Problem‐maintaining circles: Case illustrations of formulations that truly guide therapy

The cognitive behaviour therapy (CBT) emphasis on treatment relevance in assessment, and on evidence‐based intervention, has led to an increasing focus on problem maintenance factors (vs. precipitants) in both its models of psychopathology and in its individual case formulations. This article describes the reasons for this growing focus, and presents a generic CBT model based on the functional analysis of “problem‐maintaining circles” (PMCs) of causes. Some samples of the profuse literature implicating PMCs in many psychological disorders are presented, and the utility of PMC‐based functional analysis, case formulation, or modelling of psychopathology is advanced, not only as a guide to selection of therapeutic interventions, but as an alternative to standard psychiatric diagnosis. A sampling of a taxonomy of such PMCs is presented. And finally, the clinical application of PMC‐based functional analysis, case formulation, and treatment selection is illustrated in five case illustrations drawn from a recent clinical caseload.     

Genetic testing for inherited eye conditions in over 6,000 individuals through the eyeGENE network

Genetic testing in a multisite clinical trial network for inherited eye conditions is described in this retrospective review of data collected through eyeGENE®, the National Ophthalmic Disease Genotyping and Phenotyping Network. Participants in eyeGENE were enrolled through a network of clinical providers throughout the United States and Canada. Blood samples and clinical data were collected to establish a phenotype:genotype database, biorepository, and patient registry. Data and samples are available for research use, and participants are provided results of clinical genetic testing. eyeGENE utilized a unique, distributed clinical trial design to enroll 6,403 participants from 5,385 families diagnosed with over 30 different inherited eye conditions. The most common diagnoses given for participants were retinitis pigmentosa (RP), Stargardt disease, and choroideremia. Pathogenic variants were most frequently reported in ABCA4 (37%), USH2A (7%), RPGR (6%), CHM (5%), and PRPH2 (3%). Among the 5,552 participants with genetic testing, at least one pathogenic or likely pathogenic variant was observed in 3,448 participants (62.1%), and variants of uncertain significance in 1,712 participants (30.8%). Ten genes represent 68% of all pathogenic and likely pathogenic variants in eyeGENE. Cross‐referencing current gene therapy clinical trials, over a thousand participants may be eligible, based on pathogenic variants in genes targeted by those therapies. This article is the first summary of genetic testing from thousands of participants tested through eyeGENE, including reports from 5,552 individuals. eyeGENE provides a launching point for inherited eye research, connects researchers with potential future study participants, and provides a valuable resource to the vision community.     

Changes in the withdrawal bleeding pattern and endometrial histology during 17β-estradiol —dydrogesterone therapy in postmenopausal women: a 2 year prospective study

Objective: To describe changes in the withdrawal bleeding pattern and endometrial histology during a sequential 17β-estradiol —dydrogesterone regimen in postmenopausal women. Design: Open-label, non-comparative, prospective study. Setting: Gynecological outpatient department of a university hospital. Patients: Twenty-seven healthy nonhysterectomized postmenopausal women. Interventions: Continuous micronized 17β-estradiol supplementation, 2 mg daily, and cyclic administration of dydrogesterone, 10 mg daily for the first half of each 28 day treatment cycle. Main Outcome Measures: Changes in the characteristics of the withdrawal bleeding pattern and the endometrial biopsy histology during 2 years of treatment. Results: The initial withdrawal bleeding was comparable to normal menstruation with respect to amount and duration. During the 2 years of treatment the bleeding showed a significant tendency to become shorter with less blood loss. This was mainly the result of the decrease (P < 0.001) in the number of days per cycle with bleeding grade II (normal menstruation). None of the women developed endometrial hyperplasia, and in almost all women the given hormone replacement therapy regimen induced secretory or atrophic changes of the endometrium. Conclusions: This sequential 17β-estradiol —dydrogesterone regimen can be regarded as safe with respect to the prevention of endometrial disease and appeared to foster patient compliance.     

Life in the Future Versus Life in the Present

Roemer and Orsillo have provided an integrative perspective for developing more effective therapies for generalized anxiety disorder, based on existing knowledge about the disorder, cognitive behavioral approaches to its treatment, and conceptualizations and treatment methods from the acceptance/mindfulness tradition. The present commentary expands upon the notion of the adaptive value of focused attention on present-moment experience and cognitive perspectives that can facilitate that process.     

Candida and antibiotic-associated diarrhoea

The role of Candida in antibiotic-associated diarrhoea (AAD) has been controversial for many years. Since Candida exists physiologically in the gastrointestinal tract, the presence of small numbers of Candida organisms in stool has therefore been considered normal, and thus non-pathogenic. Increased Candida counts have been linked to the development of diarrhoea in antibiotic-treated patients. However, recent findings have not confirmed this. To date, there is no convincing evidence that Candida may cause AAD in adults.     

Lipofectin介导转移的外源性ADA基因在反复上感儿T淋巴细胞的表达

本文对４１例健康儿童和１７例反复上呼吸道感染患儿外周血淋巴细胞腺苷脱氨酶（ＡＤＡ）活性进行了检测。在此基础上筛选出２例反复上感伴ＡＤＡ活性低下患儿。在体外对这２例患儿的外周血Ｔ淋巴细胞进行培养后，以Ｌｉｐｏｆｅｃｔｉｎ（脂质体）介导的方法对其进行了外源性ＡＤＡ基因的基因转移。结果显示：２例患儿体外培养淋巴细胞ＡＤＡ活性较转基因前升高。同步进行的标志基因ｐＢＬａｃＺ的基因转移的检测结果也直观地证实了Ｌｉｐｏｆｅｃｔｉｎ介导的基因转移是成功的。该研究为ＡＤＡ－ＳＣＩＤ淋巴细胞基因治疗的研究提供了初步的体外实验资料。     

药物洗脱支架用于急性心肌梗死的临床观察

目的评价药物涂层支架用于急性心肌梗死的安全性及临床疗效。方法34例发病1周以内的急性心肌梗死患者梗塞相关动脉机械性再灌注治疗时使用药物涂层支架,并于术后3～12个月进行门诊及电话随访,必要时复查冠状动脉造影,观察住院及随访期间心血管事件发生率(死亡、再发急性心肌梗死及血管重建术)。结果37枚药物涂层支架(CYPHER15枚,TAXUS22枚)植入34个梗塞相关动脉(其中3处病变各植入2枚支架),支架长度(22.7±9.0)mm,支架直径(3.1±0.3)mm;10例(29.4%)接受直接经皮冠状动脉介入治疗(PCI),3例(8.8%)为挽救性PCI。支架植入成功率100%。1例(2.9%)支架内急性血栓形成,行急诊血管重建术。平均随访间期(5.9±2.8)个月,2例(5.9%)于随访期间因再发原部位心肌梗死入院治疗,1例因非靶血管病变致心绞痛于术后10个月入院治疗。住院及随访期间无死亡病例发生。结论研究提示药物涂层支架用于急性心肌梗死患者治疗梗塞相关动脉行机械性再灌注安全,可获得与药物涂层支架用于择期的、相对简单的冠状动脉病变的类似疗效。     

Intra-articular IL-10 gene transfer regulates the expression of collagen-induced arthritis (CIA) in the knee and ipsilateral paw

We studied the effects of local IL-10 application, introduced by a recombinant human type 5 adenovirus vector, in the mouse knee joint during the early phase of CIA. One intra-articular injection with the IL-10-expressing virus (Ad5E1mIL-10) caused substantial over-expression of IL-10 in the mouse knee joint, using virus dosages which did not induce distracting inflammation. High expression of IL-10 was noted for a few days, being maximal at day 1. One intra-articular injection of Ad5E1mIL-10 in the knee joints of collagen type II (CII)-immunized mice, before onset of CIA was noted, reduced the incidence of collagen arthritis in that knee. Of high interest, the protective effect of local IL-10 expression by Ad5E1mIL-10 was not restricted to the knee joint alone. The arthritis incidence in the ipsilateral paw was highly suppressed. In contrast, local IL-10 over-expression was not effective when treatment was started after onset of CIA. Further analysis in the acute streptococcal cell wall-induced arthritis model revealed that local IL-10 over-expression markedly suppressed the production of tumour necrosis factor-alpha (TNF-alpha) and IL-1alpha, but had no significant effect on IL-1beta and IL-12 production in the inflamed synovium. These data indicate that local over-expression of IL-10 in the knee joint of mice regulates the expression of collagen arthritis, probably through down-regulation of TNF-alpha.     

白细胞介素3基因疗法和白细胞介素6基因疗法的联合造血调控作用

研究了成纤维细胞介导的ＩＬ－３基因疗法，ＩＬ－６基因疗法以两者联合后对造血系统的影响。结果发现，单用ＩＬ－基因疗法的小鼠白细胞总数，中性粒细胞，骨髓ＣＦＵ－ＧＭ，ＣＦＵ－ＭＫ等显著上升，但血小板上升程度经，单用ＩＬ－６基因疗法的小鼠血小板，中性粒细胞，骨髓ＣＦＵ－ＧＭ，ＣＦＵ－ＭＫ上晚为显著。     

帕罗西汀合用心理行为干预治疗老年期抑郁症的疗效

目的探讨帕罗西汀合用心理行为治疗对老年期抑郁症的疗效。方法将60例老年期抑郁症随机分成两组，进行为期6周的对照研究，出院后随访1年，分别用心理行为合并帕罗汀治疗（研究组）和帕罗西汀治疗（对照组）；采用汉密尔顿抑郁量表（HAMD）和临床疗效总评量表（CGI—SI）进行评定。结果研究组在治疗6周后HAMD评分（9．32±2．28）较对照组（13.17±3．39）有显著性差异（P〈0．01），研究组CGI—SI较对照组有显著性差异（P〈0．01），1年末随访时HAMD评分研究组（9.19±2．33）较对照组（13．98±4．96）有显著性差异（P〈0.01）。且研究组复发率低于对照组（P〈0.05）。结论帕罗西汀合用心理行为治疗对老年期抑郁症的疗效优于帕罗西汀，且复发率低。