Brain Tumor Segmentation Using Convolutional Neural Networks in MRI Images.

In medical image processing, Brain tumor segmentation plays an important role. Early detection of these tumors is highly required to give Treatment of patients. The patient's life chances are improved by the early detection of it. The process of diagnosing the brain tumoursby the physicians is normally carried out using a manual way of segmentation. It is time consuming and a difficult one. To solve these problems, Enhanced Convolutional Neural Networks (ECNN) is proposed with loss function optimization by BAT algorithm for automatic segmentation method. The primary aim is to present optimization based MRIs image segmentation. Small kernels allow the design in a deep architecture. It has a positive consequence with respect to overfitting provided the lesser weights are assigned to the network. Skull stripping and image enhancement algorithms are used for pre-processing. The experimental result shows the better performance while comparing with the existing methods. The compared parameters are precision, recall and accuracy. In future, different selecting schemes can be adopted to improve the accuracy.

Availability and feasibility of structured, routine collection of comorbidity data in a colorectal cancer multi-disciplinary team (MDT) setting.

PURPOSE: Availability of comorbidity assessment at multi-disciplinary team (MDT) discussions is cornerstone in making the MDT process more robust and decisive in optimising treatment and improving quality of survivorship. Comorbidity assessments using tools, such as the ACE-27 questionnaire would aid in optimising the decision-making process at MDTs so that treatment decisions can be made without delay. This study determined the availability of comorbidity data in a CRC MDT and the feasibility of routine comorbidity data collection using the validated ACE-27 questionnaire. Secondary aims determined the optimal time and method of collecting comorbidity data. METHODS: A retrospective mapping exercise (phase I; 6-months) examined the availability of comorbidity data within the MDT. Phase II prospectively collected comorbidity data using ACE-27 for a 3-month period following a short pilot. RESULTS: In phase I, 73/135 (54%) patients had comorbidity data readily available informing the MDT discussion; 62 patients lacked this information. After a review of the patient records, it was clear that 41 of these 62 also had comorbidities and 21 out of the 135 had ≥ 2 major system disorders. Common referral sources to the MDT were surgical outpatient clinics (42%) and the endoscopy unit (13%). The average lead-time from referral to MDT discussion was 14 days. In phase II, an ACE-27 questionnaire was prospectively administered in 50 patients, mean age 54 years (range 20-84). Male: female ratio 26:24. Average time to administer ACE-27 was 4.8 min (range 1-15). CONCLUSIONS: The phase I study confirmed the widely acknowledged view of poor comorbidity data availability within a CRC MDT. Phase II demonstrated the feasibility of routinely collecting comorbidity data using ACE-27.

A survey to determine usual care after cancer treatment within the United Kingdom national health service.

BACKGROUND: Approximately one third of cancer survivors in the United Kingdom face ongoing and debilitating psychological and physical symptoms related to poor quality of life. Very little is known about current post-cancer treatment services. METHODS: Oncology healthcare professionals (HCPs) were invited to take part in a survey, which gathered both quantitative and free text data about the content and delivery of cancer aftercare and patient needs. Analysis involved descriptive statistics and content analysis. RESULTS: There were 163 complete responses from 278 survey participants; 70% of NHS acute trusts provided data. HCPs views on patient post-cancer treatment needs were most frequently: fear of recurrence (95%), fatigue (94%), changes in physical capabilities (89%), anxiety (89%) and depression (88%). A median number of 2 aftercare sessions were provided (interquartile range: 1,4) lasting between 30 and 60 min. Usually these were provided face-to-face and intermittently by a HCP. However, sessions did not necessarily address the issues HCPs asserted as important. Themes from free-text responses highlighted inconsistencies in care, uncertain funding for services and omission of some evidence based approaches. CONCLUSION: Provision of post-cancer treatment follow-up care is neither universal nor consistent in the NHS, nor does it address needs HCPs identified as most important.

Intestinal tuberculosis: a diagnostic challenge.

OBJECTIVE: To describe characteristics, presentation, time to diagnosis and diagnostic findings of patients with intestinal tuberculosis (ITB) in a low-burden country. METHOD: Retrospective study of 61 consecutive ITB patients diagnosed between 2008 and 2014 at a large East London hospital. RESULTS: Forty of sixty-one patients were male. Mean age was 34.6 years. 93% of patients were born abroad, mostly from TB-endemic areas (Indian subcontinent: 88%, Africa: 9%). 25% had concomitant pulmonary TB. Median time from symptom onset to ITB diagnosis was 13 weeks (IQR 3-26 weeks). Ten patients were initially treated for IBD, although patients had ITB. The main sites of ITB involvement were the ileocaecum (44%) or small bowel (34%). Five patients had isolated perianal disease. Colonoscopy confirmed a diagnosis of ITB in 77% of those performed. 42 of 61 patients had a diagnosis of ITB confirmed on positive histology and/or microbiology. CONCLUSION: Diagnosis of ITB is often delayed, which may result in significant morbidity. ITB should be excluded in patients with abdominal complaints who come from TB-endemic areas to establish prompt diagnosis and treatment. Diagnosis is challenging but aided by axial imaging, colonoscopy and tissue biopsy for TB culture and histology.

Comparison of Asymmetric Dimethylarginine Levels Between Stages Three, Four, and Five Non-dialysis of Chronic Kidney Disease.

AIM: to determine the differences of ADMA level between stages 3, 4, and 5 non-dialysis of chronic kidney disease (CKD) patients at Outpatient Nephrology Clinic, Dr. Soetomo Hospital. METHODS: a cross-sectional study was conducted on stage 3, 4, and 5 non-dialysis CKD patients at Outpatient Nephrology Clinic, Dr. Soetomo Hospital, Surabaya from January to February 2015. Stages of CKD were determined based on GFR estimation according to 4-variable MDRD formula. Statistical analysis of differences in the levels of ADMA in three subject groups use one-way ANOVA test. RESULTS: seventy-five patients were included in the study. Each group consisted of 25 patients stage 3, 4, and, 5 non-dialysis patients. Mean age of stage 3, stage 4, and stage 5 non-dialysis CKD patients were respectively 57.12 years, 54.80 years and 53.68 years. The mean levels of ADMA in stage 3, stage 4, and 5 were 0.62 (0.11) IU/mL, 0.72 (0.16) IU/mL, and 0.73 (0.18) IU/mL respectively. Analysis of the differences between the groups showed significant differences in ADMA levels (p=0.04), with the highest difference between stage 3 and stage 5. CONCLUSION: comparison of ADMA levels showed significant differences between CKD stages and the level tends to be higher along with increase severity of CKD stages.

Interventions to improve exercise behaviour in sedentary people living with and beyond cancer: a systematic review.

BACKGROUND: To systematically review the effects of interventions to improve exercise behaviour in sedentary people living with and beyond cancer. METHODS: Only randomised controlled trials (RCTs) that compared an exercise intervention to a usual care comparison in sedentary people with a homogeneous primary cancer diagnosis, over the age of 18 years were eligible. The following electronic databases were searched: Cochrane Central Register of Controlled Trials MEDLINE; EMBASE; AMED; CINAHL; PsycINFO; SportDiscus; PEDro from inception to August 2012. RESULTS: Fourteen trials were included in this review, involving a total of 648 participants. Just six trials incorporated prescriptions that would meet current recommendations for aerobic exercise. However, none of the trials included in this review reported intervention adherence of 75% or more for a set prescription that would meet current aerobic exercise guidelines. Despite uncertainty around adherence in many of the included trials, the interventions caused improvements in aerobic exercise tolerance at 8-12 weeks (SMD=0.73, 95% CI=0.51-0.95) in intervention participants compared with controls. At 6 months, aerobic exercise tolerance is also improved (SMD=0.70, 95% CI=0.45-0.94), although four of the five trials had a high risk of bias; hence, caution is warranted in its interpretation. CONCLUSION: Expecting the majority of sedentary survivors to achieve the current exercise guidelines is likely to be unrealistic. As with all well-designed exercise programmes, prescriptions should be designed around individual capabilities and frequency, duration and intensity or sets, repetitions, intensity of resistance training should be generated on this basis.

Systematic review of tibial nerve stimulation to treat faecal incontinence.

BACKGROUND: Two forms of tibial nerve stimulation are used to treat faecal incontinence (FI): percutaneous (PTNS) and transcutaneous (TTNS) tibial nerve stimulation. This article critically appraises the literature on both procedures. METHODS: A systematic review was performed adhering to the PRISMA framework. A comprehensive literature search was conducted, with systematic methodological quality assessment and data extraction. Summary measures for individual outcome variables are reported. RESULTS: Twelve articles met eligibility criteria; six related to PTNS, five to TTNS, and one to both procedures. These included ten case series and two randomized clinical trials (RCTs). Case series were evaluated using the National Institute for Health and Care Excellence quality assessment for case series, scoring 3-6 of 8. RCTs were evaluated using the Jadad score, scoring 4 of a possible 5 marks, and the Cochrane Collaboration bias assessment tool. From one RCT and case series reports, the success rate of PTNS, based on the proportion of patients who achieved a reduction in weekly FI episodes of at least 50 per cent, was 63-82 per cent, and that of TTNS was 0-45 per cent. In an RCT of TTNS versus sham, no patient had a reduction in weekly FI episodes of 50 per cent or more, whereas in an RCT of PTNS versus TTNS versus sham, 82 per cent of patients undergoing PTNS, 45 per cent of those having TTNS, and 13 per cent of patients in the sham group had treatment success. CONCLUSION: PTNS and TTNS result in significant improvements in some outcome measures; however, TTNS was not superior to sham stimulation in a large, adequately powered, RCT. As no adequate RCT of PTNS versus sham has been conducted, conclusions cannot be drawn regarding this treatment.

Systematic review of the clinical effectiveness of neuromodulation in the treatment of faecal incontinence.

BACKGROUND: Over the past 18 years neuromodulation therapies have gained support as treatments for faecal incontinence (FI); sacral nerve stimulation (SNS) is the most established of these. A systematic review was performed of current evidence regarding the clinical effectiveness of neuromodulation treatments for FI. METHODS: The review adhered to the PRISMA framework. A comprehensive search of the literature included PubMed, MEDLINE, Embase and Evidence-Based Medicine Reviews. Methodological quality assessment and data extraction were completed in a systematic fashion. RESULTS: For SNS, 321 citations were identified initially, of which 61 studies were eligible for inclusion. Of studies on other neuromodulation techniques, 11 were eligible for review: seven on percutaneous tibial nerve stimulation (PTNS) and four on transcutaneous tibial nerve stimulation (TTNS). On intention-to-treat, the median (range) success rates for SNS were 63 (33-66), 58 (52-81) and 54 (50-58) per cent in the short, medium and long terms respectively. The success rate for PTNS was 59 per cent at the longest reported follow-up of 12 months. SNS, PTNS and TTNS techniques also resulted in improvements in Cleveland Clinic Incontinence Score and quality-of-life measures. Despite significant use of neuromodulation in treatment of FI, there is still no consensus on outcome reporting in terms of measures used, aetiologies assessed, length of follow-up or assessment standards. CONCLUSION: Emerging data for SNS suggest maintenance of its initial therapeutic effect into the long term. The clinical effectiveness of PTNS is comparable to that of SNS at 12 months, although there is no evidence to support its continued effectiveness after this period. PTNS may be a useful treatment before SNS. The clinical effectiveness of TTNS is still uncertain owing to the paucity of available evidence. A consensus to standardize the use of outcome measures is recommended in order that further reports can be compared meaningfully.

The persistent challenge of parastomal herniation: a review of the literature and future developments.

AIM: The aim of this review article was to outline current evidence relating to the treatment and prevention of parastomal herniation with a view to guide surgeons dealing with patients potentially affected by this complication. METHOD: Medline and PubMed databases were searched using the keywords 'parastomal hernia/herniation', 'stoma hernia/herniation' and 'stoma complications'. Evidence was obtained from randomized and non-randomized studies. Case reports and articles not written in English were excluded. Qualitative assessment of all included studies was performed using the Oxford Centre for Evidence-Based Medicine 2011 levels of evidence. RESULTS: The search revealed a total of 228 publications of which 115 fulfilled the selection criteria. Stoma formation through the rectus muscle is complicated by parastomal herniation in up to 50% of cases. There is no conclusive evidence that alternative techniques (e.g. extraperitoneal, lateral rectus abdominis positioned stoma) are superior. Open and laparoscopic parastomal hernia repair have similar recurrence rates up to 50%. The 'Sugarbaker' technique appears to be superior to the 'keyhole' technique when a laparoscopic approach is used. Prophylactic mesh reinforcement of the stoma trephine appears to reduce the herniation rate to approximately 15% and is accompanied by a decrease in symptomatic hernias requiring repair without any difference in stoma-related morbidity. CONCLUSION: Large prospective controlled trials are required to compare surgical techniques of stoma formation in reducing the incidence of parastomal herniation. Despite limited evidence, routine prophylactic mesh reinforcement of the stoma trephine should be offered to all patients undergoing permanent stoma formation.

A rare case of bilateral synchronous renal cancer, characterized by distinct histologies; leiomyosarcoma and clear cell renal cancer.

INTRODUCTION: Renal cancer is a significant global cause of death and clear cell being the most common subtype. Bilateral synchronous renal cancers with different histologies are extremely rare and less reported. Managing bilateral renal cancer is challenging. CLINICAL PRESENTATION: A 51-year-old woman with a history of hypertension and hypothyroidism presented with right loin pain, leading to the discovery of a 7 cm right renal mass and a 2.3 × 2.6 cm mass on the upper pole of the left kidney, associated with reactive right para-aortic lymph nodes. The right kidney mass was identified as leiomyosarcoma with liver metastasis while the left kidney mass was diagnosed as clear cell renal carcinoma. Patient was managed with right side nephrectomy, left side microwave ablation and follow-up chemotherapy. DISCUSSION: Primary leiomyosarcoma of kidney is extremely rare and aggressive, leading to poor outcome. Synchronous bilateral renal cancer pose surgical challenges due to potential loss of renal function. In this case of differing histologies in synchronous bilateral renal masses, a nephron-sparing approach was taken, but despite aggressive treatment, the patient developed metastases in the liver and peritoneum. CONCLUSION: Bilateral synchronous renal cancer, particularly with differing histologies in each kidney, are exceptionally uncommon, making their management challenging. Despite the limited guidance available due to their rarity, addressing these cases aggressively and promptly is crucial, as their prognosis is generally unfavorable, necessitating further research to advance management strategies.

Percutaneous tibial nerve stimulation (PTNS) in females with faecal incontinence: the impact of sphincter morphology and rectal sensation on the clinical outcome.

BACKGROUND: Percutaneous tibial nerve stimulation (PTNS) is an acceptable second line treatment for patients with faecal incontinence (FI) unresponsive to conservative measures. There is however a paucity of data in the literature regarding its efficacy. The aim of this prospective study was to evaluate the efficacy of PTNS in an exclusively female cohort of patients and to identify factors that may predict treatment response. METHOD: A prospective cohort of female patients with FI underwent evaluation of sphincter morphology, anorectal pressures and rectal sensation as part of their physiologic assessment prior to treatment. PTNS was performed according to a specific departmental protocol. The clinical outcomes measured were: (1) Cleveland Clinic incontinence scores, (2) deferment time and (3) weekly incontinence episodes. Outcomes were compared at baseline and following treatment using appropriate statistical tests. Clinical outcomes were correlated with the results of the anorectal physiology testing (i.e. sphincter morphology, rectal sensation). RESULTS: Eighty-eight female patients with a mean age of 58.0 ± 13.6 years were included in the analysis. FI was predominantly a late consequence of obstetric injury. The mean incontinence score improved from 12.2 ± 4.0 at baseline to 9.1 ± 4.6 following treatment (p < 0.0001). Statistically significant improvements were also seen in the median deferment time and median number of weekly incontinence episodes. Sphincter damage and altered rectal sensation did not appear to influence the outcomes. CONCLUSIONS: PTNS is an effective treatment in female patients with FI. Improvements in clinical outcomes were independent of damage to the anal sphincter complex in patients with normal rectal sensation.

Diagnostic yield and economic implications of endoscopic colonic biopsies in patients with chronic diarrhoea.

AIMS: Random colonic biopsies are recommended to exclude microscopic colitis in patients with chronic diarrhoea especially when mucosa is macroscopically normal at endoscopy. This study aimed to assess the clinical outcome and economic impact of such a policy in an unselected group of patients with macroscopically normal mucosa. METHODS: All new patients undergoing colonoscopy for investigation of chronic diarrhoea between April and December 2009 were included. Patients were divided into two groups: macroscopically normal mucosa and macroscopically inflamed mucosa. Endoscopic findings were correlated with histology of random biopsies and haematological parameters. Symptom status and any treatment were established from follow-up. The breakdown and overall cost of random biopsies for each patient with a macroscopically normal mucosa were determined, and cost incurred per diagnosis of microscopic colitis was established. RESULTS: Altogether 137 (90.1%) of 152 patients with chronic diarrhoea had macroscopically normal mucosa at colonoscopy. Overall incidence of microscopic colitis in the study was 1.3% (2/152); both patients belonged to the macroscopically normal mucosa group. At follow-up, both these patients had spontaneous symptom resolution without any specific treatment. The policy of undertaking random biopsies in patients with macroscopically normal mucosa incurred an extra cost of £22,057 to diagnose two cases of microscopic colitis but did not alter medical treatment. CONCLUSIONS: In unselected patients with chronic diarrhoea and macroscopically normal mucosa, random colonic biopsies have a low diagnostic yield and incur a high cost. Continued research for predictive markers to improve patient selection for targeted biopsies is needed to develop a cost-effective investigative algorithm in chronic diarrhoea.

Short-term outcome following percutaneous tibial nerve stimulation for faecal incontinence: a single-centre prospective study.

AIM: Percutaneous tibial nerve stimulation (PTNS) is increasingly being used as a treatment for faecal incontinence (FI). The evidence for its efficacy is limited to a few studies involving small numbers of patients. The aim of the study was to assess the efficacy of PTNS in patients with urge, passive and mixed FI. METHOD: A prospective cohort of 100 patients with FI was studied. Continence scores were determined before treatment and following 12 sessions of PTNS using a validated questionnaire [Cleveland Clinic Florida (CCF)-FI score]. The deferment time and average number of weekly incontinence episodes before and after 12 sessions of treatment were estimated from a bowel dairy kept by the patient. Quality of life was assessed prior to and on completion of 12 sessions of PTNS using a validated questionnaire [Rockwood Faecal Incontinence Quality of Life (QoL)]. RESULTS: One hundred patients (88 women) of median age of 57 years were included. Patients with urge FI (n=25) and mixed FI (n=60) demonstrated a statistically significant improvement in the mean CCF-FI score (11.0 ± 4.1 to 8.3 ± 4.8 and 12.8 ± 3.7 to 9.1 ± 4.4) with an associated improvement in the QoL score. This effect was not observed in patients with purely passive FI (n=15). CONCLUSION: The study demonstrates that PTNS benefits patients with urge and mixed FI, at least in the short term.

Prospective randomised multi-centre trial comparing the clinical efficacy, safety and patient acceptability of circular stapled anopexy with closed diathermy haemorrhoidectomy.

OBJECTIVE: Unlike excisional haemorrhoidectomy, stapled anopexy (SA), which does not involve radical excision, has theoretical advantages, thus offering potential patient benefits. We compared the clinical efficacy, safety and patient acceptability of SA, with closed haemorrhoidectomy (CH). PATIENTS AND METHODS: 182 patients with symptomatic haemorrhoids (grades II, III, IV) were randomly assigned to receive SA or CH and were followed for up to 1 year (6, 12, 24, 48 weeks) after operation. Postoperative pain, symptom control, complications, re-treatment rates, patient satisfaction, and quality of life were compared on an intention-to-treat basis. RESULTS: Postoperative pain in the SA group (n = 91) was significantly lower (p = 0.004, Mann-Whitney U test). At 1 year there were no significant differences in the symptom load, symptom severity or the disease severity between the two groups. Overall complication rates were similar but faecal urgency was reported more frequently following SA (p = 0.093, Fisher's exact test). Despite a similar rate of residual symptoms, prolapse control was better with CH (p = 0.087, Fisher's exact test), and more patients in the SA group required re-treatment for residual prolapse at 1 year (p = 0.037, Fisher's exact test). However, more patients rated SA as an excellent operation at 6 and 12 weeks (p = 0.008 and 0.033, binary logistic regression) and were willing to undergo a repeat procedure if required (p = 0.018, Fisher's exact test). CONCLUSION: Stapled anopexy offers a significantly less painful alternative to excisional haemorrhoidectomy and achieves a higher patient acceptability. Although the overall symptom control and safety are similar in the majority of the patients, the re-treatment rate for recurrent prolapse at 1 year is higher following SA when compared to CH.

Correction: Evidence-Based Guideline on Laparoscopy in Pregnancy: Commissioned by the British Society for Gynaecological Endoscopy (BSGE) Endorsed by the Royal College of Obstetricians & Gynaecologists (RCOG).

[This corrects the article on p. 5 in vol. 11, PMID: 31695854.].

A Multilayer Monte Carlo Model for the Investigation of Optical Path and Penetration Depth at Different Perfusion States of the Colon.

There is a great interest in monitoring the oxygen supply delivered to the colon. Insufficient oxygen delivery may lead to hypoxia, sepsis, multiorgan dysfunction and death. For assessing colonic perfusion, more information and understanding is required relating to the light-interaction within the colonic tissue. A multilayer Monte Carlo model of a healthy human colon has been developed to investigate the light-tissue behavior during different perfusion states within the mucosal layer of the colon. Results from a static multilayer model of optical path and reflectance at two wavelengths, 660 nm and 880 nm, through colon tissue, containing different volume fractions of blood with a fixed oxygen saturation are presented. The effect on the optical path and penetration depth with varying blood volumes within the mucosa for each wavelength has been demonstrated. The simulation indicated both wavelengths of photons penetrated similar depths, entering the muscularis layer.

Evidence-Based Guideline on Laparoscopy in Pregnancy: Commissioned by the British Society for Gynaecological Endoscopy (BSGE) Endorsed by the Royal College of Obstetricians & Gynaecologists (RCOG).

Laparoscopy is widely utilised to diagnose and treat acute and chronic, gynaecological and general surgical conditions. It has only been in recent years that laparoscopy has become an acceptable surgical alternative to open surgery in pregnancy. To date there is little clinical guidance pertaining to laparoscopic surgery in pregnancy. This is why the BSGE commissioned this guideline. MEDLINE, EMBASE, CINAHL and the Cochrane library were searched up to February 2017 and evidence was collated and graded following the NICE-approved process. The conditions included in this guideline are laparoscopic management of acute appendicitis, acute gall bladder disease and symptomatic benign adnexal tumours in pregnancy. The intended audience for this guideline is obstetricians and gynaecologists in secondary and tertiary care, general surgeons and anaesthetists. However, only laparoscopists who have adequate laparoscopic skills and who perform complex laparoscopic surgery regularly should undertake laparoscopy in pregnant women, since much of the evidence stems from specialised centres.

Acute renal failure in a patient with severe malaria and dengue shock syndrome.

Malaria is an infectious disease caused by plasmodium, which lives and breeds in human blood cells, and is transmitted through the bites of Anopheles mosquitoes. Renal impairment, often caused by malaria, is acute renal failure (ARF) due to acute tubular necrosis (ATN). Dengue virus is transmitted from human to human through Aedes aegypti mosquito bites. Dengue hemorrhagic fever (DHF), the most severe stage of infection, is characterized by bleeding and shock tendencies (dengue shock syndrome, DSS). ARF is a less common complication in patients with DHF, with an incidence of less than 10%. Mixed infections of two infectious agents may cause overlapping symptoms and have been reported in Africa and India. We report here a patient with ARF due to mixed infection of severe malaria and DSS. The patient presented with fever and had a history of repeated malaria infection. Physical examination revealed stable vital signs and hepatosplenomegaly. Laboratory data showed hemoconcentration, thrombocytopenia and increased serum aminotransferase. Chest X-ray showed pleural effusion. A malarial antigen and thick smear examination showed the trophozoite stage of P. falciparum. On Day 3, blood pressure dropped to 80/60 mmHg, pulse was 120 beats/minute, weak, and body temperature 36.8 C, with icterus. Other tests revealed an increase of serum urea nitrogen and creatinine levels, and serologically anti-dengue IgG antibody (+) and anti-dengue IgM antibody (-). Based on these findings, we diagnosed the patient as having both malaria and DDS. We treated the patient with the parenteral anti-malarial agent, artemisinin. Supportive treatment and treatment of complications were also performed simultaneously for DSS. The patient experienced an oliguria episode but responded well to a diuretic. The patient was discharged after clinical and laboratory examinations showed positive progress.

Intravenous N-acetylcysteine during hemodialysis reduces asymmetric dimethylarginine level in end-stage renal disease patients.

AIM: Cardiovascular disease is the main cause of mortality in chronic kidney disease patients. Moreover, uremic patients are in a pro-oxidant state and show an increase in asymmetric dimethylarginine (ADMA) levels due to inhibition of the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Asymmetric dimethylarginine per se seems responsible for a 52% increase in the risk of death and for a 34% increase in the risk of cardiovascular events in dialysis patients. N-acetylcysteine (NAC) is a thiol molecule that has direct and indirect antioxidant effects which decrease reactive oxidant species and increase the bioavailability of the DDAH enzyme. The aim of the current study was to determine the effect of intravenous NAC on plasma ADMA level when administered during hemodialysis in end-stage renal disease (ESRD) patients. MATERIALS AND METHODS: 40 patients with ESRD were randomized to receive a 4-hour intravenous infusion of NAC or placebo during a 4-hour hemodialysis session. There were 3 diabetic patients (15%) in the treatment group and 6 patients in the control group. Plasma ADMA levels were measured before and immediately after hemodialysis. Hemodynamic parameters, including pulse pressure, were also measured. The paired t-test was used to compare the difference of ADMA levels before and after hemodialysis in each group, while the independent t-test was used to compare the difference of ADMA levels between the groups. RESULTS: Compared with the pre-dialysis condition, there was a decrease of ADMA level in the control group (1.1253 +/- 0.1797 microM to 0.8676 +/- 0.1449 microM) (p < 0.001), and in the NAC group (1.1522 +/- 0.1737 microM to 0.7844 +/- 0.1586 microM) (p < 0.001). Compared with hemodialysis alone, NAC had a greater lowering effect on the ADMA level (21.3 vs. 31.9%, p < 0.05). CONCLUSION: N-acetylcysteine (NAC) administered intravenously during hemodialysis reduced asymmetric dimethylarginine (ADMA) levels more significantly than hemodialysis alone.

Association of endothelial nitric oxide synthase Glu298Asp polymorphism with end-stage renal disease.

BACKGROUND: Impairment of nitric oxide generation caused by gene polymorphism is considered as a major factor in the deterioration of progressive renal disease, including diabetic nephropathy and hypertension. The aim of the present study was to examine the Glu298Asp polymorphism of endothelial nitric oxide synthase (eNOS) in patients with end-stage renal disease (ESRD). METHODS: The Glu298Asp polymorphism in exon 7 was determined in 100 ESRD patients who were maintained on hemodialysis at Dr. Soetomo Hospital, Surabaya, Indonesia, and in a control group of 100 unrelated healthy individuals. In the patient group, 39 patients had Type 2 diabetes mellitus (DM), 44 hypertension (HT) and 17 miscellaneous conditions. The mean length of time from onset of ESRD to the start of this study was 24.37 +/- 32.37 months (Mean +/- SD). RESULTS: The positivity of Glu298Asp in the ESRD group was significantly higher than that in the control group (p < 0.0001). The odds ratio for this group was 4.57 (95% confidence interval 2.52 - 8.31). The positivity of 298Asp in Type 2 DM ESRD with subgroup was significantly higher than that in healthy controls (p < 0.0001). The positivity of 298Asp in the subgroup of patients with HT-derived ESRD was also significantly higher (males p < 0.036, females p < 0.005) than that in healthy control group. Homozygotes with glutamate to aspartate substitution at nucleotide position 7702 showed a single band at 457 bp. CONCLUSION: It appears that Glu298Asp may be a predisposing factor in DM-derived and HT-derived ESRD.