Plasma concentrations of alpha-1-acid glycoprotein in preterm and term newborns: influence of mode of delivery and implications for plasma protein binding of local anaesthetics.

BACKGROUND: Alpha-1-acid glycoprotein (AAGP) is an acute-phase protein with high affinity for amide local anaesthetics (LAs), and a major determinant of free and potentially toxic concentrations of LAs in plasma. Neonates are known to have lower plasma concentrations of AAGP than adults, and are at risk of developing high free concentrations of LAs. Data regarding AAGP in newborns are so far sparse. The aim of this study was to determine plasma concentrations of AAGP after delivery of preterm and term infants, and to investigate correlations between AAGP and gestational age, birth weight, gender, and mode of delivery. METHODS: In this prospective observational study, blood was sampled from umbilical cords of 70 newborn infants born at gestational weeks 27-42 immediately after delivery. Blood samples were subsequently analysed for AAGP plasma concentrations with an immunoturbidimetric assay. RESULTS: We found higher concentrations of AAGP in infants born vaginally compared with those who were delivered by elective Caesarean section [median (inter-quartile range) 0.189 g litre-1 (0.142-0.263 g litre-1) vs 0.110 g litre-1 (0.094-0.157 g litre-1; P=0.0003)], respectively. There was a correlation between gestational age and AAGP concentrations (r=0.50; P=0.011), with significantly higher concentrations in the more mature infants. Gender and birth weight did not appear to influence the plasma concentrations of AAGP. CONCLUSIONS: Alpha-1-acid glycoprotein concentrations in newborns are influenced both by gestational age and mode of delivery. Thus, when dosing local anaesthetics in a parturient, these factors should be taken into account.

Volumes of the spinal canal and caudal space in children zero to three years of age assessed by magnetic resonance imaging: implications for volume dosage of caudal blockade.

BACKGROUND: The primary aim of this study was to objectively assess the different spinal and caudal volumes that are of interest for caudal block volume dosing. METHODS: Three directly assessed (volume of spinal canal/caudal space, volume of the dural sac and volume of spinal cord) and two derived volumes (volume of the epidural space and cerebrospinal fluid volume) were determined from magnetic resonance images (MRI) in 20 children (zero - three yr of age). The assessed volumes were correlated to age, height and weight. Furthermore, the volumes of the epidural space from caudal canal to three different clinically relevant target levels (L 1, Th 10 and Th 6) and the epidural volume of each individual spinal segment at the caudal, lumbar and thoracic levels were calculated. RESULTS: All volumes correlated in a linear manner to length and weight (R2 0.614 - 0.867) whereas a curvilinear correlation was associated with best curve fit for age (R2 0.696 - 0.883). The median volumes of the epidural space from caudal canal to L 1, Th 10 and Th 6 were 1.30 ml kg-1 (95%CI 1.08-1.51), 1.57 ml kg-1 (95%CI 1.29-1.81) and 1.78 ml kg-1 (95%CI 1.52-2.08), respectively. The median volumes of the epidural space per vertebral segment were Thoracic: 0.60 ml (95%CI 0.38-0.75); Lumbar: 1.18 ml (95%CI 0.94-1.43) and Caudal: 0.85 ml (95%CI 0.56-1.18). CONCLUSIONS: The spinal volumes of interest show a linear correlation to height and weight whereas a curvilinear correlation was found for age. The volume of the epidural space per segment was found to be significantly higher at the lumbar level compared with the caudal and thoracic levels.

Pharmacokinetics after a single dose of naloxone administered as a nasal spray in healthy volunteers.

BACKGROUND: There is increasing interest in the use of intranasal naloxone to reverse adverse opioid effects during management of procedural pain in children and in adults after overdose. There are limited data on the pharmacokinetics of intranasal naloxone so in this study we aimed to detail the pharmacokinetic profile of the commercially marketed injectable solution of naloxone 0.4 mg/ml when administered as an intranasal spray. METHODS: Twenty healthy volunteers received naloxone as an intranasal spray at a dose of 10 µg/kg. Venous blood sampling was carried out for 90 min after administration to determine the time profile of the plasma concentrations of using tandem mass spectrometry. Pharmacokinetic parameters were calculated using a one-compartment model. RESULTS: Median time to maximum naloxone concentration (Tmax) was 14.5 (95% CI: 9.0-16.5) min, mean maximum naloxone concentration (Cmax) was 1.09 ± 0.56 ng/ml and mean AUC0-90 min was 37.1 ± 15.0 ng*min/ml. Elimination half-life estimated from the median concentration data was 28.2 min. CONCLUSION: Our results show a faster uptake of intranasal naloxone to maximum concentration compared with previous studies although with a marked variation in maximum concentration. The findings are consistent with our clinical experience of the time profile for reversing the effects of sufentanil sedation in children.

In situ coating makes it easier for children to swallow and tolerate tablets and capsules.

AIM: Getting children to swallow tablets and capsules is a challenge, and factors that influence their ability to swallow include taste, smell and texture. The aim of this study was to explore how well paediatric patients tolerated and accepted the MedCoat(®) in situ coating for tablets and capsules. METHODS: A nonrandomised intervention study was performed at the Astrid Lindgren Children's Hospital, Karolinska University Hospital, Sweden. We identified 78 paediatric patients, 43 females and 35 males, who had problems swallowing tablets and capsules and evaluated their abilities with questionnaires. The median age of the patients was nine years old, and the range was two to 17 years old. RESULTS: Swallowing ability and palatability was improved by in situ coating. The results showed that 66 of 77 paediatric patients (86%, 95% confidence interval: 76-93%) were able to take the drugs they had been prescribed after in situ coating. Swallowing improved in 87% of cases, and palatability improved in 85% of cases. CONCLUSION: A study of 77 paediatric patients with a median age of nine years, and a range of two to 17 years, found that 86% were able to take the tablets and capsules they had been prescribed after they were coated with the MedCoat.

Reduction of cerebral mean blood flow velocity and oxygenation after high-volume (1.5 ml kg⁻¹) caudal block in infants.

BACKGROUND: We have recently described a bi-directional bulk flow of cerebrospinal fluid (CSF) (coined 'the CSF rebound mechanism') after the use of high-volume caudal block in infants, which may explain the secondary longitudinal spread of the block. If important the initial cephalad transfer of CSF should be of such a magnitude that it would cause a transient reduction in cerebral blood flow (CBF) and cerebral oxygenation. The primary aim of this observational study was to delineate the magnitude of the reduction of CBF velocity (CBFV) associated with high-volume caudal block in infants. METHODS: Ultrasound Doppler measurements of CBFV in the middle cerebral artery and also haemodynamic parameters and cerebral regional oxygenation (C(R)SO2) were followed during 5 min after the initial caudal injection (1.5 ml kg(-1), ropivacaine 0.2%) in 12 infants <3 months of age. RESULTS: The caudal injection was associated with immediate and major reductions in CBFV indicating a concomitant reduction in CBF. A significant reduction of cerebral regional oxygenation C(R)SO2 was also observed. Systemic haemodynamic parameters were unchanged during the observation period. CONCLUSION: High-volume caudal block causes a biphasic change in CBFV and was also found to affect cerebral oxygenation. Our findings lend further support to 'the CSF rebound mechanism' for secondary spread of high-volume caudal block.

Plasma concentration of ketorolac after local infiltration analgesia in hip arthroplasty.

BACKGROUND: Local infiltration analgesia (LIA) with local anaesthetic (ropivacaine), a nonsteroidal anti-inflammatory drug (ketorolac) and epinephrine after lower extremity arthroplasty has gained increasing popularity during the last decade. This method has certain advantages, which include minimal systemic side effects, faster post-operative mobilization, earlier post-operative discharge from hospital and less opioid consumption. However, information regarding plasma concentrations of ketorolac after LIA mixture is insufficient to predict the risk of renal impairment in patients subjected to arthroplasty. AIM: To determine the maximal plasma concentration and the exposure of ketorolac during the first 30 h following LIA in hip arthroplasty. METHODS: Thirteen patients scheduled for primary total hip arthroplasty with LIA (ropivacaine 200 mg, ketorolac 30 mg and epinephrine 0.5 mg in a volume of 106 ml) were included. Plasma concentration of ketorolac was quantified by liquid chromatography-mass spectrometry. In addition, we assessed the effect of increasing age and decreasing glomerular filtration rate on the maximal plasma concentration and the total exposure to ketorolac during 30 h. RESULTS: The range of the maximal plasma concentration, 0.3-2.2 mg/l, was detected 30 min-4 h after completing the infiltration. Similar plasma levels have been reported after intramuscular injection of the same dose of ketorolac to healthy elderly volunteers. CONCLUSION: Exposure to ketorolac after LIA may be comparable to an intramuscular injection of the same dose. Decision of dose reduction should be based on clinical assessment of risk factors.

Is there an association between PONV and chemotherapy-induced nausea and vomiting?

BACKGROUND: Drug-induced nausea and vomiting, both post-operatively and following chemotherapy, is often distressing for the patients. Our clinical impression is that certain patients are not prone to but instead protected against both post-operative and chemotherapy-induced nausea and vomiting (CINV). If support for this hypothesis could be generated, it might be easier to identify such patients as low-risk patients and judge all other patients as high-risk patients by default. METHODS: All patients scheduled for breast cancer surgery at Danderyd Hospital, Stockholm, Sweden during 1 year (March 2003-March 2004) were asked to participate in this prospective, observational study. A number of women went on to receive adjuvant chemotherapy. Post-operatively, patients were assessed for 24 h with regard to the occurrence of post-operative nausea and vomiting (PONV). CINV was assessed for 5 days after start of chemotherapy. RESULTS: A total of 275 women were included, 33% were classified as PONV and 67% as non-PONV. Sixty-one of the 275 women included were later subjected to adjuvant chemotherapy. In the non-PONV group, 95% of the patients did not experience CINV, whereas the association between PONV and subsequent CINV was only 38%. CONCLUSIONS: A substantially stronger interrelationship was found between non-PONV and non-CINV than between both PONV and CINV. This may suggest that certain patients, instead of being prone to nausea and vomiting, in fact in some way are protected against these unpleasant side effects.

Secondary spread of caudal block as assessed by ultrasonography.

BACKGROUND: Redistribution and secondary spread after the initial injection of local anaesthetics (LAs) are important factors that contribute to the final spread of caudal block in children. However, to date, these phenomena have yet not been studied in detail. Thus, the aim of this observational study was to define patterns of secondary spread and redistribution of a caudal block by means of real-time ultrasonography scanning and cutaneous testing. METHODS: Ultrasound assessment of LA spread within the caudal-epidural space and epidural pressure was followed during 15 min after initial injection (1.5 ml kg(-1), ropivacaine 0.2%) in 16 infants. At 15 min post-injection, cutaneous testing was also performed to assess the cranial dermatomal level of the block (at end-tidal sevoflurane 2.5%). RESULTS: The median ultrasound-assessed cranial spread was Th10 and Th8 at 0 and 15 min, respectively, and the sensory level at 15 min was Th4. The caudal injection was initially found to compress the terminal part of the dural sac, later followed by a partial re-expansion as epidural pressure was returning towards pre-injection values. An intrasegmental redistribution from the dorsal to the ventral compartment of the epidural space was also observed. CONCLUSIONS: Two separate patterns of secondary spread of caudal block could be observed, being horizontal intrasegmental redistribution and longitudinal cranial spread. The observed bi-directional movement of cerebrospinal fluid (coined 'the CSF rebound mechanism') does explain a major part of the difference between the initial ultrasound-assessed cranial level and the final level determined by cutaneous testing.

Pharmacokinetics after a single intravenous dose of the opioid ketobemidone in neonates.

BACKGROUND: Ketobemidone is often used as an alternative to morphine in children in the Scandinavian countries. In an earlier study, we have examined the pharmacokinetic properties in children in different age groups but have not focused on neonates. The aim of this clinical trial was to explore the pharmacokinetics of ketobemidone in neonates. METHODS: Fifteen full-term neonates (eight females) from 37 gestational weeks at birth and scheduled for elective surgery were included in the trial. Their median age was 3 days (range 1-18 days). Ketobemidone hydrochloride was administered as a single intravenous bolus dose, and ketobemidone concentrations were measured by liquid chromatography-mass spectrometry over 10 h. Pharmacokinetic parameters were calculated with standard compartmental methods. RESULTS: The median (range) values for ketobemidone clearance, apparent volume of distribution, volume of central compartment, distribution half-life and elimination half-life were 0.46 (0.23-0.84) l/h/kg, 4.64 (3.50-7.31) l/kg, 1.71 (0.16-3.47) l/kg, 2.85 (1.04-10.78) min and 7.26 (3.5-11.3) h. CONCLUSION: Compared with our previous study in children older than 1 year of age, the elimination of ketobemidone appeared to be slower in full-term neonates. Despite a low pharmacokinetic variability of ketobemidone as observed in the present neonatal patient population, we recommend individualizing the dose of ketobemidone based on observations of analgesic efficacy.

Effect of a small priming dose on myoclonic movements after intravenous anaesthesia induction with Etomidate-Lipuro in children.

BACKGROUND: In children, the incidence of injection pain at i.v. anaesthetic induction with Etomidate-Lipuro is low when compared with propofol mixed with lidocaine (5%). However, the incidence of involuntary myoclonic movements (MM) after induction of anaesthesia is higher compared with propofol (85% vs. 15%). In adults, the incidence of MM is reported to be significantly reduced if a small priming dose is administered immediately before the main injection of etomidate. The aim of this prospective, randomized, double-blind, placebo-controlled clinical trial was to investigate if a small priming dose of etomidate effectively can reduce the incidence of MM also in children. METHODS: Eighty ASA I-II children (1-15 yr) were randomized to receive either a small priming dose of etomidate (0.03 mg kg(-1)) or a lipid emulsion placebo. A standardized induction dose of etomidate (0.3 mg kg(-1)) was administered 60 s after the priming dose. The occurrence and severity (observational score 0-3) of MM was defined as the primary endpoint of the study and was recorded during a 2 min period after induction of anaesthesia. A post hoc analysis was performed regarding the incidence of MM with respect to age. RESULTS: No difference in the occurrence or severity of MM was found between the two study groups, the total incidence of MM being 73.8% (95% confidence interval: 62.7-83.0%). The incidence of MM (score > 0) was found to be statistically higher in the age group 5-10 yr compared with <5 yr; and >10 yr (P=0.0008 and 0.01730, respectively). The MM scores were highest in patients aged 5-10 yr (P=0.0021). CONCLUSIONS: Children in the age range of 5-10 yr appear to be especially prone to react with involuntary MM after i.v. induction of anaesthesia with etomidate. The use of a small, non-sedative, priming dose did not influence the incidence of involuntary MM after i.v. induction of anaesthesia with etomidate in children 1-15 yr of age.

Patients with rheumatoid arthritis treated with tumour necrosis factor antagonists increase their participation in the workforce: potential for significant long-term indirect cost gains (data from a population-based registry).

OBJECTIVE: To investigate the effect of tumour necrosis factor (TNF) antagonist treatment on workforce participation in patients with rheumatoid arthritis (RA). METHODS: Data from the Stockholm anti-TNFalpha follow-up registry (STURE) were used in this observational study. Patients with RA (n = 594) aged 18-55 years, (mean (SD) 40 (9) years) followed for up to 5 years were included with hours worked/week as the main outcome measure. Analyses were performed unadjusted and adjusted for baseline age, disease duration, Health Assessment Questionnaire (HAQ), 28-joint Disease Activity Score (DAS28) and pain score. RESULTS: At baseline patients worked a mean 20 h/week (SD 18). In unadjusted analyses, significant improvements in hours worked/week could already be observed in patients at 6 months (mean, 95% CI) +2.4 h (1.3 to 3.5), with further increases compared to baseline at 1-year (+4.0 h, 2.4 to 5.6) and 2-year follow-up (+6.3 h, 4.2 to 8.4). The trajectory appeared to stabilise at the 3-year (+6.3 h, 3.6 to 8.9), 4-year (+5.3 h, 2.3 to 8.4) and 5-year follow-up (+6.6 h, 3.3 to 10.0). In a mixed piecewise linear regression model, adjusted for age, sex, baseline disease activity, function and pain, an improvement of +4.2 h/week was estimated for the first year followed by an added improvement of +0.5 h/week annually during the years thereafter. Over 5 years of treatment, the expected indirect cost gain corresponded to 40% of the annual anti-TNF drug cost in patients continuing treatment. CONCLUSION: Data from this population-based registry indicate that biological therapy is associated with increases in workforce participation in a group typically expected to experience progressively deteriorating ability to work. This could result in significant indirect cost benefits to society.

Pharmacokinetics after an intravenous single dose of the opioid ketobemidone in children.

BACKGROUND: Ketobemidone is often used as an alternative to morphine in children in the Scandinavian countries. The aim of this clinical trial was to explore the pharmacokinetics of ketobemidone in children because these properties have not been reported previously. METHODS: Thirty children, newborn to 10 years, scheduled for elective surgery were included in the trial. Ketobemidone hydrochloride was administered as a single intravenous bolus dose and ketobemidone and norketobemidone concentrations were measured by LC-MS over 8 h. Pharmacokinetic parameters were determined using compartmental methods. RESULTS: Six children were excluded from pharmacokinetic analysis because of incomplete blood sampling. The values of ketobemidone clearance (l/h/kg) given as median (range) were 0.84 (0.29-3.0) in Group A (0-90 days), 0.89 (0.55-1.35) in Group B (1-2.5 years) and 0.74 (0.50-0.99) in Group C (7-10 years). The corresponding values for apparent volume of distribution (l/kg) were 4.4 (3.7-6.9) (Group A), 2.6 (2.0-5.6) (Group B) and 3.9 (2.7-5.0 (Group C), and for elimination half-life (h) 3.0 (1.4-8.9) (Group A), 2.0 (1.2-4.7) (Group B) and 3.7 (2.4-6.9) (Group C), respectively. In the two neonates the elimination half-life was almost 9 h. The metabolite norketobemidone did not reach levels above the limit of quantification (0.07 ng/ml) in any of the patients. CONCLUSION: The pharmacokinetic parameters of ketobemidone in children older than 1 month appear to be similar to those in adults. Because of the large interindividual variability of the pharmacokinetics in neonates, further studies especially in this age group are warranted.

Biochemical bone markers in the assessment and pamidronate treatment of children and adolescents with osteogenesis imperfecta.

AIM: To assess the role of biochemical bone markers in classification of children with osteogenesis imperfecta (OI), their possible association with vertebral compression fractures in milder forms of OI and their role in monitoring of intravenous pamidronate (APD) treatment. METHODS: Serum total alkaline phosphatase (ALP), bone ALP isoforms (in a subgroup), osteocalcin, type I procollagen carboxy-terminal propeptide, carboxy-terminal telopeptide of type I collagen, and urine deoxypyridinoline (DPD) were measured in a cross-sectional study of 130 untreated individuals, 0.25-20.9years (median 6.7), with OI types I, III and IV. Of those, sixty-nine were also assessed longitudinally during monthly APD treatment. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. RESULTS: Significant differences in bone markers, however not sufficient for individual clinical use, were found in the larger untreated group but not between subgroups with or without vertebral compressions. All bone markers decreased during treatment for 1.0-12.5years, but with different relative amounts. Changes were not correlated to the improvement in BMD, mobility or pain. CONCLUSION: Bone markers are, despite significant differences, not useful for the classification of OI type in the individual child and are not associated with vertebral compressions. Serum ALP and urinary DPD are sensitive in monitoring bisphosphonate treatment.

Treatment response assessment with (R)-[11CPAQ PET in the MMTV-PyMT mouse model of breast cancer.

BACKGROUND: The goal of the study was to assess the potential of the vascular endothelial growth factor receptor (VEGFR)-2-targeting carbon-11 labeled (R)-N-(4-bromo-2-fluorophenyl)-6-methoxy-7-((1-methyl-3-piperidinyl)methoxy)-4-quinazolineamine ((R)-[11C]PAQ) as a positron emission tomography (PET) imaging biomarker for evaluation of the efficacy of anticancer drugs in preclinical models. METHODS: MMTV-PyMT mice were treated with vehicle alone (VEH), murine anti-VEGFA antibody (B20-4.1.1), and paclitaxel (PTX) in combination or as single agents. The treatment response was measured with (R)-[11C]PAQ PET as standardized uptake value (SUV)mean, SUVmax relative changes at the baseline (day 0) and follow-up (day 4) time points, and magnetic resonance imaging (MRI)-derived PyMT mammary tumor volume (TV) changes. Expression of Ki67, VEGFR-2, and CD31 in tumor tissue was determined by immunohistochemistry (IHC). Non-parametric statistical tests were used to evaluate the relation between (R)-[11C]PAQ radiotracer uptake and therapy response biomarkers. RESULTS: The (R)-[11C]PAQ SUVmax in tumors was significantly reduced after 4 days in the B20-4.1.1/PTX combinational and B20-4.1.1 monotherapy groups (p < 0.0005 and p < 0.003, respectively). No significant change was observed in the PTX monotherapy group. There was a significant difference in the SUVmax change between the VEH group and B20-4.1.1/PTX combinational group, as well as between the VEH group and the B20-4.1.1 monotherapy group (p < 0.05). MRI revealed significant decreases in TV in the B20-4.1.1/PTX treatment group (p < 0.005) but not the other therapy groups. A positive trend was observed between the (R)-[11C]PAQ SUVmax change and TV reduction in the B20-4.1.1/PTX group. Statistical testing showed a significant difference in the blood vessel density between the B20-4.1.1/PTX combinational group and the VEH group (p < 0.05) but no significant difference in the Ki67 positive signal between treatment groups. CONCLUSIONS: The results of this study are promising. However, additional studies are necessary before (R)-[11C]PAQ can be approved as a predictive radiotracer for cancer therapy response.

Amphetamines for improving recovery after stroke.

BACKGROUND: Animal research shows that treatment with amphetamines improves recovery after focal cerebral ischaemia. If the effects are similar in humans, amphetamine treatment could have a major impact on recovery from stroke. OBJECTIVES: To assess the effects of amphetamine treatment in patients with stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group Trials Register (last searched January 2006), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2006), MEDLINE (1966 to January 2006), EMBASE (1980 to January 2006), CINAHL (1982 to January 2006), CINAHL (1982 to January 2006), Science Citation Index (1992 to March 2005) and registers of ongoing trials. We also checked the reference lists of all relevant articles and reviews, and contacted researchers in the field. SELECTION CRITERIA: Randomized unconfounded trials comparing amphetamine with placebo. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and assessed trial quality; one extracted the data. MAIN RESULTS: Ten studies involving 287 patients were included, but not all trials contributed data to each outcome examined in this review. The quality of the trials varied but was generally high. Based on three trials (106 patients) there was no evidence that amphetamine treatment reduced death or dependence (Peto's odds ratio (Peto OR) 1.5, 95% confidence interval (CI) 0.6 to 3.3). Imbalances at baseline with more serious stroke allocated to amphetamine may account for the trend for more deaths at the end of follow up among amphetamine-allocated patients (Peto OR 2.8, 95% CI 0.9 to 8.6). Based on two trials (73 patients) systolic (weighted mean difference (WMD) 8.4 mm Hg, 95% CI 1.6 to 15.2) and diastolic (WMD 4.9 mm Hg, 95% CI 1.1 to 8.8) blood pressure, as well as heart rate, increased (WMD 10.6 bpm, 95% CI 3.3 to 17.8) in amphetamine-allocated patients. Based on six studies (176 patients) there was evidence of a better relative change from baseline to last follow up in motor function (WMD -6.1 points; 95% CI -10.4 to -1.9) Different results with different analysis approaches emphasize caution in the interpretation of the results. AUTHORS' CONCLUSIONS: At present, too few patients have been studied to draw any definite conclusions about the effects of amphetamine treatment on recovery from stroke. The suggested benefits on motor function and the non-significant trend towards increased risk of death could be related to imbalances in prognostic variables or other bias in the studies. Further research is therefore justified.

Anemia and quality of life including anemia-related symptoms in patients with solid tumors in clinical practice.

The aim of this study was to explore in a clinical setting the association between hemoglobin (Hb) level and quality of life (QoL) including anemia-related symptoms in patients with cancer disease. The study was performed in the outpatient units at the Oncology Clinic, Karolinska University Hospital, during spring 2004. One hundred-sixty patients responded to the questionnaires and Hb levels were available in 133 of their medical files. Anemia was not a common problem as only 12 out of 133 patients had an Hb level below 110 g/L. The Hb level was not related to general QoL but to FACT-An Trial Outcome Index (rs = 0.186, p = 0.036), measuring anemia-related symptoms as well as functional and physical well-being. However, two patients with Hb < 110 g/L had minor anemia-related symptoms (FACT AnS > or = 40), while 22 patients with Hb > or = 110 g/L had more pronounced symptoms (FACT AnS < 40). There was no difference in anemia-related symptoms between patients with and without ongoing cancer treatment, but patients with ongoing cancer treatment had decreased physical (p = 0.025) and functional (p = 0.011) well-being as compared to those without ongoing treatment. Patients with lung cancer on cancer treatment had lower FACT-An Trial Outcome Index than patients with breast cancer on treatment (mean values 71.8 and 99.1 for patients with lung and breast cancer, respectively, p = 0.009), and also a tendency to lower Hb levels (mean values 119 and 127 for patients with lung and breast cancer, respectively, p = 0.052). Physical and functional aspects might be more important to consider than increasing the Hb level to reduce the fatigue.

Amifostine protects against early but not late toxic effects of doxorubicin in infant rats.

The improved prognosis and increased expected lifetime among long-term survivors of childhood malignancies have made these patients especially sensitiveto the late toxicity of cancer therapy and prone to secondary malignancies. Recently, new strategies aiming to protect against cancer treatment toxicity have been developed, including the drug amifostine (Ethyol), which is suggested to protect normal tissues from the toxic effects of radiation and cytotoxic agents. In the present study, the possible protective effect of amifostine against toxicity induced by a single injection of doxorubicin (3 mg/kg) in immature rats was evaluated. Specifically, we evaluated the protection against long-term toxicity and the effects of amifostine on growing immature tissues. Amifostine (50-200 mg/kg) given 15 min before doxorubicin had a significant protective effect against doxorubicin-induced early alopecia in young rats. Significant protection against cataract formation was obtained by the use of low-dose amifostine (50 mg/kg). However, amifostine did not protect young rats against the late toxic effect of doxoubicin on linear growth, body weight, plasma leptin levels, and heart or testicular tissue. Worrisome, and in contrast to earlier studies in adult rats, an increased doxorubicin toxicity actually was observed and mortality was increased when the higher doses of amifostine (100-200 mg/kg) were used. The present results suggest that more data from growing immature animal models are needed to analyze the safety of amifostine treatment and its mechanisms of action before wider clinical use of this drug in pediatric cancer patients is recommended.

Preoperative platelet count and volume could not help predict PONV in women undergoing breast cancer surgery: A prospective cohort study.

UNLABELLED: Postoperative nausea and vomiting (PONV) still represents one of the most distressing side effects of anaesthesia and surgery. Clinical risk scores e.g. Apfel score is today commonly used to identify patients at risk. We found in a previous study different platelet counts in patients with and without PONV. The aim of the present explorative study was to assess whether females experiencing PONV after breast surgery had any difference in preoperative platelet count and/or volume assessed by platelet testing. METHODS: All women scheduled for elective breast cancer surgery at Danderyds Hospital, Stockholm, Sweden, during one year were asked to participate in this study. Occurrence of PONV during the 24 first postoperative hours was studied. Blood samples collected preoperatively were analysed by platelet counts determined by impedance (PTLi) and optical (PTLo) methods, mean platelet volume (MPV), platelet distribution width (PDW) and plateletcrit (PCT). Platelet data were compared between patients with and without PONV. RESULTS: In all 183 patients were included in the study, 65 (35%) suffered from PONV, increasing incidence with increased risk score 4 out 5 with 4 risk factors. Mean platelet count was 266 [114-538], mean platelet volume 8.59 [5.94-12.1] and mean platelet weight 16.17 [14.2-25.9] but no differences in any platelet test variables studied were found between patients with or without PONV or with increasing risk factors. CONCLUSION: One third of patients' experienced PONV, increased incidence associated to Apfel score but platelet numbers and simple platelet test provided no additional information around risk for PONV.

Oral melphalan pharmacokinetics: influence of interferon-induced fever.

The influence of interferon-induced fever on oral melphalan pharmacokinetics has been studied in 10 myeloma patients in a randomized crossover design. The melphalan dose (0.25 mg/kg) was given alone and 5 hours after the administration of human interferon alpha (7 x 10(6) IU/m2), respectively. The plasma concentration of melphalan was determined by liquid chromatography with fluorometric detection after derivatization of melphalan with N-acetylcysteine. The area under the plasma concentration-time curve (AUC) was significantly lower (p = 0.02) when melphalan was given with interferon. There was a significant negative correlation (p = 0.008) between body temperature and dose normalized AUC, whereas no effect was noticed on the maximum plasma concentration (Cmax) and on the time to obtain Cmax. The rate of elimination showed a tendency (p = 0.06) to increase with increasing body temperature. It is suggested that the cytotoxicity of the drug is most probably enhanced because of the higher alkylating activity of the compound at elevated body temperatures.

Effects of intrapleural mitoxantrone and mepacrine on malignant pleural effusion--a randomised study.

30 patients with malignant pleuritis were randomised to be treated, either with intrapleural instillation of mepacrine chloride or with mitoxantrone. The patients were evaluated with chest X-ray and a symptom questionnaire during a follow-up period of 12 weeks. Mitoxantrone levels in the pleural space and plasma were measured at different time points in some of the patients. High concentrations of mitoxantrone were found in the pleural fluid while the plasma concentrations were low, giving a plasma/intracavity ratio generally of less than 1:60. The chest X-rays showed excellent results for both treatment modalities. However, the patients treated with mepacrine chloride experienced greater discomfort with fever and pain, and those treated with mitoxantrone reported significantly less dyspnoea and less asthenia after 4 weeks. We conclude that both treatments are equally effective in preventing the recurrence of malignant effusion. However, mitoxantrone seems to have further advantages when it comes to improving the quality of life.