16 research outputs found
Risk factors of renal cell carcinoma in a cohort of Sri Lankan patients: A case–control study
No full textHigh sperm DNA fragmentation u2013 finding a needle in the haystack: tips on selecting the best sperm for ICSI and ART
No full textInternational audienceHigh levels of sperm DNA fragmentation (SDF) are associated with reduced assisted reproductive technology (ART) outcomes. Currently, SDF is not included in routine clinical assessment of male partners of infertile couples, but the 6th edition of the World Health Organization (WHO) manual for semen analysis included the SDF assessment in the chapter on extended semen examinations. SDF evaluation may be indicated in several clinical conditions that have been shown to affect and increase DNA fragmentation. In cases with high SDF levels, the clinician will attempt to correct any reversible factors and may treat the patients empirically with antioxidants. If high levels of SDF persist despite empirical treatment, intracytoplasmic sperm injection (ICSI) may be indicated. During ICSI, embryologists can employ advanced selection procedures, to reduce the proportion of spermatozoa with DNA fragmentation, although no procedure can ensure that only non-DNA-fragmented will be spermatozoa selected
Management of Renal Malignancies in Von Hippel–Lindau Syndrome: Lessons Learned from a Series of Six Patients from Sri Lanka
No full textManagement of renal malignancies in Von Hippel-Lindau (VHL) is challenging. We present six patients [mean age = 35.1 years (range: 24–54), males = 5] with VHL syndrome with multiple bilateral renal malignancies and the lessons learned during their management. The number of tumors at the time of presentation ranged from 1 to 6, while the number of new lesions varied from 1 to 3. Different combinations of radical nephrectomy (n = 2), partial nephrectomy (n = 7), and focal therapy (n = 6) were used appropriately. Median follow-up was 36 months (range: 12–72). Two patients developed new lesions which were managed with focal therapy. Nephron-sparing approaches are successful even in bilateral, multifocal, large, and recurring renal tumors associated with VHL. Awareness about the availability of efficacious surgical and minimally invasive measures would reduce psychosocial problems faced by patients and their families due to the social stigma associated with malignancies running in a family and burden of renal replacement therapy
Outcome of uncomplicated ureteric calculi managed with medical expulsive therapy in the outpatient clinic of a urology unit in Sri Lanka
No full textOutcome of uncomplicated ureteric calculi managed with medical expulsive therapy in the outpatient clinic of a urology unit in Sri Lanka
No full textAbstract Objective Although medical expulsive therapy (MET) is shown to be effective for ureteric calculi, the optimum duration and the stone size suitable for MET are not well established yet. The objectives of the study were to determine the optimum duration and maximum stone size suitable for MET. Results All patients with radiologically confirmed uncomplicated ureteric calculi treated with MET using tamsulosin over a period of 6 months in the outpatient setting were followed up. There were 213 patients. 165 were men. Mean age was 42 years. At presentation 42 stones were in upper ureter (19.7%), 51 in mid ureter (23.9%), 120 in lower ureter (56.3%). The majority (82.7%) of stones were less than 10 mm. Seven stones (3.3%) were over 15 mm. Ninety-two (43.2%) patients had spontaneous passage of stones within 6-weeks of MET. Another 38.9% passed the stone within the next 6-weeks. Thirty-eight patients (17.8%) required surgery. Uncomplicated ureteric stones up to 10 mm can be given a trial of MET using tamsulosin which can be extended up to 12-weeks with a success rate over 92%. This may have substantial clinical and fiscal benefits by reducing the number of interventional procedures especially in resource-poor settings
Cellular roles of the human Obg-like ATPase 1 (hOLA1) and its bacterial homologue, YchF.
No full textP-loop NTPases comprise one of the major superfamilies of nucleotide binding proteins, which mediate a variety of cellular processes, such as mRNA translation, signal transduction, cell motility, and growth regulation. In this review, we discuss the structure and function of two-members of the ancient Obg-related family of P-loop GTPases: human obg-like ATPase 1 (hOLA1) and its bacterial homolog, YchF. After a brief discussion of nucleotide binding proteins in general and the classification of the Obg-related family in particular, we discuss the sequence and structural features of YchF and hOLA1. We then explore the various functional roles of hOLA1 in mammalian cells during stress response and cancer progression, and of YchF in bacterial cells. Finally, we directly compare and contrast the structure and function of hOLA1 with YchF before summarizing the future perspectives of hOLA1 research. This review is timely, given the variety of recent studies aimed at understanding the roles of hOLA1 and YchF in such critical processes as cellular stress-response, oncogenesis, and protein synthesis.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author
Role of thymulin or its analogue as a new analgesic molecule
No full textThe thymic peptide thymulin is known for its immunomodulatory role. However, several recent reports have indicated that thymulin is capable of interacting directly and-or indirectly with the nervous system. One of the first lines of evidence of this interaction was obtained in a series of experiments showing the hyperalgesic actions of this peptide. We demonstrated that, at low doses (ng), local (intraplantar) or systemic (intraperitoneal) injections of thymulin resulted in hyperalgesia with an increase in proinflammatory mediators, and that this peptide could act directly on the afferent nerve terminals through prostaglandin-E2 (PGE2)-dependent mechanisms, thus forming a neuroimmune loop involving capsaicin-sensitive primary afferent fibers. In further experiments, systemic injections of relatively high doses (1-25 μg) of thymulin or of an analogue peptide (PAT) deprived of hyperalgesic effect, have been shown to reduce the inflammatory pain and the upregulated levels of cytokines induced by endotoxin (ET) injection. In addition, PAT treatment appeared to alleviate the sickness behavior (motor behavior and fever) induced by systemic inflammation. These effects could be attributed, at least partly, to the downregulation of proinflammatory mediators. Furthermore, when compared with the effects of other anti-inflammatory drugs, PAT exerted equal or even stronger analgesic effects, and at much lower concentrations. Subsequent experiments were designed to examine the effects of intracerebroventricular (i.c.v.) injections of thymulin on cerebral inflammation induced by i.c.v. injection of ET. Pretreatment with thymulin reduced, in a dose-dependant manner, the ET-induced hyperalgesia, and exerted differential effects on the upregulated levels of cytokines in different areas of the brain, suggesting a neuroprotective role for thymulin in the central nervous system (CNS). Preliminary results demonstrate that thymulin inhibits in the hippocampus the ET-induced nuclear activation of NF-κB, the transcription factor required for the expression of proinflammatory cytokines genes. 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Acute coronary syndrome rule-out strategies in the emergency department: an observational evaluation of clinical effectiveness and current UK practice
No full text\ua9 Author(s) (or their employer(s)) 2025. Background: Numerous strategies have been developed to rapidly rule-out acute coronary syndrome (ACS) using high-sensitivity troponin. We aimed to establish their performance in terms of emergency care length of stay (LOS) in real-world practice. Methods: A multicentre observational cohort study in 94 UK sites between March and April 2023. Recruitment was preferably prospective, with retrospective recruitment also allowed. Adults presenting to the ED with chest pain triggering assessment for possible ACS were eligible. Primary outcome was emergency care LOS. Secondary outcomes were index rate of acute myocardial infarction (MI), time to be seen (TTBS), disposition and discharge diagnosis. Details of ACS rule-out strategies in use were collected from local guidelines. Mixed effects linear regression models tested the association between rule-out strategy and LOS. Results: 8563 eligible patients were recruited, representing 5.3% of all ED attendances. Median LOS for all patients was 333 min (IQR 225, 510.5), for admitted patients was 460 min (IQR 239.75, 776.25) and for discharged patients was 313 min (IQR 221, 451). Heterogeneity was seen in the rule-out strategies with regard to recommended troponin timing. There was no significant difference in LOS in discharged patients between rule-out strategies defined by single and serial troponin timing (p=0.23 and p=0.41). The index rate of acute MI was 15.2% (1301/8563). Median TTBS was 120 min (IQR 57, 212). 24.4% (2087/8563) of patients were partly managed in a same day emergency care unit and 70% (5934/8563) of patients were discharged from emergency care. Conclusion: Despite heterogeneity in the ACS rule-out strategies in use and widespread adoption of rapid rule-out approaches, this study saw little effect on LOS in real-world practice. Suspected cardiac chest pain still accounts for a significant proportion of UK ED attendances. ED system pressures are likely to be explanatory, but further research is needed to understand the reasons for the unrealised potential of these strategies
Global Andrology Forum (GAF) Clinical Guidelines on the Management of Non-obstructive Azoospermia: Bridging the Gap between Controversy and Consensus
No full textPURPOSE: Non-obstructive azoospermia (NOA), defined as the absence of sperm in the ejaculate due to testicular failure, is observed in 5% to 15% of infertile men and accounts for two-thirds of azoospermia cases. The management of NOA is marked by significant controversy and global variation in diagnostic and therapeutic approaches, highlighting the crucial need for well-designed and standardized clinical practice guidelines. We present comprehensive graded clinical practice recommendations and statements for diagnosing and treating NOA, aiming to establish standardized strategies that can globally help guide practitioners in their practice.
MATERIALS AND METHODS: A comprehensive literature review was conducted to gather evidence on the epidemiological, diagnostic, and therapeutic aspects of NOA. The Global Andrology Forum (GAF) recommendations were developed through the collaboration of a global panel of experts using the Delphi method and surveys to achieve consensus. Statements were graded according to the Oxford Centre for Evidence-Based Medicine GRADE classification as either Strong or Weak. Statements receiving at least 80% expert consensus were graded as Strong, while others were categorized as Weak.
RESULTS: The GAF has formulated a total of 49 recommendations and statements on the diagnosis and treatment of NOA, including 21 for diagnosis and 28 for treatment. The recommendations and statements were evaluated and graded by a panel of 48 GAF experts from 25 countries worldwide. The majority of experts (60.5%) had more than 10 years of clinical experience in managing NOA.
CONCLUSIONS: The GAF guidelines address discrepancies in NOA management across diverse clinical settings and provide comprehensive graded recommendations to guide clinicians in its diagnosis and treatment. Developed and graded by a large worldwide panel of experts, the current guidelines present simplified, high-standard strategies that can be seamlessly integrated into the daily global practice, offering practitioners a clear framework for managing NOA
