Effect of extracellular fluid volume contraction and expansion on plasma atrial natriuretic peptide (ANP) concentration in patients with acromegaly

Atrial natriuretic peptide (ANP) is a hormone release into the circulation by atrial cardiocytes (Gutkowska et al. 1984). Extracellular fluid volume expansion acts as a powerful stimulus for ANP secretion and results in the augmentation of its plasma concentration (Lang et al. 1985). Patients with active acromegaly demonstrate the increased extracellular fluid volume (Falkheden et al. 1964), while a successful treatment of the disease results in the disappearance of hypervolemia (Strauch et al. 1977). We have recently demonstrated that in patients with active acromegaly the increased total body plasma volumes are accompanied by the elevated plasma ANP concentrations, whereas, in the successfully treated patients, both: total plasma volumes and plasma ANP levels do not differ significantly from these in healthy subjects (Czekalski et al. 1988b).     

Isolation and characterization of a distinct immunoregulatory isoform of alpha-fetoprotein produced by the normal fetus

In this report, we examine the functional significance of the molecular microheterogeneity of alpha-fetoprotein (AFP). In doing so, we have taken the direct approach of purifying the naturally occurring isomeric forms of fetal-derived AFP using a preparative anion exchange column linked to an automated fast protein liquid chromatography (FPLC) system followed by parallel testing of each isolated molecular variant for in vitro immunoregulatory activity. The data obtained demonstrate the presence of seven distinct variants of AFP as defined by their retention volumes on FPLC elution profiles, by their pIs on analytical IEF gels, and by Western blot analysis. Molecular mass determination by SDS-PAGE showed each isomer to be equivalent in size to 69,000-dalton native unfractionated AFP molecules. All the immunosuppressive activity of AFP was localized to a single variant representing only 6% of the total composition of native AFP. The immunoregulating isomer termed AFP-1 was the least acidic of the seven isolated variants with a pI of 5.1 and displayed a sialic acid content of 1 mol/mol of protein. The inhibitory activity of AFP-1 could be readily measured on T cell-dependent antibody synthesis, Con A-induced stimulation of Lyt-1+23- thymocyte DNA synthesis, and lymphokine-activated NK cell activity. All other isomers were without effect in these test systems. The immunosuppressive AFP-1 isomer also displayed the strongest growth-promoting influence on cultured bone marrow lymphocytes. There was no correlation between functional activity and degree of expression of sialic acid residues on the AFP molecules. These findings demonstrate that the immunoregulating function of AFP is confined to a distinct and relatively small subpopulation of native AFP molecules and should therefore contribute to the resolution of outstanding questions regarding the structure/function relationship of this onco-fetal glycoprotein.     

Common forefoot deformities. How to treat, when to refer

Initial assessment of common forefoot deformities by the primary care physician is quite feasible. A thorough history, examination of the foot with the patient standing and seated, assessment of the patient's footwear, and radiographic evaluation can often lead to gratifying relief with use of simple office measures. Even in cases that require referral to an orthopedic surgeon, interim relief of symptoms and the patient's increased awareness of the problem and its cause enhance the patient's understanding and the final outcome as well.     

The method of teaching therapy--the problem approach to diagnosis

The methodology of a so-called task force approach to the diagnosis is suggested. It determines the strategy of the physician's diagnostic searches in some problems occurring in the examination of patients afflicted with the given disease. The problems (stages, levels of examination) show how one should reason, i. e. they form concrete bases for clinical thinking. According to this methodology, the symptoms should be classified with separate diagnostic problems--trends or stages of the patient's examination at the stage of a probable diagnosis establishment. The task force approach is a method of analysis which prevents potential gross diagnostic errors by means of deciding the main questions (functional, pathogenetic, etc.). A well-defined wording of the above-indicated problems--concrete regularities of the clinical thinking--are of paramount importance in teaching therapy. Examples are provided of the task force approach to the diagnosis of pyelonephritis, infectious myocarditis, anemia, and some other diseases.     

Chronic hiccups

Patients with chronic hiccups should be carefully examined for an underlying disorder while receiving symptomatic treatment. Treatment includes physical maneuvers, drugs such as chlorpromazine, metoclopramide, anticonvulsants or quinidine, and other, less tested modalities such as hypnosis. Only those patients with disabling hiccups that do not respond to conservative treatment should be considered for phrenic nerve surgery.