The aim of this study was to determine mean values for selected linear measurements on the face of children and adolescents to demonstrate gender differences in the measurements. Cross-sectional data from 262 school children (158 male, 104 female) aged between 6 and 15 years were taken by measuring certain identified facial landmarks using a sliding caliper. The landmarks were first located by careful inspection and/or palpation of the face and a mark created on the cutaneous surface, with the subject sitting in habitual occlusion in an upright position. A sliding caliper was used to measure the distances between the points. The data was analysed using SPSS version 10.0 to determine mean values, standard deviation and gender differences in the measurements. Upper facial heights, total facial height, inter-canthal distance and eye length measurements were significantly higher in male than in female for 15-year-old group (p<0.0001). The measurement between the highest and the lowest point of attachment of external ear to the head was significantly larger in male than in female for 11 year old age group.
facial growth; soft tissue facial morphometry
Tooth wear is a common finding in oral examinations. Pathological tooth wear (PTW) is the amount of wear that exceeds the normal phenomena of ageing or the normal threshold value of wear. The objective of this study was to determine the associated factors of PTW among 16-year-old secondary school children.
This case-control study involved 576 participants randomly selected from eight government secondary schools. The Smith and Knight Tooth Wear Index and WHO criteria were used for charting of tooth wear and dental caries respectively. Data were analyzed using a simplified Microsoft Excel program developed based on the index, to quantify PTW. Controls were subjects with no PTW indicated by zero scores on all tooth surfaces. Cases were subjects with PTW having at least one surface scoring 1 for tooth wear. Consequently, responses were obtained from self-administered questionnaire containing socio-demographic profile of the family, general questions, oral hygiene and food and drinks practices and other associated variables for tooth wear, which was previously developed based on expert opinions.
About 40% and 57% were males were in controls and cases respectively. On performing multivariable analysis, sex, monthly household income, carbonated drinks, duration of intake of orange juices, caries experience and swimming were significantly associated with PTW.
In conclusion the factors associated with PTW were no different from those encountered in Western societies. Realizing that some significant variables were modifiable, oral health promotion should emphasize on this information. The erosive potential of some foods and drinks require further investigation.
To determine whether the addition of low‐cost reflecting curtains to a standard phototherapy unit could increase effectiveness of phototherapy for neonatal jaundice.
Randomised controlled clinical trial.
Level‐one nursery of the Hospital Universiti Sains Malaysia, Kelantan, Malayasia.
Term newborns with uncomplicated neonatal jaundice presenting in the first week of life.
Phototherapy with white curtains hanging from the sides of the phototherapy unit (study group, n = 50) was compared with single phototherapy without curtains (control group, n = 47).
Main outcome measures
The primary outcome was the mean difference in total serum bilirubin measured at baseline and after 4 h of phototherapy. The secondary outcome was the duration of phototherapy.
The mean (standard deviation) decrease in total serum bilirubin levels after 4 h of phototherapy was significantly (p<0.001) higher in the study group (27.62 (25.24) μmol/l) than in the control group (4.04 (24.27) μmol/l). Cox proportional hazards regression analysis indicated that the median duration of phototherapy was significantly shorter in the study group (12 h) than in the control group (34 h; χ2 change 45.2; p<0.001; hazards ratio 0.20; 95% confidence interval 0.12 to 0.32). No difference in adverse events was noted in terms of hyperthermia or hypothermia, weight loss, rash, loose stools or feeding intolerance.
Hanging white curtains around phototherapy units significantly increases efficacy of phototherapy in the treatment of neonatal jaundice without evidence of increased adverse effects.
The homozygous presence of the arginine‐16 variant of the β2 adrenoceptor gene ADRB2 reverses the benefits from the regular use of short acting β2 agonists in asthmatic adults compared with the homozygous glycine‐16 genotype. We studied the effect of this polymorphic variation on asthma exacerbations in children and young adults and its relation to long acting β2 agonists.
A cross‐sectional survey was undertaken using electronic records, direct interviews, and genotype determination of position 16 and 27 of the ADRB2 gene in DNA from mouthwash samples of 546 children and young asthmatics attending paediatric and young adult asthma clinics in Tayside, Scotland during 2004–5. The primary outcome measure was asthma exacerbations over the previous 6 months.
There was an increased hazard of asthma exacerbations across all treatment steps of the British Thoracic Society (BTS) asthma guidelines when the homozygous genotypes Arg/Arg and Gly/Gly were compared (OR 2.05, 95% CI 1.19 to 3.53, p = 0.010), particularly in patients treated with salmeterol (OR 3.40, 95% CI 1.19 to 9.40, p = 0.022). The Glu27Gln polymorphism had no significant effect on asthma exacerbations in any treatment group.
The arginine‐16 genotype of ADRB2 predisposes to exacerbations in asthmatic children and young adults, particularly in those exposed to regular salmeterol. This may be explained by genotype selective salmeterol induced downregulation and impaired receptor coupling, and associated subsensitivity of the response.
asthma; children; polymorphism; salmeterol;
Background and aims
Total body iron and high dietary iron intake are risk factors for colorectal cancer. To date there is no comprehensive characterisation of iron transport proteins in progression to colorectal carcinoma. In this study, we examined expression of iron import (duodenal cytochrome b (DCYTB), divalent metal transporter 1 (DMT1), and transferrin receptor 1 (TfR1)) and export (hephaestin (HEPH) and ferroportin (FPN)) proteins in colorectal carcinoma.
Perl's staining was used to examine colonocyte iron content. Real time polymerase chain reaction (PCR) and western blotting were used to examine mRNA and protein levels of the molecules of interest in 11 human colorectal cancers. Semiquantitative immunohistochemistry was used to verify protein levels and information on cellular localisation. The effect of iron loading on E‐cadherin expression in SW480 and Caco‐2 cell lines was examined by promoter assays, real time PCR and western blotting.
Perl's staining showed increased iron in colorectal cancers, and there was a corresponding overexpression of components of the intracellular iron import machinery (DCYTB, DMT1, and TfR1). The iron exporter FPN was also overexpressed, but its intracellular location, combined with reduced HEPH levels, suggests reduced iron efflux in the majority of colorectal cancers examined. Loss of HEPH and FPN expression was associated with more advanced disease. Iron loading Caco‐2 and SW480 cells caused cellular proliferation and E‐cadherin repression.
Progression to colorectal cancer is associated with increased expression in iron import proteins and a block in iron export due to decreased expression and aberrant localisation of HEPH and FPN, respectively. This results in increased intracellular iron which may induce proliferation and repress cell adhesion.
E‐cadherin; iron; colon; cancer
Background and aims
According to the literature, 14–46% of subjects clear hepatitis C virus (HCV) from blood after infection. Controversy exists about sex differences in HCV clearance rates.
Patients and methods
We compared HCV clearance in males and females using data from a large population based study on HCV infection in Egypt. Definitions used in the paper were: cleared HCV infection (positive HCV antibody and negative HCV RNA test results) and chronic HCV infection (positive HCV antibody and positive HCV RNA test results). The study sample included 4720 village residents aged 18–65 years recruited through home based visits (n = 2425) or voluntary screening (n = 2295).
Overall, HCV antibody prevalence was 910/4720 (19.3% (95% confidence interval 18.2–20.4)). Of those with HCV antibodies (n = 910), 61.5% had chronic HCV infection. Compared with males, females were more likely to have cleared the virus (44.6% v 33.7%, respectively; p = 0.001). Control for age, schistosomiasis history, iatrogenic exposures, and sexual exposure to HCV did not alter the positive association between female sex and viral clearance.
This study provides strong evidence in favour of a higher HCV clearance rate in females compared with males.
hepatitis C virus; natural history; epidemiology
To determine whether observed changes in HIV prevalence in countries with generalised HIV epidemics are associated with changes in sexual risk behaviour.
A mathematical model was developed to explore the relation between prevalence recorded at antenatal clinics (ANCs) and the pattern of incidence of infection throughout the population. To create a null model a range of assumptions about sexual behaviour, natural history of infection, and sampling biases in ANC populations were explored to determine which factors maximised declines in prevalence in the absence of behaviour change. Modelled prevalence, where possible based on locally collected behavioural data, was compared with the observed prevalence data in urban Haiti, urban Kenya, urban Cote d'Ivoire, Malawi, Zimbabwe, Rwanda, Uganda, and urban Ethiopia.
Recent downturns in prevalence observed in urban Kenya, Zimbabwe, and urban Haiti, like Uganda before them, could only be replicated in the model through reductions in risk associated with changes in behaviour. In contrast, prevalence trends in urban Cote d'Ivoire, Malawi, urban Ethiopia, and Rwanda show no signs of changed sexual behaviour.
Changes in patterns of HIV prevalence in urban Kenya, Zimbabwe, and urban Haiti are quite recent and caution is required because of doubts over the accuracy and representativeness of these estimates. Nonetheless, the observed changes are consistent with behaviour change and not the natural course of the HIV epidemic.
epidemiology; HIV; prevalence
During embryonic development, the proepicardial organ (PEO) grows out over the heart surface to form the epicardium. Following epithelial-mesenchymal transformation, epicardium-derived cells (EPDCs) migrate into the heart and contribute to the developing coronary arteries, to the valves and to the myocardium. The peripheral Purkinje fiber network develops from differentiating cardiomyocytes in the ventricular myocardium. Intrigued by the close spatial relationship between the final destinations of migrating EPDCs and Purkinje fiber differentiation in the avian heart, viz. surrounding the coronary arteries and at subendocardial sites, we investigated whether inhibition of epicardial outgrowth would disturb cardiomyocyte differentiation into Purkinje fibers.
To this end epicardial development was inhibited mechanically with a membrane, or genetically, by suppressing epicardial epithelial-to-mesenchymal transformation with antisense retroviral vectors affecting Ets transcription factor levels(n=4, HH39-41). In both epicardial inhibition models we evaluated Purkinje fiber development by EAP-300 immunohistochemistry and found that restraints on EPDC development resulted in morphologically aberrant differentiation of Purkinje fibers. Purkinje fiber hyperplasia was observed both periarterially and at subendocardial positions. Furthermore, the cells were morphologically abnormal and not aligned in orderly Purkinje fibers.
We conclude that EPDCs are instrumental in Purkinje fiber differentiation, and we hypothesize that they cooperate directly with endothelial and endocardial cells in the development of the peripheral conduction system.
Organ transplant recipients (OTRs) have 100-fold increased risk of developing squamous cell carcinomas. Cumulative exposure to ultraviolet radiation is the main risk factor and there is evidence that lack of dermatological surveillance may be responsible for poor levels of knowledge and photoprotection among OTRs.
This study evaluated whether routine consultation in a specialist OTR dermatology clinic improves understanding of skin cancer risk and compliance with photoprotection measures.
A cross-sectional questionnaire-based study was performed in a specialist OTR dermatology clinic at Bart's and the London NHS Trust, London, U.K. The subjects were 399 white-skinned patients under surveillance in a renal transplant clinic, who were sent a postal questionnaire from the renal transplant clinic. The main outcome measures were responses to the questionnaire regarding photoprotective practices and skin cancer risk awareness.
Two hundred and ninety-two of 399 (73%) responded, of whom 89% had previously attended the specialist dermatology clinic. Ninety-six per cent recalled receiving photoprotection advice at least once (85% from dermatologists); 92% reported use of sunscreen; 88% specifically dressed to photoprotect themselves; 96% directly avoided sun exposure during summer; 68% were aware that an increased risk of skin cancer was the reason that extra photoprotective measures were important after a transplant. Photoprotective measures and level of skin cancer awareness were significantly lower in those responders who had never attended the specialist clinic. No obvious bias was identified among nonresponders.
Skin cancer awareness and compliance with photoprotective measures in our patient population is generally greater than previously reported, suggesting that delivery of educational messages regarding skin cancer may be improved if provided in a specialist dermatological setting.
audit; compliance; organ transplant recipients; photoprotection; skin cancer awareness; specialist dermatology clinics
The relationships between blood lead (PbB) and saliva lead (PbSa) concentrations and the determinants of PbB and PbSa status in 970 low-income adults in the city of Detroit, Michigan were explored. Average PbB and PbSa values in the sample population were found to be 2.7 ± 0.1 μg/dl and 2.4 ± 0.13 μg/l (equivalent to 0.24 ± 0.13 μg/dl), respectively, and a weak but statistically significant association was found between the lead levels in the two types of body fluid samples. The average PbB level for men (4.0 ± 0.56 μg/dl) was higher than that for women (2.7 ± 0.11 μg/dl); other significant predictors of PbB included age, level of education, being employed, income level, the presence of peeling paint on the wall at home and smoking. There was no gender- or age-dependent difference in blood saliva values but statistically significant correlations were found between PbSa and level of education, employment, income level and smoking. Dental caries was severe in this population. Only 0.5% of the participants had no clinical signs of caries, over 80% had cavitated carious lesions (i.e., lesions that had progressed into dentin), and the number of lost teeth and carious lesions averaged 3.4 and 30, respectively. Weak but significant associations were found between PbB as well as PbSa and measures of dental caries in the study population. The positive associations are believed to be a reflection of the fact that the risk factors for dental caries, especially in low-income populations of the US, overlap extensively with those of lead poisoning and may not have a causal significance.
Blood lead; Saliva lead; Dental caries; Lead exposure; Biomonitoring; Lead poisoning
To assess the relationship between neighborhood effects and the severity of dental caries among low-income African-Americans.
A multistage probability sample of African-American families living in the poorest 39 census tracts in Detroit was drawn. During 2002–03, cross-sectional data of a cohort that includes 1021 caregivers were collected in the first of three waves of interviews and examinations. Multilevel analyses focused on 27 neighborhood clusters and involved a combination of individual (Level-1) and neighborhood (Level-2) data including census and geocoded (address matching to census geographic areas) information.
There is significant variation in the severity of caries between low-income neighborhood clusters. Caries severity decreases with a higher number of churches, while it increases with a higher number of grocery stores in the clusters after accounting for individual characteristics. Only 14% of the inter-individual variability in caries was explained by classical individual risk factors for this condition.
Neighborhoods contribute something unique to caregivers’ oral health, beyond socioeconomic position and individual risk factors. Multilevel interventions are necessary to reduce disparities among African-Americans and churches may offer a promising venue from which to conduct them.
African-American; dental caries; multilevel analysis; neighborhood effects
The aim of this study was to examine the relationship between dietary patterns and caries experience in a representative group of low-income African-American adults. Participants were residents of Detroit, Michigan, with household incomes below 250% of the federally-established poverty level (n = 1,021). Dietary histories were obtained by trained interviewers in face-to-face interviews with the adult participants, using the Block 98.2® food frequency questionnaire developed by Block Dietary Systems, Berkeley, CA. Caries was measured by the ICDAS criteria (International Caries Detection and Assessment System). There were 200 dietary records whose data were judged to be invalid; these participants were omitted from the dietary analyses to leave n = 821. Analyses were conducted using software from SAS and SUDAAN. Factor analysis identified patterns of liquid and solid food consumption, and the resulting factor scores were used as covariates in multivariable linear regression. Caries was extensive, with 82.3% of the 1,021 participants (n=839) having at least one cavitated lesion. Nearly three-quarters of the adult participants were overweight or obese. This population has severe caries, poor oral hygiene, and diets that are high in sugars and fats and low in fruits and vegetables. Apart from tapwater, the most frequently consumed food item by adults of all ages was soft drinks; 19% of all energy from sugar came from soft drinks alone. In both the bivariate analyses and in the regression model, frequency of soft drink consumption and the presence of gingival plaque deposits were significantly associated with caries. Interventions to promote oral health are unlikely to be successful without improvements in the social and physical environment.
diet; dietary patterns; soft drinks; sugars; fat consumption; caries; plaque deposits; oral hygiene; adults; disparities; low-income
Dorsal root ganglia are oval enlargements on the dorsal nerve roots and contain the cell bodies of sensory neurons. Asymmetry of dorsal root ganglia may occur naturally, yet natural occurrence of gigantic dorsal root ganglion (DRG) is rare. The patient was 61-year-old woman who presented with atypical symptoms like neuropathic pain and urinary distention. Neuroimaging has shown left L3-4 far-lateral disc herniation and a gigantic L3 DRG. At surgery, the dural sheath of the ganglion had to be opened and a firm, yellow-colored abnormal tissue was exposed. The abnormal tissue considered to be a tumor of neural origin was gross totally excised and the patient’s symptoms ceased immediately after surgery. Histopathological examination of the specimen revealed nothing more than normal DRG morphology. At 4 months postoperatively, the patient is well with mild L3 hyperesthesia and hyperalgesia. Dural sheath opening in neurosurgery is not a routine practice. The sheath may need to be opened when surgeon suspects of a tumor, a free disc fragment and any inflammation within the ganglion. Operative morphology of a severely edematous but non-tumoral (pseudotumor) ganglion has not previously been documented.
Dorsal root ganglion; Ganglionectomy; Magnetic resonance imaging; Microsurgery
The roots of Alkanna orientalis (L.) Boiss yielded α- methyl-n-butyl alkannin (compound 1) and alkannin acetate (compound 2). The compounds were identified by UV, MS, 1H NMR and 13C NMR. Quantitative determination of α- methyl-n-butyl alkannin and alkannin acetate in Alkanna orientalis (L) Boiss roots was established by TLC densitometry.
Alkanna orientalis; naphthaquinones; NMR; α- methyl-n-butyl alkannin; alkannin acetate; TLC densitometry
Colorectal cancer (CRC) is often diagnosed at a late stage with concomitant poor prognosis. Early detection greatly improves prognosis; however, the invasive, unpleasant and inconvenient nature of current diagnostic procedures limits their applicability. No serum-based test is currently of sufficient sensitivity or specificity for widespread use. In the best currently available blood test, carcinoembryonic antigen exhibits low sensitivity and specificity particularly in the setting of early disease. Hence, there is great need for new biomarkers for early detection of CRC. We have used surface-enhanced laser desorbtion/ionisation (SELDI) to investigate the serum proteome of 62 CRC patients and 31 noncancer subjects. We have identified proteins (complement C3a des-arg, α1-antitrypsin and transferrin) with diagnostic potential. Artificial neural networks trained using only the intensities of the SELDI peaks corresponding to identified proteins were able to classify the patients used in this study with 95% sensitivity and 91% specificity.
colorectal cancer; SELDI; serum proteome; biomarker; proteomic; mass spectrometry
The relationship between the function of human immunodeficiency virus (HIV)-specific CD8 T-cell responses and viral load has not been defined. In this study, we used a panel of major histocompatibility complex class I tetramers to examine responses to frequently targeted CD8 T-cell epitopes in a large cohort of antiretroviral-therapy-naïve HIV type 1 clade C virus-infected persons in KwaZulu Natal, South Africa. In terms of effector functions of proliferation, cytokine production, and degranulation, only proliferation showed a significant correlation with viral load. This robust inverse relationship provides an important functional correlate of viral control relevant to both vaccine design and evaluation.
Explanatory models for the increased prevalence of ill health in Gulf veterans compared to those not deployed to the Gulf War 1990–1991 remain elusive. This article addresses whether multi-symptom reporting in Gulf veterans are types of medically unexplained symptoms and whether the alleged Gulf War Syndrome is best understood as a medically unexplained syndrome. A review of the epidemiological studies, overwhelmingly cross-sectional, describing ill health was conducted including those that used factor analysis to search for underlying or latent clinical constructs. The overwhelming evidence was that symptoms in Gulf veterans were either in keeping with currently defined psychiatric disorders such as depression and anxiety or were medically unexplained. The application of factor analysis methods had varied widely with a risk of over interpretation in some studies and limiting the validity of their findings. We concluded that ill health in Gulf veterans and the alleged Gulf War Syndrome is best understood within the medically unexplained symptoms and syndromes constructs. The cause of increased reporting in Gulf veterans are still not clear and requires further inquiry into the interaction between sociological factors and symptomatic distress.
medically unexplained symptoms; medically unexplained syndromes; Gulf War Syndrome; factor analysis; culture; psychiatric disorders
A 16-year-old boy presented to the emergency department with chest pain. He had no history of other health problems and did not smoke. Acute myocardial infarction (AMI) in an adolescent boy with normal coronary arteries, associated with pseudoephedrine use and acute streptococcal infection, is reported. The diagnosis of AMI was based on typical electrocardiographic signs, enzyme changes and echocardiographic evaluation. Coronary vasospasm associated with pseudoephedrine use, endothelial dysfunction and prothrombotic state caused by acute streptococcal infection may be the mechanisms responsible for AMI in this case.
The possibility of AMI should be considered even in very young adolescents that have acute streptococcal pharyngeal infection, and it is important to obtain a complete history of the drugs used.
Acute myocardial infarction; Pseudoephedrine; Streptococcal infection
Haemophilus influenzae type b (Hib) conjugate vaccine is not perceived as a public health priority in Africa because data on Hib disease burden and vaccine effectiveness are scarce. Hib immunization was introduced in Kenyan infants in 2001.
to define invasive Hib disease incidence and Hib vaccine program effectiveness.
Design, Setting, Patients
culture-based surveillance for invasive Hib disease at Kilifi District Hospital from 2000 to 2005 was linked to demographic surveillance of 38,000 children aged <5 years in Kilifi District, Kenya. HIV infection and Hib vaccination status were determined for children with Hib disease admitted 2002–2005.
Conjugate Hib vaccine within the routine childhood immunization program at ages 6, 10 and 14 weeks from November 2001
Main outcome measures
Incidence of culture-proven Hib invasive disease before and after vaccine introduction and vaccine program effectiveness (1-incidence rate ratio)
Prior to vaccine introduction the median age of Hib cases was 8 months; case fatality was 23%. Among children aged <5 years the annual incidence of invasive Hib disease 1 year before and 1 and 3 years after vaccine introduction was 66, 47 and 7.6 per 100,000, respectively. For children <2 years, incidence was 119, 82 and 16, respectively. In 2004–2005 vaccine effectiveness was 88% (95% CI 73–96%) among children <5 years and 87% (95% CI 66–96%) among children <2 years. Of 53 Hib cases admitted during 2002–2005, 29 (55%) were age-ineligible to have received vaccine, 12 (23%) had not been vaccinated despite being eligible, and 12 (23%) had received ≥2 doses of vaccine (2 were HIV-positive).
In Kenya, introduction of Hib vaccine into the routine childhood immunization program reduced Hib disease incidence among children aged <5 years to 12% of its baseline level. This impact was not observed until the third year after vaccine introduction.
A 13-year-old dog was presented with clinical signs of anemia, vomiting, weight loss, and progressive abdominal distension. Abdominal ultrasonography and radiography revealed a large mass, which was removed surgically. Cytologic and histologic evaluation of the mass revealed a mixture of fat and hematopoietic tissue, consistent with a splenic myelolipoma.
The usefulness of Candida ID 2 (CAID2) reformulated medium (bioMérieux, France) has been compared with that of the former Candida ID (CAID; bioMérieux), Albicans ID 2 (ALB2; bioMérieux), and CHROMagar Candida (CAC; Chromagar, France) chromogenic media for the isolation and presumptive identification of clinically relevant yeasts. Three hundred forty-five stock strains from culture collections, and 103 fresh isolates from different clinical specimens were evaluated. CAID2 permitted differentiation based on colony color between Candida albicans (cobalt blue; sensitivity, 91.7%; specificity, 97.2%) and Candida dubliniensis (turquoise blue; sensitivity, 97.9%; specificity, 96.6%). Candida tropicalis gave distinguishable pink-bluish colonies in 97.4% of the strains in CAID2 (sensitivity, 97.4%; specificity, 100%); the same proportion was reached in CAC, where colonies were blue-gray (sensitivity, 97.4%; specificity, 98.7%). CAC and CAID2 showed 100% sensitivity values for the identification of Candida krusei. However, with CAID2, experience is required to differentiate the downy aspect of the white colonies of C. krusei from other white-colony-forming species. The new CAID2 medium is a good candidate to replace CAID and ALB2, and it compares well to CAC for culture and presumptive identification of clinically relevant Candida species. CAID2 showed better results than CAC in some aspects, such as quicker growth and color development of colonies from clinical specimens, detection of mixed cultures, and presumptive differentiation between C. albicans and C. dubliniensis.
To determine whether observed changes in HIV prevalence in countries with generalized HIV epidemics are associated with changes in sexual risk behaviour.
We developed a mathematical model to explore the relationship between prevalence recorded at antenatal clinics (ANCs) and the pattern of incidence of infection throughout the population. To create a null model a range of assumptions about sexual behaviour, natural history of infection and sampling biases in ANC populations were explored to determine which maximised declines in prevalence in the absence of behaviour change. Modelled prevalence, where possible based on locally collected behavioural data, was compared to the observed prevalence data in urban Haiti, urban Kenya, urban Cote d'Ivoire, Malawi, Zimbabwe, Rwanda, Uganda and urban Ethiopia.
Recent downturns in prevalence observed in Kenya, Zimbabwe and Haiti, like Uganda before them, could only be replicated in the model through reductions in risk associated with changes in behaviour. In contrast, prevalence trends in urban Cote d'Ivoire, Malawi, urban Ethiopia and Rwanda show no signs of changed sexual behaviour.
Changes in patterns of HIV prevalence in Kenya, Zimbabwe and Haiti are quite recent and caution is required because of doubts over the accuracy and representativeness of these estimates. Nonetheless, the observed changes are not consistent with behaviour change not the natural course of the HIV epidemic.
Epidemiology; HIV; Prevalence
Immune responses against monocytotropic ehrlichiosis during infection with a strain of Ehrlichia from Ixodes ovatus (IOE) were evaluated using a model that closely reproduces the pathology and immunity associated with tick-transmitted human monocytotropic ehrlichiosis. C57BL/6 mice were inoculated intradermally or intraperitoneally with high-dose highly virulent IOE or intraperitoneally with mildly virulent Ehrlichia muris. Intradermal (i.d.) infection with IOE established mild, self-limited disease associated with minimal hepatic apoptosis, and all mice survived past 30 days. Intraperitoneal (i.p.) infection with IOE resulted in acute, severe toxic shock-like syndrome and severe multifocal hepatic apoptosis and necrosis, and all mice succumbed to disease. Compared to i.p. infection with IOE, intradermally infected mice had a 100- to 1,000-fold lower bacterial load in the spleen with limited dissemination. Compared to mice infected intraperitoneally with IOE, i.d. infection stimulated a stronger protective type-1 cell-mediated response on day 7 of infection, characterized by increased percentages of both CD4+ and CD8+ splenic T cells, generation of a greater number of IOE-specific, gamma interferon-producing CD4+ Th1 cells, and higher levels of tumor necrosis factor (TNF-α) in the spleen but lower concentrations of serum TNF-α and interleukin-10. These data suggest that under the conditions of natural route of challenge (i.e., i.d. inoculation), the immune response has the capacity to confer complete protection against monocytotropic ehrlichiosis, which is associated with a strong cell-mediated type-1 response and decreased systemic production of pro- and anti-inflammatory cytokines.
Bowel cancer is common and is a major cause of death. Meta-analysis of randomised controlled trials estimates that screening for colorectal cancer using faecal occult blood (FOB) test reduces mortality from colorectal cancer by 16%. However, FOB testing has a low positive predictive value, with associated unnecessary cost, risk and anxiety from subsequent investigation, and is unacceptable to a proportion of the target population. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9) have been found to be associated with colorectal cancer, and this can be measured from a blood sample. Serum MMP-9 is potentially an accurate, low risk and cost-effective population screening tool. This study aims to evaluate the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population.
People aged 50 to 69 years, who registered in participating general practices in the West Midlands Region, will be asked to complete a questionnaire that asks about symptoms. Respondents who describe any colorectal symptoms (except only abdominal bloating and/or anal symptoms) and are prepared to provide a blood sample for MMP9 estimation and undergo a colonoscopy (current gold standard investigation) will be recruited at GP based clinics by a research nurse. Those unfit for colonoscopy will be excluded. Colonoscopies will be undertaken in dedicated research clinics. The accuracy of MMP-9 will be assessed by comparing the MMP-9 level with the colonoscopy findings, and the combination of factors (e.g. symptoms and MMP-9 level) that best predict a diagnosis of malignancy (invasive disease or polyps) will be determined.
Colorectal cancer is a major cause of morbidity and mortality. Most colorectal cancers arise from adenomas and there is a period for early detection by screening, but available tests have risks, are unacceptable to many, have high false positive rates or are expensive.
This study will establish the potential of serum MMP-9 as a screening test for colorectal cancer. If it is confirmed as accurate and acceptable, this serum marker has the potential to assist with reducing the morbidity and mortality from colorectal cancer.