Successful cochlear implantation in a patient with mitochondrial hearing loss and m.625G>A transition.

OBJECTIVE: We present a patient with mitochondrial hearing loss and a novel mitochondrial DNA transition, who underwent successful cochlear implantation. CASE REPORT: An 11-year-old girl showed epilepsy and progressive hearing loss. Despite the use of hearing aids, she gradually lost her remaining hearing ability. Laboratory data revealed elevated lactate levels, indicating mitochondrial dysfunction. Magnetic resonance imaging showed diffuse, mild brain atrophy. Cochlear implantation was performed, and the patient's hearing ability was markedly improved. Whole mitochondrial DNA genome analysis revealed a novel heteroplasmic mitochondrial 625G>A transition in the transfer RNA gene for phenylalanine. This transition was not detected in blood DNA from the patient's mother and healthy controls. Mitochondrial respiratory chain activities in muscle were predominantly decreased in complex III. CONCLUSION: This case indicates that cochlear implantation can be a valuable therapeutic option for patients with mitochondrial syndromic hearing loss.

Discharge of monkey nucleus reticularis tegmenti pontis neurons changes during saccade adaptation.

Saccade accuracy is maintained by adaptive mechanisms that continually modify saccade amplitude to reduce dysmetria. Previous studies suggest that adaptation occurs upstream of the caudal fastigial nucleus (CFN), the output of the oculomotor cerebellar vermis but downstream from the superior colliculus (SC). The nucleus reticularis tegmenti pontis (NRTP) is a major source of afferents to both the oculomotor vermis and the CFN and in turn receives direct input from the SC. Here we examine the activity of NRTP neurons in four rhesus monkeys during behaviorally induced changes in saccade amplitude to assess whether their discharge might reveal adaptation mechanisms that mediate changes in saccade amplitude. During amplitude decrease adaptation (average, 22%), the gradual reduction of saccade amplitude was accompanied by an increase in the number of spikes in the burst of 19/34 neurons (56%) and no change for 15 neurons (44%). For the neurons that increased their discharge, the additional spikes were added at the beginning of the saccadic burst and adaptation also delayed the peak-firing rate in some neurons. Moreover, after amplitude reduction, the movement fields changed shape in all 15 open field neurons tested. Our data show that saccadic amplitude reduction affects the number of spikes in the burst of more than half of NRTP neurons tested, primarily by increasing burst duration not frequency. Therefore adaptive changes in saccade amplitude are reflected already at a major input to the oculomotor cerebellum.

Directional asymmetry in smooth ocular tracking in the presence of visual background in young and adult primates.

The smooth pursuit system moves the eyes in space accurately while compensating for visual inputs from the moving background and/or vestibular inputs during head movements. To understand the mechanisms underlying such interactions, we examined the influence of a stationary textured visual background on smooth pursuit tracking and compared the results in young and adult humans and monkeys. Six humans (three children, three adults) and six macaque monkeys (five young, one adult) were used. Human eye movements were recorded using infrared oculography and evoked by a sinusoidally moving target presented on a computer monitor. Scleral search coils were used for monkeys while they tracked a target presented on a tangent screen. The target moved in a sinusoidal or trapezoidal fashion with or without whole body rotation in the same plane. Two kinds of backgrounds, homogeneous and stationary textured, were used. Eye velocity gains (eye velocity/target velocity) were calculated in each condition to compare the influence of the textured background. Children showed asymmetric eye movements during vertical pursuit across the textured (but not the homogeneous) background; upward pursuit was severely impaired, and consisted mostly of catch-up saccades. In contrast, adults showed no asymmetry during pursuit across the different backgrounds. Monkeys behaved similarly; only slight effects were observed with the textured background in a mature monkey, whereas upward pursuit was severely impaired in young monkeys. In addition, VOR cancellation was severely impaired during upward eye and head movements, resulting in residual downward VOR in young monkeys. From these results, we conclude that the directional asymmetry observed in young primates may reflect a different neural organization of the vertical, particularly upward, pursuit system in the face of conflicting visual and vestibular inputs that can be associated with pursuit eye movements. Apparently, proper compensation matures later.

Vestibular evoked myogenic potential (VEMP) in patients with acoustic neuromas.

OBJECTIVE: To study the utility of VEMP (vestibular-evoked myogenic potential) in the diagnosis of acoustic neuromas. METHODS: Eighteen patients with unilateral acoustic neuromas were subjected to this study. Myogenic potential responding to loud click stimuli was recorded at ipsilateral sternocleidomastoid muscle. A normal range of VEMP was obtained from 20 controls. VEMP responses were compared with both, clinical symptoms and results of caloric tests. RESULT: Thirteen out of 18 patients showed decreased responses of VEMP at the affected side. VEMP responses seemed to have little relation with dysequilibrium, spontaneous nystagmus, canal paresis and pure-tone hearing. CONCLUSION: VEMP is useful for detecting dysfunction of inferior vestibular nerve in patients with acoustic neuromas.

Adaptive changes in smooth pursuit eye movements induced by cross-axis pursuit-vestibular interaction training in monkeys.

The smooth pursuit system interacts with the vestibular system to maintain the accuracy of eye movements in space. To understand neural mechanisms of short-term modifications of the vestibulo-ocular reflex (VOR) induced by pursuit-vestibular interactions, we used a cross-axis procedure in trained monkeys. We showed earlier that pursuit training in the plane orthogonal to the rotation plane induces adaptive cross-axis VOR in complete darkness. To further study the properties of adaptive responses, we examined here the initial eye movements during tracking of a target while being rotated with a trapezoidal waveform (peak velocity 30 or 40 degrees/s). Subjects were head-stabilized Japanese monkeys that were rewarded for accurate pursuit. Whole body rotation was applied either in the yaw or pitch plane while presenting a target moving in-phase with the chair with the same trajectory but in the orthogonal plane. Eye movements induced by equivalent chair rotation with or without the target were examined before and after training. Before training, chair rotation alone resulted only in the collinear VOR, and smooth eye movement-tracking of orthogonal target motion during rotation had a normal smooth pursuit latency (ca 100 ms). With training, the latency of orthogonal smooth tracking eye movements shortened, and the mean latency after 1 h of training was 42 ms with a mean gain, at 100 ms after stimulus onset, of 0.4. The cross-axis VOR induced by chair rotation in complete darkness had identical latencies with the orthogonal smooth tracking eye movements, but its gains were <0.2. After cross-axis pursuit training, target movement alone without chair rotation induced smooth pursuit eye movements with latencies ca 100 ms. Pursuit training alone for 1 h using the same trajectory but without chair rotation did not result in any clear change in pursuit latency (ca 100 ms) or initial eye velocity. When a new target velocity was presented during identical chair rotation after training, eye velocity was correspondingly modulated by just 80 ms after rotation onset, which was shorter than the expected latency of pursuit (ca 100 ms). These results indicate that adaptive changes were induced in the smooth pursuit system by pursuit-vestibular interaction training. We suggest that this training facilitates the response of pursuit-related neurons in the cortical smooth pursuit pathways to vestibular inputs in the orthogonal plane, thus enabling smooth eye movements to be executed with shorter latencies and larger eye velocities than in normal smooth pursuit driven only by visual feedback.

Medication for hearing loss after fractionated stereotactic radiotherapy (SRT) for vestibular schwannoma.

PURPOSE: To investigate the effectiveness of corticosteroid treatments for patients showing decreases in hearing levels after stereotactic radiotherapy for vestibular schwannoma. METHODS AND MATERIALS: Twenty-one patients experienced a hearing loss in pure-tone average at greater than 20 dB or less than 10 dB within 1 year after irradiation administration of 44 Gy/22 fractions followed by a 4 Gy boost. Eight received oral prednisone at a daily dose of 30 mg, which was gradually decreased (medicated group), and 13 received none (nonmedicated group). The average observation period was 26.7 +/- 16.6 (range: 6--69) months. RESULTS: Hearing recovery was seen after initial onset of the hearing loss in all 8 patients in the medicated group and in 2 of 13 patients in the nonmedicated group (p = 0.001). The hearing recovery, that is, the change in pure-tone average (dB) at the last follow-up from the onset of hearing loss, was 9.8 +/- 6.9 dB (recovery) in the medicated group and -9.4 +/- 12.8 dB (further loss) in the nonmedicated group (p = 0.0013). The hearing recovery rate, normalizing to the degree of the hearing loss before medication, was also significantly higher in the medicated group than in the nonmedicated group (p = 0.0014). CONCLUSIONS: Corticosteroidal intake is suggested to be effective in improving hearing loss after stereotactic radiotherapy, at least in young patients having a useful pretreatment hearing level, if the treatment for hearing loss is administered immediately after the hearing loss is first detected.

Annual rate of hearing loss falls after fractionated stereotactic irradiation for vestibular schwannoma.

PURPOSE: The rate of hearing loss in a population before and after irradiation was investigated to determine the effect of irradiation on hearing impairment. METHODS AND MATERIALS: In 72 patients with vestibular schwannoma who received fractionated stereotactic irradiation from 1992 to 1999, 21 had had their hearing levels examined 3 months or more before the treatment. The mean time between the initial examination and treatment was 18.6 months (range: 3-89 months), and the mean time between treatment and the last follow-up was 24.2 months (12-69 months). Thirty-six to 50 Gy in 20-25 fractions over 5 to 6 weeks was given using an X-ray beam from a linear accelerator. Pure tone average (PTA) was measured using the mean hearing level at five frequencies, and the annual rate of hearing loss was defined as [(hearing loss in PTA(dB))/(follow-up period (months)x12)]. RESULTS: The actual cumulative curve of decrease in tumor size of 2 mm or more was 38.3% at 2 years and 80.0% at 3 years. The mean of hearing loss in PTA was 11.6+/-10.3 dB (-1 to 35 dB) from the initial examination to the start of irradiation and 11.9+/-14.4 dB (-14 to 37 dB) from the start of irradiation to the last follow-up. The mean annual rates of hearing loss before irradiation and in the 1st,2nd,3rd and 4th years after irradiation were, respectively, 18.6, 11.2, 6.2, 5.1, and 5.0 dB/year. The annual rates of hearing loss in the 2nd year (P=0.025) and 3rd year (P=0.018) were significantly slower than the rate before irradiation. CONCLUSIONS: The mean annual rate of hearing loss was higher before irradiation than after irradiation, and hearing loss slowed rather than accelerated after irradiation. Although hearing loss after the treatment was usually permanent, fractionated stereotactic irradiation was suggested to be effective to lower the rate of hearing loss.

Fractionated stereotactic radiotherapy for vestibular schwannoma (VS): comparison between cystic-type and solid-type VS.

PURPOSE: To compare the effectiveness and complications of fractionated stereotactic radiotherapy (SRT) for cystic-type vestibular schwannoma (VS) with those of solid-type VS. METHODS AND MATERIALS: In 65 patients treated with fractionated SRT between 1991 and 1999, 20 were diagnosed with cystic VS, in which at least one-third of the tumor volume was a cystic component on magnetic resonance imaging (MRI), and 45 were diagnosed with solid VS. Thirty-six Gy to 50 Gy in 20-25 fractions was administered to the isocenter and approximately 80% of the periphery of the tumor. All cystic and solid components were included in the gross tumor volume. The mean follow-up period was 37 months, ranging from 6 to 97 months. RESULTS: The actuarial 3-year rate of no episode of enlargement greater than 2.0 mm was 55% for cystic-type and 75% for solid-type VS; the difference was statistically significant (p = 0.023). The actuarial 3-year tumor-reduction (reduction in tumor size greater than 2.0 mm) rates were 93% and 31%, respectively (p = 0.0006). The overall actuarial tumor control rate (no tumor growth greater than 2. 0 mm after 2 years or no requirement of salvage surgery) was 92% at 5 years in 44 patients with a follow-up period of 2 or more years. There was no difference in the class hearing preservation rate between cystic VS and solid VS. No permanent trigeminal or facial nerve palsy was observed in either group. CONCLUSION: Transient tumor enlargement occurs in cystic VS more frequently than in solid-type VS, but the subsequent tumor-reduction rate in cystic VS is better.

Conversion of human colonic adenoma cells to adenocarcinoma cells through inflammation in nude mice.

The roles of inflammation in the malignant progression of tumors during multistep carcinogenesis have been much discussed but remain to be elucidated. To determine the direct contribution of inflammation to colon carcinogenesis, we established a new model of progression of human colonic adenoma cells using a nude mouse; the progression is accelerated by coimplantation of a plastic plate. The FPCK-1-1 cell line, derived from a colonic polyp in a patient with familial adenomatous polyposis, is nontumorigenic when injected subcutaneously into nude mice in a cell suspension of up to 5 x 106 cells per mouse. However implantation of 1 x 10(5) FPCK-1-1 cells attached to a plastic plate induced first acute and then chronic inflammation, and formed progressively growing tumors that were histologically determined as moderately differentiated adenocarcinoma in 65% of mice. Moreover cell lines established from the growing tumors were found to be tumorigenic when injected into mice even without a plastic plate. The tumor arising from the adenoma cells implanted attached to a plastic plate was surrounded by highly proliferating fibrous stroma. This fibrous tissue was considered essential for malignant progression, rather than for attachment to the plastic plate substrate, because the tumors were formed after injection of FPCK-1-1 cells into the fibrous tissue from which the plastic plate had been removed before the cell injection. The conditioned medium (CM) obtained from the fibroblasts derived from a plastic plate-associated stromal tissue was found to contain factors that stimulated growth of FPCK-1-1 cells, but not of the derivative progressor cell lines. The factor was stable to heating and neuraminidase treatment, but labile to trypsin treatment. The main growth-potentiating activity was contained in the fraction larger than 100 kDa. In contrast, the activity to promote FPCK-1-1 cell growth was not present in the CM of subcutaneous fibroblasts from untreated nude mice or the fibroblast cell lines C3H10T 1/2 and NIH3T3. These results demonstrated that inflammation-associated stroma promoted the conversion of colonic adenoma cells to adenocarcinoma cells.

Thyroid abnormality trend over time in northeastern regions of Kazakstan, adjacent to the Semipalatinsk nuclear test site: a case review of pathological findings for 7271 patients.

From 1949 through 1989 nuclear weapons testing carried out by the former Soviet Union at the Semipalatinsk Nuclear Test Site (SNTS) resulted in local fallout affecting the residents of Semipalatinsk, Ust-Kamenogorsk and Pavlodar regions of Kazakstan. To investigate the possible relationship between radiation exposure and thyroid gland abnormalities, we conducted a case review of pathological findings of 7271 urban and rural patients who underwent surgery from 1966-96. Of the 7271 patients, 761 (10.5%) were men, and 6510 (89.5%) were women. The age of the patients varied from 15 to 90 years. Overall, a diagnosis of adenomatous goiter (most frequently multinodular) was found in 1683 patients (63.4%) of Semipalatinsk region, in 2032 patients (68.6%) of Ust-Kamenogorsk region and in 1142 patients (69.0%) of Pavlodar region. In the period 1982-96, as compared before, there was a noticeable increase in the number of cases of Hashimoto's thyroiditis and thyroid cancer. Among histological forms of thyroid cancer, papillary (48.1%) and follicular (33.1%) predominated in the Semipalatinsk region. In later periods (1987-96), an increased frequency of abnormal cases occurred among patients less than 40 years of age, with the highest proportion among patients below 20 in Semipalatinsk and Ust-Kamenogorsk regions of Kazakstan. Given the positive findings of a significant cancer-period interaction, and a significant trend for the proportion of cancer to increase over time, we recommend more detailed and etiologic studies of thyroid disease among populations exposed to radiation fallout from the SNTS in comparison to non-exposed population.

Olfactory epithelium consisting of supporting cells and horizontal basal cells in the posterior nasal cavity of mice.

The olfactory epithelium of mice generally consists of olfactory cells, progenitors of olfactory cells (globose basal cells), supporting cells, and horizontal basal cells. However, in the dorsal fossa (the roof) of the posterior nasal cavity of mice, we found seven epithelial patches consisting of only non-neuronal cell types, i.e., supporting cells and horizontal basal cells, among the normal olfactory epithelium. The supporting cells occupied three or four layers in the apical to middle regions; in the basal region, horizontal basal cells were localized in a single row adjacent to the basement membrane. Bowman's gland ducts were also present in the epithelium. Neuronal cells (olfactory cells and globose basal cells) were totally absent. The ultrastructure of the supporting cells, horizontal basal cells, and Bowman's glands was essentially similar to that in the normal olfactory epithelium. In the early postnatal period (P1-P7), cell types in the epithelium were the same as those in the normal olfactory epithelium. From P10 to P21, olfactory cells and globose basal cells had disappeared from the olfactory epithelium. At this period, the number of TUNEL-positive cells was significantly higher than that in the surrounding olfactory epithelium; ultrastructurally, many apoptotic figures were observed. This suggests that the epithelium consisting of supporting cells and horizontal basal cells is generated by the apoptotic death of olfactory cells and globose basal cells during postnatal development.

Dissociation of smooth pursuit and vestibulo-ocular reflex cancellation in SCA-6.

OBJECTIVE: To study gaze in SCA-6 patients during pursuit and passive whole-body rotation. BACKGROUND: Smooth pursuit and vestibularly induced eye movements interact to maintain the accuracy of eye movements in space (i.e., gaze). Previous studies have implicated the cerebellum, particularly the floccular lobe and dorsal vermis, in the control of gaze velocity during pursuit and vestibulo-ocular reflex (VOR) cancellation. SCA-6 has recently been identified genetically and characterized as pure cerebellar ataxia that affects the cerebellar cortex selectively. METHODS: Using infrared oculography, eye movements of five SCA-6 patients and five age-matched normal control subjects were recorded during sinusoidal pursuit and passive whole-body rotation in the horizontal plane (amplitude, +/- 10 deg; frequency, 0.2 Hz). Eye and gaze gain (eye and gaze velocity/stimulus velocity) were calculated after deleting saccades. RESULTS: Eye gain of all SCA-6 patients during pursuit was significantly lower than those of the control subjects (mean +/- SD, 0.26+/-0.06 versus 0.91+/-0.07). In contrast, eye gain of the patients was not significantly different from that of the control subjects either during VOR cancellation, when the subjects tracked a target that moved with the same amplitude and phase, like a chair (0.21+/-0.05 versus 0.12+/-0.07), or during visually enhanced VOR (x1), when the target remained stationary in space (0.85+/-0.06 versus 0.95+/-0.05). Moreover, there was no significant difference in mean VOR gain in total darkness between the two groups. Gaze gain of patients (0.26+/-0.06 versus 0.81+/-0.06) but not control subjects (0.91+/-0.07 versus 0.88+/-0.08), was significantly different during pursuit and VOR cancellation. CONCLUSION: SCA-6 patients show dissociation in the control of gaze tracking during smooth pursuit and VOR cancellation.

[Hypertensive heart disease with left ventricular diastolic dysfunction demonstrating restrictive hemodynamics: a case report].

A 47-year-old man with hypertensive heart disease and left heart failure due to left ventricular diastolic dysfunction was admitted to our hospital because of emergent hypertension. Chest radiography on admission showed slight cardiomegaly and mild pulmonary congestion with right pleural effusion Echocardiography showed concentric hypertrophy and normal contraction of the left ventricular wall Pulsed Doppler left ventricular inflow velocity wave and pulmonary venous flow velocity wave disclosed restrictive filling patterns. After Ca antagonist, nitrate, and diuretics were administered, blood pressure was normalized, and left ventricular inflow velocity wave showed the relaxation abnormality pattern and pulmonary venous flow velocity wave showed the normal pattern. Radioiodinated iodine-123 metaiodobenzyl guanidine (123I-MIBG) imaging in the state of normalized blood pressure showed decreased heart to mediastinum ratio and increased washout rate. Left heart catheterization and angiography revealed normal end-diastolic pressure and coronary arteries, but coronary flow reserve evaluated with Doppler flow wire and intracoronary adenosine triphosphate administration was impaired: Plasma level of atrial and brain natriuretic peptides, which were markedly elevated on admission, decreased with the improvement of heart failure. Doppler flow velocity patterns, plasma levels of atrial natriuretic peptide and brain natriuretic peptide, cardiac sympathetic nerve activity, and coronary flow reserve might be useful for evaluating the severity of left ventricular diastolic dysfunction in patients with hypertensive heart disease.

Immunological analysis of enhanced spontaneous metastasis in WKA rats following cryosurgery.

We have previously reported that inhibition of anti-tumor immune responses and enhancement of metastatic tumor growth occurred in rats following cryosurgery of the transplantable 3-methlcholanthrene-induced rat fibrosarcoma KMT-17. In this study, to elucidate the immunological responses in rats following cryosurgery, we examined whether rat serum obtained from rats which underwent cryosurgery (c-serum) might affect the in vivo neutralizing activity of the Winn assay. In this assay, c-serum did not reduce the anti-tumor immunity, though spleen cells obtained from rats undergoing surgical excision indicated strong anti-tumor immunity as compared with cryosurgery. Thus, we examined the anti-tumor responses of spleen cells. Macrophages were obtained from the glass adherent fraction of rat spleen cells following cryosurgery and these macrophages were used for cytostatic activity against KMT-17 cells. Cytostatic activity was not reduced by cryosurgery. The spleen cells obtained from rats receiving cryosurgery were intravenously transferred into other rats that were previously immunized with 80 Gy-irradiated KMT-17 cells, and an alteration of tumor growth modulated by this adoptive cell transfusion was observed. The anti-tumor resistance of rats was diminished by the adoptive transfusion of spleen cells treated with cryosurgery, though this diminution disappeared following anti-T serum and immune complement treatment of spleen cells. These results suggest that immuno-suppression following cryosurgery may be mainly caused by suppressor T cells.

Relationship between left atrial function and plasma level of atrial natriuretic peptide in patients with heart disease.

To investigate the relationship between left atrial function and secretion of atrial natriuretic peptide (ANP), we analyzed left ventricular inflow and pulmonary venous flow, left atrial dynamics, intracardiac pressures, and plasma ANP level in 92 patients with various cardiac diseases. From the apical four-chamber view, maximal left atrial volume and percent fractional change of the left atrial area during atrial systole (LA-%AC) were calculated. The ratio of peak early filling velocity to peak atrial systolic velocity (E/A) in the left ventricular inflow and the ratio of peak systolic velocity to peak diastolic velocity (S/D) in the pulmonary venous flow were measured with the pulsed Doppler method. A significant linear correlation was found between plasma ANP levels and pulmonary capillary wedge pressure. Significant linear correlations were also found between left ventricular end-diastolic pressure and both maximal left atrial volume and LA-%AC. Plasma ANP level was significantly correlated with maximal left atrial volume, LA-%AC, E/A, and S/D. A multivariate analysis revealed that only LA-%AC was significantly correlated with the plasma ANP level. These results suggest that left atrial systolic dysfunction associated with a left atrial afterload mismatch is closely related to the ANP secretion.

Right heart flow dynamics after tricuspid valve annuloplasty. Characteristics and time course.

To evaluate the effect of tricuspid annuloplasty (TAP) on right heart flow dynamics, we analyzed tricuspid inflow velocity pattern, jugular venous pulse and color Doppler flow signal of tricuspid regurgitation (TR) before and after surgery in 16 patients who underwent TAP (TAP group). Cardiac rhythm was atrial fibrillation in all patients. Twelve patients with lone atrial fibrillation served as controls (AF group). Patients in the TAP group were studied before and serially after surgery with a mean follow-up period of 2.7 years. TAP was performed according to the modified De Vega technique in all patients. In a comparison of the most recent data in the TAP group and the data in the AF group, the maximum tricuspid inflow velocity was significantly increased, and both the deceleration time of the tricuspid inflow velocity wave and the y-h interval of the jugular venous pulse were significantly prolonged in the TAP group compared to the AF group. Immediately after surgery, in the TAP group, the area of the TR jet was markedly decreased, and the deceleration time of the tricuspid inflow velocity wave was significantly prolonged compared to those before surgery. The area of the TR jet was dramatically decreased and remained small during the follow-up period. Thus, TAP may produce mild tricuspid stenosis but may also confer sustained preventive effects against TR.

Inhibitory effects of malotilate on invasion and metastasis of rat mammary carcinoma cells by modifying the functions of vascular endothelial cells.

Malotilate (diisopropyl,1,3-dithiol-2-ylidenemalonate, MT) is clinically used as a hepatoprotective agent. Because we noticed that MT induced the differentiation of cultured vascular endothelial cells, we have examined its effects on lung metastasis of the highly metastatic rat mammary carcinoma c-SST-2. MT was orally administered to syngeneic SHR rats from 7 days before or after s.c. inoculation of c-SST-2 cells to the end of the experiments. In the MT-treated rats, pulmonary metastasis was markedly suppressed compared with the non-treated rats. In the rats treated with MT for 19 days after i.v. inoculation of c-SST-2 cells, lung metastasis was also significantly suppressed. An in vitro invasion assay using a rat lung endothelial (RLE) cell monolayer revealed that pretreatment of the RLE cells with MT, but not c-SST-2 cells, significantly reduced the invasion of the RLE monolayer by c-SST-2 cells. An in vitro vascular permeability assay demonstrated that MT prevented the increase in permeability of the RLE monolayer by serum starvation. On the other hand, in vivo and in vitro growth, gelatinase production and adhesion to the RLE cell monolayer of c-SST-2 cells were not affected by MT treatment. These findings suggest that MT suppressed tumour metastasis by intensifying the cell-to-cell contact of endothelial cells, thus preventing tumour cells from invading vascular endothelium.

Echocardiographic assessment of right atrial function in patients with myocardial infarction with reference to obstructive lesions of the coronary arteries.

We assessed the relationship between right atrial (RA) function and obstructive lesions of the coronary arteries in 29 patients with recent or old myocardial infarction (MI). Patients were divided into 3 groups according to the location of obstructions as follows: obstruction at the proximal right coronary artery (segments 1 and 2) (RCA proximal group, n=9); obstruction at the distal RCA (segments 3 and 4) (RCA distal group, n=6); and obstruction at the left anterior descending coronary artery (LCA group, n=14). The RA volume and the fractional change in the RA area during atrial contraction (RA %AC) were evaluated by apical 2-dimensional echocardiography. The right ventricular (RV) end-diastolic pressure (RVEDP) was measured in 4 patients in the RCA proximal group and 4 patients in the LCA group. The ejection fraction of the right ventricle (RVEF) was measured by radionuclide angiography or 2-dimensional echocardiography in 7 patients in the RCA proximal group, 5 patients in the RCA distal group, and 7 patients in the LCA group. The RVEF tended to be lower in the RCA proximal group than in the RCA distal and LCA groups. The RA volume was significantly greater in the RCA proximal group than in the LCA group. The RA %AC was significantly smaller in the RCA proximal group than in the RCA distal and LCA groups. There were no significant differences in the early diastolic RV inflow velocity among groups, but the late diastolic RV inflow velocity was significantly lower in the RCA proximal group than in the RCA distal and LCA groups. There was no significant difference in the RVEDP between the RCA proximal and LCA groups. Thus, RA dysfunction in the RCA proximal group appeared to be due to myocardial damage rather than to afterload mismatch. These findings suggest that RA dysfunction may occur in patients with an inferior MI who have an obstructive lesion of the proximal RCA.

[Cardiac amyloidosis with atrioventricular valve thickening and left atrial dysfunction: a case report].

A 70-year-old man with cardiac amyloidosis was referred to our hospital because of exertional chest pain accompanied by ischemic changes on electrocardiography on April 2, 1997. Transthoracic echocardiography revealed a normal size and normally contracted left ventricle without hypertrophy and "granular sparkling" quality of the myocardium, thickening of the mitral and tricuspid valves, and enlargement of the left atrium with reduced booster pump function. Pulsed Doppler mitral inflow velocity wave showed a pseudonormalized pattern, and pulmonary venous flow velocity wave showed a non-compliant pattern. Transesophageal echocardiography revealed thickening and reduced movement of the interatrial septum and reduced flow velocity in the left atrial appendage, suggesting left atrial dysfunction. Adenosine triphosphate (ATP) stress thallium-201 myocardial scintigraphy showed reversible patchy defect mainly in the posterolateral wall. Left ventricular end-diastolic and pulmonary capillary wedge pressures were mildly elevated. Angiography showed normal coronary arteries, but coronary flow reserve measured by administering intravenous ATP in the left anterior descending artery was severely impaired. A rectal biopsy specimen was positive by Congo red staining. Thus, angina pectoris in this patient may be due to amyloid infiltration of the small intramural coronary arteries. Atrioventricular valve thickening and left atrial dysfunction are important clues to diagnose cardiac amyloidosis.