CD4+ T-cell induction of Fas-mediated apoptosis in Burkitt's lymphoma B cells

Cytotoxic function of CD4+ Th1 cells is mediated by Fas (CD95, APO-1) and its ligand (Fas ligand). Recent studies using nontransformed B cells and the Ramos Burkitt's lymphoma (BL) B-cell line cells show that CD40 ligation at the B-cell surface by activated, CD40 ligand (CD40L)- bearing, CD4+ T cells upregulates Fas expression on B cells and primes B cells for Fas-mediated death signals. In this work, we examine whether this CD4+ T-cell-dependent molecular pathway for Fas upregulation and B-cell apoptosis reflects a peculiarity of the Ramos B- cell line or is applicable to other Burkitt's tumors as well. In 5 of the 6 Epstein-Barr virus-negative BL cell lines examined, the cells constitutively express undetectable or low levels of Fas and are resistant to Fas-mediated signals induced by monoclonal anti-Fas antibody. All 6 of the BL cell line B cells upregulate Fas in response to CD40 ligation, and in 4 of the cases they become sensitive to Fas- mediated death signals. In one BL cell line, the cells are constitutively sensitive to Fas-mediated cytolysis and are unaffected by CD40 signals. Next, we applied these immunologic manipulations to cells from a refractory clinical sample and observed that the tumor cells could be induced to express Fas and undergo apoptosis in our system. These results establish CD4+ T cells and the Fas-Fas ligand system as important immune regulators of Burkitt's lymphoma B cells and indicate that the susceptibility of tumor cells to Fas-mediated death signals can be modulated by specific activation events at the cell surface.     

Normal and degenerative posterior spinal structures: MR imaging

A retrospective study of the magnetic resonance (MR) images of the lumbar spines of 13 healthy subjects and 30 patients with degenerative changes was done. In the healthy subjects, the vertebral facets, thickness of the cartilage and ligamentum flavum, signal characteristics of the bone marrow, and size of the spinal canal were studied. In the patients with degenerative changes in one of these structures, MR images in the sagittal plane were useful in demonstrating hypertrophy of the ligamentum flavum or the vertebral facets, in grading the degree of foraminal stenosis, and in measuring the sagittal diameter of the spinal cord. MR images in the axial plane facilitated detailed analysis of the facet joint and more accurate measurements of the thickness of the ligamentum flavum and spinal canal diameter. MR images were compared with computed tomography scans in 12 patients.     

Asthma: Communication between hospital and general practitioners

OBJECTIVE: To assess whether efforts to actively involve General Practitioners (GPs) in the postdischarge care of their paediatric asthma patients improved their satisfaction with communication with hospital staff. METHODOLOGY: Randomized controlled trial involving 60 patients admitted to the Royal Children's Hospital, Melbourne, with acute asthma and an identifiable GP. The GPs of the intervention patients were telephoned during the admission. Intervention patients and their GPs received printed information detailing the care the patient received in hospital and the recommended postdischarge care, as well as standardized educational booklets about asthma. Follow-up appointments were made for intervention patients to attend their GPs. RESULTS: The GPs of intervention patients were more satisfied when compared to the GPs receiving a standard level of communication (96.4% vs 48.3% of the intervention and control GPs, respectively, described the communication as good or extremely good, P = 0.0001). The intervention group GPs believed they were more involved after discharge (75.0% vs 44.8%, P = 0.005) and had greater understanding of their patient's hospitalisation (96.4% vs 62.1%, P = 0.005). These differences were noted despite there being no difference in the rate of follow-up attendance with GPs for intervention and control patients (85.7% vs 72.4%, P = 0.2). Qualitative data supported these findings with GPs expressing approval of the intervention used. CONCLUSION: Efforts to actively involve GPs in the postdischarge care of their paediatric patients with asthma resulted in a marked improvement in their satisfaction with the communication with medical staff at the Royal Children's Hospital, Melbourne. The study had insufficient power to demonstrate a difference in morbidity.     

Non-medicalization of medical science: Rationalization for future

As we delve into the intricacies of human disease, millions of people continue to be diagnosed as having what are labelled as pre-conditions or sub-clinical entities and may receive treatments designed to prevent further progression to clinical disease, but with debatable impact and consequences. Endocrinology is no different, with almost every organ system and associated diseases having subclinical entities. Although the expansion of these “grey” pre-conditions and their treatments come with a better understanding of pathophysiologic processes, they also entail financial costs and drug adverse-effects, and lack true prevention, thus refuting the very foundation of Medicine laid by Hippocrates “Primum non nocere” (Latin), i.e., do no harm. Subclinical hypothyroidism, prediabetes, osteopenia, and minimal autonomous cortisol excess are some of the endocrine pre-clinical conditions which do not require active pharmacological management in the vast majority. In fact, progression to clinical disease is seen in only a small minority with reversal to normality in most. Giving drugs also does not lead to true prevention by changing the course of future disease. The goal of the medical fraternity thus as a whole should be to bring this large chunk of humanity out of the hospitals towards leading a healthy lifestyle and away from the label of a medical disease condition.