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Biomedical subjects

H Young

Publications and source records attributed to H Young.

At least 37 records · Page 2Linked to original sources
PubMed2004

The diversity of the opa gene in gonococcal isolates from men who have sex with men.

OBJECTIVES: To use a molecular typing method (opa-typing) to characterise gonococcal isolates obtained from men who have sex with men (MSM) attending a genitourinary medicine (GUM) clinic in Edinburgh during 2001. To compare the results of opa-typing with A/S (auxotype/serovar) phenotyping, and with epidemiological information obtained by contact tracing. METHODS: Isolates were opa-typed by a PCR-RFLP method where the restriction fragments resulting from digestion with three separate restriction enzymes were resolved by polyacrylamide gel electrophoresis. Isolates were considered to have the same opa-type if the band patterns were identical or if they differed by one band between the three digestions. RESULTS: 40 opa-types were detected from a collection of 73 gonococcal isolates from 61 patients. 26 opa-types were unique, being found in one individual each, 14 different opa-types were found in more than one patient. Opa-typing was found to have a discrimination index (DI) of 0.96, compared to a DI of 0.87 for A/S phenotyping, indicating that opa-typing is better at discriminating between unrelated isolates. Opa-typing confirmed three epidemiological links established by contact tracing, and uncovered a further 13 clusters of isolates. CONCLUSIONS: Opa-typing is a more discriminative method than A/S phenotyping when determining relatedness in gonococcal isolates. The ability of opa-typing to identify sexual networks not disclosed by contact tracing and conventional phenotyping make it a useful method for studying the spread of gonorrhoea with the potential to contribute to the control of this infection.

Bacterial Outer Membrane Proteins↗
PubMed2004

The prevalence of rectal chlamydial infection amongst men who have sex with men attending the genitourinary medicine clinic in Edinburgh.

Little is known about the prevalence of rectal chlamydial infection amongst men who have sex with men (MSM). Previous studies using culture methods reported this to be between 4-6%. The emergence of nucleic acid amplification tests has significantly increased the sensitivity and specificity for chlamydial detection, making it possible to estimate the prevalence of rectal infection more accurately. A prospective cross sectional study involving 443 MSM who were screened for sexually transmitted infections (STIs) between May 1999 and January 2002. Rectal swabs for chlamydiae were obtained in addition to specimens for routine STI screening. Rectal chlamydiae were detected by ligase chain reaction (LCR) utilizing the Abbott LCX Amplicor with confirmation by COBASE amplicor for the majority of cases. Those with rectal chlamydial infection were treated with azithromycin. The characteristics of men with rectal chlamydial infection were compared with those who were not infected at this site. Rectal chlamydia was detected in 32 (7.2%) of 443 patients. Those with rectal chlamydial infection were more likely to have rectal symptoms (12/32) or having a partner with confirmed chlamydial (2/32) or gonococcal (3/32) urethritis than those MSM without rectal chlamydial infection. They were also more likely to have a history of receptive anal sex (25/32) in the previous three months compared to those MSM without rectal chlamydial infection (263/411). The most common symptoms of patients with rectal chlamydial infection were pruritus ani and peri-anal pain. Eight (25%) of those with rectal chlamydial infection were known to be HIV seropositive. Rectal chlamydial infection is common amongst MSM and is effectively diagnosed by LCR. The test should be included in the routine STI screening offered to MSM.

Adult↗
PubMed2003

Evaluation of ligase chain reaction for the non-cultural detection of rectal and pharyngeal gonorrhoea in men who have sex with men.

OBJECTIVES: To compare a nucleic acid amplification test (ligase chain reaction) with culture for detecting rectal and pharyngeal gonorrhoea in men who have sex with men (MSM). METHODS: Duplicate rectal and throat swabs from MSM attending a genitourinary medicine clinic were collected for culture on modified New York City medium and detection of gonococcal nucleic acid by the Abbott ligase chain reaction (LCR) utilising probes based on opa 1 gene sequences. LCR positive culture negative specimens were tested by a second LCR utilising probes based on pilin gene sequences. Patients with rectal and/or pharyngeal cultures yielding Gram negative diplococci confirmed as Neisseria gonorrhoeae by biochemical and immunological methods were diagnosed with rectal and/or pharyngeal gonorrhoea. The criteria for diagnosing rectal and pharyngeal infection by LCR included a positive opa LCR with a positive culture from the same site or, in the case of a negative culture, a positive opa LCR and a positive pilin LCR. RESULTS: Duplicate rectal samples were obtained from 227 MSM. The results of LCR and culture were concordant in 219 samples (96.5%). The prevalence of rectal gonorrhoea by LCR and culture was 7.0% (16/227) and 4.0% (9/227), respectively. Duplicate throat samples were obtained from 251 MSM. The results of LCR and culture were concordant in 230 (91.6%) cases. The prevalence of pharyngeal gonorrhoea by LCR and culture was 12.7% (32/251) and 6.0% (15/251), respectively. The specificity of LCR was 99.5% (210/211) for rectal and 98.2% (215/219) for pharyngeal specimens. CONCLUSIONS: The high prevalence and asymptomatic nature of pharyngeal and rectal gonococcal infection suggests that routine screening for infection at these sites by a nucleic acid amplification test method such as LCR should be considered as part of the overall strategy to control gonorrhoea in MSM.

Gonorrhea↗
PubMed2003

Central orexin A has site-specific effects on luteinizing hormone release in female rats.

Orexin A stimulates GnRH release from hypothalamic explants in vitro. The sites of action of orexin A in the regulation of LH release have been investigated in vivo in ovariectomized rats that were given vehicle or estradiol benzoate (EB), with or without an injection of progesterone 48 h later. Orexin A was administered intrahypothalamically under Saffan anesthesia, 50 h after the EB or vehicle; its effects on plasma LH levels were monitored in sequential blood samples. Orexin A (1.0 microg/side) injected into the rostral preoptic area (rPOA) at the level of the organum vasculosum of the lamina terminalis had a stimulatory effect on LH release in EB-treated ovariectomized rats. When orexin A was injected into the medial POA (mPOA) or the arcuate/median eminence, it had an inhibitory effect on the LH surge that occurs in ovariectomized rats primed with EB plus progesterone. Orexin A injected into the mPOA also reduced LH levels in ovariectomized rats untreated with ovarian steroids. Both the stimulatory and inhibitory effects of orexin A were antagonized by SB334867A, a selective orexin 1 receptor antagonist. Furthermore, when given alone into the rPOA, this antagonist attenuated the LH surge induced by EB plus progesterone. Thus, orexin appears to have a dual effect on LH release, being stimulatory in the rPOA and inhibitory in the mPOA or arcuate/median eminence. Both effects may be mediated, at least in part, by the orexin 1 receptor. Double label immunohistochemistry revealed close appositions between orexin A immunoreactive varicosities and a small proportion of GnRH cell bodies in the rPOA. It is suggested that the stimulatory effect of orexin A on LH release may involve direct actions on GnRH neurons.

Animals↗
PubMed2002

Application of chemical shift imaging for measurement of NAA in head injured patients.

Neurochemical damage following brain injury can be assessed non-invasively by measurement of N-Acetyl-Aspartate (NAA) using Proton Magnetic Resonance Spectroscopy (1HMRS). This report documents results of applying Chemical Shift Imaging (CSI) postprocessing for measuring NAA in traumatically injured brain. Following stabilization, severely head-injured patients (GCS 8 or less) were transported to the MRI suite. Semi-quantitative measurement of NAA, creatine (Cr/PCr) and choline (Cho) were obtained from single voxels (8 cm3) and CSI for acquisition of smaller voxels (2 cm3) throughout areas of the brain. Studies were completed with no complication. In focal injury, SVS positioned at the site of lesion demonstrated reduced NAA, compared to contralateral hemisphere. In diffuse injury, CSI demonstrated uniform reduction of NAA throughout the brain. NAA/Cho showed normal levels within 24 hours of injury averaging 2.4 and decreased over the next 10 days reaching a plateau of 0.75. At 30 days, NAA showed no recovery in poor outcome patients. In patients with good outcome, NAA initially low recovered near baseline levels. CSI provides a comprehensive neurochemical assessment of neuronal damage. NAA decreases and remains low in patients with poor outcome. NAA recovers in patients with favorable outcome, suggesting marginal metabolic impairment and possible re-synthesis of the NAA pool.

Aspartic Acid↗
PubMed2002

The sac-4 gene of Neisseria gonorrhoeae correlates with gonococcal subtype not co-existing chlamydial infection.

We examined the hypothesis that the sac-4 gene of Neisseria gonorrhoeae varies with gonococcal subtype and that this could account for an earlier report that sac-4 increased the likelihood of co-infection with Chlamydia trachomatis. A polymerase chain reaction (PCR) assay was used to determine the prevalence of sac-4 in 435 gonococcal isolates. The prevalence of sac-4 was analysed in relation to chlamydial co-infection, serovar, auxotype, gender and sexual orientation. Although the prevalence of sac-4 was higher in isolates from patients with chlamydial co-infection (55%) than in those without chlamydial co-infection (42%) the difference was not significant (P<0.05). Statistically significant differences in association with sac-4 were, however, shown between various serovars and auxotypes. Dual classification based on auxotype/serovar (A/S) classes showed highly significant differences in sac-4 prevalence between groups: 95% in NR/1B18 and 8% in P/1B2 (P<0.001). Sac-4 was also significantly less common (P<0.05) in isolates from homosexual men (35%) than from heterosexual men (49%) or women (49.5%). Sac-4 appears to have an epidemiological association with gonococcal auxotype and serovar rather than a direct association with chlamydial co-infection.

Bacterial Proteins↗
PubMed2001

Radiotherapy, concomitant protracted-venous-infusion 5-fluorouracil, and surgery for ultrasound-staged T3 or T4 rectal cancer.

BACKGROUND: A prospective study was undertaken to evaluate the response and toxicity of neoadjuvant chemoradiotherapy for ultrasound-staged T3 or T4 rectal cancer. PATIENTS AND METHODS: Since 1995, 30 patients (18 males; median age, 56 (range, 25-83) years) have received preoperative chemoradiotherapy for ultrasound-staged T3 or T4 rectal cancer. All patients underwent an endorectal ultrasound, CT scan, and review in our multidisciplinary Gastrointestinal Tumor Board before treatment. All patients had pathology-demonstrated invasive adenocarcinoma of the rectum. Eleven patients were Stage T3N0, 14 were T3N1, and five were T4N1. Patients received radiotherapy to the primary tumor and draining lymph nodes (45 Gy) followed by a tumor boost (50.4-54 Gy). Protracted-venous-infusion 5-fluorouracil (225 mg/m2 per day, seven days per week) was administered throughout treatment. Surgical resection was performed six to ten weeks after completing chemoradiotherapy. Using endorectal ultrasound measurements, the primary tumor was a median of 4 (range, 0-12) cm from the anal verge, encompassed 50 (range, 20-90) percent of the rectal circumference, and was 6 (range, 3-12) cm in diameter. RESULTS: No Grade 4 toxicity was observed during chemoradiotherapy. Three patients experienced Grade 3 toxicity (diarrhea), and four patients required a treatment interruption of greater than three days. All patients completed at least 90 percent of the prescribed radiotherapy dose. All patients underwent surgical resection. Ninety-four percent had clear surgical margins. All pathologic specimens had significant evidence of necrosis, hyalinization, and fibrosis. Thirty-three percent of the specimens had a complete pathologic response (defined as no evidence of viable tumor cells). Of the 19 patients with ultrasound-staged N1 disease, only five had pathologic evidence of nodal involvement after chemoradiotherapy. Of the 25 patients with ultrasound-staged T3 disease, pathologic staging revealed eight with T0, two with T1, five with T2, and ten with T3 disease. Of the five patients with ultrasound-staged T4 disease, pathologic staging revealed two with T0, one with T2, and two with T3 disease. No patient developed progressive disease while on treatment. Two patients have experienced local failure at 6 and 20 months, and one patient failed in the liver at seven months. Twenty-seven patients remain free of disease with a median follow-up of 20 (range, 3-53) months. CONCLUSION: Our experience suggests that preoperative chemoradiotherapy is well tolerated, down-stages tumors, and sterilizes regional lymph nodes.

Adenocarcinoma↗
PubMed2001

Elders' perceptions of formal and informal care: aspects of getting and receiving help for their activities of daily living.

A purposive and convenience sample of 16 women and four men receiving informal and formal care for their activities of daily living either at home or institutions in Southeast Washington, USA was interviewed. Qualitative findings related to asking for help, getting and receiving help, interpersonal aspects of receiving help, and met and unmet needs are reported. Some seniors found it more difficult to ask for and accept help and there were gender differences, with men tending to adopt a more logical and pragmatic approach while women viewed receiving help as a loss of independence and an invasion of privacy. Intimacy and nudity were also threats for women. Three styles of adjustment and acceptance were identified within the data and related to positive acceptance, resigned acceptance and passive acceptance. There appeared to be a relationship between independence and control, with elders losing some independence but retaining control through choice, payment and involvement in decision making. Reciprocity was found to bring added value to relationships between care providers and elders, with a rhythm and symmetry developing in relationships where needs were known, anticipated and met. Seniors should be encouraged to plan for their future and to find out about local help and services available to them in advance of their requiring any assistance.

Activities of Daily Living↗
PubMed2001

Elders' needs and experiences of receiving formal and informal care for their activities of daily living.

Older people living in the community or institutional settings are more likely to require help with their activities of daily living, with women more likely than men to need some help. The interviews in this qualitative study were conducted with a convenience and purposive sample of 20 elders living in Southeast Washington, USA, at home or in institutional settings, receiving informal or formal health care. Findings related to personal and instrumental activities of daily living are reported and include elders' experiences and views relating to the help and assistance they receive. The majority of elders needed help with their instrumental activities of daily living, provided by informal networks, whether living at home or in institutional settings. This help constituted social care. Formal health care with personal activities of daily living was required only by a minority of elders and constituted those with the greatest disability and dependency.

Activities of Daily Living↗
PubMed2000

Genetic restriction of HIV-1 pathogenesis to AIDS by promoter alleles of IL10.

IL10 is a powerful TH-2 cell cytokine produced by lymphoid cells that limits HIV-1 replication in vivo, ostensibly by inhibiting macrophage/monocyte and T-cell lymphocyte replication and secretion of inflammatory cytokines (IL1, TNFalpha, IL6, IL8, and IL12). A genetic epidemiological scan of patients enrolled in AIDS cohorts for candidate gene-linked short tandem repeat polymorphisms revealed significant genotype associations for HIV-1 infection and progression to AIDS with markers adjacent to and tracking (by linkage disequilibrium) common single nucleotide polymorphic variants in the IL10 promoter region. Individuals carrying the IL10-5'-592A (IL10-5'A) promoter allele possibly were at increased risk for HIV-1 infection, and once infected they progressed to AIDS more rapidly than homozygotes for the alternative IL10-5'-592 C/C (IL10-+/+) genotype, particularly in the later stages of HIV-1 infection. An estimated 25-30% of long-term nonprogressors (who avoid clinical AIDS for 10 or more years after HIV-1 infection) can be attributed to their IL10-+/+ promoter genotype. Alternative IL10 promoter alleles are functionally distinct in relative IL10 production, in retention of an avian erythroblastosis virus transcription factor recognition sequence and in binding to specific putative nuclear transcription factors, suggesting a potential mechanism whereby IL10-5'A down-regulation of inhibitory IL10 facilitates HIV-1 replication in vivo, accelerating the onset of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Increased ciprofloxacin resistance in gonococci isolated in Scotland.

A review of the susceptibility of Neisseria gonorrhoeae isolated from 4415 episodes of infection in Scotland between 1991 and 1999 showed that the proportion of isolates with lowered susceptibility (ciprofloxacin minimum inhibitory concentration [MIC] > or = 0.05 mg/L) increased from 0.5% in 1991 to 5% in 1999 (p<0.001), whereas the proportion of isolates with clinical resistance (ciprofloxacin MIC > or = 1 mg/L) was significantly higher in 1999 than the average for the preceding 4 years (2.2% vs 0.9%; p=0.02). Ciprofloxacin is a recommended treatment for gonococcal infection in the UK but if resistance continues to increase at the present rate it might not be suitable as a first-line treatment of gonorrhoea for much longer.

Anti-Infective Agents↗
PubMed2000

Genomic organization and expression of the mouse equilibrative, nitrobenzylthioinosine-sensitive nucleoside transporter 1 (ENT1) gene.

We have cloned and characterized the genomic structure of the mouse gene for the NBMPR-sensitive equilibrative nucleoside transporter (mENT1), which is located on chromosome 17C. About 12-kb of genomic DNA was sequenced including the promoter region, 12 exons, 11 introns, and the 3'-untranslated region. All exon-intron junction sequences conform to the GT/AG rule. Primer extension analysis demonstrated a transcription initiation site located 252 bp upstream of the translation start site. Analysis of the 2.5-kb 5'-flanking sequence shows putative binding sites for several transcription factors, including GATA-1, IRF-2, Pit-1, myogenin, CREB, Sp-1, Ap-2, MAZ, and GR. We demonstrated that mouse ENT1 mRNA was highly expressed in heart, spleen, lung, liver, and testis. Lower levels of expression were detected in brain and kidney. Functional analysis of the 5'-flanking region showed that the nucleotide sequence from -652 to -111 contains cis-regulatory elements that promote gene expression. We found two Sp-1 binding sites (-296/-303, -307/-313) and two MAZ binding sites (-353/-359, -522/-528) in this region. Luciferase assay results suggest that MAZ and Sp-1 transcription factors are important positive regulators of transcription for the ENT1 gene in NG108-15 cells.

3' Untranslated Regions↗
PubMed2000

The tryptophan catabolite picolinic acid selectively induces the chemokines macrophage inflammatory protein-1 alpha and -1 beta in macrophages.

We previously found that the tryptophan catabolite picolinic acid (PA) is a costimulus for the activation of macrophage effector functions. In this study, we have investigated the ability of PA to modulate the expression of chemokines in macrophages. We demonstrate that PA is a potent activator of the inflammatory chemokines MIP (macrophage inflammatory protein)-1 alpha and MIP-1 beta (MIPs) mRNA expression in mouse macrophages in a dose- and time-dependent fashion and through a de novo protein synthesis-dependent process. The induction by PA occurred within 3 h of treatment and reached a peak in 12 h. The stimulatory effects of PA were selective for MIPs because other chemokines, including monocyte chemoattractant protein-1, RANTES, IFN-gamma-inducible protein-10, MIP-2, and macrophage-derived chemokine, were not induced under the same experimental conditions and were not an epiphenomenon of macrophage activation because IFN-gamma did not affect MIPs expression. Induction of both MIP-1 alpha and MIP-1 beta by PA was associated with transcriptional activation and mRNA stabilization, suggesting a dual molecular mechanism of control. Iron chelation could be involved in MIPs induction by PA because iron sulfate inhibited the process and the iron-chelating agent, desferrioxamine, induced MIPs expression. We propose the existence of a new pathway leading to inflammation initiated by tryptophan catabolism that can communicate with the immune system through the production of PA, followed by secretion of chemokines by macrophages. These results establish the importance of PA as an activator of macrophage proinflammatory functions, providing the first evidence that this molecule can be biologically active without the need for a costimulatory agent.

Adjuvants, Immunologic↗
PubMed2000

Connexin-independent ganciclovir-mediated killing conferred on bystander effect-resistant cell lines by a herpes simplex virus-thymidine kinase-expressing colon cell line.

A novel gap junction-independent mechanism for ganciclovir-mediated bystander effect killing by a herpes simplex virus thymidine kinase (HSV-TK)-expressing SW620 human colon tumor cell line has been characterized. The mechanism of the HSV-TK/GCV bystander effect for many tumor cell lines has been demonstrated to be due to connexin gap junction transfer of phosphorylated ganciclovir (GCV) metabolites; however, there may be as yet uncharacterized connexin-independent mechanisms for the effect. To address this, the bystander effect was further evaluated in a panel of cell lines mixed with homologous HSV-TK-expressing cell lines, a SW620.TK cell line, or a high connexin43-expressing PA-317.TK cell line. Of the 10 cell lines tested, 4 were found to be resistant to bystander effect killing by their homologous HSV-TK-expressing cell lines and the PA-317.TK cells, but all of the cell lines were sensitive to GCV killing when mixed with the SW620.TK cells. The SW620.TK cells were then further evaluated for any indication of extracellular GCV metabolite efflux. Culture medium from SW620.TK cells labeled with [(3)H]GCV was evaluated for the presence of GCV nucleotides by ion-exchange column separation and HPLC analysis. The presence of GCV mono-, di-, and triphosphate metabolites in the medium was detected. Inclusion in the medium of inhibitors of extracellular phosphatases and ecto-ATPases increased the proportion of GCV metabolites recovered. These results indicate that phosphorylated GCV metabolites can be effluxed from SW620.TK cells and that some type of cellular uptake mechanism independent of gap junctions exists for nucleotide entry into neighboring cells.

Cell Count↗
PubMed2000

Clinical presentation of mucin-secreting tumors of the pancreas.

BACKGROUND: Pancreatitis and jaundice secondary to ductal obstruction are common in intraductal papillary mucinous tumors (IPMT) of the pancreas. However, the incidence and severity of the complications of obstruction are not well documented. The aim of the study was to investigate the clinical presentation and outcome of 10 patients with IPMT. METHODS: All cases of IPMT diagnosed between 1994 and 1999 were reviewed. RESULTS: Four of the 10 patients developed severe acute illness with systemic complications resulting from ductal obstruction. Three suffered acute cholangitis with sepsis, and 1 developed necrotizing pancreatitis and ARDS. There was 1 postoperative death in a patient with adenocarcinoma. All other patients are alive and well with a median follow-up of 26 months (survival 90%). CONCLUSIONS: Pancreatic or common bile duct obstruction in IPMT may result in acute, life-threatening disease. Aggressive surgical therapy is warranted before development of complications of ductal obstruction or progression of tumor occurs.

Acute Disease↗
PubMed2000

Adenocarcinoma of the rectum with associated colorectal adenomatous polyps in tuberous sclerosis: a case report.

The authors present the case of a 17-year-old girl with tuberous sclerosis (TS) who presented with symptoms of intussusception. Although endoscopically diagnosed with multiple colonic polyps, presumed to be hamartomas, and an invasive rectal adenocarcinoma, postoperative pathology findings confirmed the rectal cancer and showed multiple colonic adenomas. Multiple colonic adenomatous polyps in a young girl with tuberous sclerosis is extremely rare. Furthermore, we believe that this is the first report of an invasive adenocarcinoma of the large intestine occurring in a patient with TS.

Adenocarcinoma↗
PubMed2000

Early evaluation of tumour metabolic response using [18F]fluorodeoxyglucose and positron emission tomography: a pilot study following the phase II chemotherapy schedule for temozolomide in recurrent high-grade gliomas.

Quantitation of metabolic changes in tumours may provide an objective measure of clinical and subclinical response to anticancer therapy. This pilot study assesses the value of quantitation of metabolic rate of glucose (MRGlu) measured in mmol min(-1) ml(-1) to assess early subclinical response to therapy in a relatively non-responsive tumour. Nine patients receiving the CRC Phase II study schedule of temozolomide were assessed with [18F]fluorodeoxyglucose ([18F]FDG) dynamic positron emission tomography (PET) scans prior to and 14 days after treatment with temozolomide given as 750-1000 mg m(-2) over 5 days every 28 days. Tumour MRGlu was calculated and compared with objective response at 8 weeks. Pretreatment MRGlu was higher in responders than non-responders. The responding patient group had a greater than 25% reduction in MRGlu in regions of high focal tumour uptake (HFU). Whole tumour changes in MRGlu did not correlate with response. Percentage change in HFU standardized uptake value (SUV) did discriminate the responding from the non-responding patients, but not as well as with MRGlu. Large differences also occurred in the normal brain SUV following treatment. Thus, MRGlu appeared to be a more sensitive discriminator of response than the simplified static SUV analysis. Changes in MRGlu may reflect the degree of cell kill following chemotherapy and so may provide an objective, quantitative subclinical measure of response to therapy.

Adult↗