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Biomedical subjects

B MacDonald

Publications and source records attributed to B MacDonald.

At least 19 recordsLinked to original sources
PubMed2003

Regional genetic differentiation in Western Australian sandalwood (Santalum spicatum) as revealed by nuclear RFLP analysis.

Western Australian sandalwood, Santalum spicatum, is widespread in the semi-arid and arid regions of Western Australia, and there is some morphological variation suggestive of two ecotypes. The level and structuring of genetic diversity within the species was investigated using anonymous nuclear RFLP loci. Santalum spicatum showed moderate levels of genetic diversity compared to other Australian tree species. The northern populations in the arid region showed greater levels of diversity and less population differentiation than the southern populations in the semi-arid region due to differences in the distribution of rare alleles. Equilibrium between drift and gene flow in the northern populations indicated that they have been established for a long period of time with stable conditions conducive to gene flow. In contrast, the southern populations showed a relationship between drift and gene flow indicative of a pattern of fragmentation and isolation where drift has greater effect than gene flow. The different patterns of diversity suggest that the ecotypes in the two regions have been subject to differences in the relative influences of drift and gene flow during their evolutionary history.

Alleles↗
PubMed2002

In vivo assessment of architecture and micro-finite element analysis derived indices of mechanical properties of trabecular bone in the radius.

Measurement of microstructural parameters of trabecular bone noninvasively in vivo is possible with high-resolution magnetic resonance (MR) imaging. These measurements may prove useful in the determination of bone strength and fracture risk, but must be related to other measures of bone properties. In this study in vivo MR imaging was used to derive trabecular bone structure measures and combined with micro-finite element analysis (microFE) to determine the effects of trabecular bone microarchitecture on bone mechanical properties in the distal radius. The subjects were studied in two groups: (I) postmenopausal women with normal bone mineral density (BMD) (n = 22, mean age 58 +/- 7 years) and (II) postmenopausal women with spine or femur BMD -1 SD to -2.5 SD below young normal (n = 37, mean age 62 +/- 11 years). MR images of the distal radius were obtained at 1.5 T, and measures such as apparent trabecular bone volume fraction (App BV/TV), spacing, number and thickness (App TbSp, TbN, TbTh) were derived in regions of interest extending from the joint line to the radial shaft. The high-resolution images were also used in a micro-finite element model to derive the directional Young's moduli (E1, E2 and E3), shear moduli (G12, G23 and G13) and anisotropy ratios such as E1/E3. BMD at the distal radius, lumbar spine and hip were assessed using dual-energy X-ray absorptiometry (DXA). Bone formation was assessed by serum osteocalcin and bone resorption by serum type I collagen C-terminal telopeptide breakdown products (serum CTX) and urinary CTX biochemical markers. The trabecular architecture displayed considerable anisotropy. Measures of BMD such as the ultradistal radial BMD were lower in the osteopenic group (p<0.01). Biochemical markers between the two groups were comparable in value and showed no significant difference between the two groups. App BV/TV, TbTh and TbN were higher, and App TbSp lower, in the normal group than the osteopenic group. All three directional measures of elastic and shear moduli were lower in the osteopenic group compared with the normal group. Anisotropy of trabecular bone microarchitecture, as measured by the ratios of the mean intercept length (MIL) values (MIL1/MIL3, etc.), and the anisotropy in elastic modulus (E1/E3, etc.), were greater in the osteopenic group compared with the normal group. The correlations between the measures of architecture and moduli are higher than those between elastic moduli and BMD. Stepwise multiple regression analysis showed that while App BV/TV is highly correlated with the mechanical properties, additional structural measures do contribute to the improved prediction of the mechanical measures. This study demonstrates the feasibility and potential of using MR imaging with microFE modeling in vivo in the study of osteoporosis.

Aged↗
PubMed2002

High-resolution MRI and micro-FE for the evaluation of changes in bone mechanical properties during longitudinal clinical trials: application to calcaneal bone in postmenopausal women after one year of idoxifene treatment.

OBJECTIVE: To investigate whether recently developed in vivo high-resolution magnetic resonance-imaging and micro-finite element techniques can monitor changes in bone mechanical properties during long-term clinical trials aiming at evaluating the efficacy of new drugs for the treatment of osteoporosis. DESIGN: Comparison of baseline and follow-up mechanical parameters calculated using micro-finite element analysis of the calcaneus for subjects participating in a study investigating the effect of idoxifene. BACKGROUND: Contemporary measurements for the evaluation of bone mechanical properties, based on dual-energy X-ray absorptiometry measurements, are not very accurate and require large trial populations. METHODS: A total of 56 postmenopausal subjects received either a placebo, 5 mg or 10 mg per day of idoxifene. Magnetic resonance-images of the calcaneus were made at baseline and after one year. Mechanical parameters of a trabecular volume of interest in the calcaneus were calculated using micro-finite element analysis. RESULTS: Although there were no significant differences between the mean changes in the treated groups and the placebo group, there were significant changes from baseline within groups after one year of treatment. Significant changes, however, were found only for mechanical parameters and only in the treated groups. CONCLUSIONS: The present study is the first demonstration that longitudinal changes in bone mechanical properties due to trabecular micro-architectural changes may be quantified in long-term clinical studies. Since significant changes in mechanical parameters were obtained for the treated groups whereas no significant change in bone mass was found we conclude that the application of these techniques may increase the clinical significance of these trials. RELEVANCE: A precise diagnosis of in vivo bone mechanical properties that accounts for (changes in) trabecular bone architecture is of particular importance for longitudinal clinical trials aiming at evaluating the efficacy of new drugs since it can lead to clinically relevant results from shorter follow-up intervals and may enable a reduction of the number of patients involved in the trial.

Bone Density↗
PubMed2001

The prognosis of epilepsy.

The cardinal question for a person developing seizures is 'What is the likelihood that they will go away?' 'Prognosis' refers to the possible outcomes of a disease and the frequency at which they can be expected to occur. Prognostic factors may include demographic features, disease-specific indicators (e.g. seizure frequency, aetiology of epilepsy) or co-morbidity. Such factors do not necessarily cause the outcome, but they are associated strongly with the outcome measured. They are distinct from risk factors--which are associated with the initial development of the disorder. Ideas about the outcome for epilepsy have been altered radically in the past century by study of its epidemiology. The prognosis for epilepsy comprises a number of measurable end-points: the prediction of recurrence after a single unprovoked seizure, the chance of remission after the diagnosis of epilepsy and the risk of premature death.

Epilepsy↗
PubMed2001

An assessment of the value of ultrasonographic screening for endometrial disease in postmenopausal women without symptoms.

OBJECTIVE: Our purpose was to evaluate the use of transvaginal ultrasonography for the detection of endometrial disease in a population of postmenopausal women who were without symptoms. STUDY DESIGN: Postmenopausal women were screened for potential inclusion in 2 multicenter, double-blind, placebo-controlled studies of 2 years' duration to evaluate the safety and efficacy of idoxifene in the prevention of osteoporosis. Baseline endometrial evaluation was performed by transvaginal ultrasonography and aspiration biopsy of the endometrium. RESULTS: A total of 1926 women were screened by transvaginal ultrasonography, and 1833 of them had endometrial thickness < or =6 mm. Five cases of endometrial abnormality (adenocarcinoma [n = 1] and atypical hyperplasia [n = 4]) were detected in the 1750 women from this cohort who underwent biopsy. The negative predictive value was >99%. One case of adenocarcinoma was detected in the 42 women who had endometrial thickness >6 mm and underwent biopsy. However, the sampling rate (45%) of women with endometrial thickness >6 mm was too low for confidence in the positive predictive value of 2%. CONCLUSIONS: Despite a high negative predictive value, transvaginal ultrasonography may not be an effective screening procedure for detection of endometrial abnormality in untreated postmenopausal women who are without symptoms.

Adenocarcinoma↗
PubMed2001

Prince Edward Island Heart Health Dissemination Research Project: establishing a sustainable community mobilization initiative.

This paper provides an overview of the Prince Edward Island Heart Health Program (PEIHHP) Dissemination Research Project. Prince Edward Island (PEI) is a small province in the Atlantic region of Canada with a population of 137,980. The Island's economy is dependent on the fishery, agriculture, and tourism industries. Although unemployment rates are high (14.4%), Prince Edward Island has the lowest poverty rate in the country at 15.2%, high levels of social support (86%), and the second lowest rate of high chronic stress (Report on the Health of Canadians, 1996, 1999).

Cardiovascular Diseases↗
PubMed2000

Half-life measurement for the rp-process waiting point nuclide 80Zr

X-ray bursts have been suggested as a possible site for the astrophysical rp-process. The time scale for the process is governed by beta-decay half-lives of several even-even N = Z waiting point nuclei, in particular, N = Z = 40 80Zr. A 4.1(+0.8/-0.6)-s beta(+)/EC half-life for 80Zr was determined by observing delayed 84-keV gamma rays depopulating a T(1/2) = 4-&mgr;s isomer at 312 keV in the daughter 80Y. As this half-life is lower than many previously predicted values, the calculated excessive production of A = 80 nuclides in astrophysical x-ray burst scenarios is reduced, and less extreme conditions are necessary for the production of heavier nuclides.

Journal Article↗
PubMed2000

Patterns of HIV risk and alcohol use among African-American crack abusers.

Although the association between heavy alcohol use and HIV risk has been studied in treatment populations, we know little about patterns of alcohol use and HIV risk among out-of-treatment African-American drug users. This study examines the extent to which alcohol use affects HIV risk in a sample of 495 African-American crack users who did not inject drugs. We present differences between levels of alcohol and crack use with regard to sexual practices (including sex while impaired), number of partners, frequency of sexual activity, and condom use. The findings suggest an intimate relationship between alcohol use, crack use, and sexual risks for HIV infection. Respondents who reported frequent use (15-30 days in the last 30 days) of alcohol, crack, or both displayed significantly greater risk than those who reported less than frequent use.

Adolescent↗
PubMed2000

Chorionic villus sampling for sex determination in a western lowland gorilla (Gorilla gorilla gorilla).

Chorionic villus sampling was undertaken on an anesthetized gorilla (Gorilla gorilla gorilla) to determine the fetal sex in the first trimester of pregnancy. The tissue samples were subject to sex determination by polymerase chain reaction, fluorescent in situ hybridization, and cell culture with cytogenetic analysis. Polymerase chain reaction testing was found to be the most accurate and rapid method of sex determination on this tissue sample.

Animals↗
PubMed1999

Divergence in the chloroplast genome and nuclear rDNA of the rare western australian plant lambertia orbifolia gardner (Proteaceae)

The population genetic structure of the Australian plant Lambertia orbifolia was investigated for chloroplast DNA (cpDNA) and rDNA based on restriction fragment length polymorphism. Variation was assessed in 14-20 individuals from six populations with probes covering the majority of the chloroplast genome and the whole rRNA gene unit. For cpDNA, eight mutations were detected which were distributed over five haplotypes. Nucleotide diversity in the species was high and the majority of this diversity was distributed between populations with diversity within populations restricted to a single population. There was significant differentiation between the two regions in the species distribution with the Narrikup region being distinguished by a single haplotype that was characterized by six unique mutations. Variation in rDNA was detected with three gene length variants present in most individuals. However, the Narrikup region was characterized by homogenization of the gene unit to a single length variant in all individuals. The divergence of the Narrikup region suggests that the disjunction in the species distribution has been present for a long time and the two regions represent separate evolutionary lineages.

Journal Article↗
PubMed1999

Sonographic assessment of the endometrium in osteopenic postmenopausal women treated with idoxifene.

Idoxifene is a novel selective estrogen receptor modulator that has shown beneficial effects on bone turnover and lipid metabolism in clinical studies. Preclinical studies have demonstrated that idoxifene has estrogen antagonist activities on the endometrium. This paper describes the results of a double-blind, placebo-controlled, and dose ranging study involving 331 osteopenic postmenopausal women who were treated with either placebo or idoxifene (2.5, 5, or 10 mg/day) for 12 weeks. In these women, endometrial assessment was carried out by transvaginal sonography and endometrial biopsy on selected patients at baseline and on all women at the end of treatment. Women with an endometrial thickness greater than 10 mm were excluded from the study. Aspiration endometrial biopsy was performed on women with an endometrial thickness between 6 and 10 mm at baseline and on all women after treatment. Of the 298 biopsies performed in the subjects at the end of treatment, 99% of the women were reported to have either a benign or atrophic endometrium (85%) or insufficient tissue for diagnosis (14%). Proliferative histologic features were reported in two cases (1%) (2.5 mg idoxifene) and atypical hyperplasia in one placebo patient. Even though idoxifene use was associated with a dose related increase in endometrial thickness as evaluated by transvaginal sonography, no relationship was established between endometrial histologic features and change in endometrial thickness. On histologic analysis, the increase in endometrial thickness seen on transvaginal sonography was not associated with proliferative or hyperplastic change in the epithelial (glandular) endometrial tissue. In 48 patients (16% of total) transvaginal sonography showed endometrial thickening of 5 mm or more over the study period. The endometrial histologic features were benign in all these patients. Nineteen percent of women developed intraluminal fluid, even though endometrial thickness was normal and unchanged and histologic features were normal. Our data show that after 3 months of treatment, no significant pathologic changes of the endometrium were observed. Our data indicate that measurements of endometrial thickness by transvaginal sonography may falsely suggest the presence of endometrial pathologic changes in some postmenopausal women treated with idoxifene. Additional testing using saline infusion sonohysterography is an important part of the transvaginal sonography protocol in equivocal or abnormal cases to exclude focal lesions such as polyps. In addition, our data indicate that pathologic changes of the endometrium are extremely rare in the treated group, indicative of its short term safety. Continued investigation such as this will be needed to establish long term safety.

Aged↗
PubMed1997

In vitro and in vivo tumor growth suppression by HIV-1 Vpr.

We have previously reported that the human immunodeficiency virus type 1 (HIV-1) regulatory gene vpr induces differentiation of rhabdomyosarcoma (embryonal muscle tumor cell line) cells, an effect that is accompanied by reduced proliferative capacity of the transfected cells. In this report, we examine the effect of Vpr expression on several different tumor cell lines derived from unique lineages. These tumor cells display different patterns of modulated oncogenes including both ras and p53 mutations. Here we demonstrate that the growth of tumor cells in vitro and in vivo is arrested by the expression of HIV-1 Vpr. Expression of Vpr in several human tumor cell lines upon transfection resulted in an accumulation of cells in the G2/M phase of cell cycle with altered cellular morphology, including an increase in adherence, and growth arrest, consistent with a differentiated phenotype. Vpr expression in B78/H1 cells results in a marked reduction in colony formation in vitro and an associated reduction in melanin synthesis by the cells. Vpr-transfected melanoma cells inoculated into syngenic C57BL/6 mice showed a markedly reduced ability to form tumors in vivo. These results suggest that this retroviral regulatory gene has broad tumor suppressor effects, likely mediated by transcriptional regulation of the state of the host cell.

Animals↗
PubMed1996

Equivalent square as a predictor of depth of dose maximum for megavoltage therapy beams.

The depths of dose maxima, dmax, and surface doses of 6 MV, 10 MV, and 18 MV photon beams were measured for various square fields and rectangular fields with elongation ratios from 1 to 27. Rectangular fields with elongation ratios below 2 have essentially the same depths of dose maxima and surface doses as their corresponding equivalent square fields. For rectangular fields with elongation ratios above 2, the surface doses increase, and depths of dose maxima decrease with increasing elongation ratio in comparison to their respective values for their corresponding equivalent square fields. The shift of dmax toward the surface is more pronounced when the upper jaws rather than the lower jaws define the long axis of the field. This collimator exchange effect does not influence the surface dose. Even for the largest elongation ratios, the changes in dmax and surface dose from their equivalent square field values were minor and clinically insignificant, suggesting that the equivalent square approach provides a reliable method for predicting the values of dmax and surface dose for rectangular fields from square fields data.

Forecasting↗
PubMed1995

The potential uses of high-dose-rate brachytherapy in patients with head and neck cancer.

Brachytherapy has proven to be an extremely valuable method of treatment for head and neck cancer. The data supporting its application, however, is based on continuous low-dose-rate brachytherapy. To benefit from improved radiation protection, outpatient treatments, and increased patient tolerance of treatment set-up over that encountered in conventional low-dose-rate manually afterloaded brachytherapy, we implemented a high-dose-rate remote afterloading approach in selected patients with head and neck cancers. This treatment was utilized in two different roles in managing 29 patients. In its first role, it was used as the sole treatment in 13 patients with T1-2 N0 malignancies. A total of ten treatments of 450-500 cGy each were delivered twice a day with a minimum of 5-6 h between treatments. With a median follow-up of 9 months, only 1 patient failed locally. In a second role, brachytherapy was applied in a post-operative adjuvant setting following wide local excision of tumors in patients who presented with recurrent disease (12 cases) or a second primary in the head and neck (4 cases). All patients had previously received external irradiation to the head and neck. Due to this previous course of irradiation, only eight treatments of 300 cGy each were delivered, for a total of 2400 cGy over a period of 4 days. However, with a follow-up of 2-16 months, only 3 patients remain disease-free.

Aged↗
PubMed1993

IgA cold agglutinins recognize Pr and Sa antigens expressed on glycophorins.

Three cases of IgA kappa cold agglutinins (CAs) were studied. One had anti-Pr1 specificity, one had anti-Pra, and one had anti-Sa. The CAs recognize O-glycans of glycophorins. The findings supplement previous data on anti-Pr1 specificities of four IgA kappa CAs. Because all IgA kappa CAs described recognize O-glycans of glycophorins, a close association between the CA IgA isotype and specificities for O-glycans becomes apparent. It is unlikely, however, that the striking association reflects interrelations between IgA CA structure and specificity, because anti-Sa specificity and all anti-Pr subspecificities were originally defined with IgM CAs.

Adult↗
PubMed1992

Distributed neural network underlying musical sight-reading and keyboard performance.

Music, like other forms of expression, requires specific skills for its production, and the organization and representation of these skills in the human brain are not well understood. With the use of positron emission tomography and magnetic resonance imaging, the functional neuroanatomy of musical sight-reading and keyboard performance was studied in ten professional pianists. Reading musical notations and translating these notations into movement patterns on a keyboard resulted in activation of cortical areas distinct from, but adjacent to, those underlying similar verbal operations. These findings help explain why brain damage in musicians may or may not affect both verbal and musical functions depending on the size and location of the damaged area.

Auditory Perception↗
PubMed1992

Functional neuroanatomy of face and object processing. A positron emission tomography study.

Studies of brain-damaged patients have revealed the existence of a selective impairment of face processing, prosopagnosia, resulting from lesions at different loci in the occipital and temporal lobes. The results of such studies have led to the identification of several cortical areas underlying the processing of faces, but it remains unclear what functional aspects of face processing are served by these areas and whether they are uniquely devoted to the processing of faces. The present study addresses these questions in a positron emission tomography (PET) study of regional cerebral blood flow in normal adults, using the 15 oxygen water bolus technique. The subjects participated in six tasks (with gratings, faces and objects), and the resulting level of cerebral activation was mapped on images of the subjects' cerebral structures obtained through magnetic resonance and was compared between tasks using the subtraction method. Compared with a fixation condition, regional cerebral blood flow (rCBF) changes were found in the striate and extrastriate cortex when subjects had to decide on the orientation of sine-wave gratings. A face-gender categorization resulted in activation changes in the right extrastriate cortex, and a face-identity condition produced additional activation of the fusiform gyrus and anterior temporal cortex of both hemispheres, and of the right parahippocampal gyrus and adjacent areas. Cerebral activation during an object-recognition task occurred essentially in the left occipito-temporal cortex and did not involve the right hemisphere regions specifically activated during the face-identity task. The results provide the first empirical evidence from normal subjects regarding the crucial role of the ventro-medial region of the right hemisphere in face recognition, and they offer new information about the dissociation between face and object processing.

Adult↗