Treatment of infantile spasms with high-dose oral prednisolone.
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Administration, Oral↗
Biomedical subjects
J Osborne
Publications and source records attributed to J Osborne.
Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34.
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by the widespread development of distinctive tumors termed hamartomas. TSC-determining loci have been mapped to chromosomes 9q34 (TSC1) and 16p13 (TSC2). The TSC1 gene was identified from a 900-kilobase region containing at least 30 genes. The 8.6-kilobase TSC1 transcript is widely expressed and encodes a protein of 130 kilodaltons (hamartin) that has homology to a putative yeast protein of unknown function. Thirty-two distinct mutations were identified in TSC1, 30 of which were truncating, and a single mutation (2105delAAAG) was seen in six apparently unrelated patients. In one of these six, a somatic mutation in the wild-type allele was found in a TSC-associated renal carcinoma, which suggests that hamartin acts as a tumor suppressor.
Amino Acid Sequence↗
The future of nurse education.
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Education, Nursing, Baccalaureate↗
Student nurses on the Internet.
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Computer Communication Networks↗
Model still needed for defining and evaluating quality of ambulatory care education.
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Ambulatory Care↗
Access to care in regionalized health care systems.
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Canada↗
Missed appointments and Medicaid managed care.
OBJECTIVES: To compare the demographic characteristics of patients who miss appointments with those who do not and to identify subgroups who would benefit from specific interventions for improving attendance. DESIGN: Retrospective cohort study of an 18-month period. SETTING: An urban primary care practice. PATIENTS: A random sample (N = 477) of patients who were seen at least twice during the study period. MAIN OUTCOME MEASURES: Number of missed visits and kept visits, insurer, age, sex, race, ZIP code, and diagnoses. RESULTS: Of the established patients, 48% missed 1 or more visits. Patients in managed care programs, private and Medicaid, were likely to have missed more visits during the study period than those not in managed care programs (P < .001). Medicaid managed care patients had also scheduled more visits. Significantly higher rates of missed appointments were found in patients aged 19 to 35 years (P = .02), blacks (P < .001), patients in Medicaid managed care programs (P < .001), and patients who scheduled more visits (P < .001). After adjusting for age, race, and sex, Medicaid managed care insurance remained a significant (P < .01) predictor of rate of missed appointments. CONCLUSIONS: Patients in managed care programs missed more appointments. Patients in Medicaid managed care programs scheduled more appointments and had higher rates of missed appointments than their counterparts in other insurance groups.
Adult↗
Nippostrongylus brasiliensis: cytokine responses and nematode expulsion in normal and IL-4-deficient mice.
Infection with the nematode, Nippostrongylus brasiliensis, results in a Th2-dominated immune response. We describe the dynamics of this response in both local and systemic environments. Th2-type responses were evident first in the mesenteric lymph node, with parasite antigen-specific proliferation and IL-4/IL-5 release peaking at Days 7-9 postinfection, shortly before expulsion of the adult worms from the gut. IFN-gamma responses were not observed in the mesenteric lymph node. Responses in the spleen generally followed those in the mesenteric lymph nodes by 2-3 days and showed a greater degree of Th1-type cytokine production. N. brasiliensis was shown to be a powerful inducer of IL-4 responses with as few as six infective N. brasiliensis larvae eliciting IL-4 production in the mesenteric lymph node, but only high doses of larvae (600) elicited IL-4 secretion in the spleen. Similar levels of IL-4 production by lymph node cells stimulated with Con A or parasite antigen postinfection indicated the extent of polyclonal Th2 stimulation by this parasite. Infection of IL-4-deficient mice showed that despite the absence of IL-4-dependent Th2 responses, these mice were able to curtail egg production and expel adult N. brasiliensis in a time frame similar to that of fully immunocompetent animals. These results emphasize the magnitude of the Th2 response to N. brasiliensis and also show that IL-4 is not a prerequisite for the development of immunity to N. brasiliensis.
Animals↗
Bilingual hearing acquisition in Welsh and English following cochlear implantation.
A post lingually deafened adult equilingual in Welsh and English, receive rehabilitation in both languages following cochlear implantation. Hearing acquisition was very similar in both languages, indicating that there is no need to vary the electrode coding strategy for different languages of Indo-European origin. The situation may be difficult for tonal languages such as Chinese.
Cochlear Implants↗
Stimulation of the hypothalamo-pituitary-adrenal axis in the rat by the type 4 phosphodiesterase (PDE-4) inhibitor, denbufylline.
1. Preliminary studies in our laboratories showed that the synthetic xanthine analogue denbufylline, a selective type 4 phosphodiesterase (PDE-4) inhibitor, is a potent activator of the hypothalamo-pituitary-adrenal (HPA) axis when given orally to adult male rats. This paper describes the results of experiments in which well established in vivo and in vitro models were used to (a) examine further the effects of denbufylline on HPA function and (b) identify the site and mode of action of the drug within the axis. 2. In vivo, administration of denbufylline (0.1-2.5 mg kg-1, i.p.) produced a significant increase in the serum corticosterone concentration; maximal responses were attained at a dose of 1.0 mg kg-1 (P < 0.01 vs. vehicle control, Scheffe's test). However, when denbufylline was administered by intracerebroventricular injection (0.05-1 micrograms kg-1) it failed to influence significantly the serum corticosterone concentration (P > 0.05 vs. vehicle control, Scheffe's test). The adrenocortical responses to peripheral injections of denbufylline (1 mg kg-1, i.p.) were reduced in rats in which the secretion of endogenous corticotrophin releasing factors (CRFs) from the hypothalamus was blocked pharmacologically (P < 0.01 vs. controls, Scheffe's test). However, denbufylline (0.1 mg kg-1, i.p.) potentiated the significant (P < 0.01) increases in serum corticosterone concentration provoked in "CRF blocked rats' by hypothalamic extract (5 hypothalamic extracts kg-1, i.v.) although it failed to influence (P > 0.05) the relatively moderate increases in corticosterone secretion evoked by CRH-41 (2 mg kg-1, i.v.). 3. In vitro, denbufylline (0.01-1 mM) evoked small but significant (P < 0.05) increases in the release of ACTH from rat anterior pituitary segments; furthermore, at these and lower concentrations (0.01 microM-1 mM), it potentiated the adrenocorticotrophic responses to sub-maximal concentrations of hypothalamic extract (P < 0.01) and forskolin (0.1 mM, P < 0.01) but not those to CRH-41 (10 nM) or 8-bromo-cyclic AMP (1-100 microM). In addition, denbufyline (0.1 mM) increased the anterior pituitary cyclic AMP content (P < 0.05) and potentiated the rises in tissue content of the cyclic nucleotide induced by hypothalamic extract (0.1 hypothalamic equivalents ml-1, P < 0.01) and forskolin (0.1 mM, P < 0.01) but not by CRH-41 (10 nM, P < 0.05). By contrast, denbufylline (1 microM-1 mM) failed to influence the release of AVP from rat isolated hypothalami and stimulated the secretion of CRH-41 (P < 0.01) release only at the highest concentration tested (1 mM). 4. The results suggest that the stimulatory actions of denbufylline on the hypothalamo-pituitary-adrenocortical axis are exerted predominantly at the level of the anterior pituitary gland and that they may be attributed, at least in part, to inhibition of type 4 phosphodiesterase enzymes.
Adrenocorticotropic Hormone↗
Anti-interleukin-4 modulation of the Th2 polarized response to the parasitic nematode Brugia pahangi.
Lymphatic filariasis is a chronic disease characterized by a pronounced Th2 bias in the immune response and impaired antigen (Ag)-specific Th1 responses. We have used a mouse model of filariasis to investigate the role of the infective form (the third-stage larvae [L3]) in modulating the immune response. Subcutaneous infection of BALB/c mice with L3 of Brugia pahangi has a profound effect on Th cell function. By day 12 post-infection, spleen cells from these mice exhibited a dramatic reduction in concanavalin A-driven proliferation and interleukin-2 (IL-2) and gamma interferon (IFN-gamma) secretion in comparison with uninfected controls. However, exposure to L3 did not render the mice completely unresponsive; these animals mounted a strong Th2 response to the parasite, characterized by elevated levels of IL-4, IL-5, and IL-10 and parasite-specific serum immunoglobulin G (IgG), IgG1, and IgE. Treatment of spleen cells from L3-infected mice with neutralizing anti-IL-4 or recombinant IL-2 resulted in a dramatic increase in concanavalin A-induced proliferation and IL-2 and IFN-gamma production. Despite their defective polyclonal Th1 response, cells from L3 infected mice proliferated when stimulated with Ag, and this response was blocked by anti-IL-4. However, anti-IL-4 treatment failed to induce Ag-specific IL-2 or IFN-gamma production, indicating that B.pahangi-primed Th1 cells do not appear to be present or are still unable to respond even in the absence of IL-4.
Animals↗
Pediatric rheumatology in the United Kingdom: data from the British Pediatric Rheumatology Group National Diagnostic Register.
OBJECTIVE: To establish a computerized national diagnostic register for pediatric rheumatology in the UK; to describe the demography and diagnostic classification of children referred to pediatric rheumatology clinics; to estimate the current incidence of juvenile arthritis (JA) in the UK. METHODS: A diagnostic register was established in 1989: 23 centers have contributed data on all new cases seen since they joined the register; 18 centers have also contributed data on all current attenders. For 2 centers with well defined catchment areas, the incidence of JA was estimated. RESULTS: A total of 4948 cases were registered, of whom 2962 (60%) were female. 1991 (40%) had a diagnosis of JA. The 2nd largest category was mechanical/orthopedic problems (24%). Pauciarticular juvenile chronic arthritis was the most common subtype of JA. Seropositive RA was rare. Tertiary referral centers saw proportionately more JA and district general hospitals saw proportionately more mechanical problems. The annual incidence rate for JA from 2 centers was 10/100,000, and for all rheumatic disorders was 32-42/100,000 children under age 16. CONCLUSION: The relative proportion of patient diagnoses varies between centers. Nevertheless, the incidence of hospital referred JA seems very uniform.
Adolescent↗
Comparison of lymphokine secretion and mRNA expression in the CD45RA+ and CD45RO+ subsets of human peripheral blood CD4+ and CD8+ lymphocytes.
Flow cytometric analysis of human peripheral blood T lymphocytes demonstrated that the majority of the CD4+ cells were CD29+ or CD45RO+ "mature" cells while the CD8+ cells were primarily CD45RA+ "native" cells. After an initial separation into CD4+ and CD8+ cells and a secondary separation into CD45 subsets, lymphokine secretion was assessed after phorbol 12-myristate 13-acetate and ionomycin or fixed anti-CD3 stimulation. Within the respective CD45 subsets, CD4+ cells produced more interleukin (IL)-2, IL-4, and IL-6; but the CD8+ cells secreted more interferon-gamma and granulocyte/macrophage-colony-stimulating factor. Tumor necrosis factor-alpha secretion was similar in the matched CD45 subsets. Northern analysis revealed a parallel pattern of lymphokine mRNA expression in the four lymphocyte subsets. These results suggest that human CD8+ peripheral blood lymphocytes have a significant capacity to secrete lymphokines, and that the low lymphokine production observed in unseparated CD8+ cells reflects the higher percentage of less functional CD45RA+ cells.
CD3 Complex↗
CD8+ and CD45RA+ human peripheral blood lymphocytes are potent sources of macrophage inflammatory protein 1 alpha, interleukin-8 and RANTES.
The chemokines macrophage inflammatory protein 1 alpha (MIP 1 alpha), interleukin-8 (IL-8) and RANTES are potent regulators of leukocyte trafficking. Examination of chemokine secretion by human peripheral blood lymphocytes after stimulation with anti-CD3 or phorbol 12, 13 myristate acetate and ionomycin showed CD8+ cells were the dominant source of MIP 1 alpha and RANTES. Although production of MIP 1 alpha and IL-8 were similar in pharmacologically stimulated CD4+ CD45RA+, CD4+ CD45RO+, and CD8+ CD45RA+ cells, the largest amounts of MIP 1 alpha and RANTES were secreted by CD8+ CD45RO+ lymphocytes. A parallel pattern of prolonged chemokine mRNA expression for at least 18 h after activation was observed in the T cells subsets. These results confirm that human T lymphocytes have a unique capacity for secretion of these three chemokines. In addition, CD8+ cells have an unrecognized role in recruiting cells to sites of inflammation, and adult human CD45RA+ cells have a physiologically significant secretory capacity.
Blotting, Northern↗
Vasorelaxant and second messenger effects of maxadilan.
Maxadilan is a potent vasodilator isolated from salivary gland extracts of the sand fly. Although cutaneous vasodilatation is probably the most important physiologic effect of maxadilan (i.e., assisting the sand fly in obtaining a blood meal), it also has effects on other vascular beds. In rabbit isolated aorta, recombinant maxadilan exhibited endothelium-independent relaxations with an IC50 of 24 nM for norepinephrine-induced (1 microM) contractions. Synthetic maxadilan had one-third the potency, with a corresponding IC50 of 74 nM for norepinephrine-induced (1 microM) contractions. Pretreatment with a number of receptor and channel blockers, including tetraethylammonium (1 mM), glyburide (1 microM), barium (0.5 mM), indomethacin (10 microM), propranolol (10 microM), cimetidine (10 microM) and nifedipine (10 microM) did not affect maxadilan-induced relaxations. After treatment with maxadilan, contractions recurred very slowly over approximately 40 min. At a concentration of 1 microM, maxadilan induced a 2- to 3-fold increase in cellular cyclic AMP levels. Maxadilan's activity was selective according to vessel type, with maximal activity in rabbit aorta and mesenteric artery and no activity in porcine and bovine coronary arteries. These studies suggest that maxadilan acts by raising the intracellular levels of cyclic AMP in the smooth muscle of selected blood vessels.
Animals↗
Adult and microfilarial stages of the filarial parasite Brugia malayi stimulate contrasting cytokine and Ig isotype responses in BALB/c mice.
Natural infection with filarial nematode parasites shows many characteristics of a Th2 immune response. In these infections, long-lived adult worms inhabit the lymphatics, releasing laval microfilariae (Mf) into the blood stream. To compare the effect of these different developmental stages on the mammalian immune system, Mf and adult worms of either sex were implanted into BALB/c mice, in which they survive for at least 28 days. Serum Ab responses showed that whereas Mf stimulated specific Abs of all IgG subclasses, but little total IgE, adult worms stimulated only IgG1 and IgE responses. Splenocytes from implanted mice were stimulated in vitro with specific Ag or Con A and assayed for proliferation and profiles of cytokine secretion. Cells from Mf-infected mice secreted high levels of IFN-gamma (30 U/ml) throughout infection, but very little IL-4 at the early time points. By day 28 postinfection, however, splenocytes from Mf-infected mice showed some IL-4 secretion in response to specific Ag (40 U/ml). The IFN-gamma response to Mf was found to be independent of the inoculum dose in the range of 10(2) to 10(6) organisms. In contrast, splenocytes taken from adult worm-implanted mice on days 14, 21, and 28 postinfection produced high levels of IL-4 (up to 435 U/ml) and negligible amounts of IFN-gamma despite the production of large numbers of Mf by adult female worms. CD4+ cells were primarily responsible for this IL-4 production. These results demonstrate that adult filarial parasites, and females in particular, exert a rapid polarization of the immune response in a Th2-like direction, but that this effect may be modulated by the Mf stage.
Age Factors↗
A video-fluoroscopic study of patients treated by diverticulectomy and cricopharyngeal myotomy.
Although the short- and long-term results of surgical procedures for treatment of posterior pharyngeal diverticula are well documented, their effect on normal swallowing has not been extensively investigated. The aim of this study was to assess the changes in swallowing that occur after diverticulectomy with cricopharyngeal myotomy. Fifteen patients who underwent surgery in the previous 10 years were interviewed, examined and underwent a video-fluoroscopic barium swallow. Frame to frame analysis of the barium studies showed a multitude of abnormalities, even amongst those who were asymptomatic. Excision of a pharyngeal pouch does not appear to restore a normal swallowing mechanism.
Aged↗
Can audit improve the quality of care for routine tonsillectomy?
Tonsillectomy is the most commonly performed operation in otolaryngology practice. In order to assess outcome and improve quality of care, 65 patients were asked to answer a post-operative questionnaire. The questionnaire was then audited and patient management changed. Following this, another group of 65 patients revealed, in the same questionnaire, a significant improvement in care.
Adolescent↗