[Intrabiliary pressure changes produced by inhalational anesthetics in dogs]. The common bile duct pressure was studied in dogs under inhalation of 1.0 MAC and 2.0 MAC of halothane, enflurane, isoflurane or sevoflurane. A double lumen catheter was inserted into the common bile duct through the cholecystic duct for the measurement of intraductal pressure in the choledochoduodenal junction. The intra-bile-ductal pressure (IBP) was measured with constant rate infusion methods every 10 minutes for one hour. After obtaining control IBP measurements, 44 dogs received randomly either 1.0 MAC (n = 6 in each group) or 2.0 MAC (n = 5 in each group) of each four inhalational anesthetics, through a non-rebreathing system. The decreases in IBP produced by 1.0 MAC concentrations of four inhalation anesthetics were not statistically significant although there was a decline from control measurements obtained for each group. The elevations of IBP following 2.0 MAC halothane, isoflurane or sevoflurane were significantly depressed and were 38.3 +/- 21.2, 67.5 +/- 23.8, 63.7 +/- 23.7 (%, mean +/- SD) of the control levels, respectively. However, 2.0 MAC enflurane produced no significant decrease in IBP.


[Serum concentrations of ranitidine after intravenous administration in geriatric patients under general anesthesia]. The elimination rate of serum ranitidine was investigated in healthy geriatric patients under general anesthesia. The patients (50-90 y.o., ASA classification 1 and 2) were divided into Group 1 (age greater than or equal to 70, n = 9) and Group 2 (50 less than age less than 65, n = 6). Ranitidine (1 mg.kg-1) was administered intravenously after the induction of anesthesia, and the serum concentration was measured at 60 min and 120 min. The biological half life of serum ranitidine in Group 1 was 98.9 +/- 13.8 (M +/- SD) min, which was not significantly different from that of Group 2. The half life correlated with intraoperative urine volume (r = 0.62), but not with intraoperative bleeding or age. The duration of the above effective ranitidine concentration was calculated as about 4 and half hours after its i.v. injection. This indicates that additional administration is necessary for longer operations.


[A comparison of the effects of omeprazole with those of ranitidine on intragastric pH and volume in patients for elective surgeries]. This study compared the effect of omeprazole with those of ranitidine on intragastric secretion during perioperative period. Thirty-one patients were randomly allocated to three groups. Each group received either omeprazole, ranitidine orally or one on the night before surgery. Intragastric pH and volume were measured after induction of anesthesia. Omeprazole group and ranitidine group had a higher mean pH than control group (P less than 0.01). None of the omeprazole group had an aspirate of pH lower than 2.5. One patient (10%) in the ranitidine group and five patients (50%) in the control group and five patients (50%) in the control group had aspirates of pH lower than 2.5. Mean gastric volume was not significantly different among these groups. A single dose of omeprazole 20 mg significantly decreased the number of patients at risk of aspiration pneumonitis.


[Use of omeprazole for premedication].

[Use of omeprazole for premedication]. Omeprazole, a proton pump inhibitor was used for premedication for general anesthesia, and its effects on gastric secretion and serum gastrin level were investigated in 60 patients. The patients were divided into the following 4 groups and each group received one of the following medications; (I) a tablet of omeprazole 20 mg before sleep at the night before the surgery, (II) a tablet 2 hours before the induction of anesthesia, (III) one on the night before and another tablet 2 hours before the induction, or (0) no tablet. In the patients who received any dose of the drug, the volume of gastric juice at the beginning of the surgery was significantly less than that in those who received no drug (P less than 0.05). Gastric pH showed a tendency to increase depending on the dose of omeprazole (0 less than I less than II less than III), but it was not significant. No significant change in serum gastrin level was observed in this study. A 20 mg omeprazole tablet may not be adequate as the premedication for general anesthesia.


[Anesthetic management of a patient with right ventricular myxoma]. Right ventricular myxoma in a 79 year old male, whose pulmonary trunk was obstructed by the myxoma, was reported. Myxoma of the heart is rare, and especially right ventricular myxoma is rare. Myxomas of the heart have been reported by thirty-seven authors, but right ventricular myxoma has been reported by only one author. Anesthesia for the removal of right ventricular myxoma must be carried out carefully, because some critical troubles may happen during anesthesia for the resection of the right ventricular myxoma. Particularly, occlusion of the pulmonary artery is the most dangerous complication.


[Perioperative management of a patient with transient polyuria]. Perioperative and anesthetic management of a patient with a diabetes insipidus is reported. A 33 year old man was followed by physical therapy after spinal cord injury. At that time polyuria (4300-8600 ml.day-1) and polydipsia developed. His urine output was controlled by DDAVP (desmopressin) preoperatively. As the result of water restriction test and Carter-Robbins test the diagnosis of complete central diabetes insipidus was doubted preoperatively. We investigated the changes of his perioperative body fluids and endocrine responses. The following conclusions are made: 1) The diagnosis of this case is not renal and true diabetes insipidus, but is probably partial or transient diabetes insipidus. 2) These results indicate that endocrine examinations related to AVP secretion are essential.


[Pneumothorax during laparoscopy].

[Pneumothorax during laparoscopy]. A 28-year-old female was scheduled for laparoscopy under general anesthesia. Her history and physical examination were unremarkable. Trachea was intubated uneventfully following intravenous administration of thiopental 200 mg and vecuronium 8 mg. Anesthesia was maintained with 40% O2, 60% N2O and sevoflurane. Shortly after pneumoperitoneum was introduced, airway resistance increased and breathing sounds were hardly audible over the right side of the chest. A chest radiograph showed the right pneumothorax. Immediately after evacuating the peritoneal gas, the chest radiograph and a blood gas analysis showed that the pneumothorax had improved. Pneumothorax can occur subsequently to pneumoperitoneum due to passage of gas through weak points or defects in the diaphragm. Breathing sound should be monitored carefully during the laparoscopic surgery. Anesthetic gas analyzer and capnometer are considered to be useful to confirm the cause of the pneumothorax.


[Anaphylactoid reactions to contrast media which occurred during cholecystectomy and subsequent disseminated intravascular coagulation--a case report]. A 67-year-old woman without any history of allergic episode developed severe hypotension (40 mmHg) without skin rash one minute after the administration of amidotrizoic acid for intraoperative cholangiography during thoracic epidural and light general anesthesia. Although ephedrine, methoxamine, dopamine and norepinephrine were administered, severe hypotension persisted for three hours and epinephrine was only effective. Marked elevations of serum levels of histamine, leukotriene D4 and leukotriene E4 were noted after the episode, suggesting the occurrence of the anaphylactoid reaction to amidotrizoic acid and the activation of the immunological complement system. After the recovery from the anaphylactoid reaction, the patient developed disseminated intravascular coagulation (DIC) and severe bleeding around the wound for which reoperation was needed. It is necessary to consider some prophylactic treatments against DIC when severe anaphylactoid reaction occurred.


[Cardiac herniation after right pneumonectomy]. Cardiac herniation is a rare, but highly lethal complication of intrapericardial pneumonectomy for progressive carcinoma of lung, and occurs in early postoperative period. Our patient with this complication presented sudden onset of severe hypotension and cyanosis after several ventricular premature beats. We suspected cardiac herniation as we observed dilatation of cervical veins and rightward deviation of heart sound. The patient was immediately positioned on his left side and systemic blood pressure increased soon. After verification of the incident by chest X-ray film, emergency operation was performed. Fortunately, vital signs were stable during and after reoperation and the patient could survive.


[Herpes zoster of the right cervical region associated with right facial nerve palsy and hoarseness]. A 69-year-old man was suffering from herpes zoster on his 2nd and 3rd right cervical spinal segments and 3rd branch of the trigeminal nerve. He came to our hospital on his 10th illness day and was treated with continuous cervical epidural block, intravenous infusion of acyclovir for five days, and oral paramethasone and Vitamin B12. Oh his 18th illness day, right facial nerve palsy and hoarseness became clear. His cerebrospinal fluid showed no abnormality except cell count 23 x 3 mm-2. No clear paralysis of vocal cords was detected on laryngoscopy. He was also treated with right stellate ganglion block starting on his 21st illness day. His pain and facial nerve palsy recovered completely by his 68th illness day, but hoarseness continued about two months. The hoarseness might be a result of spread of the disease 1) by cerebrospinal fluid, 2) by contact with the 3rd cervical nerve and vagal nerve via accessory nerve, and 3) direct effect on the vocal cords and the muscles controlling them. Herpes zoster on the head and neck region shows various complications and we should follow its course cautiously.


[Transient second-degree A-V block during an epidural procedure]. A 26 year old pregnant female had a left ovarian tumor and was scheduled to have an operation. No specific complication was noted preoperatively except pregnancy of 16 weeks and one day. Spinal anesthesia for the operation and continuous epidural catheter placement for postoperative pain relief were planned. During the epidural procedure on L2-3 under left lateral recumbent position, patient developed a bradycardia when the tip of Tuohy needle touched the 3rd lumbar bone (lamina arcus vertebrae). This bradycardia occurred three times and the last episode was recorded on the ECG (Fig 2). Blood pressure at this period was 82/44 mmHg, but patient did not complain any discomfort. The recorded ECG showed II degree A-V block (Wenkebach type). We considered this A-V block is probably due to sharp pain from touching of Tuohy needle on the lamina arcus vertebrae. This kind of periosteal pain is sometime associated with vagal stimulation and it could produce II degree A-V block. During a spinal or epidural procedure, ECG should be monitored and we have to pay attention to these kinds of arrhythmia to prevent more profound hemodynamic changes.


[Pulmonary embolism was suspected during hip surgery under spinal anesthesia: a case report]. Most of the lower leg surgeries are done under spinal anesthesia. This 53 year old male had undergone a surgery for his left hip fracture previously and was scheduled for the removal of the screw. Spinal anesthesia was administered and sensory block was obtained up to T8. After the removal of the screw, he coughed weakly for several times. Suddenly ECG monitor showed severe bradycardia and hypotension was observed. He complained of chest pain, dyspnoea and went into shock. Immediately after giving atropine 0.5 mg iv, ephedrine 8 mg x 2 was necessary to raise his heart rate. About 3 minutes later he recovered from his shock state. ECG changes were transient and the bradyarrhythmia during his shock turned out to be AV dissociation. Arterial blood gas analysis showed decreased PaO2 and increased PaCo2. We suspected lung embolism. However, postoperative chest X-ray and pulmonary perfusion scans were within normal limits.


[Three cases of irritable bowel syndrome treated with stellate ganglion block]. We examined three patients with irritable bowel syndrome (IBS) who did not respond to drug therapy and who were treated by stellate ganglion block (SGB) alone. The clinical symptoms improved by the SGB in all these three patients. There was no recurrence. The pathophysiological mechanism of this disease and the therapeutic efficacy of SGB should be elucidated with respect to the autonomic nervous, endocrine and immune systems. These results suggest that SGB therapy is effective for IBS, a typical psychosomatic disease.


[Evaluation of efficacy of a disposable monitor for surface temperature (PROCHECKER) compared with thermography]. We evaluated efficacy of a disposable monitor for surface temperature (PROCHECKER) compared with thermography. Changes in surface temperature after epidural block with mepivacaine 1% were measured using both PROCHECKER and thermography. Measured areas were regions of bilateral Th 4, 6, 8, 10, 12 and along the midmammary line. The surface temperatures on all areas were measured before, 15 min after and 30 min after the epidural block. Discrepancies of the temperatures measured by the two methods were found in 16.7% of all measured areas, and discrepancies in changes in the temperature were found in 6.7%. In conclusion, a disposable monitor for surface temperature (PROCHECKER) is effective and sensitive to measure changes in the temperature.


[Hypoventilation due to disconnection of the vaporizer and negative-pressure leak test to find disconnection]. Most of Ohmeda anesthesia machines have a outlet check valve located in the low-pressure circuit, and this influences the type of leak test greatly. We report a case of hypoventilation due to a gas leakage from the junction of two vaporizers, Fluotec 3 and Enfluratec of Ohio 30/70. This gas leakage was not discovered preoperatively by performing traditional leak test of squeezing the bag filled with oxygen. Following intubation of the trachea the patient was paralyzed and mechanically ventilated. Her vital signs were stable and operation was started. Soon thereafter, she became hypertensive in spite of increases in concentration of enflurane and supplemental doses of fentanyl and diltiazem. ETCO2 showed 7.4% and spontaneous respiration started. We checked anesthesia machine and found a gas leakage at the junction of two vaporizers. Anesthesia machine was exchanged. The remainder of the procedure was uneventful and the patient showed a normal recovery. The outlet check valve closes when back-pressure is exerted on it, and a vulnerable area including flow tubes and vaporizers is not tested by the traditional positive-pressure leak test squeezing bag. Ohmeda recommends the use of a negative pressure leak test with suction bulb device. We propose manufacturers to place a cation on anesthesia machine such as -- "Negative-pressure leak test is inevitable because of presence of outlet check valve."


[Suppressive effect of sevoflurane on somato-sympathetic reflexes in cats]. Effects of sevoflurane on the reflex activity of the sympathetic nervous system in cats were investigated by observing alteration of the amplitudes of somato-sympathetic medullary reflex potentials. These reflex potentials consist of two components, A- and C-reflex potentials, which are induced from the lumbar sympathetic trunk by electric stimulation of the ipsilateral femoral nerve. It is known that A- or C-reflex potential is induced by stimulating peripheral A-fiber group or C fiber group, respectively. Sevoflurane 1, 2 and 3% in oxygen for 30 minutes for each concentration by incremental fashion, were inhalated. Neither A nor C reflex potentials were suppressed by 1 and 2% sevoflurane but 3% sevoflurane caused a significant suppression of both reflex potentials in brain intact cats. Concentration-dependent suppression of C-reflex potentials and a tendency of concentration-dependent suppression of A-reflex potentials were observed in decerebrate cats. Mean arterial blood pressure showed a concentration-dependent decrease in both brain intact and decerebrate groups. These results indicate that sevoflurane with concentrations higher than 1 MAC (2.5% for cats) significantly suppresses somato-sympathetic reflex activities. The results suggest, however, that this agent with concentrations lower than 1 MAC suppresses the descending inhibitory system from supra-medullary centers so that the integrated sympathetic outflow from the medulla oblongata are not suppressed significantly. The results also suggest that direct depressive effect on the cardiovascular system by sevoflurane rather than through suppressive effect on sympathetic reflexes may play a major role in hypotension during inhalation of concentrations below 1 MAC.


[Effect of prostaglandin E1 on peripheral body temperature in pediatric patients after open heart surgery]. The effect of prostaglandin E1 was studied to examine if it works favorably for peripheral circulation in pediatric patients after cardiac surgery. Dose of 0.1 mcg.kg-1.min-1 increased temperature of dorsal pedis significantly. Difference of temperature of dorsalis pedis and that of rectum was significantly smaller than that in control group. A significant increase in heart rate and a decrease in systolic arterial pressure produced no clinical side effects. We conclude that prostaglandin E1 is a useful and safe vasodilator for circulatory management of pediatric patients after cardiac surgery.


[The effects of prostaglandin E1 on renal function]. The effects of prostaglandin E1 on renal function were studied in surgical patients under general anesthesia. The patients were over 20 years old, and had ischemic heart disease, hypertension and/or liver dysfunction. In 67 patients (PGE1 group), prostaglandin E1 (PGE1) was in fused at a rate of 0.02 mcg.kg-1.min-1. In 55 patients (control group), only lactated Ringer solution was infused at a rate of 10 ml.kg-1.h-1. Urine output and fractional sodium excretion in PGE1 group were significantly higher than those in control group. There were no significant differences in creatinine clearance and free water clearance between the two groups. The increase in urine output in PGE1 group could be attributed to the decrease in the water reabsorption in the proximal renal tubule.


[Effects of deliberate hypotension on the ischemic heart during isoflurane anesthesia--a comparison of prostaglandin E1 and sodium nitroprusside]. The effects of hypotension induced by prostaglandin E1 (PGE1) or sodium nitroprusside (SNP) on regional myocardial function and metabolism were studied in a canine heart with coronary artery stenosis. Ultrasonic dimension technique was used to assess left ventricular performance. Fourteen open-chest mongrel dogs were anesthetized with isoflurane and mean aortic pressure was maintained at approximately 80 mmHg. The left circumflex coronary artery blood flow was reduced by 40% using a screw flow regulator without affecting global and regional myocardial function. The severity of stenosis was considered almost critical. PGE1 (n = 7) or SNP (n = 7) was administered to reduce mean aortic pressure to 50 mmHg. There were no significant differences between PGE1 and SNP regarding their effect on systemic hemodynamics. Nevertheless SNP decreased percent segment shortening in the stenosed area from the pre-hypotension value more significantly than PGE1 (55.0 +/- 10.8% versus 24.2 +/- 7.3%). This suggests that regional myocardial ischemia is more deteriorated during SNP-induced hypotension. It seems that PGE1-induced hypotension is safer when it is applied to patients with coronary artery disease.


[Effects of high-dose fentanyl anesthesia on auditory brain stem responses]. It was previously reported that high-dose (50 micrograms.kg-1) fentanyl anesthesia had no effect on auditory brainstem response (ABR). However, the effect of the dose of 100 micrograms.kg-1 of fentanyl is unknown. We examined the effects of the dose of 50 micrograms.kg-1 and 100 micrograms.kg-1 of fentanyl on ABRs in 10 patients scheduled for cardiovascular surgery. No significant change was observed immediately after infusion of 50 micrograms.kg-1 of fentanyl, but peak latencies of waves I, III and V were significantly prolonged and the amplitude of wave V was significantly decreased immediately after infusion of 100 micrograms.kg-1 of fentanyl. The interpeak latencies of I-III and I-V were not affected. Therefore, prolongations of latencies of waves III and V were due to the change of latency of wave I. These results demonstrate that high-dose (100 micrograms.kg-1) fentanyl anesthesia depresses the peripheral auditory perception but dose not depress the central conduction.


[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.


[The effect of isoflurane or sevoflurane on circulating blood volume--a study under controlled ventilation]. Changes of circulating blood volume during isoflurane or sevoflurane anesthesia were investigated by the dual indicator dilution method in eighteen mongrel dogs. The animals were randomly divided into three groups; control (C) group n = 6, isoflurane (I) group n = 6, and sevoflurane (S) group n = 6. The values of circulating blood volume (ml.kg-1) at 0, 0.5 and 1.0 MAC period were 90.1 +/- 18.7----87.5 +/- 17.2----94.1 +/- 23.6 in the I group and 91.6 +/- 12.5----96.5 +/- 15.0----94.1 +/- 8.5 in the S group, respectively. No significant changes were found in both groups concerning circulating blood volume, red cell volume, and plasma volume, but circulating blood volume and plasma volume tended to increase slightly in both groups at 0.5 and 1.0 MAC period compared with 0 MAC period. Mean arterial pressure decreased 68% of the initial value in the I group at the 1.0 and 78% stages in the S group. Cardiac index tended to increase from 2.6 +/- 0.4 l.min-1.m2 to 3.2 +/- 0.9 in the I group at the stage 1.0 but to decrease from 5.2 +/- 1.4 l.min-1.m2 to 4.1 +/- 0.9 in the S group. It was suggested that the increase of venous pressure resulted in the significant decrease of plasma volume. Increase of intrathoracic pressure during positive pressure ventilation might partially influence the blood volume change. Our data suggest that isoflurane and sevoflurane do not greatly affect the circulating blood volume under control ventilation.


[Effects of sevoflurane on intracranial pressure and formation and absorption of cerebrospinal fluid in cats]. The effects of sevoflurane on intracranial pressure (ICP) and the formation and absorption of cerebrospinal fluid (CSF) were examined in cats. Changes in ICP and superior sagittal sinus pressure (SSSP) were studied for 180 minutes during anesthesia with 1MAC sevoflurane (2.6%, inspired) and 50% N2O in O2. ICP increased significantly immediately after the start of anesthesia. The level remained for the subsequent 120 minutes, but increased significantly again 140 minutes after the start of anesthesia. There was no change in SSSP. The rate of CSF formation (Vf) was examined using the open ventriculocisternal perfusion method during anesthesia for 180 minutes with 1MAC sevoflurane or 1MAC enflurane (2.4%, inspired) and 50% N2O in O2. During sevoflurane administration, Vf decreased significantly 30 minutes after the start of anesthesia. In contrast, during enflurane administration, Vf increased significantly 10 minutes after the start of anesthesia. Finally, Vf and the rate of CSF absorption (Va) were measured under 1MAC sevoflurane or 1MAC enflurane and 50% N2O in O2 anesthesia, or under 50% N2O in O2 anesthesia. They were compared with ICP level. Vf decreased significantly when ICP level increased in all groups. The increase in Va when ICP level increased, was greater in the N2O group than in those anesthetized with sevoflurane or enflurane. The delayed increase of ICP under sevoflurane may have resulted in part from the cranial accumulation of CSF due to increased resistance to CSF absorption.


[Effects of sevoflurane on regional myocardial oxygen balance in the canine heart with coronary artery stenosis]. The effects of increasing inspired sevoflurane (Sev) concentrations (0.5, 1.0, 1.5, 2.0 MAC) on regional myocardial oxygen balance and metabolism were studied in 10 open-chest dogs with coronary artery stenosis. Regional myocardial oxygen balance was assessed by continuous recording of subendocardial and subepicardial oxygen tensions. After the basal measurement, the left circumflex coronary artery blood flow (CBFLCX) was reduced by 20% with a screw flow regulator. The institution of stenosis caused a slight but significant decline in subendocardial oxygen tension. Otherwise, there were no significant differences between basal values and those after the stenosis. During the subsequent inhalation of Sev at 0.5, 1.0 and 1.5 MAC, endocardial oxygen tension was maintained at the level of control value. Sev 2.0 MAC caused a severe reduction in systemic arterial pressure and resulted in a marked and significant decline of endocardial oxygen tension compared with control value. On the other hand, subepicardial oxygen tension remained unchanged during each Sev inhalation. The ratio of epicardial/endocardial oxygen tension did not show a significant decline with increasing Sev concentration. It seems that Sev may not possess sufficient potency to cause myocardial ischemia by redistribution of coronary blood flow.


[The effects of preanesthetic oral clonidine upon heart rate response to intravenous atropine in patients during general anesthesia]. In awake subjects the positive chronotropic effect of intravenously administered atropine 10 micrograms.kg-1 has been demonstrated to be blunted by preanesthetic medication of oral clonidine 5 micrograms.kg-1. The aim of the present study is to investigate whether general anesthesia could alter the clonidine-induced attenuation of positive chronotropic effect by atropine. Thirty-two patients were randomly assigned to one of the two groups; patients of the clonidine group received oral clonidine 5 micrograms.kg-1 (n = 12), whereas those of the control group received no clonidine. General anesthesia was induced with intravenous thiamylal 4-5 mg.kg-1, and was maintained with enflurane and nitrous oxide in oxygen after endotracheal intubation. Following the stable circulatory period of 10 min, hemodynamic measurements were made at 1 min intervals for 10 min after atropine 10 micrograms.kg-1 was administered intravenously as a bolus in both groups. A significant attenuation in heart rate response to intravenous atropine 10 micrograms.kg-1 was observed in patients receiving clonidine 5 micrograms.kg-1, as compared with that in the control group (P less than 0.01); maximal increases in heart rate were 15 +/- 8 and 22 +/- 6 beats.min-1 (mean +/- SD) in the clonidine and control groups, respectively. It is concluded that clonidine 5 micrograms.kg-1 blunts the heart rate response to intravenous atropine 10 micrograms.kg-1 in patients anesthetized with enflurane and nitrous oxide in oxygen.


[Changes in plasma LDH-isozyme in rats during hypoxia and its recovery stage]. Rats were placed in an air-tight glass dome connected to a spirometer, into which nitrogen gas was introduced gradually, to achieve oxygen concentration of about 10%. The animals gradually exhibited dyspnea, and became apneic after about 30 min. Most of the rats in this stage died after the sampling. A different group of rats were returned to the room air from the apneic stage with hypoxia, and were used for the study on the recovery stage. Blood gas analysis revealed severe acidosis and hypoxemia during the apneic stage, while PO2, O2 CT, and O2SAT increased rapidly and significantly during the recovery stage. pH was unchanged between the apneic and recovery stages. During the apneic stage, plasma LDH-zymogram was similar to that of the liver taken as the control. However, after returning from hypoxia, the LDH-isozyme patterns quickly approached that of the heart muscle with increasing LDH1 and LDH2. During hypoxia, the changes of arterial oxygen content with alteration of blood flow in the organs, brought direct effects upon the blood isozyme patterns.


[Effect of M1 blocker or H2 blocker on gastric secretion during anesthesia and surgery]. Effect of pirenzepine, famotidine or a combination of both agents on gastric secretion during anesthesia and surgery was evaluated in 42 surgical patients ranged in age from 17 y to 70 y. They underwent orthopedic, ophthalmic, ENT, plastic, oral or non-abdominal surgery under either neuroleptanesthesia or enflurane anesthesia. They received either pirenzepine 10 mg, famotidine 20 mg or the combination of both agents intravenously just before the induction of anesthesia. Volume and acidity of gastric juice were measured during 3 hours after the administration of these agents. A continued decrease in volume and acidity of gastric juice was observed 3 hrs after the administration of the agents both in the pirenzepine group and in the famotidine group. Efficacy of the combination of pirenzepine and famotidine on gastric secretion tended to be more prominent than that of either pirenzepine or famotidine alone.


[Neuromuscular blocking effect of ORG9426, a new non-depolarizing muscle relaxant, and its recovery with various antagonists in vitro]. We evaluated the neuromuscular blocking effect of ORG9426, a new non-depolarizing muscle relaxant, and its recovery by means of washout or by antagonists in vitro, using phrenic nerve-hemidiaphragm preparations of rats. IC50 and IC90 of ORG9426 in single twitch were 10.62 +/- 0.58 microM and 15.75 +/- 0.95 microM; and those in train of four ratio were 9.04 +/- 0.38 microM and 11.87 +/- 0.42 microM, respectively. The potency of ORG9426 in vitro was compared with those of other non-depolarizing muscle relaxants. The order of potency among the non-depolarizing muscle relaxants was the following: d-tubocurarine greater than pipecuronium greater than pancuronium greater than vecuronium greater than ORG9426. There was no difference between ORG9426 and vecuronium in the recovery from block with washout, neostigmine, 4-aminopyridine, 3, 4-diaminopyridine, and edrophonium. In conclusion, the potency of ORG9426 is relatively low, and it can be easily antagonized by anti-cholinesterases and aminopyridines.


[Clinical study on total intravenous anesthesia with droperidol, fentanyl and ketamine--15. Application for cardiac anesthesia]. Total intravenous anesthesia with droperidol, fentanyl and ketamine (DFK) was administered to 36 cardiac patients who underwent mostly coronary artery bypass graft or heart valve replacement. The induction and maintenance of anesthesia using this technique were almost satisfactory with little decrease in systolic blood pressure (SBP), although six patients among the early 21 patients developed hypotension below 90 mmHg (SBP) during the induction, and required vasopressors. Half of the patients had hypertensive episode of above 180 mmHg (SBP), from the start of operation to onset of cardiopulmonary bypass, which was safely and effectively overcome by a small dose of antihypertensive agents. Total intravenous anesthesia with DFK was accompanied with much more hypertensive episodes compared to anesthesia with moderate dose fentanyl (30 micrograms.kg-1) combined with enflurane. However, the incidence of cardiovascular complications following anesthesia was not statistically different between the two anesthesia groups. In addition, most of the patients with DFK showed a rapid awaking time with relatively good postoperative cardiovascular stability. These findings suggest that total intravenous anesthesia with DFK is accompanied with minimal hemodynamic changes during and after open heart surgery.


[The effect of preoperative oral administration of ranitidine on pH and volume of gastric juice]. The effect of ranitidine, administrated 2 or 4 hours prior to induction of anesthesia, on volume and pH of gastric juice was investigated in patients undergoing elective surgery. Three-hundred mg of ranitidine was administrated orally in 54 patients 2 hours prior to anesthesia and in 50 patients 4 hours prior to anesthesia. The volume and pH of gastric juice were measured immediately after induction of anesthesia. In more than 90% of patients of both groups, volume of gastric juice was smaller than 25 ml and its pH was more than 2.5. Ranitidine 450 mg was administrated orally in 7 patients, and its plasma concentration was measured 2, 4 and 6 hours after administration. In one patient, volume of gastric juice was larger than 25 ml and its pH was less than 2.5. Ranitidine concentration in this patient was below the effective level 2 hours after administration and it was above the level after 4 hours. We concluded that oral administration of ranitidine 300 mg, 4 hours preoperatively, could be more effective to prevent aspiration pneumonitis than when it is given 2 hours preoperatively.


[A case of coronary spasm during the operation for lung cancer]. We reported a case of coronary spasm during the operation for lung cancer. A 72-year-old man underwent left upper lobectomy for lung cancer under general anesthesia with the aid of thoracic epidural anesthesia. Preoperative examinations did not reveal any clinical problems in the past. Hypotension and premature ventricular beats were observed for several times during operation due to the compression of the heart and left pulmonary artery by the surgeon's hands in stopping brisk bleeding. After this event, ST-segment of ECG was elevated abruptly. Intravenous administration of nitroglycerin was effective to relieve the coronary spasm in this case. Possible triggering factors were mechanical injury of the coronary artery due to compression of the heart, vagal stimuli under thoracic epidural anesthesia and alpha-stimulating drugs to treat hypotension. The importance of preoperative evaluation of coronary lesions, perioperative treatments with nitrates and calcium-channel blockers, and avoidance of intraoperative triggering factors are emphasized to prevent the coronary spasm.


[Compression of the graft during the corrective surgery for scoliosis in a patient who has undergone a Rastelli's operation: a case study]. A 14 year-old male who had undergone Rastelli's operation for the tetralogy of Fallot had general anesthesia for the corrective spinal instrumentation and posterior fusion. The patient also suffered from the complication of Klippel-Feil syndrome. During the operation, right ventricular pressure gradually increased from 34 mmHg to 60 mmHg and systolic blood pressure decreased from 110 mg to 80 mmHg when the maneuver to correct spinal deformity was done. The hemodynamics returned to its former level after the maneuver was resumed. This change was presumably attributed to the fact that the external conduit was compressed by the sternum and vertebral bodies. In order to prevent this hazardous incidence, it is crucial to understand both the three-dimensional configuration of the thoracic structure and the influence of spinal correction on it. In the prone positioned patients with scoliosis, especially lordoscoliosis, compression or dysfunction of the artificial valve might occur and we have to be aware of the possibility of the compression during general anesthesia and after corrective surgery.


[A case of tracheobronchopathia osteoplastica discovered after difficulty in intubation]. A 77-year-old man was scheduled for Love's method to correct lumbar disc herniation. He had fracture of maxilla and mandibula during World War II. Physical examination and laboratory data revealed no abnormalities. Anesthesia was induced with oxygen, nitrous oxide and halothane. Following administration of succinylcholine, an attempt was made to insert a tracheal tube (from 8.5mm to 5.5mm), but the tubes were met with an obstruction. The operation was cancelled because tumor-like nodules were seen in the trachea. Diagnosis of tracheobronchopathia osteoplastica was made afterwards following biopsy. The patient with this disease has a good prognosis. Artificial ventilation can be performed safely by choosing an appropriate method for airway maintenance.


[A case of pulmonary embolism after abdominal surgery]. A 67-yr-old man who suffered from pulmonary embolism following abdominal surgery was reported. The patient received left hemicolectomy and cholecystectomy for cancer of descending colon and cholecystolithiasis, respectively. Anesthesia was maintained with enflurane 0.6-1.0% and pancuronium combined with epidural analgesia. The anesthetic course was uneventful. But after leaving operating room the patient showed severe hypoxemia without abnormal shadow on chest X-P and other abnormal laboratory values. The cause of hypoxemia was unclear, but on the fourth postoperative day pulmonary scintigrams revealed pulmonary embolism. Then 12000 units.day-1 of heparin infusion was started. After 10 days of anticoagulant therapy, the hypoxemia improved and he was discharged on 28th postoperative day. Although pulmonary embolism is a rare disorder, we have to take it into consideration as one of the causes of postoperative hypoxemia.


[Two cases of diffuse pulmonary lymphangiomyomatosis]. We cared 2 patients with diffuse pulmonary lymphangiomyomatosis (LAM) through the perioperative period. LAM is a disease of uncertain origin and poor prognosis because of respiratory failure. Therefore, it is important to provide not only a good anesthetic care but also a good preoperative respiratory care. In the first case (a 35-yr-old woman), an open lung biopsy was performed after dyspnea and sputum had disappeared with preoperative medications of a bronchodilator and some antibiotics. In the second case (a 35-yr-old woman), oophorectomy was performed after FEV1.0% had remarkably increased with preoperative medication of a bronchodilator. Both patients did well through the perioperative period without any trouble or complications, such as pneumonia or severe hypoxemia, presumably owing to our perioperative management system.


[Intrathecal morphine for postoperative pain relief after transvaginal hysterectomy]. We studied the effect of a low-dose intrathecal morphine (0.1 or 0.2 mg) in postoperative pain relief and the incidence of side effects. Two hundred and fifteen patients scheduled for transvaginal hysterectomy were divided into 3 groups according to intrathecal morphine doses: M1 (morphine 0.1 mg N = 75), M2 (morphine 0.2 mg N = 69) and C (control N = 71). A standard mid-line lumbar puncture was performed using a 25-gauze needle in the L3/4 interspace. Preservative-free morphine hydrochloride mixed in hyperbaric tetracaine solution was administered intrathecally. Pain relief was significantly greater for the first 24 hrs in groups M1 and M2 compared with group C. Respiratory depression was not seen in any groups. The incidence of vomiting was about 40% in all groups. We conclude that intrathecal morphine 0.1-0.2 mg is useful for pain relief after transvaginal hysterectomy and accompanies no major side effects.


[Clinical evaluation of sulbactam/cefoperazone for severe infections associated with hematological disorders]. The combination therapy of sulbactam/cefoperazone (SBT/CPZ) and piperacillin (PIPC) was evaluated in 49 patients with severe infections associated with hematological disorders. Clinical responses in 43 evaluable patients out of the 49 patients were excellent in 12, good in 18, thus, overall efficacy rate was 69.8% (excellent plus good). Efficacy rates of this combination therapy were 60% (3/5) for sepsis, 75% (21/28) for suspected sepsis, and 50% (4/8) for pneumonia. The efficacy rate was 71.4% (10/14) in patients with neutrophil counts less than 200/microliters; this combination therapy was highly effective even in the neutropenic patients. Transient increases in hepatic function test values were observed in 2 patients, but no other side effects were observed during the combination therapy. From these observations it appears that the combination therapy of SBT/CPZ and PIPC is a very useful empiric therapy for severe infections associated with hematological diseases.


[A randomized controlled study on imipenem/cilastatin sodium in comparison to aztreonam + lincomycin in treating severe infections in patients with malignant tumors or hematological diseases]. A randomized controlled study was conducted to compare effects of imipenem (IPM) (1.0-1.5 g/day) with those of aztreonam (AZT) (4 g/day) +lincomycin (LCM) (1,200-2,400 mg/day) in patients with malignant tumors or hematological diseases and severe infections. A total of 95 patients entered the study between October 1989 and March 1991. Forty-seven patients were treated with IPM and the remaining 48 patients were given AZT+LCM. No statistically significant differences existed in age, sex or underlying diseases between the 2 groups. Overall, the clinical cure rate of the IPM group was 53%; This was significantly higher than the 31% cure rate obtained in the AZT+LCM group (P less than 0.05). The difference was significant in patients whose granulocyte counts were less than 1,000/microliters, but not in those whose granulocyte counts were 1,000/microliters or higher. Side effects were observed in 5 patients given IPM and one given AZT+LCM. In conclusion, no significant differences appeared to exist regarding clinical efficacy and safety between the 2 treatment regimens.


[Clinical evaluation of imipenem/cilastatin sodium against infections in compromised children (malignancy, hematological disease, collagen disease)]. Eighteen immuno-compromised children (malignancies, hematological diseases, collagen diseases) with neutropenia and infections were treated with imipenem/cilastatin sodium (IPM/CS), and the efficacy and the safety of the drug were evaluated. 1. Responses to IPM/CS were excellent in 13 patients, good in 1, and fair in 4. None of the patients displayed a poor response to the treatment thus the efficacy rate was 77.8%. 2. Of 5 patients with sepsis, 4 had excellent or good responses. IPM/CS was effective against sepsis caused by Enterococcus faecalis and Pseudomonas aeruginosa. 3. In patients with severe neutropenia (WBC less than 100/mm3), the efficacy rate was 70%. 4. As for side effects, elevations of GOT and GPT were observed in 1 patient with liver cirrhosis. These results indicate that IPM/CS is safe and effective in immuno-compromised children with neutropenia and infections.


[Clinical studies on imipenem/cilastatin sodium in the early therapy of preterm premature rupture of the membrane or threatened abortion and premature delivery]. The efficacy and safety of early therapy with imipenem/cilastatin sodium (IPM/CS) were studied in patients who had chorioamnionitis with preterm PROM or threatened abortion and premature delivery. The following results were obtained. 1. The clinical efficacy of IPM/CS administered by intravenous drip infusion at daily dosages of 1 to 2 g as concurrent treatment with antiuteronics (ritodrine hydrochloride or terbutaline sulfate) was studied in patients with threatened abortion and premature delivery in the 11th to 34th week of pregnancy (n = 9), or premature PROM in the 23rd to 36th week (n = 9). 2. Response to IPM/CS were good in all of the patients with threatened abortion and premature delivery. Latent periods were prolonged for more than 7 days in 44.4% (4/9) of the patients with preterm PROM. 3. Changes in elastase appeared to be significant as those in CRP for inflammatory markers. 4. These findings combined with our previous results indicate that treatment of preterm PROM before the 32nd of pregnancy prolongs the latent period.


[Clinical studies on imipenem/cilastatin sodium in the field of obstetrics and gynecology]. The efficacy and safety of imipenem/cilastatin sodium (IPM/CS) were studied in patients with obstetric and gynecologic infections and in those given the drug as prophylaxis against postoperative infections. The following results were obtained: 1. Efficacy rates were 96.0% (48/50) in patients with obstetric and gynecologic infections and 100% (28/28) in those with urinary tract or other infections. The overall efficacy rate was 97.4% (76/78). Bacteriologically, 30 organisms were isolated from 28 patients. The eradication rate was 95.2% (20/21) and the efficacy rate was 96.4% (27/28). 2. Changes in blood elastase before and after treatment were compared with those in CRP, WBC, and ESR in the patients with obstetric and gynecologic infections. The changes in elastase were similar to those in CRP. 3. The efficacy rate was 98.0% (48/49) in the patients given prophylaxis against postoperative obstetric and gynecologic infections. 4. An adverse reaction was observed in only one patient (diarrhea), and abnormal laboratory findings were noted in 2 patients (elevation of GOT and GPT). These results indicate that IPM/CS is very useful for the treatment of obstetric and gynecologic infections.


[A clinical study of transfer of cefminox and piperacillin into pulmonary tissue]. Serum concentrations of cefminox (CMNX) and piperacillin (PIPC) and their transfer into pulmonary tissue during surgery were serially studied following 1-hour intravenous instillation of 1 g of CMNX or PIPC immediately before thoracotomy, and the following results were obtained. Maximum serum concentrations of CMNX and PIPC were observed 1 hour after the commencement of administration, and their levels gradually decreased thereafter. The mean peak level of CMNX was 72.21 micrograms/ml, and T 1/2 was 1.62 hours. The mean peak level of PIPC was 43.26 micrograms/ml, and T 1/2 was 1.54 hours. In the pulmonary tissue, mean concentrations of CMNX in the normal pulmonary (alveolar) tissue were 28.80, 26.50 and 17.80 micrograms/g at 2.5, 3 and 4 hours, respectively, after the commencement of administration, and the corresponding levels for bronchiolar tissue were 19.6, 18.40 and 20.53 micrograms/g, respectively. The mean concentrations of PIPC in the normal pulmonary (alveolar) tissue were 18.97, 7.34 and 5.0 micrograms/g at 2, 3 and 4 hours, respectively, after the commencement of administration, and the corresponding levels for bronchiolar tissue were 7.2, 9.20 and less than 0.2 micrograms/g, respectively. PIPC also showed favorable transfer into the hilar lymph node tissue and obstructive pneumonitic lesions. The transfer of both drugs into pulmonary tissue suggests that both drugs are useful for the treatment of respiratory infectious diseases and the prevention of postoperative infections.


[Therapeutic effects of a combination treatment with flomoxef and tobramycin against infections complicated with hematological disorders]. The efficacy and safety of a combination regimen using flomoxef (FMOX) and tobramycin (TOB) were evaluated in the treatment of infections complicated with hematological disorders. The primary diseases in 40 patients included acute leukemia, malignant lymphoma and others. Complicated infections included 35 cases with suspected septicemia, 4 cases with septicemia and 1 case with pleuritis. Clinical responses were excellent in 10 (25.0%), good in 14 (35.0%), fair in 2 (5.0%) and poor in 14 (35.0%). The efficacy rate was 73.1% in patients with neutrophil counts higher than 501/microliters after administration, but it was 35.7% in patients with counts less than 501/microliters; the difference was statistically significant. No side effects were observed in any of the 40 patients. Abnormal laboratory data in liver functions were identified in 1 patient (2.5%). Degree of this abnormality was very slight, and the continuation of treatment was not disturbed. In conclusion, this combination therapy of FMOX and TOB thus appears to be useful and safe in therapies for infections complicated with hematological disorders.


[Clinical evaluation of flucytosine in patients with urinary fungal infections]. The clinical effectiveness of flucytosine (5-FC) was evaluated in 52 patients with urinary fungal infections which were diagnosed because of the presence of both funguria (greater than or equal to 10(4) cfu/ml) and pyuria (greater than or equal to 5 WBC/hpf). The patients received oral daily doses of 5-FC ranging 20 to 150 mg/kg, with a mean treatment duration of 11 days. The 57 fungus strains isolated from urine specimens consisted of 51 Candida spp. including 28 Candida albicans, 10 Candida glabrata, 4 Candida tropicalis and 6 Trichosporon beigelii. Forty-seven (92.2%) and 4 (66.7%) of the 51 Candida spp. and 6 T. beigelii strains isolated were eradicated by the treatment, respectively, giving an overall eradication rate of 89.5%. Clinical responses in 32 patients, from whom only fungi were submitted, were excellent in 5, moderate in 22, and poor in 5, thus the overall efficacy rate was 84.4%, based on the criteria of Japanese UTI Committee. Of the 18 strains of Candida spp. tested, 5-FC showed 0.20 micrograms/ml or less of the minimum inhibitory concentrations (MICs) against 16 strains and higher than 100 micrograms/ml against the remaining 2 strains. The MICs of the 5 T. beigelii strains tested were between 3.12 and 6.25 micrograms/ml. As adverse reactions, only 2 patients (3.8%) experienced diarrhea but did not require treatment cessation. These results suggest that flucytosine is an effective drug for urinary fungal infections.


Comparisons of the bacterial flora in genital regions at non-pregnancy. In the development of infectious diseases at non-pregnancy and at pregnancy, correlations between bacterial flora in the vagina and portio vaginalis and the ascending infections of those bacteria have recently been discussed. To clarify the cause of those infectious diseases, we studied the localization of microorganisms in genital regions. Patients undergone abdominal total hysterectomy (n = 172) were employed as subjects, and microorganisms isolated from 4 genital regions were studied. In addition, the preventive effect of cefmetazole (CMZ) against postoperative infections was analyzed in 479 cases including the hysterectomy cases mentioned above. The results obtained are summarized as follows: 1. The isolation rate of microorganisms at non-pregnancy, from subjects of 30 to 69 years old, was 65.6% (82/125) in the vagina and portio vaginalis, 52.1% (25/48) in the cervical mucus, 7.3% (9/124) in the uterine cavity and 0% (0/47) in the ovarian surface. 2. Numbers of microorganisms isolated in each region were 99 strains in the vagina and portio vaginalis, 28 in the cervical mucus, 10 in the uterine cavity and none in the ovarian surface. Isolation of aerobic Gram-positive bacteria (60-89.3%) and anaerobic Gram-positive bacteria (7.1-30%) were varied in each region. Lactobacillus spp. (38 strains), Staphylococcus epidermidis (20 strains) and Propionibacterium acnes (10 strains) were isolated from vagina and portio vaginalis, and Lactobacillus spp. (17 strains) were the most often isolated bacteria from the cervical mucus.(ABSTRACT TRUNCATED AT 250 WORDS)


[A new oral cephem, cefdinir: its structure-activity relationships and biological profile]. This article reviews structure-activity relationships and biological properties of a new oral cephem, cefidinir (CFDN). It also describes a hypothesis concerning the absorption mechanism from the intestine. Antibacterial activities and the oral absorption efficiencies were studied with regard to 3-vinyl cephalosporins with various 7-acyl side chains. From the study, 2-(2-aminothiazol-4-yl)-2-hydroxyiminoacetyl group was selected and various 3-substituents were screened. As a result, it was found that the vinyl compound, CFDN, showed excellent antibacterial activity and good oral absorption in rats. In vitro and in vivo antibacterial activities, the affinity for PBPs and the stability to beta-lactamases revealed that CFDN had well balanced antimicrobial activities against Gram-positive and Gram-negative bacteria and good biological properties. The pharmacokinetics of CFDN in healthy volunteers showed that serum concentration and half life were good enough to make CFDN an effective therapeutic agent. The mechanism of intestinal absorption of CFDN and related oral cephems are discussed and a hypothesis for molecular recognition by the carrier protein in the intestine is proposed.


[Study on the pharmacokinetics of cefepime (I)]. The pharmacokinetics of 14C-cefepime dihydrochloride (14C-CFPM), were studied in rats upon both single and repeated intravenous administration. 1. Blood level of radioactivity was 59.27 micrograms eq./ml at 5 minutes after single intravenous administration at a dose of 20 mg/kg, and declined biexponentially thereafter. The values of AUC and T 1/2 were 70.1 micrograms eq..hr/ml and 38.0 hours, respectively. 2. Blood level of radioactivity was 59.41 micrograms eq./ml at 5 minutes after administration on the 7th day of repeated intravenous administration at a daily dose of 20 mg/kg, and declined more slowly as compared to the case of single administration. The values of AUC and T 1/2 after repeated administration were 159.7 micrograms eq..hr/ml and 44.5 hours, respectively. 3. Urinary and fecal excretion rates after single administration were 93.3% and 3.3%, respectively. 4. Urinary and fecal excretion rates were almost constant throughout the repeated administration; 88.4-90.7% and 2.3-3.7%, respectively. 5. 14C-CFPM distributed rapidly to the whole body except to the central nervous system. Although the radioactivity was removed rapidly from tissues, high levels of radioactivity remained in the kidney and the spleen as compared to other tissues. 6. Tissue concentrations of radioactivity at 5 minutes after the final dose of repeated administration were about the same as those after single administration but they declined more slowly than those after single administration. High levels of radioactivity were found in the kidney and the spleen as were found upon single administration. The ratios of these levels between repeated and single dosing were 4.3 and 2.6 for kidney and spleen, respectively. 7. Data obtained with autoradiograms of the whole body were consistent with measured tissue distribution obtained in both cases of single and repeated administration.


[Study on the pharmacokinetics of cefepime (II)]. The pharmacokinetics of 14C-cefepime dihydrochloride (14C-CFPM), was studied in dogs after single intravenous administration at a dose of 20 mg/kg. Protein binding was also investigated both in vitro and in vivo. 1. Blood level of radioactivity was 83.53 microns eq./ml at 5 minutes after single intravenous administration and declined biexponentially thereafter. The values of AUC and T1/2 were 229 microns eq.(.)hr/ml and 90 hours, respectively. 2. Urinary and fecal excretion rates were 95.1% and 2.7%, respectively. 3. The in vitro protein binding at 1 to 100 microns/ml of drug concentration was 7.9 to 12.7% in rat, 12.4 to 18.6% in human, and 12.5 to 14.5% in dog. In vivo protein binding, which increased with time after administration, was 10.8 to 92.9% in rat and 17.5 to 64.9% in dog at 5 minutes to 6 hours.


Cross-resistance of clinical isolates of methicillin-resistant Staphylococcus aureus to aminoglycosides and fluoroquinolones. Susceptibilities of 117 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) to aminoglycosides and fluoroquinolones were investigated during 1987 and 1990. Gentamicin, tobramycin, sisomicin, micronomicin, and astromicin showed the bimodal antimicrobial activity pattern against MRSA, revealing cross-resistance to these antibiotics. However, amikacin, netilmicin, isepamicin and arbekacin (ABK) exhibited the monomodal antimicrobial activity pattern, suggesting the presence of less resistant strains. All 117 MRSA strains were susceptible to ABK with MICs less than 3 micrograms/ml. MRSA also showed the bimodal antimicrobial susceptibility pattern to fluoroquinolones such as ofloxacin (OFLX), ciprofloxacin (CPFX) and tosufloxacin (TFLX). Frequencies of TFLX susceptible MRSA isolates decreased progressively from 1987 to 1989 when this drug was not even in general clinical use. The cross-resistance of MRSA between TFLX and OFLX or CPFX persisted. Cross-resistance between aminoglycosides and fluoroquinolones, however, was less frequently observed.


[Combined effects of arbekacin with other antibiotics against methicillin-resistant Staphylococcus aureus. I. The combined effect of arbekacin with fosfomycin or clavulanic acid/ticarcillin]. As arbekacin (ABK) has a highly potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), its combined effects with fosfomycin (FOM) and clavulanic acid/ticarcillin (CVA/TIPC) against MRSA were examined. The obtained results are summarized as follows. 1. Against MRSA either combination, FOM+ABK or CVA/TIPC+ABK showed a strong antibacterial effect at the MIC or the sub MIC of ABK in the blood expected from clinical observations. The MIC of ABK by the combination use seemed to be equivalent to the MBC value. 2. Effective concentrations of antibiotics in these combinations appeared to be strongly dependent on the effective concentration of ABK and less dependent on that of FOM or CVA/TIPC. Therefore, the antibacterial activity of a combination seems to mostly depend on the antibacterial activity and the concentration of ABK. 3. As FOM and CVA/TIPC have antibacterial activities against Pseudomonas aeruginosa, combinations of ABK with these antibiotics are likely to be effective against double infection with P. aeruginosa in MRSA infected patients.


[Combined effects of arbekacin with other antibiotics against methicillin-resistant Staphylococcus aureus. II. The combined effect of arbekacin with imipenem or cefminox]. Combined antibacterial effects of imipenem (IPM)+arbekacin (ABK) and cefminox (CMNX)+ABK against methicillin-resistant Staphylococcus aureus (MRSA) were examined and the obtained results are summarized below. 1. Either combination, IPM+ABK or CMNX+ABK, showed a strong antibacterial effect against MRSA when blood concentration of ABK were sustained at MIC as could be expected in clinical situations. While at sub MICs of ABK the antibacterial effect of these combination was slightly less than those of the previously reported combinations of ABK and other antibiotics. 2. Antibacterial effects of the combinations against MRSA were strongly dependent on the concentration of ABK and less dependent on the concentration of IPM or CMNX. As were observed in the previously tested combinations of ABK with other antibiotics, the antibacterial effect of the combination appeared to be highly dependent on the antibacterial activity and the concentration of ABK. 3. As IPM has potent antibacterial activities against Gram-negative bacteria (GNB) including Pseudomonas aeruginosa while CMNX has potent antibacterial activities against GNB except P. aeruginosa, it is likely that the combinations of IPM+ABK or CMNX+ABK are useful for treatment of infections with MRSA together with GNB.


[Antimicrobial activities of major oral antibacterial agents against clinically isolated microbial strains from inpatients]. Antimicrobial activities were examined for major antibacterial agents against clinically isolated microbial strains which were isolated and identified from materials collected from inpatients with various infections in 1988, 1989 and 1990, and the following conclusions were obtained. 1. Among strains isolated each year, methicillin-resistant Staphylococcus aureus (MRSA) were found frequently. 2. CEPs-resistant Escherichia coli strains were observed among strains isolated each year. 3. Increasing tendencies in resistances of Citrobacter freundii, Enterobacter spp., Serratia marcescens to cephems and new quinolones were observed. 4. Increasing tendencies in resistances of Proteus vulgaris to ceftazidime (CAZ) and new quinolones appeared to exist. 5. Among strains isolated each year, resistances of Pseudomonas aeruginosa to CAZ and quinolones were observed in high rates, but also their resistances to imipenem appeared to increase. 6. Many of recently increasing multiple resistant bacteria seem to have different sites of drug action and/or to have non-hydrolytic modes of resistance.


[Antimicrobial activities of major oral antibacterial agents against clinically isolated microbial strains from outpatients with respiratory tract infection]. Minimum inhibitory concentrations (MICs) were determined for major oral antibacterial agents for clinically isolated microbial strains from materials collected from outpatients with respiratory tract infections in 1988, 1989 and 1990, and the following conclusions were obtained. 1. Methicillin-resistant Staphylococcus aureus (MRSA) appeared to be responsible for community-acquired respiratory tract infections, but there also was a tendency showing that MRSA increased year by year. 2. A tendency was observed indicating that benzylpenicillin (PCG)-insensitive Streptococcus pneumoniae (PISP) increased year by year. 3. Beta-lactamase-producing strains of Haemophilus influenzae were observed in a certain ratio, and also those of Branhamella catarrhalis were found in high ratios. 4. A tendency of increasing resistance of Klebsiella pneumoniae to new quinolones was observed. 5. It is of a great importance to evaluate methods of selecting primary choice antibiotic agents since increasing numbers of new oral antibacterial agents are becoming rapidly available.


[Antibacterial activities of sisomicin against fresh clinical isolates]. To investigate antibacterial activities of sisomicin (SISO), MICs of SISO as well as other aminoglycosides (AGs) were determined against many clinical isolates which were obtained in 1991. Results are summarized below: 1. No SISO-resistant strains were observed among isolates of Escherichia coli, Citrobacter diversus, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Proteus mirabilis and Morganella morganii. 2. In comparison with the results of our previous study against isolates obtained in 1986, the rate of methicillin-resistant Staphylococcus aureus (MRSA) was higher, and SISO-resistant strains were observed at a high rate among the MRSA. Also, SISO-resistant strains of Serratia marcescens increased. However, the rate of SISO-resistant strains of Pseudomonas aeruginosa decreased, and among Citrobacter freundii, Enterobacter cloacae and Proteus vulgaris, SISO-resistant strains did not increase over the years. 3. MICs of SISO against Providencia rettgeri and Providencia stuartii were high, suggesting that antibacterial activities of SISO was weak against genus Providencia. 4. For comparison, according to MICs of ofloxacin and imipenem, new quinolone-resistant strains were observed at a high rate among various organisms, and carbapenem-resistant strains were observed at a high rate among S. marcescens and P. aeruginosa. 5. SISO is still one of the useful AGs in the 1990's since it maintains its strong antibacterial activities against most clinical isolates obtained in recent years and its potential as a combination drug with beta-lactams is being reported.


[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). I. Susceptibility distribution]. Isolation frequencies and sensitivities to antibacterial and antibiotic agents were investigated on 801 bacterial strains isolated from patients with urinary tract infections in 9 hospitals during the period of June to November 1988. Of the above total bacterial population, Gram-positive bacteria accounted for 29.3% and a majority of them were Enterococcus spp. Gram-negative bacteria accounted for 70.7% and most of them were Escherichia coli. 1. Enterococcus faecalis: Vancomycin was most active with its MIC90 < or = 0.78 microgram/ml. Ampicillin, piperacillin, ofloxacin (OFLX), ciprofloxacin (CPFX) and imipenem (IPM) were also active. 2. Staphylococcus aureus: Arbekacin and minocycline were most active with their MIC90s 0.39 microgram/ml and 1.56 micrograms/ml, respectively. Among penicillins, dicloxacillin was the most active. Activities of cephems were considerably lower. 3. E. coli: Most of the agents were tested active. Particularly the second and third generation cephems were active in a range of < or = 0.10-0.20 microgram/ml. Carumonam (CRMN), IPM, OFLX and CPFX were also active with MIC90s < or = 0.10 microgram/ml. 4. Klebsiella pneumoniae CRMN and IPM were highly active. Penicillins generally showed lower activities. Cephems and new quinolones had high activities with their MIC90s in a range of 0.39-0.78 microgram/ml. 5. Proteus mirabilis: The third generation cephems were active with their MIC90s in a range of < or = 0.10-0.20 microgram/ml. CRMN, OFLX and CPFX were also active with their MIC90s < or = 0.10 microgram/ml, 0.39 microgram/ml and 0.20 microgram/ml, respectively. 6. Pseudomonas aeruginosa: IPM and tobramycin were active with their MIC90s 1.56 micrograms/ml and 3.13 micrograms/ml, respectively. CRMN and new quinolones showed MIC80s of 25-100 micrograms/ml. Most of penicillins and cephems were not active. 7. Other Gram-negative rods: Against Citrobacter freundii, Enterobacter cloacae and Serratia marcescens, IPM, CPFX and OFLX were active. Penicillins and cephems were not so active. CRMN was active against S. marcescens with its MIC80 at 6.25 micrograms/ml.


[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). II. Background of patients]. Clinical background was investigated on 916 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period from June to November, 1988. 1. Distribution of sexes, ages and infections: Among males, fifties and older were most frequent and most of them had complicated UTIs. Among females, most cases among twenties or thirties were uncomplicated UTIs. Forties and older cases were most frequent and complicated UTIs were more frequent among them than among patients in twenties and thirties. 2. Distribution of sexes, ages and pathogens isolated from UTIs: In males, Pseudomonas spp. and Enterococcus spp. were frequently isolated. In contrast, in females, Escherichia coli was the most frequent. In thirties, E. coli was not the most frequently isolated bacterium. Frequency of Pseudomonas spp., other non-fermented Gram-negative rods and Enterococcus spp. were greater among patients with higher ages. 3. Administration of antibiotics and pathogens isolated from UTIs: (1) Before administration: In uncomplicated UTIs, E. coli accounted for the majority of causative organisms. In complicated UTIs, particularly in those cases with indwelling catheter, Enterococcus spp. and Pseudomonas spp. were rather frequently isolated. (2) After administration: In complicated UTIs, higher number of pathogens were isolated. Pseudomonas spp. and Enterococcus spp. were the most frequent. Distribution of pathogens isolated from complicated UTIs without indwelling catheter was similar to that before antibiotic administration.


[Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). III. Secular changes in susceptibility]. Sensitivities to various antibacterial and antibiotic agents of strains of Escherichia coli, Klebsiella spp., Proteus spp., Citrobacter spp., Enterobacter spp., Serratia marcescens and Pseudomonas aeruginosa isolated from patients with urinary tract infections (UTIs) in 9 hospitals during June to November 1988 were compared with those in the same period of previous year according to a classification, uncomplicated UTIs, complicated UTIs without indwelling catheter, and complicated UTIs with indwelling catheter. No remarkable changes were found in sensitivities of E. coli, Proteus spp., Citrobacter spp. and S. marcescens. The sensitivity of Klebsiella spp. to cephems decreased in complicated UTI without indwelling catheter and increased in complicated UTI with indwelling catheter. The sensitivity of Enterobacter spp. to third generation cephems decreased in complicated UTI with indwelling catheter. Sensitivities of P. aeruginosa to aspoxicillin and cefsulodin increased. The number of resistant strains to new quinolones increased slightly.


[Phosphoenolpyruvate:hexose phosphotransferase systems in Lactobacillus species]. The substrate range of phosphoenolpyruvate:hexose phosphotransferase systems (hexose-PTSs) in Lactobacillus casei subsp. casei LAC3 and L. acidophilus LAC5 was examined. Strain LAC3 demonstrated PTS activities for glucose (Glc), mannose (Man), glucosamine (GcN), 2-deoxyglucose (2DG) and fructose (Fru), while strain LAC5 showed the activities only for Man and Fru. These activities were all constitutive. Growth of both strains was strongly inhibited by 2DG. 2DG-resistant mutants DG329 and DG504 were isolated, respectively, from strains LAC3 and LAC5. Mutant DG329 grown on Glc was defective in all the above-described activities observed with strain LAC3, whereas no defect in PTS activities was found in mutant DG504. Mutant DG329, however, showed some inducible activities for Man and Fru when grown on Man, Fru or Scr. These results strongly suggest that strain LAC3 has inducible PTS(s) specific for Man and/or Fru besides the well-known, broadly specific, constitutive Man-PTS, and also that strain LAC5 lacks the Man-PTS, but has other constitutive PTS(s) specific for Man and/or Fru. L. fermentum LAC12 had the Man-PTS as reported previously (Nagasaki et al., 1992), but had no inducible activities like those found in strain LAC3.


[Effect of pH on preferential antibacterial-activity of ethylenediaminetetraacetic acid (EDTA)]. Ethylenediaminetetraacetic acid (EDTA), a chelating agent, was examined for the antibacterial activity against 15 species of bacteria by treating with a 10mM solution at pH adjusted to 5.0, 7.0 or 9.0. All bacterial species tested were classified into three groups; tentatively named the pH5 EDTA-sensitive group comprising Vibrio cholerae and Staphylococcus aureus, the pH9 EDTA-sensitive group comprising Escherichia coli and Pseudomonas aeruginosa and the EDTA-nonsensitive group comprising Proteus mirabilis. The EDTA-sensitivity grouping may be used as a tool for preferential decontamination of certain bacteria in live edible fishes, although further experiments are needed to characterize more strains and also species of bacteria.


[Clinicopathological study of 6 cases of mantle zone lymphoma]. Clinicopathological analyses of 6 cases of mantle zone lymphoma (MZL) were carried out. The median age of the patients was 62 years with a range of 41 to 71 years and the male-to-female ratio was 1:1. Superficial lymph node (LN) swelling was present only in 2 patients. Giant LN swellings of the mesenteric or inguinal regions were present in 4, and bone marrow involvement by lymphoma cells in 5. Serum protein electrophoresis revealed a monoclonal protein of IgM kappa type in 2 patients. One of these also had polyclonal hypergammaglobulinemia. An immunohistochemical study of 6 patients revealed LN-1-(-)+, LN-2+(-)++, sIgM+, sIgD+, CALLA +/-(-)+, DRC-1+(-)++. The immunohistochemical features of the cases were similar to those of small lymphocytic lymphoma or follicular lymphoma. Only 1 patients out of 6 achieved complete remission. Two patients died, one of pneumonia after chemotherapy and the other of cancer. The others were alive 4 to 100 months after the diagnoses. Although giant LN swelling and bone marrow involvement of lymphoma cells which were refractory to treatments were frequently observed, we consider MZL to be a slowly progressive and low-grade type of non-Hodgkin's lymphoma.


[Interferon therapy of idiopathic thrombocytopenic purpura]. The authors evaluated the efficacy of a daily administration of recombinant human alpha 2a interferon (IFN), given at a dose of 300MU for 12 consecutive days, in patients with steroid-nonresponsive or -dependent idiopathic thrombocytopenic purpura (ITP). Nine patients received courses of IFN therapy. Mean platelet counts rose from 1.39 to 10.9 x 10(4)/microliters and PAIgG decreased from 151.7 to 59.7 ng/10(7) cells. The maximum rise in platelet counts occurred from 10 to 42 days (mean 19.1) after the initiation of IFN. Complete response (CR) was achieved in 3 of 13 courses (23.1%), and partial response (PR) in 8 (61.5%). One CR case continued for longer than 20 months without further treatment, but intermittent IFN therapy was necessary for the other. The increment of the platelet counts was transient in all of the partial responders. No severe side effect requiring interruption of the course of IFN was experienced. Both serum IgG and PAIgG significantly correlated with the increment of platelet counts, therefore the mechanism of IFN on ITP was presumed to be associated with the inhibition of autoantibody production. Daily administration of IFN appears to be an effective and safe treatment protocol for refractory ITP.


[Differential diagnosis and course of patients with pure erythrocytosis and spurious polycythemia]. We established the diagnostic criteria of pure erythrocytosis (PE) and spurious polycythemia (SP), and investigated the different points between 4 PE patients and 4 SP patients who had clinical course longer than 5 years from diagnosis. The red cell mass (RCM) was greater in PE patients than in SP patients, but the difference was not significant. However, the actual measurement of RCM was significantly greater in PE than their predicted values (p less than 0.01), and was not significant in SP. Such laboratory data as red cell counts, Hb, Hct, reticulocyte counts, M/E ratio of bone marrow pictures, the positive rate and score of NAP, and bone marrow CFU-E numbers were not significantly different in the two groups, and serum EPO levels in patients with PE were significantly lower than those in patients with SP (p less than 0.01). When in hospital, the Hct levels of patients of both groups decreased linearly. Sustained erythrocytosis was found in two patients with PE and one patient with SP. Vascular complications in patients of both groups have not been observed. There was no essential difference between the two groups. Therefore, it is suggested that PE patients without endogenous erythroid colonies may follow almost the same clinical course as SP patients.


[Measurement of busulfan concentration in plasma and spinal fluid from transplant patients pretreated with busulfan and cyclophosphamide]. Busulfan (BU) concentrations in the blood and spinal fluid of 7 patients pretreated with BU for bone marrow transplantation (BMT) were measured using gas chromatography. The data from these periodically obtained samples were used to study the relationship between the BU concentration and complications (e.g. vomiting), indicating that vomiting leads to a lower maximum BU level. The trough level of BU concentration at 6 hours after administration was stable at around 500 ng/ml, not showing little effect of vomiting. The BU concentrations in the spinal fluid were virtually the same as those in plasma collected at the same time and the spinal fluid/plasma ratio of the BU concentration averaged 1.06. No veno-occlusive disease (VOD) was noted. Failure of engraftment occurred in one case of myelofibrosis, however, as the plasma BU concentration in this case was not lower than the others, the graft failure was not considered to be due to the preconditioning regimen including BU.


[Cold agglutinin hemolytic anemia complicating mycoplasma pneumonia]. A case of Mycoplasma pneumonia complicated with severe hemolytic anemia, which occurred as a result of a high titer of cold agglutinin is presented. A 49 year-old male was admitted because of fever, jaundice and dyspnea. Chest x-ray showed diffuse small nodular infiltrates throughout both lung fields. Laboratory studies disclosed the following values: Hb 4.6 g/dl, Ht 13.9%, reticulocyte 11.5%, direct and indirect Coombs' test positive, haptoglobin 38 mg/dl, ESR 145 mm/hr, cold agglutinin titer 1:2,048 mycoplasma antibody titer 1:640, PPD negative. The diagnosis of autoimmune hemolytic anemia associated with Mycoplasma pneumonia was made, and treatment with minocycline and prednisolone observed striking clinical improvement. It was suggested that the cold exposure was possibly a major factor in the pathogenesis of hemolysis in this patient.


[A case of monoblastic crisis of CML beginning with extramedullary tumor formation in a rib]. A patient with CML showed monoblastic crisis which started with extramedullary tumor formation in a rib before medullary involvement. She was diagnosed as having CML in 1984 at the age of 57. In February 1990, she was admitted to Furukawa City Hospital because of extramedullary blastic crisis beginning at the right 5th rib. At that time, the bone marrow revealed 4.6% blasts. On March 5, after one course of chemotherapy, she was transferred to our hospital for radiotherapy. Hematological findings were WBC 10,100/microliter with 10% blasts, Hb 10.9 g/dl, platelet 3.7 x 10(4)/microliters. Bone marrow aspiration was unsuccessful. The blasts in the peripheral blood were negative for peroxidase and chloroacetate esterase; but positive for naphtylbutyrate esterase. The leukemic cells were positive for CD13, CD33, and had phagocytic activity. Chromosomal analysis revealed 46XX with Ph1 chromosome and some additional anomalies. Southern blot analysis of tumor cells shows BCR rearrangement. These findings suggest that the blasts were immature monocytic cells, and we conclude that this is a rare case of extramedullary monoblastic crisis of CML.


[Changes in bone marrow MRI patterns in aplastic anemia before and after successful treatment with ATG]. In order to evaluate the usefulness of MRI in estimating bone marrow cellularity, we performed MRI of the lumbar spine in two patients with severe aplastic anemia, before and after successful treatment with antithymocyte globulin (ATG). Case 1, a 25-year-old man with idiopathic aplastic anemia, was treated with ATG 6 months after the onset. One month after treatment, his peripheral blood count and bone marrow cellularity recovered, and the MRI bone marrow pattern became normal. Case 2, a 78-year-old woman with drug-induced aplastic anemia, was treated with ATG 4 months after the onset. Three months after treatment, her peripheral blood count improved. Five months after treatment, her bone marrow cellularity recovered and the MRI bone marrow pattern was normal for her age. Seven months after treatment, when her peripheral blood count was almost normal, we observed hypercellular bone marrow restoration at the periphery of the vertebrae. MRI seems to be an effective method of evaluating bone marrow recovery in aplastic anemia.


[A case of T-cell prolymphocytic leukemia]. A 54-year-old man who had been known to have a high prolymphocyte count for four years was admitted to our hospital because of dyspnea in September, 1990. Physical examination revealed skin eruption, lymphadenopathy and hepatosplenomegaly. Chest X-ray demonstrated bilateral pleural effusions. The leukocyte count was 232,900/microliter with 99% lymphoid cells possessing single nucleoli. The cells expressed the phenotype CD2+, CD3-, CD4+, CD7+, and CD8-. Southern blot analysis of DNA from these cells revealed monoclonal rearrangement of T-cell receptor beta-chain genes. Anti-human T-cell lymphotropic virus type 1 (HTLV-1) antibody and HTLV-1 proviral DNA were not detected. A biopsy specimen from the skin lesions showed infiltration of the leukemic cells which were positive for anti-MT1 antibody. Histological finding of the axillary lymph node was malignant lymphoma, diffuse, medium-sized, T-cell type. Combination chemotherapy resulted in the improvement of skin eruption, lymphadenopathy, hepatosplenomegaly and pleural effusions, although his prolymphocyte count increased to 910,000/microliters. He died of cerebral bleeding in July, 1991. We diagnosed this case as T-cell prolymphocytic leukemia, observed for five years.


[Norfloxacin-induced infectious mononucleosis (IM)-like syndrome with Stevens-Johnson syndrome]. A 77-year-old male who had suffered from an upper respiratory infection and had been given Norfloxacin (NFLX) on May 2, 1990, developed generalized erythema which did not subside with prednisolone. He was hospitalized on May 8, and Stevens-Johnson syndrome was diagnosed. The WBC was 115,400/microliter (Ly 61.0%, Aty Ly 39.5%). Sternal tap revealed hypercellular marrow with increased lymphocytes (48.5%; Aty Ly 24.5%) and eosinophils (7.0%). Clinical chemistry revealed slightly abnormal liver and renal function with LDH (1,745 IU/l) and IgE (803 IU/ml) elevation. No pathognomonic result was obtained with several viral antibodies. CD4+, CD8+ lymphocytes and the 4/8 ratio were 39%, 43% and 0.9, respectively. Clinical and laboratory abnormalities were normalized within 3 weeks after the discontinuance of all drugs. Positive lymphocyte stimulation test results were obtained by NFLX. While drug allergy is known to be a cause of IM-like syndrome, there are few reports regarding the subset characterization of the increased T lymphocytes. In this case, T lymphocytosis was remarkable, but the 4/8 ratio declined only slightly, indicating that CD4+ as well as C8+ cells were activated and increased, unlike IM. The record of this case helps to clarify the mechanisms of the lymphocyte activation shared and not shared by EBV-induced IM and IM-like syndrome.


[Malignant lymphoma occurring subsequent to autoimmune disease]. The authors report six cases of non-Hodgkin's lymphoma (NHL) (3B-cell type, one T-cell type, one non-T non-B cell type, one unclassified type) occurring subsequently to autoimmune diseases. The patients were females aged 43 to 70 (median 61). Rheumatoid arthritis was most frequent as the preceding autoimmune disease, and the intervals from the onset of an autoimmune disease to that of NHL were 10 to 36 years (median 20). Polyclonal hypergammaglobulinemia was seen in 4 cases, lymphocytopenia in 3 cases, and conversion to negative PPD reaction in 2 cases. Only one patient had been given corticosteroids, and immunosuppressive agents may not contribute much to the development of lymphoma in patients with autoimmune diseases.


[Chronic lymphocytic leukemia diagnosed after corticosteroid therapy for Evans syndrome]. A 59-year-old woman was admitted in February 1991, because of abdominal distension. On admission, she had splenomegaly, autoimmune hemolytic anemia, and idiopathic thrombocytopenic purpura. Evans syndrome had been diagnosed and daily prednisolone therapy had been performed. After this therapy, a rapid increase of lymphocytes was observed accompanied with contraction of spleen. The monoclonal proliferation of B-lymphocytes and rearrangement of JH and J kappa gene were detected and chronic lymphocytic leukemia was diagnosed. With reduction of prednisolone, the lymphocyte counts decreased and the size of the spleen returned to the previous state. It is suspected that the cause of rapid lymphocytosis in this case was due to the redistribution of lymphocytes from the spleen to the peripheral blood.


[Interleukin-6 in hematological diseases with septic shock]. The authors measured the level of interleukin-6 (IL-6), endotoxin and CRP from 7 patients of documented sepsis with hematological disorders. IL-6 was higher in patients who developed septic shock, compared with patients who had only sepsis. These data revealed the importance in the level of IL-6, rather than endotoxin and CRP, in managing the patients with septic shock.


[Malignant lymphoma with subdural effusion]. A 64-year-old woman was admitted for treatment of malignant lymphoma involving the pharynx and abdomen. Lymphoma disappeared after chemotherapy and radiotherapy, but she had central nervous system symptoms; euphorism, left facial nerve palsy, right hemiplesia, and disturbance of micturition. Magnetic resonance imaging (MRI) revealed a diffuse dural thickening and a subdural fluid retention. The subdural fluid was determined to be an exudate, and a biopsy of the dura mater revealed a normal dura and a fibrin clot containing lymphoma cells and neutrophils. MRI can be very useful to detect the meningeal involvement of malignant lymphoma.


[Autoimmune hemolytic anemia induced by alpha-interferon therapy in a case of IgG-kappa type multiple myeloma]. A 47-year-old male case of IgG-kappa type multiple myeloma was treated with VMCP and recombinant human alpha-interferon (IFN-alpha 2a). The direct Coombs test was positive before treatment. Hemolytic anemia associated with massive hematuria was observed during the administration of 9 million IU IFN-alpha 2a per day for 2 weeks. The hemolytic symptoms rapidly improved after withdrawal of IFN-alpha 2a. This clinical course suggests that IFN-alpha as an immunomodulator was responsible for the progression of autoimmune hemolytic anemia in a case of multiple myeloma.


[A case of primary malignant lymphoma of the uterine body]. A 70-year-old female was found to have class V cytology on an endometrial smear, and a histological diagnosis of malignant lymphoma was made by endometrial biopsy. The pathological diagnosis was malignant lymphoma, diffuse large cell-type according to the Working Formulation classification. Immunohistochemical staining showed lymphoma cells to be positive for CD 20 (B 1), indicating B cell lineage. Two cervical lymph nodes were palpable, and swelling of a para-aortic lymph node was also found by abdominal CT scan. The clinical stage was determined to be III according to the Ann Arbor classification. After three courses of CHOP chemotherapy, lymphoma cells could no longer be detected by endometrial biopsy, and the para-aortic and cervical lymphadenopathy also disappeared. Primary malignant lymphoma of the uterus, especially of the uterine body, is very rare. Only eight cases of primary malignant lymphoma of the uterine body were reported in the literature. The cell lineage was decided in only one case, which was B cell type.


[Analysis of adhesive proteins on the surface of platelets from the patients with lung cancer: studies in histological type and clinical stage]. Flow cytometry was used to detect platelet-associated fibrinogen (PA-Fbg), platelet-associated fibronectin (PA-FN) and platelet-associated thrombospondin (PA-TSP) on the surface membrane of platelets and plasma (P)-TSP in 30 patients with lung cancer (16 case of adenocarcinoma and 14 of squamous cell carcinoma). ELISA was used to analyze beta-TG and PF4. In the lung cancer group, beta-TG and PF4 were higher than those of a normal control group. PA-Fbg values were correlated with beta-TG and PF4 values. Each adhesive protein had a higher value in the patient than in the normal control group, and the degree of the increase was related to the progression of clinical disease stage. In the squamous cell carcinoma group, the P-TSP value was significantly elevated. Platelet size increased as the clinical stage of the disease progressed. These results suggest the following: 1. An increase in PA-Fbg can indicate the presence of activated platelets. 2. In patients with lung cancer, activated platelets appear in the blood, and their numbers increase as the clinical stage of the disease progresses. 3. Differences in histologic type led to differences in binding adhesive protein.


[Renal and electrolyte disturbances in chronic myelogenous leukemia]. Renal and electrolyte disturbances in 91 patients with chronic myelogenous leukemia (CML) were analyzed over a period of these twenty years. At diagnosis, renal and electrolytes were studied in 72 patients including 65 in chronic cases, 5 in accelerated phase and 2 in blastic crisis. There were 8 cases of hypocalcemia among 62 patients and 5 cases of hyperphosphatemia among 48 patients. The cases of hyperphosphatemia and renal dysfunction had short median survival. There were no significant differences of renal and electrolyte disturbances between before and after chemotherapy. Various electrolyte disturbances, that is, hyponatremia, hypo-, hyperkalemia, hypocalcemia, hypo-, hyperphosphatemia, were found in the blastic crisis of CML. In the last admission, renal dysfunction and various electrolyte disturbances were present in almost half of the cases. Pathological studies were performed in 18 autopsy cases. Acute tubular insufficiency or necrosis, hypercalcemic nephropathy, and renal infiltration of leukemic cells were recognized in patients who had renal dysfunction.


[Studies of human bone marrow stromal cells--effects of antimetabolites on the growing dynamics of human bone marrow cells and their support of hemopoietic cells]. The effects of antimetabolites on the growing dynamics of human bone marrow stromal cells and their support of hemopoietic cells were tested by using a modified version of Dexter's culture system. Cytosine arabinoside (ara-C) was found to suppress neither the growing dynamics nor the supportability. On the other hand, methotrexate (MTX) suppressed the supportiveness, even though it hardly suppressed the growing dynamics. The recognition of injury to marrow cells could be of potential importance in cancer chemotherapy. Our in vitro evidence may provide clinical insights for cancer chemotherapy including prolonged marrow suppression or pretreatment of bone marrow transplantation.


[Clinical significance of serum erythropoietin levels in patients with multiple myeloma]. Serum erythropoietin (Epo) levels were measured in 53 patients with multiple myeloma (MM), 49 normal subjects and 53 patients with some hematological diseases including aplastic anemia (AA), iron deficiency anemia, etc. to study the significance of erythropoietin in anemia of MM. The serum Epo level was 72.0 +/- 94.4 mIU/ml (mean +/- SD) in MM patients, which was significantly higher than in normal subjects (24.1 +/- 6.1 mIU/ml), but lower than in AA patients (7069.9 +/- 9406 mIU/ml). A significant inverse correlation was found between the hemoglobin (Hb) levels and the logarithmic values of serum Epo levels (r = -0.543, p < 0.05) in MM patients. This inverse correlation was stronger (r = -0.636, p < 0.05) in MM patients without renal dysfunction than in whole MM patients, while no correlation was observed in MM patients with renal dysfunction. These results indicate that MM patients with renal dysfunction have a low ability to synthesize Epo and that the supplemental therapy of recombinant Epo is effective to improve their anemia. In addition, the circadian rhythm of serum Epo level was lower in the morning than in the afternoon in both MM patients and normal controls. Serum Epo levels after chemotherapy in MM patients were elevated temporarily and then decreased in spite of no change of blood Hb level.


[Urinary excretion of parathyroid hormone-related protein in patients with adult T-cell leukemia and other hematologic disorders]. Urinary excretion of parathyroid hormone-related protein (PTH-rP) was measured by radioimmunoassay in 25 patients with adult T-cell leukemia (ATL), in 68 patients with other hematologic disorders and in 13 asymptomatic individuals seropositive for human T-cell leukemia virus type I (HTLV-I). The mean levels of urinary PTH-rP in ATL patients with hypercalcemia (11.01 micrograms/g.Cr) were higher than in ATL patients with normocalcemia (5.16 micrograms/g.Cr). The mean levels in patients with acute type (8.84 micrograms/g.Cr), lymphoma type (4.18 micrograms/g.Cr) and crisis ATL (18.20 micrograms/g.Cr) were significantly higher than in urine of healthy controls. However, all asymptomatic carriers of HTLV-I and patients with chronic and smoldering ATL had normal urinary PTH-rP levels. In 7 patients with acute myelogenous leukemia, 1 patient with blastic crisis of chronic myelogenous leukemia and 3 patients with malignant lymphoma, the urinary levels of PTH-rP were above the normal range. Urinary levels of PTH-rP of the ATL patients with hypercalcemia correlated with the serum calcium levels. Urinary levels of PTH-rP of the all ATL correlated with serum lactic dehydrogenase level. These findings suggest that the measurement of urinary levels of PTH-rP is useful for evaluation of ATL and that some tumor cells of other hematologic diseases may produce PTH-rP.


[Prophylaxis of thrombosis in a pregnant woman with congenital antithrombin III deficiency: changes in hemostatic molecular markers before the onset of thrombosis]. A pregnant woman with congenital antithrombin III (AT III) deficiency was given AT III concentrate and warfarin at the first and after 36th week of gestation periods and at the other gestation period, respectively. The patient developed thrombosis in the left leg, but fibrinopeptide A (FPA) and thrombin-AT III complex (TAT) had already shown high values one week before, suggesting the possibility of their being forecast markers of thrombosis. The administration of AT III concentrate caused an improvement in thrombosis. Therefore, in case of high FPA and TAT values as determined one or two times a week, the administration of AT III concentrate was thought necessary. In case of warfarin, however, non-administration during the 6th-9th weeks of gestation for the purpose of avoiding teratogenicity and frequent blood coagulation tests taking heed of overdosage for the purpose of avoiding fetal central nervous system abnormalities were suggested necessary. Delivery was uneventful, both mother and child being doing very well; umbilical blood AT III activity was 18%. It is generally difficult for us to form the diagnosis as AT III deficiency only from AT III activity at neonatal stage, but in the present study, we analyzed the restriction fragment length polymorphism of the AT III gene using umbilical blood, and succeeded in diagnosing the neonatal child as AT III deficiency.


[Effect of subcutaneous administration of interleukin-1 beta on blood platelet count and serum GM-CSF in patients with myelodysplastic syndrome and aplastic anemia]. Subcutaneous administration of recombinant human Interleukin-1 beta (IL-1 beta) in a dose of 1-3 x 10(4) U/day for 14 to 72 days resulted in an increase in circulating granulocytes and bone marrow monocytes in all the 4 patients examined. Circulating platelet count was also increased in two of four patients with myelodysplastic syndrome (MDS) and aplastic anemia (AA). Bone marrow examination revealed an increase in megakaryocyte count in these patients, whereas the percentage of blast was not changed. An increase in blood platelet count was accompanied by an increase in serum GM-CSF in a patient with AA, whereas serum IL-6 level was not changed throughout the treatment with IL-1 beta. These findings suggest that IL-1 beta may be useful for the treatment of a proportion of patients with MDS and AA who are associated with thrombocytopenia.


[Clinical significance of antinuclear antibody in patients with idiopathic thrombocytopenic purpura]. The clinical significance of antinuclear antibodies (ANA) in patients with chronic idiopathic thrombocytopenic purpura (ITP) was evaluated. Serum samples of 55 patients with ITP without clinical features of systemic lupus erythematosus (SLE) were examined. The average follow-up period was 5.5 years. Positive ANA was found in 23 of the 55 patients. Twelve of these 23 showed a high-titer of ANA. There was no difference in platelet counts between ANA positive patients and negative patients, and there was no correlation between platelet counts and antibody titers. Ten of the 23 positive sera had precipitating antibodies to nuclear antigens; 7 SS-A and 3 RNP antibodies. The platelet counts of the 7 cases with anti-SS-A antibody positive were slightly low compared with those of the anti-SS-A antibody negative patients. None of the 10 patients developed SLE during the average follow-up period of 8.1 years. These results suggest that ITP patients who have a high-titer of ANA or antibody against SS-A do not always develop SLE. It was concluded that ANA with a high titer or precipitin to nuclear antigens, particularly SS-A, dose not predict a high risk of developing SLE in the future.


[Clinical significance of aldolase A in sera of patients with leukemia]. Serum aldolase A (ALD-A) levels were determined in patients with leukemia using a radioimmunoassay method. The method is a double antibody radioimmunoassay consisting of purified ALD-A as ligand, chicken antisera to ALD-A and rabbit antibodies to chicken IgG. Serum ALD-A levels of 41 normal healthy subjects ranged from 130 to 210 ng/ml (mean +/- 2 SD; 171 +/- 39 ng/ml). Serum ALD-A levels ranged from 90 to 200 ng/ml in patients with 42 non-neoplastic hematological diseases with the exception of hemolytic anemia. In contrast, 61 patients with acute leukemia before treatment exhibited increased serum ALD-A levels ranging from 125 to 1,550 ng/ml, with a mean value of 480 ng/ml. Serum ALD-A levels in 24 patients with chronic myelocytic leukemia (CML) during the chronic phase also exhibited high mean values of 481 ng/ml in a range of 270 to 1,100 ng/ml. Serum ALD-A levels were higher than 210 ng/ml in 85.2% of the patients with acute leukemia and in all patients with CML. Serum ALD-A levels tended to be decreased within the normal range, if those patients could achieve complete remission. In contrast, serum ALD-A levels showed a tendency to increase if those patients experienced a relapse of leukemia. These results suggest that the measurement of serum ALD-A levels by radioimmunoassay is useful for diagnosis and prediction of relapse in patients with leukemia.