Pathological study of corticospinal-tract degeneration in Friedreich''s ataxia

The pattern of fibre degeneration in the lateral corticospinal tract (LCST) was studied in a case of Friedreich's ataxia (FA). There was preferential involvement of the lateral area of the LCST in the cervical spinal cord. More caudally, the degeneration involved the entire area of the LCST and did not reveal a medial to lateral gradient of involvement. We suggest that this distinctive pattern of tract degeneration is a consequence of the somatotopic organization of the LCST, with the dying-back degeneration preferentially affecting those LCST fibers that extend to the lumbo-sacral spinal cord. This pattern of tract degeneration may be a useful morphological marker of dying-back degeneration in corticospinal tracts.     

Influence of left ventricular filling proffle during preceding control beats on pulse pressure during ventricular premature contractions

We investigated whether the left ventricular filling profile,defined as the early to late diastolic left ventricular fillingvolume ratio, during the preceding control beats actually affectsthe pulse pressure during a ventricular premature contraction(PVC). Twenty patients underwent invasive electrophysiologicalstudy for sinus bradycardia. VPCs with various coupling intervalswere induced by right ventricular electrical stimulation, andthe mitral filling flow velocity pulsed Doppler echocardiography,the femoral arterial pressure curve and the electrocardiogramwere simultaneously recorded The early to late diastolic velocity-rimeintegral ratio (E₁/A₁ ratio) of the mitral filling flow velocityduring the control beats which preceded the VPC was measuredas an index characterizing left ventricular filling profile.The coupling interval of each VPC and the extrasystolic beatpulse pressure were measured The ratio of the extrasystolicbeat pulse pressure to the control beat pulse pressure was expressedin % (% extrasystolic beat pulse pressure). The correlationbetween the coupling interval and the % extrasystolic beat pulsepressure was investigated. Coupling intervals of 0·80,0·70, 0·60, 0·50, and 0·45 s wereused At a coupling interval of 0·80 or 0·45 s,the % extrasystolic beat pulse pressure showed no significantcorrelation with the E₁/A₁ ratio. In contrast, the % extrasystolicbeat pulse pressure with coupling intervals of 0·70,0·60, and 0·50 s showed a significant positivecorrelation with the E₁/A₁ ratio (r=0·67, 0·74,and 0·66 P<0·01, respectively). In additionto the prematurity and the site of origin of the VPCs, the leftventricular filling profile during the preceding control beatsmay significantly affect the height of the pulse pressure duringextrasystoles with medium length coupling intervals.     

FLUMAZENIL DOES NOT ANTAGONIZE HALOTHANE, THIAMYLAL OR PROPOFOL ANAESTHESIA IN RATS{dagger}

We have studied the effects of flumazenil on sleep time andEEG in rats anaesthetized with 1.5% halothane, propofoi 20 mgkg^–1, thiamylal 30 mg kg^–1, or combinations of diazepam5 mg kg^–1 and anaesthetic agents. We also studied theeffects of flumazenil 0.3, 3 and 30 mg kg^–1 on behaviourand EEG. Flumazenil 0.3 and 3 mg kg^–1 alone had no effecton behaviour or EEG, but flumazenil 30 mg kg^–1 had depressiveeffects similar to those of diazepam on behaviour and EEG. Flumazenil0.3, 3 and 30 mg kg^–1 i.v., antagonized the effects ofdiazepam 10 mg kg^–1 i.v. on behaviour and EEG. Flumazenilhad no antagonistic effect on sleep time induced by anaestheticagents, but flumazenil 30 mg kg^–1 potentiated propofol-inducedanaesthesia. Flumazenil did not affect anaesthesia-induced EEGchanges. Diazepam 5 mg kg^–1 potentiated anaesthesia. Flumazenilantagonism of diazepam potentiation varied with anaestheticagent: flumazenil 0.3 mg kg^–1 antagonized diazepam actionin halothane anaesthesia, but 30 mg kg^–1 was requiredin propofoi anaesthesia; this large dose was insufficient inthiamylal anaesthesia. ^*Present address: Department of Anesthesia, Omiya Medical Center,Omiya 330, Japan.      

Dissolution of pancreatic stones by oral trimethadione in patients with chronic calcific pancreatitis

Abstract The effect of oral dissolution therapy for pancreatic stones was evaluated in patients with chronic calcific pancreatitis. The anti-epileptic agent trimethadione was given orally to 30 outpatients at a dose of 0.9–1.5 g daily. On plain X-ray films and CT scans of the abdomen, pancreatic stones began to be dissolved around 8 months of treatment, and diminished in size and number or disappeared in 21 patients (70%) during the mean follow-up period of 32 months. The effect of trimethadione treatment on dissolution of stones was not closely related to the aetiology of the disease, distribution and size of stones, previous history of surgical interventions, or the degree of pancreatic dysfunctions. In three patients who stopped this medication of their own accord, pancreatic stones re-increased or reappeared about 6 months later. During trimethadione treatment, impaired exocrine pancreatic function returned to normal in four of nine patients examined, and diabetes mellitus was well controlled by either diet therapy alone or oral hypoglycaemic agents in eight of 10 patients who did not need insulin before trimethadione treatment. Complete relief of pain was noted in 73% of patients during the treatment. Overall gains and no change in bodyweight were observed in 83% of patients. Mild photophobia was the most common side effect, but could be easily overcome by wearing sunglasses. No severe side effects were observed in the liver, kidney, blood or the eyeground. Pancreatic stones in 30 patients not treated with trimethadione neither disappeared nor diminished spontaneously. Trimethadione treatment may be a useful tool for chemical dissolution of pancreatic stones.     

Effect of dimethadione administered intravenously on pancreatic secretion in dogs

Abstract In order to detect both pancreatic excretion of dimethadione (DMO), a weak organic acid, and the effect of pancreatic DMO on secretin-stimulated pancreatic secretion, DMO was given intravenously to dogs with pancreatic fistulae at a dose of 50, 100 and 200 mg/kg. DMO was promptly excreted into pancreatic juice; the concentration decreased exponentially as it did in plasma at the highest dose of the compound. At equilibrium of DMO between pancreatic juice and plasma, the DMO concentration in the juice depended directly on that in plasma; the juice/plasma concentration ratios for DMO exceeded 1.0, ranging from 1.7 to 2.1. Pancreatic DMO caused a small but significant decrease in the water, bicarbonate and sodium secretion at non-equilibrium, and in the bicarbonate secretion at equilibrium. A decrease in the bicarbonate secretion may result largely from the buffer action of bicarbonate on protons provided by the undissociated form of DMO. The sum of both bicarbonate and chloride concentrations in pancreatic juice decreased with the increased DMO concentration in the juice, implying that DMO may compete with the secretion of bicarbonate and/or chloride across the apical membrane of the duct cell. Pancreatic DMO can act as a non-specific inhibitor of pancreatic water and electrolyte secretions.     

Retroperitoneal perforation of a pancreatic cyst during endoscopic retrograde pancreatography

A 70‐year‐old man was admitted to Ueno Municipal Hospital, Ueno, Japan, for evaluation of abdominal distension. Computed tomography showed a 1 × 1 cm cyst at the pancreas tail. Endoscopic retrograde pancreatography (ERP) showed a normal pancreatic duct after the first gentle injection and an enhanced cyst at the pancreas tail. Extravasation of the contrast medium occurred from the pancreatic duct to the superior‐dorsal extrapancreas at the same time of the next low‐pressure manual injection. Computed tomography showed extravasation of the contrast medium from the pancreas cyst to the retroperitoneal space after ERP. It was considered that the cyst wall weakness, in addition to slight elevated pancreatic duct pressure, caused the disruption of the cyst wall.     

ORIGINAL ARTICLE: Detection of early amnestic mild cognitive impairment without significantly objective memory impairment: a case‐controlled study

Background: We encountered eight early amnestic mild cognitive impairment (aMCI) patients (early MCI group) who did not fulfill the diagnostic criteria for aMCI. We compared the scores of neuropsychological examinations as well as the cerebral metabolic rate for glucose consumption (CMRglc) decrease on ¹⁸F‐FDG PET examination between the early MCI group and 10 aMCI patients (MCI group) or six normal elderly subjects (normal group), to examine whether the current diagnostic criteria can detect early‐stage aMCI. Methods: The three groups underwent Mini‐Mental State Examination (MMSE), Wechsler Adult Intelligence Scale – Third Edition (WAIS‐III), Wechsler Memory Scale Revised (WMS‐R), magnetic resonance imaging and 18F‐fluorodeoxyglucose positron emission tomography (¹⁸F‐FDG PET) examinations. Results: The early MCI group did not show significant memory impairment of 1.0 SD or other cognitive dysfunctions on neuropsychological examinations, and did not fulfill the diagnostic criteria of aMCI. With one‐way anova and Tukey's HSD post‐hoc test, the early MCI group showed the highest scores for WAIS‐III, whereas the MCI group showed the lowest scores for WMS‐R, although there were no significant differences between the early MCI and normal groups. In order to show a discrepancy in scores between WAIS‐III and WMS‐R, we subtracted the scores of WMS‐R from WAIS‐III. Consequently, the normal group showed significantly smaller differences in scores than the other groups, although there were no significant differences between the early MCI and MCI groups. ¹⁸F‐FDG PET recognized a CMRglc decrease in the posterior cingulate gyrus and/or part of the parietotemporal area in both the MCI and early MCI groups, of which the extent and magnitude were weaker in the early MCI group. The normal group did not show a significant CMRglc. Conclusions: The early MCI group should be included in aMCI not only based on the discrepancy between intelligence and memory scores, but also based on the ¹⁸F‐FDG PET findings. The combination of these examinations would make it possible to diagnose early‐stage aMCI.     

A Smartphone Application as a Telemedicine Tool for Stroke Care Management

Since smartphone applications are revolutionizing telemedicine, a new application specifically for stroke care (JOIN) was designed. Addition of the JOIN smartphone application to the stroke treatment workflow in our hospital was assessed. JOIN has key functions that may improve the care of stroke patients, including the ability to (1) exchange information such as patient data and medical images in real-time throughout the entire process of patient management; (2) track each step of the protocol from door to discharge; and (3) facilitate real-time interaction of all team members via text, audio, and a video chat system. Two periods, 2.7 years before the implementation of JOIN (Pre-JOIN) with 37 patients and 2.2 years after (Post-JOIN) with 54 patients, were compared, and the workflow for all 91 patients who had a cerebral infarction and were treated with tissue plasminogen activator (tPA) and/or thrombectomy between October 2012 and July 2017 was reviewed. There were noticeable reductions in overall patient management time, including times for door-to-imaging, starting tPA treatment, and endovascular intervention with JOIN. Staff members were unanimously satisfied with JOIN, due to the increased efficiency of information exchange and the ability for real-time discussions with different professionals when needed. No significant changes in patient outcomes (as assessed by modified Rankin Scale [mRS] scores) at 3 months and in the total cost for the treatment were observed. A smartphone-based application with the capability of sharing information instantaneously among healthcare professionals facilitated time-sensitive, acute care of ischemic stroke patients.     

Clinical effects of high oral dose of donepezil for patients with Alzheimer's disease in Japan

Background:  Donepezil 10 mg/day gained approval in Japan in August 2007 for the treatment of cognitive dysfunction in advanced Alzheimer's disease.
Methods:  We evaluated the efficacy and adverse effects of donepezil when the dose was increased to 10 mg/day in 61 Japanese patients with Alzheimer's disease. Cognitive function was evaluated using the Revised Hasegawa Dementia Scale and mini-mental state examination at the day before starting, and at 4, 8 and 24 weeks after starting donepezil 10 mg/day. The relationship with apolipoprotein E4 was also investigated.
Results:  The Revised Hasegawa Dementia Scale and mini-mental state examination scores were not statistically significantly different at any time after starting donepezil 10 mg/day. It can be anticipated that donepezil 10 mg/day will especially inhibit deterioration of cognitive function in advanced Alzheimer's disease. The incidence of adverse events was 11.5%, lower than the rate of 40% or higher recorded during previous clinical trials.
Conclusions:  The progression of cognitive dysfunction could be inhibited by increasing the dose of donepezil to 10 mg/day. It was suggested that longer-term treatment with 5 mg/day might lead to fewer adverse events when the dose is increased to 10 mg/day.     

Intelligence or years of education: which is better correlated with memory function in normal elderly Japanese subjects?

Background: We compared differences in intelligence and memory function between normal elderly Japanese subjects with more years of education and those with fewer years of education. We also investigated clinical and neuropsychological factors that are strongly correlated with memory function. Methods: There were 118 normal elderly subjects who underwent the Mini‐Mental State Examination, Wechsler Adult Intelligence Scale, 3rd edition (WAIS‐III), and Wechsler Memory Scale Revised. Subjects with at least 13 years of education were categorized as the H group, and those with 12 years of education or less were categorized as the L group. Results: Age and Mini‐Mental State Examination scores were not significantly different between the two groups. On the WAIS‐III, there were significant differences between the two groups in Verbal IQ and Full Scale IQ. On the Wechsler Memory Scale Revised, there were significant differences between the two groups in Visual Memory, General Memory, and Delayed Recall. Correlation coefficients between memory function and the other factors demonstrated significant but weak correlations between years of education and General Memory (R = 0.22) and between years of education and Delayed Recall (R = 0.20). Strong correlations were found between Verbal IQ and Verbal Memory (R = 0.45), between Verbal IQ and General Memory (R = 0.49), between Full Scale IQ and General Memory (R = 0.50) and between Full Scale IQ and Delayed Recall (R = 0.48). Conclusions: In normal elderly Japanese subjects, years of education weakly correlated with memory function while Verbal IQ, Full Scale IQ and Verbal Comprehension on WAIS‐III had stronger correlations with memory function. Verbal IQ and Verbal Comprehension on WAIS‐III were found to be insusceptible to the cognitive decline characteristic of Alzheimer's disease or amnestic mild cognitive impairment. Therefore, verbal intelligence, as measured by Verbal IQ and Verbal Comprehension, may be the most useful factor for inferring premorbid memory function in Alzheimer's disease or amnestic mild cognitive impairment patients.