhaled oxygen concentration on fat metabolism during propofol infusion in rabbits.

We have investigated the effect of inhaled oxygen tension on lipid metabolism during propofol infusion. Propofol is supplied as a lipid emulsion containing 10% soybean oil, which is rich in triglycerides (TG). Infused TG are metabolized via three pathways in the liver cell; Krebs cycle, ketogenesis and release as very low density lipoproteins (VLDL) into the blood. For this reason, we measured TG and the products of the three pathways; carbon dioxide, ketone bodies and VLDL. Thirty-two rabbits were anaesthetized under four different conditions: propofol under hyperoxia, normoxia, hypoxia and isoflurane anaesthesia under hyperoxia. Our results indicated that hyperoxia produced more ketone bodies, normoxia more PaCO2 and hypoxia more free fatty acids (FFA) and TG compared with the other propofol infusion groups. We conclude that hyperoxia during propofol infusion facilitated fat metabolism through ketogenesis, while normoxia did so via the Krebs cycle. Also, hypoxia suppressed utilization of TG and VLDL production in the liver.

Pharmacological classification of central post-stroke pain: comparison with the results of chronic motor cortex stimulation therapy.

In an attempt to clarify the neurochemical background of central post-stroke pain and to undertake a pharmacological analysis, the basic pharmacological characteristics of this intractable pain syndrome were investigated by the morphine, thiamylal and ketamine tests. In addition, the correlation between the pharmacological characteristics and the effects of chronic motor cortex stimulation therapy was examined. The study employed 39 central post-stroke pain patients who had intractable hemibody pain associated with dysesthesias, and radiologically demonstrated lesions in the thalamic area (thalamic pain, n = 25) or suprathalamic area (suprathalamic pain, n = 14). The pharmacological evaluations showed that definite pain reduction occurred in eight of the 39 cases (20.5%) by the morphine test, in 22 of the 39 cases (56.4%) by the thiamylal test, and in 11 of 23 cases (47.8%) by the ketamine test. Based on these pharmacological assessments, there was no obvious difference between thalamic and suprathalamic pain. A comparison of the long-term follow-up results of chronic motor cortex stimulation therapy revealed that thiamylal and ketamine-sensitive and morphine-resistant cases displayed long-lasting pain reduction with chronic motor cortex stimulation therapy, whereas the remaining cases did not show good results. We conclude that pharmacological classification of central post-stroke pain by the morphine, thiamylal and ketamine tests could be useful for predicting the effects of chronic motor cortex stimulation therapy. It has recently been suggested that excitatory amino acids may be involved in the development of central post-stroke pain. However, the fact that only 23 of the present 39 cases (59.0%) of thalamic and suprathalamic pain were sensitive to the thiamylal or ketamine test reflects the complex pharmacological background and the difficulties associated with treating central post-stroke pain.

Ocular and cerebellar defects in zebrafish induced by overexpression of the LIM domains of the islet-3 LIM/homeodomain protein.

Islet-3 is an LIM/homeodomain protein that is expressed specifically in the eyes and the presumptive tectum in the central nervous system of zebrafish (Danio rerio) embryos. Overexpression of the protein (LIM(Isl-3)) consisting only of the Islet-3 LIM domains in embryos specifically prevented formation of the optic vesicles; caused abnormal termination of the expression of wnt1, engrailed2, and pax2 in the mesencephalic and metencephalic region between 14 hr and 20 hr postfertilization; and severely impaired morphogenetic movement in this region between 20 hr and 26 hr, which should normally lead to formation of the cerebellar primordium. Such defects were all rescued by simultaneous overexpression of Islet-3, suggesting that LIM(Isl-3) acted as a specific dominant-negative variant of Islet-3. These data, combined with the results of mosaic analyses, suggest that Islet-3 is activated by putative LIM-binding cofactors and functions to promote evagination of the optic vesicles and to maintain reciprocal interaction between the mesencephalon and the mesencephalic-metencephalic boundary essential for normal development of this region.

Predicting difficult intubation with indirect laryngoscopy.

BACKGROUND: It is not always possible to predict when tracheal intubation will be difficult or impossible. The authors wanted to determine whether indirect laryngoscopy could identify patients in whom intubation was difficult. METHODS: Indirect laryngoscopy was done in 2,504 patients. The Wilson risk sum score and the modified Mallampati score were also studied in a different series of 3,680 patients for comparison. These predictive methods were compared according to three parameters: positive predictive value, sensitivity, and specificity. RESULTS: Of 6,184 patients studied, the trachea proved difficult to intubate in 82 (1.3%). Positive predictive value (31%) and specificity (98.4%) with indirect laryngoscopy were greater than the other two predictive methods (P < 0.01), whereas sensitivity with indirect laryngoscopy (69.2%) was greater than that of the Wilson risk sum score (55.4%) (P < 0.01). CONCLUSIONS: Although in 15% of patients indirect laryngoscopy could not be performed because of excessive gag reflex, indirect laryngoscopy can serve as an effective method to predict difficult intubation.