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Biomedical subjects

M Law

Publications and source records attributed to M Law.

At least 37 records · Page 2Linked to original sources
PubMed2003

Patient effective dose from sentinel lymph node lymphoscintigraphy in breast cancer: a study using a female humanoid phantom and thermoluminescent dosemeters.

The aim of this study was to measure the dose delivered to patients undergoing sentinel lymph node lymphoscintigraphy by taking into account both the transmission scan dose using a (57)Co flood source and the (99)Tc(m) internal emission dose. An adult female humanoid phantom and a set of thermoluminescent dosimeters were used in the measurements. The choice of measurement organs in the humanoid was guided by the recommendations described in the International Commission on Radiological Protection report number 60. A (57)Co flood source was used in external transmission to irradiate the humanoid at posterior, left lateral, left posterior oblique, right lateral and right posterior oblique positions. Four (99)Tc(m) deposits as internal emission sources were used to simulate patient peritumoural injection. The individual effective doses for external transmission and internal emission, normalized to the cumulated activity and expressed in micro Sv(MBq x h)(-1) were then calculated. The effective dose for a transmission scan was on average 0.061 micro Sv(MBq x h)(-1) for each (57)Co flood source position and for internal emission 0.312 micro Sv(MBq x h)(-1) and 0.291 micro Sv(MBq x h)(-1) for left and right breast injection, respectively. Using these results, the effective dose from both transmission and emission sources can be calculated according to the nuclear medicine scanning protocol and surgical procedure of the individual institution. For our protocols, the patient receives a maximum effective dose of 52 micro Sv for the 1 day protocol (18 MBq injection) and 204 micro Sv for the 2 day protocol (74 MBq injection) if only the sentinel lymph node is excised. If other tissues containing radioactivity are removed, the patient effective dose will be reduced by about 50% and 6%, respectively, for the 1 day protocol and 2 day protocol. Although the doses are low compared with other radiological examinations, the results are informative for patients concerned about radiation exposure for this new imaging technique.

Breast Neoplasms↗
PubMed2003

Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy.

OBJECTIVES: To investigate the screening performance of measuring blood pressure and other variables in identifying those who will develop, or die from, ischaemic heart disease and stroke. To quantify by how much drugs that lower blood pressure will reduce the risk of ischaemic heart disease and stroke in those designated 'screen positive'. DATA SOURCES: MEDLINE, Cochrane collaboration and Web of Science databases; Stroke registries; Health Survey for England; Office of National Statistics; BUPA (British United Provident Association) study. REVIEW METHODS: Relevant cohort studies and randomised trials were identified and analysed. Statistical analysis was used to determine drug efficacy and adverse effects. RESULTS: Lowering blood pressure by 5 mmHg diastolic reduces the risk of stroke by an estimated 34% and ischaemic heart disease by 21% from any pre-treatment level; there is no threshold. These estimates, from cohort studies, have been corroborated by the results of randomised trials in persons with high, average and below average levels of blood pressure. In spite of its importance in causing cardiovascular disease blood pressure is a poor predictor of cardiovascular events. Its poor screening performance is illustrated by the findings that in the largest cohort study, persons in the top 10% of the distribution of systolic blood pressure experienced only 21% of all ischaemic heart disease events and 28% of all strokes at a given age. Combining several reversible risk factors adds little to the screening performance of blood pressure alone; for example the 25% of men aged 5564 at highest computed risk (> or =1%) experience only 46% of all ischaemic heart disease events. The main methods of screening should be to identify all persons with a history of cardiovascular disease events (for example identifying patients at the time of hospital discharge following a first myocardial infarction detects 50% of all heart disease deaths in a population at a false positive rate of 12%), and to use a person's age. Identifying everyone with a history of myocardial infarction or stroke in a population and everyone aged 55 or more would include 98% of all deaths from ischaemic heart disease and stroke. The five main categories of blood pressure lowering drugs, thiazides, beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin-II receptor antagonists and calcium channel blockers, significantly reduce blood pressure from all pre-treatment levels though the extent of the blood pressure reduction increased with pre-treatment blood pressure. The reductions were similar at standard dose for the five categories; average reduction was 9.1 systolic and 5 diastolic. The effect of combinations of two drugs on blood pressure was additive. No effect of age was apparent, given blood pressure. There were no serious metabolic consequences of using these drugs in standard dose. CONCLUSIONS: The evidence presented indicates that three drugs in combination may reduce stroke by about two-thirds and ischaemic heart disease by half. The report suggests that the term hypertension should be avoided because it is not a disease and it implies another category (normotensives) who would not benefit from lowering blood pressure. Blood pressure reduction using combinations of safe, well-established drugs is effective in preventing cardiovascular events. It is therefore suggested that such preventive therapy be considered more widely in people who by virtue of existing disease or simply age are at risk of a heart attack or stroke regardless of initial blood pressure.

Antihypertensive Agents↗
PubMed2002

Creutzfeldt-Jakob disease in Australia 1970-1999.

OBJECTIVE: To ascertain all persons who developed a transmissible spongiform encephalopathy (TSE) within Australia during the 30-year period 1970 to 1999 through a comprehensive national surveillance program and subject the group to detailed epidemiologic analysis. METHODS: Cases were ascertained through reviews of morbidity separation coding data from all university-affiliated tertiary referral hospitals, as well as the centralized data bases of state and territory health departments, regular national death certificate searches, and semiannual mailout questionnaires to all neurologists and pathologists throughout Australia. Prospective monitoring commenced in September 1993. RESULTS: A total of 387 patients were confirmed as having TSE during this epoch. The majority of cases were sporadic Creutzfeldt-Jakob disease (CJD) (90.7%), with 7.2% heredofamilial and 2.1% iatrogenic. Over this 30-year period, the national average annual sporadic CJD incidence rate per million progressively increased from 0.31 for the decade 1970 through 1979 to 0.77 for 1980 through 1989, reaching 1.03 for 1990 through 1999. Death certificates were found to have a false-positive rate of 11.5% and sensitivity of 83.0% for sporadic CJD. CONCLUSIONS: Within Australia, there has been a gradual increase in the incidence of transmissible spongiform encephalopathy over the three-decade period 1970 through 1999, peaking in 1999 at 1.4/million/year for sporadic Creutzfeldt-Jakob disease. This increase is believed secondary to improved case ascertainment. Variant Creutzfeldt-Jakob disease was not identified during this period. Age- and sex-adjusted comparisons showed a decline in incidence rates in the elderly in both sexes, usually from age 74 years. Death certificates were a useful but imperfect method of case detection.

Adult↗
PubMed2002

Spectroscopic magnetic resonance imaging of a tumefactive demyelinating lesion.

Tumefactive demyelinating lesions can present with features similar, clinically and radiologically, to those of brain tumours. Proton MR spectroscopy has been increasingly used to characterize intracranial pathology. As the underlying pathophysiology of neoplasms is different from that of demyelinating disease, one may expect the metabolic composition of neoplasms to be significantly different from that of demyelinating lesions. We report a 49-year-old woman in whom the neurologic and radiologic findings were highly suggestive of a high-grade brain tumor, and the spectroscopic features were sufficiently similar to that of a tumor to convince the neurosurgeon to operate. This case emphasizes the need for caution when confronted with a patient who presents with a differential diagnosis of demyelinating lesion versus neoplasm.

Brain Neoplasms↗
PubMed2002

Heterozygosity for CCR5-Delta32 but not CCR2b-64I protects against certain intracellular pathogens.

OBJECTIVE: To determine the association between CCR5 and CCR2b genotype and the clinical manifestation of first and subsequent AIDS-defining illnesses (ADIs). METHODS: The distribution of ADIs was examined by CCR5 and CCR2b genotype in a subset of homosexual men enrolled in the Sydney AIDS Prospective Study. The expected number of ADIs was calculated from rates observed in the same tertiary hospital over the same period. RESULTS: Information on initial ADI was collected for 117 homosexual men diagnosed with AIDS before January 1998. Of these individuals, 17 were heterozygous for the CCR5-Delta32 mutation and 11 were heterozygous for CCR2b-64I. The number of observed cases of Pneumocystis carinii pneumonia (PCP), toxoplasmosis, Mycobacterium avium complex (MAC) and cryptosporidiosis reported as a first ADI was substantially fewer in people heterozygous for the CCR5-Delta32 mutation than for those without the mutation, despite similar age, CD4 T-cell count at AIDS diagnosis, year of AIDS diagnosis and receipt of antiretroviral treatment. In addition, among individuals heterozygous for CCR5-Delta32 there were fewer cases of PCP, toxoplasmosis, MAC, and cryptosporidiosis observed as subsequent ADIs compared to the number expected, based on rates measured in the same hospital during the same period (seven observed vs. 24 expected, RR = 0.3, 95% CI = 0.01-0.6). The distribution of first and subsequent ADIs did not differ from the number expected in individuals heterozygous for the CCR2b-64I mutation. CONCLUSION: Results from this study show that heterozygosity for CCR5-Delta32 but not CCR2b-64I appears to protect against opportunistic infections.

AIDS-Related Opportunistic Infections↗
PubMed2002

Dynamic contrast-enhanced T2*-weighted MR imaging of gliomatosis cerebri.

BACKGROUND AND PURPOSE: MR imaging characteristics of gliomatosis cerebri reiterate the diffuse nature of this tumor but are nonspecific and thus may pose a diagnostic challenge. Because perfusion MR imaging can provide a physiologic map of the microcirculation, we compared the measured relative cerebral blood volume (rCBV) at perfusion imaging with histopathologic findings in gliomatosis cerebri. MR spectroscopic findings were also reviewed. METHODS: Retrospective analysis was performed of conventional and perfusion MR images from seven patients with proved gliomatosis cerebri. The conventional MR images were evaluated for the presence or absence of contrast enhancement, necrosis, and extent of T2-weighted signal intensity abnormality. Dynamic contrast-enhanced T2*-weighted gradient-echo echo-planar images were acquired during the first pass of a bolus injection of gadopentetate dimeglumine. The rCBV was calculated by using nondiffusible tracer kinetics and expressed relative to normal-appearing white matter. Pathologic findings were reviewed in all patients and compared with the MR perfusion data. Multivoxel 2D chemical shift imaging proton MR spectroscopic data were available for three patients and single-voxel data for one patient. RESULTS: Conventional MR images showed diffuse abnormality in all cases and absence of contrast enhancement in all but one case. Average rCBV range was 0.75-1.26 (mean, 1.02 +/- 0.42 [SD]). MR spectroscopic data revealed spectra consistent with presence of tumoral disease. Histopathologic review showed absence of vascular hyperplasia in all specimens. CONCLUSION: The low MR rCBV measurements of gliomatosis cerebri are in concordance with the lack of vascular hyperplasia found at histopathologic examination; thus, perfusion MR imaging provides useful adjunctive information that is not available from conventional MR imaging techniques.

Adolescent↗
PubMed2001

HIV protease inhibitor substitution in patients with lipodystrophy: a randomized, controlled, open-label, multicentre study.

BACKGROUND: Lipodystrophy, dyslipidaemia and insulin resistance often complicate protease inhibitor-containing antiretroviral therapy. The aims of this study were to determine if these are reversible with continued HIV suppression following protease inhibitor substitution. METHODS: Eighty-one HIV protease inhibitor recipients (78 male; mean antiretroviral therapy, 55 months) with predominant peripheral lipoatrophy, HIV RNA < 400 copies/ml plasma for at least the preceding 6 months, and no prior abacavir, non-nucleoside analogue or adefovir therapy were randomized 3 : 2 to continue nucleoside analogues and substitute protease inhibitor(s) with abacavir, nevirapine, adefovir and hydroxyurea (n = 49) or to continue all therapy (n = 32) with an option to switch at week 24. The primary endpoints were total body fat and HIV RNA at week 24. Other assessments were regimen safety, regional body composition, metabolic parameters, quality of life, and CD4 T-lymphocyte counts to week 48. RESULTS: There was a greater decline in total body fat in the switch group than in the continue group (-1.6 and -0.4 kg, respectively at week 24; P = 0.006). This comprised greater declines in limb and subcutaneous abdominal fat, and in intra-abdominal fat of patients with moderate or severe abdominal fat accumulation. Viral suppression was similar, despite 18 (37%) switch group patients ceasing at least one study drug by week 24 because of adverse events. Total cholesterol and triglycerides declined more in the switch group (both P < 0.002). High density lipoprotein cholesterol increased significantly in both groups at week 48 (P < 0.02). There was no change for any glycaemic parameter. CONCLUSIONS: In predominantly lipoatrophic patients, switching from HIV protease inhibitor therapy lead to improved lipids and less intra-abdominal fat, but also to less peripheral fat, and had minimal effect on insulin resistance. Virological control in these heavily pretreated patients was unaffected, despite frequent switch drug cessations.

Adenine↗
PubMed2001

Vaccinia virus utilizes microtubules for movement to the cell surface.

Vaccinia virus (VV) egress has been studied using confocal, video, and electron microscopy. Previously, intracellular-enveloped virus (IEV) particles were proposed to induce the polymerization of actin tails, which propel IEV particles to the cell surface. However, data presented support an alternative model in which microtubules transport virions to the cell surface and actin tails form beneath cell-associated enveloped virus (CEV) particles at the cell surface. Thus, VV is unique in using both microtubules and actin filaments for egress. The following data support this proposal. (a) Microscopy detected actin tails at the surface but not the center of cells. (b) VV mutants lacking the A33R, A34R, or A36R proteins are unable to induce actin tail formation but produce CEV and extracellular-enveloped virus. (c) CEV formation is inhibited by nocodazole but not cytochalasin D or 4-amino-5-(4-methylphenyl)-7-(t-butyl)pyrazolo(3,4-d)pyrimidine (PP1). (d) IEV particles tagged with the enhanced green fluorescent protein fused to the VV B5R protein moved inside cells at 60 microm/min. This movement was stop-start, was along defined pathways, and was inhibited reversibly by nocodazole. This velocity was 20-fold greater than VV movement on actin tails and consonant with the rate of movement of organelles along microtubules.

Actin Cytoskeleton↗
PubMed2001

Randomized trial of folic acid supplementation and serum homocysteine levels.

BACKGROUND: Lowering serum homocysteine levels with folic acid is expected to reduce mortality from ischemic heart disease. Homocysteine reduction is known to be maximal at a folic acid dosage of 1 mg/d, but the effect of lower doses (relevant to food fortification) is unclear. METHODS: We randomized 151 patients with ischemic heart disease to 1 of 5 dosages of folic acid (0.2, 0.4, 0.6, 0.8, and 1.0 mg/d) or placebo. Fasting blood samples for serum homocysteine and serum folate analysis were taken initially, after 3 months of supplementation, and 3 months after folic acid use was discontinued. RESULTS: Median serum homocysteine level decreased with increasing folic acid dosage, to a maximum at 0.8 mg of folic acid per day, when the homocysteine reduction (placebo adjusted) was 2.7 micromol/L (23%), similar to the known effect of folic acid dosages of 1 mg/d and above. The higher a person's initial serum homocysteine level, the greater was the response to folic acid, but there were statistically significant reductions regardless of the initial level. Serum folate level increased approximately linearly (5.5 nmol/L for every 0.1 mg of folic acid). Within-person fluctuations over time in serum homocysteine levels, measured in the placebo group, were large compared with the effect of folic acid, indicating that monitoring of the reduction in an individual is impractical. CONCLUSIONS: A dosage of folic acid of 0.8 mg/d appears necessary to achieve the maximum reduction in serum homocysteine level across the range of homocysteine levels in the population. Current US food fortification levels will achieve only a small proportion of the achievable homocysteine reduction.

Adult↗
PubMed2001

Antibody neutralization of the extracellular enveloped form of vaccinia virus.

The extracellular enveloped form (EEV) of vaccinia virus (VV) is important for the long-range dissemination of the virus inside the host. Early work suggested that both IMV and EEV infectivity could be inhibited by antibodies, although two other studies reported that EEV was resistant to neutralization. Here, we readdressed this question, using four VV-immune antisera and their purified IgG, and showed that EEV infectivity can be inhibited by antibody produced from a live infection in plaque-reduction assays, although EEV is more resistant to neutralization by convalescent antibodies than is IMV. In parallel, indirect immunofluorescent staining and confocal microscopy showed that antibody aggregated EEV and prevented it from binding to cells. Using the IgG and Fab fragments prepared from this antiserum, we tested whether EEV made by VV mutants lacking genes A33R, A34R, A36R, A56R, B5R, F12L, or F13L can be inhibited in plaque-reduction assays. Although vDeltaB5R was slightly more resistant than other mutants, none of these mutants escaped neutralization completely, suggesting that multiple virus proteins are involved in the inhibition. Using an antibody specific to B5R protein and B5R mutants with consecutive short consensus repeat (SCR) domains deleted, the neutralization epitopes on B5R were mapped to within the SCR domain 1.

Animals↗
PubMed2001

Detection of 1p and 19q loss in oligodendroglioma by quantitative microsatellite analysis, a real-time quantitative polymerase chain reaction assay.

The combined loss of chromosomes 1p and 19q has recently emerged as a genetic predictor of chemosensitivity in anaplastic oligodendrogliomas. Here, we describe a strategy that uses a novel method of real-time quantitative polymerase chain reaction, quantitative microsatellite analysis (QuMA), for the molecular analysis of 1p and 19q loss in oligodendrogliomas and oligoastrocytomas in archival routinely processed paraffin material. QuMA is performed on the ABI 7700 and based on amplifications of microsatellite loci that contain (CA)n repeats where the repeat itself is the target for hybridization by the fluorescently labeled probe. This single probe can therefore be used to determine copy number of microsatellite loci spread throughout the human genome. In genomic DNA prepared from paraffin-embedded brain tumor specimens, QuMA detected combined loss of 1p and 19q in 64% (21 of 32) of oligodendrogliomas and 67% (6 of 9) of oligoastrocytomas. We validate the use of QuMA as a reliable method to detect copy number by showing concordance between QuMA and fluorescence in situ hybridization at 37 of 45 chromosomal arms tested. These results indicate that QuMA is an accurate, high-throughput assay for the detection of copy number at multiple loci; as many as 31 loci of an individual tumor can be analyzed on a 96-well plate in a single 2-hour run. In addition, it has advantages over standard allelic imbalance/loss of heterozygosity assays in that all loci are potentially informative, paired normal tissue is not required, and gain can be distinguished from loss. QuMA may therefore be a powerful molecular tool to expedite the genotypic analysis of human gliomas in a clinical setting for diagnostic/prognostic purposes.

Brain Neoplasms↗
PubMed2001

Health-related quality of life in childhood disorders: a modified focus group technique to involve children.

OBJECTIVES: Qualitative methodology has been under-utilized in child health research due to lack of a specific set of instruments. The objective of this study was to develop a child-centred qualitative research methodology to facilitate direct exploration of health-related quality of life (HRQL) issues and to identify the quality of life elements in pre-adolescent children with a chronic medical condition. STUDY DESIGN: Purposeful stratified sampling of children, ages 6-12, who function in a regular school class, with active epilepsy who were assembled in small focus groups. The groups met in four phases and were led by moderators who probed preset open questions and activities. RESULTS: The study demonstrated that our modified focus groups process was a powerful exploratory experience eliciting meaningful and important issues in quality of life beyond what parents and health professionals expected, and helped identify HRQL elements in childhood epilepsy. CONCLUSION: Modified focus groups are appropriate and suitable to explore quality of life issues in pre-adolescent children with a chronic medical condition. The process is feasible and trustworthy.

Child↗
PubMed2001

Insertional mutagenesis of genes required for seed development in Arabidopsis thaliana.

The purpose of this project was to identify large numbers of Arabidopsis genes with essential functions during seed development. More than 120,000 T-DNA insertion lines were generated following Agrobacterium-mediated transformation. Transgenic plants were screened for defective seeds and putative mutants were subjected to detailed analysis in subsequent generations. Plasmid rescue and TAIL-PCR were used to recover plant sequences flanking insertion sites in tagged mutants. More than 4200 mutants with a wide range of seed phenotypes were identified. Over 1700 of these mutants were analyzed in detail. The 350 tagged embryo-defective (emb) mutants identified to date represent a significant advance toward saturation mutagenesis of EMB genes in Arabidopsis. Plant sequences adjacent to T-DNA borders in mutants with confirmed insertion sites were used to map genome locations and establish tentative identities for 167 EMB genes with diverse biological functions. The frequency of duplicate mutant alleles recovered is consistent with a relatively small number of essential (EMB) genes with nonredundant functions during seed development. Other functions critical to seed development in Arabidopsis may be protected from deleterious mutations by extensive genome duplications.

Alleles↗
PubMed2001

Arabidopsis genes essential for seedling viability: isolation of insertional mutants and molecular cloning.

We have undertaken a large-scale genetic screen to identify genes with a seedling-lethal mutant phenotype. From screening approximately 38,000 insertional mutant lines, we identified >500 seedling-lethal mutants, completed cosegregation analysis of the insertion and the lethal phenotype for >200 mutants, molecularly characterized 54 mutants, and provided a detailed description for 22 of them. Most of the seedling-lethal mutants seem to affect chloroplast function because they display altered pigmentation and affect genes encoding proteins predicted to have chloroplast localization. Although a high level of functional redundancy in Arabidopsis might be expected because 65% of genes are members of gene families, we found that 41% of the essential genes found in this study are members of Arabidopsis gene families. In addition, we isolated several interesting classes of mutants and genes. We found three mutants in the recently discovered nonmevalonate isoprenoid biosynthetic pathway and mutants disrupting genes similar to Tic40 and tatC, which are likely to be involved in chloroplast protein translocation. Finally, we directly compared T-DNA and Ac/Ds transposon mutagenesis methods in Arabidopsis on a genome scale. In each population, we found only about one-third of the insertion mutations cosegregated with a mutant phenotype.

Arabidopsis↗
PubMed2001

Incident sexually transmitted infections and their risk factors in an Aboriginal community in Australia: a population based cohort study.

OBJECTIVE: To identify risk factors for incident sexually transmitted infections (STI) in a remote Aboriginal community in Australia. DESIGN: A population based cohort study. SETTING: An Aboriginal community in central Australia. PARTICIPANTS: 1034 Aboriginal people aged 12-40 years, resident in the study region, seen during the period 1 January 1996 to 30 June 1998 for STI diagnosis. MAIN OUTCOME MEASURES: Incident rate of gonorrhoea, chlamydia, and syphilis per 100 person years. RESULTS: There were 313 episodes of incident gonorrhoea, 240 of incident chlamydial infection, and 17 of incident syphilis. For gonorrhoea, risk factors were age, substance abuse, and previous prevalent chlamydial infection with a rate ratio (RR) of 3.2 in people aged 15-19 years, 1.6 in people who abused alcohol, and 3.2 in women who had sniffed petrol on a regular basis. For chlamydia, risk factors were sex, age, and a previous history of STI with a RR of 2.7 in people aged 15-19 years. Similar factors were associated with an increased risk of syphilis but the associations were not statistically significant. CONCLUSION: This study identified objective predictors of incident STI which can be used to target interventions and maximise their impact. The results of this study may well have relevance to indigenous communities in other countries that are faced with high levels of STI and substance abuse.

Adolescent↗