Pro-inflammatory cytokines and the pathogenesis of Gaucher's disease: increased release of interleukin-6 and interleukin-10

Gaucher's disease is characterized by hepatosplenomegaly, bone-marrow infiltration, osteonecrosis and bone thinning, associated with the presence of pathological macrophages that contain undegraded glycosphingolipids. To investigate the possible role of cytokines in the systemic and local manifestations of established Gaucher's disease, interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF alpha) and interleukin-10 (IL-10) were measured in freshly-separated serum. Samples from eight male and 14 female patients with type 1 Gaucher's disease were compared with sera from 22 healthy age- and sex-matched controls. Concentrations of IL-6 and IL-10 were significantly elevated in sera from patients with Gaucher's disease (11.9 +/- 1.8 (SEM) pg/ml and 5.4 +/- 0.5 (SEM) pg/ml, respectively) compared with those of controls (4.1 +/- 0.9 (SEM) and 0.8 +/- 0.3 (SEM) pg/ml, p < 0.0001). No significant differences in concentrations of TNF alpha or IL-1 beta were identified. IL-6 has been implicated in the development of localized osteolysis in multiple myeloma and in the development of post-menopausal osteoporosis. High concentrations of IL- 6 in the serum of patients with Gaucher's disease may thus reflect the development of the bone lesions commonly associated with this disorder. Since IL-6 and IL-10 are important regulators of lymphocyte growth and differentiation, and IL-6 concentrations were significantly raised in patients with oligo- or polyclonal increases in serum immunoglobulins, enhanced release of these cytokines from pathological macrophages provides a pathological link between Gaucher's disease and associated lympho-proliferative disorders.      

Stage-specific oligonucleotide uptake in murine bone marrow B-cell precursors

Fluorescein isothiocyanate (FITC)-conjugated phosphodiester and phosphorothioate oligonucleotides were used in four-color flow cytometry with murine bone marrow cells stained with monoclonal antibody specific for the differentiation markers B220, S7 (CD43), and BP-1 to show possible stage-specific oligonucleotide uptake. Relatively low uptake was observed among pre-Pro- and early Pro-B cells. Late Pro- B- and pre-B cells had increased oligonucleotide uptake, whereas B cells had a lower level. Cell membrane binding of oligonucleotides varied during B-cell differentiation in parallel with internalization, which was documented by confocal microscopy. An FITC-conjugated polyanionic dextran sulfate also showed differentiation-related B-cell association, suggesting the presence of cell membrane binding sites specific for polyanions as opposed to a unique feature of the DNA backbone. Interpretation of antisense experiments in murine bone marrow cells will need to account for the heterogeneous oligonucleotide uptake among differentiating B cells.     

Rare Presentation of Boerhaave's Syndrome – A Tale of the Unexpected

The case is described of a patient presenting with signs and symptoms of a large bowel obstruction with perforation, who at laparotomy was found to have caecal volvulus but no obvious cause for the air under the diaphragm. On dissection of the lesser sac, he was found to have an oesophageal perforation secondary to vomiting caused by the volvulus. This was repaired over a t-tube and despite delayed presentation, he made a full recovery. This cause of Boerhaave's syndrome has not previously been described, and underlines the need for careful search for the cause of air under the diaphragm when the laparotomy findings do not reveal an obvious perforation.     

Association between antipsychotics and weight gain among psychiatric outpatients in Pakistan: a retrospective cohort study

Background  

It has been known for a long time that use of antipsychotics, particularly atypical antipsychotics, is associated with weight gain and increase in risk of metabolic disturbances. In this study we have tried to find out if use of antipsychotics is associated with increase in weight and body mass index (BMI) in the Pakistani population.