Transplantation of Fetal Neocortex Ameliorates Sensorimotor and Locomotor Deficits Following Neonatal Ischemic–Hypoxic Brain Injury in Rats

Ischemic brain injury in neonates can result in the degeneration of cortical and subcortical areas of brain and is associated with neurologic deficits. One approach to restoring function in conditions of ischemic brain injury is the use of neural transplants to repair damaged connections. This approach has been shown to reestablish neural circuitry and to ameliorate associated motor deficits in models of neonatal sensorimotor cortex damage. In this study, we utilized the Riceet al.rodent model of neonatal ischemic–hypoxic (IH) brain injury (26) to assess whether transplantation of fetal neocortical tissue can promote functional recovery in tests of sensorimotor and locomotor ability throughout development and as adults. We show that animals that received neocortical grafts 3 days following the IH injury performed significantly better as adults on two measures of motor ability, the Rota-Rod treadmill and apomorphine-induced rotations, than did control animals that received sham transplants after the IH injury. Transplants were identifiable in 72% of the animals 10–12 weeks after implantation. Histochemical studies revealed that while the transplanted tissue did not establish normal cortical cytoarchitecture, cells and fibers within the grafts stained for nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d), choline acetyl transferase (ChAT), cholecystokinin (CCK), and glial fibrillary acidic protein (GFAP). These results suggest that transplantation of fetal neocortical tissue following IH injury in the neonatal period is associated with amelioration of motor deficits and that the grafted tissue demonstrated a neurochemical phenotype that resembled normal neocortex. This approach warrants continued investigation in light of potential therapeutic uses.     

Two novel missense mutations in the LDL receptor gene causing familial hypercholesterolemia

We have employed analysis of single-strand conformation polymorphisms to identify mutations in the low density lipoprotein receptor gene causing familial hypercholesterolemia. Two familial hypercholesterolemia heterozygotes had abnormal single-strand conformation polymorphism patterns of exons 4 and 8. DNA sequencing revealed that the abnormal pattern of exon 4 was due to heterozygosity (G/T) at nucleotide 502. Nucleotide 502 is the first base of codon 147, and the G→T mutation (D147Y) changes this codon from Asp_GAC to Tyr_UAC. The abnormal pattern of exon 8 was due to heterozygosity (A/G) at nucleotide 1097. Nucleotide 1097 is the second base of codon 345, and the A→G mutation (Q345R) changes this codon from Gln_CAG to Arg_CGG- Based upon screening of 437 unrelated familial hypercholesterolemia heterozygotes, both D147Y and Q345R account for about 0.5% of the mutations causing familial hypercholesterolemia in Norway.     

Metabolic effects of nicotine after consumption of a meal in smokers and nonsmokers

The thermogenic effect of nicotine intake after calorie consumption was investigated to determine if nicotine influences metabolic response to a calorie challenge. Smokers and nonsmokers (10 males in each group), matched for body weight, age, and physical fitness, each participated in four sessions that involved consuming a liquid calorie load (4.77 kcal/kg body wt) or water, followed by nicotine (15 micrograms/kg body wt) or placebo via nasal spray every 20 min for 2 h. Energy expenditure was significantly increased above baseline resting metabolic rate (RMR) over the 2 h by nicotine alone (6.5% of RMR, p less than 0.01). However, the combined effect of nicotine after calorie load (20.1% of RMR, p less than 0.001) was not significantly greater than the effect of calorie load alone (18.4% of RMR, p less than 0.001). Smokers and nonsmokers did not differ in baseline RMR or in response to nicotine or calorie load. These results confirm the thermogenic effect of nicotine but suggest that the effect of nicotine after calorie consumption is less than additive.     

Mental health advocacy: paradigm or panacea?

In May, 1982, the Ontario Minister of Health set out the bare essentials of a proposed advocacy program for psychiatric patients. In November, a Toronto family doctor, actively involved in civil rights issues, was appointed to develop and coordinate the program. In May, 1983, eleven advocates were appointed to advise and assist patients in each of the province's ten psychiatric hospitals. The advocates came from various backgrounds--legal, psychiatric nursing and social work, labour negotiation, pastoral and other public services. This paper describes the design, function and scope of Canada's first province-wide psychiatric patient advocate system and some major issues identified in the first year.     

Quantitative evaluation of sampling methods for Ixodes dammini and Amblyomma americanum (Acari: Ixodidae).

Three tick-sampling methods (dry ice-baited tick traps, cloth drags, and ambulatory human host) were evaluated to determine which technique yielded the greatest capture of host-seeking stages of Ixodes dammini Spielman, Clifford, Piesman & Corwin and Amblyomma americanum (L.). The most reliable method, catching more stages and significantly more numbers of I. dammini and A. americanum; was dry ice-baited tick traps. There were no significant differences between the drag and human-host methods for any stage of ticks (I. dammini and A. americanum) collected. The numbers of ticks caught during the study were 5,052 by dry ice-baited tick traps, 199 by cloth drags, and 89 by ambulatory human host.     

Calculation of radiation dose enhancement factors for dose enhancement therapy of brain tumours.

When brain tumours are loaded with iodinated contrast media (CM) and exposed to x-rays, the photoelectrons, Auger electrons and fluorescent x-rays from the iodine enhance the radiation dose absorbed by the tumour. A modified CT scanner, the CTX, can be used to localize the tumour and to deliver the dose enhancement therapy. Monte Carlo calculations are presented here of the central-axis radiation depth dose in a brain containing a tumour loaded with an iodine concentration of 5 mg ml-1 and irradiated with the CTX operated at various kV settings. The dose enhancement factor (DEF) is also calculated for various field sizes and for 5 mg ml-1 of gadolinium in the tumour when the CTX is operated at 140 kV. The calculated values of the DEF are close to published experimental results.     

Penetration of [3H]T-2 mycotoxin through abraded and intact skin and methods to decontaminate [3H]T-2 mycotoxin from abrasions

Penetration of 50 muCi of [3H]T-2 mycotoxin through abraded and intact skin was studied in anesthetized rats sacrificed at 5, 15, 30, 45, 60 and 90 min post-exposure. The greatest penetration was through abraded skin (49 +/- 7%) at 90 min post-exposure, whereas penetration through intact skin (2 +/- 3%) was substantially less (P less than 0.0015). Methods to decontaminate [3H]T-2 mycotoxin from abraded skin over time were studied. Treatment of [3H]T-2 contaminated abrasions by applying Trau + Medic dressing, applying Charcoal Cloth-Anti-bacterial Field Dressing (Charcoal Dressing), or swabbing with povidone-iodine 30 min post-exposure removed 17-32% of the applied [3H]T-2. Immediate blotting with immediate removal of the dressings absorbed 103 +/- 4% (Trau + Medic) and 87 +/- 4% (Charcoal Dressing) of the applied [3H]T-2, while immediate blotting and leaving the dressing in place for 30 min removed 91 +/- 5% (Trau + Medic) and 76 +/- 3% (Charcoal Dressing). It appears that immediate blotting with either dressing followed by immediate removal before application of a clean dressing is an effective method for decontaminating [3H]T-2 from abrasions.