17q-linked frontotemporal dementia-amyotrophic lateral sclerosis without tau mutations with tau and alpha-synuclein inclusions

BACKGROUND: Frontotemporal dementia (FTD) is a clinically heterogeneous condition that can be associated with clinical manifestations of an extrapyramidal disorder or motor neuron disease. A range of histologic patterns has been described in patients with FTD. The most common familial form of this condition is caused by mutations in the microtubule-associated protein tau gene (MAP tau) and is associated with neuronal or glial tau inclusions. OBJECTIVES: To determine the clinical, anatomic, and pathological features of San Francisco family A and to map the mutation responsible for disease in this family. DESIGN: A systematic clinical, neuropsychologic, neuroimaging, and chromosome segregation analysis of San Francisco family A was performed. A pathological and biochemical assessment of a family member was made. SETTING: Family study. PATIENTS: San Francisco family A, with FTD, variable extrapyramidal symptoms, and prominent motor neuron disease. Afflicted family members do not have a MAP tau coding or splice regulatory sequence mutation, and the MAP tau is genetically excluded. MAIN OUTCOME MEASURES: Comparison of clinical, neuropsychologic, neuroimaging, and linkage findings of San Francisco family A with other familial forms of FTD and amyotrophic lateral sclerosis (ALS). RESULTS: The most probable location for the mutation responsible for this condition is on chromosome arm 17q, distal to the MAP tau. All previously identified susceptibility loci for FTD and ALS are excluded. Autopsy findings from an afflicted family member show distinctive tau and alpha-synuclein inclusions. Another unique feature is that the insoluble tau protein consists predominantly of the 4R/0N isoform. CONCLUSION: The condition affecting members of San Francisco family A is clinically, pathologically, and genetically distinct from previous familial forms of FTD and ALS.     

Block design allowed for control of the Hawthorne effect in a randomized controlled trial of test ordering

BACKGROUND AND OBJECTIVE: To evaluate the value of balanced incomplete block designs in quality improvement research, and their capacity to control for the Hawthorne effect. METHODS: General practitioners teams were randomized into three arms and received an intervention on test ordering, relating to tests for two groups of clinical problems (A tests and B tests). In the two trials within the block design, we tried to control for the Hawthorne effect by comparing the complete intervention in both arms on either the A (arm I) or B tests (arm II); the arms acted as blind controls for each other. In the classical trial, the complete intervention on B tests (arm II) was compared with a control arm without any intervention on B tests (arm III). RESULTS: The trials with the block design yielded statistically significant changes in the numbers of A tests ordered (P=.013), but not in the numbers of B tests ordered (P=.29). In the classical design, the complete intervention reached a marginally significant change in the B tests (P=.068). The Hawthorne effect was the same for both arms of the block design. In the classical design, the effect could to some extent be attributed to the Hawthorne effect. CONCLUSION: Our block design allowed us to control for the Hawthorne effect. Suitable use of block designs may further our knowledge of nonspecific effects in quality improvement research.     

ADAM12: a novel first-trimester maternal serum marker for Down syndrome

OBJECTIVES: The concentration of bioavailable insulin-like growth factor (IGF) I and II is important to foetal growth. It is regulated by insulin-like growth factor binding proteins (IGFBP) 1 through 6. Proteolytic cleavage of IGFBP-3 takes place in human pregnancy serum; accordingly, IGFBP-3 serum levels decrease markedly during pregnancy. ADAM12 (A disintegrin and metalloprotease) is an IGFBP-3 and IGFBP-5 protease and is present in human pregnancy serum. The goal of this study was to determine whether ADAM12 concentration in maternal serum is a useful indicator of foetal health. METHODS: We developed an enzyme-linked immunosorbent assay (ELISA) for the quantification of ADAM12 in serum. The assay range was 42 to 667 micro g/L. Recombinant ADAM12 was used as the standard for calibration. RESULTS: We found that ADAM12 was highly stable in serum. Serum concentration increased from 180 micro g/L at week 8 of pregnancy to 670 micro g/L at 16 weeks, and reached 12 000 micro g/L at term. In 18 first-trimester Down syndrome pregnancies, the concentration of ADAM12 was decreased, thus the median multiple of mean (MoM) value was 0.14 (0.01-0.76). A detection rate for foetal Down syndrome of 82% for a screen-positive rate of 3.2% and a 1:400 risk cut-off was found by Monte Carlo estimation using ADAM12 and maternal age as screening markers. CONCLUSION: ADAM12 is a promising marker for Down syndrome.     

The Long-term Physical Health and Healthcare Utilization of Women Who Were Sexually Abused as Children

This article addresses the relationship between childhood sexual abuse and the long-term physical health and healthcare utilization of 148 female participants in an eight-year prospective study. Five factors of physical health emerged: General Health; Vegetative Health Symptoms; Colds and Flu; Gastrointestinal/Gynecological; and Healthcare Utilization. Abused females scored higher on the healthcare utilization and gastrointestinal/gynecological factors than comparison females. Abused females experiencing multiple perpetrators, violence, longer duration and older age at onset endorsed significantly more gastrointestinal/gynecological problems than did the other abused females and the comparison group. Findings suggest that: (1) sexual abuse affects long-term health outcomes and healthcare utilization; and (2) physical health sequelae of abuse may differentially affect females, depending upon the pattern of abuse characteristics.     

Legal, financial, and public health consequences of HIV contamination of blood and blood products in the 1980s and 1990s

Ensuring the safety of the blood supply connects politics and science. The business and service sectors share responsibility for the collection and processing of blood donations, and government agencies perform regulatory and surveillance roles. The onset of the AIDS epidemic has challenged the interface among these systems, leading to widespread fears about compromised safety of the blood supply. Because of public concern about blood-supply decisions made in the 1980s, developed countries in the 1990s established reimbursement programs for persons with transfusion-acquired viral infections from blood or blood products, adopted diagnostic tests and procedures that improved the safety of the blood supply, and held criminal judicial investigations of government officials and industry leaders accused of delaying implementation of potential blood-safety measures. In contrast, developing countries continue to struggle with blood-supply safety issues. This paper summarizes the current status of these safety concerns in developed countries, where viral transmission from contaminated blood or blood products is extremely rare, and in developing countries, where up to 10% of HIV infections result from transfusion of blood or blood products.     

Criminal enquiry and determination of dental damage. Analysis of a prosthetic fracture following an accident

When signing a legal insurance policy, one is not always aware of the seriousness of the reciprocal legal consequences. Physical injuries mainly involve civil procedures in spite of the fact that criminal proceedings are instituted in some cases. This article deals with the judicial inquiry concerning the notification of an accident with insurance claim. The object of this inquiry is a porcelain fracture caused by a so-called accident where verification becomes very complicated for the appointed experts. If diagnosis, anamnesis and the initial examination indicate possible fraud in the case, the expert's assessment for the insurer will rightly include the criminal section. What does this involve for the expert and his team? The violation of the public interest by making a false statement will result in the expert trying to reveal the truth instead of estimating the damage.     

Long-term adjustment of families following traumatic brain injury where comprehensive rehabilitation has been provided

Objectives : The present study aimed to examine long-term family and emotional adjustment in close relatives of individuals with TBI, who had access to comprehensive rehabilitation services. It also examined the relative influence thereon of factors including injury severity, handicap and cognitive and behavioural changes in the injured person, relationship with the injured person and caregiver status.

Methods : Participants were 143 TBI individuals and their close relatives. They completed the Family Assessment Device (FAD), Leeds Scales of Anxiety and Depression, Structured Outcome Questionnaire, CHART, SIP Psychosocial Dimension and Novaco Anger Control Questionnaire 2-5 years post-injury.

Results : Results showed that families were, on average, functioning in the normal range on the FAD. Anxiety and depression were more likely to be present in those responsible for care of their injured relative. There were no differences between spouses and parents. Presence of cognitive, behavioural and emotional changes was the strongest predictor of anxiety and depression in relatives and of unhealthy family functioning.

Conclusions : Every attempt should be made to develop models of long-term support and care that alleviate these sources of burden on relatives.     

A lifestyle intervention improves plasma insulin levels among Native American high school youth

BACKGROUND: Worldwide, type 2 diabetes prevalence is increasing, with Native American populations particularly at risk. The Zuni Pueblo, with a history of wellness activities, volunteered to test the feasibility and efficacy of a high school-based diabetes prevention intervention. METHODS: This school-based intervention used a multiple cross-sectional design to evaluate outcome measures at 0, 1.5, and 3 years against an Anglo comparison group. The Zuni high school diabetes prevention program included an educational component targeting decreased consumption of sugared beverages, knowledge of diabetes risk factors, and a youth-oriented fitness center. Main outcome measures were plasma glucose and insulin measured fasting and 30 min after a 75-g glucose challenge. RESULTS: Plasma glucose levels were normal at baseline for Zuni (n = 72) and Anglo (n = 37) youth and did not significantly change throughout the study. At baseline, fasting and 30-min plasma insulin levels were significantly elevated for Zuni youth; they showed significant steady declines for both males and females throughout the study (P = 0.06 to P = 0.000 for trends using quantile regression). By Year 3, values for Zuni males (n = 29) equaled Anglo comparison values, while Zuni female (n = 26) values had declined but were still higher than Anglo comparison values. CONCLUSIONS: Among at-risk youth, an environmentally based lifestyle intervention may significantly suppress markers of type 2 diabetes risk.     

Beyond ‘beer,fags, egg and chips’? Exploring lay understandings of social inequalities in health

This paper seeks to contribute to the limited body of work that has directly explored lay understandings of the causes of health inequalities. Using both quantitative and qualitative methodology, the views of people living in contrasting socio-economic neighbourhoods are compared. The findings support previous research in suggesting that lay theories about causality in relation to health inequalities, like lay concepts of health and illness in general, are multi-factorial. The findings, however, also illustrate how the ways in which questions about health and illness are asked shape people's responses. In the survey reported on here people had no problem offering explanations for health inequalities and, in response to a question asking specifically about area differences in health experience, people living in disadvantaged areas 'constructed' explanations which included, but went beyond, individualistic factors to encompass structural explanations that gave prominence to aspects of 'place'. In contrast, within the context of in-depth interviews, people living in disadvantaged areas were reluctant to accept the existence of health inequalities highlighting the moral dilemmas such questions pose for people living in poor material circumstances. While resisting the notion of health inequalities, however, in in-depth interviews the same people provided vivid accounts of the way in which inequalities in material circumstances have an adverse impact upon health. The paper highlights ways in which different methodologies provide different and not necessarily complementary understandings of lay perspectives on the causes of inequalities in health.