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Biomedical subjects

P J Robinson

Publications and source records attributed to P J Robinson.

At least 19 recordsLinked to original sources
PubMed2006

A multivariate analysis of the factors predicting hearing outcome after surgery for cholesteatoma in children.

OBJECTIVE: To explore factors influencing hearing outcomes in children treated by canal wall up (CWU) and canal wall down (CWD) mastoid surgery. METHODS: Retrospective cohort study including three units in Bristol and Bath, UK. Ninety consecutive children underwent cholesteatoma mastoid surgery, with the first procedure between 1998 and 2001; minimum follow up was three disease-free years. RESULTS: The CWU and CWD cohorts significantly differed in pre-operative stage and hearing. After disease eradication, air conduction (AC) thresholds changed by +4.0 dB (95 per cent confidence intervals (95% CI) -2.0, 10.1) in the CWD group and -5.3 dB (95% CI -9.3, 1.3) in the CWU group (p=0.029). Using multiple linear regression to account for cohort differences, AC thresholds were increased by: pre-operative AC threshold (p<0.0001), initial ossicular stage (p=0.013), and CWD-surgery (p=0.005). CONCLUSION: Disease-free hearing was better with CWU-surgery, less initial ossicular damage, and better pre-operative hearing. Worse initial disease increased the likelihood of CWD surgery. Wider use of ossiculoplasty in the CWU cohort (51 per cent vs 5 per cent) may partially explain the superior results.

Adolescent↗
PubMed2006

Does splenectomy in cystic fibrosis related liver disease improve lung function and nutritional status? A case series.

AIMS: To review the effect of total splenectomy on lung function and nutrition in children with cystic fibrosis related liver disease (CFLD) and associated portal hypertension. The stated indications for surgery and the short and long term risks of the procedure were also documented. METHOD: Over a 25 year period from January 1980 to June 2005, approximately 650 patients with cystic fibrosis (CF) were treated at the Royal Children's Hospital, Melbourne, Australia. Nine patients with CFLD who underwent a splenectomy during that time were identified and their medical records were reviewed. RESULTS: FEV1% predicted dropped by -16+/-11% in the two years pre-splenectomy. This contrasts with the increase in FEV1% predicted of 2+/-16% in the two years post-splenectomy (p = 0.05). The cumulative gain in WAZ score (DeltaWAZ pre) over the two years prior to splenectomy of 0.045+/-0.69 was not significantly different from the cumulative gain in WAZ score (DeltaWAZ post) for the two years after splenectomy of 0.15+/-0.36 (p = 0.65). The average age at splenectomy was 14.8 years (SD = 3 years). The average weight of an excised spleen was 983 g (SD = 414 g). There were no deaths associated with splenectomy. The median length of follow up post-splenectomy was 6.0 years (range 0.7-15.8). There were no episodes of bacterial peritonitis or overwhelming sepsis. CONCLUSIONS: Splenectomy may have a beneficial effect on lung function although this may not manifest itself until the second year post-splenectomy. Splenectomy in patients with CFLD appears to be a safe procedure.

Adolescent↗
PubMed2006

Increased levels of SNAP-25 and synaptophysin in the dorsolateral prefrontal cortex in bipolar I disorder.

OBJECTIVE: In order to identify whether the mechanisms associated with neurotransmitter release are involved in the pathologies of bipolar disorder and schizophrenia, levels of presynaptic [synaptosomal-associated protein-25 (SNAP-25), syntaxin, synaptophysin, vesicle-associated membrane protein, dynamin I] and structural (neuronal cell adhesion molecule and alpha-synuclein) neuronal markers were measured in Brodmann's area 9 obtained postmortem from eight subjects with bipolar I disorder (BPDI), 20 with schizophrenia and 20 controls. METHODS: Determinations of protein levels were carried out using Western blot techniques with specific antibodies. Levels of mRNA were measured using real-time polymerase chain reaction. RESULTS: In BPDI, levels of SNAP-25 (p < 0.01) and synaptophysin (p < 0.05) increased. There were no changes in schizophrenia or any other changes in BPDI. Levels of mRNA for SNAP-25 were decreased in BPDI (p < 0.05). CONCLUSION: Changes in SNAP-25 and synaptophysin in BPDI suggest that changes in specific neuronal functions could be linked to the pathology of the disorder.

Antibodies↗
PubMed2006

Pneumothorax in cystic fibrosis: a retrospective case series.

Pneumothorax is a known complication in cystic fibrosis (CF), associated with poor outcome. Records of CF patients with pneumothorax at the Royal Children's Hospital, Melbourne between 1990 and 2004 were reviewed, and the characteristics, sputum culture results, lung function, treatment, and outcome for the 11 patients who had pneumothoraces were described.

Adolescent↗
PubMed2005

Clinical assessment alone will not benefit patients with coronary heart disease: failure to achieve cholesterol targets in 12,045 patients--the Healthwise II study.

Healthwise II, a nurse-led audit programme in primary care during 1999-2002, assessed the uptake of secondary preventative measures for coronary heart disease (CHD). Risk factors, cardiovascular medications and blood cholesterol were recorded; 'at risk' patients were invited for a review after 6 months. Of 17,570 patients assessed, CHD was clinically present in 12,045 (69%); in these, aspirin usage was high (78%) but fewer patients were on a beta-blocker (40%), angiotensin-converting enzyme inhibitor (27%) or statin (49%). Blood pressure (BP) was controlled (<140/90) in only 41% of patients. Total cholesterol was >5 mmol/l in 49% of all CHD patients, half of whom were taking a statin. In the statin users, total cholesterol was uncontrolled (>5 mmol/l) in 38%. At follow-up, BP control remained at 42%, statin use increased to 57% and cholesterol remained elevated in 46%. Simple assessment in an audit programme fails to trigger change, and risk-factor modification for CHD remains inadequate.

Age Factors↗
PubMed2004

The use of perioperative Sofradex eardrops in preventing tympanostomy tube blockage: a prospective double-blinded randomized-controlled trial.

Around 11-12% of tympanostomy tubes are reported to become blocked by middle ear secretions or blood immediately following surgery, and so no longer function. Many otologists routinely instil an antibiotic and steroid-containing solution at the time of surgery in the belief that this may reduce this complication. The aim of the study was to investigate the efficacy of instilling the antibiotic and steroid-containing solution Sofradex at the time of grommet insertion in preventing grommet blockage. Double-blind randomized-controlled trial, comparing rates of grommet blockage in ears treated with Sofradex drops against control (no drops) in patients undergoing bilateral grommet insertion. Sixty-one pairs of results were obtained. There was a significant difference between the rates of grommet blockage in the two groups. Grommets with Sofradex drops instilled perioperatively were nine times less likely to be blocked than controls [1.6%versus 13.1%, odds ratio (Sofradex/control) = 9.06, 95% confidence interval (CI): 1.04-78.82, P = 0.05]. There was no association between grommet blockage and perioperative bleeding or the nature and presence of middle ear secretions. Sofradex eardrops are effective in reducing the rate of grommet blockage when instilled perioperatively.

Administration, Topical↗
PubMed2003

Canine trachealis muscle shortening and cartilage mechanics.

Canine trachealis muscle will shorten by 70% of resting length when maximally stimulated in vitro. In contrast, trachealis muscle will shorten by only 30-40% when stimulated in vivo. To examine the possibility that an elastic load applied by the tracheal cartilage contributes to the in vivo limitation of shortening, single pairs of sonomicrometry crystals were inserted into the trachealis muscle at the level of the fifth cartilage ring in five dogs. The segment containing the crystals was then excised and mounted on a tension-testing apparatus. Points on the active length-tension curve and the passive length-tension relation of the cartilage only were determined. The preload applied to the muscle before contraction varied from 10 to 40 g (mean 21 +/- 4 g). The afterload applied by the cartilage during trachealis contraction ranged from 13 to 56 g (30 +/- 6 g). The calculated elastic afterloads were substantial and appeared to be sufficient to explain the degree of shortening observed in four of the seven rings; in the remaining three rings, the limitation of shortening was greater than would be expected from the elastic load provided by the cartilage. Additional sources of loading and/or additional mechanisms may contribute to limited in situ shortening. In summary, tracheal cartilage applies a preload and an elastic afterload to the trachealis that are substantial and contribute to the limitation of trachealis muscle shortening in vivo.

Animals↗
PubMed2003

Laryngeal foreign bodies in children: first stop before the right main bronchus.

Laryngeal foreign bodies may produce either complete or incomplete airways obstruction. In complete airways obstruction the presentation is with calamitous respiratory difficulty. However incomplete laryngeal obstruction may present with less severe symptoms, resulting in possible misdiagnosis and confusion with other causes of upper airway obstruction such as infectious croup. This report describes three cases of incomplete laryngeal obstruction secondary to inhaled foreign bodies. In each case, the diagnosis of an inhaled foreign body was initially missed, resulting in delay in diagnosis and in one case prolonged recovery. The importance of considering laryngeal foreign bodies, both in cases of suspected foreign body inhalation and clinical cases of incomplete laryngeal obstruction are discussed.

Bronchi↗
PubMed2003

Small "indeterminate" lesions on CT of the liver: a follow-up study of stability.

Distinguishing between small benign malformations in the liver and early metastatic disease remains difficult. We identified a group of 115 patients with known or suspected malignant disease who had "indeterminate" small liver lesions and who underwent 2-16 CT examinations (median 5) over a follow up period of 6-60 months (median 16). The size, shape, edge, homogeneity and attenuation of each of these lesions was assessed. The lesions were classified by their behaviour on follow up CT as either stable (79%) or unstable (21%). The unstable lesions (n=62) included 37 that grew larger and 25 that became smaller or disappeared in patients undergoing anti-tumour therapy. Image features predictive of stable behaviour were small size and sharp edge. Heterogeneity and soft tissue attenuation were significantly associated with unstable behaviour, but these features were seen in only a small minority of cases. Shape had no predictive value. A logistic regression model was constructed based on size and edge to allow an estimate to be made of the likelihood of an individual lesion being unstable. In patients with known or suspected malignant disease, the majority of isolated small liver lesions found on CT are benign. Although size under 5 mm and a sharp margin are favourable features, this appearance does not exclude malignancy.

Colonic Neoplasms↗
PubMed2002

Decreased phorbol ester binding in the parahippocampal gyrus from subjects with schizophrenia is not associated with changes in protein kinase C.

Combining in situ radioligand binding with autoradiography, we previously identified a reduction of [(3)H]phorbol 12,13-dibutyrate binding in the parahippocampal gyrus from schizophrenic subjects. To determine whether these changes were due to decreases in the level of protein kinase C, we measured [(3)H]phorbol 12,13-dibutyrate binding, levels of the protein kinase C isoforms alpha, beta, delta, epsilon, gamma, eta and theta, as well as protein kinase C activity in crude particulate membranes from parahippocampal gyri of 15 schizophrenic and 15 control subjects. There was a significant decrease in the density (mean +/- SEM: 6.56 +/- 0.73 pmol mg(-1) vs 9.68 +/- 1.22 pmol mg(-1); P < 0.05) and affinity (mean K(D) +/- SEM: 4.64 +/- 0.34 nM vs 2.95 +/- 0.35 nM; P < 0.005) of [(3)H]phorbol 12,13-dibutyrate binding in homogenates from schizophrenic subjects. There were no significant changes in levels of the protein kinase C isoforms which are known to bind phorbol esters or in the activity of protein kinase C in membranes from schizophrenic subjects. These results suggest that there are changes in molecules capable of binding [(3)H]phorbol 12,13-dibutyrate, other than protein kinase C, in the parahippocampal gyrus from subjects with schizophrenia.

Adult↗
PubMed2002

Growth and adrenal suppression in asthmatic children on moderate to high doses of fluticasone propionate.

OBJECTIVE: Growth and adrenal suppression have been reported in asthmatic children using high-dose inhaled fluticasone propionate (FP). Inhaled FP, given at moderate doses (250-750 microg/day), has not been documented to be associated with growth or adrenal suppression in asthmatic children until recently. We report three cases illustrating these side effects. METHODS: Growth and adrenal suppression, after the introduction of inhaled FP, were observed in three prepubertal young asthmatic children referred to our asthma clinic and growth clinic. Growth centile and velocity were assessed by longitudinal stadiometry height measurements. Early morning plasma cortisol levels, and glucagon stimulation tests were used to assess the pituitary adrenal axis. RESULTS: Severe growth and adrenal suppression were noted in three children while they were on moderate doses of inhaled FP. Improvements in growth and adrenal function were observed following cessation or dose reduction of inhaled FP. CONCLUSIONS: Unexpected growth and adrenal suppression may occur in young asthmatic children using moderate doses of inhaled FP.

Absorptiometry, Photon↗
PubMed2002

Pituitary autoantibodies in lymphocytic hypophysitis target both gamma- and alpha-Enolase - a link with pregnancy?

The first target autoantigen to have been identified in lymphocytic hypophysitis is a 49 kDa protein, identified as alpha-enolase. Pituitary autoimmunity is strongly associated with pregnancy and we have shown that pituitary autoantibodies from patients with peripartum lymphocytic hypophysitis also recognise enolase in the placenta. Enolase exists in different forms as a number of isoenzymes, which are homo- or heterodimers of three subunits, alpha, beta and gamma. alphaalpha-enolase is ubiquitous, betabeta-enolase is muscle-specific and gammagamma-enolase, which is restricted to neuronal tissue and neuroendocrine cells, is known as neuron-specific enolase (NSE). NSE is expressed in normal human pituitary and pituitary neoplasms. The current study investigated which isoforms of enolase in pituitary and placenta reacted with the sera of patients with lymphocytic hypophysitis. Immunoblotting of two-dimensional gels of human pituitary cytosolic proteins showed that autoantibodies in patient sera react with both an acidic form, and more neutral forms of enolase. Immunoblotting with a monoclonal antibody to NSE confirmed the identity of the acidic enolase isoform as the gammagamma-isoform in both pituitary and placental samples. Gamma-enolase, i.e. NSE, was detected by immunohistochemistry in term placenta in decidua, syncytiotrophoblasts, anchoring villi and terminal villi. Our study is the first to describe the cellular localisation of NSE in normal human placenta, thus establishing a direct link between pituitary and placental autoantigens. This link provides a theoretical basis for the strong prediliction of lymphocytic hypophysitis to occur during or after pregnancy.

Autoantibodies↗
PubMed2001

The brain exocyst complex interacts with RalA in a GTP-dependent manner: identification of a novel mammalian Sec3 gene and a second Sec15 gene.

Ral is a small GTPase involved in critical cellular signaling pathways. The two isoforms, RalA and RalB, are widely distributed in different tissues, with RalA being enriched in brain. The best characterized RalA signaling pathways involve RalBP1 and phospholipase D. To investigate RalA signaling in neuronal cells we searched for RalA-binding proteins in brain. We found at least eight proteins that bound RalA in a GTP-dependent manner. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) identified these as the components of the exocyst complex. The yeast exocyst is a regulator of polarized secretion, docking vesicles to regions of the plasma membrane involved in active exocytosis. We identified the human FLJ10893 protein as the mammalian homologue of the yeast exocyst protein Sec3p. The exocyst complex did not contain the previously identified exocyst component rSec15, but a new homologue of both yeast Sec15p and rSec15, called KIAA0919. Western blots confirmed that two rat exocyst proteins, rSec6 and rSec8, bound active RalA in nerve terminals, as did RalBP1. Phospholipase D bound RalA in a nucleotide-independent manner. This places the RalA signaling system in mammalian nerve terminals, where the exocyst may act as an effector for activated RalA in directing sites of exocytosis.

Amino Acid Sequence↗
PubMed2001

Dynamin inhibits phosphatidylinositol 3-kinase in hematopoietic cells.

Phosphatidylinositol 3-kinase (PI 3-kinase) plays a role in late stages of endocytosis as well as in cellular proliferation and transformation. The SH3 domain of its regulatory p85 subunit stimulates the GTPase activity of dynamin in vitro. Dynamin is a GTPase enzyme required for endocytosis of activated growth factor receptors. An interaction between these proteins has not been demonstrated in vivo. Here, we report that dynamin associates with PI 3-kinase in hematopoietic cells. We detected both p85 and PI 3-kinase activity in dynamin immune complexes from IL-3-dependent BaF3 cells. However, this association was significantly reduced in BaF3 cells transformed with the BCR/abl oncogene. After transformation only a 4-fold increase in PI 3-kinase activity was detected in dynamin immune complexes, whereas grb2 associated activity was elevated 20-fold. Furthermore, dynamin inhibited the activity of both purified recombinant and immunoprecipitated PI 3-kinase. In BaF3 cells expressing a temperature-sensitive mutant of BCR/abl, a significant decrease in p85 and dynamin association was observed 4 h after the induction of BCR/abl activity. In contrast, in IL-3-stimulated parental BaF3 cells, this association was increased. Our results demonstrate an in vivo association of PI 3-kinase with dynamin and this interaction regulates the activity of PI 3-kinase.

Animals↗
PubMed2001

The dephosphins: dephosphorylation by calcineurin triggers synaptic vesicle endocytosis.

When nerve terminals in the brain are stimulated, a group of phosphoproteins called the dephosphins are coordinately dephosphorylated by calcineurin, the Ca(2+)-dependent protein phosphatase. Amazingly, the seven presently known dephosphins are not structurally related, yet each has been independently shown to be essential for synaptic vesicle endocytosis (SVE). Nowhere else in biology is there a similar example of the coordinated dephosphorylation of such a large group of proteins each sharing roles in the same biological response. This suggests that dephosphorylation and phosphorylation of the dephosphins is essential for SVE. Recent studies in synaptosomes have confirmed this view, with calcineurin-mediated dephosphorylation of the dephosphins essential for triggering SVE. The phosphorylation cycle of the dephosphins might regulate SVE by targeting the proteins to sites of action and by stimulating the assembly of several large essential endocytic protein complexes.

Animals↗