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Biomedical subjects

I Johnston

Publications and source records attributed to I Johnston.

At least 19 recordsLinked to original sources
PubMed2006

Individual and group-based parenting programmes for the treatment of physical child abuse and neglect.

BACKGROUND: Child physical abuse and neglect are important public health problems and recent estimates of their prevalence suggest that they are considerably more common than had hitherto been realised. Many of the risk factors for child abuse and neglect are not amenable to change in the short term. Intervening to change parenting practices may, however, be important in its treatment. Parenting programmes are focused, short-term interventions aimed at improving parenting practices in addition to other outcomes (many of which are risk factors for child abuse e.g. parental psychopathology, and parenting attitudes and practices), and may therefore be useful in the treatment of physically abusive or neglectful parents. OBJECTIVES: To assess the efficacy of group-based or one-to-one parenting programmes in addressing child physical abuse or neglect. SEARCH STRATEGY: A range of biomedical and social science databases were searched including MEDLINE, EMBASE, CINAHL, PsychINFO, Sociofile, Social Science Citation Index, ASSIA, the Cochrane Library, Campbell Library (including SPECTR and CENTRAL), National Research Register (NRR) and ERIC, from inception to May 2005. SELECTION CRITERIA: Only randomised controlled trials or randomised studies that compared two treatments were included. Studies had to include at least one standardised instrument measuring some aspect of abusive or neglectful parenting. In the absence of studies using objective assessments of child abuse, studies reporting proxy measures of abusive parenting were included. Only studies evaluating the effectiveness of standardised group-based or one-to-one parenting programmes aimed at the treatment of physical child abuse or neglect were included. Studies were also only eligible for inclusion if they had targeted parents of children aged 0-19 years who had been investigated for physical abuse or neglect. DATA COLLECTION AND ANALYSIS: The treatment effect for each outcome in each study was standardised by dividing the mean difference in post-intervention scores for the intervention and treatment group by the pooled standard deviation, to obtain an effect size. The results for each outcome in each study have been presented, with 95% confidence intervals. It was not possible to combine any results in a meta-analysis. MAIN RESULTS: A total of seven studies of variable quality were included in this review. Only two studies assessed the effectiveness of parenting programmes on the incidence of child abuse or number of injuries. One study showed that there were no reports of abuse in the intervention group compared with one report of abuse in the control group. In the second study the small number of injuries sustained precluded the possibility of statistical analysis. Data were also extracted on over fifty outcomes that are used as proxy measures of abusive parenting. These were on the whole diverse and measured a range of aspects of parenting (e.g. parental child management, discipline practices, child abuse potential and mental health), child health (e.g. emotional and behavioural adjustment) and family functioning, thereby precluding the possibility of undertaking a meta-analysis for most outcomes for which data were extracted. While none of the programmes were effective across all of the outcomes measured, many appeared to have improved some outcomes for some of the participating parents, although many failed to achieve statistical significance. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the use of parenting programmes to treat physical abuse or neglect (i.e. such as the incidence of child abuse using reports of child abuse/linjuries or children on the children protection register). There is, however, limited evidence to show that some parenting programmes may be effective in improving some outcomes that are associated with physically abusive parenting. There is an urgent need for further rigorous evaluation of the effectiveness of parenting programmes that are specifically designed to treat physical abuse and neglect, either independently or as part of broader packages of care. Such evaluation should include the use of objective measures of outcome such as independent assessments of parenting and the number of instances of physical abuse. In order to do this, future studies need to include long-term follow-up.

Child↗
PubMed2002

Cranial venous outflow obstruction in the pseudotumour syndrome: incidence, nature and relevance.

This study reports a retrospective analysis of the evidence of cranial venous outflow pathology in 188 patients with pseudotumour syndrome (PTS) investigated over the period 1968-1999. Standard methods of investigation appropriate to the period were used, i.e. cerebral angiography, CT and MR scanning. Recently, some patients had specific venous studies including intraluminal cranial venous sinus pressure measurements. A sub-group (25 patients) was investigated for haematological abnormalities. The overall incidence of cranial venous outflow abnormality was 19.7% (37 cases). In decades, related to the predominant investigative method, the figures were: to 1979, 4.2% (2 cases); to 1989, 15.0% (8 cases); to 1999, 31.0% (27 cases). A cause of the venous abnormality was identified in 20 cases, most commonly haematological and iatrogenic. In 17 patients (all females) no cause was identified. Fifteen of the 25 patients (60%) tested specifically were found to have a haematological abnormality, although no correlation was shown between this and a demonstrable venous outflow abnormality. The conclusion was drawn that there is a high incidence (close to one-third) of venous outflow abnormalities in PTS with detailed investigation. Issues of mechanism and therapy are discussed.

Adolescent↗
PubMed2001

BDCA-2, a novel plasmacytoid dendritic cell-specific type II C-type lectin, mediates antigen capture and is a potent inhibitor of interferon alpha/beta induction.

Plasmacytoid dendritic cells are present in lymphoid and nonlymphoid tissue and contribute substantially to both innate and adaptive immunity. Recently, we have described several monoclonal antibodies that recognize a plasmacytoid dendritic cell-specific antigen, which we have termed BDCA-2. Molecular cloning of BDCA-2 revealed that BDCA-2 is a novel type II C-type lectin, which shows 50.7% sequence identity at the amino acid level to its putative murine ortholog, the murine dendritic cell-associated C-type lectin 2. Anti-BDCA-2 monoclonal antibodies are rapidly internalized and efficiently presented to T cells, indicating that BDCA-2 could play a role in ligand internalization and presentation. Furthermore, ligation of BDCA-2 potently suppresses induction of interferon alpha/beta production in plasmacytoid dendritic cells, presumably by a mechanism dependent on calcium mobilization and protein-tyrosine phosphorylation by src-family protein-tyrosine kinases. Inasmuch as production of interferon alpha/beta by plasmacytoid dendritic cells is considered to be a major pathophysiological factor in systemic lupus erythematosus, triggering of BDCA-2 should be evaluated as therapeutic strategy for blocking production of interferon alpha/beta in systemic lupus erythematosus patients.

Amino Acid Sequence↗
PubMed2001

The historical development of the pseudotumor concept.

The author outlines the history of the development of the pseudotumor concept, first specifically formulated by Nonne in 1904 but implicit in earlier descriptions. A scheme of periodization is applied, identifying otological, neurosurgical, neurological, and neuroophthalmological periods; he relates theoretical and practical developments in the understanding of the condition to the concerns of the dominant speciality involved in diagnosis and management. Key studies from each period are discussed in relation to the issues of mechanism, origin, nomenclature, diagnosis, and treatment. During the otological period, approaches to the condition were heavily influenced by its common association with middle ear infection, often with venous sinus involvement, and this led to the idea of disturbed cerebrospinal fluid dynamics as the cause. The advent of neuroradiological systems ushered in the neurosurgical period in which the significant but unfinished debate began: which intracranial compartment is primarily implicated in the intracranial hypertension? By the time of the neurological period cerebral edema was implicated as the cause, and this coincided with the availability of appropriate treatment methods and steroidal and diuretic agents. Toward the end of this period additional major advances in investigative methods again brought the issue of mechanism into contention, although a resolution was not to follow. The neuroophthalmological period is characterized by an increased awareness of the significance of visual loss and a return to one of the original methods of treatment. Finally, the possible significance of impaired cranial venous outflow, a thread running through all periods, is considered.

History, 19th Century↗
PubMed2001

Presynaptic neuronal antigens expressed by a small cell lung carcinoma cell line.

Small cell lung carcinoma (SCLC) is a tumour of neuroendocrine origin often found in association with autoimmune paraneoplastic neurological disorders. We established a SCLC cell line from a woman with Lambert-Eaton myasthenic syndrome (LEMS) who developed antibodies to both the P/Q-type voltage-gated calcium channels (VGCC) and the muscle acetycholine receptor (AChR). We used a range of techniques to establish which neuronal antigens were expressed in her tumour cell line. The results show that many proteins involved in exocytosis are present in the SCLC cells, and that depolarisation-dependent release of [(3)H]-serotonin is linked to calcium influx through P/Q-type VGCCs. In addition, some of the subunits encoding the AChR and both agrin and ARIA, molecules released from the motor nerve during development, were expressed. These results suggest that many potential antigenic targets are present in SCLC, and indicate a surprising 'motor nerve terminal'-like characteristic of this line.

Autoantibodies↗
PubMed2001

Conjoined twins.

Explore the source record for details and available documents.

Child Advocacy↗
PubMed2001

Endovascular treatment of cranial venous sinus obstruction resulting in pseudotumor syndrome. Report of three cases.

It is probable that a significant number of cases of pseudotumor syndrome (PTS) occur because of cranial venous outflow obstruction, yet reports of direct treatment of the obstruction are few and inconclusive. In this study the authors report three cases of PTS with angiographically confirmed venous sinus obstruction treated by direct, endovascular procedures; urokinase infusion in two and balloon venoplasty in one. Two patients suffered transient complications that resolved satisfactorily. All three showed initial resolution of the signs and symptoms of PTS but one relapsed after 8 months and required surgical treatment. The possible role and methods of treatment of cranial venous outflow obstruction in PTS are discussed.

Adult↗
PubMed2000

Krp1, a novel kelch related protein that is involved in pseudopod elongation in transformed cells.

We have previously shown that the transcription factor AP-1 regulates the expression of genes which allow neoplastically transformed rat fibroblasts to become invasive. Searches for further AP-1 target genes led to the identification of a gene encoding a novel rat kelch family member, named kelch related protein 1 (Krp1). Kelch family members are characterized by a series of repeats at their carboxyl terminus and a BTB/POZ domain near their amino terminus. Rat Krp1 has a primarily cytoplasmic localization, and a small fraction appears to accumulate and co-localize with F-actin at membrane ruffle-like structures in the tips of pseudopodia. Overexpression of Krp1 in transformed rat fibroblasts led to the formation of dramatically elongated pseudopodia, while expression of truncated Krp1 polypeptides resulted in a reduction in the length of pseudopodia. We propose that the transformation-specific expression of Krp1 is required for pseudopod elongation, which are structures that are required for cell motility and invasion.

Actins↗
PubMed2000

Risk of cryptogenic fibrosing alveolitis in metal workers.

We report increased proportional mortality from cryptogenic fibrosing alveolitis in the workforce of a major UK engineering company. Measures of metal exposure from unbiased historical occupational records showed that among employees who have worked with metal, the risk of death from or with cryptogenic fibrosing alveolitis increased in relation to the duration of metal-working.

Aged↗
PubMed2000

Disorders of CSF hydrodynamics.

This article reviews the range of hydrodynamic disorders affecting the CSF circulation. Initially consideration is given to questions of definition and classification. A scheme for the practical, clinical analysis for the diagnosis of such disorders is then presented. The physiology and pathophysiology of the CSF circulation is reviewed, with particular emphasis on issues that remain unresolved. This provides a background to consideration of the adverse consequences of abnormal CSF hydrodynamics, again focusing on areas where further information is required. Methods of clinical investigation of CSF hydrodynamics are reviewed, followed by general considerations of treatment. Finally, each of the main, clinically important, forms of disordered CSF hydrodynamics is briefly considered, with particular emphasis, again, on areas where current knowledge is deficient. The conditions considered include hydrocephalus of various forms (childhood, adult, arrested, multi-compartment), infantile macrocephaly, arachnoid and glioependymal cysts, syringo- and hydromyelia, pseudotumour cerebri, impaired cranial venous outflow, altered CSF composition, shunt obstruction without ventricular enlargement and low-CSF-pressure states.

Adolescent↗
PubMed2000

The 5'-end of the porcine perinatal myosin heavy chain gene shows alternative splicing and is clustered with repeat elements.

The porcine perinatal myosin heavy chain (MyHC) is a major isoform in foetal skeletal muscles. We report here on its cDNA and genomic isolation, molecular characterisation and expression. Exon 2 and the first 4 bases of exon 3 of the perinatal MyHC gene. both part of the 5'-end untranslated region, showed differential splicing. About 2% of all perinatal MyHC transcripts of a 50-day-old foetus were without exon 2 and about half were without the 4 bases at the 5'-end of exon 3. Perinatal MyHC mRNA was expressed in all hind limb muscles of a 45-day-old foetus along with the slow and embryonic MyHC isoforms in the same fibres. Unlike other sarcomeric MyHCs reported to date, the porcine perinatal promoter is clustered with repeat elements (4 SINEs and 1 microsatellite) and is without a consensus TATA box at the predicted site upstream of exon 1. Nonetheless, in reporter gene transfections, its promoter was found to be highly muscle-specific. The absence of a TATA box may point to a fundamental difference in the regulatory function between the perinatal and adult MyHC isoforms.

Alternative Splicing↗
PubMed2000

Increased risk of fibrosing alveolitis associated with interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphisms.

Fibrosing alveolitis (FA) is characterized by persistent inflammation and elevated production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1beta), and interleukin-1 receptor antagonist (IL-1ra) in the lung. Single base variations at position +2018 in the IL-1ra gene (IL-1RN) and position -308 in the TNF-alpha gene (TNF-A) are overrepresented in other chronic inflammatory disease populations. We have tested the hypothesis that predisposition to FA may also be influenced by these polymorphisms by genotyping 88 cases and matched controls from England and 61 cases and 103 unmatched controls from Italy. The rarer allele for IL-1RN and TNF-A was designated allele 2 in each case. For IL-1RN allele 2, in the English group, the relative odds of FA were increased in homozygous subjects by an odds ratio (OR) of 10.2 (95% confidence intervals [CI], 1.26 to 81.4; p = 0.03) and for carriers by an OR of 1.85 (95% CI, 0.94 to 3.63; p = 0.075). In the Italian population, the risk of FA was increased, in IL-1RN allele 2 homozygotes (OR, 2.54; 95% CI, 0.68 to 9.50; p = 0.2) and in carriers (OR 2.40; 95% CI, 1.26 to 4.60; p = 0.008). Carriage of TNF-A allele 2 was also associated with increased risk of FA in the English (OR, 1.85; 95% CI, 0.94 to 3.63; p = 0.075) and Italian (OR, 2.50; 95% CI, 1.14 to 5.47; p = 0.022) populations. These data suggest IL-1RN (+2018) allele 2 and TNF-A (-308) allele 2 confer increased risk of developing FA and, therefore, that unopposed IL-1beta and/or excessive TNF-alpha may play a pathophysiologic role in this condition.

Aged↗
PubMed1998

The acquired Chiari malformation and syringomyelia following spinal CSF drainage: a study of incidence and management.

Firstly, 14 patients are described who developed either an acquired Chiari malformation (ACM) alone (7 cases) or ACM and syringomyelia (7 cases) after lumbar subarachnoid space (SAS) shunting or in one case, epidural anaesthesia with SAS penetration. Four groups are considered: 3 cases with craniofacial dysostosis and communicating hydrocephalus (CH), 4 cases with CH alone, 3 cases with pseudotumour cerebri (PTC) and a miscellaneous group (4 cases). Initial treatment was varied: resiting the shunt to ventricle or cisterna magna [6], adding an H-V valve [1], syrinx shunting [4] and posterior fossa decompression [3]. Further treatment was required in 6 cases. Secondly, incidence was examined in 87 patients with PTC initially treated either by lumbar SAS shunting [70] or cisterna magna shunting [17]. In the first sub-group, 11 cases (15.7 per cent) developed an ACM, 3 symptomatic (as above) and eight asymptomatic with 1 case also having syringomyelia whereas 1 case occurred in the second group with a questionanably symptomatic ACM. While accurate for symptomatic lesions, these figures are tentative with respect to asymptomatic lesions due to inadequate pre-treatment radiology and detailed MR follow-up. The main conclusions are, first, that the incidence of symptomatic ACM and/or syringomyelia is not high enough to warrant abandoning SAS shunting; second that asymptomatic lesions need not necessarily be treated and third, that when treatment is required, shunt resiting is the first choice.

Adolescent↗
PubMed1998

Exposure to commonly prescribed drugs and the etiology of cryptogenic fibrosing alveolitis: a case-control study.

Cryptogenic fibrosing alveolitis is an interstitial lung disease of unknown etiology. Since pulmonary fibrosis is a recognized, if rare, complication of certain drug exposures, including antidepressants, betablockers, antibiotics, anticonvulsants, and nonsteroidal antiinflammatory drugs (NSAIDs), we tested the hypothesis that exposure to these drugs might contribute to the etiology of cryptogenic fibrosing alveolitis. Lifetime drug exposure data were collected from general practitioner records for 141 cases of cryptogenic fibrosing alveolitis and 246 age-, sex-, and community-matched control subjects from the Trent region of England. Additional data on lifetime smoking habits were obtained by postal questionnaire. The odds of disease in relation to ever exposure to antidepressants, betablockers, antibiotics, anticonvulsants, and NSAIDs were calculated by conditional logistic regression. For drug groups significantly associated with cryptogenic fibrosing alveolitis, subset analyses were performed to investigate the effects of individual drugs. Cryptogenic fibrosing alveolitis was associated with exposure to antidepressants (odds ratio [OR] 1.79 [95% CI 1.09-2.95], p = 0.022) and specifically to imipramine (OR 4.79 [1.50-15.3], p = 0.01), dothiepin (OR 2.37 [0.99-5.69], p = 0.05), and mianserin (OR 3.27 [1.11-9.61], p = 0.03). The magnitude of the overall effect of antidepressants was not changed by excluding all drug exposures within the 5 yr preceding the diagnosis of cryptogenic fibrosing alveolitis (OR 1.62 [0.94-2.77], p = 0.081), nor were the strong individual effects of imipramine (OR 5.72 [1.54-21.2], p = 0.009) and dothiepin (OR 5.58 [1.12-27.8], p = 0.036). These estimates were not appreciably affected by controlling for smoking history. The attributable risk for antidepressant exposure was in the region of 9-14%. No significant association was noted between cryptogenic fibrosing alveolitis and the four other drug groups in the primary hypothesis. The results of this study suggest that some antidepressant drugs can cause cryptogenic fibrosing alveolitis.

Adrenergic beta-Antagonists↗