Retinoblastoma. The relationship of proliferating cells to blood vessels

In 150 retinoblastomas the authors found a uniform thickness of the cuff of viable retinoblastoma cells that surrounds blood vessels. The mean thickness was 98.7 microns with a standard deviation of 11.9 microns. The cross-sectional area of the cuff was negatively correlated with the mitotic activity in the cuff and positively correlated with the diameter of the central vessel. The mitotic activity in the cuff of cells was inversely related to the distance from the central blood vessel. When the cuff was divided into three concentric rings, the inner ring contained a mean of 6.2 mitotic figures, the middle ring contained a mean of 2.9 mitotic figures, and the outer ring contained a mean of 0.6 mitotic figures. This pattern of growth is similar to that observed in other rapidly growing neoplasms in humans and experimental animals. In these tumors this pattern results from reduction in oxygen tension with increased distance from the central blood vessel.     

Orbital infarction and melting in a patient with systemic lupus erythematosus

OBJECTIVE: To present a patient with systemic lupus erythematosus who developed infarction and melting of the orbit secondary to her systemic disease. DESIGN: A case report. PARTICIPANT: A 61-year-old white woman with a 5-year history of systemic lupus erythematosus. METHODS: The patient presented with left orbital pain, limitation of extraocular movements, and a fistula from the ethmoid sinus to the upper eyelid. A detailed examination with computerized tomography, ultrasound, and a comprehensive medical evaluation with laboratory testing was performed. Histopathologic analysis with special stains of the orbital tissues was also performed. RESULTS: Histopathologic examination of the biopsy specimens revealed the features of an inflammatory process involving the orbit, similar to a panniculitis. These include a lymphocytic reaction with a predominance of plasma cells, vasculitis with occlusion, and thickening of the vessel walls, necrosis, and hyalinization of fat. CONCLUSION: This is a unique case in which infarction and melting of the entire orbital structures occurred in the presence of systemic lupus erythematosus. The underlying disease process is a lupus-related panniculitis. The authors stress that this is a very rare entity and that other diseases should be ruled out before entertaining this diagnosis.     

Electronic monitoring of compliance to lipid-lowering therapy in clinical practice

Nonadherence to treatment is a common problem in the clinical management of hypercholesterolemic patients. This study was carried out with the aim of monitoring the daily compliance to a 6-month course of lipid-lowering therapy, using a microelectronic device, the Medication Event Monitoring System (MEMS), versus pill count. Forty men with primary hypercholesterolemia were prescribed fluvastatin 1 x 40 mg daily, provided in a MEMS package to record the date and time of each opening of the pillbox. Thirty-nine of 40 patients (98%) completed the study. Total cholesterol and LDL cholesterol levels decreased significantly (18% and 25%, p < 0.001) during the 6-month therapy period. A high mean rate of compliance was achieved by MEMS using the following three indexes--compliance to total prescribed dose (88.8% +/- 13.5%), compliance to prescribed days (82.4% +/- 19.5%), and compliance to prescribed time of day (81.86% +/- 19.5%)--and by pill count (93.4% +/- 9.5%). In addition, the MEMS provided some patterns of nonadherence to medication, undetectable by pill count alone, such as a drug holiday in 38% of cases, a drug omission for more than 7 consecutive days in 9% of cases, and, conversely, use of more than the one prescribed daily dose in 47% of cases. A significant correlation between the rate of compliance and the decrease in LDL cholesterol was observed only when the compliance was assessed by MEMS. The results indicate that MEMS is a useful tool for monitoring compliance in clinical practice and may possibly increase adherence to long-term lipid-lowering therapy.     

Increased carotid intima–media thickness in the absence of atherosclerotic plaques in an adult population with Fabry disease

Aim: Fabry disease is considered primarily as a progressive small vessel disease, with ischaemic degenerative lesions involving the kidneys, brain and heart. Macrovascular involvement in male patients includes an accelerated wall hypertrophy of the radial artery and a thickening of the intima–media of the common carotid artery. The aim of this study is to evaluate the prevalence and severity of carotid artery atherosclerosis in hemizygous and heterozygous patients with Fabry disease, compared with a matched control population.
Methods: The common carotid artery intima–media thickness (IMT) of 53 patients with Fabry disease (24 men, 29 women) was measured by high-definition ultrasonography, and the presence or absence of atherosclerotic plaques reported. Results were compared with those of 120 age-matched healthy individuals (83 men, 37 women).
Results: The common carotid artery IMT was increased to the same extent in male and female patients with Fabry disease (706±211 µm and 749±395 µm, respectively) compared with that of the control population (614±113 µm). In the Fabry population, IMT did not correlate with either systolic blood pressure or with renal function (plasma creatinine). In the control population, only systolic blood pressure was positively and significantly correlated with IMT. Atherosclerotic plaques in the common carotid artery were not observed in any patient with Fabry disease, whereas 34% of the control population had carotid artery plaques, as evidenced by focal non-homogeneous intima–media thickening greater than 1.2 mm.
Conclusion: This study presents evidence of a major increase in common carotid artery IMT, both in hemizygous and heterozygous patients with Fabry disease, in the absence of focal atherosclerotic plaques. These results suggest that the conduit arteries may be protected from atherosclerosis in Fabry disease.     

Hypoxia-Inducible Factor-1α and its Role in the Proliferation of Retinoblastoma Cells

In order to better understand the role of HIF-1α in the proliferation of the retinoblastoma cells, a siRNA knockdown of HIF-1α followed by a proliferation assay was performed. Further sequencing was then carried out in order to assess knockdown efficiency and expression of HIF-1α. Upregulation of HIF-1α gene expression in CoCl₂-treated retinoblastoma cells was demonstrated via melting curve analysis from PCR tests and was further analyzed using western blot and densitometry analysis. Reduction of HIF-1α expression in retinoblastoma, post HIF-1α knockdown, was observed after siRNA transfection into Y-79 cells. Knockdown of HIF-1α resulted in a significant decrease in proliferation thereby demonstrating that HIF-1α is involved in promoting survival and proliferation in retinoblastoma cells. Stabilization of HIF-1α in retinoblastoma cells using CoCl₂ was unsuccessful.     

Compliance with antihypertensive therapy.

Poor compliance with antihypertensive therapy is a major cause of unsatisfactory blood pressure control. The doctor has a key role in all steps that lead the patient to adopt a treatment and to take it as prescribed lifelong. Compliance with therapy is a parameter which is difficult to assess. There is often an important mismatch between the subjective views of physicians and patients regarding long-term drug taking. Electronic monitoring of compliance represents a valuable method to evaluate the "real time" compliance of the patient. Discussing a compliance recording with a patient may help to identify and solve problems linked with everyday adherence to antihypertensive treatment. Improving compliance is an important task not only for the doctors, but also for all healthcare providers.