Effectiveness of a long-acting injectable form of bromocriptine in patients with prolactin and growth hormone secreting macroadenomas

OBJECTIVE With the development of new long-acting depot preparations of bromocriptine (bromocriptine LAR), we investigated the effectiveness of intramuscular injections of long-acting bromocriptine in patients with prolactin and GH secreting macroadenomas. STUDY DESIGN AND PATIENTS Fourteen patients with PRL secreting (8 patients) and GH secreting (6 patients) macroadenomas were treated with monthly intramuscular Injections of a long-acting and repeatable form of bromocriptine for 3–6 months. A 50-mg monthly dose was administered In the majority of patients with PRL secreting macroadenomas. A 100-mg monthly dose was administered In all patients with GH secreting macroadenomas. MEASUREMENTS Plasma PRL and/or GH levels were measured 6 and 12 hours after the first injection and then on days 1, 2,14 and 28 after each Injection, up to a maximum period of 6 months. Patients were hospitalized for 48 hours after each Injection and were specifically questioned with respect to side-effects. Pituitary imaging with MRI or CT scans was performed In all patients before commencing treatment and was subsequently repeated In 5/8 patients with macroprolactinomas and 5/6 patients with GH secreting macroadenomas after the completion of a 6-month course of treatment. RESULTS In ail patients with macroprolactinomas, serum PRL levels decreased significantly after their first 50-mg injection with nadir levels obtained by 24–48-hours post Injection (12815 ± 8704 vs 1480 ± 1859 mU/l; mean ± SD, P<0.01). At their latest follow-up, on a 50-mg monthly dose, 4 patients developed normoprolactinaemia (PRL levels <360mU/l) while two patients demonstrated a significant reduction In serum PRL levels (70 and 87% of pretreatment values). In two patients, although a substantial decrement of serum PRL levels was achieved 12-24 hours post injection, serum PRL levels Increased to pretreatment values by day 14 post injection. Both patients received a higher (100mg) monthly dose which was partially effective In one patient. In two patients with GH secreting macroadenomas, a sustained decrease of elevated GH levels was observed; in two patients, while a substantial reduction of the elevated serum GH levels was achieved 12–24 hours after the first and subsequent injections, serum GH levels increased to pretreatment values by day 14 post injection; in two patients there was no effect on the elevated serum GH levels. Significant tumour shrinkage (24–50%) was observed In 5/5 patients with PRL secreting macroadenomas assessed at completion of a 6-month course of treatment. Significant tumour shrinkage was also documented In 2/5 acromegalics tested (29 and 46% respectively). CONCLUSION It is concluded that bromocriptine LAR Is an effective treatment in the majority of patients with macroprolactinomas; it is also partially effective in some patients with GH secreting macroadenomas.     

个体化下肢小腿假肢接受腔设计的生物力学评价技术研究

作为传递体重、固定假肢的部件 ,接受腔对于小腿假肢使用的舒适性和方便程度有决定性的作用。本研究建立了基于有限元应力分析的小腿假肢生物力学评价技术平台 ,实现了小腿残端 /接受腔 3D几何建模与信息交互、三维有限元自动建模及应力分析。 3D模型与信息交互的实现基于得到广泛支持的OpenGL技术 ,有限元模型的构建采用了专门针对小腿残端 /接受腔结构特点的自动建模方法 ,通过构建档案数据库系统作为整个系统的操作平台。该技术平台可与现有的CAD/CAM系统相结合 ,为接受腔的个体化设计提供生物力学定量化依据。其临床应用将改善传统的设计流程 ,提高设计效率。同时 ,它也是未来构建接受腔设计专家 /智能系统的基础。     

Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.     

碱离子水饮用后血小板聚集率的的变化(附30例报告)

目的:报告30例饮用豪斯牌碱离子水前、后血小板聚集率的变化。方法:饮用碱离子水前、后(2～3月,>3～6月)作比浊法血小板聚集试验,以1分钟、5分钟及5分钟内最大聚集率(Max％)为指标,同时检测部分血粘度指标及凝血因子,并用自动生化仪检测血糖、血脂、主要电解质及部分肝、肾功能。结果:饮碱离子水后,血小板聚集率明显下降,而以疾病组(Max>80％)下降尤为明显,P均<0.001。饮碱离子水后血小板聚集率的下降,部分可能与损伤的血管内皮得到修复有关。主要电解质及部分肝、肾功能无明显异常改变。结论:由于心、脑血管血栓性疾病患者血小板聚集率多明显升高,饮碱离子水后血小板聚集率明显下降,且长期饮用对主要电解质及部分肝、肾功能无明显异常改变,作者认为碱离子水使用方例、安全、有效、价廉,因而对心、脑血管血栓性疾病防治方面可能是一种积极的辅助方法,值得临床进一步探索。     

Cannabinoid withdrawal is dependent upon PKA activation in the cerebellum

Region-specific up-regulation of the cyclic AMP pathway is considered an important molecular mechanism in the origin of the somatic manifestations of the withdrawal syndrome to known drugs of abuse. Nevertheless, the existence of a withdrawal syndrome after prolonged cannabinoid administration has long been a controversial issue. Recent studies, in different species, have shown that withdrawal to prolonged cannabinoid exposure precipitated by the cannabinoid antagonist SR141716A is characterized by physical signs underlying impairment of motor coordination. Interestingly, cannabinoid withdrawal is accompanied by an increase of adenylyl cyclase activity in the cerebellum. Here, we investigate the functional role of the cyclic AMP pathway in the cerebellum in the establishment of cannabinoid withdrawal. We show that after SR141716A precipitation of cannabinoid withdrawal, basal and calcium-calmodulin-stimulated adenylyl cyclase activities as well as active PKA in the cerebellum increase in a transient manner with a temporal profile which matches that of the somatic expression of abstinence. Selectively blocking the up-regulation of the cyclic AMP pathway in the cerebellum, by microinfusing the cyclic AMP blocker Rp-8Br-cAMPS in this region, markedly reduced both PKA activation and the somatic expression of cannabinoid withdrawal. Our results (i) directly link the behavioural manifestations of cannabinoid withdrawal with the up-regulation of the cyclic AMP pathway in the cerebellum, pointing towards common molecular adaptive mechanisms for dependence and withdrawal to most drugs of abuse; (ii) suggest a particular role for the cerebellum as a major neurobiological substrate for cannabinoid withdrawal.     

The management of acute abdominal pain in children

Objective : Acute abdominal pain is a common problem in childhood, and appendicitis is frequently diagnosed by general practitioners and doctors working in emergency departments. The objective of the present report was to determine the frequency of appendicitis in a group of children with acute abdominal pain presenting to the emergency department of a general hospital, as well as attempting to analyse the manner in which these patients were managed.
Methodology : The initial assessment in hospital (by resident hospital staff) of the study group of patients was analysed and their subsequent clinical progress documented.
Results : The present report shows that the vast majority of children with acute abdominal pain do not have appendicitis and that appendicitis is significantly over-diagnosed by junior hospital doctors.
Conclusions : Appendicitis is a clinical diagnosis, best made by an experienced member of the paediatric surgical team. Frequent review, with a minimum of investigations, provides the best means of making a rational decision regarding surgery.     

Involvement of striatal and extrastriatal DARPP-32 in biochemical and behavioral effects of fluoxetine (Prozac)

Fluoxetine (Prozac) is the most widely prescribed medication for the treatment of depression. Nevertheless, little is known about the molecular basis of its clinical efficacy, apart from the fact that fluoxetine increases the synaptic availability of serotonin. Here we show that, in vivo, fluoxetine, given either acutely or chronically, regulates the phosphorylation state of dopamine- and cAMP-regulated phosphoprotein of M(r) 32,000 (DARPP-32) at multiple sites in prefrontal cortex, hippocampus, and striatum. Acute administration of fluoxetine increases phosphorylation of DARPP-32 at the protein kinase A site, Thr-34, and at the casein kinase-1 site, Ser-137, and decreases phosphorylation at the cyclin-dependent kinase 5 site, Thr-75. Each of these changes contributes, through distinct signaling pathways, to increased inhibition of protein phosphatase-1, a major serine/threonine protein phosphatase in the brain. Fluoxetine also increases phosphorylation of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluR1 at Ser-831 and Ser-845. Both the fluoxetine-mediated increase in AMPA receptor phosphorylation at Ser-845-GluR1 and the beneficial responsiveness to fluoxetine in an animal test of antidepressant efficacy were strongly reduced in DARPP-32 knockout mice, indicating a critical role for this phosphoprotein in the antidepressant actions of fluoxetine. Mice chronically treated with fluoxetine had increased levels of DARPP-32 mRNA and protein and a decreased ability to increase phospho-Ser-137-DARPP-32 and phospho-Ser-831-GluR1. These chronic changes may be relevant to the delayed onset of therapeutic efficacy of fluoxetine.     

Association between the PPP3CC gene, coding for the calcineurin gamma catalytic subunit, and bipolar disorder

Cocaine addiction involves a number of medical, psychological and social problems. Understanding the genetic aetiology of this disorder will be essential for design of effective treatments. Dopamine-beta hydroxylase (DbH) catalyzes the conversion of dopamine to norepinephrine and could, therefore, have an influence on both cocaine action and the basal sensitivity of neurotransmitter systems to cocaine. Recently, the -1021C>T polymorphism have been found to strongly correlated with individual variation in plasma DbH activity. To test the influence of this polymorphism on the susceptibility of cocaine addiction, we decided to genotype it in a sample of 689 cocaine addicts and 832 healthy individuals. Genotypic and allelic analyses did not show any evidence of association with cocaine addiction, even after correcting for the effect of population stratification and other possible confounders. Our results do not support a major role of the -1021C>T polymorphism or the gene itself in the development of cocaine addiction but further examination of other variants within this gene will be necessary to completely rule out an effect.     

Incremental prognostic value of <Superscript>99m</Superscript>Tc-tetrofosmin myocardial SPECT after percutaneous coronary intervention

Objective  Percutaneous transluminal coronary angioplasty is a well-established therapeutic method in selected patients with coronary artery disease. The aim of this study was to assess the incremental prognostic value of technetium-99m (^99mTc)-tetrofosmin myocardial gated-single- photon emission computed tomography (SPECT) in asymptomatic patients after coronary artery stenting. Methods  A total of 246 consecutive patients (aged 55.5 ± 8.2 years, 182 men) participated in the study with a median follow-up of 9.5 years (interquartile ra 5.8–10.5 years). All patients underwent exercise gated-SPECT myocardial imaging within 5–7 months. Myocardial scintigrams were performed using 99mTctetrofosmin, and were evaluated calculating the summed stress score (SSS), summed rest score (SRS), and summed difference score (SDS) indexes. Cardiovascular death and non-fatal myocardial infarction were considered as hard cardiac events, and late revascularization (>3 months after myocardial SPECT) procedures as soft events. Receiver-operating characteristic (ROC) analysis was used to test the prognostic ability of SSS and SDS for cardiac events. Cox proportional hazards models were used to evaluate the incremental value of SPECT variables. Results  Cardiac death occurred in 12 (4.9%) patients and non-fatal myocardial infarction in 20 (8.1%) patients. In addition, 60 (24.4%) patients underwent a late revascularization procedure. Using ROC analysis the optimal cut-offs of SSS (AUC = 0.94; 95% CI 0.92–0.97) and SDS (AUC = 0. 76; 95% CI 0.70–0.82) for the prediction of cardiac events were 10 and 1.7, respectively. Multiple Cox regression analyses revealed that SSS > 10 (HR = 24.2; 95% CI 7.44–78.79) and SDS > 1.7 (HR = 2.72; 95% CI 1.23–6.00) provided incremental prognostic value over clinical and exercise test data for the composite end points of any cardiac event. Conclusions   ^99mTc-tetrofosmin myocardial gated- SPECT, performed 6 months post-percutaneous coronary intervention (PCI), provides incremental prognostic information for the prediction of cardiac events in asymptomatic patients after PCI.