A comparison of pudendal block vs dorsal penile nerve block for circumcision in children: a randomised controlled trial.

We compared the analgesic and anaesthetic efficacy of pudendal nerve block with that of dorsal penile nerve block in male patients aged 3-5 years of age, undergoing elective circumcision. Thirty patients had a nerve stimulator-guided pudendal nerve block with two separate injection points 1.5-2 cm from the centre of the anus, and thirty patients received a dorsal penile nerve block. The same total anaesthetic volume of 0.3 ml.kg(-1) was used in both groups. The pudendal nerve group showed significantly lower postoperative pain scores than the dorsal group (SD) (p < 0.05), and significantly fewer patients consumed analgesics in the pudendal group than the dorsal group: 0 vs 5 (17%) at 0 and 6 h, respectively. This study demonstrates the effectiveness of pudendal nerve block in comparison to the dorsal nerve block, with improved postoperative outcomes in children undergoing circumcision.

PositivMasc: masculinities and violence against women among young people. Identifying discourses and developing strategies for change, a mixed-method study protocol.

INTRODUCTION: Despite public policies and legislative changes aiming to curtail men's violence against women (VAW) around the world, women continue to be exposed to VAW throughout their life. One in three women in Europe has reported physical or sexual abuse. Men who display unequitable masculinities are more likely to be perpetrators. VAW is increasingly appearing at younger ages. The aims of the project are fourfold: (1) to explore and position the discourses that young people (men and women, 18-24 years) in Sweden, Spain, Ireland and Israel use in their understanding of masculinities, (2) to explore how these discourses influence young people's attitudes, behaviours and responses to VAW, (3) to explore individual and societal factors supporting and promoting anti-VAW masculinities discourses and (4) to develop actions and guidelines to support and promote anti-VAW masculinities in these settings. METHODS AND ANALYSIS: A participatory explorative mixed-method study will be used. In Phase 1, qualitative methods will be used to identify the discourses that young people and stakeholders use to conceptualise masculinities, VAW and the actions that are needed to support and promote antiviolence masculinities. In Phase 2, concept mapping will be used to quantify the coherence, relative importance and perceived relationship between the different actions to support and promote anti-VAW masculinities. Phase 3 is a knowledge creation and translation phase, based on findings from Phases 1 and 2, where actions and guidelines to promote and support anti-VAW masculinities will be developed. ETHICS AND DISSEMINATION: Ethical clearance has been obtained from ethics review boards in each country. Results will be disseminated through peer-reviewed publications, presentations at international conferences, policy briefs, social media and through the project online hub. With its multicountry approach, our project results seek to inform policies and interventions aimed at promoting discourses which challenge hegemonic masculinities.

Objective Clinical and Radiological Response under Sunitinib in a Case of Thigh Hidradenocarcinoma.

A 56-year-old male was treated by local surgery in 1968 and 2005 for a left thigh lesion. A 2nd local relapse occurred in 2015 and was treated by complete macroscopic surgery with histology concluding to a hidradenocarcinoma. A 3rd locoregional relapse occurred in October 2018, with the presence of inflammatory ulcerated lesions. A 2nd histology and immunohistochemistry exam showed a proliferation positive for CK, CK5, and p63 suggesting the diagnosis of hidradenocarcinoma. The patient was treated by 3 lines of chemotherapy, 1st by Adriamycin, 2nd by carboplatin-paclitaxel, and then 3rd by oral capecitabine, leading to a stable clinical disease but without a clinical benefit. A locoregional plus metastatic lung progression was observed in March 2019, with the presence of lung nodules and retroperitoneal lymph nodes, multiple skin left thigh and left inguinal ulcerated lesions. The patient received then in 4th line in April 2019 oral sunitinib at 50 mg daily, with 4 weeks therapy/2 weeks pause. Side effects were represented by mucositis, anorexia, weight loss, and fatigue. We observed since the 1st week of therapy a fast response, with a decrease of the ulcerated lesions, a skin loss, and deep hemorrhagic areas. CT-scan showed after 2 weeks of sunitinib an objective response on both locoregional and metastatic lesions.

Annual hazard rate of relapse of stage II and III colorectal cancer after primary therapy.

PURPOSE: To report the annual hazard of relapse in stages II and III colorectal cancer (CRC) Tunisian patients treated with curative intent. We also aim to evaluate impact of oxaliplatine according to anatomo-clinical features. METHODS: We collected data about clinico-pathological parameters of 331 CRCs. We analyzed annual hazard of recurrence (locoregional and/or distant) of the overall population and several subgroups: colon cancer vs rectal cancer and stage II vs stage III. We also analyzed impact of adjuvant oxaliplatine on recurrence within these subgroups. RESULTS: Relapse rate was 38.1%, with a mean time to relapse of 27.6 months. We noted 23.8% local recurrence, 69.8% distant recurrence, and 6.4% both. We observed higher local relapse rate in rectal cancer (26.8 vs 3.2%) vs colon cancer (p = 0.004). Stage III had a higher metastatic relapse rate vs stage II (31.6 vs 20.8%, p = 0.043). Annual hazard of recurrence for the overall population showed two peaks: [1-2] year-interval by 10.1% and [3-4] year-interval by 11.3%. Stage III showed significantly higher and earlier recurrence hazard peak compared to stage II (16.3 vs 8.1% in [1-2] year-interval). Oxaliplatine significantly improved annual hazard of recurrence in each year-interval from year 1-4, in colon cancer and in stage III but without impact in rectal cancer and stage II. CONCLUSION: Extended follow-up to 4 years should be considered in Tunisian population. Impact of oxaliplatine showed same features to reported occidental series.

Treatment advances for cocaine-induced ischemic stroke: focus on dihydropyridine-class calcium channel antagonists.

OBJECTIVE: The authors reviewed the pathogenesis of cocaine-related cerebral ischemia, appraised current knowledge of its sequelae, and assessed the role of putative therapeutic agents, particularly dihydropyridine-class calcium channel antagonists. METHOD: The authors performed an OVID-based literature review of all indexed journals between 1966 and 2000. RESULTS: Cocaine abuse significantly increases the risk of ischemic stroke. The principal mechanism of cocaine-induced cerebral ischemia is vasospasm of large cranial arteries or within the cortical microvasculature. Increased levels of extracellular monoamines, particularly dopamine, mediate vasospasm. Neuroanatomical and labeling studies also have shown that dopamine-innervated neurons may regulate cerebral blood flow. Indeed, dopamine-rich brain regions appear to be relatively specific targets for cocaine-induced cerebral ischemia. Neuroimaging studies show that cocaine-induced hypoperfusion can persist even after 6 months of abstinence. Hypoperfusion can result in deficits on complex and simple psychomotor tasks but perhaps not on memory or attention. Severe cerebral ischemia can directly precipitate neuronal death and degradation, a condition exacerbated by liberation of the excitatory amino acid glutamate. Dihydropyridine-class calcium channel antagonists inhibit cocaine-mediated dopamine release on neurons involved in vasospasm and the control of cortical circulation. Other causes of cerebral ischemia include thrombogenesis and vasculitis. Although antithrombotic agents have potential in alleviating cocaine's neurotoxic effects, their use may be limited by the risk of spontaneous hemorrhage. CONCLUSIONS: Cocaine abuse can result in stroke, neuroischemia, and cognitive deficits that can persist even after prolonged abstinence. Dihydropyridine-class calcium channel antagonists, such as isradipine, show promise as therapeutic agents for preventing cocaine-induced cerebral ischemia.

Effects of isradipine, a dihydropyridine-class calcium channel antagonist, on D-methamphetamine-induced cognitive and physiological changes in humans.

D-methamphetamine is abused for its euphoric effects and stimulatory action on cognitive function. Its abuse can, however, be associated with massive hypertension resulting in strokes, ruptured aneurysms, or myocardial infarction. We examined the utility of isradipine, a dihydropyridine-class calcium channel antagonist, in treating d-methamphetamine induced hypertension and evaluated its effects on cognitive function, both of which are mediated by dopaminergic mechanisms. D-methamphetamine dose-dependently increased all vital signs (systolic, diastolic, and mean arterial pressure, and pulse rate) parameters. Isradipine significantly reduced d-methamphetamine-induced increases in diastolic and mean arterial pressure; however, this potentially beneficial therapeutic effect was offset by a significant reflex rise in pulse rate. D-methamphetamine also improved attention, accuracy of reasoning ability, and performance on computerized cognitive function tasks. D-methamphetamine's cognitive improving effects were not altered significantly by isradipine. Isradipine increased the false responding rate but was without significant effect on any other attentional task, or on reasoning ability, or performance. Isradipine does not appear to enhance cognitive function in healthy humans.

Reactogenicity and antigenicity of rhesus rotavirus vaccine (MMU-18006) in newborn infants in Venezuela.

The reactogenicity and antigenicity of the rhesus rotavirus vaccine, strain MMU18006, developed at the Laboratory of Infectious Diseases (National Institute of Allergy and Infectious Diseases, National Institutes of Health) were examined in a double blind, placebo-controlled study of 40 newborn infants in Caracas, Venezuela. The children were observed for the first few days after birth in the hospital nursery and by home visits for 10 days after vaccination to detect any adverse reactions. No reactions could be attributed to the vaccine. Serologic responses to the vaccine were evaluated in paired sera obtained at birth (cord blood) and 4 weeks after vaccination. Serologic responses to the vaccine were not observed by complement fixation, neutralization or a rhesus rotavirus VP7 epitope-specific competition assay. However, such responses were found in 9 of 14 tested infants by an immunoglobulin A-specific enzyme-linked immunosorbent assay. Seventeen of the 20 vaccinees also shed rhesus rotavirus vaccine in stool during the postvaccination period.

Neuropharmacological treatments for alcoholism: scientific basis and clinical findings.

Preclinical studies have exploded our knowledge about the behavioral and biological underpinnings of alcoholism. These studies suggest that certain neurotransmitters, particularly those interacting with the opioid, N-methyl-D-aspartate, and monoamine systems, may play a critical role in the expression of alcohol-drinking and other behaviors associated with its abuse liability. Built upon this foundation, important advances have been made in the development of therapeutic medications for the treatment of alcoholism. Of the medications reviewed, acamprosate's potential appears to be the most widely established. In the USA, naltrexone was approved by the Food and Drug Administration in 1995 for the treatment of alcoholism; however, the results of some studies have been less encouraging. Naltrexone's reliance on high compliance rates for efficacy may, eventually, limit its potential in clinical settings offering generic treatment for alcoholism. The relative paucity of dose-response studies on naltrexone's effects in treating alcoholics is an important gap in the literature. Recent data from a large clinical trial suggests that ondansetron, a serotonin3 antagonist, offers new hope for the treatment of early onset alcoholics; a type of alcoholism most difficult to manage with psychosocial measures alone. Different subtypes of alcoholic may, therefore, have varying treatment responses to serotonergic agents. Matching subtypes of alcoholic to effective treatment medications based upon their different biologies remains an important therapeutic goal. Combinations of effective pharmacological agents need exploration as they may prove to be synergistic, and could shepherd in a new era of treatments aimed at multiple neurotransmitter targets associated with the alcoholism disease. The coming decade promises more powerful tools for characterizing drug effects on alcohol drinking, thereby closing the gap between animal models of addiction and the human condition.

Combining ondansetron and naltrexone reduces craving among biologically predisposed alcoholics: preliminary clinical evidence.

RATIONALE: Previously, we have reported that the combination of ondansetron (a 5-HT3 antagonist) and naltrexone (a mu opioid antagonist) appears to act synergistically at improving the drinking outcomes of early onset alcoholics (EOA). a subtype of alcoholic characterized by developing problem-drinking earlier, antisocial behaviors, high familial loading, and biological disease predisposition. Presumably, this medication combination counteracts the interaction between activated central 5-HT3 receptors and the endogenous opioid system during the mediation of alcohol-induced reward. We now hypothesize further that an important mechanism by which the combination diminishes alcohol consumption is through a reduction in craving. OBJECTIVE: To determine whether the combination of naltrexone and ondansetron is superior to a placebo at reducing craving among EOA, and the relationship between craving and drinking behavior in both treatment groups. METHODS: We conducted an 8-week double-blind placebo-controlled clinical trial in which 10 EOA were randomized to receive ondansetron (4 microg/kg b.i.d.) + naltrexone (25 mg b.i.d.) and 10 EOA had a placebo (total n=20) as an adjunct to weekly standardized group cognitive behavioral therapy. Craving was measured by using the obsessive compulsive drinking scale (OCDS). RESULTS: Craving ratings were scored on four subscales which where derived empirically by principal component structure analysis of the OCDS. EOA who received the medication combination, compared with the placebo, had significantly lower scores on "automaticity of drinking" and "alcohol consumption ". Reduction in automaticity of drinking was correlated with self-reported drinking for only the medication combination group. CONCLUSIONS: By reducing automaticity of drinking, the medication combination presumably decreased drinking salience and intensity. Larger scale studies testing these medications, both alone and together, among alcoholic subtypes are needed to establish and extend these promising findings.

Isradipine, a dihydropyridine-class calcium channel antagonist, attenuates some of d-methamphetamine's positive subjective effects: a preliminary study.

RATIONALE: Dopamine (DA) pathways in the midbrain mediate d-methamphetamine's rewarding effects associated with its abuse liability. Isradipine, a dihydropyridine-class calcium channel antagonist, reduces the rewarding effects of psychostimulants such as cocaine and d-amphetamine, presumably by antagonizing these central DA pathways. This is the first experiment to test the hypothesis that the rewarding effects of d-methamphetamine, like other psychostimulants, can be reduced by isradipine. OBJECTIVE: We studied the effects of high dose isradipine (0.21 mg/kg orally), on the positive subjective effects associated with the abuse liability of low and high dose d-methamphetamine (0.21 mg/kg and 0.42 mg/kg orally, respectively). METHODS: Using a double-blind, double-dummy, placebo-controlled, Latin-Square, cross-over design, 18 healthy male and female volunteers received each of the following six treatments separated by a rest period of 2-7 days: a) placebo+placebo; b) low-dose d-methamphetamine+placebo); c) high-dose d-methamphetamine+placebo; d) high dose isradipine+placebo); e) low-dose d-methamphetamine+high dose isradipine, and f) high-dose d-methamphetamine+high dose isradipine. RESULTS: d-Methamphetamine produced orderly increases in positive subjective measures of both stimulation and mood. Pre-treatment with isradipine significantly reduced some of these positive subjective effects and craving for d-methamphetamine. CONCLUSION: Isradipine as an anti-reward or craving reducing medication is a promising therapeutic agent for the treatment of d-methamphetamine dependence.

Effects of isradipine, a dihydropyridine-class calcium channel antagonist, on d-methamphetamine-induced reduction in hunger.

1. The authors studied the effects of isradipine, a dihydropyridine-class calcium channel antagonist, on d-methamphetamine-induced changes in somatic and psychological perceptions of hunger state using a placebo-controlled, double-blind, Latin Square, cross-over design in 18 healthy volunteers. 2. D-methamphetamine significantly decreased these subjective ratings of hunger, presumably by increasing monoaminergic turnover. 3. Effects on hunger are hypothesized to be mediated by norepinephrine primarily, while dopamine plays only a modest role. Isradipine alone, an inhibitor of dopamine release, had no significant effect on the hunger measures. Additionally, isradipine pretreatment did not significantly alter d-methamphetamine's anorexic effects. 4. Isradipine may, therefore, not significantly modify the control of hunger in humans.

Alzheimer's disease: preliminary study of spatial distribution at birth place.

Alzheimer's disease (AD) is a neurodegenerative disorder which is characterized by a progressive loss of memory and the alteration of cognitive functions. At least three chromosomal segments have been associated with early-onset AD in genetic linkage studies. These results argue for a certain degree of heterogeneity in the genetic origin of some forms of AD, although environmental risk factors cannot be ruled out in late-onset AD. In this preliminary study, we analyzed the geographical distribution of the birth places of a sample of 235 AD cases born in a defined region of Quebec (Canada), between 1895 and 1935. We wished to test the hypothesis that risk factors acting at, or around birth place and time play a role in the etiology of AD. The field of study was divided into rural and urban areas. A reference population of live births was used to compute a measure of odds ratio (OR). The OR results showed a statistically significant excess of AD cases in the rural area as compared to the reference population. When stratified for sex, the OR results showed a global excess of female AD cases in both the rural and the urban areas. For men, only the urban area presented a statistically significant deficit. We also analyzed the structures of the genealogical kinships of the rural and urban sub-groups. Although AD cases from the rural sub-group were more closely related to each other than those from the urban one, removal of the kin pairs from the OR analysis seemed to have little effect on the rural/urban distribution of cases. Therefore, the OR results would not appear to be due primarily to a difference in the kinship structures of the two sub-groups. This could mean that some risk factors for AD afflict women more strongly than men, the effect being different depending on the urban or rural origin. However, potential biases such as a higher rate of report for women, differential migration between birth places or a differential mortality ratio between sexes could produce spurious results in the direction of what we have observed in this preliminary study.

The liquid chromatographic determination of theophylline in untreated plasma by simple direct injection.

A liquid chromatographic method for determination of theophylline by direct injection of untreated plasma samples is described. Theophylline is detected without interference from related compounds such as paraxanthine. A precolumn venting technique is used which considerably increases column life. The lifetimes of the separation columns are unaffected by plasma injections whereas the precolumn has to be changed after 140 injections (10 mul of plasma). The peak purity of theophylline is examined spectrophotometrically. Determinations are performed by external standardization with recoveries close to 100% with a precision better than 2.3% (RSD).

The determination of lidocaine and its metabolites by a direct injection LC method using large sample volumes of untreated plasma.

Lidocaine and its N-dealkylated metabolites (glycylxylidide and monoethyl-glycylxylidide) have been determined at their therapeutic levels. The plasma samples were centrifuged and then injected directly into a liquid chromatograph containing a reversed-phase column with LiChrosorb RP-Select B as solid phase and 1-propanolaqueous buffer containing decanesulphonate as eluent. A pre-column venting plug technique was used, in which the chromatographic system consisted of two injector valves, a precolumn, a valve and a separation column. Lidocaine and its dealkylated metabolites were detected in the eluent by UV detection (210 nm) and the quantitations were performed by measurement of the peak areas of the samples and external standards. Lidocaine and its metabolites were determined in the therapeutic range with a percentage recovery close to 100% and inter-assay precision (RSD) of 1.0-2.2%.

[Unusual aspects of the late manifestations of diaphragmatic hernia]. / Aspect inhabituel d'une hernie diaphragmatique à révélation tardive.

A 5-year-old boy investigated for abnormality in right cardiophrenic angle was found on radiologic and perioperative exploration to have a large diaphragmatic hernia allowing right intrathoracic passage of stomach and colon. The diaphragmatic defect included a wide left middle diaphragmatic Bochdalek cleft adherent to hiatal orifice due to agenesis of pillars.

[Appendectomy with intraoperative celioscopy in children. 465 cases]. / Appendicectomies chez l'enfant sous coelioscopie opératoire. 465 cas.

The authors report a retrospective series of 465 appendectomies with intraoperative celioscopy in children under age 16. The technical issues and the indications are discussed. The results are the following: No death, 3.6% intraoperative incidents of no consequence, 3% postoperative complications, including 1.3% requiring second surgery or celioscopy. These results are better than those obtained with conventional surgery. The advantages of appendicectomy with intraoperative celioscopy are the following: easy, quick search for the appendix, whatever its location, exploration of the entire abdominal cavity, possibility to perform a complete peritoneal washing, suppression of parietal complications, and almost no skin scar, definite reduction in the number of intraperitoneal residual abscesses, and likely reduction of postoperative adhesions, which are a cause of obstruction, of chronic pain and of infertility in girls, rapid resumption of transit and of all activities, including sports.

Explanatory factors for health inequalities across different ethnic and gender groups: data from a national survey in England.

BACKGROUND: The objective of this study was to examine the relative contribution of factors explaining ethnic health inequalities (EHI) in poor self-reported health (pSRH) and limiting long-standing illness (LLI) between Health Survey for England (HSE) participants. METHOD: Using HSE 2003-2006 data, the odds of reporting pSRH or of LLI in 8573 Bangladeshi, Black African, Black Caribbean, Chinese, Indian, Irish and Pakistani participants was compared with 28,470 White British participants. The effects of demographics, socioeconomic position (SEP), psychosocial variables, community characteristics and health behaviours were assessed using separate regression models. RESULTS: Compared with White British men, age-adjusted odds (OR, 95% CI) of pSRH were higher among Bangladeshi (2.05, 1.34 to 3.14), Pakistani (1.77, 1.34 to 2.33) and Black Caribbean (1.60, 1.18 to 2.18) men, but these became non-significant following adjustment for SEP and health behaviours. Unlike Black Caribbean men, Black African men exhibited a lower risk of age-adjusted pSRH (0.66, 0.43 to 1.00 (p=0.048)) and LLI (0.45, 0.28 to 0.72), which were significant in every model. Likewise, Chinese men had a lower risk of age-adjusted pSRH (0.51, 0.26 to 1.00 (p=0.048)) and LLI (0.22, 0.10 to 0.48). Except in Black Caribbean women, adjustment for SEP rendered raised age-adjusted associations for pSRH among Pakistani (2.51, 1.99 to 3.17), Bangladeshi (1.85, 1.08 to 3.16), Black Caribbean (1.78, 1.44 to 2.21) and Indian women (1.37, 1.13 to 1.66) insignificant. Adjustment for health behaviours had the largest effect for South Asian women. By contrast, Irish women reported better age-adjusted SRH (0.70, 1.51 to 0.96). CONCLUSIONS: SEP and health behaviours were major contributors explaining EHI. Policies to improve health equity need to monitor these pathways and be informed by them.

Biopsy diagnosis of intraductal carcinoma is prognostic in intermediate and high risk prostate cancer patients treated by radiotherapy.

AIM: We investigated the prognostic significance of intraductal carcinoma of the prostate (IDC-P) in biopsies and transurethral resections prior to external beam radiotherapy with or without androgen deprivation. METHODS: Cohort 1 consisted of 118 intermediate risk prostate cancer patients treated by radiotherapy, with biochemical relapse as primary end-point (median follow-up 6.5 years). Cohort 2 consisted of 132 high risk patients, enrolled in a phase III randomised trial (EORTC 22863) comparing radiotherapy alone to radiotherapy with long-term androgen deprivation (LTAD) with clinical progression free survival as primary end-point (median follow-up 9.1 years). Presence of IDC-P was identified after central review. Multivariable regression modelling and Kaplan-Meier analysis were performed with IDC-P as dichotomous variable. RESULTS: IDC-P was a strong prognosticator for early (<36 months) biochemical relapse (HR 7.3; p = 0.007) in cohort 1 and for clinical disease-free survival in both arms of cohort 2 (radiotherapy arm: HR 3.5; p < 0.0001; radiotherapy plus LTAD arm: HR 2.8, p = 0.018). IDC-P retained significance after stratification for reviewed Gleason score in the radiotherapy arm (HR 2.3; p = 0.03). IDC-P was a strong prognosticator for metastatic failure rate (radiotherapy arm: HR 5.3; p < 0.0001; radiotherapy plus LTAD arm: HR 3.6; p = 0.05). CONCLUSIONS: IDC-P in diagnostic samples of patients with intermediate or high risk prostate cancer is an independent prognosticator of early biochemical relapse and metastatic failure rate after radiotherapy. We suggest that the presence of IDC-P in prostate biopsies should routinely be reported.