Malignant hyperthermia (MH) is associated, in the majority of cases, with mutations in RYR1, the gene encoding the skeletal muscle ryanodine receptor. Our primary aim was to assess whether different RYR1 variants are associated with quantitative differences in MH phenotype.The degree of in vitro pharmacological muscle contracture response and the baseline serum creatine kinase (CK) concentration were used to generate a series of quantitative phenotypes for MH. We then undertook the most extensive RYR1 genotype-phenotype correlation in MH to date using 504 individuals from 204 MH families and 23 RYR1 variants. We also determined the association between a clinical phenotype and both the laboratory phenotype and RYR1 genotype.We report a novel correlation between the degree of in vitro pharmacological muscle contracture responses and the onset time of the clinical MH response in index cases (P < 0.05). There was also a significant correlation between baseline CK concentration and clinical onset time (P=0.039). The specific RYR1 variant was a significant determinant of the severity of each laboratory phenotype (P < 0.0001).The MH phenotype differs significantly with different RYR1 variants. Variants leading to more severe MH phenotype are distributed throughout the gene and tend to lie at relatively conserved sites in the protein. Differences in phenotype severity between RYR1 variants may explain the variability in clinical penetrance of MH during anaesthesia and why some variants have been associated with exercise-induced rhabdomyolysis and heat stroke. They may also inform a mutation screening strategy in cases of idiopathic hyperCKaemia.

Increased demand for plantation hardwood production has resulted in the progression of Eucalyptus plantations onto soils of reasonable physical structure but low nutrient status. This study was undertaken to investigate the effects of periodic fertilization through 15 yr on stand growth and soil chemistry of a Eucalyptus regnans F. Mueller plantation on a high rainfall site in southern Tasmania. Substantial response to N fertilizer, applied as ammonium sulfate, were measured, but there was no response to P applied as single superphosphate, either alone or in combination with N. Annual applications of N fertilizer, for a period of 13 yr, at 100 kg N ha−1 yr−1 doubled volume growth from 125 to 281 m3 ha−1, at Age 19 yr. Long‐term fertilization resulted in the accumulation of nutrients within the forest floor and surface soils. Significant reductions in soil pH, from 4.5 to 3.6 in the surface soil, were associated with the highest rate of fertilization. Reductions in pH occurred with both nitrogenous and phosphatic fertilizers. Substantial reductions in exchangeable Mg concentrations in surface soils, from 258 to 71 mg kg−1 were also measured. The research highlights the balance needed between obtaining growth response and causing detrimental soil effects from long‐term fertilization.

Low growth rates of Pinus radiata D. Don plantations on soils of low nutrient status in Tasmania require the development of nutrient management systems involving fertilization throughout the life of the stand. Periodic fertilization through 15 yr, in a Pinus radiata D. Don plantation in northeastern Tasmania was evaluated for effects on stand growth and soil. Substantial stem volume increases due to N and P fertilizer, applied as ammonium sulfate and single superphosphate were observed. Two applications of P fertilizer totaling 144 kg P ha−1 produced substantial increases in stem volume growth from 67 to 192 m3 ha−1 With P plus 13 annual applications of N fertilizer at 100 kg N ha−1 yr−1, stem volume growth increased from 192 to 344 m3 ha−1 over the 15‐yr period. Although fertilizing every second and fourth year produced less response, these treatments had better fertilizer‐use efficiency. Long‐term fertilization resulted in increases in concentrations of nutrients in the forest floor and the surface soil. The highest rates of fertilization were accompanied by significant reductions in soil pH throughout the soil profile, from 4.1 to 3.4 units. Reduction in pH occurred with both nitrogenous and phosphatic fertilizers. Substantial reductions in exchangeable Mg concentrations, from 235 to 88 μg g−1, were also measured throughout the soil profile. The highest rate of N application significantly increased the total O2 horizon biomass, with N mass doubling within the O2 horizon.

Introduction Two to three hundred transfusion complications are reported annually (1). Human variant CJD poses a relatively new and difficult concern with allogeneic blood transfusion. Cost (∼£100.00 per unit from donation to provision) is an additional consideration. With these and other considerations in mind the Association of Anaesthetists has published new guidelines for blood transfusion, which recommend a more cautious approach (2).A 5 year (July 1995–June 2000) retrospective review of transfusion requirements in children under 16 requiring debridement and split skin grafting was conducted in the North Trent regional burns unit, Northern General Hospital, Sheffield. In this 5 year period, 92 patients went to theatre a total of 107 times for debridement and grafting. 108 units of blood were cross‐matched for 61 cases, with a total of 66 units transfused over 44 operations. Thirty‐seven patients were over cross‐matched with 6 under cross‐matched.Analysis of the 5 year retrospective review reveals that with 10 g·dl−1 as an ideal target haemoglobin 8 patients were over transfused (to above normal range) and 19 were transfused more than necessary (to above 10 g·dl−1). Using 8 g·dl−1 as an ideal target haemoglobin the number of patients transfused more than necessary rises to 32. These results were analysed using a mathematical model based on 1st order kinetics with the equation dHb/Hb = dBL/EBV (where BL = blood loss and EBV = estimated blood volume) (3). This showed that without transfusion 17 of these patients would have had a Hb of above 8 g·dl−1 with 7 above 10 g·dl−1.Objectives Using the above mathematical model to devise a computer aided means for preoperative prediction of allowable blood loss before a threshold haemoglobin is reached peroperative realtime prediction of haemoglobin concentration peroperative realtime prediction of transfusion requirements testing the model in a clinical setting Materials and Methods Formulae developed were incorporated into a programme built using Microsoft Access 97. The programme facilitates the first 3 objectives outlined above. Ethical approval was obtained and a trial commenced in both a burns and spinal surgery setting to assess the how close computer predicted Hb results were to laboratory results.Key results Thus far, 16 measurements taken during 2 burns and 5 spinal fusion operations show close correlation between predicted and tested Hb results. This was validated using the Bland Altman statistical method (see Fig. 1).Bland Altman plot comparing predicted and measured Hb results following blood loss ranging from 5% to 23% of estimated circulating volume in 7 patients (16 measurements). The dotted lines indicate the mean difference ±2 standard deviations.imageConclusion Computer aided prediction of Hb concentration concurrent with blood lost peroperatively could provide a useful cost effective tool in rationalising the use of allogeneic blood transfusion in paediatric surgical patients.

A research study of establishment techniques in plantations of Eucalyptus nitens (Deane et Maiden) Maiden and Eucalyptus regnans F Mueller was assessed for growth at age 12 years. Biomass of trees and woody weeds was determined in the 13th year to evaluate the long‐term effect of herbicide treatment on plots established with optimum seedling tree and site preparation. Eucalyptus regnans produced only 60% of the biomass of E. nitens. Under‐storey woody weed biomass under E. regnans comprised 18–30% of the total biomass compared with 6% for E. nitens plots. There was less total under‐storey weed biomass under the herbicide‐treated plots, but a similar weed leaf biomass. Under‐storey weed leaf biomass contributed 14–40% of the total leaf biomass on the plots. Despite under‐storey weed biomass being substantially greater on the no‐herbicide plots sampled, this competition had not generally reduced growth of the trees compared with the herbicide‐treated plots. Suitable site preparation, providing weed‐free conditions at the time of planting, resulted in woody weed control adequate to establish seedlings and allow full growth without the use of herbicides, given suitable seedling material. Although pre‐planting herbicide treatment was not necessary for optimum growth of E. nitens grown from bare‐root transplants, it did improve growth of slower‐growing planting stock.