Neurohumoral activation refers to increased activity of the sympathetic nervous system, renin-angiotensin system, vasopressin and atrial natriuretic peptide. It is now known that neurohumoral activation contributes to the transition from ventricular dysfunction to clinical heart failure, and is an independent predictor of poor prognosis in heart failure. Although the treatment of heart failure has traditionally focused on drugs to improve ventricular function, there is increasing evidence that therapeutic modulation of neurohumoral activation is a key to successful treatment of heart failure. For example, there is mounting evidence that angiotensin converting enzyme inhibitors (the unquestioned cornerstone for treatment of heart failure), beta receptor blockers, digitalis, and endurance exercise training exert their benefit in heart failure in large part through neurohumoral modulation. This observation - discussed in this brief review - highlights the concept that compensatory neurohumoral activation to decreased cardiac function may itself contribute to the development of heart failure and its poor prognosis.
(Internal Medicine 37: 112-122, 1998)

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We investigated the effects of risk factors of atherosclerosis on soluble intercellular adhesion molecule-1 (sICAM-1) concentration and leukocyte count by using multivariate statistical analysis. The subjects were 90 people who were hospitalized for a complete check-up examination. Eight risk factors were selected as candidates for predictor variables: age, body mass index (BMI), uric acid, glycohemoglobin A_1c, number of cigarettes smoked daily, total cholesterol, triglyceride, and high density lipoprotein (HDL)-cholesterol. The predictor variables were selected using a stepwise method, [criterion variable - predictor variable (standardized regression coefficient)] ; sICAM1-age (0. 1859), number of cigarettes (0.2558), triglyceride (0.2447) ; leukocytes - number of cigarettes (0.2827), triglyceride (0.2526), HDL-cholesterol (-0.2800); stab leukocytes - number of cigarettes (0.2460); segmented leukocytes - glycohemoglobin A_1c (0.1495), number of cigarettes (0.2716), HDL-cholesterol (-0.3254); lymphocytes - BMI (0.2639), number of cigarettes (0.1495), triglyceride (0.3520); monocytes - glycohemoglobin A_1c (0.2617). These findings indicated that the risk factors of atherosclerosis mayinfluence sICAM1 concentration and leukocyte count.
(Internal Medicine 37: 123-126, 1998)

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Since obstructive sleep apnea syndrome (OSAS) is often linked with systemic hypertension, we sought to clarify the characteristics of prostanoid metabolism in OSAS. In 7 OSAS patients (apnea-hypopnea index, 51.0 ± 23.4) and 7 non-snorers as control, nocturnal urine was sampled and analyzed for stable metabolites of prostacyclin (PGI₂) and thromboxane A₂ (TxA₂), [6-keto-PGF_1α and thromboxane B₂ (TxB₂)]. The ratio of 6-keto-PGF_1α to TxB₂ was significantly higher in OSAS (2.97 ± 1.52) than in control (1.38 ± 0.38). Successful treatment with nasal continuous positive airway pressure (8.3 ± 1.5 cmH₂O) for 3 days caused a significant decrease in mean blood pressure in OSAS. Moreover, the 6-keto-PGF_1α to TxB₂ ratio also significantly decreased to 1.74 ± 0.58, a level which may not significantly different from control. These results suggest that the production ratio of PGI₂ to TxA₂ is shifted toward vasodilatation in untreated OSAS. We conclude that the production of prostanoids plays a role in compensating for the systemic hypertension in OSAS.
(Internal Medicine 37: 127-133, 1998)

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To clarify the characteristics of upper airway muscles under hypoxic condition in obstructive sleep apnea syndrome (OSAS), we performed the isocapnic progressive hypoxia test during wakefulness in 8 controls and 7 OSAS patients. Electromyographic activities were recorded from the genioglossal muscle (EMG_GG) and diaphragm (EMG_DIA) with ventilatory variables. Minute EMG (peak integrated EMG × respiratory rate) activity against P_ETO, ₂ was calculated by exponential equation, and its response slope represented the hypoxic sensitivity of each muscle, slope_GG and slope_DIA. There was no significant difference between the slopes of OSAS and control. In contrast, the ratio of the two responses, slope_GG/slope_DIA, was significantly higher in OSAS (1.61 ± 0.49 SD) than in control (0.98 ± 0.43). Moreover, the slope_GG/slope_DIA ratio was negatively correlated with the ratio of sleep time with SpO_2, lower than 90% to total sleep time. We conclude that the neuromuscular compensatory mechanism of upper airway muscles is effectively developed and plays an important role in preventing nocturnal hypoxemia in OSAS.
(Internal Medicine 37: 134-140, 1998)

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A diagnosis based on the presumed mechanism of stroke onset is useful for management strategies in acute ischemic stroke. Ninety-two patients with embolic (cardiac or artery-to-artery) and 107 with non-embolic (thrombotic or hemodynamic)stroke were diagnosed on strict cerebral angiographic criteria alone. To clearly discriminate between these two groups, the neurological and computed tomographic (CT) findings were then compared. Rapidity of onset, vomiting, urinary incontinence, level of consciousness, cervical bruit, anisocoria, tongue deviation, sensory disturbance, and CT findings (location of hypodense area, findings of brain edema and hemorrhagic transformation) were discriminatory factors between the two groups (p<0.01). According to these 11 items, we prepared a numerical table for quantitative differential diagnosis. A diagnostic accuracy of 98.9% for embolic and 87.9% for non-embolic stroke in internal verification, and 90.0% and 82.9%, respectively, in external verification was observed. The differences in clinical features and CT findings between embolic and non-embolic stroke may reflect the pathophysiological mechanisms of the occlusive process of cerebral artery as well as the extent and severity of ischemia.
(Internal Medicine 37: 141-148, 1998)

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We used a provocative test with dobutamine infusion to diagnose long QT syndrome (LQTS) in a girl with a history of syncope. When dobutamine was infused at a rate of 10 μg/kg/min, the QT interval corrected for heart rate (QTc) was prolonged from 460 ms to 620 ms with abnormal TU complexes and torsades de pointes developed. In 5 control subjects the QTc did not change significantly during low-dose dobutamine infusion. Low-dose dobutamine, in addition to isoproterenol, may be useful for evaluation of prolongation of the QT interval and abnormal TU complexes in patients in whom LQTS is suspected.
(Internal Medicine 37: 149-152, 1998)

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A 51-year-old woman who had been on steroid therapy for systemic lupus erythematosus (SLE) developed a high fever 3 days after visiting a hot spring resort. Chest X-ray films revealed an interstitial, pneumonia-like shadow in the left lung field, which increased rapidly with a worsening of her symptoms. She died of multiple organ failure one week after the onset of the pneumonia. Although the serum antibody titer was negative, Legionella pneumophila was recovered from her bronchoalveolar lavage (BAL) fluid. BAL seems to be a useful method to diagnose Legionnaires' disease.
(Internal Medicine 37: 153-156, 1998)

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A pharyngeal tonsil biopsy specimen from a 27-year-old male revealed epithelioid cell granulomas with noncaseating necrosis. Systemic enlargement of the lymph nodes was present. Plain chest radiographic and computed tomography (CT) images showed ground-glass attenuation in the lungs and bilateral hilar lymphadenopathy. Biopsy of inguinal region nodes confirmed the diagnosis of systemic sarcoidosis. Detailed examination of the nasopharynx should be performed in any case presenting with systemic sarcoidosis because the specimen is readily removable and the pathologic findings of the local lesion may support the diagnosis.
(Internal Medicine 37: 157-160, 1998)

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A 67-year-old man with poorly controlled diabetes mellitus (DM) had acupuncture several times a month for chronic shoulder muscle stiffness. A few days after acupuncture in the posterior nuchal region, a low-grade fever and backache developed, and subacutely progressed. Finally he complained of gait disturbance, and then respiratory distress appeared. Magnetic resonance imaging (MRI) demonstrated high cervical epidural abscess with massive soft tissue inflammation and vertebral osteomyelitis. Conservative treatment with antibiotics was effective and it was well documented by following serial MRIs. This case suggested that needle acupuncture should be avoided for immunocompromised subjects such as patients with poorly controlled DM.
(Internal Medicine 37: 161-165, 1998)

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Familial hemiplegic migraine (FHM) is an autosomal dominant syndrome characterized by recurrent episodes of varying degrees of hemiparesis associated with migraine. The aura including hemiparesis may be prolonged and in severe attacks may often be associated with confusion or coma. We describe a case of FHM whose aura was atypically prolonged and resulted in irreversible brain deficit which on magnetic resonance imaging (MRI) was suggestive of cortical hyperperfusion. A subsequent MRI showed left brain atrophy.
(Internal Medicine 37: 166-168, 1998)

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A case of rhabdomyolysis after a possible viral infection and the use of a cold medication is reported. A 41-year-old man who presented with dysarthria, dysphagia, progressive weakness of his muscles and a high grade fever was admitted. He suffered from massive rhabdomyolysis, acute renal failure, and bronchopneumonia. Hemodialysis, antibiotics, and hydration therapy were effective in the treatment of his illness. Although the cause of the rhabdomyolysis was not completely clear, he was subsequently shown to be susceptible to malignant hyperthermia (MH) based on the results of a caffeine-halothane contracture test. When a mild recurrence occurred during a follow-up muscle biopsy, intravenous dantrolene sodium was administered and he improved immediately. This case suggests that MH should be considered in patients with rhabdomyolysis when the cause is unclear. The caffeine-halothane contracture test may also be helpful in the diagnosis.
(Internal Medicine 37: 169-173, 1998)

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Sjögren's syndromeand sarcoidosis share several common features, such as keratoconjunctivitis sicca, swelling of parotid glands, lung involvement, cutaneous anergy, T cell-mediated immunodeficiency, an increased CD4⁺/CD8⁺ lymphocyte ratio, and association with the human leucocyte antigen (HLA)-B 8 and DR3 haplotypes. However, only five patients with primary Sjögren's syndrome and sarcoidosis have been previously reported in the English language literature. The rare case of a 49-year-old Japanese woman with primary Sjögren's syndrome complicated by sarcoidosis is described. The serum angiotensin-converting enzyme level was increased, and histological examination of lung and skin biopsies revealed noncaseating granulomas, indicating that her primary Sjögren's syndrome was complicated by sarcoidosis.
(Internal Medicine 37: 174-178, 1998)

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