Involvement of glucocorticoid receptor on hyperpyrexia induced by methamphetamine administration.

UNLABELLED: We have investigated the involvement of glucocorticoid on methamphetamine (MA) induced hyperpyrexia using a bio-telemetric system. A significant level of hyperpyrexia was observed in MA administered rats. In contrast, increase of body temperature was suppressed by adrenalectomy or by the administration of RU-486, an antagonist of the glucocorticoid receptor. These data suggest that the glucocorticoid receptor may be involved in hyperpyrexia induced by MA. KEYWORDS: methamphetamine - hyperpyrexia - glucocorticoid - corticosterone.

A solid-solution theory of anesthetic interaction with lipid membranes: temperature span of the main phase transition.

Anesthetics (or any other small additives) depress the temperature of the main phase transition of phospholipid bilayers. Certain anesthetics widen the temperature span of the transition, whereas others do not. The widening in a first-order phase transition is intriguing. In this report, the effects of additive molecules on the temperature and its span were explained by the solid-solution theory. By assuming coexistence of the liquid-crystal and solid-gel phases of lipid membranes at phase transition, the phase boundary is determined from the distribution of anesthetic molecules between the liquid-crystal membrane versus water and between the solid-gel membrane versus water. The theory shows that when the lipid concentration is large or when the lipid solubility of the drug is large, the width of the transition temperature increases, and vice versa. Highly lipid-soluble molecules, such as long-chain alkanols and volatile anesthetics, increase the width of the transition temperature when the lipid:water ratio is large, whereas highly water-soluble molecules, such as methanol and ethanol, do not. The aqueous phase serves as the reservoir for anesthetics. Depletion of the additive molecules from the aqueous phase is the cause of the widening. When the reservoir capacity is large, the temperature width does not increase. The theory also predicts asymmetry of the specific heat profile at the transition.

The alpha-helix to beta-sheet transition in poly(L-lysine): effects of anesthetics and high pressure.

Poly(L-lysine) exists in a random-coil formation at a low pH, alpha-helix at a pH above 10.6, and transforms into beta-sheet when the alpha-helix polylysine is heated. Each conformation is clearly distinguishable in the amide-I band of the infrared spectrum. The thermotropic alpha-to-beta transition was studied by using differential scanning calorimetry. At pH 10.6, the transition temperature was 43.5 degrees C and the transition enthalpy was 170 cal/mol residue. At pH 11.85, the measurements were 36.7 degrees C and 910 cal/mol residue, respectively. Volatile anesthetics (chloroform, halothane, isoflurane and enflurane) partially transformed alpha-helix polylysine into beta-sheet. The transformation was reversed by the application of hydrostatic pressure in the range of 100-350 atm. Apparently, the alpha-to-beta transition was induced by anesthetics through partial dehydration of the peptide side-chains (beta-sheet surface is less hydrated than alpha-helix). High pressure reversed this process by re-hydrating the peptide. Because the membrane spanning domains of channel and receptor proteins are predominantly in the alpha-helix conformation, anesthetics may suppress the activity of excitable cells by transforming them into a less than optimal structure for electrogenic ion transport and neurotransmission. Proteins and lipid membranes maintain their structural integrity by interaction with water. That which attenuates the interaction will destabilize the structure. These data suggest that anesthetics alter macromolecular conformations essentially by a solvent effect, thereby destroying the solvation water shell surrounding macromolecules.

Proton nuclear magnetic resonance spectroscopy of urine for rapid multicomponent analysis of intraoperative cellular metabolites.

We serially measured the proton nuclear magnetic resonance spectra of the urine of intraoperative patients over time to assess their potential use for rapid multicomponent analysis of cellular metabolites. Within a few minutes, the spectra provided signals of many low molecular weight urinary metabolites, including amino acids, ketone bodies, lactate, and glucose. The proton magnetic resonance spectra of the urine of most of the intraoperative patients showed large increases in urinary excretion of alanine, ketone bodies, and lactate and/or glucose, confirming alterations in energy substrate-endocrine relationships during the perioperative period. These metabolic changes appeared to be roughly proportional to the degree of surgical stress, but they were not consistent among patients who underwent the same operation. The study suggests that routine intraoperative metabolic monitoring is necessary to prevent critical metabolic disorders and that proton nuclear magnetic resonance spectroscopy of urine may meet this need by allowing rapid multicomponent analysis of cellular metabolites.

Auditory brain stem responses(ABR) in developmentally retarded infants and children.

We recorded ABR in 65 infants and children with developmental retardation and analyzed the relationship between the incidence of abnormal findings and the degree of mental retardation, which was confirmed by follow-up observation and formal intelligence tests. There were 3 cases for whom no response could be obtained. In the 21 retardates with specific causes of retardation or complications, peripheral abnormalities were noted in 13 (62%) and central abnormalities in 11 (52%). The 41 cases of idiopathic retardates were divided into three categories according to the degree of mental retardation. Of 15 cases who were ascertained to be normal or borderline retardates, 3 (20%) showed some abnormal findings. Of 13 cases who were proven to be suffering from mild to moderate mental retardation, 5 (38%) showed abnormal findings. Of 13 cases who were confirmed to be suffering from severe to profound mental retardation, 5 (39%) showed central abnormalities. The high incidence of ABR abnormalities in retardates compared to in normal controls suggests that ABR measurement is a useful tool for evaluating infants who have possible developmental delay. It seems that disturbance of acoustic information processing can disturb language acquisition, and such a consideration is necessary for the education of children who show significant elevation of the response threshold.

Developmental changes of brainstem auditory evoked potentials (BAEPs) in normal human subjects from infants to young adults.

BAEP has been found to be useful for assessment of subcortical maturation. However, the precise maturational changes of the peripheral and central transmission in normal human subjects are still open to controversy. We obtained a total of 200 BAEPs from 165 normal human subjects ranging from infants to young adults. Electrodes were placed at both mastoids and the reference at the vertex. 85 dB SL click stimuli were presented binaurally at a rate of 13/sec and 2,048 responses were summated on line with an averager. Investigation of the maturation of the transmission time indicated that the peripheral auditory apparatus attains functional maturity during the first 2 months of life, whereas the central transmission time shortens up to the age of 5 to 8 years. III-II and V-IV interpeak latencies (IPLs) showed maturational changes similar to those of V-I IPLs, in contrast II-I and IV-III showed little changes. A clear increase of the amplitude of peak V up to 4 years of age and a subsequent decreasing tendency was observed. The V-I IPLs of males were longer than those of females in each age group. Females also displayed larger BAEPs for wave V than males after 2 years of age. These data indicate that it is worthwhile to have separate latency and amplitude norms for males and females from infants to adults for attaching diagnostic significance to BAEP measures.

Quantitative determination of Tri-, Di-,monooleins and free oleic acid by the thin layer chromatography-flame lonization detector system using internal standards and boric acid impregnated chromarod.

The separation conditions for hydrolysates of triglycerides by lipase and their quantitative determination are discussed for a thin layer chromatography-flame ionization detector system utilizing internal standards. The complete separation of glyceride hydrolysis mixtures (triolein 1,3-diolein, 1,2-diolein, 1-monoolein and oleic acid) was achieved on a 3% boric acid-impregnated Chromarod S-II by development with benzene/chloroform/acetic acid (70∶30∶2, v/v/v) (mobile phase A) or hexane/ ether/acetic acid (70∶30∶1, v/v/v) (mobile phase B). Mobile phase B had an advantage over mobile phase A in terms of free space to add internal standards for simultaneous quantitation and was employed.p-Hydroxybenzoic acid andp-carboethoxy benzyl alcohol, which appeared between 1,2-diolein and 1-moloolein, were adopted as the internal standards. The calibration curves relating internal standards to each glyceride were all approximated by the equations Y=aX(b) giving high correlations. The method was applied to hydrolysis of triolein by pancreatic lipase.

Derivation of extracellular fluid volume fraction and equivalent dielectric constant of the cell membrane from dielectric properties of the human body. Part 1: Incorporation of fat tissue into cell suspension model in the arm.

The non-invasive characterisation of cell pathophysiology is clinically important. A cell suspension model is applied to derive the extracellular fluid (ECF) volume fraction and the equivalent dielectric constant of the cell membrane epsilon m from the dielectric properties of human arms. Frequency-dependent dielectric constants and electrical conductivities of arms are obtained from 35 surgical patients over a frequency range of 5-1000 kHz. The cell suspension model is applied to fit the data using a complex non-linear least-squares method. The arms show typical dielectric dispersions, although the cell suspension model yields a poor fitting in dielectric constants at lower frequencies and electrical conductivities at higher frequencies. In contrast, a new cell suspension model, taking into account the fat tissue component, remarkably improves the overall fitting performance, allowing estimation of the volume fractions of ECF (0.34 +/- 0.05) and fat tissue (0.16 +/- 0.04) and the equivalent epsilon m (23 +/- 9). The resulting estimates of the volume fraction of fat tissue are in good correlation with arm skinfold thickness (fat volume fraction of arm = 2.42 x 10(-3) x arm skinfold thickness (mm) + 0.099, R = 0.756, p < 0.0001). Therefore it is concluded that the newly derived cell suspension model is well suited for the description of the dielectric properties of human tissues and thus the derivation of the ECF volume fraction and equivalent epsilon m.

Derivation of extracellular fluid volume fraction and equivalent dielectric constant of the cell membrane from dielectric properties of the human body. Part 2: A preliminary study for tracking the progression of surgical tissue injury.

A study is conducted to determine whether the extracellular fluid (ECF) volume fraction and equivalent dielectric constant of the cell membrane epsilon m, derived from the dielectric properties of the human body can track the progression of surgical tissue injury. Frequency-dependent dielectric constants and electrical conductivities of body segments are obtained at surgical (trunk) and non-surgical sites (arm and leg) from five patients who have undergone oesophageal resections, before and at the end of surgery and on the day after the operation. The ECF volume fraction and the equivalent epsilon m of body segments are estimated by fitting the dielectric data for body segments to the cell suspension model incorporating fat tissue, and their time-course changes are compared between body segments. By the day after the operation, the estimated ECF volume fraction has increased in all body segments compared with that before surgery, by 0.13 in the arm, 0.16 in the trunk and 0.14 in the leg (p < 0.05), indicating postoperative fluid accumulation in the extracellular space. In contrast, the estimated equivalent epsilon m shows a different time course between body segments on the day after the operation, characterised by a higher change ratio of epsilon m of the trunk (1.34 +/- 0.66, p < 0.05), from that of the arm (0.66 +/- 0.34) and leg (0.61 +/- 0.11). The results suggest that the equivalent epsilon m of a body segment at a surgical site can track pathophysiological cell changes following surgical tissue injury.

Effect of continuous infusion of prostaglandin E1 on hepatic blood flow.

STUDY OBJECTIVE: To evaluate the effects of an intravenous infusion of prostaglandin E1 (PGE1) on hepatic blood flow. DESIGN: Prospective clinical study. SETTING: University-affiliated hospital. PATIENTS: 16 ASA physical status I and II surgical patients who were scheduled for abdominal surgery. INTERVENTIONS: Patients were anesthetized with 1% sevoflurane and 66% nitrous oxide. PGE1 0.05 mg/kg/min or PGE1 0.10 mg/kg/min was continuously infused, followed by an infusion of 1000 mL Ringer's acetate solution. MEASUREMENTS: The hemodynamic effect of PGE1 was examined using pulse dye densitometry (PDD). A nose probe for PDD was used, and 10 mg indocyanine green (ICG) in 2 mL distilled water was bolus-infused into a central venous catheter for each measurement. Cardiac output (CO), circulating blood volume (CBV), and plasma dye clearance rate (K) were monitored from the dye-densitogram. Hepatic blood flow was estimated using the K and CBV values. MAIN RESULTS: PGE1 did not increase CBV or CO. Even adding a 1000 mL crystalloid infusion did not expand CBV, whereas mean arterial pressure (MAP) significantly decreased from 91.1 +/- 16.5 mmHg to 84.8 +/- 13.5 mmHg (PGE1 0.05 microg/kg/min) and 80.6 +/- 14.4 mmHg (PGE1 0.10 microg/kg/min ) (p < 0.01 compared with control value), then to 72.0 +/- 6.5 mmHg (PGE1 0.10 microg/kg/min + 1000 mL Ringer's acetate) (p < 0.01 compared with control value). Hepatic blood flow changes were 1.46 +/- 0.60 L/min (control), 1.48 +/- 0.45 L/min (PGE1 0.05 microg/kg/min), 1.14 +/- 0.35 L/min (PGE1 0.10 microg/kg/min), and 1.15 +/- 0.19 L/min (PGE1 0.10 microg/kg/min + 1000 mL Ringer's acetate) (no significant difference, p < 0.05). Hepatic blood flow and K values did not statistically significantly differ at each condition. CONCLUSIONS: PGE1 does not affect blood volume shift, CO, or hepatic blood flow.

Proton NMR spectroscopic studies of serum as an aid to perioperative cellular metabolic monitoring.

Perioperative concentration changes of cellular metabolites in serum were studied by proton NMR spectroscopy in four cancer patients who underwent tumorectomies under general anesthesia. In proton NMR spectra of serum, the resonances assignable to fatty acid in lipoprotein, lactate, alanine, glucose, glycoprotein and other metabolites were observed. The concentrations of fatty acid and alanine did not show significant changes during the operations compared with those in healthy volunteers. The concentrations of lactate, glucose and glycoprotein increased during the operations above the concentration ranges in the control subjects. The time-course of concentration change for lactate, glucose and glycoprotein was roughly classified into two patterns: i) the maximums of lactate and glucose concentration were observed in the latter halves or at the ends of the operations; ii) the maximums of glycoprotein concentrations were observed three hours after the incision, regardless of the operative time. The results showed cellular metabolic changes became larger as the operations proceeded responding to surgical stress. Prompt cellular metabolic monitoring is indispensable for the screening of cellular metabolic disorders caused by excessive surgical stress and proton NMR spectroscopy can be a new tool for monitoring perioperative cellular metabolism.

Evaluation of independent-living programs.

The program report that states must submit to the federal government under the federal Title IV-E Independent-Living Initiative is, in essence, a program evaluation report and will require comprehensive program and evaluation data to complete. Because the program report will be a key factor in determining the future of this federal initiative, it is important that states improve their information system capability to generate the range of necessary data. This article offers detailed suggestions for ways in which states could establish their independent-living program information systems to produce program and evaluation data; and presented two examples of approaches to evaluating the Title IV-E independent-living program, one in Pennsylvania and another in Texas. These states were selected for the purpose of illustrating two different approaches and not necessarily for the presentation of exemplary evaluation practices.

[The anesthetic effects of steroids and their actions on the properties of model membrane].

The action of anesthetic steroid on the GABAA receptor in the postsynaptic membrane has been suggested as a mechanism of steroid anesthesia. Alphaxalone, the main component of althesin, is a strong anesthetic, whereas its analogue, delta 16-alphaxalone is not. The only structural difference between the two is a presence of the double bond in the D ring of delta 16-alphaxalone. The effects of these steroids on the model membrane structure and the hydrogen bonding between lipid membrane and water were examined by differential scanning calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR) and compared with their anesthetic potencies in goldfish. Alphaxalone decreased the phase-transition temperature from the solid-gel to the liquid-crystal state of DPPC liposome. FTIR showed that alphaxalone molecules released the bound water molecules in the lipid-water interface of D2O-in-CCl4 reversed micelles. delta 16-alphaxalone in high concentration was also an anesthetic in goldfish. It also showed a weak effect on the phase-transition temperature and the hydrogen bond breaking activity. These changes in the membrane properties correlated to the anesthetic potency. These results suggest that anesthetic potency of steroids is related to their action in destabilizing the structures of the water molecules in the macromolecule-water interface and the macromolecules.

[Measurements of extracellular water volume by bioelectrical impedance analysis during perioperative period of esophageal resection].

Segmental bioelectrical impedance analysis (BIA) was conducted in five patients who underwent esophageal resections. Resistance values fitted at zero frequency (R0) in each body segment (arm, trunk and leg) were determined before the induction of anesthesia, at the end of surgery and on the second or third postoperative day. Extracellular water volume (ECW) in each body segment was estimated using the equation derived from the cell suspension theory. ECW in whole body was obtained from the sum of each body segment. R0 in trunk and leg significantly decreased at the end of surgery compared to the values before the induction of anesthesia (P < 0.05). The change ratio of R0 in trunk before the induction of anesthesia was significantly lower at the end of surgery than that in arm (P < 0.05), resulting from the most striking fluid accumulation in the trunk. Postoperatively, R0 in all body segments, however, appeared to decrease similarly compared to the values before the induction of anesthesia, suggesting the redistribution phenomena of extracellular water among body segments. The correlation (r = 0.90, P < 0.001) and good agreement [bias = 0.01 (L)] between net fluid balances and estimates of ECW changes in whole body suggest that BIA allows close monitoring of tissue hydration during perioperative period by providing estimates of ECW in body segments.

[The effects of H2 blockers on gastric flora and sputum culture].

Gastric juice and sputum of 12 patients, who had entered the intensive care unit postoperatively and received respiratory management, were examined for bacteria and their relationship with gastric pH was investigated. Gastric bacteria were detected in only 3 specimens out of 14 (21.4%) when the pH was under 3.5, and when the pH was above 3.5, gastric bacteria were detected in 33 specimens out of 35 (94.3%). Proliferation of gastric flora was observed as the pH increased. In 7 cases, Gram-negative bacilli (important etiologically as a cause of pneumonia) were detected. Gram-negative bacilli were also detected in sputum culture and these were found to be of the same bacteria type as those found in the gastric juice. However, no evident cases of pneumonia were observed, and proliferation of gastric bacteria did not increase the incidence of postoperative pneumonia.

[Comparison of intravenous buprenorphine or fentanyl and epidural buprenorphine for pain relief after upper abdominal surgery].

In three groups [(1) intravenous buprenorphine (0.1mg) or (2) fentanyl (100 micrograms.hr-1) and (3) epidural injection of buprenorphine (0.1mg diluted with 10ml normal saline)], we determined the effects of postoperative pain relief in patients after upper abdominal surgery. There are no differences in postoperative analgesia in the three groups, but respiratory depression was seen in some patients who had intravenous buprenorphine or fentanyl. We conclude that epidural injection of buprenorphine is a useful method for postoperative analgesia because of little adverse effect. As respiratory depression caused by buprenorphine was reversed with naloxone, it is not necessary to employ fentanyl instead of buprenorphine.

[Coronary spasm during laryngoplasty].

A 63-yr-old man weighing 56kg was scheduled for pharyngoplasty under general anesthesia. The patient had no history of ischemic heart disease. Preoperative ECG showed incomplete right branch block. We administered thiopental and succinylcholine for intubation. Anesthesia was maintained with enflurane, nitrous oxide, oxygen and pancuronium bromide. Thirty minutes after the start of incision, the patient developed a severe hypotension and ECG revealed ST elevation and complete AV block. We administered ephedrine hydrochloride, phenylephrine hydrochloride and atropine sulfate. The ECG returned to sinus rhythm but ST segment was depressed this time. We considered it due to coronary spasm, so we started continuous intravenous administration of nitroglycerin (0.5 microgram. kg-1. min-1). One hour later, ST segment returned to normal. ECG showed no remarkable changes and no symptoms were seen after the operation. We found it important to suspect coronary spasm when ECG showed PVC-like abnormal waves with ST elevation. We consider that continuous administration of nitroglycerin at a rate of 0.5 microgram. kg-1. min-1 was effective for the treatment of coronary spasm in this case.

[Effect of enflurane on human somatosensory evoked potentials: differences between specific and nonspecific responses].

The effect of enflurane on somatosensory evoked potentials (SEP) was investigated in nine gynecological patients under nitrous oxide-enflurane anesthesia. SEPs were obtained from electrodes placed on the scalp C4 and earlobes by median nerve stimulation contralateral to the recording site. SEPs taken in a control study without enflurane consisted of six components; P12, N17, P23, N31, P50, and N65. Components N17, P23, N31, and P50, thought to be specific SEP responses, showed a dose-dependent increase in latencies under enflurane while P12, the initial SEP components, did not show any significant changes throughout the experiment. The longer the latency for a given response component, the greater was the increase in latency seen under enflurane anesthesia. On the other hand, N65, assumed to be a nonspecific SEP response, was completely lost with inhalation of 0.5 MAC or more of enflurane. However, the peak-to-peak amplitude between P23 and N31 was enhanced dose-dependently with enflurane up to 1.5 MAC. These results suggest that, at clinically effective doses, enflurane may inhibit nonspecific projection pathways while enhancing the primary cortical sensory area, and this enhancement may be responsible for provoking convulsive seizures under enflurane anesthesia.

Intraoperative awake tracheal intubation using the Airway Scope™ in caesarean section.

The Airway Scope™, a novel videolaryngoscope used for tracheal intubation, is minimally invasive and can be used in conscious patients. The parturient with a potentially difficult airway should sometimes be intubated while awake, without anaesthesia or neuromuscular block. Two pregnant women who experienced massive postpartum haemorrhage during caesarean section underwent unscheduled intraoperative tracheal intubation using the Airway Scope. They were conscious and were intubated with minimal local anaesthesia so as to prevent cardiovascular compromise. We believe the Airway Scope is useful for anaesthetic procedures in the parturient who has haemodynamic instability.

Crystalloid infusion rate during fluid resuscitation from acute haemorrhage.

BACKGROUND: Information is lacking concerning optimal infusion rates of crystalloid during resuscitation from acute haemorrhage. In this study, a mathematical model was used to predict infusion volume of crystalloid needed to restore and maintain blood volume after acute haemorrhage. METHODS: The scenario was a haemorrhage of 15 ml kg(-1) over 30 min in a 70 kg man. A bolus of crystalloid was administered at a rate of 40, 60, 80, 100, or 120 ml kg(-1) h(-1) until blood volume was restored. Fluid infusion rate needed to maintain blood volume for a further 1 h was computed. RESULTS: Blood volume was restored earlier at high bolus infusion rates compared with low bolus infusion rates (6 min at 120 ml kg(-1) h(-1) vs 63 min at 40 ml kg(-1) h(-1)). Fluid infusion rates for blood volume maintenance approached 33 ml kg(-1) h(-1) irrespective of bolus infusion rates. The restoration fluid volume at 40 ml kg(-1) h(-1) was 2.9 litre, three times that at 80-120 ml kg(-1) h(-1). The maintenance fluid volume at 80-120 ml kg(-1) h(-1) was 2.9 litre, 0.6 litre more than that at 40 ml kg(-1) h(-1). During the blood volume maintenance, the interstitial volume increased to 3.8 litre above normal at 40 ml kg(-1) h(-1) and to 2.5 litre at 80-120 ml kg(-1) h(-1). CONCLUSIONS: Bolus crystalloid infusion exceeding 80 ml kg(-1) h(-1) may not increase effectiveness of fluid resuscitation. Crystalloid resuscitation for more than 2 h may be detrimental in view of an excessive net fluid retention.