QUANTITATION OF THE ACCELERATING EFFECT OF METYRAPONE ON CORTISOL METABOLISM

Quantitation of the accelerating effect of metyrapone on cortisol metabolism has been made by determination of the metabolic clearance rate (MCR) of exogenous cortisol during a metyrapone load. Six adrenalectomized patients were studied. The slope of cortisol concentrations in plasma was determined after intravenous administration of 0.3 mg cortisol/kg b. w. with or without metyrapone 17.5 mg/kg b. w./h. In all six patients studied, the MCR of cortisol increased during metyrapone load from an average of 12.3 ± 5.0 (SD) 1/h to 29.6 ± 15.7 (SD) 1/h or corrected for body weight 3.0 ± 1.1 (SD) ml/kg b.w./min to 7.1 ± 2.5 (SD) ml/kg b.w./min The discrepancy discovered in clinical practice between the relatively small rise in plasma total corticosteroid concentration and the greater increase in urinary excretion of corticosteroid metabolites during the metyrapone test may be explained by the findings in this study.     

Suppression of blood monocyte and neutrophil chemotaxis in acute human malaria

Summary The host response to Plasmodia includes the production of enlarged populations of peripheral blood monocytes and tissue macrophages in the spleen and the liver. Since the hyperplasia of the mononuclear phagocyte system is believed to arise as a consequence of an enhanced blood monocyte influx, we tested monocyte chemotactic responsiveness in 19 patients with acute primary attack malaria. In addition, the neutrophil chemotaxis was measured in 12 patients. Before the initiation of antimalarial treatment a significant depression of monocyte chemotaxis was observed in approximately half of the patients when compared with healthy control subjects. The depression was found in Plasmodium falciparum malaria as well as in P. vivax or P. ovale malaria patients. The defective responsiveness was not receptor specific, since the responses towards casein and zymosan activated serum proved to be equally suppressed. The monocyte chemotaxis was followed in 14 of the patients, during treatment and after complete recovery. After 3 days of treatment the response had improved in most of the patients, and after 7 days all patients had a normal monocyte chemotaxis, which remained normal after one month. No significant differences between P. falciparum and P. vivax/ovale malaria was observed with respect to blood monocyte chemotactic responsiveness. Neutrophil chemotaxis in patients with P. falciparum infections was similarly suppressed before treatment (54% of controls), was still defective after 3 days of treatment, and nearly normalized after 7 days (87% of controls). Furthermore, monocyte phagocytic and candidacidal activities were assessed in the same patients on admission and during the follow-up. In contrast to chemotaxis, these functions were normal in all of the patients whenever measured. In conclusion, not all cell functions were altered in concert, and the previously unreported suppression of chemotactic migration might reflect a change in blood leucocyte subpopulations, deactivation in vivo or a direct suppressive effect of Plasmodia induced products.     

Mitral Annulus Calcification and Embolism

ABSTRACT. Of 388 patients consecutively referred to echocardiography, 49 were suspected of having a cardiac source of systemic arterial embolism (SE). Mitral annulus calcification (MAC) was revealed in 27% of the patients with SE and in 8% of the remaining patients (p<0.05). The group of patients with SE were slightly older (median age 67 years) and included more female patients (47%) compared to the group without SE (62 years, p<0.05; 40% female patients, p>0.05). However, the small differences in age and sex distribution did not explain satisfactorily the considerably increased prevalence of MAC in the group of patients with SE. Our preliminary data indicated that thromboembolism caused by left atrial dilatation and atrial fibrillation might be the most important cause of the condition in patients with MAC and SE. However, the significance of the possible mechanisms of embolism in patients with MAC and the incidence of the complication should be further clarified before therapy and prophylaxis can be suggested.     

Autoimmunity Related to IgM Monoclonal Gammopathy of Undetermined Significance

ABSTRACT In eight of 10 consecutive cases of IgM monoclonal gammopathy of undetermined significance (MGUS), the M-protein had specificity towards various tissues as estimated by direct and indirect immunofluorescence studies of skin and/or sural nerve biopsies. Five of the cases had neuropathy. In three of them, including two siblings with a demyelinating peripheral neuropathy, the IgM was bound to the myelin-associated glycoprotein (MAG) of peripheral nerves. One had axonal neuropathy with IgM activity against the peri- and endoneurium, while another case with post-infectious neuritis had IgM activity against structures in the endoneurium but no IgM autoimmunity in the direct fluorescence test. The latter improved clinically in parallel with a decrease in the M-protein indicating a pathogenetic role of the autoantibody. In three other cases, the IgM was bound to connective tissue structures, two of them also had plasma antibodies against the peri- and endoneurium in the indirect fluorescence test. Finally, two cases showed no reaction of the M-protein against any tissue structures. Since an autoimmune pathogenesis is suspected, the HLA types of seven patients are reported.     

Effect of nigral lesion on chlorpromazine-induced acceleration of dopamine synthesis from [14C]tyrosine

The nigro-neostriatal dopamine pathway of the rat brain was subjected to a unilateral stereotaxic lesion at the level of the hypothalamic-mesencephalic junction. Fifteen days after the operation endogenous dopamine and[¹⁴C]dopamine formed in vivo from [¹⁴C]tyrosine were reduced to about 15% in the striatum ipsilateral to the lesion. Twenty-four h after the lesion the contents of endogenous and labelled dopamine were about the same in the striata of both sides. Chlorpromazine (15 mg/kg) accelerated several fold the accumulation of [¹⁴C]dopamine formed from [¹⁴C]tyrosine in the striatum on the intact side. However, in the striatum on the side of the lesion, chlorpromazine did not increase the accumulation of [¹⁴C]dopamine. The results indicate that chlorpromazine accelerates dopamine synthesis in the striatum by an indirect mechanism, presumably by activating the nerve impulse flow in the nigro-neostriatal dopamine pathway.     

Analysis of Arrhythmias Based on Atrial Wall Motion

ABSTRACT. The usefulness and feasibility of recording atrial wall motion by M-mode echocardiography guided by two-dimensional examination was evaluated in three groups of consecutive patients'. 7 with undefined tachyarrhythmias, 25 in sinus rhythm, and 20 with atrial flutter or fibrillation. Atrial systole was recorded in the left and right atrium in 58 and 98% of the patients, respectively (p < 0.05). Six of the patients with undefined tachyarrhythmias exhibited electrocardiographic atrioventricular dissociation revealed by preceding echocardiography in all. The precise timing of left and right atrial systole could be recorded in patients in sinus rhythm; right atrial contraction preceded left atrial systole by 42±31 msec (mean ± SD). Among patients with atrial flutter or fibrillation, one case of dissimilar atrial rhythms was revealed by echocardiography. Thus, recording of atrial wall motion is feasible in the majority of patients and provides information which is otherwise available only by esophagus ECG or by invasive means.     

Nephrotoxicity of cyclosporin A. A lithium clearance and micropuncture study in rats

Renal function was studied in rats treated with cyclosporin A (CyA). Peroral CyA 25 mg kg-1 day-1 depressed glomerular filtration rate (GFR) from 1284 +/- 429 to 500 +/- 228 microliters min-1 g-1 kidney weight (KW) (P less than 0.01). Absolute rate of proximal tubular reabsorption (APR) decreased from 1075 +/- 437 to 468 +/- 203 microliters min g KW-1 (P less than 0.01). Proximal tubular fractional reabsorption (PFR) was 67.7 and 68.5% measured with the TT/OT and fractional lithium-clearance methods, respectively. Amiloride had no effect on lithium-clearance in CyA treated rats. Acute isotonic volume expansion increased GFR and APR towards normal, while PFR remained increased. Increased sodium clearance did not normalize renal function. CyA intravenously (12.5 mg kg-1) depressed GFR and APR acutely, while PFR increased. Proximal intratubular pressures were low normal (mean 11.6 mmHg). Proximal transit times were prolonged (mean 25.2 s, P less than 0.01). Renal morphology was normal. The data are evidence against a primary tubular damage of CyA, and makes it less likely that the major lesion is located to the glomerular membrane. The results suggest that CyA nephrotoxicity mainly is due to a haemodynamic effect.     

ANTINUCLEAR ANTIBODIES IN JUVENILE CHRONIC ARTHRITIS

ABSTRACT. One hundred patients with juvenile chronic arthritis (JCA) were studied with respect to granulocyte-specific and organ-nonspecific antinuclear antibodies (GS- and ON-ANA) in relation to clinical features of disease. Seventy-two were girls and 28 boys. Sixty-seven patients had IgG ANA, 31 IgM, 10 IgA, 6 IgD, 19 IgE and 35 had ANA, which fixed complement C3. Sixteen of 17 sera containing IgG GS-ANA were from girls. The prevalence of IgG GS-ANA increased with the number of joints affected. No patient with the acute febrile type of the disease had IgG GS-ANA or C3 fixing ANA. The prevalence of IgG ON-ANA did not differ significantly in the mono-, pauci-, polyarticular and acute febrile types of JCA. Patients showing clinical activity more frequently had IgG and IgM ANA and C3 fixing ANA. The high titers of ANA were most often seen in girls. Chronic uveitis occurred in 10 of the patients and IgG ANA were present in sera from all of these.