Granisetron (Kytril) suppresses methotrexate-induced nausea and vomiting among patients with inflammatory arthritis and is superior to prochlorperazine (Stemetil). (33/3693)

OBJECTIVE: Methotrexate (MTX) is an increasingly popular anti-rheumatic drug with its usefulness limited by toxicity, most commonly gastrointestinal (GI). The aim of the study was to study the effectiveness of the 5-HT3 receptor antagonist granisetron (GR) in the therapy of MTX-induced nausea. METHODS: A single-blind 8 week pilot study with random allocation to either GR 1 mg or prochlorperazine (Stemetil; PCh) 10 mg was undertaken in 13 patients who were taking or had taken MTX for either rheumatoid arthritis (10) or psoriatic arthritis (3). RESULTS: One in six patients treated with PCh completed the 8 week study compared to 7/7 treated with GR. After switching of symptomatic patients, 11 completed the study on GR and median improvement was by two grades (P < 0.001) with a significantly better visual analogue scale score for patient satisfaction compared to PCh. CONCLUSION: Treatment with GR may be useful in establishing and maintaining some patients on MTX where GI toxicity would have precluded such therapy.  (+info)

Randomised trial of two pharmacological methods of bowel preparation for day case colonoscopy. (34/3693)

AIMS: To undertake a prospective, single blind, randomised trial comparing the efficacy and tolerance of two outpatient colonoscopy bowel preparation regimens. METHODS: Patients aged between 18 months and 16 years being admitted for day case colonoscopy were allocated randomly to receive either Picolax (an oral, sugar free powder containing sodium picosulphate 10 mg/sachet with magnesium citrate) and clear fluids or bisacodyl tablets with an unrestricted diet and a phosphate enema just before colonoscopy. Patient compliance, bowel frequency, and associated symptoms were recorded, and the adequacy of the bowel preparation was assessed in a blinded manner. RESULTS: 63 of 66 patients completed the trial. Mean age, mean weight, extent of colonoscopy, and distribution of underlying pathology were similar in both groups. Bowel preparation was good or excellent in all of the patients in the Picolax group (n = 32) compared with 22 patients in the bisacodyl/phosphate enema group (n = 31). The latter group experienced more abdominal discomfort during bowel preparation but three of the Picolax group vomited and the lack of solid food distressed some children. CONCLUSIONS: All bowel preparation methods have limitations and unpleasant side effects but the use of Picolax and clear fluids proved superior to bisacodyl tablets and a phosphate enema in children undergoing day case colonoscopy.  (+info)

A randomised controlled trial of specialist health visitor intervention for failure to thrive. (35/3693)

AIMS: To determine whether home intervention by a specialist health visitor affects the outcome of children with failure to thrive. METHODS: Children referred for failure to thrive were randomised to receive conventional care, or conventional care and additional specialist home visiting for 12 months. Outcomes measured were growth, diet, use of health care resources, and Bayley, HAD (hospital anxiety and depression), and behavioural scales. RESULTS: Eighty three children, aged 4-30 months, were enrolled, 42 received specialist health visitor intervention. Children in both groups showed good weight gain (mean (SD) increase in weight SD score for the specialist health visitor intervention group 0.59 (0.63) v 0.42 (0.62) for the control group). Children < 12 months in the intervention group showed a higher mean (SD) increase in weight SD score than the control group (0.82 (0.86) v 0.42 (0.79)). Both groups improved in developmental score and energy intake. No significant differences were found for the primary outcome measures, but controls had significantly more dietary referrals, social service involvement, and hospital admissions, and were less compliant with appointments. CONCLUSIONS: The study failed to show that specialist health visitor intervention conferred additional benefits for the child. However, the specialist health visitor did provide a more coordinated approach, with significant savings in terms of health service use. Problems inherent to health service research are discussed.  (+info)

Can paediatric medical students devise a satisfactory standard of examination for their colleagues? (36/3693)

OBJECTIVES: To determine what standard paediatric medical students would set for examining their peers and how that would compare with the university standard. DESIGN: Single blinded computer marked examination with questionnaire. SETTING: University medical school. SUBJECTS: Medical students during their final paediatric attachment. INTERVENTIONS: Medical students asked to derive 10, five branch negatively marked multiple choice questions (MCQs) to a standard that would fail those without sufficient knowledge. Each 10 were then assessed by another student as to the degree of difficulty and the relevance to paediatrics. One year later student peers sat a mock MCQ examination derived from a random 40 questions (unaware that the mock MCQs had been derived by peers). MAIN OUTCOME MEASURES: Comparison of marks obtained in mock and final MCQ examinations; student perception of the standard in the two examinations assessed by questionnaire. RESULTS: 44 students derived 439 questions, of which 83% were considered an appropriate standard by a classmate. One year later 62 students sat the mock examination. Distribution of marks was better in the mock MCQ examination than the final MCQ examination. Students considered the mock questions to be a more appropriate standard (72% v 31%) and the topics more relevant (88% v 64%) to paediatric medical students. Questions were of a similar clarity in both examinations (73% v 78%). CONCLUSIONS: Students in this study were able to derive an examination of a satisfactory standard for their peers. Involvement of students in deriving examination standards may give them a better appreciation of how standards should be set and maintained.  (+info)

Correlation of imaging techniques to histopathology in patients with diabetic foot syndrome and clinical suspicion of chronic osteomyelitis. The role of high-resolution ultrasound. (37/3693)

OBJECTIVE: To investigate the role of ultrasound in the diagnosis of osteomyelitis in the diabetic foot compared with magnetic resonance imaging (MRI), bone scintigraphy (BS), and plain film radiography (PFR). RESEARCH DESIGN AND METHODS: We investigated 19 consecutive diabetic patients (2 women, 17 men, age 60.7 +/- 9.8 years, BMI 27.0 +/- 3.8 kg/m2) with clinical suspicion of bone infection of the foot. A high-resolution ultrasound system (Esaote/Biosound, Munich) with a linear array transducer up to 13.0 MHz was used. The prospective and blinded results of each method were compared with histopathology as the reference method after metatarsal resection. RESULTS: In 14 of 19 patients, histopathology confirmed osteomyelitis. Ultrasound showed a sensitivity of 79% (PFR, 69%; BS, 83%; MRI, 100%), a specificity of 80% (PFR, 80%; BS, 75%; MRI, 75%), a positive predictive value of 92% (PFR, 90%; BS, 91%; MRI, 93%), and a negative predictive value of 57% (PFR, 50%; BS, 60%; MRI, 100%). CONCLUSIONS: Our data indicate that ultrasound might have a better diagnostic power for detecting chronic osteomyelitis in the diabetic foot than PFR and has similar sensitivity and specificity as BS. MRI is superior to the other three methods. We conclude that the use of ultrasound in the management of the diabetic foot is worthy of further investigation.  (+info)

Down-regulation of nitric oxide production by ibuprofen in human volunteers. (38/3693)

Ibuprofen has been shown in vitro to modulate production of nitric oxide (NO), a mediator of sepsis-induced hypotension. We sought to determine whether ibuprofen alters NO production and, thereby, vascular tone, in normal and endotoxin-challenged volunteers. Techniques for detecting NO were validated in 17 subjects infused with sodium nitroprusside, a NO donor. Then, endotoxin (4 ng/kg) or saline (vehicle alone) was administered in a single-blinded, crossover design to 12 other subjects randomized to receive either ibuprofen (2400 mg p.o.) or a placebo. Endotoxin decreased mean arterial pressure (MAP; P =.002) and increased alveolar NO flow rates (P =.04) and urinary excretion of nitrite and nitrate (P =.07). In both endotoxemic and normal subjects, ibuprofen blunted the small fall in MAP associated with bed rest (P =.005) and decreased alveolar NO flow rates (P =.03) and urinary excretion of nitrite and nitrate (P =.02). However, ibuprofen had no effect on the decrease in MAP caused by endotoxin, although it blocked NO production to the point of disrupting the normal relationship between increases in exhaled NO flow rate and decreases in MAP (P =.002). These are the first in vivo data to demonstrate that ibuprofen down-regulates NO in humans. Ibuprofen impaired the NO response to bed rest, producing a small rise in blood pressure. Although ibuprofen also interfered with the ability of endotoxin to induce NO production, it had no effect on the fall in blood pressure, suggesting that the hemodynamic response to endotoxin is not completely dependent on NO under these conditions.  (+info)

Clinical and pharmacokinetic results with a new ultrashort-acting calcium antagonist, clevidipine, following gradually increasing intravenous doses to healthy volunteers. (39/3693)

AIMS: To investigate the tolerability and safety of clevidipine in healthy male volunteers during intravenous infusion at gradually increasing dose rates and to obtain preliminary information on the pharmacokinetics and pharmacodynamic effects of the drug. METHODS: Twenty-five subjects were enrolled in the study and twenty-one of them were included twice, resulting in a total of forty-six study entries encompassing 20 min infusions of clevidipine at target dose rates ranging from 0.12 to 48 nmol min-1 kg-1. Haemodynamic variables and adverse events were recorded throughout the study. Concentrations of clevidipine and its primary metabolite, H 152/81, were followed in whole blood, and the pharmacokinetics were evaluated by non-compartmental and compartmental analysis. An Emax model was fitted to the effect on mean arterial pressure (MAP) over heart rate (HR) and the corresponding blood concentrations of clevidipine. RESULTS: Clevidipine was administered up to a target dose rate of 48 nmol min-1 kg-1, where a pre-determined escape criterion was reached (HR>120 beats min-1 ) and the study was stopped. The most common adverse events were flush and headache, which can be directly related to the mechanism of action of clevidipine. There was a linear relationship between blood concentration and dose rate in the range studied. The median clearance value determined by non-compartmental analysis was 0.125 l min-1 kg-1. Applying the population approach to the sparse data on clevidipine concentrations, an open two compartment pharmacokinetic model was found to be the best model in describing the disposition of the drug. The population mean clearance value determined by this method was 0.121 l min-1 kg-1, and the volume of distribution at steady state was 0.56 l kg-1. The initial half-life, contributing by more than 80% to the total area under the blood concentration-time curve following i.v. bolus administration, was 1.8 min, and the terminal half-life was 9.5 min. At the highest dose rates, MAP was reduced by approximately 10%, and the HR reached the pre-determined escape criterion for this study (>120 beats min-1 ). CONCLUSIONS: Clevidipine is well tolerated and safe in healthy volunteers at dose rates up to at least 48 nmol min-1 kg-1. The pharmacokinetics are linear over a wide dose range. Clevidipine is a high clearance drug with extremely short half-lives. The effect of clevidipine on the blood pressure was marginal, probably due to a compensatory baroreflex activation in this population of healthy volunteers. A simple Emax model adequately describes the relationship between the pharmacodynamic response (MAP/HR) and the blood concentrations of clevidipine.  (+info)

Does the addition of losartan improve the beneficial effects of ACE inhibitors in patients with anterior myocardial infarction? A pilot study. (40/3693)

OBJECTIVE: To verify the efficacy of the combination of captopril (75 mg day) and losartan (25 mg/day) in early postinfarction phases of reperfused anterior acute myocardial infarction. DESIGN AND PATIENTS: 99 patients, hospitalised for suspected anterior acute myocardial infarction within four hours from the onset of symptoms, were randomised into two groups: group A included 50 patients who received captopril 75 mg/day and placebo; group B included 49 patients who received captopril 75 mg/day within three days of admission plus losartan 12.5 mg, as a first dose, and 25 mg/day successively. An additional 23 patients with anterior acute myocardial infarction received losartan 25 mg alone and acted as controls (group C) to check the effects of losartan on plasma angiotensin II (AII) concentrations. Noradrenaline (norepinephrine) (NA) and AII plasma concentrations were measured on the third and 10th day after admission in 93 patients (35 from group A, 35 from group B, and 23 from group C). 90 days after admission patients underwent echocardiography to determine end systolic volume (ESV) and ejection fraction (EF). RESULTS: Patients in groups A and B were similar with regard to age, sex, creatine kinase peak, EF, ESV, and risk factors. Group B (captopril plus losartan) patients showed a significant reduction in mean (SD) systolic blood pressure within the group (basal 128 (10) mm Hg; 10 days after admission 105 (9) mm Hg, p < 0.001), and in comparison with group A (captopril) patients (basal 127 (11) mm Hg; 10 days after admission 116 (10) mm Hg, p < 0. 001). Diastolic blood pressure was also lower in group B patients versus group A (66 (11) v 77 (11) mm Hg). Group C (losartan) patients also showed a significant reduction in systolic blood pressure (131 (13) mm Hg down to 121 (12) mm Hg, p < 0.001). Neither NA nor AII plasma concentrations in groups A and B differed significantly in basal samples (NA 673 (138) v 675 (141) pg/ml; AII 12.77 (4.79) v 12.65 (4.71) pg/ml) or 10 days after admission (NA 283 (93) v 277 (98) pg/ml; AII 5.31 (2.25) v 6.09 (3.31) pg/ml). However, patients in group C had higher plasma concentrations of AII (14.79 (5.7) pg/ml on the third day and 7.98 (4.92) pg/ml on the 10th day) than patients in either group A or B (p = 0.006). After 90 days following treatment, group B (captopril plus losartan) patients had a smaller ESV than patients in group A (captopril) and group C (losartan). CONCLUSION: The data suggest that the combination of captopril plus losartan is feasible in the early treatment of acute myocardial infarction patients, and it appears that this combination has more effect on ESV than captopril alone in the short term.  (+info)