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Biomedical subjects

C Kelly

Publications and source records attributed to C Kelly.

At least 37 records · Page 2Linked to original sources
PubMed2003

Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children.

Airway inflammation in asthma is not measured routinely in clinical practice. Fractional exhaled nitric oxide (FE(NO)), a marker of airway inflammation, is increasingly used as an outcome measure in asthma intervention studies and yet the reproducibility of FE(NO) measurements is unknown. The reproducibility, day-to-day, diurnal variation and perception of standardised FE(NO) measurements were examined in 59 subjects (40 children aged 7-13 yrs and 19 adults aged 18-60 yrs), both healthy (n=30) and with mild (n = 29) asthma. FE(NO) was measured on five consecutive days (four measurements on the same day) for adults and twice on the same day for children. The coefficient of reproducibility expressed as the mean pooled standard deviation (n = 59, 675 estimations) was 2.11 parts per billion (ppb) and intraclass correlation coefficient was 0.99 in both children and adults. FE(NO) was significantly higher in asthma subjects (32.3 ppb) than in healthy subjects (16.3 ppb). There was no diurnal or day-to-day variation, or a learning effect, as the result of FE(NO) measurements were identical at results of the beginning and at the end of the study. It was concluded that fractional exhaled nitric oxide measurements are simple, reproducible, free from diurnal and day-to-day variation, and acceptable by both healthy and asthmatic adults and children, as a part of their routine visit to a physician.

Adult↗
PubMed2003

Seventh International Meeting of the European Laboratory Working Group on Diphtheria - Vienna, June 2002.

The Seventh International Meeting of the European Laboratory Working Group on Diphtheria (ELWGD) was held in Vienna, Austria in June 2002 and brought together the microbiologists and epidemiologists responsible for diphtheria in many countries throughout the world. The ELWGD was formed in 1993 in response to the epidemics of diphtheria in Russia and the Newly Independent States (NIS) of the former Soviet Union (1,2). These epidemics, and others elsewhere, highlighted the importance of strengthening and maintaining both epidemiological surveillance and reliable laboratory screening. Since December 2001, these areas have been progressed and strengthened by European Commission (EC) funding to undertake a feasibility study for diphtheria surveillance amongst European Union (EU) member states and accession countries, and to establish a definitive and official European diphtheria surveillance network called DIPNET (EC DG SANCO Agreement No. S12.324473 (2001 CVG4-012)). This was the first international meeting of the ELWGD to be organised and funded under the auspice of the DIPNET (European Diphtheria Surveillance Network).

Adolescent↗
PubMed2002

Radiotherapy versus open surgery versus endolaryngeal surgery (with or without laser) for early laryngeal squamous cell cancer.

BACKGROUND: Radiotherapy, open surgery and endolaryngeal excision (with or without laser) are all accepted modalities of treatment for early stage glottic cancer. Case series suggest that they confer similar survival advantage. Opinions on optimal therapy vary across disciplines and between countries. OBJECTIVES: To compare the effectiveness of open surgery, endolaryngeal excision (with or without laser) and radiotherapy in the management of early glottic laryngeal cancer SEARCH STRATEGY: Electronic search of MEDLINE (from 1966 to October 2000), EMBASE (from 1980 to October 2000), CINAHL (from 1982 to October 2000) and CancerLit (from 1963 to October 2000) databases and the Cochrane Controlled Trials Register. SELECTION CRITERIA: Randomised controlled trials (RCT) comparing open surgery, endolaryngeal resection and/or radiotherapy DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed RCTs identified from the electronic searches for eligibility and methodological quality. All authors of the review discussed the results of these assessments. MAIN RESULTS: Only one RCT was identified which compared open surgery and radiotherapy among a substantial number of patients with early glottic laryngeal cancer. REVIEWER'S CONCLUSIONS: There is currently insufficient evidence to guide management decisions on the most effective treatment. Interpretation of the only large scale RCT comparing open surgery and radiotherapy in patients with early glottic cancer is limited because of concerns about the adequacy of treatment regimens and deficiencies in the reporting of the study design and analysis. Endolaryngeal resection of early glottic tumours is becoming more common and a well designed multicentre RCT is warranted.

Carcinoma, Squamous Cell↗
PubMed2002

Peripheral bone density in patients with rheumatoid arthritis and factors which influence it.

INTRODUCTION: Patients with rheumatoid arthritis (RA) frequently possess a number of risk factors for osteoporosis. Additionally, oral steroids are often used to control active rheumatoid disease and may further potentiate bone loss. We wished to establish the degree of peripheral bone loss in RA and to assess the influence of oral steroids and other risk factors. METHODS: We measured bone mineral density (BMD) in the non-dominant forearm using a DTX 200 osteometer in 191 RA patients who were receiving oral prednisone in a dose of at least 5 mg daily for over 3 months. We compared the results with those of two other groups: 165 RA patients who had never received oral prednisone and 242 normal controls without RA or any history of steroid therapy. Forward stepwise multiple regression analysis was used to determine the effects of age, disease variables and steroids on BMD. RESULTS: Age (P<0.001), RA (P<0.02) and steroid therapy (P<0.05) were all associated with reduced BMD using multiple regression analysis. Duration of RA was also associated with reduced BMD (P<0.05), but activity of disease was not. By WHO criteria (BMD T score<-2.5 S.D.), 95 (50%) of the RA steroid-treated patients (RAS) had osteoporosis, while 48 (25%) of the RA patients not exposed to steroids (RAN) were osteoporotic. Among the normal controls (NC), 48 (20%) had osteoporosis. The mean (S.D.) BMD Z scores for the three groups were -0.8 (1.3) for RAS, -0.4 (1.3) for RAN and 0.0 (1.0) for NC (P<0.01 for all differences). The percentages of patients with a Z score of -1 or less were 51% for RAS, 29% for RAN and 14% for NC. These differences were also significant (P<0.01). Male sex was associated with reduced BMD when compared to female sex (Z<-1) in the RAS (57 vs. 49%; P<0.05) but not in the RAN (25 vs. 31%) groups. For men with RA, the mean (S.D.) BMD Z scores were -1.3 (1.3) for RAS compared to -0.5 (1.3) for RAN (P<0.005), while for women the differences were less marked at -0.7 (1.3) for RAS compared to -0.4 (1.3) for RAN (P<0.05). CONCLUSIONS: In general, patients with RA have a significantly reduced forearm BMD, which correlates with increasing disease duration. Exposure to oral steroids increases bone loss, notably in male patients. Patients with RA on oral steroids need BMD measurements with a view to prophylactic therapy in those with a low result. Previous fractures and a daily dose of 15 mg or more of prednisone are also important factors in determining when prophylaxis is indicated.

Journal Article↗
PubMed2002

Homocysteine and occlusive arterial disease.

BACKGROUND: An increased plasma level of homocysteine has been proposed as an independent risk factor for atherosclerosis; this review examines the evidence. METHODS: A Medline search was undertaken for English language articles on homocysteine and vascular disease. Further papers were identified by cross-referencing from the reference lists of relevant major articles. RESULTS: Although much interest has been generated about homocysteine and atherosclerotic disease, contradictory data exist regarding its role in disease progression. There is insufficient current evidence to regard increased homocysteine level as a causative factor in atherosclerotic disease. CONCLUSION: It is not known whether lowering plasma homocysteine concentration will reduce cardiovascular risk in the long term. Until such data become available, there is no evidence for the widespread use of folic acid therapy to reduce cardiovascular disease risk.

Arteriosclerosis↗
PubMed2002

Acquired colour vision deficiency in patients receiving digoxin maintenance therapy.

BACKGROUND/AIMS: Disturbances of colour vision are a frequently reported sign of digoxin toxicity. The aim of this study was to investigate the incidence of acquired colour vision deficiency in elderly hospitalised patients receiving maintenance digoxin therapy. METHODS: 30 patients (mean age 81.3 (SD 6.1) years) receiving digoxin were tested using a battery of colour vision tests (Ishihara, AO Hardy Rand Rittler plates, City tritan test, Lanthony tritan album, and the Farnsworth D15). These were compared to an age matched control group. Serum digoxin concentrations were determined from venous blood samples. RESULTS: Slight to moderate red-green impairment was found in approximately 20-30% of patients taking digitalis, and approximately 20% showed a severe tritan deficiency. There was no correlation between colour vision impairment and serum digoxin level. CONCLUSIONS: Formal colour vision testing of elderly patients taking digitalis showed a high incidence of colour deficiency, suggesting that impairment of retinal function can occur even at therapeutic drug levels. As a result, colour vision testing in this population would have limited value for the detection of drug toxicity.

Aged↗
PubMed2002

Venlafaxine poisoning complicated by a late rise in creatine kinase: two case reports.

Newer anti-depressants are often considered to be safer than more established anti-depressants. However, clinical experience of the effects of these agents in overdose is limited. Here, we present two cases of venlafaxine overdose that were complicated by a delayed rise in plasma creatine kinase. Although the clinical consequences were not serious, physicians should be alerted to the possibility of delayed rhabdomyolysis or serotonin syndrome in patients who have taken venlafaxine in overdose.

Adult↗
PubMed2002

Psychological distress of cancer and clinical trial participation: a review of the literature.

The House of Commons Select Committee on Science and Technology 2000 state that currently less than 5% of adult patients with solid tumours are entered into clinical trials. They recommend that increasing the number of adult cancer patients entering clinical trials must become a high priority. Health-care providers need to prepare themselves for this proposed increase in trial participants by assessing the current status of care and implementing changes within the current infrastructure to provide optimal holistic care. Cancer can change a patient's life either for better or for worse. At one extreme, having cancer leads to enhanced appreciation of life and closer bonds with others. However, at the other extreme, cancer combined with its treatment is viewed as an event that evokes distress and emotional anguish taxing the individual's ability to cope. In the last 25 years, owing to the advent of clinical trials, progress has been made in cancer treatment. Clinical trials may be hailed as the saviour to many therapeutic dilemmas. Treatments are now available which can offer patients hope of cure. Nevertheless, many participants may fear, for the purpose of research, that they may be assigned to less than optimal therapy or that their care will be carried out in a sterile scientific atmosphere devoid of humane and personal consideration. These and other reasons may cause unacceptable personal distress that overrides the potential therapeutic gain. Cancer diagnosis coupled with the ramifications of clinical trial involvement can have significant psychological implications. They may trigger the onset of a mood disorder or exacerbate a present symptom. This article will identify mood disorders in the cancer population, focus on the participants' needs in the clinical trial arena and investigate the influence trial participation has on psychological status.

Anxiety↗
PubMed2001

Immune function, telomerase, and angiogenesis in patients with primary, operable nonsmall cell lung carcinoma: tumor size and lymph node status remain the most important prognostic features.

BACKGROUND: Lung carcinoma usually is advanced at the time of presentation and frequently shows metastatic spread. In recent times, prognostic factors such as c-erbB-2 in patients with breast carcinoma have provided useful information and beneficial therapeutic targets. The objective of this study was to evaluate angiogenesis, immune function, and telomerase expression in patients with nonsmall cell lung carcinoma (NSCLC) to determine their prognostic significance. METHODS: Immunohistochemistry was used to evaluate the expression of human telomerase reverse transcriptase (hTERT; n = 115 patients), interleukin-2r (IL-2r; n = 40 patients), microvessel density (MVD; n = 81 patients), and vascular endothelial growth factor (VEGF; n = 61 patients). Three-year survival follow-up information was available for most patients, and a comprehensive review of clinicopathologic features was carried out. RESULTS: Fifty percent of tumors showed nuclear staining for hTERT, 55% of tumors showed some degree of lymphocyte IL-2r expression, 33% of tumors were recorded with an MVD that was higher than average, and VEGF staining was detected in 85% of tumors. None of the parameters measured had an impact on survival. hTERT expression was correlated with lymph node status. Lymph node status and tumor size were identified as independent prognostic factors. CONCLUSIONS: This study failed to identify a marker of prognosis for patients with NSCLC other than tumor size and lymph node status in this population. Telomerase expression was associated with metastases, raising the possibility that this enzyme is involved in the metastatic process. Tumor cell VEGF expression was identified frequently: This growth factor may have potential as a target for antiangiogenic therapy. Lung carcinoma typically is the result of large numbers of mutations. Further understanding of the biologic implications of these mutations will lead to the development of effective prognostic markers and treatments for patients with NSCLC.

Adult↗
PubMed2001

Degradation signals in ErbB-2 dictate proteasomal processing and immunogenicity and resist protection by cis glycine-alanine repeat.

ErbB-2 is ubiquitinated and degraded when dissociated from its membrane chaperone or bound by specific antibody. Reagents which induce such degradation have demonstrated antitumor activity and may impact ErbB-2 immunogenicity. To further understand ErbB-2 degradation and immunogenicity, a glycine-alanine repeat (GAr) or the reverse proline-alanine repeat (PAr) which protects certain proteins from proteasome degradation, was inserted after amino acid 5 (GAr5/PAr5) or 55 (GAr55/PAr55) of ErbB-2. When dissociated from the membrane with geldanamycin, E2-GAr5 and E2-PAr5 were not protected and still ubiquitinated and degraded by the proteasome, despite the presence of GAr. Insertional mutagenesis with GAr sequences at a.a. 55 of E2 enhanced proteasome degradation rendering E2-GAr55 and E2-PAr55 unstable on the membrane, but rescued in the cytosol by proteasome inhibitors. Immunization with E2-GAr induced antitumor immunity and CTL which lysed tumor cells expressing chimeric E2-GAr or wild-type E2 proteins, demonstrating efficient presentation through MHC I pathway. Improved understanding of the strong degradation signals in ErbB-2 may facilitate the development of anticancer agents or vaccines.

Alanine↗
PubMed2001

Immunogenicity of the extracellular domains of C-C chemokine receptor 5 and the in vitro effects on simian immunodeficiency virus or HIV infectivity.

The C-C chemokine receptor CCR5 serves an important function in chemotaxis of lymphocytes, monocytes, and dendritic cells. CCR5 is also the major coreceptor in most macrophage-tropic HIV-1 infections. Immunization of rhesus macaques with a baculovirus-generated CCR5 construct or peptides derived from the sequences of the four extracellular domains of CCR5 elicited IgG and IgA Abs, inhibition of SIV replication, and CD4+ T cell proliferative responses to three of the extracellular domains of CCR5. The immune sera reacted with cell surface CCR5 expressed on HEK 293 cells. T and B cell epitope mapping revealed major and minor T and B cell epitopes in the N-terminal, first, and second loops of CCR5. The three C-C chemokines, RANTES, macrophage-inflammatory protein-1alpha, and macrophage-inflammatory protein-1beta, were up-regulated by immunization with the CCR5-derived peptides, and the cell surface expression of CCR5 was decreased. The CCR5 Abs were complementary to the C-C chemokines in inhibiting HIV replication in vitro. Immunization with the four extracellular domains of CCR5 suggests that three of them are immunogenic, with maximal T cell responses being elicited by the second loop peptide. However, maximal Abs to the cell surface CCR5 or viral inhibitory Abs in vitro were induced by the N-terminal peptide. Up-regulation of the three C-C chemokines and down-modulation of cell surface CCR5 were elicited by the second loop, N-terminal, and first loop peptides. The data suggest that a dual mechanism of C-C chemokines and specific Abs may engage and down-modulate the CCR5 coreceptors and prevent in vitro HIV or SIV replication.

Amino Acid Sequence↗
PubMed2001

Predicting the reactivity of proteins from their sequence alone: Kazal family of protein inhibitors of serine proteinases.

An additivity-based sequence to reactivity algorithm for the interaction of members of the Kazal family of protein inhibitors with six selected serine proteinases is described. Ten consensus variable contact positions in the inhibitor were identified, and the 19 possible variants at each of these positions were expressed. The free energies of interaction of these variants and the wild type were measured. For an additive system, this data set allows for the calculation of all possible sequences, subject to some restrictions. The algorithm was extensively tested. It is exceptionally fast so that all possible sequences can be predicted. The strongest, the most specific possible, and the least specific inhibitors were designed, and an evolutionary problem was solved.

Algorithms↗
PubMed2001

Exposure of juvenile roach (Rutilus rutilus) to treated sewage effluent induces dose-dependent and persistent disruption in gonadal duct development.

Wild roach (Rutilus rutilus) have been found with intersex gonads in rivers throughout the United Kingdom. The incidence of intersexuality is strongly correlated with discharges of estrogenic treated sewage effluent into those rivers, and this has led to the hypothesis that estrogenic chemicals in effluents are feminizing wild male fish. In this study, early-life stage roach (50 days post hatch, dph) were exposed for 150 days to a graded concentration (0%, 12.5%, 25%, 50%, and 100%) of treated sewage (primarily domestic) effluent to examine the effects of exposure on sexual differentiation and development. Measurement of steroid estrogens and alkylphenolic chemicals in the effluent and a resulting dose-dependent induction of vitellogenin (VTG; a female-specific, estrogen-dependent plasma protein) confirmed that the fish had been exposed and responded to "estrogen" in the effluent. Exposure to treated sewage effluent induced feminization of the reproductive ducts in "male" roach in a dose-dependent manner (in full-strength effluent, 100% of the fish had feminized ducts), indicating that the disruption of the gonad ducts seen in wild roach is the result of exposure to treated sewage effluents during early-life stages. There were no effects of treated sewage effluent exposure on germ cell development; therefore, no oocytes occurred in the testes of the feminized male roach. Subsequent, depuration of the effluent exposed fish in "clean" water for 150 days resulted in a reduction in plasma VTG but no alteration of the feminized ducts, indicating that the effect of the treated sewage effluent on reproductive duct development was permanent. The causality of oocytes in the testes of wild male roach therefore remains to be elucidated.

Animals↗
PubMed2001

Phase 1 trial of the topical microbicide BufferGel: safety results from four international sites.

AIM: To evaluate the safety of BufferGel (ReProtect LLC, Baltimore, MD), a spermicidal microbicide that acidifies semen and maintains the protective acidity of the vagina, in a high-dose tolerance trial. METHODS: HIV/STD negative, sexually abstinent, and sexually active women in India, Thailand, Malawi, and Zimbabwe were asked to insert one applicator ( approximately 5 ml) of BufferGel vaginally twice per day for 14 days. Sexually active women agreed to have sex (while using BufferGel and nonlubricated condoms) at least twice per week. RESULTS: In total, 98 women (30 sexually abstinent and 68 sexually active) were enrolled. Overall compliance with product use was 93%. Epithelial abnormalities detected by pelvic examination or colposcopy were uncommon (8 cases in 271 examinations). Irritation was reported by approximately one quarter of the women (0.58 events per woman-week) but was generally mild and of short duration. The prevalence of bacterial vaginosis (BV) fell significantly, from 30% at enrollment to 6% at one week, and 7% at two weeks of BufferGel use. Thirty-two women acquired microscopically detectable yeast during BufferGel exposure, but only 3 developed symptomatic vaginitis. CONCLUSION: BufferGel appears to be safe and well tolerated by the cervicovaginal epithelium. Its effect on BV and yeasts merits further study.

Acrylic Resins↗