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Biomedical subjects

P M Brown

Publications and source records attributed to P M Brown.

At least 19 recordsLinked to original sources
PubMed2006

Cost-effectiveness analysis of levonorgestrel intrauterine system and thermal balloon ablation for heavy menstrual bleeding.

OBJECTIVE: To compare the cost-effectiveness of levonorgestrel intrauterine system (LNG-IUS) (Mirena; Schering Co., Turku, Finland) and thermal balloon ablation (Thermachoicetrade mark; Gynecare Inc., Menlo Park, CA, USA) for the treatment of heavy menstrual bleeding. DESIGN: An open, pragmatic, prospective randomised trial. SETTING: A menstrual disorders clinic at National Women's Hospital, Auckland, New Zealand. POPULATION: Seventy-nine women with self-defined heavy menstrual bleeding randomised to the LNG-IUS (40 women) or the thermal balloon ablation (39 women). METHODS: Decision tree modelling using primary source data was used to identify the incremental cost-effectiveness of the two treatments. MAIN OUTCOME MEASURES: Direct and indirect costs of medical treatment, including treatment costs, subsequent medical procedures, lost income and medical treatment for failed procedures. The change in quality of life as assessed by the Short Form-36 (SF-36) measured between time of treatment and 24 months was the primary outcome measure. Economic modelling examined the expected cost and outcome for a woman entering each treatment. Sensitivity analysis explored the robustness of the results. RESULTS: The expected cost of treatment was $NZ1241 ($US869) for the LNG-IUS and $NZ2418 ($US1693) for the thermal balloon ablation. The LNG-IUS was associated with an increase of 15 points on the SF-36 scale, compared with 12 points for the thermal balloon ablation. Sensitivity analysis indicates that the results are robust to a 25% decrease in the price of the primary cost drivers and to variations in the rates of failed treatment between the conditions. CONCLUSION: The LNG-IUS would appear to be cost-effective when compared with the thermal balloon ablation for treatment of heavy menstrual bleeding.

Catheterization↗
PubMed2005

Are adjuvant therapies for tonsillectomy evidence based?

Our aim was to ascertain the current practice of adjuvant therapy for tonsillectomy and to determine whether it is evidence based. Anonymized postal questionnaires were sent to all UK otolaryngology consultants registered with the specialty association, and a literature search was performed using relevant search terms in all possible combinations. Among the responders there was little enthusiasm for routine intra-operative local anaesthesia, post-operative topical benzydamine hydrochloride (Difflam) spray or post-operative antibiotics. This is consistent with the lack of robust evidence to support any of these practices. Paracetamol (acetaminophen) is prescribed by almost 90 per cent for post-operative analgesia, and the current literature supports its efficacy and safety. Further, most practitioners combine paracetamol with opioids and/or non-steroidal anti-inflammatory drugs (NSAIDs). Evidence to support the additional use of these agents is, however, non-existent or limited. Some aspects of tonsillectomy care are uniform and evidence based. Others are heterogeneous and suffer from lack of adequate data in the literature.

Acetaminophen↗
PubMed2004

Coronary heart disease risk assessment in diabetes mellitus: comparison of UKPDS risk engine with Framingham risk assessment function and its clinical implications.

AIMS: To assess differences between absolute coronary heart disease (CHD) risks calculated by Joint British Societies (JBS) risk calculator and UKPDS risk engine and its impact on CHD primary prevention management in diabetes mellitus (DM). METHODS: Seven hundred Type 2 DM patients without arterial complications were identified from nine general practices in the Scarborough area. Their absolute 10-year CHD risks were calculated. The differences in the proportion of patients identified for aspirin and statin under JBS and National Institute for Clinical Excellence (NICE) guidelines by these two methods were determined. The proportion of additional patients identified for statin in the Scarborough population as a consequence of CHD risk threshold reduction from 30 to 15% (as recommended by NICE) was also determined. RESULTS: UKPDS risk engine calculated significantly higher mean 10-year CHD risk (UKPDS vs. JBS, 21.5 vs. 18.3%, P < 0.0001). Both methods identified approximately 65% of patients to be eligible for aspirin and statin if NICE recommendations were followed. At a risk threshold of 30%, the UKPDS risk engine identified more patients for statin. Reducing the CHD risk threshold from 30 to 15% for statin initiation will identify an additional 0.5% of the total population for this treatment. CONCLUSIONS: Both methods are comparable in identifying at-risk patients under NICE recommendations. A high proportion has risk levels that merits primary CHD prevention. Lowering the risk threshold for statin treatment has a small numerical impact on the whole population.

Adult↗
PubMed2002

Semiautomated data analysis of flow cytometric estimation of fetomaternal hemorrhage in D- women.

BACKGROUND: Accurate and reliable measurement of the volume of fetal D+ cells in D- women is required for adequate anti-D prophylaxis. A semiautomated flow cytometry assay based on a standardized calibration curve that was created with simulated fetomatemal hemorrhage (FMH) mixtures was developed. STUDY DESIGN AND METHODS: A calibration range of 0.083- to 2-percent D+ cells in the D-RBC mixtures (2-44 mL calculated FMH) was analyzed by use of a flow cytometer (XL-MCL, Coulter Electronics Ltd). Linear regression analysis of the calibration curve data with computer software (Excel, Microsoft) allowed semiautomated determination of the FMH volume. To optimize the assay, fresh versus frozen and thawed RBCs, RBCs from adults who are heterozygous for D or cord RBCs, and indirect- or direct-labeling techniques were evaluated by use of MoAbs. RESULTS: Fresh RBCs from adults heterozygous for D were chosen for routine use, although equivalent calibration curves were obtained with all cells tested (n = 12 calibration assays; r2 = 0.999; mean SD, 14%). A monoclonal anti-D reagent (Therad 10, Diagnostics Scotland) worked well in both indirect-(anti-IgG F(ab)-FITC) and direct-(anti-D-FITC) labeling methods compared to the use of BRAD-3 FITC. In routine practice, the FMH volumes obtained were mainly lower than those obtained in the Kleihauer Betke test when there was less than 4 mL of FMH. CONCLUSION: Semiautomated data acquisition and calibration curve analysis represents a further step toward standardization of flow cytometry for accurate FMH quantification and facilitates evaluation and control of day-to-day variations between laboratories, flow cytometers, and operators.

Antibodies, Monoclonal↗
PubMed2001

Structures underpinning pretend play and word production in young hearing children and children with hearing loss.

Relationships between pretend play and word production were investigated in 10 hearing (H) and 10 toddlers with hearing loss (D) who attended an auditory/oral early intervention program. All children were videotaped interacting in free play with their hearing primary caregiver at 28, 29, and 30 months of age. Group comparisons were made for the scores for highest and mean levels of pretend play and for the underlying structures of decontextualization, decentration, sequencing, and planning. Relationships with word production were then explored for the two groups separately. Results showed significantly higher levels of pretend play for all dimensions for the hearing children and an association between level of pretend play and word production for the children with hearing loss. Associations between word production and sequencing and planning were found for both groups of children. Word production was associated with decontextualization for the hearing children and with decentration for the children with hearing loss. We discuss theoretical implications of the findings together with implications for intervention with toddlers who have hearing loss.

Journal Article↗
PubMed2001

Extension of the therapeutic window for recombinant tissue plasminogen activator with argatroban in a rat model of embolic stroke.

BACKGROUND AND PURPOSE: Argatroban, a specific thrombin inhibitor, has been shown to reduce ischemic lesion size after focal cerebral ischemia in rats. In addition, recombinant tissue plasminogen activator (rtPA) has been shown to reduce ischemic lesion size in both rats and humans if given within 3 hours of symptom onset. We tested the hypothesis that the administration of argatroban with rtPA could extend the treatment window of stroke to 4 hours without increasing gross cerebral hemorrhage rates or reducing efficacy. METHODS: Male Wistar rats were subjected to middle cerebral artery (MCA) occlusion by a single fibrin-rich clot. After embolization, rats were administered argatroban at the following dose levels: 2.08, 6.25, and 18.75 microgram . kg(-1). min(-1). In a second experiment, rats received argatroban (6.25 microgram . kg(-1). min(-1)) or argatroban in combination with rtPA 4 hours after MCA occlusion. Tissue sections were then analyzed for lesion volume, gross hemorrhage and fibrin deposition. RESULTS: The 6.25 microgram. kg(-1). min(-1) dose demonstrated a significant reduction (P<0.05) in lesion volume after 48 hours (27.2+/-6.3%) compared with controls (35.3+/-3.7%). A significant reduction (P<0.05) in lesion volume was observed in the argatroban-plus-rtPA group (17.1+/-10.4%) compared with controls (35.3+/-3.7%). No increase in hemorrhagic transformation was observed. Fibrin deposition in the ipsilateral cortical microvasculature was significantly decreased in the 4-hour combination argatroban-plus-rtPA group compared with the controls (P<0.05). CONCLUSIONS: This study demonstrates that the combination of argatroban and rtPA extends the window of opportunity for treatment of stroke to 4 hours without increasing hemorrhagic transformation.

Animals↗
PubMed1999

Regional left ventricular systolic function in humans during off-pump coronary bypass surgery.

BACKGROUND: Controversy exists as to whether off-pump CABG with local occlusion results in clinically significant myocardial ischemia during the occlusion period. This study was undertaken to delineate the effects of transient local coronary artery occlusion on regional systolic function. METHODS AND RESULTS: Eight consenting patients undergoing left internal mammary to left anterior descending coronary artery (LAD) bypass were instrumented with a left ventricular pressure catheter and 2 subepicardial cylindrical ultrasonic dimension transducers placed in the minor axis dimension in the region served by the LAD. A digital sonomicrometer was used to collect data before, during, and after coronary occlusion from which percent systolic shortening and pressure-dimension loops were derived. Measuring devices were removed immediately after the final time point. All patients tolerated the procedure well, and there were no complications. Average duration of local occlusion needed for CABG was 15.9+/-4.4 minutes (range, 12 to 26 minutes). Local occlusion was associated with a decrease in peak systolic shortening from 5.8+/-0.8% to 1.8+/-0.8%. In all cases, function returned to baseline after restoration of flow. Pressure-dimension loops confirmed these findings and no evidence of diastolic creep. Linear repression analysis of degree of stenosis versus change in segmental shortening revealed a significant inverse correlation. CONCLUSIONS: Local occlusion of the LAD resulted in a transient decrease in myocardial function during occlusion with complete recovery during reperfusion. This change was less significant with increasing degrees of coronary stenosis. These data suggest that local occlusion is not associated with permanent myocardial injury but that ischemic changes do occur that may be clinically significant, especially in patients with lesser degrees of coronary stenosis.

Adult↗
PubMed1999

Autologous superficial femoral vein for aortic reconstruction in infected fields.

Autogenous reconstruction is one option available for patients with aortic graft infection or mycotic aneurysms. We reviewed our recent institutional experience with all patients undergoing aortic reconstruction using autologous superficial femoral vein (SFV). Between February 1995 and November 1997, eight patients (five with prosthetic aortic graft infection and three with mycotic aneurysms, including one ruptured mycotic aneurysm) underwent single-stage aortic reconstruction using autologous SFV. Therapy for graft infection included graft excision and replacement with aortobifemoral or aortofemoral (with subsequent cross femoral) grafts fashioned from the SFV. The two patients undergoing elective repair of mycotic aneurysms were treated with extensive SFV patches, and the patient with a ruptured mycotic aneurysm underwent SFV tube grafting. Autogenous reconstruction of the aorta using the SFV in infected fields shows promise for salvage of life and limb during early experiences and short-term follow-up. Morbidity and mortality rates compare favorably with those from existing series, reconstruction is anatomic, and reinfection potential is low. Long-term follow-up and more extensive experience with this technique are needed to establish its role relative to other conventional methods.

Aged↗
PubMed1999

DNA triple-helix formation on nucleosome core particles. Effect of length of the oligopurine tract.

We have used DNase I footprinting to examine the formation of intermolecular triplexes on DNA fragments which have been complexed with nucleosome core particles. We have prepared five DNA fragments, based on the 160-bp tyrT sequence, which contain different length oligopurine tracts (up to 25 bp) at two different positions along the fragment, and have examined their availability for triple-helix formation after reconstituting onto nucleosome core particles. These results are compared with the formation of shorter triplexes in the same regions. In general we find that increasing the length of the complex does not facilitate nucleosomal triplex formation and that the most important factor affecting triplex formation is the position of the target site within the nucleosome-bound fragment. In some instances we find that longer oligonucleotides inhibit triplex formation. Although successful triplex formation was achieved on the longest nucleosome-bound oligopurine tracts, this was accompanied by changes in cleavage pattern that suggest oligonucleotide-induced changes in nucleosome structure.

Animals↗
PubMed1998

Triple-helix formation at different positions on nucleosomal DNA.

We have prepared a series of seven DNA fragments, based on the 160 base-pair tyrT sequence, which contain 12-14 base-pair oligopurine tracts at different positions, and have examined their availability for triple-helix formation after reconstituting onto nucleosome core particles. By using DNase I footprinting we find that in general, triplexes can only be formed at sites located toward the ends of nucleosomal DNA fragments. For the native fragment, bases 1-145 are in contact with the protein surface. Stable triplexes can be formed on these nucleosome-bound fragments for sites located before position 33 and beyond position 94. These are formed with both CT-containing oligonucleotides, generating parallel triplexes at pH 5.5, and GT-containing oligonucleotides forming antiparallel triplexes at pH 7.5. No antiparallel triplexes were formed at sites located between these positions. Parallel triplexes were also not formed at sites between positions 39-50 and 43-54 with oligonucleotide concentrations as high as 30 microM. However parallel triplex formation was evident at a site between positions 48 and 59, albeit with a reduced affinity compared to free DNA, suggesting that this oligopurine tract is less tightly associated with the nucleosome surface or that it has an altered translational position. The introduction of an oligopurine tract in the vicinity of the nucleosome dyad caused the fragment to adopt a different nucleosomal position, which could be targeted with parallel, but not antiparallel triplexes.

Base Sequence↗
PubMed1998

DNA triple-helix formation on nucleosome-bound poly(dA).poly(dT) tracts.

We have used DNase I and hydroxyl-radical footprinting to examine the formation of intermolecular DNA triple helices on nucleosome-bound DNA fragments containing An.Tn tracts. We found that it is possible to form triplexes on these nucleosome-bound DNAs, but the stability of the complexes depends on the orientation of the A tract with respect to the protein surface. Hydroxyl-radical cleavage of these complexes suggests that the DNA fragments are still associated with the nucleosome. However, the phased cleavage pattern is lost in the vicinity of the triplex, suggesting that the DNA has locally moved away from the protein surface.

Base Sequence↗
PubMed1998

A paradox of cerebral hyperperfusion in the face of cerebral hypotension: the effect of perfusion pressure on cerebral blood flow and metabolism during normothermic cardiopulmonary bypass.

BACKGROUND: The purpose of this study was to determine the impact of perfusion pressure on cerebral blood flow (CBF) and metabolism during normothermic cardiopulmonary bypass (CPB) and after weaning. MATERIALS AND METHODS: Two groups of mongrel dogs were studied (Group A, CPB perfusion at 50 mm Hg, n = 6; and Group B, CPB perfusion at 100 mm Hg, n = 6). All animals underwent 2 h of normothermic bypass at cardiac indexes >2.1 L/min/m2 and were weaned from pump, maintained at pressures >75 mm Hg, and followed for an additional 2 h. RESULTS: In both groups CBF increased over 85% from baseline, in proportion to the hemodilution during the initiation of CPB. Intracranial pressure increased moderately in both groups during CPB, compromising CBF at 1 h in Group A, but not in Group B. The Group A cerebral metabolic rate for oxygen (CMRO2), however, remained unchanged as the percentage of oxygen extraction increased to compensate for the decreased CBF. During recovery, temperature, mean arterial pressure, and cerebral perfusion pressure were not significantly different between the two groups. However, the CBF, percentage of oxygen extracted, and CMRO2 were significantly lower in Group A. CONCLUSIONS: Normothermic CPB initiated with a crystalloid prime and performed at the lower end of a 50-70 mm Hg perfusion window resulted in a highly significant increase in CBF in order to compensate for hemodilution, while at the same time reduced the perfusion pressure available to supply the increased CBF. Together, these two events create a hemodynamic paradox of hyperperfusion in the face of hypotension. The reduction in CMRO2 in Group A is yet to be explained but seems to remain coupled to CBF and could represent a previously undescribed protective mechanism of hibernating cerebral tissue, similar to the phenomena of ischemic preconditioning in the heart, where cerebral tissue is stimulated to lower metabolism in response to inadequate CBF.

Animals↗
PubMed1998

Intraoperative MIDCABG arteriography via the left radial artery: a comparison with Doppler ultrasound for assessment of graft patency.

BACKGROUND: Minimally invasive direct coronary artery bypass grafting involving beating heart left internal mammary artery to left anterior descending coronary artery anastomoses are performed with increasing frequency. Controversy exists regarding the need for intraoperative assessment of graft patency. METHODS: We designed a technique to perform arteriography of the left internal mammary artery by using left radial artery access and standard fluoroscopy to evaluate patency in the operating room. The last 50 of 87 minimally invasive direct coronary artery bypass grafting operations were evaluated by intraoperative arteriography and Doppler ultrasound. Angiograms were performed by the surgeon and involved cannulation and direct injection of contrast medium into the origin of the left internal mammary artery via the left radial artery. RESULTS: Total procedure time was less than 15 minutes. No injuries to the left internal mammary artery were identified. Anastomotic occlusions were identified in 4 cases (8%), 2 of which involved sequential diagonal and left anterior descending anastomoses. These were corrected at the time of surgery with 2 cases requiring conversion to standard coronary artery bypass grafting. Qualitative assessment of grafts with Doppler ultrasound failed to definitively identify these occlusions. There were no deaths and no perioperative infarctions. CONCLUSION: Intraoperative arteriography of the left internal mammary artery can be performed by the surgeon, and a significant number of anastomotic problems may be identified and corrected by using this technique. Therefore, a 100% early graft patency rate may be attainable.

Adult↗
PubMed1998

ENT day surgery in England and Wales--an audit by the Royal College of Surgeons (Eng.) Comparative Audit Service.

An audit of day surgery was carried out by the Royal College of Surgeons (Eng.) Comparative Audit service. Data from 121 respondents on over 3,962 day cases were analysed from both retrospective information and from prospective individual patient proformas. The day surgery rate is 31 per cent. The variability of facilities for day-surgery, the timing of lists, type of anaesthetic used and case-mix are discussed. Outcome and the reasons for admission to an overnight bed are analysed. The overall admission rate was found to be 2.8 per cent (range 0.6-19.5 per cent between consultants). Seventy per cent of ENT day-surgery was performed on morning lists which have a lower admission rate than afternoon lists. The main reasons for admission are vomiting 30 per cent, haemorrhage 20 per cent and inadequate recovery from anaesthetic 22 per cent. A more detailed analysis of reasons for admission were given for tonsillectomy, adenoidectomy, FESS, and grommets. Recommendations are given which might increase the scope of safe day-surgery and reduce admission rate.

Aged↗
PubMed1998

Unmet needs of remand prisoners.

A needs assessment protocol which examines 11 problem areas was devised. This was administered to 277 prisoners on remand at Brixton Prison. We found high levels of unmet need for housing, treatment of substance abuse and neurotic symptoms. Twenty-nine per cent were transferred to hospital under the provisions of the Mental Health Act and about a third of those at liberty to do so complied with a discharge plan. Diversion and discharge planning can potentially meet the unmet needs of remand prisoners.

Adult↗
PubMed1997

Duodenal obstruction in thyroid storm.

A 35-year-old, previously healthy woman, known to be thyrotoxic, was transferred from a community hospital for "acute abdomen." Abdominal pain, distention, and hyperemesis resolved with placement of nasogastric tube (NGT) and return of 2,600 mL of bilious fluid. Continued high NGT output made oral or NGT administration of antithyroid drugs impossible. We gave propylthiouracil (PTU) by retention enemas with therapeutic serum levels and sublingual saturated solution of potassium iodide (SSKI) with 70% absorption based on 24-hour free iodine urinary excretion. The patient's thyroxine (T4) and triiodothyronine (T3) radioimmunoassays were normal on hospital days 10 and 12, respectively. However, free T4 and T3 resin uptake did not normalize until hospital day 31. On hospital day 32, she tolerated removal of NGT without nausea and 4 days later was taking a regular diet. We conclude that our patient's gastrointestinal symptoms were a prominent feature of her thyrotoxicosis and that rectal PTU and sublingual SSKI are effective in administration of antithyroid drugs.

Abdomen, Acute↗