Transient Brain Ischaemia Provokes Ca2+, PIP2 and Calpain Responses Prior to Delayed Neuronal Death in Monkeys

To clarify the mechanism of postischaemic delayed cornu Ammonis (CA)-1 neuronal death, we studied correlations among calpain activation and its subcellular localization, the immunoreactivity of phosphatidylinositol 4,5-bisphosphate (PIP₂) and Ca²⁺ mobilization in the monkey hippocampus by two independent experimental approaches: in vivo transient brain ischaemia and in vitro hypoxia-hypoglycaemia of hippocampal acute slices. The CA-1 sector undergoing 20 min of ischaemia in vivo showed microscopically a small number of neuronal deaths on day 1 and almost global neuronal loss on day 5 after ischaemia. Immediately after ischaemia, CA-1 neurons ultrastructurally showed vacuolation and/or disruption of the lysosomes. Western blotting using antibodies against inactivated or activated μ-calpain demonstrated μ-calpain activation specifically in the CA-1 sector immediately after ischaemia. This finding was confirmed in the perikarya of CA-1 neurons by immunohistochemistry. CA-1 neurons on day 1 showed sustained activation of μ-calpain, and increased immunostaining for inactivated and activated forms of μ- and m-calpains and for PIP₂. Activated μ-calpain and PIP₂ were found to be localized at the vacuolated lysosomal membrane or endoplasmic reticulum and mitochondrial membrane respectively, by immunoelectron microscopy. Calcium imaging data using hippocampal acute slices showed that hypoxia-hypoglycaemia in vitro provoked intense Ca²⁺ mobilization with increased PIP₂ immunostaining specifically in CA-1 neurons. These data suggest that transient brain ischaemia increases intracellular Ca²⁺ and PIP₂ breakdown, which will activate calpain proteolytic activity. Therefore, we suggest that activated calpain at the lysosomal membrane, with the possible release of biodegrading enzyme, will cause postischaemic CA-1 neuronal death.     

Should every patient undergo cardiac catheterization after myocardial infarction?

During the past few decades, management of patients with myocardial infarction has dramatically evolved. High-risk patients are now identified by a variety of noninvasive tests, and aggressive use of reperfusion strategies has improved clinical outcomes. Despite the benefits of reperfusion, only a few patients are eligible to receive thrombolytic therapy. Mortality rates among patients excluded from thrombolytic trials (15% to 20%) have been far greater than those eligible for treatment (3% to 10%). Because most deaths occur within the first few days of infarction, interventions designed to reduce mortality should be performed acutely. Immediate catheterization allows identification of high-risk anatomy that may benefit from surgery and allows coronary angioplasty to be performed as a reperfusion strategy (when appropriate). Furthermore, catheterization allows documentation of ejection fraction, vessel patency, number of diseased vessels, and residual stenosis, all of which have been predictive of prognosis. Conversely, frequently repeated noninvasive diagnostic tests are associated with increased cost, are generally performed in low-risk patients, and 60% to 80% of patients with myocardial infarction ultimately require catheterization anyway. It is possible that early catheterization and percutaneous transluminal coronary angioplasty when indicated may effectively risk stratify patients (eliminating the need for noninvasive testing), may reduce morbidity and mortality, and shorten the length of hospital stay.     

Old pulmonary embolism causing intrabronchial bleeding

A 51-year-old man was admitted because of hemoptysis. Physical examinations and chest XP revealed no abnormal findings. Fiberoptic bronchoscopy showed pulsatile bleeding at the orifice of right B6. Right bronchial arteriography showed a markedly dilated and tortous bronchial artery and shunting to the pulmonary arterial system in the middle and lower lobes. Pulmonary arteriography showed complete obstruction of the right middle lobar and lower lobe segmental arteries (A6, 9, 10). The hemoptysis was thought to be due to increased blood flow of the right bronchial artery, which compensated for reduced right pulmonary arterial flow. Right middle and lower lobe resection was done to prevent further hemoptysis. The resected specimen revealed old thromboemboli in the right middle and lower lobe pulmonary arteries. In this case old pulmonary embolism should be considered as a cause of intrabronchial bleeding.     

An international comparison of rhinomanometry between Canada and Japan.

International discussions concerning rhinomanometry have been held but no numerical comparisons have been reported. In an attempt to make international comparisons between different rhinomanometric results, nasal resistances were measured by active posterior rhinomanometry with a head-out body plethysmograph produced in Canada and by active posterior and anterior methods with a Japanese commercial rhinomanometer, and the results were compared. No significant differences were found between measurements obtained from the two types of equipment. It is believed that this study is the first project of international comparison of rhinomanometry.     

The significance of the heparin precipitable fraction in lung diseases]

The authors recently experienced a case of idiopathic interstitial pneumonia (IIP) that exhibited skin ulcers due to increased heparin precipitable fraction (HPF) in plasma. This case prompted us to investigate the occurrence and significance of HPF in interstitial pneumonia (IP). The subjects included patients with IIP (acute exacerbation 6 cases, chronic active stage 12 cases), IP associated with collagen vascular disease (CVD) (9 cases) and granulomatous lung diseases (7 cases). The data indicated that all of the cases with acute exacerbation of IIP exhibited increased plasma HPF values (218-951 mg/dl) compared to those of normal controls (less than 180 mg/dl). In contrast, the values ranged within normal limits in all of the cases with IP associated with CVD. In a companion study, we measured plasma HPF values in patients with lung cancer, bacterial pneumonia and diffuse panbronchiolitis. It was found that 22% of the subjects showed increased plasma HPF values. We also investigated whether there were correlations between plasma HPF and various inflammatory parameters. The data revealed that there were correlations between HPF and ESR, CRP, alpha 1-globulin, alpha 2-globulin, complement (C3) or fibrinogen. However, there was no correlation between HPF and fibronection. These results suggest that plasma HPF is valuable to evaluate the acute exacerbation of IIP, although the elevation of plasma HPF levels is not specific.     

Role of nuclear cardiology for determining management of patients with stable coronary artery disease

Both radionuclide angiography and myocardial perfusion imaging provide important insights that determine the management of patients with stable coronary artery disease. Both nuclear cardiology procedures have clearly demonstrated use in the noninvasvie identification of severe (left main or three-vessel) coronary artery disease and the noninvasive assessment of prognosis and thereby determine which patients should be sent to coronary angiography. Both radionuclide angiography and myocardial perfusion imaging provide prognostic information that is independent of resting left ventricular function and coronary anatomy and thereby influence the decision regarding which patients should be sent to coronary revascularization. This review considers the evidence supporting the uses of these nuclear cardiology procedures and provides suggestions regarding their cost-effective application.