The Ras inhibitor farnesylthiosalicylic acid as a potential therapy for neurofibromatosis type 1.

PURPOSE: Farnesylthiosalicylic acid (FTS) is a Ras inhibitor that dislodges all active Ras isoforms from the membrane. We assessed the ability of FTS to reverse the transformed phenotype of neurofibromatosis type 1 (NF1)-associated tumor cell lines of malignant peripheral nerve sheath tumor (MPNST). EXPERIMENTAL DESIGN: nf1 mutations were genotyped, allelic losses were analyzed, and neurofibromin expression levels were determined in MPNST cell lines ST88-14, S265P21, and 90-8. The effects of FTS on GTP-bound Ras (Ras-GTP) and its prominent downstream targets, as well as on cell morphology, anchorage-dependent and anchorage-independent growth, and tumor growth in mice, were assessed. RESULTS: The MPNST cell lines were biallelic, NF1 inactive, and neurofibromin deficient. We show that FTS treatment shortened the relatively long duration of Ras activation and signaling to extracellular signal-regulated kinase, Akt, and RalA in all NF1-deficient MPNST cell lines (NF1 cells) to that observed in a non-NF1, normally expressing neurofibromin MPNST cell line. These effects of FTS led to lower steady-state levels of Ras-GTP and its activated targets. Both anchorage-dependent and anchorage-independent growth of NF1 cells were dose dependently inhibited by FTS, and the inhibition correlated positively with Ras-GTP levels. NF1 cells were found to possess strong actin stress fibers, and this phenotype was also corrected by FTS. NF1 tumor growth in a nude mouse model was inhibited by oral FTS. CONCLUSIONS: FTS treatment of NF1 cells normalized Ras-GTP levels, resulting in reversal of the transformed phenotype and inhibition of tumor growth. FTS may therefore be considered as a potential drug for the treatment of NF1.     

Interaction between erythropoietin and peripheral polymorphonuclear leukocytes in continuous ambulatory dialysis patients

The effect of erythropoietin (EPO) on the oxidative stress (OS) and inflammation caused by polymorphonuclear leukocytes (PMNLs) in end-stage renal failure patients undergoing continuous ambulatory peritoneal dialysis (CAPD) was investigated in vivo and in vitro. The studies were performed on isolated PMNLs from peripheral blood of CAPD patients before and following 6 weeks of EPO treatment and from healthy controls. OS was expressed by the rate of superoxide release from phorbol 12-myristate 13-acetate (PMA) stimulated isolated PMNLs and the inflammatory state was evaluated by PMNL counts of the enrolled subjects. Following 6 weeks of EPO treatment in CAPD patients, both the rate of superoxide release from PMNLs and PMNL counts fell significantly when compared with the pretreatment values. In vitro incubation of PMNLs from CAPD patients with increasing amounts of EPO displayed a significant reduction in their rates of superoxide release. EPO, by direct interaction with PMNLs, attenuated their primed state, causing reduction in oxidative stress and inflammation.     

What do family planning clients and university students in Nairobi, Kenya, know and think about emergency contraception?

Currently, emergency contraception is seldom used in Kenya. As part of a larger study designed to provide insight into the possible roles for the method in Kenya, we assessed the knowledge of and attitudes towards emergency contraception in two groups of potential users, and we focus on these data specifically in this paper. We interviewed clustered samples of clients at ten family planning clinics in Nairobi (n = 282) and conducted four focus group discussions with students at two universities in Kenya (n = 42). Results show that despite relatively low levels of awareness and widespread misinformation, when the method was explained, both clients and students expressed considerable interest, but also expressed some health and other concerns.     

Unmet needs and relationship challenges of head and neck cancer patients and their spouses

ABSTRACT

In head and neck cancer (HNC), couple-based interventions may be useful for facilitating treatment completion, patient rehabilitation, and improving both partners' quality of life. With the goal of identifying targets for future interventions, we conducted a qualitative study to understand patient and spouse unmet needs and relationship challenges during curative radiotherapy for HNC. Semistructured interviews were conducted with six HNC patients (83% male) and six spouses (83% female) within 6 months of completing treatment. Interviews were audiotaped and transcribed using grounded theory analysis. Patients and spouses identified several unmet needs including better preparation regarding the severity of physical side effects, a clearer timeline for recovery, and strategies for dealing with their own and each other's emotional reactions. Caregiver's unmet needs included balancing competing roles/responsibilities, making time for self-care, and finding effective strategies for encouraging patient's self-care. Eighty-three percent of spouses and all patients reported increased conflict during treatment. Other relationship challenges included changes in intimacy and social/leisure activities. Findings suggest that couple-based interventions that emphasize the importance of managing physical and psychological symptoms through the regular practice of self-care routines may be beneficial for both patients and spouses. Likewise, programs that teach spouses ways to effectively motivate and encourage patients' self-care may help minimize conflict and help couples navigate HNC treatment and recovery together as a team.     

Evidence of chorda tympani dysfunction in patients with burning mouth syndrome

BACKGROUND: More than two-thirds of patients with burning mouth syndrome (BMS) have altered taste sensation. The authors conducted a study to assess chorda tympani and trigeminal nerve function in these patients. METHODS: The study was composed of 48 patients; 22 were diagnosed as having BMS, 14 had burning symptoms related to other diseases and were diagnosed as having secondary burning mouth syndrome (SBMS), and 12 were healthy volunteers. The authors evaluated the electrical detection thresholds of the infraorbital and mental nerves and the electrical taste and electrical detection/tingling thresholds in the anterior two-thirds of the tongue for all patients. Electrical taste threshold is thought to be dictated by chorda tympani nerve function while electrical detection/tingling thresholds are regulated by trigeminal nerve function. RESULTS: The mean electrical taste/tingling detection thresholds ratio and the taste detection thresholds were significantly higher in patients with BMS than in patients with SBMS and in control subjects, indicating chorda tympani nerve dysfunction. Eighteen (82 percent) of the 22 patients with BMS demonstrated chorda tympani dysfunction (13 unilateral and five bilateral). CONCLUSIONS: Chorda tympani hypofunction may play an important role in BMS pathology. Unilateral hypofunction may be sufficient to produce generalized burning sensation exceeding the affected nerve area. CLINICAL IMPLICATIONS: Elevated taste detection threshold levels determined via electrogustatory testing and an elevated taste/tingling detection thresholds ratio may assist clinicians in the diagnosis of BMS. More studies are needed to validate these findings.     

The Behavioural Assessment of the Dysexecutive Syndrome (BADS) in schizophrenia and its relation to functional outcomes

The purpose of this study was to establish further the validity of the Behavioural Assessment of the Dysexecutive Syndrome (BADS) in a population with schizophrenia. Specific objectives were: to examine the construct validity and sensitivity of the BADS in differentiating between adult inpatients during an acute episode of illness, adult outpatients in the chronic stages of illness, and healthy controls; and to examine the predictive validity of the BADS regarding functional outcomes within the chronic group. Participants were 30 inpatients during an acute episode of their illness; 31 outpatients in the chronic stage; and 93 healthy controls. Instruments included the BADS, the Neurobehavioral Cognitive Status Examination (Cognistat) and the Routine Task Inventory (RTI). Significant differences in BADS scores were found between participants with schizophrenia and healthy controls, and between both groups of patients, showing the chronic group to have more deficits in executive functions. In addition, within the chronic group the BADS was found to be a significant predictor of two of the RTI outcome areas, instrumental activities of daily living (IADL) and communication, beyond that accounted for by basic cognitive skills. These results support the validity of the BADS within the schizophrenic population, and highlight the importance of measuring executive functions for rehabilitation     

The relationship between emergency department volume and patient complexity

Introduction

Forecasting emergency department (ED) visits is a well-studied topic. The importance of understanding the complexity of patients along with the days and times of varying patient volumes is critical for planning medical and ancillary staffing. Though multiple studies stratify their results based on severity of disease, severity was determined by triage status. The goal of this study was to utilize a novel method to evaluate the correlation between daily emergency department patient complexity, based on Current Procedure Terminology (CPT) code, and day of the week.

Participation in leisure activities and sensory modulation deficiencies of children with atopic dermatitis

Aim: To examine whether the complexity of atopic dermatitis (AD) symptoms and the sensory modulation deficiencies (SMD) that accompany it may limit child’s preference to participate in leisure activities. Methods: Thirty‐seven children diagnosed with AD and 104 healthy peers aged 6–11 years participated in this study. Disease severity was assessed using SCORAD scores. Both groups were compared in regard to their sensory modulation abilities measured by the ‘Short Sensory Profile’ (SSP) and in regard to their activity preference measured by the ‘Preference for Activities of Children’ (PAC). Results: Children with AD showed lower preference to participate in leisure activities as compared with healthy peers (F = 4.63, p < 0.0001). Among children with AD, significant correlations were found between SMD in several modalities and preference to participate in specific leisure activities. No significant correlations were found between AD severity and the child’s preferred activities. Conclusions: Children with AD may show lower preference to participate in activities in comparison with their typical peers. This lower preference may be impacted by their SMD. Multidisciplinary intervention may be beneficial for children with AD. This intervention should refer to AD symptoms and considers the child’s sensory profile and participation in daily living.     

Development and evaluation of a cognitive-behavioral intervention for juvenile fibromyalgia

OBJECTIVE: To describe the development and test the efficacy of a cognitive-behavioral intervention (CBT) for juvenile fibromyalgia. METHOD: Sixty-seven children with fibromyalgia and their parents were recruited to participate in an 8-week intervention that included modules of pain management, psychoeducation, sleep hygiene, and activities of daily living. Children were taught techniques of cognitive restructuring, thought stopping, distraction, relaxation, and self-reward. Additionally, they kept daily pain and sleep diaries. Children completed questionnaires of pre- and post-treatment measuring physical status and psychological functioning. RESULTS: Following CBT, children reported significant reductions (p < .006) in pain, somatic symptoms, anxiety, and fatigue, as well as improvements in sleep quality. Additionally, children reported improved functional ability and had fewer school absences. CONCLUSION: Children with fibromyalgia can be taught CBT strategies that help them effectively manage this chronic and disabling musculoskeletal pain disorder.     

Assessments of the importance of provider characteristics for abortion care: data from women in Rajasthan, India

While client satisfaction is a widely recognized component of effective reproductive health care services, little is known about women's perspectives toward abortion care and providers. We use data from a large, community-based abortion knowledge, attitudes, and practices survey in Rajasthan, India, to describe women's assessments of the importance of eight attributes of potential abortion providers and to investigate the sociodemographic differentials in these assessments. Women prioritized technical aspects of abortion care, including provider skill and an equipped facility, and they deemphasized distance and postabortion contraceptive requirements. Although assessments were stable across many sociodemographic factors, the priorities of urban and rural women varied significantly. Women's prioritization of provider attributes should be incorporated into abortion services.