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Biomedical subjects

P Bunting

Publications and source records attributed to P Bunting.

At least 19 recordsLinked to original sources

Multicentre audit of the treatment of uncomplicated urinary tract infection in South Thames.

A regional audit report on the management of uncomplicated urinary tract infections (UTIs) in genitourinary (GU) medicine clinics in the UK in South Thames (South London, Kent, Surrey and Sussex). The majority of centres use trimethoprim as first-line treatment for uncomplicated UTIs. The incidence of trimethoprim resistance was 22.6%. The group has therefore recommended that cephalexin should be the first choice antibiotic for suspected UTIs within GU medicine.

Anti-Bacterial Agents↗

The role of serial free/total prostate-specific antigen ratios in a watchful observation protocol for men with localized prostate cancer.

OBJECTIVE: To examine the change in the free/total prostate specific antigen ratio (f/tPSA) with time and to assess the potential value of serial measurements of f/tPSA as a determinant of disease progression in untreated, low-to-intermediate grade prostate cancer (T1b-T2b N0M0, Gleason score < or = 7 and PSA < or = 15 ng/mL). PATIENTS AND METHODS: In a prospective single-arm cohort study from November 1995, patients were conservatively managed with watchful observation alone unless they met arbitrarily defined criteria (clinical, histological and biochemical) of disease progression. Patients were followed regularly and underwent blood tests including PSA and f/tPSA. The initial and mean f/tPSA and the rate of change of f/tPSA with time were evaluated against the rate constant for the PSA doubling time (PSATd). Correlation analyses were used to evaluate any association between baseline clinical variables and either the rate of change of f/tPSA or initial f/tPSA. RESULTS: As of December 2000, 161 of a total of 206 accrued patients had three or more f/tPSA measurements and formed the basis of the study (median age 70 years; median follow-up 2.7 years). The median initial f/tPSA was 0.16; there was a significant negative correlation between this value and the initial total PSA. The mean f/tPSA and rate of change of f/tPSA with time were significantly negatively correlated with the rate constant for PSATd. Also, the rate of change of f/tPSA correlated negatively with clinical T stage, but not with other baseline variables, including initial PSA, age and Gleason score. CONCLUSION: The f/tPSA in men with untreated, clinically localized prostate cancer varied widely. The negative correlation between the rate of change of f/tPSA with time and rate constant for PSATd suggests that both might provide valuable information to allow clinicians to develop a strategy for optimizing the timing of therapeutic intervention for those patients choosing watchful observation alone.

Adenocarcinoma↗

PSA doubling time of prostate carcinoma managed with watchful observation alone.

PURPOSE: To study prostate-specific antigen (PSA) doubling time of untreated, favorable grade, prostate carcinoma. METHODS AND MATERIALS: A prospective single-arm cohort study has been in progress to assess the feasibility of a watchful observation protocol with selective delayed intervention using clinical, histologic, or PSA progression as treatment indication in untreated, localized, favorable grade prostate adenocarcinoma (T1b-T2bN0 M0, Gleason Score < or = 7, and PSA < or = 15 ng/mL). Patients are conservatively managed with watchful observation alone, as long as they do not meet the arbitrarily defined disease progression criteria. Patients are followed regularly and undergo blood tests including PSA at each visit. PSA doubling time (Td) is estimated from a linear regression of ln(PSA) on time, assuming a simple exponential growth model. RESULTS: As of March 2000, 134 patients have been on the study for a minimum of 12 months (median, 24; range, 12-52) and have a median frequency of PSA measurement of 7 times (range, 3-15). Median age is 70 years. Median PSA at enrollment is 6.3 (range, 0.5-14.6). The distribution of Td is as follows: <2 years, 19 patients; 2-5 years, 46; 5-10 years, 25; 10-20 years, 11; 20-50 years, 6; > 50 years, 27. The median Td is 5.1 years. In 44 patients (33%), Td is greater than 10 years. There was no correlation between Td and patient age, clinical T stage, Gleason score, or initial PSA level. CONCLUSION: Td of untreated prostate cancer varies widely. In our cohort, 33% have Td > 10 years. Td may be a useful tool to guide treatment intervention for patients managed conservatively with watchful observation alone.

Adenocarcinoma↗

Human kallikrein 10: a novel tumor marker for ovarian carcinoma?

BACKGROUND: Human kallikrein 10 (hK10, encoded by KLK10 gene) is a recently discovered member of the human kallikrein family. hK10 is a secreted serine protease. With the development of a highly sensitive and specific immunoassay for hK10, quantification of hK10 in the circulation is now feasible. Our aim was to investigate whether hK10 concentration in serum changes in various malignancies. METHODS: We used a highly specific and sensitive immunofluorometric assay to quantify hK10 protein in 374 serum samples from healthy individuals and patients with various malignancies. RESULTS: Serum hK10 concentration was found to be significantly elevated in 56% of the ovarian cancer patients and such an increase was not observed in serum of healthy individuals or in serum of patients with other types of cancer, with the exception of approximately 15% of patients with gastrointestinal cancer. This hK10 elevation does not correlate well with CA 125. We have further demonstrated that hK10 concentration changes during ovarian cancer progression. CONCLUSION: This is the first report describing that hK10 serum concentration is significantly elevated in the majority of ovarian cancer patients. Our results indicate that hK10 may be a potential new serological marker for ovarian cancer diagnosis and monitoring.

Biomarkers, Tumor↗

Human kallikrein 6 (zyme/protease M/neurosin): a new serum biomarker of ovarian carcinoma.

BACKGROUND: There is an urgent need for discovery and validation of new serum biomarkers for ovarian carcinoma. Early diagnosis of ovarian cancer with serologic analysis may improve clinical outcomes through administration of effective treatment. Human kallikrein 6 (hK6, encoded by the KLK6 gene) is a serine protease of the kallikrein gene family. Recently, we were able to develop an immunofluorometric procedure for the quantitative measurement of hK6 in biologic fluids, including serum. METHODS: We have used an hK6-specific immunofluorometric assay to quantify hK6 protein in a large number of serum samples from normal individuals, as well as from patients with various malignancies. RESULTS: We report for the first time, significant increase of serum hK6 concentration in a large proportion of patients with ovarian carcinoma. The elevations of hK6 appear to be relatively specific for ovarian cancer because other malignancies did not cause any increase in the concentration of this biomarker in serum. Serial hK6 measurements appear to correlate with CA125 levels in patients monitored postsurgery. CONCLUSIONS: This is the first report describing significant elevations of hK6 concentration in serum of ovarian cancer patients. These data suggest that hK6 may represent a potential new biomarker for diagnosis and monitoring of ovarian carcinoma.

Biomarkers, Tumor↗

Phase 2 studies of adenosine cardioplegia.

BACKGROUND: Laboratory evidence supports the use of adenosine-supplemented cardioplegia. An initial phase 1 dose-ranging clinical evaluation demonstrated that an adenosine concentration of 15 mumol/L could be safely administered with warm blood cardioplegia and suggested that phase 2 studies were warranted. METHODS AND RESULTS: Two separate double-blind, randomized, placebo-controlled trials were performed in patients undergoing primary, isolated, nonemergent coronary artery bypass graft surgery. Patients were randomized to receive adenosine 15 mumol/L versus placebo in the first study (n = 200) and adenosine 50 or 100 mumol/L versus placebo in the second study (n = 128). Adenosine was infused with both initial and final doses of warm antegrade blood cardioplegia. The data from the 2 trials were combined using the methods of Mantel and Haenszel, and the results of the meta-analysis are presented as the relative risk with their associated 95% confidence intervals (CI). The different study groups were comparable with respect to all preoperative clinical characteristics, angiographic findings, and intraoperative variables. In both trials 1 and 2, no differences were found between groups in the incidence of the individual primary or secondary outcomes. Similarly, when both studies were combined, there was no significant evidence of any consistent treatment benefit (primary: death: relative risk [RR] = 1.02, 95% CI = 0.06, 16.6; myocardial infarction by CK-MB: RR = 0.84, CI = 0.54, 1.31; low output syndrome: RR = 1.38, CI = 0.29, 6.42; any of the above: RR = 0.98, CI = 0.78, 1.25; secondary: Q-wave myocardial infarction: RR = 1.30, CI = 0.41, 4.13; myocardial infarction by troponin T: RR = 0.7, CI = 0.40, 1.21; inotrope requirement: RR = 0.9, CI = 0.46, 1.79; intra-aortic balloon pump requirement: RR = 0.6, CI = 0.07, 4.81; P > 0.20). CONCLUSIONS: Despite promising experimental data, adenosine supplementation of warm blood cardioplegia did not demonstrate any statistically significant benefit in patients undergoing elective coronary artery bypass graft surgery. Although sample sizes were relatively small, based on our interim analyses, it is unlikely that increased patient enrollment would reveal any substantive clinical differences between groups.

Adenosine↗

The safety of topical anaesthetic and analgesic agents in a gel when used to provide pain relief at split skin donor sites.

Post operative pain from split skin donor sites is a recognised problem. This study was carried out to assess the safety of a 'depot' preparation of bupivacaine and ketoprofen when applied to denuded dermis of a split donor site. Two groups of six patients each received either bupivacaine gel (2.5 mg/ml) or ketoprofen gel (1.6 mg/ml). One patient from each group was excluded as protocol was not followed. The mean surface area for bupivacaine was 106 cm2 (range 64-160) and the mean for ketoprofen was 130 cm2 (range 64-180). Blood samples were obtained before application and at 10, 20, 30, 60, 120, 240 and 480 min after application. Serum levels were assayed using Gas Liquid Chromatography and High Pressure Liquid Chromatography. Bupivacaine levels peaked at 120 min, mean level obtained was 0.07 microgram/ml (range 0.03-0.1). Ketoprofen levels also peaked at 120 min and the mean level obtained was 0.20 microgram/ml (range 0.12-0.27). The reported toxic serum level for bupivacaine was 4 micrograms/ml and for ketoprofen is 1128 micrograms/ml. In conclusion, these preparations, when applied to denuded dermis of a split skin donor site, are unlikely to result in toxic levels.

Administration, Cutaneous↗

Family planning in genitourinary medicine: an opportunistic service?

OBJECTIVE: To evaluate and serve the need for contraception in those not using conventional sources of family planning services. SETTING: South London outpatient genitourinary medicine department at King's College Hospital. DESIGN AND SUBJECTS: Prospective study of 200 women seen consecutively in the clinic by the same doctor (LM) during 1993. Women at risk of unwanted pregnancy were identified, and offered immediate contraceptive provision or referral. RESULTS: 15 women (7.5%) were using no contraception, despite being sexually active and not wishing to conceive; of these two presented with an unwanted pregnancy. A further 23 women (11.5%) were not using their chosen contraception effectively, and another 20 women were unclear about contraceptive methods and wanted advice. Young women were most at risk; 14% of those aged 25 years and under were using no contraception. Eight women wished to defer contraceptive advice; of these four defaulted from follow up. Eighteen women (9%) wanted immediate contraceptive supplies. Ten of 18 returned a follow up questionnaire; all these women were satisfied with the contraceptive advice service received. CONCLUSIONS: Absent or ineffective contraception is common in women attending an inner city genitourinary medicine clinic. Immediate provision of contraceptive education, advice and supplies is welcomed by patients.

Adolescent↗

Early cardiorespiratory patterns in patients with major burns and pulmonary insufficiency.

We examined the case records of 50 consecutive patients with major cutaneous burns who required early mechanical ventilation. In 22 patients full haemodynamic and respiratory data were available within 24 h of their injury. Unexpectedly the haemodynamic and oxygen transport patterns of survivors and non-survivors were essentially similar although pulmonary artery occlusion pressure measurements and estimations of net fluid input suggest that non-survivors were relatively underresuscitated compared with survivors. Both groups showed inadequate oxygen utilization in the early stages of their injury despite normal (or above normal) levels of oxygen delivery. Invasive monitoring could possibly help this subgroup of burns patients.

Adult↗

Setting up regional audit in genitourinary medicine and HIV: the south east Thames experience.

Audit at regional level is a useful complement to local audit, especially in small specialties. Regional audit can reduce professional isolation and lead to the development of uniformly high standards in the care given by a variety of providers. The development of regional audit in genitourinary medicine in South East Thames (UK), and of HIV medicine in South Thames, is described. Meetings are held quarterly, and concentrate on standard setting and development of guidelines. Information about the practice of individual units is collected by questionnaire, the results presented, and guidelines developed. Participation in completing questionnaires and attending the meetings is good. Regional guidelines in eleven topics have been produced, and methods of auditing changes in practice are now being assessed. A regional common data-set is being developed to assist in the audit process.

Ambulatory Care↗

Phase I pharmacokinetic study of cyclosporin A combined with doxorubicin.

We performed a phase I trial of cyclosporin A (CsA) in combination with doxorubicin (dox) to determine the maximally tolerated dose (MTD) of the combination in man, to define the quantitative and qualitative toxicities of the combination, and to determine the pharmacokinetics of the two drugs when used together. CsA was administered as a continuous infusion for 6 days, and dox was administered as a single 10-min infusion 24 h after the initiation of CsA. The starting CsA infusion rate was 5 micrograms/kg/min, and the dox starting dose was 30 mg/m2. Courses were administered every 4 weeks with first CsA and then dox being escalated in consecutive cohorts of patients until the MTD was determined. Twenty-three patients and 40 courses were evaluable for toxicity. Pharmacokinetic analysis was performed in 23 patients on the first course for whole blood CsA and plasma dox and doxorubicinol. The MTD of CsA was 6 micrograms/kg/min, and for dox it was 45 mg/m2. Dose-limiting toxicity was neutropenia. Serum creatinine and creatinine clearance did not change over the infusion period. Bilirubin increased from a median of 10 mumol/liter at the initiation of the infusion to a median of 40.4 mumol/liter at the end of the infusion but returned to normal before the next cycle of therapy. Nausea and vomiting were common and marked, whereas thrombocytopenia was mild. Two patients, one with small cell lung cancer and one with breast cancer, had stable disease while receiving treatment for 5 and 6 months, respectively. Mean whole blood steady state concentrations of CsA were 2210 ng/ml during the infusion with total body clearance of 0.177 liter/h/kg. The area under the concentration x time curve (AUC) increased linearly with dose of dox, and total body clearance was independent of dose. The mean total body clearance was 2.46 liters/h/m2, and terminal half-life was 49.6 h. The AUC for dox was greater and clearance was less than has been previously reported at the doses administered in this study. The ratio of AUC for doxorubicinol to AUC for dox was less than expected, suggesting that the metabolism and/or excretion of dox was decreased when administered with CsA. We conclude that dox can be combined with infusioned CsA but at a lower dose than when given alone. This may be due to altered metabolism and/or excretion of dox or increased bone marrow stem cell sensitivity to dox.

Adult↗

Development and validation of a limited sampling strategy for 5-fluorouracil given by bolus intravenous administration.

A wide range of interindividual variability of 5-fluorouracil (5-FU) pharmacokinetics exists after bolus administration. The degree to which this variability in 5-FU exposure impacts upon the response and toxicity of the drug has not been determined. The area under the concentration time curve (AUC) is a commonly used indicator of exposure, but normally requires the collection of 8-10 timed blood samples after i.v. bolus administration. This presents difficulties if large-scale population samplings are required. This study involved the development and testing of a strategy to estimate AUC from a limited number of blood samples in patients with gastrointestinal and breast cancer. The optimal single time point for AUC estimation was 0.17 h (r2 = 0.954). Addition of the 0.75 h time point significantly improved predictability (r2 = 0.983). Addition of a third or fourth time point did not provide further benefit. These models were then tested separately in a group of women who received a higher dose of 5-FU. The two data points model performed significantly better than the single time point model (r2 = 0.70 and 0.85, respectively). The AUC of standard dose 5-FU after bolus administration can be reliably estimated from two timed samples taken 10 and 45 min after injection.

Adult↗

Comparison of intubation following propofol and alfentanil with intubation following thiopentone and suxamethonium.

We have compared a rapid sequence induction of anaesthesia using propofol 2 mg.kg-1 and alfentanil 50 micrograms.kg-1, with a standard technique using thiopentone 5 mg.kg-1 and suxamethonium 1 mg.kg-1. The incidence of complications, and the quality of conditions for intubation, were similar in both groups. The patients receiving propofol and alfentanil showed a significant decrease in blood pressure and heart rate following induction (p < 0.01), whereas the group receiving thiopentone and suxamethonium showed a significant increase in blood pressure and heart rate following induction (p < 0.01). The use of propofol and alfentanil provided a satisfactory alternative to thiopentone and suxamethonium for a rapid sequence induction of anaesthesia.

Adolescent↗