Searching one or two databases was insufficient for meta-analysis of observational studies

OBJECTIVE: To address methodologic issues in searching for observational studies by presenting database search methods and results. STUDY DESIGN AND SETTING: Results of two literature searches for publications reporting on observational studies of alcohol consumption and the risk of breast cancer and large bowel cancer were compared, to evaluate the sensitivity of various bibliographic databases and search strategies, including hand-searching reviews and meta-analyses. RESULTS: The target sensitivity of 90% of publications in the breast cancer search was achieved by starting with Medline, then adding Biosis, Embase, and SCI EXPANDED-SSCI, which provided a total of 72 (91%) of the 79 relevant publications. To reach a similar 89% sensitivity for large bowel cancer, at least Biosis, Dissertation Abstracts Online, Embase, ETOH, and Medline had to be searched, with the addition of hand search of reviews and meta-analyses. CONCLUSION: Limiting a search to one or two databases when conducting meta-analyses of observational studies will not provide a thorough summary of the existing literature. The findings support recommendations to implement a comprehensive search of electronic databases and the reference lists of recent review articles and meta-analyses.     

Gardner’s syndrome and fibromatosis: Review of the problem and report of a case

Summary Gardner’s syndrome is inherited as an autosomal dominant trait. It is characterized by intestinal polyposis, bony exostoses, and multiple soft-tissue abnormalities. Life-threatening components of the trait are the malignant potential of the colonic polyposis and the malignant behavior of the histologically benign intraabdominal fibromatosis. Colectomy or proctocolectomy is indicated for colonic polyposis; a case illustrating the feasibility of wide resection for intra-abdominal fibromas is presented.     

Increased plasma vascular endothelial growth factor (VEGF) as a surrogate marker for optimal therapeutic dosing of VEGF receptor-2 monoclonal antibodies

A major obstacle compromising the successful application of many of the new targeted anticancer drugs, including angiogenesis inhibitors, is the empiricism associated with determining an effective biological/therapeutic dose because many of these drugs express optimum therapeutic activity below the maximum tolerated dose, if such a dose can be defined. Hence, surrogate markers are needed to help determine optimal dosing. Here we describe such a molecular marker, increased plasma levels of vascular endothelial growth factor (VEGF), in normal or tumor-bearing mice that received injections of an anti-VEGF receptor (VEGFR)-2 monoclonal antibody, such as DC101. Rapid increases of mouse VEGF (e.g., within 24 hours) up to 1 order of magnitude were observed after single injections of DC101 in non-tumor-bearing severe combined immunodeficient or nude mice; similar increases in human plasma VEGF were detected in human tumor-bearing mice. RAFL-1, another anti-VEGFR-2 antibody, also caused a significant increase in plasma VEGF. In contrast, increases in mouse VEGF levels were not seen when small molecule VEGFR-2 inhibitors were tested in normal mice. Most importantly, the increases in plasma VEGF were induced in a dose-dependent manner, with the maximum values peaking when doses previously determined to be optimally therapeutic were used. Plasma VEGF should be considered as a possible surrogate pharmacodynamic marker for determining the optimal biological dose of antibody drugs that block VEGFR-2 (KDR) activity in a clinical setting.     

Amelioration of sulfur mustard skin injury following a topical treatment with a mixture of a steroid and a NSAID

The ability to ameliorate sulfur mustard (HD)-induced oedema by treatment with anti-inflammatory drugs was reported previously after screening four steroids and four non-steroidal anti-inflammatory drugs (NSAIDs) using the mouse ear vesicant model. Following the screening study, one steroid and one NSAID (Adexone and Voltaren) were selected as the most effective, and a mixture of the two was chosen for the present more extensive research. The effect of the combined treatment on clinical, biochemical and histopathological parameters following HD insult was studied. Mice ears were exposed to 0.2 micro l of HD for 10 min to produce a moderate skin injury. Oedema development peaked ca. 48 h following exposure, as determined by weighing ear biopsies. Histological observations at that time exhibited damage to the epidermis and dermis. An increase in prostaglandin E (PGE) was measured in skin homogenates, starting 8 h following exposure and lasting at least up to 48 h post-exposure. A topical treatment using the above anti-inflammatory mixture significantly reduced inflammatory parameters when applied up to 4 h following exposure. These parameters included extent of oedema, levels of PGE, area of clinical damage and extent of cytotoxic injury (vesications and damaged epithelial cells). Thus, a combination of a steroid and NSAID was found to be effective in reducing the intensity of HD skin injury and possibly shortening the time to full recovery. The treatment, however, did not prevent completely the ensuing cytotoxic processes in the epithelial layer.     

Cognitive-Functional (Cog-Fun) Dyadic Intervention for Children with ADHD and Their Parents: Impact on Parenting Self-Efficacy

Aim: The family context of children with ADHD plays a role in intervention outcomes, especially when parents are involved in treatment. Parental participation in evidence-based treatment for ADHD may play a role in improving their own parenting self-efficacy (PSE) as well as child outcomes. This study examined the impact of Cognitive-Functional (Cog-Fun) intervention in occupational therapy (OT) for school-aged children with ADHD, on PSE. Methods: In this randomized controlled trial with crossover design, 107 children were allocated to intervention and waitlist control groups. Intervention participants (n = 50) received Cog-Fun after baseline assessment and waitlist controls (n = 49) received treatment 3 months later. Intervention participants received 3-month follow-up assessment. Treatment included 10 parent-child Cog-Fun weekly sessions. PSE was assessed with the Tool to measure Parenting Self-Efficacy (TOPSE). Results: All children who began treatment completed it. Mixed ANOVA revealed significant Time x Group interaction effects on TOPSE scales of Play and Enjoyment, Control, Self-Acceptance, Knowledge and Learning and Total score, which showed significant improvement with moderate treatment effects for the intervention group. Results were replicated in the control group after crossover. Conclusion: The findings of this study suggest that Cog-Fun OT intervention may be effective for improving aspects of PSE among parents of children with ADHD.     

Melanocortin receptor 1 variants and melanoma risk: A study of 2 European populations

Variation within the melanocortin receptor 1 (MC1R) gene, that influences phenotypic traits and susceptibility to melanoma, is abundant across the populations. We assessed and compared the risk of melanoma in 2 European populations, German and Spanish, by genotyping MC1R variants through direct DNA sequencing from 1,185 melanoma cases and 1,582 controls. The presence of any variant in both populations was associated with a significantly increased risk of melanoma (odds ratio OR = 1.67, 95% confidence interval CI 1.40–1.99). The population attributable fractions (PAF) associated with the MC1R variants in both populations was over 25%. However, the results showed a statistically significant (p < 0.0001) higher frequency of MC1R variants in the German (70%) than in the Spanish population (60%). The red‐hair colour (RHC) variants, though associated with increased risk in both populations, were more common in the German than in the Spanish population (p < 0.0001). Interestingly, non‐RHC variants increased the disease risk in the Spanish (OR = 1.60, 95% CI 1.20–2.14) but not in the German population (OR = 1.07, 95% CI 0.80–1.44). Although RHC variants explained a major proportion of the observed PAF in the German population, in the Spanish population the major contributor to the PAF was the non‐RHC V60L variant. We also observed reduced historic linkage disequilibrium between the variants V92M and T314T in the gene in German melanoma cases. In conclusion, our data underscored the unambiguous importance of the MC1R variants towards the population burden of melanoma. However, the variants that are associated with the disease differ between the investigated populations. © 2009 UICC     

Coxsackievirus B3-induced myocarditis. Autoimmunity is L3T4+ T helper cell and IL-2 independent in BALB/c mice.

Male BALB/c mice inoculated with 6 X 10(4) plaque-forming units (pfu) coxsackievirus, group B, type 3 (CVB3), develop myocarditis within 7 days. Two cytolytic T lymphocyte (CTL) populations arise in infected animals. One population belongs to the Lyt 2+ T (cytolytic/suppressor) lymphocyte subset and reacts specifically with uninfected heart cells (autoreactive CTLs, ACTLs), whereas the other belongs to the L3T4+ T (helper) lymphocyte subset and reacts with infected targets (virus-specific CTLs, VSCTLs). Although both immune T lymphocyte populations can induce cardiac inflammation in vivo, ACTLs predominantly cause tissue injury. VSCTL generation can be inhibited by either anti-Tac (antibody to the interleukin 2 [IL-2] receptor) or anti-Iad but not by anti-IAk, indicating that this response is probably both IL-2-dependent and Class II (major histocompatibility complex [MHC] antigen restricted. ACTL generation is independent of IL-2, because neither anti-Tac or cyclosporin A inhibit this response.