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Purpose The current randomized, double-blind, placebo-controlled clinical trial addressed the effects on penile erectile function of relatively high daily oral doses (6 g/day) of l-ARG for 3 months (N = 51) compared to placebo (N = 47), in patients with vasculogenic ED, with comparison between mild–moderate and severe vasculogenic ED. Methods The outcome measures included IIEF-6 score and cavernous arteries peak systolic flow velocity (PSV) at dynamic penile duplex ultrasonography (PDU). Results l-ARG supplementation for 3 months significantly increased IIEF-6 score in the overall cohort (p p p = 0.007) vasculogenic ED; PSV was significantly increased in the overall cohort (p p Conclusion The results of the current study demonstrated that supplementation with relatively high doses of l-ARG as a single compound for 3 months significantly improved penile erectile function, assessed by both IIEF-6 score and PSV at dynamic PDU in patients with mild–moderate, and improved IIEF-6 score, but not PSV, in patients with severe vasculogenic ED, therefore suggesting that l-ARG might be an alternative treatment in mild–moderate vasculogenic ED patients experiencing adverse effects or with contraindications for chronic treatment with PDE5i compounds.

Background Vascular Ehlers-Danlos syndrome (vEDS) is a rare inherited connective tissue disorder, leading to mainly arterial complications, caused by COL3A1 pathogenic variations. Ong et al. (Lancet 2010) showed that the introduction of celiprolol significantly reduced arterial events in a predominantly symptomatic population on arterial level. We reported the benefit of full dose of Celiprolol in longitudinal study to prevent arterial events in Frank et al. (JACC 2019). To our knowledge, there is no data regarding the benefit of celiprolol in patients without any arterial event. Purpose The aim of this study was to assess the occurrence of arterial events during follow-up in vEDS patients without arterial event. Methods All patients – probands and relatives – with a pathogenic variation in COL3A1 diagnosed at the Referral Centre for Rare Vascular Diseases since 2001 and at least one arterial tree assessment were included. We then focused on vEDS patients without any arterial event. We retrospectively analyzed the duration of follow-up, the occurrence of arterial events during follow-up, and the introduction and dose of celiprolol, especially at the time of occurrence of an arterial event. Results Among the 230 patients included, 144 (63%) had at least one symptomatic arterial event, 44 (19%) had only silent arterial event and 67 (29%) had no arterial event at the first arterial tree assessment event. Patients with no arterial event were significantly younger at this visit compared with the two other groups with a median age of 23 vs. 38 and 39 years (silent and symptomatic) (p Conclusions Genetic testing of the relatives of probands with vEDS remains of utmost importance as one quarter presented with symptomatic arterial event and one fifth had silent arterial event at initial arterial tree assessment. For patients with no arterial event, those without celiprolol have a similar incidence of arterial events than those with celiprolol, however their follow-up duration was twice shorter suggesting a higher incidence rate or arterial event in the absence of celiprolol. Funding Acknowledgement Type of funding sources: None.

To elicit oncology nurse leaders' perceptions and experiences of accessing, using and interpreting report data at the unit level, and their suggestions for future reports.Nurse leaders are expected to use data reports for decisions about unit-level operations, yet data may be inaccessible, unavailable and lack relevance for improving patient care and unit-level outcomes.A purposeful sampling was used to recruit 12 unit-level nurse leaders. Qualitative data were collected through semi-structured interviews and analysed using thematic content analysis.Consistent themes included the lack of accurate, useful and meaningful data specifically related to patient care. Accessibility Challenges, Limits to Applicability and Suggestions for Improvement were the main themes.Nurse leaders require real-time data to effectively implement clinical interventions and practice changes for improving unit-level patient care.Nurse leaders emphasized that their insight into the development of customizable reports is crucial for obtaining meaningful data relevant to the varied unit-level health care setting. Reports targeting unit-level outcomes would provide meaningful data to facilitate clinical improvement where patient care is provided. Improved reports increase the likelihood of their use and the potential for enhancing the quality and safe care outcomes.

This study will test the feasibility and effectiveness of mobile technology intervention on the patients' self-management of oral anticancer medication. Secondary objectives include acceptability, the usefulness of text messages, and satisfaction by participants and nurses.This prospective two-arm study will recruit patients (N = 220) with metastatic breast cancer and initiating treatment with palbociclib (Ibrance ®). Allowing for attrition, patients will be randomized into the control (N = 100) or intervention (N = 100) group. Unidirectional text message reminders will be sent during the treatment cycle through a secure web application using the patient's smartphone. Self-reported survey responses will be collected at three time points; at consent, end of treatment cycles, and the follow-up clinic visit and include a demographic questionnaire, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, Post study questionnaire and the R-15 Patient Satisfaction Questionnaire. Nurses providing care for study patients will complete the Adaptation of Stamps Nurse Workload questionnaire. Data will be analysed an intent-to-treat analysis comparing the two arms. Study approval was obtained in December 2019 and funded in January 2020.Smartphones are globally available and have text messaging capability which is increasingly being used as an intervention in healthcare studies. This study will test a low-cost, nurse-led intervention that enhances the patient's experience with oral anti-cancer medications, improves access to care, reduces costs, and improves the satisfaction of nurses caring for oncology patients.Despite the ease of administering oral anti-cancer medications, oncology patients maynot take them as prescribed and consequently, these factors affect patient outcomes and disease control. Given the importance of taking oral anti-cancer medications and the difficulties patients experience in achieving it, the effective use of mobile technology interventions can actively engage patients in their care and improve medication self-management of anticancer treatment regimens.目的: 本项研究旨在验证移动技术干预对患者口服抗癌药物自我管理的可行性和有效性。次要目的包括可接受性, 短信的有用性, 以及参与者和护士的满意度。 方法: 这项前瞻性双臂研究将招募转移性乳腺癌患者 (N=220) , 并开始使用帕博西尼(爱博新®) 进行治疗。考虑到损耗, 患者将被随机分为对照组 (N=100) 或干预组 (N=100) 。在治疗周期内, 将使用患者智能手机的安全web应用程序发送单向短信提醒。将在三个时间点收集自我报告的调查结果: 同意时、治疗周期结束时和随访门诊就诊, 包括人口统计问卷、欧洲癌症研究与治疗组织生活质量调查问卷, 研究后调查问卷和R-15患者满意度调查问卷。护理研究病人的护士将完成护士工作量调查问卷的改编。将分析数据, 并对两组数据进行意向-治疗分析比较。该项研究于2019年12月获得批准, 于2020年1月获得资助。 讨论: 智能手机在全球范围内均可使用, 并具有短信功能, 因此其越来越多地被用作医疗保健研究的干预手段。此项研究将测试一种低成本的、护士主导的干预措施, 以提高患者口服抗癌药物的经验、改善获得护理的机会、降低成本, 以及提高护理人员对肿瘤患者的满意度。 影响: 尽管口服抗癌药物很容易服用, 但肿瘤患者可能不按医嘱服用, 因此, 这些因素会影响患者恢复结果和疾病控制。考虑到口服抗癌药物的重要性以及患者在服用过程中遇到的困难, 有效地使用移动技术干预可以有效地让患者参与到他们的护理中, 并改善抗癌治疗方案的药物自我管理。.

Objective: This article describes how one comprehensive cancer center in the Northeast United States reorganized their nursing research fellowship (NRF) with the goals of engaging nurses in research processes, developing a culture of inquiry, building nursing research capacity, and sustaining infrastructures for facilitating high-quality, nurse-led oncology research studies. Methods: The basis for the curriculum, course work, and research practicum is derived from academic courses taught at the undergraduate, graduate, and doctoral levels. Evidence from the current literature, expertise of nurse-scientists, and feedback from former fellows provided the background for a fellowship model that included: (1) amending curriculum timeframes; (2) incorporating protected time; (3) improving access to resources; (4) enhancing the protection, data sharing, and accessibility of data; and (5) involving nurse-scientists as mentors and facilitators of research processes. These factors were incorporated over 3 years. Metrics included individual class and overall course evaluations and ongoing assessments. Results: In three cohorts from 2016 to 2019, a total of 21 nurses were accepted, and 18 (86%) nurses completed the NRF. In cohort 1 through cohort 3, 17 fellows presented their research findings internally, and a total of nine projects were presented at external forums. There were seven fellows whose manuscript submissions resulted in 21 journal publications. Of the 18 fellows, 15 (83%) conducted institutional review board-approved studies and three (17%) fellows developed studies involving one concept analysis and two systematic reviews. Conclusions: Utilizing technology, the fellowship improved access beyond the classroom setting. Improved application processes, the inclusion of protected time for nurses, and mentoring from nurse-scientists demonstrate a commitment to fostering a culture supporting new knowledge and innovation for improving patient care.

Objective The primary objective of this review is to analyze and synthesize the best available evidence on the experiences and perceptions of psychological stress reported by pancreatic cancer patients at any time point from pre-diagnosis, diagnosis, treatment, post-treatment and/or follow-up care. Introduction A cancer diagnosis is known to be life-threatening, altering and limiting, and negatively affects an individual's activities of daily living. Despite developments in treatment options for pancreatic cancer patients, it represents the highest mortality and morbidity among cancers. Stress is a subjective phenomenon that negatively impacts an individual's psychological and emotional well-being, and interferes with the ability to cope with cancer symptoms and treatments. Identifying a patient's experience of stress could facilitate educational, spiritual and social resources to address his or her emotional and psychological needs. Inclusion criteria Qualitative studies that include individuals with pancreatic cancers, regardless of age, sex or ethnicity, will be considered for inclusion in this review. Methods The databases to be searched include PubMed, CINAHL, Cochrane, Web of Science, Embase, Scopus, BioMed Central and PsycINFO. The search for gray literature will include Biosis, OpenGrey, Open Access Theses and Dissertations, and WorldCat. This systematic review will consider all published and unpublished studies with no date limitations. Selected studies will be assessed for methodological quality by two independent reviewers. Coding will be assigned to synthesize any differences in the experiences and perceptions of psychological stress at four time points. Where textual pooling is not possible, conclusions will be presented in narrative form.

Retinal degenerative diseases (RDD) such as retinitis pigmentosa (RP) have no treatment. Stem cell-based therapies could provide promising opportunities to repair the damaged retina and restore vision. We investigated a novel approach in which human retinal progenitor cells (RPCs) derived from primitive mesenchymal stem cells (pMSCs) were examined to treat retinal degeneration in an rd12 mouse model of RP. Intravitreally transplanted cells improved retinal function and significantly increased retinal thickness. Transplanted cells homed, survived, and integrated to various retinal layers. They also induced anti-inflammatory and neuroprotective responses and upregulated neurogenesis genes. We found that RPCs were more efficacious than pMSCs in improving the retinal structure and function. RNA analyses suggest that RPCs promote neuroprotection and neuronal differentiation by activating JAK/STAT and MAPK, and inhibiting BMP signaling pathways. These promising results provide the basis for clinical studies to treat RDD using RPCs derived from pMSCs.

Background Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs). Objectives This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD. Methods This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy. Results Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life. Conclusions In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253)

OBJECTIVES: Associations between the varying levels of emotional intelligence in newly hired oncology nurses and their responses to stress and coping were examined. The secondary aim was to analyze whether emotional intelligence could moderate their choice of problem-focused or emotion-focused coping strategies. METHODS: Newly hired nurses (n = 114) were recruited from a national cancer institute. Data were collected through surveys using the Ways of Coping Questionnaire, the Nursing Stress Scale and the Emotional Quotient Inventory between the eighth and twelfth weeks post-hire date. Descriptive and bivariate statistical analyses were conducted on all variables. Regression models determined whether emotional intelligence moderated the choice of coping strategies. RESULTS: Emotional intelligence had a mean value of M = 105.24, SD = 13.02 and occupational stress scores were M = 65.57, SD =15.68. Significant negative correlations were found for occupational stress and problem-focused coping (r = −.189, p = .022), emotional intelligence and emotion-focused coping (r = − .340, p = .000) and emotional intelligence and occupational stress (r = − .428, p < 0 .001). Positive correlations were noted between occupational stress and emotion-focused coping (r = .189, p = .022) and emotional intelligence and problem-focused coping (r = .340, p = .000). Emotional intelligence did not predict the choice of coping strategies. CONCLUSIONS: Though emotional intelligence did not moderate coping strategies in newly hired nurses, using problem focused coping to address occupational stress during the initial employment period may be a protective factor for coping with stress in the oncology workplace.

Riassunto Obiettivi Descrivere l’atteggiamento clinico nella risoluzione dei piu frequenti difetti di cresta da riabilitare con implantologia, sulla base delle metodiche maggiormente validate dalla letteratura scientifica. Materiali e metodi La rigenerazione guidata dell’osso attraverso membrane barriera ad azione occlusiva e praticabile in differenti difetti ossei alveolari. Tale fenomeno si puo comprendere se si conosce la cascata degli eventi biologici a carico dei tessuti duri e molli che si innesca durante la rigenerazione guidata. E indispensabile classificare i difetti localizzati delle creste edentule per poter adottare protocolli chirurgici appropriati laddove la morfologia non si associ a una rigenerazione spontanea. Risultati Mediante casi clinici esemplificativi il lavoro mostra i risultati ottenibili con l’applicazione dei principi della GBR, inserendo gli impianti in maniera protesicamente guidata e non costringendo il protesista a realizzare una protesi di compromesso. Conclusioni I casi clinici trattati, usando un protocollo ripetibile e validato, sono l’esempio che non e solo l’anatomia del difetto l’elemento discriminante la quota di GBR ottenibile quanto il mantenimento dell’“effetto tenda” che il Gore-Tex ® con rinforzo in titanio puo fornire se opportunamente sagomato.

Objective Bicuspid aortic valve (BAV) is associated with high incidence of ascending aortic aneurysm. In BAV sporadic form, changes in outflow's hemodynamic secondary to the valvular morphotype are said to play a prominent role in the aortic dilatation. We aimed at comparing the different ascending aorta segment diameters according to the morphotype and the function of the BAV. Methods We evaluated 174 patients with sporadic BAV by transthoracic echocardiography. The valvular function was defined as either Aortic Insufficiency (AI) if Grade ≥ 2 and aortic Stenosis (AS) if mean gradient > 20 mmHg. Aortic diameters were measured at the Valsalva sinus, tubular ascending aorta and at the aortic arch. Kruskal-Wallis, Mann–Whitney and Spearman tests were used for comparisons. Results Among the non-operated patients, Sievers’ morphotype was type 1LR for 63%, type 1NR for 18%, and other types counted for 19%. The Valsalva sinus diameter did not differ according to the Sievers’ type (P = 0.78). The type 1LR type compared to the type1NR appeared to have a wider tubular aorta, but not significantly (42.3 ± 8.5 vs. 36.4 ± 7.3 mm; P = 0.06). Aortic valve function was distributed as follows: AI: 39%, AS: 20%, Both: 9%, Normal: 32%. Comparison of the different valve dysfunctions revealed a difference at the Valsalva (P Conclusion Our results showed the tremendous role of AI in the aortic dilation of all segments except the arch. However no influence of BAV morphotype was noticed on aortic diameters. Our results give rise to the relatively limited influence of the valvular morphology in the development of aortic dilation.

Acute erythroleukemia is a relatively rare disorder of a multilineal nature. Patients with this type of leukemia traditionally have been treated with a standard myeloid protocol, with a wide variation in prognosis between M6a, which has a similar prognosis to acute myelogenous leukemias, and M6b, with an extremely poor outcome despite aggressive therapy. Forty-eight archival cases of acute erythroleukemia, subtypes M6a (the traditional FAB-M6), M6b (pure erythroleukemia), and M6c (>30% myeloblasts and >30% pronormoblasts by FAB exclusion criteria), were evaluated for multidrug resistance gene (MDR-1) status. Findings were correlated with clinical course and karyotypes. Immunohistochemical stain for the protein product of MDR-1, P-glycoprotein, was variably positive in 11 of 23 patients with M6a, as well as in all of the patients with M6b (strongly positive) and M6c (weakly positive). P-glycoprotein expression positively correlated with unfavorable cytogenetic aberrations, poor response to chemotherapeutic agents, and short survival. Most significant was that P-glycoprotein expression demonstrated a negative additive effect on response to treatment and prognosis with unfavorable cytogenetic anomalies. P-glycoprotein expression and multiple cytogenetic anomalies most probably contribute to the resistance to chemotherapy and poor survival characteristic of the patients with M6b (mean survival, 3.15 +/- 4.2 mo) and M6c (mean survival, 10.5 +/- 12.7 mo). Because patients with M6b and M6c have increased numbers of pronormoblasts in their bone marrow and past chemotherapeutic attempts have failed, chemotherapy directed at these cells is appropriate. Additional therapy directed toward the MDR-1 gene and its protein product seems indicated from our findings.

Acute erythroleukemia is an aggressive leukemia derived from a multipotential stem cell. Three subtypes have been described: (1) M6a with greater than or equal to 30% blasts of the nonerythrocytic component, (2) M6b with greater than or equal to 30% pronormoblasts of the erythrocytic elements, and (3) M6c with greater than or equal to 30% blasts and greater than or equal to 30% pronormoblasts by the aforementioned exclusion criteria. The poor prognosis associated with this disorder positively correlates with a high pronormoblast:myeloblast ratio; unfavorable cytogenetic aberrations; a high proliferative index; and the presence of P-glycoprotein expression (multidrug resistance phenotype). Chemotherapeutic regimens directed toward these specific parameters should be devised in order to improve the characteristically poor outcome of this patient population.

Acute erythroleukemia (FAB M6) is a rare heterogeneous disease with an increase in red cell precursors and myeloblasts. Three subsets have been described: M6A (myeloblast-rich erythroleukemia); M6B (proerythroblast-rich erythroleukemia); and M6C (myeloblast- and proerythroblast-rich mixed variant). This study was undertaken to define and compare the clinical courses and survival outcomes among M6A, M6B, and M6C variants of erythroleukemia. Sixty-nine cases of M6 leukemia were categorized as consisting of ≥50% erythroid of all nucleated cells and M6A with ≥30% myeloblasts/nonerythroid component; M6B with ≥30% proerythroblasts/erythroid component; and M6C with ≥30% myeloblasts and ≥30% proerythroblasts. The demographics, cell type distribution, and survival (mean ± sd) of these groups were compared. There were 32 M6A, 26 M6B, and 11 M6C patients. No significant difference was seen among the groups in age, sex, or treatment. Compared to M6A, both the M6B (P< 0.0001) and M6C (P< 0.0001) variants showed a statistically significant increase in the percentage of bone marrow erythroid cells, proerythroblasts, and the proerythroblasts/erythroid ratios. Comparing the groups for survival, M6B (3 ± 3.6 months) versus M6A (25 ± 28 months), P< 0.002, and M6C (10 ± 13 months) versus M6A, P< 0.01 had a poorer prognosis. Calculating the proerythroblasts as a component of total bone marrow erythroids provides a complimentary method for delineating the pure red cell erythroleukemia (M6B) and mixed variant (M6C), similar to that for the myeloid/erythroid (M6A) leukemia. Now that it is possible to delineate erythroleukemia subtypes, innovative treatments are indicated to target the malignant erythroid population, which is resistant to myeloid-based therapies. Am. J. Hematol. 65:5–13, 2000. © 2000 Wiley-Liss, Inc.

This article summarizes the European Union (EU) activities in the ACTS program satellite component of the UMTS. The projects INSURED, NEWTEST, SECOMS, SINUS, and TOMAS are introduced, and their R&D work on the services implemented in the different test platforms, the network integration scenario into the UMTS network, the studies performed for the air interface, the mobile terminals implemented, and the demonstrated applications are summarized. Furthermore, a new approach using neural networks for adaptive channel equalization and the concept for an EHF/Ka-band system are introduced.

Bromelain (BR) is a cysteine protease with inhibitory effects on intestinal secretion and inflammation. However, its effects on intestinal motility are largely unexplored. Thus, we investigated the effect of this plant-derived compound on intestinal contractility and transit in mice.Contractility in vitro was evaluated by stimulating the mouse isolated ileum, in an organ bath, with acetylcholine, barium chloride, or electrical field stimulation. Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine. Transit was also evaluated in pathophysiologic states induced by the pro-inflammatory compound croton oil or by the diabetogenic agent streptozotocin.Bromelain inhibited the contractions induced by different spasmogenic compounds in the mouse ileum with similar potency. The antispasmodic effect was reduced or counteracted by the proteolytic enzyme inhibitor, gabexate (15 × 10(-6) mol L(-1) ), protease-activated receptor-2 (PAR-2) antagonist, N(1) -3-methylbutyryl-N(4) -6-aminohexanoyl-piperazine (10(-4) mol L(-1) ), phospholipase C (PLC) inhibitor, neomycin (3 × 10(-3) mol L(-1) ), and phosphodiesterase 4 (PDE4) inhibitor, rolipram (10(-6) mol L(-1) ). In vivo, BR preferentially inhibited motility in pathophysiologic states in a PAR-2-antagonist-sensitive manner.Our data suggest that BR inhibits intestinal motility - preferentially in pathophysiologic conditions - with a mechanism possibly involving membrane PAR-2 and PLC and PDE4 as intracellular signals. Bromelain could be a lead compound for the development of new drugs, able to normalize the intestinal motility in inflammation and diabetes.

BACKGROUND: Acne vulgaris is a complex, chronic, and common skin disorder of pilosebaceous units. The major pathogenic factors involved are ductal hyperkeratinization, obstruction of sebaceous follicles resulting from abnormal keratinization of the infundibular epithelium, stimulation of sebaceous gland secretion by androgens, and microbial colonization of pilosebaceous units by Propionibacterium acnes, which promotes perifollicular inflammation. AIM: The aim of the study was to investigate the therapeutic effects of resveratrol, a natural phytoalexin produced by some spermatophytes, such as grapes and other plants, on acneic skin. METHODS: Resveratrol was incorporated in a carboxymethylcellulose-based gel. The chemical stability of resveratrol after storage at 4°C for 30 days was investigated by high-performance liquid chromatography (HPLC). The resveratrol-containing hydrogel was administered to 20 patients affected by acne vulgaris enrolled in this single-blind study. The resveratrol-containing formulation was applied daily as a solo treatment on the right side of the face for 60 days, while the hydrogel vehicle was applied to the left side of the face as a control. To objectively evaluate the results, a digital photographic database was used to collect images. The number and type of lesions were recorded for each patient, to compare the Global Acne Grading System (GAGS) score before treatment with that obtained at the end of the study. Moreover, with the innovative technique of follicular biopsy, areas of acneic skin were prepared for histopathology. The average area occupied by microcomedones at baseline was compared with that at the end of treatment. RESULTS: HPLC analysis demonstrated that resveratrol, upon incorporation into the gel, did not convert to its cis-isomer when stored at 4°C for 30 days. All patients were satisfied with the active treatment and none experienced adverse effects. Clinical evaluation showed a 53.75% mean reduction in the GAGS score on the resveratrol-treated sides of the face compared with 6.10% on the vehicle-treated sides of the face. These data were supported by histologic analysis, which showed a 66.7% mean reduction in the average area of microcomedones on the resveratrol-treated sides of the face. The comparison with the vehicle-treated side of the face (9.7% reduction) showed a clinically relevant and statistically significant decrease of lesions in areas treated with resveratrol-containing hydrogel. CONCLUSION: This pilot study showed positive results for resveratrol gel in acne, and should be considered a valid starting point for further testing of the effectiveness of this molecule in different concentrations and formulations and in a larger group of patients.

Satellites are expected to play an essential role in bridging the ldquodigital dividerdquo; satellite networks are likely to be the only way to provide broadband services to regions that cannot be economically reached by terrestrial networks, in particular the more remote regions of Europe and the rest of the world. Security can be a problem for such global services. This paper presents a link layer security solution and how it is implemented for the unidirectional lightweight encapsulation (ULE). A satellite testbed is constructed where the ULE security implementation is validated. The experiments results are presented in this paper.

The diagnosis of granular acute lymphoblastic leukemia (ALL) can be problematic as the cytoplasmic granules found in many blast cells may mimic those seen in acute myelogenous leukemia (AML). This rare variant of B-cell ALL is more commonly diagnosed in children, but may occur in adults. We report a case of granular B-ALL in a 56-year-old female and review the literature.

Recent studies of acute erythroleukemias have reaffirmed DiGuglielmo's syndrome (M6a, myeloblast-predominant) and disease (M6b, pronormoblast-predominant). M6c (mixed myeloblast/pronormoblast) has also been described. However, MDS is still defined according to the percentage of myeloblasts (% myeloblasts) without including the pronormoblast count. A 20-year retrospective study was performed to identify cases demonstrating >or=50% erythrocytic component and

The purpose of this methods paper is to offer pediatricians and nuclear medicine physicians a diagnostic protocol for performing lymphoscintigraphy in newborns that may be useful for enhancing diagnosis and management of newborns with congenital lymphatic abnormalities. Indications for lymphoscintigraphy, choice of tracer, optimal dose, routes of administration, methods of data acquisition, timing, and interpretation of results for newborns are presented and discussed.

This paper presents the IST RELY project which aims at Integrating Satellite Digital Radio Broadcasting (S-DB), terrestrial cellular technology and EGNOS satellite navigation

We report on three infants with congenital chylothorax (CC) and congenital pulmonary lymphangiectasia (CPL). CPL appears to be a characteristic pathological finding in CC. Through the use of lymphoscintigraphy and computed tomography, this study suggests that CC and CPL are strongly correlated entities and that the dysplasia of the lymphatic system results in a pulmonary lymphatic obstruction sequence. The initial microscopic dilatation of the lymph channels may lead to progressive weeping of lymphatics and, consequently, to pleural effusion. Non-Immune Hydrops Fetalis (NIHF) may be the final consequence of impaired systemic venous return and may help to explain pleural-pulmonary involvement in this generalized lymph-vessel malformation syndrome.

The mechanism by which the immune system of a tumor-bearing host acquires tolerance toward tumor antigens is still elusive. Antigen-presenting cells (APCs) are critical regulators of the decision between immune response and tolerance. APCs that express the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) have been found to inhibit T-cell responses both in vitro and in vivo. We hypothesized that malignant tumors exploit this mechanism by recruiting IDO-expressing APCs to the tumor-draining lymph nodes. To test this hypothesis, archival tissues and records of 26 cases of lymph node dissection for invasive cutaneous melanoma were obtained. IDO immunohistochemistry was performed on 14 cutaneous tumors and 328 regional lymph nodes. Abnormal accumulations of IDO-positive cells with a monocytoid or plasmacytoid morphology were identified in the perisinusoidal regions of draining lymph nodes in 45% of nodes studied. Recruitment of IDO-positive cells was seen in nodes with and without malignancy. We hypothesize that these IDO-positive APCs may contribute mechanistically to acquired tolerance to tumor antigens. Immunostaining of tumor-draining lymph nodes for abnormal accumulation of IDO-expressing cells might thus constitute an adverse prognostic factor and could contribute to the decision process and the appropriate care of patients with this deadly disease.

In the last few years, a variety of experimental and clinical studies concerning the formation, metabolism, and cellular effects of cholesterol oxidation products (COPs) have been carried out. Nevertheless, a substantial lack of knowledge exists regarding the possible intake of these compounds by the newborn through human and/or adapted formula milk. As far as the pathological role of COPs is concerned, exhaustive studies have shown that since dietary COPs are cytotoxic and atherotoxic, they may lead to adverse effects on health. The aim of this study was to investigate the possible development of cholesterol oxidation in adapted formula and in human milk by comparing the main cholesterol oxidation biomarker (7-ketocholesterol) concentration in both. To do so, the total (bonded and free) 7-ketocholesterol content was measured in ten fresh human mature milk samples and in ten milk adapted formula samples by high performance liquid chromatography and diode array detection. The 7-ketocholesterol human milk content (0.7±0.3) was often below the quantifiable limit (0.5μg/g of extracted lipids) while 7-ketocholesterol adapted milk concentrations were often above (3.6±4.0) this limit. The 7-ketocholesterol content of adapted formula samples was significantly higher as compared to human milk samples (P This is the first study to provide data concerning the concentrations of cholesterol oxides in human milk and in formula milk. Our results clearly suggest that the manufacturing technologies employed and the nutrient extractive sources play a crucial role in the development of cholesterol oxides in the end product. Careful surveillance has to be paid in order to avoid alteration of bioactive properties of nutrients and/or development of potentially toxic derivative compounds.

A computer software package was developed to perform the calculation involved in compounding total and partial parenteral nutrition for low-birth-weight and sick newborns. The program requires a minimum of user input and is menu-driven. The flexibility of the algorithm has been increased to a considerable degree. The program calculates the overall balance of fluids, nutrients, calories, electrolytes and minerals. It allows for the possibility of total parenteral nutrition and simultaneous oral feeding. Nutrient amounts per Kg per day and combination of enteral food and parenteral infusions can be completely changed by the operator. In our experience computer-assisted system was more efficient than a manual system and the possibility of computational error was reduced.

Acute erythroleukemia (FAB M6) is a rare heterogeneous disease with an increase in red cell precursors and myeloblasts. Three subsets have been described: M6A (myeloblast-rich erythroleukemia); M6B (proerythroblast-rich erythroleukemia); and M6C (myeloblast- and proerythroblast-rich mixed variant). This study was undertaken to define and compare the clinical courses and survival outcomes among M6A, M6B, and M6C variants of erythroleukemia. Sixty-nine cases of M6 leukemia were categorized as consisting of/=50% erythroid of all nucleated cells and M6A with/=30% myeloblasts/nonerythroid component; M6B with/=30% proerythroblasts/erythroid component; and M6C with/=30% myeloblasts and/=30% proerythroblasts. The demographics, cell type distribution, and survival (mean +/- sd) of these groups were compared. There were 32 M6A, 26 M6B, and 11 M6C patients. No significant difference was seen among the groups in age, sex, or treatment. Compared to M6A, both the M6B (P0.0001) and M6C (P0.0001) variants showed a statistically significant increase in the percentage of bone marrow erythroid cells, proerythroblasts, and the proerythroblasts/erythroid ratios. Comparing the groups for survival, M6B (3 +/- 3.6 months) versus M6A (25 +/- 28 months), P0. 002, and M6C (10 +/- 13 months) versus M6A, P0.01 had a poorer prognosis. Calculating the proerythroblasts as a component of total bone marrow erythroids provides a complimentary method for delineating the pure red cell erythroleukemia (M6B) and mixed variant (M6C), similar to that for the myeloid/erythroid (M6A) leukemia. Now that it is possible to delineate erythroleukemia subtypes, innovative treatments are indicated to target the malignant erythroid population, which is resistant to myeloid-based therapies.

Acute erythroleukemia is an aggressive leukemia derived from a multipotential stem cell. Three subtypes have been described: (1) M6a with greater than or equal to 30% blasts of the nonerythrocytic component, (2) M6b with greater than or equal to 30% pronormoblasts of the erythrocytic elements, and (3) M6c with greater than or equal to 30% blasts and greater than or equal to 30% pronormoblasts by the aforementioned exclusion criteria. The poor prognosis associated with this disorder positively correlates with a high pronormoblast:myeloblast ratio; unfavorable cytogenetic aberrations; a high proliferative index; and the presence of P-glycoprotein expression (multidrug resistance phenotype). Chemotherapeutic regimens directed toward these specific parameters should be devised in order to improve the characteristically poor outcome of this patient population.

T patient was a 47-year-old man whose past medical history was significant for renal transplant, as well as refractory anemia with ringed sideroblasts (Figure 1) diagnosed 1 year previously. He re-presented to his hematologist/oncologist with fatigue and weight loss. The only medications he was taking at the time of presentation were cyclosporine and prednisone. Physical examination was noncontributory. A complete blood count revealed anemia, thrombocytopenia, and rare blasts. A bone marrow aspirate and biopsy were performed and revealed 51% erythrocytic precursors (Figure 2). Characteristic features included the presence of 41% pronormoblasts by FrenchAmerican-British (FAB) exclusion criteria, with marked dysplastic change and ‘‘block-and-blush’’ periodic acid– Schiff positivity (Figure 3) of the erythroid cell lineage. There were 22% myeloblasts by FAB exclusion criteria, with minimal dysplasia of the granulocytic cell line. A diagnosis of acute erythroleukemia, M6b (pure erythroleukemia, Di Guglielmo disease) was established. Cytogenetic analysis demonstrated a complex karyotype with abnormalities of both chromosomes 5 and 7. Review of the previous bone marrow slides confirmed the original diagnosis. The patient underwent 6 cycles of arabinosylcytosine (cytarabine)/daunorubicin therapy. Sequential intrachemotherapy and postchemotherapy bone marrow specimens revealed ablation of all hematopoietic elements, with the exception of the pronormoblasts. The patient died 21⁄2 months after initial diagnosis. A leukemia composed of purely erythrocytic precursors was first described by Di Guglielmo in 1926 and was designated Di Guglielmo disease. Until recently, this fulminant acute leukemia was alternately classified as a myeloproliferative disorder or a myelodysplastic syndrome. Nevertheless, a number of articles and books have described the complex cytogenetics and extremely poor outcome associated with this disease, which represents a distinct leukemic entity.1–4 The overall presentation and outcome of the patient described here are in keeping with previous descriptions of this condition.1,2 Investigators studying this leukemic process proposed that this disorder be renamed

A huge European effort has been deployed in the UMTS definition and standardisation framework. Since the system aims at being “universal”, and “mobile”, a great deal of the preparations consist of identifying future service needs and analysing all technical and technological problems before system development. This work has been undertaken in European research bodies, industry and standardisation organisations, and has had extensive progress in the terrestrial domain. On the other hand, a great deal of work remains for the integration of the satellite component, and this concerns all aspects of the system. Work on this has been started in previous RACE projects such as MONET and SAINT. The results obtained in these projects are used as a basis for the SINUS project. (7 pages)

This is a case of a long-term Connecticut resident who presented with both human granulocytic ehrlichiosis and Lyme disease. The etiologic agents and the probability of coinfection are discussed.

We report a rare case of testicular histiocytoid hemangioma. Pathological features and differential diagnosis of this neoplasm are discussed. Testicular vascular tumors are rare, and include cavernous hemangioma,' capillary hemangioma? papillary endothelial hyperplasia3 and hemangioend~thelioma.~*~ The term histiocytoid hemangioma was proposed by Rosai et a1 to refer to certain vascular proliferations of skin, soft tissue, large blood vessels, bone and heart.6 The microscopic marker of these lesions is the proliferation of plump endothelial cells with bland nuclear features accompanied by a mixed inflammatory cell infiltrate. Histiocytoid hemangioma has rarely been described in the We report an additional case of histiocytoid hemangioma of the testis. CASE REPORT A 33-year-old white man consulted a urologist after palpating a mass in the right testis. The patient had no history of trauma or infection and no other symptoms. Medical and family histories were unremarkable. His wife had recently given birth to their second child. Physical examination was unremarkable except for a hard, approximately 2 cm. mass in the right testis with no significant testicular enlargement. Ultrasound revealed a 1.7 cm. mass in the upper half of the right testis. Findings were most consistent with a neoplastic process and radical inguinal orchiectomy was subsequently performed. Convalescence was uneventful. PATHOLOGICAL FINDINGS

Background Rapid detection of bloodstream infections (BSIs) can be lifesaving. We investigated the sample processing and assay parameters necessary for highly-sensitive detection of bloodstream bacteria, using Staphylococcus aureus as a model pathogen and an automated fluidic sample processing – polymerase chain reaction (PCR) platform as a model diagnostic system. Methodology/Principal Findings We compared a short 128 bp amplicon hemi-nested PCR and a relatively shorter 79 bp amplicon nested PCR targeting the S. aureus nuc and sodA genes, respectively. The sodA nested assay showed an enhanced limit of detection (LOD) of 5 genomic copies per reaction or 10 colony forming units (CFU) per ml blood over 50 copies per reaction or 50 CFU/ml for the nuc assay. To establish optimal extraction protocols, we investigated the relative abundance of the bacteria in different components of the blood (white blood cells (WBCs), plasma or whole blood), using the above assays. The blood samples were obtained from the patients who were culture positive for S. aureus. Whole blood resulted in maximum PCR positives with sodA assay (90% positive) as opposed to cell-associated bacteria (in WBCs) (71% samples positive) or free bacterial DNA in plasma (62.5% samples positive). Both the assays were further tested for direct detection of S. aureus in patient whole blood samples that were contemporaneous culture positive. S. aureus was detected in 40/45 of culture-positive patients (sensitivity 89%, 95% CI 0.75–0.96) and 0/59 negative controls with the sodA assay (specificity 100%, 95% CI 0.92–1). Conclusions We have demonstrated a highly sensitive two-hour assay for detection of sepsis causing bacteria like S. aureus directly in 1 ml of whole blood, without the need for blood culture.

Cryptococcal meningitis following autologous stem cell transplantation in a patient with multiple myeloma

Background Bromelain (BR) is a cysteine protease with inhibitory effects on intestinal secretion and inflammation. However, its effects on intestinal motility are largely unexplored. Thus, we investigated the effect of this plant-derived compound on intestinal contractility and transit in mice. Methods Contractility in vitro was evaluated by stimulating the mouse isolated ileum, in an organ bath, with acetylcholine, barium chloride, or electrical field stimulation. Motility in vivo was measured by evaluating the distribution of an orally administered fluorescent marker along the small intestine. Transit was also evaluated in pathophysiologic states induced by the pro-inflammatory compound croton oil or by the diabetogenic agent streptozotocin. Key Results Bromelain inhibited the contractions induced by different spasmogenic compounds in the mouse ileum with similar potency. The antispasmodic effect was reduced or counteracted by the proteolytic enzyme inhibitor, gabexate (15 × 10−6 mol L−1), protease-activated receptor-2 (PAR-2) antagonist, N1-3-methylbutyryl-N4-6-aminohexanoyl-piperazine (10−4mol L−1), phospholipase C (PLC) inhibitor, neomycin (3 × 10−3 mol L−1), and phosphodiesterase 4 (PDE4) inhibitor, rolipram (10−6 mol L−1). In vivo, BR preferentially inhibited motility in pathophysiologic states in a PAR-2-antagonist-sensitive manner. Conclusions & Inferences Our data suggest that BR inhibits intestinal motility – preferentially in pathophysiologic conditions – with a mechanism possibly involving membrane PAR-2 and PLC and PDE4 as intracellular signals. Bromelain could be a lead compound for the development of new drugs, able to normalize the intestinal motility in inflammation and diabetes.

The following abstracts are compiled from Check Sample exercises published in 2008. These peer-reviewed case studies assist laboratory professionals with continuing medical education and are developed in the areas of clinical chemistry, cytopathology, forensic pathology, hematology, microbiology, surgical pathology, and transfusion medicine. Abstracts for all exercises published in the program will appear annually in AJCP. # 1 Fetal Lung Maturity Testing Clinical Chemistry No. CC 08-1 (CC-367) {#article-title-2} Neonatal respiratory distress syndrome (RDS) is a disorder of pulmonary immaturity with a high mortality characterized by low levels of pulmonary surfactant. Gestational age determines risk based on concentration of pulmonary surfactant, ie, as gestation progresses the concentration of pulmonary surfactant increases. As a result, newborns delivered at fewer than 28 weeks have a more than 60% risk of RDS, whereas those delivered at more than 34 weeks have a less than 5% risk of RDS. In situations where gestational age alone is not sufficient to determine RDS risk and preterm delivery is medically needed, amniotic fluid analysis can be performed to determine pulmonary surfactant concentration. Four common methods are the lecithin-sphingomyelin ratio, phosphatidylglycerol measurement, surfactant-albumin ratio, and lamellar body count. All of these tests have excellent negative predictive values but poor positive predictive values, ie, they are great at confirming maturity but poor at confirming immaturity. # 2 Alkaline Phosphatase Isoenzyme Analysis: Guiding the Differential Diagnosis of Elevated Serum Total Alkaline Phosphatase Clinical Chemistry No. CC 08-2 (CC-368) {#article-title-3} The measurement of alkaline phosphatase (ALP) has long been used in clinical medicine, primarily to aid the diagnosis and monitoring of liver and bone diseases. Its diagnostic utility is limited by the enzyme’s wide tissue distribution and by a variety of potential nonpathologic causes. Isoenzyme analysis is one of several tools available to the clinician hoping to further characterize an elevated total ALP. It provides differentiation among liver, bone, intestinal, placental, and tumor-related forms as the cause of an elevation. The case presents a patient with persistent elevated ALP and atypical bands in the isoenzyme electrophoresis gel. An atypical ALP may be the result of a macroenzyme, which, if present, complicates interpretation of the test result and may cause additional, unnecessary testing or procedures. Recognizing and reporting a macroenzyme is an important service the clinical laboratorian can provide a clinician. # 3 Indirect Phlebotomy: Is It Good Practice? Clinical Chemistry No. CC 08-3 (CC-369) {#article-title-4} Indirect phlebotomy, the collection of blood samples through vascular infusion devices, is a common practice adopted to minimize needle-stick pain and discomfort in hospitalized patients. However, this practice can lead to alteration of the specimen and medical errors associated with misrepresentation of the blood test values. Among the possible problems, dilution or concentration of a particular analyte may occur, depending on the contents of the line’s infusate. Although some studies may indicate that blood collection from lines can be acceptable for isolated laboratory tests, there are insufficient data to demonstrate the reliability of line draws as routine practice. Use of lines for specimen collection should be reserved only for those patients with truly poor vascular access or those patients who require multiple phlebotomies in a short time period. Samples should be collected from lines only under a direct physician order, with careful attention to technique and established protocols that take many variables into account, including the analytes, contents of the line, type of line, discard blood volume, time interval between interruption of infusion and sampling, and catheter size. Even with careful attention to these details, clinicians must remain wary of the potential for medical errors related to misinterpretation of laboratory test results based on such samples.

Case: A 73 year old male with no significant past medical history presented with chronic fatigue. A routine CBC revealed an H/H of 6.8/19, MCV 103, WBC 4,100 and platelet count 92,000. Reticulocyte count was 0.6%. Serum iron, B12 and red cell folate studies were within normal limits. A bone marrow aspiration and biopsy were performed. Bone Marrow Findings: The bone marrow aspirate showed an M:E ratio of 1.8:1, with 33% erythrocytic elements. There was markedly left shifted erythropoiesis, with 57% of erythrocytic precursors being pronormoblasts. 1.2% blasts were present. Moderate erythrocytic dysplasia was present, with mild granulocytic and megakaryocytic changes. Vacuolated pronormoblasts were readily identified. No ringed sideroblasts were present. A diagnosis of MDS, NOS was rendered. No cytogenetics were obtained. Follow-up: The patient was transfused 4 units of packed red cells. Due to the patient’s rapidly deteriorating condition, comfort measures only were provided. The patient died 2.5 weeks after the bone marrow procedure. No autopsy was performed. The cause of death was listed as MDS. Discussion: This case is an extremely rare instance of left shifted erythropoiesis in the absence of the requisite number of erythrocytic elements for consideration of acute erythroleukemia (50%). By current definitions, this is an example of a fulminant MDS. However, this case does beg the question of whether or not pronormoblasts should be included in the assessment of malignant disorders of bone marrow.

Our group has been actively researching the acute erythroleukaemias since the late 1980s, during which time, we have developed and extensively published our classification1–5: We have also published abstracts and presented this classification at meetings of the International Academy of Pathology, International Society of Haematology, and the American Society of Haematology, and our recommendations have also been cited in the recent literature. Therefore, we are surprised to …