Detection of Human Reagins with Rat Peritoneal Mast Cells by Histamine Release

An immunologically specific method was developed for the detection of reaginic antibodies in sera of allergic individuals. It is based on the determination of histamine release (HR) from rat peritoneal mast cells (RPMC), presensitized with the allergic serum, on challenge with the appropriate allergen. The amount of HR was shown to depend on the concentrations of reagins and allergens. From experiments involving RPMC sensitized with different fractions of allergic serum isolated by chromatography or with appropriate reverse immunosorbent, it was deduced that the bulk of HR was due to antibodies of the IgE class and that about 10% of HR was attributable to antibodies of the IgG type; however, paradoxically, IgG of normal human serum did not have the capacity to sensitize RPMC. Both classes of immunoglobulins present in reaginic serum and capable of sensitizing RPMC were inactivated at 56 °C or with 0.1 M 2-mercaptoethanol. Peritoneal mast cells or a rat, which had been immunized to produce homocytotropic (HCT) antibodies, or RPMC sensitized &lt;i&gt;in vitro &lt;/i&gt;with rat HCT antibodies, did not fix human reagins. By contrast, human reagins to two distinct allergens were fixed on the same RPMC preparation by successive sensitization of the cells with the corresponding sera. The cells sensitized with rat HCT antibodies released histamine on challenge with anti-human IgE serum. It is therefore concluded that there exist structural homologies between the groups of human and rat reaginic antibodies which are responsible for fixation on rat RPMC, as well as between the antigenic groups of these two reaginic antibodies capable of crossreacting with anti-human IgE.</jats:p

Isolation of Human Reagins Differing in Their Affinity for Ragweed Immunosorbent

Reaginic antibodies to ragweed pollen which had been adsorbed to cellulose-allergen immunosorbents were eluted in the presence of homologous or heterologous serum protein(s) at a concentration of 3–7 mg/ml with gly-HCl at pH 2.5, or 6 m urea at pH 7.4. These extraneous serum proteins exerted a stabilizing effect on the eluted reagins. Two groups of reagins differing in their affinity for the allergen(s) were sequentially eluted from the immunosorbent with gly-HCl and Nal regardless of the order of addition of these eluting agents. Moreover, specific elution of some reagins was achieved with a low molecular weight, hapten-like preparation of ragweed pollen.</jats:p

Demonstration of Reagin-Allergen Complexes Formed on Elution of Reagins from Immunosorbent with Allergens

Elution of human reagins to ragweed pollen from an immunosorbent, synthesized by coupling the non-dialyzable components of the aqueous extract of the pollen to ethylene maleic anhydride copolymer, with low molecular weight components of the dialysate or of the ultrafiltrate of this extract resulted in the formation of allergen-reagin (A-R) complexes. Evidence for these complexes was inferred from the following observations: (a) intradermal injection of A-R eluates into the skin of normal volunteers produced immediate wheal and flare reactions; (b) when normal skin sites sensitized with allergic sera were challenged with A-R eluates, in dilutions which did not elicit any reactions in non-sensitized sites or in sites sensitized with normal human serum, wheal and flare reactions were obtained; (c) sensitization of normal skin sites with A-R eluates prevented further fixation of additional reagins.</jats:p

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background: End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods: This study comprised an analysis of GlobalSurg-1 and-2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle-and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results: In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 percent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P &lt; 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P &lt; 0·001) in low-compared with middle-and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P &lt; 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P &lt; 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P &lt; 0·001). Conclusion: Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background: End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods: This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results: In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion: Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background: The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods: In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results: Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89·6 per cent) compared with that in countries with a middle (753 of 1242, 60·6 per cent; odds ratio (OR) 0·17, 95 per cent c.i. 0·14 to 0·21, P < 0·001) or low (363 of 860, 42·2 per cent; OR 0·08, 0·07 to 0·10, P < 0·001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -9·4 (95 per cent c.i. -11·9 to -6·9) per cent; P < 0·001), but the relationship was reversed in low-HDI countries (+12·1 (+7·0 to +17·3) per cent; P < 0·001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0·60, 0·50 to 0·73; P < 0·001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion: Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries