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Biomedical subjects

B Porter

Publications and source records attributed to B Porter.

At least 19 recordsLinked to original sources
PubMed2006

Hyperfine spectrum of RbCl.

The molecular beam electric resonance technique has been used to conduct a high precision examination of the hyperfine spectrum of the four isotopomers of RbCl. Coupling constants for the nuclear electric quadrupole interactions, the spin-rotation interactions, the tensor and scalar spin-spin interactions, and a rubidium nuclear octupole interaction, and their dependence on vibrational and rotational states have been determined. The dominant interaction, the rubidium nuclear electric quadrupole interaction, shows a small shift with substitution of the chlorine isotope.

Journal Article↗
PubMed2006

Liposarcoma in the nasal cavity of a cow.

Liposarcomas are rare neoplasms in domestic animals, but have been reported to occur in many species. In humans, liposarcoma is one of the most common malignant mesenchymal tumors. Classification of liposarcomas in humans has been well established and categorization by type can be of prognostic value; no such unique classification scheme has been established for liposarcomas in animals. Liposarcoma of the head and neck in humans are uncommon, and are rarely reported in the nasal cavity, sinuses, and nasopharynx. To our knowledge, a liposarcoma has never been reported in the nasal cavity of a domestic animal. In this report we describe a liposarcoma that developed in the nasal cavity of a cow, with local invasion into the oral cavity.

Animals↗
PubMed2005

Multiple sclerosis: diagnosis and the management of acute relapses.

Multiple sclerosis is an inflammatory demyelinating disease of the central nervous system that may result in a wide range of neurological symptoms and accumulating disability. Its course is unpredictable resulting in a changing pattern of clinical need. Diagnostic criteria for multiple sclerosis require objective evidence for dissemination in space and time. The diagnostic and management process should follow good practice guidelines with the person at the centre of the process. Appropriate support and information should be available from the time of diagnosis. Continuing education is key in enabling the person to actively participate in their management. In the event of an acute relapse the person should have direct access to the most appropriate local service. Provided medical causes have been excluded, corticosteroid treatment to hasten the recovery from the relapse should be considered. Management of an acute relapse should be comprehensive addressing any medical, functional, or psychosocial sequelae.

Adolescent↗
PubMed2004

Neuroendocrine lung carcinogenesis in hamsters is inhibited by green tea or theophylline while the development of adenocarcinomas is promoted: implications for chemoprevention in smokers.

Lung cancer continues to be the leading cause of cancer death in developed countries. With smoking the major etiological factor for lung cancer, there is a great need for the development of chemopreventive treatments that inhibit the progression of initiated cells and premalignant lesions into overt lung cancer in smokers who quit. Although the major focus of chemoprevention research has been on agents that inhibit the metabolic activation of genotoxic chemicals contained in tobacco products, some of these agents may additionally modulate growth-regulating signal transduction. In turn, the function of such signaling pathways is highly cell type-specific, with a given pathway inhibiting the growth of one cell type while stimulating the growth of others. The current experiment has tested the hypothesis that green tea and the methylxanthine theophylline contained in tea inhibit the progression of neuroendocrine lung carcinogenesis in hamsters with hyperoxic lung injury and initiated with the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) while promoting the development of Clara cell-derived pulmonary adenocarcinomas initiated by NNK in healthy hamsters. This hypothesis is based on published evidence that human small cell lung cancer as well as the neuroendocrine hamster tumors are regulated via autocrine signaling pathways that activate Raf-1 and the mitogen-activated (MAP) kinase pathway whereas human pulmonary adenocarcinomas of Clara cell lineage and the hamster model of this cancer type are regulated by a beta-adrenergic pathway involving the activation of cyclic adenosine 3',5'-monophosphate (cAMP) and the arachidonic acid (AA) cascade. In turn, it was hypothesized that theophylline would inhibit Raf-1-dependent tumor progression while promoting cAMP-dependent tumor progression due to its documented ability to inhibit the enzyme cAMP-phophodiesterase. The experimental design simulated chemoprevention in former smokers in that treatments with tea or theophylline started after completion of a 10-week tumor induction period with NNK. Our data show that green tea as well as theophylline significantly inhibited lung tumor multiplicity in the neuroendocrine cancer model whereas identical chemopreventive treatments significantly promoted the lung tumor multiplicity in the adenocarcinoma model. These findings indicate that green tea and theophylline as well as other chemopreventive agents that modulate signal transduction may have opposite effects on cancers of different histolopathology and cell lineage. At the current state of knowledge such chemopreventive treatments should only be used as adjuvant to cancer therapy of cancers that have been fully characterized at the pathology and molecular level.

Adenocarcinoma↗
PubMed2003

Diagnosis of MS: a comparison of three different clinical settings.

In order to compare a newly established diagnostic clinic with two existing clinical settings in the management of the diagnostic phase of multiple sclerosis (MS), a retrospective audit was performed over a 12-month period comparing the length of time, adherence to recently published standards and price charged in diagnosing MS in three different clinical diagnostic settings operating within the same hospital: a specifically designed demyelinating disease diagnostic clinic (DDC), a general neurology clinic (GNC) and an inpatient investigation unit (IIU). An audit tool was created to measure the standards advocated by the UK MS Society on management of the diagnostic phase of MS. The costing tool was the price charged to health authorities. A randomized retrospective case note and referral letter review method was used. The entry criterion was a confirmed diagnosis of MS documented in the medical notes following investigation during the period April 1999-April 2001. The time between referral and first appointment favoured the DDC with a mean time of 5.9 weeks, compared to 7.7 weeks for the GNC and 10.0 weeks for the IIU. The mean times between the first appointment and receipt of results were 4.7 weeks (DDC), 18.8 weeks (GNC) and 21.2 weeks (IIU). Prices ranged from pounds sterling 395-pounds sterling 790 (DDC), pounds sterling 95-pounds sterling 380 (GNC) and pounds sterling 1940-pounds sterling 2700 (IIU). This study suggests that the UK MS Society standards are achievable in most areas without excessive additional costs and provides evidence that the DDC offers a better service than other existing models.

Adult↗
PubMed2003

Gliomatosis cerebri in six dogs.

Gliomatosis cerebri is a well-recognized entity in human medicine characterized by unusually widespread infiltration of the neuraxis by neoplastic glial cells with relative preservation of brain architecture. This report describes the pathologic features of the disease in six dogs. The dogs ranged from 3 to 9 years of age (mean 6.1 years) without evidence of breed predilection; five of the six dogs were neutered or intact males. The clinical findings were mixed (including depression, circling, cranial nerve deficits), reflecting the diffuse nature of the disease. Histologically, there was remarkably diffuse infiltration of the white and gray matter of the brain by small numbers of elongated neoplastic cells. Areas of greater cellularity formed grossly visible lesions in four cases. Anisocytosis and pleomorphism were greater in areas of higher cellularity. Other features of tumor growth included subpial accumulation, neuronal satellitosis, perivascular cuffing, and tropism for cranial nerve and brain stem nuclei. Neoplastic cells were negative on immunohistochemical stains for glial fibrillary acid protein (GFAP) and leukocyte markers, reflecting the uncertain histogenesis of these unusual neoplasms.

Animals↗
PubMed2002

Ganglioradiculitis (sensory neuronopathy) in a dog: clinical, morphologic, and immunohistochemical findings.

A 9-year-old Labrador Retriever was diagnosed with ganglioradiculitis (sensory neuronopathy). This idiopathic disease of mature dogs is characterized by a profound loss of sensory nerve function due to mononuclear inflammatory infiltration of peripheral ganglia and spinal nerve roots, with destruction of sensory neurons. Immunohistochemistry demonstrates that the infiltrating cells are primarily T lymphocytes and that immunoglobulins are not present on the cell membranes of affected neurons. The pathogenesis of ganglioradiculitis remains unclear, but the evidence points to a cell-mediated immune mechanism.

Adrenal Cortex Hormones↗
PubMed2002

The planning and construction of an urban stormwater management scheme.

Water Sensitive Urban Design (WSUD) offers a means to integrate stormwater best management practices into urban planning and design to achieve multiple objectives. Some of these objectives relate to stormwater drainage, water quality improvements, aquatic habitat protection, stormwater harvesting and use, and landscape amenity. The Lynbrook Estate, Australia, has incorporated bio-filtration systems and wetlands into the design of major roads, local access streets and parklands that attenuate and treat roof runoff and road runoff from a 32 ha, 270 allotment residential precinct. This paper outlines the process that enabled the concept of a stormwater drainage design to be translated into on-ground works. Details of the construction activities, costs and market acceptance highlight the potential for the adoption of similar practices elsewhere.

Ecosystem↗
PubMed2001

The discovery of RPR 200765A, a p38 MAP kinase inhibitor displaying a good oral anti-arthritic efficacy.

RPR132331, a 2-(2-dioxanyl)imidazole, was identified as an inhibitor of tumour necrosis factor (TNF)alpha release from lipopolysaccharide (LPS)-stimulated human monocytes. An intensive programme of work exploring the biology, toxicity and physical chemistry of a novel series of inhibitors, derived from RPR132331, has led to the identification of RPR200765A, a development candidate for the treatment of rheumatoid arthritis (RA). RPR200765A is a potent and selective inhibitor of p38 MAP kinase (IC50 = 50 nM). It inhibits LPS-stimulated TNFalpha release both in vitro, from human monocytes (EC50 = 110 nM), and in vivo in Balb/c mice (ED50 = 6 mg/kg). At oral doses between 10 and 30 mg/kg/day it reduces the incidence and progression in the rat streptococcal cell wall (SCW) arthritis model when administered in either prophylactic or therapeutic dosing regimens. The compound, which is a mesylate salt and exists as a stable monohydrate, shows good oral bioavailabiltiy (F = 50% in the rat) and excellent chemical stability. The data from the SCW disease model suggests that RPR200765A could exhibit a profile of disease modifying activity in rheumatoid arthritis (RA) patients which is not observed with current drug therapies.

Administration, Oral↗
PubMed2000

A phase I/II trial of iodine-131-tositumomab (anti-CD20), etoposide, cyclophosphamide, and autologous stem cell transplantation for relapsed B-cell lymphomas.

Relapsed B-cell lymphomas are incurable with conventional chemotherapy and radiation therapy, although a fraction of patients can be cured with high-dose chemoradiotherapy and autologous stem-cell transplantation (ASCT). We conducted a phase I/II trial to estimate the maximum tolerated dose (MTD) of iodine 131 ((131)I)-tositumomab (anti-CD20 antibody) that could be combined with etoposide and cyclophosphamide followed by ASCT in patients with relapsed B-cell lymphomas. Fifty-two patients received a trace-labeled infusion of 1.7 mg/kg (131)I-tositumomab (185-370 MBq) followed by serial quantitative gamma-camera imaging and estimation of absorbed doses of radiation to tumor sites and normal organs. Ten days later, patients received a therapeutic infusion of 1.7 mg/kg tositumomab labeled with an amount of (131)I calculated to deliver the target dose of radiation (20-27 Gy) to critical normal organs (liver, kidneys, and lungs). Patients were maintained in radiation isolation until their total-body radioactivity was less than 0.07 mSv/h at 1 m. They were then given etoposide and cyclophosphamide followed by ASCT. The MTD of (131)I-tositumomab that could be safely combined with 60 mg/kg etoposide and 100 mg/kg cyclophosphamide delivered 25 Gy to critical normal organs. The estimated overall survival (OS) and progression-free survival (PFS) of all treated patients at 2 years was 83% and 68%, respectively. These findings compare favorably with those in a nonrandomized control group of patients who underwent transplantation, external-beam total-body irradiation, and etoposide and cyclophosphamide therapy during the same period (OS of 53% and PFS of 36% at 2 years), even after adjustment for confounding variables in a multivariable analysis.

Adult↗
PubMed2000

Selective ET(A) antagonists. 5. Discovery and structure-activity relationships of phenoxyphenylacetic acid derivatives.

The fifth paper in this series describes the culmination of our investigations into the development of a potent and selective ET(A) receptor antagonist for the treatment of diseases mediated by ET-1. Receptor site mapping of several ET(A) antagonists prepared previously identified a common cationic binding site which prompted synthesis of phenoxyphenylacetic acid derivative 13a, which showed good in vitro activity (IC(50) 59 nM, rat aortic ET(A)). Optimization of 13a led to the identification of 27b, which exhibited an IC(50) of 4 nM. Although this did not translate into the expected in vivo potency, a compound of comparable in vitro activity, 27a (RPR118031A), showed a far better pharmacokinetic profile and in vivo potency (75 micromol/kg) and was duly proposed and accepted as a development candidate.

Administration, Oral↗
PubMed2000

Beta-adrenergic modulation of NNK-induced lung carcinogenesis in hamsters.

OBJECTIVE: Lung cancer is the leading cause of cancer death in industrialized countries. Pulmonary adenocarcinoma (PAC) is the most common histologic type of lung cancer, and it is reproducibly induced by the tobacco-specific nitrosamine 4-(methylnitrosamino)- 1-(3-pyridyl)-1-butanone (NNK) in laboratory rodents. We have recently shown that the growth of cell lines derived from human PACs is controlled by beta-adrenergic receptors, and that NNK is a high affinity agonist for this receptor family. DESIGN: In the current study, we have tested the relevance of these in in vitro findings for in vivo NNK-induced lung tumorigenesis, using a well-established hamster model of NNK-induced PAC. RESULTS: Our experiments demonstrate a significant increase in NNK-induced PAC multiplicity in animals chronically exposed to the beta-adrenergic agonist epinephrine or theophylline which causes intracellular accumulation of the beta-adrenergic second messenger cAMP. On the other hand, our data show that administration of the beta-adrenergic antagonist propranolol prior to each NNK injection significantly inhibited the development of PACs. DISCUSSION: Our findings support the hypothesis that the development of tobacco-associated PAC may be modulated by beta-adrenergic agents, and that the interaction of NNK with beta-adrenergic receptors contributes to the genesis of this histologic lung cancer type.

Adenocarcinoma↗
PubMed2000

Metatarsalgia and rheumatoid arthritis--a randomized, single blind, sequential trial comparing 2 types of foot orthoses and supportive shoes.

OBJECTIVE: To compare the effects of semi-rigid and soft orthoses worn in supportive shoes, and supportive shoes worn alone, on metatarsal phalangeal (MTP) joint pain. MTP joint synovitis, and lower extremity function in patients with rheumatoid arthritis. METHODS: Twenty-eight subjects referred to occupational therapy received in random order 3 interventions for 12 week trials, separated by 2 week washouts. A crossover design compared effectiveness of interventions. RESULTS: Twenty-four subjects completed the study. A reduction in mean pain scores from baseline to final visits showed that semi-rigid orthoses had a highly significant effect on pain. Soft orthoses did not show a significant effect on pain from baseline to final visit, nor did shoes worn alone. None of the interventions had a significant effect on synovitis or function. CONCLUSION: Semi-rigid orthoses worn in supportive shoes were an effective treatment for metatarsalgia. Supportive shoes worn alone or worn with soft orthoses did not provide pain relief for metatarsalgia.

Adult↗
PubMed1999

Interleukin-4 (IL-4) and IL-13 enhance the effect of IL-1beta on production of IL-1 receptor antagonist by human primary hepatocytes and hepatoma HepG2 cells: differential effect on C-reactive protein production.

Interleukin-1 receptor antagonist (IL-1Ra) is produced by hepatocytes with characteristics of an acute-phase protein. To examine the role of IL-4 and IL-13 in production of IL-1Ra, human primary hepatocytes and HepG2 human hepatoma cells were cultured in the presence of IL-4 or IL-13 in combination with IL-1beta and/or IL-6. The results indicated that both IL-4 and IL-13 amplified the stimulatory effect of IL-1beta on production of IL-1Ra protein and messenger RNA (mRNA) by both human primary hepatocytes and HepG2 cells. IL-1Ra refers to three different peptides, one secreted (sIL-1Ra) and two intracellular (icIL-1RaI and icIL-1RaII), derived from the same gene. sIL-1Ra and icIL-1RaI are the products of two different mRNA, whereas icIL-1RaII is synthesized by alternative translation initiation mainly from sIL-1Ra mRNA. Our results show that both sIL-1Ra and icIL-1RaII, but not icIL-1RaI, are produced by HepG2 cells and human hepatocytes. Transient transfection experiments as well as mRNA stability studies indicated that IL-4 stimulated sIL-1Ra production primarly at the level of transcription. Gel retardation assays showed that IL-4 induced the formation of a STAT6-DNA complex with a STAT6 binding element within the sIL-1Ra promoter, but had no effect on IL-1-induced NF-kappaB binding activity. In contrast to IL-1Ra, production of C-reactive protein by human primary hepatocytes was stimulated by IL-6 and decreased by the addition of IL-4.

C-Reactive Protein↗
PubMed1999

Misoprostol for induction of labour at term: a more effective agent than dinoprostone vaginal gel.

OBJECTIVE: To compare the efficacy of vaginal misoprostol and dinoprostone vaginal gel for induction of labour at term. DESIGN: A single-blind randomised comparative trial. SETTING: Induction and labour wards of a UK teaching hospital. PARTICIPANTS: Two hundred and eleven pregnant women at term in whom induction of labour was indicated, and with no contra-indication to the use of prostaglandins for the induction of labour. INTERVENTION: The women were randomly assigned to receive vaginal administration of either misoprostol 50 microg four hourly (to a maximum of four doses) or dinoprostone gel 1 mg six hourly (to a maximum of three doses). MAIN OUTCOME MEASURES: Time from induction to delivery, oxytocin requirement in labour, analgesic requirement, mode of delivery, neonatal outcome. RESULTS: The misoprostol group had a highly significant reduction in median induction-delivery interval compared with the dinoprostone group (14.4 hours vs 22.9 hours; P < 0.00001). In addition, more women delivered after only one dose (77% vs 49%; P < 0.0001, OR 3.51, 95% CI 1.94-6.35), and within 12 and 24 hours. There was a reduced need for oxytocin augmentation in labour (21% vs 47%; P < 0.0001, OR 0.30, 95% CI 0.16-0.54). There was no difference in analgesia requirement in labour, or in mode of delivery. There were no adverse neonatal outcomes associated with the use of misoprostol. Women in the misoprostol group experienced more pain in the interval between induction and being given analgesia in labour, but this did not reach statistical significance. CONCLUSIONS: Misoprostol 50 microg vaginally is a more effective induction agent than 1 mg dinoprostone vaginal gel, with no apparent adverse effects on mode of delivery, or on the fetus. The higher pain scores in the misoprostol group must be balanced against the reduction in time spent having labour induced, and the reduction in need for intravenous oxytocin augmentation. Further randomised studies must continue to exclude the possibility of rare adverse side effects.

Adolescent↗