Obsessive–compulsive traits in children and adolescents with Asperger syndrome

The objective of this study is to examine the occurrence and characteristic features of obsessive–compulsive behaviours in children and adolescents with Asperger syndrome (AS), with respect to a matched obsessive compulsive disorder group (OCD) and a typically developing control group (CG). For this purpose, 60 subjects (20 OCD; 18 AS; 22 CG), aged 8–15 years, matched for age, gender and IQ were compared. AS and OCD patients were diagnosed according to the DSM-IV-TR criteria. The Autism Diagnostic Interview-Revised and the Autism Diagnostic Observation Schedule were used to assist in the AS diagnosis; the WISC-R was administered to assess IQ. Obsessive and compulsive symptoms were evaluated by using the Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS). None of the AS children received a formal diagnosis of OCD. The AS group presented significantly higher frequencies of Hoarding obsessions and Repeating, Ordering and Hoarding compulsions compared to CG. The OCD group, in turn, reported significantly higher frequencies of Contamination and Aggressive obsessions and Checking compulsions compared to both the AS group and CG. As expected, the OCD group displayed a higher severity of symptoms (Moderate level of severity) than did the AS group (Mild level of severity). Finally, in our sample, neither the OCD group nor the AS group demonstrated a completely full awareness of the intrusive, unreasonable and distressing nature of symptoms, and the level of insight did not differ between the OCD group and CG, although an absence of insight was observed in the AS group. Children with AS showed higher frequencies of obsessive and compulsive symptoms than did typically developing children, and these features seem to cluster around Hoarding behaviours. Additionally, different patterns of symptoms emerged between the OCD and AS groups. Finally, in our sample, the level of insight was poor in both the OCD and the AS children. Further research should be conducted to better understand the characteristics of repetitive thoughts and behaviours in autism spectrum disorders, and to clarify the underlying neurobiological basis of these symptoms.     

Diagnostic implications of transcription factor Pax 2 protein and transmembrane enzyme complex carbonic anhydrase IX immunoreactivity in adult renal epithelial neoplasms

Pax 2, expressed by metanephric mesenchyme is vital for renal tubule formation and development. Carbonic anhydrase IX (CA IX) is implicated in cell proliferation, adhesion, and invasion. Data regarding expression in renal epithelial tumors other than clear cell renal cell carcinoma (RCC) are limited, conflicting, from tissue microarrays, and do not encompass the entire spectrum or novel uncommon variants. Conventional sections from 200 renal tumors comprising clear cell RCC (n=30), oncocytoma (n=17), papillary RCC (n=30), chromophobe RCC (n=50), urothelial carcinomas (n=30), collecting duct carcinomas (n=5), renal tumors with Xp11.2 translocation (n=15), tubulocystic carcinoma (n=19), and mucinous tubular spindle cell carcinoma (n=4) were immunostained for Pax 2 and CA IX. Clear cell RCC (28/30, 93%), oncocytoma (17/17, 100%), papillary RCC (16/30, 53%), and mucinous tubular spindle cell carcinoma (3/4, 75%) demonstrated nuclear immunoreactivity with Pax 2, whereas the other subtypes were nonreactive. Clear cell RCC (30/30, 100%), urothelial carcinoma (27/30, 90%), papillary RCC (17/30, 57%), and renal tumors with Xp11.2 translocation (6/15, 40%) exhibited membranous immunoreactivity with CA IX, whereas the other subtypes were nonreactive. This suggests potential diagnostic utility of Pax 2 in distinction of (i) oncocytoma (positive) from chromophobe RCC (negative), (ii) clear cell RCC and papillary RCC (positive) from renal tumors with Xp11.2 translocation (negative), and (iii) high-grade clear cell RCC (positive) from urothelial carcinoma (negative). CA IX expression has potential diagnostic implications including (i) clear cell RCC (positive) versus chromophobe RCC (negative) and (ii) urothelial carcinoma (positive) versus collecting duct carcinoma (negative). These antibodies may reliably discriminate between clinically significant subtypes of RCC with overlapping cytoarchitectural features.     

Phase III double-blind,placebo-controlled,prospective randomized trial of adjuvant tamoxifen vs. tamoxifen and fenretinide in postmenopausal women with positive receptors (EB193): an intergroup trial coordinated by the Eastern Cooperative Oncology Group

Fenretinide and tamoxifen have additive antitumor effects preclinically. We performed a randomized, placebo-controlled, double-blind adjuvant trial in breast cancer patients treated for 5 years with tamoxifen, with or without fenretinide. Between October 1995 and October 1999, 426 postmenopausal women with hormone receptor-positive breast cancer were randomized. Patients were monitored for efficacy and toxicity. Four hundred and nineteen patients were evaluable. The study was terminated early due to slow accrual. There were no significant differences between treatment groups in DFS, TTR or survival. More patients stopped treatment early on the fenretinide arm than on placebo (P = 0.02). Grade 3/4 toxicities, including visual problems and musculoskeletal complaints were more common in patients receiving fenretinide (P = 0.007). A Night Blindness Questionnaire was used to monitor nyctalopia, which was slightly, but not significantly, more common on fenretinide. In this underpowered study, no significant difference was observed in efficacy between treatment groups. This trial provides important toxicity information about fenretinide, a retinoid that has been used in the prevention setting, because it is the only placebo-controlled, double-blind randomized study ever performed.     

Actuarial life-table analysis of lower impacted wisdom teeth in general dental practice

Fernandes MJ, Ogden GR, Pitts NB, Ogston SA, Ruta DA. Actuarial life‐table analysis of lower impacted wisdom teeth in general dental practice. Community Dent Oral Epidemiol 2010; 38: 58–67. © 2009 John Wiley & Sons A/S Abstract – Background: The appropriateness of extraction of asymptomatic impacted third molars has been much debated and as a result the number of extractions has fallen in the UK in the past few years. As a direct consequence of this decrease more impacted third molars are left in situ and yet, little is known about the natural history of these teeth. Objective: The aim of this study was to create an actuarial life‐table and related survival analysis that would shed light on the natural history of an impacted lower third molar. Methods: Panoramic radiographs taken in 14 different general dental practices in Scotland were analysed and matched with their respective case notes in order to generate a sample of patients with asymptomatic impacted lower third molars. Subjects were assessed to confirm the presence of impaction and absence of symptoms and then re‐assessed 1 year later for the development of symptoms during the study period to relate the incidence of symptoms within 1 year in the sample studied to age. Logistic regression was used to construct a life table based on the survival of symptom‐free teeth (independently of extraction) during the study period. Results: The number of patients included in the study was 583 and 421 for the baseline and follow‐up assessments respectively. The total number of teeth analysed in both appointments was 676; from those 37 (5.47%) were extracted during the study period. About 562 teeth (83.13%) survived the study period symptom‐free. There was a statistically significant inverse association between the development of symptoms studied and age. There was no statistically significant association between extraction and age. Conclusions: The study indicates that older patients are less likely to develop the symptoms studied. In addition the authors believe that there is evidence to suggest that general dental practitioners might not be following current guidelines when deciding whether or not to extract an impacted lower third molar in the centres studied.     

Priority setting in practice: what is the best way to compare costs and benefits?

Prioritizing candidates for health-care expenditure using cost per Quality-Adjusted Life Year (QALY) is a helpful but insufficient means of ranking alternative uses for scarce health-care funds at the local level. This is because QALYs do not by themselves capture all criteria decision makers need to take into account. Other criteria such as reducing inequalities, meeting national and local priorities and public acceptability also feature in the decision maker's utility function. Programme budgeting and marginal analysis (PBMA) is an established framework for systematic priority setting in which a 'weighted benefit score' for each option is calculated based on all relevant decision-making criteria. Ranking options as a ratio of cost to benefit is desirable and necessary to ensure efficiency. In this paper we review a number of approaches to scoring costs and benefits of options in a PBMA context. Several approaches rank by benefit score alone, rather than efficiency (cost per unit of benefit). Of those that do rank by efficiency, we discuss the benefits and drawbacks. The optimal approach is far from clear, with each technique having its own strengths and weaknesses. A deliberative approach using summaries of costs and benefits of options as a basis for discussion may be preferable.     

Cerebrospinal fluid and plasma (1-->3)-beta-D-glucan as surrogate markers for detection and monitoring of therapeutic response in experimental hematogenous Candida meningoencephalitis

The treatment, diagnosis and therapeutic monitoring of hematogenous Candida meningoencephalitis (HCME) are not well understood. We therefore studied the expression of (1-->3)-beta-D-glucan (beta-glucan) in cerebrospinal fluid (CSF) and plasma in a nonneutropenic rabbit model of experimental HCME treated with micafungin and amphotericin B. Groups studied consisted of micafungin (0.5 to 32 mg/kg) and amphotericin B (1 mg/kg) treatment groups and the untreated controls (UC). Despite well-established infection in the cerebrum, cerebellum, choroid, vitreous humor (10(2) to 10(3) CFU/ml), spinal cord, and meninges (10 to 10(2) CFU/g), only 8.1% of UC CSF cultures were positive. By comparison, all 25 UC CSF samples tested for beta-glucan were positive (755 to 7,750 pg/ml) (P < 0.001). The therapeutic response in CNS tissue was site dependent, with significant decreases of the fungal burden in the cerebrum and cerebellum starting at 8 mg/kg, in the meninges at 2 mg/kg, and in the vitreous humor at 4 mg/kg. A dosage of 24 mg/kg was required to achieve a significant effect in the spinal cord and choroid. Clearance of Candida albicans from blood cultures was not predictive of eradication of organisms from the CNS; conversely, beta-glucan levels in CSF were predictive of the therapeutic response. A significant decrease of beta-glucan concentrations in CSF, in comparison to that for UC, started at 0.5 mg/kg (P < 0.001). Levels of plasma beta-glucan were lower than levels in simultaneously obtained CSF (P < 0.05). CSF beta-glucan levels correlated in a dose-dependent pattern with therapeutic responses and with Candida infection in cerebral tissue (r = 0.842). Micafungin demonstrated dose-dependent and site-dependent activity against HCME. CSF beta-glucan may be a useful biomarker for detection and monitoring of therapeutic response in HCME.     

A randomized phase II trial of sequential gemcitabine plus vinorelbine followed by gemcitabine plus ifosfamide versus gemcitabine plus cisplatin in the treatment of chemo-naive patients with stages III and IV non-small cell lung cancer (NSCLC)

BACKGROUND: Third-generation platinum-based combinations are established as first-line treatment for advanced non-small cell lung cancer (NSCLC). Non-platinum regimens could be an alternative if they show similar efficacy with better tolerability. This randomized phase II trial compared the objective tumor response rate (ORR) of sequential gemcitabine plus vinorelbine followed by gemcitabine plus ifosfamide versus gemcitabine plus cisplatin. Secondary objectives included time to disease progression (TTP), overall survival and toxicity. METHODS: Chemo-naive patients with stages III and IV NSCLC and Karnofsky performance status >70 were assigned to receive either (a) gemcitabine 1000mg/m(2) plus vinorelbine 25mg/m(2) on days 1 and 8 for 2 cycles, followed by gemcitabine 1000mg/m(2) on days 1 and 8 plus ifosfamide 2000mg/m(2) on day 1 (GV-GI arm) for 2 cycles or (b) gemcitabine 1250mg/m(2) on days 1 and 8 with cisplatin 70mg/m(2) on day 1 (GC arm) for 4 cycles. RESULTS: Between July 2001 and January 2003, 102 patients were enrolled (50 on the GV-GI arm and 52 on the GC arm). Patient characteristics were balanced between arms (GV-GI arm: median age 59 years, 84% male, 22 stage IIIB, 24 stage IV, 4 stage IIIA; GC arm: median age 56 years, 87% male, 27 stage IIIB, 23 stage IV, 2 stage IIIA). Of the 101 patients evaluable for response, ORR was significantly higher on the GC arm than on the GV-GI arm (25% versus 6%, respectively; p=0.007). No complete responses occurred. TTP was longer on the GC arm than on the GV-GI arm (median 135 and 79 days, respectively), although this difference was not statistically significant (p=0.065). Survival was not significantly different between the arms (median 293 and 197 days, respectively; p=0.16). Although significantly more thrombocytopenia was reported on the GC arm (22% and 4%, respectively; p=0.02), it did not lead to more transfusions (15 transfusions in 5 patients versus 14 transfusions in 6 patients, respectively). There was no significant difference in other safety parameters between treatment arms. CONCLUSIONS: GC appears to produce better response in advanced NSCLC than GV-GI, with a trend towards longer TTP. Except for more thrombocytopenia with GC, similar toxicity profiles were observed.