[Pulmonary hypertension due to autoimmune mechanism].
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Biomedical subjects
Publications and source records attributed to T Kunieda.
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Acute fatal pulmonary embolism is one cause of sudden death which should be guarded against. It is the most often missed diagnosis in sudden death cases within the hospital. Clinical pictures of 10 patients with acute fatal pulmonary embolism proved by autopsy were examined to elucidate the problems of diagnosis, and to look for an effective treatment, and a method of prevention. Common risk factors were old age and immobility due to stroke or postoperative state. Common past histories were hypertension, diabetes mellitus, obesity, atrial fibrillation and hyperlipidemia. Electrocardiogram and echocardiogram showed that in these patients there was definite evidence of acute right ventricular overload. High doses of intravenous urokinase should be given whenever acute cardiovascular collapse develops in such high risk patients. Emergent pulmonary angiogram and pulmonary embolectomy could be life-saving in patients with acute massive pulmonary embolism. Prevention is, however, the best treatment. In addition to anticoagulation medication, frequent change of body position and early mobilization are important precautions to prevent fatal pulmonary embolism developing in such patients.
An endoscopic electrical stimulation method (the new method) for the examination of the rectosphincteric reflex was devised to overcome difficulties attributable to the manometric method using balloon stimulation. Safety of the electrical stimulation under the conditions used routinely, was confirmed symptomatically and histologically. It was found that the optimal parameters of electrical stimulation to obtain the recto-sphincteric reflex were: 1 ms, 20 Hz, 5 to 7mA, and for 3 sec. The degree of the reflex relaxation became less and the time lag of the response to the stimulation became longer, as the distance of the stimulation site from the anal verge was increased. These relationships were significant. In the cases which received anterior resection of the rectum, the rectosphincteric reflex was examined using the new method. In 12 of 39 cases the recto-sphincteric reflex was induced by stimulation at the oral side of the anastomosis. In all of them the reflex was observed at 9 or more months postoperatively. Incidence of postoperative reflex appearance tended to be higher after end-to-end anastomosis than after side-to-end anastomosis. In two cases which received Duhamel-Okamoto's operation and in one which received Soave-Denda's operation, it was possible to analyze the relationship between the stimulating site and presence or absence of the reflex-like phenomenon.
A novel restriction fragment length polymorphism in inbred rats was detected by Southern blot analysis with rat growth hormone cDNA as a probe. Four alleles, characterized by PstI fragments of 1.2, 1.1, 0.9, and 0.7 kb, respectively, were detected in 27 strains examined. The same distribution of polymorphisms was observed on digestion of DNAs of these strains with three other enzymes, PvuII, HindIII, and BamHI. Moreover, the same differences in length of allelic restriction fragments were obtained with these restriction enzymes as with PstI. These findings suggested that the polymorphism was caused by insertion or deletion of variable DNA segments in the second intron of the growth hormone gene. Linkage analyses using backcross progeny provided no evidence for close linkage between the restriction fragment length polymorphism locus and 10 other loci examined.
A putative Arabidopsis thaliana gene, ara, homologous to the ras-related gene family was isolated from a genomic library by low-stringency hybridization with a v-Ha-ras probe. The putative gene has a coding frame for a 218-residue protein (Mr 24,210), which is interrupted by one intron. The amino acid residues conserved in proteins of the ras gene family, which are important for GTP binding, GTP hydrolysis and membrane attachment, are also present in the ara protein. An unusually long homopyrimidine-homopurine tract was found about 100 bp upstream from the methionine start codon. A unique sequence, 5'-AACAAAACCAAAGTGATATGC-3', was found three times in the 5'-noncoding region and once in the intron.
133 patients with chronic cor pulmonale due to dysventilation syndrome were studied. Chronic obstructive pulmonary disease (COPD) was found, possibly for the first time in Japan, to be the most common etiological condition, occurring in 54% of the patients. Chronic cor pulmonale was clinically diagnosed as the appearance of right heart failure on admission. Patients were divided into two groups depending on clinical state, compensated and decompensated. There was a marked difference in arterial blood gases and electrocardiographic fluctuations between the states. Serial observations of these parameters and enlarged cardiac silhouette to the left on plain chest film provided diagnostic evidence for development to the decompensated state. Pulmonary artery pressure changes on exercise and during sleep at night has been considered to impair right heart function. Prognosis of chronic cor pulmonale largely depends on the concentrated therapy of the decompensated state. 85% of patients in the current study returned to the compensated state with active intensive therapy. Recent therapeutic progress has made control of this serious disease possible, despite the appearance of right heart failure. Laborious prolonged therapy appears to be essential in order to improve long-term prognosis.
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The difficulty in making an accurate diagnosis of acute pulmonary embolism is well known. To clarify the role of echocardiography, including Doppler echocardiography, in acute pulmonary embolism, we examined hemodynamic and echocardiographic parameters in 9 patients with acute pulmonary embolism just before and after treatment with urokinase. As hemodynamic parameters normalized after treatment, echocardiographic parameters such as deformity index of the left ventricle (LV-DI), end-diastolic dimension of the right ventricle (RVDd), the left ventricle (LVDd), the inferior vena cava, and RVDd/LVDd all significantly changed toward normal. Highly significant correlations were found between the echocardiographic and hemodynamic parameters, the best of which was between the LV-DI and systolic pulmonary artery pressure (r = -0.885, p less than 0.001). Doppler echocardiography quantitatively evaluated the grade of tricuspid regurgitation, and accurately estimated systolic pulmonary artery pressure. We conclude that echocardiography, including Doppler echocardiography, sensitively reflects the right ventricular pressure and volume overload of acute pulmonary embolism, is quite useful for its diagnosis which is often difficult, and is suitable for noninvasive follow up of these patients.
The distribution of an RFLP in EcoRI fragments of the cardiac myosin heavy chain gene among 29 strains of laboratory rats was examined. Southern blot hybridization of rat genomic DNAs with rat cardiac myosin heavy chain cDNA as a probe demonstrated an interstrain variation in one of eight EcoRI fragments. Of the 28 inbred strains examined, 10 had a fragment of 10 kbp, whereas 18 had a fragment of 7.5 kbp. The 15 samples of the remaining strain (Iar: WI outbred stock) had fragments of either 7.5 kbp or 10 and 7.5 kbp, indicating that this strain has maintained heterogeneity of these fragments.
Alveolar components in single breath tests were studied in normal subjects and patients with COPD using simultaneous He and N2 single breath washout and the "Air N2 method" developed in our laboratory since 1979, which was summarized as follows: Special device for the N2 fractional output of a mass spectrometer (Perkin Elmer MGA1100B) was made using a DC cancellation amplifier with inspired N2 concentration (FIN2) suppressed to zero voltage and the changing fraction (FEN2-FIN2) of expired N2 concentration (FEN2) was magnified by the high fidelity DC amplifier. FAirN2 (=FEN2-FIN2) versus expired volume (VE) was designated "Air N2 Curve" with prominent cardiac oscillations (CO) on its mild ascending plateau in normal subjects. Air N2 curve of COPD, however, showed a much steeper ascending plateau without CO. The slope of the air N2 curve under normal resting tidal volume breathing, expressed as the increase in nitrogen concentration per liter BTPS expired (delta AirN2), has been of particular value in the diagnosis of COPD as a new indicator of V A/Q inequality. The air N2 curve expired from tidal volume breath to residual volume (RV) was utilized to analyze phase IV and V. Fractional concentration of Air N2 ceased to increase with the appearance of phase IV and thereafter began to decrease, and then showed abrupt terminal rise at the onset of phase V. High VA/Q units must contribute to phase IV and to the contrary low VA/Q units must contribute to phase V. This provided supporting evidence of the contribution of upper lung regions in causing phase IV and of lower lung regions in causing phase V. Combined He bolus and N2 washout and Air N2 methods with changing expiratory flow rates proved phase IV and V to be flow-dependent. Closing volume (CV) in a static condition could be determined by the extrapolation of phase IV volume to zero flow. Phase IV and V were also shown to be parallel compartments of gravity dependence by the technique of postural change between inspiration and expiration. Simultaneous He and N2 washout curves revealed terminal falling He against continuous rising N2 without CO in COPD. This dissociation of slopes of alveolar plateaus was never seen in normal subjects when the usual amount of He bolus (200 ml) was introduced properly on RV. This offers the possibility of a unique, physiologically significant method to diagnose COPD indicating the disappearance of interregional non-homogeneity and the development of much more serious intraregional non-homogeneity with increased residual volume of poorly ventilated units.
The present study investigated whether or not, in addition to the oral glucose tolerance test, oral alanine loading was a useful diagnostic tool for hormonal and metabolic diseases. Fifty g of L-alanine was administered orally in 14 normal, 12 diabetic, and 8 liver cirrhotic subjects. The influence of oral alanine loading on hormones and metabolites was compared with the results of 100 g oral glucose loading. The results obtained were as follows: 1) In the normal subjects and cirrhotics, lactate and pyruvate concentrations gradually increased with time and reached their peak levels at 60 min, whereas they remained unchanged throughout the course in the diabetic group at glucose loading. 2) Alanine administration accelerated ureogenesis but did not affect blood glucose levels. 3) In both glucose and L-alanine administration, free fatty acid, glycerol and ketone body levels declined nonspecifically in all groups. 4) Serum glucagon levels during L-alanine loading increased in all groups, especially in liver cirrhotics. 5) L-alanine was a potent stimulus for insulin secretion in diabetics, while no insulin release during glucose loading was observed. 6) The molar ratio of insulin levels (during glucose loading)/glucagon levels (during L-alanine loading) was a good indicator of systemic glucose homeostasis from the hormonal aspect. It is suggested that, in addition to the oral glucose tolerance test, the oral administration of L-alanine can be a useful tool for the diagnosis of the status in diabetes mellitus and cirrhosis.
Nodular regenerative hyperplasia (NRH), a rare hyperplastic condition of the liver, is reported in two patients with primary pulmonary hypertension (PPH). The first patient was a 26-year-old man who died of PPH and showed multiple NRH without cirrhosis of the liver. The second patient was a 25-year-old man who had a PPH with pulmonary arterial thrombi and NRH of the liver. NRH has been described in association with immune disease, hematopoietic disorder, and diabetes mellitus, so that NRH with PPH is considered to be very rare. Histologic findings of the lungs show typically plexogenic pulmonary arteriopathy in both cases, and the livers of these patients are composed of multiple nodules that are histologically represented by slightly larger hepatocytes arranged in a cobblestone-like fashion, and are ultramicroscopically characterized by massive proliferation of mitochondria. The pathogenetic association of nodular regenerative hyperplasia with primary pulmonary hypertension will be discussed.
The acute effects of the selective alpha 1-blocker, E-643 (Bunazosine), on experimental pulmonary hypertension (PH) caused by hypoxic pulmonary vasoconstriction (HPV) in mongrel dogs were examined. Ninety second ventilation with 5% O2 and 95% N2 was used for hypoxic stimulation. The effects of E-643 were evaluated at doses of 1, 5, 10, 20 and 50 micrograms/kg in this order until the systemic arterial mean pressure (SAm) had decreased by 20 mmHg when compared with the control value during room air ventilation. PaO2 and PaCO2 decreased by 64.6 +/- 11.0 Torr and 2.4 +/- 2.5 Torr, respectively, and the pH increased by 0.031 +/- 0.012 during hypoxic ventilation. These blood gas changes affected during hypoxic stimulation were almost the same before E-643 administration. Progression of arterial blood hypoxemia due to E-643 administration during room air ventilation was not observed. SAm decreased by 8.0 +/- 11.9 mmHg after E-643 administration, while left atrial mean pressure (LAm) and cardiac output (CO) did not change significantly. Prior to E-643 administration, mean pulmonary arterial pressure (PAm) and pulmonary vascular resistance (PVR) increased by 6.4 +/- 3.3 mmHg and 6.2 +/- 3.8 HRU, respectively, during the 90 sec hypoxic ventilation period. After E-643 administration, the increases in PAm and PVR were 3.9 +/- 1.7 mmHg and 3.3 +/- 2.3 HRU, respectively. The suppression of increases in PAm and PVR was significant. The conclusion is that E-643, a selective alpha 1-blocker, is effective at restraining HPV in the dog model.
Multiple obstructions of the proximal pulmonary arteries were found in a patient with pulmonary hypertension and chronic cor pulmonale without any systemic arterial lesions. An operation to relieve severe stenosis at the right main pulmonary artery provided great clinical improvement. Pathologic examination of the biopsied specimen revealed a nonspecific panarteritis with giant cells consistent with idiopathic isolated pulmonary arteritis.
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Most patients with primary pulmonary hypertension (PPH) die within two to four years of the onsets of their symptoms. However, several reports have described patients with PPH who have lived more than 10 years including a case with regression. We studied prognoses and the various determinants in 21 patients (7 men and 14 women; 18 deceased and three living) with PPH to elucidate its pathophysiology. Age at the onset of the disease varied from 12 to 73 years, with a mean of 29 years. All causes of death were of right heart failure, except for two cases of non-cardiac deaths. The prognoses were as follows: less than one year, two cases; 1-2 years, seven (one living); 2-3 years, five; 3-4 years, two; 4-5 years, one; more than six years, four (two living), with a mean of three years and five months. Pulmonary artery pressure decreased 10 years later (mean pressure, from 54 to 41 mmHg) in one patient, who lived for 13 years, followed by a non-cardiac death. Various clinical and pathological factors, including age at the onset of disease, sex, relationship to pregnancy, immunological abnormalities (4, positive; 17, negative), patent foramen ovale (five, patent; 16, not patent), PaO2, hemodynamic parameters, treatments, pathological subtypes (10, plexogenic pulmonary arteriopathy; two, pulmonary micro-thromboembolism; one, pulmonary veno-occlusive disease) numbers of plexiform lesion/cm2 were examined for prognostic correlations. None of the above factors were found to correlate significantly with prognoses. The only significant correlation was between the cardiac index (r = 0.981, p less than 0.001, n = 6), and total pulmonary resistance (r = -0.894, p less than 0.02, n = 6) in patients with pregnancy-related PPH. There was variability in the state of progression, namely, from rapid progression to regression. Clinically as well as pathologically, PPH may consist of several subgroups. However, whether it is due to differences in etiology or reactions of the disease is not clear. The pregnancy-related cases may comprise a homogenous subgroup within PPH.
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Lymphocyte subpopulation as well as other hematological properties were compared between arterial and venous bloods of Wistar-Imamichi rats. Lymphocyte subsets were defined with four monoclonal antibodies which were specific to the respective cell surface glycoproteins. Using these monoclonal antibodies, subsets of B lymphocytes, T lymphocytes, helper T lymphocytes, and suppressor and cytotoxic T lymphocytes in the peripheral lymphocytes were identified. The blood samples were taken from aorta abdominalis and venae cava caudalis. The population of these subsets were enumerated by a laser flow-cytometry system. The result showed that there was no significant difference in hematological properties between the arterial and venous blood except in leukocyte count and hemoglobin concentration. The difference in leukocyte counts was thought to depend mainly on the fluctuation of the lymphocyte counts. However, no significant difference was recognized in the proportion of positive cells to each monoclonal antibody. It was concluded that the difference in leukocyte counts found between the arterial and venous bloods of the Wistar-Imamichi rat did not produce any effects on the proportion of the subpopulation in the peripheral lymphocytes, and the lymphocyte subpopulations in both arterial and venous bloods were substantially equivalent to each other.