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Biomedical subjects

A J Carmichael

Publications and source records attributed to A J Carmichael.

At least 55 records · Page 3Linked to original sources

The occurrence of bacteraemia with skin surgery.

The need for chemoprophylaxis for bacterial endocarditis is partly dependent on the risk of bacteraemia associated with the procedure, which has not been adequately defined for skin surgery. The incidence of postoperative bacteraemia in 149 immunocompetent out-patients with non-infected lesions was 0.7% (95% CI 0.3-3.8%). Procedures included excisions, flaps, grafts and micrographically controlled surgery. Coagulase-negative staphylococcus was the most common skin isolate at the site of surgery, present in 68.5% of patients. The most effective chemoprophylaxis would be intravenous vancomycin, which is inconvenient and has an inherent risk of morbidity. Given the low incidence of bacteraemia and the disadvantages of the optimum chemoprophylaxis, surgery on non-infected lesions does not warrant prophylactic antibiotics to prevent the very low risk of bacterial endocarditis.

Adult↗

Radiation chemistry of the hippocampal brain slice.

The in vitro hippocampal brain slice is a 0.4 mm thick neural network that can be used to study brain responses to radiation and related injuries. This preparation is unique in that it responds to ionizing radiation within minutes after exposure without complications from changes in vascularity, blood flow, blood pressure, etc. Electrophysiological studies have shown that x- and gamma-rays alter synaptic transmission and spike generation, elements of normal brain activity. To evaluate the role of hydroxyl free radicals (OH) in these changes, slices were exposed to dilute H2O2 solutions. EPR spin trapping experiments verified that OH is produced. Neural responses, while similar, were not identical to those due to radiation, possibly because of a different distribution of OH. Although H2O2 is freely diffusible, it produces OH at specific sites where, e.g. iron reduces it. In contrast, x- and gamma-rays produce OH more uniformly throughout the tissue. H2O2 may provide a better model for high-LET radiation where yields of radical products of water radiolysis are decreased and peroxide reactions predominate.

Cosmic Radiation↗

Skin sensitivity and transdermal drug delivery. A review of the problem.

Transdermal devices are now marketed for the delivery of systemic medication through the skin. Advantages associated with transdermal drug delivery include avoidance of first-pass metabolism and improved patient compliance. Drugs currently available by this route include scopolamine (hyoscine), nitroglycerin (glyceryl trinitrate), estradiol, nicotine and clonidine. This novel development has brought in its wake a specific constellation of skin sensitivity problems, which vary widely in incidence between drugs. Varying the site of drug administration to minimise these reactions is important. Any eczematous reaction can be treated with a moderately potent topical steroid. Tolerance to oral challenge in those with topical sensitivity occurs, but caution is still advocated before proceeding to this step. The increasing use of transdermal drug delivery systems across many specialties means that problems of skin sensitivity are of growing relevance to the dermatologist, the hospital specialist and the primary care physician.

Administration, Cutaneous↗

Adult onset Mongolian spot.

We report a case of adult onset, unilateral, progressive, grey-blue pigmentation on the back of an Asian male. Histology showed the pigmentation to be due to deep dermal melanocytes. The spectrum of clinical presentations of dermal melanocytosis is reviewed and the unique features of this case outlined.

Adult↗

Reactions of active oxygen and nitrogen species studied by EPR and spin trapping.

The reactions of hydrogen peroxide (H2O2) with nitrite (NO2-) and of superoxide (O2-.) with nitric oxide (NO.) were studied using EPR and spin trapping techniques. These reactions reportedly have a common peroxynitrite (OONO-) intermediate. It has been suggested that this intermediate when protonated rapidly decomposes producing hydroxyl radicals (.OH) and the nitrogen dioxide radical (NO2.). The production of .OH in the reaction between H2O2 and NO2- was confirmed in spin trapping experiments using the spin trap 5,5-dimethyl-1-pyrroline-1-oxide (DMPO). H2O2 and NO2- were mixed at neutral pH and then the pH was decreased to pH 3-3.5 in the presence of DMPO or DMPO and ethanol. In these experiments, the EPR spectrum of the DMPO-OH adduct was obtained in addition to a weak EPR spectrum consisting of a triplet of triplets (a N = 1.415 mT and a N beta = 0.35 mT) indicating the addition of a nitrogen centered radical to DMPO. The formation of .OH was confirmed using ethanol as an .OH scavenger. The DMPO-hydroxyethyl adduct was produced from the reaction of .OH with ethanol. However, in experiments using an excess of ethanol, the formation of DMPO-OH was not prevented. This suggests that the DMPO-OH formed in the decomposition of HOONO does not entirely originate from a direct addition of .OH to DMPO. The reaction of O2-. with NO. was carried out in deaerated and air-saturated solutions at pH 12.3 where the dismutation of O2-. is minimal. The pH was then decreased to pH 3-3.5 in the presence of DMPO or DMPO and ethanol. In these experiments, the most prominent EPR spectrum obtained was a triplet of triplets (aN = 1.415 mT and a beta N = 0.35 mT) suggesting the addition of a nitrogen centered radical to DMPO. The formation of DMPO-OH was minimal and there was no formation of DMPO-hydroxyethyl adducts in the presence of ethanol. The results suggest that NO. in solution yields additional reactive species which act as nitrating agents in the presence of DMPO.

Electron Spin Resonance Spectroscopy↗

Nitric oxide interaction with lactoferrin and its production by macrophage cells studied by EPR and spin trapping.

The production of nitrate (NO3-) and nitrite (NO2-) from macrophage-derived NO was studied using EPR and spin trapping. The formation of NO3- was determined via EPR in reactions involving the iron-binding protein, lactoferrin. The formation of NO2- was determined via EPR/spin trapping in the reaction between NO2- and H2O2. Dissolved nitric oxide (NO.) was reacted with lactoferrin yielding an EPR spectrum (77 degrees K) different from the normal EPR spectrum obtained for lactoferrin, suggesting that NO. interacts with the ferric ions bound to lactoferrin forming a ferric-nitrosyl type complex. The EPR spectrum (77 degrees K) of this ferric-nitrosyl type complex was also observed in the supernatant fluid of macrophage cell suspensions following their stimulation with lipopolysaccharide (LPS). During LPS stimulation of macrophages, these cells generate NO. which in turn produces NO3- and NO2-. The ferric-nitrosyl type complex is formed in a reaction mixture containing apolactoferrin and bicarbonate following the reaction of Fe+2 with NO3-, generated from macrophage-derived NO(.), to produce Fe+3 and NO(.). Furthermore, in an acidic medium, NO2- reacts with H2O2 forming peroxynitrous acid (HOONO) which rapidly decomposes into hydroxyl radicals (.OH) and the nitrogen dioxide (NO2.) radical. In the supernatant fluid of LPS-stimulated macrophage suspensions, the production of .OH was verified by spin trapping using 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) as the spin trap and ethanol as the .OH scavenger. The EPR spectra corresponding to the DMPO-OH and the DMPO-hydroxyethyl adducts were identified.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Sonochemistry of acetone and acetonitrile in aqueous solutions. A spin trapping study.

The 50 kHz sonolysis of argon-saturated water-acetone and water-acetonitrile mixtures was studied by EPR and spin trapping with 3,5-dibromo-4-nitrosobenzenesulfonate over a wide range of solvent composition. For both systems a single maximum was observed for the spin adduct yield of methyl radicals and of the radicals formed by H-abstraction from acetone and acetonitrile. These results combined with previous studies of water-methanol and water-ethanol mixtures indicate that the greater the vapor pressure of the volatile organic component, the lower the concentration of organic solute at which the maximum radical yield occurs. Methyl radicals from acetone are formed by C-C bond scission in the collapsing argon bubbles. For acetonitrile, C-H bond scission at high temperature is followed by H-addition to the triple bond and the decomposition of this intermediate radical to form methyl radicals. Since Anbar has shown (Science 161, 1343, 1961) that sonoluminescence and acoustic cavitation occur during the impact of liquid water on water with linear velocities similar to those of collapsing ocean waves, the sonochemistry of nitriles is of interest to chemical evolution studies.

Acetone↗

Detection of antibodies to acetaldehyde-albumin conjugates in alcoholic liver disease.

The principal metabolite of ethanol, acetaldehyde, conjugates with various proteins that form antibody-inducing neo-antigens. We have analysed sera from patients with biopsy-proven alcoholic liver disease (hepatitis = 10, cirrhosis = 11, steatosis = 3) and controls = 19 (normal teetotallers and 6 non-alcoholic liver disease). Sera were examined with an enzyme-linked immunoabsorbent assay (ELISA) for antibodies binding preferentially to an acetaldehyde-albumin conjugate. Reactive sera from alcohol misusers were then purified using an amino-hexyl Sepharose affinity column. Antibodies binding to the acetaldehyde-albumin epitopes were significantly raised (P < 0.005) in all groups of alcohol misusers, and were present in greatest titre in those with alcoholic hepatitis. These antibodies were successfully purified using the gel affinity column. We conclude that alcohol misusers have significant titres of antibodies reacting to the acetaldehyde-albumin complex. The role of these antibodies remains nuclear, but may be related to the initiation of an inflammatory response and tissue damage following ethanol consumption.

Acetaldehyde↗