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Biomedical subjects

E G Smith

Publications and source records attributed to E G Smith.

At least 19 recordsLinked to original sources
PubMed2003

Chest physicians' and microbiologists' awareness and demand for drug monitoring in the treatment of TB.

There is a role for therapeutic drug monitoring (TDM) to achieve the optimum therapeutic concentration of anti-tuberculous drugs. This work aimed to determine the current awareness of TDM in TB control among chest physicians and to estimate the demand for this service. Responses from a sample of chest physicians in the West Midlands revealed that 60% were aware of TDM and 33% had used it. Responses were received from half of a UK group of microbiologists who reported a median of nine requests in the past year. It appeared that more was known about services for rifampicin and streptomycin than other first-line drugs. There appears to be a need for both increased awareness among potential service users and for coordination of assay services.

Antitubercular Agents↗
PubMed2002

Chronic fatigue following infection by Coxiella burnetii (Q fever): ten-year follow-up of the 1989 UK outbreak cohort.

BACKGROUND: Some patients exposed to Q fever (Coxiella burnetii infection) may develop chronic fatigue. AIM: To determine whether subjects involved in the West Midlands Q fever outbreak of 1989 had increased fatigue, compared to non-exposed controls, 10 years after exposure. DESIGN: Matched cohort study comparing cases to age-, sex- and smoking-history-matched controls not exposed to Q fever. METHODS: A postal questionnaire was sent to subjects at home, followed by further assessment in hospital, including a physical examination and blood tests. RESULTS: Of 108 Q-exposed subjects, 70 (64.8%) had fatigue, 37 idiopathic chronic fatigue (ICF) (34.3%), vs. 29/80 (36.3%) and 12 (15.0%), respectively, in controls. In 77 matched pairs, fatigue was commoner in Q-exposed subjects than in controls: 50 (64.9%) vs. 27 (35.1%), p<0.0001. ICF was found in 25 (32.5%) of Q-exposed patients and 11(14.3%) of controls (p=0.01). There were 36 (46.8%) GHQ cases in Q-exposed subjects, vs. 18 (23.4%) controls (p=0.004). A matched analysis of those more intensively studied showed fatigue in 48 (66.7%) Q-exposed patients and 25 (34.7%) controls, (p<0.0001), ICF in 25 (34.7%) Q-exposed and 10 (13.9%) controls (p=0.004), and chronic fatigue syndrome (CFS) in 14 (19.4%) Q-exposed patients and three (4.2%) controls (p=0.003). Thirty-four (47.2%) Q-exposed patients were GHQ cases compared to 17 (23.6%) controls (p=0.004). DISCUSSION: Subjects who were exposed to Coxiella in 1989 had more fatigue than did controls, and some fulfilled the criteria for CFS. Whether this is due to ongoing antigen persistence or to the psychological effects of prolonged medical follow-up is uncertain.

Case-Control Studies↗
PubMed2002

Long-term follow-up of patients from the 1989 Q fever outbreak: no evidence of excess cardiac disease in those with fatigue.

BACKGROUND: In 1989, an outbreak of Q fever (C. burnetii infection) with 147 confirmed cases occurred in Solihull, West Midlands. Three patients developed cardiomyopathy in the subsequent 10 years. The cohort has been followed up with respect to the development of fatigue and, in this instance, cardiac effects after the original infection. AIM: To determine whether persisting fatigue after Q fever represented sub-clinical cardiomyopathy. DESIGN: Prospective follow-up study. METHODS: All traceable subjects from the original outbreak, and community age-, sex- and smoking-matched controls, were studied. Questionnaires for idiopathic fatigue, 12-lead ECG, echocardiography, spirometry and shuttle walk distance were undertaken, and a subset with CDC-defined chronic fatigue syndrome had gated cardiac scans. RESULTS: Of the original cohort, 19 had died, three had emigrated and 10 were untraceable. Of the remaining 115, 108 responded to a mailed questionnaire and 87 were investigated further, of whom 85 provided complete data. Two developed aortic valve vegetations, one of whom died. Chronic fatigue syndrome was found in 20% of cases and 5.3% of controls (including those with co-morbidities), falling to 8.2% and 0 when excluding those with co-morbidities. There were no significant differences in ECG and echocardiographic investigations or shuttle-walk distance between those with fatigue and those without. Six of the seven patients with CFS had gated cardiac scans: all were within normal limits. CONCLUSIONS: These findings do not support the existence of a sub-clinical cardiomyopathy in the patients in this cohort who suffer from fatigue after acute Q fever, although endocarditis can occur after acute infection.

Cardiomyopathies↗
PubMed2002

Antibiotic resistant tuberculosis in the United Kingdom: 1993-1999.

BACKGROUND: The re-emergence of tuberculosis as a global health problem over the past two decades, accompanied by an increase in tuberculosis drug resistance, prompted the development of a comprehensive national surveillance system for tuberculosis drug resistance in 1993. METHODS: The UK Mycobacterial Resistance Network (Mycobnet), which includes all mycobacterial reference and regional laboratories in the UK, collects a minimum dataset on all individuals from whom an initial isolate of Mycobacterium tuberculosis complex has been isolated and submitted by source hospital laboratories. Data sought include susceptibility to first line antibiotics, demographic, geographical, and risk factor information. RESULTS: There were 25 217 reports of initial isolates of M tuberculosis complex in the UK between 1993 and 1999. All were tested for sensitivity to isoniazid, rifampicin, and ethambutol and 12 692 of the isolates were also tested for sensitivity to pyrazinamide and streptomycin. A total of 1523 (6.1%) isolates were resistant to one or more drugs, 1397 isolates (5.6%) were resistant to isoniazid with or without resistance to other drugs, and 299 (1.2%) were multidrug resistant. Although the numbers of drug resistant isolates increased over the period, the proportions remained little changed. Certain groups of people were at a higher risk of acquiring drug resistant tuberculosis including younger men, residents of London, foreign born subjects, patients with a previous history of tuberculosis and those infected with HIV. CONCLUSION: Although the proportion of drug resistant tuberculosis cases appears to be stable in the UK at present, more than one in 20 patients has drug resistant disease at diagnosis and more than one in 100 has multidrug resistant disease. Tuberculosis control measures should be strengthened to minimise the emergence of drug resistance through rapid diagnosis, rapid identification of drug resistance, supervised treatment, and maintenance of comprehensive surveillance.

AIDS-Related Opportunistic Infections↗
PubMed2002

A national study of clinical and laboratory factors affecting the survival of patients with multiple drug resistant tuberculosis in the UK.

BACKGROUND: This study aimed to describe the clinical, microbiological, molecular epidemiology and treatment of multidrug resistant tuberculosis (MDRTB) cases in the UK and to determine factors associated with survival. METHODS: Ninety MDRTB cases were identified from 1 January 1996 to 30 June 1997; 69 were DNA fingerprinted. Date of diagnosis was determined and data were collated on key demographic factors, clinical, radiological and treatment details. Variables associated with survival were included in a Cox proportional hazards model. RESULTS: Most of the patients (72.4%) were male, born outside the UK (57.1%), were sputum smear positive (82.2%), and had entered the UK more than 5 years previously (61.9%). Thirty eight of 78 cases (48.7%) had prior TB. Sufficient data on 82 patients were available for survival analysis; 20/27 (74.1%) known to be dead at the end of the observation period had died of tuberculosis. Median survival time overall was 1379 days (95% CI 1336 to 2515) or 3.78 (95% CI 3.66 to 6.89) years (858 days (95% CI 530 to 2515) in immunocompromised individuals (n=32) and 1554 (95% CI 1336 to 2066) days in immunocompetent cases (n=48)). Median survival in patients treated with three drugs to which the bacterium was susceptible on in vitro testing (n=62) was 2066 days (95% CI 1336 to 2515) or 5.66 years, whereas in those not so treated (n=13) survival was 599 days (95% CI 190 to 969) or 1.64 years. CONCLUSIONS: Immunocompromised status, failure to culture the bacterium in 30 days or to apply appropriate three drug treatment, and age were significant factors in mortality. An immunocompromised patient was nearly nine times more likely to die, while application of appropriate treatment reduced the risk (risk ratio 0.06). Increasing age was associated with increasing risk of death (risk ratio 2.079; 95% CI 1.269 to 3.402)-that is, for every 10 year increase in age the risk almost doubled. Overall survival was lower than that reported in previous studies.

Adolescent↗
PubMed1999

A national audit of the laboratory diagnosis of tuberculosis and other mycobacterial diseases within the United Kingdom.

In order to audit United Kingdom laboratory diagnostic and reference services including novel molecular methods for tuberculosis, a questionnaire was sent to laboratories submitting specimens to the PHLS Mycobacterium Reference Unit (MRU) and regional centres and to the Scottish Mycobacteria Reference Laboratory (SMRL) in 1996-7. Nationally, 67.2% of laboratories responded. Most UK laboratories were fully or conditionally CPA accredited and take part in the NEQAS proficiency scheme. On average only 3.3% of primary samples submitted for mycobacterial diagnosis in 1995 produced a mycobacterial culture from approximately half as many patients (that is, a mean of 1488 specimens producing 49 isolates from 23 patients). Potentially over 380,000 specimens are processed for mycobacteria in the UK each year. The majority of laboratories use 4% NaOH +/- NALC for specimen decontamination. Culture on solid media was used by most laboratories and 62.9% also use liquid media. Most laboratories incubated cultures for eight weeks. Few laboratories use molecular diagnostic methods. Laboratories were most likely to use molecular methods for diagnosing tuberculous meningitis and for specimens from immunocompromised patients, although usage was strongly influenced by cost. Within England and Wales 43.9% (47/107) and 56% (61/109) of laboratories wanted a rapid service for rifampicin resistance detection in M tuberculosis from immunocompetent and immunocompromised patients, respectively. In regard to a tuberculous meningitis service, 80.5% (43/112) and 84.3% (102/121) of laboratories wanted this service for immunocompetent and immunocompromised patients, respectively. The quality of reference services was rated as "very good"/"good" by 85.6% of respondents nationally. Rapid molecular amplification diagnostic services were established at the PHLS MRU for rifampicin drug resistance detection nationally and for tuberculous meningitis at the MRU.

Bacteriological Techniques↗
PubMed1998

Regional microbiology of the cystic fibrosis lung: a post-mortem study in adults.

Although the majority of patients with cystic fibrosis (CF) become chronically colonized with Pseudomonas aeruginosa, the mode of acquisition of infection remains unclear. Epidemiological studies using genotyping techniques suggest that person-to-person transmission of this organism may occur. All these studies have utilized sputum or throat swab samples. We have studied the regional microbiological flora of the lungs of five CF patients at post-mortem and genotyped P. aeruginosa strains found therein and in the major airway. We have shown that although in most cases major airway secretions accurately reflect the peripheral lung flora, in cases of multiple strain carriage, major airway cultures may not reflect all strains present in the periphery of the lung. This finding has implications for the interpretation of epidemiological studies that use genotyping of strains from sputum and throat swab samples to assess possible routes of transmission.

Adult↗
PubMed1998

Post-infection fatigue syndrome following Q fever.

In 1989, 147 individuals in the West Midlands, UK, were infected with Q fever. Five years later, following anecdotal reports of fatigue, we used a questionnaire-based case-control study to determine the prevalence of chronic fatigue syndrome symptoms in this group. Replies from 71 patients were compared with those from 142 age- and sex-matched controls. Increased sweating (52.9% vs. 31.6%, p = 0.006), breathlessness (50.7% vs. 30.6%, p = 0.006), blurred vision (34.3% vs. 17.8%, p = 0.016) and undue tiredness (68.7% vs. 51.5%, p = 0.03) were found in controls compared to cases. These findings were similar to those in Australian abbatoir workers occupationally exposed to Q fever. CDC criteria for chronic fatigue syndrome were fulfilled by 42.3% of cases and 26% of controls. Using visual analogue scores, symptoms were more severe in cases than in controls. Our findings support the existence of a chronic fatigue state following acute Q fever, in a group of patients exposed just once to the organism, and in circumstances free of such confounding factors as lawsuits over compensation.

Acute Disease↗
PubMed1998

Reference laboratory surveillance of syphilis in England and Wales, 1994 to 1996.

Routine surveillance of syphilis of public health importance (infectious, congenital, and neurosyphilis) began in England and Wales in 1994, using reports from six PHLS laboratories that undertook serological and other reference work. One hundred and thirty-one cases were reported in the first two years, including 100 cases of infectious syphilis, with all regions reporting some infectious syphilis. Reports from PHLS laboratories represented one sixth of the number of cases seen in genitourinary clinics (KC60 data), but both systems produced comparable results. Laboratory reports provided more data on risk factors, which were not available elsewhere. This study documents the risk in England and Wales from infections originating in eastern Europe, where sexually transmitted infections including syphilis have reached epidemic proportions. Forty-five per cent of cases of infectious syphilis were reported to have been acquired in the United Kingdom (UK) and 59% of people with infectious syphilis were reported to have been born in the UK. Twenty per cent of the infectious cases were associated directly or indirectly with transmission in Russia or elsewhere in eastern Europe. The majority of infectious cases were from the white ethnic group. Eighty-five per cent of cases of infectious syphilis were reported to have been acquired heterosexually; 26% of male cases were reported to have been acquired homosexually. The PHLS laboratory reporting system is now well established, and could usefully be expanded to include other, non PHLS, laboratories that undertake reference work. It has the capacity to detect changes in the national epidemiology of syphilis, including imported infections.

Adult↗
PubMed1998

A large outbreak of Q fever in the West Midlands: windborne spread into a metropolitan area?

The largest outbreak of the zoonotic disease Q fever recorded in the United Kingdom (UK) occurred in Birmingham in 1989. One hundred and forty-seven cases were identified, 125 of whom were males, and 130 of whom were between 16 and 64 years of age. Fewer cases of Asian ethnic origin were observed than expected (p < 0.01), and more smokers (p < 0.005). A case control study (26 cases and 52 matched controls) produced no evidence that direct contact with animals or animal products had caused the outbreak. The epidemic curve suggested a point source exposure in the week beginning 10 April. The home addresses of cases were clustered in a rectangle 11 miles (18.3 km) north/south by 4 miles (6.7 km) east/ west, and attack rates became lower towards the north. Directly south of this area were farms engaged in outdoor lambing and calving, a potent source of coxiella spores. A retrospective computerised analysis showed that the geographical distribution of cases was associated with a source in this area (p < 0.00001). On 11 April, unusual southerly gales of up to 78 mph (130 km/h) were recorded. The probable cause of the outbreak was windborne spread of coxiella spores from farmland to the conurbation.

Adolescent↗
PubMed1997

PHLS mycobacteriology reference services in England and Wales.

Tuberculosis (TB) is the most important cause of infectious disease in the world, with eight million new cases and three million deaths each year. The increasing incidence of TB in the developed and the developing world, increasing drug resistance, and the occurrence of nosocomial outbreaks of drug sensitive as well as drug resistant TB has led the PHLS to establish TB as a priority area. This article reviews the enhanced reference services for mycobacteriology provided by the PHLS in England and Wales. These include microscopy and culture on solid and liquid media, rapid culture systems, identification of mycobacteria using macroscopic, microscopic, growth, and biochemical characteristics, and molecular DNA analysis. The Mycobacterium Reference Unit (MRU) provides rapid molecular DNA amplification techniques to identify Mycobacterium tuberculosis in specimens. All four PHLS Regional Centres test isolates for drug susceptibility. This work is quality controlled by MRU, which is one of the World Health Organisation's reference centres for global surveillance on drug resistance in tuberculosis. National data on drug resistance are collated through 'Mycobnet', a surveillance scheme run through the collaboration of PHLS and other UK reference centres and the PHLS Communicable Disease Surveillance Centre.

Bacteriological Techniques↗
PubMed1997

Serum IgG response to an outer membrane porin protein of Burkholderia cepacia in patients with cystic fibrosis.

Early and accurate diagnosis of Burkholderia cepacia infection is important, particularly if segregation is to prevent patient-to-patient transmission. We have examined the serum response to a B. cepacia-specific 80-kDa outer membrane protein. 21 patients colonised with B. cepacia and Pseudomonas aeruginosa for 2-51 months (mean 11 months) were age- and sex-matched with 21 patients colonised with P. aeruginosa but not B. cepacia. The 80-kDa protein was recovered by electroelution from outer membrane proteins, separated by SDS-PAGE, coated onto ELISA plates, reacted with patient sera diluted 1:200, protein A-peroxidase and chromogenic substrate. We found that 19/24 patients colonised with B. cepacia and P. aeruginosa had high values, 2/24 patients had intermediate values, and 2/24 patients had a low value. 20/21 patients colonised with P. aeruginosa alone had low values and 1/21 had an intermediate value. We found that in the longitudinal serum samples studied from four patients only one patient developed high values after the first isolation of B. cepacia suggesting that seroconversion does not occur immediately after the first sputum culture of B. cepacia. We conclude that an ELISA test using B. cepacia-specific 80-kDa outer membrane protein can distinguish B. cepacia colonised and non-colonised patients and may be useful in the early diagnosis of B. cepacia infection.

Adolescent↗
PubMed1997

Information processing through the first year of life: a longitudinal study using the visual expectation paradigm.

This Monograph uses a developmental function approach to describe age-related change and individual differences in infant information processing during the first year of life. The Visual Expectation Paradigm (VExP) is used to measure speed of information processing, response variability, and expectancy formation. Eye-movement reaction times and anticipatory saccades were gathered from 13 infants assessed monthly from 2 to 9 months and then again at 12 months. Analysis of response patterns demonstrated the applicability of the paradigm throughout the age range studied. Converging operations strongly indicate that the traditional estimate of the minimum time required for infants to initiate a saccade to a peripheral stimulus may be as much as 100 milliseconds (ms) too long. Moreover, the newly estimated minimum of 133 ms does not appear to change during the 2-12-month period. Reanalysis of the present data and past research reveals that the new, shorter minimum reaction time is unlikely to affect findings based on mean reaction time. However, using the traditional minimum reaction time will inflate estimates of percentage anticipation, especially in infants older than 5 months. Group and individual growth curves are described through quantitative models of four variables: reaction time, standard deviation of reaction time, percentage anticipation, and anticipation latency. Developmental change in reaction time was best described by an asymptotic exponential function, and evidence for a local asymptote during infancy is presented. Variability in reaction time was found to decline with age, independent of mean reaction time, and was best described by a polynomial function with linear and quadratic terms. Anticipation showed little lawful change during any portion of the age span, but latency to anticipate declined linearly throughout the first year. Stability of individual differences was strong between consecutive assessments of mean reaction time. For nonconsecutive assessments, stability was found only for the 6-12-month period. Month-to-month stability was inconsistent for reaction-time variability and weak for both anticipation measures. Analyses of individual differences in growth curves were carried out using random regressions for the polynomial models. The only significant individual difference (in growth curves) was found for reaction-time variability. Parameter estimates from the exponential models for reaction time suggested two or three developmental patterns with different exponential trajectories. This finding indicates that the strong form of the exponential growth hypothesis, which states that processing speed develops at the same rate for all individuals, does not hold for the first year of life. In the concluding chapter, Grice's Variable Criterion Model (Grice, 1968) is used to integrate three key findings: regular age changes in mean reaction time and variability but no age change in the minimum reaction time. It is argued that the rate of growth of sensory-detection information is developmentally constant during much of the first year but that age changes occur in the level and spread of the distribution of response threshold values. The unique strengths of the paradigm are discussed, and future directions are suggested for further developing the paradigm itself and for using it as a tool to study broad issues in infant cognition.

Eye Movements↗