Relationship between severity and symptoms of reflux oesophagitis in elderly patients in Japan

Since information concerning reflux oesophagitis in the elderly is limited, particularly in Japan, the severity and symptomatic profiles of reflux oesophagitis in elderly patients were investigated. One hundred and nineteen patients with reflux oesophagitis found among 2278 endoscopy cases between 1993 and 1996 were investigated in this study. The patients were divided into two groups, elderly and non-elderly. The severity of reflux oesophagitis was estimated by the Los Angeles classification. The presence or absence of typical symptoms (heartburn and regurgitation) was determined by interview. Reflux oesophagitis was not only more frequently found in the elderly group, but was more severe than in the non-elderly. Although the degree of manifestation of typical symptoms was similar between the elderly and the non-elderly with high-grade oesophagitis, the elderly patients with mild reflux oesophagitis were less symptomatic than the non-elderly. Mild reflux oesophagitis in the elderly may be missed due to its rarity of typical reflux symptoms and a substantial number of elderly persons might have subclinical reflux oesophagitis.     

An interplay of alleviating mutations in the clinical phenotype of β‐thalassaemia intermedia

Prediction of a β‐thalassaemia major phenotype from the β‐genotype is generally relatively straightforward. However, despite the ability to accurately define the β‐thalassaemia mutations, prediction of a β‐thalassaemia intermedia phenotype from the genotype sometimes remains problematic and this has important implications in genetic counselling and prenatal diagnosis. We report a 11‐year‐old Indian male child with a thalassaemia intermedia phenotype. β‐Globin gene analysis of the family showed that he was a compound heterozygote with the ?88 (C→T) β⁺‐mutation and the IVS1 nt 130 (G→C) β⁰‐mutation. Both these mutations are rare among Indians. The propositus was also found to be heterozygous for the XmnI polymorphism and had a normal α‐genotype. In this family interplay of two alleviating mutations (a milder promoter mutation along with a gene for raised HbF) might have synergistically compensated for lack of globin chains in the patient. Hence, the nature of the β‐genotype as well as the knowledge of the presence or absence of alleviating factors will help the clinician to decide whether early commencement of a regular transfusion regime is necessary.     

Effects of Nonanal,trans-2-Nonenal and 4-Hydroxy-2,3-trans-nonenal on Cyclooxygenase and 12-Lipoxygenase Metabolism of Arachidonic Acid in Rabbit Platelets

The effects of nonanal, trans-2-nonenal and 4-hydroxy-2,3-trans-nonenal on the formation of thromboxane B₂ (TXB₂), 12-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 12-hydroxy-5,8,10,14-eicosatetraenoic acid (12-HETE) from exogenous arachidonic acid in washed rabbit platelets were examined. Nonanal and trans-2-nonenal at concentrations ranging from 0.25 to 2 μm inhibited TXB₂, HHT and 12-HETE formation, reducing the amounts of these three arachidonic acid metabolites by 50% at nonanal and trans-2-nonenal concentrations of approximately 0.25 μm. The inhibition of TXB₂, HHT and 12-HETE formation induced by 4-hydroxy-2,3-trans-nonenal (50% inhibition by 4-hydroxy-2,3-trans-nonenal at a concentration of approximately 100 μm) was 400 times weaker than that induced by nonanal and trans-2-nonenal. These results suggest that nonanal and trans-2-nonenal can be modulators of platelet arachidonic acid metabolism by affecting the activity of cyclooxygenase and 12-lipoxygenase.     

Current Density Distribution by Ring and Diagonally Arranged Half‐Ring Electrodes in Bipolar and Overlapping Biphasic Impulse Stimulation

Background: We have studied the acute and long‐term efficacy of overlapping biphasic impulse (OLBI) stimulation for atrial pacing with VDD pacemakers and demonstrated the feasibility of DDD pacing in OLBI with diagonally arranged half‐ring (Half‐Ring) electrodes. We made two three‐dimensional computational analysis models to verify our clinical studies. Methods and Results: Model I was composed of a heart, a pacemaker, and a human body. Model II was a cube with dimensions of 20 by 20 by 20 mm quarried from Model I for the detailed study of current density distributions. Laplace's equation was solved using the finite element method and the current density J was calculated. For Model I, the distal and proximal voltages were ?10 V, 0 V in bipolar and ?5 V, +5 V in OLBI, using Ring electrodes. In Model II, the actual measurements of electrode impedances obtained from the clinical study (1,180 Ω for Ring and 630 Ω for Half‐Ring) were added to the analysis conditions. Model I showed that OLBI produced more concentrated current density distributions than those by bipolar. According to Model II, at the atrial myocardium position current density produced by Half‐Ring was larger than that by Ring electrodes, 70 μA/mm² versus 30 μA/mm² in OLBI configuration. It also indicated that even if electrode impedances were equal between Half‐Ring and Ring electrodes, the maximum current density produced by Half‐Ring would be greater than that by Ring electrodes. Conclusions: It was considered that OLBI configuration with Half‐Ring electrodes provides more effective current density distributions. (PACE 2010; 33:1063–1073)     

Effects of Isoquinolinesulphonamide Compounds on Multidrug-resistant P388 Cells

Abstract— The effects of eight isoquinolinesulphonamide compounds on resistance to vinblastine in adriamycin-resistant mouse leukaemia cells (P388/ADR) which overexpress the relative molecular weight (M_r) 140 kDa P-glycoprotein in the plasma membrane were investigated. N-[2-(Methylamino)ethyl]-5-isoquinolinesulphonamide (H-8) and N-(2-aminoethyl)-5-isoquinolinesulphonamide (H-9) did not reverse vinblastine resistance. N-[2-[N-[3-(4-Chlorophenyl)-2-propenyl]amino]ethyl]-5-isoquinolinesulphonamide (H-86) and N-[2-[N-[3-(4-chlorophenyl)-1-methyl-2-propenyl]amino]ethyl]-5-isoquinolinesulphonamide (H-87) caused accumulation of intracellular vinblastine and inhibition of vinblastine efflux from the cells and reversed the resistance. Addition of an aminoethyl group to the nitrogen atom of the sulphonamide group (W-66) or a formyl group at the terminal amino group (H-85) of H-86 reduced those activities. Conversion of the chlorophenyl group of H-87 to pyridinyl (H-31) or furanyl (H-34) markedly decreased activities against the drug resistance. The activity against vinblastine accumulation closely correlated with the apparent partition coefficient of compounds. These compounds dose-dependently inhibited photoaffinity labelling of a photosensitive analogue of vinblastine, N-(p-azido-(3-[¹²⁵I])salicyl)-N′-β-aminoethylvindesine ([¹²⁵I]NASV), and there was a good correlation between inhibition of [¹²⁵I]NASV-photolabelling and hydrophobicity. Although these isoquinolinesulphonamides inhibited protein kinase A with different magnitudes, this activity did not correlate with the effect on the drug resistance. These results indicate that isoquinolinesulphonamide compounds with a hydrophobic group interact with antitumour drugs on P-glycoprotein and reverse multidrug resistance without involvement of their activity on protein kinase A.     

Incremental Value of Objective Frailty Assessment to Predict Mortality in Elderly Patients Hospitalized for Heart Failure

Background

The impact of frailty on long-term prognosis in patients with heart failure (HF) remains unclear, and there is no simple and objective assessment for it. This study was performed to examine the association between frailty score and clinical outcome in elderly patients hospitalized for HF.

Renal functional measurements in young rats with chronic inhibition of nitric oxide synthase

The purpose of the present study was to examine renal functional changes caused by chronic blockade of nitric oxide (NO) synthesis in young rats. Two types of NO synthase inhibitor were used: N^G-nitro-L-arginine methyl ester (L-NAME) as a non-selective inhibitor and aminoguanidine (AG) as a selective inhibitor of the inducible isoform. Oral administration of L-NAME (20–80 mg/dL of drinking water), not AG (400 mg/dL), for 4 weeks induced systemic hypertension in the treated rats. Both inhibitors caused a significant reduction in urinary excretion of NO₂^?/NO₃^?. Rats treated with L-NAME developed proteinuria and tubular enzymuria (high excretion of N-acetyl-β-D-glucosaminidase) in a dose-dependent fashion, with normal serum levels of creatinine, albumin and cholesterol. Chronic AG administration did not alter the urinary levels of protein and N-acetyl-β-D-glucosaminidase or serum laboratory values. Overall, these observations highlight the importance of the continuous generation of NO by the constitutive isoform in the control of vascular tone and the maintenance of renal glomerular and tubular function. Oral administration of L-NAME may serve as a model of chronic NO-deficient hypertension with renal injury in young rats.     

Anatomical and histological studies of so-called Müllerian duct cyst

BACKGROUND: We examined so-called Müllerian duct cysts both histologically and immunohistochemically with anatomical observation to investigate the etiology of the 'Müllerian duct cyst'. METHODS: Five cystic lesions located in the prostatic midline were obtained from surgical specimens. A communication between the cystic lesion and the urethra via the utricular orifice was looked for and the specimens were subjected to histological and immunohistochemical testing. RESULTS: A communication between the cyst and the urethra was confirmed in four cases, but not in one case. Histological and immunohistochemical examinations of the epithelium lining indicated that its characteristics were identical to those of the prostatic utricle in all cases. CONCLUSIONS: The so-called Müllerian duct cyst exhibits features comparable to those previously described in the prostatic utricle. There is no evidence that these cystic lesions originate from the Müllerian duct remnant, at least in the epithelial lining. We suggest that they should be termed a prostatic utricular cyst or cystic dilation of the prostatic utricle, depending on whether an outlet to the urethra is absent or present, respectively.     

The possibility of ''de novo'' cancer in the prostate

BACKGROUND: To investigate the possibility of 'de novo' prostate cancer by analyzing the relationship between high grade prostatic intraepithelial neoplasia (HGPIN) and latent prostate cancer. MATERIALS AND METHODS: Latent prostate cancers found at autopsy were examined and 55 cancer foci with a poorly (Gleason grade 4 and 5) or moderately (Gleason grade 3) differentiated component were selected. The 55 foci were separated into two groups: (i) foci with either a poorly or moderately differentiated component only (single differentiation group, SDG); and (ii) mixed foci with two or more types of differentiation components (mixed differentiation group, MDG). High grade intraepithelial neoplasia was defined as positive if it was observed within 2 mm from the edge of the cancer focus and the relationship between HGPIN and the two groups was investigated. RESULTS: The MDG had 39 cancer foci (71.0%) and there were 16 in the SDG (29.0%). There were 31 foci that were small-volume cancers (<0.2 mL). In the MDG, 13 small-volume cancer foci were HGPIN positive, but in the SDG, none of the small-volume cancers were HGPIN positive. CONCLUSIONS: Small-volume cancer foci without HGPIN in the SDG may be candidates for de novo prostate cancers.