Epidural hematoma after epidural anesthesia in a patient with hepatic cirrhosis.
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Biomedical subjects
Publications and source records attributed to H Morisaki.
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AMP deaminase (AMPD) is a complex allosteric enzyme encoded by a multigene family in higher eukaryotes. The amino terminus of each AMPD gene is unique, while the mild and carboxy termini have been highly conserved among all the AMPD genes. Mutational analyses of the AMPD1 gene demonstrate that the catalytic site and a regulatory site, likely an ATP binding site, are located in the highly conserved carboxy terminus. Deletion mutants and a normal splice variant of AMPD1 demonstrate that the amino terminus has a profound influence on catalytic activity of AMPD and by inference from prior studies this region also influences binding of AMPD1 to myosin. Results of these studies suggest a regulatory model in which alternative splicing in the amino terminal region of AMPD1 generates isoforms of AMPD that exhibit differential sensitivity to effector molecules such as ATP.
We tested the hypothesis that the type of fluid infused to chronically maintain intravascular volumes would modify both microvascular integrity and cellular structure in extrapulmonary organs in hyperdynamic sepsis. After cecal ligation and perforation, awake sheep were treated for 48 h with 10% pentastarch (n = 9), 10% pentafraction (Du Pont Critical Care; n = 8), or Ringer lactate (n = 8) titrated to maintain a constant left atrial pressure. After 48 h of fluid therapy, biopsy samples were taken from the left ventricle and gastrocnemius for electron microscopy. At this time, all groups demonstrated a similar hyperdynamic circulatory response, increased systemic O2 utilization and organ blood flows, measured by radioactive microsphere injection. However, greater capillary luminal areas with less endothelial swelling and less parenchymal injury were found in septic sheep treated with pentastarch vs. Ringer lactate infusion in both muscle types. Pentafraction showed few benefits in study end points over pentastarch. Thus, we conclude that chronic intravascular volume resuscitation of hyperdynamic sepsis with pentastarch ameliorated the progression of both microvascular and parenchymal injury. These findings indicate that microvascular surface area for tissue O2 exchange in sepsis may be better preserved with chronically infused colloid, resulting in less parenchymal injury.
Since the original technique using the Bullard laryngoscope requires considerable practice to be reliable, we have developed an easier method with a directional-tip endotracheal tube through the nostril. We first examined the feasibility of our method in patients with or without difficult airways. All 26 patients with difficult airways were successfully tracheally intubated with our method, and times for visualization and intubation were not different from those in 10 patients with normal airways. We further examined the direction of the tips of endotracheal tubes through the nostril in 128 patients with normal airways using four combinations of two kinds of both laryngoscopes (Bullard and Macintosh) and endotracheal tubes (directional-tip tube: Endotrol, Mallinckrodt Laboratories, Athlone, Ireland; or straight distal-end tube: Blue Line, Portex Ltd., Hythe Kent, United Kingdom). We found that a combination of the Bullard laryngoscope and the Endotrol tube had a higher probability of accessing the center of the glottis than the others. In conclusion, nasal insertion of a directional-tip tube assisted by the Bullard laryngoscope is an assured and prompt procedure for intubating the tracheas of patients with difficult airways.
We investigated the effects of intravenous injections of bifemelane hydrochloride, nicergoline and trapidil on cochlear blood flow (CoBF) and cerebral blood flow (CBF) using laser Doppler flowmetry, while monitoring arterial blood pressure (BP), in 40 guinea pigs. Each animal was anesthetized with 40mg/kg of intraperitoneal pentobarbital sodium. After tracheotomy, the animals were artificially ventilated with a respirator. The left middle ear was approached ventrally and the bulla was opened. The middle ear mucosa over the bony cochlea was removed. The tip of the probe was placed on the curvature of the basal or second turn of the cochlea, connecting it to a laser Doppler flowmeter. For the measurement of CBF, part of the parietal bone was exposed. The tip of the probe connected to a laser Doppler flowmeter was placed over the area. A catheter was inserted into the right carotid artery and connected to a pressure transducer. Another catheter for drug administration was cannulated via the jugular vein. Of 40 animals, 22 animals were given bifemelane hydrochloride, 10 animals received nicergoline and 8 animals were given trapidil. The drugs were administered in increasing concentrations, by intravenous injection, for 1 min at intervals of about 20 min in a volume equivalent to 1ml/kg. Asphyxia was induced by stopping the respirator for 2min before and after the experiment. CoBF, CBF and BP were simultaneously recorded. CoBF, CBF and BP rose after bifemelane hydrochloride administration. Nicergoline injection slightly decreased BP, but CoBF and CBF were unchanged. Trapidil injection slightly decreased BP and CBF, but increased CoBF at some concentrations. The high concentration injections of all drugs resulted in increases in normalized cochlear blood flow (CoBF/BP; nCoBF). After asphyxia, CoBF, nCoBF, CBF and BP tended to reach high levels in guinea pigs pretreated with bifemelane hydrochloride, as compared with untreated animals. While administration of nicergoline and trapidil exerted no influence on the changes caused by asphyxia in CoBF, nCoBF, CBF and BP. In this experiment, BP, CoBF and CBF responded in various ways to the three drugs tested, but analysis of nCoBF indicated that these drugs had a vasodilatory effect in the cochlea.
Approximately 2% of Caucasians and African-Americans are homozygous for a nonsense mutation in exon 2 of the AMPD1 (AMP deaminase) gene. These individuals have a high grade deficiency of AMPD activity in their skeletal muscle. More than 100 patients with AMPD1 deficiency have been reported to have symptoms of a metabolic myopathy, but it is apparent many individuals with this inherited defect are asymptomatic given the prevalence of this mutant. Results of the present study provide a potential molecular explanation for "correction" of this genetic defect. Alternative splicing eliminates exon 2 in 0.6-2% of AMPD1 mRNA transcripts in adult skeletal muscle. Expression studies document that AMPD1 mRNA, which has exon 2 deleted, encodes a functional AMPD peptide. A much higher percentage of alternatively spliced transcripts are found during differentiation of human myocytes in vitro. Transfection studies with human minigene constructs demonstrate that alternative splicing of the primary transcript of human AMPD1 is controlled by tissue-specific and stage-specific signals. Alternative splicing of exon 2 in individuals who have inherited this defect provides a mechanism for phenotypic rescue and variations in splicing patterns may contribute to the variability in clinical symptoms.
AMP deaminase (AMPD; EC 3.5.4.6) is encoded by a multigene family in mammals. The AMPD1 gene is expressed at high levels in skeletal muscle, where this enzyme is thought to play an important role in energy metabolism. Deficiency of AMPD activity in skeletal muscle is associated with symptoms of a metabolic myopathy. Eleven unrelated individuals with AMPD deficiency were studied, and each was shown to be homozygous for a mutant allele characterized by a C----T transition at nucleotide 34 (codon 12 in exon 2) and at nucleotide 143 (codon 48 in exon 3). The C----T transition at codon 12 results in a nonsense mutation predicting a severely truncated AMPD peptide. Consistent with this prediction, no immunoreactive AMPD1 peptide is detectable in skeletal muscle of these patients. This mutant allele is found in 12% of Caucasians and 19% of African-Americans, whereas none of the 106 Japanese subjects surveyed has this mutant allele. We conclude from these studies that this mutant allele is present at a sufficiently high frequency to account for the 2% reported incidence of AMPD deficiency in muscle biopsies. The restricted distribution and high frequency of this doubly mutated allele suggest it arose in a remote ancestor of individuals of Western European descent.
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Inhibitory effects of diazepam and flunitrazepam on the superoxide anion (O2-)-generating system in granulocytes were examined for their clinical relevance. When the effects of commercial solutions and pure preparations were compared using porcine and human polymorphonuclear leucocytes in vitro, the solutions were found to be more inhibitory than the pure drugs by 4-11 times, indicating that inhibition was caused mainly by the additives in the solutions. Concentrations of the additives required for 50% maximal inhibition of the system were 2.3, 7.5 and 0.9 microliters ml-1 for propylene glycol, ethanol and diazepam and flunitrazepam were 220 and 190 micrograms ml-1, respectively, under comparable conditions. However, plasma concentrations of the benzodiazepines and their additives during clinical use were far less than these inhibitory concentrations, indicating that they had no appreciable effect on the O2(-)-generating system in polymorphonuclear leucocytes of patients.
Blood flow in the cochlea, vestibular apparatus and facial nerve was investigated in the 12 temporal bones of 6 guinea pigs using non-radioactive microspheres. The cochlear blood flow volume was 1.80 +/- 0.82 microliters/min and the blood flow volume of the vestibular apparatus was 0.43 +/- 0.16 microliters/min. The blood flow volume of the facial nerve in the temporal bone was 0.29 +/- 0.17 microliter/min. Regarding these blood flow volumes, the difference between the right and left was not significant, although there were large interanimal differences. The distribution of the blood flow in the cochlea, vestibular apparatus and facial nerve is also described.
Halothane was administered in oxygen to a young man in status asthmaticus whose bronchospasm did not respond to usual treatments. Plasma catecholamine concentrations were measured during and after bronchospasm. Fifteen minute inhalation of halothane produced marked bronchodilatation as reflected in decreased peak airway pressure, decreased wheezing and fall in PaCO2 from 110 mmHg to 45 mmHg. Treatment with halothane was discontinued after 120 min inhalation. Arterial blood samples were obtained to determine free and total catecholamine (CA) on the following four occasions: 1. during status asthmaticus, 2. fifteen minutes after inhalation of halothane, 3. one day after bronchospasm and 4. two days after bronchospasm. During attack, free norepinephrine and epinephrine concentrations were markedly elevated. These values decreased remarkably after administration of halothane. Total norepinephrine and epinephrine were also elevated during bronchoconstriction, and these high concentrations persisted after bronchodilatation. The changes in CA levels suggest that sympathoadrenal hyperactivity elicited by acute asthma can be suppressed by halothane as evidenced by the decreased concentration in free catecholamines, which are physiologically active. The levels in total catecholamine did not correlate with the patient's condition. Therefore, judgement based only on the levels in total CA might lead to misinterpretation in estimating sympathoadrenal activity.
This study was done to clarify whether end-tidal carbon dioxide (ETCO2) concentration is an effective monitor as an indicator of survival and prognosis of patients who arrived with cardiac arrest. We measured ETCO2 concentration in 30 patients with pre-hospital cardiac arrest during cardiopulmonary resuscitation (CPR). Six patients were resuscitated successfully and the others were not. The values of ETCO2 of the resuscitated patients, at the time of starting advanced life support were varied from 0 to 4.5% (mean 1.4%), which were not different from the values in patients who were not resuscitated (mean 0.87%). In 13 patients who were not resuscitated, the initial values of ETCO2 during CPR were below 1.0%, whereas the other 11 patients showed high ETCO2 values (above 1.5%), which were dependent on the degree of chest compression. This suggests that ETCO2 monitoring during cardiopulmonary resuscitation is a good non-invasive indicator to evaluate the efficacy of chest compression itself, but its initial values during CPR are not correlated with success of resuscitation in patients with pre-hospital cardiac arrest.
We measured plasma endothelin (ET) in 11 patients undergoing cardiac valve replacement under high dose fentanyl (116.6 +/- 15.4 micrograms.kg-1, mean +/- SD) anesthesia. Arterial blood samples were obtained: 1) before induction of anesthesia (control), 2) just before the start of cardiopulmonary bypass (CPB), and 3) just before the end of CPB. Endothelin levels were analyzed by radioimmunoassay based on double antibody method using Silica ODS suspension. ET concentrations in period 1, 2, and 3 were 3.0 +/- 1.1, 4.2 +/- 1.7 and 4.5 +/- 1.8 pg.ml-1 (mean +/- SD), respectively. There were no significant differences among these three values (P less than 0.05). The results suggest that under high dose fentanyl anesthesia, surgical stress including that of CPB might not affect ET concentration in plasma.
A total of eight patients, including three infants, received left or biventricular assist using centrifugal pump (CFP) following open heart surgery. Three infants, aged 9-11 months and with complex cardiac lesions, were supported by left heart bypass (LHB) using pediatric type CFP for 63 h, 64 h, and 13 days. All were weaned from LHB, but long-term survival was not obtained, mainly due to complications. In five adult patients, LHB alone was used in three, and biventricular support in two for 33-240 h with three survivals. The factors related to unsuccessful recovery were delayed start of support and multiorgan failure.
This study was undertaken to determine whether midazolam alleviates sympathoadrenal response evoked by tracheal intubation in elderly patients with hypertension. Anesthesia was induced with midazolam in a sleep dose followed by vecuronium 0.1 mg.kg-1. Heart rate and blood pressure were recorded before, 1 and 3 minutes after induction with intubation. Free and total catecholamine (CA) in plasma were measured at each time. Dopamine, norepinephrine and epinephrine (EN) were determined using fluorescence derivatization with diphenylethylenediamine by HPLC. Although heart rate and diastolic pressure rose in some degree 1 min after intubation, free and total CA concentrations did not increase during study period. Free and total EN levels decreased significantly 3 min after intubation. The absence of elevation in plasma CA concentrations, especially in free CA, which is physiologically active, would contribute to produce circulatory stability on laryngoscopy and tracheal intubation. However, the mystery of why hyperdynamic state was produced without the increase in CA concentrations remains to be solved, even though it occurred for a short period of time.
In ten cases of "early" Krukenberg tumor with only slight swelling of the ovary, histomorphological studies were performed to clarify the process of the formation of Krukenberg tumor. 1) The histological features of early metastatic lesion were classified into 3 types; lymph vessel permeation only, solid alveolar structure, and diffuse infiltration type. 2) Lymph vessel permeation in the ovarian hilum was observed in all cases. 3) In the diffuse infiltration type, signet-ring cells extended diffusely and radially via the lymph vessels, and, in the periphery, tumor cells leaked from the lymph vessels, infiltrating the stroma. At this stage, the response of ovarian stroma was slight, and signet-ring cells were present more abundantly in the vicinity of the infiltrated area. 4) In the solid alveolar type, the stroma was interposed in these lesions. 5) CEA staining revealed many CEA positive tumor cells in the proliferated stroma in which tumor cells failed to be detected. In summary, tumor cells infiltrate via the lymph vessels and leak into the stroma. Following the destruction of signet-ring cells, the mucus leaks into the stroma and it produces stromal edema and proliferation, eventually leading to a swollen ovary.
Five adult patients (pts) with age 15-67 (mean 43) received mechanical circulatory support with centrifugal pump (Biomedicus, BP-80, Sarns centrifugal pump) for postcardiotomy profound shock. Three pts underwent left ventricular support (LVS) alone, and the other 2 required biventricular support (BVS). Duration of the LVS ranged from 33 to 240 hours (mean 126 hours) and the right ventricular support 92, 120 hrs. Pump flow rate was 1.1 to 2.5 (mean 1.9) L/min/m2. Sixteen pumps were used and the pump exchange was performed 9 times in five pts and an average perfusion time per pump was 57 hrs. Two of 3 pts with LVS alone survived and one died of multiorgan failure associated with right heart dysfunction. In two pts with BVS, one survived and the other died of persistent low cardiac output early after pump removal. As the complication during mechanical support, bleeding was seen in 3 pts and cerebral infarction in one. Although centrifugal pump has potential limitation in antithrombogenicity and durability, this device provides a simple and effective mechanical circulatory support.