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Biomedical subjects

H Young

Publications and source records attributed to H Young.

At least 109 records · Page 6Linked to original sources

Is the construction of an ileoanal pouch associated with the development of arthritis?

The construction of an ileoanal pouch in patients who have undergone total colectomy for ulcerative colitis is claimed to be associated with the development of arthritis. The pattern and prevalence of reported musculoskeletal symptoms in the 15 patients with ileoanal pouches attending our hospital was not significantly different to a control group of 60 patients with an ileostomy for inflammatory bowel disease. There was no clinical or serological evidence of arthritis in the eight patients from the study group reporting symptoms. We conclude that the majority of symptoms occurring following pouch construction are not attributable to an inflammatory arthropathy.

Adolescent↗

Rapid identification of pathogenic neisserias using the Identicult-Neisseria test.

A rapid enzymatic method using chromogenic substrates for the rapid identification of pathogenic neisseria (Identicult-Neisseria, Scott Laboratories Inc., CA, USA) was tested in parallel with the rapid carbohydrate utilization test (RCUT) and the Phadebact Monoclonal GC Test against 198 consecutive clinical isolates of oxidase-positive Gram-negative diplococci (118 Neisseria gonorrhoeae, 76 N. meningitidis and four N. lactamica). On initial testing the Identicult-Neisseria gave a 95% overall concordance (97.5% N. gonorrhoeae, 90.8% N. meningitidis) with the RCUT and Phadebact tests; the corresponding figures after repeat testing were 98% overall concordance (98.3% N. gonorrhoeae, 97.4% N. meningitidis). Two of the three strains of N. gonorrhoeae mis-identified as N. meningitidis on primary testing were also mis-identified on repeat testing. Seven strains of N. meningitidis were mis-identified on initial testing (six as Moraxella catarrhalis and one as N. lactamica) and two on repeat testing (both as Mor. catarrhalis). We conclude that the Identicult-Neisseria is not sufficiently reliable for the culture confirmation of gonococci and meningococci.

Agglutination Tests↗

Gonococcal infection in Edinburgh and Newcastle: serovar prevalence in relation to clinical features and sexual orientation.

AIMS: The variable distribution of gonococcal serovars in different areas is well recognised but the factors that are important determinants of serovar prevalence are less clear. The aim of this study was to identify relevant clinical variables by comparing serovar prevalence in two cities over the same time period. METHODS: A prospective analysis of serovar prevalence was made between January and December 1992 in Edinburgh and Newcastle with respect to age, sex, sexual orientation, antibiotic sensitivity and presence of symptoms. RESULTS: 224 infective episodes of gonorrhoea were studied. The serovar distribution varied between the two cities with serovar 1B-1 being more common in Edinburgh (20/91 cf. 4/133, p < 0.01) and serovar 1B-6 more common in Newcastle (26/133 cf. 2/91, p < 0.01). Serovar 1A-2 was associated with heterosexual infection (35/114 in heterosexuals cf. 0/85 in homosexuals, p < 0.01) and was more sensitive to penicillin than average (39/39 1A-2 strains highly penicillin sensitive cf. 98/184 for all other strains, p < 0.01) whilst 1B-6 was mostly acquired through homosexual contact (22/26 cf. 63/142 for all other strains, p < 0.01) and tended to show reduced penicillin susceptibility (13/28 1B-6 strains less penicillin sensitive cf. 45/195 for all other strains, p < 0.01). Infection with serovar 1A-2 was significantly less often symptomatic in heterosexuals than average (15/33 asymptomatic 1A-2 infections cf. 17/59 for all other serovars, p = 0.015). Subgroup analysis of male heterosexual infections confirms an association between asymptomatic infection and serovar 1A-2 (2/14 asymptomatic 1A-2 infections cf. 1/72 for all other serovars, p = 0.02). The distribution of infections over the year differed between the cities. CONCLUSIONS: A variety of factors including penicillin sensitivity and virulence may be important in determining the prevalence of gonococcal serovars within a given area.

Adult↗

Gonorrhoea in Aberdeen: a serovar analysis.

The serotyping of gonococcal isolates has enabled detailed studies of the epidemiology of gonorrhoea in different geographical areas. This study reports the patterns of infection found in 1992 in Aberdeen and relates these to a variety of clinical parameters. 140 cases of gonorrhoea were isolated the majority of which belonged to one strain (lA-2) in contrast to the diversity of strains seen in other Scottish cities. Most isolates were highly sensitive to penicillin and only 3 penicillinase producing strains were found. A low rate of infections in homosexual men is reported again in contrast to the situation seen in other geographically close cities. Compared to the rest of Scotland Aberdeen has a high prevalence of gonorrhoea.

Adolescent↗

Tissue blood flow estimation with copper(II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) and PET.

Copper (II)-pyruvaldehyde bis (N-4-methylthiosemicarbazone) (Cu-PTSM) labelled with 62Cu or 64Cu is currently under investigation as a radiotracer for imaging the distribution of blood flow with positron emission tomography (PET). The application of a simple trapped tracer model in conjunction with tissue uptake and continuous arterial sampling to estimate blood flow has been compared with the 57Co-microsphere method in the rat. After intraventricular injection the cumulative arterial function for 64Cu increased progressively due to the presence of circulating non lipophilic complexes. The cumulative function for lipophilic 64Cu-PTSM extracted in n-octanol plateaued at levels corresponding to those reached by 57Co-microspheres. No consistent disagreement was found between cardiac output and blood flow estimated by 64Cu-PTSM and 57Co-microspheres in low to moderate flow tissues: muscle (0.08, 0.07 mL/min/g; 64Cu mean, 57Co mean), brain (0.52, 0.43 mL/min/g) and kidney (2.29, 2.45 mL/min/g). However, 64Cu-PTSM underestimated blood flow measured by 57Co-microspheres in myocardium (4.09, 6.55 mL/min/g). A simple tissue trapping model may therefore be suitable for the derivation of blood flow estimates in low to moderate flow tissues using 62,64Cu-PTSM, PET imaging and continuous arterial sampling with n-octanol extraction.

Animals↗

Biodistribution and kinetics of radiolabelled pyrrolidino-4-iodo-tamoxifen: prospects for pharmacokinetic studies using PET.

With a view to evaluating the role of PET imaging in early clinical studies of new anticancer drugs, we are investigating the recently developed antiestrogen compound pyrrolidino-4-iodo-tamoxifen (idoxifene). Preliminary experimental studies have been undertaken using [125,131I]idoxifene, following synthesis of a tributyl-stannyl-idoxifene precursor to facilitate radioiodination. We have investigated the tissue biodistribution and kinetics of [125I]idoxifene following i.v. infusion in hooded rats bearing the hormone-dependent transplantable mammary tumour OES.HR1. Clearance of idoxifene from the circulation is accompanied by an increase in uptake by tumour and uterus, to peak levels after 24 hours (0.33 +/- 0.037% dose/g (mean +/- 1 SD) and 0.40 +/- 0.033% dose/g, respectively). Highest uptake of idoxifene was found in the liver (11.0 +/- 0.8% dose/g), with a progressive fall after 24 hours consistent with hepatobiliary excretion of the radiotracer. No evidence of idoxifene metabolism was found in tissue extracts taken up to 48 hours. Whole body clearance of [131I]idoxifene was characterised by a single exponential decay (t1/2 = 140 hours) up to 350 hours post administration. We conclude that 124I-labelled idoxifene combined with PET imaging would facilitate human in vivo pharmacokinetic studies of this new anticancer drug and provide an opportunity to investigate relationships between drug uptake and tumour response.

Animals↗

Teenage obstetric and gynaecological problems in an African city.

OBJECTIVE: To measure the prevalence of sexually transmitted diseases (STD), pelvic inflammatory disease (PID), cervical cancer, pregnancy and use of contraception in teenagers, and to determine socioeconomic factors associated with these conditions to aid planners of medical services and promotion of sexual health. SUBJECTS: 181 Ethiopian teenagers and 1,845 women aged 20 to 45 years for comparison. SETTING: Gynaecological outpatient department, antenatal, postnatal and family planning clinics, in two teaching hospitals and a mother and child heath centre in Addis Ababa, Ethiopia. METHODS: Results of serologic tests for STD, clinical evidence of PID, and cervical cytology were analysed against socio-economic factors. RESULTS: In teenagers early age at first marriage/coitus, more common in those of rural origin, was associated with poverty, a greater number of lifetime sexual partners, and prostitution: 40 pc were first sexually active before the menarche. Prevalence of seropositivity to specific STD pathogens was; Treponema pallidum (TPHA) 21 pc, Neisseria gonorrhoeae (gonococcal antibody test: GAT) 40 pc, genital chlamydiae 51 pc, hepatitis B virus 36 pc, herpes simplex virus (HSV-2) 32 pc, and Haemophilus ducreyi 16 pc: 92 pc of teenagers were seropositive to one or more STD's. STD seroprevalence was higher in those with more than one sexual partner, those sexually active by age 15 (very high in those sexually active by age 12), those involved in prostitution and those attending the family planning clinic. Forty three pc had clinical evidence of PID; one married at age 10 had invasive cervical cancer by age 18; 40 pc of teenagers were pregnant compared with 25 pc of those aged 20 to 45; 21 pc attended for family planning; of regular FPC attenders 81 pc were GAT seropositive. CONCLUSION: Despite legislation early age of sexual debut is common, STD and PID are widely prevalent, the pregnancy rate in adolescents is high and contributes to the national population growth rate. Action is required at family, medical and governmental level to encourage cultural acceptance that marriage and sexual activity should not occur before the age of 16 years, with education appropriate to culture to prevent STD. Similar studies are recommended in other countries to establish a baseline for informed strategy regarding prevention of STD and health education.

Adolescent↗

Risk factors for development of flucloxacillin associated jaundice.

OBJECTIVES: To identify risk factors predisposing to the development of flucloxacillin associated jaundice. DESIGN: Case-control study. Medical records of cases and controls were reviewed and information recorded on standard data collection forms. SETTING: Alfred Hospital recruiting subjects from Melbourne, Sydney, and Brisbane. SUBJECTS: Cases were defined as patients who had developed jaundice within eight weeks of stopping flucloxacillin, biochemical test results suggesting cholestasis, normal calibre bile ducts, and not been taking recognised hepatotoxic drugs. 51 of the 53 patients referred were included in the study. Four controls for each case were randomly selected from the patient register of the prescribing doctor. These were defined as patients who had been prescribed flucloxacillin without developing jaundice. MAIN OUTCOME MEASURES: Demographic characteristics, medical history, indication for flucloxacillin, dose, route and duration of treatment, other drugs, smoking, and previous drug allergies or use of flucloxacillin. RESULTS: Increasing age and a prolonged duration of flucloxacillin treatment were found to be risk factors for the development of jaundice. Patients aged over 55 years had an odds ratio of 18.61 (95% confidence interval 5.16-67.17) compared with patients under 30. The odds ratio for patients prescribed flucloxacillin for over 14 days was 7.13 (2.90 to 17.58) compared with patients treated for 14 days or less. Dose and route of administration were not related to the risk of jaundice. CONCLUSIONS: Older patients and those receiving flucloxacillin for longer than two weeks are at a substantially greater risk of jaundice. Careful consideration of the risk-benefit ratio is required when flucloxacillin is used in these settings.

Adult↗

Serotype patterns of gonococcal infection in contact pairs.

The use of gonococcal serovars in studying the epidemiology of Neisseria gonorrhoeae is well established. Most studies assume that the isolated serovar remains stable in vivo indefinitely. This study was designed to observe the correlation between serovars isolated in patients naming each other as sexual contacts. The overall rate of discordant transmission episodes was 12% (26/220). There were however significantly more discordant transmission episodes for partners of patients infected with IB serovars than IA serovars: 19% (23/124) versus 3% (3/96) - p < 0.01. The overall prevalence of serogroup IB isolates although significantly higher at 53% (p < 0.01) was thought insufficient to account for the correlation between discordant pairs and serogroup IB infection. Reasons considered for the discrepancies in contact pairs included: problems of partner reporting involving inaccurate or incomplete information; technical problems with reagents; culture induced phenotypic variation in antigenic expression or differences in the in vitro recognition of epitopes; and antigenic differences resulting from genetic mutation within the Protein I gene. It was concluded that carefully planned and controlled prospective studies involving duplicate parallel testing of isolates from patients and their well documented partners are needed to assess the extent to which these various factors contribute to discordancies in serovars isolated from contact pairs. Serotyping should be combined with other methods such as auxotyping for detailed microepidemiological studies involving partner notification.

Bacterial Typing Techniques↗

Broadband ultrasound attenuation compared with dual-energy X-ray absorptiometry in screening for postmenopausal low bone density.

Broadband ultrasound attenuation (BUA) was investigated as an inexpensive, simple and radiation-free method of screening for low perimenopausal bone density. A total of 587 women (50-54 years), invited for screening had bone mineral density (BMD) measured at the femoral neck and the lumbar spine by dual-energy X-ray absorptiometry (DXA). At the same visit the BUA of the calcaneus was measured. The correlation between BUA and BMD was approximately 0.4 compared with 0.67 between femoral neck and spinal BMD. Receiver operating characteristic (ROC) curve analysis demonstrated BUA to have the same ability for discriminating between low BMD at either the femoral neck or lumbar spine. BUA with a cut-off for normality at the median (BUA = 80) had a sensitivity of 68% and specificity of 67% for low bone density identified by a BMD less than the 25th centile at the femoral neck or lumbar spine. The correlation between BUA and BMD was insufficient to allow identification of the same groups as having low bone density.

Absorptiometry, Photon↗

Effect of blood perfusion on the ablation of liver parenchyma with high-intensity focused ultrasound.

This paper discusses the effect of blood perfusion on the ablation of rat liver tissue with high-intensity focused ultrasound (HIFU). For this study a practical method has been developed, in which the liver blood flow can be reduced by ligation of the hepatic artery and portal vein. During the treatment the rat liver was mobilized out of the abdomen and the blood flow was measured using both the radioactive microsphere method and a laser Doppler blood-flow monitor. The results show that the hepatic blood flow was about 23 ml/100 g min-1 via the hepatic artery and about 227 ml/100 g min-1 via the portal vein. The total liver blood flow was reduced by 98% when both the hepatic artery and portal vein were ligated. Comparative lesions were made on the same liver lobes of rats with both normal and reduced blood flow using a focused ultrasound beam of 1.7 MHz, 67-425 W cm-2 spatially averaged focal intensity ISAL and 2-20 s exposure duration. A marked difference has been found between the lesion dimensions obtained with normal blood flow and that with reduced blood flow. For exposures at 169 W cm-2 the lesion diameter with normal blood flow was reduced by 14% for 3 s exposure duration compared to that obtained with both hepatic artery and portal vein ligated, while the reduction was more than 20% for longer durations.

Animals↗

Comparative evaluation of AccuProbe culture identification test for Neisseria gonorrhoeae and other rapid methods.

The AccuProbe chemiluminescent culture identification test for Neisseria gonorrhoeae (Gen-Probe Inc., San Diego, Calif.) was assessed in a comparative evaluation with other rapid methods by using 269 isolates of oxidase-positive, gram-negative diplococci. Chemiluminescence was read with a PAL luminometer, and results were expressed as PAL light units (PLUs): the cutoff value for a positive identification was 1,500 PLUs. All 200 isolates of gonococci confirmed by carbohydrate utilization and serotyped with monoclonal antibodies were identified correctly by AccuProbe on initial testing. The API Quadferm system (Bio Merieux, Marcy l'Etoile, France) identified 95% (n = 190) of the gonococci correctly on initial testing and 99.5% (n = 199) on repeat testing, while the Phadebact Monoclonal GC test (Kara Bio Diagnostics AB, Huddinge, Sweden) identified 95.5% (n = 191) of the gonococci on both initial and repeat testing; 8 of the Phadebact-negative isolates were all of the same rare serovar (serovar 1B-17). The mean PLU for the gonococcal isolates was 9,014 (range 2,264 to 10,845) compared with a mean of 51 (range, 8 to 109) for the 69 nongonococcal isolates. We conclude that the AccuProbe culture confirmation test provides a rapid and accurate objective means of identifying cultured N. gonorrhoeae isolates.

Bacteriological Techniques↗

Effect of THAM upon outcome in severe head injury: a randomized prospective clinical trial.

Although mortality and morbidity rates from head injury have been reduced substantially by improved prehospital interventions, intensive care, and aggressive management of intracranial pressure (ICP), successful treatment of the primary brain injury has been elusive. In experimental models, tromethamine (THAM) has been effective in treating head injury; this drug acts by entering the cerebrospinal fluid compartment, reducing cerebral acidosis and ICP, and reversing the adverse effects of prophylactic hyperventilation on early recovery. In this randomized prospective clinical trial, THAM was studied to determine if it had beneficial effects in the early management of severe head injuries and if the adverse effects of hyperventilation could be prevented. A total of 149 patients with severe head injury (Glasgow Coma Scale scores of < or = 8) were randomly assigned to either a control or a THAM group. Both groups of patients matched in terms of clinical parameters, including age, sex, number of surgical mass lesions, number in each Glasgow Coma Scale stratum, and first ICP measurement. All patients were treated by a standard management protocol, intubated, mechanically ventilated, and maintained in the pCO2 range of 32 to 35 mm Hg for 5 days. Tromethamine was administered as a 0.3-M solution in an initial loading dose (body weight x blood acidity deficit, average 4.27 cc/kg/hr) given over 2 hours, followed by a constant infusion of 1 ml/kg/hr for 5 days. Outcome was measured at 3, 6, and 12 months postinjury. Although analysis indicated no significant difference in outcome between these two groups at 3 months, 6 months, and 1 year, there was a difference regarding ICP. The time that ICP was above 20 mm Hg in the first 48 hours postinjury was less in patients treated with THAM (p < 0.05). Also, the number of patients requiring barbiturate coma was significantly less in the THAM group (5.48% vs. 18.4%, p < 0.05). The authors conclude that THAM ameliorates the deleterious effect of prolonged hyperventilation, may be beneficial in ICP control, and warrants further study as to the dosage and timing of administration.

Adolescent↗

Typing of Neisseria gonorrhoeae by auxotype, serovar and lectin agglutination.

A total of 267 strains of Neisseria gonorrhoeae, comprising 129 serogroup IA and 138 serogroup IB, isolated in Edinburgh over a two-year period were analysed to assess the discrimination given by three typing methods: auxotyping; serotyping using the Genetic Systems (GS) and Pharmacia (PH) monoclonal antibody panels; and lectin agglutination. Each typing system was assessed individually and in combination. Serotyping subdivided the strains into 14 GS and 18PH serovars. Auxotyping (Aux) yielded 11 separate auxotypes while lectin agglutination yielded 22 different reaction patterns (LP). The standard auxotype/GS serovar (A/S) classification system yielded 37 classes. Lectin agglutination allowed further subdivision of the main A/S classes. AHU/IA-2 strains,which accounted for 70% of IA strains, yielded nine different lectin patterns (A/S/LP classes). Likewise, lectin agglutination allowed subdivision of the main IB A/S classes. NR/IB-1, NR/IB-2 and NR/IB-3, which accounted for 28%, 38% and 20% respectively of the IB strains, yielded 7, 7 and 6 A/S/LP classes respectively. It was concluded that lectin agglutination is a useful adjunct to the standard A/S classification system for studying the micro-epidemiology of gonococcal infection.

Agglutination Tests↗

Preoperative imaging of colorectal cancers. Targeting the epithelial membrane antigen with a radiation-labeled monoclonal antibody.

The epithelial membrane antigen (EMA) is expressed by the majority of colorectal cancers but has not previously been investigated as a target for radiation-labeled monoclonal antibodies (MoAb) in the imaging of patients with colorectal cancer. A rat IgG2a MoAb that recognizes EMA, ICR2, was labeled with Indium-111 (100 megabecquerel per milligram [MBq/mg]MoAb) using the bicyclic anhydride of the chelating agent diethylene triamine pentacetic acid (ccDTPA) and was administered intravenously to 22 patients known to have or thought to have colorectal cancer. Daily gamma camera imaging was performed for 3 days during the time between the administration of the radiation-labeled antibody and surgical procedure. At operation, the biopsies were done of the tumors and the normal colon, and the uptake of radiation-labeled MoAb was measured in a gamma well-counter. Immunocytochemistry for EMA expression also was done on resected tumors. Independent unblinded and blinded reporting was done on all scans. The sensitivity of 111In-ICR2 for detecting cancers preoperatively was 80% and 60%, respectively, on unblinded and blinded reporting, and the corresponding specificity 20% and 60%. The low unblinded specificity was attributable to a false-positive localization in severely dysplastic benign tumors (n = 2) and inflammatory tissue (n = 2). Liver metastases present in three patients were cold relative to normal liver. Lymph node metastases were localized in 1 of 6 patients preoperatively. The mean absolute uptake of 111In-ICR2 in tumor tissue was 7.75 +/- 3.77 x 10(-3) percent of injected dose per gram, and the ratio to normal colon was 2.10 +/- 0.92:1. On immunohistochemistry, EMA was expressed by 16 of the 17 primary cancers, both dysplastic adenomas, and all nodal metastatic deposits. EMA-negative tumors (1 cancer + 1 colonic lipoma) had negative antibody scans, and patients whose tumor was negative or only focally positive for EMA expression had lower tumor/normal colon ratios of radioactivity (1.30 +/- 0.26 versus 2.45 +/- 0.65, P = 0.005) on gamma well-counting of excised specimens. These results suggest a possible role for 111In-ICR2 in the detection of colorectal cancer and metastases but not its liver deposits.

Aged↗