PubMed Health⌕ Search

Biomedical subjects

B J Ward

Publications and source records attributed to B J Ward.

At least 19 recordsLinked to original sources
PubMed2000

Development and durability of measles antigen-specific lymphoproliferative response after MMR vaccination.

The correlates of long-term protection from measles infection are poorly understood. We followed the development of measles-specific antibody and lymphoproliferative (LP) responses in 60 children for 6 months after MMR vaccination. Prevaccine plaque reduction neutralization antibody (PRN Ab) values were low (mean+/-SEM 9.9+/-1. 1). Ninety-three percent (56/60) had excellent PRN values at 6 months (PRN 1816+/-207). Prevaccine LP activity was also low (stimulation index (SI)=1.4+/-0.1) but increased rapidly (SI 10. 7+/-4.5 at 2-3 weeks; p<0.05). However, only 61% (37/60) of the children had both significant cellular and antibody responses (SI>/=3 and PRN>/=120: Ab(hi)CMI(hi)). One child had a strong LP response (SI=6.7) despite little antibody production (PRN=19 at 6 months: Ab(lo)CMI(hi)). We also conducted a cross-sectional study in a separate group of 87 children 5-13 years after MMR vaccination. PRN values >/=120 were present in most children at 5-8 (n=28) and 9-13 years (n=59) after vaccination (PRN 550+/-120 and 360+/-60, respectively) but a significant minority had either undetected or 'subprotective' values (29 and 34%, respectively). LP responses (SI>/=3) were detectable in 19/28 (66%) and 36/59 (56%) of the children 5-8 and 9-13 years after vaccination (SI 11.4+/-2.4 and 7. 75+/-1.9, respectively). Almost two thirds (18/28) of the children in the cross-sectional study with low or absent antibody titers (PRN 41+/-6) had strong LP responses to measles antigens (SI 6.8+/-1.3). These data suggest that LP responses may be better sustained than antibody titers in some children. The susceptibility of Ab(lo)CMI(hi) children to infection and the value of the early LP response for predicting the durability of immunity remain to be determined.

Adolescent↗
PubMed2000

Performance of indirect immunoglobulin M (IgM) serology tests and IgM capture assays for laboratory diagnosis of measles.

As progress is made toward elimination of measles, the laboratory confirmation of measles becomes increasingly important. However, both false-positive and false-negative results can occur with the routinely used indirect measles immunoglobulin M (IgM) serology tests. The measles IgM capture assay is considered to be more specific, and therefore, its use is indicated for confirmatory testing, but its relative performance has not been fully assessed. Four commercial indirect measles IgM serology test kits (the Behring, Clark, Gull, and PanBio assays) and a commercial IgM capture assay (the Light Diagnostics assay) were evaluated for their abilities to detect measles virus-specific IgM antibody with a total of 308 serum samples from patients involved in a measles outbreak and with confirmed cases of measles and 454 samples from subjects without measles. The Centers for Disease Control and Prevention (CDC) IgM capture assay was also used in a part of the evaluation. Among the indirect assays, the overall sensitivities ranged from 82.8% (Clark assay) to 88.6% (Behring assay) and specificity ranged from 86.6% (PanBio assay) to 99.6% (Gull assay). These rates were 92.2 and 86. 6%, respectively, for the Light Diagnostics capture assay and 87.0 and 94.8%, respectively, for the CDC capture assay. While the Light Diagnostics capture assay had the best detection rate (80%) with the acute-phase samples compared with those for the rest of the tests (CDC capture assay, 77%; Behring assay, 70%; Gull assay, 69%; PanBio assay, 58%; and Clark assay, 57%), all tests showed a significantly improved sensitivity in the range of 92% (Clark and PanBio assays) to 97% (Light Diagnostics and CDC capture assays) with the convalescent-phase samples, as expected. The best seropositivity rates (in the range of 92 to 100%) were observed with samples collected 6 to 14 days after the onset of symptoms. The Gull assay showed the highest positive predictive value (99.6%), followed by the Behring assay (97.8%) and the CDC capture assay (96.1%). Overall, the Gull and Behring assays were found to be as good as or better than the capture assays. In conclusion, laboratory diagnosis of measles based on IgM serology varies depending on the timing of specimen collection and the test used, and the case for the use of the IgM capture assay as the confirmatory test appears to be uncertain.

Antibodies, Viral↗
PubMed2000

Vaccine adverse events in the new millennium: is there reason for concern?

As more and more infectious agents become targets for immunization programmes, the spectrum of adverse events linked to vaccines has been widening. Although some of these links are tenuous, relatively little is known about the immunopathogenesis of even the best characterized vaccine-associated adverse events (VAAEs). The range of possible use of active immunization is rapidly expanding to include vaccines against infectious diseases that require cellular responses to provide protection (e.g. tuberculosis, herpes viral infections), therapeutic vaccines for chronic infections (e.g. human immunodeficiency virus (HIV) infection, viral hepatitis B and C), and vaccines against non-infectious conditions (e.g. cancer, autoimmune diseases). Less virulent pathogens (e.g. varicella, rotavirus in the developed world) are also beginning to be targeted, and vaccine use is being justified in terms of societal and parental "costs" rather than in straightforward morbidity and mortality costs. In the developed world the paediatric immunization schedule is becoming crowded, with pressure to administer increasing numbers of antigens simultaneously in ever simpler forms (e.g. subcomponent, peptide, and DNA vaccines). This trend, while attractive in many ways, brings hypothetical risks (e.g. genetic restriction, narrowed shield of protection, and loss of randomness), which will need to be evaluated and monitored. The available epidemiological and laboratory tools to address the issues outlined above are somewhat limited. As immunological and genetic tools improve in the years ahead, it is likely that we shall be able to explain the immunopathogenesis of many VAAEs and perhaps even anticipate and avoid some of them. However, this will only happen if the human and financial resources needed for monitoring and studying vaccine safety stay in step with the accelerating pace of vaccine development. Failure to make such a commitment would put all immunization programmes at risk.

Adverse Drug Reaction Reporting Systems↗
PubMed1999

Measurement of measles virus-specific neutralizing antibodies: evaluation of the syncytium inhibition assay in comparison with the plaque reduction neutralization test.

Plaque reduction neutralization (PRN) is the "gold-standard" for the measurement of measles-specific neutralizing antibodies. However, it is a complicated assay and tends to be operator-dependent. It has been suggested that the simpler syncytium inhibition assay (SIA) can give results comparable to the PRN test. We compared these two assays using 594 serum or plasma samples obtained from children at various times after natural infection, primary measles immunization, and measles revaccination. The results of the two assays correlated well overall (r = .86; p < 0.0001). The strain of challenge virus (wild-type versus vaccine strain) did not significantly influence SIA titers and the assay performed equally well with serum and plasma. PRN titers > or = 120 and > 800 are thought to indicate protection against clinical illness and infection respectively. The equivalent SIA cut-off values using 125 plaque-forming units as the challenge inoculum were > or = 16 and > 128 respectively. At low PRN titers (< 200), the correlation between PRN and SIA values was reasonable (r = 0.60; p < 0.001) when a challenge inoculum of 12.5 plaque-forming units was used. At the lowest PRN titers (< 100), 15% of the samples gave divergent results. These data confirm the utility of the SIA in the determination of measles-specific neutralizing antibodies when antibody titers are high. However, the PRN assay remains the test of choice when maximum sensitivity at low titers is required.

Adolescent↗
PubMed1999

Mycobacterium ulcerans infection (Buruli ulcer): first reported case in a traveler.

A chronic, painless sore developed over a 2-month period on the left calf of a Canadian man traveling for 8 months in Africa. A presumptive diagnosis of a Mycobacterium spp. infection was made despite initially negative biopsy and culture results, after failure of several courses of anti-bacterial antibiotics. Mycobacterium ulcerans was eventually isolated and the lesion progressed despite treatment with multiple anti-mycobacterial agents. The lesion finally responded to wide and repeated excision, aggressive treatment with anti-mycobacterial antibiotics, and split-thickness skin grafting. The isolation and treatment of this unusual organism are discussed.

Adult↗
PubMed1998

Measles vaccines: a review of adverse events.

A great deal of controversy has recently been generated over the publication of several articles implicating measles vaccine in the induction of Crohn's disease and autism. The publication of this work has already had a negative impact on measles vaccine acceptance in the UK. These allegations are particularly troubling because they arise in the context of increased use of measles vaccine as global control of measles nears and the international community considers strategies for a drive towards eradication. In 1994, the US Institute of Medicine reviewed the world literature and published a comprehensive review of adverse events associated with measles-containing vaccines. Reviewing the literature published between 1994 and the present day, reveals that there is considerable new data suggesting that modified gelatin rather than egg proteins is responsible for most episodes of anaphylaxis following measles vaccination. New work weakens the possible links between measles vaccine and subacute sclerosing panencephalitis and Guillain-Barré syndrome, but strengthens the rare association of measles-containing vaccines with post infectious encephalomyelitis. The alleged associations between measles vaccination and Crohn's disease and autism are based upon weak science and have largely been refuted by a large volume of stronger work. A review of the data generated in the last 4 years amply demonstrates the continued efforts of the scientific community to monitor and understand true measles vaccine-associated adverse events. The rapidity and clarity of this same community's debunking of the spurious associations with Crohn's disease and autism suggests that those charged with vaccination programmes have learned from past mistakes. During 30 years of worldwide use, measles vaccination has proven to be one of the safest and most successful health interventions in the history of mankind. It is not a 'perfect' vaccine, but the benefits of measles vaccination far outweigh the risks even in countries with low incidence of measles and high rates of measles vaccine coverage.

Child↗
PubMed1998

A beta-actin isotype is present in rat cardiac endothelial cells but not in cardiac myocytes.

OBJECTIVE: Active constriction in cardiac capillary endothelial cells (CCECs) is controversial. It is thought by many researchers that CCECs are not actively involved in constriction; others believe that these cells do contribute some of the force required for capillary constriction. Because actin is a major component of most contractile mechanisms responsible for changing cell shape, we compared two probes as potential monitors of actin distribution in CCECs in situ. METHODS: We used SDS-PAGE, Western blotting, electron microscopy, conventional epifluorescence and confocal microscopy to evaluate an antibody against non-muscle beta-actin and fluorescently labeled phalloidin to detect actin in CCECs. RESULTS: Fluorescently labeled phalloidin detected actin in cardiac muscle and faintly in CCECs. The antibody probe detected non-muscle beta-actin CCECs. However, this actin isotype did not occur in cardiac myocytes. In endothelial cells non-muscle beta-actin was concentrated at the cell periphery, and arranged as bundles of fibers, not as typical stress fibers. CONCLUSIONS: Phalloidin is not suitable as a probe to monitor actin distribution in CCEC's in situ. The antibody is a potentially useful tool in monitoring the actin cytoskeleton and determining the capacity of CCECs for active vasoconstriction in vivo. Non-muscle beta-actin in CCECs is arranged in filament bundles which are not typical stress fibers.

Actins↗
PubMed1997

Diabetes mellitus and echocardiographic left ventricular function in free-living elderly men and women: The Cardiovascular Health Study.

This report describes the relation among diabetes, blood pressure, and prevalent cardiovascular disease, and echocardiographically measured left ventricular mass and filling (transmitral valve flow) velocities in the Cardiovascular Health Study, a cohort of 5201 men and women > or = 65 years of age. Ventricular septal and left posterior wall thicknesses were greater in diabetic than in nondiabetic subjects, showing a significant linear trend (p = 0.025 for ventricular septal thickness in both sexes combined, p = 0.002 for posterior wall thickness) with increased duration of diabetes. Increased wall thickness of the ventricular septum or the left posterior wall was not associated with prevalent coronary heart disease (CHD) in the cohort. Increased left ventricular mass was associated with diabetic persons not reporting CHD and with all subjects with CHD regardless of glucose tolerance status. After adjusting for body weight, blood pressure, heart rate, and prevalent coronary or cerebrovascular disease, diabetes (as measured by glucose level, insulin use, oral hypoglycemic use, and a positive history of diabetes before baseline examination) remained an independent predictor of increased left ventricular mass among men and women (174.2 gm in diabetic men vs 169.8 gm in normal men, 138.2 gm in diabetic women vs 134.0 gm in normal women, p = 0.043 for both sexes combined). Both early and late diastolic transmitral peak flow velocities were higher with increased duration of diabetes, but the calculated ratio of the early peak flow velocity to the late velocity (E/A ratio) did not differ significantly between subjects with historical diabetes and those with normal fasting glucose (both genders combined, p = 0.190). Glucose level, insulin use, oral hypoglycemic use, and a positive history of diabetes before baseline examination were significant independent predictors of the late transmitral peak flow velocity and its integrated flow-velocity curve but not for the integral of the early peak flow velocity or the E/A ratio. Diabetes is associated with abnormal left ventricular structure and function in elderly persons. This association persists after adjustment for body weight, blood pressure, heart rate, and reported coronary or cerebrovascular disease.

Aged↗
PubMed1997

Structural changes in the cardiac microvasculature of the rat in response to acute high glucose levels: a comparison with diabetes.

OBJECTIVE: Isolated rat hearts were used to determine whether structural changes in the coronary microcirculation caused by diabetes mellitus occur soon after the onset of hyperglycemia and whether early changes might be reversed by return to normoglycemic conditions. METHODS: Three experimental groups of hearts were used. The perfusate was Krebs-Henseleit medium with the addition of (a) 25 mmol/L glucose for 60 minutes, (b) as (a) followed by 5 mmol/L glucose for 30 minutes, and (c) hearts from diabetic rats perfused for 15 minutes. All the hearts were fixed and processed for electron microscopy. Measurements were made of various capillary dimensions and basal lamina thickness. RESULTS: The high glucose concentration caused an overall reduction in capillary dimensions which was partly reversed by reperfusion with 5 mmol/L glucose. Diabetic hearts showed enlarged whole capillary and luminal area and thinning of the endothelial cells without any change in cross-sectional area. Endothelial gaps, consistent with increased permeability, were observed in the high glucose group but not in diabetic hearts. The basal lamina was thickened in all three experimental groups compared with controls. CONCLUSIONS: The results show that morphological changes in the microcirculation occur much earlier than was previously thought and, with the possible exception of the basal lamina thickening may be reversible.

Animals↗
PubMed1996

Common-source outbreak of acute infection due to the North American liver fluke Metorchis conjunctus.

BACKGROUND: We investigated an outbreak of acute clinical illness among 19 people who ate raw fish (sashimi) prepared from the white sucker, Catostomus commersoni, caught in a river north of Montreal, Canada. METHODS: We collected epidemiological, clinical, laboratory, and serological data on 19 individuals who ate the sashimi and six who did not. Because of the suggestive clinical picture, we set out to recover helminth parasites from uneaten fish. FINDINGS: The illness consisted of persistent upper abdominal pain, low grade fever, high blood eosinophil concentrations, and raised liver enzymes. After 10 days, opisthorchild-like eggs were found in stools. Symptoms persisted for 3 days to 4 weeks without treatment, but responded rapidly to praziquantel therapy. Necropsy of golden hamsters infected with metacercariae from uneaten fish revealed adult flukes identified as Metorchis conjunctus. INTERPRETATION: We describe an acute illness caused by the North American liver fluke M conjunctus. This is a new human disease and is the first report of a common-source outbreak of an acute illness caused by liver flukes of the family Opisthorchiidae.

Adult↗
PubMed1996

Retinol (vitamin A) supplements in the elderly.

Aging is associated with many changes in epithelial tissues, immune function and haematopoiesis-myelopoiesis. There is increasing evidence that retinoids can significantly influence some of these changes. Retinoids may also have anticancer effects and protect against age-associated conditions such as macular degeneration. However, retinol (vitamin A) can be toxic when taken in excess and the elderly may be at particular risk for hypervitaminosis A. Evaluation of elderly people ingesting significantly more or less than the recommended daily intake of retinol requires an understanding of the biology of retinoids and consideration of the relative risks and benefits of supplementation.

Aged↗
PubMed1996

Asthma and its association with cardiovascular disease in the elderly. The Cardiovascular Health Study Research Group.

Cardiovascular disease (CVD) is more prevalent in elderly than in middle-aged patients. Symptoms such as intermittent wheezing with dyspnea may then be due to either CVD or asthma. The objective of this study was to determine the prevalence and correlates of asthma in the elderly and their associations with CVD and CVD risk factors. A community sample of 5201 elderly persons from the Cardiovascular Health Study was asked if they had a physician diagnosis of asthma, and multiple cardiovascular risk and disease variables were measured. Six percent of the participants (309) recalled a history of asthma, and half of these were never smokers. Thirty percent of those with asthma were currently taking a bronchodilator, 14% inhaled steroids, and 10% oral prednisone. Men and women with asthma who were cigarette smokers were more likely to report a concurrent diagnosis of congestive heart failure than smokers without asthma (p = .04). However, when we determined the independent CVD correlates of asthma in this cohort, controlling for smoking status, age, gender, and diagnoses of chronic bronchitis and emphysema, only higher levels of high-density lipoprotein cholesterol (HDL-C) and higher plasma fibrinogen levels were significantly associated with asthma. It was concluded that asthma is as prevalent in the elderly as in middle-aged persons and is associated with higher HDL-C and higher fibrinogen levels, but not with prevalent cardiovascular disease.

Aged↗
PubMed1995

The influence of hypoxia on transvascular leakage in the isolated rat heart: quantitative and ultrastructural studies.

1. The multiple indicator dilution method was used to study the transvascular movement of gamma-globulin, bovine serum albumin, insulin and cyanocobalamin in the isolated rat heart. 2. Perfusion of the heart with well-oxygenated solution for 75 min (constant flow) did not produce a significant change either in the total area under the dilution curve or the 'leakage index' (an arbitrary measure of transvascular flux) for all the tracers. 3. Perfusion of the heart with hypoxic solution produced a significant increase in leakage of gamma-globulin of 38.6 +/- 18, 48.5 +/- 17.6, 60.5 +/- 24 and 58 +/- 20% after 15, 30, 45 and 60 min, respectively, compared with the well-oxygenated equilibration period. Permeability- surface area products (PS) for the smaller diffusible solutes, therefore, could not be estimated. 4. The flux of albumin, insulin and cyanocobalamin in response to hypoxia was similar to that of gamma-globulin. 5. Ultrastructural examination of well-oxygenated hearts revealed that Monastral Blue-labelled albumin remained within the lumen and that endothelial integrity remained intact. 6. Conversely biopsies from hypoxic hearts showed that the labelled albumin had passed to the interstitium through gaps (approximately 3 microns) in venular endothelium. 7. The results showed that, in intact hearts, hypoxia produced gaps in the endothelium of venules and that these gaps could be the possible route for transvascular leakage of macromolecules.

Animals↗
PubMed1995

Measles, mumps, and rubella antibodies in children 5-6 years after immunization: effect of vaccine type and age at vaccination.

The levels of antibody against measles, mumps, and rubella were determined at 5-6 years postimmunization in 468 children vaccinated with two different trivalent vaccines. The proportions of children without detectable antibody levels were 12 and 3.6% for measles (p < 0.001), 14.9 and 7% for mumps (p = 0.006), and 3.3 and 3.1% for rubella (p = 0.88), respectively, in MMR II and Trivirix recipients. A higher proportion of those vaccinated at younger ages had undetectable or low levels of measles antibody. These data indicate that a large proportion of children vaccinated under routine conditions do not have detectable measles and mumps antibody.

Age Factors↗