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Biomedical subjects

C Brown

Publications and source records attributed to C Brown.

At least 37 records · Page 2Linked to original sources

Population variation in lateralized eye use in the poeciliid Brachyraphis episcopi.

Differential use of each hemisphere of the brain for specific tasks is a widespread phenomenon that appears to have arisen in the early history of tetrapod lineage. Despite a high degree of conformity in the development of lateralization among the tetrapods, some variation exists. The mechanisms underlying this variation remain largely unresolved. We exposed fish from regions of high and low predation pressure to a series of visual experiences, including viewing an empty compartment, a novel object and a live predator. Fish from each region differed in their preferential use of each eye to view the scenes. For example, fish from high predation regions viewed a live predator by using their right eye, whereas fish from low predation sites showed no eye preference. These results suggest that the degree of lateralization varies between populations of the same species that have been exposed to different ecological/evolutionary pressures.

Animals↗

A unique patient with an Ullrich-Turner syndrome variant and mosaicism for a tiny r(X) and a partial proximal duplication 1q.

A 7-year old female with global cognitive impairment, short attention span, hyperactivity, impulsivity, and many compulsive behaviors was referred to the Genetics Clinic. Height was below the 5th centile and weight was at the 5th centile while head circumference was at the 50th centile. Minor anomalies included bluish sclera, low set and slightly posteriorly rotated auricles and a narrow palate with marked overbite. There was no significant family history. Chromosome analysis showed an unbalanced, mosaic female karyotype consisting of three cell lines: 46,X,+r[46]/45,X[37]/45,X,dup(1)(q11q21.3) [17] de novo.ish r(X)(DXZ1+,XIST+). Expression of XIST was observed in cDNA from the patient, suggesting the presence of an inactive X chromosome. Inactivation was confirmed by detection of a methylated allele of androgen receptor. This methylated allele was under-represented in undigested DNA, consistent with it arising from the r(X) which was present in only a minority of the patient's cells. The clinical phenotype of the tiny r(X) syndrome in our patient is obviously further influenced by mosaicism for the dup(1). Few cases of duplication of the proximal portion of chromosome 1 have been reported. Of these, the duplication either was present in all cells or involved different band regions so that a direct comparison would be difficult. However, the lower percentage of mosaicism for the dup(1) in our patient would suggest a milder influence on the clinical phenotype.

Child↗

Mobilized blood cells vs bone marrow harvest: experience compared in 171 donors with particular reference to pain and fatigue.

This prospective study compared the donor experience of blood cell (BC) mobilization and leukapheresis (n=116) with that of bone marrow (BM) harvest (n=55). Internal jugular catheters were inserted electively in 89% of BC donors. Most (80%) BM donors had a harvest with general anesthesia; 20% had epidural or spinal anesthesia. Pain and fatigue were frequent with both procedures and were compared in responses to questionnaires. A total of 85% of BM donors reported moderate or severe pain compared with 68% of BC donors (P=0.02). The median duration of pain was 14 days for BM donors compared with 3 days after BC mobilization (P<0.0001). More BM donors had pain for more than 7 days (75% vs 0%, P<0.0001). Severe fatigue was experienced by more BM donors (49 vs 16%, P<0.0001). Fatigue lasted significantly longer in BM donors (median 11 vs 4 days, P<0.0001) and more BM donors were fatigued for more than 1 week (69 vs 0%, P<0.0001). A total of 11 donors had both BM and BC collection; seven preferred the latter. Simply considered with respect to pain and fatigue, BC donation appears better tolerated by donors. However, there are other sequelae of both influencing the acceptability for individual donors.

Adolescent↗

Pneumonic lesions in lambs in New Zealand: patterns of prevalence and effects on production.

AIM: To describe temporal and spatial patterns of the prevalence of pneumonia in lambs in three regions of New Zealand, and determine effects on liveweight gain. METHODS: A longitudinal study was conducted in 1999- 2000 on 14 commercial sheep farms, five from the Southland region of the South Island, and five from the King Country and four from the Northland regions of the North Island. Pneumonia was known to be a problem in lambs on all farms selected. On each farm, 400 lambs were randomly selected at weaning and allocated at random to one of two groups (Groups I and II). Lambs in both groups were weighed at 4-weekly intervals. The extent of pneumonic lesions in lungs was scored visually at slaughter in 40 randomly selected lambs after each weighing (Group I). Lambs in Group II were selected for slaughter by the farm manager on a commercial basis of liveweight and body condition, then assessed for pneumonic lesions. RESULTS: Prevalence of extensive pneumonic lesions (>/=10% lung surface area affected) increased from December to March from 1.4 to 10.1% lambs in Southland (n=1,917), 1.2 to 25.7% in the King Country (n=1,831), and 4.7 to 21.4% in Northland (n=1,485). Overall, 42.3% of lambs in both groups had pneumonic lesions (n=5,233) and in 15.1% of these, >/=5% of the lung surface area was affected. Daily weight gain in the month prior to slaughter was reduced in lambs for which >/=20% lung surface area was affected in Group I (p<0.05) but not in Group II. CONCLUSIONS: The association between pneumonic lesions and reduced weight gain was highly significant in lambs from Group I, but not from Group II. Thus, pneumonia had a negative impact on weight gain, and selection by farmers of lambs for slaughter counteracted this association in lambs from Group II. CLINICAL RELEVANCE: Pneumonia occurs commonly as a subclinical disease in lambs in New Zealand. It has no public health significance and is not recorded at slaughter plants nor reported to farmer clients. Effects of the disease on daily weight gain of lambs is considerable and costly for lamb producers.

Journal Article↗

Intensified treatment of patients with type 2 diabetes mellitus and overt nephropathy.

BACKGROUND: Diabetic nephropathy is the single most common cause of chronic renal failure requiring dialysis. Effective treatment exists, but no clinical audit or large trial has reduced the rate of loss of renal function as effectively as in small groups of intensively managed patients. AIM: To determine the effect of intensive vs. standard medical management on the rate of progression of renal failure in patients with diabetic nephropathy. DESIGN: Prospective randomized controlled study. METHODS: Patients with type 2 diabetes and nephropathy were randomly allocated to an intensive group (n = 47) or control group (n = 43). Treatment targets were the same for both groups, but the intensive group were seen as often as required to meet the targets; controls were seen at their normal clinics. The primary end-point was the rate of progression of renal disease in the second year. RESULTS: The groups were well matched at baseline. During follow-up, the intensive group had lower mean SBP, DBP and cholesterol. Median rate of progression of renal failure in the intensive group fell from 0.44 ml/min/month in the first year to 0.14 ml/min/month in the second year, compared to 0.49 ml/min/month and 0.53 ml/min/month in the control group (p = 0.04 for second year). Patients in the intensive group spent significantly less time in hospital. DISCUSSION: Intensive treatment slowed progression of renal disease within 2 years in patients with established diabetic nephropathy. Mean creatinine clearance at the start of the trial was 55 ml/min, so assuming that the rates of progression achieved at the end of the second year persisted, onset of dialysis would be delayed by 20 years in the intensive group compared with the control group.

Aged↗

Molecular studies of anti-HLA-A2 using light-chain shuffling: a structural model for HLA antibody binding.

Human leukocyte antigen (HLA) A2 is one of the most immunodominant HLA antigens. Through a process of light-chain variable domain (VL) shuffling, we analyzed the VL domains' role in anti-HLA-A2/A28-binding site diversity. This was achieved by combining a VH3-30-encoded HLA-A2/A28-specific heavy-chain variable domain with 10(4) non-immune VL domains. Twelve HLA-A2/A28-specific antibodies were subsequently identified. VL gene analysis demonstrated an absence of Vlambda domains and that all have VkappaI-encoded light chains. The affinities correlated with the VkappaI gene present, with the seven highest affinity antibodies using Vkappa domains encoded by the O18 gene segment. A 300-fold difference in affinity was observed between the 12 antibodies, and homology modeling demonstrated a correlation between electrostatic surface potential of the antigen-binding site and affinity for HLA. Overlap between the T-cell receptor-binding site and that of the antibodies was indicated by inhibition of cytotoxic T-lymphocyte killing of peptide-pulsed target cells. A model of antibody binding to HLA-A2 suggested contact with both alpha helices of the HLA molecule, such that the antigen-binding site spans the peptide-binding groove. These data increase the understanding of antibody recognition of HLA and may facilitate the production of clonotypic antibodies with peptide-specific binding.

Antibodies, Monoclonal↗

Emerging zoonoses and pathogens of public health significance--an overview.

Emerging zoonotic diseases have assumed increasing importance in public and animal health, as the last few years have seen a steady stream of new diseases, each emerging from an unsuspected quarter and causing severe problems for animals and humans. The reasons for disease emergence are multiple, but there are two main factors--expansion of the human population and globalisation of trade. Current issues such as the increasing movement of a variety of animal species, ecological disruption, uncultivatable organisms, and terrorism, all imply that emerging zoonotic diseases will in all probability, not only continue to occur, but will increase in the rate of their emergence. The recurring nature of the crises dictates that closer integration of veterinary and medical communities is warranted, along with improved education of the general public and policy makers.

Animals↗

Inhuman shields--children caught in the crossfire of domestic violence.

BACKGROUND: Child abuse is a worldwide scourge. One of its most devastating manifestations is non-accidental head injury (NAHI). METHODS: This is a retrospective chart review of children presenting to the Red Cross Children's Hospital trauma unit with a diagnosis of NAHI over a 3-year period. RESULTS: Sixty-eight children were included in the study and 2 different groups were identified. Fifty-three per cent of the children were deliberately injured (median age 2 years), while 47% were allegedly not the intended target of the assailant (median age 9 months). The assailant was male in 65% of the intentional assaults and male in 100% of the unintentional assaults, with the intended adult victim female in 85% of the latter cases. Overall, 85% of the assaults were committed in the child's own home. CONCLUSIONS: The high proportion of cases in which a young child was injured unintentionally suggests that these infants effectively become shields in assaults committed by adults. In this context any attempts to deal with child abuse must also address the concurrent intimate partner violence.

Adult↗

Dynamics of supercooled water in mesoporous silica matrix MCM-48-S.

Using three different quasielastic neutron spectrometers with widely different resolutions, we have been able to study the microscopic translational and rotational dynamics of water, in a mesoporous silica matrix MCM-48-S, from T=300 K to 220 K, with a single consistent model. We formulated our fitting routine using the relaxing cage model. Thus, from the fit of the experimental data, we extracted the fraction of water bound to the surface of the pore, the characteristic relaxation times of the long-time translational and rotational decays, the stretch exponent describing the shape of the relaxation processes, and the power exponent determining the Q-dependence of the translational relaxation time. A tremendous slowing down of the rotational relaxation time, as compared to the translational one, has been observed.

Journal Article↗

Vascular and metabolic response to isolated small muscle mass exercise: effect of age.

To determine the effect of age on quadriceps muscle blood flow (QMBF), leg vascular resistance (LVR), and maximum oxygen uptake (QVO2 max), a thermal dilution technique was used in conjunction with arterial and venous femoral blood sampling in six sedentary young (19.8 +/- 1.3 yr) and six sedentary old (66.5 +/- 2.1 yr) males during incremental knee extensor exercise (KE). Young and old attained a similar maximal KE work rate (WRmax) (young: 25.2 +/- 2.1 and old: 24.1 +/- 4 W) and QVO2 max (young: 0.52 +/- 0.03 and old: 0.42 +/- 0.05 l/min). QMBF during KE was lower in old subjects by approximately 500 ml/min across all work rates, with old subjects demonstrating a significantly lower QMBF/W (old: 174 +/- 20 and young: 239 +/- 46 ml. min-1. W-1). Although the vasodilatory response to incremental KE was approximately 142% greater in the old (young: 0.0019 and old: 0.0046 mmHg. min. ml-1. W-1), consistently elevated leg vascular resistance (LVR) in the old, approximately 80% higher LVR in the old at 50% WR and approximately 40% higher LVR in the old at WRmax (young: 44.1 +/- 3.6 and old: 31.0 +/- 1.7 mmHg. min. ml-1), dictated that during incremental KE the LVR of the old subjects was never less than that of the young subjects. Pulse pressures, indicative of arterial vessel compliance, were approximately 36% higher in the old subjects across all work rates. In conclusion, well-matched sedentary young and old subjects with similar quadriceps muscle mass achieved a similar WRmax and QVO2 max during incremental KE. The old subjects, despite a reduced QMBF, had a greater vasodilatory response to incremental KE. Given that small muscle mass exercise, such as KE, utilizes only a fraction of maximal cardiac output, peripheral mechanisms such as consistently elevated leg vascular resistance and greater pulse pressures appear to be responsible for reduced blood flow persisting throughout graded KE in the old subjects.

Adolescent↗

Parental perceptions surrounding risks and benefits of immunization.

In recent years, parental concerns about vaccine safety have increased as the threat of disease has decreased. A national survey showed that, in general, parents agree that vaccines benefit their children and that their children may be at risk for contracting a disease if unvaccinated. When asked about understanding the benefits and risks of vaccines, most parents (57%) found numbers and statistics most helpful. A substantial minority (17%) of parents were somewhat or not confident in vaccine safety. Parents less confident in vaccine safety agreed less with the statement that they usually followed the advice of their child's doctor. Incomes and education levels affected responses. This positive relationship between confidence in vaccine safety and reliance on doctors for advice may indicate the need for healthcare providers to identify opportunities to (1) solicit questions about vaccine safety, (2) address vaccine safety-related questions in a way meaningful to parents, and (3) strengthen doctor-patient relationships. A parent communication tool is proposed.

Attitude to Health↗

Micrometastases in apheresis products predict shorter progression-free and overall survival in patients with breast cancer undergoing high-dose chemotherapy (HDCT) and autologous blood stem cell transplantation (ABSCT).

The presence of cancer cells in autografts of breast cancer patients has been described to have prognostic value or directly lead to relapse. Previously, we demonstrated that apheresis products (APs) collected after induction chemotherapy have a significantly lower likelihood of tumor cell contamination. Here, we examine the prognostic value of micrometastases in autografts. Data from 83 patients with breast cancer treated with autologous blood stem cell transplantation were analyzed. Pan-cytokeratin-FITC conjugated antibodies were used to detect contaminating breast cancer cells in the APs. Progression and survival data analyzed on the basis of three or fewer cancer cells showed no significant differences in outcomes. Of the 83 patients, 11 had more than three cancer cells detectable in their APs. In total, 72 patients were shown to have less than three cells detectable. When patients with more than three cells were compared to patients with 0-3, we found statistically significant differences in progression-free survival. We also found a significant difference in overall survival (OS) between the two groups. No difference was observed in OS since the time of diagnosis. We conclude that patients with more than three contaminating cells in their APs have micrometastases and represent a poor prognosis group.

Adult↗

Vascular and metabolic response to cycle exercise in sedentary humans: effect of age.

We measured leg blood flow (LBF), drew arterial-venous (A-V) blood samples, and calculated muscle O(2) consumption (VO(2)) during incremental cycle ergometry exercise [15, 30, and 99 W and maximal effort (maximal work rate, WR(max))] in nine sedentary young (20 +/- 1 yr) and nine sedentary old (70 +/- 2 yr) males. LBF was preserved in the old subjects at 15 and 30 W. However, at 99 W and at WR(max), leg vascular conductance was attenuated because of a reduced LBF (young: 4.1 +/- 0.2 l/min and old: 3.1 +/- 0.3 l/min) and an elevated mean arterial blood pressure (young: 112 +/- 3 mmHg and old: 132 +/- 3 mmHg) in the old subjects. Leg A-V O(2) difference changed little with increasing WR in the old group but was elevated compared with the young subjects. Muscle maximal VO(2) and cycle WR(max) were significantly lower in the old subjects (young: 0.8 +/- 0.05 l/min and 193 +/- 7 W; old: 0.5 +/- 0.03 l/min and 117 +/- 10 W). The submaximally unchanged and maximally reduced cardiac output associated with aging coupled with its potential maldistribution are candidates for the limited LBF during moderate to heavy exercise in older sedentary subjects.

Adult↗

Rotational dynamics of hydration water in dicalcium silicate by quasielastic neutron scattering.

Quasielastic neutron scattering (QENS) has been used to investigate the single-particle dynamics of interfacial water in dicalcium silicate (C2S)/water paste. Our previous neutron-scattering studies on interfacial water have focused attention on the translational dynamics of the center of mass of water molecules. In this paper, we have collected QENS data on a wider range of wave-vector transfer so that both translational and rotational motions of water molecules are detected. The data have been analyzed by models for translation and rotation we recently proposed for supercooled water. The evolution of the parameters describing the relaxational dynamics of water embedded in the C2S matrix is given at temperature T=303 K as a function of the curing time.

Journal Article↗