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.     

Nonoperatively treated burst fractures of the thoracic and lumbar spine in adults: a 23- to 41-year follow-up

BACKGROUND CONTEXT: Several studies report a favorable short-term outcome after nonoperatively treated two-column thoracic or lumbar burst fractures in patients without neurological deficits. Few reports have described the long-term clinical and radiological outcome after these fractures, and none have, to our knowledge, specifically evaluated the long-term outcome of the discs adjacent to the fractured vertebra, often damaged at injury and possibly at an increased risk of height reduction and degeneration with subsequent chronic back pain. PURPOSE: To evaluate the long-term clinical and radiological outcome after nonoperatively treated thoracic or lumbar burst fractures in adults, with special attention to posttraumatic radiological disc height reduction. STUDY DESIGN: Case series. PATIENT SAMPLE: Sixteen men with a mean age of 31 years (range, 19-44) and 11 women with a mean age of 40 years (range, 23-61) had sustained a thoracic or lumbar burst fracture during the years 1965 to 1973. Four had sustained a burst fracture Denis type A, 18 a Denis type B, 1 a Denis type C, and 4 a Denis type E. Seven of these patients had neurological deficits at injury, all retrospectively classified as Frankel D. OUTCOME MEASURES: The clinical outcome was evaluated subjectively with Oswestry score and questions regarding work capacity and objectively with the Frankel scale. The radiological outcome was evaluated with measurements of local kyphosis over the fractured segment, ratios of anterior and posterior vertebral body heights, adjacent disc heights, pedicle widths, sagittal width of the spinal canal, and lateral and anteroposterior displacement. METHODS: From the radiographical archives of an emergency hospital, all patients with a nonoperatively treated thoracic or lumbar burst fracture during the years 1965 to 1973 were registered. The fracture type, localization, primary treatment, and outcome were evaluated from the old radiographs, referrals, and reports. Twenty-seven individuals were clinically and radiologically evaluated a mean of 27 years (range, 23-41) after the injury. RESULTS: At follow-up, 21 former patients reported no or minimal back pain or disability (Oswestry Score mean 4; range, 0-16), whereas 6 former patients (of whom 3 were classified as Frankel D at baseline) reported moderate or severe disability (Oswestry Score mean 39; range, 26-54). Six former patients were classified as Frankel D, and the rest as Frankel E. Local kyphosis had increased by a mean of 3 degrees (p<.05), whereas the discs adjacent to the fractured vertebrae remained unchanged in height during the follow-up. CONCLUSIONS: Nonoperatively treated burst fractures of the thoracic or lumbar spine in adults with or without minor neurological deficits have a predominantly favorable long-term outcome, and there seems to be no increased risk for subsequent disc height reduction in the adjacent discs.     

<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.     

Neutrophil alkaline phosphatase activity increase in bacterial infections is not associated with a general increase in secretory vesicle membrane components.

The content of alkaline phosphatase (ALP) was determined in neutrophils isolated from patients with acute bacterial infections by a standard enzyme assay. Compared with control cells, patient cells exhibited about a fivefold increase in ALP activity. There was no difference between the ALP Km values of control and patient cells, which indicates that the elevated activity in patient cells was due to the presence of increased amounts of the enzyme. The ALP isozyme in both cell types was determined to be the tissue-unspecific ALP. The fact that much of the ALP activity was measurable only in the presence of detergent suggested that the enzyme was localized in the secretory vesicles, a putative reservoir of plasma membrane components. The amount and subcellular distribution of two other secretory vesicle membrane proteins, i.e., cytochrome b and complement receptor 3, were not altered; hence, we conclude that there was no general increase in amounts of secretory vesicle membrane constituents in the patient cells.