Search PubMed⌕ Search

Biomedical subjects

C A Hart

Publications and source records attributed to C A Hart.

At least 181 records · Page 10Linked to original sources

Variation in flagellin genes and proteins of Burkholderia cepacia.

The majority of isolates of Burkholderia cepacia, an important opportunistic pathogen associated with cystic fibrosis, can be classified into two types on the basis of flagellin protein size. Electron microscopic analysis indicates that the flagella of strains with the larger flagellin type (type I) are wider in diameter. Flagellin genes representative of both types were cloned and sequenced to design oligonucleotide primers for PCR amplification of the central variable domain of B. cepacia flagellin genes. PCR-restriction fragment length polymorphism analysis of amplified B. cepacia flagellin gene products from 16 strains enabled flagellin type classification on the basis of product size and revealed considerable differences in sequence, indicating that the flagellin gene is a useful biomarker for epidemiological and phylogenetic studies of this organism.

Amino Acid Sequence↗

Prospective study of "door to needle time" in meningococcal disease.

OBJECTIVE: To measure the promptness of antibiotic treatment in children with meningococcal disease. METHODS: "Door to needle time" for parenteral antibiotics in children with meningococcal disease was recorded prospectively as part of a larger study. The time from arrival at hospital until the first dose of parenteral antibiotics was recorded in 100 children with meningococcal disease (median (range) age 21 (3-168) months) admitted to four Merseyside hospitals. RESULTS: Forty five children presented directly to the accident and emergency (A&E) department. Parenteral penicillin was given before admission to 19 of the 55 children referred by general practitioners (GPs). Median door to needle time was 36 minutes. All children with a typical petechial rash on arrival received antibiotics within 60 minutes. Antibiotics were given sooner to those with severe disease (p = 0.01) and later to those without a rash (p = 0.007). CONCLUSIONS: The first dose of parenteral antibiotics for most children with meningococcal disease was given in A&E. When awareness of meningococcal disease is heightened by ongoing research, those with a petechial rash are treated within 60 minutes. Strategies to improve immediate treatment of meningococcal disease should include education of A&E staff as well as GPs.

Adolescent↗

Placental antibody transfer: influence of maternal HIV infection and placental malaria.

AIM: To determine the influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia on transplacental IgG antibody transfer. METHODS: One hundred and eighty materno-neonatal pairs from a Malawian population were assessed. Cord and maternal serum samples were tested for total serum IgG antibody titres using nephelometry, and for specific IgG antibody titres to Streptococcus pneumoniae, measles, and tetanus toxoid antibodies using an enzyme linked immunosorbent assay (ELISA). RESULTS: Multiple regression analyses showed that placental malaria was associated with a decrease in placental IgG antibody transfer to S pneumoniae and measles to 82% and 81%, respectively. Maternal HIV infection was associated with a reduction in IgG antibody transfer to S pneumoniae to 79%; raised maternal total serum IgG titres were correlated with S pneumoniae and measles IgG antibody transfer reduction to 86% and 87%, respectively. No effect was seen with tetanus toxoid antibody transfer. CONCLUSION: The combined influence of placental malaria, maternal HIV infection, and maternal hypergammaglobulinaemia seems to be linked to the low transplacental antibody transfer observed in the Malawian population.

Adult↗

Risk factors for laparoscopically confirmed pelvic inflammatory disease: findings from Mumbai (Bombay), India.

OBJECTIVES: Sexually transmitted diseases (STDs) are an important cause of pelvic inflammatory disease (PID) but have often not been detected in microbiological studies of Indian women admitted to hospital gynaecology wards or private clinics. In this cross sectional study, women living in the inner city of Mumbai (Bombay) were investigated for socioeconomic, clinical, and microbiological risk factors for PID. METHODS: Microbiological tests and laparoscopic examination were carried out on 2736 women aged < or = 35 years who came to a health facility with suspected acute salpingitis or infertility or for laparoscopic sterilisation. 86 women with a clinical diagnosis of PID were not referred for laparoscopy although their characteristics are described. Associations between various risk factors and PID status were investigated and logistic regression performed on all factors that remained significant. RESULTS: Of women with a laparoscopically confirmed evaluation, 26 women had acute and 48 chronic pelvic infection. Independent risk factors for PID were later age at menarche (> or = 14 years), a history of stillbirth and no previous pregnancy, history of tuberculosis, STD, dilatation and curettage or previous laparoscopy, and presence of Gardnerella vaginalis. CONCLUSIONS: It is concluded that STD related risk factors applied to only a small proportion of PID cases and that other determinants of PID are important, including obstetric complications, invasive surgical procedures such as laparoscopy, and tuberculosis.

Adult↗

Cross infection between cystic fibrosis patients colonised with Burkholderia cepacia.

Whilst patient to patient spread of the respiratory pathogen Burkholderia cepacia is well recognised between patients with cystic fibrosis, prompting a strict segregation policy, cross colonisation between cystic fibrosis patients already infected with B cepacia has not been described and surveys show a very low incidence of patients with more than one strain. Five adult cystic fibrosis patients with B cepacia are presented who became cross colonised with a second B cepacia (UK epidemic) strain, four of whom then died, three from the cepacia syndrome. These cases show that, amongst segregated patients, cross colonisation with different B cepacia strains is possible, and even in these patients the acquisition of the UK epidemic strain may have a fatal outcome. In future it may be necessary to segregate cystic fibrosis patients colonised with the UK epidemic strain from all other patients with cystic fibrosis.

Adolescent↗

Reproductive tract infections, gynaecological morbidity and HIV seroprevalence among women in Mumbai, India.

Reported are the prevalence of reproductive tract infections and their contribution to pelvic inflammatory disease (PID), as well as the seroprevalence of human immunodeficiency virus (HIV), among women living in three inner city wards of Mumbai, India. Women aged < or = 35 years were recruited and screened as cases if they had been admitted to hospital for gynaecological investigation for suspected PID (n = 151) or infertility (n = 295); controls were healthy fertile women attending for laparoscopic tubal ligation (n = 2433). The women were mainly of low socioeconomic status. A total of 59.4% were migrants and 14.9% of these came to Mumbai to seek treatment. Cases reported a history of adverse pregnancy outcomes significantly more often than controls, and 30.5% of suspected PID cases had previously undergone laparoscopic tubal ligation. At examination 24.2% of cases and 8.4% of controls had a vaginal discharge. Pelvic infection was confirmed in 42.0% of suspected PID cases and 14.6% of infertile cases for whom diagnostic laparoscopy was performed. The prevalence of sexually transmitted diseases was low: Chlamydia trachomatis was found in 0.2%; and Neisseria gonorrhoeae was cultured from the cervix in only four cases. Neither of these infections was detected in laparoscopic aspirates. The prevalence of HIV1/2 infections in unlinked samples was 1.9%. Sexually transmitted diseases were not major factors leading to gynaecological morbidity. Heterosexual spread of HIV infection to this population of married women is still relatively low but needs to be carefully monitored. The gynaecological morbidity detected may be a consequence of widespread use of invasive methods of fertility regulation.

Adult↗

Characterization of intestinal morphologic, biochemical, and ultrastructural features in gluten-sensitive Irish Setters during controlled oral gluten challenge exposure after weaning.

OBJECTIVE: To characterize histologic, biochemical, and ultrastructural changes in the intestine of Irish Setters susceptible to gluten-sensitive enteropathy (GSE) during controlled oral challenge exposure with gluten after weaning. ANIMALS: Six gluten-sensitive and 12 healthy Irish Setters and 3 healthy Greyhounds. PROCEDURE: Jejunal biopsy specimens were taken at 4 and 12 months of age from the 6 gluten-sensitive Irish Setters, which had been reared on a gluten-free diet to which a controlled dose of gluten (0.5 g/kg of body weight/d) was added. Control specimens were obtained at 4 (n = 5) and 12 (7) months of age from the healthy Irish Setters, which had been fed a conventional gluten-containing diet, and at 4 months of age from the healthy Greyhounds fed the controlled dose of gluten. The specimens were subjected to histologic and ultrastructural examinations and assay of brush border enzymes. RESULTS: Gluten-sensitive Irish Setters developed abnormalities characteristic of GSE at 4 months. Abnormalities were comparable to changes not seen previously until 12 months in dogs with GSE fed a conventional gluten-containing diet. In addition, microvilli were stunted and irregular, and a few were vesiculated and reduced in number; the glycocalyx was reduced or absent. By 12 months of age, there was improvement in morphologic and biochemical parameters, indicating partial recovery despite continued exposure to gluten. CONCLUSIONS: Relative early onset of intestinal damage, compared with that previously reported, and subsequent partial recovery suggestive of oral tolerance to gluten may be attributable to oral administration of gluten as a purified extract rather than in dietary cereal, but alternative explanations include differences in environment or genetic susceptibility to gluten.

Alkaline Phosphatase↗

Epidemiology of rotavirus diarrhoea in Africa: a review to assess the need for rotavirus immunization.

Rapid progress towards the development of rotavirus vaccines has prompted a reassessment of the disease burden of rotavirus diarrhoea in developing countries and the possible impact of these vaccines in reducing diarrhoeal morbidity and mortality among infants and young children. We examined the epidemiology and disease burden of rotavirus diarrhoea among hospitalized and clinic patients in African countries through a review of 43 published studies of the etiology of diarrhoea. The studies were carried out from 1975 through 1992, and only those in which a sample of more than 100 patients with diarrhoea were specifically screened for rotavirus by using an established diagnostic test were included. Rotavirus was detected in a median of 24% of children hospitalized for diarrhoea and in 23% who were treated as outpatients; 38% of the hospitalized patients with rotavirus were < 6 months and 81% were < 1 year of age. Rotavirus was detected year-round in nearly every country and generally exhibited distinct seasonal peaks during the dry months. In 5 countries where rotavirus strains had been G-typed, 74% of strains were of one of the four common serotypes (G1 to G4), G1 was the predominant serotype, and 26% were non-typeable. This cumulative experience from 15 African countries suggests that rotavirus is the most important cause of severe diarrhoea in African children and that most strains in circulation today belong to common G types that are included in reassortant vaccines. Wherever large numbers of cases of rotavirus diarrhoea occur early in infancy, immunization at birth may protect the children before their first symptomatic infection.

Africa↗

p53 mutations in relation to human papillomavirus type 16 infection in squamous cell carcinomas of the head and neck.

The relationship between human papillomavirus (HPV) type 16 infection and p53 gene mutations was investigated in squamous cell carcinomas of the head and neck (SCCHN). HPV was detected by general primer-mediated and type-specific PCR. Alterations in the p53 gene were investigated using single-strand conformation polymorphism and sequence analysis in 27 SCCHN, of which 12 were HPV 16-positive and 15 were HPV-negative. Mutations were detected in 2/12 (16.7%) HPV 16-positive and 7/15 (46.7%) HPV-negative tumours; this difference was not statistically significant. The predominant mutations were deletions and C --> T transitions; G --> T transversions were found in only 2 tumours. Our results indicate that the presence of HPV 16 and p53 mutations is not mutually exclusive and detection of a p53 mutation does not exclude a potential role for HPV 16 in the pathogenesis of a subset of SCCHN.

Carcinoma, Squamous Cell↗

Evaluation of two simplified methods for genotyping hepatitis C virus.

A number of different approaches have been used for genotyping hepatitis C virus (HCV). Two simplified methods were evaluated, both of which used polymerase chain reaction (PCR) to amplify products from the 5' non-coding region of HCV: non-isotopic restriction fragment length polymorphism (RFLP) analysis and type-specific PCR. Sixty-four viraemic patients suffering from chronic HCV infection were studied using these two techniques; 25/64 samples were further tested with a commercial serotyping ELISA based on synthetic NS4 antigen (Murex, U.K.). The results of the three typing methods were generally in agreement with each other. When only the predominant genotype identified by each method was analysed, the 3 methods had 100% agreement. RFLP did not detect any mixed infections and it was unsuccessful in 16/64 (25%) samples. Both type-specific PCR and serotyping ELISA detected mixed infections. However, serotyping ELISA did not give typeable results in 7/25 (28%) samples, whereas type-specific PCR gave typeable results in all 64 samples. Type-specific PCR detected more mixed infections than serotyping ELISA. Direct sequencing of four PCR products with indeterminate RFLP confirmed changes in restriction enzyme recognition sites. The sequences also confirmed the validity of the predominant genotype in cases of apparent mixed infections. It is possible that some of these cases were artefacts as a result of quasispecies.

Base Sequence↗

Plasma fibronectin levels in meningococcal disease.

UNLABELLED: Fibronectin (a glycoprotein which modulates inflammation) may decrease mortality in systemic infection. Children with meningococcal disease (MCD) may have low fibronectin levels. We aimed to compare plasma fibronectin levels in children with MCD and controls, correlate fibronectin levels with interleukin-6 (IL-6), shock and death, and assess fibronectin as an aid to early diagnosis in MCD. Samples were taken on admission from 99 children with MCD and 49 controls. Plasma fibronectin was measured using a turbidimetric immunoassay. Plasma fibronectin was significantly lower in MCD compared to controls (57 micrograms/ml vs 105 micrograms/ml; P < 0.005). Children who died had significantly lower levels than survivors (29 micrograms/ml vs 62 micrograms/ml; P = 0.01). Fibronectin levels were negatively correlated with IL-6 levels. Fibronectin was a poor predictor of MCD. CONCLUSION: Plasma fibronectin levels are decreased in children with MCD, especially in shock and death. This decrease is associated with high IL-6 levels. Fibronectin could be a novel therapy in severe MCD.

Biomarkers↗

A case of hepatitis B in a haemodialysis unit.

A patient probably acquired hepatitis B virus (HBV) from a transfused infected unit of fresh frozen plasma. She had been on regular haemodialysis for four months before her infection was discovered. One hundred and seventy-six patients and 304 staff contacts were screened and there were no secondary cases. At donation the infected blood donor was hepatitis B surface antigen (HBsAg) negative but subsequently proved to be anti-hepatitis B core (HBc)-positive and positive for HBV DNA. Consideration should be given to screening blood donations for anti-HBc in addition to HBsAg. Vigilance needs to be maintained on dialysis units against sporadic cases of hepatitis B. All staff should be immunized and be able to demonstrate protective levels of anti-HBs.

Adult↗

Low-dose vancomycin prophylaxis reduces coagulase-negative staphylococcal bacteraemia in very low birthweight infants.

Very low birthweight (VLBW) infants undergoing neonatal intensive care are at risk of infection with coagulase-negative staphylococci (CONS). This study investigates the efficacy of twice daily, 1 h infusions of vancomycin (5 mg kg) in reducing CONS infection in VLBW infants receiving parenteral nutrition. Of 72 infants in the study, 37 were randomized to vancomycin and 35 to the control group. Clinical variables and mortality were similar in both groups. In the vancomycin group, 11 infants had one or more episodes of CONS bacteraemia compared with 17 in the control group. Two babies in the treatment group had more than one episode of CONS bacteraemia, compared with nine in the control group (P = 0.02). There were 13 episodes of CONS bacteraemia in the vancomycin group compared with 29 in the control group. When only positive blood-cultures associated with a rise in C-reactive protein were considered, there were six episodes of CONS bacteraemia in the vancomycin group compared with 18 in the control group. Similarly there were five infants with one or more CONS infections compared with 11 in controls and one with more than one episode compared with six in the control group (P = 0.05). Prophylaxis with intermittent low-dose vancomycin infusions may help reduce recurrent CONS bacteraemia in VLBW infants receiving parenteral nutrition.

Anti-Bacterial Agents↗

Antimicrobial susceptibility of Bordetella bronchiseptica isolates from cats and a comparison of the agar dilution and E-test methods.

One hundred and fifty-two predominantly feline isolates of Bordetella bronchiseptica were tested for their susceptibility to seven antimicrobial agents using an agar dilution method. The majority of isolates tested by the agar dilution method were resistant to trimethoprim (MIC90 500 micrograms/ml) and ampicillin (MIC90 > 32 micrograms/ml) but sensitive to tetracycline, doxycycline and enrofloxacin (MIC90 2 micrograms/ml for all three agents). The isolates showed a spectrum of susceptibility to sulphadiazine and clavulanate potentiated amoxycillin. The MIC's of twenty-nine of the 152 isolates were then compared for five of the antimicrobial agents using the E-test (AB Biodisk, Sweden), a recently introduced method for measuring the MIC's of antimicrobial agents based on the diffusion of a pre-defined antibiotic gradient from a plastic strip. Comparisons with the E-test demonstrated an overall agreement (+/- 1 log2 dilution) with the agar dilution method of 79.4% and an agreement within +/- 2 log2 dilutions of 96.2%.

Agar↗

Localization of IL-4 and IL-4 receptors in the human term placenta, decidua and amniochorionic membranes.

There has been much recent interest in cytokine expression at the materno-fetal interface. Although T-helper 2 (Th2)-type cytokines have been described in the murine feto-placental unit, few studies have as yet been performed in human pregnancy. We have examined the production of interleukin-4 (IL-4) and expression of IL-4 receptors in the human term placenta, decidua and amniochorionic membranes. Immunohistochemical analyses revealed that cytotrophoblast, decidual macrophages and both maternal and fetal endothelial cells consistently expressed IL-4, whereas syncytiotrophoblast and placental macrophages showed an inconsistent pattern between specimens. High- and low-affinity IL-4 receptors were demonstrated by immunohistochemistry at the same cellular sites as stained for IL-4, and detection of IL-4 receptors was also variable in syncytiotrophoblast. Reverse-transcribed-polymerase chain reaction (RT-PCR) analysis showed that both IL-4 and its alternative splice variant, IL-482, are produced both in placental villi and in amniochorionic and decidual tissue. Ligand-binding assays identified the presence, on isolated term syncytiotrophoblast microvillous plasma membrane vesicle preparations, of functional high-affinity binding sites for IL-4 with a Kd in the range 102-112 pM and an apparent receptor density in the range 99-102 x 10(8) sites/mg protein. Three human choriocarcinoma (BeWo, JEG-3 and Jar) and one amnion-derived (AV3) cell lines expressed IL-4 and both high- and low-affinity IL-4 receptors. The constitutive expression of both IL-4 and IL-4 receptors, together with the novel finding of the alternative splice variant IL-482 in the immediate tissues at the materno fetal interface suggest an immunobiological role for IL-4 in human pregnancy.

Antigens, CD↗

Detection, distribution and probable fate of Escherichia coli O157 from asymptomatic cattle on a dairy farm.

The use of commercial anti-Escherichia coli O157-labelled magnetic beads was investigated to improve detection of E. coli O157 by immunomagnetic separation (IMS) from a range of environments on a dairy farm. Immunomagnetic separation proved effective for separation of target cells from laboratory mixtures and during stress in sterile and non-sterile pond water. The IMS procedure was possible with a range of samples (water, faeces, slurry, grass and soil). Non-specific binding of non-target bacterial cells proved problematic in a number of sample types. However, indigenous E. coli O157 cells were detected from samples with a high faecal load, and only with use of IMS. Data on the probable survival and spread of the organism around the farm environment are also discussed.

Animals↗

Plasmid diversity of multi-drug-resistant Escherichia coli isolated from children with diarrhoea in a poultry-farming area in Kenya.

Biotin-labelled DNA probes and restriction-endonuclease digestion (RED) with HindIII were used to study the diversity of resistance plasmids (R-plasmids) from 414 Escherichia coli isolates: 168 from children living in close contact with antibiotic-fed poultry and 246 from the chickens. Full sensitivity to all 10 antimicrobials tested was more common in the isolates from poultry than in those from the children (36.2% v. 9.5%; P < 0.001). Multi-drug resistance, to at least two of the antimicrobials, was relatively common in the isolates from the children (85.5% v. 26.00%; P < 0.001). Overall, 31% of the poultry isolates were resistant to tetracycline alone. Resistance to amoxycillin was due to production of TEM-1 (89%) and TEM-2 (11%). In > 71% of the isolates from children and 79% of those from poultry, resistance was encoded on a 100-110-kb transferable plasmid belonging to incompatibility group FII. However, RED patterns of R-plasmids from the two groups of isolates were highly diverse and not indicative of any close relatedness. This difference in patterns and in the levels of multi-drug resistance indicate that the isolates from the children and those from the poultry represent two distinct pools of resistance plasmids.

Animal Husbandry↗