Unilateral necrosis of the tongue caused by embolisation of cholesterol crystals.

Cholesterol crystals embolise when an aortic atherosclerotic lesion ruptures and cholesterol crystals are scattered and obstruct small peripheral arterioles. Risk factors include both iatrogenic factors such as intravascular catheterisation, and spontaneous factors for atherosclerosis such as aging, hypertension, dyslipidaemia, and smoking. We describe the case of an 83-year-old Japanese man who developed unilateral, superficial necrosis of the tongue as a result of spontaneous embolisation of cholesterol crystals.

Anti-aquaporin-4 antibody-positive neuromyelitis optica presenting with syndrome of inappropriate antidiuretic hormone secretion as an initial manifestation.

The distribution of neuromyelitis optica (NMO)-characteristic brain lesions corresponds to sites of high aquaporin-4 (AQP4) expression, and the brainstem and hypothalamus lesions that express high levels of AQP4 protein are relatively characteristic of NMO. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is one of the important causes of hyponatremia and results from an abnormal production or sustained secretion of antidiuretic hormone (ADH). SIADH has been associated with many clinical states or syndromes, and the hypothalamic-neurohypophyseal system regulates the feedback control system for ADH secretion. We report the case of a 63-year-old man with NMO, whose initial manifestation was hyponatremia caused by SIADH. Retrospective analysis revealed that the serum anti-AQP4 antibody was positive, and an MRI scan showed a unilateral lesion in the hypothalamus. SIADH recovered completely with regression of the hypothalamic lesion. As such, NMO should even be considered in patients who develop SIADH and have no optic nerve or spinal cord lesions but have MRI-documented hypothalamic lesions.

Changes in gait associated with acute stage II posterior tibial tendon dysfunction.

The purpose of this study was to examine differences in gait mechanics between patients with acute stage II PTTD and healthy volunteers. Hindfoot and midfoot kinematics, plantar foot pressures and electromyographic (EMG) activity of the posterior tibialis, gastrocnemius, anterior tibialis and the peroneals were measured in five patients with acute stage II PTTD. Kinematics and kinetics were compared to a database of 20 healthy volunteers. EMG and plantar pressure data were obtained from five healthy volunteers. Hindfoot moments and powers were also calculated. The center of pressure excursion index (CPEI) was calculated from the plantar pressures. Significant differences were observed between the two groups, which confirmed clinical observations. Limited hindfoot eversion and increased midfoot external rotation occurred during the first and third rockers. The EMG data suggested that tendon dysfunction in the posterior tibialis is associated with compensatory activity, not only in its antagonists (the peroneals), but also in the anterior tibialis and the gastrocnemius. These data suggest that non-operative treatment of patients with PTTD should consider minimizing the activity of the posterior tibialis as well as the peroneals, the anterior tibialis and the gastrocnemius.

Endothelin-1 gene variant associates with blood pressure in obese Japanese subjects: the Ohasama Study.

A recent report based on the results of 2 epidemiological studies, the Etude Cas-Temoin de l'Infarctus Myocarde (ECTIM) and the Glasgow Heart Scan Study, revealed that a G/T polymorphism with an amino acid substitution (Lys-->Asn) at codon 198 in exon 5 of the endothelin-1 gene (ET-1) is associated with blood pressure in overweight people. They suggested that G/T polymorphism of ET-1 strongly interacted with body mass index (BMI) in the determination of BP levels. To examine interaction among G/T polymorphism of ET-1, BMI, and BP, we performed an association study in a general Japanese population. Subjects (n=1250) were recruited from Ohasama, a cohort in a rural community of northern Japan. DNA was extracted from buffy coat of participants, and G/T polymorphism of ET-1 was determined by the TaqMan probe polymerase chain reaction method, a powerful tool for semiautomatic genotype determination of a large number of samples. Frequency of T (Asn 198) allele in Japanese (27%) was slightly but significantly higher than in whites (24%). Baseline characteristics (age, BMI, systolic and diastolic BP, and antihypertensive treatment) of all subjects were not significantly different according to the genotype of G/T polymorphism. However, in obese subjects (> or =25 kg/m(2)) diastolic BPs were significantly associated with G/T polymorphism of ET-1. After adjustment for confounding factors, significant association remained; for overweight subjects, diastolic BP level in those with T allele (GT + TT) was 1.8 mm Hg (P=0.04) higher than in those with GG genotype. That similar results were obtained from subjects of different races suggests that the Lys198Asn polymorphism of ET-1 is involved in determination of BP levels in obese subjects.

Aldosterone synthase gene (CYP11B2) C-334T polymorphism, ambulatory blood pressure and nocturnal decline in blood pressure in the general Japanese population: the Ohasama Study.

OBJECTIVE: The C-344T polymorphism in the 5'-flanking region of the aldosterone synthase (CYP11B2) gene has been suggested to be associated with hypertension and disturbed circadian blood pressure (BP) rhythm through its effect on aldosterone synthesis. However, previous findings on this topic have been inconsistent. DESIGN: A cross-sectional study. SUBJECTS AND METHODS: We investigated the CYP11B2 C-344T genotype in 802 subjects, aged 40 and over, in a Japanese community, who gave written informed consent and were monitored for 24 h ambulatory BP. RESULTS: The frequencies of the CC, CT, and TT genotypes in these Japanese subjects were 0.14, 0.44, and 0.42, showing a higher frequency of the T allele (0.64) than in Caucasians. Although there was no significant difference in 24 h ambulatory BP levels among the genotypes, the nocturnal decline in BP was significantly greater in the CC homozygous subjects than in other subjects (P = 0.0065 for systolic and P = 0.031 for diastolic decline in nocturnal BP). Detailed analyses demonstrated that this association was significant only in aged (60 years and over) or male subjects. The prevalence of previous cardiovascular disease was significantly less in these subjects with the CC genotype than in those with the TC and TT genotypes, although age, body mass index, male gender, smoking, use of alcohol and antihypertensive medication did not differ among the three genotypes. There was no significant difference among the three genotypes in biochemical and hormonal parameters. CONCLUSION: Although the C-344 T polymorphism of CYP11B2 did not directly influence the level of 24 h BP, the CC genotype was associated with decreased nocturnal BP in elderly or male Japanese. Since prevalence of previous cardiovascular disease was significantly less in homozygous CC subjects, greater nocturnal BP decline in this genotype appears to be beneficial in the circadian BP rhythm.

Antioxidative properties of probucol estimated by the reactivity with superoxide and by electrochemical oxidation.

The reaction of probucol with superoxide (O2(*-)) was investigated in acetonitrile using both electron spin resonance (ESR) and electrochemical techniques. The formation of phenoxyl radical was observed during the reaction of probucol with O2(*-) by ESR spectroscopy. The reaction of probucol with O2(*-) in acetonitrile was followed by cyclic voltammetry. With the addition of probucol, the oxidation peak current of O2(*-) decreased concentration dependently. This suggests that probucol reacts with O2(*-), that is, probucol scavenges O2(*-) in acetonitrile. 2,6-Di-tert-butyl-p-benzoquinone was identified as the major product of the reaction of probucol with O2(*-) in acetonitrile. Electrochemical oxidation of probucol was also performed. Probucol gives an irreversible oxidation peak at ca. +1.4 V vs. the saturated calomel electrode in the cyclic voltammogram. Controlled-potential electrolysis was carried out at +1.2 V in a divided cell. 2,6-Di-tert-butyl-p-benzoquinone, 4,4'-dithiobis(2,6-di-tert-butylphenol), and 4,4'-trithiobis(2,6-di-tert-butylphenol) were identified as the products of anodic oxidation. These redox properties of probucol may correlate with the physiological activities.

Hypertrophic cardiomyopathy in the elderly: significance of atrial fibrillation.

BACKGROUND AND OBJECTIVES: Atrial fibrillation (Af) is an important prognostic indicator for clinical deterioration in patients with hypertrophic cardiomyopathy (HCM), particularly in elderly patients, but its significance may vary from unselected to selected populations. This study investigated the risk of Af as a prognostic factor in long-term mortality and morbidity in Japanese patients with HCM at our institution. METHODS: All fatal and non-fatal cardiovascular events were estimated in 91 patients with HCM (mean age 51 +/- 14 years, 62 men) and follow up continued for 6.7 +/- 4.8 years. RESULTS: Either chronic or paroxysmal Af documented by standard electrocardiography (ECG) or ambulatory ECG monitoring at diagnosis and during follow-up were included with other clinical features in the survival analysis. Af was documented in 22 patients (24%). They were older than those without Af (57 +/- 10 vs 48 +/- 14 years, p < 0.005) and had larger left atrial dimensions (43 +/- 6 vs 36 +/- 5 mm, p < 0.01). Cardiovascular events occurred in 12 patients with Af (embolic events in five, heart failure in four, and sudden death in three), and in four patients without Af (embolic event in one, and sudden death in three). Death occurred in 10 patients (seven with Af and three without Af); sudden death in six patients (three with Af and three without Af) and four patients died of cerebrovascular embolism (four with Af and none without Af). Cox's regression analysis showed the occurrence of Af was the most useful predictor of cardiovascular death in patients with HCM. The event-free rate was significantly worse in patients with Af than in those without Af (p < 0.0001). CONCLUSIONS: Af is an important prognostic feature in patients with HCM, which occurs in older patients and in those with left atrial dilation.

The mechanism of reaction of ebselen with superoxide in aprotic solvents as examined by cyclic voltammetry and ESR.

The mechanism of the redox reaction of ebselen with superoxide was investigated using both ESR and electrochemical techniques. The reaction with superoxide in aprotic solvents was followed by means of cyclic voltammetry and ESR spin-trapping. A decrease in the oxidation current due to superoxide as a result of the addition of ebselen was clearly observed in the cyclic voltammograms. Ebselen reduced the ESR signal intensity of 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-superoxide in a dose-dependent manner. The formation of an amidyl radical in this redox reaction was confirmed by rapid mixing continuous-flow ESR. The selenonate form and the seleninate form of ebselen were identified as the final products of the reaction of ebselen with superoxide. The following mechanism for this redox reaction can be proposed: First, ebselen reacts with superoxide and is converted to an ebselen anion radical; second, the ebselen anion radical reacts with superoxide and is converted to the amidyl radical. Hydrogen abstraction by the amidyl radical occurs and gives both a seleninate form and a selenonate form.

Acarbose improved severe postprandial hypotension in a patient with diabetes mellitus.

Postprandial hypotension (PPH) is defined as a decrease of systolic blood pressure by more than 20 mmHg after meals. Severe PPH is a troublesome diabetic complication, which has no established means of treatment. We encountered a patient who had diabetes mellitus complicated by severe PPH and attempted to treat this problem using several medications (octreotide, midodrine hydrochloride, and acarbose). A 58-year-old male with diabetic triopathy complained of orthostatic dizziness and vertigo after meals. The blood pressure was monitored for 24 h with an ambulatory blood pressure monitor, revealing that the systolic blood pressure decreased markedly after breakfast and dinner by 45 and 50 mmHg, respectively. PPH was not improved by a subcutaneous injection of octreotide. Administration of midodrine hydrochloride reduced the frequency of hypotensive episodes from twice to once daily, but the magnitude of the postprandial fall in blood pressure was still around 30 mmHg. After the patient started to receive acarbose therapy, the postprandial fall in blood pressure was diminished to 18 mmHg and his symptoms largely disappeared. For the treatment of PPH in diabetic patients, our experience suggests that it may be appropriate to try first on alpha-glucosidase inhibitor like acarbose.

Mechanical behavior of the Lisfranc and dorsal cuneometatarsal ligaments: in vitro biomechanical study.

OBJECTIVES: To define the anatomy and mechanical properties of two ligaments stabilizing the medial tarsometatarsal joints: the Lisfranc ligament and the dorsal cuneometatarsal ligament. DESIGN: Cadaveric study in normal feet. SETTING: Biomechanics laboratory. PATIENTS OR PARTICIPANTS: Twelve fresh-frozen cadaveric feet were studied. INTERVENTION: The Lisfranc and dorsal cuneometatarsal ligaments were dissected, dimensions measured, and material properties determined with a servohydraulic MTS machine on bone-ligament-bone preparations. MAIN OUTCOME MEASUREMENTS: Stiffness, strain, stress, modulus, failure load, ligament length, width, thickness, and cross-sectional area were determined. RESULTS: Dorsal ligament stiffness was 66.3+/-18.3 newtons per millimeter and the Lisfranc ligament stiffness was 189.7+/-57.2 newtons per millimeter. The failure load of the dorsal ligament averaged 150.7+/-33.1 newtons and for the Lisfranc ligament, 368.8+/-126.8 newtons. CONCLUSIONS: The stiffness and load to failure of the dorsal cuneometatarsal ligament were much higher than anticipated, which indicates that it contributes significantly to stabilizing the second metatarsal to the first cuneiform.

Predictive values of automated blood pressure measurement: what can we learn from the Japanese population - the Ohasama study.

BACKGROUND: Measurements of ambulatory blood pressure (ABP) and of home blood pressure (HBP) as an adjunct to casual/clinic blood pressure (CBP) measurements are currently widely used for the diagnosis and treatment of hypertension. We have monitored a rural cohort of people from the population of Ohasama, Japan, with respect to their prognosis and have previously reported that ABP and HBP are superior to CBP for the prediction of cardiovascular mortality. One reason that CBP is a poor predictor of prognosis is that it incorporates several biases, including the white-coat effect. METHODS AND RESULTS: We examined the prognostic significance of white-coat hypertension for mortality and found that the relative hazard for the overall mortality of patients with white-coat hypertension was significantly lower than that for true hypertension. Short-term blood pressure variability has recently attracted attention as a cause of target-organ damage and cardiovascular complications. Our results confirmed that short-term blood pressure variability (as measured every 30 min) was independently associated with cardiovascular mortality. In addition, research has recently focused on isolated systolic hypertension and pulse pressure as independent risk factors for poor cardiovascular prognosis. The Ohasama study also clearly demonstrated that isolated systolic hypertension and increased pulse pressure, as assessed by HBP, were associated with an increase in the risk of cardiovascular mortality. Circadian blood pressure variation is characterized by a diurnal elevation and a nocturnal decline in blood pressure. We therefore compared morbidity from stroke between dippers (subjects who show an ordinal nocturnal dipping of blood pressure) and non-dippers (those with a diminished nocturnal dipping or nocturnal elevation of blood pressure [inverted dippers]) in the Ohasama study. The incidence of stroke increased with an increased length of observation in dippers using antihypertensive medication but not in non-dippers using antihypertensive medication. In contrast, the relative hazard for mortality increased in non-dippers and inverted dippers. These results suggest a cause-and-effect relationship for both dippers and non-dippers. CONCLUSION: The Ohasama study showed that the level and variability of hypertension as assessed by ABP and HBP are independent predictors of cardiovascular mortality. It also demonstrated an independent association between the prognosis of hypertension and each component of ABP and HBP, indicating the prognostic significance of these blood pressure measurements.

Calcaneocuboid distraction arthrodesis for posterior tibial tendon dysfunction and flatfoot: a cadaveric study.

Nine fresh-frozen foot specimens were studied to determine the mechanical behavior of the foot using calcaneocuboid distraction arthrodesis, an operation designed for treatment of posterior tibial tendon dysfunction with flatfoot deformity. Flatfoot deformity was created in cadaveric specimens, and to simulate toe-off phase of gait, loads were applied to the plantar surface of the foot and six tendons. Three-dimensional tarsal bone positions were determined with a magnetic tracking system. With ligament sectioning, flatfoot deformity was observed and average arch height decreased 53 +/- 3.5 mm. Height arch increased after calcaneocuboid distraction arthrodesis an average of 3.2 +/- 3.6 mm and was less than normal arch at an average of 2.1 +/- 2.4 mm. Metatarsotalar alignment compared with flatfoot improved after calcaneocuboid distraction arthrodesis in adduction and inversion to the extent that these were not significantly different from intact foot positions. Calcaneotalar position improved after calcaneocuboid distraction arthrodesis in adduction and inversion. Calcaneocuboid alignment compared with flatfoot improved after calcaneocuboid distraction arthrodesis in adduction, plantar flexion, and eversion, but compared with an intact foot was overcorrected in all three planes of motion. Arch alignment in simulated toe-off phase of gait in cadaveric feet was improved significantly with calcaneocuboid distraction arthrodesis but was not reduced anatomically.

Effect of angiotensin-converting enzyme inhibitor (enalapril or imidapril) on ventilation during exercise in patients with chronic heart failure secondary to idiopathic dilated cardiomyopathy.

Eighteen patients with heart failure were studied to clarify whether angiotensin-converting enzyme inhibitor treatment improves excess ventilation during exercise. Treatment with angiotensin-converting enzyme inhibitors had a beneficial effect on excess ventilation during exercise, without significant improvement in exercise capacity in patients with moderate congestive heart failure.

The manual stress test may not be sufficient to differentiate ankle ligament injuries.

OBJECTIVE: To assess the accuracy of stress tests (anterior drawer, talar tilt) in the diagnosis of lateral ligament injuries.Design. Stress tests were performed in vitro, and rotation and displacement of the calcaneus relative to the tibia were measured. BACKGROUND: Stress tests are commonly used to diagnose ankle injuries. However, it is controversial as to whether stress tests can accurately differentiate between isolated anterior talofibular ligament injuries and combined anterior talofibular and calcaneofibular ligament injuries. METHODS: Stress tests were performed in vitro under three conditions with both ligaments intact, after sectioning the anterior talofibular ligament, and after sectioning the anterior talofibular and calcaneofibular ligament. Motion of the calcaneus relative to the tibia was measured in neutral and in 20 degrees of plantarflexion at the ankle. RESULTS: There were statistically significant differences among cadavers, examiners and positions. There was a difference between isolated anterior talofibular ligament sectioning and combined anterior talofibular and calcaneofibular ligament sectioning in lateral tilt but not in anterior displacement. In contrast, a difference was found between intact and anterior talofibular ligament sectioned specimens in anterior displacement but not in lateral tilt. However the differences were not great enough to differentiate between the two conditions. CONCLUSIONS: Each of the stress tests provides reasonable hindfoot displacement but neither is sufficient for accurate diagnosis of specific ligament involvement due to the large amount of individual variation. RELEVANCE: Many clinicians rely on stress tests to diagnose lateral ligament injuries and to assess the extent of anatomic disruption. This in vitro study has demonstrated poor correlation between clinical stress tests and the degree of ligamentous disruption.

A three-dimensional model of the human pulmonary acinus.

A three-dimensional (3-D) model of the human pulmonary acinus, a gas exchange unit, is constructed with a labyrinthine algorithm generating branching ducts that fill a given space completely. Branching down to the third respiratory bronchioles is generated with the proposed algorithm. A subacinus, a region supplied by the last respiratory bronchiole, is approximated to be a set of cubic cells with a side dimension of 0.5 mm. The labyrinthine algorithm is used to determine a pathway through all cells only once, except at branching points with the smallest path lengths. In choosing each step of a pathway, random variables are used. Resulting labyrinths have equal mean path lengths and equal surface areas of inner walls. An alveolus can be generated by attaching alveolar septa, 0.25 mm long and 0.1 mm wide, to the inner walls. Total alveolar surface area and numbers of alveolar ducts, alveolar sacs, and alveoli in our 3-D acinar model are in good accordance with those reported in the literature.