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Biomedical subjects

C E Collins

Publications and source records attributed to C E Collins.

At least 37 records · Page 2Linked to original sources

Picotamide inhibition of excess in vitro thromboxane B2 release by colorectal mucosa in inflammatory bowel disease.

BACKGROUND: Inflammatory bowel disease is associated with increased mucosal release of eicosanoids. Among these, thromboxane A2 has been proposed as a possible inflammatory mediator; its suppression may be a useful therapeutic option. METHODS: Using a tissue incubation technique, we compared release of immunoreactive thromboxane B2 by colonic biopsies from patients with ulcerative colitis, Crohn's disease and controls, and assessed the inhibitory effect of picotamide, a thromboxane synthesis inhibitor-receptor antagonist, which has been widely used in Italy for management of ischaemic heart and cerebrovascular disease. RESULTS: Increased amounts of thromboxane B2 were released from biopsies from patients with active ulcerative colitis (median 238 pg/20 min/mg wet weight (interquartile range 147-325), n = 12) and active Crohn's disease (252 (174-450), 6) compared with those from patients with quiescent ulcerative colitis (95 (61-140), 12) or Crohn's disease (105 (57-201), 13), or controls (136 (64-206), 8). Incubation with picotamide at concentrations between 100 microM and 1 mM reduced thromboxane B2 release (IC50 890 microM). CONCLUSION: Since increased thromboxane A2 production may have pathogenetic importance, thromboxane synthesis inhibitor-receptor antagonists such as picotamide merit therapeutic trial in the management of inflammatory bowel disease.

Adult↗

Developmental changes in the distribution of NADPH-diaphorase-containing neurons in telencephalic nuclei of the zebra finch song system.

Extensive recent research has focused on the potential role of nitric oxide (NO) in synaptic plasticity. Could the capacity to synthesize NO be associated with neural and behavioral plasticity in the song system? The timing of song learning and of major developmental changes in song system anatomy are known. We searched for an association between NO and these developmental events by observing the distribution of neurons staining for NADPH-diaphorase, an enzyme used in the synthesis of NO, in the brains of zebra finches. Both male and female brains were taken at different developmental ages from day 21 to adulthood. We found that the incidence of stained neurons in the song system nuclei is lower than in surrounding areas. The incidence of staining decreases with development, with most of the decrease occurring prior to the auditory learning phase of song learning. The developmental changes were quantified for area X and found to be highly significant, with a 56% decrease in staining frequency from day 21 to adulthood in males and a 23% decrease in females for the equivalent region. We also found a sexual dimorphism in the song system of adult birds, consisting of a reduced incidence of stained neurons in song system nuclei area X, high vocal center (HVC), and nucleus robustus (RA) archistrialis in males compared with females. These findings suggest that NO is less involved in the plasticity underlying song acquisition than in the earlier formation of the song system.

Animals↗

Myopathy in acquired partial lipodystrophy.

We describe two women with acquired partial lipodystrophy, one with significant myopathic symptoms and signs. Muscle biopsy of deltoid and quadriceps was performed in each case. The light microscopy findings were of type 1 and type 2 fibre hypertrophy, with an increase in intracytoplasmic fat in both cases. Electron microscopy showed normal fibres, with accumulations of electron-lucent fat droplets between the myofibrils. The cause of the lipodystrophies is uncertain, but myopathy may be a feature, and muscle biopsy studies may help in further defining the syndrome.

Adipose Tissue↗

Platelets circulate in an activated state in inflammatory bowel disease.

BACKGROUND/AIMS: Platelets show proinflammatory as well as prothrombotic properties. Patients with inflammatory bowel disease are at increased risk of systemic thromboembolism, and multifocal microvascular infarction has been proposed as a pathogenetic mechanism in Crohn's disease. The aim of this study was to determine if inflammatory bowel disease is associated with abnormal platelet behavior. METHODS: Platelet activation and aggregability were assessed using flow cytometry, Born aggregometry, and the modified method of Wu and Hoak. Serum beta-thromboglobulin was measured in patients with Crohn's disease and ulcerative colitis and, as controls, in healthy volunteers and patients with active rheumatoid arthritis. RESULTS: Platelet surface expression of P-selectin and GP53 (markers of activation) were increased in Crohn's disease (13 of 30 patients abnormal for P-selectin; 9 of 28 abnormal for GP53) (P < 0.01) and ulcerative colitis (9 of 21 for P-selectin; 10 of 21 for GP53) (P < 0.01) compared with healthy controls. Increased circulating platelet aggregates (15 of 24 patients with Crohn's disease and 8 of 16 with ulcerative colitis) (P < 0.01), platelet aggregability in vitro, and serum beta-thromboglobulin were detected in active inflammatory bowel disease compared with healthy controls. Platelet behavior in active rheumatoid arthritis resembled that in healthy controls. CONCLUSIONS: Increased platelet activation and aggregation are features of inflammatory bowel disease and may contribute to the risk of systemic thromboembolism and the pathogenesis of mucosal inflammation. Therefore, antiplatelet agents may be valuable in the management of inflammatory bowel disease.

Adult↗

The costs of family contributions to the care of persons with dementia.

This study focuses on the costs of dementia care incurred by families. Cost components operationalized include: costs of unpaid caregiver labor services, paid and unpaid family labor, paid and unpaid services of nonfamily persons, and cash outlays for equipment and services. Among 182 families of dementia patients, average care costs for a 3-month period amount to $4,564. Cash expenditures average only 29% of total care costs, with unpaid labor accounting for 71% of the family care costs. Total care costs rise by $1,158 for each additional dependency in an activity of daily living (ADL), while reliance on paid services is 5% higher for each additional $10,000 household income and drops by 25% if the patient lives in the caregiver's household.

Activities of Daily Living↗

Relationship between infective load of Helicobacter pylori and reactive oxygen metabolite production in antral mucosa.

Helicobacter pylori infection has been associated with stimulation of gastric mucosal reactive oxygen metabolite production. To provide further evidence of a causal relationship we looked for a dose-response relationship. We studied antral biopsy material from 110 patients. Quantitative H. pylori assessments were made using histologic and microbiologic methods. Reactive oxygen metabolite production was measured by luminol-dependent chemiluminescence. The usefulness of timed urease test colour changes as a guide to infective load was assessed. There was a positive association between mucosal reactive oxygen metabolite production and histologic (p = 0.002, n = 69) and microbiologic (Spearman's R = +0.6, p = 0.05, n = 18) quantitative H. pylori assessments. H. pylori infective load varied markedly over small areas (coefficient of repeatability of paired cultures (in colony-forming units/mg) = 1.9 x 10(6). Urease test timing correlated with histologic (p = 0.01) and microbiologic (p = 0.03) H. pylori quantitation. Histologically assessed mucosal damage was related to quantitative H. pylori assessment and to mucosal reactive oxygen metabolite production (p = 0.0001). These results support the hypothesis that H. pylori stimulates gastric mucosal reactive oxygen metabolite production and that this phenomenon is of pathogenic importance.

Adolescent↗

Grieving: facilitating the process for dementia caregivers.

1. Grief is a psychological and physiological process that occurs in response to a specific loss. Through the grieving process, those who have experienced a loss come to terms with the finality of the loss and the meaning of the loss in their life. 2. Dementias bring a number of predeath losses that cause caregivers to grieve. Because such losses are often hard to recognize, nurses can plan interventions to facilitate predeath grief. 3. Even when dementia caregivers are able to work through their predeath grief, they cannot fully re-establish their lives until after their relative dies. Some caregivers may never completely resolve the predeath and postdeath losses that have resulted from caring for their relative.

Adaptation, Psychological↗

Review article: thromboxanes in inflammatory bowel disease--pathogenic and therapeutic implications.

Recent work suggests that thromboxanes may play a major pathogenic role in inflammatory bowel disease. Thromboxanes are produced in excess not only in inflamed mucosa but also in Crohn's disease, by uninflamed bowel and by isolated intestinal and peripheral blood mononuclear cells. Their cellular source is likely to include platelets, neutrophils, endothelial and epithelial cells as well as mononuclear cells, possible stimuli to their overproduction being chemotactic peptides, lipopolysaccharide, leukotrienes, platelet activating factor, interleukin-1, bradykinin and angiotensin II. The pro-inflammatory effects of thromboxanes are both direct (diapedesis and activation of neutrophils, mucosal ulceration, reduction of suppressor T-cell activity) and indirect (vasoconstriction, platelet activation). Although corticosteroids and aminosalicylates inhibit thromboxane synthesis, this action does not necessarily explain their therapeutic effect in inflammatory bowel disease. Selective thromboxane synthesis inhibitors and receptor antagonists, however, ameliorate experimental colitis in animals. Picotamide and ridogrel are dual thromboxane pathway blockers already used in man. Drugs of this type could prove useful not only for the prevention of systemic thrombo-embolism but also for suppressing intestinal mucosal inflammation in patients with inflammatory bowel disease.

Eicosanoids↗

Sources of stress among families caring for relatives with Alzheimer's disease.

We have described the different sources of stress and burden that are imposed by caring for a family member with AD. We have provided an approach to assessing each of these possible sources of stress and burden and have indicated how such assessments must take a family-based approach and consider the broader social roles and family dynamics that may color the way in which family members view and carry out their caregiving roles.

Aged↗

Suppression of the cutaneous immune response following topical application of the prostaglandin PGE2.

UVB irradiation (290-320 nm) and topical applications of arachidonic acid (AA) in mice decrease the number of identifiable Langerhans cells and alter the cutaneous immune response. Application of contact allergens such as dinitrofluorobenzene (DNFB) to irradiated or AA-treated skin induces antigen-specific tolerance. Indomethacin (IM), a cyclooxygenase inhibitor, administered orally to mice prior to UVB irradiation or prior to the topical application of arachidonic acid, abrogates suppression of contact hypersensitivity (CHS) to DNFB. This suggests a byproduct of arachidonic acid generated through the cyclooxygenase pathway may be involved in the immune suppression. Topical application of various prostaglandins (PGE2, PGD2, PGF2 alpha, and CTXA2) did not cause alterations in the population density of the identifiable Ia+ dendritic Langerhans cells. PGE2, but no other tested agent, produced a suppression of the CHS response to DNFB. These observations suggests that of the various prostaglandins, PGE2 might be one of several biochemical signals which mediate the suppression of contact hypersensitivity reactions following ultraviolet radiation exposure. However, the mechanisms by which PGE2 produces its suppressive effects have not been identified.

Administration, Topical↗

Prostaglandin E2 and D2 but not MSH stimulate the proliferation of pigment cells in the pinnal epidermis of the DBA/2 mouse.

Epidermal melanocytes proliferate following a variety of physical stimuli, for example, mechanical injury to the skin or exposure to UV radiation. We suggest that some transducer in the epidermis converts the physical modality into a biochemical signal which is responsible for initiation of mitosis. Melanocyte stimulating hormone, both alpha and beta variants, administered parenterally for periods up to 4 weeks do not alter the number of melanocytes per mm2 in several strains of neonatal or adult mice. Ultraviolet B and arachidonic acid both stimulate proliferation of pigment cells. Indomethacin which inhibits cyclooxygenase and the formation of prostaglandins (PGs) blocks the proliferation induced by both agents. We tested a wide variety of PGs. We observed that PGD2 applied daily to the skin of a mouse causes a small increase in melanocyte density (cells/mm2). PGE2 in similar doses applied topically caused a large increase. PGE2 caused an increase in the uptake of tritiated thymidine by dopa-positive dendritic cells. This indicates that PGE2 stimulated some melanocytes to proliferate. Histologic studies indicate that PGE2 also enhances melanogenesis. PGE2 is synthesized in the skin and affects keratinocytes and Langerhans cells as well as pigment cells. We postulate that it is one compound that can modulate the interaction of these 3 main cells of the epidermis.

Animals↗

Social vulnerability and reactions to caregiving in daughters and daughters-in-law caring for disabled aging parents.

Variables that have been conceptually linked with social vulnerability--income, educational level, employment, cessation of work to provide care, marital status, social support, and health--were used to predict four categories of reaction to caregiving in 159 daughters and daughters-in-law caring for their disabled aging parents. Social support, income, and health best predicted negative reactions to caregiving; social support alone best predicted negative reactions to caregiving; social support alone best predicted feelings of family abandonment, impact on health, and impact on schedule. Compared with daughters and daughters-in-law who had not quit work to provide care, those who had quit work were significantly older, had lower incomes and fewer social supports, and were more involved in care. The results suggest that quitting work may be a precursor to social isolation that places the caregiver at increased risk for social vulnerability and negative reaction to caregiving. The implications of the findings for health care policy are discussed.

Aged↗

Comparison of closed and open kinetic chain exercise in the anterior cruciate ligament-deficient knee.

The purpose of this study was to quantify the amount of anterior tibial displacement occurring in anterior cruciate ligament-deficient knees during two types of rehabilitation exercises: 1) resisted knee extension, an open kinetic chain exercise; and 2) the parallel squat, a closed kinetic chain exercise. An electrogoniometer system was applied to the anterior cruciate ligament-deficient knee of 11 volunteers and to the uninvolved normal knee in 9 of these volunteers. Anterior tibial displacement and the knee flexion angle were measured during each exercise using matched quadriceps loads and during the Lachman test. The anterior cruciate ligament-deficient knee had significantly greater anterior tibial displacement during extension from 64 degrees to 10 degrees in the knee extension exercise as compared to the parallel squat exercise. In addition, the amount of displacement during the Lachman test was significantly less than in the knee extension exercise, but significantly more than in the parallel squat exercise. No significant differences were found between measurements in the normal knee. We concluded that the stress to the anterior cruciate ligament, as indicated by anterior tibial displacement, is minimized by using the parallel squat, a closed kinetic chain exercise, when compared to the relative anterior tibial displacement during knee extension exercise.

Adolescent↗