13Carbon mixed triglyceride breath test and pancreatic enzyme supplementation in cystic fibrosis

Children with cystic fibrosis have variable degrees of exocrine pancreatic insufficiency which, if untreated, is the main cause of fat malabsorption. The impact of pancreatic enzyme supplementation on fat digestion was measured in 41 children with cystic fibrosis, 11 healthy controls, and five children with mucosal diseases by a non-invasive test of intraluminal lipolysis using 13carbon (13C) labelled mixed triglyceride (1,3-distearyl, 2[13C] octanoyl glycerol). The children with cystic fibrosis without pancreatic supplements had a median (range) 13C cumulative percentage dose recovered over six hours (cPDR) of 3.1% (0-31.7), the controls 31.0% (21.8-41.1), and the subjects with mucosal disease 27.8% (19.7-32.5). In 23 subjects with cystic fibrosis the usual dose of pancreatic enzyme supplements increased the cPDR to a median of 23.9% (0-45.6), and twice the usual dose of enteric coated microspheres increased the cPDR to 31.1% (11.1-47.8). There was no significant difference between the median cPDR of normal controls and children with mucosal disease, but there was a highly significant difference between these groups and children with untreated cystic fibrosis. Thirteen children with cystic fibrosis had no 13C recovery in their breath without enzymes and 10 showed marked increases with regular enzymes. In eight children doubling the dose of enzymes caused no or minimal improvement. The mixed triglyceride breath test offers a simple, non-invasive way of assessing the need for pancreatic enzyme supplementation in children with cystic fibrosis and could be used to optimise treatment.     

MR imaging of facial nerve enhancement in Bell palsy or after temporal bone surgery

The authors evaluated magnetic resonance (MR) images obtained with intravenously administered gadolinium in ten patients who had facial paralysis and no facial nerve tumor. In patients with either Bell palsy (four patients) or facial paralysis after temporal bone surgery (six patients), intratemporal facial nerve enhancement was seen. Facial nerve enhancement on MR images proved to be a nonspecific finding.     

Injury prior to neurectomy alters the pattern of autotomy in rats. Behavioral evidence of central neural plasticity

A common property of phantom limb pain is that a preamputation lesion continues to be felt in the same location of the phantom limb after amputation. A model of the phantom limb in the rat is provided by sectioning the sciatic and saphenous nerves. This procedure leads to self-mutilation of the denervated hindpaw, a behavior known as autotomy. There is strong evidence that autotomy is a response to painful or dysesthetic sensations referred to the anesthetic limb. The present study examined the hypothesis that the site of autotomy behavior can be altered by an injury given prior to denervation. Experiment 1 evaluated the effects of a thermal injury applied (under sodium pentobarbital anesthesia) to the medial or lateral hindpaw and digits before or after sciatic and saphenous nerve transections in order to determine whether autotomy is directed specifically to a previously injured site. The results revealed that autotomy onset occurred in the injured region of the paw in a significantly greater proportion of rats, compared to an uninjured control group, if the thermal injury had been induced before denervation: 100% of the rats with medial paw injury induced prior to neurectomy initiated autotomy in the medial digits, and 55.6% of rats with lateral paw injury initiated autotomy in the lateral digits. Rats injured after autotomy showed no such preference (medial, 33.3% and lateral, 37.5%) relative to the uninjured controls (medial, 33.3% and lateral, 17%). These results suggest that central cells, sensitized by the thermal injury, contribute to enhanced autotomy in the absence of further inputs from the injured paw.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ankle joint urate arthritis (AJUA) in rats: an alternative animal model of arthritis to that produced by Freund's adjuvant

Injection of sodium urate crystals into one ankle joint in the rat produces arthritis which is fully developed within 24 h. The time-course and dose-response of associated inflammation and sensory abnormalities are described. Following intra-articular sodium urate rats reduce the weight placed on the paw of the treated hind limb and develop a limp in their gait. The ankle swells and becomes more sensitive to pressure and passive movements. Touch, pressure and thermal stimuli applied to the foot distal to the treatment produce decreased responses, presumably because active flexion movements are noxious. Joint pathology is reflected by tissue oedema and the infiltration of polymorphonuclear leucocytes. However, there is no destruction or decrease in density of bone. It is proposed that this model of arthritis may have ethical and scientific advantages over adjuvant arthritis in the study of some aspects of the neural mechanisms of arthritis.     

A study of adaptive responses in cell signaling in migraine and cluster headache: correlations between headache type and changes in gene expression

The project was an investigation into whether changes in the expression of G-proteins underlie altered cell signaling in migraine and cluster headache. The basis for this assumption is that altered physiological responses are seen in migraineurs and that differences in cell signaling are detected biochemically in various cell types isolated from peripheral blood. Levels of three G-protein mRNAs—Gsα, Giα, and Gqα were quantified in lymphocytes from clinically well-defined migraine and cluster headache patients and correlated with headache type and influence of drug treatment. Giα mRNA was reduced by 50% in all migraine patients compared with control subjects; similarly in patients with or without aura, in patients with a migraine headache at the time of sampling, and patients in a quiescent state. No reduction in the levels of Gsα or Gqα mRNA were seen in migraine patients. A smaller reduction was seen in cluster headache patients, most marked in those without medication. Levels of Gsα. mRNA were significantly reduced in cluster headache patients compared with migraine patients. The marked down-regulation of Giα mRNA in migraine, whether quiescent or acute, indicates either an adaptive response to headache in this group of patients or that low levels of Giα mRNA make individuals more susceptible to migraine.     

The effect of hypotonicity, glutamine, and glycine on red cell preservation

BACKGROUND : Red cells (RBCs) stored in hypo-os-molar additive solutions with the same concentrations of adenine, dextrose, mannitol, and sodium chloride and varied amounts of ammonium, phosphate, glycerol, and glutamine were better preserved than RBCs in the standard additive solution (Adsol). Cell swelling occurred in all the experimental additives. This observation prompted the evaluation of glutamine and glycine alone, as well as a combination of glutamine and glycine, all of which have been described as producing swelling of rat liver cells. STUDY DESIGN AND METHODS : Aliquots of RBCs were stored at 4°C in Adsol or experimental additive solutions (EASs) all containing adenine, 2 mM; dextrose, 110 mM; mannitol, 55 mM; and sodium chloride, 50 mM. EAS 42 had, in addition, glutamine, 10 mM; glycine 5 mM; and phosphate, 20 mM. EAS 43 had glutamine, 10 mM; glycine, 10 mM; and phosphate 20 mM. EAS 44 had glutamine, 10 mM; EAS 45 had glutamine, 10 mM, and phosphate, 20 mM; and EAS 46 had only glycine, 10 mM. At intervals, measurements were made of mean corpuscular volume, mean corpuscular hemoglobin concentration, morphology, ATP, hemolysis, supernatant potassium, ammonia, pH, and microvesicles shed. RESULTS : The initial mean corpuscular volumes were larger in all EASs than in Adsol, but the greatest difference was between EASs 44 and 46 (108 fL) and Adsol (86 fL) (p<0.001). The morphology scores were significantly better in all the EASs (p<0.04). The ATPs were significantly greater in all the EASs (p<0.001), and highest in those with phosphate. Potassium leakage and hemolysis were less in the EASs (p<0.001). The ammonia levels were higher in all the EASs than in Adsol, with the exception of EAS 46. During storage, the extracorpuscular and intracorpuscular pH levels were essentially identical. The shedding of microvesicles was greatly reduced in all the EASs. CONCLUSION : Cell swelling induced in RBCs after collection appears to improve preservation. Ammonia and phosphate enhance RBC ATP maintenance. Glycine decreases the formation of ammonia by RBCs stored in a hypotonic medium.     

Boron neutron capture therapy for malignant gliomas

Boron neutron capture therapy (BNCT) represents a promising modality for a relatively selective radiation dose delivery to the tumour tissue. Boron-10 nuclei capture slow 'thermal' neutrons preferentially and, upon capture, promptly undergo 10B(n,alpha)7Li reaction. The ionization tracks of energetic and heavy lithium and helium ions resulting from this reaction are only about one cell diameter in length (approximately 14 microm). Because of their high linear energy transfer (LET) these ions have a high relative biological effectiveness (RBE) for controlling tumour growth. The key to effective BNCT of tumours, such as glioblastoma multiforme (GBM), is the preferential accumulation of boron-10 in the tumour, including the infiltrating GBM cells, as compared with that in the vital structures of the normal brain. Provided that a sufficiently high tumour boron-10 concentration (approximately 10(9) boron-10 atoms/cell) and an adequate thermal neutron fluence (approximately 10(12) neutrons/cm2) are achieved, it is the ratio of the boron-10 concentration in tumour cells to that in the normal brain cells that will largely determine the therapeutic gain of BNCT.