New ghrelin agonist, HM01 alleviates constipation and L-dopa-delayed gastric emptying in 6-hydroxydopamine rat model of Parkinson's disease.

BACKGROUND: Constipation and L-dopa-induced gastric dysmotility are common gastrointestinal (GI) symptoms in Parkinson's disease (PD). We investigated the novel ghrelin agonist, HM01 influence on GI motor dysfunctions in 6-hydroxydopamine (6-OHDA) rats. METHODS: HM01 pharmacological profiles were determined in vitro and in vivo in rats. We assessed changes in fecal output and water content, and gastric emptying (GE) in 6-OHDA rats treated with orogastric (og) HM01 and L-dopa/carbidopa (LD/CD, 20/2 mg/kg). Fos immunoreactivity (ir) cells in specific brain and lumbosacral spinal cord were quantified. KEY RESULTS: HM01 displayed a high binding affinity to ghrelin receptor (Ki: 1.42 ± 0.36 nM), 4.3 ± 1.0 h half-life and high brain/plasma ratio. 6-OHDA rats had reduced daily fecal output (22%) and water intake (23%) compared to controls. HM01 (3 and 10 mg/kg) similarly reversed the decreased 4-h fecal weight and water content in 6-OHDA rats. Basal GE was not modified in 6-OHDA rats, however, LD/CD (once or daily for 8 days) delayed GE in 6-OHDA and control rats that was prevented by HM01 (3 mg/kg acute or daily before LD/CD). HM01 increased Fos-ir cell number in the area postrema, arcuate nucleus, nucleus tractus solitarius, and lumbosacral intermediolateral column of 6-OHDA rats where 6-OHDA had a lowering effect compared to controls. CONCLUSIONS & INFERENCES: 6-OHDA rats display constipation- and adipsia-like features of PD and L-dopa-inhibited GE. The new orally active ghrelin agonist, HM01 crosses the blood-brain barrier and alleviates these alterations suggesting a potential benefit for PD with GI disorders.

Preparation of tartary buckwheat protein product and its improving effect on cholesterol metabolism in rats and mice fed cholesterol-enriched diet.

Tartary buckwheat protein product (TBP) was prepared from buckwheat flour by alkali extraction and isoelectric precipitation. The protein content of TBP was 45.8%, and its amino acid composition of TBP was similar to that of common buckwheat protein product (BWP). SDS-PAGE analysis showed that the protein profile of TBP was partially different from that of BWP. TBP contained more quercetin (1710 mg/100 g) than BWP (5.4 mg/100 g), while there was a small difference in the contents of rutin between them. In experiment 1, the consumption of BWP and TBP at 20% net protein level for 13 d caused 32% and 25% reductions in serum cholesterol of rats fed cholesterol, respectively, when compared to the consumption of casein (P < 0.05). The reduction of serum cholesterol by BWP and TBP was associated with enhanced excretion of fecal neutral sterols. In experiment 2, the consumption of BWP and TBP for 27 d caused 62% and 43% reductions in the lithogenic index in mice fed cholesterol, respectively (P < 0.05). The reduction in lithogenic index was associated with enhanced excretion of fecal bile acids. Taken together, these results suggest a potential source of TBP as a functional food ingredient as well as BWP.

[Anterior cerebral artery dissecting aneurysm associated with fibromuscular dysplasia (FMD): a case report].

We have recently encountered a rare case of anterior cerebral artery dissecting aneurysm, presenting cerebral infarction and subarachnoid hemorrhage, associated with fibromuscular dysplasia (FMD). A 50-year-old woman was admitted to our hospital with complaints of headache and hemiparesis. A right carotid angiogram obtained 9 hours after the onset revealed stenosis and slight dilatation in the A1 portion of the anterior cerebral artery. At 12 hours after the onset, the patient fell into a coma. CT scan showed diffuse subarachnoid hemorrhage. An angiogram had revealed aneurysmal dilatation and double lumen in the A1 portion, but, 34 days after the onset, angiogram showed growth of the aneurysm in the A1 portion and stenosis in the A2 and A3 portions. At 38 days after the onset, the trapping of the dilated aneurysm to prevent rerupture was performed. Pathological diagnosis was concluded to be FMD. We concluded that FMD caused stenosis as well as the formation and rupture of the dissecting aneurysm in the anterior cerebral artery.

[A case of Sjögren's syndrome with dermatomyositis who died of rapidly progressive interstitial pneumonia].

We report a case of 55 year-old woman with six year history of Sjögren's syndrome developed fatal rapidly progressive interstitial pneumonia. She had been well until February 1999. She developed swelling and erythematous lesions in the cheek and hands in spring 1999. She was admitted to our hospital for investigations of skin lesions in May 1999. Physical examination on admission revealed small hemorrhagic lesions in the nailfold. Serum CK level was slightly elevated. Electromyogram and MRI suggested mild myositis in the proximal upper extremities. She was suspected to have dermatomyositis along with Sjögren's syndrome. Prednisolone 10 mg/day had been given for her skin problems since March 1999. Suddenly, dyspnea on exertion was appeared on 34th day of admission. Chest X-ray film showed an acute worsening of interstitial pneumonia. Methylprednisolone pulse therapy (1000 mg for 3 days) and cyclophosphamide pulse therapy (500 mg for a day) were started, and she was subsequently treated with 60 mg/day of prednisolone and 250 mg/day of Cyclosporin A. However, interstitial pneumonia did not respond to the treatment, and pneumomediastinum and pneumothorax have developed. She died of respiratory failure on 55th day. We consider that most likely explanation for fatal interstitial pneumonia is concomitantly occurred dermatomyositis.

Intracranial electroencephalographic changes in deep anesthesia.

OBJECTIVE: It is well known that electroencephalograms (EEGs) show electrical silence in deep anesthesia as well as brain death. This is the first report on intracranial EEG changes in deep anesthesia. METHODS: We developed a new direct brain monitoring system capable of recording intracranial EEGs. This study included 13 patients with head trauma or cerebrovascular accident under deep anesthesia. RESULTS: The intracranial EEGs showed different patterns of wave activity in depth compared with the cortical surface. In 3 of the cases, the scalp EEG showed a flat tracing at 2.0-2.5% of isoflurane. In two of the cases, the intracranial EEGs showed electrical silence when the scalp EEG was flat. Decreasing the concentration of isoflurane to 1.5%, the intracranial EEG showed single paroxysmal appearance of 'revival' theta waves on the electrocorticogram (ECoG) or electroventriculogram (EVG). The intracranial 'revival' wave was followed by high-voltage burst-waves. In another case, at 2.0-2.5% of isoflurane, the amplitude of the waves was greatest on the EVG. CONCLUSION: There is wave activity difference in the brain depth, which the scalp EEG is unable to show. Intracranial EEGs are able to show the first signs of revival after a nearly flat tracing in deep anesthesia.

[Marginal zone lymphoma associated with Sjögren's syndrome and hepatitis C virus infection].

A 64-year-old female was admitted in May 1997, because of salivary gland swelling. Histology of the right parotid gland revealed malignant lymphoma, diffuse medium-sized B-cell type, and she was treated with local radiotherapy and chemotherapy. She was rehospitalized in April 1998, because of recurrence of lymphoma in the stomach and the sigmoid colon. She had splenomegaly and lymphadenopathy (neck and inguinal). Laboratory findings revealed marked elevation of rheumatoid factor and RNA of hepatitis C virus. A diagnosis of Sjogren's syndrome was made by dryness and the histological findings of labial biopsy. Marginal zone B-cell lymphoma mainly consisted of centrocyte-like cells and lymphoepithelial lesions, and CD 20 and IgM-kappa were positive with immunohistochemical staining. Lymphoma involved the gut and spleen. We discuss the correlation of malignant lymphoma with Sjogren's syndrome and HCV infection.

Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype.

Muscarinic acetylcholine receptors consist of five distinct subtypes and have been important targets for drug development. In the periphery, muscarinic acetylcholine receptors mediate cholinergic signals to autonomic organs, but specific physiological functions of each subtype remain poorly elucidated. Here, we have constructed and analyzed mutant mice lacking the M(3) receptor and have demonstrated that this subtype plays key roles in salivary secretion, pupillary constriction, and bladder detrusor contractions. However, M(3)-mediated signals in digestive and reproductive organs are dispensable, likely because of redundant mechanisms through other muscarinic acetylcholine receptor subtypes or other mediators. In addition, we have found prominent urinary retention only in the male, which indicates a considerable sex difference in the micturition mechanism. Accordingly, this mutant mouse should provide a useful animal model for investigation of human diseases that are affected in the peripheral cholinergic functions.

Mapping of five subtype genes for muscarinic acetylcholine receptor to mouse chromosomes.

Muscarinic acetylcholine receptors in mammals consist of five subtypes (M1-M5) encoded by distinct genes. They are widely expressed throughout the body and play a variety of roles in the peripheral and central nervous systems. Although their pharmacological properties have been studied extensively in vitro, colocalization of the multiple subtypes in each tissue and lack of subtype-specific ligands have hampered characterization of the respective subtypes in vivo. We have mapped mouse genomic loci for all five genes (Chrm1-5) by restriction fragment length variant (RFLV) analyses in interspecific backcross mice. Chrm1, Chrm2, and Chrm3 were mapped to chromosome (Chr) 19, 6, and 13, respectively. Both Chrm4 and Chrm5 were mapped to Chr 2. Although a comparison of their map positions with other mutations in their vicinities suggested a possibility that the El2 (epilepsy 2) allele might be a mutation in Chrm5, sequencing analyses of the Chrm5 gene in the El2 mutant mice did not support such a hypothesis.

Acute hydrocephalus in posterior fossa injury.

This is the first known report of the use of computerized tomography (CT) scanning to examine acute hydrocephalus in posterior fossa injury. Of the 1802 patients with acute head trauma treated at Funabashi Municipal Medical Center, 53 (2.9%) had suffered injury to the posterior fossa. Of these, 12 patients (22.6%) had associated acute hydrocephalus: nine patients with acute epidural hematoma (AEH) and three with intracerebellar hematoma and contusion (IH/C). There was a significant relationship between cases of AEH with hydrocephalus and supratentorial extension, hematoma thickness of 15 mm or more, and abnormal mesencephalic cisterns. In cases of IH/C, bilateral lesions and no visible fourth ventricle were significant causes of hydrocephalus. According to these results, possible mechanisms of acute hydrocephalus in posterior fossa injury may be as follow: in cases of AEH, hematoma that extends to the supratentorial area compresses the aqueduct posteriorly and causes hydrocephalus; in cases of IH/C, hematoma and contusional lesions may directly occlude the fourth ventricle and cause acute hydrocephalus. Seven patients suffering from AEH with acute hydrocephalus underwent evacuation of their hematoma without external ventricular drainage. In these cases, CT scanning showed that the hydrocephalus improved immediately after evacuation of the hematoma. Two patients suffering from IH/C with hydrocephalus underwent a procedure for evacuation of the hematoma and external ventricular drainage. The authors do not believe that ventricular drainage is necessary in treating posterior fossa AEH. However, both evacuation of the hematoma and ventricular drainage are necessary in cases of IH/C with hydrocephalus to provide the patient with every chance for survival. There was no significant difference in mortality rates when cases of AEH with acute hydrocephalus (0%) were compared with cases of AEH without hydrocephalus (7.7%). The observed mortality rates in cases of IH/C with hydrocephalus and those without hydrocephalus were 100% and 15.4%, respectively; this is statistically significant.

[Trigeminal neuralgia caused by tortuous vertebrobasilar system--the clinical and imaging features].

Ten (6.8%) out of 146 patients with trigeminal neuralgia (TN) who underwent SPGR-MRI and 3D-TOF-MRA from August 1993 to October 1996, were found to have vascular compression caused by a tortuous vertebrobasilar system (TVBS). They were mostly males, demonstrated left-sided predominance, and had ipsilateral hemifacial spasm, compared with other 52 patients whose offending arteries were either superior cerebellar artery (SCA), anterior inferior cerebellar artery (AICA)or posterior inferior cerebellar artery (PICA). The patients who showed vascular compression by TVBS, presented an artery which compresses and dislocates the rootentry zone (REZ) of the trigeminal nerve, presses the brain stem at REZ and simultaneously compresses the REZ of the facial nerve. In addition, the diameters of the two branches of vertebrobasilar artery were not equal. These features indicate that the atherosclerotic change of the offending artery in TN caused by TVBS is more severe than that caused by SCA, AICA or PICA. This change causes an irregular running of artery which leads a strong compression of the trigeminal nerve REZ and of the brain stem. Consequently, the facial nerve REZ is severely affected leading to the presence of tic convulsif in TN caused by TVBS.

Angiographically unrecognized microaneurysms: intraoperative observation and operative technique.

Twenty operated cases of angiographically unrecognized microaneurysm (AUM) have been analysed with special reference to intra-operative observations and clipping-technique. Among the patients with intracranial aneurysms that the authors' facility has operated upon, the incidence of asymptomatic incidental AUM that was 2 mm or smaller amounted to 3.7%. Thirteen cases of AUM were found on the middle cerebral artery; four AUMs arose from the M1 portion, four from the bifurcation, and five from the second bifurcation. Sixty percent of AUMs were recognized on the parent arteries of ruptured aneurysms. In 90% of cases the AUMs were broad based in shape and in 70% of cases exhibited a thin-walled neck and a thin-walled fundus. Intra-operative findings revealed four reasons why AUMs were not visible in the pre-operative angiograms: (1) the AUM was sandwiched between two arteries; (2) the AUM was completely hidden by a contiguous large or giant aneurysm; (3) the AUM was diagnosed by pre-operative angiogram as a bleb of the contiguous aneurysm; (4) the AUM was not visible on angiograms because the height of the AUM was extremely low. Twelve cases of AUM were successfully clipped using four different clipping techniques; (1) clipping parallel to the bifurcation in four, (2) clipping parallel to the parent artery in four, (3) pinch-clipping in two of the cases, and (4) cross clipping in two of the cases. The other eight cases were wrapped and coated. AUMs may be present during the direct operation of intracranial aneurysms and in intravascular surgery. Neurosurgeons and neuroradiologists need to explain the possible existence of AUMs to patients and their families.

Distribution of referred pain from the lumbar zygapophyseal joints and dorsal rami.

OBJECTIVE: The purpose of this study was to determine the distribution of referred pain from the lumbar zygapophyseal joints (L1/2 to L5/S1) and the medial branches of the lumbar dorsal rami (Th12 to L5) in a large number of patients with chronic low back pain. SETTING: This study was conducted at the pain clinics of Kanto Teishin Hospital and Hannan Central Hospital from March 1994 to May 1996. PATIENTS AND DESIGN: Chronic low back pain patients who underwent zygapophyseal joint injection or radiofrequency facet denervation were studied. Under fluoroscopic control, the joints from L1/2 to L5/S1 were stimulated by injection of contrast medium, and the lumbar medial branches of the dorsal rami from Th12 to L5 underwent electrical stimulation during radiofrequency facet denervation. OUTCOME MEASURES: If the injection or electrical stimulation reproduced the patient's usual pain, the distribution of induced pain was determined, and the sites of induced pain were divided into six areas. RESULTS AND CONCLUSIONS: A total of 71 joints and 91 medial branches were studied in 48 patients. The distribution of referred pain from the L1/2 to L5/S1 zygapophyseal joints, and the medial branches of the dorsal rami from L1 to L5 were similar for each level stimulated, and the overlap of referred pain between each level was considerable.

[Identification of offending vessels in trigeminal neuralgia and hemifacial spasm using SPGR-MRI and 3D-TOF-MRA].

We investigated 100 consecutive patients with trigeminal neuralgia (TN) and 53 patients with hemifacial spasm (HFS) concerning the anatomical relationship between the root entry (exit) zone (REZ) of cranial nerve and the offending artery, using spoiled GRASS MRI (SPGR-MRI) and three dimensional-time of fly-MRA (MRA). In 67 of 100 (67%) patiets with TN, this new radiological method, SPGR-MRI and MRA demonstrated the relationship between the fifth cranial nerve root and offending artery causing neurovascular compression (NVC), and in 46 of 53 (87%) with HFS, demonstrated the similar relationship between seventh and eighth nerve complex and offending artery. Microvascular decompression (MVD) was performed in 10 with HFS, and NVC of the REZ of the facial nerve caused by the offending artery was exactly predicted by SPGR-MRI and MRA in 9 (90%). The combination of SPGR-MRI and MRA is very useful for demonstrating NVC as the cause of TN and HFS. On the other hand, we investigated asymptomatic 206 trigeminal and 253 facial nerves about the relationship between their REZ and the surrounding structures using the similar method. The contact of REZ of cranial nerve with surrounding artery is demonstrated in 31.6% of trigeminal nerves and in 22.5% of facial nerves. These results indicate that the contact of REZ of cranial nerve with surrounding artery is not rare in healthy subjects, though causing TN and HFS in particular patients. In this context, we discussed the difference between the contact which is asymptomatic and the compression which is symptomatic.

Development and evaluation of oral reporting system for PACS.

Experimental workstations for oral reporting and synchronized image filing have been developed and evaluated by radiologists and referring physicians. The file media is a 5.25-inch rewritable magneto-optical disk of 600-Mb capacity whose file format is in accordance with the IS&C specification. The results of evaluation tell that this system is superior to other existing methods of the same kind such as transcribing, dictating, handwriting, typewriting and key selections. The most significant advantage of the system is that images and their interpretation are never separated. The first practical application to the teaching file and the teaching conference is contemplated in the Osaka University Hospital. This system is a complete digital system in terms of images, voices and demographic data, so that on-line transmission, off-line communication or filing to any database will be easily realized in a PACS environment. We are developing an integrated system of a speech recognizer connected to this digitized oral system.

[Development of oral reporting system in PACS environment].

An experimental radiologic reporting system using oral presentations has been developed and tested. The rewritable and compact magneto-optical disk (MOD) is employed to store oral diagnostic reports together with read radiologic images. The MOD is 5.25 inches in diameter, has a 600 MB memory capacity, and is erasable, light and compact. Advantages of the system are simultaneous retrieval of oral reports by a radiologist and the images he or she interpreted, and the capability of media circulation in addition to the function of filing. Thus MOD has a multimedia function of both off-line communication and filing. When medical images are interpreted and oral presentations are registered, automatically digitized oral reports and digitized images are filed in the MOD. Referring physicians can get oral diagnostic reports and can see the images at the same time on a personal computer. Furthermore, integration with voice recognition capability is being tried in our experiment.

[Treatment of cancer pain with the percutaneous electrocoagulation of spinal nerves].

To our knowledge, this is the first report of high-frequency thermocoagulation applied to the spinal root. We treated 34 patients suffering from cancer pain with this technique. Among these patients, cancer pain occurred due to intrapelvic metastasis in 11 patients, and 13 complained of chest pain due to cancer. Every patient was considered to have good or excellent response when his or her pain score was reduced to 6 points or less from the score before thermocoagulation; 10 points. Based on this criterion, 54.5% and 30.8% of the above-mentioned patients showed good and excellent responses respectively one month after treatment. This technique, therefore, was considered to be effective with less side effects compared with other nerve blocking techniques.

[Six cases of epidural abscess probably caused by epidural block and examination by gadolinium-MRI imaging].

We treated six cases of epidural abscess caused probably by epidural block. Three patients were given only chemotherapy and the other three underwent surgical treatment. Four patients were cured completely, but bilateral paresis in the lower limbs persisted in two patients. The symptoms at onset, laboratory findings, imaging findings including MRI and CT, treatment methods and prognosis were reported. Accelerated blood sedimentation rate, positive CRP results and abnormal findings at the site of the catheter insertion appeared to be important initial signs for the early discovery of epidural abscesses. The route of infection, selection of treatment methods, methods of prevention and examination by Gadolinium-MRI imaging were also discussed.