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Biomedical subjects

G Scott

Publications and source records attributed to G Scott.

At least 181 records · Page 10Linked to original sources

Antioxidants in food packaging: a risk factor?

It is current practice to test all new additives for packaging polymers for toxicity before permitting them to be used in food contact applications. However, many antioxidants and stabilizers act sacrificially and are converted to oxidation products in the process of preventing polymer degradation. In most cases, little is known about the toxicity of antioxidant transformation products, and in some cases there is reason to suspect that they may be more toxic than the chemicals from which they are derived. Two possible solutions are presently showing promise. The first is to chemically react the antioxidant or stabilizer with the polymer, either at the polymer synthesis stage or preferably during processing, so that neither the antioxidant nor its transformation products can be leached into food. The second is to use a biological antioxidant (e.g. alpha-tocopherol) whose oxidation chemistry and toxicology are known.

Antioxidants↗

Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.

BACKGROUND AND METHODS: Maternal-infant transmission is the primary means by which young children become infected with human immunodeficiency virus type 1 (HIV). We conducted a randomized, double-blind, placebo-controlled trial of the efficacy and safety of zidovudine in reducing the risk of maternal-infant HIV transmission. HIV-infected pregnant women (14 to 34 weeks' gestation) with CD4+ T-lymphocyte counts above 200 cells per cubic millimeter who had not received antiretroviral therapy during the current pregnancy were enrolled. The zidovudine regimen included antepartum zidovudine (100 mg orally five times daily), intrapartum zidovudine (2 mg per kilogram of body weight given intravenously over one hour, then 1 mg per kilogram per hour until delivery), and zidovudine for the newborn (2 mg per kilogram orally every six hours for six weeks). Infants with at least one positive HIV culture of peripheral-blood mononuclear cells were classified as HIV-infected. RESULTS: From April 1991 through December 20, 1993, the cutoff date for the first interim analysis of efficacy, 477 pregnant women were enrolled; during the study period, 409 gave birth to 415 live-born infants. HIV-infection status was known for 363 births (180 in the zidovudine group and 183 in the placebo group). Thirteen infants in the zidovudine group and 40 in the placebo group were HIV-infected. The proportions infected at 18 months, as estimated by the Kaplan-Meier method, were 8.3 percent (95 percent confidence interval, 3.9 to 12.8 percent) in the zidovudine group and 25.5 percent (95 percent confidence interval, 18.4 to 32.5 percent) in the placebo group. This corresponds to a 67.5 percent (95 percent confidence interval, 40.7 to 82.1 percent) relative reduction in the risk of HIV transmission (Z = 4.03, P = 0.00006). Minimal short-term toxic effects were observed. The level of hemoglobin at birth in the infants in the zidovudine group was significantly lower than that in the infants in the placebo group. By 12 weeks of age, hemoglobin values in the two groups were similar. CONCLUSIONS: In pregnant women with mildly symptomatic HIV disease and no prior treatment with antiretroviral drugs during the pregnancy, a regimen consisting of zidovudine given ante partum and intra partum to the mother and to the newborn for six weeks reduced the risk of maternal-infant HIV transmission by approximately two thirds.

Adult↗

Staining of amyloid precursor protein to study axonal damage in mild head injury.

The most common definition of cerebral concussion is that of a transient loss of neurological function without macroscopic or microscopic abnormality in the brain. However, some patients have persistent symptoms and subtle neuropsychological deficits, particularly affecting memory. We have studied five patients aged 59-89 years who sustained mild concussive head injury and died of other causes (2-99 days post-injury). Immunostaining with an antibody to amyloid precursor protein, a marker of fast axonal transport, showed multifocal axonal injury in all five. All had axonal damage in the fornices, which are important in memory function.

Aged↗

HIV in Zambia: myth or monster?

Despite attempts by a few journalists to portray the spread of AIDS in African countries as fictitious, the situation in Zambia shows that such views are completely misguided.

Female↗

The effects of BTS 54,505, a metabolite of sibutramine, on monoamine and excitatory amino acid-evoked responses in the rat dorsolateral geniculate nucleus in vivo.

1. The effects of BTS 54,505, the primary amine metabolite of the non-tricylic putative antidepressant sibutramine, on the responses evoked by visual stimulation and ionophoretic application of noradrenaline (NA), 5-hydroxytryptamine (5-HT) and excitatory amino acids (EAAs) in the rat dorsolateral geniculate nucleus (dLGN) have been investigated. 2. Ionophoretic application of 5-HT to dLGN neurones attenuated visually-evoked (n = 46), NMDA-evoked (n = 21) and AMPA-evoked responses (n = 21), while ionophoretic application of NA potentiated visually-evoked activity in these cells (n = 27). 3. Simultaneous application of BTS 54,505 with 5-HT (over 120 s) resulted in a prolongation of the recovery time (i.e. the period required by a neurone to recover by 50%, RT50) from the 5-HT-mediated suppression of discharge activity (approximately 275% increase in RT50). BTS 54,505 also prolonged the recovery time from a NA-mediated potentiation of firing (approximately 450% increase in RT50). These effects on recovery time are attributed to the inhibition of uptake of both 5-HT and NA by BTS 54,505. The amplitude of the response to 5-HT or NA was unaffected by co-ejection of BTS 54,505. 4. Ionophoretic application of N-methyl-D-aspartate (NMDA) produced a current-dependent increase in neuronal firing, as did application of the non-NMDA receptor agonist alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). A simultaneous 120 s application of BTS 54,505 inhibited the NMDA response in all cells studied (mean ED50 = 16 +/- 5 nA) but had no effect on AMPA-evoked activity in the majority of the same cells (n = 15/21).5. Short 10 s applications of BTS 54 505, at ejecting currents (>30 nA) that attenuated NMDA-evoked activity in all cells studied, had no effect on either response amplitude or recovery time from ionophoretic application of 5-HT, suggesting that inhibition of NMDA-evoked activity by BTS 54 505 was not mediated by 5-HT uptake blockade.6. These results suggest that BTS 54 505 inhibits NMDA-evoked activity, and the observation that this effect is unlikely to be due to raised levels of endogenous 5-HT following monoamine uptake blockade indicate that BTS 54 505 may interact directly with the NMDA receptor ionophore complex.

Animals↗

Hypertrophic lichen planus in three HIV-positive patients: a histologic and immunological study.

It is well known that several dermatoses, such as psoriasis vulgaris and seborrheic dermatitis, present with more extensive and severe disease in patients infected with the human immunodeficiency virus (HIV-1). Except for one report, however, lichen planus (LP) has not been described in patients with HIV infection. In this report we describe the clinical and morphological features of 3 HIV-positive patients who presented with extensive hypertrophic LP. To determine if alteration in the immune status in HIV-positive hosts is reflected in the nature of the infiltrate in LP, we determined the proportion of T-helper and T-suppressor cells in the infiltrate in 1 case. The majority of the infiltrating lymphocytes in the dermis were of the T-helper phenotype. Epidermal lymphocytes, however, were predominantly of the T-suppressor phenotype. We conclude that LP in HIV-positive hosts may present with more extensive disease than in immunocompetent hosts. Based on our immunohistochemical studies, we conclude that, similar to immunocompetent hosts, T-helper cells are the predominant cells in the dermal infiltrate of LP in HIV-positive patients. However, in contrast with reports in the literature on LP in immunocompetent hosts, we found that, in the case studied, the epidermal lymphocytes were predominantly of the T-suppressor phenotype.

Adult↗

Stem cell factor regulates human melanocyte-matrix interactions.

Stem cell factor (SCF) is hypothesized to play a critical role in the migration of melanocytes during embryogenesis because mutations in either the SCF gene, or its ligand, c-kit, result in defects in coat pigmentation in mice and in skin pigmentation in humans. In this report we directly show that SCF alters the adhesion and migration of human melanocytes to extracellular matrix (ECM) ligands and regulates integrin expression at the protein level. SCF decreased adhesion of neonatal and fetal cells to collagen IV, and increased attachment of fetal cells to laminin. Attachment of fetal cells to fibronectin was decreased, but was unchanged in neonatal cells. Flow cytometry analysis of neonatal melanocytes showed that SCF down-regulated the expression of the alpha 2 receptor, and up-regulated the expression of the alpha 3, alpha 5 and beta 1 integrin receptors. SCF down-regulated expression of alpha 2, alpha 5 and beta 1 integrins by fetal melanocytes, and up-regulated expression of the alpha v and alpha 3 integrin receptors. Analysis of melanocyte migration using time-lapse videomicroscopy showed that SCF significantly increased migration of neonatal, but not fetal, melanocytes on fibronectin (FN). We conclude that SCF regulates integrin expression at the protein level and that SCF has pleiotropic effects on melanocyte attachment and migration on ECM ligands. We suggest that this may be one mechanism by which SCF regulates melanocyte migration during development of the skin.

Cell Adhesion↗

A prospective, double-blind trial of electrical capacitive coupling in the treatment of non-union of long bones.

Twenty-three patients who had an established non-union of a long bone were entered into a prospective, double-blind trial in which electrical capacitive coupling was used for treatment. Twenty-one patients completed the study: ten who were actively managed and eleven who were managed with a placebo unit. The non-union healed in six of the ten patients who had been managed actively but in none of the patients who had been managed with the placebo unit. This difference in the rates of healing between the actively managed and the placebo groups is highly significant (p = 0.004).

Adolescent↗

Brain injury patterns in fatally injured pedestrians.

To study the relationship between the severity of impact to the head and the severity and distribution of injury to the brain in fatally injured pedestrians, events in vehicle-pedestrian collisions were reconstructed to determine the peak linear and angular acceleration sustained by the pedestrians' heads. The nature and distribution of injuries to the brain were determined by neuropathologic examination of coronal sections of the brain. Study of 13 cases with occipital impacts and 18 with lateral impacts showed that the brain appeared to be more susceptible to injury from lateral impacts. The frontal and temporal regions appeared to be more susceptible to injury at low accelerations in occipital impacts, providing an explanation for "coup" and "contrecoup" injuries. For occipital impacts, a positive relationship was found between linear acceleration and the extent of injury to the brain, suggesting that there was a threshold for observable and concussive brain injury at about 1500 m/s2 peak linear acceleration. These findings are important for the development of measures for preventing brain injuries.

Accidents, Traffic↗

Subpopulations of bone marrow fibroblasts support VLA-4-mediated migration of B-cell precursors.

Proliferation of normal human lymphoid progenitors in culture is dependent on interaction with bone marrow-derived fibroblast-like cells (BM-FB). To investigate possible heterogeneity in this lymphoid-supportive microenvironment, we studied the interaction of a human B-precursor cell line (NALM-6) with BM-FB. NALM-6 cells associate with BM-FB by either adhesion or migration underneath the fibroblast. Individual fibroblasts in the BM-FB layer showed significant variation in the number of migrating NALM-6 cells. Migration of NALM-6 cells was primarily VLA-4-dependent, although residual migration observable after blocking with anti-VLA-alpha 4 antibody was inhibited by anti-VLA-alpha 5 antibody. Migration was not inhibited by blocking either of the known VLA-4 counterreceptors (VCAM-1 or fibronectin), although slight inhibition was observed using a combination of blocking antibodies to VCAM-1 and fibronectin. In contrast, NALM-6 adhesion without migration was significantly inhibitable by anti-VCAM-1 antibody. VCAM-1 or fibronectin expression on individual BM-FB did not correlate with NALM-6 migration. These results indicate that the adhesion and migration of human B-lymphoid precursors in the bone marrow microenvironment are mechanistically separable events and suggest the possibility of novel VLA-4 ligand(s), which may be important in human lymphopoiesis. Subpopulations of cells in the bone marrow microenvironment may preferentially support important aspects of lymphoid progenitor development.

Adult↗

Audit: an exploration of some tensions and paradoxical expectations.

There can be very few nurses, at the moment, whose daily activity is not in some way influenced by the notion of audit and related concepts. Yet despite an impressive growth in the literature relating to audit, conceptual clarity on a number of key issues remains elusive. This paper suggests that there are major tensions inherent in much of the current thinking about audit. In outlining the arguments supporting our position, we term these tensions primary and secondary. The potential effects of ignoring such tensions are illustrated by reference to the development of day hospital care for older people in the United Kingdom. This is used to highlight a number of paradoxical expectations and deleterious consequences for day hospital services which have arisen from a failure adequately to address a number of fundamental questions. The lessons to be drawn are then applied to audit in general, with particular reference to services for individuals with on-going health care needs.

Attitude of Health Personnel↗

[Nutritional evaluation of sweet potato cultivars Ipomea batata (L.) Lam used in bread as partial substitute of wheat flour].

Four hundred and forty entries of sweet potato tubers from the International Potato Center were evaluated for chemical characteristics related to nutritional value. Dry matter range in the group was 15 to 45g/100g. The native entries DLP 2393, DLP 1120, DLP 2312, DLP 1908 and the foreign RCB 361F were selected for use in bread manufacture. Their average dry matter and crude protein was 38.5 and 9.2% respectively. Sweet potato bread was made replacing 30% of wheat flour with grinded sweet potato tubers. This bread had 11.0% crude protein in dry matter basis which were the same for bread made of wheat flour. There were no differences in organoleptic characteristics or protein quality (Apparent biological value: 37 vs 42%; apparent digestibility: 81 vs 80%; net protein utilization: 33 vs 39%) between sweet potato or full wheat flour breads respectively.

Bread↗

Effect of cilofungin on phagocytosis and intracellular killing of Candida albicans by human neutrophils.

The effect of a beta glucan synthase inhibitor, cilofungin, amphotericin B and 5-fluorocytosine on opsonization, phagocytosis and intracellular killing of Candida albicans blastospores by glass-adherent human neutrophils was determined by microscopy and dye exclusion staining. Pretreatment of blastospores for 2, 4, 6 and 18 h with 1.25 mg/l cilofungin resulted in 24-28% of neutrophils ingesting compared to 24% with no drug present. There was no significant difference in the phagocytic index with increased incubation time. Percentage ingestion and phagocytic index values were not significantly different when blastospores were pretreated for 2 h in the presence of 3, 7, 15, 31 and 62 mg/l cilofungin. Comparable concentrations of amphotericin B and 5-fluorocytosine gave similar results. In the absence of cilofungin, intracellular killing after 2 h was 54%. In the presence of 1 and 10 mg/l cilofungin, 85-90% of intracellular blastospores were killed. Therapeutic levels of amphotericin B or 5-fluorocytosine did not enhance intracellular killing. These data demonstrate the potentiation of intracellular killing of Candida albicans by neutrophils in the presence of cilofungin.

Amphotericin B↗

A simple and rapid method for improving recording characteristics using multibarrelled micropipettes.

A method for the simple and rapid fabrication of multibarrelled micropipettes with improved signal-to-noise characteristics is described. The process of silicone coating the exterior of the multibarrel assembly was found to improve recording characteristics greatly and to reduce recording noise during the passage of ionophoretic current. This simple process of fabrication and silicone coating is completed within 15-20 min and is technically undemanding.

Action Potentials↗

Progressive multifocal leukoencephalopathy in HIV-1-infected children.

OBJECTIVE: To describe the clinical and pathologic features of two HIV-1-infected children with progressive multifocal leukoencephalopathy (PML). DESIGN: Case report. SETTING: University-affiliated, public-health trust hospital. METHODS: Two HIV-1-infected children with PML are described. A 13-year-old girl, presumed to be congenitally infected with HIV-1, presented with dysarthria and paresthesias of the tongue and chin that evolved rapidly to dementia, muteness and severe spastic quadriparesis. The other patient, a 10-year-old boy who developed HIV-1 infection from a blood transfusion at the age of 3 years, presented with a facial palsy with subsequent development of right hemiparesis and aphasia. RESULTS: Brain biopsy in the first child and autopsy in the second confirmed the diagnosis of PML. In both patients, the CD4 T-lymphocyte count was less than 100 x 10(6)l at the time of neurological presentation. CONCLUSION: Despite seroepidemiological studies suggesting that the majority of individuals are infected with JC virus during childhood, PML is rare in children with impaired cell-mediated immunity. Our patients illustrate that PML is among the neurological complications of HIV-1 infection in children.

Adolescent↗

Molecular mechanisms of human melanocyte attachment to fibronectin.

In this report we show that fetal and neonatal melanocyte attachment to fibronectin (FN) is inhibited by antibodies to the beta 1 integrin subunit, suggesting a role for these molecules in melanocyte attachment to FN. The VLA-5 integrin was shown to be the predominant receptor for fetal melanocyte attachment to FN, in contrast with neonatal melanocytes in which the very late antigen (VLA)-5, VLA-3, and alpha v integrins each contributed to melanocyte attachment to FN. Peptides containing the arginyl-glycyl-aspartyl-serine (RGDS) sequence inhibited fetal and neonatal melanocyte attachment to FN by a maximum of 48% and 85%, respectively. The almost complete inhibition of neonatal melanocyte attachment to FN by RGDS-containing peptides suggests that the central cell-binding domain of FN is the primary recognition site for neonatal cell attachment to FN. Fetal and neonatal melanocytes showed a concentration-dependent attachment to two proteolytically derived fragments of the FN molecule: a 75-kD fragment, which contains the central cell-binding domain, and 33/66-kD fragments of the FN molecule, which encompass the heparin-binding domains V and VI. Antibodies to the beta 1 subunit inhibited fetal and neonatal melanocyte attachment to the 33/66-kD fragments by a maximum of only 15% and 24%, respectively, suggesting that other, non-integrin, receptors are involved in melanocyte recognition of this portion of the FN molecule. We propose that human fetal and neonatal melanocytes attach to FN by different complements of receptors and ligand target sequences, and that these differences may direct melanocyte interactions with FN during development.

Antibodies↗