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Biomedical subjects

J Hogg

Publications and source records attributed to J Hogg.

At least 19 recordsLinked to original sources
PubMed2005

Determination of guinea-pig cortical gamma-secretase activity ex vivo following the systemic administration of a gamma-secretase inhibitor.

(2S)-2-{[(3,5-Diflurophenyl)acetyl]amino}-N-[(3S)-1-methyl-2-oxo-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-3-yl]propanamide (compound E) is a gamma-secretase inhibitor capable of reducing amyloid beta-peptide (1-40) and amyloid beta-peptide (1-42) levels. In this study we investigated the effect of in vivo administration of compound E on guinea-pig plasma, CSF and cortical amyloid beta-peptide (1-40) concentration. Using repeated sampling of CSF, compound E (30 mg/kg p.o.) was shown to cause a time-dependent decrease in CSF amyloid beta-peptide (1-40) levels, which was maximal at 3 h (70% inhibition), compared to baseline controls. After 3 h administration, compound E (3, 10 and 30 mg/kg p.o.), reduced plasma, CSF and DEA-extracted cortical amyloid beta-peptide (1-40) levels by 95, 97 and 99%; 26, 48 and 78%; 32, 33, and 47%, respectively, compared to vehicle control values. In the same animals, compound E (3, 10 and 30 mg/kg p.o.) inhibited cortical gamma-secretase activity, determined ex vivo using the recombinant substrate C100Flag, by 40, 71 and 79% of controls, respectively. These data demonstrate the value of determining not only the extent by which systemic administration of a gamma-secretase inhibitor reduces amyloid beta-peptide, but also the inhibition of brain gamma-secretase activity, as a more direct estimate of enzyme occupancy.

Administration, Oral↗
PubMed2001

Utility of a lung biopsy for the diagnosis of idiopathic pulmonary fibrosis.

It is not known if a surgical lung biopsy is necessary in all patients for the diagnosis of idiopathic pulmonary fibrosis (IPF). We conducted a blinded, prospective study at eight referring centers. Initially, cases were evaluated by clinical history and examination, transbronchial biopsy, and high-resolution lung computed tomography scans. Pulmonologists at the referring centers then assessed their certainty of the diagnosis of IPF and provided an overall diagnosis, before surgical lung biopsy. The lung biopsies were reviewed by a pathology core and 54 of 91 patients received a pathologic diagnosis of IPF. The positive predictive value of a confident (certain) clinical diagnosis of IPF by the referring centers was 80%. The positive predictive value of a confident clinical diagnosis was higher, when the cases were reviewed by a core of pulmonologists (87%) or radiologists (96%). Lung biopsy was most important for diagnosis in those patients with an uncertain diagnosis and those thought unlikely to have IPF. These studies suggest that clinical and radiologic data that result in a confident diagnosis of IPF by an experienced pulmonologist or radiologist are sufficient to obviate the need for a lung biopsy. Lung biopsy is most helpful when clinical and radiologic data result in an uncertain diagnosis or when patients are thought not to have IPF.

Biopsy↗
PubMed2001

Consistency, context and confidence in judgements of affective communication in adults with profound intellectual and multiple disabilities.

Twenty-four service providers rated 12 video samples of four service users with whom they were familiar for affective behaviour (i.e. 'like'/'dislike') and confidence (i.e. 'certain'/'uncertain') in their judgement. Each video sample had been recorded as part of a stimulus preference assessment during which a wide range of specific stimuli were presented to each service user. Each video sample was presented twice in a counterbalanced design either with contextual information, i.e. what the presented stimulus was (C) or without such information, i.e. context free (CF). The observers showed considerable individual variation in their judgements, largely uninfluenced by the availability or otherwise of contextual information. However, as a group, observers significantly distinguished between video samples with regard to affective communication (determined through multiple analyses of variance) and the pattern of judgements, i.e. the relative judgement of positive or negative affect, from one sample to another. This showed a good level of consistency between observers (determined through principal components analysis). The impact of contextual information was not apparent for all video samples. However, contextual information significantly influenced judgements in four samples, typically making them more extreme; for example, a response indicative of positive affect in the CF situation became more positive when contextual information was provided, indicating that the stimulus was one that the participant was thought to like.

Adult↗
PubMed2001

Patterns of offending among people with intellectual disability: a systematic review. Part I: methodology and prevalence data.

A systematic review of research on offenders with intellectual disability (ID) was conducted. In the present study, the first of a two-part presentation of the findings, the authors outline the methodology of the review and present data on the prevalence of offending by adults with ID. The review highlights the methodological problems of the research and the low level of rigour in many of the studies. The organization of the penal and 'care' systems are seen to have a huge impact on research findings. In addition, studies which adopt an IQ-based concept of ID show low rates of offending, whilst those which use wider definitions (e.g. attendance at special school) show higher ones. There is also preliminary evidence for believing that the prevalence of arson and sexual offences may be higher relative to other kinds of crimes for people with ID than for other offenders.

Conduct Disorder↗
PubMed2001

Patterns of offending among people with intellectual disability: a systematic review. Part II: predisposing factors.

In the present study, the second part of a review of offending by adults with intellectual disability (ID), data on predisposing factors are presented and there is a discussion of the overall conclusions. The available data are shown to be problematic in a number of respects: there is no offence-specific data; and a number of dimensions are under-explored, specifically race, class and subjective accounts of offenders. Age and gender were the most highly correlated factors, as they are with offenders generally; however, there does appear to be evidence that the average age of offenders with ID is higher than for other offenders. The present authors note with concern the inattention to mainstream criminological research, and a tendency to downplay the extent to which an 'offender' is the outcome of complex and multifarious social processes. The authors also argue that the literature is dominated by unsubstantiated assumptions regarding the direction which policy and practice should take.

Causality↗
PubMed2000

Continuity and change in the use of residential services by adults with intellectual disability: the Aberdeen cohort at mid-life.

The present paper reports a follow-up study of a representative cohort of people with intellectual disability, now in middle age, who entered adult services on leaving school in the late 1960s, and whose adult years have coincided with a period of radical policy change and considerable service expansion. The present authors focus on the changes which have taken place in their use of residential services over this period. Firstly, the situation in early adulthood when they were last studied is examined. At this time, 60% of the cohort were still living at home, almost all with both parents. The remaining 40% were in institutions, mainly long-stay mental handicap hospitals. Out-of-home placement is associated with gender (maleness), challenging behaviour, and the absence of one or both parents. The present authors compare this with the situation 20 years later. The most significant change in this time is the expansion of the community sector, accounting for about half of the surviving cohort, with numbers still at home or in hospital correspondingly reduced. Almost half of the cohort had experienced little or no change in residential situation. On average, they were less intellectually and socially able than those who had moved into community provision.

Activities of Daily Living↗
PubMed1999

Behavior states: now you see them, now you don't.

Guess, Roberts, Behrens, and Rues (1998) presented reliability data from recordings of behavior state using a 13-category coding system. Interobserver agreement was reported at 63% to 91% across categories. In an attempt at replication, we found lower levels of reliability (0% to 80%). To determine the reasons for different results, we obtained measurements of behavior states from video-recordings by five of Guess et al.'s observers. Again, replication was unsuccessful. Obtained mean percentage agreement on occurrence for individual behavior states and participants ranged across observer pairs from 0% to 58% (kappa range was 0 to .64). Some possible reasons for failures to replicate are discussed.

Humans↗
PubMed1999

Cellular distribution and ontogeny of insulin-like growth factors (IGFs) and IGF binding protein messenger RNAs and peptides in developing rat pancreas.

To determine the role of insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) in the development of the pancreas, and specifically of the islets of Langerhans, we have examined the cellular distribution and developmental changes in the expression of IGFs and IGFBPs in the pancreas of the fetal and neonatal rat between 19.5 days of gestation and postnatal day 28. This represents a period of substantial growth and restructuring of the beta cell component in islets of this species. IGF-I, IGF-II, and IGFBPs-1 to -6 mRNAs were localized by in situ hybridization, and peptides by immunohistochemistry, in histological sections. IGF-II mRNA was highly expressed in islet cells and some ductal epithelial cells in late fetal and early neonatal life, but was barely detectable by postnatal day 28. IGF-II peptide showed a similar distribution. IGF-I mRNA was barely detected in the fetus or neonate and was localized predominantly in the ductal and acinar tissues after postnatal day 7. IGF-I immunoreactivity was associated with some islet cells in the fetus and neonate, suggesting an endocrine rather than a paracrine source. We performed co-localization studies to assess whether the distribution of IGFs within the pancreas might be due to a sequestration by locally produced IGFBPs. The presence of mRNAs for both IGFBPs-1 and -2 was minimal in the pancreas prior to postnatal day 7, although subsequently IGFBP-1 mRNA was seen in islet cells, while IGFBP-2 mRNA was localized in both islets and acinar tissues. In contrast, both IGFBPs-1 and -2 immunoreactivities were identified in islets from late fetal life, suggesting a circulatory source for these IGFBPs during early pancreatic development. IGFBPs-3 to -5 mRNAs and immunoreactivities were identified within islet cells throughout fetal and neonatal life, with IGFBPs-3 and -5 being mainly associated with the alpha cell-rich islet mantle. The results show a compartmentalization of IGFs within pancreatic tissue, reflecting both paracrine and endocrine sources. The localization and action of IGFs in pancreas likely involves sequestration and distribution by endogenous as well as circulating IGFBPs.

Animals↗
PubMed1997

Intellectual disability and ageing: ecological perspectives from recent research.

Ageing in people with intellectual disabilities has become a central concern of service providers and research workers during the past 20 years. Their emergence as an identifiable population of older people with intellectual disabilities reflects, in part, improvements in medical and social service provision. However, interest in this group is primarily a reflection of the fact that, despite services developed in the light of principles of normalization, they remain readily identifiable as people in receipt of specialist intellectual disability services, in consequence typically clearly differentiated from the mainstream of older people generally. Analysis of this situation and other factors impacting on older people with intellectual disabilities can be undertaken through the use of ecological models conceptualized in terms of interacting, nested ecologies. The emergence of research on the impact of cultural influences on family carers and service provision is addressed within the framework of the ecological model, and methodological cautions are offered. The enduring the role of family carers and their motivation to continue caring is described.

Adult↗
PubMed1997

Interobserver agreement and disagreement in continuous recording exemplified by measurement of behavior state.

Continuous observational recording was used to measure behavior state of 3 adults with profound and multiple disabilities. Observations were made over 56.7 hours, including 21.9 hours with two observers recording independently. Overall percentage agreement was satisfactory (i.e., exceeded 80%). Agreement on occurrence was, however, generally unsatisfactory at a mean of 63.5%, with 5 of 16 Subject x State Agreement Indices over 80%. Percentage disagreement on occurrence, a previously unreported measure, was computed to quantify sources of disagreement. The agreement data were superimposed on participants' behavior state profiles to demonstrate how conclusions can be drawn from the data, despite their generally inadequate reliability. This approach to interobserver agreement and presentation of data is suggested for researchers investigating entities that are not directly amenable to observation.

Adult↗
PubMed1996

Colour duplex ultrasonography versus angiography in the diagnosis of lower-extremity arterial disease.

Colour duplex scanning is reported to be an accurate non-invasive tool for the diagnosis of lower-extremity arterial disease. The authors at the South Coast Vascular Laboratory have conducted a prospective audit to determine the efficacy of colour duplex scanning in a vascular surgical practice. The aims of this prospective trial were to compare the accuracy of colour duplex scanning with intra-arterial digital subtraction angiography (DSA) in the localization and classification of aortoiliac and femoropopliteal artery disease. Ninety-one lower limbs in 50 patients were evaluated independently by colour duplex scanning and DSA. The lower-limb vasculature was divided into eight segments: infrarenal aorta, common iliac artery, external iliac artery, common femoral artery, proximal, middle and lower thirds of the combined length of the superficial femoral and above-knee popliteal artery, and lastly the below-knee popliteal artery. A total of 558 arterial segments were examined. The Kappa value of duplex scanning compared with 'gold standard' DSA was 0.57. For detecting haemodynamically significant arterial lesions of > 50% reduction in diameter, duplex scanning had a sensitivity of 75%, specificity of 90%, positive predictive value of 77% and negative predictive value of 89% compared with DSA. The level of accuracy obtained does not support the use of duplex as a sole method of investigation for lower-extremity arterial disease in the authors' case. However, the high negative predictive value of colour duplex may be useful in excluding haemodynamically significant disease. This study emphasizes the importance of prospective auditing to determine individual accuracy with duplex examination for arterial disease, and enables clinical decision making to be based on tests with a known accuracy.

Angiography, Digital Subtraction↗
PubMed1996

Practice guidelines for the clinical assessment and care management of Alzheimer's disease and other dementias among adults with intellectual disability. AAMR-IASSID Workgroup on Practice Guidelines for Care Management of Alzheimer's Disease among Adults with Intellectual Disability.

The AAMR/IASSID practice guidelines, developed by an international workgroup, provide guidance for stage-related care management of Alzheimer's disease, and suggestions for the training and education of carers, peers, clinicians and programme staff. The guidelines suggest a three-step intervention activity process, that includes: (1) recognizing changes; (2) conducting assessments and evaluations; and (3) instituting medical and care management. They also provide guidance for public policies that reflect a commitment for aggressive care of people with Alzheimers's disease and intellectual disability, and avoidance of institutionalization solely because of a diagnosis of dementia.

Activities of Daily Living↗
PubMed1995

Gene for the catalytic subunit of mouse DNA-dependent protein kinase maps to the scid locus.

The gene encoding the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) has been proposed recently as a candidate gene for the mouse severe combined immune deficiency (scid) locus. We have used a partial cDNA clone for human DNA-PKcs to map the mouse homologue using a large interspecific backcross panel. We found that the mouse gene for DNA-PKcs does not recombine with scid, consistent with the hypothesis that scid is a mutation in the mouse gene for DNA-PKcs.

Animals↗
PubMed1995

Basic fibroblast growth factor increases dopaminergic graft survival and function in a rat model of Parkinson's disease.

The clinical use of fetal neural grafts as an intracerebral source of dopamine for patients with Parkinson's disease has met with limited success. Since basic fibroblast growth factor (bFGF) enhances the survival and growth of dopaminergic neurons in vitro, we explored whether cells genetically modified to produce bFGF would improve the functional efficacy of dopaminergic neurons implanted into rats with experimental Parkinson's disease. Results show that bFGF-producing cells grafted together with fetal dopamine neurons have potent growth-promoting effects on the implanted neurons in vivo. Moreover, rats implanted with such co-grafts display the most pronounced behavioural improvements post-grafting. These findings not only provide insight into the function of bFGF in situ, but also suggest an approach for enhancing the survival and function of dopamine neurons grafted into the damaged brain.

Animals↗
PubMed1995

Expression of biologically active basic fibroblast growth factor by genetically modified rat primary skin fibroblasts.

Basic fibroblast growth factor (FGF-2) is normally expressed as a cell-associated protein, and accordingly it is not clear how it exerts its action on target cells in vivo. It has been proposed that cells release, by death or other mechanisms, small amounts of FGF-2 that then acts in an autocrine manner. To address the question of whether it is necessary that FGF-2 remain cell associated or needs to be secreted from cells to have biological activity, we expressed the 18-kDa form of FGF-2 in primary fibroblasts as a cell-associated (FGF-2-B) or as a secreted (FGF-2-S) protein. FGF-2 protein is detected in cell lysates and membrane fractions of both cell types, whereas it is present in significant amounts only in the conditioned medium of FGF-2-S cells. No FGF-2 is detected in control (untransfected) cells. FGF-2-S cells also grow faster than the control of FGF-2-B cells. Yet, when evaluated for their ability to promote the survival of embryonic hippocampal neurons in vitro, both the cell types are active, establishing the activity of the transgene product. We conclude that FGF-2 is active when engineered to be expressed as a cell-associated form or secreted from cells.

Animals↗