After the Court of Appeal: R v Harris and others [2005] EWCA crim 1980.
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Biomedical subjects
Publications and source records attributed to M Mackey.
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Differential compartmentalization of signaling molecules in cells and tissues is being recognized as an important mechanism for regulating the specificity of signal transduction pathways. A kinase anchoring proteins (AKAPs) direct the subcellular localization of protein kinase A (PKA) by binding to its regulatory (R) subunits. Dual specific AKAPs (D-AKAPs) interact with both RI and RII. A 372-residue fragment of mouse D-AKAP2 with a 40-residue C-terminal PKA binding region and a putative regulator of G protein signaling (RGS) domain was previously identified by means of a yeast two-hybrid screen. Here, we report the cloning of full-length human D-AKAP2 (662 residues) with an additional putative RGS domain, and the corresponding mouse protein less the first two exons (617 residues). Expression of D-AKAP2 was characterized by using mouse tissue extracts. Full-length D-AKAP2 from various tissues shows different molecular weights, possibly because of alternative splicing or posttranslational modifications. The cloned human gene product has a molecular weight similar to one of the prominent mouse proteins. In vivo association of D-AKAP2 with PKA in mouse brain was demonstrated by using cAMP agarose pull-down assay. Subcellular localization for endogenous mouse, rat, and human D-AKAP2 was determined by immunocytochemistry, immunohistochemistry, and tissue fractionation. D-AKAP2 from all three species is highly enriched in mitochondria. The mitochondrial localization and the presence of RGS domains in D-AKAP2 may have important implications for its function in PKA and G protein signal transduction.
PURPOSE: The high-powered holmium:YAG laser can be used for incision, ablation and resection of the prostate. The technique of holmium laser resection of the prostate is compared to transurethral prostatic resection for surgical management of benign prostatic hyperplasia in this prospective randomized study. MATERIALS AND METHODS: A total of 120 urodynamically obstructed cases were randomized to holmium laser or transurethral prostatic resection. All eligible patients were assessed preoperatively and at 3 weeks, and 3, 6 and 12 months postoperatively with an American Urological Association symptom score, peak urinary flow rate, and questionnaires concerning sexual function and continence. Preoperative pressure flow study, ultrasound prostate volume assessment and post-void residual volume measurement were repeated at the 6-month visit. All complications were noted. RESULTS: Holmium laser and transurethral resections resulted in significant improvements in symptom score, quality of life score, peak urinary flow rate and post-void residual urine measurements. Operating time was significantly longer in the holmium group but nursing contact time, catheter time and hospital stay were significantly less compared to the transurethral prostatic resection group. Urodynamic results were equivalent at 6 months. There were fewer side effects in the holmium group. Effects on continence, potency and symptoms were similar with 1-year followup. CONCLUSIONS: Holmium and transurethral resections of the prostate appear to be equivalent in surgical management of bladder outflow obstruction due to benign prostate hyperplasia. Perioperative morbidity was less in the holmium group.
BACKGROUND AND PURPOSE: Despite the arms being used extensively in the performance of many occupational tasks, little is known about the pattern of breathing and physiological cost of such work. The purpose of this study was to establish whether a simple change in arm support could alter the workload, pattern of breathing and respiratory muscle recruitment during a low intensity arm task. METHODS: Ten normal subjects performed a simulated work task when sitting, once with the arms supported and once unsupported. Subjects were required, over a five-minute period, to repeatedly pick up a 2 kg object, inspect and hold it for 15 seconds and then pack it in a box. Breathing pattern responses, measured by pneumotachograph and respiratory inductive plethysmography, were minute ventilation (VE), respiratory frequency (Rf), tidal volume (VT) and change in functional residual capacity (FRC). RESULTS: The main findings were that unsupported arm work was more physiologically demanding than supported arm work. During work VE increased as a result of a change in respiratory frequency but not VT which was much more limited when the arms were unsupported. At the completion of activity, when the arms were unloaded, VT initially increased as VE decreased. FRC and VT were reduced during arm work and increased during recovery, mainly as a result of a change in ribcage excursion. CONCLUSIONS: These findings support the theory that during arms activity, intercostal and accessory respiratory muscles act to stabilize the arms and torso, impeding chest wall movement and shifting the respiratory load from these muscles to the diaphragm. This may adversely effect performance of workers who have ventilatory limits to arm work tasks.
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BACKGROUND: Cell death occurs by either necrosis or apoptosis. The role of apoptosis in the neuronal degeneration after ischemia remains to be defined. We studied (1) the nature of neuronal death and (2) the neuroprotective action of methylprednisolone in a rat model of spinal cord ischemia. METHODS: Spinal cord ischemia was induced in adult Long-Evans rats by occluding the aortic arch for 14 minutes and simultaneously equilibrating the femoral artery pressure to the atmospheric pressure. Twenty rats were subjected to ischemia without treatment and another twenty to ischemia after treatment with methylprednisolone (30 mg/kg, 4 hours before ischemia). The animals were sacrificed and the lumbar spinal cords were examined on postoperative days 1 and 2. RESULTS: On day 1, neurons with morphology indicative of apoptosis were present in the gray matter. Their numbers increased from the ventral to the dorsal location. There were significantly fewer apoptotic neurons in the dorsal horn of the methylprednisolone-treated animals. DNA obtained from the spinal cord of untreated rats on days 1 and 2 showed laddering after electrophoresis, a feature of apoptosis. Pretreatment with methylprednisolone inhibited the development of DNA laddering. Methylprednisolone treatment was not associated with significantly improved neurologic function in the postoperative period. CONCLUSIONS: Apoptotic neuronal death occurs in the rat spinal cord after transient ischemia and is attenuated by pretreatment with methylprednisolone.
Epidemiologic, animal, clinical, and metabolic studies demonstrate the independent roles of physical activity and nutrition in the prevention and treatment of several chronic diseases. Fewer data are available to describe the synergistic effects of exercise and diet, and questions remain as to whether and how these two lifestyle factors work together to promote health and prevent disease. This paper briefly reviews many of the known effects of physical activity and nutrition on the prevention and treatment of coronary heart disease, non-insulin-dependent diabetes mellitus, obesity, and osteoporosis as well as how exercise and diet may work together. A discussion of how to increase physical activity levels and how to improve dietary intake also is included. Finally, current exercise and dietary recommendations are summarized, as are directions for future research.
Chemical packs are recent innovations in the delivery of dry heat. Because these delivery systems do not have any mechanism for verifying temperature during application, research to determine their safety seems warranted. The purpose of this study was to measure the skin temperature of adults during a 30-minute application of the MediHeat adult heating pad (MH-AHP). Seventy-seven subjects received a 30-minute application of the MH-AHP to their backs while lying in both supine and prone positions. The mean skin temperature in both positions was 101 degrees F. There were significant differences, however, in minimum and maximum skin temperature between positions. Subjects in the prone position had significantly higher maximum skin temperature and significantly lower minimum skin temperature than subjects in the supine position. It is possible that the prone position allows for more air flow over the MH-AHP and that more heat was generated causing the higher maximum temperature. This explanation does not account for the lower minimum temperature. There were no significant differences in perception of heat between the positions at either 5 minutes or 30 minutes. Findings suggest that caution is necessary when applying heating devices that depend on air circulation for heat generation.
Testicular cancer is the most common malignancy in young men and is frequently associated with delays in presentation. It has been postulated that ignorance and poor awareness of this type of cancer may contribute to such delays, which may result in high stage disease and subsequent treatment-related morbidity. This study was undertaken to assess the level of awareness of testicular cancer in a sample of 500 men from Wellington, New Zealand, and to specifically examine awareness related to the age, race, and socio-economic level of the respondents. Sixty-one per cent of men returned a satisfactorily completed questionnaire. Most (70%) were unaware that cancer of the testis could develop. Of those who correctly identified testis cancer as occurring, half recognized the most commonly affected age group, 40% understood testis cancer could be treated, and 14% believed testis cancer could be cured with treatment. The lowest awareness score (mean +/- s.d.) were found in the 18-30 age group. The score in this group (2.82 +/- 1.47) was significantly lower than that seen in the 31-40 (mean 3.66 +/- 1.81, P = 0.009) or 41-50 (mean 3.57 +/- 2.16, P = 0.036) age groups. Differences were also seen between ethnic groups, with Maori having significantly lower scores than non-Maori (Maori, mean 2.69 +/- 1.52; non-Maori, 3.45 +/- 1.83; P = 0.044). Higher scores were associated with higher socio-economic grouping. The overall poor awareness of men in this study supports the need for a public education programme aimed at encouraging men to seek early advice following the recognition of testicular masses.
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Psyllium hydrophilic mucilloid, rich in soluble fiber, significantly lowers serum cholesterol concentrations. To investigate the lipid-lowering effects of a ready-to-eat cereal enriched with psyllium, we studied 44 hypercholesterolemic ambulatory individuals for 7 wk, using a randomized, double-blind, parallel design. After a 1-wk baseline period, subjects were randomly assigned to consume 114 g/d of a psyllium-flake or wheat-bran-flake cerearl for 6 wk adjunctive to an American Heart Association Step I diet. Serum high-density-lipoprotein cholesterol and triglycerides remained unchanged throughout the study; however, serum cholesterol and low-density lipoprotein (LDL) concentrations were significantly lower on psyllium than on wheat-bran cereal. Additionally, serum total and LDL cholesterol values were significantly lower than baseline values in the psyllium group. The dietary nutrient intake of the two groups did not differ except for soluble fiber. Adding psyllium-enriched cereal to a prudent low-fat diet may enhance dietary management of hypercholesterolemia.
A unique dialysis device was developed to allow direct comparison of permeability characteristics of different membranes to various solutes under identical conditions. Studies with Cuprophan (CM), polycaronate (PCM), and peritoneal membrane (P) yielded the following results: 1. PCM is similar to CM in permeability to low molecular weight solutes. 2. PCM is significantly more permeable to middle molecular weight substances than CM or P. 3. P is more permeable to middle molecules than CM.
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