Shozo Kusama

Early identification of amyloid heart disease by technetium-99m-pyrophosphate scintigraphy: A study with familial amyloid polyneuropathy

To determine whether technetium-99m-pyrophosphate (Tc-99m-PYP) scanning or two-dimensional echocardiography can detect amyloid heart disease in an earlier stage of familial amyloid polyneuropathy, 15 patients were examined. Although 10 of the 15 patients had no clinical evidence of congestive heart failure, as well as normal ventricular wall thickness and normal values for left ventricular systolic function, five (50%) of them showed mild or moderate myocardial uptake. On the other hand, none had characteristic highly refractile myocardial echoes on the two-dimensional echocardiographic images (p less than 0.01), and values for diastolic function were reduced in four of the five and normal in the remaining one. In 85 control subjects, diffuse positive pyrophosphate scans of the heart were found in four (5%) of them (three with dilated cardiomyopathy and one with sarcoidosis), and highly refractile granular sparkling echoes were observed in nine (11%) (five with hypertrophic cardiomyopathy, three with aortic stenosis, and one with hypereosinophilic syndrome). We conclude that Tc-99m-PYP scanning is a more sensitive and specific method and may have the potential ability to detect amyloid heart disease in the earlier stage of familial amyloid polyneuropathy than two-dimensional echocardiography.

Effects of ONO-6240, a platelet-activating factor antagonist, on endotoxin shock in unanesthetized sheep

To determine the role of platelet-activating factor (PAF) in endotoxin shock, we studied the effects of ONO-6240, a PAF antagonist, on endotoxin shock in unanesthetized sheep. Changes in hemodynamics, lung lymph balance, leukocyte and platelet counts, and arterial blood gas tensions were measured in four groups; endotoxin alone; endotoxin plus ONO-6240; ONO-6240 alone; vehicle control. Pretreatment with ONO-6240 in sheep given endotoxin significantly prevented the decreases in systemic arterial pressure, left atrial pressure and cardiac output observed in sheep given endotoxin alone. A partial effect on diminishing the magnitude of peripheral leukopenia was also noted. However, pretreatment with ONO-6240 had little effect on pulmonary hypertension and lung lymph balance. We conclude that endotoxin causes two different effects: vascular collapse and direct lung injury; and that PAF is involved only in the circulatory manifestations.

PPD‐Specific Proliferative Response in Humans: I. Analysis of PPD‐Specific Proliferative Cells from Tuberculous Pleurisy Patients and Healthy Controls with Monoclonal Antibodies Specific for Human T Subsets

Peripheral mononuclear cells (PBL) from tuberculin reaction (TR)‐negative tuberculous pleurisy patients proliferated poorly with PPD, while the cells of pleural effusion from these patients showed a proliferative response to PPD as well as did the healthy control PBL. Surface antigens of peripheral blood and pleural effusion were examined by using monoclonal antibodies. The Leu 1‐positive cell population can be divided into four groups, namely (1) Leu 1+, Leu 2a+, Leu 3a+, (2) Leu 1+, Leu 2a+, Leu 3a−, (3) Leu 1+, Leu 2a−, Leu 3a+, and (4) Leu 1+, Leu 2a−, Leu 3a− cell populations. Results of analysis of surface antigens of PPD‐specific proliferative cells in peripheral blood and pleural effusion from tuberculous pleurisy patients as well as healthy controls indicate that the PPD‐specific proliferative response is mediated by Leu 1+, Leu 2a−, Leu 3a+ cells and Leu 1+, Leu 2a−, Leu 3a− cells.

Serological cross-reactivity of murine A.TH anti-A.TL antibody (anti-I-Ek antibody) with la-like molecules of human antigen-presenting cells

The purified protein derivative (PPD)-specific proliferative responses of T cells from human peripheral blood are shown to be dependent on antigen-presenting cells (APC) which bear HLA-DR antigen detected by the monoclonal anti-HLA-DR antibody. The serological cross-reactivity of murine A.TH anti-A.TL antibody was observed in human APC. By absorption experiments using H-2 congenic mice, the serological cross-reactivity of A.TH anti-A.TL antibody with human APC is mapped in the I-E subregion. Thus, anti-I-Ek antibody reacts with the Ia-like molecule(s) on human APC. Murine allo-anti-I-Ek antibody does not always react with determinants of Ia-like molecule(s) on human APC, since this antibody did not eliminate PPD-specific proliferative responses in one particular case. Thus, anti-I-Ek antibody seems to react some type of the polymorphic determinants but not of the shared determinants of human Ia-like molecule(s) on APC. The relationship between the cross-reactive molecule detected by murine allo-anti-I-Ek antibody and the HLA-DR antigen remains to be analyzed.

Effects of polycations on pulmonary vascular permeability in conscious sheep.

The role of charged sites on the permeability characteristics of the pulmonary microvascular barrier were investigated using chronically instrumented unanesthetized sheep. In one series of experiments we studied the effects of the cationic amphiphile, dodecyl trimethylamine (DTA; 297 mol wt), and the anionic amphiphile, SDS (288 mol wt), on lung lymph flow rates (Ql), lung lymph to plasma protein ratios (L/P), pulmonary hemodynamics, and systemic hemodynamics. DTA significantly increased both Ql and L/P, whereas SDS had a more modest and transient effect on these variables. In a second series of experiments the polycations polybrene and poly-l-lysine were found to have very similar effects as those of DTA. In another series of experiments we tested the pretreatment inhibition potential of chlorpheniramine (an H1 receptor antagonist), dibutyryl-cyclic AMP (db-cAMP), and the calcium channel antagonists verapamil and nifedipine on polybrene-induced lung injury. We found that only verapamil and db-cAMP significantly attenuated the permeability effects of polybrene. We conclude that both cationic amphiphiles and polycations cause hemodynamic and permeability alterations in the pulmonary circulation of unanesthetized sheep. In addition, the permeability alterations induced by polybrene can be modulated by intracellular calcium and/or cAMP levels.

Development of High-Grade Ventricular Arrhythmias in Familial Amyloid Polyneuropathy

To determine which subsets of patients with amyloid heart disease are particularly susceptible to the development of clinically significant ventricular arrhythmias, 16 patients with familial amyloid polyneuropathy (FAP) were studied by serial 24-hour electrocardiographic monitorings and echocardiography. During a mean follow-up period of 26.6 months, seven patients (44%) developed repetitive premature ventricular complexes (PVCs), including ventricular couplets in four and ventricular tachycardia in three. One of them showed syncope at the time when the arrhythmia was identified. Although there were no significant differences in the mean age, duration of the illness before the beginning of the study, and the initial echocardiographic results, the mean follow-up periods were more prolonged and neurologic disabilities were more advanced in patients with repetitive PVCs compared with those without any significant arrhythmias. In addition, patients who developed repetitive PVCs showed significantly greater percent changes in ventricular wall thickness with resultant wall hypertrophy than those who did not. One of the three patients who died within one year of the final study experienced sudden cardiac death and had showed frequent episodes of ventricular tachycardia at the final study. We conclude that (1) high-grade ventricular arrhythmias develop frequently in patients with FAP in the far-advanced stage in whom progressive and marked myocardial amyloid infiltration occurs and (2) identification of subsets of patients with repetitive PVCs may be helpful for the treatment as well as management of amyloid heart disease.

Noninvasive Evaluation of Left Ventricular Systolic and Diastolic Time Intervals in Familial Amyloid Polyneuropathy

To determine left ventricular (LV) systolic and diastolic properties in patients with familial amyloid polyneuropathy (FAP), we analyzed simultaneous recordings of the electrocardiogram, phonocardiogram, carotid arterial pulse, and apex cardiogram (ACG) in 13 patients and 20 normal subjects. The following variables were measured: (1) LV systolic time intervals = iso-volumic contraction time (ICT), corrected preejection period (PEPi), corrected ejection time (ETi), corrected Q-I interval (Q-Ii), corrected Q-II interval (Q-IIi), PEP/ET, and ICT/ETi; (2) 1EA-O interval (IIA-O) = the time interval from the onset of the aortic component of the second heart sound to the 0 point on the ACG; (3) ΔT = the time interval from the onset of the aortic component of the second heart sound to the point on the ACG down-stroke where the curve falls to 50% of the total height of the diastolic deflection; and (4) ΔT/IIA-O. Patients with FAP had significantly greater Q-Ii, PEPi, Q-IIi, and PEP/ET than normal subjects, whereas there were no differences in the ETi, ICT, and ICT/ETi. Patients with FAP also showed slightly greater IIA-O than normal subjects but the difference was not significant. In addition, AT and AT/IIA-0 were significantly greater in patients with FAP than in normal subjects. We conclude that in patients with FAP, LV relaxation is impaired, especialy in early diastole, whereas systolic function is generally preserved, and that electromechanical delay is markedly increased.

Impaired Left Ventricular Diastolic Properties in Patients with Familial Amyloid Polyneuropathy : A Study by Computerized M-Mode Echocardiography

To determine left ventricular (LV) diastolic properties in patients with familial amyloid polyneuropathy (FAP), we examined 17 patients by means of computerized M-mode echocardiography and compared the results with 25 normal subjects. Patients with FAP showed a significantly lower peak rate of diastolic LV internal dimension (dD/dt) as well as a lower peak rate of diastolic thinning of the LV posterior wall (dW/dt) than normal subjects, whereas LV systolic parameters, including cardiac index, ejection fraction, and ejection time, were nearly identical. Furthermore, although eight of the 17 patients had normal LV posterior wall thickness, they had a significantly lower dD/dt, as well as a lower dW/dt, than normal subjects. We conclude that in patients with FAP LV diastolic properties are changed, whereas systolic function is almost preserved, and diastolic abnormalities can be seen even in the absence of LV hypertrophy.

Early Detection of Amyloid Heart Disease by Technetium-99M-Pyrophosphate Single-Photon Emission-Computed Tomography : A Study with Familial Amyloid Polyneuropathy

Eighteen patients with familial amyloid polyneuropathy (FAP) were studied to determine whether technetium-99m-pyrophosphate (Tc-99m-PYP) scintigraphy or two-dimensional echocardiography (2-DE) can detect myocardial involvement in an earlier stage. Thirteen of them were considered to be in the early stage of myocardial amyloid infiltrative process because they showed no clinical evidence of overt heart disease, as well as normal ventricular wall thickness and normal values for left ventricular systolic function. Although planner scintigraphy showed mild or moderate myocardial uptake in six (46 %) of the 13 patients, single-photon emission-computed tomography, performed in 12 of them, demonstrated an unevenly distributed biventricular uptake in ten (83 %), including four who were judged to be negative by the planner scanning. On the other hand, none had characteristic highly refractile myocardial echoes on the 2-DE images. In additional 95 control patients with nonischemic heart disease, planner scintigraphy showed diffuse positive pyrophosphate scans of the heart in five (4%) of them and 2-DE demonstrated granular sparkling echoes in 10 (10%). In conclusion, (1) planner Tc-99m-PYP scanning is a more sensitive and specific procedure to detect amyloid heart disease in the earlier stage of FAP than 2-DE and (2) single-photon emission-computed tomography may be more sensitive for diagnosing this condition.

An infiltrative right ventricular myxoma

SummaryComputed tomographic findings in a 71-year-old patient with an infiltrative right ventricular myxoma are described. The findings included multiple lesions in the right ventricle and stenosis of the trunk of the pulmonary artery.