We measured pretreatment serum levels of tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) in 25 patients with myelodysplastic syndrome receiving recombinant human erythropoietin (rhEPO) at dosages up to 300 U/kg thrice weekly for 12 weeks. Both TNF-alpha and IL-1 beta levels were measured using commercially available enzyme-linked immunoassays. A complete response (CR) was defined as a rise in untransfused haemoglobin concentrations of at least 2 g/dl or a 100% decrease in RBC transfusion requirements over the treatment period; a partial response (PR) was an increase in untransfused haemoglobin values of 1-2 g/dl or a decrease in RBC transfusion requirements equal to or greater than 50%; no response (NR) was defined as a response less than a PR. After 12 weeks of rhEPO treatment, four patients showed a CR, five patients a PR, and 16 patients NR. Serum levels of both TNF-alpha (80.5 %/- 64.8 vs 8.1 +/- 4.2 ng/l, P < 0.001) and IL-1 beta (60.4 +/- 49.9 vs 8.9 +/- 4.7 ng/l, P < 0.001) were higher in MDS patients than in a group of 28 normal controls. Responders (CR + PR) showed significantly lower serum levels of TNF-alpha than non-responders (21.6 +/- 26.2 vs 106.3 +/- 60.8 ng/l, P < 0.001), whereas IL-1 beta concentrations between those who benefited from therapy and unresponsive cases were not significantly different (39.8 +/- 48.9 vs 73.4 +/- 48.2 ng/l, P = 0.120). It is noteworthy that TNF-alpha levels were within the normal range in all responsive patients but one, whereas all non-responders presented elevated cytokine concentrations. No relationship was found between TNF-alpha or IL-1 beta values and haemoglobin levels, transfusion requirement, serum EPO or ferritin concentrations. We conclude that pre-treatment TNF-alpha levels might help to select those MDS patients who are most likely to benefit from rhEPO treatment.

Cow's milk is thought to be an environmental trigger for autoimmune response in Type 1 diabetes. In the present study, our aim was to investigate the antibody response to bovine beta-casein in different immune- and non-immune-mediated diseases and to establish whether such an antibody response is specific to Type 1 diabetes. We measured antibodies to bovine beta-casein using an enzyme-linked immunosorbent assay in a total of 519 sera from subjects as follows: 71 patients with Type 1 diabetes, 33 patients with coeliac disease, 100 patients with latent autoimmune diabetes in adults (LADA), 50 patients with autoimmune thyroid disease (ATD), 50 patients with Type 2 diabetes, 24 patients with multiple sclerosis (MS), and 3 different groups of controls (n = 191). Significantly increased levels of antibodies to beta-casein were found in patients with Type 1 diabetes, coeliac disease and in LADA compared to age-matched controls (p = 0.01, p = 0.02 and p = 0.01, respectively). No differences were observed in beta-casein antibody titres between patients with other disease conditions (MS, and ATD) and age-matched controls. The highest antibody response to beta-casein in Type 1 diabetic patients and in patients with coeliac disease could reflect the gut mucosal immune disorders common to Type 1 diabetes and coeliac disease. Furthermore, the elevated beta-casein antibody levels found in LADA patients suggest that the antibody response to this protein may be relevant in autoimmune diabetes.

Four coagulation indices [fibrinopeptide A (FpA), X degradation products (XDPs), platelet factor (PF4), β-thromboglobulin (β-TG)] were assessed in 38 patients affected by large bowel cancer at different stages before surgery, 7 and 30 days after it, to evaluate the capacity of such neoplasia to influence coagulation. The reported study showed that (1) FpA levels were elevated in nearly all cases both before and after surgery (thus it is a useful index for the diagnosis of such neoplasia, although its levels are not influenced by the presence of metastases), (2) increased levels of XDPs were found in a significantly (p < 0.05) higher percent of patients 7 days after surgery (no significant differences were observed in relation to the cancer stage), (3) PF4 levels were in the normal range throughout the study, and (4) β-TG levels were increased throughout the study in a high percentage of cases. It may be inferred that large bowel cancers may affect coagulation in either way(s), by triggering platelet activation and/or fibrinolysis. The most useful index for the diagnosis and follow-up of this neoplasia is FpA, although its levels are unaffected by the presence of metastases. The comprehensive evaluation of the four above-mentioned coagulation indices may give rise to the suspicion of large bowel cancer.

The clinical usefulness of neuron-specific enolase (NSE), thymidine kinase (TK), and tissue polypeptide-specific antigen (TPS) was investigated in 41 patients (53-80 years old) with recently discovered small-cell lung cancer (SCLC). Eleven patients exhibited limited disease (LD) and 30 extensive disease (ED). Serum samples for NSE, TPS (immunoradiometric assay), and TK (radioenzymatic assay) evaluations were drawn from all patients at the time of diagnosis and before each cycle of chemotherapy in the treated patients. Therapy consisted of i.v. carboplatin 300 mg/m2 on the first day and i.v. etoposide 120 mg/m2 from the first to the third day every 3 weeks. Nine patients refused or were not eligible for chemotherapy. Five patients received only one course and showed no response (NR); 9 patients received two courses; 18 patients received three or more courses. In the last group, complete remission (CR) was obtained in 9 cases, partial remission (PR) in 18 cases. The tumor markers studied did not show any significant difference in distinguishing LD from ED. NSE and TPS were significantly more often abnormal than TK, either at the time of diagnosis (p < 0.05) or in PR or NR patients (p < 0.05). In relation to chemotherapy response, NSE and TPS serum patterns were shown to be more reliable than TK in PR (p < 0.05) and NR patients (computed error between 10% and 15%). No significant difference was observed between serum NSE and TPS patterns. Serum NSE and TPS seem to be more useful in the diagnosis and follow-up of SCLC patients undergoing chemotherapy. Further trials are necessary to ascertain whether the associated assessment of NSE and TPS can add useful information to that provided by the assessment of NSE alone.