Blockade of stimulant-induced preprodynorphin mRNA expression in the striatal matrix by serotonin depletion

Cocaine and methamphetamine (METH) induce preprodynorphin (PPD) mRNA expression in the striatum. Cocaine induces PPD expression in both the patch and matrix compartments of the rostral striatum, whereas METH induces PPD expression in the patch compartment of the rostral striatum. In middle striatum, both stimulants increase PPD expression in the patch and matrix compartments. METH and cocaine treatment also increase extracellular serotonin (5-HT). Several studies have shown that 5-HT receptors are present on striatonigral neurons that express PPD mRNA, and that 5-HT is a positive regulator of striatal neuropeptide expression. The current study examined whether 5-HT plays a role in the patch/matrix expression of PPD mRNA induced by cocaine and METH in striatum. Male Sprague-Dawley rats were treated with p-chloroamphetamine (PCA; 8 mg/kg, i.p), a serotonin neurotoxin, 1 week prior to cocaine (30 mg/kg, i.p) and METH (15 mg/kg, s.c.) treatment. The 80% loss of 5-HT induced by PCA-pretreatment blocked cocaine-induced PPD expression in the rostral matrix compartment. Cocaine- and METH-induced PPD expression in the rostral patch compartment was unaffected by PCA-pretreatment. PCA-pretreatment also decreased both cocaine- and METH-induced PPD expression in the matrix, but not patch of middle striatum. PCA-induced 5-HT depletion did not affect stimulant-induced increases in PPT mRNA expression in the striatum. These data suggest that 5-HT plays a role in stimulant-induced PPD expression in the matrix compartment of rostral and middle striatum. Thus, 5-HT innervation may play a critical role in basal ganglia function.     

A case of relapsing flitting bilateral idiopathic orbital inflammation

Idiopathic orbital inflammation (IOI) is defined as a benign non-infective clinical syndrome characterized by features of non-specific inflammation of the orbit without identifiable local or systemic causes. This can be called orbital myositis if the inflammation is predominantly in the orbital muscles. It is a diagnosis of exclusion based on clinical, radiological, and if necessary, histological findings. The most commons symptoms are swelling, ptosis, proptosis and painful eye movements. To our knowledge, this patient is the first with IOI to demonstrate relapsing flitting bilateral involvement of several individual extra-ocular muscles.     

Human papillomavirus DNA and TP53 mutations in lung cancers from butchers.

To investigate whether the high frequency of human papillomavirus infection in butchers may be linked to their higher than average incidence of lung cancer, we have examined lung cancers from 40 butchers and 26 controls for the presence of DNA from both HPV type 7, which is found almost uniquely in hand warts from butchers and fishermen, and for those HPV types associated with laryngeal and genital cancers. No HPV 7, and only a low frequency of HPV DNA was found, suggesting that HPV infection does not make an important contribution to the elevated levels of lung cancer in meat handlers. In addition, the frequency of p53 mutation was shown to be slightly lower than previously reported in lung cancers.     

Perceived benefits of word prediction intervention on written productivity in children with spina bifida and hydrocephalus

Word prediction has been commonly used as a tool to enhance written productivity. However, the effectiveness of word prediction as a strategy to meet this targeted outcome has not been established. Using a single-subject alternating treatments design, this study evaluated the effect of word prediction on written productivity from the users' perspectives. Three girls and one boy aged 10-12 with spina bifida and hydrocephalus participated in the study over a period of 20 days. The Canadian Occupational Performance Measure (COPM) was used to measure changes in perception of written productivity. Analysis of individual participant data showed that participants perceived word prediction to have the potential to influence written productivity on some writing tasks. Quantitative analysis using a randomization test did not reveal any significant changes in COPM scores after using word prediction. The varied abilities of the participants in the study and the small sample size may be the reasons why statistical analysis did not show any changes. The limitations of this study included use of a copy task, lack of a supporting measure to COPM and limited generalizability. Further studies with a larger sample are necessary to explore the skills required for successful use of word prediction and the impact of word prediction on specific tasks.     

Trastuzumab-associated cardiotoxicity

Trastuzumab is a monoclonal antibody used for the treatment of metastatic breast carcinoma in women whose tumors overexpress the HER2 protein. Cardiotoxicity has been reported to occur with trastuzumab when administered alone and in combination with antineoplastic agents, particularly anthracyclines. The risk of cardiotoxicity with trastuzumab has been reported to be 4% with monotherapy and 27% when administered in combination with an anthracycline and cyclophosphamide, but to the author's knowledge severe outcomes, such as death or permanent disability, are uncommon. The majority of reported cardiac effects are mild to moderate, nonspecific, and medically manageable. Signs and symptoms are similar to those observed in patients who develop anthracycline-induced cardiomyopathy and include tachycardia, palpitations, and exertional dyspnea, which may progress to congestive heart failure. The pathogenesis and histologic changes responsible for trastuzumab-associated cardiotoxicity currently are under investigation. Unlike anthracycline-induced toxicity, trastuzumab-associated toxicity usually responds to standard treatment or the discontinuation of trastuzumab, and there is no evidence that the toxicity is dose related. Current methods for the early detection of cardiotoxicity in trastuzumab-treated patients are similar to those used in anthracycline-treated patients. Cardiac function is established at baseline and monitored regularly during treatment by physical examination and measurement of left ventricular ejection fraction. The majority of patients improve with proper treatment, and some are able to continue to receive trastuzumab.     

颅内动脉瘤栓塞后并发脑缺血的原因分析

1 临床资料我们总结2004-02/2004-06在第四军医大学唐都医院神经外科住院行栓塞治疗颅内动脉瘤患者27(男12,女15)例,年龄32～72岁.     

Unusual presentation of perirenal lung metastases

Lung cancer is not commonly known to metastasise to the perirenal space, with only five such cases previously published. We present an unusual case of perirenal lung metastases manifesting as diffuse perinephric stranding which to our knowledge has not been described before.     

Effects of coping on health outcome among women with gastrointestinal disorders

BACKGROUND: Studies have shown that the nature and quality of coping may positively or negatively affect health outcome; however, this relationship has not been well studied among patients with gastrointestinal (GI) disorders. OBJECTIVES: The primary objective was to study the effect of different coping strategies on the health outcome of women with GI disorders and how these coping strategies may modify the effects of education, GI disease type, neuroticism, and abuse severity on health outcome. METHODS: We followed 174 patients in a referral GI clinic for 12 months to assess their health status as a derived variable of daily pain, bed disability days, psychological distress, daily dysfunction, number of visits to physicians, and number of surgeries and procedures. We obtained at baseline their GI diagnosis (functional vs. organic), neuroticism score (NEO Personality Inventory), sexual and/or physical abuse history, and scores on two coping questionnaires. Regressions analyses were used to determine the relative effect of the coping measures on health outcome and their modifying effects on education, GI disease type, neuroticism, and abuse severity. RESULTS: A higher score on the Catastrophizing scale and a lower score on the Self-Perceived Ability to Decrease Symptoms scale (Coping Strategies Questionnaire) predicted poor health outcome. Less education, a functional GI diagnosis, a higher neuroticism score, and greater abuse severity also contributed to poor health status. However, the effect of GI disease type and neuroticism on health outcome was significantly reduced by the coping measures. CONCLUSIONS: Maladaptive coping (eg, catastrophizing) and decreased self-perceived ability to decrease symptoms may adversely affect health outcome and may modify the effect of GI disease type and neuroticism on health outcome.     

Chemotherapy for cancer causes apoptosis that precedes hypoplasia in crypts of the small intestine in humans

BACKGROUND AND AIMS: The mechanism of gastrointestinal damage (mucositis) induced by cancer chemotherapy remains uncertain. The aims of this study were to define the time course and mechanism of small intestinal damage following chemotherapy in humans. METHODS: Patients receiving chemotherapy underwent upper gastrointestinal endoscopy (a maximum of two per patient) with duodenal biopsy prior to chemotherapy and again at 1, 3, 5, and 16 days after chemotherapy. Tissue was taken for morphometry, disaccharidase assays, electron microscopy, and for assessment of apoptosis using the Tdt mediated dUTP-biotin nick end labelling (TUNEL) method. Villus area, crypt length, and mitotic index were measured by a microdissection technique. RESULTS: Apoptosis increased sevenfold in intestinal crypts at one day, and villus area, crypt length, mitotic count per crypt, and enterocyte height decreased at three days after chemotherapy. Disaccharidase activities remained unchanged. Electron microscopy showed increased open tight junctions of enterocytes at day 3, consistent with more immature cells. All indices improved by 16 days. CONCLUSION: Small intestinal mucositis is associated with apoptosis in crypts that precedes hypoplastic villous atrophy and loss of enterocyte height.     

High prevalence of HIV infection among homeless and street-involved Aboriginal youth in a Canadian setting

Aboriginal people experience a disproportionate burden of HIV infection among the adult population in Canada; however, less is known regarding the prevalence and characteristics of HIV positivity among drug-using and street-involved Aboriginal youth. We examined HIV seroprevalence and risk factors among a cohort of 529 street-involved youth in Vancouver, Canada. At baseline, 15 (2.8%) were HIV positive, of whom 7 (46.7%) were Aboriginal. Aboriginal ethnicity was a significant correlate of HIV infection (odds ratio = 2.87, 95%CI: 1.02 – 8.09). Of the HIV positive participants, 2 (28.6%) Aboriginals and 6 (75.0%) non-Aboriginals reported injection drug use; furthermore, hepatitis C co-infection was significantly less common among Aboriginal participants (p = 0.041). These findings suggest that factors other than injection drug use may promote HIV transmission among street-involved Aboriginal youth, and provide further evidence that culturally appropriate and evidence-based interventions for HIV prevention among Aboriginal young people are urgently required.