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Biomedical subjects

A Morgan

Publications and source records attributed to A Morgan.

At least 19 recordsLinked to original sources
PubMed2006

Histological examination of circular stapled 'doughnuts': questionable routine practice?

BACKGROUND: Left-sided colonic resections are often anastomosed by the use of the circular stapling gun. Most surgeons routinely submit the resulting set of 'doughnuts' for histological examination. AIM: The aim of this study is to question the need for this practice by providing our own experience of the impact of 'doughnut' submission on patient management. PATIENTS AND METHODS: Patients who had undergone a stapled anastomosis for colorectal cancer resection (1998-2004) were identified from the department cancer database and clinical records and histopathological reports were reviewed for all cases. RESULTS: From a consecutive series of 100 sets of doughnuts only two showed histological abnormality (inflammatory change and a metaplastic polyp). Three patients had local recurrence over the follow-up period: 12, 14 and 36 months after surgery. Histological review of the 'doughnuts' in these patients did not show any abnormality. None of the above findings had any influence on subsequent management. CONCLUSION: Histological examination of the 'doughnuts' has a considerable impact in terms of time and resource use. This study has shown no benefit in performing routine histological examination of the 'doughnuts'.

Adenocarcinoma↗
PubMed2005

An African American family with early-onset Alzheimer disease and an APP (T714I) mutation.

The occurrence of an APP T174I mutation is described in a large American family of African descent with Alzheimer disease. The clinical characteristics were an unusually early onset of disease (early 30s), similar to a previously reported age at onset of this mutation in an Austrian family. Distinct from that family, seizures and myoclonus were prominent features of the disease in this kindred.

Adult↗
PubMed2005

Regulation of exocytosis by protein kinase C.

PKC (protein kinase C) has been known for many years to modulate regulated exocytosis in a wide variety of cell types. In neurons and neuroendocrine cells, PKC regulates several different stages of the exocytotic process, suggesting that these multiple actions of PKC are mediated by phosphorylation of distinct protein targets. In recent years, a variety of exocytotic proteins have been identified as PKC substrates, the best characterized of which are SNAP-25 (25 kDa synaptosome-associated protein) and Munc18. In the present study, we review recent evidence suggesting that site-specific phosphorylation of SNAP-25 and Munc18 by PKC regulates distinct stages of exocytosis.

Animals↗
PubMed2005

Alveolar nitric oxide in adults with asthma: evidence of distal lung inflammation in refractory asthma.

Recent studies have suggested that alveolar nitric oxide (NO) concentration is a noninvasive test of distal lung inflammation. The current study determined whether alveolar NO concentration can be measured in patients with asthma of varying severity, tested the hypothesis that there is an association between alveolar NO and bronchoalveolar lavage (BAL) eosinophil count and determined whether refractory asthma is characterised by a raised alveolar NO concentration. Finally, the present authors assessed the effect of 2 weeks of prednisolone (30 mg q.d.) on alveolar NO concentration. Alveolar NO concentration was both measurable and repeatable in patients with refractory asthma. A positive correlation was found between alveolar NO concentration and BAL eosinophil count but not with bronchial wash or sputum eosinophil count. Alveolar NO concentration was increased in patients with refractory asthma (7.1 ppb) compared with mild-to-moderate asthma (3.4 ppb) and normal controls (3.4 ppb) and reduced by treatment with prednisolone. In conclusion, these findings support the hypothesis that alveolar nitric oxide is a measure of distal airway inflammation and suggest that distal lung inflammation is present in refractory asthma.

Administration, Inhalation↗
PubMed2005

The use of CT-MR image registration to define target volumes in pelvic radiotherapy in the presence of bilateral hip replacements.

Increasing numbers of patients with hip replacements are presenting for pelvic radiotherapy, which is usually planned using CT images. Image artefacts caused by the presence of metallic implants tend not to be severe for single hip replacements and allow for adequate definition of target volumes. When bilateral hip replacements are present, the image artefacts can render CT images useless for target definition, particularly for tumours of the prostate and bladder. MR images are not susceptible to such severe artefacts. This note describes a small series of patients with bilateral hip replacements on whom CT-MR image registration has been used to successfully define adequate target volumes.

Aged↗
PubMed2004

The clinical implications of the collapsed cone planning algorithm.

AIMS: The accuracy of computer treatment planning systems is important in achieving clinically acceptable dose distributions. The pencil beam (PB) algorithm on Helax-TMS is currently used for all clinical treatment planning at the two centres involved in this study. However, it has been shown that the Helax-TMS collapsed cone (CC) algorithm is more accurate in regions of heterogeneity, such as the thorax, and head and neck. The aim of this study was to show the actual dose delivered to the patient when treating with a Helax-TMS PB plan, by using the corresponding Helax-TMS CC plan as the reference standard. MATERIALS AND METHODS: Thirty PB treatment plans (for lung and oesophageal treatments) were recalculated using the CC algorithm, and plans were then compared. RESULTS: The number of monitor units required to deliver the prescription dose differed between algorithms, by up to 3.4%. In most cases, the CC algorithm calculated more monitor units than the PB, indicating under-dosage at the prescription point during treatment. The dose distributions also seemed less homogeneous when calculated using the CC algorithm. The minimum dose to the planning target volume (PTV) was lower than the PB plan suggested in every case, by up to 23.2%. ICRU homogeneity requirements (i.e. a minimum 95% of the prescription dose in the PTV) were not met in any of the cases. Even with some attempts at optimisation, conformance to these requirements was difficult. CONCLUSION: The CC algorithm has several factors limiting its suitability for routine clinical use. However, it is an important milestone in radiotherapy treatment planning, and should be used to show expected changes in computer planned dose distributions with new accurate dose algorithms. It is worthwhile considering dose homogeneity requirements well before the advent of anticipated Monte Carlo-based models.

Algorithms↗
PubMed2004

Nontypeable Haemophilus influenzae strain 2019 produces a biofilm containing N-acetylneuraminic acid that may mimic sialylated O-linked glycans.

Previous studies suggested that nontypeable Haemophilus influenzae (NTHI) can form biofilms during human and chinchilla middle ear infections. Microscopic analysis of a 5-day biofilm of NTHI strain 2019 grown in a continuous-flow chamber revealed that the biofilm had a diffuse matrix interlaced with multiple water channels. Our studies showed that biofilm production was significantly decreased when a chemically defined medium lacking N-acetylneuraminic acid (sialic acid) was used. Based on these observations, we examined mutations in seven NTHI strain 2019 genes involved in carbohydrate and lipooligosaccharide biosynthesis. NTHI strain 2019 with mutations in the genes encoding CMP-N-acetylneuraminic acid synthetase (siaB), one of the three NTHI sialyltransferases (siaA), and the undecaprenyl-phosphate alpha-N-acetylglucosaminyltransferase homolog (wecA) produced significantly smaller amounts of biofilm. NTHI strain 2019 with mutations in genes encoding phosphoglucomutase (pgm), UDP-galactose-4-epimerase, and two other NTHI sialyltransferases (lic3A and lsgB) produced biofilms that were equivalent to or larger than the biofilms produced by the parent strain. The biofilm formed by the NTHI strain 2019pgm mutant was studied with Maackia amurensis fluorescein isothiocyanate (FITC)-conjugated and Sambucus nigra tetramethyl rhodamine isocyanate (TRITC)-conjugated lectins. S. nigra TRITC-conjugated lectin bound to this biofilm, while M. amurensis FITC-conjugated lectin did not. S. nigra TRITC-conjugated lectin binding was inhibited by incubation with alpha2,6-neuraminyllactose and by pretreatment of the biofilm with Vibrio cholerae neuraminidase. Matrix-assisted laser desorption ionization-time of flight mass spectometry analysis of lipooligosaccharides isolated from a biofilm, the planktonic phase, and plate-grown organisms showed that the levels of most sialylated glycoforms were two- to fourfold greater when the lipooligosaccharide was derived from planktonic or biofilm organisms. Our data indicate that NTHI strain 2019 produces a biofilm containing alpha2,6-linked sialic acid and that the sialic acid content of the lipooligosaccharides increases concomitant with the transition of organisms to a biofilm form.

Biofilms↗
PubMed2004

Tracheal stenting: a better method of dealing with airway obstruction due to thyroid malignancies than tracheostomy.

Tracheostomy remains the primary method of treatment of acute airway obstruction due to malignant invasion and compression of the trachea. However, the development of tracheal stents has provided an alternative effective treatment modality. This case report and literature review highlights the benefits of intra-luminal stenting, including resolution of distressing obstructive symptoms, and subsequent improvement in quality of life.

Aged↗
PubMed2003

Dysarthria and dysphagia following treatment for a fourth ventricle choroid plexus papilloma.

The present case report describes the presence of a persistent dysarthria and dysphagia as a consequence of surgical intervention for a choroid plexus papilloma (CPP). WM was a nine year ten month old male who at the time of the present study was seven years post-surgery. A comprehensive perceptual and instrumental test battery was used to document the nature of the dysarthria incorporating all components of speech production including respiration, phonation, resonance, articulation, and prosody. The nature of the dysphagia was evaluated through the use of videofluoroscopic evaluation of swallowing (VFS). Assessments confirmed the presence of a LMN dysarthria, marked by deficits in phonation, respiration, and prosody. Dysphagia assessment revealed deficits in oral preparatory, oral and pharyngeal stages of the swallow. The presence of persistent dysarthria and dysphagia in this case has a number of important implications for the management of children undergoing surgery for fourth ventricle CPPs, in particular the need for appropriate treatment, as well as counselling prior to surgery of the possible negative outcomes related to speech and swallowing.

Child↗
PubMed2003

Regulation of the exocytotic machinery by cAMP-dependent protein kinase: implications for presynaptic plasticity.

For over a decade, the enhancement of regulated exocytosis by cAMP-dependent protein kinase (PKA) has remained unexplained at the molecular level. The fact that this phenomenon has been observed in such a wide variety of secretory cell types, from pancreatic beta-cells to neurons, suggests that it is an important and fundamental mechanism. Extensive analysis of the phosphorylation of exocytotic proteins has yielded few substrates of PKA in vitro, and fewer still have had physiological effects attributed to their phosphorylation. Here we review two proteins that do fulfil these criteria: the synaptic vesicle proteins cysteine string protein (CSP) and Snapin. Phosphorylation of these proteins by PKA produces changes in their respective protein-protein interactions, and has been attributed to modulation of the vesicle priming (Snapin) and vesicle fusion (CSP) stages of exocytosis. We also discuss how the function of CSP and Snapin phosphorylation might fit into an interesting aspect of the PKA-dependent enhancement of exocytosis: presynaptic plasticity in the brain.

Animals↗
PubMed2003

Clinical and cost-effectiveness of new and emerging technologies for early localised prostate cancer: a systematic review.

OBJECTIVES: To evaluate the clinical and cost-effectiveness of new and emerging technologies for early, localised prostate cancer. DATA SOURCES: Electronic databases, reference lists of relevant articles and various health services research-related resources. REVIEW METHODS: A list of new and emerging technologies was identified and agreed. A systematic review was undertaken and selected studies were reviewed against a set of criteria. An economic model was developed and used to compare the specified newer treatments with the traditional approaches. RESULTS: For neoadjuvant hormonal therapy, no evidence of benefit was seen in terms of biochemical disease-free survival. For adjuvant hormonal therapy, there was no evidence of benefit in terms of survival, but some conflicting evidence that higher risk patients may benefit. The largest number of studies reported results for brachytherapy, where some evidence suggested that it may be more effective than standard treatments for lower risk patients, although less effective for intermediate- and high-risk patients, in terms of biochemical disease-free survival. Lower quality evidence reported fewer complications than for standard treatments. Higher quality evidence suggested that disease-specific quality of life (QoL) for brachytherapy patients was lower than for patients receiving standard treatments. The review of three-dimensional conformal radiotherapy (3D-CRT) considered treatment-related morbidity, where significantly fewer gastrointestinal complications occurred than with standard radiotherapy. It was suggested that higher radiation doses achieved better disease control, although patient characteristics were often reported as independent indicators of control. The review of intensity-modulated conformal radiotherapy suggested that late gastrointestinal toxicity may be reduced compared with 3D-CRT. For cryotherapy, high rates of impotence were reported. Owing to the paucity and poor quality of evidence identified for other interventions, conclusions regarding their clinical effectiveness cannot be drawn. Cost-effectiveness estimates were based on the impact of adverse events on quality-adjusted life-years and the assessment was restricted to brachytherapy, 3D-CRT and cryotherapy compared with standard treatments. Of the new treatments included, only cryotherapy appeared not to be potentially cost-effective compared with traditional treatments, owing to the associated high incidence of impotence. CONCLUSIONS: The results of the clinical effectiveness review should be viewed in the context of the quality of the available evidence. Very few randomised controlled trials (RCTs) were identified, with the majority of included studies being descriptive case series, open to patient selection bias and measuring surrogate end-points with short-term follow-up. It is difficult therefore to draw conclusions on the relative benefits or otherwise of the newer technologies owing to the lack of substantive evidence of any quality and the lack of comparisons between the newer technologies and with standard treatments. Given the lack of high-quality clinical evidence with long-term follow-up and the uncertainty surrounding the assumptions in the economic analysis, the following areas are recommended for further research: RCTs with sufficient follow-up to measure benefits in terms of overall survival to include QoL measurement to establish trade-offs between potential adverse events and benefits of treatment; the identification of prognostic risk factors among men diagnosed with early prostate cancer; QoL studies to compare the utility of health states among patients on active monitoring, patients receiving treatment and the comparable healthy population; the relationship between surrogate end-points and survival; and the adoption of standard definitions for adverse events.

Cost-Benefit Analysis↗
PubMed2001

Phosphorylation of cysteine string protein by protein kinase A. Implications for the modulation of exocytosis.

Cyclic AMP-dependent protein kinase (PKA) enhances regulated exocytosis in neurons and most other secretory cells. To explore the molecular basis of this effect, known exocytotic proteins were screened for PKA substrates. Both cysteine string protein (CSP) and soluble NSF attachment protein-alpha (alpha-SNAP) were phosphorylated by PKA in vitro, but immunoprecipitation of cellular alpha-SNAP failed to detect (32)P incorporation. In contrast, endogenous CSP was phosphorylated in synaptosomes, PC12 cells, and chromaffin cells. In-gel kinase assays confirmed PKA to be a cellular CSP kinase, with phosphorylation occurring on Ser(10). PKA phosphorylation of CSP reduced its binding to syntaxin by 10-fold but had little effect on its interaction with HSC70 or G-protein subunits. Furthermore, an in vivo role for Ser(10) phosphorylation at a late stage of exocytosis is suggested by analysis of chromaffin cells transfected with wild type or non-phosphorylatable mutant CSP. We propose that PKA phosphorylation of CSP could modulate the exocytotic machinery, by selectively altering its availability for protein-protein interactions.

Amino Acid Sequence↗
PubMed2001

The conjoint importance of the hippocampus and anterior thalamic nuclei for allocentric spatial learning: evidence from a disconnection study in the rat.

A disconnection procedure was used to test whether the hippocampus and anterior thalamic nuclei form functional components of the same spatial memory system. Unilateral excitotoxic lesions were placed in the anterior thalamic (AT) nuclei and hippocampus (HPC) in either the same (AT-HPC Ipsi group) or contralateral (AT-HPC Contra group) hemispheres of rats. The behavioral effects of these combined lesions were compared in several spatial memory tasks sensitive to bilateral hippocampal lesions. In all of the tasks tested, T-maze alternation, radial arm maze, and Morris water maze, those animals with lesions placed in the contralateral hemispheres were more impaired than those animals with lesions in the same hemisphere. These results provide direct support for the notion that the performance of tasks that require spatial memory rely on the operation of the anterior thalamus and hippocampus within an integrated neural network.

Animals↗
PubMed2001

Inhibition of astrocyte TNFalpha expression by extracellular potassium.

TNFalpha and IL-6 are cytokines of great interest, given the numerous biological activities and the documented expression in several central nervous system (CNS) pathologies. In this report, we have examined cultures of IL-1- or IL-1/IFNgamma-activated human fetal astrocytes as a model to study mechanisms of cytokine regulation in the inflamed CNS. Since one of the major functions of astrocytes is spatial buffering of K(+) ions, we examined the effect of high extracellular KCl on astrocyte cytokine expression by ribonuclease protection assay and ELISA. Results demonstrate that astrocyte TNFalpha production was potently inhibited by K(+) with 44 and 89% inhibition at 25 and 55 mM K+, respectively. In contrast, astrocyte IL-6 inhibition required higher concentrations of K+ (>/=75 mM). These results demonstrate a novel role for astrocyte potassium channel activity in modulation of glial cytokine production.

Astrocytes↗
PubMed2001

Clinical features and risk of recurrence among patients with vaginal intraepithelial neoplasia.

OBJECTIVE: The best treatment modality and factors affecting recurrence among women with vaginal intraepithelial neoplasia (VAIN) are yet to be determined. The aims of the current study were to describe the clinical features, results of treatment, and factors affecting recurrence among patients with VAIN. METHODS: We conducted a retrospective review of 121 women with VAIN after confirming the histologic diagnosis. Patient demographics, clinical features, and results of therapy were recorded. Factors affecting recurrence were assessed using the odds ratio and the 95% confidence intervals among patients who were followed up for 7 months or more and had at least one posttreatment Papanicolaou smear. Significant univariate odds ratios were assessed jointly in a multivariate model with a stratified analysis. RESULTS: The mean age of the patients was 35.0 (+/-17), 41% of the patients smoked, 39% had a history of human papillomavirus infection, 27% had history of sexually transmitted diseases, 22% had history of surgery for cervical intraepithelial neoplasia (CIN), and 23% had total hysterectomy. The upper third of the vagina was the most common site of VAIN and 61% of the lesions were multifocal. Associated cervical and vulvar intraepithelial neoplasia (VIN) were present in 65 and 10%, respectively. Recurrences of VAIN and progression to invasive vaginal cancer occurred in 33 and 2%, respectively. Recurrences following partial vaginectomy, laser, and 5-fluorouracil were 0, 38, and 59%, respectively (P = 0.0001). Multifocality and method of treatment were significant independent predictors of VAIN recurrences (odds ratio 3.3, 95% CI 1.2, 9.2, P = 0.02, and 22.4, 95% CI 1.3, 393.6, P = 0.001, respectively), with no interaction, based on a stratified analysis. CONCLUSIONS: VAIN occurs most often among women with CIN or VIN, commonly involves the upper third of the vagina, and is often multifocal. Partial vaginectomy provides the highest cure rate and multifocality is a risk factor for recurrence.

Adolescent↗
PubMed2001

The DNA helicase activity of yeast Sgs1p is essential for normal lifespan but not for resistance to topoisomerase inhibitors.

The Saccharomyces cerevisiae SGS1 gene is a member of the RecQ family of ATP-dependent DNA helicases, which includes the human WRN, BLM and RECQ4 genes. Mutations in the WRN gene cause the human premature ageing disorder, Werner's syndrome. Deletion of the SGS1 gene also causes premature ageing in yeast, suggesting that the molecular mechanisms of cellular ageing may be evolutionarily conserved. To investigate the role of the RecQ helicase domain in ageing, a point mutation (SGS1 K(706)-->A) known to eliminate the DNA helicase activity of Sgs1p was constructed. This mutant allele failed to rescue the premature ageing of the sgs1Delta strain, demonstrating that Sgs1p DNA helicase activity is required for a normal lifespan. In contrast, the SGS1 K(706)-->A allele was sufficient to rescue the hypersensitivity of the sgs1Delta strain to topoisomerase inhibitors, but not other genotoxic agents. These findings support the idea that Sgs1p fulfils multiple cellular functions, and that DNA helicase activity is dispensable for some of these (e.g. functional interaction with topoisomerases), but essential for others (e.g. longevity).

4-Nitroquinoline-1-oxide↗
PubMed2001

Adnexal mass evaluation in the emergency department.

Female patients who have stable vital signs presenting to the emergency department with abdominopelvic pain and an adnexal mass can be extremely difficult to manage. However, by performing a rapid problem-oriented history and physical with emphasis on the age of patient, menstrual history, and pelvic exam, a detailed differential diagnosis can be compiled. With the addition of a complete blood count and HCG, if appropriate, and a CA-125 for your consultant, additional information can be obtained while a ultrasound examination is being performed. With the above information, consultation and disposition should be readily accomplished.

Adnexal Diseases↗