STAT3-Deficient hyperimmunoglobulin E syndrome: report of a case with orofacial granulomatosis–like disease

Hyperimmunoglobulin E syndrome (HIES) is a rare heterogeneous primary immunodeficiency disorder characterized by infections of the lung and skin, elevated serum immunoglobulin E, and involvement of soft and bony tissues. Autosomal dominant HIES and related disorders are caused by defects in the Janus activated kinase–signal transducer and activator of transcription signaling pathway, leading to reduced numbers of T helper cell type 17 and impaired production of interleukin (IL)-17 A, IL-17 F, and IL-22. In addition, neutrophils have chemotactic defects, resulting in impaired responses at skin and lung sites. We report here a case of orofacial granulomatosis–like disease in a teenage boy ultimately found to have autosomal dominant HIES caused by a heterozygous mutation in the STAT3 gene

The prevalence and characteristics of breakthrough cancer pain in patients receiving low doses of opioids for background pain

The aim of this study was to assess the prevalence and characteristics of breakthrough cancer pain (BTcP) in patients receiving low doses of opioids for background pain. A consecutive sample of advanced cancer patients receiving less than 60 mg/day of oral morphine equivalent (OME) was selected. Epidemiological data, background pain intensity, and current analgesic therapy were recorded. The presence of BTcP was diagnosed according to a standard algorithm. The number of BTcP episodes, intensity of BTcP, its predictability and triggers, onset duration, interfer-ence with daily activities, BTcP medications, satisfaction with BTcP medication, and time to meaningful pain relief were collected. A total of 126 patients were screened. The mean intensity of background pain was 2.71 (1.57), and the mean OME was 28.5 mg/day (SD15.8). BTP episodes were recorded in 88 patients (69.8 %). The mean number/day of BTP episodes was 4.1 (SD 7.1, range 1– 30). In a significant percentage of patients, BTcP was both predictable and unpredictable (23%). The BTcP onset was less than 20 min in the majority of patients. The mean duration of untreated episodes was 47.5 (SD 47.6) minutes. The mean time to meaningful pain relief after taking a BTcP medication was >20 min in 44.5% of patients. The efficacy of BTcP medication was not considered good in more than 63% of patients. Gender (females) (OR = 4.16) and lower Karnofsky (OR = 0.92) were independently associated with BTcP. A higher number of BTcP episodes/day was associated with gender (females) (p = 0.036), short duration of BTcP (p = 0.005), poorer efficacy of BTcP medication (none or mild) (p = 0.001), and late meaningful pain relief (p = 0.024). The poor efficacy of BTcP medication was independently associated with a higher number of episodes/day (OR = 0.22). In patients who were receiving low doses of opioids, BTcP prevalence was 69.8%. Many patients did not achieve a sufficient level of satisfaction with BTcP medications, particularly with oral morphine. Data also suggest that better optimization of background analgesia, though apparently acceptable, may limit the number of BTcP episodes

Sneutrino Mass Measurements at e+e- Linear Colliders

It is generally accepted that experiments at an e+e- linear colliders will be able to extract the masses of the selectron as well as the associated sneutrinos with a precision of ~ 1% by determining the kinematic end points of the energy spectrum of daughter electrons produced in their two body decays to a lighter neutralino or chargino. Recently, it has been suggested that by studying the energy dependence of the cross section near the production threshold, this precision can be improved by an order of magnitude, assuming an integrated luminosity of 100 fb^-1. It is further suggested that these threshold scans also allow the masses of even the heavier second and third generation sleptons and sneutrinos to be determined to better than 0.5%. We re-examine the prospects for determining sneutrino masses. We find that the cross sections for the second and third generation sneutrinos are too small for a threshold scan to be useful. An additional complication arises because the cross section for sneutrino pair to decay into any visible final state(s) necessarily depends on an unknown branching fraction, so that the overall normalization in unknown. This reduces the precision with which the sneutrino mass can be extracted. We propose a different strategy to optimize the extraction of m(\tilde{\nu}_\mu) and m(\tilde{\nu}_\tau) via the energy dependence of the cross section. We find that even with an integrated luminosity of 500 fb^-1, these can be determined with a precision no better than several percent at the 90% CL. We also examine the measurement of m(\tilde{\nu}_e) and show that it can be extracted with a precision of about 0.5% (0.2%) with an integrated luminosity of 120 fb^-1 (500 fb^-1).Comment: RevTex, 46 pages, 15 eps figure

Opioids Switching with Transdermal Systems in Chronic Cancer Pain

<p>Abstract</p> <p>Background</p> <p>Due to tolerance development and adverse side effects, chronic pain patients frequently need to be switched to alternative opioid therapy</p> <p>Objective</p> <p>To assess the efficacy and tolerability of an alternative transdermally applied (TDS) opioid in patients with chronic cancer pain receiving insufficient analgesia using their present treatment.</p> <p>Methods</p> <p>A total of 32 patients received alternative opioid therapy, 16 were switched from buprenorphine to fentanyl and 16 were switched from fentanyl to buprenorphine. The dosage used was 50% of that indicated in equipotency conversion tables. Pain relief was assessed at weekly intervals for the next 3 weeks</p> <p>Results</p> <p>Pain relief as assessed by VAS, PPI, and PRI significantly improved (p < 0.0001) in all patients at all 3 follow up visits. After 3 weeks of treatment, the reduction in the mean VAS, PPI, and PRI scores in the fentanyl and buprenorphine groups was 68, 77, 74, and 69, 79, and 62%, respectively. Over the same time period the use of oral morphine as rescue medication was reduced from 27.5 ± 20.5 (mean ± SD) to 3.75 ± 8.06, and 33.8 ± 18.9 to 3.75 ± 10.9 mg/day in the fentanyl and buprenorphine groups, respectively. There was no significant difference in either pain relief or rescue medication use between the two patient groups The number of patient with adverse events fell during the study. After the third week of the treatment the number of patients with constipation was reduced from 11 to 5, and 10 to 4 patients in the fentanyl and buprenorphine groups, respectively. There was a similar reduction in the incidence of nausea and vomiting. No sedation was seen in any patient after one week of treatment.</p> <p>Conclusion</p> <p>Opioid switching at 50% of the calculated equianalgesic dose produced a significant reduction in pain levels and rescue medication. The incidence of side effects decreased and no new side effects were noted. Further studies are required to provide individualized treatment for patients according to their different types of cancer.</p

Analysis of Long-Lived Slepton NLSP in GMSB model at Linear Collider

We performed an analysis on the detection of a long-lived slepton at a linear collider with $\sqrt{s}=500$ GeV. In GMSB models a long-lived NLSP is predicted for large value of the supersymmetry breaking scale $\sqrt{F}$. Furthermore in a large portion of the parameter space this particle is a stau. Such heavy charged particles will leave a track in the tracking volume and hit the muonic detector. In order to disentangle this signal from the muon background, we explore kinematics and particle identification tools: time of flight device, dE/dX and Cerenkov devices. We show that a linear collider will be able to detect long-lived staus with masses up to the kinematical limit of the machine. We also present our estimation of the sensitivity to the stau lifetime.Comment: Minor changes, Ref. 10 fixed. 12 pages, RevTex, 4 eps figure

C4BQ0: a genetic marker of familial HCV-related liver cirrhosis.

Source Department of Medicine and Pneumology, V Cervello Hospital, Via Trabucco 180, 90146 Palermo, Italy. [email protected] Abstract BACKGROUND AND METHODS: Host may have a role in the evolution of chronic HCV liver disease. We performed two cross-sectional prospective studies to evaluate the prevalence of cirrhosis in first degree relatives of patients with cirrhosis and the role of two major histocompatibility complex class III alleles BF and C4 versus HCV as risk factors for familial clustering. FINDINGS: Ninety-three (18.6%) of 500 patients with cirrhosis had at least one cirrhotic first degree relative as compared to 13 (2.6%) of 500 controls, (OR 7.38; CI 4.21-12.9). C4BQ0 was significantly more frequent in the 93 cirrhotic patients than in 93 cirrhotic controls without familiarity (Hardy-Weinberg equilibrium: chi2 5.76, P = 0.016) and in 20 families with versus 20 without aggregation of HCV related cirrhosis (29.2% versus 11.3%, P = 0.001); the association C4BQ0-HCV was found almost only in cirrhotic patients with a family history of liver cirrhosis. CONCLUSIONS: Our studies support the value of C4BQ0 as a risk indicator of familial HCV related cirrhosis

Epidemiology and Characteristics of Episodic Breathlessness in Advanced Cancer Patients: An Observational Study

CONTEXT: Episodic breathlessness is a relevant aspect in patients with advanced cancer. OBJECTIVES: The aim of this study was to assess the different aspects of this clinical phenomenon. METHODS: A consecutive sample of patients with advanced cancer admitted to different settings for a period of six months was surveyed. The presence of background breathlessness and episodic breathlessness, their intensity (numerical scale 0-10), and drugs used for treatment were collected. Factors inducing episodic breathlessness and its influence on daily activities were investigated. RESULTS: Of 921 patients, 29.3% (n = 269) had breathlessness and 134 patients (49.8%) were receiving drugs for background breathlessness. In the multivariate analysis, the risk of breathlessness increased with chronic obstructive pulmonary disease, although it decreased in patients receiving disease-oriented therapy and patients with gastrointestinal tumors. The prevalence of episodic breathlessness was 70.9% (n = 188), and its mean intensity was 7.1 (SD 1.6). The mean duration of untreated episodic breathlessness was 19.9 minutes (SD 35.3); 41% of these patients were receiving drugs for episodic breathlessness. The majority of episodic breathlessness events (88.2%) were triggered by activity. In the multivariate analysis, higher Karnofsky Performance Status levels were significantly related to episodic breathlessness, although patients receiving disease-oriented therapy were less likely to have episodic breathlessness. CONCLUSION: This study showed that episodic breathlessness frequently occurs in patients with breathlessness in the advanced stage of disease, has a severe intensity, and is characterized by rapid onset and short duration, which require rapid measures

Multidimensional statistical technique for interpreting the spontaneous breakthrough cancer pain phenomenon. A secondary analysis from the IOPS-MS study

: Breakthrough cancer pain (BTcP) is a temporary exacerbation of pain that "breaks through" a phase of adequate pain control by an opioid-based therapy. The non-predictable BTcP (NP-BTcP) is a subtype of BTcP that occurs in the absence of any specific activity. Since NP-BTcP has an important clinical impact, this analysis is aimed at characterizing the NP-BTcP phenomenon through a multidimensional statistical technique. This is a secondary analysis based on the Italian Oncologic Pain multiSetting-Multicentric Survey (IOPS-MS). A correlation analysis was performed to characterize the NP-BTcP profile about its intensity, number of episodes per day, and type. The multiple correspondence analysis (MCA) determined the identification of four groups (phenotypes). A univariate analysis was performed to assess differences between the four phenotypes and selected covariates. The four phenotypes represent the hierarchical classification according to the status of NP-BTcP: from the best (phenotype 1) to the worst (phenotype 4). The univariate analysis found a significant association between the onset time &gt;10 min in the phenotype 1 (37.3%)' vs. the onset &gt; 10 min in phenotype 4 (25.8%) (p &lt; 0.001). Phenotype 1 was characterized by the gastrointestinal type of cancer (26.4%) with respect to phenotype 4, where the most frequent cancer affected the lung (28.8%) (p &lt; 0.001). Phenotype 4 was mainly managed with rapid-onset opioids, while in phenotype 1, many patients were treated with oral, subcutaneous, or intravenous morphine (56.4% and 44.4%, respectively; p = 0.008). The ability to characterize NP-BTcP can offer enormous benefits for the management of this serious aspect of cancer pain. Although requiring validation, this strategy can provide many indications for identifying the diagnostic and therapeutic gaps in NP-BTcP management

Viable Supersymmetric Models with an Inverted Scalar Mass Hierarchy at the GUT Scale

Supersymmetric models with an inverted mass hierarchy (IMH: multi-TeV first and second generation matter scalars, and sub-TeV third generation and Higgs scalars) have been proposed to ameliorate phenomenological problems arising from flavor changing neutral currents (FCNCs) and CP violating processes, while satisfying conditions of naturalness. Models with an IMH already in place at the GUT scale have been shown to be constrained in that for many model parameter choices, the top squark squared mass is driven to negative values. We delineate regions of parameter space where viable models with a GUT scale IMH can be generated. We find that larger values of GUT scale first and second generation scalar masses act to suppress third generation scalars, leading to acceptable solutions if GUT scale gaugino masses are large enough. We show examples of viable models and comment on their characteristic features. For example, in these models the gluino mass is bounded from below, and effectively decouples, whilst third generation scalars remain at sub-TeV levels. While possibly fulfilling criteria of naturalness, these models present challenges for detection at future pp and e^+e^- collider experiments.Comment: 16 page REVTEX file with 6 PS figure

Yukawa Unified Supersymmetric SO(10) Model: Cosmology, Rare Decays and Collider Searches

It has recently been pointed out that viable sparticle mass spectra can be generated in Yukawa unified SO(10) supersymmetric grand unified models consistent with radiative breaking of electroweak symmetry. Model solutions are obtained only if $\tan\beta \sim 50$, $\mu <0$ and positive $D$-term contributions to scalar masses from SO(10) gauge symmetry breaking are used. In this paper, we attempt to systematize the parameter space regions where solutions are obtained. We go on to calculate the relic density of neutralinos as a function of parameter space. No regions of the parameter space explored were actually cosmologically excluded, and very reasonable relic densities were found in much of parameter space. Direct neutralino detection rates could exceed 1 event/kg/day for a $^{73}$Ge detector, for low values of GUT scale gaugino mass $m_{1/2}$. We also calculate the branching fraction for $b\to s \gamma$ decays, and find that it is beyond the 95% CL experimental limits in much, but not all, of the parameter space regions explored. However, recent claims have been made that NLO effects can reverse the signs of certain amplitudes in the $b\to s\gamma$ calculation, leading to agreement between theory and experiment in Yukawa unified SUSY models. For the Fermilab Tevatron collider, significant regions of parameter space can be explored via $b\bar{b}A$ and $b\bar{b}H$ searches. There also exist some limited regions of parameter space where a trilepton signal can be seen at TeV33. Finally, there exist significant regions of parameter space where direct detection of bottom squark pair production can be made, especially for large negative values of the GUT parameter $A_0$.Comment: Added comparison to Blazek/Raby results and added Comments on de Boer et al. b->s gamma result