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Biomedical subjects

D Ramsay

Publications and source records attributed to D Ramsay.

At least 19 recordsLinked to original sources
PubMed2005

Virtual colonoscopy: issues in implementation.

The following issues and requirements related to the implementation of a CT colonography (CTC) service are important: (i) policies are needed regarding the indications for CTC. Concomitant with this is the need for education of potential referrers and patients. Expectations of the procedure, particularly by general practitioners, may be unrealistic and indications for referral may otherwise be inappropriate. At present there is not general acceptance of CTC for screening asymptomatic persons; (ii) a flexible approach to CT protocols is useful, dependent on the indication for and clinical context of referral, the age and body habitus of the patient; (iii) attention to the issues related to the special skills required by the reporting radiologist. While there is a temptation to regard CTC interpretation as an extension of skills used in interpreting other cross-sectional images, there is a need to realise that there are skills required specific to CTC and there should be adequate provision for training; (iv) matters related to reporting, such as reporting format, and lesions that will be reported/not reported; and (v) informed consent from the patient. Information should be provided with regard to the limitations of CTC, the implications of a positive finding and radiation dosage.

Colonic Diseases↗
PubMed2004

G protein-coupled receptor fusion proteins in drug discovery.

A wide range of peptides and polypeptides can be appended to either the N- or C-terminus of G protein-coupled receptors without disrupting substantially ligand binding and signal transduction. Following fusion of fluorescent proteins, reporter gene constructs or G protein alpha subunits to the C-terminal tail of a receptor high content and G protein activation assays can be employed to identify agonist ligands. Further modification of the receptor fusions to introduce enhanced levels of constitutive activity and to physically destabilise the protein allows antagonist/inverse agonists screens to be developed in parallel. Equivalent C-terminal addition of pairs of complementary, non-functional, polypeptide fragments allows the application of enzyme complementation techniques. Introduction of N-terminal tags to receptors has also allowed the introduction of novel assay techniques based on a pH-sensitive cyanine dye. These have the capacity to overcome certain limitations of GPCR-fluorescent protein fusions.

Animals↗
PubMed2002

Continuous left hemidiaphragm sign revisited: a case of spontaneous pneumopericardium and literature review.

In pneumopericardium, a rare but potentially life threatening differential diagnosis of chest pain with a broad variety of causes, rapid diagnosis and adequate treatment are crucial. In upright posteroanterior chest radiography, the apical limit of a radiolucent rim, outlining both the left ventricle and the right atrium, lies at the level of the pulmonary artery and ascending aorta, reflecting the anatomical limits of the pericardium. The band of gas surrounding the heart may outline the normally invisible parts of the diaphragm, producing the continuous left hemidiaphragm sign in an upright lateral chest radiograph. If haemodynamic conditions are stable, the underlying condition should be treated and the patient should be monitored closely. Acute haemodynamic deterioration should prompt rapid further investigation and cardiac tamponade must be actively ruled out. Spontaneous pneumopericardium in a 20 year old man is presented, and its pathophysiology described.

Adult↗
PubMed2001

Cervical flexion myelopathy after valproic acid overdose.

STUDY DESIGN: Case report and literature review of cervical flexion myelopathies. OBJECTIVE: To increase awareness that prolonged extreme neck flexion, in association with profound muscular relaxation, can produce a severe cervical myelopathy. SUMMARY OF BACKGROUND DATA: Similar case reports of cervical myelopathies have been documented in the neurosurgical literature after intraoperative prolonged neck flexion, and after forcible prolonged neck flexion during a robbery. To the authors' best knowledge, this is the first report of a cervical flexion myelopathy after a medication overdose, and the only clinical-pathologic correlation. METHODS: Retrospective case report with clinical, radiographic, and postmortem data available for analysis. RESULTS: A transverse myelopathy at the sixth cervical level developed in a 25-year-old woman after an overdose of valproic acid in a suicide attempt. She was found in the sitting position, with her neck in extreme flexion, where she had been for an estimated 18 hours. Magnetic resonance imaging showed that her cervical cord was enlarged, maximally at C6, with prominent paraspinal soft tissue swelling. The patient died of pulmonary embolism and pneumonia. Pathologic findings included transverse spinal cord necrosis at C6; central gray matter necrosis extended to several segments below this. CONCLUSION: Prolonged extreme neck flexion, in association with profound muscular relaxation, can produce a severe myelopathy that is at least partly related to compromise of the spinal cord's microcirculation.

Adult↗
PubMed2001

Therapeutic benefits of increasing natriuretic peptide levels.

Natriuretic peptides play an important role in water and salt homeostasis and in the regulation of the cardiovascular system. In recent years, exogenous administration of natriuretic peptides has primarily been used to improve our understanding of the role of natriuretic peptides. Also, it became evident that natriuretic peptides may be used therapeutically. Because of their peptide character, they cannot be administered orally and, therefore, may be used for short-term intravenous therapy only. In recent years, inhibitors of neutral endopeptidase, which degrades natriuretic peptides to inactive metabolites, have been investigated. This review focuses on the potential benefits of increasing natriuretic peptide levels, either through exogenous administration or inhibiting the degradation of endogenous natriuretic peptides.

Atrial Natriuretic Factor↗
PubMed2001

Monitoring receptor oligomerization using time-resolved fluorescence resonance energy transfer and bioluminescence resonance energy transfer. The human delta -opioid receptor displays constitutive oligomerization at the cell surface, which is not regulated by receptor occupancy.

Oligomerization of the human delta-opioid receptor and its regulation by ligand occupancy were explored following expression in HEK293 cells using each of co-immunoprecipitation of differentially epitope-tagged forms of the receptor, bioluminescence resonance energy transfer and time-resolved fluorescence resonance energy transfer. All of the approaches identified constitutively formed receptor oligomers, and the time-resolved fluorescence studies confirmed the presence of such homo-oligomers at the cell surface. Neither the agonist ligand [d-Ala(2),d-Leu(5)]enkephalin nor the inverse agonist ligand ICI174864 were able to modulate the oligomerization status of this receptor. Interactions between co-expressed delta-opioid receptors and beta(2)-adrenoreceptors were observed in co-immunoprecipitation studies. Such hetero-oligomers could also be detected using bioluminescence resonance energy transfer although the signal obtained was substantially smaller than for homo-oligomers of either receptor type. Signal corresponding to the delta-opioid receptor-beta(2)-adrenoreceptor hetero-oligomer was increased in the presence of agonist for either receptor. However, substantial levels of this hetero-oligomer were not detected at the cell surface using time-resolved fluorescence resonance energy transfer. These studies demonstrate that, following transient transfection of HEK293 cells, constitutively formed oligomers of the human delta-opioid receptor can be detected by a variety of approaches. However, these are not regulated by ligand occupancy. They also indicate that time-resolved fluorescence resonance energy transfer represents a means to detect such oligomers at the cell surface in populations of intact cells.

Blotting, Western↗
PubMed2001

Severe infantile axonal neuropathy with respiratory failure.

We describe 5 infants (4 male, 1 female) with a severe intractable form of motor-sensory axonal neuropathy. All became ventilator-dependent, 4 have since died and 1 remains static. Diaphragmatic paralysis was an early feature with generalized neuropathy evolving rapidly. Nerve conduction studies and biopsies were consistent with axonal disease. This disorder could be a new condition or part of the spectrum of inherited neuropathies of the axonal degenerative type. It may be that there is a "switching-off" in the infant's Schwann cell-axonal interactions in utero or in the early postnatal period, resulting in severe progressive deterioration and then a static period without recovery.

Biopsy↗
PubMed2001

Detection of receptor ligands by monitoring selective stabilization of a Renilla luciferase-tagged, constitutively active mutant, G-protein-coupled receptor.

The wild-type beta2-adrenoceptor and a constitutively active mutant of this receptor were C-terminally tagged with luciferase from the sea pansy Renilla reniformis. C-terminal addition of Renilla luciferase did not substantially alter the levels of expression of either form of the receptor, the elevated constitutive activity of the mutant beta2-adrenoceptor nor the capacity of isoprenaline to elevate cyclic AMP levels in intact cells expressing these constructs. Treatment of cells expressing constitutively active mutant beta2-adrenoceptor-Renilla luciferase with antagonist/inverse agonist ligands resulted in upregulation of levels of this polypeptide which could be monitored by the elevated luciferase activity. The pEC50 for ligand-induced luciferase upregulation and ligand affinity to bind the receptor were highly correlated. Similar upregulation could be observed following sustained treatment with agonist ligands. These effects were only observed at a constitutively active mutant of the beta2-adrenoceptor. Co-expression of the wild-type beta2-adrenoceptor C-terminally tagged with the luciferase from Photinus pyralis did not result in ligand-induced upregulation of the levels of activity of this luciferase. Co-expression of the constitutively active mutant beta2-adrenoceptor-Renilla luciferase and an equivalent mutant of the alpha1b-adrenoceptor C-terminally tagged with green fluorescent protein allowed pharmacological selectivity of adrenoceptor antagonists to be demonstrated. This approach offers a sensitive and convenient means, which is amenable to high throughput analysis, to monitor ligand binding to a constitutively active mutant receptor. As no prior knowledge of receptor ligands is required this approach may be suitable to identify ligands at orphan G protein-coupled receptors.

Adenylyl Cyclases↗
PubMed2001

Pancreatic islet cell tumours presenting as recurrent acute pancreatitis: imaging features in three cases.

We present three cases of recurrent pancreatitis that occurred in patients with small islet cell tumours of the pancreas which were obstructing the main pancreatic duct. This is a very uncommon presentation of pancreatic islet cell tumours. The radiological findings in these cases are shown and the implications for imaging of 'idiopathic' relapsing pancreatitis are discussed.

Adult↗
PubMed2000

Myeloablative chemotherapy for recurrent aggressive oligodendroglioma.

The objective of this study was to ascertain the duration of tumor control and the toxicities of dose-intense myeloablative chemotherapy for patients with recurrent oligodendrogliomas. Patients with previously irradiated oligodendrogliomas, either pure or mixed, that were contrast enhancing, measurable, and behaving aggressively at recurrence were eligible for this study. Only complete responders or major partial responders (75 % reduction in tumor size) to induction chemotherapy--either intensive-dose procarbazine, lomustine, and vincristine or cisplatin plus etoposide-could receive high-dose thiotepa (300 mg/m2/day for 3 days) followed by hematopoietic reconstitution using either bone marrow or peripheral blood stem cells. Thirty-eight patients began induction chemotherapy and 20 (10 men, 10 women; median age 46 years; median Karnofsky score 80) received high-dose thiotepa. For the high-dose group, the median event-free, progression-free, and overall survival times from recurrence were 17, 20, and 49 months, respectively. Tumor control in excess of 2 years was observed in 6 patients (30%). Four patients (20%) are alive and tumor free 27 to 77 months (median, 42 months) from the start of induction therapy; however, fatal treatment-related toxicities also occurred in 4 patients (20%). Three patients died as a result of a progressive encephalopathy which, in 2 instances, was accompanied by a wasting syndrome; 1 patient died as a consequence of an intracerebral (intratumoral) hemorrhage. Fatal toxicities occurred in patients with pretreatment Karnofsky scores of 60 or 70. High-dose thiotepa to consolidate response was a disappointing treatment strategy for patients with recurrent aggressive oligodendroglial neoplasms, although several patients had durable responses. Moreover, as prescribed, high-dose thiotepa had significant toxic effects in previously irradiated patients, especially those with poorer performance status.

Adult↗
PubMed1997

A review of captopril renal scintigraphy and its effect on patient management.

Renal artery stenosis is an important and potentially curable cause of hypertension. Captopril renography is now recognized to have a high sensitivity and specificity in its diagnosis. Ultimately, however, the result is of little benefit if it does not lead to a change in patient management. To assess how patient management was changed following the result of a captopril renogram, we reviewed the notes of 95 patients who had undergone this test over a 5 year period to identify renal artery stenosis. Of these patients, significant renal artery stenosis was suggested in 16 (17%), of whom only 9 (56%) underwent a change in management (7 proceeding to angiography with or without angioplasty, 2 having alterations in medication). In the 67 patients who had a negative renogram, 16 (24%) had an alteration in management (13 angiography, 3 altered drug treatment). Finally, of the 12 patients who had a non-diagnostic renogram, 7 (60%) had a management change (3 angiography, 4 altered drug therapy). Our results suggest that, despite evidence from the literature that captopril renography is both sensitive and specific for renal artery stenosis, clinicians still rely on other factors when determining who has significant stenosis and, therefore, who should proceed to a further investigation or have a change in medication. Ultimately, this reduces the clinical value of the test at present.

Angiography↗