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Biomedical subjects

M Lockwood

Publications and source records attributed to M Lockwood.

At least 19 recordsLinked to original sources
PubMed2006

Prophylactic versus preemptive oral valganciclovir for the management of cytomegalovirus infection in adult renal transplant recipients.

Prophylaxis reduces cytomegalovirus (CMV) disease, but is associated with increased costs and risks for side effects, viral resistance and late onset CMV disease. Preemptive therapy avoids drug costs but requires frequent monitoring and may not prevent complications of asymptomatic CMV replication. Kidney transplant recipients at risk for CMV (D+/R-, D+/R+, D-/R+) were randomized to prophylaxis (valganciclovir 900 mg q.d. for 100 days, n=49) or preemptive therapy (900 mg b.i.d. for 21 days, n=49) for CMV DNAemia (CMV DNA level>2000 copies/mL in >or=1 whole blood specimens by quantitative PCR) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. More patients in the preemptive group, 29 (59%) than in the prophylaxis group, 14 (29%) developed CMV DNAemia, p=0.004. Late onset of CMV DNAemia (>100 days after transplant) occurred in 11 (24%) randomized to prophylaxis, and none randomized to preemptive therapy. Symptomatic infection occurred in five patients, four (3 D+/R- and 1 D+/R+) in the prophylactic group and one (D+/R-) in the preemptive group. Peak CMV levels were highest in the D+/R- patients. Both strategies were effective in preventing symptomatic CMV. Overall costs were similar and insensitive to wide fluctuations in costs of either monitoring or drug.

Administration, Oral↗
PubMed2001

Structure-activity investigation of the inhibition of 3-hydroxypyridin-4-ones on mammalian tyrosine hydroxylase.

3-Hydroxypyridin-4-ones are currently one of the main candidates for the development of orally active iron chelators. Small bidentate ligands tend to inhibit iron-containing metalloenzymes and therefore can cause undesirable side effects. A range of 3-hydroxypyridin-4-ones with different R2 substituents was selected for the investigation of the structure-activity relationship between the chemical nature of the ligand and the inhibition of mammalian tyrosine hydroxylase. Results indicated that lipophilicity was the dominant factor in controlling the ability of this class of chelator to inhibit mammalian tyrosine hydroxylase. Ligands with hydrophilic R2 substituents tended to be weak inhibitors. No significant correlation was found in this study between iron-binding affinity, extended R2 chain length, and enzyme inhibitory activity. In contrast, both the LogP values of the entire molecule and of the R2 segment correlated well with inhibitory activity.

Animals↗
PubMed2001

The moral status of the human embryo.

I first delineate the concept of personhood--that cluster of capacities that distinguish us from non-human animals--and then argue that mere potentiality for personhood does not by itself confer upon the embryo a serious right to life. What is required, in addition, is the presence of brain life, which almost certainly does not develop until the second trimester.

Abortion, Induced↗
PubMed2000

Radiolabeled leucocyte imaging in diffuse granulomatous involvement of the meninges in Wegener's granulomatosis: scintigraphic findings and their role in monitoring treatment response to specific immunotherapy (humanized monoclonal antilymphocyte antibodies).

BACKGROUND AND PURPOSE: Diffuse involvement of the meninges by remote granulomas in Wegener's granulomatosis is rare. This study reports the radiolabeled leucocyte imaging findings in five such patients. The diagnosis was made by MR imaging in five patients and confirmed in four by findings at meningeal biopsy. The potential role of serial radiolabeled leucocyte examinations in assessing treatment response is discussed. METHODS: Three of the five patients underwent whole-body planar 111In-labeled leucocyte imaging. Two of these patients had serial imaging and one had, in addition, a 99mTc-HMPAO-labeled leucocyte single-photon emission CT brain examination. Two of the five patients had whole-body planar 99mTc-HMPAO-labeled leucocyte imaging. Of these, one patient had serial imaging. The radiolabeled leucocyte imaging findings were correlated with MR findings and with the patients' clinical course. RESULTS: In four patients there was a midline linear area of increased tracer uptake in the brain, and in one of these, tracer uptake also extended laterally over the brain convexity. In two patients linear tracer uptake extended in an inferolateral direction from the midline. These abnormalities correlated with meningeal thickening in the falx, over the brain convexity, and in the tentorium cerebelli on MR images. Serial imaging in three patients revealed a reduction or disappearance in tracer uptake after treatment with anti-CD52, which correlated with clinical improvement. CONCLUSION: In patients with Wegener's granulomatosis, abnormal uptake corresponding to meningeal thickening can be seen on planar radiolabeled leucocyte images. Leucocyte imaging may be useful for monitoring treatment response.

Adult↗
PubMed1999

Wegener granulomatosis: MR imaging findings in brain and meninges.

PURPOSE: To determine the spectrum of intracranial magnetic resonance (MR) imaging appearances of Wegener granulomatosis. MATERIALS AND METHODS: MR imaging studies in 19 patients with Wegener granulomatosis and possible central nervous system involvement were reviewed by two neuroradiologists. Intermediate-weighted and T2-weighted fast spin-echo MR images of the brain had been acquired in all patients, and spin-echo T1-weighted nonenhanced and gadolinium-enhanced images had been acquired in 18 patients. RESULTS: MR imaging findings included diffuse linear dural thickening and enhancement (n = 6); focal dural thickening and enhancement contiguous with orbital, nasal, or paranasal disease (n = 5); infarcts (n = 4); nonspecific white matter areas of high signal intensity on intermediate-weighted and T2-weighted images (n = 10); enlarged pituitary gland with infundibular thickening and enhancement (n = 2); a discrete cerebellar lesion that was probably granulomatous in origin (n = 1); and cerebral (n = 8) and cerebellar atrophy (n = 2). CONCLUSION: MR imaging demonstrated the wide spectrum of findings of central nervous system involvement in patients with Wegener granulomatosis and was particularly useful for the evaluation of direct intracranial spread from orbital, nasal, or paranasal disease.

Adolescent↗
PubMed1998

Primary heart angiosarcoma detected by computed tomography and magnetic resonance imaging.

We report a case of primary heart angiosarcoma and its appearance on plain and post-contrast computed tomography and magnetic resonance imaging in 21-year-old woman. The tumour involved the right atrium, expanded superiorly among the superior vena cava, ascending aorta and innominate vein, and infiltrated the pericardium. The tumour was disseminated into lungs, liver and bones at the time of its clinical presentation.

Adult↗
PubMed1998

Cutaneous vasculitis in a defined population--clinical and epidemiological associations.

OBJECTIVE: To examine the value of the American College of Rheumatology (ACR) 1990 criteria for Henoch-Schönlein purpura (HSP) and hypersensitivity vasculitis (HSV) and the Chapel Hill Consensus Conference (CHCC) definition of cutaneous leukocytoclastic angiitis (CLA) in the classification of cutaneous vasculitis and to estimate the annual incidence of biopsy proven cutaneous vasculitis in a well defined population. METHODS: ACR criteria for HSP and HSV and the CHCC definition for CLA and HSP were applied to an unselected cohort of 84 patients with biopsy proven cutaneous vasculitis attending a single district hospital in the United Kingdom between January 1990 and December 1994. RESULTS: Thirty-seven patients fulfilled ACR criteria for HSV, of whom 27 also fulfilled the ACR criteria for HSP. Thirty-two patients met the CHCC definition for CLA and 7 the CHCC definition for HSP. The overall annual incidence of cutaneous vasculitis was 38.6/million (95% CI 30.6-48.1), and for CLA 15.4/million (95% CI 10.6-21.8). CONCLUSION: The ACR 1990 criteria for HSP and HSV overlap; the CHCC definitions for CLA and HSP provide clearer distinction. Cutaneous vasculitis is as common as systemic vasculitis.

Antibodies, Antinuclear↗
PubMed1997

Integrated Protected Area Selection in Australian Biogeographic Regions

/ This paper reports on the development of abiogeographic-based protected area selection procedure (PASP) that addresseslimitations of current reserve selection methods such as inflexibility,restrictive criteria structures, and disregard of social criteria. We arguethat selection criteria are legitimately identified through the politicalprocess and can therefore have both social and biological content. PASPprovides a systematic, flexible and efficient procedure for identifying anetwork of protected areas that satisfies a given set of selection criteria.PASP has 11 steps divided into three main stages: compilation, selection, andvalidation. A selection algorithm is used into which criteria specific to thebiogeographic region under study can be incorporated. The procedure is ableto accommodate both nominal and ranking criteria and gives the analyst theopportunity to specify thresholds and targets for each criterion. Otherfeatures of PASP include the minimization of data collection effort,consideration of reserve design principles, and inclusion of a networkevaluation as a check to ensure that politically determined objectives havebeen met.KEY WORDS: Land use; Protected area networks; Selection algorithms

Journal Article↗
PubMed1997

Of persons and organisms: a reply to Howsepian.

Howsepian has presented a number of thought experiments, which are designed to undermine my claim that our identity through time is grounded in the continued existence of those structures in our brains which directly underlie mental functioning. I argue that the conclusions which Howsepian draws from these thought experiments are mistaken, and that his discussion of them is vitiated, in particular, by his failure to distinguish between personal identity and the identity of the associated human organism.

Beginning of Human Life↗
PubMed1997

Vasculitis and bronchiectasis in a patient with antibodies to bactericidal/permeability-increasing protein and alpha1-antitrypsin deficiency.

A patient with alpha1-antitrypsin deficiency is reported herein; this subject developed aggressive bronchial disease and recurrent cutaneous vasculitis after pulmonary infection with Pseudomonas aeruginosa. Autoantibodies to neutrophil cytoplasmic antigens were detected, which produced granular cytoplasmic staining by indirect immunofluorescence with specificity for a newly characterized antigen: bactericidal/permeability-increasing protein (BPI). The bronchial disease and vasculitis improved, and the IgA anti-BPI titer fell after antipseudomonal treatment. This raises the possibility that anti-BPI antibodies contributed to both the bronchial disease and vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1996

Effect of classification on the incidence of polyarteritis nodosa and microscopic polyangiitis.

OBJECTIVE: Polyarteritis nodosa (PAN) has been used as a generic term for systemic vasculitis. The distinction between classic PAN and microscopic polyangiitis (MPA) has not always been made. The aims of this study were to compare the American College of Rheumatology (ACR) criteria for PAN with the Chapel Hill Consensus Conference (CHCC) definitions of classic PAN and MPA, and to estimate the annual incidence of PAN and MPA. METHODS: The 1990 ACR criteria and CHCC definitions for systemic vasculitis were applied to an unselected cohort of 130 patients with systemic vasculitis attending a single district hospital in the UK between February 1, 1988 and January 31, 1994. RESULTS: Eight patients who met the ACR criteria for PAN and who also met the CHCC definition of MPA but not classic PAN were identified. A further 5 patients met the CHCC definition of MPA but not the ACR criteria for any other type of systemic vasculitis. No patient who met the CHCC definition of classic PAN was identified. The annual incidence of MPA was calculated to be 3.6/million (95% confidence interval 1.7-6.9), and the annual incidence of PAN (ACR criteria) was 2.4/million (95% confidence interval 0.9-5.3). CONCLUSION: Classic PAN as defined by the CHCC is rare, because small vessel involvement is excluded from this definition.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Increases in rat striatal extracellular dopamine and vacuous chewing produced by two sigma receptor ligands.

The present studies were carried out to analyze the neurochemical and behavioral effects of peripheral sigma ligand administration in the rat. Based upon previous studies which showed an increase in turning behavior following unilateral intranigral administration of sigma ligands, we determined the effects of two sigma ligands, 1,3-di-o-tolylguanidine (DTG) and (+)-pentazocine, on extracellular dopamine levels in the rat striatum. Dopamine levels were monitored via microdialysis in awake freely moving animals following i.p. injection of the ligands. Both DTG (1 and 3 mg/kg) and (+)-pentazocine (10 mg/kg) produced a significant (30-50%) increase in extracellular dopamine. Given the relatively high concentration of sigma receptors in brain nuclei involved in facial and mouth movements, we have also determined the effects of the two sigma ligands on facial movements. Both ligands produced a significant increase in vacuous chewing movements, suggesting that studies on the consequences of sigma receptor activation may have relevance to animal models of human dystonia and/or dyskinesia.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1992

Ethanol inhibits production of messenger ribonucleic acid for kappa-chain in stimulated B lymphocytes.

Alcohol consumption can adversely affect an individual's response to infection. We have shown that alcohol has a direct suppressive effect on numbers of antibody-secreting cells in antigen-activated B lymphocytes but does not suppress the early membrane and intracellular events that are associated with binding of antigens to specific receptors. The studies reported here were designed to determine whether alcohol inhibits immunoglobulin synthesis. When 150 mg/dl ethanol was added to anti-mu-stimulated purified B cells, proliferation was inhibited. Similar exposure to ethanol inhibited production of messenger RNA for kappa chain in anti-mu-stimulated B cells but did not affect total RNA production or messenger RNA for beta-actin. Thus alcohol inhibits both the proliferation of antigen-activated B lymphocytes and their synthesis of immunoglobulin.

Animals↗