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Biomedical subjects

C Parry

Publications and source records attributed to C Parry.

At least 19 recordsLinked to original sources

The role of the polymerase chain reaction in the diagnosis of bacterial meningitis in Vietnam.

Bacterial meningitis remains an important cause of morbidity and mortality in Vietnam. Diagnosis is hampered by the ready availability of antibiotics in the community, leading to late presentation, masked clinical signs, and poor organism detection during the microscopical examination and culture of cerebrospinal fluid (CSF). In order to improve organism detection at the Hospital for Tropical Diseases in Ho Chi Minh City, a diagnostic PCR-based protocol was developed. This protocol was followed in the investigation of CSF samples from 36 patients with clinical signs of bacterial meningitis. Each sample was first tested in a semi-nested PCR using primers for the 16sRNA gene common to all bacteria. The products of this reaction were then amplified using a 16sru8 primer and primers specific for Neisseria meningitidis, Haemophilus influenzae or Streptococcus spp. The samples found positive for Streptococcus were further investigated in a nested PCR using primers specific for the pneumolysin gene of S. pneumoniae. The sensitivity of detection was increased from 36% with culture to 44% with PCR. Although the sample size was small, the results indicate that PCR would be a feasible and useful adjunct in the diagnosis of bacterial meningitis, particularly in areas where community antibiotic use is common.

Antigens, Bacterial↗

Complete genome sequence of a multiple drug resistant Salmonella enterica serovar Typhi CT18.

Salmonella enterica serovar Typhi (S. typhi) is the aetiological agent of typhoid fever, a serious invasive bacterial disease of humans with an annual global burden of approximately 16 million cases, leading to 600,000 fatalities. Many S. enterica serovars actively invade the mucosal surface of the intestine but are normally contained in healthy individuals by the local immune defence mechanisms. However, S. typhi has evolved the ability to spread to the deeper tissues of humans, including liver, spleen and bone marrow. Here we have sequenced the 4,809,037-base pair (bp) genome of a S. typhi (CT18) that is resistant to multiple drugs, revealing the presence of hundreds of insertions and deletions compared with the Escherichia coli genome, ranging in size from single genes to large islands. Notably, the genome sequence identifies over two hundred pseudogenes, several corresponding to genes that are known to contribute to virulence in Salmonella typhimurium. This genetic degradation may contribute to the human-restricted host range for S. typhi. CT18 harbours a 218,150-bp multiple-drug-resistance incH1 plasmid (pHCM1), and a 106,516-bp cryptic plasmid (pHCM2), which shows recent common ancestry with a virulence plasmid of Yersinia pestis.

Chromosome Mapping↗

Typhoid fever and genetic polymorphisms at the natural resistance-associated macrophage protein 1.

Control of Salmonella enterica serovar Typhimurium (S. typhimurium) infection in the mouse model of typhoid fever is critically dependent on the natural resistance-associated macrophage protein 1 (Nramp1). In this study, we examined the role of genetic polymorphisms in the human homologue, NRAMP1, in resistance to typhoid fever in southern Vietnam. Patients with blood-culture-confirmed typhoid fever and healthy control subjects were genotyped for 6 polymorphic markers within and near NRAMP1 on chromosome 2q35. Four single base-pair polymorphisms (274 C/T, 469+14 G/C, 1465-85 G/A, and D543N), a (GT)(n) repeat in the promoter region of NRAMP1 and D2S1471, and a microsatellite marker approximately 130-kb downstream of NRAMP1 were examined. The allelic and genotypic frequencies for each polymorphism were compared in case patients and control subjects. No allelic association was identified between the NRAMP1 alleles and typhoid fever susceptibility. In addition, neither homozygotes nor heterozygotes for any NRAMP1 variants were at increased risk of typhoid fever.

Alleles↗

Different effects of a single amino acid substitution on three adjacent epitopes in the gp41 C-terminal tail of a neutralizing antibody escape mutant of human immunodeficiency virus type 1.

The envelope protein of human immunodeficiency virus type 1 (HIV-1) comprises the outer gp 120 SU domain and the anchoring gp41 TM domain, and the conventional view is that it has a single transmembrane region with the following C-terminal sequence situated entirely within the virion. However, we have recently proposed that the gp41 C-terminal region comprises three transmembrane regions and an external loop structure. Part of this loop is the peptide 731PRGPDRPEGIEEEGGERDRDRS752 that carries three antibody epitopes, 734PDRPEG739, 740IEEE743, and 746ERDRD750. PDRPEG is not detected in virions but reacts with its cognate MAb (C8) in Western blots, IEEE is a linear and non-neutralizing epitope, and ERDRD is a conformational and neutralizing epitope. Here we show that escape mutants selected with neutralizing ERDRD-specific antibody had a single 732R-->G substitution, 14 residues upstream of the cognate epitope, and no longer bound the selecting antibody. The same amino acid substitution altered epitope PDRPEG in the virion so that it now reacted with MAb C8, but left epitope IEEE unaffected. Introduction of 732R-->G by site-specific mutagenesis into the gp41 of cloned HIV-1 NL4-3 virions allowed them to escape neutralization by ERDRD-specific IgG, and confirms that 732R makes a major contribution to the neutralizing conformation of the 731-752 region of the C-terminal tail of gp41.

Amino Acid Substitution↗

Typhoid fever: pathogenesis and disease.

Typhoid fever is an infectious disease of global distribution. Although there is a wealth of data on Salmonella typhimurium infection in the mouse and the interaction of this serovar with human cell lines in vitro, there is a relatively small amount of data on S. typhi and the pathogenesis of typhoid fever. In this review we focus on three areas: adherence to and invasion of gut epithelial cells, dissemination to systemic sites, and survival and replication within host cells. In addition, we attempt to put current salmonella research into the context of typhoid fever.

Bacterial Adhesion↗

Gender roles and/or styles in crisis: an integrative analysis of the experiences of fathers of children with cancer.

Despite a proliferation of research with families of children with cancer and gender differences in parental coping, few studies have explicitly explored the experiences of fathers of children with cancer. Using several different data collection efforts, including semistructured in-depth interviews and open workshops, this integrative analysis views fathers' experiences through the lens of gender. Findings suggest that fathers' experiences can be understood as influenced by gender identities, gender roles, and the gendered organization of support systems, employment, and health care institutions. The results suggest the need for interventions that provide fathers and entire families with the opportunity to develop new skills and coping strategies for dealing with the stresses and challenges of childhood cancer.

Adaptation, Psychological↗

Epidemic typhoid in vietnam: molecular typing of multiple-antibiotic-resistant Salmonella enterica serotype typhi from four outbreaks.

Multidrug-resistant Salmonella enterica serotype Typhi isolates from four outbreaks of typhoid fever in southern Vietnam between 1993 and 1997 were compared. Pulsed-field gel electrophoresis, bacteriophage and plasmid typing, and antibiotic susceptibilities showed that independent outbreaks of multidrug-resistant typhoid fever in southern Vietnam are caused by single bacterial strains. However, different outbreaks do not derive from the clonal expansion of a single multidrug-resistant serotype Typhi strain.

Bacterial Typing Techniques↗

Patient doses in abdominal aortogram and aorta femoral runoff examinations.

Radiation doses to adult male patients from abdominal aortogram and aorta femoral runoff examinations in a medical center were determined with the help of a dose-area product meter. The abdominal aortogram and aorta femoral runoff examination consisted of scout radiographs, fluoroscopy (to position a catheter near the area of interest), and serial films (to record the flow of contrast media). Measurements were converted to effective doses with the help of published results from Monte Carlo simulation calculations. Data from 19 male adult patients weighing 53 to 86 kg were analyzed. The resulting total effective dose had a value of 14.0 +/- 4A mSv (mean and standard deviation). The percent contribution by fluoroscopy was 18.5 +/- 9.9%. The fluoroscopy effective dose had a stronger correlation with the dose-area product (correlation coefficient of 0.97) than with duration of exposure (correlation coefficient of 0.84). Most of the radiation exposure in the observed abdominal aortogram and aorta femoral runoff examination was attributed to radiography.

Adult↗

The pattern of tuberculosis in Queen Elizabeth Central Hospital, Blantyre, Malawi: 1986-1995.

SETTING: Queen Elizabeth Central Hospital (QECH), Blantyre, Malawi. OBJECTIVE: To determine the pattern of tuberculosis (TB) cases over a period of ten years. DESIGN: TB registers for QECH for the years 1986-1995 (January 1st to December 31st) were obtained and clinical information on the type of TB in each patient was recorded. Human immunodeficiency virus (HIV) test results of adults with smear-positive pulmonary TB (PTB) and children with TB between 1993 and 1996 were recorded from case notes. RESULTS: There were 19,377 TB cases, 10,982 men and 8,395 women, registered over the ten-year period. Of these, 4,691 (24%) cases were in children aged 0-14 years and 11,890 (61%) cases were in adults aged 15-44 years. The number of cases increased from 657 in 1986 to 2,734 in 1995, and the proportion of cases with extra-pulmonary TB (EPTB) rose from 11% in 1986 to 33% in 1995. The largest increase in cases was in children and in young adults aged 15-44 years. In all age groups, PTB was more common than EPTB. There were significant increases in the proportion of adult TB cases with pleural effusion. Of those who were tested, 72% of adults with smear-positive PTB and 64% of children with TB were found to be HIV-seropositive. CONCLUSION: There has been a dramatic increase in cases of TB and changes in disease pattern in QECH during the last 10 years, which is related to the HIV epidemic.

AIDS-Related Opportunistic Infections↗

Prevalence of psychiatric morbidity in the adult population of a rural South African village.

We report on the first South African two-stage community prevalence study of psychiatric morbidity, conducted in Mamre, a rural "coloured' village, 50 km from Cape Town. Randomly selected adults (N = 481) were assessed using the Self-Reporting Questionnaire (SRQ) as a first-stage screen and the Present State Examination (PSE-9) was administered to a proportion of the sample (N = 121) as the second-stage criterion. Demographic, health care utilization, and substance abuse data were also collected. Using the PSE-9 CATEGO Index of Definition of 5, the weighted prevalence of psychiatric morbidity was 27.1% (confidence interval of 19.5-34.7%), the majority of cases being given a tentative diagnosis of depressive or anxiety disorder. The CATEGO algorithm may not be fully appropriate in this cultural context as there was an apparent over-diagnosis of paranoid states. The SRQ's weighted sensitivity and specificity were 0.49 and 0.82 respectively. Overall, the SRQ correctly identified 67% of cases and non-cases. No demographic variables predicted psychiatric morbidity, but there was an indirect link between morbidity and primary care utilization. Further South African studies of the validity of both the SRQ and of criterion instruments are needed. These may contribute to knowledge regarding cultural factors affecting psychiatric diagnosis.

Adolescent↗

Alcohol attributable fractions for trauma in South Africa.

The misuse and abuse of alcohol is widespread in South African society and is likely to have a large impact on the economy. A major burden is borne by the hospital care system, in particular the cost of alcohol-related trauma. The purpose of this study was to estimate the cost of alcohol misuse in terms of fatal and non-fatal trauma. The design of the study was a cross-sectional survey of key informants. Each key informant was mailed a list of 11 trauma categories found to be linked to alcohol in both the local and international literature. They were asked to make an estimate of the alcohol attributable fraction (AAF) for each trauma category, based on their clinical experience and knowledge of empirical research. The median estimates for each trauma category showed that alcohol misuse could be linked to a substantial amount of mortality and morbidity, particularly with respect to motor vehicle trauma and interpersonal violence. These AAF estimates were supported by the findings of other empirical research conducted in South Africa, as well as by the literature on mortality data in the U.S.A. This suggests that there is potential for a vast amount of injuries and deaths to be eliminated if alcohol misuse could be controlled or eliminated.

Adolescent↗

Structural analysis of affinity maturation: the three-dimensional structures of complexes of an anti-nitrophenol antibody.

Affinity maturation of the immune response to nitrophenol-containing antigens has been extensively investigated. Significant strides made during the past several years with the advent of PCR technology have provided a wealth of biochemical knowledge. Structural investigations of the phenomena have however been limited. We have determined the three-dimensional structure of the Fab fragment of 88C6/12, an anti-4-hydroxy-3-nitrophenyl acetic acid antibody complexed with the immunizing hapten and with a heteroclitic iodinated hapten. The crystallographic structure of the complexes reveals that the binding is stabilized by a number of hydrogen bonds and extensive van der Waals interactions between the hapten and the antibody. In addition, the Fab binding pocket contains a region of positive electrostatic potential well suited for interaction with the predominant resonance form of the nitrophenyl ring system. The observed heteroclicity towards the iodinated hapten is not a direct result of iodine-protein interactions, but results from the enhanced stability in the iodinated ring of the resonance form that binds the antibody. In addition this investigation provides a rationale for the strong preference for the substitution in the heavy chain from the germ-line gene encoded Trp 33 to Leu 33 in the mature anti-nitrophenol response.

Amino Acid Sequence↗

Production of long-lived neutralizing antibodies to HIV-1 IIIB in mice with a vaccinia recombinant virus-infected cell vaccine expressing gp160.

A formaldehyde-fixed cell vaccine in adjuvant (syngeneic cells infected with a vaccinia virus recombinant expressing gp160: vacc-gp160) stimulated only nonneutralizing antibody when used on its own in four strains of mice, but a similar nonfixed cell vaccine stimulated neutralizing antibodies up to a titer of 1/320 in C57BL/6 (H-2b) mice previously infected with live vacc-gp160. Synthesis of ELISA antibodies to rgp120 or rgp160 did not correspond closely to the synthesis of neutralizing antibodies and should not therefore be used to monitor the production of neutralizing antibody. The ELISA antibody response produced by boosting with the cell vaccine made with the vaccinia virus expressing gp160 under the control of a T7 promoter (vacc-gp160-PT7) was as high as that in mice given an approximately 10-fold higher dose of purified rgp160. The ELISA antibody response to the cell vaccine made with vacc-gp160-PT7 was better than that in which gp160 was expressed under the vaccinia early/late promoter (vacc-gp160-P7.5). Nearly all mice (92%; 11 of 12) primed by infection with vacc-gp160 produced comparable levels of neutralizing antibodies after a single boost with rgp160, vacc-gp160-PT7-infected cells, or vacc-gp160-P7.5-infected cells. Neutralization titers peaked at around day 22 after boost, and declined by day 29. A second boost with the same vacc-gp160-infected cells gave increased neutralizing titers in all (eight of eight) mice.(ABSTRACT TRUNCATED AT 250 WORDS)

3T3 Cells↗

Hyaluronic acid-filled mammary implants: an experimental study.

Issues of radiolucency and biocompatibility of currently available mammary implants have prompted the search for alternatives. Several new filler materials have been suggested recently but have involved the use of materials foreign to the body. We have studied the use of a naturally found polysaccharide molecule, hyaluronic acid, as an alternative filler material to silicone gel. We tested hyaluronic acid-filled implants using standard mammographic techniques, applanation tonometry, and in an in vivo animal model (n = 24) up to 1 year after implantation. The present study demonstrates that hyaluronic acid-filled implants have softness comparable with that of silicone gel and saline implants and are more radiolucent, allowing better visualization of breast structures around the implant. Furthermore, in vivo studies fail to demonstrate any adverse reactions to the material over a period of 1 year. Hyaluronic acid has unique properties in modulating the process of wound healing, and these properties may be applied to the tissues surrounding the implants as a result of leaching of hyaluronic acid through the covering shell. Although further studies using larger volumes of filler, characterization of the hyaluronic acid within the implant, quantification of the exact amounts of hyaluronic acid leached into surrounding tissues, and a more appropriate primate model need to be undertaken, this pilot study points out that there may be more biologically compatible materials for the use in breast implants that warrant further investigation.

Animals↗

Kohl: a lead-hazardous eye makeup from the Third World to the First World.

Kohl is a widely used traditional cosmetic. It is mainly worn around the eyes in Asia, Africa, and the Middle East. It may be a pervasive source of lead poisoning in those areas and among individuals from those areas who have immigrated to developed nations. Samples of kohl were purchased in Morocco, Mauritania, Great Britain, and the United States. Some of these samples originated from Pakistan, India, and Saudi Arabia. Kohl is widely believed to consist of antimony, but analysis consistently revealed only trace amounts of antimony. Nine of the twenty-two samples tested contained less than 0.6% lead; however, seven samples had lead levels in excess of 50%. The remainder ranged from 3.31 to 37.3%. Third-world-manufactured kohls were purchased in the United States and Britain, suggesting that this hazard is no longer confined to the third world. Those kohls that contained lead were sold in violation of laws on lead in cosmetics in both of these nations. Third-world physicians and health care workers appear to be unaware of possible lead uptake from unsuspected traditionally used items. Physicians in developed nations with patients from Asia, the Middle East, and North Africa need to factor in the possibility of past or present lead intake from unorthodox sources such as kohl.

Antimony↗