Pre-treatment with Aloe vera juice does not enhance the in vitro permeation of ketoprofen across skin.

BACKGROUND/AIMS: The potential of pre-treating skin with Aloe vera juice as a penetration enhancer was evaluated in vitro using ketoprofen as model permeant. METHODS: To excised porcine skin mounted in Franz diffusion cells was applied either: (1) commercial Aloe vera; (2) commercial Aloe vera followed by massaging; (3) previously boiled commercial Aloe vera; (4) water (negative control); (5) tea tree oil (positive control). After 1 h, the pre-treatment was removed and the skin dosed with a saturated solution of ketoprofen in polyethylene glycol 400; the appearance of drug in the receptor phase was then monitored by HPLC. RESULTS: No statistically significant differences in the transdermal delivery of ketoprofen were observed between water and all the Aloe vera pre-treatments (p > 0.05). The tea tree oil pre-treatment was significantly different to all others (p < 0.05). CONCLUSION: Aloe vera appears to have no value as a penetration enhancer when used as a pre-treatment, although the data indirectly support the mechanism of action proposed previously, work when used 'within-vehicle'. Handling household products containing Aloe vera appears not to leave the user at elevated risk of subsequent absorption of exogenous chemicals.

C-reactive protein: relation to total mortality, cardiovascular mortality and cardiovascular risk factors in men.

BACKGROUND: There is much interest in reported associations between serum C-reactive protein and incident ischaemic heart disease. It is uncertain what this association represents. We aimed to assess the effect of confounding from a number of different sources in the Caerphilly Prospective Heart Disease Study and in particular whether the low grade inflammation indicated by C-reactive protein may be the mechanism whereby non-circulating risk factors may influence pathogenesis of ischaemic heart disease. METHODS: Plasma specimens collected during 1979-83 from 1395 men with sufficient sample remaining were assayed for serum C-reactive protein by ELISA. Subsequent mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records and electrocardiographic changes at 5-yearly follow-up examinations. RESULTS: There was a positive association between C-reactive protein and incident ischaemic heart disease (P<0.005) mainly with fatal disease (P<0.002). There was also a positive association with all-cause mortality (P<0.0001). C-reactive protein was significantly associated with a number of non-circulating risk factors including body mass index (P<0.0001), smoking (P<0.0001), low forced expiratory volume in 1 s (P<0.0001), height (P=0.025), low childhood social class (P=0.014) and age (P=0.036). C-reactive protein was also associated positively with circulating risk factors including viscosity, leukocyte count, fibrinogen (all P<0.0001) and insulin (P=0.0058). After adjustment for non-circulating risk factors the association with all-incident ischaemic heart disease and ischaemic heart disease death became non-significant, but the association with all-cause mortality remained (P=0.033). Further adjustment for fibrinogen however removed any hint of an increasing trend in odds for all three outcomes. CONCLUSION: C-reactive protein levels are raised in association with a variety of established cardiovascular risk factors. Neither C-reactive protein nor the systemic inflammation it represents appears to play a direct role in the development of ischaemic heart disease.

Western blotting is useful in the salivary diagnosis of Helicobacter pylori infection.

BACKGROUND: The salivary diagnosis of Helicobacter pylori infection offers attractive possibilities for the epidemiological study of infection in children. Salivary enzyme linked immunosorbent assay (ELISA) is less reliable then serum ELISA, owing to variable transudation of immunoglobulin. In addition, children are more difficult to study because of lower specific serum antibody concentrations to H pylori. The performance of salivary western blotting in comparison with serum western blotting and serum ELISA was investigated in school children. SUBJECTS AND METHODS: Paired serum and saliva specimens were obtained from 669 [corrected] school children aged 9-11 in 10 British towns. All saliva and serum specimens were first analysed by ELISA; subsequently, western blotting of both specimens was performed on 31 and 34 specimens, respectively, to establish the criteria for positivity for western blotting. The remaining 121 specimens were then tested blindly and saliva was compared with the serum. RESULTS: The sensitivity and specificity of salivary ELISA in the 669 [corrected] specimens was 32 of 50 (64%) and 530 of 619 (86%) [corrected], respectively, when compared with serum ELISA. The western blotting validation was performed on 28 subjects with positive serum and positive salivary ELISA, 28 saliva positives with negative serum, 16 saliva negatives with positive serum, and 50 doubly negative subjects. Compared with serum western blots, the sensitivity and specificity of salivary western blots was 38 of 47 (81%) and 68 of 75 (91%), respectively. Using serum ELISA as the gold standard, the sensitivity and specificity were 32 of 44 (73%) and 72 of 78 (92%), respectively, the specificity being significantly higher than salivary ELISA (p < 0.001). CONCLUSION: Salivary western blotting for IgG is useful in the diagnosis of H pylori infection and is superior to ELISA. It also permits the identification of pathogenic strains.

C-reactive protein concentration in children: relationship to adiposity and other cardiovascular risk factors.

Whether or not C-reactive protein (CRP) predicts heart disease in adults because it is a marker of damage or atherosclerosis is difficult to assess. In children, there is no confounding with coronary disease or active smoking. We measured CRP in 699 children aged 10-11 years. CRP levels were 47% higher in girls than boys, and rose with age by 15%/year. CRP levels were 270% (95% CI, 155-439%) higher in the top fifth than the bottom fifth of Ponderal index (weight/height(3)). After adjustment, CRP levels remained 104% (95% CI, 23-236%) higher in the 56 children of South Asian origin. CRP was unrelated to: birth weight, height, social class, Helicobacter pylori infection or passive smoke exposure. CRP was correlated with several cardiovascular risk factors, but only fibrinogen (r = 0.33, P = 0.0001), HDL-cholesterol (r = -0.13, P = 0.0006), heart rate (r = 0.12, P = 0.002) and systolic blood pressure (r = 0.08, P = 0.02) remained statistically significant after adjustment. We conclude that adiposity is the major determinant of CRP levels in children while physical fitness has a small independent effect. The strong relationships with fibrinogen and HDL-cholesterol suggest a role for inflammation throughout life in the development of atherosclerosis and cardiovascular disease. Longitudinal studies are needed to determine whether these associations reflect long term elevations of these risk factors in some individuals, or short term fluctuations in different individuals.

Relation of Chlamydia pneumoniae serology to mortality and incidence of ischaemic heart disease over 13 years in the caerphilly prospective heart disease study.

OBJECTIVES: To investigate the effect of Chlamydia pneumoniae infection on future development of ischaemic heart disease and mortality. DESIGN: Prospective longitudinal study. SETTING: Caerphilly, South Wales. SUBJECTS: Plasma specimens were collected during 1979-83 from 1773 men aged 45-59 years. These were tested for IgG and IgA antibodies to C pneumoniae (TW183) by microimmunofluorescence. OUTCOME MEASURES: 13 year mortality and incident ischaemic heart disease events were ascertained from death certificates, hospital records, and electrocardiographic changes at follow up every 4 to 5 years. RESULTS: 642 men (36.2%) had IgG antibodies at a titre of >/=1 in 16, of whom 362 (20.4% of all men) also had detectable IgA antibodies. The prevalence of ischaemic heart disease (a history of past or current disease) at entry was similar at all IgG antibody titres but was positively related to IgA antibody titre. IgA antibody titre was positively correlated with plasma viscosity but not with other cardiovascular risk factors. Incidence of ischaemic heart disease was not associated with either IgG antibody titre or IgA antibody titre, but there were stronger and significant relations of IgA antibodies with all cause mortality and fatal ischaemic heart disease, which persisted after adjustment for conventional cardiovascular risk factors. The odds ratios associated with detectable IgA antibodies were 1.07 (95% confidence interval 0.75 to 1.53) for all incident ischaemic heart disease, 1. 83 (1.17 to 2.85) for fatal ischaemic heart disease, and 1.50 (1.10 to 2.04) for all cause mortality. CONCLUSION: This is the first prospective demonstration of an association between IgA antibodies to C pneumoniae, a putative marker of chronic infection, and subsequent risk of death from ischaemic heart disease. In contrast to earlier case-control studies, IgG antibodies were not associated with either prevalent or incident ischaemic heart disease.

Relationship between Helicobacter pylori, gastric parietal cell antibodies and heat shock proteins.

BACKGROUND: The relationship between Helicobacter pylori and autoimmune (type A) gastritis is unclear. Infections may trigger autoimmune phenomena but the underlying mechanisms are unknown. AIM: To determine the relationships between H. pylori infection and gastric parietal cell antibodies (PCA), and PCA and heat shock protein (HSP) antibody. METHODS: Fifty-five serum samples positive for PCA, 22 males and 33 females (median age 61 years, range 29-108 years) were compared with 60 control samples negative for PCA, 24 males and 36 females (median age, 48 years, range 11-91 years). H. pylori infection and HSP65K antibodies were determined by enzyme-linked immunosorbent assay. CagA and VacA status were determined by Western blotting. RESULTS: The prevalence of H. pylori was higher in PCA-positives than controls, 29/55 [53%, 95% confidence interval (CI) 39-66%] versus 13/60 (22%, 95% CI 12-34); P= 0.0009. Age was not a confounding factor. Odds ratio for PCA seropositivity if H. pylori-positive was 4.0 (1.79-9.07), P= 0.003. There was an interaction between age and H. pylori, particularly in younger patients. CagA strains were less common in PCA-positives than controls, 10/29 (35%, 95% CI 19-54) versus 9/13 (69%, 39-91), P< 0.05. HSP65K antibodies were elevated in H. pylori infection but to a similar degree for both PCA-positives and controls. CONCLUSION: H. pylori, particularly CagA-negative strains, are associated with autoimmune gastritis and may be implicated in the pathogenesis of autoimmune (type A) gastritis, particularly in younger persons.

Screening dyspeptic patients for Helicobacter pylori prior to endoscopy: laboratory or near-patient testing?

BACKGROUND: It is unclear whether near-patient whole-blood diagnostic tests for Helicobacter pylori are of comparable accuracy to laboratory based ELISA for screening of dyspeptic patients prior to endoscopy. AIM: To compare two ELISA and two whole-blood tests in order to determine whether near-patient H. pylori diagnostic tests are an acceptable alternative to laboratory based ELISA tests for screening of dyspeptic patients prior to endoscopy. METHOD: One hundred and seven consecutive patients with dyspepsia (median age, 32 years; range, 16-45 years) were evaluated with Helico-G ELISA, Hmcap ELISA and Helisal whole-blood tests. A further 111 dyspeptic patients (median age, 51 years; range, 16-96 years) were evaluated with the Immunocard whole-blood test only. The 'gold standard' for infection was based on histology and the rapid urease test (CLO). RESULTS: Compared to the Helico-G test, both near-patient tests had a higher false negative rate (23-37% vs 5%, P< 0.003), and lower sensitivity and negative predictive value. The Immunocard had a higher specificity than did the Helisal (87% vs 63%, P=0.006); otherwise both near-patient whole-blood tests had similar performance. At a sensitivity of 95%, the Hmcap ELISA was more specific than the Helico-G ELISA (75% vs 67%) and had fewer false positives (25% vs 32%). The near-patient tests would wrongly classify up to 40% H. pylori positive dyspeptic patients and exclude them from endoscopy, compared to 5-6% for ELISA. CONCLUSIONS: Near-patient whole-blood H. pylori diagnostic tests are less accurate and thus not an acceptable alternative to laboratory based ELISA tests.

A randomized trial of endoscopy vs no endoscopy in the management of seronegative Helicobacter pylori dyspepsia.

BACKGROUND: It is unclear whether endoscopy influences the management of Helicobacter pylori negative dyspepsia. AIM: To determine whether endoscopy alters health-care resource utilization, quality of life and symptom outcome in H. pylori seronegative dyspeptic patients aged under 45 years; and to determine which factors predict outcome of symptoms. METHOD: One hundred and fifty-four H. pylori seronegative subjects were randomized to have an endoscopy or no endoscopy before subsequent management by their GPs. Assessment was carried out at 6 months and supplementary information obtained at 12 months. RESULTS: There was no significant difference between the two groups for progression of dyspeptic symptoms (better, same and worse) at 6 months (47%, 46%, 7% vs 43%, 52%, 5%), and at 12 months (55%, 34%, 11% vs 57%, 28%, 15%). Prescriptions were lower in both groups at 6 and 12 months than on entry into the study, independent of endoscopy. Endoscopy did not influence quality of life, visits to GPs and days lost from work. Prognostic factors for symptom resolution at 6 months were lower severity of initial symptoms, non-smoking, non-Caucasians, less anxious patients and those not on acid suppressants. CONCLUSIONS: H. pylori negative dyspeptic patients aged under 45 years without sinister symptoms could be managed without the need of an endoscopy.

Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease.

OBJECTIVE: To determine whether serum concentrations of the cytokines tumour necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6), which regulate C reactive protein, are associated with cardiovascular risk factors and prevalent coronary heart disease. DESIGN: A population based cross sectional study. SUBJECTS AND METHODS: 198 men aged 50 to 69 years were part of a random population sample drawn from south London. Serum cytokine and C reactive protein concentrations were determined by enzyme linked immunosorbent assay. The presence of coronary heart disease was determined by Rose angina questionnaire and Minnesota coded electrocardiogram. RESULTS: Serum TNF alpha concentrations were positively related to body mass index and Helicobacter pylori infection, but inversely related to alcohol consumption. IL-6 concentrations were positively associated with smoking, symptoms of chronic bronchitis, age, and father having a manual occupation. TNF alpha was associated with increased IL-6 and triglycerides, and reduced high density lipoprotein cholesterol. IL-6 was associated with raised fibrinogen, sialic acid, and triglycerides. ECG abnormalities were independently associated with increases in IL-6 and TNF alpha, each by approximately 50% (P < 0.05 for TNF alpha, P < 0.1 for IL-6). The corresponding increases in men with an abnormal ECG or symptomatic coronary heart disease were 28% for TNF alpha and 36% for IL-6 (P = 0.14 for TNF alpha and P < 0.05 for IL-6). CONCLUSIONS: This study confirms that many of the phenomena with which C reactive protein is associated, are also associated with serum levels of cytokine, which may be the mechanism.

C reactive protein and its relation to cardiovascular risk factors: a population based cross sectional study.

OBJECTIVE: To test the hypothesis that minor chronic insults such as smoking, chronic bronchitis, and two persistent bacterial infections may be associated with increases in C reactive protein concentration within the normal range and that variations in the C reactive protein concentration in turn may be associated with levels of cardiovascular risk factors and chronic coronary heart disease. DESIGN: Population based cross sectional study. SETTING: General practices in Merton, Sutton, and Wandsworth. SUBJECTS: A random sample of 388 men aged 50-69 years from general practice registers. 612 men were invited to attend and 413 attended, of whom 25 non-white men were excluded. The first 303 of the remaining 388 men had full risk factor profiles determined. INTERVENTIONS: Measurements of serum C reactive protein concentrations by in house enzyme linked immunosorbent assay (ELISA); other determinations by standard methods. Coronary heart disease was sought by the Rose angina questionnaire and Minnesota coded electrocardiograms. MAIN OUTCOME MEASURES: Serum C reactive protein concentrations, cardiovascular risk factor levels, and the presence of coronary heart disease. RESULTS: Increasing age, smoking, symptoms of chronic bronchitis, Helicobacter pylori and Chlamydia pneumoniae infections, and body mass index were all associated with raised concentrations of C reactive protein. C Reactive protein concentration was associated with raised serum fibrinogen, sialic acid, total cholesterol, triglyceride, glucose, and apolipoprotein B values. C Reactive protein concentration was negatively associated with high density lipoprotein cholesterol concentration. There was a weaker positive relation with low density lipoprotein cholesterol concentration and no relation with apolipoprotein A I value. C Reactive protein concentration was also strongly associated with coronary heart disease. CONCLUSION: The body's response to inflammation may play an important part in influencing the progression of atherosclerosis. The association of C reactive protein concentration with coronary heart disease needs testing in prospective studies.