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Biomedical subjects

D Gibbs

Publications and source records attributed to D Gibbs.

At least 19 recordsLinked to original sources

Hemoperitoneum due to spontaneous rupture of the umbilical vein.

Portal hypertension often leads to collateralization of blood flow via variceal vessels that shunt blood from the portal to the systemic circulation. Rupture of an intra-abdominal varix is an unusual complication of portal hypertension that can lead to life-threatening hemoperitoneum. We describe a patient with portal hypertension secondary to liver cirrhosis who presented with acute intra-abdominal hemorrhage. At laparotomy, she was found to have a rupture of the umbilical vein. The vessel was ligated, and the patient recovered uneventfully. The causes of hemoperitoneum in cirrhosis are discussed, and the previously reported cases of intra-abdominal variceal bleeding are reviewed.

Female

Fluconazole treatment of children with severe fungal infections not treatable with conventional agents.

Fluconazole was evaluated prospectively in 173 children aged between 4 months and 16 years in whom conventional antifungal therapy was ineffective or contraindicated. Children entered the study on an individual compassionate request basis for treatment of confirmed or presumed fungal infection or for prophylaxis of fungal infections. Sixty-two children had cancer, 40 had undergone transplantation, 14 had AIDS and 52 had other conditions. The mean fluconazole dosage was 3.4 mg/kg/day (range 0.16-11.1 mg/kg/day) and the mean duration of therapy was 36 days (range 1-340 days). Efficacy was evaluated in 63 children with confirmed fungal infection as documented by the presence of a fungal pathogen at baseline; clinical cure or improvement was achieved in 83% (52/63), pathogen eradication in 73% (43/59). All 173 children were assessed for safety. Related or possibly related adverse events occurred in 6% (11/173) of patients; seven children were withdrawn from therapy because of adverse events. Results of this study demonstrate that the clinical efficacy and safety profile of fluconazole in the treatment of fungal infections in children are favorable, results being similar to those obtained in adults.

AIDS-Related Opportunistic Infections

Fluconazole treatment of neonates and infants with severe fungal infections not treatable with conventional agents.

Fluconazole was evaluated prospectively in 40 neonates and infants between the ages of 2 days and 3 months in whom conventional antifungal therapy was ineffective or contraindicated. The patients received therapy on an individual compassionate request basis for microbiologically documented or presumed fungal infection. The mean fluconazole dosage was 5.3 mg/kg/day (range 1-16 mg/kg/day) and the mean duration of therapy was 26 days (range 2-80 days). Efficacy was evaluated in neonates with proven fungal infection as documented by the presence of a pathogen at baseline. A positive clinical response was achieved in 97% (31/32) of the clinically evaluable patients; eradication of the fungal organism was achieved in 97% (30/31) of evaluable patients. Adverse events occurred in two patients (5%); therapy was not discontinued in either patient. These favorable safety and efficacy data are similar to results obtained with fluconazole in older children and adults.

Age Factors

Fungal infections in cancer patients: an international autopsy survey.

In an attempt to estimate the frequency of fungal infections among cancer patients, a survey of autopsy examinations was conducted in multiple institutions in Europe, Japan and Canada. Fungal infections were identified most often in leukemic patients and transplant recipients (25% each). Fifty-eight percent of fungal infections were caused by Candida spp. and 30% by Aspergillus spp. There was considerable variability in the frequency of fungal infections in different countries. Nevertheless, this study clearly demonstrates that fungal infections represent a common complication in cancer patients, especially in patients with leukemia.

Aspergillosis

A direct comparison of pharmacologic effects of retinoids on skin cells in vitro and in vivo.

The purpose of these studies was to directly compare the pharmacologic effects of retinoids on cutaneous cells in vitro and in vivo. Previously, it was demonstrated that all-trans-retinoic acid stimulates the proliferation of growth-arrested human keratinocytes and fibroblasts in culture. In the present studies, all-trans-retinoic acid was compared to three other retinoids--13-cis-retinoic acid, P-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthalenyl-1-p ropenyl] benzoic acid (TTNPB) and M-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-napthalenyl-1-p ropenyl] benzoic acid (meta-carboxy-TTNPB]--for growth stimulation using a cultured human squamous epithelial cell line (UM-SCC-1) and human dermal fibroblasts. These four retinoids were also evaluated for their effects on reduction of horn-filled utriculi when topically applied to the skin of rhino mice. All-trans-retinoic acid stimulated proliferation of both fibroblasts and epithelial cells over concentrations ranging from 0.01 to 1.0 micrograms/ml. In fibroblasts, 13-cis-retinoic acid was less potent than all-trans-retinoic acid, whereas, in epithelial cells these two retinoids were equipotent. In contrast, TTNPB was more potent than all-trans-retinoic acid at stimulating the growth of both fibroblasts and epithelial cells. The analog, meta-carboxy-TTNPB was essentially inactive as a growth stimulator of both cell types. In the rhino mouse utriculus reduction model, the rank order of potency for the retinoids was the same as that for in vitro cell growth stimulation (TTNPB greater than all-trans-retinoic acid greater than 13-cis-retinoic acid). Meta-carboxy-TTNPB was inactive at reducing utriculi at a dose of 5,000 times the ED50 of TTNPB.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

All-trans retinoic acid stimulates growth and extracellular matrix production in growth-inhibited cultured human skin fibroblasts.

All-trans retinoic acid was examined for effects on human dermal fibroblast proliferation and for effects on fibroblast production and expression of non-collagenous and collagenous components of the extracellular matrix in vitro. Fibroblast proliferation was blocked when the cells were cultured in the presence of a serum-free culture medium containing epidermal growth factor, hydrocortisone, insulin, ethanolamine, phosphoethanolamine, and bovine pituitary extract as growth supplements and 0.15 mM Ca++. This level of extracellular Ca++ is lower than that needed to support fibroblast growth. Under these conditions, growth was stimulated by all-trans retinoic acid. Proliferation was also stimulated in the same basal medium without the growth supplements. Growth-promoting concentrations of all-trans retinoic acid ranged from 0.5-2.0 micrograms/ml (1.7-6.6 X 10(-6) M). Stimulation of proliferation was not seen at higher or lower concentrations. Concentrations of all-trans retinoic acid that stimulated proliferation also induced increased production of fibronectin as indicated by biosynthetic labeling/immunoprecipitation and by enzyme-linked immunosorbent assay. Increased production was associated with increased staining for fibronectin in the extracellular matrix. Increased production of two other non-collagenous extracellular matrix component, i.e., thrombospondin and laminin, also occurred in all-trans retinoic acid-treated cells. At 0.5 micrograms/ml, all-trans retinoic acid also stimulated production of type I collagen by the dermal fibroblasts, but at higher concentrations (2.5 micrograms/ml) production of type I collagen was inhibited. These data indicate that all-trans retinoic acid can induce changes in dermal fibroblasts in vitro (i.e., increased proliferation and extracellular matrix production) that mimic the major changes seen in the dermis after topical treatment with this agent.

Cell Division

Formation and use of poly-L-histidine-catalase complexes: protection of cells from hydrogen peroxide-mediated injury.

Insoluble complexes of poly-L-histidine (polyhistidine) and catalase were prepared by mixing the two reactants together in solution at pH 5.5 and subsequently elevating the pH to approximately 7.0, at which point they precipitated. Complexes formed at optimal ratios of polyhistidine to catalase contained essentially all of the catalase present in the original solution. The catalase present in such complexes contained greater than 50% of the H2O2-inhibiting activity of the native catalase used to prepare the complexes. The insoluble complexes rapidly bound to viable endothelial cells and were resistant to removal by extensive washing. The presence of polyhistidine-catalase complexes on the cell surface protected the cells against injury mediated by H2O2 or activated polymorphonuclear leukocytes. These data show that polyhistidine-catalase complexes can be prepared that have a high affinity for cells and that retain catalase activity. These complexes may be useful in treating inflammatory conditions in which it is necessary to maintain a high local concentration of inhibitor.

Animals

Augmentation of ACTH-releasing activity of synthetic corticotropin releasing factor (CRF) by vasopressin in women.

In order to study the interaction between vasopressin (VP) and hypothalamic corticotropin releasing factor (CRF) on the release of ACTH, VP and CRF were administered separately and in combination to normal cycling women. The combined hormones raised plasma ACTH levels higher than the sum of the separate responses and 5 times more than CRF alone. This study reveals for the first time synergism between VP and CRF in their ACTH releasing effects in humans.

Adrenocorticotropic Hormone

The nutritional status of the elderly.

Data are presented relating to the nutritional status of over 1500 elderly subjects seen in three community surveys. There was s decline in weight, arm circumference and skinfold thickness, and to a lesser extent in Quetelet's index (weight + height2), with advancing age. Haemoglobin levels declined with age in one area but not in the others, probably due to differences in nutritional state. Plasma protein and albumin concentrations showed no decline with age and were similar to values reported from younger subjects. Men who ate alone tended to have a poorer vitamin C and thiamine status than men whose meals were cooked or shared by another person, but no such difference was found among women; indeed, women eating alone had significantly higher leucocyte ascorbic acid levels.

Aged

ESR.

The ESR is a long-established, simple, and reliable test. Results must be interpreted in the context of its known limitations. It is a preliminary sorting test in which an abnormal result may prompt further consideration and investigation. Normal results do not exclude serious physical disorders. During treatment it may provide some objective assessment of improvement or deterioration.

Aged

The anatomy of neurons projecting to the corpus cardiacum from the larval brain of the tobacco hornworm, Manduca sexta (L.).

Retrograde cobalt filling followed by silver intensification revealed new features of the anatomy of neurons which project from the brain to the corpus cardiacum (CC) of the fifth instar larva of Manduca sexta. Filling via the fused nervi corporis cardiaci (NCC) I + II demonstrated four groups of cell bodies (Ia, Ib, II, and III) previously described by Nijhout (1975), plus three major axonal tracts (A, B, and C), and four previously unobserved areas of dendritic branching, dendritic fields (DF) 1, 2, 3, and 4. Tract C is unusual in that it originates from cell bodies on the side contralateral to the filled nerve, travels ventrally and crosses over to the ipsilateral side where it turns dorsally, forming a hook in the center of the brain. It then turns ventrally again to join with tract A. DF 1 and 2 are located ventrally on the ipsilateral and contralateral sides of the brain respectively. DF3 and 4 are situated in the dorsal protocerebrum, on the ipsilateral and contralateral sides respectively. Fills via the NCC III revealed one cell group (IV) and a fifth dendritic field (DF 5). Simultaneous fills of both the fused NCC I + II and the NCC III showed an overlapping of DF 1 and 5, indicating the possibility of synaptic connections between these two fields.

Animals

Template-directed synthesis and selective adsorption of oligoadenylates on hydroxyapatite.

Polyuridylic acid is adsorbed completely from aqueous solution by hydroxyapatite under conditions that permit template-directed synthesis of oligoadenylates in free solution. The yield of oligoadenylates is enhanced to almost the same extent by poly(U) in the presence or the absence of hydroxyapatite. Under very similar conditions small quantities of hydroxyapatite adsorb higher molecular-weight oligoadenylates selectively from a mixture of oligomers. On the basis of these results we propose a mechanism for prebiotic oligonucleotide formation in which selective adsorption on hydroxyapatite or some other immobilized anion-exchanging material plays a major role. Monomers are released from the surface for reactivation, while oligomers are retained in a protected environment by adsorption to the apatite surface.

Adenine Nucleotides