RESUMEN

Oral complications of salivary hypofunction often afflict cancer patients undergoing radiotherapy for head and neck cancers. Dry mouth or xerostomia is an undesirable consequence of radiotherapy that compromises normal oral functions in addition to causing odynophagia and increasing the patient's risk of oral infections and dental caries. Radiation-induced xerostomia is irreversible, and palliative measures to provide symptomatic relief remain the mainstay of treatment. Previously, we identified a splice variant of a cellular kinase, Tousled-like kinase 1B (TLK1B), which when overexpressed protects normal epithelial cells against ionizing radiation (IR)-induced cell death. To address the need to protect salivary glands in patients undergoing regional radiotherapy, we investigated whether preemptive expression of TLK1B in salivary glands protects against IR. In stably-derived salivary cell lines in vitro, TLK1B expression increased cell survival after IR. Cells expressing exogenous TLK1B were less radiosensitive (A5-TLK1B, α/ß=0.67 Gy; ParC5-TLK1B, α/ß=4.3 Gy) compared to control cells (A5-BK, α/ß=1.7 Gy; ParC5-BK, α/ß=32.7 Gy). Using a recombinant adenovirus serotype 5 viral vector for TLK1B gene transfer into rat submandibular salivary glands in vivo, we demonstrated that TLK1B protects the saliva-secreting acinar cells and better preserves salivary gland function against IR relative to control glands. After a single fraction of 16 Gy, the decline in salivary function at 8 weeks was less pronounced in TLK1B-treated animals (40%) as compared to saline-treated controls (67%). Histopathological analysis demonstrated increase in acinar atrophy, decrease in acinar cell number, and increase in inflammatory infiltrate and fibrosis in irradiated control tissues relative to TLK1B-treated glands. These results show the radioprotective benefits of TLK1B and implicate its usefulness in the management of regional radiotherapy-induced xerostomia.

Asunto(s)

Asunto(s)

RESUMEN

ETO (MTG8) was first described due to its involvement in the (8;21) translocation frequently observed in acute myeloid leukemias. In the t(8;21) the AML1 gene on chromosome 21 is fused to ETO on chromosome 8. The resultant hybrid protein is comprised of the DNA binding domain of AML-1 and the majority of ETO. This study examines the subnuclear distributions of ETO, AML-1B and AML-1/ETO proteins fused to green fluorescence protein in living cells using fluorescence microscopy. Further, we identified a 40 amino acid portion of ETO (amino acids 241-280) that was sufficient to cause nuclear import of green fluorescent protein. Mutational analysis demonstrated that lysine 265 and/or arginine 266 were required for nuclear import of ETO, but that the surrounding basic residues were not critical. ETO interacted with the nuclear import proteins importin-alpha and beta in vitro, and mutations in ETO that abolish nuclear localization also abolished the in vitro interaction with importin-alpha and beta. These data suggest that ETO enters the nucleus via an importin-mediated pathway. Additionally, ETO and AML-1/ETO co-localized to punctate nuclear bodies distinct from those containing promyelocytic leukemia protein. Nuclear body formation was dependent upon a region of ETO N-terminal to the nuclear localization signal. Thus, ETO and AML-1/ETO reside in potentially novel subnuclear compartments.

Asunto(s)

RESUMEN

Reductive metabolism of halothane in phenobarbital-pretreated rats is known to increase free radical formation that results in hepatotoxicity. It also is associated with a marked induction of microsomal heme oxygenase-1 (HO-1), suggesting that there is an alteration in heme metabolism. In this study, we examined heme metabolism in rats pretreated with phenobarbital, followed by exposure to halothane-hypoxia. In this model, there was a significant decrease in microsomal cytochrome P450 content in the liver, followed by a rapid increase in free heme concentration and a decrease in the level of mRNA for the nonspecific delta-aminolevulinate synthase. A transient but dramatic induction of HO-1 mRNA and a prolonged induction of heat shock protein 70 mRNA also occurred. The HO-1 protein was detected principally in the hepatocytes around the central vein. Serum alanine transaminase (ALT) activity, an indicator of hepatic dysfunction, increased continuously throughout the experiment. Hemin pretreatment induced hepatic HO-1 with abrogation of the halothane-induced hepatotoxicity in this model, as judged by ALT activity and normal histology. Our findings in this study thus indicate that halothane-induced hepatotoxicity is due not only to its reductive metabolite formation, but also to an increase in hepatic free heme concentration, which is a potent prooxidant; HO-1 induction is an important protective response against such changes. This is also the first study to demonstrate that hemin pretreatment, which induces HO-1 prior to exposure to halothane, effectively prevents halothane-induced hepatotoxicity.

Asunto(s)

RESUMEN

OBJECTIVE: To examine the role of heme oxygenase-1 (HO-1) induction in the recovery of renal function in rats with ischemic acute renal failure. DESIGN: Randomized, masked, controlled animal study. SETTING: University-based animal research facility. SUBJECTS: Sprague-Dawley male rats, weighing 200-250 g. INTERVENTIONS: Anesthetized rats were subjected to bilateral flank incisions, and the right kidney was removed. Renal ischemia was performed by left renal microvascular clamping, followed by reflow of the blood. MEASUREMENTS AND MAIN RESULTS: Ischemia of the kidney in the uninephrectomized rat significantly induced HO-1 messenger RNA, protein, and enzyme activity, reaching a maximum at 6 hrs, which was mediated in part through an increase in microsomal heme concentration. Heat shock protein 70 was induced extremely rapidly, reaching a maximum at 1 hr, suggesting that HO-1 and heat shock protein 70 gene expression are regulated separately. Inhibition of HO activity by tin mesoporphyrin, which resulted in an increase in microsomal heme concentration, significantly exacerbated renal function, as judged by the sustained increase in serum creatinine concentration and extensive tubular epithelial cell injuries. In contrast, animals that did not receive tin mesoporphyrin showed normal creatinine concentration and microsomal heme concentration 24 hrs after reperfusion, as well as restoration of abnormal renal histology. CONCLUSION: These findings indicate that the expression of HO-1 in the ischemic kidney may be critical in the recovery of renal cell function in this animal model. These findings also suggest that H0-1 induction may play an important role in conferring protection on renal cells from oxidative damage caused by heme.

Asunto(s)

RESUMEN

Midazolam has a slow onset of action, while thiamylal causes pain on injection and circulatory changes. To compensate for these drawbacks, the usefulness of a combination of midazolam and thiamylal in anesthesia induction was studied. The combination method was compared to the induction with single use of thiamylal in 40 patients (20 patients in each group). The combination of 0.2 mg.kg-1 of midazolam and 1.9 mg.kg-1 of thiamylal showed a shorter onset of action than the 4-5 mg.kg-1 of thiamylal. Pain on injection was observed in 5 cases of thiamylal group but in no cases of combination group. The changes in blood pressure, heart rate and rate pressure product were obviously smaller in combination group than in thiamylal group. Although the recovery time from anesthesia of combination group (13.2 minutes) was longer than that of thiamylal group (10.5 minutes), this was not clinically important. It is concluded that anesthesia induction with the combination of midazolam 0.2 mg.kg-1 and thiamylal 1.9 mg.kg-1 is more useful than that of thiamylal alone.

Asunto(s)

RESUMEN

In bank blood, red blood cells are destroyed and free hemoglobin increases during preservation. Concentrations of haptoglobin and free hemoglobin were measured in 73 packages of preserved whole blood which had been kept for various periods, 1 to 21 days. Those blood samples were divided into 7 groups depending on preserved period, 1 to 3, 4 to 6, 7 to 9 days, and so on. Total haptoglobin decreased to less than 100 mg.dl-1 in the blood preserved over 7 days. Total hemoglobin increased with the passage of preserved period. Free hemoglobin appeared in 40% or more of the blood preserved over 7 days and its concentration increased depending on preserved time. Free hemoglobin of 10 mg.dl-1 or more was detected in the blood preserved over 7 days. It is recommended that for massive blood transfusion the whole bank blood under 7 days of preservation should be used.

Asunto(s)

RESUMEN

The effects of nicardipine 1 mg bolus injection under enflurane anesthesia were compared with those under isoflurane anesthesia. Twelve neurosurgical patients were divided into 2 groups, enflurane group (n = 6) and isoflurane group (n = 6). In all patients anesthesia was induced with midazolam, thiamylal, fentanyl and vecuronium. Anesthesia was maintained with fentanyl, nitrous oxide, pancuronium plus enflurane (enflurane group) or plus isoflurane (isoflurane group). After incision of dura mater, nicardipine 1 mg was given through forearm venous line. For about 30 minutes before and after nicardipine injection, concentration of inhalational anesthetics was kept constant and no drugs were given. Blood pressure (BP), heart rate (HR), rate pressure product (RPP), and serum concentrations of catecholamine and nicardipine were monitored for 30 minutes after nicardipine injection. In isoflurane group, BP decreased more and longer, and increases of HR and serum concentration of catecholamine continued longer compared with enflurane group. Elimination half life of nicardipine was shorter, area under the curve (AUC) was smaller and clearance of nicardipine was larger in isoflurane group than in enflurane group. It was concluded that isoflurane increased the effects of nicardipine, which were BP depression and reflex sympathetic stimulation, than enflurane and that metabolism and elimination of nicardipine were accelerated more by isoflurane than by enflurane.

Asunto(s)

RESUMEN

Optimal dose of epidural midazolam with bupivacaine for postoperative pain relief was investigated. Forty seven patients for upper abdominal surgery were divided into 5 groups. Each group had either 0.25% bupivacaine 6 ml (control group), 0.25% bupivacaine 6 ml + midazolam 0.025 mg.kg-1 (0.025 group), 0.05 mg.kg-1 (0.05 group), 0.075 mg.kg-1 (0.075 group), or 0.1 mg.kg-1 (0.1 group) administered epidurally for complaint of first postoperative pain. Blood pressure (BP), heart rate (HR), respiratory rate (RR) and sedation score (SS) were monitored for 120 minutes, and the time interval for next analgesics (TNA) was checked. In each group, BP fell down 10 minutes after injection, HR was unchanged, and RR (except for 0.1 group) decreased, compared with the preinjection level. There was no difference between control group and others in BP, HR and RR. But 3 cases in 0.075 group and 4 cases in 0.1 group needed chin lift with a pillow under the shoulder for slight airway obstruction. The most optimal SS was obtained in 0.05 group. TNA was significantly longer in 0.025 and 0.05 groups than in the control group. It was concluded that the optimal dose of epidural midazolam with 0.25% bupivacaine 6 ml was 0.05 mg.kg-1 for postoperative pain relief after an upper abdominal surgery.

Asunto(s)

RESUMEN

The studies were performed to find out whether increased serum levels of polymorphonuclear leukocyte elastase (PMNE) depend on increase of segmented neutrophils or increase of PMNE release from a segmented neutrophil on 17 patients for various elective surgeries. Serum levels of PMNE, leukocyte count and leukogram were determined before incision (preoperation), as well as on the 1st, 3rd and 5th day after operation. Serum levels of PMNE, segmented cell count, stab cell count, stab cell-segmented cell ratio increased most on the 1st postoperative day and decreased thereafter. Leukocyte count showed no significant changes. Serum levels of PMNE correlated well with PMNE released from a segmented neutrophil, but not with leukocyte count or segmented cell count. It was concluded that increased serum levels of PMNE by surgical stress depend on the increased PMNE release from a segmented neutrophil but not on the increased segmented cell count.

Asunto(s)

RESUMEN

Optimal dose of epidural midazolam with saline for postoperative pain relief was investigated. Forty three patients for upper abdominal surgery were divided into 5 groups. Each group had either 10 ml saline only (saline group), 10 ml saline + midazolam 0.025 mg.kg-1 (0.025 group), 10 ml saline + midazolam 0.05 mg.kg-1 (0.05 group), 10 ml saline + midazolam 0.075 mg.kg-1 (0.075 group), or 10 ml saline + midazolam 0.1 mg.kg-1 (0.1 group) administered epidurally for complaint of postoperative pain. Blood pressure (BP), heart rate (HR), respiratory rate (RR) and sedation score (SS) were monitored for 120 minutes, and the time interval for next analgesics (TNA) was checked. In each group, BP was unchanged compared with preinjection level. HR changes were less in 0.05 and 0.1 group than in others. RR changes were less in 0.025 and 0.05 group than in others. Optimal SSs were obtained in 0.025 and 0.05 groups. In 0.075 and 0.1 groups, many patients fell into complete sleep (not responded to verbal command). TNA was about 2 hours in 0.025 and 0.05 groups, over 6 hours in 0.075 and 0.1 groups. Complete sleep was the cause of long TNA in 0.075 and 0.1 groups. It was concluded that optimal dose of epidural midazolam with saline 10 ml was 0.05 mg.kg-1 for postoperative pain relief after upper abdominal surgery.

Asunto(s)

RESUMEN

Postoperative pain relief and sedation with epidural midazolam-saline or midazolam-bupivacaine were studied in 46 patients after elective upper abdominal surgery. They were divided into 6 groups. In each group, 10 ml saline, 10 ml saline+midazolam 0.05 mg.kg-1, 10 ml saline+midazolam 0.1 mg.kg-1 (saline group), 0.25% bupivacaine 6 ml, 0.25% bupivacaine 6 ml + midazolam 0.05 mg.kg-1 or 0.25% bupivacaine 6 ml + midazolam 0.1 mg.kg-1 (bupivacaine group) was administered via epidural catheter for complaint of pain. For 120 minutes after epidural injection, blood pressure (BP), heart rate (HR), respiratory rate (RR), sedation score, and serum concentration of midazolam (conc midazolam) were evaluated. The time interval until next complaint of pain (pain relief time) was measured. In midazolam injected group, BP, HR, RR were not changed from preinjection value, but sufficient sedation was obtained and pain relief time was significantly prolonged compared with saline or bupivacaine injected group. Midazolam level was lower than that of sedation level. There were no significant differences between saline group and bupivacaine group, but the pain relief effect was slightly stronger in bupivacaine group. It is concluded that epidural saline - midazolam or 0.25% bupivacaine - midazolam is useful for postoperative pain relief after upper abdominal surgery.

Asunto(s)

RESUMEN

Postoperative pain relief and sedation with epidural midazolam were studied. Twenty-one patients for elective upper abdominal surgery were divided into 3 groups. Epidural catheter was inserted into thoracic epidural space before induction of general anesthesia. In each group, either 10 ml saline only, midazolam 0.05 mg.kg-1 + 10 ml saline, or midazolam 0.1 mg.kg-1 + 10 ml saline was injected into epidural catheter for complaint of pain in recovery room. For 120 minutes after epidural injection, blood pressure, heart rate, respiratory rate, serum concentration of midazolam, and sedation score were monitored. In midazolam injected groups, only slight changes were seen in blood pressure, heart rate, and respiratory rate. Sedation score was graded from 1 to 6:1 means complete sleep, and not responded to verbal command, 6 means agitated and many complaints. Midazolam 0.1 mg.kg-1 + 10 ml saline group had the lowest score, and saline 10 ml group had the highest score. Prolonged sedation and pain relief were obtained in midazolam injected group, especially 0.1 mg.kg-1 + 10 ml saline group. Serum midazolam concentrations were lower than 200 ng.ml-1. These values were considered as the lower limit for sedation by intravenous administration. In conclusion, epidural midazolam was useful for postoperative pain relief. The mechanism is considered to involve spinally mediated CNS action or direct spinal action.

Asunto(s)

RESUMEN

Total intravenous anesthesia was performed with continuous infusion of midazolam and bolus injection of fentanyl. A bolus injection of midazolam 0.3 mg.kg-1 was followed by an infusion regimen with an initial infusion rate of 0.68 mg.kg-1.hr-1 for 15 min followed by a maintenance infusion of 0.125 mg.kg-1.hr-1 and infusion was stopped at about 30 min before the end of operation. Fentanyl and pancuronium were injected as required. Nicardipine was given for intraoperative hypertension. Plasma concentrations of epinephrine and norepinephrine decreased significantly at 10 min after induction, but increased significantly during operation. Therefore, this anesthetic method was considered not to be so deep. Plasma concentrations of midazolam were higher than 200 ng.ml-1 during operation. After discontinuation of midazolam infusion, its concentration decreased quickly, and the elimination half life of midazolam was 1.675 +/- 0.2807 hr. The value was not so large as we had anticipated. Total intravenous anesthesia with continuous infusion of midazolam and bolus injection of fentanyl is thought to produce light anesthesia. Plasma concentration of midazolam decreased quickly.

Asunto(s)

RESUMEN

Effects of induction with midazolam on serum histamine levels (Study 1) and the volume as well as pH of gastric juice (Study 2) were studied. Anesthesia was induced with midazolam 0.2 mg.kg-1 in midazolam group, thiamylal 4 mg.kg-1 in control group. In Study 1, serum histamine levels were measured with high performance liquid chromatography till 180 minutes after intubation. There were no statistical significance between the two groups in serum histamine levels at all points. But in midazolam group, at 30 minutes after intubation, the histamine level was significantly lower than the preinduction level. In control group, serum concentration of histamine increased but not significantly. In Study 2, gastric juice was sampled through naso-gastric tube inserted on the morning of operation. Gastric juice pH was measured with the use of pH Strip (E. Merck, F.R. Germany). There were no significant differences between the two groups in volume as well as pH of gastric juice at all points. It is concluded that midazolam used for induction of anesthesia might decrease histamine release, but it has no clinical effects on gastric juice secretion.

Asunto(s)

RESUMEN

Continuous infusion of midazolam and fentanyl were used in total intravenous anesthesia. Anesthesia was induced with midazolam 0.3 mg.kg-1 in 100% O2. Tracheal intubation was facilitated with succinylcholine 1 mg.kg-1 after precurarization with pancuronium 1 mg. The infusion regimen of midazolam was as follows; an initial infusion of 0.68 mg.kg-1.hr-1 for 15 min followed by a maintenance infusion of 0.125 mg.kg-1.hr-1, and about 30 min before the end of operation infusion was stopped. Fentanyl and pancuronium were injected as required. During operation, blood pressure and heart rate were stable with a small dose of nicardipine. Total dose of fentanyl was the same as in NLA. Extubation was done as quickly as in NLA, after aminophylline infusion which was said to reverse midazolam. In the recovery room, patients were asleep and snored. But they opened eyes and responded to verbal command. Respiratory rate and PaCO2 were in normal ranges. Total intravenous anesthesia was possible with midazolam and fentanyl but a further study is necessary.

Asunto(s)

RESUMEN

The effects of midazolam on stress response during surgery compared with thiamylal were studied. Twelve patients were divided into 2 groups at random; midazolam group and thiamylal group. Anesthesia was induced with midazolam 0.2 mg.kg-1 or thiamylal 4 mg.kg-1 in each group, and maintained with O2 2 l.min-1, N2O 4 l.min-1 and enflurane. The plasma concentration of catecholamine was measured at preinduction, 10, 30, 60, 120 and 180 minutes after intubation. No significant differences were seen between 2 groups in plasma concentration of catecholamine. In midazolam group, plasma concentration of epinephrine decreased significantly 10 minutes after intubation as compared with preinduction level. The plasma concentration of norepinephrine in midazolam group tended to decrease. In thiamylal group, plasma concentration of norepinephrine tended to increase and increased significantly at 120 and 180 minutes after intubation as compared with preinduction level. These results suggest that induction with midazolam suppresses stress response during anesthetic induction and surgery more intensely than induction with thiamylal.

Asunto(s)

RESUMEN

We compared midazolam 0.2 mg.kg-1 and fentanyl 50 micrograms with thiamylal 4 mg.kg-1 for rapid sequence induction. We could use midazolam safely in patients with bronchial asthma or drug allergy. There was no difference in time from the beginning of induction to intubation between midazolam treated group and thiamylal treated group. Changes in systolic as well as diastolic blood pressure and heart rate during 2 hours from intubation were smaller in midazolam treated group than in thiamylal treated group. In midazolam treated group, no arrhythmias were observed at the time of intubation. We could reduce the amount of anesthetics in midazolam treated group during 2 hours from intubation. From the results mentioned above, we conclude that midazolam is a useful agent for rapid sequence induction.

Asunto(s)

RESUMEN

Arterial infusion therapy was applied to 77 patients with 18 unresectable, 29 non-curatively resected and 20 recurrent gastric cancers. 5-fluorouracil (5-FU) was administered by arterial continuous infusion, and adriamycin (ADM) and mitomycin C (MMC) by bolus infusion. The clinical effectiveness of each was evaluated. One-year cumulative survival rate of primary case by Kaplan-Meier method was 19.2%, and that of recurrent gastric cancer was 5.3%. Median survival time of primary case was 6.5 months, showing prolongation compared with recurrent ones. Also, in primary cases, the arterial infusion therapy was more effective in non-curatively resected cases than in unresectable ones. Two of the patients are now alive and another is apparently free of tumor and the remaining one had a recurrence. Continuous arterial 5-FU infusion and ADM low-dose intermittent bolus infusion chemotherapy (AF therapy) were considered an effective supportive treatment without any serious side effects for unresectable, noncuratively resected and recurrent gastric cancer.

Asunto(s)

Asunto(s)