A case of acute lithium poisoning and hypermagnesemia involving advanced colon cancer-induced colonic obstruction.

An 83-year-old woman presented with disturbance of consciousness and hand tremor. She had taken lithium carbonate 300 mg/day for bipolar disorder and magnesium oxide 660 mg/day for constipation. Blood tests revealed lithium poisoning, hypermagnesemia and acute kidney injury. Computed tomography showed colonic obstruction caused by cancer of the descending colon. In the outpatient section, her blood pressure decreased to 89/54 mmHg, and her heart rate dropped to 40 bpm. We considered that the obstructive ileus induced intravascular dehydration, which led to toxic serum concentrations of lithium and magnesium, triggering the emergence of severe arrythmia induced by sinus dysfunction. The patient was treated with fluid resuscitation and hemodialysis, followed by endoscopic stent replacement for the descending colon cancer obstruction. These treatments improved her general condition and alleviated the lithium poisoning, hypermagnesemia and colonic obstruction. Such a case is considered extremely rare.

Novel Utility of Leucine-Rich Alpha-2-Glycoprotein as a Biomarker in Ulcerative Colitis: A Predictor of Endoscopic Remission Independent of Symptoms.

Introduction: Leucine-rich alpha-2-glycoprotein (LRG) is a potential biomarker for disease activity and reflects mucosal healing in patients with ulcerative colitis (UC). However, only a few studies have described a detailed sensitivity analysis of LRG in predicting mucosal healing in patients. This study aimed to evaluate the association between LRG and the endoscopic activity of UC and its predictability for mucosal healing and explore the utility and clinical application of LRG. Methods: The diagnostic accuracy of biomarkers, including LRG, in predicting the endoscopic activity of UC was evaluated. All consecutive patients who underwent total colonoscopy between April 2021 and September 2022 were included. The Mayo endoscopic subscore (MES) was used for assessing endoscopic activity. Furthermore, endoscopic remission was defined as an MES of ≤1. Clinical activity was evaluated based on stool frequency and bloody stool. Receiver operating characteristic curve analysis and binary logistic regression were performed to assess the diagnostic accuracy of the biomarkers. We evaluated LRG trends and treatment response in patients with MES ≥2 who underwent induction therapy. Results: This study comprised 214 patients. The proportions of endoscopically and clinically active patients were 33.6% and 49.1%, respectively. LRG had an area under the curve (AUC) of 0.856, with a higher diagnostic accuracy than other biomarkers, such as C-reactive protein, leukocyte, neutrophil, platelet, and albumin. The cutoff value for LRG was 15.6 µg/mL (sensitivity, 72.2%; specificity, 86.6%). Using the MES, patients with higher scores had higher LRG levels than those with lower scores. The cutoff value, AUC, sensitivity, and specificity varied with a higher AUC for left-sided colitis and pancolitis than for proctitis. Logistic regression analysis showed that LRG was an independent predictor of endoscopic remission using multivariate analysis, even with the factor of clinical activity. The change ratio of LRG pre- and post-treatment was statistically significant in the higher LRG group. Conclusion: LRG reflected endoscopic activity independently, regardless of clinical symptoms. An LRG below the cutoff value could indicate a significantly low probability of endoscopic activity in asymptomatic patients, and follow-up endoscopy (not for cancer screening) may be unnecessary. Furthermore, a higher LRG level might be more useful as an indicator of treatment efficacy.

Functional involvement of endothelial lipase in hepatitis B virus infection.

BACKGROUND: HBV infection causes chronic liver disease and leads to the development of HCC. To identify host factors that support the HBV life cycle, we previously established the HC1 cell line that maintains HBV infection and identified host genes required for HBV persistence. METHODS: The present study focused on endothelial lipase (LIPG), which binds to heparan sulfate proteoglycans (HSPGs) in the cell membrane. RESULTS: We found HBV infection was impaired in humanized liver chimeric mouse-derived hepatocytes that were transduced with lentivirus expressing short hairpin RNA against LIPG. Long-term suppression of LIPG combined with entecavir further suppressed HBV replication. LIPG was shown to be involved in HBV attachment to the cell surface by using 2 sodium taurocholate cotransporting peptide (NTCP)-expressing cell lines, and the direct interaction of LIPG and HBV large surface protein was revealed. Heparin and heparinase almost completely suppressed the LIPG-induced increase of HBV attachment, indicating that LIPG accelerated HBV attachment to HSPGs followed by HBV entry through NTCP. Surprisingly, the attachment of a fluorescently labeled NTCP-binding preS1 probe to NTCP-expressing cells was not impaired by heparin, suggesting the HSPG-independent attachment of the preS1 probe to NTCP. Interestingly, attachment of the preS1 probe was severely impaired in LIPG knockdown or knockout cells. Inhibitors of the lipase activity of LIPG similarly impaired the attachment of the preS1 probe to NTCP-expressing cells. CONCLUSIONS: LIPG participates in HBV infection by upregulating HBV attachment to the cell membrane by means of 2 possible mechanisms: increasing HBV attachment to HSPGs or facilitating HSPG-dependent or HSPG-independent HBV attachment to NTCP by its lipase activity.

Super-Resolution Microscopy Analysis of Hepatitis B Viral cccDNA and Host Factors.

Infection with hepatitis B virus (HBV) cannot be cured completely because of the persistence of covalently closed circular DNA (cccDNA). We previously found that the host gene dedicator of cytokinesis 11 (DOCK11) was required for HBV persistence. In this study, we further investigated the mechanism that links DOCK11 to other host genes in the regulation of cccDNA transcription. cccDNA levels were determined by quantitative real-time polymerase chain reaction (qPCR) and fluorescence in situ hybridization (FISH) in stable HBV-producing cell lines and HBV-infected PXB-cells®. Interactions between DOCK11 and other host genes were identified by super-resolution microscopy, immunoblotting, and chromatin immunoprecipitation. FISH facilitated the subcellular localization of key HBV nucleic acids. Interestingly, although DOCK11 partially colocalized with histone proteins, such as H3K4me3 and H3K27me3, and nonhistone proteins, such as RNA Pol II, it played limited roles in histone modification and RNA transcription. DOCK11 was functionally involved in regulating the subnuclear distribution of host factors and/or cccDNA, resulting in an increase in cccDNA closely located to H3K4me3 and RNA Pol II for activating cccDNA transcription. Thus, it was suggested that the association of cccDNA-bound Pol II and H3K4me3 required the assistance of DOCK11. DOCK11 facilitated the association of cccDNA with H3K4me3 and RNA Pol II.

Hepatitis B Virus Utilizes a Retrograde Trafficking Route via the Trans-Golgi Network to Avoid Lysosomal Degradation.

BACKGROUND & AIMS: Hepatitis B virus (HBV) infection is difficult to cure owing to the persistence of covalently closed circular viral DNA (cccDNA). We performed single-cell transcriptome analysis of newly established HBV-positive and HBV-negative hepatocellular carcinoma cell lines and found that dedicator of cytokinesis 11 (DOCK11) was crucially involved in HBV persistence. However, the roles of DOCK11 in the HBV lifecycle have not been clarified. METHODS: The cccDNA levels were measured by Southern blotting and real-time detection polymerase chain reaction in various hepatocytes including PXB cells by using an HBV-infected model. The retrograde trafficking route of HBV capsid was investigated by super-resolution microscopy, proximity ligation assay, and time-lapse analysis. The downstream molecules of DOCK11 and underlying mechanism were examined by liquid chromatography-tandem mass spectrometry, immunoblotting, and enzyme-linked immunosorbent assay. RESULTS: The cccDNA levels were strongly increased by DOCK11 overexpression and repressed by DOCK11 suppression. Interestingly, DOCK11 functionally associated with retrograde trafficking proteins in the trans-Golgi network (TGN), Arf-GAP with GTPase domain, ankyrin repeat, and pleckstrin homology domain-containing protein 2 (AGAP2), and ADP-ribosylation factor 1 (ARF1), together with HBV capsid, to open an alternative retrograde trafficking route for HBV from early endosomes (EEs) to the TGN and then to the endoplasmic reticulum (ER), thereby avoiding lysosomal degradation. Clinically, DOCK11 levels in liver biopsies from patients with chronic hepatitis B were significantly reduced by entecavir treatment, and this reduction correlated with HBV surface antigen levels. CONCLUSIONS: HBV uses a retrograde trafficking route via EEs-TGN-ER for infection that is facilitated by DOCK11 and serves to maintain cccDNA. Therefore, DOCK11 is a potential therapeutic target to prevent persistent HBV infection.

Clinical Features and Resistance to Entecavir Monotherapy of Patients with Hepatitis B.

Aim: Hepatitis B virus (HBV) infection is a major public health concern worldwide. Entecavir (ETV), a first-line nucleos(t)ide analogue (NA) for HBV, has a low risk of resistance. We evaluated the efficacy of ETV monotherapy, ratio of ETV-resistant, and the clinical features of patients with ETV resistance. Methods: A total of 130 patients (72 males, 58 females; mean age, 61 ± 15 years) were divided into a NA-naïve group (n = 108) and NA-experienced group (n = 22). We examined the clinical outcomes of ETV monotherapy and associated factors. We also assessed the clinical features of 15 patients with resistance to ETV (mean, 51.0 ± 27.4 weeks). Results: Among the 130 patients, 94.1% achieved ALT normalization and 63.6% achieved serum HBV DNA negativity after ETV monotherapy for 96 weeks. Of the patients in the NA-naïve group, 93.1% and 60.4% achieved ALT normalization and HBV DNA negativity, respectively. Of the patients in the NA-experienced group, 100% and 74.9% achieved ALT normalization and HBV DNA negativity, respectively. Compared to patients on ETV continuously, 15 ETV-resistant patients had a higher baseline HBV viral load. There was a significant difference in the time to HBV DNA negativity, but not ALT normalization after ETV monotherapy in these groups. Rescue treatment with other NAs led to ALT normalization in all of these patients, but not HBV DNA negativity. Conclusions: ETV monotherapy has a long-term clinical efficacy. While some patients especially with HBV DNA high viral load developed ETV resistance, rescue treatment led to ALT normalization in these patients.

[Case report of a patient with recurrence after endoscopic submucosal dissection for superficial esophageal cancer, diagnosed with mediastinal lymph node endoscopic ultrasound-fine needle aspiration based on the symptom of hoarseness].

The patient was an 81-year-old man who presented with a complaint of hoarseness. When he was 80 years old, he had developed superficial esophageal cancer and had undergone endoscopic submucosal dissection (ESD) at our hospital. Two months after the ESD, he developed hoarseness. Computed tomography (CT) scan showed no abnormal findings at that time;therefore, he was diagnosed with idiopathic vocal cord paralysis, and followed up with symptom treatment in the Gastroenterology and Otolaryngology Departments. Ten months after the ESD, a CT scan revealed mediastinal lymph node swelling. He was admitted to our hospital for histopathological examination of the lymph node using endoscopic ultrasound-fine needle aspiration (EUS-FNA). The histopathological examination revealed squamous cell carcinoma of the lymph node, similar to the primary esophageal tumor. This result suggests that laryngeal nerve paralysis involving hoarseness is caused by lymph node metastasis of superficial esophageal cancer. We report that histopathological examination with EUS-FNA helps in determining the cause of hoarseness that develops after ESD.

Imaging features and pathological evaluation by EUS-FNA enable conservative management in patient of lymphoepithelial cyst of the pancreas: a case report.

Pancreatic lymphoepithelial cysts (LECs) are rare cystic lesions filled with a keratinous substance and lined by squamous epithelium with underlying lymphoid tissue. Because pancreatic LECs are entirely benign, correct preoperative diagnosis is important to avoid unnecessary surgery. However, the imaging features of pancreatic LECs are not specific and preoperative diagnosis has proven difficult. A pancreatic mass was incidentally detected through abdominal ultrasonography in a 63-year-old male presenting without any symptoms. Computed tomography showed an exophytic cystic lesion in the pancreatic head. The lesion had heterogeneous high signal intensity with partial low intensity on T2-weighted magnetic resonance imaging (MRI) and high signal intensity on diffusion MRI. Endoscopic ultrasound (EUS) examination showed an encapsulated cystic lesion with relatively homogenous and highly echoic contents. EUS-guided fine-needle aspiration (EUS-FNA) revealed caseous appearance and rare fragments of apparently benign squamous epithelium on a background of keratinous debris, cyst contents, and scattered lymphocytes. We diagnosed a pancreatic LEC and opted for conservative management without surgery. Pathological evaluation based on images obtained through EUS-FNA showed macro- and microscopic features that were critical to determining the management strategy. In conclusion, the imaging and pathological features of pancreatic LECs can inform preoperative diagnosis, which may enable conservative management.

Clinical Features and Dynamics of T Cells-Related Markers in Immunocompetent Patients with Cytomegalovirus Hepatitis.

Aim: Cytomegalovirus (CMV) can cause hepatitis, encephalomyelitis, and pneumonitis in immunocompromised patients. In contrast, CMV infection of immunocompetent patients can lead to the development of infectious mononucleosis and is typically self-limiting; severe complications are rare. We evaluated the pathophysiology and immunological aspects of CMV hepatitis in recently immunocompetent adult patients. Methods: We examined the clinical features and outcomes of 47 adult immunocompetent patients with CMV hepatitis (29 men, 18 women; mean age, 34 ± 11 years) from January 2005 to August 2019 treated in our hospital. We also assayed T-cell activation to evaluate the immune responses in these patients. Results: Fever (74.5%), hepatosplenomegaly (74.5%), sore throat (36.2%), headache (31.9%), abdominal pain (27.7%), lymphadenopathy (23.4%), and skin rash (6.4%) were present at admission. Complications included gastrointestinal injury (25.5%), neuropathy (4.3%), thrombocytopenia (2.1%), and splenic infarction (2.1%). All patients had a good clinical course without liver failure or transition to chronic liver injury. The time to recover from liver injury ranged from 12 to 142 days (mean, 43.4 ± 28.7 days). The serum sIL-2R level, which reflects T-cell activation, was transiently elevated and correlated with the extent of hepatic inflammation. Conclusions: CMV hepatitis in immunocompetent individuals has a satisfactory outcome, but occasionally results in complications in other organs. The sIL-2R level has potential as a surrogate marker of hepatic inflammation in immunocompetent patients with CMV hepatitis.

Citrullinated Histone H3: Early Biomarker of Neutrophil Extracellular Traps in Septic Liver Damage.

BACKGROUND: Neutrophil extracellular traps (NETs) play a crucial role in host defense, but excess and prolonged interaction of NETs with platelets can cause severe inflammation and host organ damage. Modification of histone H3 by citrullination is involved in in vitro NET formation. The phosphodiesterase III inhibitor, cilostazol (Ciz), which has a protective effect on liver sinusoidal endothelial cells and inhibits platelet aggregation, may prevent organ damage caused by excess NETosis. In this study, we investigated whether citrullinated histone H3 (H3Cit) could serve as a biomarker for the detection of critical liver damage in sepsis and the efficacy of phosphodiesterase-III inhibition for preventing the liver dysfunction induced by NETosis. MATERIALS AND METHODS: Mice injected with lipopolysaccharide (LPS; 1 mg/kg) were used as a sepsis model with or without treatment with Ciz (200 mg/kg). H3Cit, myeloperoxidase, and neutrophil elastase levels were measured by immunohistochemistry. We evaluated H3Cit-positive neutrophils in the peripheral blood by flow cytometry. RESULTS: Immunohistochemistry revealed that H3Cit-, neutrophil elastase-, and myeloperoxidase-positive cell numbers in the livers peaked at 12 h after LPS administration. However, flow cytometry showed a significant increase in H3Cit-positive neutrophils in the peripheral blood only 4 h after LPS injection. Treatment with Ciz significantly ameliorated all parameters. CONCLUSIONS: H3Cit is a useful biomarker for early detection of NETosis or liver dysfunction, and Ciz may be an effective treatment for septic liver damage.

Detection of prior myocardial infarction patients prone to malignant ventricular arrhythmias using wavelet transform analysis.

Ventricular tachycardia (VT) and ventricular fibrillation (VF) leading to sudden cardiac death remains responsible for significant mortality in patients with prior myocardial infarction (MI). The study population consisted of 50 normal controls and 50 patients with prior MI. The MI subjects were divided into 3 groups: VT/VF (-) group; 25 patients without ventricular tachyarrhythmia, VT group; 13 patients with sustained VT, and VF group; 12 patients with resuscitated VF. The parameters on the signal-averaged ECG and the frequency components recorded from the wavelet-transformed ECG were compared. The high-frequency components (HFC; 80-150 Hz) were developed in the MI group to a greater extent than those in the control group. Among the MI patients, the HFC were more developed in the VT and VF groups than in the VT/VF (-) group. In the VF group, the positive rate of LP was 50%. Meanwhile, when the peak power value at 150 Hz > 300 was defined as abnormal, the HFC was detected in 13 (100%) patients in the VT group and 12 (91.7%) in the VF group. The sensitivity of the abnormal HFC in identifying patients with VT/VF was higher than that of SAECG (96% versus 72%), although the specificity remained similar (68.5% versus 64.3%). Abnormal HFC recorded from the wavelet-transformed ECG may be a novel factor in detecting patients who are prone to VT/VF.

A new approach for the comparison of conduction abnormality between arrhythmogenic right ventricular cardiomyopathy/dysplasia and Brugada syndrome.

BACKGROUND: Right ventricular outflow tract ventricular tachycardia (RVOT-VT), arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/ARVD), and Brugada syndrome (BrS) were characterized by arrhythmias originating in the right ventricle, and the pathophysiologic mechanism underlying these arrhythmias has not been fully understood. METHODS: This study consisted of 40 subjects, including 20 patients with RVOT-VT, 10 patients with BrS, and 10 ARVD patients. The parameters on the signal-averaged electrocardiography (ECG) and the frequency components recorded from the wavelet-transformed ECG were compared between the three groups. Late potentials were positive in none of the patients with RVOT-VT, seven of the patients with BrS, and all of ARVD patients. RESULTS: In Brugada and ARVD patients, the power of high-frequency components (80-150 Hz) was developed to a greater extent than in RVOT-VT patients. In the power analysis of the high-frequency components between BrS and ARVD, the frequency showing the greatest power was significantly higher in ARVD patients than that in BrS patients (145.4 ± 27.9 Hz vs 81.7 ± 19.9 Hz, P < 0.01). CONCLUSIONS: High-frequency components were developed in ARVD and BrS, but not in RVOT-VT. The frequency levels showing high power by wavelet analysis obviously differ between ARVD and BrS. Wavelet analysis may provide new insight into unsolved mechanisms in arrhythmogenic right heart disease.

Effect of corticosteroid therapy on ventricular arrhythmias in patients with cardiac sarcoidosis.

BACKGROUND: Ventricular arrhythmias are one of the main causes of sudden death in cardiac sarcoidosis (CS). Little is known about the efficacy of corticosteroid therapy for ventricular arrhythmias in CS. METHODS: Thirty-one CS patients presenting premature ventricular contractions (PVCs, ≥300/day) were investigated. Fourteen patients had nonsustained ventricular tachycardia (NSVT). All of patients were treated with corticosteroid, and the initial dosage is 30 mg/day of prednisone, which was tapered over a period of 6 months to a maintenance dosage of 10 mg/day. Twenty-four hour Holter monitoring, signal averaged electrocardiography (SAECG), echocardiography, gallium-67 scintigraphy, serum angiotensin converting enzyme (ACE) and plasma B-type natriuretic peptide (BNP) concentrations were assessed before and after corticosteroid therapy. RESULTS: As a whole, there were no significant differences in the number of PVCs and in the prevalence of NSVT before and after steroid therapy. However, the less advanced LV dysfunction patients (EF ≥ 35%, n = 17) showed significant reduction in the number of PVCs (from 1820 ± 2969 to 742 ± 1425, P = 0.048) and in the prevalence of NSVT (from 41 to 6%, p = 0.039). Late potentials on SAECG were abolished in 3 patients. The less advanced LV dysfunction group showed a significantly higher prevalence of gallium-67 uptake compared with the advanced LV dysfunction group (EF < 35 %, n = 14). In the advanced LV dysfunction patients, there were no significant differences in these parameters. CONCLUSIONS: Corticosteroid therapy may be effective for ventricular arrhythmias in the early stage, but less effective in the late stage.

Non-invasive detection of latent cardiac conduction abnormalities in patients with pulmonary sarcoidosis.

BACKGROUND: Electrocardiographic conduction abnormalities including development of atrioventricular block, bundle branch block or ventricular arrhythmias are characteristic manifestations of cardiac sarcoidosis (CS). The present study seeks to show the minute conduction abnormality by detection of late potentials (LP) on signal averaged electrocardiogram (SAECG). METHODS AND RESULTS: Ten patients with CS, 52 patients with pulmonary sarcoidosis (PS) but no obvious cardiac manifestations and 52 normal controls were studied. All participants underwent SAECG to detect LP. In patients with CS (the CS group), LP were detected in 8 patients (80%). In 52 patients with PS, LP were detected in 25 patients (46.2%, PS-LP(+) group), comparing only 3 (5.8%) of normal controls (p<0.0001). The remaining 27 patients with PS with negative LP were classified in the PS-LP(-) group. In the CS group, premature ventricular contraction frequency on Holter's monitoring and plasma B-type natriuretic peptide concentrations were significantly higher than those in the PS group. However, no significant difference in these parameters between PS-LP(+) and PS-LP(-) groups were found. CONCLUSIONS: In the PS patients without obvious cardiac manifestations, LP were detected as high as 46.2%, suggesting latent minute conduction abnormality. The higher incidence of LP in PS might be considered as an expression of latent myocardial fibrosis. Close follow-up is needed in these patients.

High-frequency potentials developed in wavelet-transformed electrocardiogram as a novel indicator for detecting Brugada syndrome.

BACKGROUND: A reliable alternative method for detecting Brugada syndrome is desirable because the diagnosis of Brugada syndrome using 12-lead ECG is not optimal. OBJECTIVES: The purpose of this study was to assess the usefulness of the wavelet-transformed ECG in detecting Brugada syndrome. METHODS: The study consisted of 15 patients with Brugada syndrome and 15 healthy subjects (control group). The parameters on the signal-averaged ECG and the frequency components recorded from the wavelet-transformed ECG were compared between the two groups. Measurements were repeated after pilsicainide infusion in the two groups of patients, after an isoproterenol infusion following pilsicainide injection, and after administration of cilostazol in the group of patients with Brugada syndrome. RESULTS: The positive rate of late potentials was 80% in the Brugada syndrome group and 0% in the control group (P <.01). The high-frequency components (80-150 Hz) were developed in the Brugada syndrome group to a greater extent than in the control group, but the low-frequency components (10-50 Hz) did not differ (mean peak power at 80 Hz; 713 +/- 36 vs 488 +/- 60, P <.001). After pilsicainide injection, high-frequency components significantly increased in both groups. However, after isoproterenol and cilostazol administration, high-frequency components significantly decreased but remained higher than in the control group (80 Hz; 655 +/- 40 vs 488 +/- 60, P <.001). The sensitivity of the development of high-frequency components in detecting Brugada syndrome was higher than that of signal-averaged ECG (100% vs 80%), but specificity remained high and similar (100% for both methods). CONCLUSION: Abnormally high-frequency components recorded from the wavelet-transformed ECG might be a novel factor in detecting Brugada syndrome.

Evaluation of arrhythmogenic substrate in patients with hypertrophic cardiomyopathy using wavelet transform analysis.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is thought to have a microvolt-level electrical disarrangement in the myocardium that leads to ventricular tachyarrhythmias and sudden cardiac death. Although signal-averaged electrocardiography (ECG) has been used to detect late potential as a parameter of electrical instability, its predictability is not high. The focus of the present study was the ability of high-resolution wavelet transform from beat-to-beat analysis to detect arrhythmogenic substrates and to evaluate its relationship to the severity of ventricular tachycardia. METHODS AND RESULTS: The study group comprised 50 healthy subjects and 50 patients with HCM. The filtered-QRS duration from the signal-averaged ECG, the high-power duration (HPD) and number of disarrangement points (NDP) from the wavelet-transform ECG were measured. When HPD was defined >114 ms and/or NDP >9 points as abnormal, the sensitivity and specificity for ventricular tachycardia was 93.8% and 79.4%, respectively. When a mean +/- standard deviation of the HPD in normal subjects was defined as normal, 93.8% of patients with a positive late potential were out of the normal range. CONCLUSIONS: The newly developed color-display 3-dimensional wavelet transform system showed good time-frequency resolution in analyzing every single beat without signal-averaging. The analysis could be used to detect arrhythmogenic substrates in patients with HCM.

Relationship between brain natriuretic peptide, myocardial wall stress, and ventricular arrhythmia severity.

We previously demonstrated that the severity of arrhythmias is reflected by circulating brain natriuretic peptide (BNP) concentrations in patients without signs of congestive heart failure. In the present study, we evaluated the relationships between the severity of the arrhythmia, BNP concentration, and echocardiographic findings. The subjects consisted of 52 patients with ventricular premature contractions (VPC) but no manifestations of heart failure and no digoxin or beta-blocker therapy. Patients underwent Holter monitoring, plasma sampling for BNP measurement, and transthoracic echocardiography (TTE). We scored the motion of 16 left ventricular segments, deriving a wall-motion score index (WMSI) by totaling the scores and dividing by the number of segments scored. Twenty-three patients with Lown grade I to II arrhythmias constituted group A while group B consisted of 29 Lown III to IV patients. Group B had BNP concentrations triple those in group A (57.2 versus 18.1 pg/mL, P < 0.01). Left ventricular ejection fraction (LVEF) was similar in groups A and B (65.2% versus 62.1%, NS). Although left ventricular end-diastolic dimension (LVEDD) was normal in both groups, group B exhibited a larger LVEDD than group A (50 versus 46 mm, P < 0.005). The correlation (r) between BNP and interventricular septum thickness (IVST) was 0.27 (P = 0.013) in group A and 0.37 (P < 0.0001) in group B. Between BNP and posterior wall thickness (PWT), the correlation was 0.23 (P = 0.014) in group A versus 0.33 (P < 0.0001) in group B. The WMSI in group B was higher than in group A (1.34 versus 1.11, P < 0.05). We believe that besides the changes in echocardiographic parameters, the BNP elevation in group B could be a response to abnormal wall stress from the severe ventricular arrhythmias.

Therapeutic monitoring of class I antiarrhythmic agents using high-resolution electrocardiography instead of blood samples.

Antiarrhythmic therapy requires monitoring of serum drug concentrations to determine a patient's optimal oral dose of medication. Repeated examination of blood samples, however, is costly and time-consuming, so the present study evaluated whether changes in serum concentrations could be estimated from changes in electrocardiographic (ECG) parameters. Of 36 patients receiving antiarrhythmic drugs for supraventricular or ventricular arrhythmias, 12 were treated with flecainide, 12 with pilsicainide, and 12 with pirmenol. Signal-averaged ECG (SAECG) were recorded before starting drug administration, 1 month later, and twice during ongoing therapy. At the time of the 2nd to the 4th recordings, serum concentrations of the drugs were also measured. As previously reported, all agents, but especially flecainide and pilsicainide, prolonged the filtered QRS (f-QRS) and the duration of low-amplitude signals at the terminal portion of the QRS complex. The SAECG parameters varied between the recordings made during therapy. Differences in the duration of the f-QRS between 2 recordings correlated significantly with differences in serum drug concentrations (r=0.91 for flecainide, r=0.70 for pilsicainide, and r=0.61 for pirmenol). No significant correlation between drug concentration and other SAECG parameters was found. Changes in the serum concentration of flecainide, pilsicainide and pirmenol can be estimated from changes in the duration of the f-QRS on the SAECG and periodic monitoring of such could help reduce the number of repeat measurements of drug concentrations in blood samples.

Spontaneous isolated dissection of the superior mesenteric artery.

A case of a 63-year-old man with isolated dissection of the superior mesenteric artery (SMA), demonstrated by enhanced computed tomography (CT) and abdominal angiography, was admitted to our hospital. The severity of this disease varies from mild to severe; the severe cases require surgery. But the mild cases, like the one presented here, only need conservative therapy. This case demonstrated the usefulness of anticoagulation therapy and the indications for surgical and radiological intervention.