The effect of thrombin on ACL fibroblast interactions with collagen hydrogels.

Premature loss of provisional scaffold formation has been identified as one of the factors responsible for poor healing of intraarticular tissues. To address this deficiency, substitute provisional scaffolds are being developed. The function of these scaffolds can be enhanced by the addition of specific extracellular matrix proteins. In this study, it was hypothesized that the addition of thrombin to a provisional scaffold material would result in increases in cell proliferation, collagen production, and cell migration within the scaffold. These three parameters are thought to be critical components of wound healing. Gels containing fibrin and collagen supplemented with either 0, 10.5, 21, or 42 U/mL of thrombin were placed in contact with explants of tissue from the anterior cruciate ligament. The addition of thrombin stimulated cell migration at low concentrations and impaired migration at higher concentrations, and had no significant effect on cell proliferation or collagen production. The use of all concentrations of thrombin resulted in mechanically weaker gels. Thus, the use of thrombin to optimize a collagen-platelet rich plasma (PRP) provisional scaffold must be done with caution, and use of high concentrations of thrombin (>42 IU/mL) should be avoided specifically in situations where gel strength or cell ingrowth is important. Use of low concentrations of thrombin (10.5 IU/mL) may be beneficial in applications where a faster set time and enhanced cell migration are desirable and the gel mechanical strength is of secondary importance.

Multisystemic Therapy for social, emotional, and behavioral problems in youth aged 10-17.

BACKGROUND: Multisystemic Therapy (MST) is an intensive, home-based intervention for families of youth with social, emotional, and behavioral problems. Masters-level therapists engage family members in identifying and changing individual, family, and environmental factors thought to contribute to problem behavior. Intervention may include efforts to improve communication, parenting skills, peer relations, school performance, and social networks. Most MST trials were conducted by program developers in the USA; results of one independent trial are available and others are in progress. OBJECTIVES: To provide unbiased estimates of the impacts of MST on restrictive out-of-home living arrangements, crime and delinquency, and other behavioral and psychosocial outcomes for youth and families. SEARCH STRATEGY: Electronic searches were made of bibliographic databases (including the Cochrane Library, C2-SPECTR, PsycINFO, Science Direct and Sociological Abstracts) as well as government and professional websites, from 1985 to January 2003. Reference lists of articles were examined, and experts were contacted. SELECTION CRITERIA: Studies where youth (age 10-17) with social, emotional, and/or behavioral problems were randomised to licensed MST programs or other conditions (usual services or alternative treatments). DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed 266 titles and abstracts; 95 full-text reports were retrieved, and 35 unique studies were identified. Two reviewers independently read all study reports for inclusion. Eight studies were eligible for inclusion. Two reviewers independently assessed study quality and extracted data from these studies. Significant heterogeneity among studies was identified (assessed using Chi-square and I(2)), hence random effects models were used to pool data across studies. Odds ratios were used in analyses of dichotomous outcomes; standardised mean differences were used with continuous outcomes. Adjustments were made for small sample sizes (using Hedges g). Pooled estimates were weighted with inverse variance methods, and 95% confidence intervals were used. MAIN RESULTS: The most rigorous (intent-to-treat) analysis found no significant differences between MST and usual services in restrictive out-of-home placements and arrests or convictions. Pooled results that include studies with data of varying quality tend to favor MST, but these relative effects are not significantly different from zero. The study sample size is small and effects are not consistent across studies; hence, it is not clear whether MST has clinically significant advantages over other services. AUTHORS' CONCLUSIONS: There is inconclusive evidence of the effectiveness of MST compared with other interventions with youth. There is no evidence that MST has harmful effects.

Multisystemic Therapy for social, emotional, and behavioral problems in youth aged 10-17.

BACKGROUND: Multisystemic Therapy (MST) is an intensive, home-based intervention for families of youth with social, emotional, and behavioral problems. Masters-level therapists engage family members in identifying and changing individual, family, and environmental factors thought to contribute to problem behavior. Intervention may include efforts to improve communication, parenting skills, peer relations, school performance, and social networks. Most MST trials were conducted by program developers in the USA; results of one independent trial are available and others are in progress. OBJECTIVES: To provide unbiased estimates of the impacts of MST on restrictive out-of-home living placements, crime and delinquency, and other behavioral and psychosocial outcomes for youth and families. SEARCH STRATEGY: Electronic searches were made of bibliographic databases including the Cochrane Library, C2-SPECTR, PsycINFO, Science Direct and Sociological Abstracts) as well as government and professional websites, from 1985 to January 2003. Reference lists of articles were examined, and experts were contacted. SELECTION CRITERIA: Studies where youth (age 10-17) with social, emotional, and/or behavioral problems were randomised to licensed MST programs or other conditions (usual services or alternative treatments). DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed 266 titles and abstracts; 95 full-text reports were retrieved, and 35 unique studies were identified. Two reviewers independently read all study reports for inclusion. Eight studies were eligible for inclusion. Two reviewers independently assessed study quality and extracted data from these studies.Significant heterogeneity among studies was identified (assessed using Chi-square and I(2)), hence random effects models were used to pool data across studies. Odds ratios were used in analyses of dichotomous outcomes; standardised mean differences were used with continuous outcomes. Adjustments were made for small sample sizes (using Hedges g). Pooled estimates were weighted with inverse variance methods, and 95% confidence intervals were used. MAIN RESULTS: Pooled results show no significant effects of MST on the likelihood or duration of restrictive out-of-home placements, proportion of youth who were arrested or convicted, or numbers of arrests/convictions within one-year post-intervention. There were no significant differences on drug tests or self-reported drug use at a 6-month follow-up. In analyses of post-treatment data for program completers, there were no significant between-group differences on self-reported delinquency, peer relations, youth behavior problems, youth psychiatric symptoms, parent psychiatric symptoms, or family functioning. AUTHORS' CONCLUSIONS: There is little evidence of the superiority of MST over other interventions with youth. There is also no evidence that MST has harmful effects.

Ocular findings in patients with solid tumours treated with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839) in Phase I and II clinical trials.

PURPOSE: To describe the strategy used for large-scale ophthalmological monitoring in the clinical development of the novel anticancer agent gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor tyrosine kinase inhibitor, which had demonstrated ocular effects in preclinical animal models. METHODS: In this extensive clinical trial programme, patients in Phase I and II trials underwent frequent and intensive ophthalmological monitoring at baseline and during the trials. Data were reviewed by an external independent Ophthalmology Advisory Board. RESULTS: Ophthalmological data for 221 patients in Phase I trials of gefitinib and 425 patients in Phase II trials revealed no evidence of any consistent or drug-related ophthalmological toxicity. Interestingly, the baseline data revealed that, in an asymptomatic population, transient ophthalmological events are identified during monitoring. CONCLUSIONS: This study reports the methodology and normative data in an ophthalmological screening programme that should prove useful for future studies.

The New Poor Law and the County Pauper Lunatic Asylum--the Devon experience 1834-1884.

In this article we examine the impact of the policies and practices of the Guardians of the New Poor Law Unions on the management of pauper lunatics in four Devon Poor Law Unions in the critical period 1834-84. The central role of the Victorian Poor Law in provision made for the insane has only recently been recognized in the research literature. Scholars have been much more concerned with the activities of professionalizing physicians and the general project of state management than they have with the micro-politics of the local Poor Law and the magistracy who were responsible for the legal disposition of the insane. In this paper we argue that not only were the Guardians of the Poor Law Unions central in the determination of the lunatic's journey through the institutional systems provided in the mid-nineteenth century, but also that there were significant variations within the Poor Law system which made for contrasting systems of disposal of lunatics as between the Unions themselves. These variations in disposal of lunatics in Devon raise important questions of ideology, policy, and practice which, if repeated elsewhere, point to a need to refine significantly our assumptions regarding the disposal of pauper lunatics in England and Wales in the fifty years following the 1834 Poor Law Amendment Act.

Infantile hypothalamic hamartoma with multiple congenital abnormalities.

This case report describes a hypothalamic hamartoma with multiple congenital abnormalities in a male infant, with a post-mortem examination and histology of the lesion.

A group model for adoption studies for special-needs children.

A comparison of the effectiveness of the group model with the individual method for adoption studies reveals that the group method had a greater success in permanent placement and used adoption staff members' time most efficiently.