Giant-cell myocarditis without a symptom of heart failure seen in a patient with myasthenia gravis and concurrent Hashimoto's disease]

A 69-year-old Japanese woman initially noticed difficulty in squatting in the last two years, followed by nasal voice, fatiguability in mastication, and blepharoptosis. On admission to our hospital, in addition to these neurological findings, we detected ectopic arrhythmia and Levine II systolic murmur at the apex region, without any subjective symptoms. The serum titer of anti-acetylcholine receptor antibody was elevated to 28 nmol/l (normal: < 0.2), and she responded to repetitive nerve stimulation at a frequency of 3 Hz showing 13% waning, she had positive test for edrophonium administration, and was diagnosed as having myasthenia gravis (MG). There was no thymoma by radiographic examination. She also had Hashimoto's disease confirmed by the laboratory findings. Chest X-p revealed dilatation of the heart, and 24-hour Holter ECG revealed non-sustained ventricular tachcardia (VT). Ventriculography revealed prominent dilatation of the left ventricle and diffuse hypokinetic ventricular wall motility. Endomyocardial biopsy revealed muscle fiber degeneration, cellular infiltration, and scattered multinucleated giant cells, confirming a diagnosis of giant cell myocarditis (GCM). Quadriceps muscle biopsy revealed a small number of muscle fibers with giant nuclei, but no giant cells were seen. Immunological study revealed elevation of CD4/CD8 ratio and memory CD4 cells. Antibody to anti-cardiac and anti-striate muscle were strongly positive in the serum. Four months later, she developed dyspnea on effort and hypoxia, accompanied by severe bradycardia leading to sinus arrest. For acute cardiac deterioration, steroid pulse therapy was started followed by oral predonisolone and azathioprine, which aggravated myasthenic symptoms. The patient was ventilated for respiratory hypercapnia. During immunoabsobent therapy, she developed VT which caused a cardiac arrest, leading to fatal outcome. In case of MG, especially overlapped with other autoimmune diseases, evaluation of cardiac function should be conducted to detect GCM.     

Preserved sympathetic skin response at the distal phalanx in patients with carpal tunnel syndrome.

OBJECTIVE: To assess the viability of sympathetic sudomotor fibers in carpal tunnel syndrome (CTS). METHODS: We recorded sympathetic skin response (SSR) with a multichannel recording system. Forty-four patients with CTS (51 hands), 7 patients (7 hands) with asymptomatic median mononeuropathy at the wrist (MMW), and 20 normal subjects (20 hands) were studied. We classified the patients into 4 grades of increasing severity. RESULTS: In the hands of normal subjects, SSR was evoked easily at all recorded sites. SSR at the wrist in patients with asymptomatic MMW decreased in amplitude. SSR was markedly distorted at the wrist in severe grades of CTS. The SSR amplitude ratio (wrist/distal phalanx) decreased significantly with more severe grade (rh=-0.4; P<0.05), but the sensitivity was lower than that of other electrodiagnostic criteria. A patient with persistent allodynia at the wrist after surgery showed the slight recovery of SSR amplitude ratio; the other two patients without allodynia showed substantial recovery of SSR amplitude ratio within 24 weeks after surgery. CONCLUSION: SSR amplitude ratio is a poor indicator of CTS diagnosis, but may be useful in assessing the viability of sympathetic sudomotor fibers and may assist in evaluating the response to surgery.     

Comparison of the effect of blood pressure on the development of stroke, acute myocardial infarction, and end-stage renal disease.

Hypertension is a known risk factor for cardiovascular disease, but few epidemiological studies have examined simultaneously the effect of baseline blood pressure on the development of stroke, acute myocardial infarction (AMI), and end-stage renal disease (ESRD). In 1983, a large, community-based mass screening covered about 14% of the adult population in Okinawa, Japan. The total number of people screened was 107,192 (51,122 men, 56,070 women). We had access to two independent registries of end-organ damage: the Co-operative Study Group of Morbidity and Mortality of Cardiovascular Diseases in Okinawa (COSMO) registry for stroke and AMI, and the Okinawa Dialysis Study (OKIDS) registry for ESRD. The total number of people registered was 4,756 with stroke, 1,059 with AMI, and 641 with ESRD during the study period from April 1, 1988, to March 31, 1991. By using the name, sex, birth date, and ZIP code of registrants, we identified those registrants who were screened in 1983 and had developed stroke, AMI, or ESRD. Hypertension was defined as systolic blood pressure (SBP) of 140 mmHg or higher or diastolic blood pressure (DBP) of 90 mmHg or higher. Other readings were regarded as normotensive. The prevalence of hypertension was 35.8% (N=37,299). The cumulative incidence of stroke, AMI, and ESRD was 154, 21, and 19 subjects among those with SBP < or = 119 mmHg, and 1933, 315, and 71 subjects among those with SBP > or = 160 mmHg. Similarly, the incidence of stroke, AMI, and ESRD was 234, 44, and 25 subjects among those with DBP < or = 69 mmHg and 1980, 381, and 364 subjects among those with DBP > or = 110 mmHg. Hypertension was prevalent in the adult population in Okinawa, Japan, and was a significant predictor of stroke, AMI, and ESRD. However, the effect of blood pressure on target organs differed and was more evident in those with stroke than in those with AMI and ESRD.     

Neural effects of natural behavior on renal blood flow in spontaneously hypertensive rats

Background In states of stress and exercise, renal blood flow is shown to be depressed, mainly through neural mechanisms. Little is known, however, about the effects of natural or spontaneous behaviors on renal blood flow and renal sympathetic nerve activity. Methods We simultaneously measured renal sympathetic nerve activity and renal blood flow as a Doppler shift during grooming and exploring behaviors in spontaneously hypertensive rats. We also tested the effects of vasodilating drugs on changes in renal blood flow. Results Grooming behavior (n=21) increased renal sympathetic nerve activity, mean arterial pressure, and decreased renal blood flow. Percentage changes in renal sympathetic nerve activity correlated negatively with percentage changes in renal blood flow. Exploring with rearing (n=14) induced similar but larger changes in these variables. Denervation of renal nerves suppressed a reduction in renal blood flow during these behaviors. After intravenous injection of manidipine (a calcium channel blocker) or CV-11974 (an angiotensin II receptor antagonist), the behavior-induced reduction in renal blood flow was significantly smaller than that found before treatment, despite similar increases in renal sympathetic nerve activity. Conclusion Natural behaviors decrease renal blood flow in relation to the enhancement of renal sympathetic nerve activity, which is similar to the responses of the animals to stressful psychologic stimuli. Vasodilating drugs can attenuate the reduction in renal blood flow.     

Large Duodenal Tumor with Positive K-ras Mutation Mimicking Lateral Spreading Tumor of the Colon — a Case Report

Abstract: A 69-year-old woman was referred to our hospital with discomfort on swallow ing. Endoscopic examination revealed a large elevated tumor with multiple nodules at the end portion of the duodenal bulbus. The diagnosis obtained by biopsy was tubular adenoma with severe atypia. Upper gastrointestinal series and CT showed a tumor ap proximately 3.5 cm in diameter and the possibility of malignancy could not be ruled out. Partial duodenectomy was performed. Macroscopically the tumor measured 4.7X 3.1 cm. Endoscopic appearance and operational specimen of the tumor mimicked so-called lateral spreading tumor (LST) of the colon, which spreads horizontally and cir-cumferentially along the wall. Microscopically the tumor involved the mucosal and sub-mucosal layers, with no invasion of the muscular layer. Pathological diagnosis of the resected specimen was a borderline lesion between well-differentiated adenocarcinoma and adenoma with severe atypia. Using polmerase chain reaction and hybridization protection assay (PCR-HPA), we identified a point mutation at codon 12 of the K-ras onco-gene from glycine (GGT) to alanine (GCT). The tumor stained negative for p53 on immunohistochemistry, and PCR non radioisotopic single strand conformational polymor phism (non RI PCR-SSCP) for the analysis of exons5–8 of the p53 gene was also negative. This case seemed to be a duodenal epithelial tumor mimicking colonic LST with a rather benign nature despite its large size. (Dig Endosc 1999; 11: 70–75)     

Brain circulation in cerebral transient ischemic attacks.

Cranial blood flow, mean cranial transit time and cranial blood volume were measured by the intravenous RISA technique in 10 patients with cerebral transient ischemic attacks (TIA) at the various time intervals from the onset of last attack. Cranial blood flow was subnormal in 5 out of 11 determinations and mean transit time trended to be prolonged in the diseased hemisphere in cases suggestive of the unilateral hemispheric lesion. A decrease in cranial blood flow was observed in TIA with lowering of heart rate below 60/min, or with atrial fibrillation, whereas no obvious correlation was present between heart rate and cranial blood flow either in 94 patients with, or with 62 patients without cerebrovascular diseases. Cardiac dysrhythmias including bradycardia, leading to reduce perfusion to the brain was discussed as a possible factor for producing TIA.     

Office blood pressure variability as a predictor of acute myocardial infarction in elderly patients receiving antihypertensive therapy

Larger variability of office blood pressure (BP) was reportedly associated with a higher risk of stroke or mortality from all causes. In the present study, we focused on the relationship of variability of office BP and occurrence of acute myocardial infarction (MI). We registered 139 patients receiving antihypertensive therapy for more than 1 year who experienced first-ever episode of MI at the age of 60 years or over. At least two sex- and age-matched (+/- 5 years) control patients were registered for every MI patient. Average systolic and diastolic BP during the 12-month period prior to the occurrence of MI, or the time of registration in the case of control patients, was similar in both patient groups. The office BP variability was evaluated by calculating the variation coefficient (VC) of BP. VC of diastolic BP was significantly higher in the MI patients (10.0 +/- 4.0%) compared with the control patients (8.8 +/- 3.4%). VC of systolic BP was not different between the MI and the control patients. Multiple logistic analysis revealed the relationship of the VC for office diastolic BP to the occurrence of MI was significant after adjustment for BP level, age, gender, body mass index, serum total cholesterol concentrations, diabetes mellitus, and current smoking. In conclusion, larger long-term variability of office diastolic BP during antihypertensive therapy is a predictor of MI.     

Binswanger's disease: clinical and computed tomography neuroradiological study of seven cases

Background: Binswanger's disease is a special type of vascular dementia, which requires further reappraisal and redefinition. In a geriatric psychiatry hospital (with 207 beds), we treated several patients who probably had this disease, and tried to establish a basis for making a clinical diagnosis. Methods: From 2001 to 2005, we treated seven inpatients with noteworthy symptoms, who had been under observation in hospital wards for between 4 and 19 months. Here, for these patients, we examine the history of the illness, the condition of the patients at admission, the clinical course, and serial computed tomography (CT) findings. Results: Characteristic features of the clinical courses and symptoms of these patients were: (i) onset occurred late in life (patients were aged in their 70s and 80s); (ii) vascular events were atypical and transient, leaving few permanent neurological sequelae; (iii) progression of dementia and other somatic or neurologic symptoms was continuous and fast in four patients, and rather gradual in three patients; (iv) there was an alternating or changing pattern in all patients’ state of consciousness, mood, behavior, or manner of respiration; symptoms such as mutism, lack of facial expression, and apparent indifference were counterbalanced with such behaviors as occasional unexpected smiles, pertinent verbal responses, and sincere gazes; (v) significant negative symptoms were a lack of dysarthria, lack of dysphagia, lack of involuntary movement, and occasional lack of muscle rigidity. The primary CT findings were: (i) moderate to severe generalized (involving whole of centrum semiovale), diffuse and homogeneous (except one patient) leukoaraiosis of the hemispheric white matter, including the temporal lobe (except one patient), all (except one patient) frontal and parietal dominant, with the corpus callosum involved in one case; (ii) diffuse and generalized atrophy of the pallium, most marked in the frontal and parietal lobes, restricted to the frontal and parietal lobes in three patients, and to the frontal, parietal and temporal lobes in four patients; (iii) atrophy of the medial temporal lobe was inconstant and, when present, ambiguous in degree; (iv) slight to moderate enlargement of the bilateral lateral and third ventricles; (v) a few small lacunae in the basal ganglia and thalamus in one patient, inhomogeneous macular changes of density in the basal ganglia and thalamus in two patients, and no such findings in the remaining four patients. Conclusion: We have described a group of patients with dementia characterized by a clinical course with episodes of rather transient vascular intervention, psychopathology characteristic of organic dementia, fluctuating psychotic symptoms in combination, and intensive extensive homogeneous leukoaraiosis of the hemispheric white matter on CT. These clinical and CT neuroradiological findings seem to warrant the clinical diagnosis of Binswanger's disease, which should be reconfirmed at autopsy. Early research on this disease by Binswanger, Alzheimer, Nissl and others is reviewed. Some points of differential diagnosis in serial neuroradiology are discussed in relation to multilacunar dementia.     

Cardiovascular and sympathetic effects of L-glutamate and glycine injected into the rostral ventrolateral medulla of conscious rats.

The aim of the present study was to examine the effects of L-glutamate and glycine microinjected into the rostral ventrolateral medulla (RVLM) in conscious unrestrained rats. Microinjection of 2 nmol of L-glutamate increased the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in the conscious rats. The RSNA responses were significantly larger in the conscious rats than in anesthetized rats, while the magnitude of the pressor responses was similar in conscious and urethane-anesthetized rats. L-Glutamate injection significantly decreased heart rate in the conscious rats, whereas it increased the heart rate slightly but not significantly in the anesthetized rats. Microinjection of 100 nmol of glycine into the RVLM of conscious rat decreased MAP and RSNA. In 2 of the 6 rats examined, the depressor and sympathoinhibitory responses were preceded by a few seconds of a pressor and sympathoexcitatory phase. The decreases of RSNA in response to glycine injection were significantly larger in the conscious rats than in the anesthetized rats, whereas the magnitude of the depressor responses was similar in the two groups of rats. Heart rate decreased in response to glycine injection into the RVLM in the conscious and the anesthetized rats. In conclusion, in conscious unrestrained rats, as well as in urethane-anesthetized rats, L-glutamate acts as a sympathoexcitatory agent and glycine acts as a sympathoinhibitory agent in the RVLM. The sympathetic responses to these amino acids are larger in conscious rats than in anesthetized rats.     

Control of blood pressure and lifestyle-related risk factors in elderly Japanese hypertensive subjects.

The aim of this study was to analyze the treatment of elderly hypertensive patients by Japanese physicians specializing in hypertension. We enrolled 939 patients with hypertension who were treated in the outpatient clinics of 11 hospitals in 1995; 793 of these patients (388 men and 405 women; mean age, 66.6+/-9.0 years) received follow-up examinations in 1996, and the data on these patients was used for the present analysis. Blood pressure (BP), body mass index, lifestyle, and laboratory data were analyzed in all patients. The average BP was 143+/-16/81+/-10 mmHg in 1995 and 142+/-15/80+/-10 mmHg in 1996. The patients whose baseline BP was at the level of Grade 2 or 3 in the WHO-ISH classification (n=117) were characterized by a higher women-to-men ratio, higher age, a higher serum total cholesterol concentration, and higher QRS voltage. In these patients, from 1995 to 1996, the average BP significantly decreased, whereas fasting plasma glucose, serum total cholesterol and serum creatinine concentrations showed only negligible changes. In 220 patients (28%), BP was <140/<90 mmHg at both the initial and the follow-up examinations, whereas 351 patients (44%) were hypertensive in both 1995 and 1996. Thirty-three percent of the patients were smokers. More smokers than nonsmokers had had prior cardiovascular events, diabetes mellitus, or overt proteinuria. In conclusion, the average BP level among the patients treated by Japanese physicians specializing in hypertension was somewhat higher than that recommended by WHO-ISH Guidelines (1999). Patient education to control lifestyle-related risk factors, particularly to stop smoking, should be emphasized.