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Biomedical subjects

L Kelly

Publications and source records attributed to L Kelly.

At least 37 records · Page 2Linked to original sources
PubMed2002

Estimating the risk of importation of foot-and-mouth disease into Europe.

The opinions of a number of recognised world experts on foot-and-mouth disease (FMD) were sought in order to answer key questions relating to the importation of the disease into European countries from countries outside Europe. In addition, their opinions were sought on where in Europe a primary outbreak of FMD was most likely to occur and the number of outbreaks likely to occur within European countries in the next five years. The Balkans group of countries was considered to be the most likely group within Europe to have a primary outbreak of FMD and also most likely to have the highest number of primary outbreaks. Turkey was considered to be the country outside Europe which was most likely to be the source of an outbreak within Europe as a whole, and the illegal importation of livestock was considered to be the most likely route of introduction of FMD into Europe. Results specific to the Islands group of countries, which included the UK and Ireland, suggested that this group was likely to have a mean of one primary outbreak of FMD in the five years from September 2000, and that the importation of foodstuffs by people entering those countries from Turkey was the most likely source of an outbreak.

Animals↗
PubMed2002

Influenza virus carrying neuraminidase with reduced sensitivity to oseltamivir carboxylate has altered properties in vitro and is compromised for infectivity and replicative ability in vivo.

Oseltamivir phosphate (Tamiflu, Ro 64-0796) is the first orally administered neuraminidase (NA) inhibitor approved for use in treatment and prevention of influenza virus infection in man. Oseltamivir phosphate is the pro-drug of the active metabolite oseltamivir carboxylate (Ro 64-0802). Extensive monitoring throughout the oseltamivir development programme has identified a very low incidence of patients who have carried drug-resistant virus. The predominant mutation seen is the substitution of arginine for lysine at position 292 of the viral NA. The fitness of clinically isolated influenza virus A/Sydney/5/97 (H3N2) carrying this mutation was markedly reduced in animal models of influenza virus infection. The infectivity and replicative abilities of R292K mutant virus were reduced by at least 2 logs in a mouse model of influenza infection and by 2 and 4 logs, respectively, in the ferret model. Pathogenicity of R292K influenza virus A/Sydney/5/97 was reduced in ferrets as measured by inflammatory and febrile responses at least in parallel to the decrease in replicative ability. The data indicate that the R292K NA mutation compromises viral fitness such that virus carrying this mutation is unlikely to be of significant clinical consequence in man.

Acetamides↗
PubMed2002

The H274Y mutation in the influenza A/H1N1 neuraminidase active site following oseltamivir phosphate treatment leave virus severely compromised both in vitro and in vivo.

Oseltamivir carboxylate is a potent and specific inhibitor of influenza A and B neuraminidase (NA). Oseltamivir phosphate, the ethyl ester prodrug of oseltamivir carboxylate, is the first orally active NA inhibitor available for the prophylaxis and treatment of influenza A and B. It offers an improvement over amantadine and rimantadine which are active only against influenza A and rapidly generate resistant virus. The emergence of virus resistant to oseltamivir carboxylate in the treatment of naturally acquired influenza infection is low (about 1%). The types of NA mutation to arise are sub-type specific and largely predicted from in vitro drug selection studies. A substitution of the conserved histidine at position 274 for tyrosine in the NA active site has been selected via site directed mutagenesis, serial passage in culture under drug pressure in H1N1 and during the treatment of experimental H1N1 infection in man. Virus carrying H274Y NA enzyme selected in vivo has reduced sensitivity to oseltamivir carboxylate. The replicative ability in cell culture was reduced up to 3 logs, as was infectivity in animal models of influenza virus infection. Additionally, pathogenicity of the mutant virus is significantly compromised in ferret, compared to the corresponding wild type virus. Virus carrying a H274Y mutation is unlikely to be of clinical consequence in man.

Acetamides↗
PubMed2002

Dose-response relationships for foot and mouth disease in cattle and sheep.

The relationships between the inhaled dose of foot and mouth disease virus and the outcomes of infection and disease were examined by fitting dose-response models to experimental data. The parameters for both the exponential and beta-poisson models were estimated using maximum likelihood and Bayesian methods. The median probability of infection given a single inhaled TCID50 was estimated to be 0.031 with 95% Bayesian credibility intervals (CI) of 0.018-0.052 for cattle, and 0.045 (CI = 0.024-0.080) for sheep. These estimates were used to construct dose-response curves and uncertainty distributions for use in quantitative risk assessments.

Animals↗
PubMed2002

Anti-human epidermal growth factor receptor 2 monoclonal antibody therapy for breast cancer.

BACKGROUND: Advances in molecular biology and improved understanding of tumour biology have led to the development of novel treatments for cancer. Trastuzumab (Herceptin; Genentech, San Francisco, California, USA) is a monoclonal antibody directed against human epidermal growth factor receptor (HER) 2 protein, which is overexpressed in a wide variety of human cancers, including 20-30 per cent of human breast cancers. HER-2 plays an important role in oncogenic transformation, tumorigenesis and metastatic spread. Overexpression is associated with a poor prognosis and predicts a poor response to several treatment modalities. METHOD: Literature relating to the monoclonal antibody was identified by a Medline literature search and by cross-referencing from the references of seminal articles on the subject. Four major clinical trials were identified and reviewed. RESULTS AND CONCLUSION: In clinical trials approximately 15-20 per cent of patients with HER-2-overexpressing tumours benefited from treatment with trastuzumab. In sensitive patients the antibody appeared to have intrinsic anticancer activity when given as a single agent. In combination chemotherapy it appeared to act synergistically with other agents. Ongoing research is evaluating trastuzumab in combination with numerous standard chemotherapy regimens and with other novel chemotherapeutic agents. Clinical trials have also revealed several serious side-effects of monoclonal antibody therapy. Most notable is an unpredictable cardiotoxicity, especially when used in combination with anthracycline-based chemotherapy regimens.

Anthracyclines↗
PubMed2002

Genetic characterisation of the Uruguayan Creole horse and analysis of relationships among horse breeds.

The genetic variability within the Uruguayan Creole horse and its relationship to a group of geographically or historically related breeds (Spanish Pure-bred, Barb, Quarter horse, Paso Fino, Peruvian Paso, Arabian and Thoroughbred horse), was evaluated using 25 loci (seven of blood groups, nine of protein polymorphisms and nine microsatellites) analyzed on a total of 145 Uruguayan Creole horses. In this study, blood group and protein polymorphism variants that are considered to be breed markers of Spanish Pure-bred and Barb horses were detected in the Creole breed. Conversely, some microsatellites and protein polymorphisms alleles were found uniquely in the Creole horse. American horse breeds together with Barb and Arabian horses clearly formed a separate cluster from the Spanish pure-bred and Thoroughbred breeds, as shown by an UPGMA dendrogram based on Nei's standard genetic distance. Data in this study provided evidence for considerable genetic variation within Uruguayan Creole horses and of a distinctive breed profile. Both traits were most likely inherited from the XVIth century Spanish horses, more closely related to Barb than to Spanish Pure-bred.

Animals↗
PubMed2002

Pregnancy-associated breast cancer.

Twelve premenopausal women diagnosed with pregnancy-associated breast cancer between May 1985 and October 1999 were reviewed. Three patients were diagnosed in the first trimester of pregnancy, five in the second trimester, and three during the third trimester. There was one patient who was five weeks postpartum. At the time of diagnosis nine patients had lymph node involvement and two of these had metastatic disease. Four patients received primary chemotherapy. The remainder had surgery. Five patients died, two had metastatic disease at time of diagnosis, median survival was 31 months. There were three fetal deaths, one termination and two during primary chemotherapy. The diagnosis of breast cancer during pregnancy is difficult. Presentation is usually at an advanced stage. Surgery can be safely performed during pregnancy and adjuvant chemotherapy should not be postponed until after delivery.

Adult↗
PubMed2002

Research electives in rural health care.

PROBLEM BEING ADDRESSED: As academic medical institutions being to address the education and service needs of rural Canadians, research will make its way to the foreground. Rural physicians are well positioned to lead in this venture, but often have little time or energy to take on extra duties. Rural populations differ in essential ways from urban populations. Certainly, the limitations of geography, funding, and population density alter medical surveillance, treatment, and research in ways that are largely undocumented. OBJECTIVE OF PROGRAM: To undertake research projects of interest to our group of rural clinicians and to expose medical students to both research and rural practice. MAIN COMPONENTS OF PROGRAM: Seven rural family physicians welcomed medical students into their group practice for summer research electives. Topics were chosen in advance by the medical group, and one member was designated as supervisor for each student. A local nurse educator also provided support to students and to clinicians after the students' departure. Several projects were undertaken simultaneously each summer; the result was several published peer-reviewed articles and good teaching and learning experiences. CONCLUSION: Rural research electives provide a valuable experience for students and preceptors. Such initiatives deserve broad promotion and support.

Family Practice↗
PubMed2001

A high-resolution radiation hybrid map of the human genome draft sequence.

We have constructed a physical map of the human genome by using a panel of 90 whole-genome radiation hybrids (the TNG panel) in conjunction with 40,322 sequence-tagged sites (STSs) derived from random genomic sequences as well as expressed sequences. Of 36,678 STSs on the TNG radiation hybrid map, only 3604 (9.8%) were absent from the unassembled draft sequence of the human genome. Of 20,030 STSs ordered on the TNG map as well as the assembled human genome draft sequence and the Celera assembled human genome sequence, 36% of the STSs had a discrepant order between the working draft sequence and the Celera sequence. The TNG map order was identical to one of the two sequence orders in 60% of these discrepant cases.

Algorithms↗
PubMed2001

Complex high-resolution linkage disequilibrium and haplotype patterns of single-nucleotide polymorphisms in 2.5 Mb of sequence on human chromosome 21.

One approach to identify potentially important segments of the human genome is to search for DNA regions with nonrandom patterns of human sequence variation. Previous studies have investigated these patterns primarily in and around candidate gene regions. Here, we determined patterns of DNA sequence variation in 2.5 Mb of finished sequence from five regions on human chromosome 21. By sequencing 13 individual chromosomes, we identified 1460 single-nucleotide polymorphisms (SNPs) and obtained unambiguous haplotypes for all chromosomes. For all five chromosomal regions, we observed segments with high linkage disequilibrium (LD), extending from 1.7 to>81 kb (average 21.7 kb), disrupted by segments of similar or larger size with no significant LD between SNPs. At least 25% of the contig sequences consisted of segments with high LD between SNPs. Each of these segments was characterized by a restricted number of observed haplotypes,with the major haplotype found in over 60% of all chromosomes. In contrast, the interspersed segments with low LD showed significantly more haplotype patterns. The position and extent of the segments of high LD with restricted haplotype variability did not coincide with the location of coding sequences. Our results indicate that LD and haplotype patterns need to be investigated with closely spaced SNPs throughout the human genome, independent of the location of coding sequences, to reliably identify regions with significant LD useful for disease association studies.

Animals↗
PubMed2001

Developing actionable dietary guidance messages: dietary fat as a case study.

Although consumers say they are concerned about nutrition and are aware that eating a healthful diet is important for good health, this knowledge does not always translate into healthful diet behaviors or motivate behavior change. In an effort to better understand consumer attitudes about nutrition and to explore alternatives for communicating dietary advice in language that is meaningful and motivates behavior change, the International Food Information Council (IFIC) conducted qualitative research with consumers (using focus groups) and registered dietitians (using telephone interviews) in 1998 and 1999. Results of the research are presented using dietary fat as a case study. Findings from the IFIC research were reported to the Dietary Guidelines Advisory Committee to assist the Committee in developing meaningful and action-oriented dietary advice related to dietary fat for inclusion in the 2000 Dietary Guidelines for Americans that would be motivating and easy for consumers to implement. The recommendation to moderate fat intake in the new dietary guideline, "Choose a diet that is low in saturated fat and cholesterol and moderate in total fat" is consistent with communication recommendations in the IFIC research. Further, the moderate fat message is empowering because it suggests an achievable dietary regimen and reduces guilt and worry about foods. It allows flexibility to enjoy desired foods and promotes using common sense when it comes to diet. Several issues emerged from the IFIC research that apply to general nutrition communications with consumers, whether it be through national nutrition recommendations or in one-on-one counseling situations: to be effective, messages to consumers about nutrition, and specifically dietary fat, must address sources of discomfort about dietary choices; they must engender a sense of empowerment; and they should motivate both by providing clear information that propels toward taking action and appeals to the need to make personal choices.

Adult↗
PubMed2001

Adolescents at risk for mistreating their children. Part I: Prenatal identification.

OBJECTIVE: To determine if the Family Stress Checklist helps prenatal care providers identify adolescents who are at risk for mistreating their children. METHODS: We studied 262 participants in a comprehensive, adolescent-oriented maternity program. During the prenatal period, the Family Stress Checklist was used to quantify abuse potential, with scores >25 defining high risk. Information about the social context of the pregnancy and the pattern of health care utilization was obtained with a self-administered questionnaire, and by reviewing the medical records. Major disruption of primary care giving by the adolescent mother was classified hierarchically as abuse, neglect, and abandonment. RESULTS: Family Stress Checklist scores ranged from 0 to 65 (mean + SD = 20.1 + 1.4); 113 (43%) of the 262 teenagers were classified as high risk. High and low risk adolescent mothers made an equivalent number of health maintenance and Emergency Department visits, but the high risk group initiated significantly more acute care visits (6.0 + 4.1 compared to 3.9 + 3.3; p < .0001). After controlling for pre-existing sociodemographic differences, high risk 1-year-olds were 8.41 (95% CI: 1.77-40.01) times and high risk 2-year-olds 5.19 (95% CI: 1.99-13.60) times more likely to have been mistreated than their low risk counterparts. CONCLUSIONS: Prenatal care providers can use the Family Stress Checklist to systematically identify a subgroup of adolescent mother whose excessive use of the acute medical care services and propensity for mistreating their children suggests the need for additional support services.

Adolescent↗
PubMed2001

Adolescents at risk for mistreating their children. Part II: A home- and clinic-based prevention program.

OBJECTIVE: To determine if adding an intensive home visitation component to a comprehensive adolescent-oriented maternity program prevents child abuse and neglect. METHODS: We studied 171 participants in a comprehensive, adolescent-oriented maternity program who were deemed to be at high risk for child abuse and neglect. Half were randomly assigned to receive in-home parenting instruction. Major disruptions of primary care-giving by the adolescent mother were classified hierarchically as abuse, neglect, and abandonment. RESULTS: Compliance with home visits varied in relation to the support the teenage mothers received from their families and the fathers of their babies (p < .0001). There were no significant treatment group differences in the pattern of health care utilization, the rate of postpartum school return, repeat pregnancies, or child abuse and neglect. The incidence of maltreatment rose in tandem with the predicted risk status of the mother. Ultimately, 19% of the children were removed from their mother's custody. CONCLUSIONS: Prediction efforts were effective in identifying at-risk infants, but this intensive home- and clinic-based intervention did not alter the incidence of child maltreatment or maternal life course development. A parenting program that was more inclusive of the support network might be more popular with teenagers and therefore more effective. Our findings also emphasize the importance of including counseling specifically designed to prevent teenagers from abandoning their children.

Adolescent↗
PubMed2001

A village would be nice but...it takes a long-acting contraceptive to prevent repeat adolescent pregnancies.

OBJECTIVE: To determine which components of a comprehensive, multidisciplinary, adolescent-oriented maternity program help teenage mothers delay subsequent pregnancies. DESIGN/SETTING/PATIENTS: A cohort of 373 participants in a comprehensive, multidisciplinary, adolescent-oriented maternity program was studied. INTERVENTION: The program was designed to prevent rapid subsequent pregnancies directly by simplifying access to contraceptives and indirectly by discouraging school drop-out and encouraging the pursuit of careers incompatible with closely spaced childbearing. Parents and children were seen together; nine visits were scheduled during the first postpartum year and four visits during the second year. MAIN OUTCOME MEASURE: Repeat adolescent pregnancy. RESULTS: The repeat pregnancy rate was 14% at 1 year and 35% at 2 years. Teenage mothers who became pregnant exhibited significantly more repeat pregnancy risk factors but were as compliant with clinic visits as their nonpregnant peers. The contraceptive choices the teenagers made during the puerperium had the most profound effect on their subsequent fertility. A logistic regression analysis identified failure to use Norplant during the puerperium as the strongest predictor of repeat pregnancy during the first 2 postpartum years (relative risk [RR]=8.89; 95% confidence interval [CI]=2.80-28.50). Exhibiting nine or more repeat pregnancy risk factors (RR=2.37; 95% CI=1.38-4.06) and not using Depo-Provera during the puerperium (RR=2.30; 95% CI=1.60-3.29) also predicted repeat conception, but clinic visits and return to school postpartum did not. CONCLUSIONS: Using a long-acting hormonal contraceptive during the puerperium was associated with pregnancy prevention during the first 2 postpartum years, but frequent clinic visits, contact with supportive healthcare and social service providers, and return to school were not.

Adolescent↗
PubMed2001

A quantitative risk assessment for the occurrence of campylobacter in chickens at the point of slaughter.

A quantitative risk assessment model investigating the risk of human infection with campylobacter from the consumption of chicken meat/products is currently being formulated. Here such an approach is used to evaluate the probability that a random bird, selected at slaughter from Great Britain's national poultry flock, will be campylobacter-positive. This is determined from the probability that a flock chosen at random contains at least one colonized bird and the within-flock prevalence of such a flock at slaughter. The model indicates that the probability bird chosen at random being campylobacter-positive at slaughter is 0.53. This probability value has associated uncertainty, the 5th percentile being 0.51 and the 95th percentile 0.55. The model predicts that delaying the age at first exposure to campylobacter can have a significant impact on reducing the probability of a bird being campylobacter-positive at slaughter. However, implementation of current biosecurity methods makes this difficult to achieve.

Animals↗
PubMed2001

Comparison of dobutamine-based and milrinone-based therapy for advanced decompensated congestive heart failure: Hemodynamic efficacy, clinical outcome, and economic impact.

BACKGROUND: The use of parenteral positive inotropic agents still remains a major component of therapy for patients with advanced decompensated congestive heart failure (CHF). However, no consensus guidelines have been developed for the appropriate selection of a first-line inotropic therapy. We sought to compare the clinical outcome and economic cost of dobutamine-based and milrinone-based therapy in patients with acute exacerbation of CHF. METHODS AND RESULTS: We retrospectively analyzed the outcome of 329 patients admitted to the heart failure unit with acute exacerbation of CHF. More patients were treated with dobutamine-based therapy (269/329, 81.7%) than with milrinone-based therapy (60/329, 18.3%). Both groups had similar baseline characteristics and similar hemodynamic profiles at baseline, with the exception of higher mean pulmonary arterial pressure in the milrinone group (47 mm Hg vs 42 mm Hg, P <.001). One hundred nine patients (40%) of the dobutamine group required parenteral nitroprusside for hemodynamic optimization compared with 11 patients (18%) in the milrinone group (P <.001). The use of parenteral nitroglycerin and dopamine was similar in both groups. There was no significant difference in the in-hospital mortality rate (dobutamine 7.8% vs milrinone 10%) or clinical outcome between the 2 groups. However, the average direct drug cost per patient was significantly reduced in the dobutamine group compared with the milrinone group ($45 +/- $10 vs $1855 +/- $350, P <.0001). CONCLUSION: Dobutamine-based therapy is an attractive approach for the treatment of decompensated advanced heart failure, achieving comparable clinical efficacy to milrinone with a significantly reduced economic cost.

Cost-Benefit Analysis↗