Topical nitrogen mustard therapy in patients with Langerhans cell histiocytosis

Background Langerhans cell histiocytosis (LCH) is characterized by abnormal proliferation and infiltration of Langerhans cells in different organs. The skin is frequently involved either as unisystem or multisystem disease. Objectives To review the clinical response and side‐effects of nitrogen mustard therapy in LCH in children and adults with unisystem or multisystem disease. Patients and methods This retrospective study includes 10 children and four adults with LCH, treated with nitrogen mustard from 1975 to 2010. The median extent of skin involvement was 46% (range 5–100%). Results Overall, 13 patients had complete or partial response. Although eight patients achieved a complete response with a median time of 12·3 months (range 36 days to 1·9 years), six of these patients ultimately relapsed. One patient, who had unisystem disease limited to the skin, initially showed progression of her cutaneous lesions with nitrogen mustard treatment. Although subsequently the cutaneous lesions completely regressed, concomitant systemic involvement was noted. Four other patients similarly experienced improvement of their skin lesions with treatment, but also exhibited progression of the LCH systemically. The patients were treated with other therapies prior and adjunctive to nitrogen mustard. However, five patients had progression to other organs, despite regression of skin lesions, which supports that the treatment effect in the skin is related to topical nitrogen mustard. Six patients developed contact dermatitis to nitrogen mustard. Conclusions Topical nitrogen mustard can be an effective and safe therapy in both children and adults with cutaneous LCH, although relapses are common.     

Cortisol awakening response and negative emotionality linked to asymmetry in major limbic fibre bundle architecture

The limbic system plays an important role in regulating the hypothalamic-pituitary-adrenal (HPA) axis as well as aspects of emotion, and both neuroendocrine disturbance and increased negative emotionality are associated with risk for developing affective disorders. However, the extent to which the architecture of connections between limbic structures may be linked to individual differences in basal HPA-axis reactivity and negative emotionality is unknown. Here we tested the hypotheses that microstructural asymmetry of the major limbic fibre bundles would be associated with cortisol awakening response (CAR) and neuroticism, a personality trait associated with the tendency to experience negative emotions. Sixty-nine healthy adults were studied with diffusion-weighted imaging, and fractional anisotropy (FA) was extracted from the cingulum and uncinate fasciculus. Higher neuroticism scores, which were associated with higher CAR, were also correlated with higher right relative to left cingulum FA. Elevated CAR was associated with the degree of FA asymmetry within both the cingulum and the uncinate fasciculus, but in opposing directions. These results suggest that the balance between left- and right-sided limbic circuits may bear an important relationship to hypothalamic-pituitary-adrenal axis reactivity, and to the tendency to experience negative emotions, and they raise important questions about the significance of limbic system architecture.     

Design issues and priorities in team and nonpharmacological arthritis care research

Nonpharmacologic and team care research present unique design challenges. Nonpharmacologic care by nature is multifaceted and complex. Rarely do patients receive an intervention in isolation. The delivery of a single or group of interventions can be provided by one provider but is frequently provided by teams. Therefore, it is imperative that clinical researchers design studies that evaluate single and multimodal interventions as well as studies that best reproduce the team model of service delivery to accurately examine interventions. While it is well accepted that the research question drives the design, it is imperative to recognize that certain aspects of nonpharmacologic and team care restrict the implementation or effectiveness of specific design components. For example, as patients are required to actively engage in lifestyle changes, double-blinding cannot be employed. In addition, there is no accepted operational definition of team care in arthritis. It is important to keep in mind the characteristics of these interventions in the selection of a research design and develop strategies to best examine these interventions. Combining aspects of randomized controlled trials with qualitative methods is one technique to enrich data collected on these interventions. Certain features of pharmacovigilance studies may also serve as an alternative model. The use of national or regional registries for longterm clinical followup as seen in orthopedic surgery may prove to be applicable in the design of studies for evaluation of team care. Our article will discuss issues related to the design and synthesis of arthritis care research, and the role of patients in the design of clinical trials; describe collaborative international activities furthering team and nonpharmacological arthritis care research; and identify research activities that may influence future practice and the health of people with arthritis.     

Cytomegalovirus infection in lung transplant patients: the role of prophylaxis and recipient-donor serotype matching

Cytomegalovirus (CMV) remains an important cause of morbidity and mortality in lung transplant recipients. We investigated the incidence of CMV infection in relation to CMV prophylaxis, and recipient-donor CMV serotype, in a cohort of 250 consecutive lung transplant recipients. All patients received 3 months CMV prophylaxis with acyclovir (n = 67) or gancyclovir (n = 183). Recipient-donor CMV serotype matching was performed in patients receiving acyclovir: R+/D+(n = 38), R+/D-(n = 10), R-/D+(n = 1), R- /D-(n = 16), unknown (n = 2). Recipient-donor CMV serotype matching was not performed in patients receiving gancyclovir: R+/D+(n = 71), R+/D-(n = 42), R-/D+(n = 38), R-/D-(n = 31), unknown (n = 1). The overall incidence of CMV infection was 51% (n = 34) in the acyclovir group, and 42% (n = 77) in the gancyclovir group (p = 0.14). During the first 9 months after transplantation, the rate of CMV infection was higher in the acyclovir group (42%) compared with the gancyclovir group (30%) (p = 0.005). Multivariate analysis demonstrated the incidence of CMV infection during the first 9 months was higher for acyclovir prophylaxis (p<0.001) and R-/D+ serostatus (p<0.001) and lower with R-/D- serostatus (p = 0.02). In conclusion, gancyclovir significantly delays the onset of first CMV infection among lung transplant patients. CMV surveillance and choice of prophylaxis may be modified according to donor-recipient CMV serotype.     

口服避孕药：不会增加死亡风险

本研究旨在确定服用口服避孕药的女．胜其死亡风险是否高于未服用者。本次前瞻性试验研究，由英国全科医生资料库和（或）国家健康服务中心登记处提供始于1968年的死亡资料，对46112位女性持续观察了39年，其中未使用口服避孕药的女性为378006人年，曾服用者为819175人年，主要观察终点未口服和口服避孕药者之间全因和特异性死亡的相对风险。     

Bolus Intravenous Injection of Phosphorothioate Oligonucleotides Causes Hypotension by Acting as α1-Adrenergic Receptor Antagonists

Bolus intravenous injections of phosphorothioate oligonucleotides (PS-ODN) into primates cause profound hypotension, which has been attributed to complement activation, the biochemical pathway leading to acute inflammatory response. Because the hypotension was not accompanied by peripheral or pulmonary edema and epinephrine was not effective, but administration of 200 ml Ringer's lactate was effective, we examined the possibility that the 15-base PS-ODN interferes with sympathetic tone. We administered doses ranging from 3.3 to 10 mg/kg of a 15-base PS-ODN as a 30–60 s iv bolus into the right atrium of conscious Macaca mulatta. Blood pressure fell to 27 mm Hg following a 5.0 mg/kg dose, but no hypotension was observed after a 3.3 mg/kg dose; 10 mg/kg was lethal. Adrenergic receptor binding was evaluated in radioligand binding assays using rat cerebral cortex membranes with radiolabeled prazosin. The 15-base PS-ODN competes with prazosin for the α₁-adrenergic receptor with an IC50 of 14 μM, which favors binding over serum albumin (K_d = 37 to 48 μM). Admixing serum albumin with 5.0 mg/kg 15-base PS-ODN prior to injection prevented hypotension, suggesting that unbound PS-ODN interferes with sympathetic tone before binding to plasma proteins. Interactions of the 15-base PS-ODN with the α₁-adrenergic receptor in vivo were confirmed by a decreased response to phenylephrine. Reducing the length from 15 to 9 or 5 bases abolished α₁-adrenergic receptor binding in vitro and bolus infusion of 5.0 mg/kg of 9-base PS-ODN no longer produced hypotension. In conclusion, the 15-base PS-ODN shows cooperative binding to the α₁-adrenergic receptor, which produces cardiovascular effects that are oligomer length, dose, and formulation dependent.     

LMW-400型MRI装置RF激励脉冲中尖刺噪声的消除

ＬＭＷ－４００型ＭＲＩ装置的射频激励信号中有尖刺噪声。此尖刺噪声在ＲＦ脉冲之后出现，具有约４０％的最大ＲＦ脉冲值。由于它存在于读出梯度期间。故必须消除此尖刺噪声以减少图像伪像。在调制板上进行的试验表明，由于两个控制信号的沿边突然升起，这种噪声是固有的。对此两种信号采用简单的积分电路，可成功地消除此种尖刺噪声。