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Biomedical subjects

Y Kosaka

Publications and source records attributed to Y Kosaka.

At least 19 recordsLinked to original sources

Herbal medicine "sho-saiko-to" induces in vitro granulocyte colony-stimulating factor production on peripheral blood mononuclear cells.

The herbal medicine "Sho-saiko-to (Xiao-Chai-Hu-Tang)" has been used in China for about 3000 years for the treatment of pyretic diseases. This medicine is now available as one of the prescribing drugs approved by the Ministry of Health and Welfare of Japan, and has also been widely used for patients with chronic viral liver disease as one of biological response modifiers in the field of Japan's Western Medicine. However, its mode of action has not been fully described. In the present in vitro study, we added "Sho-saiko-to" (TJ-9, Tsumura, Tokyo) to the culture of peripheral blood mononuclear cells (PBMC) obtained from healthy volunteers, and observed a dose-dependent increase in the production of granulocyte colony-stimulating factor (G-CSF). The same experiment was conducted using other herbal medicines "Dai-saiko-to" (TJ-8) and "Saiko-keishi-to" (TJ-10) which showed similar effects, or "Sho-seiryu-to" (TJ-19) which consists of very different compounds and shows different efficacy. The increases of G-CSF production were similar when "Sho-saiko-to" (TJ-9) or one of the 2 reference drugs (TJ-8 and 10) was added, whereas the increase when the control drug "Sho-seiryu-to" (TJ-19) was added, was quite small. This result shows that G-CSF induction is not a common effect of herbal medicines, but a specific effect of TJ-8, 9, and 10. Among these 3 drugs the increase produced by "Sho-saiko-to" was the largest. Based on this result, we conclude that administration of "Sho-saiko-to" may be useful not only for the treatment of chronic liver disease, but also for malignant diseases and acute infectious diseases where G-CSF is efficacious.

Anti-Inflammatory Agents, Non-Steroidal

Effects of methylcobalamin (vitamin B12) on in vitro cytokine production of peripheral blood mononuclear cells.

Recently in Japan, one form of vitamin B12, methylcobalamin also known as methyl B12, has attracted the attention of physicians as a therapy for patients with rheumatoid arthritis. However, its immunological actions in vivo are still unknown. In this study, we induced the in vitro production of such cytokines as interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and interleukin-1 beta (IL-1 beta) by adding various mitogens (phytohemagglutinin:PHA, concanavalin A: ConA, or pokeweed mitogen:PWM) as well as recombinant interleukin-2, and we investigated the effects of methyl B12 (final concentration, 8-8,000 ng/ml) on the production of these cytokines by peripheral mononuclear cells. As compared to the controls, IL-6 production induced by PHA and ConA on Day 4 of the culture was suppressed by an average 60-70% when methyl B12 (80-8,000 ng/ml) was added to the medium. IFN-gamma production decreased dose-dependently with methyl B12, i.e., it decreased to 46% of the control when this production was induced by rIL-2, and decreased to 56-66% when it was induced by mitogens. The effect of methyl B12 on IL-1 beta production on Day I of the culture was small. These findings indicate that methyl B12 suppresses mainly the cytokine production of T lymphocytes. Such suppressive effects as shown in the in vitro situation are expected to be expressed also in vivo in patients with rheumatoid arthritis, especially at articulation lesion sites.

Arthritis, Rheumatoid

Efficacy of a herbal medicine "sho-saiko-to" on the improvement of impaired cytokine production of peripheral blood mononuclear cells in patients with chronic viral hepatitis.

Peripheral blood samples were collected from normal subjects and chronic viral hepatitis patients, and the in vitro capability of the peripheral blood mononuclear cells to produce various cytokine (interleukin-1 beta, interleukin-6, interferon-gamma, and granulocyte-macrophage colony-stimulating factor) were analyzed by adding pokeweed mitogen. We then investigated the effects of a herbal medicine "Sho-saiko-to" on the levels of cytokine production. The production levels of the 4 cytokines were significantly lower in the peripheral blood mononuclear cells of the patients (Patient Group) than in those of normal subjects (Control Group). The addition of Sho-saiko-to to the Patient Group resulted in improved productions of those cytokines, as well as an remarkable improvement of interleukin-1 beta production. The results demonstrated that Sho-saiko-to acts to improve such immunological abnormalities as decreased cytokine productions. Administration of Sho-saiko-to to chronic viral hepatitis patients is also expected to have immunological benefits.

Anti-Inflammatory Agents, Non-Steroidal

Effects of the streptococcal preparation OK-432 on in vitro cytokine production of peripheral blood mononuclear cells in patients with chronic viral hepatitis.

We obtained peripheral blood mononuclear cells from 12 chronic hepatitis Type B patients, 12 Type C patients, and 15 healthy volunteers, and investigated the effects of OK-432, a streptococcal preparation, on in vitro production of 3 types of cytokines. Mononuclear cells in a concentration of 1 x 10(6) cell/ml were prepared in the culture medium. OK-432 (Chugai Pharmaceutical Co., Ltd., Tokyo) was added to this preparation and incubated for one to 4 days. Thereafter interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) levels in the culture supernatant were measured using enzyme-linked immunoassay kits. Cytokine production levels in cultures with OK-432 were significantly increased in the mononuclear cells of both patients and healthy volunteers. The largest increase was observed with IFN-gamma (p < 0.01), and then with IL-1 beta (p < 0.05). Responses of the cells from chronic hepatitis Type C patients to OK-432 were relatively good. When interferon (alpha and beta) treatment was first introduced, there were high hopes for a high efficacy. However, we now know 50-70% of patients with chronic hepatitis Type C do not respond satisfactorily to interferon. Some physicians suggest the necessity of using biological response modifier (BRM) as an adjuvant treatment for these patients. From our findings, OK-432 could be a useful BRM in patients with chronic hepatitis Type C.

Cells, Cultured

[A case of pneumonitis and hepatic injury caused by a herbal drug (sho-saiko-to)].

We report a case of pneumonitis and hepatic injury caused by Sho-saiko-to. A 56-year-old man was admitted to our hospital because of hepatic disorder. The levels of serum transaminases returned to normal within two months without specific treatment and he was discharged. Four weeks later, he was readmitted because of severe pneumonitis and mild hepatic disorder. Under the suspicion of drug-induced pneumonitis, all medications were discontinued and high-dose glucocorticoid including "pulse therapy" was given. Consequently, pneumonitis and hepatic function markedly improved. Careful history taking revealed the ingestion of Sho-saiko-to before both admissions. Lymphocyte stimulation test against Sho-saiko-to was positive. Challenge test using Sho-saiko-to resulted in decrease of PaO2 and elevation of serum transaminases. Based on these findings, the diagnosis of pneumonitis and hepatic injury induced by Sho-saiko-to was established.

Alveolitis, Extrinsic Allergic

[Effects of prostaglandin E1 and epidural block on circulatory, hepatic and renal functions during anesthesia for major upper abdominal surgeries].

The effects of low dose (0.02 microgram.kg-1.min-1) prostaglandin E1 (PGE1), epidural block (EP) or combination of PGE1 and EP (PGE1 + EP) under general anesthesia on circulatory, hepatic and renal functions were studied in 31 patients undergoing major upper abdominal surgeries without hepatic or renal dysfunction preoperatively. Mean arterial pressure decreased by 10% in PGE1 and EP groups, while 20% in PGE1 + EP group. Cardiac output decreased significantly in EP group, increased in PGE1 group and was unaltered in PGE1 + EP group during anesthesia and the operation. The arterial ketone body ratio as a hepatic function test increased following the administration of PGE1 or epidural block. Urine output, osmotic clearance and free water clearance were higher in PGE1 + EP group during the operation. These results suggest that the combination of low dose PGE1 and epidural block maintain cardiac output and organ blood flow during anesthesia and surgery in spite of a greater decrease in arterial blood pressure.

Abdomen

A case of acute intermittent porphyria with acute pancreatitis.

A case of acute pancreatitis in a 29-year-old female associated with an attack of acute intermittent porphyria (AIP) is reported. Following the attack of AIP, serum pancreatic amylase originating from the pancreas increased transiently, and mild swelling of the pancreas was detected by ultrasonography. On this basis acute pancreatitis was diagnosed. Additionally, this patient had mild hepatic dysfunction. Laparoscopy disclosed diffuse slightly dark bluish pigmentation on the irregular surface of the liver. Mild fibrous dilatation of the portal area with lymphocytic infiltration was seen histologically. Acute pancreatitis and hepatic damage with AIP is extremely rare, however it is possible that these findings are etiologically connected in this patient.

Acute Disease

Fulminant hepatitis B: induction by hepatitis B virus mutants defective in the precore region and incapable of encoding e antigen.

Clones of hepatitis B virus were propagated from 10 cases of fulminant hepatitis B after amplification by polymerase chain reaction and their nucleotide sequences of the precore region were determined. All 113 clones from 9 cases had a point mutation from guanine to adenine at nucleotide 83 in the precore region, which converted codon 28 for tryptophan (TGG) to a stop codon (TAG) and prohibited the synthesis and secretion of hepatitis B e antigen. Precore-region defects were not detected in any of 23 clones from the remaining 1 case. By contrast, precore-region defects were not found in any of 180 clones from 8 cases of acute hepatitis B without hepatic failure serving as controls. The source of infection was traceable in 3 cases. The same precore-region defect, along with the sequence identity of 435 nucleotides, was observed in clones from the case of a baby and his grandmother, who carried the virus and was implicated in the transmission, and also in clones from two pediatricians and the carrier patients they attended. These findings support the hypothesis that precore-defective mutants have stronger activity to induce fulminant hepatitis than nondefective viruses.

Adolescent

Epidural analgesia in Eaton-Lambert myasthenic syndrome. Effects on respiratory function.

The anaesthetic management of a patient with Eaton-Lambert myasthenic syndrome undergoing thoracotomy is described. Epidural anaesthesia, in combination with a light level of general anaesthesia, provided good operating conditions and postoperative analgesia. Pulmonary function and ventilatory responses to carbon dioxide and hypoxia were measured before operation. These tests were repeated after the epidural administration of 8 ml 2% lignocaine before surgery and after 2 mg morphine sulphate in 10 ml saline postoperatively. Minor reductions in some of the ventilatory parameters were observed. The epidural technique appears to be a useful and safe method by which to manage patients with Eaton-Lambert syndrome undergoing thoracotomy.

Analgesia, Epidural

Pharmacokinetics of pirarubicin in pediatric patients.

The pharmacokinetics of pirarubicin and its active metabolite, doxorubicin, were studied after intravenous administration of pirarubicin (25-45 mg/m2) to ten pediatric patients. The concentration-time curves of pirarubicin in both blood and plasma showed representative biphasic patterns. Pirarubicin concentrations decreased rapidly from 0.5 to 2 h after administration and then decreased slowly until 24 h in all subjects. High concentrations of the metabolite, doxorubicin, were detected at 0.5 h after administration of pirarubicin which decreased gradually until 24 h. The area under the concentration-time curve from 0 to 24 h (AUC0-24) of pirarubicin and doxorubicin in blood were 3-4 times higher than those in plasma, suggesting that these drugs had a high affinity for blood cells. The AUC0-24 ratio of doxorubicin to pirarubicin in plasma was calculated to be 0.441. It might be indicated that not only pirarubicin but also doxorubicin are responsible for the therapeutic efficacy and the incidence of toxicity of pirarubicin. The pharmacokinetics of pirarubicin in pediatric patients was fundamentally similar to that of adults, but it was recognized that considerable interindividual variation in the disposition of pirarubicin and doxorubicin exists.

Adolescent

[Effects of intravenous lidocaine administration on auditory brainstem response].

The effect of lidocaine on the auditory brainstem response (ABR) was investigated in 14 neurologically normal patients. Lidocaine 1.5 mg.kg-1.min-1 was injected intravenously over a 5 min period immediately followed by a continuous infusion of lidocaine 60 micrograms.kg-1.min-1. The seven peak latencies (waves I-VII) and amplitudes (waves I-VII) of the ABR were recorded before and 7-8 min after lidocaine infusion. Peak latencies of waves IV, V, VI, VII increased after epidural anesthesia compared with control values. Amplitudes of all waves were unchanged following intravenous lidocaine injection compared with control values. Interpeak latencies (I-II, II-III, III-IV, IV-V, V-VI, VI-VII), of every second peak (I-III, II-IV, III-V, IV-VI, V-VII), of every third peak except (III-VI, IV-VII) were unchanged compared with control values. Interpeak latencies of every fourth peak, of fifth peak increased after lidocaine injection compared with control values. The data obtained in this study with lidocaine injection were similar to the data after epidural anesthesia with lidocaine. One of the reason of the latency changes of ABR after epidural anesthesia was the systemic effect of lidocaine absorbed intravenously from the epidural space.

Adult

[Effects of lumbar epidural anesthesia on brainstem auditory response].

Auditory brainstem responses (ABR) are used increasingly to monitor the integrity of neural pathways in anesthetized patients. To evaluate the effect of epidural anesthesia on the central nervous system, we studied the effects of lumbar epidural anesthesia with lidocaine on the ABR in 10 patients. The seven peak latencies (waves I-VII) and amplitudes (waves I-VII) of the ABR were recorded before and 15 min after epidural anesthesia. Peak latencies of waves III, IV, V, VI, VII increased after epidural anesthesia compared with control values. Amplitude of waves II only decreased significantly following epidural anesthesia compared with control values. We further compared the interpeak latencies to investigate the brainstem transmission. Interpeak latencies (I-II, II-III, III-IV, IV-V, V-VI, VI-VII) were unchanged from the control values except waves VI-VII interval. Interpeak latencies of every second peak (II-IV, IV-VI, V-VII), of every third peak (II-V, III-VI, IV-VII), of every forth peak (I-VI, II-VII), of every fifth peak (I-VII) increased after epidural anesthesia compared with control values. The data obtained in the study demonstrated that lumbar epidural anesthesia with lidocaine prolonged the interpeak latencies of ABR. Considering that the waves of ABR are related to anatomically distinct sites in the auditory pathway (I; Acoustic nerve, II; Cochlear nucleus, III; Superior olivary complex, IV; Lateral lemniscus, V; Inferior colliculus, VI: Medial geniculate body, VII; Auditory radiation), the delay in the latencies of ABR seems to be present in the time intervals which involve more than two or three synaptic transmissions.

Anesthesia, Epidural

[Effects of rectal premedication and the mother's presence on induction of pediatric anesthesia].

The effects of the rectal premedication and the mother's presence on induction of anesthesia were studied with 67 children between the ages of 1 and 6 years. All children were induced with mask using nitrous oxide-oxygen-halothane. Children's emotional states during induction were categorized as excellent, good or fair. Rating of excellent or good was considered to indicate satisfactory induction. Forty-seven children were accompanied by their mother. Twenty-two of them were premedicated with rectal bromazepam (3 mg), while another twenty-five children were not premedicated. Satisfactory induction after premedication was performed on 78% of the 1-3 year olds and 100% of the 4-6 year olds, whereas without rectal premedication, satisfactory induction was achieved in 42% of the 1-3 year olds and 69% of the 4-6 year olds. Rectal premedication was important for satisfactory induction. Another twenty of all children were premedicated with rectal bromazepam (3 mg) and induced without mother presence. Satisfactory induction was performed on 38% of the 1-3 year olds and 100% of the 4-6 year olds. Mother's presence tended to lead to satisfactory induction. Furthermore, we sought feedback from the mothers about their presence during induction of anesthesia. Almost all of the mothers said they appreciated the opportunity to be present, with the exception of four mothers (8.5%) who reported feeling of some anxiety to be in an operating room.

Administration, Rectal

[A case report of anesthetic management of orthotopic liver transplantation from a living donor to his son].

In November 1989, transplantation of a liver graft from a living related donor was performed at Shimane Medical University Hospital. The donor was a 26-year-old man and the recipient his 1-year-old son. The child had been in end stage of liver cirrhosis. Before the surgery, he required intensive care because of massive bleeding from varices. Anesthesia of the recipient was rapidly induced with ketamine and the trachea was intubated with succinylcholine using cricoid pressure. Anesthesia was maintained with enflurane, fentanyl and pancuronium. Nitrous oxide was used only in the preanhepatic period. Total surgical time and anesthetic time were 945 min and 1065 min, respectively. Total estimated blood loss was 3650 ml and 2780 ml of fresh whole blood was transfused. Careful attention was paid to body temperature, serum potassium, ionized calcium and blood coagulation function, as well as to general cardiovascular and respiratory functions. During anhepatic period, the inferior caval vein was not clamped. Hemodynamic function was relatively stable throughout the operation. At the time of reperfusion of the transplanted graft, there was little change in serum potassium levels or other parameters. Postoperative mechanical ventilation was required for 8 days.

Adult

[Cardiac arrest during anesthesia--a case of effective open chest massage].

A 58-year-old man suffering from esophageal cancer was scheduled for radical resection and reconstruction of the esophagus. Immediately after the start of the operation, with the patient under general anesthesia, cardiac arrest occurred. The operation was immediately discontinued and closed chest heart massage was started. As the patient did not respond, open chest massage was initiated. Cardiac arrest can be caused by any one of a number of factors. This case was suspected to have had a coronary artery spasm. It took a total of 100 minutes to resuscitate the patient. But resuscitation was successful without any resulting neurological damage. This was attributed to appropriate open chest massage. If a case of cardiac arrest due to any coronary artery disease does not respond to the usual cardiopulmonary resuscitation, we should consider open chest massage.

Anesthesia, General

[Effects of intravenous lidocaine administration on median nerve somatosensory evoked potentials].

The effect of lidocaine on the median nerve somatosensory evoked potential (SSEP) was investigated in 14 neurologically normal patients. Lidocaine 1.5 mg.kg-1.min-1 was injected intravenously over a 5 min period immediately followed by a continuous infusion of lidocaine 60 micrograms.kg-1.min-1. The peak latencies (N1, P2, N2) and amplitudes (N1-P2, P2-N2) of the SSEP response over the sensory cortex were recorded before and after lidocaine infusion. The peak latencies in the control group and in the experimental group after lidocaine infusion of N1, P1, N2 were 19.4 +/- 1.0 msec, 19.7 +/- 1.0 msec (N1), 24.6 +/- 1.4 msec, 25.0 +/- 1.5 msec (P2), 32.5 +/- 2.5 msec, and 33.3 +/- 2.8 msec (N2), respectively. The amplitudes in the control group and in the experimental group after lidocaine infusion of N1-P2, P2-N2 were 9.0 +/- 4.3 microV, 10.3 +/- 4.7 microV (N1-P2), 7.2 +/- 3.6 microV, 8.6 +/- 3.9 microV (P2-N2), respectively. Peak latencies of all components (N1, P2, N2) increased after lidocaine infusion compared with control values. Amplitude of N1-P2 and P2-N2 increased significantly following lidocaine infusion compared with control values. The data obtained in this study suggested that the changes in peak latencies and amplitude after epidural anesthesia with lidocaine were due to the systemic effect of lidocaine absorbed intravenously from the epidural space.

Aged

Determination of 2,5-hexanedione and N-methylformamide in urine by gas chromatography.

Methods for the clinical testing of 2,5-hexanedione and N-methylformamide, urinary metabolites of n-hexane and N,N-dimethylformamide, respectively, were established by capillary column GLC. Recovery rates of 2,5-hexanedione and N-methylformamide from urine were 80.2-108.9% and 99.6-104.2%, respectively. Coefficients of variation (C.V.) for the amount of each product added were 3.1%, 1.8% (intra-assay) and 5.7%, 3.3% (inter-assay), respectively. The concentration ranges of metabolites from urine of healthy subjects without exposure to these organic solvents were less than or equal to 0.5 mg/l (2,5-hexanedione), less than or equal to 1.5 mg/l (N-methylformamide), respectively.

Air Pollutants, Occupational