Health‐related quality of life after kidney transplantation: who benefits the most?

The influence of dialysis modalities on HRQoL before and after kidney transplantation (KT) and the role of adherence to medication on HRQoL have not been fully studied. Sixty four dialysis patients who answered the 15D HRQoL survey during dialysis were surveyed again after KT. Adherence and employment were also investigated. The mean 15D score was highest among home hemodialysis patients (HHD) and lowest among in‐center hemodialysis patients (icHD). After KT, the mean 15D score improved significantly in 78.6% of peritoneal dialysis patients (PD), 47.6% of HHD, and 53.8% of icHD. Then, mean 15D score remained unchanged in 28.6% of HHD and in 23.1% of icHD patients. A deterioration in the 15D score occurred in 14.3% of PD, 23.1% of icHD, and 23.8% of HHD patients, and this was influenced by the number of pills (P = 0.04). Adherence to medication was the lowest in PD, timing being the most challenging task showing a connection to higher creatinine concentration (never forgot 1.41 mg/dl vs. forgot 2.08 mg/dl P = 0.05). Employed patients had a higher mean 15D score. The icHD and PD patients benefited the most from KT and HHD the least. Low pill burden and employment were linked to a better HRQoL.     

Evaluation of a semi-automated Seegene PCR workflow with MTB,MDR, and NTM detection for rapid screening of tuberculosis in a low-prevalence setting

In areas of low tuberculosis (TB) prevalence, laboratory diagnosis of TB may essentially cover non-tuberculous mycobacteria (NTM) in addition to Mycobacterium tuberculosis (MTB). In this study, a semi-automated PCR workflow distinguishing MTB and NTM (Anyplex™ MTB/NTMe, Seegene) and subsequently detecting MTB isoniazid/rifampicin resistance (Allplex™ MTB/MDRe, Seegene) was evaluated for replacing smear microscopy of acid-fast bacilli as the rapid screening method for TB. With 279 clinical samples, 47 cultures positive for MTB and 76 for NTM, the Anyplex™ MTB/NTMe assay and smear microscopy showed equal sensitivities (49.6% vs 50.8%, respectively) but Anyplex™ MTB/NTMe was more sensitive for MTB (63.8% vs 25.6%) than for NTM (40.8% vs 64.5%). Allplex™ MTB/MDRe showed a slightly higher sensitivity of 68.1% for MTB (32/47 positive, n = 222). Antibiotic resistance profiles were correctly identified for all MTB isolates (one MDR isolate). Specificity was 100% for both assays. Anyplex™ MTB/NTMe detected all the 18 NTM species present in the study. The analytical performance of the evaluated high-throughput workflow was relatively weak compared to culture but potentially adequate as a rapid screening method analogous to smear microscopy with additional differentiation between TB, MDR-TB, and NTM.     

Effects of sea buckthorn oil intake on vaginal atrophy in postmenopausal women: A randomized,double-blind,placebo-controlled study

Background

Vaginal atrophy, the thinning and drying of vaginal mucosa, is associated with menopause. The standard estrogen treatment is not suitable for all women.

Objective

To investigate the effects of oral sea buckthorn (SB) oil supplementation on vaginal atrophy.

Method

A total of 116 postmenopausal women experiencing symptoms of vaginal dryness, itching or burning were randomized to this placebo-controlled, double-blind study. Ninety-eight participants completed the intervention of three months, during which they consumed 3 g of SB or placebo oil daily. At the beginning and end, factors of vaginal health were scored by a gynecologist, vaginal pH and moisture were measured and vaginal health index was calculated. Symptoms of atrophy and menopause were evaluated at study visits and by daily logbooks. Serum samples were collected for the analysis of circulating lipids, liver enzymes and C-reactive protein.

Results

Compared to placebo, there was a significantly better rate of improvement in the integrity of vaginal epithelium in the SB group when both compliant and noncompliant participants were included (odds ratio (OR) = 3.1, 95% CI 1.11–8.95). A beneficial trend was observed when only the compliant participants were included (OR = 2.9; 95% CI 0.99–8.35). There was a tendency (P = 0.08) toward better improvement of vaginal health index from baseline to the end in the SB group [(0.8 (SD 2.8)] compared to placebo [−0.1 (SD 2.0)].

Conclusions

SB oil showed beneficial effects on vaginal health, indicating it is a potential alternative for mucosal integrity for those women not able to use estrogen treatment for vaginal atrophy.     

Association between bone mineral density and lumbar disc degeneration

Objectives

Higher vertebral bone mineral density (BMD) has been found to be related with lumbar disc degeneration (LDD), while relationship between femoral neck BMD and LDD remains controversial. The aim of our research was to study the relationship between LDD and BMD of the lumbar spine and femoral neck.

Study design

The study population consisted of 168 postmenopausal women (aged 63.3–75.0 years, mean 68.6 years) from the prospective OSTPRE and OSTPRE-FPS study cohorts. The severity of LDD was graded from T2-weighted MRI images using the five-grade Pfirrmann classification. Four vertebral levels (L1-L4) were studied (total 672 discs). The association between lumbar BMD and Z-score and the severity of LDD was studied separately for each vertebral level with AN(C)OVA analysis, using potential confounders as covariates.

Results

Higher lumbar BMD and Z-score were associated with more severe LDD at all studied levels (L1-L4): between L4-L5 disc and L4 BMD (p = 0.044) and L4 Z-score (p = 0.052), between L2-L3 disc and L3 BMD (p = 0.001) and at all other levels (p < 0.001). The mean degeneration grade of the studied discs was associated with the mean L1-L4 BMD and Z-score (p < 0.001). Statistical significance of any result did not alter after controlling for confounding factors. There was no significant association between femoral neck BMD and LDD.

Conclusions

Higher lumbar BMD/Z-score were associated with more severe LDD. There was no significant association between femoral neck BMD and disc degeneration. Femoral neck BMD may be a more reliable measurement for diagnosing osteoporosis in postmenopausal women with degenerative changes in the lumbar spine.     

Long-term outcomes after ascending aortic replacement and aortic root replacement for type A aortic dissection

 Open in a separate windowOBJECTIVESWe investigated whether the selective use of supracoronary ascending aorta replacement achieves late outcomes comparable to those of aortic root replacement for acute Stanford type A aortic dissection (TAAD).METHODSPatients who underwent surgery for acute type A aortic dissection from 2005 to 2018 at the Helsinki University Hospital, Finland, were included in this analysis. Late mortality was evaluated with the Kaplan–Meier method and proximal aortic reoperation, i.e. operation on the aortic root or aortic valve, with the competing risk method.RESULTSOut of 309 patients, 216 underwent supracoronary ascending aortic replacement and 93 had aortic root replacement. At 10 years, mortality was 33.8% after aortic root replacement and 35.2% after ascending aortic replacement (P = 0.806, adjusted hazard ratio 1.25, 95% confidence interval, 0.77–2.02), and the cumulative incidence of proximal aortic reoperation was 6.0% in the aortic root replacement group and 6.2% in the ascending aortic replacement group (P = 0.65; adjusted subdistributional hazard ratio 0.53, 95% confidence interval 0.15–1.89). Among 71 propensity score matched pairs, 10-year survival was 34.4% after aortic root replacement and 36.2% after ascending aortic replacement surgery (P = 0.70). Cumulative incidence of proximal aortic reoperation was 7.0% after aortic root replacement and 13.0% after ascending aortic replacement surgery (P = 0.22). Among 102 patients with complete imaging data [mean follow-up, 4.7 (3.2) years], the estimated growth rate of the aortic root diameter was 0.22 mm/year, that of its area 7.19 mm²/year and that of its perimeter 0.43 mm/year.CONCLUSIONSWhen stringent selection criteria were used to determine the extent of proximal aortic reconstruction, aortic root replacement and ascending aortic replacement for type A aortic dissection achieved comparable clinical outcomes.     

Noncoding RET variants explain the strong association with Hirschsprung disease in patients without rare coding sequence variant

The pathogenesis of Hirschsprung disease is complex. Although the RET proto-oncogene is the most frequently affected gene in Hirschsprung disease, rare coding sequence variants explain only a small part of Hirschsprung disease cases. We aimed to assess the genetic background of Hirschsprung disease using a genome-wide association analysis combined with sequencing all RET exons in samples from 105 Hirschsprung disease cases (30 familial and 75 sporadic) and 386 controls.As expected, variants in or near RET showed the strongest overall association with Hirschsprung disease and the most statistically significant association was observed when using a recessive genetic model (rs2435357, NC_000010.10:g.43582056T?>?C; genotype TT, OR?=?17.31, P?=?1.462?×?10^?21). Previously published associations in variants in SEMA (rs11766001, NC_000007.13:g.84145202A?>?C; allele C, OR?=?2.268, P?=?0.009533) and NRG1 (rs4541858, NC_000008.10:g.32410309A?>?G; allele G, OR?=?1.567, P?=?0.015; rs7835688, NC_000008.10:g.32411499G?>?C; allele C, OR?=?1.567, P?=?0.015) were also replicated in the genome-wide association analysis. Sequencing revealed a total of 12 exonic RET rare variants. Of these, eight amino acid changing rare variants and two frameshift variants caused or possibly caused Hirschsprung disease.Only a minority of the Hirschsprung disease cases (9/30 familial; 7/75 sporadic) carried one of the rare variants. Excluding the rare variant carriers from the genome-wide association analysis did not appreciably change the association of rs2435357 with Hirschsprung disease. We estimate that approximately two thirds of the sporadic cases may be statistically attributed to the recessive action of the common non-coding RET variants. Thus, even though most cases do not carry rare RET variants, combinations of rare variants and the common non-coding RET variant cause the majority of the cases in our population.     

Double-guidewire-assisted cannulation in ERCP: novel applications

Even in experienced hands, a common problem at endoscopic retrograde cholangiopancreatography (ERCP) is difficulty in reaching a selective cannulation of the common bile duct or pancreatic duct. The success rate of biliary cannulation has improved markedly in many centers after the adoption of double-guidewire-assisted cannulation technique in cases in which the guidewire repeatedly passes into the pancreatic duct although the common bile duct is intended. Here, we describe 2 novel applications of the double-guidewire technique for difficult cannulation in ERCP. In particular, we emphasize that in addition to difficult biliary cannulation, double-guidewire technique may prove useful in difficult pancreatic cannulation. The double-guidewire technique is feasible also in cases in which the guidewire repeatedly passes into the cystic duct instead of the intended common hepatic duct and intrahepatic radicals. ERCP endoscopists should be aware of all modifications of double-guidewire technique to further increase the success rates of selective cannulations in ERCP.     

Characterization of the in vitro metabolic profile of amlodipine in rat using liquid chromatography-mass spectrometry.

In the present study, the metabolic profile of amlodipine, a well-known calcium channel blocker, was investigated employing liquid chromatography-mass spectrometric (LC/MS) techniques. Two different types of mass spectrometers - a triple-quadrupole (QqQ) and a quadrupole time-of-flight (Q-TOF) mass spectrometer - were utilized to acquire structural information on amlodipine metabolites. The metabolites were produced by incubation of amlodipine with primary cultures of rat hepatocytes. Incubations from rat hepatocytes were analyzed with LC-MS/MS, and 21 phase I and phase II metabolites were detected. Their product ion spectra were acquired and interpreted, and structures were proposed. Accurate mass measurement using LC-Q-TOF was used to determine the elemental composition of metabolites and thus to confirm the proposed structures of these metabolites. Mainly phase I metabolic changes were observed including dehydrogenation of the dihydropyridine core, as well as reactions of side chains, such as hydrolysis of ester bonds, hydroxylation, N-acetylation, oxidative deamination, and their combinations. The only phase II metabolite detected was the glucuronide of a dehydrogenated, deaminated metabolite of amlodipine. We propose several in vitro metabolic pathways of amlodipine in rat, based on our analysis of the metabolites detected and characterized.     

Expression and function of α2,3-sialyl- and α,3/l,4-fucosyltransferases in colon adenocarcinoma cell lines: Role in synthesis of E-selectin counter-receptors

We show here that colon-carcinoma cell lines adhere to E-selectin via sialyl Lewis x and sialyl Lewis a (sLex and sLea) oligosaccharides and that this adhesion can be enhanced by TNF stimulation. To study in greater detail this endothelial binding, we analysed the mRNA expression and function of the enzymes participating in the generation of sLex and sLea on cancer cells. These oligosaccharides are synthesized by sequential action of α2,3 sialyl (α2,3-ST) and α1,3/1,4 fucosyltransferases (α1,3/1,4-FT) on existing (poly)N-acetyllactosamine chains. We report here that mRNAs of 2 recently cloned α2,3-STs and 4 α1,3/l,4-FTs are expressed in adenocarcinoma cells. In functional assays α2,3-ST and α1,3- or 1,4-FT activities were observed in adenocarcinoma cell lysates to exogenous N-acetyllactosamine and lacto-N-biose acceptors and to their sialytated derivatives, leading to the synthesis of the sialyl-N-acetyllactosamine and sLex or the sialyllacto-N-biose and sLea, respectively. Furthermore, the inflammatory cytokine TNF could enhance some α2,3-ST and α1,3/1,4-FT activities capable of generating E-selectin counter-receptors. Taken together, these data show that COLO 205 and HT-29 adenocarcinoma cell lines adhere to E-selectin in a TNF-inducible manner via their cell-surface sLex and sLea. These cells also express mRNA as well as inducible enzyme activities of several α2,3-STs and α,3/1,4-FTs responsible for the final steps in the synthesis of sLex and sLea. We show here that the TNF-induced adhesion to E-selectin might be due to the increased synthesis of sLex and sLea in colon-carcinoma cells.     

p53 protein accumulation and the presence of human papillomavirus dna in bronchiolo-alveolar carcinoma correlate with poor prognosis

Accumulation of the tumour suppressor gene p53 product due to a gene mutation is frequently seen in human carcinomas, including lung carcinoma. Another indirect mechanism involving p53 in malignant growth relates to the E6 protein of the human papillomavirus (HPV), which is able to bind and degrade wild-type p53 protein, thus eliminating its tumour suppressor activities. Bronchiolo-alveolar carcinoma (BAC) is a rare type of lung carcinoma. The aim of our study was to examine the occurrence of p53 accumulation and the presence of HPV DNA in BAC. Sections of 22 BACs were immunohistochemically stained using a p53 antibody, CM-1. The presence of HPV DNA in BACs was verified by in situ hybridisation for HPV types 6, 11, 16, 18, 31 and 33 and confirmed by PCR. Thirty-six percent of the tumours showed abnormal p53 nuclear accumulation, and HPV DNA, revealed by in situ hybridisation, was found in 36%. Unexpectedly, only 13% of the type 1 BACs were positive for p53, whereas 45% of the type 2 BACs were positive. During a follow-up of 12-176 months, only 10% of the patients with BACs negative for both p53 and HPV died of the disease, compared with 42% of the patients with either p53 or HPV positivity. No inverse relationship between abnormal p53 protein accumulation and the presence of HPV DNA was found. © 1995 Wiley-Liss, Inc.