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1.  Detection, evaluation, and management of preoperative anaemia in the elective orthopaedic surgical patient: NATA guidelines 
Previously undiagnosed anaemia is common in elective orthopaedic surgical patients and is associated with increased likelihood of blood transfusion and increased perioperative morbidity and mortality. A standardized approach for the detection, evaluation, and management of anaemia in this setting has been identified as an unmet medical need. A multidisciplinary panel of physicians was convened by the Network for Advancement of Transfusion Alternatives (NATA) with the aim of developing practice guidelines for the detection, evaluation, and management of preoperative anaemia in elective orthopaedic surgery. A systematic literature review and critical evaluation of the evidence was performed, and recommendations were formulated according to the method proposed by the Grades of Recommendation Assessment, Development and Evaluation (GRADE) Working Group. We recommend that elective orthopaedic surgical patients have a haemoglobin (Hb) level determination 28 days before the scheduled surgical procedure if possible (Grade 1C). We suggest that the patient's target Hb before elective surgery be within the normal range, according to the World Health Organization criteria (Grade 2C). We recommend further laboratory testing to evaluate anaemia for nutritional deficiencies, chronic renal insufficiency, and/or chronic inflammatory disease (Grade 1C). We recommend that nutritional deficiencies be treated (Grade 1C). We suggest that erythropoiesis-stimulating agents be used for anaemic patients in whom nutritional deficiencies have been ruled out, corrected, or both (Grade 2A). Anaemia should be viewed as a serious and treatable medical condition, rather than simply an abnormal laboratory value. Implementation of anaemia management in the elective orthopaedic surgery setting will improve patient outcomes.
PMCID: PMC3000629  PMID: 21148637
anaemia; blood transfusion; orthopaedic surgery; preoperative assessment; preoperative preparation
2.  Protective effect of NO on gastric lesions and inhibition of expression of gastric inducible NOS by flurbiprofen and its nitro-derivative, nitroflurbiprofen. 
British Journal of Pharmacology  1995;116(2):1713-1714.
Nitroflurbiprofen (NFP) causes significantly less gastric lesions than flurbiprofen (FP), probably because of its capacity to release nitric oxide (NO) in the stomach. Lipopolysaccharide (LPS), which induces the expression of an inducible type of NO synthase (iNOS) in rat stomach, also reduces gastric mucosal damage elicited by FP. Furthermore, both FP and NFP decrease significantly the amount of mRNA encoding iNOS induced by LPS in the stomach. The inhibitory effect of NFP seems to be due at least in part to its ability to release NO.
PMCID: PMC1909099  PMID: 8528547
3.  Effect of a new non-steroidal anti-inflammatory drug, nitroflurbiprofen, on the expression of inducible nitric oxide synthase in rat neutrophils. 
British Journal of Pharmacology  1995;115(2):225-226.
The effects of a non-steroidal anti-inflammatory drug, flurbiprofen, and its nitro-derivative, nitroflurbiprofen, on inducible nitric oxide synthase in rat neutrophils were examined. Nitroflurbiprofen was shown to inhibit nitric oxide synthase induction caused by lipopolysaccharide administration, while flurbiprofen had no effect on nitric oxide synthase induction. This inhibitory action may be ascribed to nitric oxide released from nitroflurbiprofen.
PMCID: PMC1908334  PMID: 7545516
4.  Inhibition by sodium nitroprusside of the expression of inducible nitric oxide synthase in rat neutrophils. 
British Journal of Pharmacology  1995;114(6):1105-1106.
A well-known nitric oxide (NO)-releasing compound, sodium nitroprusside (SNP), decreases in a dose-dependent manner NO synthase (NOS) activity induced in rat neutrophils by treatment with lipopolysaccharide (LPS). This inhibitory action of SNP seems not to be due to its direct effect on the enzyme activity. The strong nitrosonium ion (NO+) character of SNP could be responsible for its inhibition of NOS induction in neutrophils.
PMCID: PMC1510353  PMID: 7542530
5.  Pharmacokinetics and renal tolerance of aztreonam in premature infants. 
Aztreonam (30 mg/kg of body weight) was administered intravenously over 3 min every 12 h to 30 preterm neonates divided into two groups according to gestational age (mean age for group A was less than 30 weeks and mean age for group B was greater than 30 weeks) and birth weight (mean weight for group A was less than 1,500 g and mean weight for group B was greater than 1,500 g). Blood and urine samples were analyzed by microbiological assay. The pharmacokinetics were described by one-compartment and noncompartment models. The mean half-life and clearance for premature infants weighing less than 1,500 g were 5.33 +/- 3.61 h and 1.52 +/- 1.33 ml/min/kg, respectively; for those weighing more than 1,500 g, the values were 4.08 +/- 2.28 h and 2.41 +/- 2.10 ml/min/kg, respectively. The mean urinary concentration of aztreonam in 15 premature infants during the first 6 h of therapy was 242.72 +/- 188.19 micrograms/ml, with a mean percentage of elimination of 13.29%. Urinary excretion of N-acetyl-beta-D-glucosaminidase (a specific and sensitive test for the detection of drug-induced renal tubule damage) did not show significant differences in our group of premature infants compared with that in a control group. The dose of 30 mg/kg and a dosage interval of 8 to 12 h could be recommended for the treatment of suitable bacterial infections in all premature infants.
PMCID: PMC245258  PMID: 1952838
6.  Pharmacokinetics and human tissue penetration of flurithromycin. 
Antimicrobial Agents and Chemotherapy  1988;32(12):1875-1878.
The relationship between concentrations in serum and levels in tissue of flurithromycin, a new fluorinated macrolide, was determined in patients undergoing maxillofacial surgery and thoracotomy. All patients received 500 mg of flurithromycin orally every 8 h. Drug levels in serum, bone, soft tissue, lung, and pericardial fluid were determined microbiologically. The total amount of antibiotic per gram of tissue was calculated on the basis of the concentration in the supernatant of the homogenate. From the parallel course between free concentrations in serum and calculated contents in interstitial fluid tissue, it was concluded that the tissues examined were easily accessible by flurithromycin; penetration values measured by the ratio of areas under the curve were 8.3 for lung, 3.6 for bone, and 0.8 for soft tissue. The results of the pharmacokinetic study suggest that accumulation of the drug during repetitive multiple doses is predictable. Mean residence times were 10.2 and 8.3 h in groups 1 and 2, respectively. For bacteriostatic drugs such as macrolides, not only very high but also prolonged concentrations in tissue lead to favorable therapeutic result.
PMCID: PMC176036  PMID: 3245699
7.  Penetration of ceftriaxone into human pleural fluid. 
The pharmacokinetics of ceftriaxone were studied for seven patients with pleural effusion of various etiologies. All patients received 1 g of antibiotic, administered as an intravenous bolus. The pleural fluid had a high total protein content (6.0 g/dl). Ceftriaxone levels in plasma and in pleural fluid were determined by the agar well diffusion technique. Total and free drug concentrations in pleural fluid reached 7 to 8.7 and 3.8 to 2.3 micrograms/ml, respectively, in 4 to 6 h. The disappearance of the drug from the pleural fluid was very slow. In these patients, therapeutic ceftriaxone levels were present for at least 53 h in pleural fluid.
PMCID: PMC284176  PMID: 3729347
8.  Distribution of ceftazidime in ascitic fluid. 
The pharmacokinetics of ceftazidime were investigated in eight normal subjects and eight patients with ascites after intravenous administration of 1 g of the drug. Samples of blood and ascitic fluid were collected for 6 h after dosage, and urine samples were collected for 24 h. Pharmacokinetic data were calculated by using a one-compartment model. The apparent volume of distribution and half-life of elimination (t1/2 beta) in patients with ascites were approximately three times those in normal subjects. In contrast, renal clearance was greater in the normal subjects. With respect to ascites, the mean area under the concentration-time curve was 95.3 +/- 38.3 micrograms X h/ml. The mean ratio of the area under the concentration-time curve for ascitic fluid to that for plasma was 69.9% (+/- 38.2). These data show that ceftazidime rapidly diffuses into the peritoneal space, in which concentrations greater than 10 micrograms/ml were present for at least 6 h.
PMCID: PMC185636  PMID: 6378086

Results 1-8 (8)