多囊卵巢综合征患者使用屈螺酮与心血管事件相关性分析

本研究探讨多囊卵巢综合征（PCOS）患者使用含屈螺酮的口服避孕药（OC）发生心血管事件的风险。28例PCOS（Rotterdam标准）患者,根据体重指数分成两组,其中16例体瘦者（A组）和12例体胖者（组B）,年龄在18—35岁,未使用激素治疗时间均在6个月以上。给予一种OC药治疗。观察治疗前与治疗6个月后来普汀、同型半胱氨酸、内皮素-1的水平和肱动脉血流介导的血管舒张等指标的变化。     

Neuroimaging of inhibitory control areas in children with attention deficit hyperactivity disorder who were treatment naive or in long-term treatment

OBJECTIVE: Difficulty with response inhibition is a cardinal symptom of attention deficit hyperactivity disorder (ADHD), combined type. Prefrontal and cingulate brain regions are known to be involved in inhibitory control. Event-related functional magnetic resonance imaging (fMRI) might establish if these regions differ in their activity in ADHD children relative to healthy comparison subjects. METHOD: Fifteen healthy comparison subjects and 17 children with ADHD, combined type, completed fMRI studies while performing the Stop Signal Task. Eight ADHD subjects were treatment naive; the remainder had a history of long-term treatment with stimulants, but they were medication free at the time of the fMRI. No subject had a learning disorder or a comorbid psychiatric condition (other than oppositional defiant disorder in the ADHD subjects). RESULTS: Both the ADHD and comparison subjects activated the right dorsolateral prefrontal cortex on "stop" trials relative to "go" trials; this increase was greater in ADHD subjects. When inhibition was unsuccessful (relative to successful inhibition), healthy comparison subjects strongly activated the anterior cingulate cortex and the left ventrolateral prefrontal cortex. In contrast, the ADHD subjects did not show these differences. Activations in treatment-naive and ADHD subjects treated in the long term did not differ significantly in any brain regions. CONCLUSIONS: In relation to comparison subjects, ADHD subjects failed to activate the anterior cingulate cortex and the left ventrolateral prefrontal cortex after unsuccessful inhibition. These findings appear in treatment-naive ADHD individuals and are unlikely to be an artifact of long-term treatment with stimulants or of abrupt termination of stimulants before imaging.     

“Kiss myAsthma”: Using a participatory design approach to develop a self-management app with young people with asthma

Objective: Young people with asthma often lack engagement in self-management. Smartphone apps offer an attractive, immediate method for obtaining asthma information and self-management support. In this research we developed an evidence-based asthma app tailored to young peoples needs, created using a participatory design approach to optimize user engagement. This paper describes the participatory design process. Methods: This multi-phased research included concept generation and ideation of app design by young people with asthma, and development of asthma information by the research team. Clinical review was sought regarding safety and accuracy of app content. Participants suggestions for improvement and any problems with the app were logged throughout. Our young co-designers were invited back to test a high fidelity prototype app using a “think aloud” process and completed a usability questionnaire. Results: Twenty asthma patients aged 15-24 years contributed to the initial app design. Three respiratory specialists and two pharmacists suggested minor corrections to clinical terminology in the app which were all incorporated. Nine co-designers acted as expert reviewers of the prototype app, of whom eight completed a usability questionnaire. Median usability scores (maximum score 6) indicated high satisfaction with app content, usefulness and ease of use [median item score 5.3 (range 4.7-6.0)]. All feedback was incorporated to create an updated prototype app. Conclusions: A clinically sound asthma app has been developed which is considered highly acceptable to the young co-designers. A six-week test of the engagement, acceptability, and usefulness of the app in young people not involved in the participatory design will follow.     

Incongruent reduction following post-traumatic hip dislocations as an indicator of intra-articular loose bodies: A prospective study of 117 dislocations

Background:

Intra-articular loose bodies following simple dislocations can lead to early degeneration. Nonconcentric reduction may indicate retained loose bodies and offer a method to identify patients requiring exploration so that this undesirable outcome can be avoided.

Materials and Methods:

One hundred and seventeen consecutive simple dislocations of the hip presenting to the hospital from January 2000 to June 2006 were assessed for congruency after reduction by fluoroscopic assessment of passive motion in the operating room as well as with good quality radiographs. Computerized tomography (CT) scan with 2-mm cuts was done for confirmation of reduction and to identify the anatomy of loose bodies. Patients with nonconcentric reduction underwent open exploration to identify the etiology of the dislocation and for removal of loose bodies. Thomson and Epstein clinical and radiological criteria were used to assess the outcome.

Results:

Twelve of the one hundred and seventeen (10%) dislocations had incongruent reduction, which was identified by the break in Shenton’s line and increase in medial joint space in seven patients, increase in the superior joint space in three patients, or increase in the joint space as a whole in two patients. CT scan identified the origin of the osteocartilaginous fragment as being from the acetabulum in six patients, the femoral head in four, and from both in one. One patient had an inverted posterior labrum. Following debridement, congruent reduction was achieved in all patients. At an average follow-up of 5 years (range: 2 years 5 months to 8 years), the outcome as evaluated by Thompson and Epstein clinical criteria was excellent in eleven cases and good in one case; the radiological outcome was excellent in eight cases and good in four cases.

Conclusions:

Intra-articular loose bodies were identified by nonconcentric reduction in 12 out of 117 patients with simple hip dislocation. Careful evaluation by fluoroscopy and good quality radiographs are indicated following reduction of hip dislocations.     

Patterns of hematopoietic chimerism following bone marrow transplantation for childhood acute lymphoblastic leukemia from volunteer unrelated donors

Hematopoietic chimerism was analyzed in serial bone marrow samples taken from 28 children following T-cell depleted unrelated donor bone marrow transplants (UD BMT) for acute lymphoblastic leukemia (ALL). Chimeric status was determined by polymerase chain reaction (PCR) of simple tandem repeat (STR) sequences (maximal sensitivity, 0.1%). At least two serial samples were examined in 23 patients. Of these, two had evidence of complete donor engraftment at all times and eight showed stable low level mixed chimerism (MC) (<1% recipient hematopoiesis). All 10 of these patients remain in remission with a minimum follow-up of 24 months. By contrast, 13 patients demonstrated a progressive return of recipient hematopoiesis. Five of these relapsed (4 to 9 months post BMT), one died of cytomegalovirus pneumonitis and seven remain in remission with a minimum follow-up of 24 months. Five children were excluded from serial analysis as two serial samples were not collected before either relapse (3) or graft rejection (2). We conclude that as with sibling transplants, ex vivo T depleted UD BMT in children with ALL is associated with a high incidence of MC. Stable donor engraftment and low level MC always correlated with continued remission. However, detection of a progressive return of recipient cells did not universally correlate with relapse, but highlighted those patients at greatest risk. Serial chimerism analysis by PCR of STRs provides a rapid and simple screening technique for the detection of relapse and the identification of patients with progressive MC who might benefit from detailed molecular analysis for minimal residual disease following matched volunteer UD BMT for childhood ALL.     

A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis

We have examined the prothrombin gene as a candidate gene for venous thrombosis in selected patients with a documented familial history of venous thrombophilia. All the exons and the 5'- and 3'-UT region of the prothrombin gene were analyzed by polymerase chain reaction and direct sequencing in 28 probands. Except for known polymorphic sites, no deviations were found in the coding regions and the 5'-UT region. Only one nucleotide change (a G to A transition) at position 20210 was identified in the sequence of the 3'-UT region. Eighteen percent of the patients had the 20210 AG genotype, as compared with 1% of a group of healthy controls (100 subjects). In a population-based case-control study, the 20210 A allele was identified as a common allele (allele frequency, 1.2%; 95% confidence interval, 0.5% to 1.8%), which increased the risk of venous thrombosis almost threefold odds ratio, 2.8; 95% confidence interval, 1.4 to 5.6. The risk of thrombosis increased for all ages and both sexes. An association was found between the presence of the 20210 A allele and elevated prothrombin levels. Most individuals (87%) with the 20210 A allele are in the highest quartile of plasma prothrombin levels (> 1.15 U/mL). Elevated prothrombin itself also was found to be a risk factor for venous thrombosis.     

Identification of the molecular defect in the erythrocyte membrane skeleton of some kindreds with hereditary spherocytosis

We have localized the molecular alteration in the membrane skeleton of two of four kindreds with hereditary spherocytosis (HS) to an alteration in the spectrin-protein-4.1 interaction due to a defective spectrin molecule. The defective spectrin-protein-4.1 interaction in these kindreds (referred to as type I HS) leads to a weakened spectrin- protein-4.1-actin ternary complex, which in turn may lead to the friable membrane skeleton and suggested membrane instability related to this disorder. Type I HS spectrin binds approximately 63% as much protein-4.1 as normal spectrin (with equal affinity). This defect does not correlate with splenic function or erythrocyte age in the circulation. However, the approximately 37% reduction in binding of protein-4.1 to HS spectrin approaches the theoretical value of 50% expected in this autosomal dominant disorder. All other type I membrane skeletal interactions (spectrin-syndein, spectrin heterodimer- heterodimer, syndein-band-3) were found to be normal. It would appear therefore that the defective HS spectrin-protein-4.1 interaction in type I hereditary spherocytosis may be the primary molecular defect rather than a secondary phenomena.     

A comparative histological analysis of human pulp following direct pulp capping with Propolis, mineral trioxide aggregate and Dycal

Background:  Permanent teeth pulp exposures have traditionally been treated with calcium hydroxide pulp capping. The aim of this study was to investigate the response of human pulp tissue which were mechanically exposed to a new material, Propolis and compare it with two existing and commonly used pulp capping agents (mineral trioxide aggregate and Dycal).
Methods:  Thirty-six intact human premolars were mechanically exposed. Teeth were divided into six groups of 6 teeth each and were capped with Propolis, mineral trioxide aggregate and Dycal. Final restoration was done with posterior composite resin using light cured glass ionomer cement as a liner. The teeth were then extracted on the 15th or the 45th day and processed for histological evaluation.
Results:  Differences in inflammatory response and dentine bridge formation of the exposed pulp to the three different materials were statistically calculated using chi-square test and were found to be non-significant. There was more pulp inflammation in teeth treated with Dycal than with Propolis and MTA on the 15th as well as on the 45th day. Propolis and MTA showed bridge formation in more teeth, and the bridges were in closer proximity to pulp capping material than teeth treated with Dycal on the 45th day.
Conclusions:  The response of pulps to Propolis as a pulp capping agent was comparable to MTA and Dycal.     

Involvement of guanine nucleotide binding proteins in neutrophil activation and priming by GM-CSF

Pre-incubation of human neutrophils with pertussis toxin significantly inhibited the neutrophil-directed biologic actions of granulocyte- macrophage colony-stimulating factor (GM-CSF) in three separate assays: the induction of c-fos mRNA, the enhancement of both platelet- activating factor-induced mobilization of intracellular calcium, and stimulation of leukotriene synthesis by the calcium ionophore A23187. Cholera toxin did not have an effect on the latter two assays. Pre- treatment of human neutrophils with pertussis toxin did not affect the binding of GM-CSF to its surface receptor. These results provide the first evidence that a pertussis toxin substrate plays an important mediatory role in the mechanism of action of GM-CSF.     

PGE1 accelerates thrombolysis by tissue plasminogen activator

Platelets are an active element in the generation of thrombus and may influence rates of thrombolysis during the administration of plasminogen activators. To assess the potential importance of platelet aggregation in the thrombolytic response to plasminogen activators, we measured rates of thrombolysis induced by tissue plasminogen activator in the presence and absence of a coinfusion of prostaglandin E1 in a rabbit jugular vein model of thrombosis. Rates of lysis were quantified by measuring the half-time for lysis of the thrombus. At all concentrations of tissue plasminogen activator used, prostaglandin E1 markedly reduced the half-time for clot lysis and enhanced somewhat the overall extent of thrombolysis, without affecting significantly either the degree of fibrinogen depletion or the animals' mean arterial pressures. These effects on thrombolytic efficacy were accompanied by ex vivo evidence of platelet inhibition. These data suggest that the antiplatelet prostaglandin E1 may be a very useful adjunctive agent in thrombolytic therapy primarily by virtue of the significant improvement in the rate of thrombolysis that its use affords.