Biomedical subjects
Publications and source records attributed to K Hiwada.
Pulmonary sequestration is a relatively rare anomaly. The arterial supply usually is derived from the aorta or its major branches. We present a 65-year-old female patient with pulmonary sequestration receiving arterial supply from the right coronary artery, complicated with sick sinus syndrome.
Cystic lesion, malignancy and interstitial pneumonia are well-known as pulmonary complications of patients with von Recklinghausen's disease. We report herein an unusual patient with distal acinar emphysema and interstitial pneumonia of prominent hypercellularity demonstrated by transbronchial biopsy and broncho-alveolar lavage fluid (BALF). Six months after quitting smoking, the total cell count of BALF was remarkably reduced. This patient remains stable under 5-year observation in terms of symptoms and findings of both BALF and pulmonary function tests. Quitting smoking may have facilitated a favorable prognosis for the particular lung disease complicated in this patient.
A 72-year-old man was admitted to our hospital because of a tumor-like shadow on a chest X-ray film. At the initial examination, he had clinical signs of Cushing's syndrome: moon face, central obesity, and hypertension. A computed tomographic scan of chest showed an abnormal shadow in the lung (5 x 6 cm) with involvement of the right paratracheal and anterior tracheal lymph nodes, and a right-sided pleural effusion. Small cell lung cancer (extended disease; T2N2M6 stage IV) was diagnosed after a transbronchial biopsy. The concentrations of adrenocorticotropic hormone, cortisol, and parathyroid hormone in plasma were markedly elevated, and there was no circadian rhythm (336 pg/ml. more than 60.1 micrograms ml. and 805 pg/ml, respectively). Fluid obtained by thoracentasis had malignant cells, and the levels of adrenocorticotropic hormone and parathyroid hormone in the effusion (1120 pg/ml and 1810 pg/ml, respectively) were higher than those in serum, which indicates that these hormones were produced by the tumor cells. The patient received chemotherapy and responded well, but he died of respiratory failure 26 months later. The response rate to chemotherapy in elderly patients with lung cancer is said to be comparable to that in younger patients, but treatment may be difficult because of poor performance status and diminished physical capacity. Although patients with lung cancer complicated by Cushing's syndrome have a poor prognosis, this patient survived for more than 2 years after the disease was diagnosed.
The Guidelines on Treatment of Hypertension in the Elderly, 1995 was published by the Research Group for Guidelines on Treatment of Hypertension in the Elderly Comprehensive Research Projects on Aging and Health, the Ministry of Health and Welfare. To assess the guidelines, and to further investigate the changes in the therapeutic policy for hypertension in the elderly, we mailed a questionnaire to 133 Japanese hypertension specialists who had replied to the first mailed questionnaire in 1993. We received 102 replies (77%). Overall, the guidelines were scored 4.3/5.0. More than 95% of the specialists agreed with levels of blood pressure (BP) indicative for treatment, as well as the goal of BP control. The guidelines propose that the rate of increase of the drug dose should be very slow, at least every four weeks, and that the target BP be reached after two months. The majority of the specialists agreed with this. However, 10% of them preferred to follow patients every two weeks. The guidelines propose long-acting Ca antagonists and ACE inhibitors as the first choice of drug for the treatment of uncomplicated hypertension in the elderly. Two-thirds of the specialists agreed. However, 17% of specialists proposed adding diuretics or beta-blockers to the first line therapy. Ten specialists (10%) expressed concerns about Ca antagonists and three (3%) insisted on withdrowing them from the first line of drugs. In the guidelines, alpha and beta blockers are designated as relatively contraindicated in elderly patients with hypertension, but half the specialists answered that these drugs can be used safely in elderly patients. These findings indicate that the therapeutic policy of Japanese specialists in hypertension in the elderly has not changed substantially for three years.
A 70-year-old man was admitted to our hospital for further evaluation of recurrent fever, which had begun in October 1994. The patient had 5 to 7 days without fever, and then 2 to 3 days of fever. He had headaches during the febrile periods. On admission, he had abnormal pyramidal, extrapyramidal, and celebellar signs, and nuchal rigidity during the febrile period. However, these neurological abnormalities were completely absent during the afebrile period. Examination of cerebrospinal fluid revealed pleocytosis of mononuclear cells. During the febrile period, pleocytosis was associated with high levels of IgG, IL-6, TNF-alpha, and PGE2 in the cerebrospinal fluid. Administration of indomethacin prevented the fever, which suggests that abnormal production of cytokines in the cerebrospinal fluid contributes to fever in Mollaret meningitis.
In order to examine the current status of antihypertensive drug therapy for elderly hypertensive patients, and the effect of clinical characteristics and drugs on their prognosis, 1669 hypertensive patients in the Chugoku and Shikoku districts, aged between 65 and 84 years, were enrolled and followed for 3 years. Of the 1669 patients enrolled, 1459 were selected for evaluation and 1127 patients were followed. Group A comprised 955 patients who had not suffered from any accident, group B comprised 139 patients who had suffered from a cerebral, cardiac, renal or other non-fatal accident, and group C comprised 33 patients who died. The mortality rate was 10.7/1000 patient.years and the morbidity rate was 55.6/1000 patient.years. The number of patients who received monotherapy was 736 (calcium channel blockers: #436, beta blockers: #100, angiotensin converting enzyme inhibitors: #80, diuretics: #64, alpha blockers: #16; others: #13). In group C, there were more male, and the patients were older and showed a higher level of serum creatinine concentration at enrollment compared with other groups. The use of diuretics and beta blockers tended to be low in this group. Among the three groups, however, there was no difference in blood pressure, heart rate or the use of each drug at enrollment. In summary, it is suggested that the different antihypertensive drug therapies die not influence the prognosis of elderly hypertensive patients.
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Carcinoembryonic antigen (CEA) has been clinically used as a serum marker for lung cancer, especially for pulmonary adenocarcinoma. Since we had developed a tumor marker against pulmonary adenocarcinoma, CAM 123-6 belonging to KL-6 MUC 1 mucin, we compared its clinical value with that of CEA, in combination with squamous cell carcinoma-related antigen (SCC) and neuron-specific enolase (NSE). The subjects were 30 patients with adenocarcinoma, 23 with squamous cell carcinoma, 16 with small cell carcinoma, and 20 with benign lung disease. For discriminating lung cancer from benign lung disease, the combination of CAM 123-6, SCC, and NSE showed 64% diagnostic accuracy, and the combination of CEA, SCC, and NSE 65%. In differentiating pulmonary adenocarcinoma from other lung cancer, the diagnostic accuracy of CAM 123-6 was 81% and that of CEA was 74%, although there was no significant difference between them. These observations indicate that the diagnostic accuracy of CAM 123-6 is similar to that of CEA. Neither marker is sufficiently specific to differentiate pulmonary adenocarcinoma from other forms of lung cancer.
A 38-year-old man was admitted to our hospital for detailed examination of fever, cough and yellow sputum. At the age of 32, be had mitral prosthesis for the first time, because of mitral regurgitation due to mitral valve prolapse. Four years previously, he had again undergone mitral prosthetic valve replacement due to prosthetic valve endocarditis due to staphylococcus epidemidis. This occasion, staphylococcus aureus was isolated by arterial blood culture. Transesophageal echocardiography detected vegetation attached to the mitral prosthetic valve and paravalvular leakage. The diagnosis was prosthetic valve endocarditis. He underwent a third mitral prosthetic valve replacement. Detection of the source of infection was difficult only by transthoracic echocardiography, and immediate transesophageal echocardiography seemed mandatory to diagnose bacterial endocarditis.
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Autonomic nervous function in elderly essential hypertensive patients was investigated by power spectral analysis of heart rate variability. Fifty-seven essential hypertensive patients participated in this study. They were divided into two groups: the middle-aged group (age < or = 59 years, n = 30) and the elderly group (age > or = 60 years, n = 27). All examinations were performed during hospitalization. Power spectral analysis of R-R interval was performed from Holter electrocardiogram every 10 min by the maximum entropy method to obtain the low frequency band (LFB; 0.04 to 0.15 Hz), which is an index of both sympathetic and parasympathetic nervous activity. Twenty-four-hour blood pressure measurement was performed by the cuffoscillometric method to evaluate the nocturnal decrease in blood pressure. Nondipper patients were defined as those whose nocturnal decrease in systolic blood pressure was < 10% of daytime blood pressure. Both LFB and HFB were significantly lower in elderly hypertensive patients than in middle-aged patients (P < .001 and P < .05, respectively). Elderly nondipper patients had further reduced power spectral densities throughout the day. Both LFB and HFB showed a negative correlation with age. However, the age-related decline of power densities was more prominent in dipper patients and was not statistically significant in nondipper patients. These findings indicate that the nondipper phenomenon is superimposed on age-related attenuation of autonomic nervous function in essential hypertension.
Generation of soluble cytokine receptors is a general phenomenon, and the roles of several such receptors have been investigated in clinical settings. Unlike other soluble cytokine receptors, soluble interleukin-6 receptor (sIL-6R) can act as an agonist and thus is implicated as an important modulator in the acute-phase reaction of prolonged inflammation. The purpose of the present study was to determine the roles of pleural sIL-6R in both differential diagnosis of pleural diseases and in the induction of acute-phase protein. Specific sandwich enzyme-linked immunosorbent assays were used to determine sIL-6R and IL-6 in 19 tuberculous, 48 malignant and 10 transudative effusions. Although IL-6 levels in pleural effusions were strikingly different, no significant differences in pleural sIL-6R levels were found between the groups. Pleural levels of IL-6 were invariably much higher, whereas those of SIL-6R were invariably lower than serum levels. Furthermore, IL-6, but not sIL-6R, levels in effusions correlated significantly with serum C-reactive protein levels. These results suggest that: (1) pleural levels of sIL-6R are not increased even in strong inflammation such as tuberculous pleurisy, nor significantly different among pleural diseases; and (2) the local levels of sIL-6R are not as important as expected for the induction of acute-phase proteins in patients with pleural diseases.
1. We assessed the changes of atrial natriuretic peptide and brain natriuretic peptide gene expression associated with progression and regression of cardiac hypertrophy in renovascular hypertensive rats (RHR). 2. Two-kidney, one-clip hypertensive rats (6-week-old male Wistar) were made and studied 6 (RHR-1) and 10 weeks (RHR-2) after the procedure. Regression of cardiac hypertrophy was induced by nephrectomy at 6 weeks after constriction, and the nephrectomized rats were maintained further for 4 weeks (nephrectomized rat: NEP). Sham operation was performed, and the rats were studied after 6 (Sham-1) and 10 weeks (Sham-2). Atrial natriuretic peptide and brain natriuretic peptide gene expression in the left ventricle was analysed by Northern blotting. 3. Plasma atrial natriuretic peptide and brain natriuretic peptide were significantly higher in RHR-1 and RHR-2 than in Sham-1, Sham-2 and NEP. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels in RHR-1 were approximately 7.2-fold and 1.8-fold higher than those in Sham-1, respectively, and the corresponding levels in RHR-2 were 13.0-fold and 2.4-fold higher than those in Sham-2, respectively. Atrial natriuretic peptide and brain natriuretic peptide mRNA levels of NEP were normalized. Levels of atrial natriuretic peptide and brain natriuretic peptide mRNA were well correlated positively with left ventricular weight/body weight ratios. There was a significant positive correlation between the levels of atrial natriuretic peptide and brain natriuretic peptide mRNA (r = 0.86, P < 0.01). 4. We conclude that the expression of atrial natriuretic peptide and brain natriuretic peptide genes is regulated in accordance with the degree of myocardial hypertrophy and that the augmented expression of these two natriuretic peptides may play an important role in the maintenance of cardiovascular haemodynamics in renovascular hypertension.
Interleukin 6 (IL-6) is a multifunctional inflammatory cytokine whose abnormal production has been implicated in a variety of diseases. Our previous study demonstrated that exudative pleural effusions contain a large amount of IL-6, and the levels of IL-6 in pleural effusion have diagnostic and pathophysiologic values. Although IL-6 is produced by a variety of cells, the origin of IL-6 in pleural effusion has not been determined clearly. We hypothesized that pleural mesothelial cells (PMCs) are an important source of IL-6 in pleural diseases. In this study, we tried to demonstrate whether PMCs could produce IL-6 and to characterize the modulation of its production. PMCs were established from patients with nonmalignant pleural effusion. Immunoreactive IL-6 could be detected in cultured supernatants of all PMCs from five patients, and all IL-6 detected in the supernatants were biologically active. IL-6 production was augmented by the addition of interleukin 1 alpha (IL-1 alpha) in a dose-dependent manner and suppressed by dexamethasone. Expression of IL-6 mRNA was spontaneously observed and was increased by IL-1 alpha. PMCs also expressed mRNA for IL-6 receptors gp80 and gpl30. Spontaneous cell growth and DNA synthesis of PMCs were inhibited by the addition of a neutralizing anti-IL-6 monoclonal antibody and were promoted by the addition of IL-6 to the culture. These results suggest that IL-6 is an autocrine growth factor for PMCs.
To evaluate the aortic wall sclerosis in patients with coronary artery disease (CAD), the authors measured the aortic distensibility (AD) at the ascending and descending aorta by using cine magnetic resonance (MR). Cine MR was performed in 15 patients with CAD and 15 normal controls (NCs). Patients with CAD had angiographically significant coronary arterial stenosis and almost normal left ventricular function. Age and sex were matched in the patients with CAD and the NCs. Ascending and descending aortic areas of transverse image were measured in the maximum and minimum frames. AD was calculated from the following formula: (max area - min area)/(min area x pulse pressure). Although systolic and diastolic blood pressures showed no significant differences between patients with CAD and NC, AD was significantly lower in patients with CAD than in the NCs in each transverse section (P < 0.05). In conclusion, it is indicated that aortic wall sclerosis is advanced in patients with CAD.
In order to evaluate aortic wall sclerosis in hypertension, the authors studied the following two parameters of carotid pulse tracing and ascending aortic wall distensibility by using cine magnetic resonance (MR) in 15 age- and sex-matched normal volunteers (NC) (mean age, fifty-four years old) and 15 hypertensive patients (HT) (mean age, fifty-four years old). As the parameters of carotid pulse tracing, they measured the interval from aortic second heart sound to dicrotic notch (A2-DN), and the height from dicrotic notch to top/total height of carotid pulse tracing (b/a ratio). Ascending aortic distensibility was calculated from the following formula: (max area - min area)/(min area x pulse pressure). A2-DN interval was lower in HT than in NC (18.4 +/- 7.9 vs 31.5 +/- 9.2 ms, P < 0.01). The b/a ratio was lower in HT than in NC (0.34 +/- 0.07 vs 0.44 +/- 0.09, P < 0.01). Ascending aortic distensibility was lower in HT than in NC (2.08 +/- 1.37 vs 7.26 +/- 2.51 x 10(-3) mmHg(-1), P < 0.01). In conclusion, ascending aortic wall sclerosis is advanced in hypertension. A2-DN interval and b/a ratio measured by carotid pulse tracing are useful indicators in evaluating the ascending aortic wall distensibility in hypertension.
Oral calcium (Ca) supplementation mildly reduces blood pressure. The authors studied the effects of Ca supplementation on the cardiovascular system in patients with mild to moderate essential hypertension. Twelve patients aged forty-nine to seventy years (7 men and 5 women, mean age with 60.3 +/- 7.2 years) participated. The investigators orally administered Ca (1.0 g/day for one week) under hospitalization, adding to a dietary intake of Ca (0.6 g/day). Left ventricular function and systemic arterial compliance were evaluated by M-mode and pulsed Doppler echocardiographies before and after seven days of Ca supplementation. Left ventricular contractility and afterload were not changed. Preload indicated by end-diastolic volume was significantly decreased after Ca supplementation (109.6 +/- 8.5 vs 107.3 +/- 8.2 mL, P < 0.05). Myocardial relaxation evaluated by IIa-mitral valve opening time (87.7 +/- 6.7 vs 82.1 +/- 6.2 ms, P < 0.01) and maximum descending rate of the left ventricular posterior wall (10.6 +/- 1.0 vs 12.4 +/- 1.0 cm/s, P < 0.01), and atrioventricular net compliance assessed by the descending slope of rapid filling flow in the left ventricular inflow tract (2.63 +/- 0.24 vs 2.26 +/- 0.17 m/s2, P <0.05), as well as systemic arterial compliance (2.05 +/- 0.20 vs 2.73 +/- 0.26 mL/mmHg, P < 0.01) were significantly improved by Ca supplementation. Oral Ca supplementation improved the disturbed left ventricular diastolic function and systemic arterial compliance.