Elevated levels of somatic mutation in a manifesting BRCA1 mutation carrier.

Homozygous loss of activity at the breast cancerpredisposing genes BRCA1 and BRCA2 (FANCD1) confers increased susceptibility to DNA double strand breaks, but this genotype occurs only in the tumor itself, following loss of heterozygosity at one of these loci. Thus, if these genes play a role in tumor etiology as opposed to tumor progression, they must manifest a heterozygous phenotype at the cellular level. To investigate the potential consequences of somatic heterozygosity for a BRCA1 mutation demonstrably associated with breast carcinogenesis on background somatic mutational burden, we applied the two standard assays of in vivo human somatic mutation to blood samples from a manifesting carrier of the Q1200X mutation in BRCA1 whose tumor was uniquely ascertained through an MRI screening study.

Clinical prediction rules can be derived and validated for injured Australian workers with persistent musculoskeletal pain: an observational study.

Questions: Can clinical prediction rules be derived for injured Australian workers with persistent musculoskeletal pain? Are they valid?

Design: Longitudinal observational study.

Participants: 847 injured workers with persistent musculoskeletal pain undergoing rehabilitation.

Outcome Measures: At baseline, 12 putative predictors were measured.

Assessment of diclofenac or spinal manipulative therapy, or both, in addition to recommended first-line treatment for acute low back pain: a randomised controlled trial.

Background: We aimed to investigate whether the addition of non-steroidal anti-inflammatory drugs or spinal manipulative therapy, or both, would result in faster recovery for patients with acute low back pain receiving recommended first-line care.

Methods: 240 patients with acute low back pain who had seen their general practitioner and had been given advice and paracetamol were randomly allocated to one of four groups in our community-based study: diclofenac 50 mg twice daily and placebo manipulative therapy (n=60); spinal manipulative therapy and placebo drug (n=60); diclofenac 50 mg twice daily and spinal manipulative therapy (n=60); or double placebo (n=60). The primary outcome was days to recovery from pain assessed by survival curves (log-rank test) in an intention-to-treat analysis.

The reproducibility of a clinical grading system of motor control in patients with low back pain.

Objective: Over the past decade, instrument and palpation methods for quantifying the activation and recruitment of the transversus abdominis and lumbar multifidus have been proposed. Palpation methods however have recently been described and therefore have been subjected to little evaluation. One such palpation method is the Wisbey-Roth grading system.

Psychometric characteristics of the Brazilian-Portuguese versions of the Functional Rating Index and the Roland Morris Disability Questionnaire.

Study Design: Translation, cross-cultural adaptation and psychometric testing of self-report outcome measurements.

Objectives: The aims of this study were to adapt the Functional Rating Index (FRI) to Brazilian-Portuguese and to test the psychometric properties of this new questionnaire and the Brazilian-Roland Morris Disability Questionnaire (RMDQ).

Summary Of Background Data: Self-report measures are commonly used in clinical practice and in research studies.

Systematic review of tests to identify the disc, SIJ or facet joint as the source of low back pain.

Clinical practice guidelines state that the tissue source of low back pain cannot be specified in the majority of patients. However, there has been no systematic review of the accuracy of diagnostic tests used to identify the source of low back pain. The aim of this systematic review was therefore to determine the diagnostic accuracy of tests available to clinicians to identify the disc, facet joint or sacroiliac joint (SIJ) as the source of low back pain.

Diagnosis, dysmorphology, and the family: knowledge, motility, choice.

This article examines the specific ways in which the gene, the clinic, and the family interact in clinical consultations over children with suspected congenital problems. It draws upon an ethnography of dysmorphology, a specialty in genetic medicine that involves the study of abnormal human forms and the description of complex syndromes. Dysmorphologists describe what they do as "genetic counselling," a twin process of differential diagnosis and the calculation of risk of recurrence in other pregnancies.

Self-report outcome measures for low back pain: searching for international cross-cultural adaptations.

Study Design: Systematic review.

Objectives: To describe the available cross-cultural adaptations of low back pain (LBP) self-report outcome measures and the psychometric testing that has occurred for each adaptation.

Summary Of Background Data: Self-report measures are commonly used in clinical practice and in research studies.

Becoming in-formed: genetic counselling, ambiguity and choice.

The paper presents findings from an ethnography of dysmorphology, a specialism in genetic medicine, to explore genetic counselling as a process through which parents 'become informed.' Current professional and policy debate over the use of genetic technology in medicine emphasises the need for informed choice making, and for genetic services that provide parents with what is referred to as 'non-directive genetic counselling.' In the paper the process of becoming informed is shown to be very specific and to have its own effects.

Gynaecological malignancies in pregnancy.

Purpose Of Review: To review the management of gynaecological cancers occurring in association with pregnancy. To consider the impact of the cancer on the pregnancy, and the impact of the pregnancy on the cancer.

Recent Findings: The management of gynaecological cancers in pregnancy remains, fortunately, a rare problem for the gynaecological oncology team.

Efficacy of manipulation for non-specific neck pain of recent onset: design of a randomised controlled trial.

Background: Manipulation is a common treatment for non-specific neck pain. Neck manipulation, unlike gentler forms of manual therapy such as mobilisation, is associated with a small risk of serious neurovascular injury and can result in stroke or death. It is thought however, that neck manipulation provides better results than mobilisation where clinically indicated.

Comparison of general exercise, motor control exercise and spinal manipulative therapy for chronic low back pain: A randomized trial.

Practice guidelines recommend various types of exercise and manipulative therapy for chronic back pain but there have been few head-to-head comparisons of these interventions. We conducted a randomized controlled trial to compare effects of general exercise, motor control exercise and manipulative therapy on function and perceived effect of intervention in patients with chronic back pain. Two hundred and forty adults with non-specific low back pain 3months were allocated to groups that received 8weeks of general exercise, motor control exercise or spinal manipulative therapy.

Prospective screening study of 0.5 Tesla dedicated magnetic resonance imaging for the detection of breast cancer in young, high-risk women.

Background: Evidence-based screening guidelines are needed for women under 40 with a family history of breast cancer, a BRCA1 or BRCA2 mutation, or other risk factors. An accurate assessment of breast cancer risk is required to balance the benefits and risks of surveillance, yet published studies have used narrow risk assessment schemata for enrollment. Breast density limits the sensitivity of film-screen mammography but is not thought to pose a limitation to MRI, however the utility of MRI surveillance has not been specifically examined before in women with dense breasts.

Selecting an appropriate placebo for a trial of spinal manipulative therapy.

Selecting an appropriate control group or placebo for randomised controlled trials of spinal manipulative therapy is essential to the final interpretation and usefulness of these studies. Prior to starting a randomised controlled trial of spinal manipulative therapy for acute low back pain we wanted to ensure that the placebo selected would be considered appropriate by experts in the field thereby making the results more likely to be accepted and more likely to influence clinical practice. We developed ten placebo techniques that aimed to mimic spinal manipulative therapy as closely as possible which, while not including the active component of spinal manipulative therapy, were still credible.

The effect of an exercise intervention on aerobic fitness, strength and quality of life in children with haemophilia (ACTRN012605000224628).

Background: Children with haemophilia have lower levels of fitness and strength than their healthy peers. We present the protocol of a study designed to determine whether an exercise intervention improves quality of life, aerobic fitness and strength in children with haemophilia.

Methods/design: The study will be a randomised, assessor-blinded, controlled trial of exercise treatment.

Providing effective substance abuse treatment for young-offender populations: what works!

Previous research has documented a strong linkage between substance abuse and criminal activity among young offenders. Consequently, the provision of effective substance-abuse interventions for this population is of paramount importance to the criminal justice system. This article explores the literature on the treatment of substance abuse in offender and nonoffender populations.

Haemophilus ducreyi targets Src family protein tyrosine kinases to inhibit phagocytic signaling.

Haemophilus ducreyi, the etiologic agent of the sexually transmitted disease chancroid, has been shown to inhibit phagocytosis of both itself and secondary targets in vitro. Immunodepletion of LspA proteins from H. ducreyi culture supernatant fluid abolished this inhibitory effect, indicating that the LspA proteins are necessary for the inhibition of phagocytosis by H.

Manipulative therapy and/or NSAIDs for acute low back pain: design of a randomized controlled trial [ACTRN012605000036617].

Background: Acute low back pain is a common condition resulting in pain and disability. Current national and international guidelines advocate general practitioner care including advice and paracetamol (4 g daily in otherwise well adults) as the first line of care for people with acute low back pain. Non-steroidal anti-inflammatory drugs (NSAIDs) and spinal manipulative therapy (SMT) are advocated in many guidelines as second line management options for patients with acute low back pain who are not recovering.

The effect of motor control exercise versus placebo in patients with chronic low back pain [ACTRN012605000262606].

Background: While one in ten Australians suffer from chronic low back pain this condition remains extremely difficult to treat. Many contemporary treatments are of unknown value. One potentially useful therapy is the use of motor control exercise.

Dysmorphology and the spectacle of the clinic.

Dysmorphology is the medical study of abnormal forms in the human and is concerned with the identification and classification of a variety of congenital malformations. Such diagnostic work rests on the inspection of images of affected individuals. Based on physical appearance individuals are classified in terms of a wide range of conditions, often with 'exotic' nomenclatures.

Haploinsufficiency for BRCA1 is associated with normal levels of DNA nucleotide excision repair in breast tissue and blood lymphocytes.

Background: Screening mammography has had a positive impact on breast cancer mortality but cannot detect all breast tumors. In a small study, we confirmed that low power magnetic resonance imaging (MRI) could identify mammographically undetectable tumors by applying it to a high risk population. Tumors detected by this new technology could have unique etiologies and/or presentations, and may represent an increasing proportion of clinical practice as new screening methods are validated and applied A very important aspect of this etiology is genomic instability, which is associated with the loss of activity of the breast cancer-predisposing genes BRCA1 and BRCA2.

The UspA2 protein of Moraxella catarrhalis is directly involved in the expression of serum resistance.

Many strains of Moraxella catarrhalis are resistant to the bactericidal activity of normal human serum. Previous studies have shown that mutations involving the insertion of an antibiotic resistance cartridge into the M. catarrhalis uspA2 gene resulted in the conversion of a serum-resistant strain to a serum-sensitive phenotype.