Biomedical subjects

M Robinson

Publications and source records attributed to M Robinson.

At least 37 records · Page 2Linked to original sources

PubMed2004

Frequency analyses of gastric pH in control and gastro-oesophageal reflux disease subjects treated with a proton-pump inhibitor.

BACKGROUND: We are unaware of any solid theoretical or pathophysiological basis for selecting pH 4 or any other pH value to assess gastric acidity. AIM: To examine the frequency of different gastric pH values in control and GERD subjects. METHODS: Gastric pH was measured for 24 h in 26 control subjects, 26 gastro-oesophageal reflux disease subjects at baseline and the same 26 gastro-oesophageal reflux disease subjects during treatment with a proton-pump inhibitor. Histograms were constructed using the 21 600 values generated from each recording and bins of 0.25 pH units. RESULTS: The distribution of gastric pH values in gastro-oesophageal reflux disease subjects was significantly different from that in controls and in some instances the distributions detected significant differences that were not detected by integrated acidity. Proton-pump inhibitor treatment significantly altered the distribution of gastric pH values and the nature of this alteration during the postprandial period was different from that during the nocturnal period. Using time pH< or =4 can significantly underestimate the magnitude of inhibition of gastric acidity caused by a proton-pump inhibitor. CONCLUSIONS: The distribution of gastric pH values provides a rationale for selecting a particular pH value to assess gastric acidity. In some instances, the distribution of gastric pH values detects significant differences between gastro-oesophageal reflux disease and normal subjects that are not detected by integrated acidity.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2004

Scale and corrosion control with combined dolomite/calcite filter.

Water quality is a major operational issue for boiler operation and control. If the water is hard scale control is required and if it is soft then corrosion control is an issue. Here a two stream boiler test rig has been used to test the effect a fixed bed filter has on the scaling and corrosion properties of both hard and soft waters. The filter effectively controlled the pH, hardness and alkalinity of both waters leading to significant decreases in scale formation and effective control of corrosion.

Calcium Carbonate↗

PubMed2003

The basis for the decreased response to proton pump inhibitors in gastro-oesophageal reflux disease patients without erosive oesophagitis.

BACKGROUND: The reason why heartburn in gastro-oesophageal reflux disease subjects without oesophagitis is less responsive to proton pump inhibitors than heartburn in those with erosive oesophagitis is not known. METHODS: Gastric and oesophageal pH were determined in 26 subjects with gastro-oesophageal reflux disease at baseline and on days 1, 2 and 8 of treatment with 20 mg omeprazole or 20 mg rabeprazole in a randomized, two-way cross-over fashion. The presence or absence of erosive oesophagitis at baseline was documented by upper gastrointestinal endoscopy. RESULTS: At a given value of the integrated gastric acidity during treatment with a proton pump inhibitor, the probability of pathological oesophageal reflux was significantly higher in subjects with no oesophagitis than in those with erosive oesophagitis. This occurred because the post-prandial gastric acidity in subjects with no oesophagitis showed a decreased response to the antisecretory agent. CONCLUSIONS: Compared with gastro-oesophageal reflux disease subjects with erosive oesophagitis, those with no oesophagitis are relatively refractory to the pharmacodynamic effects of proton pump inhibitors on the post-prandial integrated gastric acidity.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2003

Heartburn severity can predict pathologic oesophageal reflux in gastro-oesophageal reflux disease patients treated with a proton-pump inhibitor.

BACKGROUND: In gastro-oesophageal reflux disease (GERD) subjects treated with a gastric anti-secretory agent, it is not known whether there is a relationship between heartburn severity and oesophageal acid exposure. METHODS: Oesophageal pH and heartburn severity were determined in 27 GERD subjects at baseline and on days 1, 2 and 8 of treatment with 20 mg omeprazole or 20 mg rabeprazole in a randomized, two-way crossover fashion. RESULTS: Receiver operating characteristic (ROC) analysis was used to determine values for heartburn severity that gave optimal cut-off points for distinguishing between normal and pathologic oesophageal reflux. Using these cut-off points, we found that the probability of no pathologic oesophageal reflux (Y) could be best fitted by an exponential equation: Y = a(e-bX) + c, where a, b and c are constants and X is the value of heartburn severity. There was close agreement between predicted and observed percentages of subjects with pathologic oesophageal reflux during different days of treatment. CONCLUSIONS: In GERD subjects treated with a proton-pump inhibitor, the value of heartburn severity following a single standard meal can predict the likelihood of pathologic oesophageal reflux over the entire 24-h period.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2003

Determination of the reduction in gastric acidity necessary to prevent pathological oesophageal reflux in patients with gastro-oesophageal reflux disease treated with a proton pump inhibitor.

BACKGROUND: In subjects with gastro-oesophageal reflux disease treated with a gastric antisecretory agent, the extent to which gastric acidity needs to be reduced to prevent pathological oesophageal acid exposure is not known. METHODS: Gastric and oesophageal pH were measured in 26 healthy subjects and in 59 subjects with gastro-oesophageal reflux disease. In 27 of the subjects with gastro-oesophageal reflux disease, pH was also recorded on days 1, 2 and 8 of treatment with 20 mg omeprazole and 20 mg rabeprazole in a randomized, two-way, cross-over fashion. RESULTS: Receiver operating characteristic analysis was used to determine values for the integrated oesophageal acidity and time oesophageal pH<or=4 that gave optimal cut-off points for distinguishing between normal and pathological oesophageal reflux. Using these cut-off points, we found that the probability of no pathological oesophageal reflux (Y) could be best fitted by an exponential equation, Y = a(e-bX) + c, where a, b and c are constants and X is the value of the integrated gastric acidity. There was close agreement between the predicted and observed percentages of subjects with pathological oesophageal reflux during different days of treatment. CONCLUSIONS: In subjects with gastro-oesophageal reflux disease treated with a proton pump inhibitor, the value of the integrated gastric acidity can predict the likelihood of pathological oesophageal reflux.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2003

Meal-stimulated gastric acid secretion and integrated gastric acidity in gastro-oesophageal reflux disease.

BACKGROUND: No current methods exist to determine meal-stimulated gastric acid secretion in humans under conditions that approximate those of daily living with the ingestion of breakfast, lunch and dinner. METHODS: Gastric and oesophageal pH were measured in 26 healthy subjects and in 59 subjects with gastro-oesophageal reflux disease. Meal-stimulated gastric acid secretion was calculated from the buffer capacity of the meals determined in vitro and from the time required for the gastric pH to decrease to pH 2 in vivo following ingestion of the meal. RESULTS: There was a significant correlation between gastric secretion with each meal and the corresponding post-prandial integrated gastric acidity. There was also a significant correlation between meal-stimulated gastric secretion and integrated gastric acidity from 09.00 to 22.00 h in both subjects with gastro-oesophageal reflux disease and controls. In subjects with gastro-oesophageal reflux disease, gastric secretion and integrated gastric acidity from 09.00 to 22.00 h were significantly higher than those in controls. There was a significant correlation between oesophageal acidity and integrated gastric acidity from 09.00 to 22.00 h in subjects with gastro-oesophageal reflux disease. CONCLUSIONS: As post-prandial gastric acidity is increased in subjects with gastro-oesophageal reflux disease, it seems likely that increased gastric acidity is an important aetiological factor in this disease.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2003

The effect of anti-integrin monoclonal antibodies on antigen-induced pulmonary inflammation in allergic rabbits.

The integrin adhesion molecules are involved in the recruitment and activation of inflammatory cells at sites of inflammation in a variety of diseases. In the present study, we have investigated the effects of blocking monoclonal antibodies (mAbs) directed against CD49d (alpha(4) integrin), CD18 (beta(2) integrin) and the alpha sub-units of beta(2) integrin CD11a (LFA-1 integrin) and CD11b (Mac-1 integrin), on antigen (Ag)-induced acute bronchoconstriction and cellular recruitment in allergic rabbits in vivo. Inhaled Ag (Alternaria tenuis) challenge of neonatally sensitised rabbits caused an acute bronchoconstriction demonstrated by an increase in lung resistance (R(L)) and decrease in dynamic compliance (C(dyn)) and pulmonary inflammation characterised by an increase in bronchoalveolar lavage (BAL) inflammatory cells, particularly eosinophils, 24 h after challenge. Pre-treatment with the anti-CD49d mAb (Max-68P), significantly inhibited the Ag-induced acute bronchoconstriction in terms of R(L) and (C(dyn)). Treatment with the other anti-integrin mAbs had no effect on the acute bronchoconstriction after inhaled Ag challenge.Pre-treatment with the anti-integrin mAbs had differential effects in blocking the recruitment of inflammatory cells 24 h after inhaled Ag in the allergic rabbits. The data show that in the allergic rabbit model of asthma, VLA-4 (CD49d/CD29) only, is involved in the acute bronchoconstriction, suggesting an involvement of mast cell degranulation. Furthermore, eosinophil recruitment and activation appears to be mediated by a combination of VLA-4 (CD49d/CD29) and LFA-1 (CD18/CD11a). However in contrast, lymphocyte recruitment appears to be mediated by a combination of LFA-1 (CD18/CD11a) and Mac-1 (CD18/CD11b).

Airway Obstruction↗

PubMed2003

ICP34.5 deleted herpes simplex virus with enhanced oncolytic, immune stimulating, and anti-tumour properties.

Herpes simplex virus type-1 (HSV1) in which the neurovirulence factor ICP34.5 is inactivated has been shown to direct tumour-specific cell lysis in several tumour models. Such viruses have also been shown to be safe in Phase I clinical trials by intra-tumoral injection in glioma and melanoma patients. Previous work has used serially passaged laboratory isolates of HSV1 which we hypothesized may be attenuated in their lytic capability in human tumour cells as compared to more recent clinical isolates. To produce ICP34.5 deleted HSV with enhanced oncolytic potential, we tested two clinical isolates. Both showed improved cell killing in all human tumour cell lines tested compared to a laboratory strain (strain 17+). ICP34.5 was then deleted from one of the clinical isolate strains (strain JS1). Enhanced tumour cell killing with ICP34.5 deleted HSV has also been reported by the deletion of ICP47 by the up-regulation of US11 which occurs following this mutation. Thus to further improve oncolytic properties, ICP47 was removed from JS1/ICP34.5-. As ICP47 also functions to block antigen processing in HSV infected cells, this mutation was also anticipated to improve the immune stimulating properties of the virus. Finally, to provide viruses with maximum oncolytic and immune stimulating properties, the gene for human or mouse GM-CSF was inserted into the JS1/34.5-/47- vector backbone. GM-CSF is a potent immune stimulator promoting the differentiation of progenitor cells into dendritic cells and has shown promise in clinical trials when delivered by a number of means. Combination of GM-CSF with oncolytic therapy may be particularly effective as the necrotic cell death accompanying virus replication should serve to effectively release tumour antigens to then induce a GM-CSF-enhanced immune response. This would, in effect, provide an in situ, patient-specific, anti-tumour vaccine. The viruses constructed were tested in vitro in human tumour cell lines and in vivo in mice demonstrating significant anti-tumour effects. These were greatly improved compared to viruses not containing each of the modifications described. In vivo, both injected and non-injected tumours showed significant shrinkage or clearance and mice were protected against re-challenge with tumour cells. The data presented indicate that JS1/ICP34.5-/ICP47-/GM-CSF acts as a powerful oncolytic agent which may be appropriate for the treatment of a number of solid tumour types in man.

Animals↗

PubMed2003

The safety and efficacy of indinavir and ritonavir (400/400 mg BID) in HIV-1-infected individuals from an inner-city minority population: a pilot study.

We evaluated the safety and efficacy of indinavir 400 mg and ritonavir 400 mg twice daily (RIT/IND 400/400) in HIV-1-infected individuals, using an open label, proof of concept study. All patients received indinavir 400 mg and ritonavir 400 mg twice daily. Patients were followed up to 48 weeks. Nineteen subjects were enrolled, 11 (58%) men and eight (42%) women. The majority were American Black (nine; 47%) or Haitian (eight; 42%). The median baseline plasma HIV-1 viral load (VL) was 5.13 log10 copies/mL and the median CD4 cell count was 112 cells/mm(3). The proportion of compliant patients with VL <400 copies/mL at week 24 was 60% compared with 0% for non-compliant patients (P=0.011 [intent-to-treat] or P=0.085 [on-treatment]). VL at week 4 predicted week 24 VL response. Compliant patients had a median average CD4 cell count increase of 83.2 cells/mm(3) compared with 42.0 cells/mm(3) for non-compliant patients (P=0.010). The median average changes in triglycerides and cholesterol were significantly higher in compliant patients. This is a potent, safe combination for the treatment of HIV-1. VL at week 4 is predictive of viral outcome at week 24. Fasting serum cholesterol and triglycerides were significantly elevated during the study.

Black People↗

PubMed2002

Melatonin improves deferoxamine antioxidant activity in protecting against lipid peroxidation caused by hydrogen peroxide in rat brain homogenates.

Deferoxamine (DF) is an antioxidant molecule because of its ability to chelate iron. This study compared the ability of DF alone or in combination with melatonin, 5-methoxytryptophol or pinoline in preventing lipid peroxidation due to hydrogen peroxide (H(2)O(2)) in rat brain homogenates. Malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) in the homogenates were measured as indices of lipid peroxidation. Incubation of homogenates with DF reduced, in a dose-dependent manner, MDA+4-HDA formation due to H(2)O(2). When melatonin, 5-methoxytryptophol or pinoline were added to the incubation medium, the efficacy of DF in preventing lipid peroxidation was enhanced. These cooperative effects between DF, melatonin, and related pineal products may be important in protecting tissues from the oxidative stress due to iron overload.

Animals↗

PubMed2002

Integrated acidity and rabeprazole pharmacology.

BACKGROUND: Integrated gastric and oesophageal acidity can be calculated from measurements of gastric and oesophageal pH and used to quantify gastric and oesophageal acidity over time. Rabeprazole is a new proton pump inhibitor that is effective in treating gastro-oesophageal reflux disease (GERD). AIM: To use measurement of integrated gastric and oesophageal acidity to determine the onset, duration and overall effect of rabeprazole in subjects with GERD. METHODS: Subjects with GERD were required to have oesophageal pH less-than-or-equal 4 for at least 10% of a 24-h recording. Effects of 20 mg rabeprazole on 24-h gastric and oesophageal pH were measured on days 1 and 7 of dosing. Integrated gastric and oesophageal acidity were calculated from time-weighted average hydrogen ion concentrations at each second of the 24-h record. RESULTS: At steady-state, 20 mg rabeprazole inhibited gastric acidity by 89% and oesophageal acidity by 95%. The first dose of rabeprazole inhibited gastric and oesophageal acidity by at least 70% of the steady-state effect. Oesophageal acidity could be divided into monophasic and biphasic patterns, and rabeprazole had different effects on oesophageal and gastric acidity in these two GERD subpopulations. The onset of action of the first dose of rabeprazole on gastric acidity was 4 h and on oesophageal acidity was 4 h in monophasic subjects and 7 h in biphasic subjects. Integrated acidity was more sensitive than time pH less-than-or-equal 4 in measuring the inhibitory actions of rabeprazole. CONCLUSIONS: Integrated gastric and oesophageal acidity are quantitative measurements that provide useful and novel information regarding the pathophysiology of GERD as well as the impact of antisecretory agents such as rabeprazole.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2002

Effects of antacid formulation on postprandial oesophageal acidity in patients with a history of episodic heartburn.

BACKGROUND: Heartburn self-treatment with antacids is extremely common. If the oesophagus is the primary site of antacid action, chewable antacids might raise the oesophageal pH more effectively than swallowable tablets. AIM: To establish a model to assess postprandial acid reflux and to compare the onset and duration of action on oesophageal pH of different antacid formulations. METHODS: Twenty subjects with a history of episodic heartburn underwent eight pH monitoring sessions each for 5.5 h postprandially. One hour after consuming a meal consisting of chili, cheese, raw onions and cola, subjects received 750 mg, 1500 mg and 3000 mg of either chewable or swallowable CaCO3 tablets, an effervescent bicarbonate solution or placebo. Oesophageal and gastric pH data were collected. RESULTS: Mean intra-oesophageal pH remained lower than baseline for more than 1 h (pH range 5-5.5) postprandially, indicating reflux of somewhat acidic intragastric contents into the oesophagus. The onset of action on oesophageal pH was similar for all antacids (30-35 min). The duration of action on pH varied: chewable tablets and effervescent bicarbonate had relatively long durations of action (oesophagus, 40-45 min; stomach, 100-180 min); swallowable tablets had little effect. CONCLUSIONS: The meal model used in this study dependably produced acidic gastro-oesophageal reflux. Antacids increased oesophageal pH independent of gastric pH, demonstrating that chewing antacids controls oesophageal acidity more effectively than swallowing antacid tablets.

Adult↗

PubMed2002

Onset of symptom relief with rabeprazole: a community-based, open-label assessment of patients with erosive oesophagitis.

BACKGROUND: In numerous clinical trials, proton pump inhibitors have demonstrated potent acid suppression and healing of erosive oesophagitis, as well as successful symptom relief for the entire spectrum of gastro-oesophageal reflux disease. AIM: The 'Future of Acid Suppression Therapy' (FAST) trial evaluated, in actual clinical practice, the timing of symptom relief, changes in symptom severity, health-related quality of life and safety in endoscopically confirmed erosive gastro-oesophageal reflux disease treated with rabeprazole. METHODS: This open-label, multicentre study enrolled 2579 patients to receive rabeprazole treatment using 20 mg once daily for 8 weeks. Between two clinical visits (at enrollment and week 8), patients used an interactive voice response system to rate gastro-oesophageal reflux disease symptoms. Subgroup analyses of efficacy were conducted for gender, age, Hetzel-Dent grade, presence of Barrett's oesophagus and for patients reporting previously ineffective symptom relief with omeprazole or lansoprazole. RESULTS: On day 1, rabeprazole significantly decreased daytime and night-time heartburn severity, regurgitation and belching. Complete relief of daytime and night-time heartburn was achieved in 64.0% and 69.2% of symptomatic patients, respectively, on day 1, and in 81.1% and 85.7% of patients, respectively, on day 7. Patients with moderate or severe heartburn symptoms at baseline achieved an even greater degree of satisfactory symptom relief (none or mild) from day 1 onwards. The median time to satisfactory heartburn relief was 2 days. Subgroup analyses showed no consistent differences in efficacy compared to the overall population treated. Health-related quality of life in patients was significantly lower than that of the US general population and improved significantly after 8 weeks of rabeprazole therapy. Rabeprazole was well tolerated, with headache as the most common adverse event, reported by less than 2% of the study population. CONCLUSIONS: In this large, open-label trial, rabeprazole rapidly and effectively relieved gastro-oesophageal reflux disease symptoms in most patients with erosive oesophagitis. Substantial symptom relief was noted on day 1; improvement continued over the first week and at week 4. By week 8, the health-related quality of life had also improved vs. baseline.

2-Pyridinylmethylsulfinylbenzimidazoles↗

PubMed2002

Determination of the time of onset of action of ranitidine and famotidine on intra-gastric acidity.

BACKGROUND: No standard methods exist for determining the onset of action of gastric antisecretory agents in human subjects. METHODS: Intragastric pH was measured when placebo, ranitidine 150 mg, ranitidine 75 mg or famotidine 10 mg were administered 30 min after the end of a meal. RESULTS: When the onset of action was defined as the earliest time that mean gastric pH with active treatment was statistically significantly higher (P < 0.05) than the corresponding placebo value, the onsets of action of ranitidine 75 mg and 150 mg were 55 min, and of famotidine 10 mg, 90 min. When onset was defined in terms of a particular decrease in gastric acid concentration for the group as a whole or for individual subjects, there was an important variation in the relative times of onset of ranitidine 75 mg and famotidine 10 mg. CONCLUSIONS: When administered after a meal, the onset of action of ranitidine and famotidine on gastric pH can be determined for individual subjects as well as for the group as a whole. When onset was determined for the group using statistical significance, which does not depend on arbitrary cut-off points, ranitidine 75 mg had an earlier onset of action than did famotidine 10 mg.

Adolescent↗

PubMed2002

Cisapride inhibits meal-stimulated gastric acid secretion and post-prandial gastric acidity in subjects with gastro-oesophageal reflux disease.

BACKGROUND AND AIMS: KCNQ1 potassium channels in human gastric parietal cells are thought to be involved in gastric acid secretion. As cisapride can inhibit similar channels in other tissues and is an effective treatment for nocturnal heartburn, we examined the effects of cisapride on gastric and oesophageal acidity, gastric emptying and heartburn severity in subjects with gastro-oesophageal reflux disease. METHODS: Subjects (n = 11) had suffered from heartburn four times or more per week for at least 6 months. Gastric pH and oesophageal pH were measured before, during and after a standard meal ingested over 15 min. Each subject received placebo or 10 mg cisapride orally, 30 min before the beginning of the meal. Meal-stimulated gastric acid secretion was calculated from the amount of HCl required to titrate the homogenized standard meal to pH 2 in vitro and the time required for the pH of the ingested meal to decrease to pH 2 in vivo. Heartburn severity was assessed at 15-min intervals beginning at the end of the meal. Gastric emptying of solids was measured using a [(13)C]-octanoic acid breath test. RESULTS: Cisapride significantly decreased meal-stimulated gastric acid secretion by 20%, decreased integrated gastric and oesophageal acidity by 50-60% and transiently increased the expiration of (13)CO(2). Cisapride did not significantly alter heartburn severity. CONCLUSIONS: The cisapride-induced decreases in meal-stimulated gastric acid secretion, gastric acidity and oesophageal acidity in subjects with gastro-oesophageal reflux disease can account for its beneficial clinical effects. These results also raise the possibility that gastric KCNQ1 potassium channels are important in meal-stimulated gastric acid secretion and possibly in the pathophysiology of gastro-oesophageal reflux disease.

Adult↗

PubMed2002

Clinical effectiveness of a new antacid chewing gum on heartburn and oesophageal pH control.

BACKGROUND: Oesophageal acid neutralization with antacids depends on the duration of oesophageal antacid exposure and acid neutralizing capacity. A gum that releases antacid as it is chewed could take advantage of both mechanisms to enhance heartburn relief. METHODS: Twenty-four subjects were crossed over to four regimens: placebo, chewable antacid tablets (1000 mg CaCO3), lower dose gum (600 mg CaCO3) and higher dose gum (900 mg CaCO3). A dual pH probe was placed, subjects ate a standardized provocative meal and self-dosed once as needed. Symptoms were recorded every 15 min using visual analogue and Likert scales. RESULTS SYMPTOMS: Both gums decreased heartburn compared to placebo for 120 min. Higher dose gum decreased heartburn more than chewable antacids up to 120 min post-dose. pH: Active chewable antacid and gums immediately increased oesophageal pH, with significant improvement 15-30 min post-dose. SUMMARY: (i) both gums promptly decreased heartburn and elevated oesophageal pH; (ii) both gums provided sustained relief for 120 min; (iii) antacid gums provided faster and more prolonged symptom relief and pH control than chewable antacids. CONCLUSIONS: Calcium carbonate gum effectively neutralizes oesophageal acidity and relieves symptoms following a meal, and is superior to chewable antacids in terms of the duration of heartburn relief.

Adolescent↗

PubMed2002

The PFA-100: a potential rapid screening tool for the assessment of platelet dysfunction.

The PFA-100 is a device that simulates high shear dependent platelet function in vitro and thus is particularly useful for screening for von Willebrand's disease (VWD). The aim of this study was to assess the overall potential of the PFA-100 as a primary clinical screening tool using the wide spectrum of clinical samples assessed for platelet function within our institution. The PFA-100 test was performed using both collagen/ADP (CADP) and collagen/epinephrine (CEPI) cartridges on samples from 337 patients with a wide variety of haemostatic defects. One hundred and eighty-two patients were defined as having normal platelet function based on classical laboratory tests and von Willebrand factor levels. The overall clinical sensitivity of the PFA-100 for platelet abnormalities (including VWD) was 81% for CADP and 86% for CEPI. The overall specificity was found to be 82% for CADP and 80% for CEPI. When utilizing both cartridges in combination (with both results either higher or lower than the upper cutoff of the normal ranges), the overall false positive and false negative rates were 12% and 6%, respectively. The PFA-100 proved to be sensitive in detecting classical defects by giving prolonged closure times in samples from patients with major platelet function defects (e.g. von Willebrand's disease, Glanzmann's thrombasthenia and Bernard Soulier syndrome). However, there were a small number of false negative results (6%) obtained with various milder platelet defects (e.g. Hermansky Pudlak syndrome, storage pool and release defects, type I VWD and macrothrombocytopenia). The PFA-100 test provides a useful rapid screening tool and should increase the efficiency and reduce the cost of the routine diagnosis of platelet dysfunction.

Adenosine Diphosphate↗

PubMed2002

The Leeds University Maternity Audit Project.

OBJECTIVES: To measure levels of and changes in compliance with evidence-based recommendations in obstetrics in the UK. To identify barriers to and factors associated with compliance. DESIGN: A quantitative case-note audit for 1988 and 1996, and a qualitative interview study of key staff. SETTING: Twenty maternity units, selected at random from all UK units SUBJECTS: Fifty consecutive cases of pre-term delivery (PTD), Caesarean section (CS), instrumental delivery (ID), and perineal repair (PR) operations in each period in each unit. The lead clinician, midwifery manager, a senior midwife, neonatologist, and middle-grade obstetrician in each unit. MAIN OUTCOME MEASURES: Maternal steroid use in PTD, antibiotic use in CS, use of the ventouse (vacuum extractor) rather than forceps as instrument of first choice for ID, and use of polyglycolic acid (PGA) sutures for PR in each time period. Facilities for implementing, staff attitudes to, and the degree of planning to follow each recommendation. MAIN RESULTS: The median proportion of ventouse as instrument of first choice in each unit was 8% (range 0-32%) in 1988, rising to 64% (range 0-98%) in 1996. PGA use for PR was 0% (range 0-30%) in 1988, and 72% (range 0-100%) in 1996. Steroid use for eligible PTD was median 0% (range 0-23%) in 1988, rising to 82% (range 63-95%) in 1996. Antibiotic use for CS was 7% (range 0-25%) rising to 84% (range 10-100%) in 1996. There was no relationship between unit size, type of unit, facilities, staff attitudes or degree of planning, and compliance with the recommendations, nor was the level of adherence to one standard typically correlated with adherence to the others. However, there was a positive correlation (R = 0.6, P < 0.005) between local availability of the Cochrane database of perinatal trials and unit compliance with the audit standards in the latter time period. CONCLUSIONS: We have documented a massive shift in practice in line with the evidence, although many units still have substantial room for improvement. About 2000 wound infections, 200 deaths due to prematurity, nearly 8000 women in pain from catgut sutures, and 1500 cases of severe perineal trauma from forceps remain preventable. The reasons why units vary remain obscure, although the qualitative interviews often revealed local factors such as key enthusiastic staff. There was no sign of evidence being positively driven into practice by any systematic managerial process. The relationship between Cochrane availability and high-standard care may be simply a marker of commitment to the evidence, but it remains plausible that if senior staff make Cochrane available for their juniors, audit compliance improves.

Adult↗