Secondary haemophagocytic lymphohistiocytosis: Experience from the Uppsala University Hospital

Background. Haemophagocytic lymphohistiocytosis (HLH) is a rare clinical syndrome characterized by fever, hepatosplenomegaly, cytopenia, and progressive multiple-organ failure. HLH in adults is often secondary to autoimmune diseases, cancer, or infections in contrast to familial HLH. Treatment of secondary HLH is directed against the triggering disease in addition to immunosuppressive therapy, the latter commonly according to the HLH-2004 protocol.Methods. We conducted a retrospective study to identify triggering diseases, disease-specific and immunosuppressive therapy administered, and prognosis in adult patients with secondary HLH. Patient data were collected from October 2010 to January 2015.Results. Ten adult patients with secondary HLH were identified. Seven were men, and the median age at diagnosis was 62 years. Five cases were triggered by malignant disease and five by infection. The median patient fulfilled five of the eight HLH-2004 diagnostic criteria. All patients fulfilled the criteria fever, cytopenia, and ferritin >500 µg/L. Median time from hospital admission to HLH diagnosis was 20 days. Four patients received immunosuppressive therapy according to the HLH-2004 protocol. The prognosis was dismal, especially for the patients with malignancy-associated HLH, of whom all died.Conclusion. HLH should be suspected in patients who present with fever, cytopenia, and ferritin >500 µg/L. Secondary HLH has a dismal prognosis. None of the patients with HLH triggered by malignancy survived. Achieving remission of the triggering disease seems to be important for a favourable outcome as, in all surviving patients, the haemophagocytic syndrome resolved after remission of the underlying infection.     

EQUAL FREQUENCY OF TEL/AML1 ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN WITH AND WITHOUT DOWN SYNDROME

Constitutional trisomy 21 is the most prominent predisposing factor to childhood leukemia, whereas the t(12;21)(p13;q22) with its molecular genetic counterpart, the TEL/AML1 fusion gene, is the most common acquired chromosomal rearrangement in childhood B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). Thus, it was somewhat surprising that according to the currently available literature the incidence of TEL/AML1+ BCP ALL is extremely low in patients with Down syndrome (DS). To further investigate this issue in a population-based fashion, the authors retrospectively assessed the number of DS patients with a TEL/AML1+ ALL in two consecutive Austrian ALL multicenter trials. Accordingly, they were able to analyze 8 of 10 individuals with DS and a BCP ALL, including 2 who suffered from a TEL/AML1+ leukemia. Based on this observation we concluded that individuals with a constitutional trisomy 21 may have the similar likelihood to develop a TEL/AML1+ leukemia as BCP ALL patients without this specific predisposing factor.     

Results of Transplanting Developing Third Molars as Part of Orthodontic Space Management

PATIENTS AND METHOD: The aim of the present study was to contribute to a more accurate indication and better integration of developing third molar transplantation into orthodontic space management, using the results gleaned from the authors' own pool of patients. For this purpose, a clinical and radiographic examination of 61 transplanted developing molars in 57 patients was carried out after an average of 3.3 years. RESULTS: The overall success rate was 85%. Failure was due in 10% of cases to impaired periodontal healing (inflammatory root resorption, ankylosis, or increased pocket probing depths) and in 5% of cases to insufficient or arrested postoperative root development accompanied by increased transplant mobility. The incidence of postoperative cessation of further root development was significantly higher (p = 0.011) in transplants at early developmental stages, which also had a negative impact on the final root length, the crown-root ratio and the mobility values of these transplants. CONCLUSIONS: The transplantation of developing third molars should be given stronger consideration in treatment plans for orthodontic space management although it represents a real alternative to orthodontic space closure only in exceptional cases. However, unlike implantological or prosthodontic treatment, it offers an opportunity to replace a missing or non-retainable tooth with a patient's own vital and fully functional tooth, provided the appropriate transplant is selected.     

Insulin and glucagon secretion in swimming mice: effects of adrenalectomy and chemical sympathectomy

Swimming-stress is known to inhibit glucose-stimulated insulin secretion and stimulate glucagon secretion. In the present study, in mice, we investigated the relative contribution of sympathetic nerves and the adrenals to these effects. Mice were pretreated either with adrenalectomy or chemical sympathectomy induced by i.v. injection of 6-hydroxydopamine (6-OHDA), which destroys sympathetic nerve terminals. Two days later, the mice were injected i.v. with either glucose (5.6 mmol/kg) or saline, immediately before being subjected to 2 min swimming-stress or 2 min resting. Directly thereafter, blood was sampled. In normal controls, swimming inhibited glucose-stimulated insulin secretion and elevated plasma glucagon levels (P less than 0.01). Both these responses were absent both in adrenalectomized and in chemically sympathectomized mice. We also found that in resting animals, adrenalectomy reduced plasma levels of glucagon (P less than 0.05) and glucose (P less than 0.01), and that in adrenalectomized mice, swimming lowered basal plasma insulin levels (P less than 0.05). Furthermore, 6-OHDA-treatment elevated basal plasma glucagon levels (P less than 0.01). Thus, we show that, in the mouse, the inhibition of glucose-stimulated insulin secretion and the stimulation of glucagon secretion that occur during swimming-stress are both dependent on mechanisms requiring both the adrenals and intact sympathetic nerve terminals.     

Mechanical function of intermediate filaments in arteries of different size examined using desmin deficient mice

Protein composition and mechanical function of intermediate filaments were examined in arteries of different sizes using desmin deficient mice (Des−/−) and their wild-type controls (Des+/+). Using SDS-PAGE gels and Western blots we found a gradient in desmin expression in the arterial tree; the desmin content increased from the elastic artery aorta, via the muscular mesenteric artery to the resistance-sized mesenteric microarteries ∼150 μm in diameter in Des+/+ mice. Mechanical experiments were performed on the aorta, the mesenteric artery and resistance-sized arteries using wire myographs. For aorta and mesenteric artery, no differences in passive or active circumference- stress relations were found between Des−/− and Des+/+ mice. In microarteries, both passive and active stress were lower in the Des−/− group. In conclusion, large elastic and muscular arteries contain a relatively low amount of desmin, and the desmin intermediate filaments do not seem to play a major role in the mechanical properties of these larger arterial vessels. In the microarteries, where expression of desmin is high, desmin plays a role in supporting both passive and active tension.     

Die Prothrombinkonzentration im Blute von Frauen Während der Schwangerschaft und des Wochenbettes

Zusammenfassung Es wurden 112 Frauen in verschiedenen Stadien der Schwangerschaft untersucht und 25 Frauen in den ersten 4 Wochen nach der Geburt. Der Durchschnittswert der Prothrombinkonzentration steigt nach dem 3. Monat bedeutend an, diese Steigerung hält bis zum 6. Monat an, dann findet man bis zum Abschluß der Schwangerschaft konstante Prothrombinwerte. Bei 7 von 85 Frauen, die nach dem 3. Schwangerschaftsmonat untersucht wurden, wurden normale Prothrombinwerte festgestellt, bei allen anderen waren die gefundenen Werte absolut erhöht. Der höchste gefundene Wert war 310%. Die Prothrombinkonzentration fällt im Laufe von 1–3 Wochen nach der Geburt wieder zu normalen Werten ab.Die bei den verschiedenen Frauen stark variierende Hyperprothrombinämie ist bei Primiparen und Multiparen praktisch genommen gleich und ist unabhängig davon, ob die Frauen lange dauernde Molimina, Proteinurie oder Ödeme gehabt hatten. Es wurde kein Zusammenhang zwischen der Prothrombinkonzentration und dem Blutverlust bei der Geburt nachgewiesen. Von 57 der untersuchten Frauen liegen Angaben über den Verlauf der ganzen Schwangerschaft und Wochenbett vor; keine dieser Frauen hatten eine Thrombosie.Wieweit die Hyperprothrombinämie durch Irritation der Leber oder Hyperaktivität des Knochenmarks verursacht wird, ist nicht zu entscheiden.Es ist anzunehmen, daß die Hyperprothrombinämie der Grund für die erhöhte Koagulationsfähigkeit des Blutes von graviden Frauen ist, wie bereits von anderen nachgewiesen wurde.