Noncompliance may render migraine prophylaxis useless, but once-daily regimens are better

Medicines work better if taken, which must be true of migraine prophylaxis. There is evidence that compliance with regular medication can be badly deficient. To assess how serious the problem might be in routine migraine management, we undertook a covert observational 2-month survey in a specialist headache clinic using objective measures of compliance. Subjects were 38 patients needing prophylaxis with medication prescribed once (od), twice (bd), or three times daily (tds). Medication was dispensed, unknown to them, in Medication Event Monitoring Systems (MEMS) to record openings in real time. Number, timing, and pattern of actual openings were compared with what was expected. Compliance rates averaged 66%, although returned pill counts indicated 91%. A substantial and significant difference was shown between od and bd or tds regimens. Measures of dosing interval—used-on-schedule rate and therapeutic coverage—averaged between 44% and 71%. Once-daily treatment was associated with a used-on-schedule rate more than double those of multiple daily dosing, but still only 66%. We conclude that routine use of drug prophylaxis in migraine may be so seriously undermined by poor compliance that it has little chance of efficacy. Returned-pill counting is inadequate for compliance assessment.     

The human genes for GM-CSF and IL 3 are closely linked in tandem on chromosome 5

As demonstrated by long-range mapping of restriction endonuclease recognition sequences and genomic cloning, we found that the human genes encoding interleukin 3 (IL 3) and granulocyte/macrophage colony- stimulating factor (GM-CSF) are tandemly arrayed on the long arm of chromosome 5, separated by 9 kilobases (kb) of DNA. This close physical linkage of genes with similar structure and biologic function suggests that these cytokines may have evolved from a common ancestral gene. This linkage in evolution of two relatively divergent genes further implies that some of the other lymphokine and cytokine genes that appear to share as much or more sequence similarity than do IL 3 and GM- CSF may be distantly related members of a cytokine gene family.     

Acute radiation effects on cutaneous microvasculature: evaluation with a laser Doppler perfusion monitor

Laser Doppler perfusion monitoring is a noninvasive technique for measuring blood flow in epidermal microvasculature that makes use of the frequency shift of light reflected from red blood cells. Measurements in patients undergoing radiation therapy show increases in blood flow of ten to 25 times baseline at doses above 50 Gy, and increases are observed with doses as low as 2 Gy. Follow-up measurements show rapid decreases in flow levels after completion of therapy, but levels remain elevated even at 1 year.     

Angiography of liver transplantation patients

Over 45 months, 119 angiographic examinations were performed in 95 patients prior to liver transplantation, and 53 examinations in 44 patients after transplantation. Transplantation feasibility was influenced by patency of the portal vein and inferior vena cava. Selective arterial portography, wedged hepatic venography, and transhepatic portography were used to assess the portal vein if sonography or computed tomography was inconclusive. Major indications for angiography after transplantation included early liver failure, sepsis, unexplained elevation of liver enzyme levels, and delayed bile leakage, all of which may be due to hepatic artery thrombosis. Other indications included gastrointestinal tract bleeding, hemobilia, and evaluation of portal vein patency in patients with chronic rejection who were being considered for retransplantation. Normal radiographic features of hepatic artery and portal vein reconstruction are demonstrated. Complications diagnosed using results of angiography included hepatic artery or portal vein stenoses and thromboses and pancreaticoduodenal aneurysms. Intrahepatic arterial narrowing, attenuation, slow flow, and poor filling were seen in five patients with rejection.     

Transplantation of organ cultured fetal pig pancreas in non-obese diabetic (NOD) mice and primates (Macaca fascicularis)

Abstract: Xenografts of organ cultured fetal pig pancreas in prediabetic NOD mice can survive for prolonged periods (>20 weeks) in recipients treated with anti-T cell monoclonal antibodies (MAb) directed against host CD4 and CD3 cell surface molecules. Anti-CD4 MAb treatment alone is only partly effective and xenograft rejection occurs over a period of many weeks. In diabetic recipients, by contrast, recurrence of autoimmune disease in isografts is rapid (<28 days) despite similar depletion of CD4+ve T cells. In spontaneously diabetic NOD mice immunosuppressed with anti-CD3 and anti-CD4 MAbs xenograft function occurs and the recipient's blood glucose levels fall into the pig range. Organ cultured fetal pig pancreas transplanted into cynomolgus monkeys is rapidly but not hyperacutely rejected when azathioprine-cyclosporin A-prednisolone immunosuppression is used. Anti-T-cell MAb treatment is now being studied in this primate model.     

Dendritic reticulum cell sarcoma? Four cases of a lymphoma probably derived from dendritic reticulum cells of the follicular compartment

This paper describes the histological picture of four tumours of the follicular compartment of the lymph node, in which the proliferating cell appeared to be the dendritic reticulum cell (DRC). This assumption was based on the results of light microscopical, ultrastructural, immunological, and enzymehistochemical investigations. The tumour cells resembled DRC's closely in (1) the striking pattern of interdigitations and occasional tight junction-like contacts between the neoplastic cells on electron microscopical analysis; (2) presence of receptors for the activated third component of complement on the membrane of the cells; (3) absence of monoclonal immunoglobulins and T-cell antigen on the surface and of lysozyme, alpha 1-antitrypsin or alpha 1-antichymotrypsin in the cytoplasm of the neoplastic cells. Moreover, (4) the tumour cells showed moderate alpha-naphtyl acetate esterase, weak to absent acid phosphatase and (with one exception) strong 5-nucleotidase activity. Furthermore, (5) the neoplastic cells expressed Ia-like antigens on the surface in all four cases. The relation with follicle centre cell lymphomas, the differential diagnosis and clinical data are discussed.     

Immunohistology of the human spleen: an inventory of the localization of lymphocyte subpopulations

The immunohistochemistry of the cell population of the human spleen was studied. As controls, a strictly defined group of five specimens were used. This study stresses the need for the utmost care in this selection procedure. Using enzyme- and immuno-histochemistry the lymphocyte subpopulations were studied as to their localization in the several specific compartments in the red and white pulp. The findings were compared to those in idiopathic thrombocytopenic purpura, autoimmune haemolytic anaemia and Hodgkin's disease. In the controls a consistent pattern was found. There were specific changes in each of the disease groups consisting mainly of shifts between the compartments.