Effects of dietary potassium on the hemodynamics and plasma norepinephrine kinetics in patients with essential hypertension

The effects of dietary potassium on the hemodynamics and plasma norepinephrine (NE) kinetics were studied in 10 patients with borderline hypertension. Potassium supplement (96 mEq daily for 5-7 days) induced a significant (p less than 0.05) fall in blood pressure and a slight decrease in cardiac output. Both urine volume and urinary sodium excretion increased significantly (p less than 0.05) for a first few days following the potassium supplement. The baseline values of the half-time of the rapid NE removal from plasma was significantly delayed in the hypertensive patients (1.05 +/- 0.06 min, p less than 0.05) when compared with those (0.88 +/- 0.04) in normal controls. Potassium supplement induced a significant rise in both plasma NE levels and NE outflow rate (p less than 0.01) in the hypertensive patients, while their half-times were significantly shortened (0.89 +/- 0.07 min, p less than 0.01). The pressor responsiveness to exogenously infused NE tended to diminish during the potassium supplement. These findings indicate that a high potassium intake might accelerate the slowed neuronal NE uptake in the hypertensive patients, while a potassium-induced fall in blood pressure might exert a baroreflex stimulation of NE release. As a net result, an increased NE outflow into the circulation has been confirmed. It is likely that a natriuresis-induced volume contraction might be a predominant factor responsible for the early reduction of blood pressure during the high potassium intake.     

Long-term outcome of implanted cardioverter defibrillators in survivors of out-of-hospital cardiac arrest of cardiac origin.

BACKGROUND: Little is known about the long-term outcome of implantable cardioverter defibrillator (ICD) therapy in survivors of out-of-hospital cardiac arrest (OHCA). METHODS AND RESULTS: The frequency of lethal ventricular arrhythmias and whether ICD implantation can prevent recurrence of cardiac arrest were examined. Long-term (24.4+/-11.9 months) outcome was examined in 23 patients with OHCA who were treated with an ICD (OHCA group) and 35 patients without OHCA (non-OHCA group) who were treated with an ICD. Patients in both groups had same clinical backgrounds; however, those in the OHCA group showed a significantly lower incidence of induced ventricular arrhythmias (71%) than the non-OHCA group (96%). In the follow-up period, patients in the OHCA group had almost the same incidence of ICD discharge (30%) as patients in the non-OHCA group (40%). The rate of recurrence of ventricular fibrillation in the OHCA patients was 13%, and it was difficult to estimate the rate by induced ventricular arrhythmia. CONCLUSION: The results suggest that ICD implantation for survivors of OHCA with favorable neurological recovery might be effective for preventing recurrence of cardiac arrest.     

Impact of oral beta-blocker therapy on mortality after primary percutaneous coronary intervention for Killip class 1 myocardial infarction

The use of beta-blockers therapy has been recommended to reduce mortality in patients with left ventricular dysfunction after acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PCI), which has become the mainstay of treatment for AMI, is associated with a lower mortality than fibrinolysis. The benefits of beta-blockers after primary PCI in AMI patients without pump failure are unclear. We hypothesized that oral beta-blocker therapy after primary PCI might reduce the mortality in AMI patients without pump failure. The assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (ALPS-AMI) study was a multi-center study that enrolled 508 AMI patients to compare the efficacy of hydrophilic and lipophilic statins in secondary prevention after myocardial infarction. We prospectively tracked cardiovascular events for 3 years in 444 ALPS-AMI patients (median age 66 years; 18.2 % women) who had Killip class 1 on admission and were discharged alive. The primary endpoint was all-cause mortality. The 3-year follow-up was completed in 413 patients (93.0 %). During this follow-up, 21 patients (4.7 %) died. In Kaplan–Meier analysis, patients on beta-blockers had a significantly lower incidence of all-cause mortality (2.7 vs. 7.3 %, log-rank p = 0.025). After adjusting for the calculated propensity score for using beta-blockers, their use remained an independent predictor of all-cause mortality (hazard ratio 0.309; 95 % confidence interval 0.116–0.824; p = 0.019). In the statin era, the use of beta-blocker therapy after primary PCI is associated with lower mortality in AMI patients with Killip class 1 on admission.     

Gabexate mesilate, a synthetic protease inhibitor, attenuates carbon tetrachloride-induced liver injury in rats

Background Gabexate mesilate, a synthetic protease inhibitor, is used to treat acute pancreatitis and disseminated intravascular coagulation because it inhibits various serine proteases; however, whether gabexate mesilate prevents acute liver failure has not yet been studied. The aim of the present study was to investigate the effect of gabexate mesilate in carbon tetrachloride (CCl₄)-induced liver injury in rats.Methods Acute hepatic failure was induced by administration of CCl₄ intragastrically to male Sprague–Dawley rats. The effects of gabexate mesilate were examined in terms of serum transaminase levels, liver histology, and the prognosis of rats.Results Gabexate mesilate treatment significantly decreased the elevation of serum transaminase levels and improved liver histology 24h after the administration of CCl₄ (0.2ml/100g rat weight). Plasma tumor necrosis factor- (TNF-) and interleukin-1 (IL-1) decreased significantly in the gabexate mesilate-treated rats compared with saline-treated rats. Gabexate mesilate treatment also significantly improved survival rate after a lethal dose of CCl₄ (0.5ml/100g rat weight) from 0% to 20%.Conclusions Gabexate mesilate treatment attenuated CCl₄-induced liver injury via a suppression of proinflammatory cytokine production. In addition, these investigations suggest that gabexate mesilate treatment may provide therapeutic strategies for human acute liver failure.     

Fulminant pneumonia due to Aeromonas hydrophila in a man with chronic renal failure and liver cirrhosis

A 40-year-old man on hemodialysis was admitted due to dyspnea and chest pain and was diagnosed with pneumonia and pericarditis. Ampicillin was administered, but thereafter severe septic shock developed. The fulminant type of pneumonia progressed rapidly, and he died only 48 hours after the onset of symptoms. The autopsy and sputa culture revealed pneumonia due to Aeromonas hydrophila. The source of this infection remained unkown. Interestingly, there were two types of A. hydrophila found during such a short period. The physician should suspect this disease by questioning the patient's history. Early treatment with adequate antibiotics is the only means of saving such a patient's life.     

Response of the left anterior descending coronary artery to acetylcholine in patients with chest pain and angiographically normal coronary arteries

Because atherosclerotic plaque burden affects the likelihood of plaque rupture, it is important to determine the presence and extent of atherosclerotic plaque. We hypothesized that endothelial dysfunction becomes more prominent with development of atherosclerotic plaque; therefore, we examined the relation between coronary endothelial dysfunction and the presence of atherosclerotic plaque. In 36 patients with normal coronary arteries, acetylcholine (ACh; 3 and 30 μg/min) and nitroglycerin were infused into the left coronary ostium, and the diameter of the left anterior descending (LAD) coronary artery was quantitatively measured in response to each drug. The plaque burden was measured in the same segment using intravascular ultrasonography. The plaque burden was 31.2 ± 2.1% and correlated inversely with changes in coronary diameter induced by 3 μg/min of ACh (r = −0.754, p <0.0001), 30 μg/min of ACh (r = −0.552, P = 0.0005), and nitroglycerin (r = −0.531, P = 0.0009). Multivariate regression analysis showed that the change in coronary diameter induced by 3 μg/min of ACh was associated with plaque burden, independent of the effects of nitroglycerin-induced dilation. Receiver-operating characteristics analysis demonstrated that a cut-off value for the change in coronary diameter induced by 3 μg/min of ACh for predicting a plaque burden of>30% was 0%, with a sensitivity of 0.82 and a specificity of 0.95. These findings suggest that coronary endothelial dysfunction is correlated with atherosclerotic plaque burden, indicating that atherosclerotic plaque may be detected based on coronary endothelial function as assessed by low-dose ACh infusion.     

Characterization of recombinant monoclonal antithyrotropin receptor antibodies (TSHRAbs) derived from lymphocytes of patients with Graves' disease: epitope and binding study of two stimulatory TSHRAbs

Anti-TSH receptor autoantibodies (TSHRAbs) are known to be involved in Graves' disease. To elucidate the molecular mechanism of the pathogenesis of Graves' disease, we previously isolated and reconstituted the Ig genes of two B cell clones (101-2 and B6B7) producing a monoclonal thyroid-stimulating antibody (TSAb), a stimulating type of TSHRAb, obtained from patients with Graves' disease. In the present study, we produced a large amount of recombinant monoclonal TSAbs in eukariotic cells using these genes and characterized them. First, we tried to identify their epitopes in the TSHR, by using a panel of mutants of the extracellular domain of the TSH receptor (TSHR). Substantial cell surface expression level of each mutant was confirmed by fluorescence-activated cell sorter analysis using a TSHRAb. Mutations in the N-terminal (but not C-terminal) region of the extracellular domain of TSHR abrogated or reduced TSAb activities of both antibodies, whereas they had opposite effects on TSH activity; cAMP generation by 101-2 significantly decreased in the receptors mutated in amino acids 52-56 and 58-61, and that by B6B7 decreased in amino acids 34-37 and 58-61. Secondly, purified antibodies were radiolabeled and tested for binding to cells expressing high levels of TSHR. Although their affinities were lower than that of TSH, their binding was not displaced by TSH. The antibody binding was not mutually competitive. These findings suggest that these antibodies interact with the N-terminal region of the receptor and transduce a signal through binding sites different from TSH. We believe that this is the first report of the characterization of human monoclonal TSHRAbs on their epitopes and bindings, confirming previous reports using patient sera or murine monoclonal antibodies.     

Improvement of Splenomegaly and Pancytopenia by Enzyme Replacement Therapy Against Type 1 Gaucher Disease: A Report of Sibling Cases

Gaucher disease is a genetic lipid storage disease and represents a potentially serious health problem. It arises from a deficiency of glucocerebrosidase activity with secondary accumulation of large quantities of glucocerebroside. Symptoms are usually multisystemic, often debilitating or disabling, and sometimes disfiguring, and they can lead to death. We report objective clinical response's to repeated infusion of human placental and recombinant glucocerebrosidase in 2 patients with type 1 Gaucher disease and increased hemoglobin levels and platelet counts. Splenic volume decreased during the period of enzyme administration. Enzyme replacement therapy has improved the treatment of type 1 Gaucher disease by safely and effectively arresting, decreasing, or normalizing many of its major signs and symptoms. Consideration by physicians must be given to Gaucher disease, and appropriate treatments must be given when confronted with cryptogenic pancytopenia or hepatosplenomegaly.