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H Young

Publications and source records attributed to H Young.

At least 73 records · Page 4Linked to original sources
PubMed1998

Differential effects of the absence of interferon-gamma and IL-4 in acute graft-versus-host disease after allogeneic bone marrow transplantation in mice.

Graft-versus-host disease (GVHD), in which immunocompetent donor cells attack the host, remains a major cause of morbidity after allogeneic bone marrow transplantation (BMT). To understand the role of cytokines in the pathobiology of GVHD, we used cytokine knockout (KO) mice as a source of donor T cells. Two different MHC-disparate strain combinations were examined: BALB/c (H2(d)) donors into lethally irradiated C57BL/6 (H2(b)) recipients or C57BL/6 (H2(b)) donors into B10.BR (H2(k)) recipients. Donor cells were from mice in which either the interferon-gamma (IFN-gamma) or the IL-4 gene was selectively disrupted to understand the role of these cytokines in acute GVHD. In both strain combinations the same pattern was noted with regard to GVHD onset and morbidity. All mice exhibited the classic signs of acute GVHD: weight loss with skin, gut, and liver pathology resulting in morbidity and mortality. Surprisingly, donor cells obtained from mice lacking IFN-gamma gave rise to accelerated morbidity from GVHD when compared with cells from wild-type control donors. Similar results were obtained using normal donors when neutralizing antibodies to IFN-gamma were administered immediately after the BMT. These results suggest that IFN-gamma plays a role in protection from acute GVHD. In marked contrast, cells obtained from IL-4 KO mice resulted in protection from GVHD compared with control donors. Splenocytes from IFN KO mice stimulated with a mitogen proliferated to a significantly greater extent and produced more IL-2 compared with splenocytes obtained from IL-4 KO or control mice. Additionally, there was increased IL-2 production in the spleens of mice undergoing GVHD using IFN-gamma KO donors. These results therefore indicate, with regard to the TH1/ TH2 cytokine paradigm, the absence of a TH1-type cytokine can be deleterious in acute GVHD, whereas absence of a TH2 cytokine can be protective.

Animals↗
PubMed1998

Naturally occurring isolates of Neisseria gonorrhoeae, which display anomalous serovar properties, express PIA/PIB hybrid porins, deletions in PIB or novel PIA molecules.

The por gene of Neisseria gonorrhoeae encodes the Protein I porin responsible for serovar specificity. In this study the por genes have been sequenced from clinical isolates which exhibited anomalous serovar reactivity. One group of 'intermediate' strains differed significantly from both Protein IA and IB strains, were more closely related to IA but appeared to represent a distinct class of Protein I. Another strain was closely related to Protein IB of serovar IB-6 but contained a deletion of six amino acids in surface exposed loop 6 which removed epitopes recognized by IB specific monoclonal antibodies. The third group of strains, which reacted with both IA and IB specific monoclonal antibodies, expressed hybrid Protein I molecules containing both IA and IB epitopes. These strains appeared to originate from a double crossover between Proteins IA and IB with the amino and carboxy terminal residues homologous to IB while the surface exposed loop 6 demonstrated close homology to IA. This is the first demonstration of naturally occurring gonococci expressing a hybrid Protein IA/IB.

Amino Acid Sequence↗
PubMed1998

Identification of de novo chromosomal markers and derivatives by spectral karyotyping.

Despite major advances in molecular cytogenetics during the past decade and the important diagnostic role that fluorescence in situ hybridization (FISH) plays in the characterization of chromosomal abnormalities, the usefulness of this technique remains limited by the number of spectrally distinguishable fluorochromes or fluorochrome combinations. Overcoming this major limitation would allow one to use FISH to screen the whole human genome for chromosomal aberrations which, until recently, was possible only through conventional karyotyping. A recently described molecular cytogenetics technology, 24-color FISH using spectral karyotyping (SKY), permits the simultaneous visualization of all human chromosomes in 24 different colors. Most chromosomal aberrations detected during cytogenetic evaluation can be resolved using routine cytogenetic techniques alone or in combination with single- or dual-color FISH. However, some cases remain unresolved, in particular de novo supernumerary marker chromosomes and de novo unbalanced structural rearrangements. These findings cause particular diagnostic and counseling concerns when detected during prenatal diagnosis. The purpose of this report is to demonstrate the application of SKY in the characterization of these de novo structural chromosomal abnormalities. Eight cases are described in this report. SKY has considerable diagnostic applications in prenatal diagnosis because of its reliability and speed. The identification of the chromosomal origin of markers and unbalanced translocations provides the patient, physician, and genetic counselor with better predictive information on the phenotype of the carrier.

Amniotic Fluid↗
PubMed1998

Syphilis. Serology.

Microbiologic tests are essential in the diagnosis and management of patients with syphilis. Apart from the very early stage of disease (when T. pallidum may be detected in the lesions of primary syphilis before an antibody response is detectable) serology is the mainstay of laboratory testing. The performance of cardiolipin antigen ("reagin") and treponemal antigen (native and recombinant) tests is discussed in relation to the stage of syphilis, treatment status, and interactions between syphilis and HIV infection. Screening with cardiolipin antigen tests detects early stage disease, but treponemal antigen tests are required for the reliable detection of late-stage infection and the exclusion of syphilis in HIV-infected patients. EIA tests using treponemal antigen are sensitive and specific and fit well into current laboratory practices. Although the FTA-abs test is often considered the "gold standard" confirmatory test, its sensitivity is slightly lower than that of certain other treponemal antigen tests. A reactive antitreponemal IgM test correlates well with untreated or recently treated early infection, but specific IgM tests are often negative in untreated late-stage disease. Serial quantitative cardiolipin antigen tests remain the method of choice for monitoring the efficacy of treatment. The role of the laboratory in aiding a diagnosis of neurosyphilis and congenital infection is discussed briefly, as is the current status of newer technologies, such as PCR and immunoblotting.

Antibodies, Bacterial↗
PubMed1998

Novel recombinant-antigen enzyme immunoassay for serological diagnosis of syphilis.

Enzyme immunoassay (EIA) is an ideal method for screening large numbers of patients for syphilis. We evaluated a novel immune-capture EIA (ICE Syphilis; Murex Diagnostics) that uses three recombinant Treponema pallidum antigens (TpN15, TpN17, and TpN47) and compared the results with those obtained by the native T. pallidum antigen EIA (Captia SelectSyph-G; Centocor) that we currently use for the serodiagnosis of syphilis. Specificity was evaluated by screening 1,184 unselected serum specimens in parallel by the ICE Syphilis and SelectSyph-G assays, while sensitivity was tested with a panel of 101 serum specimens containing antitreponemal antibodies (treated and untreated) from patients with various stages of infection. The specificity of the ICE Syphilis EIA (99.8%) on screening was significantly higher (P < 0.02) than that of the SelectSyph-G EIA (99.2%). The sensitivity of the ICE Syphilis EIA was significantly higher (P < 0.01) than that of the SelectSyph-G EIA on both initial (99 versus 91.4%) and repeat (100 versus 92.4%) testing. The ICE Syphilis EIA was also significantly more sensitive (P < 0.01) than the fluorescent treponemal antibody-abs (92.4%) but not the T. pallidum hemagglutination assay (97.1%). Sera containing antitreponemal antibodies gave a much higher antibody index (absorbance of test serum/kit cutoff) by the ICE Syphilis EIA than by the SelectSyph-G EIA. This combined with the overall high sensitivity makes the ICE Syphilis EIA an ideal test for excluding or detecting treponemal infection in human immunodeficiency virus (HIV)-infected patients. The ICE Syphilis EIA was positive with sera from all 15 HIV-infected patients in the study, whereas sera from 3 HIV-infected patients were negative by the SelectSyph-G EIA. We conclude that the high sensitivity and specificity of the ICE Syphilis EIA and its suitability for automation make it an ideal screening test.

Antigens, Bacterial↗
PubMed1998

PCR testing of genital and urine specimens compared with culture for the diagnosis of chlamydial infection in men and women.

Our aim was to determine the number of chlamydial infections detected by Cobas Amplicor CT/NG multiplex polymerase chain reaction (PCR) testing of genital and first-voided urine (FVU) specimens compared with routine culture. Two hundred and eighty-six female and 276 male patients attending the Genito-Urinary Medicine (GUM) Unit at Edinburgh Royal Infirmary were included in the study. Case notes were analysed retrospectively to determine how many infected patients would not have been treated had diagnosis relied on routine culture. Polymerase chain reaction on FVU from women had a sensitivity, specificity, positive and negative predictive value of 91%, 100%, 100% and 99.1%: corresponding values for genital PCR and culture were 96%, 100%, 100%, 99.6% and 65%, 100%, 100%, 96.7% respectively. PCR on FVU from men had a sensitivity, specificity, positive and negative predictive value of 96%, 99.1%, 92.6% and 99.5%: corresponding values for genital PCR and culture were 89%, 99.5%, 95.8%, 98.6% and 48%, 100%, 100%, 94.3% respectively. In both men and women genital PCR and urine PCR were significantly more sensitive than culture. PCR almost doubled the number of patients detected by culture (49 vs 27). Of the 22 cases detected only by PCR 8 would not have received treatment on the basis of clinic treatment policy.

Chi-Square Distribution↗
PubMed1998

A new recombinant antigen latex agglutination test (Syphilis Fast) for the rapid serological diagnosis of syphilis.

We report an assessment of Syphilis Fast, a new latex test that uses a pool of 3 recombinant Treponema pallidum antigens (TpN15, TpN17, and TpN47) for the serodiagnosis of syphilis. Specificity was evaluated by screening 1518 unselected blood specimens in parallel with Syphilis Fast, the Captia SelectSyph-G EIA and the Venereal Disease Research Laboratory (VDRL) cardiolipin antigen test while sensitivity was tested using a panel of 99 treponemal sera (treated and untreated) representing various stages of infection and 15 treponemal sera detected on screening. The specificity of Syphilis Fast on initial testing (99.8%) was significantly higher (P<0.02) than that of Captia SelectSyph-G (99.2%) and the VDRL (99.1%): the specificity of Syphilis Fast remained significantly higher (P<0.02) after repeat testing (respective values 99.9%, 99.5% and 99.4%). There was no difference in the sensitivity of Syphilis Fast and Captia SelectSyph-G on initial (93% vs 92.1%) or repeat (95.6% vs 94.7%) testing: both were significantly more sensitive (P<0.001) than the VDRL (46.5% on initial and 43.9% on repeat testing). The sensitivities of the Treponema pallidum haemagglutination test (TPHA) and FTA-abs were 98.2% and 95.6% respectively. Negative reactions in Syphilis Fast and SelectSyph-G were associated with treated infections and correlated with low TPHA titres (< or = 80). We conclude that Syphilis Fast is a highly specific, simple and fast screening test with a sensitivity comparable to native antigen treponemal tests and that it merits consideration as a front-line screening test.

Antibodies, Bacterial↗
PubMed1998

Surveillance of sexually transmitted infections in Scotland.

Applications of the surveillance of sexually transmitted infections (STIs) include setting priorities for and planning preventive and treatment services, evaluating interventions, and shaping research hypotheses. In Scotland routine data on STIs, (other t

Journal Article↗
PubMed1997

Comparison of Tc-99m sestamibi perfusion imaging and echocardiography using an arbutamine infusion for the detection of coronary artery disease.

Arbutamine, a synthetic catecholamine, coupled with a closed-loop, computerized delivery system was evaluated in conjunction with technetium-99m sestamibi scintigraphy and echocardiography for the detection of coronary artery disease. Concordance between the imaging methods was 68%, with a similar sensitivity for coronary disease using echocardiography (78%) and technetium-99m sestamibi (76%), although more arbutamine-induced ischemia was noted with perfusion imaging.

Adrenergic beta-Agonists↗
PubMed1997

Traumatic brain swelling in head injured patients: brain edema or vascular engorgement?

Brain edema and vascular engorgement have been used interchangeably to describe brain swelling associated with severe brain trauma and their relative contribution of these compartments to the swelling process remains controversial. In this report, imaging techniques for measurement of brain water and blood volume have been used to study the relative contribution of blood volume and tissue water to the swelling process in severely brain injured patients. More specifically, magnetic resonance techniques for non-invasive tissue water measures founded on mathematical models and later substantiated in laboratory and clinical studies were used for measure of brain tissue water. These studies were combined with measures of cerebral blood volume utilizing indicator dilution methods. Studies indicated that brain water was increased while blood volume decreased. These studies provide compelling evidence that the major contributor to brain swelling is brain edema and not blood volume. Therapies should now be targeted toward preventing edema development and enhancing edema resolution.

Adolescent↗
PubMed1997

ECAT ART - a continuously rotating PET camera: performance characteristics, initial clinical studies, and installation considerations in a nuclear medicine department.

Advances in fully three-dimensional (3D) image reconstruction techniques have permitted the development of a commercial, rotating, partial ring, fully 3D positron emission tomographic (PET) scanner, the ECAT ART. The system has less than one-half the number of bismuth germanate detectors compared with a full ring scanner with the equivalent field of view, resulting in reduced capital cost. The performance characteristics, implications for installation in a nuclear medicine department, and clinical utility of the scanner are presented in this report. The sensitivity (20 cm diameterx20 cm long cylindrical phantom, no scatter correction) is 11400 cps.kBq-1.ml-1. This compares with 5800 and 40500 cps.kBq-1.ml-1 in 2D and 3D respectively for the equivalent full ring scanner (ECAT EXACT). With an energy window of 350-650 keV the maximum noise equivalent count (NEC) rate was 27 kcps at a radioactivity concentration of approximately 15 kBq.ml-1 in the cylinder. Spatial resolution is approximately 6 mm full width at half maximum on axis degrading to just under 8 mm at a distance of 20 cm off axis. Installation and use within the nuclear medicine department does not appreciably increase background levels of radiation on gamma cameras in adjacent rooms and the dose rate to an operator in the same room is 2 microSv. h-1 for a typical fluorine-18 fluorodeoxyglucose (18F-FDG) study with an initial injected activity of 370 MBq. The scanner has been used for clinical imaging with18F-FDG for neurological and oncological applications. Its novel use for imaging iron-52 transferrin for localising erythropoietic activity demonstrates its sensitivity and resolution advantages over a conventional dual-headed gamma camera. The ECAT ART provides a viable alternative to conventional full ring PET scanners without compromising the performance required for clinical PET imaging.

Equipment Design↗
PubMed1997

STDS in women attending family planning clinics: a case study in Addis Ababa.

For cultural reasons modern contraception has been slow to gain acceptance in Ethiopia. Knowledge about contraception and abortion is still limited in many family and community settings in which it is socially disapproved. By 1990 only 4% of Ethiopian females aged 15-49 used contraception. Little is known of sexually transmitted disease (STD) prevalence in family planning (FP) attenders in Africa in general and Ethiopia in particular, even though attenders of family planning clinics (FPCs) are appropriate target groups for epidemiological studies and control programmes. A study of 2111 women of whom 542 (25.7%) attended FPCs in Addis Ababa showed utilisation rates to be highest in women who were: Tigre (33%) or Amhara (31%), aged 20-34 years (30%), age 16 or older at first marriage/coitus (28%:38% in those first married after 25 years); who had a monthly family income of 10 Ethiopian Birr (EB) or more (33%:36% for those with income 100-500 EB), three or more children (37%), more than five lifetime husbands/sexual partners (39%); or were bargirls (73%) or prostitutes (43%). The seroprevalence rates for all STDs, higher in FPC attenders compared with other women, were syphilis (TPHA) 39%, Neisseria gonorrhoeae 66%, genital chlamydia 64%, HSV-2 41%, HBV 40% and Haemophilus ducreyi 20%. Only 4% of FPC attenders had no serological evidence of STD: 64% were seropositive for 3 or more different STD. Clinical evidence of pelvic inflammatory disease (PID) was also more common in the FPC attenders (54%), 37% having evidence of salpingitis. The FPC provides a favourable setting for screening women likely to have high seroprevalence of STD, who for lack of symptoms will not attend either an STD clinic nor a hospital for routine check up. We recommend that measures be taken to adequately screen, treat and educate FPC attenders, their partners, and as appropriate and when possible their clients, in an attempt to control STDs and ultimately HIV in the community. Social, economic and cultural factors in the occurrence of STDs, prostitution, family planning and modern contraception coverage in Ethiopia are identified and deficiencies of current programmes briefly discussed with the objective of targeting services more effectively.

Cultural Characteristics↗
PubMed1997

Failure of Neisseria gonorrhoeae to grow in the ATB NH susceptibility test system.

The ATB NH system designed for antibiotic susceptibility testing of Neisseria gonorrhoeae, Neisseria meningitidis and Haemophilus influenzae was evaluated using 94 clinical isolates of gonococci representing a wide variety of serovar/auxotype strains. Using the manufacturer's automated system 55% of the clinical isolates failed to grow, compared with a 33% failure rate for manual processing and visual reading. Growth failure was significantly higher with 1A isolates (73% automated and 69% manual) than with 1B isolates (49% automated and 25% manual). The higher failure rate of 1A isolates correlated with multiple auxotrophy. The inability of the ATB NH system to support the growth of common serovar/auxotypes makes the ATB NH system unsuitable for antibiotic susceptibility testing of N. gonorrhoeae.

Humans↗
PubMed1997

Routine antenatal screening for syphilis in Lothian: a study of the results 1988 to 1994.

A retrospective study was carried out of the cases of positive syphilis serology detected by routine antenatal screening within Edinburgh (and surrounding district) over the six years 1988 to 1994. The study demonstrated a low incidence of syphilis with only 15 pregnancies in 58,445 screened. In eight cases serology and history were suggestive of late latent syphilis and in the remainder of previous infection which had been treated. All women were delivered of liveborn infants at term without stigmata of congenital syphilis. Lack of identifiable risk factors in women with positive serology suggests that routine rather than selective screening should continue.

Adult↗
PubMed1997

Non-cultural detection of rectal and pharyngeal gonorrhoea by the Gen-Probe PACE 2 assay.

OBJECTIVE: To assess the sensitivity and specificity of the Gen-Probe PACE 2 assay, which uses a chemiluminescent labelled single-stranded DNA probe to detect gonococcal ribosomal RNA (rRNA), for the non-cultural detection of rectal and pharyngeal gonorrhoea in homosexual men. SUBJECTS: 161 homosexual men attending the Department of Genitourinary Medicine, Edinburgh Royal Infirmary during the latter half of 1995 and the first quarter of 1996. METHODS: Duplicate rectal and pharyngeal swabs were collected for culture on modified New York City (MNYC) medium and detection of gonococcal nucleic acid by the Gen-Probe assay. Repeatedly reactive Gen-Probe specimens from culture negative patients were also tested by the Gen-Probe competition assay (PCA). RESULTS: Of the 161 patients, 23 (14.3%) gave a positive culture at one or both sites (rectum 10, throat 8, rectum and throat 5) compared with 28 (16.7%) who gave a positive Gen-Probe result at one or both sites (rectum 9, throat 11, rectum and throat 8). After resolution of discrepant results by PCA the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of Gen-Probe was 94.1%, 100%, 100% and 99.3% for rectal specimens while the corresponding values for pharyngeal specimens were 86.4%, 100%, 100%, and 97.9%. The sensitivity and NPV of rectal culture were 88.2% and 98.6% while the corresponding values for pharyngeal culture were 59% and 93.9%. Gen-Probe was significantly more sensitive than throat culture (p < 0.05) but not rectal culture (p > 0.2). The average Relative Light Units (RLU) value for the cut-off was 386 (range 351-450) while the average for a positive result was 20306 (range 403-110104): this was, however, significantly higher (p = 0.019) in rectal specimens 31325 (range 1705-110104) than in throat specimens 10447 (range 403-15633). CONCLUSIONS: Gen-Probe PACE 2 assay is a sensitive and specific method for the detection of rectal and pharyngeal gonorrhoea. As the Gen-Probe assay may detect nucleic acid from non viable gonococci the clinical significance of a probe positive culture negative specimen from a patient without culture evidence of gonorrhoea at another site is uncertain and requires further consideration. Nevertheless a positive result does indicate exposure to infection and could be important in ensuring appropriate partner notification action. If non-cultural methods are used to screen for gonococcal infection cultures should be obtained from patients with positive results in order that the antibiotic susceptibility and molecular epidemiology of the gonococcal population can be monitored.

Bacteriological Techniques↗
PubMed1997

Azithromycin and erythromycin resistant Neisseria gonorrhoeae following treatment with azithromycin.

A pre-treatment and a 3-week post-treatment isolate of Neisseria gonorrhoeae from a 13-year-old boy treated with azithromycin in a single 1 g oral dose were characterized microbiologically. Both isolates were of the same serovar/auxotype (1B6/non-requiring) and had similar antibiograms apart from erythromycin and azithromycin: the pre- and post-treatment MICs (minimum inhibitory concentrations) were: 1 mg/L and 32 mg/L to erythromycin and 0.125 mg/L and 3 mg/L to azithromycin. The finding that both isolates were 1B6/NR, had similar antibiograms (other than azithromycin and erythromycin), and no other 1B6/NR isolates were resistant to erythromycin supports the view that macrolide resistance developed following treatment. A high overall level of azithromycin susceptibility was confirmed by testing 67 clinical isolates: MIC90 0.5 mg/L (range 0.023-0.75 mg/L). We conclude that the long half-life of azithromycin which is beneficial in treating chlamydial infection may result in increased selective pressure for resistance in gonococci. This report also highlights the importance of antibiotic susceptibility surveillance of gonococci and stresses the need for appropriate treatment of gonococcal infection, particularly when it is prescribed outwith departments of genitourinary medicine.

Adolescent↗
PubMed1996

An evaluation of pre-poured selective media for the isolation of Neisseria gonorrhoeae.

Fourteen commercial media supplied as pre-poured plates were compared with an 'in-house' selective medium for their ability to support the growth of 105 gonococcal isolates (representing a wide variety of serovars encountered in natural infection), 25 meningococcal and 20 Neisseria lactamica isolates, and to inhibit the growth of 71 isolates of non-pathogenic neisseriae and miscellaneous organisms. Only two of the pre-poured plate media and the in-house selective medium yielded growth of duplicate cultures of all 105 gonococcal isolates after incubation for 24 h: one other medium provided growth of all the isolates after incubation for 48 h. The ability of the various media to suppress the growth of the 71 isolates of non-pathogenic neisseriae and miscellaneous organisms ranged from 97.2 to 71.8% of isolates inhibited. Of the four media that enabled growth of all the gonococcal strains, inhibition was 94.4% for the in-house medium, 85.9% and 80.3% for the two media on which all gonococci grew after 24 h and 71.8% for the medium on which all of the gonococci grew after 48 h. Failure of growth of gonococci was associated with: serogroup IA isolates (p<0.001), AHU auxotype (p<0.001) and the presence of vancomycin rather than lincomycin in the selective medium (p < 0.02). The use of 10% blood and a highly nutritious medium based on the original New York City (NYC) or modified New York City (MNYC) formulation were also important in supporting growth of gonococci. One of the main problems in lack of selectivity was a failure to inhibit the growth of yeasts. As effective inhibition of yeasts was obtained with other media containing the same concentration of amphotericin, failure may be due to batch variation of supplement, media preparation, or reduced shelf life of the media. None of the commercially available pre-poured media performed as well as the in-house medium despite the fact that some of the media were prepared to a very similar formula.

Culture Media↗