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Biomedical subjects

D W Brown

Publications and source records attributed to D W Brown.

At least 19 recordsLinked to original sources
PubMed2005

National survey of diagnostic services for genital herpes.

OBJECTIVE: To investigate the provision of diagnostic services for genital herpes simplex virus (HSV) infection in the United Kingdom. METHODS: National survey of laboratories providing diagnostic services for genital herpes. RESULTS: Completed questionnaires were returned from 25/32 (78%) laboratories participating in the Clinical Virology Network, including seven in London, 12 in the rest of England, one in Wales, four in Scotland, and one in Northern Ireland. Virus culture was the diagnostic method of choice in 20/25 (80%) laboratories; 5/25 (20%) routinely used HSV DNA detection by polymerase chain reaction (PCR). HSV PCR for DNA detection in cerebrospinal fluid (CSF) was available in 17/25 (68%) laboratories. Typing of isolates (HSV-1 or HSV-2) was performed routinely in 22/25 (88%) laboratories. Only 2/25 (8%) laboratories offered HSV type specific serology, although an additional 12/25 (48%) referred requests elsewhere. Consistent with this finding, the number of HSV type specific antibody tests referred to the Health Protection Agency increased by nearly fivefold between 1997 and 2003. CONCLUSIONS: Virus culture remains the preferred diagnostic method for genital herpes, despite evidence indicating that its sensitivity is suboptimal compared to PCR. As HSV PCR is widely available for testing of CSF, it is recommended that clinicians and virologists discuss ways to implement PCR testing of genital swabs, thus enabling greater diagnostic accuracy. A call is made for studies to assess the use of HSV type specific serology in genitourinary medicine (GUM) settings, now that rapid and validated assays have become available and guidelines have been issues to provide recommendations on their use.

Diagnostic Services↗
PubMed2004

Deletion and complementation of the mating type (MAT) locus of the wheat head blight pathogen Gibberella zeae.

Gibberella zeae, a self-fertile, haploid filamentous ascomycete, causes serious epidemics of wheat (Triticum aestivum) head blight worldwide and contaminates grain with trichothecene mycotoxins. Anecdotal evidence dating back to the late 19th century indicates that G. zeae ascospores (sexual spores) are a more important inoculum source than are macroconidia (asexual spores), although the fungus can produce both during wheat head blight epidemics. To develop fungal strains to test this hypothesis, the entire mating type (MAT1) locus was deleted from a self-fertile (MAT1-1/MAT1-2), virulent, trichothecene-producing wild-type strain of G. zeae. The resulting MAT deletion (mat1-1/mat1-2) strains were unable to produce perithecia or ascospores and appeared to be unable to mate with the fertile strain from which they were derived. Complementation of a MAT deletion strain by transformation with a copy of the entire MAT locus resulted in recovery of production of perithecia and ascospores. MAT deletion strains and MAT-complemented strains retained the ability to produce macroconidia that could cause head blight, as assessed by direct injection into wheat heads in greenhouse tests. Availability of MAT-null and MAT-complemented strains provides a means to determine the importance of ascospores in the biology of G. zeae and perhaps to identify novel approaches to control wheat head blight.

Base Sequence↗
PubMed2003

Seroepidemiological study of herpes simplex virus types 1 and 2 in Brazil, Estonia, India, Morocco, and Sri Lanka.

BACKGROUND: The association between herpes simplex virus type 2 (HSV-2) and human immunodeficiency virus (HIV) and the development of HSV vaccines have increased interest in the study of HSV epidemiology. OBJECTIVES: To estimate the age and sex specific seroprevalence of HSV-1 and HSV-2 infections in selected populations in Brazil, Estonia, India, Morocco, and Sri Lanka. METHODS: Serum samples were collected from various populations including children, antenatal clinic attenders, blood donors, hospital inpatients, and HIV sentinel surveillance groups. STD clinic attenders were enrolled in Sri Lanka, male military personnel in Morocco. Sera were tested using a common algorithm by type specific HSV-1 and HSV-2 antibody assay. RESULTS: 13,986 samples were tested, 45.0% from adult females, 32.7% from adult males, and 22.3% from children. The prevalence of HSV-1 varied by site ranging from 78.5%-93.6% in adult males and from 75.5%-97.8% in adult females. In all countries HSV-1 seroprevalence increased significantly with age (p<0.001) in both men and women. The prevalence of HSV-2 infection varied between sites. Brazil had the highest age specific rates of infection for both men and women, followed by Sri Lanka for men and Estonia for women, the lowest rates being found in Estonia for men and India for women. In all countries, HSV-2 seroprevalence increased significantly with age (p<0.01) and adult females had higher rates of infection than adult males by age of infection. CONCLUSIONS: HSV-1 and HSV-2 seroprevalence was consistently higher in women than men, particularly for HSV-2. Population based data on HSV-1 and HSV-2 will be useful for designing potential HSV-2 vaccination strategies and for focusing prevention efforts for HSV-1 and HSV-2 infection.

Adolescent↗
PubMed2002

Immunogenicity of second dose measles-mumps-rubella (MMR) vaccine and implications for serosurveillance.

Measles and mumps, but not rubella, outbreaks have been reported amongst populations highly vaccinated with a single dose of measles-mumps-rubella (MMR) vaccine. Repeated experience has shown that a two-dose regime of measles vaccine is required to eliminate measles. This paper reports the effect of the first and second MMR doses on specific antibody levels in a variety of populations.2-4 years after receiving a first dose of MMR vaccine at age 12-18 months, it was found that a large proportion of pre-school children had measles (19.5%) and mumps (23.4%) IgG antibody below the putative level of protection. Only a small proportion (4.6%) had rubella antibody below the putative protective level. A total of 41% had negative or equivocal levels to one or more antigens. The proportion measles antibody negative (but not rubella or mumps) was significantly higher in children vaccinated at 12 months of age than at 13-17 months. There was no evidence for correlation of seropositivity to each antigen, other than that produced by a small excess of children (1%) negative to all three antigens. After a second dose of MMR, the proportion negative to one or more antigens dropped to <4%. Examination of national serosurveillance data, found that following an MR vaccine campaign in cohorts that previously received MMR, both measles and rubella antibody levels were initially boosted but declined to pre-vaccination levels within 3 years. Our study supports the policy of administering a second dose of MMR vaccine to all children. However, continued monitoring of long-term population protection will be required and this study suggests that in highly vaccinated populations, total measles (and rubella) IgG antibody levels may not be an accurate reflection of protection. Further studies including qualitative measures, such as avidity, in different populations are merited and may contribute to the understanding of MMR population protection.

Antibodies, Viral↗
PubMed2002

Human caliciviruses in Europe.

Caliciviruses are single-stranded RNA viruses, which are divided into four genera based on their morphology and genomic structure. Viruses from two genera, the Norwalk like viruses and Sapporo like viruses, are a common cause of acute, nonbacterial gastroenteritis in humans. Although the first human calicivirus discovered nearly 30 years ago, much of the epidemiological and biological character of these viruses is only now beginning to unfold. Investigation has been difficult due to a number of factors, the viruses cannot be amplified by in vitro cell culture or animal models and electron microscopy (EM) is often not sensitive enough to detect the viruses in stool samples. Recent advances in molecular diagnostic techniques and the advent of a baculovirus expression system have highlighted the clinical and public health importance of calicivirus in all age groups, their ability to cause infection via a number of transmission routes as well as their considerable genetic diversity. These characteristics, in conjunction with the inability of humans to develop long-term immunity make HuCV an important public health issue in Europe and worldwide.

Animals↗
PubMed2001

Measles virus strains circulating in Ethiopia in 1998-1999: molecular characterisation using oral fluid samples and identification of a new genotype.

A measles outbreak in December 1998 in Bedelle (vaccine coverage <40%) and two sporadic cases in Addis Ababa, Ethiopia, were investigated. Paired serum and oral fluid samples were collected 2-8 days after the onset of symptoms. A total of 53 of 55 outbreak cases and both sporadic cases were positive for serum measles virus-specific IgM. Oral fluid measles-specific IgM was positive in 71% of cases collected up to 5 days after onset and in 90% collected at 6-8 days. By contrast, 100% of oral fluid samples were positive for measles virus RNA by RT-PCR, suggesting that early collection of samples favoured the detection of measles virus RNA by RT-PCR. The measles virus strain in the outbreak was identified as genotype D4. One strain from a sporadic case was also genotype D4; the strain from the other sporadic case was assigned to clade D but was distinct. The degree of divergence from recognised clade D strains suggested that, together with three strains from the United Kingdom, it represents an additional genotype of clade D (GenBank accession numbers AF280800-280807).

Adolescent↗
PubMed2001

A genetic and biochemical approach to study trichothecene diversity in Fusarium sporotrichioides and Fusarium graminearum.

The trichothecenes T-2 toxin and deoxynivalenol (DON) are natural fungal products that are toxic to both animals and plants. Their importance in the pathogenicity of Fusarium spp. on crop plants has inspired efforts to understand the genetic and biochemical mechanisms leading to trichothecene synthesis. In order to better understand T-2 toxin biosynthesis by Fusarium sporotrichioides and DON biosynthesis by F. graminearum, we compared the nucleotide sequence of the 23-kb core trichothecene gene cluster from each organism. This comparative genetic analysis allowed us to predict proteins encoded by two trichothecene genes, TRI9 and TRI10, that had not previously been described from either Fusarium species. Differences in gene structure also were correlated with differences in the types of trichothecenes that the two species produce. Gene disruption experiments showed that F. sporotrichioides TRI7 (FsTRI7) is required for acetylation of the oxygen on C-4 of T-2 toxin. Sequence analysis indicated that F. graminearum TRI7 (FgTRI7) is nonfunctional. This is consistent with the fact that the FgTRI7 product is not required for DON synthesis in F. graminearum because C-4 is not oxygenated.

DNA, Fungal↗
PubMed2001

Disparities in cholesterol screening: falling short of a national health objective.

BACKGROUND: The objective of this study was to determine whether the Year 2000 national health objective for cholesterol screening was attained and to identify disparities in cholesterol screening across racial or ethnic and socioeconomic groups. METHODS: Using data from 149,692 persons interviewed by the 1999 Behavioral Risk Factor Surveillance System, we estimated the proportion of adults age > or =20 years who were screened for high blood cholesterol within the preceding 5 years. RESULTS: Overall, an estimated 70.8% of the U.S. population was screened for cholesterol, falling short of the Year 2000 objective of 75%. Screening prevalence was lowest at ages 20-44 years (58.2%), in contrast to ages 45-64 years (81.9%) and > or =65 years (87.1%). Screening prevalence was also low among Asian or Pacific Islanders (62.7%) and Hispanics (60.7%), particularly Hispanic men (55.3%). After multivariate adjustment, Asian Pacific Islanders were significantly less likely to be screened compared with white non-Hispanics (OR = 0.76, 95% CI 0.65, 0.89). The likelihood of screening decreased with decreasing income level (P < 0.05) and persons with health insurance were 1.6 times more likely to have been screened during the past 5 years than adults with no insurance (P < 0.05). CONCLUSIONS: Significant disparities in cholesterol screening exist across age, gender, racial or ethnic, and socioeconomic groups in the United States. As we look to attain the objectives of Healthy People 2010, state and local health officials and policy makers should be aware of these disparities in order to design and target effective cholesterol screening programs and cardiovascular disease prevention programs to those most in need.

Adult↗
PubMed2001

Non-M protein(s) on the cell wall and membrane of group A streptococci induce(s) IFN-gamma production by dermal CD4+ T cells in psoriasis.

Recently we have demonstrated that a disease-specific subpopulation of CD4+ T cells isolated from skin lesions of chronic plaque psoriasis produces interferon-gamma in response to group A streptococcal (GAS) antigens. To determine if these T cells recognize M or non-M protein, extracts from cell wall of type M6 GAS (M6W) and its isogenic M gene deletion mutant (M-W), M6 membrane extract (M6M) and recombinant M6 protein (rM6) were used to stimulate GAS-reactive T-cell lines from nine patients with chronic plaque psoriasis. T-cell lines were incubated with or without streptococcal extracts for 18 h in the presence of a transport inhibitor, stained for surface CD4 and intracellular cytokine expression, and analysed by flow cytometry. Variable numbers (0.2-34%) of CD4+ T cells produced interferon-gamma, in all but one of the T-cell lines tested, in response to M6W, M-W and M6M extracts. No significant difference between the response to M6W and M-W extracts was detected. In addition, rM6 protein failed to increase CD4+/interferon-gamma+ T-cell numbers in seven of nine T-cell lines compared to medium alone. For the group, there was a highly significant correlation between the responses to the three extracts (M6W vs M-W, P = 0.0005; M6W vs M6M, P = 0.0003; M-W vs M6M, P = 0.0001). Low or minimal numbers of interleukin-4- and interleukin-10-producing CD4+ T cells were occasionally induced. These findings suggest that a subpopulation of CD4+ T cells isolated from skin lesions of chronic plaque psoriasis patients produces interferon-gamma in response to non-M protein(s) present on the cell wall and membrane of GAS.

Adult↗
PubMed2001

White blood cell count: an independent predictor of coronary heart disease mortality among a national cohort.

An association between elevated white blood cell (WBC) count and coronary heart disease (CHD) mortality has been previously observed. However, the relationship between WBC count and CHD mortality independent of cigarette smoking and the possible interaction between WBC count and smoking remains unclear. We examined the association between WBC count and CHD mortality with Cox regression analyses of data from 8914 adults, aged 30-75, in the NHANES II Mortality Study (1976-1992). Covariates included age, sex, race, education, physical activity, smoking status, hypertensive status, total serum cholesterol, body mass index, hematocrit, and history of cardiovascular disease, stroke, and diabetes. During 17 follow-up years, there were 548 deaths from CHD (ICD-9 410-414) and 782 deaths from diseases of the heart (ICD-9 390-398, 402, 404, 410-414, 415-417, 420-429). Mean WBC count (x10(9) cells/L) was greater among persons who died from CHD (7.6 vs 7.2, P <.001). Compared to persons with a WBC count <6.1, persons with a WBC count > 7.6 were at increased risk of death from CHD (relative risk = 1.4, 95% confidence interval = 1.1-1.8) after adjustment for smoking status and other CVD risk factors. Similar results were observed among nonsmokers (RR = 1.4, 95% CI = 0.9-2.0). These results suggest that higher WBC counts are a predictor of CHD mortality independent of the effects of smoking and other traditional CVD risk factors, which may indicate a role for inflammation in the pathogenesis of CHD. Additional studies are needed to determine whether interventions to decrease inflammation can reduce the risk for CHD associated with elevated WBC.

Adult↗
PubMed2001

The aetiology of maculopapular rash diseases in Niterói, State of Rio de Janeiro, Brazil: implications for measles surveillance.

A study investigating the causes of rash diseases using systematic laboratory testing was conducted in Niterói, Rio de Janeiro, between January 1994 to April 1998. Sera from 327 patients were tested for evidence of anti-rubella virus, measles virus, human parvovirus B19 and dengue fever virus specific immunoglobulin IgM and anti-human herpes virus type 6 (HHV-6) IgG antibodies. A laboratory confirmed diagnosis was achieved in 71.3% of the cases investigated: dengue fever (33.0%), rubella (20.2%), parvovirus B19 (9.2%), measles (6.7%) and HHV-6 (2.1%). No diagnosis was established for 94 cases (28.7%). An outbreak of measles was detected during 1997, with a peak in September and October. All of the diseases studied here presented with clinical features similar to measles and classical symptoms were found in all measles confirmed cases. The large overlap of combinations of signs and symptoms seen in this study highlights the difficulties of diagnosing a rash illness on clinical grounds alone.

Adolescent↗
PubMed2001

Epidermal CD8+ T cells in chronic plaque psoriasis are Tc1 cells producing heterogeneous levels of interferon-gamma.

The majority of epidermal CD8+ T cells in chronic plaque psoriasis are activated Tc1 cells producing interferon-gamma and no interleukin-4, a small proportion of which express NK-T receptors. To quantitate their level of cytokine production and characterize them further, CD8+ T cells were isolated from epidermal cell suspensions of lesional biopsies from 24 patients with chronic plaque psoriasis. T-cell lines (TCL) were established by culture of CD8+ T cells with feeders and IL-2 for 11 days and expansion with PHA. Ten TCL were stained for surface markers; 6 were cloned with PHA by limiting dilution. Interferon-gamma, interleukin-4 and interleukin-10 production was measured by ELISA after PMA/anti-CD3 activation of 15 TCL and 39 CD8+ T-cell clones. The 10 TCL stained were CD8alphabeta+ (93.3%), T-cell receptor-alphabeta+ (99.5%), costimulatory molecule CD28+ (90.1%), with a small CD8alphaalpha+ population (2.3%). No NK-T-cell receptor CD158a or CD158b expression was detected, whilst CD94 was expressed on 6.2% of cells in 6/9 TCL. All the TCL and 37/39 CD8+ T-cell clones produced interferon-gamma but no or minimal interleukin-4 or interleukin-10. The TCL produced a wide range of interferon-gamma levels (138 to 15,020 pg/ml). Clones from 3 patients showed low levels (60 to 1,410 pg/ml), from 2 patients high levels (6,105 to 43,040 pg/ml) and from 1 patient a wide range (405 to 36,010 pg/ml) of interferon-gamma production. Thus epidermal CD8+ Tc1 cells in chronic plaque psoriasis produce highly heterogeneous levels of interferon-gamma, which may reflect clinical diversity.

Adult↗
PubMed2001

Skin T cell proliferative response to M protein and other cell wall and membrane proteins of group A streptococci in chronic plaque psoriasis.

To determine and compare the T cell response to M protein and other group A streptococcal (GAS) antigens, T cell lines (TCL) were cultured from the lesional skin of 33 psoriatic patients and 17 disease controls. GAS-reactive skin TCL were tested in proliferation assays with recombinant M6 protein, and extracts of cell wall and membrane from type M6 GAS and its corresponding M gene deletion mutant. Initially, GAS-reactive skin TCL were obtained from 16 of 25 (64%) psoriasis, and from seven of 17 (41%) control patients. Eleven psoriatic and four control GAS-reactive TCL proliferated to M6 cell wall extract, whereas all the TCL from both groups responded to the extract of M6 membrane proteins. This difference in response to the two extracts was significant for both groups of patients (psoriasis, P = 0.0335, controls, P = 0.0156). GAS-reactive TCL from a further eight psoriasis patients showed no difference in response to cell wall extract from M6 GAS (containing the M protein minus its C-terminus) compared to that of its corresponding M gene deletion mutant. Furthermore, GAS-reactive TCL did not proliferate to recombinant M6 protein. However, a small, but significant reduction in proliferation by the eight psoriatic GAS-reactive TCL to the M-negative (lacking the M protein C-terminus) compared to M6-positive membrane extract was observed (P = 0.01). These findings suggest that GAS-reactive T cells in skin lesions of chronic plaque psoriasis proliferate to streptococcal membrane and, to a lesser extent, cell wall proteins. However, psoriatic skin T cells do not recognize cell wall M protein.

Adult↗
PubMed2001

Hematocrit and the risk of coronary heart disease mortality.

BACKGROUND: An association between hematocrit (Hct) and coronary heart disease (CHD) mortality has been previously observed. However, the relationship of Hct and CHD independent of other cardiovascular disease (CVD) risk factors and differences between men and women remain unclear. METHODS: We examined the association between Hct and CHD mortality with Cox regression analyses of data from 8896 adults, aged 30-75 years, in the Second National Health and Nutrition Examination Survey (NHANES II) Mortality Study (1976-1992). Covariates included age, sex, race, education, smoking status, hypertensive status, total serum cholesterol, body mass index, white blood cell count, and history of CVD and diabetes. Hct was categorized by use of sex-specific tertiles, and all analyses were stratified by sex. RESULTS: During 16.8 years of follow-up, there were 545 (men 343, women 202) deaths from CHD (International Classification of Diseases, 9th revision [ICD-9] 410-414), 778 (men 426, women 279) deaths from diseases of the heart (ICD-9 390-398, 402, 404, 410-414, 415-417, 420-429), and 2046 (men 1216, women 830) all-cause deaths. Among men, the crude CHD mortality rate per 10,000 population was 42.6, 31.9, and 46.3 among those with Hct in the lower, middle, and upper tertiles, respectively. The corresponding crude CHD mortality rates among women were 12.6, 18.6, and 27.7. After adjustment for age and other CVD risk factors, there was no association between Hct in the upper tertile compared with the lower tertile and mortality from either CHD, diseases of the heart, or all causes among men. Women with Hct in the upper tertile were 1.3 times (95% CI 0.9-1.9) more likely to die from CHD than were women with Hct in the lowest tertile, after multivariate adjustment. The effect of high Hct on CHD mortality among women younger than 65 years of age was slightly stronger (relative risk 2.2, 95% CI 1.0-4.6). CONCLUSIONS: These results suggest that the association between Hct and mortality from CHD and all causes is complex, differing both by sex and age. Further research is needed to gain a better understanding of these age and sex differences.

Adolescent↗
PubMed2001

Bile duct injury during laparoscopic cholecystectomy: results of a national survey.

OBJECTIVE: To determine whether surgical residency training has influenced the occurrence of common bile duct injuries during laparoscopic cholecystectomy, and to asses the anatomic and technical details of bile duct injuries from the practices of surgeons trained in laparoscopic cholecystectomy after residency versus surgeons trained in laparoscopic cholecystectomy during residency. SUMMARY BACKGROUND DATA: Shortly after the introduction of laparoscopic cholecystectomy, the rate of injury to the common bile duct increased to 0.5%, and injuries were more commonly reported early in each surgeon's experience. It is not known whether learning laparoscopic cholecystectomy during surgery residency influences this pattern. METHODS: An anonymous questionnaire was mailed to 3,657 surgeons across the United States who completed an Accreditation Council for Graduate Medical Education (ACGME)-approved residency between 1980 and 1990 (group A) or 1992 and 1998 (group B). All surgeons in group A learned laparoscopic cholecystectomy after residency, and all those in group B learned laparoscopic cholecystectomy during residency. Information obtained included practice description, number of laparoscopic cholecystectomies completed since residency, postgraduate training in laparoscopy, and annual volume of laparoscopic cholecystectomy in the surgeon's hospital. In addition, technical details queried included the completion of a cholangiogram, the interval between injury and identification, the method of repair, and the site of definitive treatment. The primary endpoint was the occurrence of a major bile duct injury during laparoscopic cholecystectomy (bile leaks without a major bile duct injury were not tabulated). RESULTS: Forty-five percent (n = 1,661) of the questionnaires were completed and returned. Mean practice experience was 13.6 years for group A and 5.4 years for group B. At least one injury occurrence was reported by 422 surgeons (37.6%) in group A and 143 surgeons (26.5%) in group B. Forty percent of the injuries in group A occurred during the first 50 cases compared with 22% in group B. Thirty percent of bile duct injuries in group A and 32.9% of all injuries in group B occurred after a surgeon had performed more than 200 laparoscopic cholecystectomies. Independent of the number of laparoscopic cholecystectomies completed since residency, group A surgeons were 39% more likely to report one or more biliary injuries and 58% more likely to report two or more injuries than their counterparts in group B. Bile duct injuries were more likely to be discovered during surgery if a cholangiogram was completed than if cholangiography was omitted (80.9% vs. 45.1%). Sixty-four percent of all major bile duct injuries required biliary reconstruction, and most injuries were definitively treated at the hospital where the injury occurred. Only 14.7% of injuries were referred to another center for repair. CONCLUSIONS: Accepting that the survey bias underestimates the true frequency of bile duct injuries, residency training decreases the likelihood of injuring a bile duct, but only by decreasing the frequency of early "learning curve" injuries. If one accepts a liberal definition of the learning curve (200 cases), it appears that at least one third of injuries are not related to inexperience but may reflect fundamental errors in the technique of laparoscopic cholecystectomy as practiced by a broad population of surgeons in the United States. Intraoperative cholangiography is helpful for intraoperative discovery of injuries when they occur. Most injuries are repaired in the hospital where they occur and are not universally referred to tertiary care centers.

Adult↗
PubMed2001

Rotavirus G and P genotypes in rural Ghana.

An epidemiological study of rotavirus infection was conducted on specimens collected from patients with gastroenteritis and domiciled in the rural Upper Eastern Region of Ghana during 1998. Fifty isolates, randomly selected from 165 human group A rotavirus-positive samples, were G and P characterized by a reverse transcription (RT)-PCR assay using a seminested multiplex method. Rotaviruses of the G3 genotype were found to be the predominant strain (78%), followed by G2 (14%) and G1 (2%). Mixed infections, as shown by combinations of G3 and G2 (4%) and G3 and G1 (2%), were also observed. P typing showed P[4] (72.34%) to be the prevalent strain, followed by P[6] (21.3%), P[8] (2.13%), and a combination of P[4] and P[6] (4.3%).

Child, Preschool↗
PubMed2001

Impaired fasting glucose, diabetes mellitus, and cardiovascular disease risk factors are associated with prolonged QTc duration. Results from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Impaired glucose tolerance and diabetes mellitus have been associated with a prolonged QT interval among select populations. However, these associations remain unclear among the general population. METHODS: We examined these relationships using data from 5833 adults aged 40-90 years from NHANES III (1988-1994). Univariate differences in cardiovascular disease (CVD) risk factors were examined across tertiles of heart rate corrected QT (QTc). The association between glucose intolerance, CVD risk factors and a prolonged QTc (> or = 0.440 s) was also assessed with logistic regression adjusting for age, race, gender, education, and heart rate. RESULTS: Prolonged QTc was observed among 22.0% of persons with normal glucose tolerance (NGT), 29.9% of those with impaired fasting glucose (IFG), and among 42.2% of persons with diabetes. Hypertension, serum cholesterol, obesity, heart rate, and fasting C-peptide and serum insulin levels were associated with prolonged QTc (all: P < or = 0.05). After multivariate adjustment, persons with IFG were 1.2 times (95% CI=0.7-2.0) as likely and persons with diabetes 1.6 times (95% CI=1.1-2.3) as likely to have a prolonged QTc as persons with NGT. In addition, persons with diabetes and two or more additional CVD risk factors were 2.3 times (95% CI=1.3-4.0) as likely to have a prolonged QTc as persons with NGT and no CVD risk factors after multivariate adjustment. CONCLUSION: Diabetes was associated with an increased likelihood of prolonged QTc independent of age, race, gender, education, and heart rate. In addition, persons with diabetes and multiple CVD risk factors were more likely to have a prolonged QTc than those with NGT and no additional risk factors, suggesting that these persons may be at increased risk for cardiac arrhythmia and sudden death.

Blood Glucose↗