The EBSD spatial resolution of a Timepix-based detector in a tilt-free geometry.

Performing EBSD with a horizontal sample and a parallel EBSD detector sensor, enables safer specimen movements for data collection of large specimen areas and improves the longitudinal spatial resolution. The collection of electron backscattering patterns (EBSPs) at normal incidence to the electron beam has been revisited via the use of a direct electron detection (DED) sensor. In this article we present a fully operational DED EBSD detection system in this geometry, referred to as the tilt-free geometry. A well-defined Σ=3[101]{121} twin boundary in a Molybdenum bicrystal was used to measure the physical spatial resolution of the EBSD detector in this tilt-free geometry. In this study, two separate methods for estimating the spatial resolution of EBSD, one based on a pattern quality metric and the other on a normalised cross correlation coefficient were used. The spatial resolution was determined at accelerating voltages of 8 kV, 10 kV, 12 kV, 15 kV and 20 kV ranging from ~22-38 nm using the pattern quality method and ~31-46 nm using the normalised cross correlation method.

Effect of WEB 2086 on myocardial infarct size and regional blood flow in the dog.

OBJECTIVE: Systemic administration of platelet activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-phosphocholine) produces hypotension and decreased cardiac output; in isolated heart preparations PAF increases coronary vascular resistance and depresses inotropic state. A precursor of PAF bioactivity has been found early in myocardial ischaemia and other reports have suggested that PAF antagonists can reduce myocardial damage and ventricular arrhythmia. This study concerns the effects of WEB 2086, a PAF antagonist, on myocardial infarct size and coronary blood flow after total coronary artery occlusion. METHODS: Open chest anaesthetised dogs (n = 26) were pretreated with either WEB 2086 (5 mg.kg-1) or saline before proximal occlusion of the circumflex artery and constant infusion of WEB 2086 (1 mg.kg-1.h-1) or saline was maintained for 5 h. Cardiac output and regional myocardial flow were measured with radiolabelled microspheres (46Sc, 57Co, and 113Sn) before and immediately after occlusion and 5 h later. In the 22 dogs surviving occlusion, infarct size was determined by planimetry of cross sectional slices after exposure to triphenyltetrazolium chloride. RESULTS: Infarct size was not different between treated and control groups, at 23.6(SEM 2.3)% v 24.8(3.7)% of left ventricle, and was not different between groups when related to vasculature at risk and to collateral blood flow determined with microspheres. CONCLUSIONS: No beneficial effect of a relatively large dose of the potent PAF antagonist, WEB 2086, on myocardial infarct size or collateral blood flow was found after relatively short duration of myocardial ischaemia in the dog.

Plasma platelet activating factor degradation and serum lipids after coronary bypass surgery.

OBJECTIVE: Platelet activating factor (PAF) is a potent mediator in inflammatory responses and maybe involved in various disease states. Degradation of PAF in plasma results from the action of a specific, lipoprotein associated, acetylhydrolase. The aim was to determine plasma acetylhydrolase activity under optimised conditions, PAF half life, phospholipase A2 activity, the lyso-derivative of PAF (lyso-PAF), and lipids in patients undergoing coronary artery bypass grafting. METHODS: The study variables were determined 3 d and 7 d following coronary artery surgery and compared to presurgical values in 15 males, age 55(SEM 4) years. RESULTS: Three days following coronary bypass grafting, total, LDL and HDL cholesterol fell significantly by 30%, 45%, and 15% respectively (p less than 0.001), all decreases correlating with bypass time (p less than 0.025). Concentrations remained low at 7 d (p less than 0.005). Acetylhydrolase activity fell by 38% (p less than 0.001) at 3 d post-surgery and remained depressed, but plasma PAF half life did not change after surgery. The inverse relationship between acetylhydrolase activity and plasma PAF half life preoperatively (p less than 0.01) was not evident after surgery. There was a direct linear relationship between acetylhydrolase activity and both total (p less than 0.002) and LDL cholesterol (p less than 0.001) before surgery. The fall in acetylhydrolase activity correlated with the fall in these lipids (p less than 0.01) but not with that of HDL cholesterol. Plasma lyso-PAF decreased by 65% (p less than 0.001) at 3 d and remained depressed (p less than 0.001). Plasma phospholipase A2 activity increased by 60% (p less than 0.01) and remained raised (p less than 0.05), the increase at 3 d being related to bypass time (p less than 0.05). CONCLUSIONS: The large fall in plasma acetylhydrolase activity after coronary bypass grafting is consistent with the fall in plasma lipids. However, the absence of a significant change in the measured PAF half life in plasma raises questions as to the pathophysiological significance of the decrease in acetylhydrolase activity.

Selective expression of immune-associated surface antigens by keratinocytes in irritant contact dermatitis.

The expression of three immunoregulatory surface antigens by epidermal keratinocytes was studied in irritant contact dermatitis (ICD), in order to assess whether keratinocytes have a modulatory role in the pathogenesis of this disorder. Biopsies were taken from 48-h patch test reactions to six structurally unrelated irritants, and frozen sections immunolabeled with monoclonal antibodies to the major histocompatibility complex class II antigen, HLA-DR, intercellular adhesion molecule-1 (ICAM-1), and the 88-Kd glycoprotein CD36 (OKM5), as well as to the CD3 (T cells) and CD11a (lymphocyte function associated antigen-1, LFA-1) antigens. We found that there was very limited expression of HLA-DR by keratinocytes, with no correlation between the extent of HLA-DR positivity and the degree of T cell infiltration into the epidermis and dermis, suggesting that interferon gamma may not be a significant mediator of ICD at 48 h. In contrast, keratinocytes showed extensive upregulation of ICAM-1, with an excellent spatial association between ICAM-1 expression and LFA-1 positive leucocytes in the epidermis. This indicates that keratinocyte ICAM-1 induction is not restricted to diseases in which antigen presentation is pivotal, but that it has a generalized role in cutaneous inflammatory reactions, promoting the infiltration of leucocytes into the epidermis. Immunolabeling with OKM5 revealed that CD36 is present to a variable degree on keratinocytes in normal skin. Differential changes in the pattern of keratinocyte expression occurred between irritants, in a manner that suggested that the CD36 antigen does not act as an adhesion molecule in ICD, but rather that its expression is related to the proliferative state of the epidermis. The results of this study demonstrate that immune-associated antigens are selectively expressed on the surface of keratinocytes in 48-h ICD biopsies, implying that these cells play an important regulatory role in the development of the inflammatory response to irritant chemicals.

Differential effects of structurally unrelated chemical irritants on the density of proliferating keratinocytes in 48 h patch test reactions.

Alterations in the proliferative capacity of human epidermis following topical exposure to structurally unrelated chemical irritants were investigated, with the aim of improving our understanding of the cellular changes that take place during the development of irritant contact dermatitis (ICD). Healthy volunteers were patch tested for 48 h with the following six irritants and their appropriate vehicle and occlusion controls: 5% sodium lauryl sulphate (SLS), 0.5% benzalkonium chloride, 80% nonanoic acid (NAA), 0.02% dithranol, 0.8% croton oil, and 100% propylene glycol (PG). After the degree of inflammation induced was visually graded, biopsy samples were removed and the dividing keratinocytes were identified immunocytochemically by using the monoclonal antibody Ki-67, with quantification being performed on the basis of the number of positive cells/100 basal keratinocytes. Statistically significant increases in the density of proliferating cells occurred in the reactions to SLS, NAA, and PG, whereas, in contrast, dithranol caused a marked decrease in the number of dividing keratinocytes. Overall, the density of proliferating keratinocytes did not show a linear relationship with the visually assessed intensity of inflammation, indicating that the changes observed were related to the chemical nature of the individual irritants and their specific biochemical interactions with the keratinocytes, rather than being the consequence of a generalized inflammatory response. Differential release of epidermal cytokines and mediators by the six irritants may account for these varying states of keratinocyte proliferation. Application of the Spearman rank coefficient of correlation revealed that the changes in mitotic activity of keratinocytes were unrelated either to the total density of leukocytes infiltrating the epidermis and dermis, or to the individual densities of the major phenotypic classes of inflammatory cells present. This makes it unlikely that the localized release of cytokines by infiltrating leukocytes is, by itself, the primary factor in the alteration in epidermal cell kinetics seen in ICD. Our results provide a further demonstration of the diverse actions of different chemical irritants on human skin and emphasize the need to regard ICD as a heterogeneous disorder.

Differential patterns of epidermal leukocyte infiltration in patch test reactions to structurally unrelated chemical irritants.

In previous studies, we showed that a number of aspects of the histopathology of irritant contact dermatitis are profoundly influenced by the chemical nature of the irritant applied. We report here that this phenomenon also extends to the infiltration of leukocytes into the epidermis. Healthy volunteers were patch tested with the following irritants and their appropriate controls: benzalkonium chloride, sodium lauryl sulphate, croton oil, dithranol, nonanoic acid, and propylene glycol. After visually grading the intensity of the resulting inflammation, biopsies were removed and the major phenotypic classes of leukocytes identified immunocytochemically. Dermal and epidermal cell densities were determined, and the expression of several activation/proliferation antigens studied. We found a similar pattern of cellular infiltration in the dermis of all irritant groups; the densities of most of the cell types rising in line with the intensity of inflammation. Within the epidermis, however, there were marked differences in the patterns of cellular infiltration between the irritant groups, leading to poorer correlations between leukocyte density and visual grading. The greatest disparity occurred between croton oil and nonanoic acid biopsies, the former being characterized by the influx of large numbers of leukocytes, the latter showing remarkably little exocytosis. Infiltration of neutrophils occurred to varying degrees with all irritants, but a disproportionately large number were present in sodium lauryl sulphate biopsies. All control groups showed a rise in CD4+ cells, with distilled water also producing increases in CD11c+ cells and neutrophils. A selective influx of CD25+ cells occurred in the epidermis of both irritant and control groups. Our observations further highlight the heterogeneous nature of irritant contact dermatitis, and confirm previous findings that visually negative control patch tests show marked cellular reactivity.

Epidermal damage induced by irritants in man: a light and electron microscopic study.

Irritant contact dermatitis may be induced by many chemicals and has a far greater incidence than allergic contact dermatitis. Despite this, it receives relatively little attention and its pathogenesis remains poorly understood. To gain a greater understanding of the interaction of irritants with the skin, we investigated the histopathological changes resulting from the topical application of a series of structurally unrelated irritants. Human volunteers were patch-tested with appropriate concentrations of nonanoic acid, sodium lauryl sulphate, dithranol, benzalkonium chloride, croton oil, and propylene glycol, which produced generally mild to moderate responses. Biopsy specimens were taken after 48 h and examined by light and electron microscopy. Spongiosis and the infiltration of predominantly mononuclear cells were observed in the epidermis of the majority of biopsy specimens, and were particularly pronounced and extensive in croton oil reactions. In addition, several irritants induced distinct and characteristic patterns of keratinocyte damage. Nonanoic acid and sodium lauryl sulphate caused morphologic changes indicative of disturbances in keratinocyte metabolism and differentiation, giving rise to dyskeratosis and parakeratosis respectively, while dithranol induced marked swelling of keratinocytes in the upper epidermis. The results suggest that there is a diversity and specificity in the histopathology of irritant contact dermatitis, reflecting the different ways in which chemicals may interact with components of the skin.

Differential effects of structurally unrelated chemical irritants on the density and morphology of epidermal CD1+ cells.

In order to gain a greater insight into the complex mechanisms of action of different irritant chemicals on the skin, we have studied the behavior of epidermal CD1+ cells in experimentally induced irritant contact dermatitis. Healthy, human volunteers were patch tested for 48 h with the following six chemically unrelated irritants and their appropriate vehicle controls; benzalkonium chloride, sodium lauryl sulphate, dithranol, nonanoic acid, croton oil, and propylene glycol. After visually assessing and grading the resulting inflammatory reactions, punch biopsies were taken and the morphology and density of CD1+ cells in the epidermis studied using immunocytochemical techniques in combination with image analysis and electron microscopy. Statistically significant decreases in the epidermal density of CD1+ cells occurred in the responses to dithranol (p less than 0.05) and nonanoic acid (p less than 0.01). Importantly, these changes in density were not simply due to variations in the intensity of inflammatory response (r = 0.1157). Alterations in the length of the dendritic processes of CD1+ cells were also induced, and semi-quantitative analysis revealed significant decreases in dendrite length in the reactions to sodium lauryl sulphate (p less than 0.05), nonanoic acid (p less than 0.001), croton oil (p less than 0.05), and dithranol (p less than 0.005). Unlike epidermal density, however, this effect on cell morphology was directly related to the severity of inflammation (r = -0.74, p less than 0.01). Morphologic evidence of cellular injury to Langerhans cells was seen by electron microscopy in the majority of biopsies, although relatively few cells were affected in sodium lauryl sulphate and propylene glycol reactions. Benzalkonium chloride, unlike the other irritants, also induced a state of metabolic activation in a high proportion of epidermal Langerhans cells. Lymphocyte/Langerhans cell apposition was observed in most samples, but was particularly prevalent in the reactions to dithranol. The results of this study demonstrate that significant changes in the morphology and density of Langerhans cells occur in irritant contact dermatitis, some of which are directly influenced by the chemical nature of the irritant.

Urticarial vasculitis in a connective tissue disease clinic: patterns, presentations, and treatment.

Findings in 27 patients with typical skin lesions of urticarial vasculitis (UV) who were seen at a connective tissue disease clinic over a 5-year period (1986 to 1990) are reviewed. The majority suffered from systemic lupus erythematosus (SLE) or from "lupus-like" disease (18 patients), 1 from "mixed" connective tissue disease (MCTD), and 5 from primary UV. All of the latter patients had normal serum complement levels (normocomplementemic urticarial vasculitic syndrome; NUVS). No patients with hypocomplementemic UV were encountered. Two patients suffered from necrotizing vasculitis (polyarteritis nodosa, Wegener's granulomatosis); one had a C1-esterase inhibitor deficiency and also demonstrated an immunoglobulin G paraproteinemia. Angioedema occurred in many patients and could not be used as a differential diagnostic feature. The course of the illness was chronic in most patients, lasting for up to 23 years, and the response to therapy was unpredictable, erratic, and unsustained. The use of intravenous "pulse" methylprednisolone, cyclophosphamide, or high-dose oral steroids helped selected patients. Colchicine was dramatically effective in one patient with NUVS of 15 years duration. Azathioprine was not beneficial. None of the five patients with NUVS suffered from severe systemic involvement or renal disease, confirming observations by others that this form of UV represents a milder example of the condition.

Alcohol consumption and casualties; drinking in the event.

The data reported are from a 20% probability sample (n = 2516) of all adult patients seeking care in the emergency room at San Francisco General Hospital during a 60-day period. Thirty-five percent (35%) of the injured and 18% of the non-injured reported drinking prior to the event. This paper compares the following variables related to drinking-in-the-event for injured and non-injured: drinking places, drinking companions, amount consumed, time lapsed between drinking and the event, effects of drinking and causality attributed by the patient to drinking and the event. When these variables were entered into a logistic regression to evaluate their predictive value on injury status, only time lapsed since the last drink and drug use prior to the event were predictive of injury with both being negatively associated with admission to the emergency room for an injury. Injuries were more likely than non-injuries to occur in close proximity to drinking (44% of injuries occurred in less than 1 h of the last drink), and close to a third of the injured attributed a causal association of drinking with the event, with 60% of these feeling they were drunk at the time of injury.

Alcohol consumption during pregnancy among Southern city women.

As national survey data on American drinking practices have suggested a higher rate of heavy drinking among Southern city women compared to women in other regions, this study sought to determine drinking patterns during pregnancy in this group. A consecutive sample of 428 prenatal patients, who were residents of a Southern metropolitan area, were interviewed during the fourth month prenatal clinic visit. Although close to 50% of this sample were abstainers, 11% of the drinkers were found to be heavy drinkers, averaging more than two drinks daily, while 18% were high-maximum drinkers, consuming at least five drinks on an occasion prior to pregnancy. Forty-eight percent of the drinkers had become abstainers during the first 4 months of pregnancy, which was significantly higher than the 35% found in a representative non-Southern population (P less than 0.01). More frequent high-maximum drinking and increased drinking during pregnancy, both of which are potentially risky drinking practices for fetal outcome, were found primarily among blacks and those 14-19 years of age. The large proportion of both blacks (85%) and those 14-19 (33%) in this sample may put this population at high risk for adverse fetal outcomes related to alcohol consumption during pregnancy.

Sneddon's syndrome.

Sneddon's syndrome refers to the rare association of extensive livedo reticularis with multiple ischaemic cerebrovascular episodes. Endarteritis obliterans is the most common cutaneous pathology. It is likely that several pathogenic mechanisms may give rise to Sneddon's syndrome, as the condition is associated with a high incidence of generalised atherosclerosis, hypertension, valvular heart disease and the presence of antiphospholipid antibodies.

Variation in plasma platelet-activating factor degradation and serum lipids after acute myocardial infarction.

BACKGROUND: Platelet-activating factor is a biologically potent phospholipid that may mediate cell damage in patients with myocardial ischemia. In plasma, its inactivation to lyso-platelet-activating factor is catalyzed by a specific, lipoprotein-associated acetylhydrolase. Because lipoprotein levels decrease after myocardial infarction, a possible reduction was suspected to occur in plasma degradation of platelet-activating factor. METHODS: Degradation of platelet-activating factor was examined in an optimized assay of acetylhydrolase activity and in relation to the in vitro plasma half-life of platelet-activating factor. These, plasma lyso-platelet-activating factor and serum lipids, were measured in 12 men with acute myocardial infarction at presentation and at 2 and 7 days later. RESULTS: Acetylhydrolase activity was depressed at day 2 and at day 7. The corresponding increase in plasma half-life of platelet-activating factor was minimal and insignificant. A significant linear relation existed between the half-life of platelet-activating factor and the reciprocal of acetylhydrolase activity at each time of study, indicating a hyperbolic relation between the two. By day 2, total and low-density lipoprotein cholesterol had decreased but showed no further change by day 7; high-density lipoprotein cholesterol had not decreased at day 2 but was depressed by day 7. Plasma lyso-platelet-activating factor had decreased by day 2 and had returned to its initial level by day 7. CONCLUSIONS: Acute myocardial infarction is associated with depression of plasma acetylhydrolase activity, and because of the hyperbolic relation between the plasma enzyme activity and the half-life of platelet-activating factor, the latter shows negligible change. Hence, the mechanism for the inactivation of any platelet-activating factor that might be released as a consequence of tissue damage is preserved.

The effects of social support on alcohol consumption during pregnancy: situational and ethnic/cultural considerations.

While the effects of alcohol consumption during pregnancy have been well documented, variables associated with drinking during pregnancy have received little attention. This study sought to determine the importance of situational and ethnic/cultural-specific support on alcohol consumption during pregnancy among Black and White women in a U.S. southern urban prenatal population. A consecutive sample of 311 prenatal patients were interviewed during both the fourth month and the eighth month of pregnancy. Using standard regressions, the two components of expressive support--general support and pregnancy support--were found to be working in opposite directions, with pregnancy support showing a negative association with alcohol consumption during pregnancy. Pregnancy support was found to contribute significantly to the variance in alcohol consumption among Whites but was not found to be a significant contributor among Blacks. These findings suggest that social support, specifically pregnancy support, is a significant variable in accounting for alcohol consumption during pregnancy, but this association may not be consistent across ethnic groups.

Perception of pregnancy and social support as predictors of alcohol consumption during pregnancy.

Although an association between alcohol consumption during pregnancy and adverse fetal outcomes has been well documented, variables related to alcohol consumption during pregnancy have remained neglected. Since pregnancy has been considered a time of crisis and stress for pregnant women, this study sought to determine the association of perceptions of pregnancy and social support to alcohol consumption during pregnancy. The 311 Southern metropolitan prenatal patients sampled were interviewed twice during pregnancy. Perception of pregnancy was not found to be correlated with either social support or alcohol consumption during pregnancy. Social support was significantly associated with decreased alcohol consumption during pregnancy. Using standard multiple regressions, two components of social support, general support and pregnancy support, were found to be working in opposite directions prior to pregnancy, with general support showing a positive association with alcohol consumption. Only pregnancy support continued to account for a significant amount of the variance in alcohol consumption during the first 4 months of pregnancy. Pregnancy support, additionally, showed a significant negative association with high maximum drinking (consuming five or more drinks on occasion) prior to pregnancy. These findings suggest that social support may be an important predictor of alcohol consumption both prior to and during pregnancy and merits further investigation.