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Biomedical subjects

J Morrison

Publications and source records attributed to J Morrison.

At least 37 records · Page 2Linked to original sources

The effects of cardioplegic arrest and reperfusion on the microvasculature of the heart.

OBJECTIVES: Despite laboratory evidence of leucocyte involvement in reperfusion injury, cardiac surgical clinical trials do not support the therapeutic effectiveness of leucocyte filtration. Furthermore, the direct effects of crystalloid cardioplegia and reperfusion on the capillaries of the heart have yet to be elucidated. We tested the effects of cardioplegic arrest and reperfusion both with and without leucocyte depletion, in a model of cardiopulmonary bypass that mimics clinical cardiac surgical conditions. METHODS: Four groups of Landrace pigs were studied. Group A (n = 6) underwent 30 min of hypothermic (28 degrees C) cardiopulmonary bypass. Groups B (n = 6), C (n = 6) and D (n = 6) also had 90 min of cardioplegic arrest. Group C was then reperfused with whole blood, while Group D was reperfused with leucocyte-depleted blood. Microvascular methylmethacrylate corrosion casts were made at the end of the experimental period. Myocardial vascular anatomy was defined by electron microscopy and capillary abundance derived from this and from the weight of casts from representative areas. Leucocyte deposition was assessed using radioisotope-labelled leucocytes. Ischaemic damage to tissues was graded according to light and electron microscopic findings. RESULTS: In Group A the mean (+/- S.D.) vascular cast weight/volume of myocardium (density) was 125 +/- 9 mg/mm3. After cardioplegic arrest (Group B), it fell to 74 +/- 7 mg/mm3 (P < 0.0001) due to absence of capillaries, although arterioles, venules and non-nutritive bypass vessels remained patent. Following reperfusion with whole blood (Group C), capillary numbers partially recovered but luminal diameters were reduced with a cast density of 94 +/- 5 mg/mm3 (P < 0.0001 versus Group A and B). Leucocyte-depleted (87-92%) reperfusion in Group D did not affect cast density (90 +/- 3 mg/mm3; P = 0.17). Coronary vascular resistances in Groups C and D rose slightly, but not significantly, during reperfusion. CONCLUSIONS: Following cardioplegic arrest, microvascular changes are marked. These changes are partially reversed by 30 min reperfusion. Leucocyte depletion does not ameliorate these effects in this model.

Animals

Vertical transmission of human immunodeficiency virus.

We discuss the interactions between mother and infant that influence the transmission of HIV. Potential routes of infection are identified, and maternal and infant risk factors for transmission are explored. The role of the immune system in controlling HIV infection in the infant is discussed. Finally, preventive measures for reducing vertical transmission are proposed and evaluated.

Anti-HIV Agents

Dystrophic neurite formation associated with age-related beta amyloid deposition in the neocortex: clues to the genesis of neurofibrillary pathology.

The formation of dystrophic neurites associated with beta amyloid plaques in Alzheimer's disease (AD) appears to involve a transformation of normal neuronal cytoskeletal proteins. In order to investigate what may be the earliest neuronal changes associated with the development of dystrophic neurites, we have examined the neurochemical profile of abnormal neuritic processes associated with the beta amyloid deposition in non-AD, aged cases. In all non-AD individuals demonstrating some degree of beta amyloid deposition in the superior frontal gyrus, clustered swollen and ring-like structures, located principally in layers II and III, were labeled with antibodies to phosphorylated and nonphosphorylated domains of the middle and high molecular weight neurofilament subunits. These abnormal neurites were not immunolabeled for tau or ubiquitin or stained with thioflavine S. Double labeling for neurofilaments and thioflavine S confirmed that these clusters of dystrophic neurites were associated with plaque-like deposits. These results show that anatomically and neurochemically specific forms of dystrophic neurites can occur in non-AD cases that contain beta amyloid deposition. If these abnormal neurites correspond to an immature form of the dystrophic neurites found in the neuritic plaques of Alzheimer's disease, then neurofibrillary pathology associated with this disease may begin with an initial misprocessing and accumulation of neurofilament proteins. Furthermore, these data are consistent with the proposal that the development of neurofibrillary pathology may begin with neurofilamentous hypertrophy in damaged distal processes followed by reactive changes in the cell bodies of origin of these fibers involving cytoskeletal alterations that ultimately lead to neurofibrillary tangle formation.

Aged

Yeast artificial chromosome cloning and chromosomal localization of the abundant odontogenic keratocyst protein elafin.

An imbalance in human leucocyte elastase (HLE) activity is widely recognized to play an important pathological role in a number of human diseases. An earlier report has described greater transcription of elafin, an endogenous inhibitor of HLE, in epithelia of odontogenic keratocysts of the jaw than in normal oral mucosa. The elafin gene was now localized to chromosome 20q11.2-13.1 using a combination of somatic cell-hybrid panel screening and fluorescence in situ hybridization using a biotinylated DNA probe prepared from isolated yeast artificial chromosomes. No other positive fluorescent signals were observed. This eliminates the elafin gene as a candidate gene for naevoid basal-cell carcinoma syndrome, as the gene for this syndrome localizes to chromosome 9q23.1-31. The elafin yeast artificial chromosome DNA is to be subcloned to identify polymorphic microsatellite markers that will establish whether this gene is frequently amplified in oral neoplastic tissue.

Basal Cell Nevus Syndrome

The benefits of active rewarming after cardiac operations: a randomized prospective trial.

We conducted a prospective, randomized trial of three methods of rewarming patients after hypothermic cardiopulmonary bypass. Patients underwent either coronary artery bypass grafting or first-time valve replacement and were cooled to 32 degrees C during bypass. No significant differences existed among the groups as regards operative or preoperative parameters including hemodynamics and blood use. The patients actively warmed with a convective (Bair Hugger system, 3 hours) or a conductive blanket (electric overblanket, 4 hours) reached normothermia more quickly than those warmed with the space blanket (7 hours). This was reflected in significantly earlier extubation in the former two groups: Bair Hugger system 10.8 +/- 0.6 hours, electric blanket 11.3 +/- 1.0 hours, and space blanket 14.8 +/- 0.8 hours. Patients warmed with the space blanket required a higher dosage of morphine over the first 12 hours than those warmed with the electric blanket (10.4 vs 6.5 mg; p = 0.004), which may account for some of the differences between these two groups. No differences could be demonstrated between the two active blankets. On economic grounds we therefore recommend the reusable electric blanket for routine use.

Aged

Comparison between broad-band ultrasound attenuation of the calcaneum and total body bone mineral density in children.

We measured broad-band ultrasound attenuation (BUA) in the calcaneum using the prototype Paediatric Contact Ultrasound Bone Analyser (CUBA) and total body bone mineral density (TBBMD) using dual-energy X-ray absorptiometry (DXA) (Hologic QDR-1000W) in 58, 7-17-year-old healthy children and adolescents. Calcaneal BUA was significantly related to TBBMD (r = 0.74, p < 0.001), and both the calcaneal BUA and TBBMD were significantly correlated with age and body weight. We conclude that calcaneal BUA reflects bone mineral density (BMD) in healthy children and adolescents; however, BMD measured by CUBA appears to be less sensitive than that measured by DXA. Since BUA reflects structural properties of bone, as well as density, it may complement radiological techniques of bone density measurement in the assessment of paediatric conditions associated with fracture risk.

Absorptiometry, Photon

Genetic epidemiologic analysis of quantitative phenotypes using Gibbs sampling.

We analyzed two quantitative traits (Q1 and Q2) provided in the 'Common Disease' data set with the aim of detecting both genetic and environmental determinants. We used linear regression for screening measured variables, maximum likelihood segregation and linkage analyses for detecting and localizing unmeasured genes, and Gibbs sampling for joint segregation and linkage analyses with estimation of gene-environment interaction and polygenic effects. For both Q1 and Q2, we successfully detected the unmeasured codominant major gene (MG) that was tightly linked to candidate gene C2. We also detected all of the measured variables used in generating Q1 (age, Q3, candidate gene C5) and Q2 (EF). Although our final models differed slightly from the true data generation models, our multifaceted analytic approach was successful in characterizing the determinants of Q1 and Q2.

Alleles

Pregnancy-induced alterations of relaxation in response to magnesium in the rat aorta may be due to plasma-borne agents.

The influence of plasma from pregnant and nonpregnant humans was examined, using magnesium-induced relaxation of precontracted rat aortic rings. The results showing magnesium-induced relaxation of aortic rings from pregnant and nonpregnant rats were compared. In rat aortic rings incubated in plasma from pregnant patients, magnesium was more potent in relaxing the precontractions induced by potassium chloride than in relaxing those induced by phenylephrine. The magnesium-induced relaxation of rings incubated in plasma from normal pregnant subjects was similar to that in unincubated rings from normal pregnant rats. Neither the removal of endothelium nor pretreatment with indomethacin affected the pattern of responses in the rings. The results suggest that the effects of pregnancy on magnesium-induced relaxation of the rat aorta may be mediated by plasma-borne agents, and the mechanisms by which the agents alter the relaxation do not involve either the vascular endothelium or prostaglandin synthesis.

Animals

The role of the vascular endothelium in the contractile responses of human chorionic plate artery in pre-eclampsia to prostaglandin F2 alpha, 5-hydroxytryptamine, and potassium chloride.

This study characterises the reactivity of chorionic plate artery in pre-eclampsia to prostaglandin F2 alpha (PGF2 alpha), 5-hydroxytryptamine (5-HT), and potassium chloride (KCl) and examines the role of the vascular endothelium in these responses. Ring segments of the chorionic plate arteries of women after normal and pre-eclamptic pregnancies were contracted by PGF2 alpha, 5-HT, and KCl. The experiments were carried out in the presence and absence of endothelium, and on intact rings treated with 10(-6)M indomethacin. The maximal contractile responses of rings from pre-eclamptic women to 5-HT, PGF2 alpha, or KCl were significantly greater than those of rings from normotensive pregnant women. The EC50 values of responses were significantly lower in rings from pre-eclamptic subjects. Endothelium removal and treatment of the rings with indomethacin had no effect on the contractile responses of rings from normotensive pregnant women to all the agents, but significantly increased the EC50 value and decreased the maximal contractile responses of rings from pre-eclamptic women to 5-HT and PGF2 alpha. While de-endothelialisation increased the EC50 value for responses of the rings from pre-eclamptic women to KCl, pretreatment with indomethacin did not significantly affect the KCl-induced responses. The results of the study suggest that pre-eclampsia enhanced the reactivity of human chorionic plate artery to 5-HT, PGF2 alpha, and KCl through the involvement of endothelial derived contracting factors. The increased responses to 5-HT and PGF2 alpha were inhibited by indomethacin, but those to KCl were not.

Arteries

Screening for gestational diabetes in a multi-ethnic population.

A multi-ethnic population was screened for gestational diabetes mellitus (GDM) using a venous plasma glucose estimation, 1 h following a standard 50 g glucose load. A significant difference in the ethnic distribution of screen-positivity was found. Amongst the screen-positive group the odds ratio (OR) for special care baby facility (SCBU) admission and birthweight > 3999 g were both increased (OR = 1.87 and 1.99). Only limited diagnostic testing by a glucose tolerance test (GTT) could be achieved for the screen-positive population. For patients with confirmed GDM (two or more abnormal values on a GTT) the OR for SCBU admission was further increased to 5.1, while the OR for increased birthweight was only 1.34. Clinical attention should be directed towards outcome assessment in order to properly evaluate the nature of and place for screening for GDM in multi-ethnic populations.

Africa, Northern

Structure and composition of the rodent lamina cribrosa.

To define the architecture and extracellular matrix composition of the lamina cribrosa in rodents, normal, adult pigmented rat and guinea pig eyes were frozen and sectioned for light microscopic immunohistochemistry. Antibodies specific for collagens I, III, IV and VI, laminin, elastin, and chondroitin and dermatan sulfate proteoglycans were exposed to longitudinal and cross-sections of optic nerve heads and their binding distributions observed with the avidin-biotin-peroxidase complex technique. Cross-sections of the intraocular portion of the rat optic nerve head revealed a horizontally oval shape with distinct, vertically oriented, laminar beams. The guinea pig optic nervehead cross-section was circular, with randomly oriented beams. In both animals, collagens I, III and VI were found throughout the laminar beams, along with elastin fibrils. Collagen IV and laminin antibodies deposited along laminar beam margins and within the beams, representing astrocytic and vascular endothelial cell basement membranes. Both animals showed evidence for dermatan and chondroitin sulfate-containing proteoglycans in all connective tissue structures of the nerve head. In the rat, chondroitin-4 sulfate proteoglycans appeared localized to the sclera and laminar beams. The rat and the guinea pig optic nerve head possess an identifiable lamina cribrosa with structural proteins nearly identical to that of the primate. Both animals may provide affordable alternative animal models for in vivo studies on the role of the lamina cribrosa in glaucomatous optic nerve damage.

Animals

An evaluation of fructosamine estimation in screening for gestational diabetes mellitus.

Although persuasive arguments against routine screening for gestational diabetes mellitus (GDM) have been made, it is widely but not universally performed as a part of antenatal care. There is no international agreement on methods or criteria used for screening (or for diagnosis), and administered glucose-load methods have significant practical difficulties in a busy antenatal clinic setting. However, recent evidence supports the concept of an increased level of importance being given to a diagnosis of GDM, with interest in the fetal and neonatal origins of adult disease being added to the short-term obstetric and fetal concern during pregnancy. A second generation fructosamine test, corrected for total protein, has been evaluated as a practical alternative to glucose screening for GDM in a busy, multi-ethnic antenatal clinic. This achieved a 79.4% sensitivity and a 77.3% specificity for a diagnosis of GDM confirmed by a glucose tolerance test using Carpenter's modified criteria. In view of the organizational simplicity of this sample/test requirement, a wider evaluation is suggested together with a re-evaluation of clinical outcome criteria rather than blood glucose levels alone.

Adult