Aprindine blocks the sodium current in guinea-pig ventricular myocytes

Summary Aprindine is a class Ib antiarrhythmic agent. We studied effects of aprindine (3 µmol/l) on the Na⁺ current using whole cell voltage clamp (tip resistance = 0.5 , [Na]_i and_o = 10 mmol/l at 18°C). Aprindine revealed tonic block (Kd_rest = 37.7 µmol/l, Kd_i = 0.74 µmol/l; n = 4). Aprindine, shifted inactivation curve to hyperpolarizing direction by 11.4 ± 3.5 mV (n = 4) without changes in slope factor. In the presence of 3 µmol/l aprindine, aprindine showed phasic block, i.e., duration-dependent block at 2 Hz (64% ±3070 at 1.5 ms, 82%±6% at 20 ms, 93%±7% at 200 ms; n = 4). Short single prepulse also produced aprindine-induced phasic block (12% at 1.5 ms, 22% at 100 ms; n = 2). After removal of fast inactivation of Na⁺ current by 3 mmol/l tosylchloramide sodium, aprindine revealed phasic block, independent of holding potential. The recovery time constant from aprindine-induced phasic block was 4.8 s at holding potential = –100 mV and 5.0 s at holding potential = –140 mV. This use-dependent block of aprindine had pH dependency. Under acidic condition (pH 6.0), 3 µmol/l aprindine showed smaller use-dependent block (14% ± 7% at 2 Hz; n = 4) comparing with either at pH 7,4 (68% ± 13%; n = 4) or at pH 8.0 (90% ±12%; n = 4).The results suggest that aprindine could bind to the receptor via activation process through channel pore, resulting in decrease of Na⁺ current, and egress from the receptor through the lipid bilayer. These effects might be attenuated under acidic condition due to changes in intracellular ratio of charged to neutralized form of drug molecule. Send offprint requests to: R. Sato at the above address     

Overexpression of the aldo-keto reductase family protein AKR1B10 is highly correlated with smokers' non-small cell lung carcinomas.

PURPOSE: Squamous cell carcinoma (SCC) and adenocarcinoma of the lung are currently subject to similar treatment regimens despite distinct differences in histology and epidemiology. The aim of this study is to identify a molecular target with diagnostic and therapeutic values for SCC. EXPERIMENTAL DESIGN: Genes specifically up-regulated in SCC were explored through microarray analysis of 5 SCCs, 5 adenocarcinomas, 10 small cell lung carcinomas, 27 normal tissues, and 40 cancer cell lines. Clinical usefulness of these genes was subsequently examined mainly by immunohistochemical analysis. RESULTS: Seven genes, including aldo-keto reductase family 1, member B10 (AKR1B10), were identified as SCC-specific genes. AKR1B10 was further examined by immunohistochemical analysis of 101 non-small cell lung carcinomas (NSCLC) and its overexpression was observed in 27 of 32 (84.4%) SCCs and 19 of 65 (29.2%) adenocarcinomas. Multiple regression analysis showed that smoking was an independent variable responsible for AKR1B10 overexpression in NSCLCs (P < 0.01) and adenocarcinomas (P < 0.01). AKR1B10 staining was occasionally observed even in squamous metaplasia, a precancerous lesion of SCC. CONCLUSION: AKR1B10 was overexpressed in most cases with SCC, which is closely associated with smoking, and many adenocarcinoma cases of smokers. These results suggest that AKR1B10 is a potential diagnostic marker specific to smokers' NSCLCs and might be involved in tobacco-related carcinogenesis.     

Improved trends in survival and engraftment after single cord blood transplantation for adult acute myeloid leukemia

Unrelated cord blood transplantation (CBT) is an alternative curative option for adult patients with acute myeloid leukemia (AML) who need allogeneic hematopoietic cell transplantation (HCT) but lack an HLA-matched related or unrelated donor. However, large-scale data are lacking on CBT outcomes for unselected adult AML. To investigate the trends of survival and engraftment after CBT over the past 22 years, we retrospectively evaluated the data of patients with AML in Japan according to the time period of CBT (1998–2007 vs 2008–2013 vs 2014–2019). A total of 5504 patients who received single-unit CBT as first allogeneic HCT for AML were included. Overall survival (OS) at 2 years significantly improved over time. The improved OS among patients in ≥ complete remission (CR)3 and active disease at CBT was mainly due to a reduction of relapse-related mortality, whereas among patients in first or second CR at CBT, this was due mainly to a reduction of non-relapse mortality. The trends of neutrophil engraftment also improved over time. This experience demonstrated that the survival and engraftment rate after CBT for this group has improved over the past 22 years.Subject terms: Acute myeloid leukaemia, Cancer immunotherapy     

Case of follicular mucinosis showing brownish yellow and red dots via dermoscopy

We herein describe a 68‐year‐old man with follicular mucinosis. A dermoscopic examination showed multiple, round, brownish yellow dots with a whitish rim in the follicular ostium and red dots in the interfollicular area. This case report is the first to suggest that follicular mucinosis shows these dermoscopic findings.     

Involvement of catalase in the endometrium of patients with endometriosis and adenomyosis

OBJECTIVE: To determine the distribution of catalase in eutopic and ectopic endometria in patients with endometriosis or adenomyosis. DESIGN: Retrospective randomized study. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENT(S): Thirty-three patients with endometriosis, 36 with adenomyosis, and 47 fertile controls (total, 116 women). MAIN OUTCOME MEASURE(S): Semiquantitative immunostaining of endometrial cells obtained by biopsy sampling, followed by calculation of an evaluation nomogram score. RESULT(S): The score of catalase in the glandular epithelium of controls group fluctuated during the menstrual cycle; it was lowest in the early proliferative phase and peaked in the late secretory phase. In patients with endometriosis, catalase scores did not fluctuate during the cycle, and scores were high compared with controls throughout the menstrual cycle. Catalase scores did not vary in patients with adenomyosis, and scores in this group were consistently higher than those in patients with endometriosis throughout the cycle. CONCLUSION(S): Abnormal expression of catalase in the eutopic and ectopic endometrium strongly suggests pathologic involvement of free radicals in endometriosis and adenomyosis.     

Endoloop ligation technique for prolapsed pedunculated submucous uterine myoma: utility and reliability

Purpose

We use a non-surgical endoloop snare technique to remove prolapsed pedunculated submucous uterine myomas under the concept that ligating the pedicle causes tumor necrosis and natural elimination of the tumor. We evaluated our method on the basis of clinical outcomes.

Methods

For pertinent clinical data, we reviewed the hospital records of 11 patients treated by our new method between July 2009 and 2010 and followed up for 22–31 months.

Results

Patients’ mean age was 40.9 years, and the mean hemoglobin level was 10.6 g/dl. None required urgent hospitalization, blood transfusion, or laparotomy. The tumors were eliminated naturally or removed by cutting necrotic pedicle within 4–11 days. One patient required a second endoloop application. Another one patient required follow-up surgery for a second submucous myoma, adenomyosis, and persistent hypermenorrhea.

Conclusions

Endoloop ligation is feasible for eliminating prolapsed pedunculated submucous myoma. It is simple and safe and can be performed in the outpatient setting.     

Localization of the pathogenic gene of Behçet's disease by microsatellite analysis of three different populations

PURPOSE: Beh?et's disease (BD) is known to be associated with HLA-B51 in many ethnic groups. However, the pathogenic gene responsible for BD is as yet unknown. To localize the critical region of the pathogenic gene, microsatellite markers distributed around the HLA-B gene were investigated. The BD patients studied were of three ethnic origins: Japanese, Greek, or Italian. METHODS: The total group consisted of 172 BD patients, of whom were 95 Japanese, 55 Greek, and 22 Italian. Eight polymorphic microsatellite markers distributed within 1100 kb of the HLA-B gene were analyzed using PCR and subsequent automated fragment detection by fluorescent-based technology. RESULTS: Among the eight markers, allele 348 of the MIB microsatellite was remarkably common in all three BD populations (Japanese, PC: = 0.000014; Greek, PC: = 0. 00047; Italian, PC: = 0.11). However, HLA-B51 was found to be the marker most strongly associated with BD in each population (Japanese, PC: = 0.000000000017; Greek, PC: = 0.00000032; Italian, PC: = 0. 0074). In genotypic differentiation between the patients and controls, only HLA-B51 was found to be significantly associated with BD in all three populations. Stratification analysis suggested that significant associations of BD with MICA and other microsatellites resulted from a linkage disequilibrium with HLA-B51. CONCLUSIONS: These results suggest that the pathogenic gene of BD is HLA-B51 itself and not other genes located in the vicinity of HLA-B.     

Ureteral catheter placement for prevention of ureteral injury during laparoscopic hysterectomy

AIM: Ureteral injury is among the most devastating complications of gynecologic surgery. Estimated incidence of ureteral injury during laparoscopic hysterectomy is 2.6-35 times (0.2-6.0%) that in abdominal hysterectomy. We investigated preoperative ureteral catheter (UC) placement as a way to prevent ureteral injury in laparoscopic hysterectomy. METHODS: Clinical records of 94 women who underwent laparoscopic hysterectomy between February 2006 and January 2007 in Yazaki Hospital, Kanagawa, Japan, were reviewed retrospectively. Thirty-four patients between February and June 2006 underwent the surgery without ureteral catheterization and 60 patients between July 2006 and January 2007 underwent surgery with ureteral catheterization. Clinical outcomes were statistically compared between the two groups. RESULTS: The average time required for catheter insertion was 9.35 min. The ureter in which the catheter was placed was visualized clearly. In one patient, whose left ureter was deviated by a massive myoma, catheter insertion was not possible. No complications arose from catheter placement except for minor complaints including low back pain, urinary discomfort, and transient hematuria. While one injury occurred in a patient without ureteral catheterization (1/34), no ureteral injury occurred in any patient with ureteral catheterization (0/60). Operative time, total blood loss, and hospital stay were not significantly different between the two groups. CONCLUSIONS: UC placement is simple, helping to prevent ureteral injury during laparoscopic hysterectomy and enhancing safety of this procedure.     

Tribal Odisha Eye Disease Study # 11 - Particularly vulnerable tribal group eye health program. Program protocol and validation

Purpose:To describe and validate the eye health program protocol of Dongria tribal community, a particularly vulnerable tribal group (PVTG) in Rayagada district, Odisha, India.Methods:The program would consist of three segments. At people’s residences, trained community health workers (CHWs) will measure the vision and collect demographic data. In addition, vision technicians (VTs) will refract using a hand-held device and prescribe spectacles to people who improve to >6/12, N8. Others would be referred to the vision center (VC). At VC, the VT will perform a slit-lamp examination and re-refract. They would refer people with vision ≤6/12 to the secondary center (SC). At SC, referred people will receive a comprehensive eye examination and treatment. The ophthalmologist will assign the cause of blindness and visual impairment for people with visual acuity <6/12. The entire process was rehearsed in a pilot study.Results:The target population is approximately 10,000 people residing in 101 hutments on the hills of Rayagada district. The pilot study included 126 people. The mean age was 44 ± 18 years; 70% of the people were illiterate, and in this cohort, 97.6% (n = 123) had never worn spectacles. In the pilot study, 41% of the people had cataract, and 12% had pterygium. The agreements between optometrist versus VTs and between optometrist versus CHWs were good (k = ~0.8–1.0) in all eye conditions except for strabismus (k = ~0.56–0.65)Conclusion:The pilot study confirms the program modality, and when completed, it would help in the planning and resource allocation of Odisha PVTG eye care.