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Biomedical subjects

G McGregor

Publications and source records attributed to G McGregor.

17 recordsLinked to original sources

The impact of the 2003 heat wave on daily mortality in England and Wales and the use of rapid weekly mortality estimates.

This paper describes a retrospective analysis of the impact of the 2003 heat wave on mortality in England and Wales, and compares this with rapid estimates based on the Office for National Statistics routine weekly deaths reporting system. Daily mortality data for 4 to 13 August 2003, when temperatures were much hotter than normally seen in England, were compared with averages for the same period in years 1998 to 2002. The August 2003 heat wave was associated with a large short-term increase in mortality, particularly in London. Ozone and particulate matter concentrations were also elevated during the heat wave. Overall, there were 2139 (16%) excess deaths in England and Wales. Worst affected were people over the age of 75 years. The impact was greatest in the London region where deaths in those over the age of 75 increased by 59%. Estimated excess mortality was greater than for other recent heat waves in the United Kingdom. The estimated number of deaths registered each week is reported by the Office for National Statistics. The first clear indication of a substantial increase in deaths was published on 21 August 2003. This provided a quick first estimate of the number of deaths attributable to the heat wave and reflected the pattern of daily deaths in relation to the hottest days, but underestimated the excess when compared with the later analysis.

Aged↗

Measurement of the total active 8B solar neutrino flux at the Sudbury Neutrino Observatory with enhanced neutral current sensitivity.

The Sudbury Neutrino Observatory has precisely determined the total active (nu(x)) 8B solar neutrino flux without assumptions about the energy dependence of the nu(e) survival probability. The measurements were made with dissolved NaCl in heavy water to enhance the sensitivity and signature for neutral-current interactions. The flux is found to be 5.21 +/- 0.27(stat)+/-0.38(syst) x 10(6) cm(-2) s(-1), in agreement with previous measurements and standard solar models. A global analysis of these and other solar and reactor neutrino results yields Deltam(2)=7.1(+1.2)(-0.6) x 10(-5) eV(2) and theta=32.5(+2.4)(-2.3) degrees. Maximal mixing is rejected at the equivalent of 5.4 standard deviations.

Journal Article↗

Constraints on nucleon decay via invisible modes from the Sudbury Neutrino Observatory.

Data from the Sudbury Neutrino Observatory have been used to constrain the lifetime for nucleon decay to "invisible" modes, such as n-->3nu. The analysis was based on a search for gamma rays from the deexcitation of the residual nucleus that would result from the disappearance of either a proton or neutron from 16O. A limit of tau(inv)>2 x 10(29) yr is obtained at 90% confidence for either neutron- or proton-decay modes. This is about an order of magnitude more stringent than previous constraints on invisible proton-decay modes and 400 times more stringent than similar neutron modes.

Journal Article↗

Hepatitis C antibody detection in dried blood spots.

In the UK, there have been few studies of the seroprevalence of antibodies to hepatitis C virus (anti-HCV). As part of an ongoing prevalence study of HCV in injecting drug users, we have developed a technique for detecting anti-HCV in blood spots dried on filter paper using a commercially available assay. Subjects with and without serum anti-HCV were studied. The manufacturer's recommended cut-off (CO) for a positive anti-HCV result is kit-dependent, and therefore a ratio of test result (T) to kit CO was used to standardize results. T/CO values greater than 0.99 had a sensitivity of 100% and a specificity of 87.5% for anti-HCV detection. T/CO values greater than 1.99 had a sensitivity of 97.2% and a specificity of 100%. Hence, testing dried blood spots may be useful for detecting anti-HCV in epidemiological studies and as a diagnostic test in patients with poor peripheral venous access.

Blood Specimen Collection↗

Evaluation of 201Tl SPET myocardial perfusion imaging in the detection of coronary artery disease after orthotopic heart transplantation.

Accelerated coronary artery disease is a common complication following orthotopic cardiac transplantation. The relationship between acute rejection and accelerated coronary artery disease remains unclear. While thallium-201 (201Tl) imaging has been advocated in the diagnosis of post-transplant coronary arteriopathy, other investigators have found little role for this technique in the evaluation of such patients. We undertook a retrospective review of 13 stress/rest (10 exercise, 2 dobutamine, 1 dipyridamole) and 2 rest/rest 201Tl single photon emission tomographic (SPET) imaging studies performed in seven patients post-cardiac transplantation (mean duration post transplantation = 2.5 years). Four of these patients had serial studies with an average interval between studies of 8.3 months (range 3-14 months). Coronary angiography was performed within 12 months of each 201Tl study (mean = 4.2 months). Using the coronary angiographic diagnostic criterion of > or = 50% stenosis in one or more vessels, one or more fixed or reversible segmental defects were found on 201Tl imaging with a sensitivity of 78% and specificity of 33%. When the angiographic criterion of > 70% stenosis in one or more vessels was used the sensitivity increased to 100%, and where reversible segments were diagnostic the sensitivity was 67% and the specificity range from 42 to 58%. Although based on a small sample of patients, these results suggest that use of appropriate test methods and interpretive criteria may improve the utility of 201Tl SPET myocardial imaging in the diagnosis of coronary artery disease in cardiac transplant patients. Limited specificity may reflect associated pathological processes in these patients, including rejection, oedema and focal inflammation.

Adult↗

The effects of two FMRFamide related peptides (A-18-F-amide and F-8-F-amide; 'morphine modulating peptides') on the endocrine and exocrine rat pancreas.

The effects of two recently isolated mammalian FMRFamide related peptides (A-18-F-amide and F-8-F-amide) on the encocrine and exocrine rat pancreas were investigated. A-18-F-amide (10, 100, 1000 pM) inhibited concentration dependently glucose (10 mM)- and arginine (10 mM)-induced insulin secretion from the isolated perfused rat pancreas during the first (controls: 100%; 10 pM: 114%; 100 pM: 63%, p less than 0.05; 1000 pM: 31%, p less than 0.05) and the second secretion phase (controls: 100%; 10 pM: 102%; 100 pM: 78%; 1000 pM: 27%, p less than 0.05). The inhibitory actions of A-18-F-amide on pancreatic D-cell secretion were more pronounced during the first than the second phase (first phase: controls: 100%; 10 pM: 95%; 100 pM: 37%, p less than 0.05; 1000 pM: 39%, p less than 0.05%; second phase: controls: 100%; 10 pM: 113%; 100 pM: 72%; 1000 pM: 59%, p less than 0.05). F-8-F-amide (at 1000 pM) inhibited stimulated insulin (controls: 100%; first phase: 26%, p less than 0.05%; second phase: 20%, p less than 0.05) and somatostatin release (controls: 100%; first phase: 14%, p less than 0.05; second phase: 29%, p less than 0.05). Both peptides were without effect on basal and CCK-8-stimulated amylase release from isolated incubated rat pancreatic acini.

Amino Acid Sequence↗

Direct measurement of lateral transport in membranes by using time-resolved spatial photometry.

Spatially resolving light detectors allow, with proper calibration, quantitative analysis of the variations in two-dimensional intensity distributions over time. An ultrasensitive microfluorometer was assembled by using as a detector a microchannel plate-intensified video camera. The camera was interfaced with a software-based digital video analysis system to digitize, average, and process images and to directly control the timing of the experiments to minimize exposure of the specimen to light. The detector system has been characterized to allow its use as a photometer. A major application has been to perform fluorescence recovery after photobleaching measurements by using the camera in place of a photomultiplier tube (video-FRAP) with the goal of detecting possible anisotropic diffusion or convective flow. Analysis of the data on macromolecular diffusion in homogenous aqueous glycol solutions yielded diffusion constants in agreement with previous measurements. Results on lipid probe diffusion in dimyristoylphosphatidylcholine multibilayers indicated that at temperatures above the gel-to-liquid crystalline phase transition diffusion is isotropic, and analysis of video-FRAP data yielded diffusion coefficients consistent with those measured previously by using spot photobleaching. However, lipid probes in these multibilayers held just below the main phase transition temperature exhibited markedly anisotropic diffusive fluxes when the bleaching beam was positioned proximate to domain boundaries in the P beta' phase. Lipid probes and lectin receptor complexes diffused isotropically in fibroblast surface membranes with little evidence for diffusion channeled parallel to stress fibers. A second application was to trace the time evolution of cell surface reactions such as patching. The feasibility of following, on the optical scale, the growth of individual receptor clusters induced by the ligand wheat germ agglutinin was demonstrated.

Animals↗

Peptides, the limbic lobe and schizophrenia.

The human brain contains several peptides with probable synaptic actions, some of which form complex neuronal networks in the limbic lobe (amygdala, hippocampus and temporal cortex). A limbic lobe abnormality has been postulated in schizophrenia on the basis of similarities between schizophrenic symptoms and symptoms in cases of known limbic pathology. Cholecystokinin (CCK), somatostatin (SRIF), neurotensin (NT), vasoactive intestinal polypeptide (VIP) and substance P (SP)-like immunoreactivities were measured by radioimmunoassay in 10 brain areas of 14 schizophrenics and 12 controls. In the schizophrenic group symptoms had been rated in life and the group was divided into Type I (n = 7) and Type II (n = 7) subgroups on the basis of the absence or presence of morbid negative symptoms. In control brains each peptide showed a characteristic distribution with high levels in cortex (CCK), limbic lobe (SOM, NT, VIP) or striatal areas (SP) and low levels of each of the peptides in thalamus. Significant (P less than 0.05) differences between groups were: reductions of CCK and SOM in hippocampus and CCK in amygdala in Type II schizophrenics, and CCK in the temporal cortex of the total schizophrenic group; and elevations of VIP in amygdala in Type I schizophrenics and of SP in the hippocampus in the total schizophrenic group. The findings could not be explained by variables such as age, delay between death and necropsy or to neuroleptic medication. These clinical-state related alterations in the peptide content of the limbic system in schizophrenia may illuminate the pathophysiological basis of the disease, particularly the distinction between Type I and II syndromes.

Brain↗

Local application of capsaicin to one sciatic nerve of the adult rat induces a marked depletion in the peptide content of the lumbar dorsal horn.

In an earlier study we have shown that local application of capsaicin directly to one sciatic nerve induces a decrease of substance P and cholecystokinin octapeptide (CCK8)-like peptide from the dorsal spinal cord using immunocytochemical analysis. Here the effect of locally applied capsaicin on seven peptides known to be present in the L4 segment was assessed by radioimmunoassay and immunocytochemistry. The peptides investigated were substance P, somatostatin and CCK8-like peptide (which are present in small diameter primary afferent fibres), neurotensin, enkephalin (which are intrinsic to the spinal cord), neurophysin (of supraspinal origin) and bombesin (whose origin is unknown). Fourteen days after a single application of 49 mM solution of capsaicin a significant depletion of substance P and somatostatin was detected. These results were confirmed by parallel immunocytochemical analysis which localised the dramatic decreases of substance P and somatostatin to lamina 1 and lamina 2. In addition a depletion of CCK8-like immunoreactivity was observed by immunocytochemistry in this area, but quantitative radioimmunoassay of CCK8-like peptide did not detect this depletion. The capsaicin-induced changes were dose-dependent and reversible. Small decreases were noted with concentrations of capsaicin as low as 0.1 mM. The changes were apparent from day 9 onwards, maximal depletion seen by day 14. By 200 days post-operatively, a recovery to normal peptide levels in the ipsilateral dorsal horn was observed. In addition, a significant depletion of cutaneous substance P was noted in the area of the skin innervated by the capsaicin-treated nerve. These changes were accompanied by a significant increase in noxious thermal response (hind paw immersion test, T = 49 degrees C, ipsilateral leg 9.11 +/- 1.3 seconds, contralateral leg: 5.1 +/- 1.3 seconds, P = less than 0.005). The peptides neurotensin, enkephalin, neurophysin and bombesin were not affected by capsaicin treatment. These findings suggest that local application of capsaicin induces an indiscriminate depletion of peptide-containing primary sensory afferent fibres which is dose-dependent, long-lasting, but reversible.

Administration, Topical↗