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Biomedical subjects

L Brown

Publications and source records attributed to L Brown.

At least 19 recordsLinked to original sources
PubMed2006

Susceptibility of highly pathogenic A(H5N1) avian influenza viruses to the neuraminidase inhibitors and adamantanes.

Since 2003, highly pathogenic A(H5N1) influenza viruses have been the cause of large-scale death in poultry and the subsequent infection and death of over 140 humans. A group of 55 influenza A(H5N1) viruses isolated from various regions of South East Asia between 2004 and 2006 were tested for their susceptibility to the anti-influenza drugs the neuraminidase inhibitors and adamantanes. The majority of strains were found to be fully sensitive to the neuraminidase inhibitors oseltamivir carboxylate, zanamivir and peramivir; however two strains demonstrated increased IC50 values. Sequence analysis of these strains revealed mutations in the normally highly conserved residues 116 and 117 of the N1 neuraminidase. Sequence analysis of the M2 gene showed that all of the A(H5N1) viruses from Vietnam, Malaysia and Cambodia contained mutations (L26I and S31N) associated with resistance to the adamantane drugs (rimantadine and amantadine), while strains from Indonesia were found to be a mix of both adamantane resistant (S31N) and sensitive viruses. None of the A(H5N1) viruses from Myanmar contained mutations known to confer adamantane resistance. These results support the use of neuraminidase inhibitors as the most appropriate class of antiviral drug to prevent or treat human A(H5N1) virus infections.

Acids, Carbocyclic↗
PubMed2006

Widespread neonatal brain damage following calcium channel blockade.

An abundance of evidence exists that shows calcium channel blockade promotes injury in cultured neurons. However, few studies have addressed the in vivo toxicity of such agents. We now show that the L-type calcium channel antagonist nimodipine promotes widespread and robust injury throughout the neonatal rat brain, in an age-dependent manner. Using both isolated neuronal as well as brain slice approaches, we address mechanisms behind such injury. These expanded studies show a consistent pattern of injury using a variety of agents that lower intracellular calcium. Collectively, these observations indicate that postnatal brain development represents a transitional period for still developing neurons, from being highly sensitive to reductions in intracellular calcium to being less vulnerable to such changes. These observations directly relate to current therapeutic strategies targeting neonatal brain injury.

Animals↗
PubMed2006

MK801-induced caspase-3 in the postnatal brain: inverse relationship with calcium binding proteins.

Age-dependent, neuronal apoptosis following N-methyl-D-aspartate receptor blockade has been linked to loss of calcium. To further explore this relationship, we examined expression of activated caspase-3, as well as the calcium binding proteins, calbindin-D 28K, calretinin and parvalbumin, following injection of vehicle or the N-methyl-D-aspartate receptor blocker, MK801, in postnatal day 7 or 21 rats. At postnatal day 7, MK801-induced activated caspase-3 expression was most frequently found in mutually exclusive cell populations to those expressing any of the three calcium binding proteins. For example, in the somatosensory cortex, most immunoreactivity for activated caspase-3 was found in layers IV/V, layered between areas of high calbindin or calretinin expression. Further, in the caudate putamen, activated caspase-3 rarely invaded zones of intense calbindin immunoreactivity. Suggesting expression patterns of these proteins were inversely related, these same brain regions no longer displayed MK801-induced activated caspase-3 at postnatal day 21, but instead robustly expressed calcium binding proteins. This later surge in expression was especially true for parvalbumin in regions such as the somatosensory and retrosplenial cortex, as well as the subicular complex. Calbindin-D 28K was also found to increase in the same regions though not as impressively as parvalbumin. Thus, developmental regulation of calcium binding protein expression may be a critical factor in age-dependent sensitivity to agents that disrupt calcium homeostasis in maturing neurons, providing a possible mechanistic explanation for age-dependent MK801 toxicity.

Age Factors↗
PubMed2006

Antioxidant supplementation enhances erythrocyte antioxidant status and attenuates cyclosporine-induced vascular dysfunction.

The aim of this study was to determine the effects of dietary antioxidant supplementation with alpha-tocopherol and alpha-lipoic acid on cyclosporine-induced alterations to erythrocyte and plasma redox balance, and cyclosporine-induced endothelial and smooth muscle dysfunction. Rats were randomly assigned to either control, antioxidant, cyclosporine or cyclosporine + antioxidant treatments. Cyclosporine A was administered for 10 days after an 8-week feeding period. Plasma was analyzed for alpha-tocopherol, total antioxidant capacity, malondialdehyde and creatinine. Erythrocytes were analyzed for glutathione, methemoglobin, superoxide dismutase, catalase, glutathione peroxidase, glucose-6-phosphate dehydrogenase, alpha-tocopherol and malondialdehye. Vascular endothelial and smooth muscle function was determined in vitro. Antioxidant supplementation resulted in significant increases in erythrocyte alpha-tocopherol concentration and glutathione peroxidase activity in both of the antioxidant-supplemented groups. Cyclosporine administration caused significant decreases in glutathione concentration, methemoglobin concentration and superoxide dismutase activity. Antioxidant supplementation attenuated the cyclosporine-induced decrease in superoxide dismutase activity. Cyclosporine therapy impaired both endothelium-independent and -dependent relaxation of the thoracic aorta, and this was attenuated by antioxidant supplementation. In summary, dietary supplementation with alpha-tocopherol and alpha-lipoic acid attenuated the cyclosporine-induced decrease in erythrocyte superoxide dismutase activity and attenuated cyclosporine-induced vascular dysfunction.

Animals↗
PubMed2005

Does leucocytosis identify bacterial infections in febrile neonates presenting to the emergency department?

OBJECTIVE: This study was undertaken to evaluate the discriminatory power of the peripheral white blood cell (WBC) count to identify bacterial infections in a cohort of febrile neonates ( or=38 degrees C, underwent lumbar puncture, and had a WBC count obtained were included. They were divided according to microbiological and radiographic findings into four groups: bacterial infections, viral infections, pneumonia, and negative sepsis evaluations. RESULTS: A total of 69 febrile neonates met the inclusion criteria. The number of neonates in each group was as follows: 8 with bacterial infections, 10 with viral infections, 3 with pneumonias, and 48 with negative sepsis evaluations. There was substantial overlap in WBC counts among the groups. The area under the ROC curve was 0.7231 (95% CI 0.5665 to 0.8797). CONCLUSION: In a cohort of febrile neonates evaluated in the emergency department, the WBC count had modest discriminatory power in identifying neonates with bacterial infections and demonstrated substantial overlap among groups. The present data suggest against the use of any WBC count threshold to identify bacterial infections in febrile neonates presenting to the emergency department.

Bacterial Infections↗
PubMed2005

Mucinous metaplasia of the vulva in a case of lichen sclerosus. A case report.

Mucinous metaplasia of the genital area is a rare condition characterised by the emergence of mucin containing cells in stratified squamous epithelium. This report describes a unique case of benign mucinous metaplasia of the vulva associated with lichen sclerosus in a 60 year old woman. Histopathology revealed cervical type metaplasia with otherwise typical lichen sclerosus. This report discusses the pathogenesis and differential diagnosis of mucinous epithelium.

Epithelial Cells↗
PubMed2005

Seasonal occurrence and production effects of the biting louse Damalinia limbata on Angora goats and 2 treatment options.

Adult biting lice Damalinia limbata (Gervais 1844) were most numerous on Angora goats in southwestern Free State Province from November to May with the smallest numbers present during August. Nymphs were most numerous from January to March with the smallest numbers present during July. The largest proportion of adult lice was present on the ventral surface of goats during winter, when population numbers were lowest, and the largest proportion of nymphs during summer, when population numbers were highest. Infestation did not affect the body weight of goats, but adversely affected both the quantity and quality of mohair produced. A single treatment with deltamethrin, applied as a pour-on along the mid-line of the backs of the goats, effectively controlled infestation and resulted in a significant increase in mohair production compared with untreated goats. Deltamethrin sprayed along the sides of the animals was equally effective in controlling infestation.

Animals↗
PubMed2003

Risk management models in netball.

Risk management strategies have been used in a wide range of sports. Many issues involved in the implementation of risk management models in sport have not been investigated especially the sport specific and location specific nature of such models. The aim of this study was to ascertain the usefulness of Occupational Health & Safety risk management (RM) models in a mainly voluntary sporting organisation and to investigate the requirements of a netball population in developing "user friendly" risk management plans. The industry RM plans were trialled in a rural setting at various netball associations over a six week period. After these trials focus groups and interviews were conducted and the trials evaluated. The requirements of the netball population for a RM plan were investigated using focus groups from regional and rural areas. The industry RM models presented were not generally accepted by the trial participants. They found that the level of expertise required did not exist in netball at the club/team level. The focus groups on the needs of netball for a user friendly model brought out a number of issues including the specific needs of rural football/netball leagues, the need to develop strategies for all levels of netball (coach, player, umpire, administrator). Barriers to the uptake of risk management models were discussed. An effective RM plan can be developed for voluntary sports associations but they must be specific to the sport and flexible. The RM plan must also take into account the barriers to implementation for each sporting culture.

Athletic Injuries↗
PubMed2003

A histological analysis of lens capsules stained with trypan blue for capsulorrhexis in phacoemulsification cataract surgery.

PURPOSE: Staining of anterior lens capsules with dye to facilitate completion of continuous curvilinear capsulorrhexis is now being used more frequently in phacoemulsification of white and mature cataracts with poor red reflexes. This study examined the histological characteristics of anterior lens capsules stained with trypan blue. The layer(s) of the lens capsule that stained with dye and the extent of accumulation of dye in these layers of the lens capsule were determined. To the best of our knowledge this has not been described before. METHODS: A series of 10 stained lens capsules were analysed histologically. The dye used in this study consisted of a standard sterile, noninflammatory, nonpyrogenic, 2 ml solution containing 0.6 mg/ml of trypan blue. Following capsulorrhexis, samples were sent to the laboratory for histological analysis. Frozen sections (8 microm) were prepared and examined with the light microscope. All 10 capsules were cut by frozen section to preserve trypan blue staining (which would be leached by processing) and then subjected to immunohistochemistry for collagen IV. Immunohistochemical analysis using markers for type IV collagen were done on formalin-fixed specimens for morphological comparison with the frozen sections. A counterstain highlighted the epithelium. RESULTS: Continuous curvilinear capsulorrhexis was successfully and easily completed in all cases without any complications. Frozen section analysis using light microscopy demonstrated accumulation of trypan blue dye in the basement membrane of the lens capsule. Staining was concentrated in the portion of the membrane adjacent to the lens epithelium. The lens epithelium could not be clearly identified on the frozen sections. Consequently, immunohistochemical analysis with markers for type IV collagen was performed. A counterstain highlighted the epithelium. This confirmed that the layer staining with trypan blue was the basement membrane, a consistent feature on all the specimens. CONCLUSION: Trypan blue selectively stains the basement membrane of the anterior lens capsule. There is a concentration of dye in the basement membrane adjacent to the lens epithelial cell layer. The lens cortex does not appear clinically to stain with trypan blue. This enables surgeons to distinguish the lens capsule from the cortex and provides sufficient contrast for successful completion of continuous curvilinear capsulorrhexis during cataract surgery.

Basement Membrane↗
PubMed2002

A single-centre study of treatment outcomes and survival in 120 patients with peripheral T-cell non-Hodgkin's lymphoma.

We conducted a retrospective study of treatment outcomes and survival in 120 consecutive, unselected patients with peripheral T-cell non-Hodgkin's lymphoma, presenting at a single centre over a 20-year period. Cases met the criteria of the Revised European-American Lymphoma (REAL) Classification and patients with peripheral T-cell lymphoma of the following subtypes were included: anaplastic large T-cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AILD), peripheral T-cell lymphoma unspecified (PTCLu), and intestinal T-cell lymphoma (ITCL). The study population consisted of 120 patients with a presenting diagnosis of peripheral T-cell lymphoma. Cases that had been previously confirmed as T-cell lymphoma at formal pathology review were identified from the lymphoma database of this institution. Staging investigations, treatment type and outcomes were taken from patient records. For each subtype, clinical characteristics, response to initial treatment, duration of response and any subsequent relapse were recorded. Overall, relapse, and progression-free survival figures were calculated. The ALCL group had the best response rate to first line treatment 19 of 22 (86 percent) while the AILD group had the lowest response 12 of 29 (41 percent). Relapse rates were PTCLu 13 of 35 (37 percent), ITCL 10 of 34 (29 percent), ALCL 6 of 22 (27 percent) and AILD 7 of 29 (24 percent). In terms of median overall survival, a significantly superior survival was demonstrated for the ALCL group (7.05 years) compared to the remaining three groups. The ALCL group had the lowest risk of death while the ITCL group had the highest risk (hazard ratio: 2.82). Five-year survival rates were estimated to be ALCL 60 percent, PTCLu 40 percent, AILD 30 percent and ITCL 25 percent. This single-centre study demonstrated different outcomes for each group with significant differences in overall survival rates. These findings support the clinical utility of the REAL lymphoma classification in respect to the PTCL subgroups included in this study.

Adult↗
PubMed2002

Psychological adjustment to familial-genetic risk assessment for ovarian cancer: predictors of nonadherence to surveillance recommendations.

OBJECTIVE: To evaluate whether self-report measures of psychological distress and perceived risk were associated with nonadherence to recommended ovarian cancer surveillance. METHODS: Eighty-three patients attending the Familial Ovarian Cancer Clinic (FOCC) at Princess Margaret Hospital were assessed psychosocially prior to and during initial familial-genetic assessment and then monitored for adherence with recommended follow-up surveillance over a period of 12-18 months. The assessment protocol included an investigator-designed clinic questionnaire, the State-Trait Anxiety Inventory (STAI), Center for Epidemiologic Studies Depression Scale (CESD), Life Orientation Test (LOT), Medical Outcomes Study Social Support Survey (MOSSS), Texas Inventory of Grief, and the COPE. Nonadherence was measured in terms of unexplained absences at one or two recommended and scheduled surveillance appointments following the familial-genetic assessment. RESULTS: Univariate tests revealed a significant association between higher perception of ovarian cancer risk, as assessed immediately after the familial-genetic risk assessment in the clinic and nonadherence to physician-recommended surveillance (chi2 (2, N = 83) = 9.75, P < 0.008). Empirically based estimates of risk, conveyed by the clinic team to subjects, were not significantly associated with nonadherence (chi2 (2, N = 83) = 0.19, P = 0.91). Logistic regression analysis revealed that subjects who perceived themselves to be at high ovarian cancer risk were five times more likely to be nonadherent than participants who perceived themselves to be at low or medium ovarian cancer risk. CONCLUSIONS: These results suggest that higher self-perceived risk may predict adherence difficulties to recommended surveillance in women attending a familial-genetic risk clinic.

Adult↗