Therapeutic controversies in the management of acute anaphylaxis.
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Biomedical subjects
Publications and source records attributed to A F Brown.
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PURPOSE: This study examined the rheological and textural characteristics (hardness, compressibilty, adhesiveness and cohesiveness) of bioadhesive oral gels containing the antimicrobial agent chlorhexidine. METHODS: Textural analysis was performed using a Stable Micro Systems texture analyser (model TA-XT 2) in texture profile analysis (TPA) mode. In this, an analytical probe was twice compressed into each formulation to a defined depth (15 mm) and at defined rates (2, 4, 6, 8, 10 mm s-1), allowing a delay period (15 s) between the end of the first and beginning of the second compressions. Flow rheograms were performed using a Carri-Med CSL2-100 rheometer with parallel plate geometry under controlled shearing stresses at 20.0 +/- 0.1 degrees C. RESULTS: All formulations exhibited pseudoplastic flow with thixotropy. Increasing concentrations of each polymer significantly increased formulation hardness, compressibility, adhesiveness and zero-rate viscosity. Increased hardness and compressibility were due to the attendent increased viscosities of these formulations. Increased adhesiveness was related to the concentrations of the (bioadhesive) polymers employed in these formulations and, in addition, was dependent on the physical state of polycarbophil. Formulation viscosity contributed to product adhesiveness, reflecting the importance of product rheology on this parameter. Decreased formulation cohesiveness, observed as the concentrations of the PVP, PC and HEC (3-5% w/w) were increased, was due an increase in semi-solid character. Numerical values of hardness, compressibility and adhesiveness were affected by the choice of probe speed, a parameter related to rate of shear in flow rheometry. Statistical interactions were observed and were assigned to the effects of HEC on the physical state of PVP (dissolved or dispersed) and PC (swollen or unswollen). CONCLUSIONS: This study has demonstrated both the applicability of textural analysis for the mechanical characterisation of bioadhesive semi-solid gel systems and, additionally, the direct influence of viscosity on the parameters defined by textural analysis, namely, hardness, compressibility and adhesiveness.
OBJECTIVE: To determine whether the higher rate of hospitalization among African Americans for congestive heart failure (CHF) could be explained by racial differences in the prevalence of clinical risk factors for CHF. DESIGN: Retrospective cohort study. SETTING: A large health maintenance organization (HMO). PATIENTS: A sample of 64,877 enrollees (27% African American and 73% white) of the Northern California Kaiser Permanente Medical Care Program who took at least one multiphasic health checkup (MHC) at or after the age of 40 years and were free of CHF at that time. MAIN OUTCOME MEASURES: First hospitalization with a principal diagnosis of CHF. RESULTS: Among cohort members younger than 60 years at baseline MHC, the age-adjusted risk ratio (RR) (African American/white) for CHF hospitalization was 2.14 for men and 2.73 for women, while for persons 60 years of age and older at MHC, the age-adjusted RR was 1.48 for both sexes. Cox proportional hazards models were used to adjust for risk factors and length of follow-up. In persons aged 60 years and older, the race difference was explained by greater prevalence of hypertension and diabetes in African Americans (RR = 1.12; 95% confidence interval [CI], 0.94 to 1.34 after adjustment for hypertension and diabetes). In those younger than 60 years, findings differed by sex. For men, African-American race was no longer a significant predictor of CHF after adjusting for hypertension, diabetes, left ventricular hypertrophy on electrocardiogram, and body mass index (adjusted RR = 1.16; 95% CI, 0.86 to 1.56). However, among younger women, African Americans continued at increased risk despite adjustment for these variables as well as smoking, plasma cholesterol, renal function, alcohol use, and myocardial infarction (adjusted RR = 1.49; 95% CI, 1.00 to 2.21). CONCLUSIONS: In this HMO population, the race differences in first hospitalization for CHF are largely explained by known clinical and behavioral risk factors, although in younger women these risk factors do not completely explain the excess risk among African Americans. These findings highlight the role of hypertension and diabetes in the development of CHF, particularly among African Americans.
A genome-wide search for linkage of microsatellite markers to chromosomal loci containing genes responsible for the major psychoses is a laborious task which can be carried out with greater speed and economy by introducing automation to several steps in the procedure. We describe the use of the Automated Linkage Preprocessor (ALP) program for the computer analysis of the waveform generated by fluorescein-labelled markers after electrophoretic separation. (To obtain a copy send a request to A.F. Brown at the below MRC address or use Anonymous FTP to ftp.hgu.mrc.ac.uk. Software is in directory pub/ALP). The program runs on a PC in the Microsoft Windows environment, and is used in conjunction with an automated laser fluorescence (ALF) sequencer (Pharmacia) and its Fragment Manager software to detect and size the PCR products, filter out peaks of fluorescence due to nonallele fragments, and generate genotypes in a format suitable for direct input to standard linkage analysis programs. The method should offer the advantages of speed, accuracy, and reduced cost. Its use in linkage studies in a large family with manic-depressive illness is discussed.
A case of chainsaw injury to the neck is described. Previous reports in the English language are exceedingly rare. A brief discussion of safety features on chain saws is followed by a review of selective vs. mandatory surgical exploration in penetrating neck trauma, including the role of ancillary diagnostic tests.
This paper reviews the mechanisms of anaphylactic shock in terms of the immunoglobulin and non-immunoglobulin triggering events, and the cellular events based on the rise in intracellular cyclic AMP and calcium that release preformed granule-associated mediators and the rapidly formed, newly synthesized mediators predominantly based on arachidonic acid metabolism. These primary mediators recruit other cells with the release of secondary mediators that either potentiate or ultimately curtail the anaphylactic reaction. The roles of these mediators in the various causes of cardiovascular collapse are examined. The treatment of anaphylactic shock involves oxygen, adrenaline and fluids. The importance and safety of intravenous adrenaline are discussed. Combined H1 and H2 blocking antihistamines and steroids have a limited role. Glucagon and other adrenergic drugs are occasionally used, and several new experimental drugs are being developed.
Automation of the typing of genetic markers offers advantages of speed, accuracy, and cost in the mapping of genetic traits and the construction of high-resolution linkage maps. We have developed an automated linkage analysis system by (i) using a robotic pipettor to set up polymerase chain reactions (PCR) to amplify microsatellites with incorporation of a single fluorescent label; (ii) using an automated sequencing apparatus for detection of the PCR products; (iii) sizing alleles automatically by the use of internal and external standards; (iv) iteratively filtering out nonallelic fragments and checking for Mendelian consistency; (v) calculating the probabilities of selected genotypes; and (vi) automatically formatting the results for input to linkage analysis programs. The method provides accurate sizing of alleles, minimizes the risk of error during manual reading and transcription of data, and increases the throughput of reliable data. It brings any inconsistencies or ambiguities in the data to the attention of the user and facilitates examination of the raw data. The ALF/ALP system, together with new, optimized microsatellite sets, particularly tetranucleotide repeats, is likely to be well-suited to fully automatic genetic linkage analysis.
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A new form of chamber for studying chemotaxis, similar in principle to the Zigmond chamber, allows the behaviour of the cells in a linear concentration gradient to be observed directly. The chamber was developed mainly for studying chemotaxis in fibroblasts using interferometric microscopy and the main design criteria were that it should have better optical characteristics, a higher dimensional precision and better long-term stability than the Zigmond chamber. It is made entirely from glass by grinding a blind circular well centrally in the counting platform of a Helber bacteria counting chamber. This procedure leaves an annular 'bridge', approximately 1 mm wide, between the new inner circular well and the original outer annular well. This bridge fulfils the same function as the linear bridge of the Zigmond chamber but the precise construction of the counting chamber ensures that a gap of 20 microns between bridge and coverslip can be accurately and repeatedly achieved when the chamber is assembled. It is envisaged that the improved optical clarity, dimensional accuracy and long-term stability of the new chamber will be advantageous in other applications, particularly in studies requiring critical microscopy or a precise knowledge of the gradient and in studies of cells, such as fibroblasts, that move much more slowly than neutrophils.
Quantitative analysis of cell size and shape has shown that the tumour promotor 12-o-tetradecanoylphorbol-13-acetate (TPA) alters one of three parameters of cell shape, dispersion. It has no effect on cell area or elongation. This reflects the fact that TPA causes cells to form long narrow processes extending from the cell body. The ability to measure alterations in specific parameters of cell shape is important for correlating changes in the observed behaviour of cells with effects on cytoskeletal organisation.