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N Cox

Publications and source records attributed to N Cox.

At least 37 records · Page 2Linked to original sources
PubMed2000

Cruise ships: high-risk passengers and the global spread of new influenza viruses.

In 1997, passengers on North American cruises developed acute respiratory illnesses (ARIs); influenza was suspected. We reviewed 1 ship's medical records for 3 cruises: cruise 1 (31 August to 10 September 1997), cruise 2 (11-20 September 1997), and cruise 3 (20-30 September 1997). Medically attended ARI was defined as any 2 of the following symptoms: fever (temperature, > or =37.8 degrees C) or feverishness, sore throat, cough, nasal congestion, chills, myalgia, and arthralgia. During cruise 2, we collected nasopharyngeal swabs for viral culture from people with ARI and surveyed passengers for self-reported ARI (defined as above except feverishness was substituted for fever). The outbreak probably began among Australian passengers on cruise 1 (relative risk, 3.3; 95% confidence interval, 1.89-5.77). Of 1284 passengers on cruise 2, 215 (17%) reported ARI, 994 (77%) were aged > or =65 years, and 336 (26%) had other risk factors for respiratory complications. An influenza strain not previously identified in North America was isolated. We concluded that an "off-season" influenza outbreak occurred among international travelers and crew on board this cruise ship.

Adolescent↗
PubMed2000

Avian-to-human transmission of H9N2 subtype influenza A viruses: relationship between H9N2 and H5N1 human isolates.

In 1997, 18 cases of influenza in Hong Kong (bird flu) caused by a novel H5N1 (chicken) virus resulted in the deaths of six individuals and once again raised the specter of a potentially devastating influenza pandemic. Slaughter of the poultry in the live bird markets removed the source of infection and no further human cases of H5N1 infection have occurred. In March 1999, however, a new pandemic threat appeared when influenza A H9N2 viruses infected two children in Hong Kong. These two virus isolates are similar to an H9N2 virus isolated from a quail in Hong Kong in late 1997. Although differing in their surface hemagglutinin and neuraminidase components, a notable feature of these H9N2 viruses is that the six genes encoding the internal components of the virus are similar to those of the 1997 H5N1 human and avian isolates. This common feature emphasizes the apparent propensity of avian viruses with this genetic complement to infect humans and highlights the potential for the emergence of a novel human pathogen.

Animals↗
PubMed2000

Genetic inheritance of body mass index in African-American and African families.

Numerous studies have shown recessive major gene inheritance of body mass index (BMI) in white populations; few have examined the inheritance of BMI in the African-American population where obesity is more prevalent, nor in African populations where obesity is comparatively rare. To evaluate the inheritance of obesity in two different populations of African origin, we used segregation analysis to determine the transmission of BMI in 95 African-American families and 400 Nigerian families. Probands were selected from participants in the population-based International Collaborative Study on Hypertension in Blacks. Using class D regressive models, results from the segregation analysis of the African-American data showed evidence of a major gene effect on BMI. The Nigerian results were strikingly similar, with comparable estimates for the genotype frequencies and means and strong evidence for a major effect in the transmission of BMI. The high BMI allele frequency estimate of 24% is consistent with estimates in other studies, but the mode of transmission appeared codominant, which differs from studies involving predominantly white populations. In the Nigerian analysis, however, the probability of a high BMI homozygote parent transmitting a low BMI allele to his/her offspring was significantly different from the Mendelian expectation of zero (estimated tau(BB) = 0.45), suggesting that additional complexities exist in the major gene inheritance of BMI in this population. The strong similarity of the genotype frequencies and means obtained from the African-American and Nigerian samples suggests that a common codominant major gene effect may contribute to the variation in BMI in both populations.

Alleles↗
PubMed2000

Influenza.

Influenza is an acute respiratory illness of global importance that causes considerable morbidity and mortality every year. At the beginning of the millennium, influenza will still be an emergent or re-emergent infection because of the viral ability to mutate. Global influenza surveillance indicates that influenza viruses may vary within a country and between countries and continents during an influenza season. Virologic surveillance is of critical importance in monitoring antigenic shift and drift. Disease surveillance is important in assessing the impact of the epidemics. Both types of information provide the basis of vaccine composition and the correct use of antivirals. Laboratory diagnosis is of critical importance for the global surveillance of influenza and may allow the timely use of antiviral drugs. Viral isolation remains the gold standard for laboratory diagnosis; however, several new rapid diagnostic tests are available or in development. The clinical spectrum of the disease varies from asymptomatic infection to the classic flu syndrome, and respiratory and nonrespiratory complications are observed particularly in high-risk groups. Current inactivated influenza vaccines have shown efficacy and effectiveness in preventing influenzalike illness, hospitalization for pneumonia, and death and in reducing health care costs. Because of the annual administration of the vaccine and the short period of time where it can be administered, strategies directed at improving vaccine coverage are of critical importance. In this sense, experiences obtained in different countries, such as with the National Immunization Campaigns developed in Argentina, provide one model of massive vaccine administration. In addition to current vaccines, new live attenuated vaccines will permit a most effective prevention of influenza in the community in the near future. A new type of antiviral, neuraminidase inhibitors, offers valuable benefits in the prevention and treatment of influenza A and B. A future pandemic of influenza seems inevitable. There is wide recognition that preparation for the next pandemic requires that infrastructure be in place during interpandemic periods for implementing preventive and therapeutic measures. The WHO has established a pandemic influenza task force, and a number of countries in Latin America have developed formal pandemic plans. These national and international efforts are essential to reduce the mortality and morbidity in the next influenza pandemic.

Aged↗
PubMed2000

Developing clinical indication for multisite pacing.

The artificial activation of the heart modifies the mechanics of contraction and relaxation. While only little basic research has been addressed to this question, clinical observations showed that for hypertrophic as well as dilated cardiomyopathies appropriate pacing techniques can be useful. Pacing can influence the activation sequence. The spread out from a single site is slow, and so hypercontractility deminshed. With the use of multiple electrodes, two atrial and/or two ventricular, conduction delays in the atria or ventricles can be eliminated. Synchronisation of the cardiac activation has an anti-arrhythmic and positiv inotropic effect. This may lead to new indications for pacemakers or better to be named cardiac synchronisers.

Cardiac Pacing, Artificial↗
PubMed2000

How does functional disability in early rheumatoid arthritis (RA) affect patients and their lives? Results of 5 years of follow-up in 732 patients from the Early RA Study (ERAS)

OBJECTIVES: To assess the impact of rheumatoid arthritis (RA) on function and how this affects major aspects of patients' lives. METHODS: The inception cohort of RA patients was recruited from rheumatology out-patient departments in nine National Health Service (NHS) hospital trusts in England. All consecutive patients with RA of less than 2 yr duration, prior to any second-line (disease-modifying) drug treatment were recruited and followed-up for 5 yr. Standard clinical, laboratory and radiological assessments, and all hospital-based interventions were recorded prospectively at presentation and yearly. The outcome measures were clinical remission and extra-articular features, functional ability [functional grades I-IV and Health Assessment Questionnaire (HAQ)], use of aids, appliances and home adaptations, orthopaedic interventions, and loss of paid work. RESULTS: A total of 732 patients completed 5 yr of follow-up, of whom 84% received second-line drugs. Sixty-nine (9.4%) had marked functional loss at presentation, compared with normal function in 243 (33%), and by 5 yr these numbers had increased in each group, respectively, to 113 (16%) and 296 (40%). Home adaptations and/or wheelchair use by 5 yr were seen in 74 (10%). Work disability was seen in 27% of those in paid employment at onset. One hundred and seventeen (17%) patients underwent orthopaedic surgery for RA, 55 (8%) for major joint replacements. Marked functional loss at 5 yr was more likely in women [odds ratio (OR) 1.63, 95% confidence interval (CI) 1.04-2.5], patients older than 60 yr (OR 1.94, 95% CI 1.3-2.9), and with HAQ > 1.0 at presentation (OR 4.4, 95% CI 2.8-7.0). CONCLUSIONS: Clinical profiles of RA patients treated with conventional drug therapy over 5 yr showed that a small proportion of patients (around 16%) do badly functionally and in terms of life events, whereas around 40% do relatively well. The details and exact figures of cumulative disability are likely to be useful to clinicians, health professionals and patients. The rate of progression and outcome in these patients can be compared against future therapies with any disease-modifying claims.

Adult↗
PubMed2000

Immunohistochemical and in situ hybridization studies of influenza A virus infection in human lungs.

Influenza viruses are responsible for acute febrile respiratory disease. When deaths occur, definitive diagnosis requires viral isolation because no characteristic viral inclusions are seen. We examined the distribution of influenza A virus in tissues from 8 patients with fatal infection using 2 immunohistochemical assays (monoclonal antibodies to nucleoprotein [NP] and hemagglutinin [HA]) and 2 in situ hybridization (ISH) assays (digoxigenin-labeled probes that hybridized to HA and NP genes). Five patients had prominent bronchitis; by immunohistochemical assay, influenza A staining was present focally in the epithelium of larger bronchi (intact and detached necrotic cells) and in rare interstitial cells. The anti-NP antibody stained primarily cell nuclei, and the anti-HA antibody stained mainly the cytoplasm. In 4 of these cases, nucleic acids (ISH) were identified in the same areas. Three patients had lymphohistiocytic alveolitis and showed no immunohistochemical or ISH staining. Both techniques were useful for detection of influenza virus antigens and nucleic acids in formalin-fixed paraffin-embedded tissues and can enable further understanding of fatal influenza A virus infections in humans.

Adolescent↗
PubMed1999

Characterization of the surface proteins of influenza A (H5N1) viruses isolated from humans in 1997-1998.

Influenza A (H5N1) viruses infected humans in Hong Kong between May and December, 1997. Sixteen viruses, including 6 from fatal cases, were isolated during this outbreak. Molecular analysis of the surface proteins genes encoding the hemagglutinin (HA) and neuraminidase (NA) of these H5N1 isolates, of a subtype not previously known to infect humans, are presented. The 16 human H5 HA sequences contain multiple basic amino acids adjacent to the cleavage site, a motif associated with highly pathogenic avian influenza A viruses. The phylogenetic relationship among both avian and human H5 hemagglutinins indicates that the human isolates are related directly to isolates that circulated among chickens in the live poultry markets in Hong Kong prior to and during the outbreak in humans. HA sequences from the human isolates and a recent chicken isolate represent a separate clade, within which there are two subgroups that are distinguishable antigenically and by the presence of a potential glycosylation site. Likewise the N1 neuraminidases of the human H5 isolates represent a clade that is evolutionarily distinct from previously characterized N1 neuraminidases. The recent human H5N1 virus NA genes are avian-like, indicating direct introduction from an avian source rather than evolution of a human N1 NA. All of the 16 human NA genes encode a shortened stalk due to a 19-amino acid deletion, also found in the recent avian H5N1 isolates from Hong Kong. Two unique amino acids were identified in the N1 NAs of the recent human isolates; however, it is not known if these residues influence host range. Neither the HA nor the NA genes of the human H5N1 virus isolates show evidence of adaptive changes during the outbreak. Although analyses of the surface protein genes of the H5N1 viruses from this outbreak did not provide immediate answers regarding the molecular basis for virulence, the analyses provided clues to potentially important areas of the genes worth further investigation.

Adolescent↗
PubMed1999

Influenza vaccination of human immunodeficiency virus (HIV)-infected adults: impact on plasma levels of HIV type 1 RNA and determinants of antibody response.

We assessed the effect of influenza vaccination on plasma levels of human immunodeficiency virus type 1 (HIV-1) RNA and the impact of age, plasma HIV-1 RNA level, CD4 cell count, and anti-HIV therapy on immune response. Forty-nine adults (mean age, 38.7 years; mean CD4 cell count +/- SD, 190 +/- 169/mL; mean plasma HIV-1 RNA level +/- SD, 154,616 +/- 317,192 copies/mL) were immunized. Elevations of > or = 0.48 log in plasma HIV-1 RNA levels occurred in two (4%) of 49 subjects within 4 weeks of vaccination. A fourfold or greater increase in antibody titer occurred in 13 (45%) of 29 subjects, correlating directly with CD4 cell count (P = .002) and inversely with plasma HIV-1 RNA level (P = .034). By multivariate analysis, CD4 cell count was a stronger predictor of antibody response than was plasma HIV-1 RNA level. We conclude that increases in plasma HIV-1 RNA levels following influenza vaccination are rare and transient and that antibody response is impaired with CD4 cell counts of < 100/mL and plasma HIV-1 RNA levels of > 100,000 copies/mL. Prospective trials are needed to evaluate the impact of highly active therapy on immune response after vaccination.

Adult↗
PubMed1999

Larsen scoring of digitized X-ray images.

OBJECTIVE: To determine how Larsen scores from digitized X-rays compare to those from film originals. METHODS: A hundred sets of radiographs of patients recruited with early rheumatoid arthritis (RA) were assessed using the Larsen scoring system. Digitized copies of these sets were then viewed on a computer screen and scored according to Larsen in a random order. The quality of the digitized image was also recorded. For each set of X-rays, the signed difference between the score from film and the score from the digitized images was calculated. RESULTS: A total of 95% of the digitized X-ray sets were scored successfully; 5% were not scored due to the images being unreadable. The mean difference between the two sets of scores was -1.2 (95% CI [-2.06, -0.37]). There was no trend in the difference with respect to the mean of the two scores (P>0.1). CONCLUSION: The Larsen scoring of digitized X-ray images has been validated.

Analog-Digital Conversion↗
PubMed1999

Two different mutations in the thyroid peroxidase gene of a large inbred Amish kindred: power and limits of homozygosity mapping.

Approximately 10% of newborns with congenital hypothyroidism are unable to convert iodide into organic iodine. This iodide organification defect has a prevalence of 1 in 40,000 newborns and may be caused by defects in the thyroid peroxidase enzyme (TPO), the hydrogen peroxide-generating system, the TPO substrate thyroglobulin, or inhibitors of TPO. We identified a high incidence of severe hypothyroidism due to a complete iodide organification defect in the youngest generation of five nuclear families belonging to an inbred Amish kindred. Genealogical records permitted us to trace their origin to an ancestral couple 7-8 generations back and to identify an autosomal recessive pattern of inheritance. Initial studies of homozygosity by descent using two polymorphic markers within the TPO gene showed no linkage to the phenotype. In fact, 4 of 15 affected siblings from 2 of the nuclear families were heterozygous, resulting in homozygosity values of 73% and 53% in affected and unaffected family members, respectively. A genome-wide homozygosity screen using DNA pools from affected and unaffected family members localized the defect to a locus close to the TPO gene. Linkage analysis using 4 additional polymorphic markers within the TPO gene reduced the number of homozygous unaffected siblings to zero without altering the percent homozygosity initially found in the affected. Sequencing of the TPO gene revealed 2 missense mutations, E799K and R648Q. TPO 779K was found in both alleles of the 11 affected homozygotes, both mutations were present in each of the 3 affected compound heterozygotes, and there were no TPO mutations in 1 subject with hypothyroidism of different etiology. These results demonstrate the power of the DNA pooling strategy in the localization of a defective gene and the pitfalls of linkage analysis when 2 relatively rare mutations coexist in an inbred population.

Child, Preschool↗
PubMed1999

Genome-wide screen for atopy susceptibility alleles in the Hutterites.

A genome-wide screen for loci influencing positive skin prick tests (SPT) to airborne allergens was conducted in the Hutterites, a founder population of European ancestry. Positive SPT to 14 standardized allergens was measured in 370 subjects in our primary sample and 324 subjects in a replication sample. Evidence for linkage to positive SPT was assessed using the transmission disequilibrium test (TDT) with 337 autosomal markers (average spacing 9.13 cM, SD = 7.8 cM). Three loci showed the strongest overall evidence of linkage to atopy, with at least one allele-specific and a locus-specific p< 1 x 10(-4). This study provides evidence for at least three atopy-susceptibility loci in the Hutterites on chromosomes 1, 6 and 16.

Adult↗