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S Pugh

Publications and source records attributed to S Pugh.

At least 19 recordsLinked to original sources
PubMed2006

Sentinel laboratory surveillance of hepatitis C antibody testing in England: understanding the epidemiology of HCV infection.

This paper describes sentinel laboratory surveillance of hepatitis C antibody testing in England. Demographic and test result data were supplemented by follow-up questionnaires sent to the requesting clinician. Between October 2002 and September 2003 almost 75000 anti-HCV tests were performed in eight sentinel centres. More males were tested than females and over half of those tested were aged 25-44 years. Overall 5.7% (3333/58144, range 2.8-7.7%) individuals tested positive. Follow-up questionnaire data showed that 82% (1043/1277) of the positives had injecting drug use reported as the main risk exposure. The majority of negative individuals were undergoing routine screening as recommended for specific patient groups. Most individuals were asymptomatic. Antibody prevalence was estimated to be 34% in current injecting drug users and 42% in former injectors. Comparing positives to routine national surveillance suggests that only 53% (1782/3333) of diagnosed cases were reported. Sentinel laboratory data can provide valuable supplementary data to national surveillance.

Acute Disease↗
PubMed2006

Clinical pathways for patients with newly diagnosed hepatitis C - what actually happens.

Management of hepatitis C virus (HCV)-infected individuals requires referral to specialist care. To determine whether patients newly diagnosed as anti-HCV positive are appropriately referred for further investigation and management, and if not, to determine why not. We studied patients tested for antibodies to HCV by Nottingham Public Health Laboratory in a 2-year period (2000-2002). The progress of newly diagnosed anti-HCV positive patients into specialist clinics for further management was documented. For patients not referred for specialist care, a questionnaire was sent to the clinician requesting the initial anti-HCV test, to identify reasons for nonreferral. Eleven thousand one hundred and seventy-seven patients were tested for anti-HCV. Two hundred and fifty-six (2.3%) were newly diagnosed as being anti-HCV positive. Two per cent of samples sent from primary care were anti-HCV positive, compared to 18.8, 18.9 and 1.3% sent from prison, drug and alcohol units, and secondary care, respectively. About 64.3% of positive patients diagnosed in primary care were referred to specialist care, compared to 18.4, 42.4 and 62.6% of patients diagnosed in the other three settings. One hundred and twenty-five (49%) newly diagnosed patients were referred appropriately for further management. 68 of these attended clinic, 45 underwent liver biopsy and 26 (10%) began treatment. One hundred and thirty-one patients (51%) were not referred. In 54 cases, there was no evidence that the anti-HCV positive result reached the patient. In 15, referral was considered but rejected, and 20 patients were referred to non-HCV-specialists (their general practitioners or to genito-urinary medicine). Hence less than 50% of newly diagnosed anti-HCV positive patients are referred to an appropriate clinic for further investigation and management. Reasons for this are multifarious and complex, reflecting both systems failure and patient choice. Unless these are understood and addressed, the Department of Health Hepatitis C Strategy (2002) and Action Plan for England (2004) will fail to achieve their intended objectives.

Adolescent↗
PubMed2005

Histamine release during adult cardiopulmonary bypass.

Histamine, an inflammatory mediator in its own right, may also be a marker for a more widespread systemic inflammatory process. In this study we have examined variations in plasma histamine concentrations produced during the course of cardiac surgery involving cardiopulmonary bypass, the relationship between these variations and intra-operative events. By assays of serum tryptase and CD-63 expression we have also attempted to identify the source of histamine. Histamine concentrations that were significantly raised from baseline level were demonstrated. These were elevated from the time of aortic cross-clamping and continued to be raised for 24 h postoperatively (p < 0.00625). This was associated with an increase in CD-63 expression (p < 0.025) (but not an increase in tryptase concentration) following aortic cross-clamping and protamine administration, suggesting that basophils are the source of histamine. 41% of patients had arrhythmias in the post bypass period. The rise in histamine levels was not related to the incidence of cardiac arrhythmias.

Adult↗
PubMed2003

Who is being tested for genital chlamydia in primary care?

OBJECTIVES: To explore current patterns of testing for genital chlamydial infection in primary care, and to identify practice characteristics influencing testing rates. METHOD: Aggregate numbers of chlamydia tests and results for each practice in Nottingham Health District were matched to practice characteristics. Age specific testing rates and diagnosed prevalence were calculated, and characteristics of the practice tested for association with chlamydia testing rates. RESULTS: Most tests (63.1%) were performed on women over the age of 25, but the proportion of positive tests was highest in 15-19 year olds (13.3%) followed by 20-24 year olds (8.2%). A higher ratio of GP principals to female practice population was associated with higher testing rates and more chlamydia isolations, but the ratio of female GP principals to patients was associated with higher testing rates only in 20-24 year olds. Diagnosed incidence was greatest in more socioeconomically deprived practice populations, and this was not explained by higher testing rates. Men were rarely tested. CONCLUSION: Current testing practice in primary care does not reflect the known epidemiology of genital chlamydia infection. Practices with lower doctor-patient ratios do less testing, and measures to enable their active participation in the envisaged screening programme will be important in reaching all at-risk groups.

Adolescent↗
PubMed2001

Vital capacity inhalation induction with sevoflurane: an alternative to standard intravenous induction for patients undergoing cardiac surgery.

OBJECTIVE: To determine the respiratory and cardiovascular effects of a high concentration vital capacity induction with sevoflurane compared with an intravenous induction with etomidate in patients scheduled for elective coronary artery bypass graft (CABG) surgery. DESIGN: Prospective, randomized, double-blind, controlled clinical trial. SETTING: Cardiothoracic unit at a university hospital referral center. PARTICIPANTS: Twenty-two patients undergoing elective CABG surgery. INTERVENTIONS: The study group (group S) received a vital capacity gaseous induction with sevoflurane 8% (n = 12) and the control group (group E) were given etomidate, 0.2 to 0.3 mg/kg (n = 10). Anesthesia was supplemented with fentanyl, 8 microg/kg, and vecuronium, 0.1 mg/kg, in both groups. MEASUREMENTS AND MAIN RESULTS: The speed of induction of anesthesia was comparable between the groups. There was a significant increase in minute ventilation after induction of anesthesia in both groups. This increase was associated with a small reduction in PaCO2. There were no clinically significant changes in pH and PaO(2). The incidence of breath-holding and the need for an oropharyngeal airway were similar between the groups. Both groups had similar reductions in mean arterial pressure and cardiac output during the study period; however, a downward trend in mean pulmonary artery pressure was noted in group S, whereas in group E it remained unchanged. Absolute plasma epinephrine and norepinephrine values were low during the precardiopulmonary bypass period in both groups. CONCLUSIONS: The technique of vital capacity inhalation induction with 8% sevoflurane offers a rapid onset of anesthesia, satisfactory airway control, and a good hemodynamic profile. Consideration should be given to the benefits of single-agent anesthesia and lowered pulmonary artery pressure during the precardiopulmonary bypass period. In addition to CABG surgery, this technique could be considered in patients with coronary artery disease undergoing noncardiac surgery, particularly for procedures in which spontaneous ventilation is preferred.

Aged↗
PubMed1999

Preclinical efficacy of thioxanthone SR271425 against transplanted solid tumors of mouse and human origin.

A highly active and broadly active thioxanthone has been identified: N-[[1-[[2-(Diethylamino)ethyl]amino]-7-methoxy-9-oxo-9H-thioxanthen++ +-4-yl] methylformamide (SR271425, BCN326862, WIN71425). In preclinical testing against a variety of subcutaneously growing solid tumors, the following %T/C and Log10 tumor cell kill (LK) values were obtained: Panc-03 T/C = 0, 5/5 cures; Colon-38 (adv. stage) T/C = 0, 3/5 cures, 4.9 LK; Mam-16/C T/C = 0, 3.5 LK; Mam-17/0 T/C = 0, 2.8 LK; Colon-26 T/C = 0, 1/5 cures, 3.2 LK; Colon-51 T/C = 0, 2.7 LK; Panc-02 T/C = 0, 3.1 LK; B16 Melanoma T/C = 13%, 4.0 LK; Squamous Lung-LC12 (adv. stage) T/C = 14%, 4.9 LK; BG-1 human ovarian T/C = 16%, 1.3 LK; WSU-Brl human breast T/C = 25%, 0.8 LK. The agent was modestly active against doxorubicin (Adr)-resistant solid tumors: Mam-17/AdrT/C =23%, 0.8 LK; and Mam-16/C/Adr T/C = 25%, 1.0 LK, but retained substantial activity against a taxol-resistant tumor: Mam-16/C/taxol T/C = 3%, 2.4 LK. SR271425 was highly active against IV implanted leukemias, L1210 6.3 LK and AML1498 5.3 LK. The agent was equally active both by the IV and oral routes of administration, although requiring approximately 30% higher dose by the oral route. Based on its preclinical antitumor profile, it may be appropriate to evaluate SR271425 in clinical trials.

Animals↗
PubMed1998

Preclinical antitumor efficacy of analogs of XK469: sodium-(2-[4-(7-chloro-2-quinoxalinyloxy)phenoxy]propionate.

A series of quinoxaline analogs of the herbicide Assure was found to have selective cytotoxicity for solid tumors of mice in a disk-diffusion-soft-agar-colony-formation-assay compared to L1210 leukemia. Four agents without selective cytotoxicity and 14 agents with selective cytotoxicity were evaluated in vivo for activity against a solid tumor. The four agents without selective cytotoxicity in the disk-assay were inactive in vivo (T/C > 42%). Thirteen of the fourteen agents with selectivity in the disk-assay were active in vivo (T/C < 42%). Five of the agents had curative activity. These five agents had a halogen (F, Cl, Br) in the 7-position (whereas Assure had a CI in the 6 position). All agents with curative activity were either a carboxylic acid, or a derivative thereof, whereas Assure is the ethyl ester of the carboxylic acid. All other structural features were identical between Assure and the curative agents. Assure had no selective cytotoxicity for solid tumors in the disk-assay, and was devoid of antitumor activity. The analog XK469 is in clinical development.

Animals↗
PubMed1997

Rapid detection and serotyping of adenovirus by direct immunofluorescence.

Four fluorescent antibody reagents were evaluated for their suitability for the identification of adenovirus isolates by immunofluorescence. The antibodies used in the reagents consist of monoclonal antibodies against adenovirus type 3 (Ad3), Ad4, Ad8, and adenoviruses of subgroup C (Ad1,2,5,6), serotypes known to occur in outbreaks of disease. Most of the monoclonal antibodies employed were reactive against type-specific antigens found on the hexon protein. Reagents employing two noncompeting anti-hexon antibodies were more sensitive than reagents prepared with only one monoclonal antibody, although both types of reagents exhibited a high degree of specificity. Five hundred and seventeen adenovirus isolates (359 of which had previously been typed by other methods) and 46 nonadenovirus isolates were examined with all four type-specific reagents in parallel with an adenovirus group-specific reagent. The results indicate that direct typing of adenovirus isolates is feasible, leading to significant savings in time compared to other typing methods and should contribute to the management of certain adenovirus infections, particularly during outbreaks.

Adenoviridae Infections↗
PubMed1997

Treatment of human prostate tumors PC-3 and TSU-PR1 with standard and investigational agents in SCID mice.

Both the PC-3 and the TSU-PR1 prostate tumor models were found to be satisfactory for chemotherapeutic investigations in ICR-SCID mice. The 30 to 60 mg fragments implanted took in all mice (as judged by 100% takes in the controls of all experiments as well as the passage mice). The tumor volume doubling time was 4.0 days for PC-3 and 2.5 days for TSU-PR1. Nine agents were evaluated IV against early stage subcutaneous PC-3 tumors, with Nano-piposulfan being the only agent highly active (4.9 log kill). Three other agents were moderately active: Taxol (1.5 log kill), Cryptophycin-8 (1.6 log kill), Vinblastine (1.0 log kill). Five agents were inactive: VP-16, Adriamycin, CisDDPt, 5-FUra, and Cyclophosphamide. Ten agents were evaluated IV against early stage subcutaneous TSU-PR1 tumors. Three agents were highly active, producing > 6 log kill and cures: Taxol (5/5 cures), Cryptophycin-8 (5/5 cures), Vinblastine (2/4 cures). Two other agents were moderately active: Nano-piposulfan (1.2 log kill), and Cyclophosphamide (1.1 log kill). Five agents were inactive: VP-16, Adriamycin, CisDDPt, 5-FUra, and BCNU. In part, activity was determined by the ability of the SCID mice to tolerate meaningful dosages of the agents. Agents producing granulocyte toxicity (e.g., Adriamycin) were poorly tolerated and appeared less active than expected. Vinblastine, producing little or no granulocyte toxicity was very well tolerated and appeared to be more active than expected.

Aged↗
PubMed1997

Discovery of cryptophycin-1 and BCN-183577: examples of strategies and problems in the detection of antitumor activity in mice.

Historically, many new anticancer agents were first detected in a prescreen; usually consisting of a molecular/biochemical target or a cellular cytotoxicity assay. The agent then progressed to in vivo evaluation against transplanted human or mouse tumors. If the investigator had a large drug supply and ample resources, multiple tests were possible, with variations in tumor models, tumor and drug routes, dose-decrements, dose-schedules, number of groups, etc. However, in most large programs involving several hundred in vivo tests yearly, resource limitations and drug supply limitations have usually dictated a single trial. Under such restrictive conditions, we have implemented a flexible in vivo testing protocol. With this strategy, the tumor model is dictated by in vitro cellular sensitivity; drug route by water solubility (with water soluble agents injected intravenously); dosage decrement by drug supply, dose-schedule by toxicities encountered, etc. In this flexible design, many treatment parameters can be changed during the course of treatment (e.g., dose and schedule). The discovery of two active agents are presented (Cryptophycin-1, and Thioxanthone BCN 183577). Both were discovered by the intravenous route of administration. Both would have been missed if they were tested intraperitoneally, the usual drug route used in discovery protocols. It is also likely that they would have been missed with an easy to execute fixed protocol design, even if injected i.v.

Animals↗
PubMed1997

Environmental monitoring during gaseous induction with sevoflurane.

Recent research has shown that gaseous induction in adults with sevoflurane is an acceptable technique. This study was undertaken to assess if gaseous induction using sevoflurane carried in both oxygen alone, and in nitrous oxide and oxygen combined, would provide acceptable pollution levels. As an occupational exposure standard has not been set for sevoflurane, we used the target level of 20 ppm set by the manufacturer. Environmental monitoring was carried out in the anaesthetic room during eight lists where consecutive triple vital capacity sevoflurane inductions were performed. Time-weighted averages for both gases over the duration of the lists were well below the occupational exposure standards (mean 1.1 (range 0.6-1.7) for sevoflurane and 17.3 (12-23) for nitrous oxide). There were high peak concentrations during the induction process (8.3 (4.1-17) for sevoflurane and 172.4 (65-310) for nitrous oxide) although these decreased to low concentrations between anaesthetic inductions. Personal sampling was carried out from the anaesthetist's breathing zone and concentrations were also low (1.2 (0.8-2.1) for sevoflurane and 45.9 (10.1-261.6) for nitrous oxide.

Adult↗
PubMed1997

Pharmacokinetic studies in mice of two new thioxanthenones (183577 and 232759) that showed preferential solid tumor activity.

Two new thioxanthenones, 183577 and 232759, have rekindled interest in the development of representatives from this class of structures as useful anticancer agents. Although the mechanism of action is unknown, both compounds demonstrated a similar spectrum of solid tumor selectivity. 232759 was selected for clinical development because it showed no hepatotoxicity in preliminary studies, whereas 183577 showed hepatotoxicity but only at the maximum tolerated dose (MTD). The limiting toxicity for the clinical candidate was myelosuppression in preliminary studies. Plasma and tissue drug levels, as well as protein binding, were studied in mice using optimal administration times at the MTD for each drug (for 183577, this was a 4-h infusion at 1350 mg/m2 and for 232759, it was a 5-min injection at 240 mg/m2), as well as at one-half the MTD for the clinical candidate. The drugs were 96-100% bound by plasma proteins. The peak drug concentrations, half-life, and area under the concentration-time curve in plasma for 183577 were 3483 ng/ml, 465 min, and 2018 microgram/ml. min, respectively. The peak drug concentration, half-life, and area under the concentration-time curve in plasma for 232759 were 5257 ng/ml, 44 min, and 276 microgram/ml. min, respectively, at the MTD and 2810 ng/ml, 40 min, and 110 microgram/ml. min at one-half the MTD. In all instances of simultaneous measurements, drug concentrations were equal or higher in tissues than they were in plasma. Unlike the plasma and kidney concentrations of 183577, the liver concentrations did not show a declining trend over the 8-h observation period. Declines in plasma, liver, kidney, and tumor levels of 232759 were detected over the 8-h observation period. The sustained high 183577 concentration in liver is believed to be responsible for its prolonged half-life and hepatotoxicity. Evidence for metabolism of the parent drugs was based on the finding of additional peaks on the high-pressure liquid chromatography tracings. Future studies will focus on identification and antitumor studies of these presumed metabolites in hopes of a better understanding of the solid tumor activity profiles and toxic effects of these compounds.

Adenocarcinoma↗
PubMed1996

Formulation and antitumor activity evaluation of nanocrystalline suspensions of poorly soluble anticancer drugs.

PURPOSE: Determine if wet milling technology could be used to formulate water insoluble antitumor agents as stabilized nanocrystalline drug suspensions that retain biological effectiveness following intravenous injection. METHODS: The versatility of the approach is demonstrated by evaluation of four poorly water soluble chemotherapeutic agents that exhibit diverse chemistries and mechanisms of action. The compounds selected were: piposulfan (alkylating agent), etoposide (topoisomerase II inhibitor), camptothecin (topoisomerase I inhibitor) and paclitaxel (antimitotic agent). The agents were wet milled as a 2% w/v solids suspension containing 1% w/v surfactant stabilizer using a low energy ball mill. The size, physical stability and efficacy of the nanocrystalline suspensions were evaluated. RESULTS: The data show the feasibility of formulating poorly water soluble anticancer agents as physically stable aqueous nanocrystalline suspensions. The suspensions are physically stable and efficacious following intravenous injection. CONCLUSIONS: Wet milling technology is a feasible approach for formulating poorly water soluble chemotherapeutic agents that may offer a number of advantages over a more classical approach.

Animals↗
PubMed1996

Bile duct stenting: a comparison of the One-Action Stent introduction system with the conventional delivery system.

BACKGROUND AND STUDY AIMS: A "One-Action Stent Insertion System" (OASIS) for use with biliary stents has been produced, which is said to be easier to use than conventional insertion systems. The aim of this study was to assess whether there was any measurable difference in the technique in a comparison between the two methods. PATIENTS AND METHODS: A prospective study was carried out. Twenty consecutive patients requiring stents for biliary obstructing lesions were randomly allocated to have the stent inserted either using the OASIS system or the conventional system. All the sent insertions were performed by two experienced endoscopists. The actual time of the insertion procedure and the screening time were recorded. RESULTS: Patients' tolerance for the procedure was similar in the two groups. In nine out of ten OASIS stent insertions, the endoscopist considered the procedure to be easy, compared with five out of ten conventional stent placements. Both techniques resulted in satisfactory positioning of the stent in nine out of ten patients. Although there was no statistically significant difference in the screening times for the two methods (p = 0.16), the actual time taken using the conventional method was significantly longer than with the OASIS method (p < 0.001). CONCLUSION: The One-Action Stent Insertion Set (OASIS) allows easier insertion of biliary stents. The system decreases the number of exchanges that need to be undertaken, precluding inadvertent wire displacement and the need to reinitiate cannulation and guide wire insertion. The actual time required for insertion is significantly less using this method, and this may also reduce the radiation exposure.

Adult↗
PubMed1996

Duodenal mucosal histology and histochemistry in active, treated and healed duodenal ulcer: correlation with duodenal prostaglandin E2 production.

We investigated whether impaired duodenal mucosal prostaglandin E2 (PGE2) production previously observed in duodenal ulcer (DU) was a primary pathophysiological abnormality or secondary to mucosal architectural changes that accompany ulceration. One hundred patients were studied: at endoscopy, paired duodenal biopsies were taken in patients with normal endoscopies and from the ulcer edge or scar and background mucosa in active or healed DU. One of the pair of biopsies was used to estimate PGE2 synthesis ability, the other was processed for histology and histochemistry. The following features graded: goblet cell numbers and staining with Periodic acid-Schiff reagent (PAS), epithelial staining with PAS, villous atrophy, columnar cell height, inflammatory cell infiltrate and micro-erosions and gastric metaplasia taken as a whole. Patients were found to have normal endoscopy (n = 31), active untreated DU (n = 20) active DU on treatment with either cimetidine or ranitidine (n = 13), healed DU on maintenance treatment (n = 27) and healed DU off treatment (n = 9). Active duodenal ulceration was found to be associated with decreased numbers of goblet cells, loss and blunting of villi, increased columnar cell height, increased epithelial cell PAS staining and with gastric metaplasia. After healing, only villous blunting remained. These changes were present, but less marked, at sites removed from the ulcer and were not apparent in the patient groups with healed ulcers. A strong correlation between overall gastric metaplasia and epithelial cell PAS staining and the reduced ability to synthesize PGE2 (P < 0.001) was only apparent when biopsies from all patients were grouped together, but not within individual patient subgroups. There was no consistent correlation between PGE2 generation and individual parameters of pathological change in duodenum. We conclude that, although inflammatory and mucosal changes may contribute, the evidence suggests that the impaired PGE2 generation in DU disease is, to a large extent, independent of histological and histochemical features.

Analysis of Variance↗
PubMed1996

Self-reports on the Eating Disorder Inventory by female aerobic instructors.

This study examined the possibility of eating disorders in 30 female aerobic dance instructors. All subjects completed a biographical questionnaire and the Eating Disorder Inventory. The results showed that the aerobic instructors yielded scores which were comparable to similarly aged female weight lifters but tended to be lower than those of women distance runners (also of similar age). Interestingly, 23% (n = 7) of the subjects reported a previous history of bulimia and 17% (n = 5) reported a previous history of anorexia. Thus, 40% of the instructors indicated a previous experience with eating disorders. Based on all 30 participants, the mean scores associated with Body Dissatisfaction, Drive for Thinness, Ineffectiveness, and Perfectionism were quite comparable to those previously established for anorexic groups. In addition, a relatively high percentage of the sample yielded scores which were actually greater than mean values associated with anorexia patients on nine of the 11 subscales. Based on these results, a number of the aerobic dance instructors possessed scores suggesting behaviors and attitudes consistent with female athletes whose sports emphasize leanness and comparable to those who have eating disorders.

Adult↗
PubMed1996

Preclinical anticancer activity of cryptophycin-8.

Cryptophycin-8 was prepared by the conversion of the epoxide group on cryptophycin-1 to a chlorohydrin. In the studies reported here, cryptophycin-8 was evaluated for preclinical activity against subcutaneous tumors of both mouse and human origin. At the highest non-toxic single course treatment, the following results were obtained (Table A). Cryptophycin-8 was less potent than cryptophycin-1 by approximately 4-fold; however, it was both more water soluble and had greater therapeutic efficacy, as demonstrated by % T/C, tumor cell log kill values, range of dose effectiveness and host cures.

Animals↗