Reaction rates in allogeneic donors

In Canada and several other countries, there is an upper age limit for blood donation. In order to evaluate the safety of whole blood donation in elderly Canadian allogeneic donors, we analysed reaction rates following whole blood donation. Reactions rates in allogeneic whole blood donors who donated at Canadian Blood Services were reviewed retrospectively. Rates were analysed by age, donation frequency and by donation frequency for each age group. A total of 5478 reactions were available for analysis in 469 837 donors. The highest rate of mild reactions occurred in donors less than 20 years of age. Moderate and severe reactions decreased with increasing age and with donation frequency. Age-adjusted rates for mild reactions were less frequent in donors aged 66-77 years than in donors younger than 20 years. Although age-adjusted moderate reactions varied with donation frequency, after seven donations, rates were not increased for donors aged 60 years or older (0.61% for donors aged less than 20 years compared to 0.03% for donors aged 60-65 years compared to 0% for donors aged 66-71 years). Age-adjusted rates for severe reactions generally did not increase with donation frequency. These results confirm the safety of whole blood donation in regular donors who are 66-71 years of age.     

Tyrosine-free amino acid mixture attenuates amphetamine-induced displacement of [11C]raclopride in striatum in vivo: a rat PET study

Previous neurochemical and behavioural studies show that tyrosine depletion using a nutritionally balanced tyrosine-free amino acid mixture attenuates the dopamine-releasing and psychostimulant properties of amphetamine. Here we investigate the effect of a tyrosine-free amino acid mixture on striatal binding of [(11)C]raclopride, and amphetamine-induced [(11)C]raclopride displacement, using positron emission tomography in the rat. Rats were scanned for 60 min after an i.v. injection of approximately 11 MBq [(11)C]raclopride using a quad-HIDAC system. Amphetamine (2 mg/kg i.p., 30 min prior to scan) caused a 12% reduction in [(11)C]raclopride distribution volume ratio (DVR) compared to saline-injected controls. The tyrosine-free amino acid mixture (1 g/kg i.p.) caused a small (+7%) but statistically insignificant increase in [(11)C]raclopride DVR and attenuated, although it did not fully block, the amphetamine-induced reduction. These data are in keeping with previous neurochemical, immunocytochemical, and behavioural studies showing that tyrosine-free amino acid mixtures reduce dopamine function and offer promise for future PET studies testing the effect of tyrosine-depleting paradigms on dopamine release in humans.     

An inadequate glycaemic response to glucagon is linked to insulin resistance in preterm infants?

AIMS: To define clinical, metabolic, and hormonal characteristics of preterm infants relative to glucagon responsiveness. METHODS: Two phase study of 78 preterm infants (25-36 weeks gestation) on regular four hourly feeds anticipating discharge home at 36 weeks mean corrected gestation. In phase 1 infants were fasted until hypoglycaemic, or maximally for eight hours. Endocrine and metabolic profiles were obtained at completion. Phase 2 was performed the following day. A feed was omitted and replaced by a bolus dose of intravenous glucagon (100 micro g/kg). Main outcome measures were measurements of blood glucose and lactate concentrations, taken immediately pre-glucagon, and thereafter every 15 minutes for 60 minutes. A rise in glucose concentration of >1 mmol/l (55 infants) was defined as an adequate response to glucagon. An inadequate glycaemic response was <1 mmol/l (23 infants). RESULTS: Several differences in fasting blood glucose and hormone concentrations were identified in infants with an inadequate glycaemic response to glucagon compared to those with an adequate response: relative fasting hyperglycaemia (mean 3.7 v 3.3 mmol/l, p = 0.008); fasting hyperinsulinaemia (mean 4.3 v 2.6 mU/l, p = 0.014); an increased insulin:glucagon ratio (0.19 v 0.11, p = 0.014), and a lower insulin sensitivity QUICKI index (0.19 v 0.22, p = 0.04). There was no distinctive phenotype to reliably predict response to glucagon. CONCLUSION: Some preterm infants show an inadequate glycaemic response to glucagon and have features suggestive of insulin resistance. The potential long term implications of such insulin resistance may have appreciable public health consequences.     

The effect of fetal acidemia on fetal-placental vascular tone and production of the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha

OBJECTIVE: Our purpose was to determine the effects of fetal acidemia on placental vascular tone and production of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha). STUDY DESIGN: With use of an ex vivo placental perfusion model, the maternal and fetal circulation of two cotyledons from five human placentas were perfused for 4 hours. The fetal circulation of one cotyledon was perfused with acidemic (pH 6.90) Hanks' balanced salt solution (HBSS), whereas the fetal circulation of the other cotyledon was perfused with physiologic (pH 7.35) HBSS. Fetal venous effluents were collected hourly, and IL-6 and TNF-alpha concentrations were determined by enzyme-linked immunosorbent assay. Cotyledon perfusion pressures were recorded every 10 minutes. Paired t tests were used to compare differences in cytokine production and perfusion pressure between the cotyledons. RESULTS: Fetal-placental vascular perfusion pressure was consistently reduced from baseline under acidemic, but not physiologic, conditions with statistical significance achieved from 20 minutes onward (P <.05). IL-6 and TNF-alpha increased exponentially over time for both conditions (P <.05). There was no difference in cytokine production when acidemic conditions were compared with physiologic conditions (P <.05). CONCLUSION: Fetal-placental vasodilation may be a compensatory mechanism to improve acidemic conditions. Unlike fetal hypoperfusion or fetal hyperoxia, fetal acidemia does not result in elevated placental cytokine levels.     

Perioperative blood transfusion therapy in pediatric patients

In general, transfusion guidelines for non-neonatal pediatric patients are similar to those for adults. However, some differences do exist and certain precautions may be necessary particularly in the setting of massive transfusions. We review these differences as they apply to general pediatric surgery outside of the neonatal period, with respect to the transfusion of red blood cells (RBCs), platelets, fresh-frozen plasma (FFP), and cryoprecipitate. We include a discussion of the indications for transfusion and practical considerations such as dosing and administration. Finally, we briefly review the use of directed donations and specialized (irradiated, CMV seronegative) blood components.     

Toxicokinetic of HEMA in guinea pigs

Objective. Unconverted 2-hydroxyethylmethacrylate (HEMA) can be released from dental resin materials and can enter the body in humans. In the present study the uptake, distribution and excretion of ¹⁴C-HEMA applied via different routes were examined in vivo in guinea pigs.

Methods. HEMA (0.02 mmol/kg bw labelled with a tracer dose ¹⁴C-HEMA 0.3 Bq/g bw) was administered by gastric tube or by subcutaneous injection. Urine, feces, and exhaled carbon dioxide were collected for 24 h after administration. Guinea pigs were killed 24 h after the beginning of the experiment and various organs removed and ¹⁴C radioactivity measured.

Results. Low fecal ¹⁴C levels (about 2% of the dose) and urinary levels of about 15% after 24 h were noted with either route of administration. Direct measurement of exhaled CO₂ showed that about 70% of the dose left the body via the lungs. Two pathways for the metabolism of ¹⁴C-HEMA can be described. It is likely that ¹⁴C-pyruvate is formed in vivo resulting in the formation of toxic ¹⁴C-HEMA intermediates. ¹⁴C-HEMA was taken up rapidly from the stomach and small intestine after gastric administration and was widely distributed in the body following administration by each of the routes.

Conclusions. Clearance from most tissues following gastric and intradermal administration was essentially complete within one day. The peak HEMA levels in all tissues examined after 24 h were at least onemillion-fold less than known toxic levels.     

Suspected pediatric ingestions: effectiveness of immunoassay screens vs. gas chromatography/mass spectroscopy in the detection of drugs and chemicals

Rapid and accurate analytical testing can be of great value when determining treatment for pediatric patients suspected of ingesting an unknown chemical. Though often overlooked, gas chromatography/mass spectroscopy (GC/MS) can be a valuable resource in emergency toxicology testing. In a recent 24-month period (July 1999-June 2001), the Analytical Toxicology Laboratory at the University of Mississippi Medical Center, Jackson, MS, compared the results of GC/MS analysis to results obtained by immunoassay testing. The laboratory tested 139 urine samples referred for STAT toxicology testing from the hospital's Pediatric Emergency Department. All samples were tested in parallel using an immunoassay technique (EMIT) and GC/MS. With analysis by immunoassay, 17.3% of the samples were positive for a drug of abuse. The number of positive drug classes ranged from 0 to 2 per sample (mean 0.17 +/- 0.43) using immunoassay. With analysis by GC/MS, drugs were detected in 88.5% of the samples. The number of drugs detected ranged from 0 to 11 per sample (mean 2.2 +/- 1.8) with GC/MS. A total of 64 different pharmaceuticals were identified by GC/MS. This study shows that analysis by GC/MS offers the clinician a more comprehensive view into the exposure of the pediatric patient presenting with an unknown chemical ingestion.