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H Campbell

Publications and source records attributed to H Campbell.

At least 37 records · Page 2Linked to original sources

Mismatch repair genes hMLH1 and hMSH2 and colorectal cancer: a HuGE review.

Evidence to support a role for the mismatch repair genes human mutL homolog 1 (hMLH1) and human mutS homolog 2 (hMSH2) in the etiology of colorectal cancer has come from linkage analysis, segregation studies, and molecular biologic analysis. More recently, carriers of potentially pathogenic mutations in the hMLH1/hMSH2 genes have consistently been shown to be at a greatly increased risk of developing colorectal cancer compared with the general population. When considered together, the available evidence shows a strong, consistent, and biologically plausible association between mismatch repair gene mutations and colorectal cancer. The penetrance of mutations in hMLH1/hMSH2 is incomplete and is significantly higher in males (approximately 80%) than in females (approximately 40%). To date, evidence for gene-gene or gene-environment interactions is limited, although preliminary studies have revealed a number of avenues that merit exploration. Population screening for mutation carriers is not currently a feasible option, and mutation analysis remains restricted to either relatives of mutation carriers or colorectal cancer cases selected on the basis of phenotype.

Adaptor Proteins, Signal Transducing↗

Non-invasive pneumococcal disease and antimicrobial resistance: vaccine implications.

We reviewed laboratory data on non-invasive pneumococcal isolates reported from all diagnostic laboratories in Scotland during the period 1988-99. Of 4491 isolates from hospitalized patients, 654 (64.7%) were from sputum, 79 (7.8%) from the nasopharynx and 278 (27.5%) from other superficial sites. The serogroups included in the 23-valent polysaccharide vaccine caused 96.9% of all non-invasive disease in all age groups. The 7-, 9-, and 11-valent conjugated vaccine serogroups were responsible for 87-94%, 85-93%, 74-81% and 75-84% of non-invasive disease respectively in age groups < 2 years, < or = 5 years, > or = 65 years and all ages. The coverage of non-susceptible penicillin and erythromycin non-invasive isolates was > 99% and > 95% with the 23-valent polysaccharide and 7-11-valent conjugate vaccines respectively. The eight most common serogroups were 23, 9, 6, 19, 14, 3, 15 and 11 (in descending order). The serogroups associated with antimicrobial resistance in non-invasive disease were similar to those found in invasive disease. The finding of a similar serogroup distribution in both invasive and non-invasive disease (regardless of the site of clinical isolate), is consistent with serogroups colonizing non-sterile sites and having the potential to invade. The availability of conjugated vaccines reinforces the importance of systematic surveillance to determine accurately and regularly the coverage of pneumococcal serogroups and types causing both invasive and non-invasive disease.

Adolescent↗

Prevalence of moderate penicillin resistant invasive Neisseria meningitidis infection in Scotland, 1994-9.

We examined the serological characteristics of 774 invasive meningococcal isolates collected through an active laboratory-based surveillance system in Scotland from 1994 to 1999. Of these, 72-73% of isolates were tested for susceptibility to several antimicrobial agents. Meningococci with high-level resistance to sulphadiazine had a prevalence of 10% and incidence of 0.22 per 100,000 population. High-level resistance to penicillin and other antibiotics was not detected. The prevalence of moderate penicillin resistant meningococci was 8.3%. There was no increase in moderate penicillin resistant meningococcal isolates during the study period, but there were temporal and geographic variations. The estimated incidence of moderate penicillin resistant meningococci was 0.15 per 100,000 population. High and low incidence of moderate penicillin resistant meningococci appeared to correlate with the number of doses of penicillin prescribed in some geographic locations. The majority of moderate penicillin resistant isolates belonged to serogroups B (52.2%) and C (39.2%). However, the prevalence of moderate penicillin resistance in serogroup W135 was substantially higher (51.7%) than serogroups B (7.8%) and C (7.6%). Serogroup W135 accounted for a higher proportion of moderate penicillin resistance (8.7%) than disease (1%). There was no predominant penicillin resistant serotype/subtype within any serogroup. Constant surveillance is necessary to monitor the emergence and spread of resistance and to guide appropriate public health interventions in preventing drug resistant meningococci.

Humans↗

Influenza and pneumococcal vaccine distribution and use in primary care and hospital settings in Scotland: coverage, practice and policies.

A survey of the coverage, distribution and the factors associated with use of influenza and pneumococcal vaccines among general practitioners (GPs) in primary care and in hospital settings was carried out in 53 general practices in Scotland taking part in the 'Continuous Morbidity Recording' (CMR) programme. The annual vaccine distribution increased substantially among 53 general practices from 1993 to 1999 and in Scotland as a whole from 1984 to 1999. From the questionnaire, overall coverage was 43% (95% CI 38-48) for influenza vaccine in the 2000-1 season and 13% (95% CI 9-16) for pneumococcal vaccine in the last 5 year period, in high-risk patients recommended for these vaccines by the Department of Health (DoH). Influenza vaccine coverage was highest in the elderly (65 years of age and above) at 62% (95% CI 59-74). Although pneumococcal vaccination is not currently recommended for all elderly, coverage of this vaccine was also higher in this group (22%, 95% CI 16-29). In the majority of patients (influenza vaccine, 98% and pneumococcal vaccine, 94%), vaccination was carried out in general practice. Only 2% of patients had received pneumococcal vaccination in a hospital setting. The level of influenza and pneumococcal vaccination varied with the level of deprivation. Most GPs considered that the responsibility for influenza and pneumococcal vaccination lay with them. Forty-five percent of GPs reported having a written policy with set target for influenza vaccination and 11% for pneumococcal vaccination.

Aged↗

A capture-recapture model to estimate prevalence of children born in Scotland with developmental eye defects.

BACKGROUND: Microphthalmia, anophthalmia and coloboma (MAC) are closely related structural developmental eye defects that have caused public concern in the UK following media reports of apparent clusters of cases. An extensive search was carried out to identify potential cases, and diagnoses were confirmed by ophthalmological review. Despite this effort, it was recognised that some cases would remain unidentified. Capture-recapture methods could improve the accuracy of the study's birth prevalence estimate. METHODS: A register of all children born with the developmental eye defects of MAC in Scotland (1981-96) was compiled. This identified 188 cases from eight national ascertainment sources. The methods described by Hook and Regal were used to determine possible estimates for each source. A log-linear method of capture-recapture was used to fit a model to the number of children identified by the different combinations of the eight national sources, and the individual sources were included in the model as main effects. RESULTS: Maximum-likelihood estimates were calculated for tables of captured/not captured by one source versus any other source. The estimated number of unobserved cases for the most complete source, the register of congenital anomalies for Scotland, and the seven others combined is 78 (95% CI 53-115). Estimates calculated from two different log-linear models of the numbers of cases unobserved by all sources were 61 (95% CI 43-86) and 175 (95% CI 106-287). An external check with an independent congenital-anomalies register in one region, which is known to have high completeness, gave an estimate of 120. The study found a birth prevalence of MAC in Scotland of 1.9/10000, based on total live births during the study period. The capture-recapture analysis suggests that the true birth prevalence lies between 2.4/10 000 and 3.5/10000. DISCUSSION: Our experience shows that, even with multiple sources of ascertainment and considerable resources directed at case identification, a considerable level of under-ascertainment of congenital eye-anomalies still results, and suggests that the use of capture-recapture analysis would be a useful addition to congenital anomalies registers for needs assessment, disease-burden estimates and health-service planning.

Eye Abnormalities↗

A survey of vaccine coverage and antibiotic prophylaxis in splenectomised patients in Scotland.

AIMS: To determine the coverage of vaccine and antibiotic prophylaxis in splenectomised patients in Scotland. METHODS: Patients who had undergone splenectomy between 1 January 1988 and 31 December 1998 were identified. A questionnaire was sent to general practitioners to validate vaccine and antibiotic status for these patients. RESULTS: A total of 974 living splenectomised patients were identified during the study period. Information on vaccine and antibiotic status was available for 708 (73%) and 770 (79%) of living patients, respectively. Coverage of pneumococcal vaccine (88%) was higher than that of Haemophilus influenza type b (Hib) conjugate vaccine (70%) or meningococcal vaccine (51%). Only 47% of patients received all three vaccines. A higher coverage was also documented for pneumococcal vaccine (28%) than Hib (19%) and meningococcal vaccine (14%) before elective splenectomy. Only 13% received all three vaccines before splenectomy. Coverage of influenza vaccine increased significantly, from 76% in the 1997/1998 season to 96% in the 2000/2001 season. Antibiotic prophylaxis was received by 67% of all patients. The current recommendation, comprising pneumococcal and Hib vaccination and antibiotic prophylaxis, was received by only 52% of the patients. There was no association between the coverage of vaccine and socioeconomic status. CONCLUSION: Further improvement in coverage of recommended vaccines and antibiotic prophylaxis is still needed to reduce the risk of serious infection in this high risk group.

Adult↗

National study of microphthalmia, anophthalmia, and coloboma (MAC) in Scotland: investigation of genetic aetiology.

We report an epidemiological and genetic study attempting complete ascertainment of subjects with microphthalmia, anophthalmia, and coloboma (MAC) born in Scotland during a 16 year period beginning on 1 January 1981. A total of 198 cases were confirmed giving a minimum live birth prevalence of 19 per 100 000. One hundred and twenty-two MAC cases (61.6%) from 115 different families were clinically examined and detailed pregnancy, medical, and family histories obtained. A simple, rational, and apparently robust classification of the eye phenotype was developed based on the presence or absence of a defect in closure of the optic (choroidal) fissure. A total of 85/122 (69.7%) of cases had optic fissure closure defects (OFCD), 12/122 (9.8%) had non-OFCD, and 25/122 (20.5%) had defects that were unclassifiable owing to the severity of the corneal or anterior chamber abnormality. Segregation analysis assuming single and multiple incomplete ascertainment, respectively, returned a sib recurrence risk of 6% and 10% in the whole group and 8.1% and 13.3% in the OFCD subgroup. Significant recurrence risks were found in both unilateral and bilateral disease. In four families, one parent had an OFCD, two of which were new diagnoses in asymptomatic subjects. All recurrences in first degree relatives occurred in the OFCD group with a single first cousin recurrence seen in the non-OFCD group. A total of 84/122 of the MAC cases were screened for mutations in the coding regions of PAX6, CHX10, and SIX3. No pathogenic mutations were identified in the OFCD cases. A single PAX6 homeodomain missense mutation was identified in a subject with partial aniridia that had been initially misclassified as coloboma.

Anophthalmos↗

Incidence of invasive pneumococcal disease in Scotland, 1988-99.

A review of the epidemiology of invasive pneumococcal disease in Scotland was carried out using data from laboratory-based systems during the period 1988-99. This comprised 5456 (90.8%) isolates of Streptococcus pneumoniae from blood, 467 (7.8%) from cerebrospinal fluid (CSF) and 84 (1.4%) from other sterile sites. The mean annual incidence of invasive disease was 9.8/10(5) population (9.0/10(5) for bacteraemia and 0.8/10(5) for meningitis). Invasive disease was highest in children < 2 years of age and in the elderly > or = 65 years (44.9/10(5) and 28.4/10(5) population in these age groups respectively). The highest incidence of pneumococcal meningitis, 11.8/10(5) persons occurred in children < 2 years of age. Males had a higher incidence of pneumococcal bacteraemia and meningitis than females (male:female = 1.2:1 for bacteraemia (RR = 1.17, 95 % CI 1.11, 1.24) and 1.5:1 for meningitis (RR = 1.41, 95 % CI 1.18, 1.70)). Pneumococcal disease was highest in winter periods and coincided with influenza activity. The proportion of penicillin and erythromycin non-susceptible isolates increased from 4.2% in 1992 to 12.6% in 1999 and from 5.6% in 1994 to 16.3% in 1999 respectively. Our data confirm the substantial and increasing disease burden from pneumococcal disease and rise in prevalence of antibiotic non-susceptibility among pneumococci in Scotland. Continued surveillance of groups at increased risk for pneumococcal disease and the antibiotic susceptibility and serotype distribution of isolates are important to develop appropriate policies for the prevention of pneumococcal disease in Scotland.

Adolescent↗

Inbreeding and nephrolithiasis in Croatian island isolates.

The aim of this study was to investigate a recessive genetic component in susceptibility to nephrolithiasis (NL) by comparing its prevalence in highly inbred, moderately inbred and non-inbred villages of three Croatian islands: Brac, Hvar and Korcula. The average inbreeding coefficient of each village population (F) was estimated in a random sample of 20-30% adults from 14 villages using Wright's path method (based on genealogical information), isonymy data and average deviation from Hardy-Weinberg expectations for MN, Ss and Kk serogenetic polymorphisms. The six villages with the greatest genealogical F value (0.025-0.049; current total population N=1,401), the four with intermediate value (0.012-0.015; N=998) and the four with the smallest value (0.002-0.008; N=1,500) were chosen for this study. Medical records of entire populations were reviewed and the diagnosis of NL was established according to unified criteria, based on the information from the specialists in general hospitals and on the agreement in diagnosis between the investigators and local general practitioners. The variance in environmental and socio-cultural factors between villages was shown to be minimal. Prevalence of NL in each village was standardised by sex and age to the total population of all 14 villages. The standardized prevalence of NL was 1.5% in the group of villages with low F, 2.3% in the group with moderate F (p<0.10), and 5.4% in the group with high F (p<0.001). The correlation factor between F values by villages and the standardized prevalence of NL was 0.45 (p<0.05). The study showed that a large number of predominantly recessive genetic factors might mediate the susceptibility to formation of renal stones in humans.

Consanguinity↗

Parental confidence in measles, mumps and rubella vaccine: evidence from vaccine coverage and attitudinal surveys.

BACKGROUND: The measles, mumps and rubella (MMR) vaccine has been the focus of considerable adverse publicity in recent years. AIM: To describe recent trends in parental attitudes to, and coverage of, MMR vaccine. DESIGN OF STUDY: Routine surveillance of vaccine coverage and cross-sectional surveys of parental attitudes. SETTING: All health authorities in England (vaccine coverage) and 132 enumeration districts in England (attitude survey). METHOD: Quarterly MMR vaccine coverage for all resident children in England at two years of age was requested from computerised child health information systems. Data was also obtained from 26 English health authorities/trusts on MMR coverage at 16 months of age. The proportion of mothers who believed that MMR vaccine was safe or carried only a slight risk, and the proportion who intended to fully vaccinate any future children, was obtained from biannual interviews with a national representative sample of over 1000 mothers of children under three years of age. RESULTS: Vaccine coverage at two years of age fell 8.6% (95% confidence interval [CI] = 8.4 to 8.8) between April and June 1995 and between April and June 2001. In September 2001, 67% of mothers reported that the MMR vaccine was safe or carried only a slight risk and 92% of mothers agreed with the statement: 'If I had another child in the future I would have them fully immunised against all childhood diseases'. CONCLUSIONS: Despite considerable adverse publicity, the fall in MMR coverage has been relatively small, mothers' attitudes to MMR remain positive, and most continue to seek advice on immunisation from health professionals. As the vast majority of mothers are willing to have future children fully immunised, we believe that health professionals should be able to use the available scientific evidence to help to maintain MMR coverage.

Attitude to Health↗

Inbreeding and learning disability in Croatian island isolates.

The aim of this study was to investigate the prevalence of learning disability (LD) in isolate populations with different inbreeding coefficients (F). Prevalence of LD and F were determined in 10 villages from five Croatian islands: Brac, Hvar, Korcula, Lastovo and Susak. For the purpose of this study, LD was defined as the inability to attend the public school system. As the elementary schools (grade 1-8) in the place of the study are both public and compulsory, the assessment of child's inability to attend the school is performed at the age of six. This is required by all children in the country based on standard set of tests of cognitive performance defined by the Ministry of Education and Culture of the Republic of Croatia. The average inbreeding coefficients in each village population (F) were estimated in a random sample of 20-30% adults in each of the 10 villages based on 4 ancestral generations and using Wright's path method. Prevalence of LD ranged from 0.43% to 2.47%, and the inbreeding coefficients ranged from 0.8% to 4.9%. The Pearson's correlation coefficient between F and LD prevalence was 0.80 (p < 0.01). Although the relative risk per 5% inbreeding appeared very high (about 10), the absolute risk only increased from 0.18% to 1.77%. The genetic effect of inbreeding (GEI) was approximately 0.69% and the population-attributable fraction 76.6%. A review of the literature and the results of this study lead to a conclusion that a very large number of predominantly recessive genetic factors might mediate the genetic susceptibility to various forms of LD in these populations.

Adult↗

Effect of plasma scale length on multi-MeV proton production by intense laser pulses.

The influence of the plasma density scale length on the production of MeV protons from thin foil targets irradiated at I lambda(2) = 5 x 10(19) W cm(-2) has been studied. With an unperturbed foil, protons with energy >20 MeV were formed in an exponential energy spectrum with a temperature of 2.5+/-0.3 MeV. When a plasma with a scale length of 100 microm was preformed on the back of the foil, the maximum proton energy was reduced to <5 MeV and the beam was essentially destroyed. The experimental results are consistent with an electrostatic accelerating mechanism that requires an ultrashort scale length at the back of the target.

Journal Article↗

The evidence of mtDNA haplogroup F in a European population and its ethnohistoric implications.

Mitochondrial DNA polymorphism was analysed in a sample of 108 Croatians from the Adriatic Island isolate of Hvar. Besides typically European varieties of human maternal lineages, haplogroup F was found in a considerable frequency (8.3%). This haplogroup is most frequent in southeast Asia but has not been reported before in Europe. The genealogical analysis of haplogroup F cases from Hvar suggested founder effect. Subsequent field work was undertaken to sample and analyse 336 persons from three neighbouring islands (Brac, Korcula and Krk) and 379 more persons from all Croatian mainland counties and to determine if haplogroup F is present in the general population. Only one more case was found in one of the mainland cities, with no known ancestors from Hvar Island. The first published phylogenetic analysis of haplogroup F worldwide is presented, applying the median network method, suggesting several scenarios how this maternal lineage may have been added to the Croatian mtDNA pool.

DNA, Mitochondrial↗

Influence of chronic alcohol abuse and ensuing forced abstinence on static subjective accommodation function in humans.

PURPOSE: Acute alcohol ingestion can change accommodation, but the long term effects of sustained alcohol consumption on accommodative function have not been studied in detail. This study was thus undertaken on individuals with a history of alcohol abuse. METHODS: Thirty-seven male individuals aged 25-56 years (average 40 years) from an alcohol rehabilitation centre in Inverness, Scotland, were assessed on admission and after a week of forced abstinence. The results were compared to a paired age-matched set of control male subjects. The static amplitude of accommodation was measured by an RAF rule, and the pupil size measured with a pupil gauge. RESULTS: On admission, the group mean measured amplitude of accommodation was 4.7 +/- 2.2 D (mean +/- SD). These values for the alcoholics were lower than age-matched controls (of 5.9 +/- 2.9 D). The slope of the age-dependent decline in RAF rule accommodation measures was significantly smaller for the alcoholics compared to controls (at 0.215 +/- 0.027 D/year versus 0.332 +/- 0.015 D/year, respectively; p < 0.001), with the younger alcoholics showing a greater impairment. Following abstinence, there was no measurable change in accommodation measured, indicating the lower amplitude in the alcoholics was not attributable to circulatory alcohol levels. The resting pupil diameter in the alcoholics was 4.37 +/- 0.63 mm compared to the controls of 3.97 +/- 0.75 mm, with a higher incidence of small pupils (< or = 3 mm) in the controls. CONCLUSIONS: The results indicate that chronic alcohol use can adversely affect subjective static accommodation, especially in younger alcoholics, as well as cause slight mydriasis.

Accommodation, Ocular↗

Nucleotide excision repair gene XPD polymorphisms and genetic predisposition to melanoma.

The nucleotide excision repair pathway has evolved to deal with UV light-induced DNA damage. Individuals with the rare inherited nucleotide excision repair deficiency disease xeroderma pigmentosum have a 1000-fold increased incidence of skin cancer. We are interested in the possibility that more subtle changes in nucleotide excision repair genes, resulting in either a reduced capacity for repair or in altered interactions between repair proteins and components of the cell cycle control machinery, might constitute important genetic risk factors for the development of skin cancer in the general population. To investigate this hypothesis we have compared the frequency of polymorphisms in exons 6, 22 and 23 of the XPD gene in melanoma patients and a control group. For each of these two allele polymorphisms one of the alleles was over-represented in the melanoma group and there was a significant association with melanoma. Importantly, this association did not extend to markers immediately flanking the XPD gene, thus providing evidence that XPD gene polymorphisms might predispose to melanoma in the general population. There is a report that one of the polymorphic XPD alleles (exon 23 Lys), which is over-represented in the melanoma group, has reduced repair proficiency and we discuss the possibility that this is the causal change to the XPD gene that predisposes to melanoma.

Alleles↗