Presence of IgA and IgG antigliadin antibodies in healthy adults as measured by micro-ELISA. Effect of various cutoff levels on specificity and sensitivity when diagnosing coeliac disease.

In this study a micro-ELISA (ELISA = enzyme-linked immunosorbent assay) was established and used to evaluate IgA and IgG antigliadin antibodies in 1,866 healthy adults. There was a covariation between the level of IgA antigliadin antibodies and the total serum IgA concentration, probably due to an increased IgA response in some healthy subjects. We could not find any correlation between the presence of IgG and IgA antibodies in the healthy population using the 97.5th percentile as a cutoff value. The specificity of various cutoff levels was compared with the sensitivity of the test in a population of 40 patients with coeliac disease. IgA antigliadin antibodies had a high specificity (95%) at a cutoff value giving a high sensitivity (80%). This was not possible with IgG antigliadin antibodies which had a low sensitivity (40%) when the cutoff value was selected to give a high specificity. Due to the low prevalence of coeliac disease, a decrease in the specificity of the test will have a pronounced effect on the positive predictive value. The results indicate that only IgA antigliadin antibodies are useful markers when screening subjects with few typical symptoms for biopsy when diagnosing coeliac disease, whereas IgG antibodies are of low value because of their low specificity.

Plasma exchange in endocrine ophthalmopathy.

We studied the effects of intensive plasma exchange on endocrine ophthalmopathy in 12 patients with Graves' disease and one with Hashimoto's thyroiditis. All patients were euthyroid at the time of plasma exchange. All but five had concomitant treatment with azathioprine. Each patient had a treatment period consisting of six plasma exchanges performed in 2-3 weeks; two patients were treated in two periods. Each time a mean of 2.4 liters plasma was exchanged. There was a prompt reduction in the concentration of circulating immune complexes and/or thyrotropin receptor antibodies following plasma exchange. Six of the 13 patients improved their proptosis; their median duration of eye symptoms before treatment was less than 8 months. In patients suffering from eye symptoms for more than 1 year improvement was rare. Overall the Hertel values were 24.1 +/- 4.4 (SD) before and 22.8 +/- 3.4 after plasma exchange for the left eyes (P = 0.07) and 23.8 +/- 4.0 before and 23.0 +/- 3.8 after for the right eyes (P = 0.09). Nine patients altogether improved their ophthalmopathy index and periorbital oedema. In patients with disabling endocrine ophthalmopathy plasma exchange may sometimes be of value to induce a relief of the ophthalmopathy; when it is used it should be instituted before fibrotic changes occur. We suggest that concomitant immunosuppressive drugs should be given to prevent rebound phenomenon induced by plasma exchange. To establish the role of plasma exchange in the treatment of endocrine ophthalmopathy controlled studies should be performed.

Cryoprecipitate infusion fails to improve organ function in septic shock.

Plasma fibronectin may be of critical importance for the septic patient through its proposed function as the major opsonin for macrophage clearance of circulating, noncellular debris. As a rule, critically ill, septic patients are depleted of fibronectin. In earlier uncontrolled studies, infusion of fibronectin-rich cryoprecipitate had resulted in improved renal and pulmonary functions and changes in peripheral hemodynamics. In this controlled study, 32 septic ICU patients (mean initial fibronectin level = 60% of normal) received cryoprecipitate or control infusions. Although the fibronectin level was significantly elevated to the normal range in the cryoprecipitate group, no effects were seen in hemodynamics, oxygen metabolism, or lung and kidney functions. Our results indicate that this form of fibronectin therapy does not influence the impaired organ function in septic shock.

Long-term remission of pure red cell aplasia after plasma exchange and lymphocytapheresis.

A 57-year-old man with idiopathic pure red cell aplasia went into remission after plasma exchange. He relapsed after 5 months and then failed to respond to treatment with intensive plasma exchange and immunosuppressive agents. Because of a high proportion of T-suppressor cells in the peripheral blood he was treated with lymphocytapheresis in addition to the previous treatment. The patient achieved a long-term haematological remission which has now persisted for more than 3 yr.

Plasma exchange and leukapheresis in psoriasis--no effect?

Nine patients with severe or therapy-resistant psoriasis were treated by plasma exchanges or leukapheresis; one received both treatments in succession. None of the patients showed convincing signs of improvement. We therefore conclude that there is little evidence for the existence of a "psoriasis factor", the removal of which, it has been suggested, would explain the beneficial effects of dialysis. Nor is there anything to indicate that the removal of large numbers of leukocytes would bring about healing.

Fibronectin and other DIC-related variables in patients with moderately severe infections receiving cryoprecipitate.

Plasma fibronectin (Fn), a glucoprotein of suggested importance in host defence during infections also seems to be involved in blood coagulation and to be consumed during clot formation. Low Fn concentrations have been found in patients with DIC, but also in patients with infections without signs of overt DIC. In a randomized trial of Fn supplementation 28 patients with moderately severe infections, hospitalized in the Department for Infectious Diseases, were scheduled to receive either cryoprecipitate from 30 donors (n = 14) or 250-300 ml of stored plasma (n = 14). To elucidate the relationship between Fn plasma levels, Fn-rich cryoprecipitate infusion, and possible low-grade DIC in these patients, we measured platelet count, prothrombin complex (NT), fibrinogen, F V, F VIIIR:Ag, F VIII:C, F XII, plasminogen (Plg), antiplasmin (AP), antithrombin III (AT), kallikrein-inhibiting activity (KI) and spontaneous proteolytic activity (SPA). Compared to healthy controls, high initial values (p less than .001) were found for fibrinogen, F VIIIR:Ag, F VIII:C and SPA. Most values for platelets, F V, Plg, AP and KI were within the reference range. Low levels (p less than .001) were found for Fn, NT, F XII, AT and for the ratio F VIII:C/F CIIIR:Ag. A significant correlation was found between F XII, Plg and AT. Fn correlated poorly to the other variables. Cryoprecipitate infusion normalized the Fn concentration, but had no influence on other measured variables. Thus, although no patient had clinically overt DIC, and all survived, we observed a distinct pattern indicating activation of the coagulation system. Fn levels were low, but were not specifically related to this activation.

Fibronectin and other DIC-related variables in septic ICU patients receiving cryoprecipitate.

In a controlled study of fibronectin supplementation in sepsis, 11 ICU patients in septic shock were scheduled to receive either cryoprecipitate from 20-40 donors (n = 6) or 250-300 ml of stored plasma (n = 5) (two infusions over 24 h). We wanted to: compare some "conventional" DIC variables in the ICU (platelet count, prothrombin complex = NT, FDP) to additional variables: Fibronectin (Fn), fibrinogen (Fg), F V, FVIII R:Ag, F VIII:C activity, F XII, plasminogen (Plg), antiplasmin (AP), antithrombin (AT), kallikrein inhibiting activity (KI) and spontaneous proteolytic activity (SPA): study the effects of cryoprecipitate or plasma infusion on three variables. Samples were taken before the first infusion, and 24 and 48 h after. At onset, high levels (p less than .001 when compared to blood donors) of Fg, VIIIR:Ag and VIII:C were seen. KI levels were within the normal range. F V was low (p less than .05). Fn, NT, XII, Plg, AP and AT were markedly low (p less than .001). SPA showed great variation. When compared to 28 patients with severe infections, but not in septic shock, the ICU group had higher VIIIR:Ag (p less than .05) and VIII:C (p less than .01), and lower XII, Plg, AP and AT (p less than .001). FDP was elevated in all ICU patients. Five patients were thrombocytopenic, and in these a pattern with low levels of Plg and AT was observed. Fn did not correlate well to the other variables measured. These results indicate a marked activation of coagulation and fibrinolysis in these severely ill patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumour regression after extracorporeal affinity chromatography of blood plasma across agarose beads containing staphylococcal protein A.

The therapeutic effect of absorbing plasma from tumour patients with immobilized staphylococcal protein A was tested. Plasma prepared by centrifugation was passed over protein A-Sepharose and then reinfused into the patient. Five patients were thus treated. One with malignant melanoma and one with renal adenocarcinoma showed measurable regression of metastatic lesions. In another with malignant melanoma a subcutaneous metastasis showed histopathological changes compatible with a therapeutic effect. In two patients, one with malignant melanoma and one with renal adenocarcinoma, no signs of regression were found. No severe adverse effects of the treatment were observed.

Changes in circulating immune complexes in tumour patient serum after in vitro or ex vivo affinity chromatography of blood plasma or whole blood over immunoglobulin-binding staphylococcal protein A-Sepharose.

Circulating immune complexes (CIC) were determined in tumour patient sera using three methods. One is based on PEG-precipitation, one on C1q-reactivity, and one on protein A-reactivity. About 25-30% of the sera were positive in at least one of the tests. Incubation of serum with protein A-Sepharose in vitro removed PEG-precipitable CIC from most sera, whereas C1q-reactive CICs had a much lower affinity to protein A. The protein A-reactive complexes showed considerable variation in their binding to protein A-Sepharose, and in some sera the amount of these CICs was actually increased. Similar changes in protein A-reactive CIC were also found during ex vivo treatment of tumour patients with immune adsorption. It is proposed that the binding of immune complexes to protein A can result in remodelling of protein A itself. Results from ultracentrifugation and fractionated PEG-precipitation support this hypothesis.

Plasma fibronectin deficiency during chemotherapy of acute myeloid leukaemia.

Plasma fibronectin was determined using a laser nephelometric method in 10 patients with acute myeloid leukaemia undergoing chemotherapy. There was a continuous fall during the first 3 weeks to about 50% of the normal level. The decrease of fibronectin may contribute to the lowered resistance against infection characteristic of these patients.

Plasmapheresis in the initial treatment of insulin-dependent diabetes mellitus in children.

Several factors indicate that autoimmune mechanisms may play a part in the aetiology of insulin-dependent diabetes mellitus. At the onset of the disease in 10 children (aged 11-16 years) plasmapheresis was performed four times over one to two weeks. Seventeen age-matched children with the same clinical features served as controls. The C-peptide concentrations at onset were the same in the two groups, but after one month the children treated with plasmapheresis had significantly higher values. This difference became even more pronounced after three, nine, and 18 months, both during fasting and at the maximum response to a standardised meal. The study group also had a significantly more stable metabolism, longer partial remission, and no higher insulin requirement. Of the 10 treated children islet-cell cytoplasmic antibodies were present in seven before plasmapheresis and in nine during treatment. The antibodies remained detectable in five and six out of nine patients at one and six months respectively after plasmapheresis. Although the mechanisms are obscure, plasmapheresis performed at the onset of insulin-dependent diabetes mellitus may help to preserve beta-cell function.

Thyroid function after thermal trauma.

The thyroid function was analyzed for 4-6 weeks in a prospective study of 12 thermally injured patients. The burn size range was 15-90%. Serum concentrations of 3,5,3'-triidothyronine (T3) was suppressed and 3,3',5'-triidothyronine (rT3) was increased. The ratio T3/rT3 was subnormal on the third day after the trauma and normalized after 3 weeks. Thyroxine and the free T4-index were within the normal range. The free T3-index were within the normal range. The TSH concentration was initially low but slowly increasing during the period of study. The concentration of the thyroxine-binding globulin (TBG) varied within the normal range. The T3 resin uptake test varied inversely with the TBG concentration. The concentration of thyroxine-binding prealbumin (TBPA) was subnormal. A control experiment excluded possible interference on the hormone concentrations of administered donor blood and plasma. It is concluded that the thyroid hormones are not responsible for the posttraumatic hypermetabolism in burn injury. The present findings further indicate a depletion of metabolically active thyroid hormones at the cellular level after burn injury.

Dose-related levodopa-induced haemolytic anaemia.

A 71-year-old white man developed direct antiglobulin positive haemolytic anaemia after 16 months of levodopa therapy for Parkinson's disease. Immunoglobulin G autoantibodies directed against Rh antigens were found in the patient's serum and on his erythrocytes. Reduction of levodopa dosage to one sixth with the aid of a peripheral decarboxylase inhibitor (benserazide) largely eliminated autoimmune haemolysis while maintaining adequate control of neurologic symptoms.

Iron supplement to blood donors. I. Trials with intermittent iron supply.

A series of 58 male blood donors has been studied with regard to stainable bone marrow iron, desferrioxamine test, sideroblasts, total iron-binding capacity, serum iron, and haemoglobin values. With one conventional blood donation every second month the storage iron was found to be significantly decreased after four blood donations both when placebo and oral ferrous iron in doses of up to 2000 mg were given over a period of two weeks after each blood-letting. The iron state in donors given 2000 mg was superior to that in donors given 1000 mg, and better in the latter group than when placebo was given. A moderate increase in the total iron-binding capacity could be discerned in subjects treated with placebo or only 1000 mg iron after each donation, but no changes in serum iron or haemoglobin were noted. A smaller series of 13 donors was also investigated after six donations and was found to show essentially the same pattern in the iron state variables as after four donations. When the interval between donations was four months and 2000 mg ferrous iron was given over two weeks after each donation, all variables including the amount of bone marrow iron and the desferrioxamine test remained unchanged in ten subjects after four donations. Two subjects showed a moderate decrease in the stainable bone marrow iron, but it did not disappear completely.

Changes in certain iron metabolism variables after a single blood donation.

Signs of iron deficiency have been studied after the first blood donation in 11 healthy men. Six were given 100 mg iron daily, and five received placebo tablets. The total iron-binding capacity and iron absoprtion remained raised for more than 26 days, but had almost returned to the initial values after 70 days. A significant decrease in the stainable bone marrow iron could be shown in all subjects after 26 days; later some restitution was seen in subjects given iron supplements, but not in those given placebo. As the restitution times are long, the interval after blood donation must be taken into account when judging iron metabolism variables in active donors.