The Diagnosis and Process of Healing of Myocardial Infarction: An Electrocardiographic Study

Abstract Not Provided

Anaesthesia for colonic surgery : studies of the effects of anaesthetic techniques and other perioperative factors on colonic anastomoses and colonic blood flow

The disruption of an anastomosis is the most significant single cause of morbidity and mortality following colonic surgery. A number of factors are known to increase the risk of anastomotic breakdown in the colon, and these are reviewed. The physiology of the intestines is discussed, with particular emphasis on the effects on the bowel of anaesthetic drugs, techniques employed during anaesthesia, and other factors pertaining to the peri-operative period. A retrospective clinical study of patients who had undergone colonic anastomosis either during spinal nerve block with a light general anaesthetic or under conventional general anaesthesia is pre¬ sented and the findings discussed. There appeared to be a trend sugg¬ esting that spinal nerve block might result in a rather lower incid¬ ence of anastomotic breakdown. Because oxygen delivery is an important factor in wound heal¬ ing, and because anastomotic healing is known to be impaired by an inadequate blood flow, an animal model was developed for the measure¬ ment of colonic blood flow. The model was designed in such a way that the integrity of the nerve and blood supply was maintained, and was validated by comparison with other techniques. The effects of a number of factors of relevance to the peri-op¬ erative period were investigated using the model. Hypocapnia was found to reduce colonic blood flow, and hypercapnia to increase it. The increase in flow associated with hypercapnia diminished over a 60 min period. Moderate hypovolaemia decreased blood flow to the colon. Spinal nerve block and halothane both resulted in increased flow, al¬ though i.v. methoxamine or hypovolaemia during spinal nerve block produced substantial reductions. The clinical relevance of these findings is discussed

Source, production and export of dissolved organic carbon and nitrogen

The purpose of this research was to quantify the major sources of dissolved organic carbon (DOC) and nitrogen (DON) in forest soils and ascertain mechanisms for their production and export to surface waters. To quantify the source of DOC we made use of the on-going litter manipulation study (DIRT) at Harvard Forest, Massachusetts. The organic horizon supplies 74% of DOC to bulk soil solution, 12% is supplied by leaf litter, and 13% from root exudate and decay. In plots with no inputs, DON concentrations were 9% higher than the control plots. When either roots or litter were excluded, DON concentrations increased by 17% and 12% respectively. Both DON and DOC concentrations were significantly related to fungal biomass (R2 = 0.99 and 0.90; p \u3c 0.01). We investigated the mechanisms of DOC and DON production and their relationship with CO2 and soil C:N ratio and the effect of chronic carbon and nitrogen manipulation on these relationships. DOC was significantly related to soil respiration in the hardwood plots (R2 = 0.61; p \u3c 0.05), chronic carbon and nitrogen manipulation did not affect this relationship. In the coniferous control plots, the relationship between DOC and soil respiration was strong and significant (R2 = 0.93 p \u3c 0.05) but nitrogen fertilization affected the relationship. DOC was significantly related to soil C:N among forest type and treatment suggesting that the overall mechanisms of DOC production are unaffected by either carbon or nitrogen manipulation. We examined the effect of cold and warm temperature on the relationships between DOC, DON soil respiration and soil C:N in a laboratory controlled study. Temperature had no significant effect on the relationships between DOC and soil C:N, DOC and DON, DON and soil C:N but a significant temperature effect was apparent between both DOC and DON and soil respiration. We used mean biome soil C:N ratio and mean biome DOC export to derive an empirical model (R2 = 0.99 p \u3c 0.001). The model predicted DOC export from contrasting forest types to within 4.5% of their observed exports. We estimated global annual riverine DOC export to be between 0.41--0.48 Pg yr-1

The use of ultrasound to create tissue hyperthermia to support the treatment of cancer

The value of mild hyperthermia in improving the outcome of radiotherapy and chemotherapy treatments is well established. However, clinical applications are currently restricted to accessible tumours, with the application of controlled hyperthermia in solid tumours deep within the body presenting an unresolved problem. Ultrasound is an attractive heating technique because of its ability to create a focus at depth which can be steered around the tumour volume. However, despite considerable research no clinically usable transducers for deep tumour applications have resulted. In this thesis the underlying principles that govern the characteristics of phased array transducers have been examined. The concept of an idealised phased array has been introduced, and analysis of simulated fields from such arrays has enabled a new set of equations to be defined which relate the geometry of the field to the fundamental array design parameters (including the array diameter, radius of curvature and frequency of operation). Further simulations have examined the impact of secondary array design parameters (such as the individual element size, number density and layout geometry) which modify the field from that of the idealised case. Analysis of these has enabled an upper limit to be placed on the element size within any planar array in order to prevent undesirable changes in the characteristics of the focal region. A fifteen element phased array with a random element distribution has been constructed based on the design principles established in the simulation work. Measurements of the inter-element cross-coupling have been made, demonstrating that acoustic coupling dominated for inter-element pitches of less than 8 mm, while electrical coupling dominated at larger inter-element pitches. The field produced by the array in an acoustic tank has been characterised and compared against simulation predictions, showing good agreement in terms of the geometries of the focal region and the grating lobes. However, a number of differences have also been identified. In particular, the focal region was closer to the surface of the physical transducer in the measured fields compared to the simulation results, and there were numerous small high intensity regions between the surface of the transducer and the focus which were absent from the simulated fields. A sensitivity analysis, using a simulated factorial experiment, has been performed to identify the origin of these differences, with the results indicating that the presence of a secondary vibrational mode within the elements of the array was the principal causative factor. Finally, calculations have been performed which demonstrate the feasibility of manufacturing an array suitable for the application of mild hyperthermia in deep tumours based on the array design scheme presented in this thesis. Potential extensions of the array design have also been described which would improve the behaviour of the array under steering and provide further increase in the focal intensity

Inaccuracies in plasma oxytocin extraction and enzyme immunoassay techniques

Numerous studies have reported extensive associations between plasma oxytocin (OXT) concentrations and various human physiological and neurobehavioral processes. Measurement of OXT is fraught with difficulty due to its low molecular weight and plasma concentrations, with no consensus as to the optimal conditions for pre-analytical sample extraction, standards for immunoassay validation or the ideal protease inhibitors to prevent OXT degradation. Previous attempts at determining the efficacy of various purification techniques such as solid phase extraction (SPE) or ultrafiltration have only utilized human plasma samples, making it difficult to dissect out whether the effect of interference comes from the extraction process itself or cross-reactivity with other proteins. By testing these on pure OXT solutions, we demonstrate poor recovery efficacy and reliability of reversed phase SPE (maximum 58.1%) and ultrafiltration (<1%) techniques, and the potential for the former to introduce interference into enzyme immunoassay (EIA) measurements. The clonality of antibodies used in EIA kits also potentially contributes to the differences in the readings obtained, and we validate an EIA kit which did not require pre-analytical sample extraction with low cross-reactivity and high reliability (intraclass correlation coefficient 0.980 (95% CI 0.896–0.999). Biochemical techniques used for measuring plasma OXT concentrations must therefore be internally validated prior to translation into clinical studies

Structures of Two Melanoma-Associated Antigens Suggest Allosteric Regulation of Effector Binding

The MAGE (melanoma associated antigen) protein family are tumour-associated proteins normally present only in reproductive tissues such as germ cells of the testis. The human genome encodes over 60 MAGE genes of which one class (containing MAGE-A3 and MAGE-A4) are exclusively expressed in tumours, making them an attractive target for the development of targeted and immunotherapeutic cancer treatments. Some MAGE proteins are thought to play an active role in driving cancer, modulating the activity of E3 ubiquitin ligases on targets related to apoptosis. Here we determined the crystal structures of MAGE- A3 and MAGE-A4. Both proteins crystallized with a terminal peptide bound in a deep cleft between two tandem-arranged winged helix domains. MAGE-A3 (but not MAGE-A4), is pre- dominantly dimeric in solution. Comparison of MAGE-A3 and MAGE-A3 with a structure of an effector-bound MAGE-G1 suggests that a major conformational rearrangement is required for binding, and that this conformational plasticity may be targeted by allosteric binders