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Biomedical subjects

Andrew Taylor

Publications and source records attributed to Andrew Taylor.

At least 19 recordsLinked to original sources

Therapeutic efficacy and safety of chaperonin 10 in patients with rheumatoid arthritis: a double-blind randomised trial.

BACKGROUND: Chaperonin 10 (heat shock protein 10, XToll) has anti-inflammatory properties related to the inhibition of Toll-like receptor signalling pathways. Our aim was to establish whether chaperonin 10 is safe and effective in the treatment of rheumatoid arthritis. METHODS: In this randomised, double-blind, multicentre study, 23 patients with moderate to severe active rheumatoid arthritis receiving disease-modifying antirheumatic drugs were randomly allocated to three treatment groups receiving intravenous chaperonin 10 twice weekly for 12 weeks at doses of 5 mg (n=8), 7.5 mg (8), or 10 mg (7). The primary outcomes were change in disease activity score (DAS28) and improvement of core disease measures (American College of Rheumatology response score) from baseline to week 12. All analyses were done by intention to treat. This study is registered with the Australian Clinical Trials Registry, number ACTRNO12606000041550. FINDINGS: Primary endpoint measures improved from day 14 in all groups and continued to improve to day 84. By end of study, a 20% improvement of core disease measures was seen in six (86%, 95% CI 43-100), a 50% improvement in four (57%, 14-86), and a 70% improvement in two (29%, 0-57) patients given the highest dose of chaperonin 10. Clinical remission (as defined by a DAS28 <2.6) was achieved in three (13%) of 23 patients. Three individuals dropped out during the study: one in the 5 mg group (rheumatoid arthritis not controlled), one in the 7.5 mg group (adverse event), and one in the 10 mg group (lost to follow-up). The most common adverse events were exacerbation of rheumatoid arthritis (both during and after the study) and upper respiratory tract infection. Only one adverse event was judged to be of severe intensity. INTERPRETATION: Chaperonin 10 seems to be well tolerated and efficacious in treatment of the symptoms of rheumatoid arthritis, at least in the short term.

Adult↗

Anti-tumour necrosis factor-alpha therapy over conventional therapy improves endothelial function in adults with rheumatoid arthritis.

Rheumatoid arthritis (RA) is associated with cardiovascular morbidity and mortality and inflammation contributes to related endothelial dysfunction. We aimed to investigate the effect of anti-TNFalpha therapy on endothelial function in subjects with rheumatoid arthritis. We measured flow-mediated (FMD) and GTN-mediated dilation of the brachial artery before and following 36 weeks of anti-TNFalpha therapy in nine RA patients and in a group of RA patients on conventional therapy. Thirty-six weeks of anti-TNFalpha therapy improved FMD relative to those on conventional therapy (8.65 +/- 1.50 vs. 1.70 +/- 1.36%, P = 0.02). No significant changes in GTN responses were evident. Significant improvements in tender (P = 0.03) and swollen (P = 0.02) joint counts, patients' global self-assessment (P = 0.01) and DAS-28 scores (P = 0.04) were observed in the anti-TNFalpha treated group. The addition of anti-TNFalpha treatment to conventional therapy, in those with severe RA, reduces inflammatory symptoms and improves endothelial function, potentially lowering future atherosclerotic risk.

Adult↗

Differences in national legislation for the implementation of lead regulations included in the European directive for the protection of the health and safety of workers with occupational exposure to chemical agents (98/24/EC).

BACKGROUND: The European Council Directive 98/24 on the protection of the health and safety of workers exposed to chemical agents sets out provisions for environmental and biological monitoring, making specific reference to binding limit values and health surveillance measures for those with exposure to lead OBJECTIVES: To compare how the Directive has been implemented at a national level in EU countries and to determine whether workers receive equivalent protection. METHODS: Information on selected key issues was collected from 14 EU countries by means of a structured questionnaire. RESULTS: National occupational exposure limit values generally reflect that set by the Directive (0.15 mg/m(3)), but in five cases lower limits are set. National binding biological limit values range from 20 microg/100 ml blood in one country up to 80 microg/100 ml blood in others. The risk to the unborn child is generally recognised with specific measures for women of child-bearing potential or those that are pregnant or breast feeding. In only three countries are special arrangements included for young workers. Limits at which medical surveillance is put into effect are more consistent at 40 microg/100 ml in most countries. The Directive also refers to guidelines for health surveillance but none have been issued with respect to lead. Thus monitoring strategies and requirements for analytical performance vary considerably. CONCLUSIONS: The results of this survey suggest that protection of workers against the risk of exposure to lead at work is far from uniform across the European Union. Such disparity may also have implications on the requirements set at national level for laboratories measuring lead in blood and/or air. In the interest of harmonisation within the EU, further consideration should be given to the Annex II of the EC Directive 98/24, taking into account the suggestions for lower binding limit values for lead; this should include full guidelines for medical surveillance and requirements for laboratories should be issued.

Environmental Monitoring↗

Comparison of camera-based 99mTc-MAG3 and 24-hour creatinine clearances for evaluation of kidney function.

OBJECTIVE: The 24-hour creatinine clearance is the standard clinical technique for measuring kidney function; however, this measurement is cumbersome and inconvenient for patients. We hypothesized that a camera-based technetium-99m mercaptoacetyltriglycine (MAG3) clearance obtained simultaneously with a standard MAG3 scan would correlate well with the 24-hour creatinine clearance and could serve as a simple marker of kidney function. MATERIALS AND METHODS: Data were obtained from a retrospective analysis of 28 patients with varying degrees of kidney dysfunction and 85 subjects evaluated for kidney donation. The MAG3 clearance was calculated using a camera-based technique without blood or urine sampling. The creatinine clearance was measured using the plasma creatinine and a 24-hour urine collection. The MAG3 and creatinine clearances were corrected for body surface area, and clearance values in healthy subjects and patients were compared using the paired Student's t test. The linear association between the MAG3 and creatinine clearances was expressed by Pearson's correlation coefficient. RESULTS: The mean MAG3 clearance in the potential kidney donors was 321 +/- 95 mL/min/1.73 m2 (95% CI, 171-546 mL/min/1.73 m2), significantly higher than the mean creatinine clearance of 152 +/- 51 mL/min/1.73 m2 (79-278 mL/min/1.73 m2, p < 0.001). The mean MAG3 clearance in patients was 153 +/- 70 mL/min/1.73 m2 (32-316 mL/min/1.73 m2) and was also significantly higher than the mean creatinine clearance of 74 +/- 36 mL/min/1.73 m2 (21-138 mL/min/1.73 m2, p < 0.001). The ratio of the mean creatinine clearance to the mean MAG3 clearance was essentially the same for volunteers and patients, 0.47 and 0.48, respectively. The Pearson's correlation between the MAG3 and creatinine clearances was 0.80 (0.72-0.86). CONCLUSION: The camera-based 99mTc-MAG3 clearance correlates well with the 24-hour creatinine clearance and can provide a simple and convenient index of kidney function.

Adult↗

99mTc-MAG3 renography: normal values for MAG3 clearance and curve parameters, excretory parameters, and residual urine volume.

OBJECTIVE: Specific quantitative measurements have been recommended to assist in the interpretation of technetium-99m mercaptoacetyltriglycine (MAG3) renal studies. Our objective was to define the sex- and age-specific normal ranges for these recommended parameters. MATERIALS AND METHODS: Data were obtained from a retrospective analysis of 106 subjects who were evaluated for kidney donation. The MAG3 clearance was calculated using a common camera-based method. The relative uptake, prevoid/postvoid and postvoid/maximum count ratios were determined using whole-kidney regions of interest (ROIs). Time to peak, time to half-peak, 20 min/maximum and 20 min/2-3 min count ratios were determined for cortical and whole-kidney ROIs. Residual urine volume was calculated on the basis of the pre- and postvoid bladder counts and voided urine volume. RESULTS: The mean camera-based MAG3 clearance was 321 +/- 69 mL/min/1.73 m2, essentially the same as the mean plasma sample MAG3 clearance in comparable populations. The percentages of relative uptake in the right and left kidneys were 49% and 51% +/- 4%, respectively; no difference was seen between men and women. Cortical values were lower than the whole-kidney values (p < 0.001); the mean cortical 20 min/maximum count ratio was 0.19 (SD, 0.07 and 0.04 for right and left kidneys, respectively). The mean postvoid/maximum whole-kidney count ratio was < 0.1, and the mean postvoid residual bladder volume was < 30 mL. CONCLUSION: Normal limits adjusted for age and sex have been established. Applying normal ranges to quantitative MAG3 parameters may assist in the interpretation of MAG3 scintigraphy and facilitate appropriate patient management.

Adult↗

RENEX: an expert system for the interpretation of 99mTc-MAG3 scans to detect renal obstruction.

UNLABELLED: A renal expert system (RENEX) has been developed to assist physicians detect renal obstruction in patients undergoing pre- and postfurosemide 99mTc-mercaptoacetyltriglycine (99mTc-MAG3) scans. RENEX uses quantitative parameters extracted from the dynamic renal scan data and heuristic rules in the form of a knowledge base (KB) obtained from expert interpreters to conclude whether a kidney is obstructed. METHODS: Normal limits were established for 47 quantitative parameters extracted from the 99mTc-MAG3 scans of 100 potential renal donors. From these data the domain expert estimated 5 boundary conditions for each parameter: (i) definitely abnormal, (ii) probably abnormal, (iii) equivocal, (iv) probably normal, and (v) definitely normal. A sigmoid-type curve was then generated from these 5 boundary conditions, creating a parameter knowledge library used for converting the value of a prospective patient's individual quantitative parameters to a certainty factor (CF). Sixty heuristic rules were extracted from the domain expert to generate the KB for detecting obstruction. A forward-chaining inference engine was developed using the MYCIN combinatories (an approximation of Bayes theorem) to determine obstruction. A justification engine was implemented, which recorded the sequence of each rule that was fired and the current CF value of all input and output parameters at the time of instantiation to track and justify the logic of the conclusions. The entire system was fine tuned and tested using a pilot group of 32 patients (11 males, 21 females; mean age, 56.8 +/- 17.2 y; 63 kidneys) deemed by an expert panel to have 41 unobstructed kidneys, 13 obstructed kidneys,and 9 equivocal findings. RESULTS: RENEX agreed with the expert panel in 92% (12/13) of the obstructed kidneys, 93% (38/41) of the unobstructed kidneys, and 78% (7/9) of the kidneys interpreted as equivocal for obstructions. Processing time per patient was practically instantaneous using a 3.0-GHz personal computer programmed using interactive data language. CONCLUSION: We have developed a renal expert system for detecting renal obstruction using pre- and postfurosemide 99mTc-MAG3 renal scans, at a standardized expert level. These encouraging preliminary results warrant a prospective study in a large population of patients with and without renal obstruction to establish the diagnostic performance of this system.

Expert Systems↗

First evaluation of a 99mTc-tricarbonyl complex, 99mTc(CO)3(LAN), as a new renal radiopharmaceutical in humans.

UNLABELLED: (99m)Tc-Mercaptoacetyltriglycine ((99m)Tc-MAG3), (99m)Tc-dd- and ll-ethylene-dicysteine ((99m)Tc-EC), and (99m)Tc-mercaptoacetamide-ethylene-cysteine ((99m)Tc-MAEC) contain N(3)S or N(2)S(2) ligands designed to accommodate the 4 ligating sites of the ((99m)TcO)(3+) core; they are all excellent renal imaging agents but have renal clearances lower than that of (131)I-orthoiodohippurate ((131)I-OIH). To explore the potential of the newly accessible but less polar [(99m)Tc(CO)(3)](+) core with 3 ligating sites, we decided to build on the success of (99m)Tc-EC, with its N(2)S(2) ligand and 2 dangling carboxylate groups; we chose an N(2)S ligand that also has 2 dangling carboxylate groups, lanthionine, to form (99m)Tc(CO)(3)(LAN), a new renal radiopharmaceutical. METHODS: Biodistribution studies were performed on Sprague-Dawley rats with (99m)Tc(CO)(3)(LAN) isomers, meso-LAN and dd,ll-LAN (an enantiomeric mixture), coinjected with (131)I-OIH. Human studies also were performed by coinjecting each (99m)Tc-labeled product ( approximately 74 MBq [ approximately 2 mCi]) and (131)I-OIH ( approximately 7.4 MBq [ approximately 0.2 mCi]) into 3 healthy volunteers and then performing dual-isotope imaging by use of a camera system fitted with a high-energy collimator. Blood samples were obtained from 3 to 90 min after injection, and urine samples were obtained at 30, 90, and 180 min. RESULTS: Biodistribution studies in rats revealed rapid blood clearance as well as rapid renal extraction for both preparations, with the dose in urine at 60 min averaging 88% that of (131)I-OIH. In humans, both agents provided excellent renal images, with the plasma clearance averaging 228 mL/min for (99m)Tc(CO)(3)(meso-LAN) and 176 mL/min for (99m)Tc(CO)(3)(dd,ll-LAN). At 3 h, both (99m)Tc(CO)(3)(meso-LAN) and (99m)Tc(CO)(3)(dd,ll-LAN) showed good renal excretion, averaging 85% and 77% that of (131)I-OIH, respectively. Plasma protein binding was minimal (10% and 2%, respectively), and erythrocyte uptake was similar (24% and 21%, respectively) for (99m)Tc(CO)(3)(meso-LAN) and (99m)Tc(CO)(3)(dd,ll-LAN). CONCLUSION: Although the plasma clearance and the rate of renal excretion of the (99m)Tc(CO)(3)(LAN) complexes were still lower than those of (131)I-OIH, the results of this first application of a (99m)Tc-tricarbonyl complex as a renal radiopharmaceutical in humans demonstrate that (99m)Tc(CO)(3)(LAN) complexes are excellent renal imaging agents and support continued renal radiopharmaceutical development based on the (99m)Tc-tricarbonyl core.

Adult↗

Percutaneous pulmonary valve implantation in humans: results in 59 consecutive patients.

BACKGROUND: Right ventricular outflow tract (RVOT) reconstruction with valved conduits in infancy and childhood leads to reintervention for pulmonary regurgitation and stenosis in later life. METHODS AND RESULTS: Patients with pulmonary regurgitation with or without stenosis after repair of congenital heart disease had percutaneous pulmonary valve implantation (PPVI). Mortality, hemodynamic improvement, freedom from explantation, and subjective and objective changes in exercise tolerance were end points. PPVI was performed successfully in 58 patients, 32 male, with a median age of 16 years and median weight of 56 kg. The majority had a variant of tetralogy of Fallot (n=36), or transposition of the great arteries, ventricular septal defect with pulmonary stenosis (n=8). The right ventricular (RV) pressure (64.4+/-17.2 to 50.4+/-14 mm Hg, P<0.001), RVOT gradient (33+/-24.6 to 19.5+/-15.3, P<0.001), and pulmonary regurgitation (PR) (grade 2 of greater before, none greater than grade 2 after, P<0.001) decreased significantly after PPVI. MRI showed significant reduction in PR fraction (21+/-13% versus 3+/-4%, P<0.001) and in RV end-diastolic volume (EDV) (94+/-28 versus 82+/-24 mL.beat(-1).m(-2), P<0.001) and a significant increase in left ventricular EDV (64+/-12 versus 71+/-13 mL.beat(-1).m(-2), P=0.005) and effective RV stroke volume (37+/-7 versus 42+/-9 mL.beat(-1).m(-2), P=0.006) in 28 patients (age 19+/-8 years). A further 16 subjects, on metabolic exercise testing, showed significant improvement in VO2max (26+/-7 versus 29+/-6 mL.kg(-1).min(-1), P<0.001). There was no mortality. CONCLUSIONS: PPVI is feasible at low risk, with quantifiable improvement in MRI-defined ventricular parameters and pulmonary regurgitation, and results in subjective and objective improvement in exercise capacity.

Adolescent↗

Recommendations for an update of the current (2001) regulatory requirements for registration of drugs to be used in the treatment of osteoporosis in postmenopausal women and in men.

Recent advances in the understanding of the epidemiology of osteoporosis suggest that certain parts of the current European guidelines for the registration of drugs in osteoporosis might be no longer substantiated. The object of this review is to provide the European regulatory authorities with an evidence-based working document providing suggestions for the revision of the "Note for guidance for the approval of drugs to be used in postmenopausal osteoporosis" (CPMP/EWP/552/95). Following an extensive review of the literature (1990-2004), the Group for the Respect of Ethics and Excellence in Science (GREES) organized a workshop including European regulators, academic scientists and representatives of the pharmaceutical industry. The outcomes of this meeting reflect the personal views of those who attended and should not, in any case, be seen as an official position paper of any regulatory agency. The group identified a certain number of points that deserve discussion. They mainly relate to the nature of the indication being granted to new chemical entities (treatment of osteoporosis in women at high risk of fracture instead of prevention and treatment of osteoporosis), the requirements of showing an anti-fracture efficacy on all or on major nonvertebral fractures (instead of the hip), the duration of pivotal trials (2 years instead of 3) and the possibility of considering bridging studies for new routes of administration, new doses or new regimens of previously approved drugs. The group also recommends that an indication could be granted for the treatment of osteoporosis in males on the basis of a placebo-controlled study, with bone mineral density changes after 1 year as the primary endpoint, for medications approved in the treatment of osteoporosis in women at high risk of fractures.

Female↗

The coupling mechanism of P-glycoprotein involves residue L339 in the sixth membrane spanning segment.

The transmembrane (TM) domains in P-glycoprotein (P-gp) contain the drug binding sites and undergo conformational changes driven by nucleotide catalysis to effect translocation. However, our understanding of exactly which regions are involved in such events remains unclear. A site-directed labelling approach was used to attach thiol-reactive probes to cysteines introduced into transmembrane segment 6 (TM6) in order to perturb function and infer involvement of specific residues in drug binding and/or interdomain communication. Covalent attachment of coumarin-maleimide at residue 339C within TM6 resulted in impaired ATP hydrolysis by P-gp. The nature of the effect was to reduce the characteristic modulation of basal activity caused by transported substrates, modulators and the potent inhibitor XR9576. Photoaffinity labelling of P-gp with [(3)H]-azidopine indicated that residue 339C does not alter drug binding per se. However, covalent modification of this residue appears to prevent conformational changes that lead to drug stimulation of ATP hydrolysis.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

A new polymorph and two inclusion compounds of 9,9'-spirobifluorene.

Two new inclusion compounds of 9,9'-spirobifluorene (SBF) incorporating benzene [(I), C25H16.C6H6] and biphenyl [(II), C25H16.C12H10], and a new polymorph of SBF [(III), C25H16] are reported. All three exhibit C-H...pi(arene) hydrogen bonds between adjacent SBF molecules. Compound (II) also contains biphenyl C-H to SBF pi-arene interactions. Collectively, hydrogen bonding gives rise to a chain and a layered motif in compounds (I) and (II), respectively.

Journal Article↗

Effect of statin therapy on serum trace element status in dyslipidaemic subjects.

Patients previously not treated with a lipid-lowering agent (n = 20; mean age 49.15 +/- 3.28 years) were treated with either 10 mg/day of Simvastatin (n = 11), or Atorvastatin (n = 9) for 4 months. Fourteen additional patients were recruited from the same clinic at the same hospital as a control group. The medication of these latter patients was unaltered for 4 months and the same parameters were measured as for the statin groups. Serum concentrations of zinc, copper, caeruloplasmin, selenium, glutathione peroxidase (GPx) and C-reactive protein (CRP) were measured together with their lipid profiles pre- and post-treatment. In addition to reducing serum total and low-density lipoprotein (LDL) cholesterol (p < 0.0001), statin treatment was associated with a significant reduction in mean serum zinc (9%, p = 0.03), copper (9%, p < 0.01), caeruloplasmin (24%, p < 0.05), and median CRP (45%, p < 0.03). Similar changes were not observed in the control patients. No significant effects were observed for serum selenium, copper/caeruloplasmin ratio, or GPx (p > 0.05) in either statin or control groups. These changes may be related to the known anti-inflammatory properties of the statin class of drugs.

Adult↗

Capsule endoscopy vs. push enteroscopy and enteroclysis in suspected small-bowel Crohn's disease.

BACKGROUND: The diagnosis of small-bowel Crohn's disease sometimes is difficult and may be missed by conventional imaging studies. Capsule endoscopy might identify small-bowel disease undetected by other investigations. METHODS: Patients with or without known Crohn's disease who were suspected to have small-bowel Crohn's disease were prospectively evaluated with push enteroscopy, enteroclysis, and capsule endoscopy. Each examiner was blinded to results of other investigations. Referring doctors were required to complete questionnaires before and after the investigations. RESULTS: Twenty-two patients were known to have Crohn's disease (Group 1), and 21 were suspected to have small-bowel Crohn's disease (Group 2). In Group 1, capsule endoscopy detected more erosions than the other two investigations (p < 0.001). In Group 2, a new diagnosis of Crohn's disease was made in two patients, but there was no significant difference in yield compared with the other two investigations. Referring physicians rated the usefulness of capsule endoscopy as 4.4 on a scale of 5. Capsule endoscopy changed management for 30 patients (70%). CONCLUSIONS: Capsule endoscopy has a higher yield than push enteroscopy and enteroclysis in patients with known Crohn's disease when small-bowel mucosal disease is suspected, and this leads to a change in management in the majority of these patients.

Adolescent↗

Novel method of quantifying pulmonary vascular resistance by use of simultaneous invasive pressure monitoring and phase-contrast magnetic resonance flow.

BACKGROUND: Pulmonary vascular resistance (PVR) quantification is important in the treatment of children with pulmonary hypertension. The Fick principle, used to quantify pulmonary artery flow, may be a flawed technique. We describe a novel method of PVR quantification by the use of magnetic resonance (MR) flow data and invasive pressure measurements. METHODS AND RESULTS: In 24 patients with either suspected pulmonary hypertension or congenital heart disease requiring preoperative assessment, PVR was calculated by the use of simultaneously acquired MR flow and invasive pressure measurements (condition 1). In 19 of the 24 patients, PVR was also calculated at 20 ppm nitric oxide +30% (condition 2) and at 20 ppm nitric oxide +100% oxygen (condition 3), with the use of the MR method. This method proved safe and feasible in all patients. In 15 of 19 patients, PVR calculated by Fick flow was compared with the MR method. At condition 1, Bland-Altman analysis revealed a bias of 2.3% (MR > Fick) and limits of agreement of 50.2% to -45.5%. At condition 2, there was poorer agreement (bias was 28%, and the limits of agreement were 151.3% to 95.2%). At condition 3, there was very poor agreement (bias was 54.2%, and the limits of agreement were 174.4% to -66.0%). CONCLUSIONS: We have demonstrated the feasibility of using simultaneous invasive pressure measurements and MR flow data to measure PVR in humans.

Adolescent↗

Regional accumulation of aluminium in the rat brain is affected by dietary vitamin E.

The regional accumulation of aluminium in the brain of male albino Wistar rats was investigated following 4 weeks of administration by intraperitoneal injection of aluminium lactate (10mg aluminium/kg body weight). The consequences of concomitant dietary vitamin E (5, 15, or 20 mg vitamin E/g of food) were also studied. Rat brains were dissected into functional regions, for the measurement of aluminium and markers of oxidative stress. Plasma aluminium levels were increased in all groups of animals receiving aluminium lactate (p < 0.01), and these levels were significantly reduced in rats receiving concomitant vitamin E (p < 0.05). In the group of rats receiving aluminium alone, levels of brain tissue aluminium were increased in all regions of brain examined (p< 0.01). Brain tissue aluminium levels were reduced by concomitant dietary vitamin E. Catalase and reduced glutathione levels were both reduced in several regions of brain in animals treated with aluminium (p < 0.05). Aluminium treatment was not associated with a significant increase in reactive oxygen species (ROS) generation (p > 0.05), although ROS production was attenuated by dietary vitamin E (p < 0.05) in some regions.

Aluminum Compounds↗

Meat consumption is positively associated with psychomotor outcome in children up to 24 months of age.

OBJECTIVE: The impact of specific complementary foods on health outcomes has been poorly studied. We aimed to determine if meat consumption and breastfeeding influence growth and neurocognitive outcome in infants up to 24 months of age. METHODS: In a longitudinal cohort study, 144 full-term infants were recruited at 4 months. Their red and white meat consumption was recorded in sequential 7-day weighed food intake diaries at 4, 8, 12, 16, 20 and 24 months. Growth data were collected at the same census points as the dietary data. Neurocognitive outcome (psychomotor developmental indices and mental developmental indices) derived from the Bayley Scales of Infant Development II was measured at 22 months. RESULTS: Meat intake from 4-12 months was positively and significantly related to weight gain (P < 0.05); further analysis suggested this association might be mediated via protein intake but was independent of energy, zinc or iron intake. There was no interaction between meat intake and breastfeeding on growth. Meat intake from 4-12 and 4-16 months was positively and significantly related to psychomotor developmental indices (P < 0.02 and 0.013, respectively) but there was no association between breastfeeding and psychomotor developmental indices nor any interaction between meat intake and breastfeeding. Conversely, breastfeeding was positively and significantly related to mental developmental indices (P < 0.01) but there was no association between meat intake and mental developmental indices nor any interaction between breastfeeding and meat intake. These findings remained after adjustment for potential confounding factors. CONCLUSION: Meat intake, possibly via its effect on protein intake, is associated with increased weight gain in infants up to 12 months of age. Meat intake is also positively associated with psychomotor development at 22 months. These findings highlight the need for further investigation of the role of complementary foods in relation to health outcomes.

Breast Feeding↗

Increasing the dose of furosemide in patients with azotemia and suspected obstruction.

Diuresis renography is widely used to distinguish obstructed from nonobstructed kidneys; however, the delivery of furosemide to its site of action in the loop of Henle is impaired in patients with azotemia. Consequently, the standard adult dose of 40 mg furosemide could be insufficient to generate an adequate diuretic response. This problem is illustrated by a patient with azotemia with bilateral nephrostomies who underwent Tc-99m MAG3 (mercaptoacetyltriglycine) diuresis renography with 40 mg furosemide to determine if his bilateral ureteral obstruction had resolved. The study showed findings typical for obstruction despite the fact that the patient could not have been obstructed because the nephrostomy tubes had not been clamped. When the study was repeated 6 days later with 80 mg furosemide and clamped nephrostomy tubes, there was good drainage bilaterally excluding obstruction. The nephrostomy tubes were removed and the patient's creatinine has subsequently remained stable for 3 years. In summary, this report illustrates the rationale for increasing the dose of furosemide in patients with azotemia referred for diuresis renography and shows how increasing the dose of furosemide could improve the diuretic response and minimize false-positive or indeterminate results.

Aged↗