Increased nitric oxide is accompanied by lipid oxidation in adolescent varicocele

Summary One of the mechanisms of injury in varicocele has been proposed to be elevated nitric oxide (NO). We aimed to determine the association between the elevation of NO and lipid oxidation in varicocele compared with peripheral venous levels of these two substances as it has not been studied before. The study group consisted of 13 adolescents with left idiopathic varicocele of grades II-III. Blood specimens were obtained from dilated spermatic and peripheral veins simultaneously. Peripheral samples were also collected from 13 healthy children as controls. Nitrite/nitrate levels (NO(x)) and levels of malonedialdehyde (MDA) were determined using Griess reaction and thiobarbituric acid test, respectively. Results were compared with Kruskal-Wallis and Mann-Whitney tests. Peripheral NO(x) and MDA were the same in the study and control groups (p = 0.069 and p = 0.27, respectively). Spermatic vein NO(x) and MDA levels were elevated significantly compared with the peripheral levels in the study group (p = 0.005 and p = 0.048, respectively). Increased NO(x) levels with lipid oxidation occur locally in adolescent varicocele, implying that these events could be reversed by early treatment.     

Pancreas Pseudocyst Associated with L-asparaginase Treatment: a Case Report

A major complication of L-asparaginase used in the treatment of paediatric malignancies in children is pancreatitis (2%-16%). However, only seven paediatric cases of pancreatic pseudocyst caused by the utilization of the agent have been reported in literature. We present the case of a 5-year old girl who had abdominal pain and epigastric dullness after the third course of BMF-95 protocol with a diagnosis of ALL. A pancreatic pseudocyst of 10 χ 10 cm size was found by abdominal tomography. The cyst was treated by percutaneous external drainage, total parenteral nutrition (TPN), administration of octreotide and antibiotherapy for one month. Percutaneous external drainage has proven to be an effective, noninvasive method in this special case with a systemic disorder and the high risk of mortality should a surgical intervention have been performed.     

Different strategies of mixed chimerism induction may determine stem/progenitor cell populations in recipient mice

Mixed chimerism has been suggested to induce tolerance to transplanted alloantigens. As the precise influence of mixed chimerism induction on the host organism has still not been fully elucidated, the aim of the present study was to explore this phenomenon in relation to the stem cell compartment.The experiment was performed on B6.SJL-Ptprc^aPep3^b mice. Mixed chimerism induction protocols involved 3 Gy TBI (Day − 1 of the experiment), injection of 20-30 × 10⁶ Balb C bone marrow cells (Day 0), and administration of blocking antibodies against CD40L (Day 0 and Day 4), anti-CD8 (Day − 2) with/without anti-NK1.1 (Day − 3). Selected groups of mice were also treated with cyclophosphamid (175 mg/kg) on Day 2. The presence of mixed chimerism was assessed in peripheral blood, bone marrow, and spleen, as well as in various subpopulations of leukocytes (CD4⁺, CD8⁺, CD45/B220⁺, Gr-1⁺, lin⁻/Sca-1⁺/c-kit⁻, lin⁻/Sca-1⁺/c-kit⁺, lin⁻/Sca-1⁻/c-kit⁺). Furthermore, the percentage of stem/progenitor cells (lin⁻/Sca-1⁺/c-kit⁻, lin⁻/Sca-1⁺/c-kit⁺, lin⁻/Sca-1⁻/c-kit⁺, VSEL, HSC) was analysed for the first time in bone marrow and peripheral blood of chimeric mice.The range of mixed chimerism differed significantly among various cell populations: it was lowest in CD8-positive cells and lin⁻/Sca-1⁺/c-kit⁻ cells, and highest in granulocytes. The induction of mixed chimerism revealed a significant impact on the stem/progenitor cell frequency in recipient mice, providing potential therapeutic insights into the long-term immunologic tolerance observed in chimeric mice. Collectively, these findings contribute to further optimization of mixed chimerism induction protocols and might help in the introduction of this phenomenon into clinical practice.     

Markers of inflammation before and after renal transplantation

BACKGROUND: This study aims to compare serum C-reactive protein (CRP), interleukin (IL-6), and tumor necrosis factor (TNF)-alpha in end-stage renal disease (ESRD) patients before versus after receiving renal transplantation (RT) and versus donors. METHODS: Serum samples from 37 ESRD patients (24 male, age 34+/-13 years) were collected before and after RT; in addition, samples from 31 donors were obtained at transplantation. CRP concentrations were measured using nephelometry, and TNF-alpha and IL-6 were measured by enzyme-linked immunoadsorbent assay. RESULTS: Ninety-two percent of recipients had a living donor, 73% received cyclosporine A, 27% tacrolimus, and 70% induction with daclizumab. Thirteen percent had acute rejection and 16% chronic allograft nephropathy. All inflammation markers decreased 6 months after RT, but only CRP was below baseline values (baseline: 5.0+/-3.5; 6 months: 3.0+/-0; 12 months: 3.2+/-0.7; 18 months: 3.2+/-0.6; donors: 3.6+/-1.5 mg/L; P<0.05), whereas median TNF-alpha (baseline: 0.1 [0.03-0.2]; 6 months: 0 [0-0.1]; 12 months: 0.3 [0.1-2.6]; 18 months: 0.6 [0.1-1.9]; donors: 0 [0-0.1] pg/mL; P<0.05) and IL-6 (baseline: 1.9 [1.2-7.1]; 6 months: 1.2 [0.6-28.3]; 12 months: 2.6 [1.3-3.4]; 18 months: 2.7 [1.7-4.2]; donors: 1.1 [0.6-1.9] pg/mL; P<0.05) significantly increased up to the end of follow-up. Before RT, CRP correlated with age (r 0.45, P=0.006) and albumin (r -0.36, P=0.04). TNF-alpha and IL-6 were correlated before (r 0.34, P=0.04) and after (r 0.55, P=0.02) RT. Inflammation markers were not different in patients who had acute rejection episodes or chronic nephropathy. CONCLUSIONS: Compared with controls, patients displayed an inflammatory phenomenon before receiving RT. Serum CRP decreased significantly after RT, whereas TNFalpha and IL-6 increased.     

Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment

To assess platelet function profiles in diabetic and nondiabetic patients on aspirin and clopidogrel therapy, two patient populations were included to investigate the 1) acute effects of a 300-mg clopidogrel loading dose (group 1, n = 52) and 2) long-term effects of clopidogrel (group 2, n = 120) on platelet function in diabetic compared with nondiabetic patients already on aspirin treatment. Patients were stratified according to the presence of type 2 diabetes. Platelet aggregation was assessed using light transmittance aggregometry (groups 1 and 2). Platelet activation (P-selectin expression and PAC-1 binding) was determined using whole-blood flow cytometry (group 2). Clopidogrel response was also assessed. In group 1, platelet aggregation was significantly increased in diabetic (n = 16) compared with nondiabetic (n = 36) patients at baseline and up to 24 h following a 300-mg loading dose (P = 0.005). In group 2, platelet aggregation and activation were increased in diabetic (n = 60) compared with nondiabetic (n = 60) subjects (P < 0.05 for all platelet function assays). Diabetic subjects had a higher number of clopidogrel nonresponders (P = 0.04). Diabetic patients have increased platelet reactivity compared with nondiabetic subjects on combined aspirin and clopidogrel treatment. Reduced sensitivity to antiplatelet drugs may contribute to the increased atherothombotic risk in diabetic patients.     

Idiopathic sudden sensorineural hearing loss: a review

Idiopathic Sudden Sensorineural Hearing Loss (ISSHL) remains one of the major unsolved otologic emergencies. It is characterized by the onset of an unilateral sensorineural hearing loss developing within 24 hours, and averaging on pure tone audiogram at least 30 dB HL for three subsequent octave steps, with no marked vestibular symptoms and no identifiable cause. ISSHL is a syndrome covering several heterogeneous entities resulting from different pathogenetic mechanisms. At this time, the audiogram is the unique tool which may help clinicians to identify these entities and provide a classification based on 5 types of hearing loss. Numerous experimental and clinical studies have investigated the mechanisms by which infectious, ischemic, mechanic or immunologic insults may induce cochlear dysfunction. However, extrapolation to humans and rationale therapeutic approaches to ISSHL remain uncertain. SSHL being a diagnosis of exclusion, retrocochlear and neurologic etiologies should be eliminated. No argument allows to consider ISSHL a therapeutic emergency. More precisely, the experimental data presently available on cochlear physiology suggests that a treatment could have some chance to be effective if undertaken within minutes following the onset of ISSHL, a condition never encountered in daily practice. Conversely, it is not justifiable to impute the absence of hearing recovery to a delay in therapy. The various therapeutic strategies currently recommended are highly empirical and should be questionned in terms of cost-effectiveness, the most common being high-dose corticosteroids. New investigation tests are required for improving our approach to ISSHL.     

Migration of biliary plastic stents: experience of a tertiary center

Background and study aims  Stent migration occurs in about 5–10% of patients undergoing biliary stenting. The aim of this study was to analyze the risk factors for stent migration in patients with benign and malignant strictures. Patients and methods  We retrospectively analyzed records of 524 biliary plastic stent placement procedures. Details noted included the cause and localization of stricture, characteristics and number of stents, direction of stent migration, presentation of patient with migrated stent, and the methods used for retrieval of migrated stents. Results  Two hundred and four (38.9%) of the procedures were performed for benign biliary strictures (BBS) and 320 (61.1%) for malignant biliary strictures (MBS). Thirty-four patients had 45 migrated biliary stents. The rate of migration was 8.58% (proximal 4.58% and distal 4.00%). Migration frequency was higher in BBS compared with MBS (13.7% versus 5.3%, p = 0.001). In BBS, the rate of stent migration was higher in cases with one (19.3%) and two stents (20.9%) when compared with cases with multiple stents (2.7%) (p = 0.001; p = 0.001, respectively). Migration occurred more frequently (10.9%) in cases with two stents when compared both to cases with one stent (3.0%) and those with multiple stents (0%) in MBS (p = 0.008; p = 0.020, respectively). In BBS, short stents migrated more frequently proximally (77%) and long stents more frequently distally (73%) (p = 0.008). In BBS, migration in cases with proximal stricture occurred more frequently distally (76.9%), while in those with distal stricture, migration was more frequently proximal (73.3%) (p = 0.008). All of the proximally migrated stents could be successfully retrieved endoscopically. Conclusions  The risk of stent migration is higher in BBS compared with in MBS. The cases with multiple stents had significantly lower stent migration. In BBS, long stent, proximal and postcholecystectomy strictures were associated with distal migration, while short stent, distal and non-postcholecystectomy strictures were associated with proximal migration.     

Combined low‐dose flutamide plus finasteride vs low‐dose flutamide monotherapy for recurrent prostate cancer: a comparative analysis of two phase II trials with a long‐term follow‐up

OBJECTIVE

To compare the efficacy and tolerability of peripheral androgen blockade using combined low‐dose flutamide plus finasteride vs low‐dose flutamide monotherapy for treating biochemical relapse after the definitive management of prostate adenocarcinoma.

PATIENTS AND METHODS

Fifty‐six men treated for biochemical relapse of prostate cancer were enrolled prospectively in a phase II trial at the Walter Reed Army Medical Center from 1997 to 2001. Thirty‐six men were treated with flutamide (125 mg twice daily) and finasteride (5 mg twice daily), and 20 men received low‐dose flutamide only after biochemical recurrence (prostate‐specific antigen, PSA, level ≥0.4 ng/mL). Cox proportional hazards analyses were used to compare the risk of progression between the groups.

RESULTS

Patients on combined and monotherapy had a median follow‐up of 54 and 43.5 months, respectively. Seven men (19%) in the combined arm remain in the study with no progression, while five (25%) on monotherapy continue and are progression‐free. Men on combined therapy had a greater decrease in their PSA level (P = 0.002). Multivariate analysis showed that men on combined therapy had significantly less risk of progression than men on monotherapy (hazard ratio 0.21, 95% confidence interval 0.07–0.63, P = 0.005). There was no significant difference in the frequency of side‐effects between the groups. Toxicities were reported to be mild.

CONCLUSIONS

Our analysis suggests the therapeutic value of low‐dose flutamide alone or combined with finasteride as first‐line agents in a possible graduated approach for treating PSA‐only recurrent prostate cancer. Due to unwanted metabolic effects associated with traditional hormonal agents, phase III trials comparing both regimens with current therapies are warranted.     

封闭负压引流技术治疗56例骨外露创面的临床疗效

目的观察封闭负压引流技术治疗骨外露创面的临床效果。方法取本院骨科于2010—2012年收治的骨外露创面患者56例作为研究对象,根据治疗方式不同分为使用负压封闭引流术的观察组与使用常规治疗方法的对照组,每组各28例。比较两组患者的治疗效果、日常生活活动能力和肢体功能、疼痛及负面情绪评分等差异。结果观察组患者的治疗效果明显优于对照组患者(P<0.05);观察组患者接受治疗后的日常生活活动能力和肢体功能评分均明显高于对照组患者(P<0.05);观察组患者接受治疗后的疼痛及负面情绪评分均明显低于对照组患者(P<0.05)。结论使用负压封闭引流技术治疗骨外露创面可以显著提高治疗效果,改善患者的生活能力及肢体功能,减轻患者的疼痛及负面情绪。