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.     

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.     

<Emphasis Type="Italic">Bcl11b</Emphasis>mutations identified in murine lymphomas increase the proliferation rate of hematopoietic progenitor cells

Background  

The telomeric region of mouse chromosome 12 has previously shown frequent allelic loss in murine lymphoma. The Bcl11b gene has been identified and suggested as a candidate tumor suppressor gene within this region. In this study, we aimed to elucidate whether Bcl11b is mutated in lymphomas with allelic loss, and whether the mutations we detected conferred any effect on cell proliferation and apoptosis.     

Positron Emission Tomography in Tumor Diagnosis and Treatment Follow-Up

The technique of positron emission tomography (PET) is described. PET is an in vivo imaging and quantitative technique which allows the visualization of various functional and biochemical parameters. PET is a tracer technique in which bioactive tracer substances are labelled with short-lived positron emitting radionuclides. The most important of these are ¹⁵O, ¹³N, ¹¹C and ¹⁸F with decay times ranging from 2 min to 2 h. The radiolabeled substance is injected intravenously and the distribution, uptake and binding are registered externally with the PET camera using of the order of 4 000 small detectors. The camera produces simultaneously 15 tomographic slices in which the absolute concentration of the tracer substance can be measured. Using a dynamic imaging sequence starting after the injection of the tracer, the dynamics of the tracer uptake is recorded and can be used to deduce functional parameters, such as perfusion flow, tracer distribution, binding to receptor or enzyme systems, etc. depending on the choice of tracer substance. The great versatility of PET and its potential of direct noninvasive study of tumor function will make it a very important clinical and research tool in oncology. With the choice of substances selective for a certain aspect of a tumor's biochemistry the potential opens for a better diagnosis, improved differential diagnosis and, especially with the use of metabolic tracers, an improved possibility to evaluate the response to treatment.