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Biomedical subjects

C A Hart

Publications and source records attributed to C A Hart.

At least 73 records · Page 4Linked to original sources
PubMed2002

Spread of an epidemic Pseudomonas aeruginosa strain from a patient with cystic fibrosis (CF) to non-CF relatives.

Colonisation with Pseudomonas aeruginosa is common in adults with cystic fibrosis (CF) and there is increasing evidence that transmissible strains may cross colonise patients. However, transmission of these strains by social contact to healthy non-CF individuals has not been described. A case is presented where an adult CF patient colonised by an epidemic P aeruginosa strain infected her parents with subsequent morbidity.

Adult↗
PubMed2002

Zoonotic species of Cryptosporidium are as prevalent as the anthroponotic in HIV-infected patients in Thailand.

The epidemiology of chronic diarrhoea in adults with late-stage HIV infection was investigated in a prospective study in Bangkok, Thailand. During this investigation, 34 Cryptosporidium isolates were obtained from the faeces of 36 patients, with mean CD4(+) counts of only 14 x 10(6) CD4(+) cells/litre (range = 2 x 10(6) - 53 x 10(6)/litre), who had symptomatic cryptosporidiosis. Genotyping of these isolates, by RFLP analysis and DNA sequencing of the hypervariable region of the 18S rRNA gene, indicated that only 17 (50%) were of the C. parvum human genotype. The rest were of C. meleagridis (seven), the C. parvum 'bovine' genotype (five), C. felis (three) and C. canis (two). Extensive genotypic heterogeneity was observed among the C. parvum isolates, and two other isolates, one of C. meleagridis and the other of C. felis, produced atypical restriction patterns and were only identified by sequencing. This appears to represent the first report of C. canis and the 'bovine' genotype of C. parvum in HIV-infected Thai patients.

Adult↗
PubMed2002

Effect of zinc on the tuberculin response of children exposed to adults with smear-positive tuberculosis.

The tuberculin test (PPD) is used frequently in the diagnosis of tuberculosis. PPD, however, relies on an intact cell-mediated immunity and infected children often have false negative results. This study assessed whether a single oral zinc supplement modifies the PPD induration size and its association with nutritional status in Brazilian children. Ninety-eight children below 15 years of age who had been exposed to adults with smear-positive pulmonary TB in 1998 were tested by PPD in 1998 and 2000. Children were randomised in 2000 to receive a single oral dose of zinc sulphate or a placebo at the time of administering the PPD. Forty-three (44%) children were PPD-positive in 1998 and 54 (55%) in 2000. A higher proportion of children were classified as PPD-positive in 2000 in the zinc-supplemented group (57.1%) than in the placebo group (53.1%). PPD indurations were larger in children receiving zinc (mean 18.5 and 15.5 mm in the zinc and placebo groups, respectively) (p < 0.03). Mean induration sizes in 2000 were larger in zinc-supplemented children, regardless of their nutritional status. Our study demonstrates that zinc increases the PPD induration size in children irrespective of nutritional state. Zinc supplementation could work by correcting asymptomatic or marginal zinc deficiencies or as a non-specific booster of immunological mechanisms (whether or not there is a deficiency).

Administration, Oral↗
PubMed2002

The transplacental transfer of IgG subclasses: influence of prematurity and low birthweight in the Gambian population.

Having established previously that prematurity in The Gambia is associated with impaired maternofetal transfer of some specific antibodies, we investigated the influence of low birthweight and prematurity on placental transfer of IgG subclasses in 180 Gambian mothers and their newborn babies. A physician-blinded, cross-sectional study of 180 mother-baby pairs was carried out in the labour ward of Bansang Hospital, The Gambia. Paired maternal and cord serum samples were collected from mothers and their newborns. Serum IgG subclass levels were measured by laser nephelometry. Placental transfer of all IgG subclasses was significantly reduced in preterm newborns compared with term newborns (p < 0.01). In low birthweight (LBW) babies, the transfer of IgG1 (p = 0.03) and IgG2 (p < 0.01) subclasses, but not IgG3 and IgG4, was significantly reduced. In preterm neonates with an adequate birthweight and term neonates with a low birthweight, all IgG subclasses were transferred with reduced efficiency, but IgG1 and IgG2 subclasses were transferred with significantly less efficiency than IgG3 and IgG4. These results confirm that prematurity and low birthweight are associated with impaired placental transfer of IgG1 and IgG2 subclasses in this Gambian population. This impairment might explain the susceptibility of these newborns to certain polysaccharide-encapsulated organisms.

Adolescent↗
PubMed2001

Zidovudine phosphorylation and mitochondrial toxicity in vitro.

Zidovudine (ZDV) is a thymidine analogue activated to its triphosphate (ZDVTP) by the host's intracellular enzymes. The initial phosphorylation step is conversion to ZDV monophosphate (ZDVMP). The poor affinity of ZDVMP for thymidylate kinase results in intracellular accumulation of ZDVMP. Clinical use of ZDV is associated with cytotoxicity, thought to be mediated through mitochondrial damage. It has been suggested that ZDV cytotoxicity correlates with intracellular ZDVMP. Here we have further studied the role of ZDVMP in cytotoxicity and some of the mechanisms involved. Intracellular metabolism of ZDV in five lymphocyte/monocyte cell lines, U937, BSM, MOLT 4, JJAHN, and RAJI (4 x 10(6) cells), was investigated following 24 h incubation with [(3)H]ZDV (1.2 microCi; 0.1 microM) and cytotoxicity was determined by the MTT assay. Cytotoxicity was closely related to intracellular concentrations of the major metabolite (ZDVMP) but not with the active metabolite ZDVTP. ZDVMP was the only metabolite detected following incubation of viable mitochondria isolated from U937 cells with ZDV (1.2 microCi; 0.1 microM; 24 h) with mitochondrial levels of 0.27 +/- 0.11 pmol/microg protein (mean +/- SD; n = 3). No MTT toxicity was seen in isolated mitochondria. Following phytohemagglutinin (PHA) stimulation of peripheral blood mononuclear cells there was an increase in ZDV cytotoxicity compared to unstimulated cells. The results suggest that the mitochondrial isozyme of thymidine kinase (TK2) plays only a minor part in ZDVMP formation. Following PHA stimulation, activation of the cytosolic thymidine kinase isozyme (TK1) is associated with increased toxicity of ZDV. We conclude that ZDVMP responsible for mitochondrial toxicity is formed in the cytosol.

Dose-Response Relationship, Drug↗
PubMed2001

A putative type III secretion gene cluster is widely distributed in the Burkholderia cepacia complex but absent from genomovar I.

Using probes constructed from Ralstonia solanacearum and Burkholderia pseudomallei, putative type III secretion (TTS) genes were identified in Burkholderia cepacia J2315 (genomovar III). A cosmid clone containing DNA with homology to five TTS genes was sub-cloned and regions were sequenced in order to design oligonucleotides for polymerase chain reaction assays. These indicated that two putative TTS genes (bcscQ and bcscV) were present in all members of the B. cepacia complex with the exception of strains from genomovar I. Southern blot assays confirmed this observation, suggesting that the lack of a TTS gene cluster may define a major difference between B. cepacia genomovar I and other members of the B. cepacia complex, including genomovar III. In contrast to TTS gene clusters in other bacteria, a putative gene homologous to the virB1 gene of Brucella suis was located directly downstream of bcscQR.

Burkholderia cepacia↗
PubMed2001

Epidemiologic and clinical features of HIV-infected and HIV-uninfected Ugandan children younger than 18 months.

METHODS: Groups of HIV-infected and HIV-uninfected infants younger than 18 months (mainly younger than 6 months) were compared to identify clinical features that could differentiate the two groups. The HIV-infected group also was compared with HIV-infected children older than 18 months. Recruitment was as follows for the group younger than 18 months: 708 children admitted with sepsis and clinical features suggestive of HIV infection were screened for HIV1 and HIV2 by HIV enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR) was undertaken on all ELISA-seropositive blood samples (270). HIV infection was confirmed in 136 (19.2%), 438 (61.9%) were HIV-seronegative, 27 (3.8%) were HIV seroreverters, 36 (5.1%) were HIV-seropositive but PCR negative (uninfected), and 71 (10.0%) were indeterminate. One hundred thirty-six HIV-infected children were compared with 501 uninfected children. Confirmed HIV-infected children older than 18 months attending the pediatric HIV clinic were compared with the 136 HIV-infected children younger than 18 months. RESULTS: Under 18 months, the median age of HIV-infected children (n = 136) was 4.0 months (range, 3 d -18 mo ) and the median age of the uninfected children (n = 501) was 1.0 month (range, 3 d -18 mo ). HIV-infected children were more likely to have had injections, chloroquine, and nystatin, and to have attended a health center or hospital (p <.001). In the HIV-infected group, the Z score for weight-for-age was -1.75, length-for-age -0.78, and weight-for-length 1.86, significantly lower scores than those of the uninfected group, which were -0.60, -0.23, and 3.05, respectively (p <.05). The mean head circumference was below the third percentile in 40% of HIV-infected compared with 22% of uninfected children (p <.001). Overall, 56 (8%) children had marasmus, 6 (0.8%) kwashiorkor, and 3 (0.4%) marasmic kwashiorkor. Sixteen percent of the HIV-infected and 7% of uninfected children had marasmus (p <.05). The 1989 revised World Health Organization clinical criteria for diagnosis of AIDS had sensitivity, specificity, and positive predictive values of 28%, 98%, and 93%, respectively. Older than 18 months (n = 109), the median age was 24 months (range, 18-60 mo ). The following were significantly more common in HIV-infected children older than 18 months than in those younger than 18 months: bacille Calmette-Guérin vaccination scar, parotid enlargement, nonspecific generalized dermatitis, and chronic diarrhea ( p <.001). Oral candidiasis was more common in the group younger than 18 months (p <.001). In infants examined in the hospital for infective conditions, oropharyngeal candidiasis, ear discharge, dermatologic disorders, generalized lymphadenopathy, lobar consolidation, hepatosplenomegaly, and failure to thrive, especially marasmus, were important indicators of HIV infection.

Enzyme-Linked Immunosorbent Assay↗
PubMed2001

Effect of concomitant HIV infection on presentation and outcome of rotavirus gastroenteritis in Malawian children.

BACKGROUND: Rotaviruses represent important causes of severe diarrhoea in early childhood. We examined the effect of HIV infection on the presentation and outcome of rotavirus gastroenteritis in Malawian children. METHODS: Children younger than 5 years who were treated for acute gastroenteritis at the Queen Elizabeth Central Hospital in Blantyre from July, 1997, to June, 1999, were enrolled. Children with rotavirus diarrhoea, with and without HIV infection, were followed up for up to 4 weeks after hospital discharge. Rotavirus disease severity (assessed with a 20-point score), duration of rotavirus shedding, and seroresponse to rotavirus were compared between HIV-infected and HIV-uninfected children. FINDINGS: 786 inpatients (median age 8 months, 271 [34%] of whom were HIV-1-infected) and 400 outpatients (median age 9 months, 65 [16%] of whom were HIV-infected) were enrolled. Rotavirus was detected less frequently among HIV-infected children (102 of 336 [30%]) than among HIV-uninfected children (348 of 850 [41%], (relative risk 0.71 [95% CI 0.53-0.87], p=0.0007). There were no differences in rotavirus disease severity for hospitalised children with and without HIV infection, but HIV-infected children were more likely to die during follow-up (11/50 [22%]) than HIV-uninfected children (0/61, p<0.0001). Of 29 HIV-infected and 45 HIV-uninfected children who completed follow-up, six (21%) HIV-infected children shed rotavirus, compared with two (4%) HIV-uninfected children (4.66 [1.01-21.51], p=0.05), but shedding was not associated with diarrhoea. Three-quarters of children exhibited a four-fold rise of serum IgG or IgA to rotavirus, which did not vary by HIV status. INTERPRETATION: Malawian children with concomitant HIV infection resolved acute rotavirus infections. Rotavirus vaccine safety and immunogenicity in HIV-infected infants should now be determined.

Chi-Square Distribution↗
PubMed2001

Superinfection with a transmissible strain of Pseudomonas aeruginosa in adults with cystic fibrosis chronically colonised by P aeruginosa.

Infection with transmissible strains of Pseudomonas aeruginosa can occur in uncolonised patients, but cross infection (superinfection) of patients already colonised withP aeruginosa has not been reported. With genotypic identification, we found superinfection by a multiresistant transmissible strain of P aeruginosa in four patients with cystic fibrosis (CF) who were already colonised by unique strains of P aeruginosa. No evidence of environmental contamination was found, but all patients became superinfected after contact with colonised individuals during inpatient stays. Inpatients with CF who are colonised with P aeruginosa should be separated by strain type. Such strain typing can only be reliably done by genomic methods, but this has resource implications.

Adult↗
PubMed2001

Plasma HIV burden in Malawian children co-infected with rotavirus.

Fifty-eight HIV-infected children with acute rotavirus diarrhea were tested for plasma HIV RNA. There was no difference between acute and convalescent mean viral loads, and little change in CD4 cell counts. Compared with the 16 children who died within 4 weeks, 31 survivors had slightly lower viral loads at presentation and significantly higher CD4 cell counts. Low CD4 cell counts, but not HIV-1-RNA concentrations, were predictive of Death. Local, enteric rotavirus infection did not appear to affect blood HIV viral load or CD4 cell counts in this small group of children.

Acute Disease↗
PubMed2001

Association of tumour necrosis factor alpha and interleukin 6 levels with cytomegalovirus DNA detection and disease after renal transplantation.

Cytokines such as tumour necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) are thought to be important in the pathogenesis of post-transplant cytomegalovirus (CMV) disease. CMV infection increases the production of TNF-alpha and IL-6. Conversely, TNF-alpha switches on the replication of CMV. To study the association of these two cytokines with CMV activity and disease, TNF-alpha and IL-6 levels were assayed in plasma samples taken serially from three groups of renal transplant recipients. Group A (n = 12) had CMV disease and syndrome; Group B (n = 11) had detectable CMV DNA in plasma or peripheral blood leucocytes without disease, i.e., presumed asymptomatic CMV infection, and Group C (n = 11) had no detectable CMV DNA nor disease. The median peak TNF-alpha levels in patients with CMV disease (Group A) were significantly higher than that in Group B or Group C (P < 0.02) whereas the median peak IL-6 levels in group C patients were significantly lower than that in group A (P < 0.04) or group B (P < 0.03). A TNF-alpha level of above 100 pg/ml was significantly associated with CMV disease and high plasma CMV load (> 10,000 copies/ml). IL-6 levels above 15 pg/ml were significantly associated with CMV DNA detection, but not with CMV disease or elevated CMV load. High levels of TNF-alpha or IL-6 were not associated with CMV donor/recipient serostatus, HHV-6 or HHV-7 DNA detection, immunosuppressive regimen or rejection episodes. The role of TNF-alpha in the pathogenesis of CMV disease deserves further investigation.

Adult↗
PubMed2001

The influence of prematurity and low birthweight on transplacental antibody transfer in a rural West African population.

OBJECTIVE: To determine the influence of prematurity and low birthweight (LBW) on transplacental antibody transfer. METHOD: In a physician-blinded, cross-sectional study of 213 mother--baby pairs in the labour ward of Bansang Hospital, The Gambia, paired maternal and cord serum samples were tested for specific IgG antibody titres for measles virus (MeV), herpes simplex virus type 1 (HSV1), respiratory syncytial virus (RSV), varicella-zoster virus (VZV), tetanus toxoid (TT) and diphtheria toxoid (DT) antigens using enzyme linked immunosorbent assay (ELISA). RESULTS: Prematurity was significantly associated with reduced placental antibody transfer for MeV, HSV1, TT, DT, RSV and VZV. Maternal antibody transfer for MeV, HSV1, TT, DT, RSV and VZV was significantly lower in neonates with LBW than in babies with adequate birthweight (ABW). CONCLUSION: Materno--foetal transfer of antibodies is impaired in prematurity and LBW babies in this Gambian population. Reduction in antibody transfer may further predispose these already vulnerable neonates to bacteria and viral infections. Therefore, alternative vaccination strategies, including earlier vaccination schedules, are needed to provide better protection to these young infants.

Adult↗
PubMed2001

Use of temporal temperature gradient gel electrophoresis to identify flaA and fim3 sequence types in Bordetella bronchiseptica.

AIMS: The aim of this study was to develop an approach to detect variation in the flaA and fim3 genes amongst animal isolates of Bordetella bronchiseptica using temporal temperature gradient gel electrophoresis (TTGE). METHODS AND RESULTS: Amplicons representing three flaA and two fim3 sequence types were subjected to TTGE analysis. It was possible to distinguish clearly between each of the sequence types using TTGE. CONCLUSION: This suggests that TTGE could be a useful tool for studying the epidemiology of B. bronchiseptica. SIGNIFICANCE AND IMPACT OF THE STUDY: PCR amplification coupled to TTGE offers a general method for the rapid screening of large numbers of microbial strains for variations in gene sequences.

Animal Population Groups↗
PubMed2001

SHV-27, a novel cefotaxime-hydrolysing beta-lactamase, identified in Klebsiella pneumoniae isolates from a Brazilian hospital.

From a collection of cefotaxime-resistant Klebsiella pneumoniae isolated from neonatal blood culture specimens in a maternity hospital in Aracaju, Brazil, two isolates (strains KPBRZ-842 and -843, indistinguishable by pulsed-field gel electrophoresis) were found to produce beta-lactamases with isoelectric points (pI) of 5.4 and 8.2, respectively. Using a gel overlay method, cefotaxime hydrolysis was shown to be associated with the pI 8.2 protein. Nucleotide sequencing of the gene encoding the pI 8.2 beta-lactamase revealed a bla(SHV-ESBL)-type gene differing from the gene encoding SHV-1 by three silent point mutations, and a fourth that resulted in an amino acid substitution, aspartate for glycine, at position 156. This novel SHV-type extended-spectrum beta-lactamase is designated SHV-27.

Anti-Bacterial Agents↗
PubMed2001

In vitro activity of antimicrobial agents against the endosymbiont Wolbachia pipientis.

Arthropod-transmitted (filarial) nematodes are important causes of disease in humans in tropical countries, yet no safe drug appropriate for mass delivery kills the adult worms. However, most filarial nematodes contain rickettsia-like bacteria of the genus Wolbachia, and related bacteria also occur in insects. There is increasing evidence that these bacteria have significant functions in the biology of filarial nematodes. They are thus important targets in the search for antifilarial drugs and experiments in animals and humans have suggested that antibiotic therapy has potential in treating filarial infections. To optimize future clinical trials there is a need for a fast and simple in vitro drug screen to compare drug efficacies against Wolbachia. In the absence of Wolbachia-infected nematode cell lines, we have utilized an Aedes albopictus insect cell line, naturally infected with Wolbachia, to test the activity of antimicrobial agents. Of the five antibiotics tested, doxycycline, oxytetracycline and rifampicin showed good activity (MICs of 0.0625, 4 and 0.0625 mg/L, respectively) whereas ciprofloxacin and penicillin were shown to have no effect.

Animals↗