Vagn Andersen

Immunological studies in children before and after splenectomy.

Abstract. Fourteen children underwent splenectomy for congenital spherocytosis, splenomegaly, or thrombocytopenia. The patients were studied twice before the operation, three times during the first postoperative month, and one year later. A transitory rise in neutrophils and serum IgA was seen postoperatively; there was a modest but long‐lasting increase in lymphocytes and a marked elevation of eosinophils. An immediate decline in serum IgM concentration was observed only in patients with an uncomplicated postoperative course, but one year after splenectomy the average IgM concentration had decreased by 23 %. The in vitrolymphocyte transformation response to a panel of mitogens and antigens fell in the immediate postoperative period but was largely normalized 10 days postoperatively, except in the youngest of the patients who had repeated infections following the splenectomy. One year postoperatively the transformation response and the number of T‐ and B‐lymphocytes in the blood were normal.

Macrophage-lymphocyte clusters in the immune response to soluble protein antigen in vitro. III. DNA synthesis of lymphocytes in clusters.

Abstract The lymphocytes which engage in DNA synthesis during the in vitro immune response to PPD (purified protein derivative of tuberculin) were studied by scintillation counting and in autoradiographs prepared from cultures of macrophages and immune T-lymphocyte-enriched lymphocytes. The lymphocytes in these cultures were located in three compartments: lymphocytes in macrophage-lymphocyte clusters, lymphocytes attached to macrophages but not involved in clusters, and not macrophage-attached lymphocytes. One of the cluster cells, the central lymphocyte, which is attached directly to the macrophage, was identified as the only DNA-synthesizing lymphocyte in the cluster early in the culture period. In cultures extended beyond 20 hr the increase in percentage of DNA-synthesizing lymphocytes in the cluster and macrophage-attached compartments exceeded the increase in the compartment of not macrophage-attached lymphocytes. The total amount of radiolabeled thymidine incorporated into lymphocytes in a blast transformation assay was directly proportional to the number of macrophage-lymphocyte clusters produced by the same lymphocytes in a cluster assay.

Low noise alternating current amplifier and compensator to reduce stimulus artefact

Action potentials of sensory nerve evoked by stimuli of 70 mA may be as small as 0·05 μV. They are buried in noise and require electronic averaging. The signal-to-noise ratio can be improved by the use of an input transformer and by limiting the frequency range (Buchthal andRosenfalck, 1966). When recording near the point of stimulation the amplitude of the artefact exceeds that of the sensory potential by a factor of 104 and prevents its recording because of the pulse distortion caused by the limited frequency range. This was diminished by decreasing the lower limiting frequency of the input transformer by means of positive feedback. To diminish the pulse distortion in the high-pass and low-pass filter of the output stage, the filter elements were placed in the feed-back loop of an amplifier with high closed loop gain.The small tail of the stimulus artefact arising mainly from the transmission through the isolating transformer in the output of the stimulator was reduced by compensation with a pulse of the same shape and amplitude but of opposite sign.SommaireLes potentiels daction du nerf sensitoire évoqué par des stimulants de 70 mA peuvent être aussi bas que 0,05 μV. Ils sont enfouis dans le bruit et demandent à être moyennés électroniquement. Le rapport signal/bruit peut être amélioré par lemploi dun transformateur dentrée et en limitant la gamme des fréquences (Buchthal etRosenfalck, 1966). Lorsque lon enregistre près du point de stimulation lamplitude de lartefact dépasse celle du potentiel sensitoire dun facteur de 104 et rend son enregistrement impossible du fait de la distortion de limpulsion causée par la gamme de fréquence limitée. Ceci a été réduit en diminuant la limite inférieure de la fréquence du transformateur dentrée par une rétroaction positive. Afin de diminuer la distortion de limpulsion dans le filtre de passe haute et basse du stage de sortie les éléments du filtre ont été placés dans la boucle de rétroaction dun amplificateur avec un gain élevé de boucle fermée.La petite queue de lartefact de stimulant provenant surtout de la transmission par le transformateur disolation dans la sortie du stimulateur a été réduite par compensation avec une impulsion de la même forme et de la même amplitude mais de signe opposé.ZusammenfassungMit Stimulus von 70 mA hervorgerufene Wirkungspotentiale der Sinnesnerven können bis 0,05 μV klein sein. Sie sind in Störungen eingebettet und machen elektronische Durchschnittsermittlung erforderlich. Das Störverhältnis kann bei Verwendung eines Eingangstransformators verbessert werden und durch Begrenzung des Frequenzbereichs (Buchthal undRosenfalck, 1966). Bei Aufnahme nahe des Erregungspunktes überragt die Amplitude des Artefakts die des Sinnespotentials um einen Faktor von 10: und verhindert dessen Aufnahme infolge der durch den begrenzten Frequenzbereich verursachten Pulsverzerrung. Dies wurde durch Verkleinerung der unteren Grenzfrequenz des Eingangstransformators mittels positiver Rückkoppelung abgeschwächt. Zur Verkleinerung der Pulsverzerrung in dem oberen und unteren Durchlassfilter der Ausgangsstufe wurden die Filterbestandteile in den Rückkoppelungskreis eines Verstärkers mit hoher Stromkreisverstärkung gelegt.Der kleine Schwanz des Stimulus Artefakts, der hauptsächlich in der Übertragung durch den Isoliertransformator in der Ausgangsstufe des Erregers entsteht, wurde durch Kompensierung mit einem Puls der gleichen Form und Amplitude, aber mit umgekehrtem Vorzeichen, reduziert.

FATAL GRANULOMATOUS DISEASE

Two brothers with Fatal granulomatous disease of childhood (FGD) are presented. Both patients exhibited pronounced food allergy. Otherwise, the course of the disease was typical of FGD. From infancy recurrent infections, notably suppurative lymphadenitis, and a fatal outcome before puberty.

Treatment of Wegener's granulomatosis with trimethoprim-sulfamethoxazole.

The fist observations of a beneficial effect of treatment of Wegener’s granulomatosis (WG) with trimethoprimsufamethoxazole (T-S) were published by DeRemee et al. in 1985 (1). They incidentally found a complete remission in a patient with WG using T-S to treat a urinary tract infection prior to immunosuppressive treatment. As the patient got well she denied further treatment. She later relapsed but got well again on renewed treatment with T-S. They originally described 11 further cases and subsequently expanded their experience to 46 patients (2). Others have also published on the beneficial effects of T-S treatment in smaller series (3,4 ) and several case stories have appeared. In general, most of the patients reported on have been treated in the course of the disease after having received immunosuppressive treatment. Moreover, half of the reported cases received additional immunosuppressive treatment. As the patient materials in the reports are quite different it is difficult to compare the results but a cautious summary is given in table 1. Our experience is based on the patient material summarized in tables 2 and 3 according to the treatment given (Table 2) and the stage of disease (Table 3). The diagnosis was based on a positive C-ANCA and clinical findings compatible with WG in all cases with biopsies compatible with WG in 6 patients. The effect of treatment is illustrated in fig. 1 and 2. In fig. 1 (patient EC) the uncertain effect is illustrated. Although the patient felt better the first few months with a slow decline in CRP she later developed a saddle nose and finally got worse and was switched to cyclophosphamide and prednisolone treatment with good effect. It is noted that the C-ANCA titer slowly increased. In fig. 2 the rapid remission in patient LS is illustrated with a steep fall in C-ANCA titer measured by ELISA. However, she became allergic and treatment with tetracycline did not have the same effect. Treatment with prednisolone and cyclophosphamide was resumed and the disease is now in remission. The remaining 6 patients, including those that immediately did well on T/S treatment, are now all on regular immunosuppressive Table 1. Cures or improvements with T/S treatment of WG.

Soluble interleukin-2 receptor and soluble CD8 antigen levels in serum from patients with non-resectable lung cancer

SummaryIn a preliminary longitudinal study two women with histologically verified adenocarcinoma of the lung, without simultaneous infectious or inflammatory conditions, were seen every 2 weeks until death. In one of the patients serum soluble interleukin-2 receptor (sIL-2R) levels rose progressively while the levels for the other patient increased during the second half of the observation period. Serum soluble CD8 antigen (sCD8 Ag) showed a pattern dissimilar to the one for sIL-2R. In a retrospective cross-sectional study circulating levels of sIL-2R and sCD8 Ag were measured before explorative thoracotomy in a total of 65 patients with histologically proven non-resectable carcinoma of the lung. The sIL-2R levels were significantly increased independently of histological subclassification while sCD8 Ag was increased only in patients with small-cell lung cancer. There was no correlation between pre-operative values and length of survival.

Cyclosporine‐induced renal morphologic and immunohistologic changes in patients with chronic uveitis

Ten long‐term cyclosporine‐treated patients with chronic uveitis underwent percutaneous renal biopsy in order to evaluate a) abnormalities of renal morphology and b) the nature of lymphocytic infiltrates by immunohistochemistry. Pretransplant renal biopsies from eleven cadaveric donors served as controls. Eight of the ten patients had lymphocytic infiltrates consisting predominantly of T lymphocytes with a CD4+/CD8+ ratio of 1.46, which is identical to that of peripheral blood in healthy donors. Evidence of immune activation as estimated by the presence of interleukin‐2 receptors, transferrin receptors or by the expression of MHC class 11 antigens was not demonstrated in any of the patients. The severity of morphologic alterations did not correlate with any of the clinical or paraclinical data. Percutaneous renal biopsy should be performed within 18 months of treatment to identify patients susceptible to renal side effects of cyclosporine.

CHANGES IN BLOOD LYMPHOCYTES DURING THE NEONATAL PERIOD

Abstract. Andersen, V. and Andersen, E. (Departments of Paediatrics and Medicine, Rigshospitalet, Copenhagen, Denmark). Changes in Blood Lymphocytes during the Neonatal Period. Acta Paediat Scand, 63:266, 1973.–Blood lymphocytes were studied in 6 normal neonates during the first 2 weeks after delivery. At birth, the larger lymphocytes constituted 90%; these cells decreased in number until day 3 and then increased again. Small, adult type lymphocytes showed a steady increase in numbers during the observation period. DNA‐synthesizing cells were demonstrated by means of 3H‐thymidine incorporation followed by autoradiography. At birth, their average concentration was 47 per µl; they decreased in number to 8 per µl on day 3 and rose to a maximum of 76 per µl on day 6. RNA metabolic activity was evaluated by the uptake of 3H‐cytidine. Similar but less pronounced findings were obtained, preceding the changes in the number of DNA‐synthesizing cells by one or two days. It is hypothesized that the increase from day 2 is due to activated lymphocytes and reflects the stimulation of the immune apparatus through antigenic exposure.

Circumvention of Early Graft‐versus‐Host Disease in Hemiallogeneic Bonc Marrow Transplantation in a Case of Severe Combined Immunodeficiency

A girl with severe combined immunodeficiency and pronounced malnutrition from chronic diarrhoea is presented. Immunological reconstitution was attempted by transplantation of bone marrow cells from the HL‐A hemiallogeneic father. An initial transplant failed to induce a permanent take of the graft, whereas a second transplant with an increased cell dose ensured a take, which was followed by reconstitution of cell‐mediated immune functions. Fractionation of the transplanted bone marrow cells apparently led to a delay in development of graft‐versus‐host symptoms. Germ‐free isolation and extensive bacterial decontamination markedly reduced the microbial flora and was highly protective against contaminating microorganisms but failed to eradicate completely one strain of Escherichia coli that had invaded the child before institution of this regimen. During a moderate, delayed graft‐versus‐host reaction this strain caused widespread severe infection, to which the child succumbed 10 weeks after the second transplantation. This child presented some additional features, the most conspicuous being a deficiency of erythrocyte adenosine deaminase.