The effect of percutaneous oestradiol on atheroma formation in ovariectomized cholesterol-fed rabbits

OBJECTIVE: The aim of this study was to examine the effect of percutaneous oestradiol on the lipid profile and on atheroma formation using an animal model. METHODS: The study was of 12 weeks duration. Fifty sexually mature female New Zealand White rabbits were divided into five groups of equal size. Two groups acted as controls and received normal rabbit chow. Rabbits in one of these groups were ovariectomized. The remaining three groups were ovariectomized but received 1% cholesterol enriched rabbit chow. One of these cholesterol-fed groups received 0.3 mg/kg percutaneous oestradiol daily whilst another received 0.1 mg/kg oral oestradiol daily. Measurements of concentrations of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) were made at the beginning and end of the study. Aortic atheroma formation was measured using computerized image analysis of uptake of Sudan III staining. RESULTS: After 12 weeks there were significant increases in the mean concentrations of TC in the three cholesterol-fed groups compared with controls (P < 0.001). Changes in HDL-C and TG concentrations were less consistent. The mean area of aortic atheroma formation was significantly less in both the percutaneous oestradiol group (4.9%) and the oral oestradiol group (8.6%) compared with the non-oestrogen-treated cholesterol-fed group (19.5%) (P < 0.001, < 0.01 respectively). CONCLUSION: These results suggest that percutaneous oestradiol has a direct protective effect on atheroma formation independent of serum concentrations of total cholesterol.     

Variations in COL15A1 and COL18A1 influence age of onset of primary open angle glaucoma

Primary open angle glaucoma (POAG) is a genetically and phenotypically complex disease that is a leading cause of blindness worldwide. Previously we completed a genome‐wide scan for early‐onset POAG that identified a locus on 9q22 (GLC1J). To identify potential causative variants underlying GLC1J, we used targeted DNA capture followed by high throughput sequencing of individuals from four GLC1J pedigrees, followed by Sanger sequencing to screen candidate variants in additional pedigrees. A mutation likely to cause early‐onset glaucoma was not identified, however COL15A1 variants were found in the youngest affected members of 7 of 15 pedigrees with variable disease onset. In addition, the most common COL15A1 variant, R163H, influenced the age of onset in adult POAG cases. RNA in situ hybridization of mouse eyes shows that Col15a1 is expressed in the multiple ocular structures including ciliary body, astrocytes of the optic nerve and cells in the ganglion cell layer. Sanger sequencing of COL18A1, a related multiplexin collagen, identified a rare variant, A1381T, in members of three additional pedigrees with early‐onset disease. These results suggest genetic variation in COL15A1 and COL18A1 can modify the age of onset of both early and late onset POAG.     

Hemostatic plug formation in normal and von Willebrand pigs: the effect of the administration of cryoprecipitate and a monoclonal antibody to Willebrand factor

Hemostatic plug (HP) formation was investigated in the ear bleeding time incision in normal and von Willebrand pigs. HP volume was calculated by integrating the areas of serial sections. In normal pigs (n = 11), platelets immediately formed a layer on the surface of the cut channel. Platelet aggregates formed at the ends of transected vessels and gradually enlarged. Finally, all transected vessels were occluded by HP and bleeding stopped. In contrast, large HPs were formed in the incision in von Willebrand's disease (vWD) pigs (n = 4); these HPs did not cover the ends of the transected vessels, which continued to bleed, allowing the formation of large hemostatically ineffective platelet aggregates in the incision. Canals traversed these HPs, and bleeding from the open vessels may have continued through them. After infusion of cryoprecipitate into a vWD pig, the bleeding time shortened, and the morphological findings of the HPs were similar to those of normal pigs. In normal pigs (n = 3) infused with an anti- Willebrand factor monoclonal antibody, which prolonged the bleeding time, a large HP formed in the incision, similar to that observed in the vWD pig. The volume of the normal and vWD HPs increased with time. These in vivo findings suggest that Willebrand factor is involved in the localization of the HP to the damaged vessel and may also play a role in platelet-platelet interaction. A computerized morphometric technique was used for measuring the volume of the hemostatic plugs and the distance of sequential points on the perimeter of the HP from the center of selected bleeding vessels.     

Lung cancer: diagnosis and management

Lung cancer is the leading cause of cancer-related death in the United States, with an average five-year survival rate of 15 percent. Smoking remains the predominant risk factor for lung cancer. Lung cancers are categorized as small cell carcinoma or non-small cell carcinoma (e.g., adenocarcinoma, squamous cell carcinoma, large cell carcinoma). These categories are used for treatment decisions and determining prognosis. Signs and symptoms may vary depending on tumor type and extent of metastases. The diagnostic evaluation of patients with suspected lung cancer includes tissue diagnosis; a complete staging work-up, including evaluation of metastases; and a functional patient evaluation. Histologic diagnosis may be obtained with sputum cytology, thoracentesis, accessible lymph node biopsy, bronchoscopy, transthoracic needle aspiration, video-assisted thoracoscopy, or thoracotomy. Initial evaluation for metastatic disease relies on patient history and physical examination, laboratory tests, chest computed tomography, positron emission tomography, and tissue confirmation of mediastinal involvement. Further evaluation for metastases depends on the clinical presentation. Treatment and prognosis are closely tied to the type and stage of the tumor identified. For stages I through IIIA non-small cell carcinoma, surgical resection is preferred. Advanced non-small cell carcinoma is treated with a multimodality approach that may include radiotherapy, chemotherapy, and palliative care. Chemotherapy (combined with radiotherapy for limited disease) is the mainstay of treatment for small cell carcinoma. No major organization recommends screening for early detection of lung cancer, although screening has interested researchers and physicians. Smoking cessation remains the critical component of preventive primary care.     

Do medical procedures in the arm increase the risk of lymphoedema after axillary surgery? A review

Lymphoedema of the arm is a potentially serious consequence of any axillary procedure performed during the management of breast cancer. In an attempt to reduce its incidence and severity, patients are instructed to avoid venepunctures and blood pressure measurements on the treated arm. These precautions are not possible in some patients and attempts to adhere to them can cause discomfort, anxiety and stress for both patients and their health‐care workers. The strength with which these recommendations are made is in contrast to the level of evidence underpinning them. This paper reviews this evidence regarding the safety, or lack thereof, of blood pressure monitoring and intravenous puncture in women who have had axillary surgery. With this evidence generally being anecdotal in nature, there appears to be no rigorous evidence‐based support for the risk‐reduction behaviours of avoiding blood pressure monitoring and venepuncture in the affected arm in the prevention of lymphoedema after axillary procedure. A clinical trial was proposed to investigate whether such avoidance measures were valuable, but failed during its inception. There remains a need for research from prospective trials on this controversial topic to determine the most appropriate patient recommendations that should be provided after axillary procedure regarding the risks for development of lymphoedema.