Two Cases of Cesarean Sections Performed with Combined Spinal-Epidural Anesthesia with Perioperative Asthma Attacks / 日本東洋医学雑誌

Asthma attack difficulty breathing rapidly worsens the condition over time. Especially when the condition worsens before surgery, general anesthesia (GA) may be indicated depending on the type of surgery. In Japan, there is a tendency to avoid GA in cesarean section (C/S) due to the risk of difficult intubation, adverse effects on the fetus, and concerns about resuscitation of the newborn. This time, foreign body sensation in the throat (baikakuki) was found in a case of asthma-like attack accompanied by difficulty breathing caused by disturbance symptoms on the day of C/S and in a case of difficulty breathing due to preoperative antibiotic intravenous drip. After oral administration of hangekobokuto to the patients, dyspnea disappeared in either case, and I was able to avoid GA and perform C/S with combined spinal-epidural anesthesia. Considering asthma in Kampo medicine, it is thought that psychoactive predispositions such as anxiety and impatience are the triggers that cause qi counter flow and qi stagnation, which causes phlegm to condense, resulting in baikakuki and symptoms. Therefore, it was thought that hangekobokuto, which remove phlegm, was adapted.

Hangekobokuto, a traditional Japanese herbal medicine, ameliorates postoperative ileus through its anti-inflammatory action.

BACKGROUND/AIMS: Gastroprokinetic agents are used for patients with postoperative ileus (POI), and the Japanese traditional herbal medicine daikenchuto (DKT) is one such agent used in the clinical setting. POI is caused by inflammation. DKT and rikkunshito have anti-inflammatory abilities in addition to their gastroprokinetic effects. The efficacy of Kampo formulations, including hangekobokuto (HKT), in patients with POI has been reported recently. Several authors have described the efficacy of honokiol, the primary component of Magnoliae Cortex, in HKT in mouse models of POI. We therefore analyzed the effect of HKT on POI model mice to determine the similarities in the mechanism of action between HKT and DKT. METHODS: HKT was administered orally to each mouse before and after intestinal manipulation was performed on the distal ileum. The gastrointestinal transit in vivo, leukocyte infiltration, and levels of inflammatory mediators, such as cytokines and chemokines, were analyzed. RESULTS: HKT significantly inhibited the infiltration of neutrophils and macrophages and led to the recovery of delayed intestinal transit. In addition, it significantly decreased inducible nitric oxide synthase (iNOS) as well as honokiol levels, suggesting anti-inflammatory activity. However, it did not inhibit the increase in levels of interleukin (IL)-1beta and IL-6, which are related to iNOS induction. In contrast, HKT increased levels of nerve growth factor (NGF) and suppressed those of nuclear factor-κB (NFκB), which are related to iNOS induction, suggesting the possibility of a neuronal anti-inflammatory mechanism. CONCLUSIONS: HKT exerted a POI-relieving effect similar to DKT in a murine POI model, and findings suggest that it may exert its anti-inflammatory activity through NGF.

Safety of Japanese herbal Kampo medicines for the treatment of depression during pregnancy.

OBJECTIVE: To clarify the fetal safety of herbal Kampo medicines, including Hange-koboku-to, Koso-san, Nyoshin-san, Yokukansan, Yokukansan-kachinpi-hange, Saiko-keishikankyo-to, Keishi-karyukotu-borei-to, and Kanbaku-taisou-to, when administered to pregnant women with depression using a large healthcare administrative database. METHODS: We extracted data from the JMDC Claims Database (2005-2018) for this retrospective cohort study of pregnant women aged 19 years or older admitted to obstetric clinics or hospitals for delivery. Participants were classified into four groups: those without depression, those diagnosed with depression without medication, those given Kampo medicines for depression, and those given western medicines for depression. Neonatal outcomes (congenital anomalies, low birth weight, and preterm birth) were considered as the safety outcome measures. RESULTS: We identified 179 707 eligible mothers. The adverse outcomes did not differ significantly between participants receiving Kampo medicine and those not diagnosed with depression during pregnancy. The proportion of low-birth-weight neonates did not differ significantly between the Kampo medicine and non-depression groups (adjusted odds ratio [aOR] 1.28; 95% confidence interval [CI] 0.86-1.91), but was significantly higher in the unmedicated depression group (aOR 1.31; 95% CI 1.07-1.61) and western medicine group (aOR 1.47; 95% CI 1.18-1.83). CONCLUSION: Kampo medicines are safe for treating depression during pregnancy without increasing the incidence of congenital anomalies, low birth weight, or preterm birth.

Three Cases of Easy Fatigability and Tiredness Successfully Treated with Hangekobokuto / 日本東洋医学雑誌

We describe 3 cases of easy fatigability successfully treated with hangekobokuto. Case 1 was a 44-year-old woman who had been experiencing fatigue for a long time due to her busy work schedule. Juzentaihoto was ineffective, and she felt abdominal swelling and showed epigastric resistance upon abdominal examination. Case 2 was a 13-year-old woman who became easily tired, had palpitations, felt uneasy, and showed epigastric resistance upon abdominal examination, after moving from overseas to Japan. Case 3 was an 18-year-old woman who became easily tired under the pressure of her studies after entering university, felt uneasy, felt abdominal swelling, and showed epigastric resistance upon abdominal examination. Hangekobokuto relieved these symptoms. In Case 2 and Case 3, there were obvious stressors, and qi stagnation was strongly suspected. In Case 1, although the patient did not complain of obvious stress, she did not respond well to juzentaihoto, which compensates for qi deficiency, so we also considered qi stagnation. For symptoms such as “get tired easily,” qi-tonifying formulas are often used, but qi-regulating formulas including hangekobokuto may also be effective. It is also important to focus on the patient’s mental state and living environment.

Rosmarinic acid in Perilla frutescens and perilla herb analyzed by HPLC.

High-quality perilla leaves are defined as those having purple upper and lower surfaces and a pleasant smell. The Japanese Pharmacopoeia specifies the content of essential oils in perilla leaves but not the content of rosmarinic acid. Rosmarinic acid is a common component of Labiatae plants such as shiso (Perilla frutescens Britton var. crispa W. Deane). Rosmarinic acid has been reported to exhibit anti-inflammatory and anti-oxidant activity but the factors affecting the content of rosmarinic acid in plants remain unknown. This study describes a simple and reproducible method for quantifying rosmarinic acid. We elucidated the main causes for the different rosmarinic acid contents of plants by examining various samples of perilla using the proposed method. Significant differences in rosmarinic acid content between varieties and cultivators were observed. The rosmarinic acid content was higher in green perilla compared with red perilla, in wild species compared with cultivated species, and in plants cultivated in outdoor nurseries compared with in indoor nurseries. The proposed quantitative method was used to examine the rosmarinic acid content in a Kampo formula, Hangekobokuto, and was found to be higher in decoctions prepared using the Kouge method compared with the typical preparation method. We examined the chlorophyll and caffeic acid contents of several samples and their relationship with the rosmarinic acid content.

A Case of Hangekobokuto Improved Dysphagia and Aspiration Pneumonia Considered to be Caused by Late-Stage Neurosyphilis / 日本東洋医学雑誌

We investigated the effectiveness of hangekobokuto in alleviating dysphagia and aspiration pneumonia attributed to late­stage neurosyphilis. Our study subject, a 67-year-old man treated for his leg pain in our department, hoped this treatment would relieve his severe cough and sore throat. According to a neurological investigation and the analysis of blood and cerebrospinal fluid, his symptoms (swallowing disturbance and aspiration pneumonia in the lower lobes of both lungs) led to the diagnosis of cerebral bulbar paralysis caused by latestage neurosyphilis. The patient requested drug therapy ; thus, we prescribed 7.5 g/day of hangekobokuto, to be administered orally, based on his medical findings of qi stagnation and tan yin. Dysphagia was relieved one week after oral administration of hangekobokuto, and after three weeks, the patient's discomfort had almost disappeared. Moreover, aspiration pneumonia was also improved in his chest CT image finding. Late-stage neurosyphilis symptoms usually develop within 20 to 30 years of contracting syphilis, an infection caused by the bacterium Treponema pallidum. Symptoms may include a loss of swallowing reflex and cough reflex due to the paralysis of cerebral basal ganglia. However, hangekobokuto was found to increase the concentration of substance P released in the pharyngeal head and tracheal mucosa, and thus improve swallowing function. We conclude that hangekobokuto is a useful agent for alleviating the swallowing abnormality of late-stage neurosyphilis.

A Double-Blind Randomized Controlled Trial to Determine the Preventive Effect of Hangekobokuto on Aspiration Pneumonia in Patients Undergoing Cardiovascular Surgery.

PURPOSE: This study aimed to assess whether hangekobokuto (HKT) can prevent aspiration pneumonia in patients undergoing cardiovascular surgery. METHODS: We performed a single-center, double-blinded, randomized, placebo-controlled study of HKT in patients undergoing cardiovascular surgery. JPS HKT extract granule (JPS-16) was used as HKT. The primary endpoint was defined as the prevention of postoperative aspiration pneumonia. The secondary endpoints included complete recovery from swallowing and coughing disorders. RESULTS: Between August 2014 and August 2015, a total of 34 patients were registered in this study. The rate of subjects with postoperative aspiration pneumonia was significantly lower in the HKT group than in the placebo group (p = 0.017). In high-risk patients for aspiration pneumonia, the rate was significantly lower in the HKT group than in the placebo group (p = 0.015). The rate of subjects with swallowing disorders tended to be lower in the HKT group than in the placebo group (p = 0.091), and in high-risk patients, the rate was significantly lower in the HKT group than in the placebo group (p = 0.038). CONCLUSIONS: HKT can prevent aspiration pneumonia in patients undergoing cardiovascular surgery. In high-risk patients for aspiration pneumonia, HKT can prevent aspiration pneumonia and improve swallowing disorders.

<b>Cyclic Vomiting Syndrome Successfully Treated with </b><b>Hangekobokuto</b> / 日本東洋医学雑誌

<p>A 19-year-old man was referred to our clinic for frequent nausea and vomiting. At age 16, he started to have periodic bouts of nausea and vomiting. During an attack, he would experience vomiting more than ten times a day and was unable to eat, which resulted in hospitalization for a week. Inpatient investigations did not reveal any abnormalities except dehydration. Between attacks, he was asymptomatic. Initially, he had attacks a few times a year. However, beginning at age 19, the attacks occurred almost every month. At our clinic, routine physical examination and laboratory tests were unremarkable. On Kampo medical examination, he had <i>qi </i>stagnation and <i>qi </i>counter-flow. He was diagnosed with cyclic vomiting syndrome. Hangekobokuto was administered with improvement of his symptoms. Hangekobokuto may be effective for cyclic vomiting syndrome with <i>qi </i>stagnation and <i>qi </i>counter-flow as diagnosed with Kampo medicine. This suggests the effectiveness of Kampo medicine in functional gastrointestinal disorders.</p>

Effect of a traditional herbal medicine, hangekobokuto, on the sensation of a lump in the throat in patients with respiratory diseases.

The sensation of a lump in the throat (SLT) is not a rarely encountered symptom. The etiology of SLT appears to be multifactorial, and the psychological characteristics, stress and pressure of a psychiatric disorder may be significant factors in SLT. Hangekobokuto, one of the traditional herbal medicines, is a known drug that has an effect on SLT. The efficacy of a short-term hangekobokuto treatment on SLT was evaluated. To assess whether a 2-week prescription of hangekobokuto improves SLT mainly in patients with respiratory diseases, a retrospective study was performed between April 2013 and August 2015. During the study period, a total of 43 patients were treated with hangekobokuto. Twelve (27.9%) of the 43 patients were reported to experience completely effective treatment (SLT completely disappeared), and 14 (32.6%) experienced moderately effective treatment (25-99% SLT disappeared). Patients with bronchial asthma and those without a medical history of respiratory disease exhibited a good response to hangekobokuto. No specific predictive factor of the response to hangekobokuto on SLT was identified in the multivariate regression analysis. Therefore, the present results suggested that hangekobokuto could be one of the treatment choices for uncontrolled SLT.

<b>Two Cases of Persistent Hiccups with a Previous History of Cerebral Hemorrhage, Successfully Treated with Hangekobokuto Extract</b> / 日本東洋医学雑誌

We report our experience with two patients who had a previous history of cerebral hemorrhage and presented with persistent hiccups. Hangekobokuto was found to be effective in these patients. Case 1 was a 49-year-old man with a history of cerebral hemorrhage who experienced persistent hiccups as a result of pulmonary aspiration that occurred while he was admitted to the hospital for heat stroke. Abdominal palpation revealed epigastric resistance and tenderness. Metoclopramide and shakuyakukanzoto were administered without any amelioration of the symptoms, but the symptoms disappeared 1 hr after changing the drug regimen to hangekobokuto. Case 2 was a 64-year-old man who experienced persistent hiccups 28 days after suffering a cerebral hemorrhage. Abdominal palpation revealed epigastric resistance and tenderness and a lack of resistance at the lower abdomen. Because a regimen of metoclopramide and shakuyakukanzoto was similarly ineffective, we changed the drug regimen to hangekobokuto, and the symptoms subsequently disappeared 7 hr after administration. The symptoms did not recur in either patient following treatment. Hangekobokuto can be effective in cases of persistent hiccups is worth considering as a treatment option.

<b>Two Cases of Stress-induced Chronic Cough Successfully Treated with H</b><b>achimijiogan</b> / 日本東洋医学雑誌

<p>In Kampo, respiratory symptoms are treated with prescriptions related not only to “lung”, but also other parenchymatous viscera. We report 2 patients whose stress-induced chronic cough was ameliorated by <i>hachimijiogan</i>. Case 1 was a 25-year-old female who was working under stressful circumstances at her company and reported an oppressive feeling in the chest. She was initially prescribed <i>hangekobokuto </i>because of a feeling that something was stuck in the pit of her stomach on abdominal examination, but her cough did not get better. As she also noted a dull feeling in her back ; she was switched to <i>hachimigan</i>, and her cough disappeared. Case 2 was 42-year-old female who suffered from depression, sore throat and an obstructive feeling in the throat ; she had been receiving infertility treatment for several years. <i>Hangekobokuto </i>and <i>bakumondoto </i>showed insufficient effect on her persistent cough. Her coughing stopped when she was prescribed <i>hachimigan </i>for back pain. Neither of these patients showed lack of resistance of the lower abdomen on abdominal examination.<br>Chronic <i>ki </i>(qi) stagnation under stressful conditions may cause <i>ki </i>deficiency, especially kidney deficiency. The symptom of stress-induced cough in our cases was considered to be due to kidney deficiency, and therefore <i>hachimijiogan</i>, but not <i>hangekobokuto</i>, was effective. The short duration of the complaints and relatively young age (20-40's) of the patients may account for the absence of the typical abdominal sign of kidney deficiency. Back stiffness and pain may also be important signs for cough due to kidney deficiency.</p>

<b>A Case of Glaucoma Successfully Treated with H</b><b>angekobokuto</b> / 日本東洋医学雑誌

We reported a case of a 69-year-old male who had been diagnosed with left eye glaucoma with surgical indication complicated by an eyesight view obstacle. His left intraocular pressure did not decrease regardless of the eye drop treatment he underwent at another hospital. At the initial visit to our hospital, his left intraocular pressure was 27 mmHg. As we noted marked tympanitic sounds in his abdomen, we prescribed hangekobokuto. After one month of his medication, his left eye intraocular pressure fell to 22 mmHg ; furthermore, the marked abdominal tympanitic sounds disappeared. Two years after his initial treatment, his left intraocular pressure still stayed generally within the normal range, and it did not require surgery. In this case, predominant sympathetic nervous system may have been the mechanism behind some cases of increased intraocular pressure ; therefore, the possibility that hangekobokuto reduces intraocular pressure by acting on this was suggested. As there have been no such reports that hangekobokuto itself has an effect on intraocular pressure decrease, this is considered as a novel case.

<b>Three Cases of the Same Kampo Treatment Applied to a Mother and Daughter with Different Complaints </b> / 日本東洋医学雑誌

We describe three cases in which the same Kampo formulas were applied to a mother and daughter with different complaints. In cases 1 a, b, a mother with general fatigue after an operation for gastric and colon cancer, and her daughter with migraine and menopausal symptoms were effectively treated with kamishoyosan. In cases 2 a, b, a mother with menstrual disorder, and her daughter with palmar eruption were effectively treated with hangekobokuto. In cases 3 a, b, a mother with lumbago and her daughter with back pain were effectively treated with keishikaryukotsuboreito. These Kampo formulas are thought to improve <i>qi </i>circulation.<br>It is considered that improving <i>qi </i>disturbance is important for the Kampo treatment of female patients. Taking into account parent-child genetic similarities, it is possible that application of the same Kampo formula to familiarly related patients with different complaints could be effective. It is important to consider not only the patient's complaints, but also the patient's condition, from the Kampo viewpoint so-called “Sho”. Therefore,since our cases all involved a mother-daughter relationships, it may be reasonable to assume that Kampo formulas improving <i>qi </i>circulation were effective for their different complaints.

<b>Efficacy of Kampo Therapy in Chronic Tinnitus Patients </b> / 日本東洋医学雑誌

Treating tinnitus with modern Western medicines is difficult. Several studies have reported that Kampo medicines are efficacious for treating tinnitus, and therefore, it is expected that these medicines will gain widespread use in the future for tinnitus treatment. We retrospectively examined the efficacy of Kampo medicines prescribed on the basis of Kampo diagnoses for chronic tinnitus patients. The study population included 331 patients (114 men, 217 women) and average age was 57.8 years. The overall effective rate of Kampo medicines in tinnitus was 38.4% and increased to 64.6% after including effects for the accompanying symptoms (e.g., dizziness, insomnia, and headache). Hangekobokuto was prescribed most frequently. The effective rate for hangekobokuto in tinnitus was 32.1% and significantly increased when it was used in combination with a herb, chotoko (Hook of Uncaria, rhynchophylla Miquel) (p < 0.05, Fisher's exact test). The effects and modern pharmacological action of chotoko indicate that it may be effective for tinnitus. Given that tinnitus was intractable in study subjects who had been treated using other therapy approaches earlier (84% of the population), the findings indicate that Kampo medicine may be partially effective for tinnitus.

Treatment of Patients with Floating Sensation after the Great East Japan Earthquake / 日本東洋医学雑誌

We would like to report on the treatment of 15 patients with floating sensation after the Great East Japan Earthquake (2011 Tohoku Earthquake) in 2011.Twelve cases were effectively treated with hangekobokuto, while two cases were effectively treated with hangebyakujutsutemmato, but not with hangekobokuto.One case was effectively treated with ryokeijutsukanto. We discuss how to treat this floating sensation, focusing on the usage of hangekobokuto.<BR>Most patients who were successfully treated with hangekobokuto reported an uneasy feeling with a floating sensation. On the other hand, those who were successfully treated with hangebyakujutsutemmato or ryokeijutsukanto did not feel uneasy, but reported vertigo and upset stomach.Upon abdominal examination, epigastric resistance was frequently observed in the patients treated with hangekobokuto.This resistance decreased as the floating sensation was improved.<BR>Our results indicate that hangekobokuto could be efficacious for patients with floating sensation after an earthquake, who also felt uneasy and showed epigastric resistance upon abdominal examination.

Application of Bukuryoingohangekobokuto and Hangekobokuto for Perniosis with Ki Obstruction / 日本東洋医学雑誌

We experienced four cases of perniosis successfully treated with bukuryoingohangekobokuto, or hangekobokuto. Swollen tongue, pulsation at the pit of the navel, and tympanitic abdominal sounds were taken as common objective findings in all four cases. In addition, decreased surface body temperature was diagnosed at the bilateral hands and feet, so as to be distal from the trunk in palpation. These four cases had both symptoms of an eminent Ki obstruction, and a disorder of body fluid metabolism. For the two cases administered bukuryoingohangekobokuto especially, a state of strong Ki deficiency was diagnosed. Efficacy in each case was prompt. Thus, we consider bukuryoingohangekobokuto and hangekobokuto to be prescriptions worth trying for perniosis that does not responding to the usual Western medicines, or Kampo treatment.

A Case of Hyperhydrosis Patient Treated with Combined Formulation of Hangekobokuto and Ryokeijutsukanto / 日本東洋医学雑誌

We report a case of a 65-year old man who suffered from hyperhydrosis for 15 years and was treated with the combined formulation of hangekobokuto and ryokeijutsukanto as determined by Kampo diagnosis according to traditional logic. Not only excessive sweating but also complications such as a feeling of obstruction in the throat, palpitation at rest, panting at times of light work, and a feeling of residual urine were diagnosed. We conclude that these symptoms were induced by a dysfunction of the qi (vital energy) and jin (nourishing fluids) circulation between the upper and the middle aspect of the body caused by the existence of wet phlegm, which were ameliorated by the effects of eliminating phlegm, and regulating stagnated or regurgitated qi with this combined formulation.

Efficacy of Hangekobokuto on Patients with Functional Dyspepsia, with Special Reference to its Clinical Indication and Gastrointestinal Function / 日本東洋医学雑誌

We have limited evidence as to the clinical indications for Kampo medicines, especially as they relate to gastrointestinal function. Thus, we investigated the efficacy of the Kampo medicine hangekobokuto (HKT) on patients with functional dyspepsia (FD), with special reference to its clinical indications for gastrointestinal function, including gastric emptying and bowel gas volume.Gastric emptying rate (GER) in FD patients was significantly facilitated by HKT. HKT also improved the gastrointestinal symptoms of the patients. Among these, patients who had inchuusharen, or a symptom of globus sensation, and a representative indication for HKT, showed significant improvement of both their GER and gastrointestinal symptoms compared with patients who did not have inchuusharen. As for bowel gas, the bowel gas volume calculated from a plain abdominal radiogram (gas volume score, GVS) in FD patients decreased significantly, after administration of HKT. Patients who had fukuman, or a feeling that one's stomach is full or bloated, and another representative indication for HKT, showed significant decrease of their GVS to normal levels, compared with patients who did not present with fukuman.These results suggest that the presence of clinical indications, such as inchuusharen or fukuman, are strongly related to HKT efficacy in patients with FD, and that these are useful, scientifically validated markers for the efficient use of HKT.

Practice and Perspective of Clinical Research on Kampo Medicine / 日本東洋医学雑誌

I will illustrate our research, which elucidate the efficacy of Kampo medicines for “Ki”.In order to compare hangekobokuto with kososan, we assessed them by binocular infrared video pupillography. The results revealed that sympathetic nerve activity was inhibited by taking hangekobokuto in the patients belonging to sympathetic dominant group, while it was stimulated by taking kososan in the patients belonging to parasympathetic dominant group.Administration of hangekobokuto has decreased the value of brachial-ankle pulse wave velocity. This result suggests that hangekobokuto ameliorates the elasticity of vascular wall, which is closely related to autonomic nervous system.The gastric emptying rate, which was evaluated by ultrasonographic method in FD patients, showed its significant increase after administration of hangekobokuto.Global gene expression analysis using a DNA chip has shown the pharmacological actions of kososan.In the animal study using depression-like model mice, we have found that kososan decreased the suppression of neurogenesis.

Investigation of Clinical Indications of Hangekobokuto / 日本東洋医学雑誌

Hangekobokuto, on the basis of Jin-kui-yao-lue, has been used to treat acute and chronic gastric disease, psychiatric disorders, abnormal sensation in the throat, and edema which gives the feeling of a small food particle obstructing the throat. We experienced 2 cases involving a sense of incongruity in the interscapular region (pain and/or stiffness), which were successfully treated with hangekobokuto extract.On the basis of these first cases, we investigated the efficacy of hangekobokuto extract in 15 patients having both “ki-utsu” and “suitai”, and a sense of incongruity (pain and/or stiffness) in the interscapular region, without the throat-obstructive feeling of a small in-situ food particle.Improvements in complaints were observed in all patients, with a reduction or disappearance of their sense of incongruity in the interscapular region. Thus, it is possible that hangekobokuto could be widely applicable where symptoms of tenderness or a sense of incongruity in the interscapular region occur (especially the sides of the spinous process of thoracic vertebrae 4-7), in addition to the previously documented indications (heart burn, epigastric discomfort and abdominal fullness).