Relation of atrial fibrillation to glomerular filtration rate

Although both atrial fibrillation (AF) and decreasing glomerular filtration rate (GFR) are strongly related to advanced age and share common associated vascular risk factors, few studies have explored the relation between AF and GFR. From residents (age >or=40 years) in Kurashiki City, a total of 41,417 subjects (median age 72 years; 13,956 men) were enrolled in the Kurashiki City Annual Medical Survey from May to December 2006. The estimated overall prevalence of AF was 1.6% (2.8% in the low-GFR tertile, 1.2% in the middle tertile, and 0.9% in the high tertile, p <0.001). After all subjects were categorized into age tertiles (age thresholds 68 and 76 years), AF was identified in 0.9% in the low-GFR tertile, 0.6% in the middle tertile, and 0.5% in the high tertile in the low-age tertile (p = 0.018); 2.6% in the low-GFR tertile, 1.2% in the middle tertile, and 1.1% in the high tertile in the middle-age tertile (p <0.001); and 3.9% in the low-GFR tertile, 2.4% in the middle tertile, and 1.7% in the high tertile in the high-age tertile (p <0.001). The odds ratio for AF adjusted for age, gender, vascular risk factors, cardiac disease, and hemoglobin was 1.91 (95% confidence interval 1.54 to 2.38, p <0.001) for the low-GFR tertile versus the high tertile and 1.12 (95% confidence interval 0.88 to 1.42, p = 0.364) for the middle-GFR tertile versus the high tertile. The prevalence of AF gradually increased with decreasing GFR. In conclusion, AF appears to be associated with decreasing GFR.     

Discordant and heterogeneous expression of GPI-anchored membrane proteins on leukemic cells in a patient with paroxysmal nocturnal hemoglobinuria

We performed a flow cytometric analysis using monoclonal antibodies to decay accelerating factor (DAF) and CD59/membrane attack complex inhibitory factor (CD59/MACIF) in order to investigate the leukemic cells and erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria (PNH) who developed acute myelocytic leukemia. In May 1990, the leukemic cells comprised 70% of the mononuclear cells in the bone marrow and 76% of those in the peripheral blood. They consisted of a mixture of positive and negative populations, including single DAF- positive cells. In August 1990, almost 100% of the peripheral mononuclear cells were leukemic blasts, and these consisted of a single population with reduced DAF expression. Single-color flow cytometric analysis showed that the leukemic cells lacked CD59/MACIF, while control leukemic cells (n = 3) expressed both DAF and CD59/MACIF. Leukemic blasts from this patient and six control patients expressed lymphocyte function-associated antigen 3 and FcIII receptors (CD 16) both before and after treatment with phosphatidylinositol-specific phospholipase C. The patient's erythrocytes lacking DAF and CD59/MACIF expression corresponded to the proportion of complement-sensitive cells at the onset of acute leukemia. These DAF- and CD59/MACIF-deficient erythrocytes disappeared almost completely with progression of the leukemia. In conclusion, it appears that the expression of glycosylphosphatidylinositol-linked membrane proteins by leukemic cells was heterogeneous and discordant in our patient, and that the leukemic cells were derived from the PNH clone because of their deficiency of CD59/MACIF. It is also suggested that DAF could compete more effectively than CD59/MACIF for a limited number of anchor molecules available on the proliferating leukemic cells.     

Choledochoduodenal fistula at the anterior wall of the duodenal bulb: a rare complication of duodenal ulcer

A 38 year-old man was admitted to our hospital with the chief complaint of epigastralgia. His laboratory data revealed leukocytosis and increased serum amylase, and abdominal ultrasonography revealed diffuse swelling of the pancreas. Thus, he was diagnosed as having acute pancreatitis. Moreover, abdominal computed tomography showed pneumobilia in the gallbladder and the common bile duct. Gastroduodenal fiberscopy demonstrated peptic ulcer scars around a foramen with smooth margins at the anterior wall of the duodenal bulb. The bile juice flowed from the bottom of the foramen. Endoscopic retrograde cholangiopancreatography revealed the fistula between the common bile duct and the anterior wall of the duodenal bulb, but not the posterior wall. However, there was no pancreatico-biliary maljunction and no stones in the gallbladder or bile duct. This is a rare case of choledochoduodenal fistula at the anterior wall of the duodenal bulb caused by duodenal peptic ulcer disease.     

Prognostic significance of circadian variability of RR and QT intervals and QT dynamicity in patients with chronic heart failure

BACKGROUND: In patients with chronic heart failure (CHF), circadian variability of RR and QT intervals may be altered because of neurohumoral activation and functional and structural remodeling of the heart. OBJECTIVE: The aim of this study was to evaluate the prognostic significance of circadian variability of the RR and QT intervals and QT dynamicity (QT/RR slope) in CHF patients. METHODS: We prospectively enrolled 121 patients with stable CHF in sinus rhythm (age 67 +/- 14 years, mean +/- SD; range 34 to 87 years). The RR, QT, and rate-corrected QT (QTc) intervals and the QT/RR slope measured from 24-hour Holter electrocardiogram were fitted by cosine curves. RESULTS: During the follow-up period of 34 +/- 17 months, 40 (33%) patients died of cardiac causes, 10 of which were sudden. All patients showed significant circadian rhythms in the RR, QT, and QTc intervals and the QT/RR slope by cosine-curve fitting. In addition to the expected higher heart rate, longer QT interval, and steeper QT/RR slope, we found that patient who died of cardiac causes had reduced circadian variability of QT interval (10 +/- 10 ms vs 21 +/- 13 ms) and a later maximum RR interval (4.1 +/- 0.9 AM vs 2.3 +/- 2.1 AM) compared with survivors, among many other statistically significant circadian parameter differences. These 2 parameters were independent predictors of cardiac death in multivariate Cox proportional hazards regression analysis. CONCLUSION: Circadian variability analyses of Holter-derived RR and QT intervals may provide prognostic information beyond that provided by 24-hour averages of these parameters.     

Oral vaccination against HPV E7 for treatment of cervical intraepithelial neoplasia grade 3 (CIN3) elicits E7-specific mucosal immunity in the cervix of CIN3 patients

Background

Cervical intraepithelial neoplasia grade 3 (CIN3) is a mucosal precancerous lesion caused by high-risk human papillomavirus (HPV). Induction of immunological clearance of CIN3 by targeting HPV antigens is a promising strategy for CIN3 therapy. No successful HPV therapeutic vaccine has been developed.

Methods

We evaluated the safety and clinical efficacy of an attenuated Lactobacillus casei expressing modified full-length HPV16 E7 protein in patients with HPV16-associated CIN3. Ten patients were vaccinated orally during dose optimization studies (1, 2, 4, or 6 capsules/day) at weeks 1, 2, 4, and 8 (Step 1). Seven additional participants were only tested using the optimized vaccine formulation (Step 2), giving a total of 10 patients who received optimized vaccination. Cervical lymphocytes (CxLs) and peripheral blood mononuclear cells (PBMCs) were collected and E7 specific interferon-γ-producing cells were counted (E7 cell-mediated immune responses: E7-CMI) by ELISPOT assay. All patients were re-evaluated 9 weeks after initial vaccine exposure using cytology and biopsy to assess pathological efficacy.

Results

No patient experienced an adverse event. E7-CMI in both CxLs and PBMCs was negligible at baseline. All patients using 4–6 capsules/day showed increased E7-CMI in CxLs, whereas patients using 1–2 capsules/day did not. No patient demonstrated an increase in E7-CMI in their PBMCs. In comparison between patients of cohorts, E7-CMI at week 9 (9 wk) in patients on 4 capsules/day was significantly higher than those in patients on 1, 2, or 6 capsules/day. Most patients (70%) taking the optimized dose experienced a pathological down-grade to CIN2 at week 9 of treatment. E7-CMI in CxLs correlated directly with the pathological down-grade.

Conclusions

Oral administration of an E7-expressing Lactobacillus-based vaccine can elicit E7-specific mucosal immunity in the uterine cervical lesions. We are the first to report a correlation between mucosal E7-CMI in the cervix and clinical response after immunotherapy in human mucosal neoplasia.     

Three Dimensional Ultra-short Echo Time MRI Can Depict Cholesterol Components of Gallstones Bright

PurposeNon-calcified cholesterol stones that are small in size are hard to be depicted on CT or magnetic resonance cholangiopancreatography. This institutional review board (IRB)-approved retrospective in vitro study aims to characterize contrast behaviors of 3 main components of the gallstones, i.e., cholesterol component (CC), bilirubin calcium component (BC) and CaCO₃ (CO) on 3D radial scan with ultrashort TE (UTE) MRI, and to test the capability of depicting CC of gallstones as bright signals as compared to background saline.MethodsFourteen representative gallstones from 14 patients, including 15 CC, 6 BC and 4 CO, were enrolled. The gallstones underwent MRI including fat-saturated T1-weighted image (fs-T1WI) and UTE MRI with dual echoes. The contrast-to-noise ratio (CNR) and the chemical analysis for the 25 portions of the stones were compared.ResultsBC was bright on fs-T1WI, which did not change dramatically on UTE MRI and the signal did not remain on UTE subtraction image between dual echoes. Whereas the CC was negative or faintly positive signal on fs-T1WI, bright signal on UTE MRI and the contrast remained even higher on the UTE subtraction, which reflected their short T2 values. Median CNRs and standard errors of the segments on each imaging were as follows: on fs-T1WI, −10.2 ± 4.2 for CC, 149.7 ± 27.6 for BC and 37.9 ± 14.3 for CO; on UTE MRI first echo, 16.7 ± 3.3 for CC, 74.9 ± 21.3 for BC and 17.7 ± 8.4 for CO; on UTE subtraction image, 30.2 ±2.0 for CC, −11.2 ± 5.4 for BC and 17.8 ± 10.7 for CO. Linear correlations between CNRs and cholesterol concentrations were observed on fs-T1WI with r = −0.885, (P < 0.0001), UTE MRI first echo r = −0.524 (P = 0.0072) and UTE subtraction with r = 0.598 (P = 0.0016).ConclusionUTE MRI and UTE subtraction can depict CC bright.     

Claudin-6 is a single prognostic marker and functions as a tumor-promoting gene in a subgroup of intestinal type gastric cancer

Gastric Cancer - We aimed to identify novel tumor-promoting drivers highly expressed in gastric cancer (GC) that contribute to worsened prognosis in affected patients. Genes whose expression was...     

Treatment of acute hypernatremia caused by sodium overload in adults: A systematic review

Background:Rapid-onset, acute hypernatremia caused by sodium overload is a rare, life-threatening condition. Although experts recommend rapid correction of sodium concentration [Na] based on pathophysiological theories, only a few reports have documented the specific details of sodium correction methods. The objective of this study was to systematically review the reported treatment regimens, achieved [Na] correction rates, and treatment outcomes.Methods:PubMed, Ichushi-database, and references without language restrictions, from inception to January 2021, were searched for studies that described ≥1 adult (aged ≥18 years) patients with rapid-onset hypernatremia caused by sodium overload, whose treatment was initiated ≤12 hours from the onset. The primary outcome of interest was the [Na] correction rate associated with mortality.Results:Eighteen case reports (18 patients; median [Na], 180.5 mEq/L) were included. The cause of sodium overload was self-ingestion in 8 patients and iatrogenic sodium gain in 10 patients; baseline [Na] and symptoms at presentation were comparable for both groups. Individualized rapid infusion of dextrose-based solutions was the most commonly adopted fluid therapy, whereas hemodialysis was also used for patients already treated with hemodialysis. The correction rates were more rapid in 13 successfully treated patients than in 5 fatal patients. The successfully treated patients typically achieved [Na] ≤160 within 8 hours, [Na] ≤150 within 24 hours, and [Na] ≤145 within 48 hours. Hyperglycemia was a commonly observed treatment-related adverse event.Conclusion:The limited empirical evidence derived from case reports appears to endorse the recommended, rapid, and aggressive sodium correction using dextrose-based hypotonic solutions.     

Luteinizing hormone releasing hormone (LHRH) neuroterminals mapped using the push-pull perfusion method in the rhesus monkey

In vivo luteinizing hormone releasing hormone (LHRH) release was measured in conscious, ovariectomized rhesus monkeys using a push-pull cannula inserted into the stalk-median eminence, and the relationship between sampling location and LHRH release was examined. Within an individual animal in which multiple experiments were conducted with different cannula placements, LHRH pulse frequency was consistent. In contrast, LHRH pulse amplitude and mean LHRH release varied with cannula tip location in a pattern which reflected the anatomical distribution of LHRH-immunoreactive fibers described for the rhesus monkey. These results suggest that our push-pull perfusion method is reliable for the in vivo measurement of LHRH and perhaps other neuropeptides and/or neurotransmitters, as well.