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Biomedical subjects

C Ward

Publications and source records attributed to C Ward.

At least 73 records · Page 4Linked to original sources

Role of neutrophil apoptosis in the resolution of pulmonary inflammation.

Neutrophil-mediated lung injury may result from one or more of the following possible causes: 1) loss of the normal mechanisms that regulate and switch off neutrophil influx, 2) inappropriate or uncontrolled neutrophil activation within the lung, 3) inhibition of neutrophil apoptosis, and 4) impairment or saturation of the normal macrophage-dependent process for the removal of apoptotic neutrophils. Current in vitro data indicate that many factors operating at the inflamed site (e.g. cytokines, growth factors, chemotactic peptides, hypoxia, acidosis, etc.) serve a dual function in both priming and activating these cells, and delay apoptosis. The observation that the rate of eosinophil apoptosis can be accelerated by corticosteroid therapy in vivo suggests a novel mode of action for this drug and indicates that targeting this process in other granulocyte-dependent inflammatory conditions may offer a novel therapeutic approach in inflammatory lung disease.

Animals↗

Furcation depth and interroot separation dimensions for 5 different tooth types.

The purpose of this study was to document mean, standard deviation, and range of furcation depth and Interroot separation dimensions of 5 multirooted tooth types. A total of 412 extracted teeth were examined and classified as: maxillary first molar, maxillary second molar, maxillary first premolar, mandibular first molar, and mandibular second molar. The furcation depth was measured at the level of the furcation dome and 3 and 5 mm apical to the dome. Interroot separation was measured 3 and 5 mm apical to the furcation dome. Mean furcation depth at the dome was 7.48 mm buccally and 6.67 mm mesiodistally for maxillary first molars; 6.69 mm buccally and 5.94 mm mesiodistally for maxillary second molars; 3.54 mm mesiodistally for maxillary first premolars; 7.96 mm buccolingually for mandibular first molars; and 7.46 mm buccolingually for mandibular second molars. Interroot separation dimensions 3 mm apical to the dome were: 2.58 mm buccally, 4.17 mm mesially, and 4.48 mm distally for maxillary first molars; 1.92 mm buccally, 3.89 mm mesially, and 4.04 mm distally for maxillary second molars; 2.47 mm mesially and 2.58 mm distally for maxillary first premolars; 3.15 mm buccally and 2.95 mm lingually for mandibular first molars; and 2.54 mm buccally and 2.75 mm lingually for mandibular second molars.

Bicuspid↗

New specimens and confirmation of an early age for Australopithecus anamensis.

The discovery of Australopithecus anamensis fossils from strata lying between tephra dated at 4.17 and 4.12 million years ago, and from slightly higher strata not well constrained in age by overlying dated units, provoked the claim that more than one species might be represented: it was suggested that the stratigraphically higher fossils, which include the important tibia, humerus and a large, presumed male, mandible (KNM-KP 29287), might belong to a later, more derived hominid. We have recovered new fossils from Kanapoi and Allia Bay, Kenya, during field work in 1995-1997 that confirm the primitive status of Australopithecus anamensis, the earliest species of Australopithecus. Isotope dating confirms A. anamensis' intermediate age as being between those of Ardipithecus ramidus and Australopithecus afarensis. New specimens of maxilla, mandible and capitate show that this species is demonstrably more primitive than A. afarensis. A lower first deciduous molar (dm 1) is intermediate in morphology between that reported for Ardipithecus ramidus and A. afarensis. Single-crystal 40Ar-39Ar age determinations on the Kanapoi Tuff show that, except for a large mandible, all of the hominid fossils from Kanapoi are from sediments deposited between 4.17+/-0.03 and 4.07+/-0.02 million years ago.

Animals↗

Differential regulation of allergen-specific T(H2)- but not T(H1)-type responses by alveolar macrophages in atopic asthma.

BACKGROUND AND OBJECTIVE: Previous studies have suggested that quantitative differences in TH2-type cytokine responses in the airways are of particular importance in the pathogenesis of asthma. In this study we investigated whether alveolar macrophages (AMs) and peripheral blood monocytes (PMNs) are able to significantly influence the profiles of allergen-induced TH1 (IFN-gamma) and TH2 (IL-4 and IL-5) cytokine production by CD4+ T cells in atopic asthmatic subjects versus atopic nonasthmatic subjects and nonatopic normal subjects. METHODS: Peripheral blood CD4+ T cells were cultured alone or cocultured with either PMNs or AMs with allergen stimulation in the 3 groups. RESULTS: Although allergen stimulation did not change TH1 or TH2 cytokine responses in cultures of CD4+ T cells alone, the addition of PMNs to the cultures induced a significant increase in production of IL-4, IL-5, and IFN-gamma (P < .01 or P < .001) in atopic asthmatic subjects and atopic nonasthmatic subjects. However, PMNs induced a significant increase for IFN-gamma (P < .05) only in normal subjects. AMs from atopic asthmatic subjects significantly enhanced production of all 3 cytokines (P < .01 or P < .001), whereas the AMs from atopic nonasthmatic subjects significantly increased only production of IL-4 (P < .01) and IFN-gamma (P < .05) but not IL-5. Furthermore, IL-4 (P = .066) and IL-5 (P < .01) production in allergen-stimulated AM-CD4+ cell cocultures was higher in atopic asthmatic subjects but significantly lower in atopic nonasthmatic subjects (P < .05) as compared with the PMN-cocultures. For IFN-gamma, no difference was found between the AM and PMN cocultures in either atopic group. Allergen-stimulated IL-5 production in coculture with both AMs and PMNs inversely correlated with both baseline FEV1 percent predicted and PD20 methacholine in atopic asthmatic subjects (P < .05, P < .01, or P < .001). CONCLUSION: These data suggest that AMs from atopic asthmatic subjects but not atopic nonasthmatic subjects, play a significant role in airway pathogenic immunity through enhancing TH2-type cytokine production.

Adolescent↗

The frequency and clinical significance of specific IgE to both wasp (Vespula) and honey-bee (Apis) venoms in the same patient.

BACKGROUND: Changeover from Phadebas RAST to Pharmacia AutoCAP increased double-positivity to both honey-bee and common wasp (vespula) venom in our patients. OBJECTIVE: We examined the frequency of IgE double-positivity, its clinical relevance and utility in investigating potentially allergic patients. METHODS: One hundred and eighty-two patients with hymenoptera allergy were tested using RAST (n = 51) and AutoCAP (n = 131) assays over 4 years. Patients had a history of reactions to vespulae (22), honey-bee (10) and unidentified hymenoptera (vespinae) (7). RESULTS: After changing from RAST to AutoCAP double-positivity increased from 10 (5/ 51) to 30% (39/131) (P < 0.01). RAST and CAP assays gave similar median class results (vespula = 3, honey-bee = 2). Thirty-six CAP patients had systemic reactions of Mueller grade II and above. In vespula-allergic double-positive subjects, high CAP classes (> or = class 3) to honey-bee were common (30%). In 25% the CAP classes were equal. In honey-bee-allergic subjects, all vespula venom CAP IgE was low titre (class 1 or 2) and 20% were equal for both venoms. In 43% of vespinae-allergic patients the CAP class was equal to both (class 2 and 3). In contrast, intradermal skin test double-positivity was uncommon. Double-negative skin test results were common in the CAP double-positive population (22% of honey-bee-allergic, 13% of vespula-allergic and 43% of vespinae-allergic patients). Vespula allergic patients have higher bee-venom IgE than vice versa. Twenty-seven per cent of CAP double-positive patients (representing 8% of all venom allergic patients tested over this period) had equal class IgE to both venoms which was not helpful in diagnosis. Combination of skin testing and CAP is unhelpful in only 5/37 (14%) of patients with double-positive serology. CONCLUSION: If used in isolation CAP may be misleading, especially if only one venom is tested. Identification of the causative venom must utilize both clinical history and skin testing in these double-positive patients, and challenge testing if indicated.

Adolescent↗

Alveolar macrophages from atopic asthmatics, but not atopic nonasthmatics, enhance interleukin-5 production by CD4+ T cells.

Recent studies have demonstrated that different antigen-presenting cell (APC)-related factors in the microenvironment of a T cell may determine its profile and quantity of cytokine expression and production. We have therefore examined the effects of alveolar macrophages and peripheral blood monocytes on interleukin (IL)-5 production by peripheral blood CD4+ T cells from atopic people with asthma (AA), atopic people without asthma (AN), and nonatopic normal subjects (N). In response to allergen stimulation, IL-5 production was significantly enhanced by the addition of monocytes to CD4+ cell cultures in AA and AN patients (p < 0.05 and 0.01, respectively), but not in N subjects. In mitogen-stimulated CD4+ cell plus monocyte cocultures, there was a small increase in IL-5 production in all three groups (p < 0.05 for AN). In contrast, the addition of alveolar macrophages to parallel cultures significantly amplified IL-5 production only in AA patients (p < 0.05 or 0.01). Furthermore, IL-5 production by CD4+ cells in alveolar macrophage cocultures, stimulated by allergen or mitogen, was higher than that in monocyte cocultures in AA patients (p < 0.05). Conversely, in AN and N subjects, the IL-5 values for alveolar macrophage cocultures were lower than those for peripheral blood monocytes. In blocking studies, antibodies against IL-1alpha, IL-1beta, IL-6, or tumor necrosis factor-alpha differentially suppressed macrophage-enhanced IL-5 production (p < 0.05 for IL-1beta and IL-6) and expression of the activation marker CD25 (p < 0.05 for IL-1alpha and IL-6) by allergen-stimulated CD4+ cells in AA patients. These observations suggest that alveolar macrophages influence the quantity of IL-5 production by T cells in the airways and, as a consequence, the development of asthma in atopic individuals.

Adult↗

Endobronchial biopsy and bronchoalveolar lavage in stable lung transplant recipients and chronic rejection.

We have obtained endobronchial biopsies (EBB), bronchoalveolar lavage (BAL), and transbronchial biopsies (TBB) in 17 stable lung transplant recipients (sLTR), 8 subjects with physiologic evidence of chronic rejection (BOS), and 9 normal subjects. A striking finding was the marked neutrophilia in BAL samples from patients with BOS, in the carefully screened absence of infection. A statistically higher neutrophil count was also present in the sLTR group relative to the normal group. Median BAL neutrophil count in BOS was 100 x 10(3)/ml, range 13-1,661 10(3)/ml (p < 0.001 relative to normal subjects and sLTR). Median BAL neutrophil count in sLTR was 7 x 10(3)/ml, range 1-81 10(3)/ml (p < 0.01 relative to normal subjects). Normal subjects had a median BAL neutrophil count of 3 x 10(3)/ml, range 1-7 10(3)/ml. There was evidence of a predominance of CD8 lymphocytes in BAL from sLTR and BOS with a lower CD4/CD8 ratio in both compared to normal subjects (p < 0.05). EBB mononuclear cell counts, class II major histocompatibility complex expression, and T-cell activation markers were normal in BOS, in contrast to the sLTR group. Our data may be consistent with BOS, representing a relative resolution of an active mononuclear cell chronic inflammation, perhaps at the expense of airway fibrosis. The relevance of the BAL neutrophilia and its role in BOS pathogenesis need further longitudinal investigation.

Adult↗

Risperidone for the treatment of behavioral disturbances in dementia: a case series.

The authors describe a series of 22 patients with dementia and behavioral disturbances, including agitation, aggression, delusions, and hallucinations, who were treated with risperidone. Risperidone, in low doses, was well tolerated; 50% of patients experienced significant improvement, although 50% experienced some extrapyramidal symptoms.

Aged↗

The role of atropine premedication in fiberoptic bronchoscopy using intravenous midazolam sedation.

OBJECTIVE: Atropine premedication is widely used for fiberoptic bronchoscopy and may help by drying secretions, producing bronchodilatation, or preventing vasovagal reactions. The objective of this study was to see whether atropine premedication is really of practical benefit when patients are sedated with i.v. midazolam. DESIGN: In a double-blind study, patients were randomly allocated to receive i.m. atropine (0.6 mg) or saline placebo (1 mL) as premedication 30 to 60 minutes before they were sedated with progressive doses of i.v. midazolam until judged to be lightly asleep. SETTING: A District General Hospital in England. PARTICIPANTS: One hundred consecutive patients referred for bronchoscopy. MEASUREMENTS AND RESULTS: Samples taken during the procedure were washings for microbiology and cytology and brushings for cytology and biopsy, but no transbronchial biopsies. Peak flow readings were recorded before premedication and before the start of the procedure. During the procedure an estimate was made of pharyngeal and tracheobronchial secretions, bleeding, use of saline to wash out secretions, and local anesthetic needed to control coughing. Patients were monitored for saturation and cardiac rhythm. There was no significant bronchodilatation after premedication in either group, nor were there differences in secretions, use of saline, tracheobronchial bleeding, desaturation, and arrhythmias. More local anesthetic was needed to control coughing in the placebo group (mean 357 mg vs 331 mg in the atropine group, p=0.02), but this was not of practical significance. CONCLUSION: When intravenous midazolam sedation is used for bronchoscopy, atropine premedication is not of benefit.

Atropine↗

The treatment of craniosynostosis: an ethical perspective.

The parents of children with craniofacial deformity have expectations that cannot always be reasonably met in a world of clinical uncertainty. In order to bridge the "reality gap," the members of the cranofacial team must be open and honest in discussing the known harms and benefits of a proposed treatment, so that a relationship of trust evolves between the health care professional and the patient/parent. It is only through this trust that a truthful implementation of consent, within its moral framework, can be achieved. This, in turn, requires an analysis of the outcomes of the various options for treatment as well as evidence that the cranofacial team is able to provide high standards of care. All this leads to the ethical imperative of respecting the right of parents to make an informed choice and allowing them to see that their child is treated in a way that provides maximum benefit and minimum harm.

Child↗

Caring by degrees.

Caring is synonymous with nursing and, regardless of the culture, race, lifestyle or sexuality of clients, nurses should care for all clients. However, the emergence of HIV/AIDS brought a new and quite different challenge to nurses with regard to willingness to care. Some nurses expressed a negative attitude toward, and reluctance to care for, those clients with HIV/AIDS, mainly due to fear of contagion based on ignorance about the disease. The purpose of this cross-sectional study was firstly to determine if there were differences in attitudes toward caring for clients with HIV/AIDS in the three different at-risk groups (homosexuals, intravenous drug users and haemophiliacs), as expressed by nursing students at the beginning (Semester 1) and at the end (Semester 7) of a three-and-a-half-year nursing degree programme. The second determination was whether or not there were differences between the two groups of students regarding their knowledge of HIV/AIDS. Data results indicated no significant difference between the two groups of students in regard to caring attitude towards members of the at-risk groups and knowledge of AIDS. This paper discusses the implications of the research findings for nursing and further research.

Acquired Immunodeficiency Syndrome↗

Arylsulphatase A pseudodeficiency in vascular dementia and Alzheimer's disease.

The carrier rates of a genetic marker for arylsulphatase A pseudodeficiency (ASA-PD) were determined in three series of patients with vascular dementia (VaD) or Alzheimer's disease (AD). In the first community-based sample, the 1524 + 95A-->G mutation, which is known to be associated with ASA-PD, was present in 35% of VaD cases and none of the AD cases. In a second sample of cases drawn from a Dementia Register, the mutation rates were 18% (VaD) and 16% (AD). Brain DNA from a post-mortem sample revealed the ASA-PD mutation in 60% of VaD cases and 34% of AD cases. These rates are higher than previous studies of culturally similar populations and suggest that ASA-PD may be a risk factor for dementia.

Adenine↗

The antihypertensive efficacy of the novel calcium antagonist mibefradil in comparison with nifedipine GITS in moderate to severe hypertensives with ambulatory hypertension.

Mibefradil is a novel calcium antagonist that blocks selectively the T-type calcium channels. In this double-blind forced titration study design we compared the effects of mibefradil 50, 100, and 150 mg and nifedipine GITS 30, 60, and 90 mg monotherapies or combined with lisinopril 20 mg in 71 moderate to severe hypertensives (59 men and 12 women) with confirmed ambulatory hypertension. An incremental dose-response effect was observed both in clinic and ambulatory blood pressure parameters during treatment with mibefradil and nifedipine GITS alone and combined with lisinopril. At maximal dosage, patients treated with mibefradil experienced a greater (P < .05) reduction in clinic and ambulatory diastolic blood pressures as well as a greater response rate (86% v 69%). Trough:peak ratios for systolic and diastolic blood pressures were > 90% at each dose level. Significant decrease in baseline heart rate was observed with mibefradil 150 mg alone or combined with lisinopril, but no patients experienced clinically significant atrioventricular conduction abnormalities. Adverse events related to vasodilation were more prevalent in the nifedipine GITS group. Consequently, the results of the present study demonstrate that the novel calcium channel blocker mibefradil, either alone or in combination with lisinopril, is effective in reducing clinic and 24-h blood pressures while decreasing heart rate and is well tolerated in patients with moderate to severe hypertension.

Adult↗

Allergen-induced airway reactions in atopic asthmatics correlate with allergen-specific IL-5 response by BAL cells.

Allergen-specific cytokine responses in the airways are thought to play a critical role in the pathogenesis of atopic asthma. This study examined whether there is a quantitative difference in bronchoalveolar lavage (BAL) cell allergen-induced IL-5 production between atopic subjects with and without asthma which may relate to a difference in airway response induced by allergen exposure. Twelve atopic asthmatics (AA), nine atopic non-asthmatics (AN) and 10 normal controls (N) underwent inhalation challenge with house dust mite allergen (HDM) extract. AA differed from AN in having late airway reactions (LAR) after HDM inhalation (P < 0.01), which correlated with an increased percentage of BAL eosinophils and increased BAL cell IL-5 production after in vivo or in vitro HDM challenge for the AA group (P < 0.01). IL-5 production by PBMC from both atopic groups was elevated with HDM stimulation in vitro, but AA again had a higher level under baseline conditions than AN (P < 0.02). Furthermore, there was a greater effect of BAL fluid from AA on ECP release by eosinophils compared to that for AN (P < 0.01). These findings suggest that increased IL-5 production in atopic asthmatic airways contributes to the increased physiological response to allergen inhalation, by modulating local eosinophil recruitment and activation.

Adult↗