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Biomedical subjects

C J Brooks

Publications and source records attributed to C J Brooks.

At least 19 recordsLinked to original sources

How much did cold shock and swimming failure contribute to drowning deaths in the fishing industry in British Columbia 1976-2002?

BACKGROUND: The Workers' Compensation Board of British Columbia requested a retrospective analysis of all fishermen's deaths from immersion in water in British Columbia. AIMS: To identify the underlying cause of drowning and make recommendations to improve safety in the fishing industry. METHOD: Eighty-nine inshore and offshore fishing accidents were analysed. Where possible, deaths were classified into the four stages of cold-water immersion: cold shock, swimming failure, hypothermia and post-rescue collapse. Other factors that led up to the drowning were also identified. RESULTS: One hundred and thirty fishermen died from immersion between 1976 and 2002. One hundred and twenty-eight drownings were certified by the coroner as drowning or drowning/hypothermia and two were certified as cardiac event after immersion. The underlying causes of drownings were reclassified as: cold shock (5.4%), swimming failure (5.4%), hypothermia (5.4%), post-rescue collapse (0.8%), cardiac event (0.8%) and drowning/other (10%). In the remaining 72.2% of deaths, there was insufficient information to determine an underlying cause. All deaths occurred in water below 17.5 degrees C but 95% were in water less than 15 degrees C. CONCLUSIONS: Immersion in water below 15 degrees C is dangerous and this should be emphasized on marine survival courses. Accident investigators, coroners and pathologists need a common checklist to record vital data. A recommended format is included as Supplementary data available at Occupational Medicine Online. Fishermen should be educated about the dangers of sudden, unexpected immersion in cold water. Consideration should be given to making marine survival courses mandatory for fishermen.

Accidents, Occupational↗

Fractalkine expression on human renal tubular epithelial cells: potential role in mononuclear cell adhesion.

Fractalkine (CX3CL1) is a transmembrane molecule with a CX3C chemokine domain attached to an extracellular mucin stalk which can induce both adhesion and migration of leucocytes. Mononuclear cell infiltration at renal tubular sites and associated tubular epithelial cell damage are key events during acute renal inflammation following renal allograft transplantation. Using northern and Western blot analysis, we have demonstrated the expression of fractalkine message and protein by renal tubular epithelial cells in vitro. The expression was up-regulated by TNF-alpha, a key proinflammatory cytokine in acute rejection. Investigation of surface expression of fractalkine on cultured proximal tubular epithelial cells revealed only a subpopulation of positively staining cells. Immunohistochemistry revealed that only a proportion of tubules in renal allograft biopsies showed induction of fractalkine expression. Studies using a static model of adhesion demonstrated CX3CR1/fractalkine interactions accounted for 26% of monocytic THP-1 cell and 17% of peripheral blood natural killer cell adhesion to tubular epithelial cells, suggesting that fractalkine may have a functional role in leucocyte adhesion and retention, at selected tubular sites in acute renal inflammation. Thus, fractalkine blockade strategies could reduce mononuclear cell mediated tubular damage and improve graft survival following kidney transplantation.

Acute Disease↗

The basis for the development of a fuselage evacuation time for a ditched helicopter.

HYPOTHESIS: When a helicopter ditches or crashes in water, unless the buoyancy bags are inflated, it commonly sinks inverted. Thus, crew and passengers must make an underwater escape. It is postulated that later passengers in the escape sequence do not have the breath-holding ability to conduct a successful escape, particularly if the water is cold. This contributes to the 20-50% mortality rate in survivable accidents. METHODS: There were 132 immersed subject evaluations which were conducted in daylight and darkness to measure escape times from a helicopter underwater escape trainer, configured to the Super Puma, seated for 15 and 18 passengers. The subjects were highly experienced instructors or Navy clearance divers. RESULTS: The time from when each subject's head disappeared underwater until each subject surfaced and total fuselage evacuation time were measured and any problems hampering escape were noted. Breath-holding for the last subject out ranged from 28 to 92 s. An emergency breathing system was used by a minimum of four subjects each time and a maximum of 11 subjects in one condition. The buoyancy of the survival suit was the principal component that hampered escape. CONCLUSION: Breath-holding times were too long for the later subjects to escape without resorting to an EBS, in spite of the fact that they were highly trained. For regular crew and passengers flying over water, this would explain the high mortality, etc. Therefore, a new helicopter standard should be developed requiring fuselage design to accommodate total evacuation within 20 s from underwater. For current helicopters, where this cannot be achieved, passengers should be provided with some form of air supply, or, after ditching, the helicopter should be modified so that it will stay afloat on its side and retain an air space in the cabin.

Accidents, Aviation↗

Breath-holding ability of offshore workers inadequate to ensure escape from ditched helicopters.

BACKGROUND: Following a helicopter ditching in water, the survival rate of individuals not mortally injured by the impact ranges from 50-85%. One possible cause for this low survival rate is that the crew and passengers cannot hold their breath underwater long enough to make the often difficult escape from an inverted and submerged helicopter. METHODS: We investigated pulmonary function, breath-holding times in air (BHTa) and water (BHTw) of 228 students enrolled in offshore survival courses required to work in either the offshore petroleum industry or in military marine aviation. Comparisons were performed based on occupation, SCUBA experience, and smoking. RESULTS: In 25 degrees C pool water, the overall BHTw ranged from 5.4 to 120 s with a median of 37 s. Of the 228 subjects, 34% had a BHTw less than the 28 s required for the complete evacuation of a Super Puma helicopter under ideal conditions. No significant differences in BHTw were observed based on either smoking history (Non-Smoker, 41.5 +/- 21.6 s; Smoker, 37.2 +/- 20.2 s) or occupation (Novice, 37.5 +/- 21.1 s; Offshore, 40.5 +/- 21.1 s; Military, 45.2 +/- 20.9 s). However, SCUBA-trained individuals had a significantly longer BHT, (47.4 +/- 21.6 s) than non-SCUBA (37.6 +/- 20.6 s), as well as a greater force vital capacity (FVC), BHTa, and subjective comfort in water. CONCLUSIONS: It is concluded that the inability to breath-hold in emergency situations is a major contributor to the low survival rates of marine helicopter ditchings. Therefore, efforts must be made to both decrease escape times and to increase survival time underwater.

Accidents, Aviation↗

Cholesterol oxidase: sources, physical properties and analytical applications.

Since Flegg (H.M. Flegg, An investigation of the determination of serum cholesterol by an enzymatic method, Ann. Clin. Biochem. 10 (1973) 79-84) and Richmond (W. Richmond, The development of an enzymatic technique for the assay of cholesterol in biological fluids, Scand. J. clin. Lab. Invest. 29 (1972) 25; W. Richmond, Preparation and properties of a bacterial cholesterol oxidase from Nocardia sp. and its application to enzyme assay of total cholesterol in serum, Clinical Chemistry 19 (1973) 1350-1356) first illustrated the suitability of cholesterol oxidase (COD) for the analysis of serum cholesterol, COD has risen to become the most widely used enzyme in clinical laboratories with the exception of glucose oxidase (GOD). The use is widespread because assays incorporating the enzyme are extremely simple, specific, and highly sensitive and thus offer distinct advantages over the Liebermann-Burchard analytical methodologies which employ corrosive reagents and can be prone to unreliable results due to interfering substances such as bilirubin. Individuals can now readily determine their own serum cholesterol levels with a simple disposable test kit. This review discusses COD in some detail and includes the topics: (1) The variety of bacterial sources available; (2) The various extraction/purification protocols utilised in order to obtain protein of sufficient clarification (purity) for use in food/clinical analysis; (3) Significant differences in the properties of the individual enzymes; (4) Substrate specificities of the various enzymes; (5) Examples of biological assays which have employed cholesterol oxidase as an integral part of the analysis, and the various assay protocols; (6) New steroidal products of COD. This review is not a comprehensive description of published work, but is intended to provide an account of recent and current research, and should promote further interest in the application of enzymes to analytical selectivity.

Brevibacterium↗

Repellent and antifeedant activity of salicylic acid and related compounds against the biting midge, Culicoides impunctatus (Diptera: Ceratopogonidae).

An artificial membrane, blood-feeding method was used to assess the repellent and antifeedant effects of derivatives of salicylic acid on the biting midge Culicoides impunctatus Goetghebeur. Trans-2-hydroxycyclohexanecarboxylic acid, 6-methylsalicylic acid, 2,6-dihydroxy-4-methylbenzoic acid, and salicyluric acid caused highly significant inhibition of feeding, with salicyluric acid performing significantly greater than the other compounds. Investigating the effects of alkyl substitution of salicylic acid, o-thymotic and o-cresotic acids were also effective. A pilot clinical trial using salicyluric acid indicated that it provided a protective effect and it was hypothesized that this may have resulted primarily from contact, because no significant repellent effects were shown for this compound in a microscope slide test, designed to demonstrate repellency with volatile compounds.

Animals↗

Underwater disorientation as induced by two helicopter ditching devices.

BACKGROUND: Spatial orientation is based on the integration of concordant and redundant information from the visual, vestibular, and somatosensory systems. When a person is submerged underwater, somatosensory cues are reduced, and vestibular cues are ambiguous with respect to upright or inverted position. Visual cues may be lost as a result of reduced ambient light. Underwater disorientation has been cited as one of the major factors that could inhibit emergency egress after a helicopter ditching into water. One countermeasure to familiarize aircrew with underwater disorientation is emergency egress training. This study examined the relative degree of underwater disorientation induced by the Modular Egress Training Simulator (METS) and the Shallow Water Egress Trainer (SWET). METHODS: There were 36 healthy subjects (28 males and 8 females) who participated in the study. Underwater disorientation was quantified by measuring the deviation of subjective vertical-pointing from the gravitational vertical, time to egress, and subjective reports of disorientation and ease of egress. A repeated measure design was employed with seat position (SWET chair, METS window, and METS aisle) as the sole factor. RESULTS: Subjective response data indicated that the degree of disorientation is rated significantly higher, and the ease of egress is rated worse from the two METS seat positions than from the SWET. This is supported by the findings that subjective vertical-pointing accuracy is worse in the METS seat positions than in the SWET (p < 0.01). The time to egress is longer from the two METS seat positions than from SWET (p < 0.01). CONCLUSION: Our results indicate that the METS device is effective for inducing underwater disorientation as provoked by simulated helicopter ditching. disorientation, vestibular, subjective pointing.

Accidents, Aviation↗

Interleukin-8: A pathogenetic role in antineutrophil cytoplasmic autoantibody-associated glomerulonephritis.

BACKGROUND: In neutrophil trafficking, the role of interleukin-8 (IL-8) is location dependent. Tissue IL-8 directs transmigration, whereas intravascular IL-8 frustrates this process. The bystander damage of glomerular endothelium by antineutrophil cytoplasmic autoantibody (ANCA)-activated neutrophils is believed to be an early event in the pathogenesis of ANCA-associated glomerulonephritis. We have studied the role of IL-8 in this process. METHODS: Intraglomerular expression of IL-8 in patients with ANCA-associated glomerulonephritis was studied by in situ hybridization and immunohistochemistry and location of neutrophils by serial section immunohistochemistry. In vitro, we analyzed ANCA-stimulated neutrophil IL-8 production by enzyme-linked immunosorbent assay, and the IL-8 attributable effect of ANCA-stimulated neutrophil supernatant by chemotactic and transendothelial assays. RESULTS: There was intraglomerular expression of IL-8 at segmental, crescentic, and parietal epithelial sites. IL-8 protein expression colocalized to intraglomerular neutrophils; many localized within glomerular capillary loops, suggesting failed trafficking to tissue IL-8. ANCAs differentially stimulated time- and dose-dependent neutrophil IL-8 production, and ANCA-stimulated neutrophil supernatant demonstrated potent IL-8-dependent chemotactic activity and inhibited transendothelial migration of normal human neutrophils toward an IL-8 gradient. CONCLUSION: Despite heavy tissue expression of IL-8 in ANCA-associated GN, the production of IL-8 by ANCA-stimulated neutrophils within the intravascular compartment may frustrate neutrophil transmigration, encourage intravascular stasis, and contribute to bystander damage of glomerular endothelial cells.

Antibodies, Antineutrophil Cytoplasmic↗

Evaluation of a new universal jettison mechanism for helicopter underwater escape.

BACKGROUND: To date, there is no standard jettison mechanism for doors, windows, or hatches in ditched helicopters. A new Universal Escape Exit (UEE) has been invented and the performance has been compared with two current in-service systems in a helicopter underwater escape trainer. METHOD: A total of 416 evacuations were conducted by 40 subjects in two experiments using the Survival Systems Limited's underwater escape trainer. RESULTS: The UEE had a distinct 2-s advantage to escape; and, in the majority of cases, was preferred to a rotating lever or a straight push out system. CONCLUSIONS: Further work should continue with UEE development for qualification in an operational helicopter.

Accidents, Aviation↗

T lymphocyte responses to anti-neutrophil cytoplasmic autoantibody (ANCA) antigens are present in patients with ANCA-associated systemic vasculitis and persist during disease remission.

ANCA with specificity for myeloperoxidase (MPO) and proteinase 3 (PR3) are present in patients with systemic vasculitis. The aim of this work was to determine whether such patients have T cell responses to these antigens and whether these responses are related to disease activity. Peripheral blood lymphocytes from 45 patients and 19 controls were cultured with ANCA antigens and proliferation measured. The antigens used were heat-inactivated (HI) MPO, HI PR3, native (non-HI) PR3, HI whole alpha-granules, and 25 overlapping peptides covering the entire PR3 sequence. Significant responses to both whole PR3 preparations were seen from patient and control groups, and to the alpha-granules from the patient group. Patients responded at all stages of disease: active, remitting, treated or untreated. Only two patients responded significantly to MPO. Responses were significantly higher with the patient group than the control group to all four whole ANCA antigens. Responses to those PR3 peptides containing epitopes known to be recognized by ANCA were detected from one patient. Thus, these studies demonstrate that T cells from vasculitis patients can proliferate to PR3 and occasionally to associated ANCA antigens. Further, responses may persist even after disease remission has been achieved.

Amino Acid Sequence↗

Options for liferaft entry after helicopter ditching.

METHOD: Dry and wet evacuations were conducted by 24 male and 19 female subjects from the Nutec Super Puma Simulator into two different types of aviation liferaft. RESULTS: Dry evacuation on the windward side is the method of choice. The non-canopy raft is subjectively and objectively easier to enter both from the helicopter and the sea. CONCLUSIONS: The non-canopy raft is the raft of choice, the canopy raft needs a redesign to ensure that it always inflates the correct way and both rafts need a redesign of the painter anchor point. Aircrew should have special training in open water after traditional pool training. A helicopter ditching survival compass has been developed for training all who fly over water for a living.

Accidents, Aviation↗

The effect of wave motion on dry suit insulation and the responses to cold water immersion.

METHODS: Six subjects who were each wearing a dry immersion suit system were immersed for 1 h in 16 degrees C water in a number of different wave conditions, ranging from still water to 70 cm in height. Physiological and physical parameters were measured in order to calculate the total thermal resistance of the suit system and its components. RESULTS: None of the physiological parameters were affected significantly by the wave conditions, except for skin heat flux, which increased with wave height from 72.0 +/- 1.9 W x m(-2), at 0 cm of height, to 85.5 +/- 2.9 W x m(-2), at 70 cm of height. Wave heights up to 70 cm decreased the insulation (including boundary layer) of the dry suit system by 14%, and the only component of the suit affected by the wave motion was the insulation of the water boundary layer, which decreased by 75%. The body sites that were most affected by wave motion were the head and the trunk, with an average 45% decrement in suit system thermal resistance at those sites at wave heights of 0 to 70 cm. No significant effect was observed at sites on the distal limbs. CONCLUSION: To simulate open ocean conditions in the laboratory, the standards must take the reduction of suit insulation into account.

Adult↗

Cell adhesion molecule expression within human glomerular and kidney organ culture.

A glomerular and kidney organ culture method was developed to study cytokine inducibility of adhesion molecules and MHC antigen expression. Glomerular cells showed constitutive expression of intercellular cell adhesion molecule-1 (ICAM-1) and MHC class I and II antigens, but not vascular cell adhesion molecule-1 (VCAM-1), E-selectin, or P-selectin. Expression of E-selectin on glomerular endothelial cells (ECs) was induced by interleukin-1 (IL-1), tumour necrosis factor (TNF), interferon-gamma (IFN-gamma) and granulocyte/ macrophage-colony stimulating factor (GM-CSF); this induction was inhibited by transforming growth factor beta (TGF beta) and by IL-4. P-selectin expression was never seen within glomeruli. VCAM-1 was constitutively expressed by Bowman's capsule and proximal tubules and was weakly induced on glomerular ECs by TNF and IL-4 in combination. Glomerular endothelial ICAM-1 expression was increased by IL-1, TNF, IFN-gamma, and GM-CSF, while TGF beta inhibited induction by TNF and IL-1. Expression of MHC class I and II antigens by glomerular ECs was constitutive; further upregulation of MHC class II by IFN-gamma was observed. These studies suggest that leukocyte-endothelial cell interactions that occur within the kidney follow broadly similar principles as are proposed to occur elsewhere in the body but, in addition, there are subtle differences that reflect local conditions.

Cell Adhesion Molecules↗

Liferaft evacuation from a ditched helicopter: dry shod vs. swim away method.

METHODS: There were 23 male and 21 female subjects who conducted a series of evacuations from the NUTEC Super Puma helicopter simulator into an RFD heliraft in the Bergen Fjord. The dry shod and swim-away methods were compared both on the windward and leeward side. RESULTS: The dry shod method is the method of choice, although the swim-away method should be taught as an alternative in the event of imminent capsizing. Irrespective of method, evacuation wherever possible should be on the windward side. CONCLUSIONS: Because it is critical for the aircrew to make a split-second decision concerning which method to use, they should have special training in open water after traditional pool training.

Accidents, Aviation↗

Helicopter door and window jettison mechanisms for underwater escape: ergonomic confusion!

There are 23 different door, hatch, and window release mechanisms identified in 35 types of helicopters that earn their living over water. There is no standardization of the mechanism within each cockpit or among helicopter types, nor is there any standardization of the location relative to the operation; whether the mechanism matches the task or in which direction the door/hatch/window is jettisoned. New regulations are needed by military and civilian authorities to address the ergonomic confusion.

Accidents, Aviation↗

IL-1 beta production by human polymorphonuclear leucocytes stimulated by anti-neutrophil cytoplasmic autoantibodies: relevance to systemic vasculitis.

Neutrophils accumulate in the acute blood vessel lesions of patients with autoimmune systemic vasculitis. They have been shown previously to produce the cytokine IL-1 beta in response to stimulation with TNF. This study demonstrates that neutrophils can be stimulated by anti-neutrophil cytoplasmic antibodies (ANCA), which are present in patients with systemic vasculitis, to express mRNA and protein for IL-1 beta. Both human ANCA and MoAbs to a variety of autoantigens recognized by ANCA, including proteinase 3, myeloperoxidase, bactericidal/permeability increasing protein and elastase, are effective. This response can be inhibited by actinomycin and cycloheximide, suggesting a requirement for de novo protein synthesis. IL-1 beta production can be inhibited by pooled human intravenous immunoglobulins but not by FK506 or cyclosporin A. These data suggest that ANCA in patients with active vasculitis may stimulate neutrophils to produce cytokines. It is hypothesized that cytokine production from neutrophils that accumulate in significant numbers in vasculitic lesions contribute to and augment the local inflammatory response by the activation of vascular endothelial cells and infiltrating leucocytes.

Antibodies, Antineutrophil Cytoplasmic↗

Human vascular endothelial cells do not induce anergy in allogeneic CD4+ T cells unless costimulation is prevented.

Human vascular endothelial cells expressing MHC class II molecules have previously been shown to stimulate the proliferation of allogeneic CD4+ human T lymphocytes. Here we show that allogeneic CD4+ T cells from individual A (TA) respond to class II+ endothelial cells from individual B (EB) by inducing interleukin (IL)-2 mRNA, detectable by semiquantitative polymerase chain reaction, within 12 hr. Responding T cells (TA) that are harvested after 12 hr, rested for 3 days, and then re-exposed to the same class II+ EB stimulators can again respond by proliferation that is equivalent in degree to that observed with third-party class II+ endothelial cells (EC) as stimulators and a little greater than that observed in the primary responses. Incorporation of antibodies to LFA-3, an endothelial costimulatory molecule for T cells, or to both IL-2 and IL-2 receptor (R) during the first-round stimulation prevented the subsequent second-round proliferation of TA to class II+ EB but not to class II+ EC. This nonresponsiveness induced by anti-LFA-3 or anti-IL-2/IL-2R could be overcome by the incorporation of cyclosporine during the first-round stimulation or by incorporation of IL-2 during the second-round stimulation. These observations suggest that class II+ endothelial cells within allografts will not induce anergy in host CD4+ T cells unless costimulation is blocked or the ability of CD4+ T cells to respond by proliferation is prevented; even then the response may be modified by prevailing cyclosporine or IL-2 levels.

Antibodies↗

Human vascular endothelial cells process and present autoantigen to human T cell lines.

The effectiveness of cultured human umbilical vein endothelial cells as accessory cells for T cell activation has been investigated using T cell clones and lines derived from patients with myasthenia gravis which were specific for different epitopes on the alpha subunit of the human acetylcholine receptor. The endothelial cells were induced with IFN-gamma to express HLA-DR and -DQ at high and low levels respectively. They could then efficiently present specific peptides of the alpha subunit to an HLA-DR- and an HLA-DQw5-restricted T cell line. They could also process epitopes for both T cell lines from the full-length recombinant alpha subunit (r1-437) of the human acetylcholine receptor, where the known epitopes are 80 amino acid residues apart. The endothelial presentation of r1-437, but not of the peptides, was sensitive to chloroquine inhibition. Presentation appeared slightly less efficient (by 1.5- to 3.0-fold) with endothelial cells than with presenting cells from peripheral blood. This may reflect differences in accessory signalling since mAb blocking studies suggested that ligands for CD28 provided important accessory signalling by peripheral blood presenting cells while LFA-3 was used by endothelial cells.

Antigen Presentation↗