Postmortem serum levels of tryptase and total and specific IgE in fatal asthma.

Sera were obtained postmortem from 55 subjects classified into three groups; death due to asthma (FA, n = 21), asthmatic but death not due to asthma (NFA, n = 24) and a nonasthmatic control group (NAC, n = 10). A full autopsy was performed on all cases and a medical history, including details of allergies, was obtained by questionnaire from the next of kin. Grading of asthma severity by either questionnaire or autopsy was comparable (tP = 0.435, p > 0.05) and the mean pathology-grade was significantly higher for the FA group (3.375) compared to the NFA group (2.375), p < 0.05. Tryptase was elevated (> 2.0 micrograms/L) in 21/55 sera (38%) and there was no significant difference between the groups. ROC plots showed that tryptase levels did not discriminate between the FA and NFA groups, even if specimens were collected within 24 hours after death. Total IgE was significantly elevated in the FA group (geometric mean 140.3 kU/L) compared to the other two groups (NFA 30.2 kU/L, NAC 9.4 kU/L), p = 0.05. Fatal asthmatics also had a greater positivity (67%) to a screen for common inhalant allergens than did the other groups (NFA 30%, NAC 20%). Sera with a positive screen were tested against a panel of 10 common aero-allergens. Each sample was then assigned a number (N) and a score (S), dependent on either the number of allergens positive (N) or the total sum of pluses for all allergens (S). Both the N and S values were higher for the FA group (N = 98, S = 264) than the NFA group (N = 52, S = 151) and NAC group (N = 4, S = 8). The ratio (S/N) which gives an index (I) was 2.69, 2.90, and 2.00, respectively. Tryptase was poorly correlated to the total IgE level (r = 0.036); however, mean values for N and S were significantly different (N 6.81, S 4.50, and N 19.25, S 11.5, p < 0.05) for sera with tryptase levels < 2.0 or > or = 2.0 micrograms/L, respectively. We conclude that total and specific IgE may be useful predictors of asthma severity but that postmortem tryptase is not useful in the diagnosis of a fatal asthmatic attack.

A retrospective study of the relative utility of electrophoresis, immunoelectrophoresis, immunofixation, and nephelometry in the investigation of serum proteins.

OBJECTIVES: To assess the relative value of visual inspection of protein electrophoresis patterns, immunoelectrophoresis, immunofixation, and specific protein quantitation in the investigation of serum proteins. DESIGN AND METHODS: A retrospective study of protein results on 372 sera analyzed by electrophoresis and immunoelectrophoresis. A subsection of specimens (276) also had immunoglobulin quantitation by immunonephelometry and 30 were studied by immunofixation. RESULTS: Total gamma globulin levels were correctly assessed visually in 84.4% of cases. Discrete bands seen visually were mainly monoclonal in 74 of 80 (92.5%). Six monoclonal proteins were not detected visually. Twenty-five monoclonal proteins required immunofixation for typing, and 60 were typed by immunoelectrophoresis. The visual assessment of the level of normal immunoglobulins in the presence of a monoclonal gammopathy was correct in 58% of cases. CONCLUSIONS: The majority of monoclonal gammopathies could be evaluated by a combination of protein electrophoresis and immunoelectrophoresis. Except for quantitating monoclonal immunoglobins, protein electrophoresis was unreliable as a quantitative procedure and nephelometry was preferred.

Anti-plasticizer specific IgE is present in the serum of transfused patients.

Sera from 29 patients who had reacted to a platelet (27) or packed red cell (2) transfusion and from 5 patients who had received platelets without reacting were collected over a 13-month period. The sera were assayed for total IgE, and IgE specific for ethylene oxide, phthalic anhydride, hexamethylene diisocyanate, methylene diphenyl diisocyanate, toluene diisocyanate, and mast cell tryptase. Three patients with reactions had elevated total IgE levels, and specific IgE was positive for hexamethylene diisocyanate in 2 of 28 (7.1%), methylene diphenyl diisocyanate in 1 of 29 (3.4%), and toluene diisocyanate in 14 of 27 (51.9%). No positives were found in patients without reactions and no patients had an elevated tryptase level. It is unlikely that anti-plasticizer hypersensitivity was responsible for the transfusion reactions, but the prevalence and significance of such antibodies in both the hospital population and the general population would merit further investigation.

Role of clinical laboratory in allergy testing.

The clinical laboratory has a well defined role to play in the diagnosis and management of patients with allergy. Elevated serum levels of total IgE and/or allergen-specific IgE indicate that an IgE mediated event has occurred. Methods such as basophil degranulation and basophil or leukocyte histamine release can provide similar information. Sensitive and precise methods suitable for automation are available for quantitation of histamine in whole blood or plasma. Methyl histamine can be assayed in urine. Eosinophil cationic protein levels in serum can be used as an indicator of eosinophil activation in disorders such as asthma and atopic dermatitis. Similarly, serum mast cell tryptase levels can confirm or exclude an anaphylactic reaction both in life and as a cause of death. This review documents and compares commercially available methods for these assays and discusses their application to screening, diagnosis, and management of patients with allergy.

Allergens in the workplace.

Allergy is an important cause of work-related illness. Data are presented concerning the prevalence and relationship of atopy and hypersensitivity states in persons working as grain handlers, pathologists, and medical laboratory technologists. Studies were carried out in the above occupational groups in the Province of Alberta. A survey of male grain handlers failed to demonstrate significant differences between their serum total IgE levels and allergen specific IgE profiles and those of a control group of sedentary workers. Investigation of pathologists in active practice indicated that 46% of the study group had problems related to formaldehyde. There was no tendency for atopic subjects to be more sensitive to formaldehyde and no subjects had detectable circulating formaldehyde-specific IgE. Since the introduction of Universal Precautions into the clinical laboratory, there has been an increased incidence of hypersensitivity reactions to latex. A controlled investigation of medical laboratory technologists found that, although most subjects with latex glove-related problems had no in vitro evidence of IgE mediated hypersensitivity to latex, three subjects (2.5%) were RAST positive for latex and hence at risk of an anaphylactic reaction with continued exposure to the allergen. A history of atopy was more common in the group with glove-related problems and the severity of the skin reactions documented were more severe in smokers.

The prevalence of atopy and hypersensitivity to latex in medical laboratory technologists.

Members of the Alberta Society of Medical Laboratory Technologists were invited to take part in a study of sensitivity to latex gloves. A total of 230 persons volunteered; 108 (47%) had no problems with gloves, and 122 (53%) reacted to latex gloves. A history was obtained regarding atopy, smoking, years in laboratory medicine, and the nature of the problem with latex gloves. Serum was assayed for the total IgE level and the presence of IgE with specificity to common inhalant allergens and to latex. The affected group had an increased population of subjects with an atopic history and a higher incidence of a raised IgE level and a positive screen for inhalant allergens. In the affected group, there was no relationship between the total IgE level and severity of skin reaction. However, smoking was related to severity of reaction and was more common in the groups with a more severe reaction. Three subjects were positive for IgE specific for latex; there were no other data distinguishing them from latex-negative subjects.

The prevalence of atopy and hypersensitivity to formaldehyde in pathologists.

Sixty-three pathologists in active practice in the province of Alberta, Canada, provided a history regarding atopy and sensitivity to formaldehyde. Serum samples were assayed for total IgE level and the presence of IgE with specificity toward timothy grass, cat, house dust, and formaldehyde. Twenty-nine of the subjects (46.0%) gave a history of atopy that was confirmed in 12 by either IgE level or a positive radioallergosorbent test. Twenty-nine (46.0%) complained of formaldehyde sensitivity. In this study, no pathologist had allergen-specific IgE directed against formaldehyde, and there was no evidence of a tendency for atopic subjects to be more prone to sensitivity to formaldehyde. However, this may be related to a deliberate reduction in exposure by individuals experiencing adverse effects.

The Phadiatop test allows adequate screening for atopy with a marked reduction in cost.

Sera from 35 patients aged 5 years or younger and sera from 95 patients 6 years and older were assayed for both total IgE level, allergen-specific IgE by RAST and either the Phadiatop Paediatric or Phadiatop procedures, depending on age. Good agreement was found allowing exclusion of specimens anticipated to be RAST negative with an expected reduction in RAST testing of up to 80% of the present workload, without significant exclusion of RAST positive specimens.

Observations on the electrophoretic and immunoelectrophoretic appearance of the prealbumin region in biological fluids.

Variations in the level of prealbumin in serum and spinal fluid were noted on routine electrophoresis. Low serum levels were associated with infection, liver disorders, and malignant disease, whereas high levels were seen in inflammatory disorders. A high spinal fluid prealbumin was noted in a young child with a disseminated medulloblastoma. A second arc with prealbumin mobility was seen on immunoelectrophoresis of one urine specimen and four sera from patients with varied pathologies. Sixteen duplicated arcs were seen in the spinal fluid of patients with neoplastic disorders, multiple sclerosis, suspected multiple sclerosis, epilepsy, cerebellar and cerebral atrophy, and chronic renal failure.

Enprostil reduces G-cell hyperplasia and hypergastrinemia in duodenal ulcer.

A 42-year-old man with a 26-year history of duodenal ulcer volunteered for a 24-hour intragastric pH monitoring study, at which time his fasting gastrin concentration was found to be elevated. Secretin injection decreased the serum gastrin concentration. When not on treatment his total gastrin, gastrin-17 (G-17), and gastrin-34 (G-34) response to a protein-containing breakfast was marked. Immunocytochemical staining of antral biopsies showed hyperplasia of gastrin-containing cells, more pronounced for G-17 than for G-34. Cimetidine or cimetidine plus pirenzepine increased 24-hour intragastric pH, whereas pirenzepine alone rendered the gastric contents more acidic, particularly overnight. The total serum gastrin concentrations increased after meals and were unaffected by cimetidine or pirenzepine; enprostil, however, reduced the postprandial increase in total gastrin, G-34, and G-17. After six weeks of treatment with enprostil, the number of cells containing G-17 and G-34 was reduced. The findings show that G-cell hyperplasia may occur in the presence of a normal fasting serum gastrin concentration; fasting serum gastrin concentrations may fluctuate widely over time; the food-stimulated increase in G-17 was greater than that for G-34, and is associated with more pronounced antral hyperplasia for G-17 and G-34; and enprostil blunts the postprandial increase in G-17, G-34, and total gastrin. These observations suggest that enprostil may reduce G-cell hyperplasia and hypergastrinemia.

Appearance of light chain disease in serum electrophoresis. Report of 11 cases.

Over a five year period, 13 cases of light chain disease were identified. Ten patients had abnormalities noted on serum immunoelectrophoresis with anti-whole-human antiserum. Eight of these ten patients had a distinctive rainbow-like arc between the IgG and transferrin arcs, and two had splitting of the IgG arc. These patterns may be seen in the presence of free light chains; their recognition should lead to further studies with appropriate antisera.

The influence of anatomical site and hormonal status on the copper and zinc levels of human uterine smooth muscle.

Copper and zinc levels were measured in smooth muscle from 47 uteri. Results were obtained for myocervix, isthmus and corpus in the secretory and proliferative phases and also from post-menopausal subjects. The levels were found to vary both with site sampled and the physiological state of the uterus.

Synergistic interaction between an H2-receptor antagonist and enprostil on 24-hour intragastric pH, serum gastrin concentration, and tissue immunoperoxidase staining for gastrin, somatostatin, and serotonin in a patient with metastatic gastrinoma.

A 56-year-old woman newly diagnosed as having Zollinger-Ellison syndrome due to a metastatic gastrinoma underwent 24-hour intragastric pH monitoring, serum gastrin (total, G-17 and G-34) measurements, and immunoperoxidase staining of duodenal, antral, and gastric body biopsies for gastrin, somatostatin, and serotonin. Determinations were made while the patient was given different doses of ranitidine, enprostil (a synthetic orally administered prostaglandin E2), or ranitidine plus enprostil. Following are the findings from this single-patient study: Intragastric pH was persistently low but varied in response to food when the patient was given ranitidine. Immunocytochemical staining of antral biopsies obtained before the patient was treated revealed a reduced number of cells containing G-17 and G-34 but an increase in the antral somatostatin-containing D-cells. Treatment with 35 micrograms of enprostil BID plus 300 mg of ranitidine BID for two and 11 weeks was associated with an increased number of duodenal G-cells, a decrease in antral D-cells, and a decrease in the number of antral serotonin-containing cells. Enprostil in a dosage of 35 or 70 micrograms BID had no effect on intragastric pH, but when enprostil was given in combination with ranitidine, postprandial and nocturnal intragastric alkalinity was accentuated along with a return of duodenal and antral G-cells and a loss of the antral D-cell hyperplasia. Optimal pH control was achieved with 300 mg of ranitidine BID; more frequent dosing with ranitidine did not further increase intragastric pH. Both the total serum gastrin concentration and G-17 levels fluctuated in response to meals. The serum concentrations of total gastrin, G-17, and G-34 were reduced with enprostil and with ranitidine.

Copper and zinc content of human leiomyomas.

The copper and zinc levels of leiomyomas were determined and compared to the levels in the uninvolved myometrium and myocervix. In general the levels found in leiomyomas were similar to those of the smooth muscle of isthmus and corpus but different to those of the myocervix. There were no significant differences in the levels found in smooth muscle of uteri with or without leiomyoma.

The influence of season and of sex on the serum level of total IgE and on the distribution of allergen-specific IgE.

Serum IgE levels were higher in males than in females. The number of positive RAST results peaked in April and November. Timothy grass, birch, cat and dog epithelia and horse dander, house dust, egg and peanut showed a seasonal variation. There was a difference in allergenic specificity between men and women.

The characterization of hemoglobin Manitoba or alpha (2)102(G9)Ser----Arg beta 2 and hemoglobin Contaldo or alpha (2)103(G10)His----Arg beta 2 by high performance liquid chromatography.

Hb Contaldo with a His----Arg substitution at position 103(G10) of the alpha chain is a newly discovered unstable Hb variant observed in an Italian child. Its instability is probably due to the disruption of the hydrogen bond between alpha 103(G10)His and beta 108(G10)Asn. The structural variation in the core segment was determined through analysis of tryptic peptides from digests of the alpha X and oxidized alpha X (with performic acid) chains, which were separated by HPLC. Similar analyses were made for the alpha X chain of the rare Hb Manitoba in which alpha 102(G9) Ser is replaced by Arg. This variant was observed for the first time in an Italian patient, and was also studied in a member of a previously described Canadian family.