Apnoea-hypopnoea index during rapid eye movement and non-rapid eye movement sleep in obstructive sleep apnoea.

This study investigated the differences in apnoea-hypopnoea index (AHI) during rapid eye movement (REM) sleep (AHI-REM) and AHI during non-REM (NREM) sleep (AHI-NREM) in patients with obstructive sleep apnoea (OSA). Nocturnal polysomnography was performed in 102 Japanese OSA patients and their AHI along with a variety of other factors were retrospectively evaluated. Regardless of the severity of AHI, mean apnoea duration was longer and patients' lowest recorded oxygen saturation measured by pulse oximetry was lower during REM sleep than during NREM sleep. Approximately half of the patients (n = 50) had a higher AHI-NREM than AHI-REM. In subjects with AHI >or= 60 events/h, AHI-NREM was significantly higher than AHI-REM. On multivariate logistic regression, severe AHI >or= 30 events/h was the only predictor of a higher AHI-NREM than AHI-REM. This may indicate that important, but unknown, factors related to the mechanism responsible for the severity of OSA are operative during NREM sleep.

Correlation between genetic alterations and histopathological subtypes in bronchiolo-alveolar carcinoma and atypical adenomatous hyperplasia of the lung.

Bronchiolo-alveolar carcinoma (BAC) is a type of lung adenocarcinoma characterized by growth along the alveolar wall. It is divided into two subtypes: sclerosing BAC (SBAC), which has central fibrosis, and non-sclerosing BAC (NSBAC), which lacks central fibrosis. We compared the genetic alterations in these two types of BAC with those in atypical adenomatous hyperplasia (AAH). There were 39 cases of SBAC, 19 of NSBAC and 20 of AAH. To detect the loss of heterozygosity (LOH) we used the microsatellite markers D3S1234 and D3S1300 on chromosome 3p, IFNA and D9S144 on 9p, and TP53 on 17p. We also used polymerase chain reaction-SSCP analysis and direct sequencing to examine a point mutation of the p53 gene at exons 5-8. At the TP53 locus, the frequencies of LOH showed a statistical rank-difference correlation among AAH, NSBAC and SBAC. On chromosomes 3p and 9p there were no statistical differences of LOH among AAH, NSBAC and SBAC. We detected a significant statistical rank-difference correlation in the p53 mutation among AAH, NSBAC and SBAC. These findings suggest that a process of multistep carcinogenesis from AAH through NSBAC to SBAC might occur in some cases of adenocarcinoma, and LOH of 3p and 9p might be an early event of carcinogenesis, while the p53 mutation might be a later event.

[Coronary flow after successful angioplasty in patients with acute myocardial infarction: comparison between coronary flow reserve by nicorandil and papaverine].

In order to evaluate coronary flow response to 2 different vasodilators, nicorandil and papaverine, in patients with myocardial infarction, we measured coronary flow reserve using a Doppler guide wire in infarct-related and non infarct-related arteries. The study group consisted of 28 patients with first acute myocardial infarction 3 weeks after successful coronary angioplasty within 6 hr after symptom onset. Twelve patients with atypical chest pain served as the control group. Coronary flow reserve induced by intracoronary papaverine(12 mg) was lower in infarct-related arteries than in non infarct-related arteries, but there were no differences in coronary flow reserve induced by intracoronary nicorandil(1 mg) between infarct-related and non infarct-related arteries. Coronary flow reserve induced by nicorandil was lower than that by papaverine in non infarct-related arteries and the control group. However, there were no differences between coronary flow reserve induced by nicorandil and papaverine in infarct-related arteries. Vasodilatory response induced by nicorandil was relatively preserved in infarct-related arteries compared with papaverine. These results suggest that impairment of coronary microvascular response in infarct myocardium varies in the different sites acted on by different vasodilator agents.

Clinical characteristics of patients with fresh left ventricular thrombus.

The present study analyzed the clinical backgrounds of 9 patients with fresh left ventricular thrombus (LVT) detected by two-dimensional echocardiography during the past 5 years. Patients with acute myocardial infarction were excluded. Left ventricular systolic function was disturbed either diffusely or segmentally in all patients with a mean ejection fraction of 33%. In 7 patients, echocardiography was performed shortly after furosemide therapy for New York Heart Association class IV congestive heart failure; echocardiography was also performed just before treatment in 4 of the 7 patients and LVT was not detected in any of them. Two patients died of underlying disorders within 2 months of detection of the thrombus. However, the LVT disappeared in the other 7 patients without any thromboembolic episodes during the 6 months after starting anticoagulant therapy. As fresh LVT developed shortly after diuretic therapy in patients with severe congestive heart failure associated with left ventricular systolic dysfunction, concomitant anticoagulant therapy is recommended.

Decreased left ventricular filling pressure 8 months after corrective surgery in a 55-year-old man with tetralogy of Fallot: adaptation for increased preload.

A 55-year-old man with tetralogy of Fallot underwent corrective surgery. Left ventricular filling pressure increased markedly with increased left ventricular volume one month after surgery, then decreased over the next 7 months, presumably due to increased left ventricular compliance.

Partial pressure of oxygen is lower in the left upper pulmonary vein than in the right in adults with atrial septal defect: difference in P(O2) between the right and left pulmonary veins.

BACKGROUND: The right-to-left shunt at the atrial level is responsible for arterial hypoxemia in patients with atrial septal defect. OBJECTIVES: This study investigated the mechanism of arterial hypoxemia in patients with atrial septal defect by measuring the P(O2) in both the right and left upper pulmonary veins. SUBJECTS AND METHOD: We prospectively measured the P(O2) in the femoral artery and the right and left upper pulmonary veins during cardiac catheterization in 13 adults (median age, 53 years) and 7 children (median age, 7 years) with secundum atrial septal defect. The adults and children were studied consecutively. Contrast echocardiography was performed to evaluate right-to-left shunt in all adults. RESULTS: Among the children, there were no patients showing arterial hypoxemia, and there was no difference in the P(O2) (+/-SD) between the right and left upper pulmonary veins (right, 100+/-3.8 mm Hg vs left, 100+/-7.8 mm Hg; p = 0.92). However, arterial hypoxemia was present in 11 of the 13 adult patients, although contrast echocardiography showed more than a moderate degree of right-to-left shunt in only four adults. The P(O2) was lower in the left upper pulmonary vein than it was in the right upper pulmonary vein in all adult patients (right, 91.6+/-13.8 mm Hg vs left, 73.0+/-11.5 mm Hg; p < 0.0001). CONCLUSION: The P(O2) was lower in the left upper pulmonary vein than it was in the right upper pulmonary vein in adults with atrial septal defect. Care must be taken in measuring pulmonary blood flow if the P(O2) in the left upper pulmonary vein is low enough to influence oxygen content. The decreased P(O2) in the left upper pulmonary vein may contribute to arterial hypoxemia in addition to right-to-left shunt at the atrial level in adults with atrial septal defect.

Malignant paraganglioma arising from the posterior mediastinum: a case report and review of the literature.

An unusual case of paraganglioma of posterior mediastinum occurred in a young adult with local recurrence and multiple distant metastasis. Because of its rarity, the determinants of prognosis factor between benign and malignant paraganglioma are uncertain. In this case, we investigated abnormalities of the p53 gene and ras gene mutations in tissues of primary and metastatic lesions. Neither abnormalities of p53 gene nor ras gene mutations were detected. The molecular approach is recommended as a means of clarifying the trend towards the malignancy of paraganglioma.

Two cases of hypertrophic cardiomyopathy with coronary vasospasm.

Chest pain in patients with hypertrophic cardiomyopathy seems to be caused by relative myocardial ischemia due to the left ventricular outflow pressure gradient and myocardial hypertrophy. However, in 2 cases of hypertrophic cardiomyopathy chest pain was associated with coronary vasospasm. Thus, chest pain in these cases was decreased not by a beta-blocker but by isosorbide dinitrate and a calcium antagonist. Because beta-blockers are commonly used for hypertrophic obstructive cardiomyopathy and chest pain may be aggravated by beta-blockers in patients with coronary vasospasm, a combination of beta-blocker, isosorbide dinitrate and calcium antagonist was necessary for this hypertrophic cardiomyopathy with variant angina.

Increased thrombin-antithrombin III complex during an episode of paroxysmal atrial fibrillation.

Thrombin-antithrombin III complex (TAT) is a marker of thrombin generation, indicating increased coagulability. To investigate whether paroxysmal atrial fibrillation (PAf) is associated with an increased coagulation system, we measured TAT within 24 h after the documentation of PAf in 50 patients with structurally normal hearts. The mean age of the study population was 62 years old. In 32 patients, PAf was documented during routine physical examinations, electrocardiograms or echocardiograms and in the remaining 18 patients, it was reproducibly documented on more than two Holter electrocardiograms. Group I consisted of 38 TAT data sets from 38 patients who did not receive anticoagulant therapy during PAf episodes. At least one week after starting anticoagulant therapy, TAT was measured again in ten patients in whom there was evidence of PAf on the day of measurement. In the remaining 12 patients, PAf occurred while the patients were receiving anticoagulation. Group II consisted of 22 TAT data sets from 22 patients who received anticoagulation during PAf episodes. The average TAT value was 5.8 ng/ml in group I, while it was 2.8 ng/ml in group II (P<0.0001). TAT was greater than 5 ng/ml in 15 of the 38 patients in group I, and in four of the 22 patients in group II. In 20 symptomatic patients, we measured TAT again when the patients maintained sinus rhythm under the same anticoagulant therapy; four patients were receiving and 16 patients were not receiving anticoagulation therapy. TAT decreased from 6.4 to 2.3 ng/ml on average when PAf disappeared and sinus rhythm was maintained (P=0.0009). Increase in the coagulation system occurred transiently during or shortly after PAf episodes in about 40% of PAf patients. As patients with prior anticoagulation had a relatively low TAT value, anticoagulant therapy might be useful in patients with PAf.

p21WAF1/CIP1 expression in primary lung adenocarcinomas: heterogeneous expression in tumor tissues and correlation with p53 expression and proliferative activities.

p21WAF1/CIP1 protein is a cyclin-dependent kinase inhibitor, discovered to be a downstream effector of p53-dependent cell cycle regulation. In order to elucidate the significance of p21 expression in lung adenocarcinomas, we performed immunohistochemical analysis of p21, p53 and Ki-67 expression in surgically resected lung adenocarcinomas. In non-neoplastic tissue, a few bronchial and bronchiolar suprabasal and ciliated cells, and a few type II alveolar cells and alveolar macrophages in the peripheral lung, were p21 positive, but the positive rate in normal lung tissue was very low (<1%). All 91 lung adenocarcinomas examined showed p21 immunoreactivity: 39 cases (42.9%) and 52 cases (57.1%) showed high and low p21 expression levels, respectively. There was no significant correlation between p21 expression and p53 expression, the loss of heterozygosity status of the p53 gene, histological grade determined by the predominant histology, lymph node metastasis, pathological stage, tumor size, smoking history or gender. A positive, not inverse, correlation between p21 and Ki-67 expression was observed. We also observed heterogeneous expression of p21 in lung adenocarcinomas, i.e. in about two-thirds of the tumors, the tumor cells in the peripheral regions were p21 positive more frequently than were those in the central regions. More intense p21 expression tended to occur in the more highly differentiated areas. These results suggest that p21 is involved in tumor cell differentiation and the physiological mechanism that protects against tumor extension.

Polymorphic ventricular tachycardia in a patient with adrenal insufficiency and hypothyroidism.

We describe a 60-year-old patient with adrenal insufficiency and hypothyroidism who experienced syncope as a result of polymorphic ventricular tachycardia associated with long QT intervals. The deep inverted T waves and long QT intervals were normalized about 8 weeks after starting steroid replacement therapy. Although there have been some reports on electrocardiographic abnormality or polymorphic ventricular tachycardia in patients with adrenal insufficiency, the pathogenesis remains unknown. Hormonal disorders should be considered as a cause of polymorphic ventricular tachycardia associated with long QT intervals, even if plasma electrolyte levels are normal, because life-threatening arrhythmia is treatable by supplementation of the hormone that is lacking.

[Hypertrophic obstructive cardiomyopathy in an elderly patient manifesting as refractory congestive heart failure of acute onset: a case report].

An 84-year-old woman was admitted to our hospital because of left heart failure of acute onset. Transthoracic echocardiography showed diffuse hypertrophy of the normal sized hyperkinetic left ventricle and chordae-like fluttering echoes attached to the mitral valve with severe mitral regurgitation signals. Mosaic flow signals were seen at the left ventricular outflow tract, but the velocity could not be measured. Emergent transesophageal echocardiography detected no obvious mitral valve prolapse. Cardiac catheterization showed greater than 100 mmHg pressure gradient between the left ventricle and femoral artery. Pressures in the femoral artery and pulmonary capillary wedge changed reciprocally in the intensive care unit; a bisferient narrow pulse pressure of the femoral artery was associated with increased v wave of the pulmonary capillary wedge pressure, and a wide pulse pressure of the femoral artery with absent v wave of the pulmonary capillary wedge pressure. Pressure monitoring in the intensive care unit, catheterization laboratory and transesophageal echocardiography were useful to understand the pathophysiology of the patient.

Proliferative activity, p53 expression and loss of heterozygosity on 3p, 9p and 17p in atypical adenomatous hyperplasia of the lung.

We examined the preneoplastic nature of atypical adenomatous hyperplasia (AAH) of the lung by comparing the proliferative activity, p53 oncosuppressor gene product and loss of heterozygosity (LOH) on 3p, 9p and 17p of 20 AAH lesions (8 cases) with corresponding normal peripheral lung tissue and adenocarcinoma from the same cases. Analysis of proliferative activity with the Ki-67 labelling index and argyrophilic nucleolar organizer regions (AgNORs) score indicated that AAH had a proliferative activity intermediate between that of normal cell and adenocarcinoma. Although low level expression of p53 was detected in 7 AAH lesions, the intensity of p53 expression in AAH was weaker than that in carcinomas. Microsatellite analysis of chromosome 3p, 9p and 17p showed LOH of 18%, 13% and 6% respectively in the AAH lesions, while the corresponding carcinomatous lesions showed LOH of 67%, 50% and 17% respectively. All AAH lesions that showed LOH had moderate or severe histological atypia. One AAH lesion with moderate atypia showed LOH both on 3p and 17p. In conclusion, these results indicated that AAH lesions with moderate or severe atypia may show the preneoplastic stage of lung adenocarcinoma.

[Clinical evaluation of cholesterol embolization syndrome after cardiac catheterization].

The clinical features and outcomes of patients with cholesterol embolization syndrome after cardiac catheterization were evaluated. Among 4,920 patients undergoing cardiac catheterization during 1991 to 1996, the symptoms, signs, laboratory data, treatment and prognosis of eight (6 males and 2 females, mean age 69 years old) were reviewed who were pathologically or clinically diagnosed as having cholesterol embolization syndrome. All patients had more than two coronary risk factors. Mobile plaque of the aortic arch was detected in all five patients who underwent transesophageal echocardiography. All patients had one or more precipitating factors, including coronary angiography, percutaneous transluminal coronary angioplasty, cardiovascular surgery and cardiopulmonary resuscitation. The first symptom was renal dysfunction in four patients, skin findings of purple toes in two, muscle pain in one and new onset of refractory hypertension in one. The time after the precipitating factor to the onset of symptoms was 32 +/- 9 days on average. Eosinophilia was found in all patients and six patients revealed eosinophilia before the onset of symptoms. Four patients showed skin findings of purple toes which progressed in three of the four patients even after anticoagulant therapy was discontinued. Epidural anesthesia was markedly effective for skin findings of purple toes in two of the three patients. Diagnosis of cholesterol embolization syndrome is difficult because patients show various symptoms and there is an interval between the precipitating factor and the onset of symptoms. However, the conditions of the patients deteriorate rapidly and the prognosis is generally poor without supportive therapy in the early stage. Our study demonstrated that eosinophilia might be an important clue to early detection of cholesterol embolization syndrome. Furthermore, epidural anesthesia is effective for skin findings of purple toes in patients with cholesterol embolization syndrome. In conclusion, cholesterol embolization syndrome should be detected in the early stage based on eosinophilia or clinical symptoms after cardiac catheterization, and supportive therapy started as soon as possible, including discontinuance of anticoagulant therapy, hemodialysis for renal dysfunction and epidural anesthesia for skin findings of purple toes.

Aortic regurgitation in a patient with primary antiphospholipid syndrome--a case report.

We present the case of a 39-year-old woman with aortic regurgitation that may have been induced by primary antiphospholipid syndrome. The patient had suffered recurrent miscarriages, thrombocytopenia, and deep-vein thrombosis for the previous 16 years, and had been diagnosed as having primary antiphospholipid syndrome 9 years previously because of a high titer of anticardiolipin antibody. She had been receiving medication for moderate hypertension for 7 years. The patient was admitted to Tenri Hospital because of heart failure, which was thought to be caused by moderate aortic regurgitation, moderate hypertension, and mild chronic renal failure. Echocardiography revealed thickened aortic and mitral valves. Primary antiphospholipid syndrome might have induced valve regurgitation as a result of valvular thickening.

Problems in pharmacological evaluation of patients with paroxysmal atrial fibrillation: clinical analysis of more than 100 consecutive patients.

To address the problems of pharmacological evaluation in paroxysmal atrial fibrillation (PAf), we interviewed 108 consecutive patients with documented PAf regarding symptoms, frequency and trigger factors of PAf and analyzed the 24-hour ambulatory electrocardiographic monitoring (Holter monitoring) records in relation to symptoms. Twenty-nine patients were totally asymptomatic, while 79 patients were symptomatic of which 49 patients had obvious trigger factors. PAf was documented by Holter monitoring in 22 of 79 symptomatic patients. On analysis of PAf-documented 25 Holter monitoring records, the patients checked event marks as PAf in only 20 of 155 PAf episodes. Six episodes of 26 event marks that patients thought to be PAf proved to be premature atrial or ventricular contractions. Nine patients in whom PAf persisted for more than 24 hours became asymptomatic. Patients suitable for pharmacological evaluation constituted about one-fifth of the PAf patients in our consecutive study. Even with the selection of these patients, pharmacological evaluation based on symptoms is difficult because disappearance of PAf may be associated with persistent atrial fibrillation.

Problems in the initial diagnosis of renal infarction.

We retrospectively analyzed 20 cases of renal infarction to identify the problems in tentatively diagnosing renal infarction. The subjects consisted of 12 outpatients and 8 inpatients whose diagnosis was confirmed by renal scintigram and/or contrast computed tomography. Renal infarction was tentatively diagnosed in only 4 of the 12 outpatients. Causes of hospitalization were cerebral emboli in 5 cases, peripheral emboli in the extremities in 2 cases and one case involved percutaneous transmitral commissurotomy. On initial urinalysis, 11 cases (55%) showed less than 2+ hematuria using dipsticks to test for occult blood. The mean lactic dehydrogenase value was as high as 2,096 IU while the mean aspartate aminotransferase and mean alanine aminotransferase were 83.1 IU and 78.6 IU. Abdominal ultrasonography revealed abnormalities in only one of 18 cases. In conclusion, since only a moderate degree of hematuria was seen in about half the cases and it was difficult to detect renal abnormalities by ultrasonography, a tentative diagnosis of renal infarction may be difficult in some cases.

p16/CDKN2 gene and p53 gene alterations in Japanese non-smoking female lung adenocarcinoma.

Primary lung adenocarcinomas in non-smoking females are increasing in the USA and Japan. Environmental factors such as passive smoking, asbestos, domestic radon, and hormonal effects have been implicated, but the etiology is still uncertain. We therefore analyzed point mutations of p16 gene, a newly characterized tumor suppressor gene, and compared the results with alterations of p53 gene in 28 primary lung adenocarcinomas in non-smoking Japanese females. There were no cases with somatic point mutation of p16 gene, except for one case with two germline mutations (silent mutations). In contrast, six out of 16 informative cases showed loss of heterozygosity of p53 gene using a TP53 microsatellite marker and 19 out of 28 cases showed expression of oncoprotein using DO-7 immunohistochemistry. These findings suggest that p16 gene alteration is a rare event in primary lung adenocarcinomas in Japanese non-smoking females, compared with alterations of the p53 gene.

[A comparison of lymphocyte stimulation test results and challenge test results in 19 cases of antituberculous drug-induced allergy].

We clinically investigated 19 cases of antituberculous drug-induced allergy. The results of the challenge tests were positive in 30 out of the 55 drugs tested. The results of the lymphocyte stimulation tests were positive in 19 out of the 55 drugs tested. In 84.2% of the cases with positive lymphocyte stimulation test findings, the challenge test was also positive. It can be concluded from these results that the lymphocyte stimulation test may be useful in the detection of the causes of drug induced allergies in patients undergoing drug therapy for tuberculosis.

[A case of acetaminophen-induced pneumonitis].

A 20-year-old woman took 1.2 g of acetaminophen for toothache. She subsequently developed a dry cough, pyrexia, and dyspnea. Chest X-ray revealed diffuse reticulo-nodular shadows in both lung fields. Broncho-alveolar lavage examination showed a marked increase in the total cell number and an increase in the percentage of eosinophils, neutrophils, and lymphocytes. Because drug-induced pneumonitis was suspected, all drugs were stopped and she was administered methylprednisolone. Consequently her symptoms resolved, and pulmonary function and chest X-ray findings improved remarkably. The lymphocyte stimulation test was positive for Norshin and its acetaminophen element. Based on these findings, the diagnosis of acetaminophen-induced pneumonitis was made. Acetaminophen intoxication is well-known, but to our knowledge this is the first reported case of acetaminophen-induced allergic pneumonitis in Japan.