Properties of cryptic epitopes and their corresponding antibodies as indicated by the study of human and ovine growth hormones.

Antibodies (Ab) directed to hidden antigenic determinants (cryptotopes) are undesirable because they are not neutralizing. Additionally, we have previously demonstrated a close association between the extent of Ab to cryptic determinants and the expression of autoantibodies (autoAb) under some experimental conditions. Thus, the first objective of this work was to establish the physicochemical characteristics of Ab to cryptotopes and the second one was to examine the structural features of cryptic epitopes themselves. Using human and ovine growth hormones (hGH and oGH) as antigenic models and competition ELISA under different conditions of temperature, pH or ionic strength, we did not find any difference between the binding properties of anti-cryptic epitope antibodies (Ab) and anti-native epitope Ab. Then, using synthetic peptides and tryptic digests and direct and competition ELISAs we studied the structures of cryptic hGH and oGH epitopes. Isolated peptides either in solution or adsorbed on microplates failed to react. Partially digested hGH was recognized only when insolubilized on microplates, and anti-oGH Ab only reacted with a large fragment of the hormone either in solution or insolubilized. These results indicate that, at least in the case of hGH and oGH, cryptic epitopes are not simple linear sequences, as commonly referred without any evidence, but new exposed conformational structures different from those found in the native antigen.

[Severe hyponatremia in acute porphyria. Central pontine myelinolysis as a complication of its treatment]. / Hiponatremia severa en porfiria aguda. Mielinolisis pontina central como complicación de su tratamiento.

Two patients developed severe hyponatremia attributed to inappropriate antidiuretic hormone secretion during a crisis of acute porphyria, and were treated with intravenous hypertonic sodium solution. One of them developed clinical and radiological findings of pontine and extrapontine myelinolysis, which may constitute a risk in the treatment of this complication.

[Imipenem/cilastatin versus ceftazidime-amikacin in the treatment of febrile neutropenic patients]. / Imipenem/cilastatina versus ceftazidima-amikacina para el tratamiento de pacientes neutropénicos febriles.

AIM: To compare the efficacy of imipenem/cilastatine and ceftazidime-amikacin in the treatment of febrile neutropenic patients. DESIGN: Open, prospective and randomized clinical study. PATIENTS: Fifty two patients (26 female) aged 16 to 80 years old with 60 episodes of neutropenia were studied. They were randomly assigned to receive imipenem/cilastatine in doses of 500 mg iv qid or the combination of ceftazidime 1 to 1.5 g iv tid and amikacin 7.5 mg/kg iv bid. RESULTS: Global response to initial therapy was 53% in patients receiving imipenem/cilastatine and 37% in those receiving ceftazidime-amikacin (p = ns). When other antimicrobial were added, a 90 and 85% infection eradication success was achieved respectively. Six febrile episodes in the group receiving imipenem/cilastatine and 12 episodes in the group receiving ceftazidime-amikacin had Gram positive cocci as the sole infectious agent (p < 0.04). A lower duration of neutropenia had a favorable influence on treatment outcome. Three patients receiving imipenem/cilastatine (10%) and four receiving ceftazidime-amikacin (13%) died. Superinfections and toxicity related to antibiotics were minimal in both groups. CONCLUSIONS: Imipenem/cilastatine and the combination of ceftazidime with amikacin were equally effective in the treatment of febrile episodes in neutropenic patients.

[Allogenic bone marrow transplantation in the treatment of malignant hematologic disease]. / Trasplante alogeneico de médula ósea en el tratamiento de enfermedades hematológicas malignas.

We have treated 28 patients (pts) with malignant hematological diseases with allogeneic bone marrow transplantation (BMT). 18 pts had acute lymphoblastic (ALL) and non lymphoblastic leukemia (ANLL), 5 chronic myeloid leukemia (CML), 2 severe aplastic anemia (SAA), 1 myelodisplasia, 1 Fanconi's anemia and 1 advanced Non Hodgkin's lymphoma. All but three received the graft from HLA identical sibling donors. We used conditioning with total body irradiation and chemotherapy (cyclophosphamide, cytarabine and etoposide) in 17 pts and chemotherapy alone in 11. 24 pts had full hematological recovery 18 to 25 days post BMT. 15 pts died after BMT as a consequence of toxicity or early infection (4), graft failure (2), graft versus host disease (4) or relapse (5). Actuarial event free survival for the group with favorable prognosis (SAA, ALL and ANLL in first or second remission and CML in chronic phase) is 57% at 36 months. Allogeneic BMT is an effective and feasible therapeutic procedure for selected patients with hematological malignancies.