Pulmonary artery catheter usage in diagnosis of Shoshin beriberi presented with unexplained lactic acidosis.

Wet beriberi is a rare but fatal disease in modern society. The nonspecific clinical manifestations, including symptoms of heart failure and recalcitrant lactic acidosis, can prevent timely diagnosis. The use of a pulmonary artery catheter can promptly confirm a high cardiac output state and plays a crucial role in rapidly deteriorating cases. Appropriate treatment with intravenous administration of thiamine leads to dramatic recovery within hours. We present two cases of Shoshin beriberi, a fulminant variant of wet beriberi, diagnosed in 2016 and 2022 at our institute. The patients experienced haemodynamic collapse and refractory lactic acidosis, which were successfully diagnosed with the use of a pulmonary artery catheter and reversed by thiamine supplementation. We also reviewed 19 cases of wet beriberi reported between 2010 and 2022.

Comparative effectiveness of generic nifedipine versus Adalat long-acting nifedipine for hypertension treatment: A multi-institutional cohort study.

This retrospective multi-institutional database analysis aimed to evaluate the blood-pressure-lowering efficacy and clinical outcomes of a generic versus brand-name nifedipine for hypertension management. A total of 12 693 patients who were prescribed a generic or brand-name nifedipine between January 1, 2011, and December 31, 2018, were identified from the Chang Gung Research Database of Chang Gung Memorial Hospitals, Taiwan. Among them, 2112 (21.4%) were prescribed generic nifedipine. After propensity score matching, both the generic and brand-name groups consisted of 2102 patients. At a mean follow-up of 3 years, the changes in office systolic (p for interaction = .791) and diastolic blood pressure (p for interaction = .689) did not differ significantly between the patients who received the generic and the brand-name nifedipine. There was no significant difference between the two study groups regarding the composite of all-cause mortality, acute myocardial infarction, stroke, coronary revascularization, or hospitalization for heart failure (hazard ratio 0.98, 95% confidence interval 0.85-1.13; p = .774). In conclusion, the generic nifedipine was comparable to its brand-name counterpart regarding office blood pressure reduction and the composite cardiovascular outcome for the treatment of patients with hypertension.

Baicalein Cardioprotection via Oxidant Scavenging and Akt-Nitric Oxide Signaling: Identification of Early Reperfusion Phase as the Critical Therapeutic Window.

Baicalein is a natural flavonoid with anti-oxidant activities protecting against ischemia/reperfusion (I/R) injury. Previous studies suggest that oxidative burst early after reperfusion accelerates cell death. We therefore investigated the critical therapeutic window of baicalein by examining the timing of baicalein treatment in relation to its oxidant modulating and cytoprotective effects. Using an established chick cardiomyocyte model of I/R, we administered baicalein at various time points after reperfusion and assessed cell viability and the profiles of reactive oxygen species (ROS), nitric oxide (NO), and Akt phosphorylation. Baicalein administered at the onset of reperfusion resulted in a concentration-dependent reduction of cell death (25 µM 48.2±1.9%, 50µM 43.8±1.5%, 100µM 36.6±2.1%, vs. I/R control 57.3±1.4%, all p<0.05). Baicalein (100µM) timely and effectively scavenged ROS burst and enhanced NO production in the early reperfusion phase. Cotreatment with NO synthase (NOS) inhibitor l-NAME (200µM) partially abrogated the cytoprotective effect. Baicalein (100µM) given after reperfusion lost protective effect in a time-dependent manner with cytoprotection completely lost if >60min. Even with only 15-min delay after reperfusion, the ROS scavenging effect was abolished and the NO enhancing effect markedly reduced. The phosphorylation of Akt, an upstream regulator of eNOS, also diminished as the delay lengthened. In conclusion, baicalein treatment after reperfusion confers cardioprotection in a concentration- and time-dependent manner. The critical therapeutic window lies in the early reperfusion phase, during which ROS scavenging and Akt-eNOS mediated NO signaling are most effective.

Baicalein Preventive Treatment Confers Optimal Cardioprotection by PTEN/Akt/NO Activation.

Baicalein is a flavonoid with excellent oxidant scavenging capability. It has been reported to protect against a variety of oxidative injuries including ischemia/reperfusion (I/R). However, the optimal treatment strategy for I/R injury and the protective mechanisms are not fully understood. In this study we employed an established chick cardiomyocyte model of I/R and investigated the effects of three baicalein treatment strategies on reactive oxygen species (ROS) scavenging, nitric oxide (NO) production and cell viability. The molecular signaling pathways were also explored. Compared to the I/R control (cell death 52.2[Formula: see text][Formula: see text][Formula: see text]2.0%), baicalein preventive treatment (25[Formula: see text][Formula: see text]M, pretreated for 72[Formula: see text]h and continued through I/R) conferred the best protection (19.5[Formula: see text][Formula: see text][Formula: see text]3.9%, [Formula: see text]), followed by I/R treatment (treated during I/R) and reperfusion treatment (treated at reperfusion only). Preventive and I/R treatments almost completely abolished ROS generation during both ischemic and reperfusion phases, and increased NO production and Akt phosphorylation. Reperfusion treatment reduced the ROS burst in the early reperfusion phase only, and had no effect on NO production and Akt activation. Further, the phosphorylation of phosphatase and tensin homolog (PTEN), a phosphatase negatively regulating Akt activation, was significantly increased by baicalein preventive treatment and slightly by the I/R treatment. PTEN protein expression was reduced in the same trend accordingly. Baicalein reperfusion treatment had no effects on PTEN phosphorylation and expression. Our results indicate that baicalein preventive treatment confers optimal cardioprotection against I/R injury, and this protection involves effective oxidant scavenging and the activation of PTEN/Akt/NO pathway.

Unusual causes of hyperammonemia in the ED.

Plasma ammonia measurement is a simple yet important screening in the ED for patients with unexplained stupor or delirium. Acute hyperammonemia is a medical emergency for which immediate steps must be taken to minimize permanent brain damage. Although the most common causes of hyperammonemia are severe abnormal liver function, the absence of liver disease in some cases has been observed. This brief report describes four hyperammonemia cases with normal liver function in the ED. On careful history and speculated examinations, ornithine carbamoyltransferase (OTC) deficiency, hematologic malignancy, and the side effects of valproic acid and 5-fluorouracil (5-FU) were considered. Therapy was first aimed at correcting the hyperammonemia. Once a specific diagnosis was reached, protein restriction, essential amino acid supplementation, efficient chemotherapy, and valproic acid and 5-FU level discontinuance were instituted. In this report, the clinical presentation, pathogenesis, and diagnostic workup for various hyperammonemia causes are discussed. Every EP should understand that the clinical symptoms for hyperammonemia and prognosis are related to early diagnosis.

Usefulness of ST-segment elevation in lead aVR during tachycardia for determining the mechanism of narrow QRS complex tachycardia.

In the present study, we analyzed ST-segment elevation in lead aVR during tachycardia to differentiate the narrow QRS complex tachycardia. A total of 338 12-lead electrocardiograms during narrow QRS complex tachycardia were analyzed. Each patient underwent a complete electrophysiologic study. There were 161 episodes of atrioventricular nodal reentrant tachycardia (AVNRT), 165 episodes of atrioventricular reciprocating tachycardia (AVRT), and 12 episodes of atrial tachycardia (AT). The prevalence of aVR ST-segment elevation was 71% for AVRT, 31% for AVNRT, and 16% for AT. For ST-T changes in different leads, logistic regression analysis showed aVR ST-segment elevation was the only significant factor to differentiate the types of narrow QRS complex tachycardia (p<0.001 for AVRT and AVNRT; p=0.02 for AVRT and AT). The sensitivity, specificity, and accuracy of aVR ST-segment elevation to differentiate AVRT from AVNRT and AT were 71%, 70%, and 70%, respectively. Among 117 episodes of AVRT with aVR ST-segment elevation, there were 76 (65%) left side, 23 (20%) right side, 14 (12%) posterior septal, and 4 (3%) antero- and mid-septal accessory pathways (p=0.002). In conclusion, aVR ST-segment elevation during narrow QRS complex tachycardia favors the atrioventricular reentry through an accessory pathway as the mechanism of the tachycardia.

Attenuation of increased myocardial ischaemia-reperfusion injury conferred by hypercholesterolaemia through pharmacological inhibition of the caspase-1 cascade.

1. Hypercholesterolaemia has been shown to be associated with greater myocardial ischaemia-reperfusion injury, in which apoptosis and inflammation-mediated necrosis both play a key role. 2. Caspase-1 is involved in the activation of both apoptosis and inflammation, through the intermediate of interleukin-1beta (IL-1beta). We herein examined whether pharmacological inhibition of the caspase-1 cascade, using Ac-Tyr-Val-Ala-Asp-CH(2)Cl (Ac-YVAD.cmk), after myocardial ischaemia have greater protective effects on myocardial ischaemia-reperfusion injury in diet-induced hypercholesterolaemic rabbits. 3. Male rabbits fed with standard chow or chow supplemented with 0.5% cholesterol and 10% coconut oil for 8 weeks were subjected to 30 min of left circumflex artery occlusion followed by 4 h of reperfusion. An intravenous bolus of Ac-YVAD.cmk (1.6 mg kg(-1)) or vehicle was given 20 min after coronary occlusion. 4. Postischaemic administration of Ac-YVAD.cmk markedly decreased infarct size from 26+/-3% to 12+/-2% in normally fed rabbits (P=0.005) and from 41+/-6% to 14+/-2% in cholesterol-fed rabbits (P<0.001). 5. In the ischaemic non-necrotic area, treatment with Ac-YVAD.cmk markedly reduced the percentage of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labelling (TUNEL)-positive cardiomyocytes from 15.5+/-0.8% to 2.2+/-0.1% in normally fed rabbits (P<0.001) and from 39.0+/-2.3% to 2.2+/-0.1% in cholesterol-fed rabbits (P<0.001). 6. Ac-YVAD.cmk treatment resulted in a reduction not only of IL-1beta and caspase-1, but also of caspase-3 in the ischaemic myocardium in both normally fed and cholesterol-fed rabbits. 7. No differences in infarct size, the percentage of TUNEL-positive cardiomyocytes, IL-1beta levels or activity of caspase-1 and caspase-3 were observed between Ac-YVAD.cmk-treated normally fed and cholesterol-fed rabbits. 8. This study demonstrates that injection of a selective caspase-1 inhibitor after myocardial ischaemia markedly reduced the detrimental effect conferred by hypercholesterolaemia on myocardial ischaemia-reperfusion injury by attenuating both necrotic as well as apoptotic cell death pathways through inhibition of IL-1beta production and activation of caspase-1 and caspase-3.

Increased cardiomyocyte apoptosis following ischemia and reperfusion in diet-induced hypercholesterolemia: relation to Bcl-2 and Bax proteins and caspase-3 activity.

It has been reported that apoptosis is a significant contributor to myocardial cell death as a result of reperfusion injury. However, whether the extent of cardiomyocyte apoptosis following ischemia and reperfusion varies in different pathophysiological backgrounds is still uncertain. In this study, we examined whether hypercholesterolemia increases the extent of myocardial reperfusion injury by aggravating cardiomyocyte apoptosis and the effects of hypercholesterolemia on the expression of Bcl-2 and Bax proteins and the activation of caspase-3. Twenty-eight male New Zealand white rabbits were fed standard chow (control, n = 14) or chow supplemented with 10% cholesterol (hypercholesterolemic, n = 14) for 8 wk. Anesthetized rabbits were then subjected to 30 min of left circumflex artery occlusion followed by 4 h of reperfusion. Apoptosis was identified as "DNA ladders" by gel electrophoresis and confirmed histologically using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. The infarct size (% of risk region) was significantly greater in hypercholesterolemic rabbits than in controls (39 +/- 6 vs. 23 +/- 2%, P = 0.02). Very few TUNEL-positive cardiomyocytes could be identified in the nonischemic regions in both groups, consistent with an absence of DNA laddering. In contrast, TUNEL-positive cardiomyocytes were significantly displayed in the ischemic, nonnecrotic myocardium, and DNA ladder occurred in all animals. The percentage of TUNEL-positive cardiomyocytes in the ischemic nonnecrotic myocardium was significantly higher in hypercholesterolemic rabbits compared with controls (40 +/- 5 vs. 17 +/- 11%, P < 0.001). Western blot analysis showed that, in the nonischemic myocardium, hypercholesterolemic rabbits exhibited an approximately 50% increase in the expression of Bcl-2 (P < 0.05), but not Bax, than control rabbits. However, compared with controls, hypercholesterolemic rabbits exhibited a more pronounced decrease in the expression of Bcl-2 (42 +/- 4 vs. 26 +/- 2%, P < 0.01) and a similar extent of increase in the expression of Bax in the ischemic myocardium. Furthermore, hypercholesterolemic rabbits were associated with a markedly increased activation of caspase-3 within the ischemic myocardium compared to control rabbits. This study demonstrates that although hypercholesterolemia is associated with an increased myocardial Bcl-2/Bax ratio at baseline, it still significantly exacerbates cardiac reperfusion injury, not only by increasing the infarct size but also by increasing the extent of cardiomyocyte apoptosis.