Ibuprofen Compared to Acetazolamide for the Prevention of Acute Mountain Sickness: A Randomized Placebo-Controlled Trial.

INTRODUCTION: Acetazolamide is recommended for the prevention of acute mountain sickness (AMS); however, its use is limited in some areas because of side effects. Previous studies report ibuprofen to be similar to or slightly inferior to acetazolamide. This randomized, triple-blinded, parallel-group, placebo-controlled trial was designed to compare ibuprofen with acetazolamide for the prevention of AMS. METHODS: Four hundred forty-three healthy Asian Indian men with a mean age of 29 (range: 20-49) years were randomized into three groups A, B, and P at 350m (SL). Acetazolamide (A): 85 mg; ibuprofen (B): 600 mg; or placebo (P): calcium carbonate was administered thrice daily, starting one day prior and continuing for three days after arrival at 3500m (HA). Participants were evaluated for AMS using the Lake Louise Questionnaire and for pulse, BP, SpO2, and respiratory rate twice daily for the first two days during rest and once a day for days three to six at HA. RESULTS: Of the 443 participants recruited at SL, 139 could not be airlifted due to logistical limitations, and 304 were available for follow-up at HA. Among these, 254 had ascended as per protocol. By intent to treat (IT) (N = 304; A = 99, B = 102, P = 103), the incidence of AMS (LLQS>/=3) was 12%, 5%, and 13%, and the incidence of severe AMS was 1%, 2%, and 6%, in groups A, B, and P, respectively. Using per protocol analysis (PP) (N = 254; A = 83, B = 87, P = 84), the incidence of AMS was 12%, 6%, and 13% in groups A, B, and P, respectively. The relative risk for developing AMS vs. placebo was A-0.96 (CI:0.46-2.0, p=0.91), B-0.39 (CI:0.14-1.04, p=0.06), A-0.94 (CI:0.42-2.1, p=0.88), and B-0.45 (0.16-1.24, p=0.12) by IT and PP, respectively. CONCLUSION: Ibuprofen is effective in males for the prevention of AMS with rapid ascent to 3500 m-rest for the first two days. Acetazolamide was superior to ibuprofen in the prevention of moderate-to-severe AMS.

Effects of Varicocele Repair on Sperm DNA Fragmentation and Seminal Malondialdehyde Levels in Infertile Men with Clinical Varicocele: A Systematic Review and Meta-Analysis.

PURPOSE: Varicoceles can be a source of elevated seminal oxidative stress (OS) and sperm DNA fragmentation (SDF). However, it remains unclear whether varicocele repair (VR) could reduce these parameters. This systematic review and meta-analysis (SRMA) aims to investigate the impact of VR on SDF and seminal malondialdehyde (MDA). MATERIALS AND METHODS: A literature search was performed in Scopus, PubMed, Ovid, Embase, and Cochrane databases. This SRMA included randomized controlled trials and observational studies reporting the pre- and postoperative levels of SDF and seminal OS in infertile men with clinical varicocele that underwent VR. Subgroup analyses included techniques of VR and SDF testing. The effect size was expressed as standardized mean difference (SMD). RESULTS: Out of 1,632 abstracts assessed for eligibility, 29 studies with 1,491 infertile men were included. The analysis showed a significant reduction in SDF after VR, compared to preoperative values (SMD -1.125, 95% confidence interval [CI] -1.410, -0.840; p<0.0001) with high inter-study heterogeneity (I²=90.965%). Reduction in SDF was evident with microsurgical technique and non-microsurgical inguinal approaches (SMD -1.014, 95% CI -1.263, -0.765; p<0.0001, and SMD -1.495, 95% CI -2.116, -0.873; p<0.0001), respectively. Reduction in SDF was significant irrespective of testing was done by sperm chromatin dispersion (SMD -2.197, 95% CI -3.187, -1.207; p<0.0001), sperm chromatin structure assay (SMD -0.857, 95% CI -1.156, -0.559; p<0.0001) or TUNEL (SMD -1.599, 95% CI -2.478, -0.719; p<0.0001). A significant decrease in seminal MDA levels was observed following VR (SMD -2.450, 95% CI -3.903 to -0.997, p=0.001) with high inter-study heterogeneity (I²=93.7%). CONCLUSIONS: Using pre- and post-intervention data, this SRMA indicates a significant reduction in SDF and seminal MDA levels in infertile men with clinical varicocele treated with VR. These findings may have important implications for the future management of this selected group of infertile patients.

Impact of Varicocele Repair on Semen Parameters in Infertile Men: A Systematic Review and Meta-Analysis.

PURPOSE: Despite the significant role of varicocele in the pathogenesis of male infertility, the impact of varicocele repair (VR) on conventional semen parameters remains controversial. Only a few systematic reviews and meta-analyses (SRMAs) have evaluated the impact of VR on sperm concentration, total motility, and progressive motility, mostly using a before-after analytic approach. No SRMA to date has evaluated the change in conventional semen parameters after VR compared to untreated controls. This study aimed to evaluate the effect of VR on conventional semen parameters in infertile patients with clinical varicocele compared to untreated controls. MATERIALS AND METHODS: A literature search was performed using Scopus, PubMed, Embase, and Cochrane databases following the Population Intervention Comparison Outcome (PICOS) model (Population: infertile patients with clinical varicocele; Intervention: VR [any technique]; Comparison: infertile patients with clinical varicocele that were untreated; Outcome: sperm concentration, sperm total count, progressive sperm motility, total sperm motility, sperm morphology, and semen volume; Study type: randomized controlled trials and observational studies). RESULTS: A total of 1,632 abstracts were initially assessed for eligibility. Sixteen studies were finally included with a total of 2,420 infertile men with clinical varicocele (1,424 patients treated with VR vs. 996 untreated controls). The analysis showed significantly improved post-operative semen parameters in patients compared to controls with regards to sperm concentration (standardized mean difference [SMD] 1.739; 95% CI 1.129 to 2.349; p<0.001; I²=97.6%), total sperm count (SMD 1.894; 95% CI 0.566 to 3.222; p<0.05; I²=97.8%), progressive sperm motility (SMD 3.301; 95% CI 2.164 to 4.437; p<0.01; I²=98.5%), total sperm motility (SMD 0.887; 95% CI 0.036 to 1.738; p=0.04; I²=97.3%) and normal sperm morphology (SMD 1.673; 95% CI 0.876 to 2.470; p<0.05; I²=98.5%). All the outcomes showed a high inter-study heterogeneity, but the sensitivity analysis showed that no study was sensitive enough to change these results. Publication bias was present only in the analysis of the sperm concentration and progressive motility. No significant difference was found for the semen volume (SMD 0.313; 95% CI -0.242 to 0.868; I²=89.7%). CONCLUSIONS: This study provides a high level of evidence in favor of a positive effect of VR to improve conventional semen parameters in infertile men with clinical varicocele. To the best of our knowledge, this is the first SRMA to compare changes in conventional semen parameters after VR with changes in parameters of a control group over the same period. This is in contrast to other SRMAs which have compared semen parameters before and after VR, without reference to a control group. Our findings strengthen the available evidence and have a potential to upgrade professional societies' practice recommendations favoring VR to improve conventional semen parameters in infertile men.

Consensus and Diversity in the Management of Varicocele for Male Infertility: Results of a Global Practice Survey and Comparison with Guidelines and Recommendations.

PURPOSE: Varicocele is a common problem among infertile men. Varicocele repair (VR) is frequently performed to improve semen parameters and the chances of pregnancy. However, there is a lack of consensus about the diagnosis, indications for VR and its outcomes. The aim of this study was to explore global practice patterns on the management of varicocele in the context of male infertility. MATERIALS AND METHODS: Sixty practicing urologists/andrologists from 23 countries contributed 382 multiple-choice-questions pertaining to varicocele management. These were condensed into an online questionnaire that was forwarded to clinicians involved in male infertility management through direct invitation. The results were analyzed for disagreement and agreement in practice patterns and, compared with the latest guidelines of international professional societies (American Urological Association [AUA], American Society for Reproductive Medicine [ASRM], and European Association of Urology [EAU]), and with evidence emerging from recent systematic reviews and meta-analyses. Additionally, an expert opinion on each topic was provided based on the consensus of 16 experts in the field. RESULTS: The questionnaire was answered by 574 clinicians from 59 countries. The majority of respondents were urologists/uro-andrologists. A wide diversity of opinion was seen in every aspect of varicocele diagnosis, indications for repair, choice of technique, management of sub-clinical varicocele and the role of VR in azoospermia. A significant proportion of the responses were at odds with the recommendations of AUA, ASRM, and EAU. A large number of clinical situations were identified where no guidelines are available. CONCLUSIONS: This study is the largest global survey performed to date on the clinical management of varicocele for male infertility. It demonstrates: 1) a wide disagreement in the approach to varicocele management, 2) large gaps in the clinical practice guidelines from professional societies, and 3) the need for further studies on several aspects of varicocele management in infertile men.

Synthesis and biological evaluation of imidazoline derivatives as potential CNS and CVS agents.

A series of substituted imidazoline derivatives were synthesized and characterized. Compounds were tested in-vivo for their antihypertensive, analgesic, antiaggressive, depressant, antidepressant, and ALD50 activities. The compounds 3a, 3c, 4c, 5a, and 6c showed cardiovascular as well as central nervous system activities and are potential candidate as drug among all fifteen compounds tested. All these compounds have shown better activity for antihypertensive, analgesic, antiaggressive, and depressant-antidepressant, properties than reference compounds clonidine, morphine, diazepam, and imipramine respectively. Most of the compounds have shown ALD50 > 500 mg/kg with maximum in 4a and 5a (>1000 mg/kg).

Prevalence and risk factors of hypertension in acclimatized lowlanders staying at high altitude for different durations.

Hypoxic exposure at high-altitude (HA) modulates blood pressure (BP). High prevalence of hypertension among native highlanders (NH) has been reported. However, information on prevalence and determinants of hypertension in acclimatized young lowlanders (ALL) staying at HA for different durations is sparse. We aimed to determine the prevalence of hypertension in ALL staying at HA for different durations and its association with cardiovascular risk factors. Male volunteers were categorized on the basis of their duration of stay at HA; Lowlanders (LL) (0 months; n = 151), ALL (1-24 months; n = 519) and NH (n = 103). ALL were sub grouped into ALL 1 (1-6 months; n = 165), ALL 2 (6-12 months; n = 181), and ALL 3 (12-24 months; n = 173). BP, sympathetic activity, arterial stiffness, lipid profile, and homocysteine were estimated. Regression analysis was performed to determine association of risk factors with hypertension. Prevalence of hypertension among ALL was highest with 17.53% followed by NH (11.6%) and LL (9.27%). Prevalence of hypertension in ALL sub group was in order ALL 1 < ALL 2 < ALL 3. Hypertension was significantly associated with sympathetic dominance (p < 0.001) in ALL 1. Hypertension in ALL 2 was associated with dyslipidemia (p < 0.01) while in ALL 3 hypertension was associated with hyperhomocysteinemia (hHCY, p < 0.001), arterial stiffness and dyslipidemia (p < 0.01). In conclusion, our report suggests higher prevalence of hypertension in ALL. The association of studied risk factors and hypertension in different ALL sub groups varied significantly. Our findings suggest the need for a differential clinical approach to control hypertension in ALL considering their duration of stay at HA.

Pulmonary Embolism in Young Natives of High Altitude.

Thrombotic events are relatively common in high altitude areas and known to occur in young soldiers working at high altitude without usual risk factors associated with thrombosis at sea-level. However, till now, cases with thrombotic events were reported only in lowlanders staying at high altitude. These two cases of pulmonary embolism demonstrate that thrombotic events can occur in highlanders after a prolonged stay at the extreme altitude.

Synthesis and antihypertensive activity of novel quinazolin-4(3H)-one derivatives.

A series of novel substituted quinazolin-4(3H)-one derivatives were synthesized and screened in vivo for their antihypertensive activities. Out of eighteen synthesized compounds, seven i.e. 2a, 2c, 4a, 4d, 5d, 6a & 6b compounds have shown hypotensive effect and produced bradycardia. These compounds have shown better activity than reference drug Prazosin (which acts as anti-hypertensive agent by α1 blocking action). All the compounds have shown ALD50>1000mg/kg with maximum in 2c & 4d (>1200mg/kg).

Hypoxic preconditioning with cobalt ameliorates hypobaric hypoxia induced pulmonary edema in rat.

Exposure to high altitude results in hypobaric hypoxia which is considered as an acute physiological stress and often leads to high altitude maladies such as high altitude pulmonary edema (HAPE) and high altitude cerebral edema (HACE). The best way to prevent high altitude injuries is hypoxic preconditioning which has potential clinical usefulness and can be mimicked by cobalt chloride. Preconditioning with cobalt has been reported to provide protection in various tissues against ischemic injury. However, the effect of preconditioning with cobalt against high altitude induced pulmonary edema has not been investigated in vivo. Therefore, in the present study, rats pretreated with saline or cobalt (12.5mg/kg body weight) for 7days were exposed to hypobaric hypoxia of 9142m for 5h at 24°C. Formation of pulmonary edema was assessed by measuring transvascular leakage of sodium fluorescein dye and lung water content. Total protein content, albumin content, vascular endothelial growth factor (VEGF) and cytokine levels were measured in bronchoalveolar lavage fluid. Expression of HO-1, MT, NF-κB DNA binding activity and lung tissue pathology were evaluated to determine the effect of preconditioning on HAPE. Hypobaric hypoxia induced increase in transvascular leakage of sodium fluorescein dye, lung water content, lavage total protein, albumin, VEGF levels, pro-inflammatory cytokine levels, tissue expression of cell adhesion molecules and NF-κB DNA binding activity were reduced significantly after hypoxic preconditioning with cobalt. Expression of anti-inflammatory protein HO-1, MT, TGF-ß and IL-6 were increased after hypoxic preconditioning. These data suggest that hypoxic preconditioning with cobalt has protective effect against HAPE.

Substituted imidazole derivatives as novel cardiovascular agents.

A series of novel substituted imidazole derivatives were synthesized and have been screened in vivo for their hypotensive and acute toxicity activities. Out of seventeen compounds eight compounds (2b, 2c, 3b, 3c, 3f, 4a, 4b and 4c) have shown good hypotensive and bradycardiac responses. Compounds 3b, 3c, 3f and 4c have shown better activity than reference drug clonidine. All the compounds have shown ALD50>1000 mg/kg with maximum in 2e and 4c (>1200 mg/kg).

Transperitoneal laparoscopic pyeloplasty in children.

BACKGROUND AND PURPOSE: Ureteropelvic junction (UPJ) obstruction remains the most common cause of hydronephrosis in newborns and children. Open pyeloplasty has been the gold standard for management of UPJ obstruction in these patients. We report our technique and outcome with laparoscopic transperitoneal dismembered pyeloplasty in children. PATIENTS AND METHODS: Nineteen patients, ages 2 to 14 years, underwent laparoscopic pyeloplasty at our center between June 2004 and December 2006. Thirteen pyeloplasties were on the left side and six on the right side. A transmesocolic approach was used in five left-sided UPJ obstructions. All operations were performed by the transperitoneal route using either three or four ports. RESULTS: Sixteen patients underwent dismembered (Anderson-Hynes) pyeloplasty, while three had a nondismembered Foley's Y-V pyeloplasty. Mean operative time was 198 minutes (range 105-300 min). Mean estimated blood loss was 45 mL (range 30-130 mL). Mean length of stay was 4 days (range 3-5 d). Mean followup was 13.8 months (range 2-30 mos). Postoperatively, one child had a urinary tract infection that necessitated hospital admission and administration of intravenous antibiotics. Eighteen of 19 patients demonstrated improved drainage with no evidence of obstruction on diuretic renography and/or excretory urography. One patient is awaiting follow-up. There was no conversion to open surgery. CONCLUSION: Laparoscopic pyeloplasty in children is a safe, minimally invasive treatment option that duplicates the principles and techniques of definitive open surgical repair. It is technically challenging; with increasing expertise, operative times are reduced significantly.