Changes in amino acid and glucose transport in brush-border membrane vesicles of hyperglycemic guinea-pig small intestine.

Changes in intestinal transport of L-amino acid and D-glucose in streptozotocin (STZ)-induced hyperglycemic guinea-pig were examined using brush-border membrane vesicles. The vesicles were prepared from guinea-pigs on days 3, 10, and 21 after intravenous injection of STZ (150 mg/kg body weight), and from control animals injected with sodium citrate buffer (pH 4.5) in the same manner. Blood glucose concentration rose to greater than 300 mg/dl in the hyperglycemic guinea-pigs 24 h after STZ injection, and then remained constant. All vesicles obtained under different conditions showed a similar specific activity of alkaline phosphatase, a marker enzyme of the intestinal brush-border membrane, indicating a similar purity of the membrane vesicles. On day 3, Na(+)-dependent amino acid transport was found to be approx. 30% higher in the hyperglycemic than in the control group, and Na(+)-dependent glucose transport was 35% lower in the hyperglycemic than in the control group. On days 10 and 21, Na(+)-dependent amino acid transport had recovered to the control levels, whereas Na(+)-dependent glucose transport was twice as high as in the hyperglycemic than in the control group. Na(+)-independent amino acid and Na(+)-independent glucose transport showed no difference between the hyperglycemic and control groups after STZ injection. The changes in both Na(+)-dependent amino acid and glucose transport were attributed to significant changes in the Vmax values with no change in the apparent Km values. This study clearly demonstrates that hyperglycemia is associated with reciprocal changes in intestinal transport of amino acid and glucose in its acute phase, suggesting an important pathophysiological regulatory mechanism for absorption of nutrients by control of the numbers of specific carriers.

Characterization of amino-acid transport systems in guinea-pig intestinal brush-border membrane.

The amino-acid transport systems have been characterized in brush-border membrane vesicles prepared from guinea-pig small intestine. Uptake of all amino acids tested was measured at the initial velocity for 5 s. L-Proline, alpha-(methylamino)isobutyrate, glycine, L-alanine and L-methionine were transported dependent solely on an Na+ gradient from the outside to the inside of the vesicles, and L-cysteine, L-phenylalanine and L-leucine were transported dependent largely on the Na+ gradient with a small fraction of Na+-independent transport. The transport of L-aspartic acid and L-lysine was independent of the Na+ gradient and L-lysine transport was somewhat inhibited by the presence of cations, including Na+, K+ and Li+. A cross-inhibition study of the uptake of these amino acids in the brush border of guinea-pig intestine revealed the presence of at least three Na+-dependent and three Na+-independent carrier-mediated systems. One Na+-dependent system interacted mainly with imino acid. Another Na+-dependent system interacted with neutral amino acids, while a third system was selective for glycine. One Na+-independent system is for acidic amino acids, another is responsible for neutral amino acids and a third for cationic amino acids. These transport systems of amino acids in guinea-pig small intestine are compared with those in rabbit and mouse intestine.

Childhood bacterial meningitis in Japan.

Haemophilus influenzae type b (Hib) vaccines currently are not used in Japan, but interest in preventing H. influenzae disease by immunization has grown. We performed a retrospective survey for bacterial meningitis in 6 prefectures of Japan. Questionnaires requested the age, sex, clinical outcome and identity of the etiologic organism, if known, of all patients with meningitis younger than 16 years of age who were admitted during calendar year 1994. Of 876 hospitals within the 6 study prefectures, 363 (41.4%) returned a completed questionnaire. There were 1769 cases of meningitis reported, of which 160 (9%) were considered bacterial in origin. H. influenzae was the most common cause of bacterial meningitis, accounting for 68 cases (43%). Sixty-six cases (97%) of H. influenzae meningitis occurred in children 4 years of age or younger, and 27 (40%) occurred in children <1 year of age. Calculated incidence rates based on the population of children 4 years of age or less for each prefecture ranged from 3.4 to 9.9 cases per 100000 (mean, 4.7 cases/100000). H. influenzae is the most common cause of meningitis in Japan, and the estimated incidence rates from this study are very similar to those previously reported from Japan. More comprehensive, prospective surveillance studies will be needed to define better the incidence of Hib meningitis and to aid in making rational decisions regarding the use of Hib vaccination in Japan.

Membrane structure of the hepatitis B virus surface antigen particle.

Expression of S protein, an envelope protein of hepatitis B virus, in the absence of other viral proteins, leads to the secretion of hepatitis B virus surface antigen (HBsAg) particles that are formed by budding from the endoplasmic reticulum membranes. The HBsAg particles produced by mouse fibroblast cells show a unique lipid composition, with 1,2-diacyl glycerophosphocholine being the dominant component. The lipid organization of the HBsAg particles was studied by measuring electron spin resonance (ESR) using various spin-labeled fatty acids, and the results were compared with a parallel study on HVJ (Sendai virus) and vesicles reconstituted with total lipids of the HBsAg particles (HBs-lipid vesicles). HVJ and the HBs-lipid vesicles showed typical ESR spectra of lipids arranged in a lipid bilayer structure. In contrast, the ESR spectra obtained with the HBsAg particles showed that the movement of lipids in the particle is severely restricted and a typical immobilized signal characteristic of tight lipid-protein interactions was also evident. Phosphatidylcholine (PC) in the HBsAg particles was not exchangeable by a PC-specific exchange protein purified from bovine liver, while phospholipase A(2) from Naja naja vemon was able to hydrolyze all the PC in the particles. These analyses suggest that the lipids in the HBsAg particles are not organized in a typical lipid bilayer structure, but are located at the surface of the particles and are in a highly immobilized state. Based on these observations we propose a unique lipid assembly and membrane structure model for HBsAg particles.

Rupture of pulmonary artery induced by balloon occlusion pulmonary angiography.

A case of pulmonary artery rupture induced by balloon occlusion pulmonary angiography (BOPA) is reported. A flow-directed pulmonary artery catheter had been inserted for hemodynamic monitoring in a septic shock patient complicated by acute respiratory distress syndrome. To check for pulmonary damage, BOPA was performed immediately after hemodynamic measurement. Just as the hand injection of contrast medium was ending, the patient began to cough and a small amount of hemoptysis was observed. The angiogram showed the extravasation of contrast medium from the distal pulmonary artery to the situation of catheter tip. Pulmonary hemorrhage was controlled with mechanical ventilatory support with 10 cmH2O positive end-expiratory pressure and no specific therapy was required. This complication should be kept in mind and using a power injector to avoid injurious transient high pressure pulse is recommended.

Roles of monoaminergic, glycinergic and GABAergic inhibitory systems in the spinal cord in rats with peripheral mononeuropathy.

The current study was designed to determine if the monoaminergic descending inhibitory system and the glycinergic and GABAergic inhibitory systems were activated in the spinal cord in the presence of peripheral mononeuropathy produced by loose ligatures around the common sciatic nerve. The time course of withdrawal latencies to thermal stimuli were assayed in lesioned and sham-operated rats. The levels of monoamines (serotonin; 5-HT, noradrenaline, and dopamine), glycine and gamma-aminobutyric acid (GABA) in the dorsal half of the spinal cord were measured using HPLC with electrochemical detection. Furthermore, on day 7 after nerve ligation, intrathecal methysergide, yohimbine, strychnine or bicuculline was administered in order to investigate the roles of these inhibitory neuromodulators in this pathological pain state. The levels of 5-HT and noradrenaline significantly increased in both ipsi- and contralateral sides of the dorsal half of the lumbar spinal cord in the lesioned, but not sham-operated animals. The levels of glycine and GABA in the ipsilateral dorsal half of the spinal cord increased significantly and were significantly higher than in the contralateral side. Intrathecal antagonists of 5-HT, noradrenaline, glycine and GABA produced enhancement of the magnitude of hyperalgesia on the lesioned hindpaw. We also examined the effects of four daily single treatments with intrathecal MK-801 beginning 15 min prior to nerve ligation on the development of thermal hyperalgesia and on the contents of the neuromodulators in the ligation model. MK-801 treatment effectively abolished the increases in 5-HT, noradrenaline, glycine and GABA levels as well as preventing the development of hyperalgesia. The results of the present study suggest that the pathological pain state activates or increases the activity of these inhibitory systems.

Analgesic effect of epidural neostigmine after abdominal hysterectomy.

STUDY OBJECTIVE: To evaluate the effects of epidurally administered neostigmine on pain after abdominal hysterectomy. DESIGN: Prospective, randomized, double-blind study. SETTING: Teaching hospital. PATIENTS: 45 ASA physical status I adult patients scheduled for abdominal hysterectomy. INTERVENTIONS: All patients received identical general and epidural anesthesia. At the end of the surgery, they received epidural bupivacaine (10 mg) with either saline (control group, n = 15), 5 micro g/kg (5-micro g group, n = 15), or 10 micro g/kg neostigmine (10-micro g group, n = 15). Postoperatively, 50 mg diclofenac suppository was given for pain relief on patient demand. MEASUREMENTS AND MAIN RESULTS: The time to first diclofenac administration and the number of times diclofenac was required during the first 24 postoperative hours were recorded. Pain was assessed using a 10-cm visual analog pain scale (VAS) at rest at the first diclofenac request, and at 15 and 24 hours after surgery. The time to first diclofenac administration was significantly longer (p < 0.05) in the 10-micro g group (223 +/- 15 min) than in the control (78 +/- 17 min) or 5-micro g groups (88 +/- 18 min). However, epidural neostigmine at both doses did not reduce the number of postoperative diclofenac administrations. There were no differences in VAS among the three groups. CONCLUSIONS: Epidural neostigmine of 10 micro g/kg in bupivacaine provides a longer duration of analgesia than does bupivacaine alone or with 5 micro g/kg of neostigmine after abdominal hysterectomy.

[The suppressive effect of pyrrole-2-carboxylic acid on platelet aggregation].

In the course of a search for novel antibiotics, an antiplatelet substance was isolated from the fermentation broth of Streptomyces sp. No. 82-85. Thereafter, the active substance was identified as pyrrole-2-carboxylic acid (P2C) by structural studies. The effects of P2C on adenosine diphosphate (ADP)-, arachidonic acid-, collagen- or tumor cell-induced platelet aggregation were examined in vitro and ex vivo. In in vitro studies, P2C (25-100 micrograms/ml) suppressed the aggregation of platelets of normal Wistar rats. The intraperitoneal administration of P2C (200 mg/kg) to rats and rabbits suppressed platelet aggregation induced by ADP, arachidonic acid and collagen when examined for 0.5-3 hours after administration. The agent also suppressed platelet aggregation induced by both mouse syngenic tumors, Meth-A fibrosarcoma and IMC carcinoma in vitro.

[Effects of oral alpha 2 adrenergic agonists, clonidine and tizanidine, on tetracaine spinal anesthesia].

This study was conducted to evaluate the effects of oral clonidine and tizanidine, alpha 2 adrenergic agonists, as premedication for tetracaine spinal anesthesia in 63 gynecological patients. The patients were randomly allocated to one of six groups. Group 1 (n = 7), group 2 (n = 8) and group 3 (n = 7) received 13 mg of tetracaine intrathecally in 10 % glucose solution 2.6 ml. Group 4 (n = 13), group 5 (n = 14) and group 6 (n = 13) received 13 mg of tetracaine intrathecally in a volume of 2.6 ml of 10 % glucose solution which contained 0.65 mg of phenylephrine. As premedication, group 1 and 4 received 0.25 mg of oral triazolam; group 2 and 5 received 3 mg of oral tizanidine; group 3 and 6 received 0.15 mg of oral clonidine. Group 2 and 3, or group 5 and 6 (clonidine or tizanidine group, respectively) needed significant longer time for regression of Th10 sensory blockade than group 1 or 4 (triazolam). The time for appearance of postoperative pain and the time to require postoperative analgesics were longer in the groups which had received either clonidine or tizanidine than in the groups which had received triazolam. Heart rate and systolic blood pressure in group 6 (clonidine-tetracaine-phenylephrine group) showed significant decreases (P < 0.05) after the spinal anesthesia. We concluded that oral premedication of clonidine and tizanidine prolonged tetracaine spinal anesthesia. From the view point of the prolongation of spinal anesthesia and the hemodynamic stability, oral premedication with tizanidine seems to be useful.

[Study of administration of buprenorphine suppository for postoperative pain relief following transvaginal hysterectomy].

Buprenorphine suppository (BSP) has been available as an analgesic agent in Japan since 1990. It has gained considerable popularity in various clinical situations; however, its usefulness for postoperative pain relief has been controversial. The present study is addressed to postoperative pain in fifty-seven women who underwent transvaginal hysterectomy under spinal anesthesia with tetracaine and phenylephrine. We examined the analgesic effects of buprenorphine (0.4 mg) suppository. Patients were divided into four groups according to the timing of buprenorphine suppository administration: group A1, preoperative administration of BSP, n = 12; group A2, postoperative administration of BSP, n = 17; group A3, intravenous injection of 0.1 mg of buprenorphine during surgery and postoperative administration of BSP, n = 14; group C, control group, n = 14. All the patients in group C complained of pain within 24 hr. The onset time of pain after surgery was significantly longer in patients in group A1 (372 +/- 220 min) and A3 (481 +/- 161 min) than in control group C (282 +/- 97 min). The percentage of patients who did not complain of pain within 24 hr was the largest in group A3 (36%). However there were no significant differences in age, body weight, effective analgesic time, analgesic level or operation time among the four groups. Nausea and vomiting were observed in all groups: C (36%), A1 (41%), A2 (18%), and A3 (29%). From these results, we conclude that preoperative or intraoperative administration of buprenorphine is useful for control of postoperative pain; the method of administration of buprenorphine suppository needs further study.

[Open heart surgery in patient with hyperthyroidism].

A 57-yr-old male with atrial septal defect (ASD) was scheduled for the patch closure operation. The patient had a history of hyperthyroidism due to giant adenoma of the thyroid gland. The patient was controlled under euthyroid state by thiamazole for four years. With this treatment, his thyroid function became normal and he was doing well for over the last seven years. On the morning of the day of operation, thiamazole was given orally to this patient. When the ASD patch closure was performed, the examination of his thyroid gland revealed hypothyroidism, but the operation could be performed without any thyroidal trouble. After the operation thiamazole was given intramuscularly to this patient and from the next day it was continued orally. Thyroid storm did not occur after the operation until discharge. We conclude that in a case of heart disease with hyperthyroidism, it is important to keep the patient's thyroid function under normal for a long time before surgery.

[Efficacy of bispectral index for anesthetic management of combined off-pump coronary artery bypass grafting and abdominal aortic aneurysm replacement].

A 57-year-old female patient underwent combined off-pump coronary artery bypass grafting and abdominal aortic aneurysm replacement. Anesthesia was maintained with propofol, fentanyl, and thoracic epidural anesthesia. Propofol doses were adjusted to maintain bispectral index (BIS) between 40-60. Despite the remarkable hemodynamic changes, BIS remained stable at about 50 during the surgery. The average dose of propofol was 3.3 mg.kg-1.hr-1. The patient awoke an hour after the surgery and was extubated 1.5 hours thereafter. This case report suggests that BIS is a useful index to determine the depth of anesthesia during surgeries which induce marked hemodynamic changes.

[The effect of lidocaine on the bispectral index during anesthesia induction with propofol].

We investigated the effect of premixing lidocaine with propofol on a bispectral index (BIS) during propofol infusion. We studied 40 adult patients given mixture of 1% propofol 20 ml with 2 ml of normal saline (control group) or 2% lidocaine (lidocaine group) infused at 2 ml.kg-1.hr-1 for 10 minutes. Heart rate, mean arterial pressure, and BIS were measured every minute. The addition of lidocaine to propofol reduced the incidence of injection pain from 85% to 10% but did not change the induction time. Propofol significantly decreased mean arterial pressure and BIS but there was no difference between the groups. In conclusion, premixing lidocaine with propofol reduces injection pain without affecting the hypnotic effect.

[Plasma concentration of lidocaine in patients undergoing hepatectomy with continuous epidural anesthesia--influence of extent of hepatectomy and prostaglandin E1 infusion].

We investigated changes in plasma concentration of lidocaine during continuous epidural anesthesia in 21 patients undergoing hepatectomy. According to the extent of hepatectomy, patients were assigned into one of the three groups: partial resection group, lobectomy group, and extended lobectomy group. Lidocaine 2.0 mg.kg-1 with 1: 200,000 epinephrine was epidurally administered in a bolus followed by continuous infusion of lidocaine at the rate of 1.5mg.kg-1.h-1. Plasma lidocaine concentration in the extended lobectomy group showed a significantly higher value than those of other two groups (P < 0.05). Plasma lidocaine was detected in the extended lobectomy group at 12 hs after the surgery, but not in the other two groups. Furthermore we investigated the effects of prostaglandin E1 infusion in 7 patients undergoing extended lobectomy. Plasma lidocaine concentration was not increased in this group. In conclusion, we recommend caution regarding the dose of lidocaine administered for epidural anesthesia during hepatectomy; PGE1 infusion appears to be safe in patients undergoing extended hepatectomy.

[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.

[A case of right cranial polyneuropathy following the onset of herpetic eruptions associated with severe pain on the left cranial and cervical regions].

We describe a case presenting herpetic eruptions and pain in the left cranial and cervical regions, followed by right cranial polyneuropathy. The patient, a 66-yr-old male, developed a diphasic syndrome which was first characterized by herpetic eruptions on the whole of his left cranial and cervical regions with severe pain and left facial nerve palsy. Two weeks later, right multiple cranial nerve palsies of III, V, and VII and an increase in CSF protein appeared in a second phase. Neuroimaging technique (MRI) did not provide any evidence of brain involvement. The immediate use of steroid therapy led to improvement of the symptoms of cranial polyneuropathy. The clinical course suggests that reactivation of a latent herpes simplex virus may have been the etiologic cause of the cranial polyneuropathy. Steroid therapy should be applied to the treatment of cranial polyneuropathy in patients showing a similar pattern to this case.

[Deep neck infection following endotracheal intubation].

A 71-year-old woman was transferred to Kushiro City General Hospital because of fever, sore throat, diffuse neck swelling and dyspnea. She had received right mastectomy for breast cancer under general anesthesia 6 days before the admission. The lateral X-ray film of the neck revealed abscess in the retropharyngeal space and the retroesophageal space. CT scan revealed mediastinitis. Next day she received neck dissection for drainage of the abscess under general anesthesia. Although the posterior pharyngeal wall was swollen, endo-tracheal intubation was not difficult. Brown tinged and purplish pus was aspirated from the interspace of carotid sheath and trachea, the retropharyngeal space, and the superior mediastinal space. The infected site was irrigated with a lot of peroxide and saline and draining tubes were placed in each interspace. Tracheostomy was not done but the patient was admitted to the ICU with her trachea intubated. The day after operation, she was extubated. Three days after the operation chest X-ray revealed pyothorax and chest tube was inserted for drainage. Seven days after the operation she was transferred to the ENT ward. Thereafter her recovery course was uneventful. It seems that the deep neck infection was probably caused by the injury on endotracheal intubation at the first operation in this case. Although this patient was cured of mediastinitis following deep neck infection, which is still lethal, early diagnosis and surgical drainage of the abscess are necessary.

[Distribution of pulsed intra arterial infusion chemotherapy in hepatic carcinomas].

Evaluation of "Gianturco-Wallace chemotherapy pulser," which was developed to produce a more homogeneous drug distribution of the tumors in intra-arterial infusion chemotherapy, was assessed by comparative study of pulsed and nonpulsed arterial radionuclide infusion using Tc-99m pertechnetate for 18 cases of hepatic carcinomas (11 cases of hepatocellular carcinomas and 7 cases of metastatic hepatic carcinomas). Tc-99m pertechnetate, 740 MBq (20 mCi) diluted with saline (30 mL) was infused with or without pulse through the catheter into the hepatic artery at a rate of 1mL per minute. The intrahepatic dynamic radionuclide distribution was analyzed by the time activity curves of ROIs in the tumor and nontumor areas. Pulsed infusion interrupted laminar flow and produced more homogeneous radionuclide distribution in the liver, and combination of pulsed and nonpulsed infusion also produced better radionuclide distribution in the areas of the tumors. This method using Tc-99m pertechnetate was very useful as a simulation to determine the dynamic drug distribution of the tumor and non-tumor region in intraarterial infusion methods.

[The analysis of superselective catheterization technique; transcatheter segmental arterial embolization using lipiodol for hepatocellular carcinoma].

The practical limitations of catheters used for infusion were studied by their types in 47 patients with hepatocellular carcinoma who were treated by Segmental Lp-TAE. For catheterization into the arterial branches of S5 and S8, a coaxial infusion catheter was helpful. However, a coaxial infusion catheter was seldom used for catheterization into the arterial branches of S6 and S7. For infusion into vessels having diameters of less than 1.9 mm at the tip end of the catheter, positive use of a coaxial infusion catheter is strongly recommendable. A Tracker-18 catheter was especially helpful for catheterization into the vessels of S5.

[Transarterial hepatic embolization of metastatic liver cancers with reference to 17 cases of survival for more than 2 years].

The evaluation of TAE was studied for 73 patients with metastatic liver cancers but without metastasis in other organs, who were treated with initial TAE more than 2 years ago. Seventeen patients survived for more than 2 years. The primary lesions consisted of colon cancer in 9 patients, the Langerhans islet cell tumor of the pancreas in 4, gastric cancers in 2, breast cancer in 1 and leiomyosarcoma of the colon in 1. The overall 2-year survival rate calculated by the direct method was 23.3% and mean survival period was 15.8 months. The prognosis was good in H1 and V3. Lp-TAE produced better effects but no statistically significant difference was found between the 2-year survivals by Lp-TAE and by GS-TAE.