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Biomedical subjects

D MacDonald

Publications and source records attributed to D MacDonald.

At least 37 records · Page 2Linked to original sources
PubMed1999

In vitro susceptibility to pexiganan of bacteria isolated from infected diabetic foot ulcers.

During two clinical trials involving the treatment of 835 outpatients with infected diabetic foot ulcers, 2515 bacterial isolates, including 2337 aerobes and 178 anaerobes, were grown from cultures of the ulcers. The in vitro susceptibility of these isolates was determined to pexiganan, a peptide anti-infective evaluated in these clinical trials, and to other classes of antibiotics. Pexiganan demonstrated broad spectrum antimicrobial activity against Gram-positive and Gram-negative aerobes and anaerobes. The MIC90 values for the most common species among 1735 Gram-positive aerobes isolated, such as Staphylococcus aureus, coagulase-negative staphylococci, Group A streptococci, and Group B streptococci, were 16 micrograms/mL or less. Of 602 Gram-negative aerobes tested, the MIC90 values for pexiganan were 16 micrograms/mL or less for Acinetobacter, Pseudomonas, Stenotrophomonas, Citrobacter, Enterobacter, Escherichia, Klebsiella, and Flavobacterium species. Pexiganan had a MIC90 of 4 to 16 micrograms/mL against the anaerobic isolates of Bacteroides, Peptostreptococcus, Clostridium, and Prevotella species. Importantly, pexiganan did not exhibit cross-resistance with other commonly used antibiotics, including beta-lactams, quinolones, macrolides, and lincosamides. The broad spectrum in vitro antimicrobial activity of pexiganan against clinical isolates from infected diabetic foot ulcers supports its potential as a local therapy for infected diabetic foot ulcers.

Adult↗
PubMed1999

Early acquisition of TT virus (TTV) in an area endemic for TTV infection.

TT virus (TTV) is widely distributed, with high frequencies of viremia in South America, Central Africa, and Papua New Guinea. The incidence and timing of infection in children born in a rural area of the Democratic Republic of Congo was investigated. TTV viremia was detected in 61 (58%) of 105 women attending an antenatal clinic and in 36 (54%) of 68 infants. Most infants acquired the infection at >/=3 months postpartum. Surprisingly, TTV infection was detected in a large proportion of children with TTV-negative mothers (13 [43%] of 30). Nucleotide sequences of TTV-infected children were frequently epidemiologically unlinked to variants detected in the mother. These three aspects contrast with the maternal transmission of hepatitis G virus/GB virus C in this cohort and suggest an environmental source of TTV infection comparable to hepatitis A virus and other enterically transmitted infections.

DNA Virus Infections↗
PubMed1999

Cell synthesis, proliferation and apoptosis in human dental periapical lesions analysed by in situ hybridisation and immunohistochemistry.

OBJECTIVE: The role of structural and host defensive cells in periapical lesions has been assessed previously by morphometric and immunohistochemical studies. The aim of this study was to investigate the function of peri- apical cells by employing molecular techniques to estimate the cell synthetic activity, proliferation and apoptosis in these lesions. We specifically sought answers to the following questions. Which cells of the periapical lesions are quiescent or actively synthesising proteins? Do immune cells proliferate in this region in the same way as epithelial cells proliferate? Furthermore do cells in peri- apical lesions undergo apoptosis, and if so which cells exhibit this programmed cell death? MATERIALS: Twenty-five periapical tissue samples (15 granulomas and 10 radicular cysts) were assessed. Poly-adenosine (poly (A)) RNA and ribosomal RNA (rRNA) bearing cells in formalin-fixed/paraffin-embedded peri- apical tissues were analysed by in situ hybridization (ISH) using digoxigenin-labelled oligo d (T) and 28S rRNA probes respectively in order to estimate cell synthetic activity. Furthermore, S-phase proliferating and cycling cells were examined by ISH using a histone probe and Ki-67 immunostaining so as to assess cellular proliferation. Mononuclear cells were further differentiated by immunohistochemistry (IHC) as T cells, B cells and macrophages. Apoptotic cells were determined by in situ end-labelling methodology for detecting fragmented DNA. RESULTS: Poly (A) RNA (mostly messenger RNA) and 28S rRNA-expressing cells were detected in all samples. Plasma cells exhibited strongest staining for the two probes, with slight to moderate staining found in the epithelium, fibroblasts, macrophages, endothelial cells and lymphocytes, whereas almost all polymorphonuclear leucocytes (PMN) were negative for these probes. A few histone mRNA-expressing cells were detected in basal and suprabasal epithelial cells and mononuclear cells in 15/25 cases but their reactivity was weak. Ki-67 positive cells were found in all samples and their numbers were generally higher than histone mRNA positive cells. Apo- ptotic cells were detected in 23/25 cases and the majority of apoptotic cells were PMN which were engulfed by large cytophagocytic macrophages. CONCLUSION: This study indicates that in dental periapical lesions, apoptosis occurs predominantly in PMN. It is evident that most cells apart from PMN are exhibiting synthetic activity but only epithelial cells undergo proliferation which implies that immune cells must proliferate at distant lymph nodes and travel to the periapical lesion rather than proliferating within the lesion. These results suggest considerable advantages in estimating gene expression within cells in addition to the immunohistochemical detection of cells to determine cell activity at inflamed sites. Clearly, functional cell synthetic activity, resolution and clearance systems operate in peri- apical cystic and granuloma lesions.

Adult↗
PubMed1999

Subglottic haemangioma: controversies in management.

OBJECTIVE: To discuss treatment modalities for subglottic haemangioma (SGH). METHODOLOGY: Case report of two children definitively managed by different modalities. RESULTS: Management by CO2 laser vaporization in one child, and laser followed by interferon 2-alpha in the second child were both successful in controlling the SGH without the need for tracheostomy. CONCLUSION: The stepped-care approach at John Hunter Children's Hospital, Newcastle, New South Wales, is presented. Both laser surgery and interferon can help control SGH. Careful surveillance and interdisciplinary cooperation are essential to achieve a good outcome.

Antineoplastic Agents↗
PubMed1999

Detecting changes in nonisotropic images.

If the noise component of image data is nonisotropic, i.e., if it has nonconstant smoothness or effective point spread function, then theoretical results for the P value of local maxima and the size of suprathreshold clusters of a statistical parametric map (SPM) based on random field theory are not valid. This assumption is reasonable for PET or smoothed fMRI data, but not if these data are projected onto an unfolded, inflated, or flattened 2D cortical surface. Anatomical data such as structure masks, surface displacements, and deformation vectors are also highly nonisotropic. The solution offered here is to suppose that the image can be warped or flattened (in a statistical sense) into a space where the data are isotropic. The subsequent corrected P values do not depend on finding this warping; it is sufficient only to know that such a warping exists.

Brain↗
PubMed1999

A computer generated interactive transurethral prostatic resection simulator.

PURPOSE: We developed a computer generated model of the prostate gland and an interactive simulator for use in training urologists in transurethral resection of the prostate. MATERIALS AND METHODS: Software was developed on a standard personal computer which allowed images of the lumen of the prostatic urethra and resectoscope loop to be generated and interacted with using a magnetic position sensor input device attached to a dummy resectoscope. RESULTS: An anatomically accurate computer model of the prostate was generated at low cost which permitted user interaction and which simulated key elements of transurethral prostatic resection. CONCLUSIONS: Although not a substitute for learning transurethral prostatic resection on patients, the simulator enabled the user to become familiar with the technique of transurethral prostatic resection in the absence of time constraints and without risk to patients. The simulator may become an important tool in training and assessing surgeon competency, and may reduce the costs of training. Further development is needed to refine the transurethral prostatic resection simulator and expand its surgical range.

Computer Simulation↗
PubMed1998

Endothelin-A and -B antagonists protect myocardial and endothelial function after ischemia/reperfusion in a rat heart transplantation model.

OBJECTIVE: Previous studies suggested that endothelin-1 (ET-1) may play a pathophysiological role in myocardial ischemia/reperfusion injury. This study was designed to investigate the effects of the selective ET-A receptor antagonist BQ123 and the selective ET-B receptor antagonist BQ788 on myocardial and endothelial function after reversible deep hypothermic ischemia in a heterotopic rat heart transplantation model. METHODS: Isogenic intraabdominal heterotopic transplantation was performed in Lewis rats. After 1 h of cold ischemic preservation reperfusion was started either after application of placebo (control), BQ123 (3 mumol/kg/min). BQ788 (3 mumol/kg/min), ET-1 (8 pmol/kg/min) or simultaneous infusion of BQ123 or BQ788 and ET-1, respectively (n = 12 each). An implanted balloon was used to obtain pressure-volume relations of the transplanted heart. Myocardial blood flow (MBF) was assessed by the hydrogen-clearance method. Measurements were taken after 1 and 24 h of reperfusion. Endothelium-dependent vasodilation to acetylcholine (ACH) and endothelium-independent vasodilation to sodium nitroprusside were also determined. RESULTS: Both BQ123 and BQ788 significantly improved myocardial and endothelial functional recovery during early reperfusion, whereas ET-1 significantly impaired myocardial and endothelial function. Simultaneous infusion of ET-1 diminished the effects of BQ123 and BQ788. Although myocardial function and baseline MBF were similar in all groups after 24 h of reperfusion, endothelium dependent vasodilation to ACH was still significantly higher in the BQ123 and BQ788 groups and lower in the ET-1 groups (p < 0.05). CONCLUSIONS: These results suggest that endogenous ET release is involved in the pathogenesis of reperfusion injury after heart transplantation. ET-A and ET-B receptor antagonists may be useful to reduce ischemia/reperfusion injury.

Acetylcholine↗
PubMed1998

Endothelin-A receptor antagonist BQ123 protects against myocardial and endothelial reperfusion injury.

BACKGROUND: This study was designed to investigate the effects of the selective endothelin-A receptor antagonist BQ123 on myocardial and endothelial function after reversible deep hypothermic ischemia and reperfusion. METHODS: Isogenic intra-abdominal heterotopic heart transplantation was performed in Lewis rats. After one hour of cold ischemic preservation reperfusion was started after application of either saline vehicle or BQ123 (1 micromol/L). Left-ventricular pressure-volume relations and myocardial blood flow were assessed after one and 24 hours of reperfusion. Responses to endothelium-dependent vasodilator acetylcholine and endothelium-independent vasodilator sodium nitroprusside were also determined. RESULTS: BQ123 significantly improved myocardial contractility, as indicated by the leftward shift of the systolic pressure-volume relation and significantly increased myocardial blood flow during early reperfusion (p < 0.05). Although myocardial function and baseline myocardial blood flow were similar in both groups after 24 hours of reperfusion, endothelium-dependent vasodilatation was still significantly higher in the BQ123 group (p < 0.05). CONCLUSIONS: These results suggest that endothelin-A receptor antagonists may be useful in reducing ischemia/reperfusion injury after heart transplantation by preservation of myocardial and endothelial function.

Animals↗
PubMed1998

Morphometric analysis of the temporal lobe in temporal lobe epilepsy.

PURPOSE: Using high-resolution magnetic resonance imaging (MRI), we examined the temporal neocortex and the underlying white matter in patients with unilateral temporal lobe epilepsy (TLE) and in control subjects. METHODS: The images of 27 patients and 42 control subjects were registered into stereotaxic space, corrected for image intensity inhomogeneity, and automatically segmented into gray matter, white matter, and cerebrospinal fluid (CSF) over a predetermined extent of the temporal lobe. The surface between the gray matter and CSF was extracted, indices of curvature (IOC) of the surface were calculated, and a frequency histogram of the IOC was obtained. RESULTS: There was significant bilateral reduction in the total volume of the temporal lobe and in the volume of gray matter. White matter volume was significantly reduced only in the temporal lobe ipsilateral to the seizure focus. There were significant changes in the position and amplitude of peaks in the frequency histogram of the IOC. CONCLUSIONS: The volume of gray matter was negatively correlated with duration of epilepsy, suggesting that neocortical changes may be a consequence of seizures. Changes in the frequency histogram of the IOC suggested an additional alteration in the surface morphology of the temporal lobe in TLE, possibly related to sulcal widening.

Adolescent↗
PubMed1998

Interleukin-9 promotes allergen-induced eosinophilic inflammation and airway hyperresponsiveness in transgenic mice.

Human atopic asthma is a complex heritable inflammatory disorder of the airways associated with clinical signs of allergic inflammation and airway hyperresponsiveness. Recent studies demonstrate that the degree of airway responsiveness is strongly associated with interleukin (IL)-9 expression in murine lung. To investigate the contribution of IL-9 to airway hyperresponsiveness, and to explore directly its relationship to airway inflammation, we studied transgenic mice overexpressing IL-9. In this report we show that IL-9 transgenic mice (FVB/N-TG5), in comparison with FVB/NJ mice, display significantly enhanced eosinophilic airway inflammation, elevated serum total immunoglobulin E, and airway hyperresponsiveness following lung challenge with a natural antigen (Aspergillus fumigatus). These data support a central role for IL-9 in the complex pathogenesis of allergic inflammation.

Allergens↗
PubMed1997

A comparison of fertility control and lethal control of bovine tuberculosis in badgers: the impact of perturbation induced transmission.

In this paper we use mathematical modelling to consider the broad advantages and disadvantages of fertility control over lethal control for bovine tuberculosis in badger populations. We use a deliberately simple model, attempting to capture only the key transmission processes. The model is parametrized with reference to the long-term Woodchester Park study. Estimates of mortality rate from this study suggest no significant extra mortality risk for animals with evidence of infection as indicated by the presence of anti-Mycobacterium bovis antibodies or M. bovis isolation. We find that large reductions in prevalence are sometimes the consequence of only moderate reductions in population numbers. If we assume that the act of control does not in itself affect transmission rates, then as far as eradication is concerned, both fertility control and mortality control operate through the same epidemiological mechanism, the removal of susceptibles: if one is in principle capable of keeping a population low enough to be infection free then so is the other. It is necessary to continue either form of control at regular intervals to maintain a constant level of infection in the long term. If control were to be stopped, return to precontrol levels of badger population and infection prevalence would be expected within a few years. Fertility control is less effective in reducing population density than lethal control since it can only act, at maximum, to remove one age cohort per year. It is also less effective in reducing transmission as it can only ever remove susceptibles, while lethal control also removes infectious badgers. However, if the social disturbance caused by lethal control does in fact increase contact rates for the remaining infectious badgers, the relative efficacies of the two strategies become a great deal less clear. While we have no quantitative data on the extent to which social perturbation does act to promote transmission, model simulations show that it is possible to develop plausible scenarios in which the lethal control may actually act to increase the absolute numbers of animals infected, while reducing the number of uninfected animals to very low numbers.

Animals↗
PubMed1997

Ongoing Y-chromosome instability defines sub-clonal variants in radiation-induced leukaemias in the mouse.

Forty primary leukaemias that arose in vivo as a consequence of 3 Gy X-irradiation of inbred mouse strains were analysed for Y-chromosome aberrations by conventional cytogenetics and fluorescent in situ hybridization (FISH). Compared with control mice which were X-irradiated but which exhibited no overt signs of leukaemia, the loss and gain of Y-chromosomes in leukaemic spleen cells defined subclonal variants in the radiation-induced haemopoietic malignancies that arose in CBA/H, DBA/2 and (C57BL/6 x DBA/2)F1 mice. This Y-chromosome instability was significantly higher than that observed in spleen cells of age-matched (or older) irradiated control mice that had not developed overt leukaemia. The detection of Y-chromosome aberrations is considered in the context of the high numbers of potential gene regulatory sequences in the murine Y-chromosome and the potential for the insertional activation of cellular genes during multi-stage radiation leukaemogenesis.

Acute Disease↗
PubMed1997

Supratentorial low-grade glioma in adults: an analysis of prognostic factors and timing of radiation.

PURPOSE: To review the outcomes of patients with low-grade glioma diagnosed by modern imaging and treated at a center where postponing radiotherapy was common practice. METHODS: We reviewed the records of patients (age > or = 18 years) with pathologically confirmed supratentorial low-grade fibrillary astrocytoma, oligodendroglioma, and mixed glioma treated at a regional cancer center in Canada between 1979 and 1995. RESULTS: Median survival for the entire group (N = 167; mean age 40.6 years) was 10.5 years with 5- and 10-year survival rates of 72% and 50%, respectively. Median progression-free survival was 4.9 years with 5- and 10-year progression-free rates of 50% and 12%, respectively. Overall and progression-free survivals were longer for patients with an oligodendroglioma or mixed glioma than with astrocytoma (median 13 v 7.5 years, P = .003; progression-free 5.6 v 4.4 years, p = .054). Age at diagnosis < or = 40 years, seizures at presentation, minimal residual tumor after surgery, Karnofsky performance status > or = 70, and oligodendroglioma or mixed glioma pathology were associated with significantly longer median survival on univariate and multivariate analyses. Radiotherapy deferred until tumor progression (v immediate radiotherapy) was associated with longer survival on univariate analysis, but an imbalance in other variables accounted for this advantage such that timing of radiotherapy was not an independent (favorable or adverse) prognostic factor on multivariate analysis. CONCLUSION: Patients with low-grade glioma diagnosed by modern imaging can be expected to live a long time; timing of radiotherapy may be a less important determinant of survival than nontreatment variables and residual tumor bulk.

Actuarial Analysis↗
PubMed1996

Serial changes in cardiac output during normal pregnancy: a Doppler ultrasound study.

OBJECTIVES: To determine the direction and magnitude of change in cardiac output (CO) during pregnancy. STUDY DESIGN: We performed serial measurements of CO on five occasions from 24 weeks gestation to term and once during the puerperium in 26 normal pregnancies (156 measurements) using Doppler ultrasound measurement of flow velocity profiles and aortic root cross sectional area. RESULTS: CO increased to 7.0 l/min by 32 weeks gestation, 49% above baseline values. It fell to 5.7 l/min by term, 21% above baseline. The peak in CO corresponded with an increase in heart rate to 91 beats/min, 32% above baseline. Stroke volume peaked at 36 weeks gestation, by which time CO had already begun to decline. CONCLUSIONS: CO increased in a linear fashion until 32 weeks gestation and then declined to term, but to a value still greater than the postpartum baseline. These findings have obvious management implications for patients with serious heart disease complicating pregnancy.

Blood Pressure↗
PubMed1996

In vivo morphometry of the intrasulcal gray matter in the human cingulate, paracingulate, and superior-rostral sulci: hemispheric asymmetries, gender differences and probability maps.

Volumes of the intrasulcal gray matter were measured in three cerebral sulci located on the medial wall of the human frontal lobe: cingulate sulcus (CS), paracingulate sulcus (PCS), and superior-rostral sulcus (SRS). The measurements were carried out on T1-weighted 3-D high-resolution magnetic-resonance (MR) images acquired in 105 young right-handed volunteers (42 female and 63 male). Before the measurement, the images were transformed into a standardized stereotaxic space (Talairach and Tournoux [1988] Human Brain: 3-Dimensional Proportional System. An Approach to Cerebral Imaging. Stuttgart, New York: Georg Thieme Verlag), thus removing inter-individual differences in brain size. The intrasulcal gray matter was segmented in a semi-automatic manner. Significant gender differences were found in the volume of the CS (female > male) and the PCS (male > female). Hemispheric asymmetries were observed between the left and right volumes of the intrasulcal gray matter in the anterior (right > left) and posterior (left > right) segments of the CS, as well as between the left and right volumes of the PCS (left > right). There was no interaction between the asymmetries and gender. In addition, significant positive correlations were found between the left and right gray-matter volumes in the anterior (r = 0.43) and posterior (r = 0.66) segments of the CS, whereas significant negative correlations were observed between the gray-matter volumes of the anterior segment of the CS and those of the PCS (left hemisphere: r = -0.48; right hemisphere: r = -0.42). The observed hemispheric asymmetries in the CS and PCS gray-matter volumes are consistent with the proposed role of these structures in the integration of emotions with cognition (CS) and in the control of speech/vocalization (PCS). The pattern of inter-hemispheric correlations in the sulcal gray-matter points to an increasing asynchrony in the foetal development of primary (CS), secondary (SRS), and tertiary (PCS) sulci, respectively. The presence of negative correlations between the two neighbouring sulci (CS and PCS) suggests that a process of compensation could underlie interactions between adjacent primary and tertiary sulci. Besides the above volumetric analysis, we also provide average (probability) maps of the three sulci; the use of such maps for the parcellation of the medial frontal lobe and localization of "peaks" obtained in blood-flow activation studies is discussed.

Brain Mapping↗