Aspirin resistance: possible roles of cardiovascular risk factors, previous disease history, concomitant medications and haemorrheological variables

BACKGROUND AND OBJECTIVE: Recent studies have described the incidence (approximately one in eight high-risk patients will experience a further atherothrombotic event over a 2-year period) of aspirin (acetylsalicylic acid) resistance and its possible background. The aim of this study was to compare the characteristics (risk profile, previous diseases, medications and haemorrheological variables) of patients in whom aspirin provided effective platelet inhibition with those in whom aspirin was not effective in providing platelet inhibition. METHODS: 599 patients with chronic cardio- and cerebrovascular diseases (355 men, mean age 64 +/- 11 years; 244 women, mean age 63 +/- 10 years) taking aspirin 100-325 mg/day were included in the study. Blood was collected between 8:00am and 9:00am from these patients after an overnight fast. The cardiovascular risk profiles, history of previous diseases, medication history and haemorrheological parameters of patients who responded to aspirin and those who did not were compared. Platelet and red blood cell (RBC) aggregation were measured by aggregometry, haematocrit by a microhaematocrit centrifuge, and plasma fibrinogen by Clauss' method. Plasma and whole blood viscosities were measured using a capillary viscosimeter. RESULTS: Compared with aspirin-resistant patients, patients who demonstrated effective aspirin inhibition had a significantly lower plasma fibrinogen level (3.3 g/L vs 3.8 g/L; p < 0.05) and significantly lower RBC aggregation values (24.3 vs 28.2; p < 0.01). In addition, significantly more patients with effective aspirin inhibition were hypertensive (80% vs 62%; p < 0.05). Patients who had effective platelet aggregation were significantly more likely to be taking beta-adrenoceptor antagonists (75% vs 55%; p < 0.05) and ACE inhibitors (70% vs 50%; p < 0.05), whereas patients with ineffective platelet aggregation were significantly more likely to be taking HMG-CoA reductase inhibitors (statins) [52% vs 38%; p < 0.05]. Use of statins remained an independent predictor of aspirin resistance even after adjustment for risk factors and medication use (odds ratio 5.92; 95% CI 1.83, 16.9; p < 0.001). CONCLUSIONS: The mechanisms underlying aspirin resistance are multifactorial. Higher fibrinogen concentrations increase RBC aggregation and can also result in increased platelet aggregation. The higher rate of hypertension in patients with effective platelet aggregation on aspirin could explain the differences in beta-adrenoceptor antagonist and ACE inhibitor use between these patients and aspirin-resistant patients. Furthermore, an additive effect of these drugs may contribute to effective antiplatelet therapy. It is also possible that drug interactions with statins might reduce aspirin bioavailability and/or activity, thereby reducing platelet inhibition in aspirin-resistant patients.     

The use of the distal Syme's procedure for treating onychopathy

There are many procedures available to the podiatric surgeon to deal with a painful, deformed nail. The Syme's procedure should not be overlooked, though more conservative options should be attempted before this procedure. With the proper surgical candidate (ie, intact neurovascular status), this is a successful, safe procedure easy to perform under local anesthesia.     

Vitamin D receptor gene polymorphism in hypercalciuric children

Idiopathic hypercalciuria is a complex disease resulting from an interaction between environmental and genetic factors. Recently, the relationship between vitamin D receptor (VDR) alleles and calcium homeostasis has been investigated. This study was conducted to explore the association of VDR gene polymorphism with the risk of absorptive hypercalciuria (AH). We investigated the VDR gene polymorphisms, ApaI, BsmI, and TaqI, in relation to intact parathormone (PTH), osteocalcin, and 25-hydroxyvitamin D in 80 children (42 males, 38 girls) with AH and in 86 healthy children without hypercalciuria. A significant difference in the ApaI genotype was observed between the AH group and the control group (²=7.21, P=0.027). The AA genotype was associated with a 3.5-fold increased risk for idiopathic hypercalciuria compared with the Aa/aa genotype (odds ratio 3.5, 95% confidence interval 1.1–11). The BsmI and TaqI polymorphisms did not show any significant association with AH. Serum osteocalcin levels were significantly higher in the group with the AA genotype compared with those with the Aa or aa genotype (P=0.02, P=0.05, respectively). The results indicate that the ApaI AA genotype of the VDR gene is not only associated with AH but is also related to differences in serum osteocalcin.     

Taking a different path: menstrual preparation for adolescent girls living apart from their mothers

Menarche is a significant yet anxiety producing event. Preparation for menarche combats this anxiety. When adolescent girls reach menarche they often seek information about menstruation from their mothers. Yet not every girl lives with her mother. The purpose of my grounded theory study is to explore the menarcheal experience of 16 girls living without their mothers. The findings indicate that prior to menarche participants experienced similarities to girls who lived with their mothers. Differences became apparent at menarche when participants had to wait for an available female to answer questions, did not have a female available to ask, or felt embarrassed discussing menstruation with their fathers. Providers need to be sensitive to menarcheal preparation issues for girls living without their mothers.     

Assessment of PCB Congener Analytical Methods: Do They Meet Risk Assessment Needs?

Congener-specific PCB analysis allows use of toxic equivalency (TEQ) TCDD-based risk assessment approaches when analytical methods are sufficiently sensitive. Many efforts to analyze fish samples for PCB congeners report the majority of samples as non-detects; these data are of little use for human health risk assessment if the limits of analytical detection exceed levels of potential health concern. However, increasing analytical sensitivity is costly and technically difficult. An approach to assess analytical sensitivity needs for risk assessment by defining toxicological endpoints of concern and acceptable risk levels is presented. This framework was applied to assessment of potential PCB TEQ cancer risks to the general United States population and tribal consumers of Columbia River fish, but may be easily adjusted for other situations. A probabilistic model was used to calculate the necessary analytical sensitivity for PCB TEQ cancer risk assessment using the Environmental Protection Agency's new draft cancer risk slope factor for TCDD and fish consumption data. Desired levels of analytical sensitivity were estimated for the congener expected to contribute the most to PCB TEQ, PCB 126, and compared to limits of detection for various analytical methods. The financial and health value of methods with different levels of analytical sensitivity were compared using a value of information approach, which includes analytical cost and cost of potential health outcomes, and a proposed risk assessment utility approach which considers the relative health protectiveness of analytical options non-monetarily. Sensitivity analyses indicate that average consumption rate, cancer risk slope factor choice, and knowledge of existing PCB contamination are important considerations for planning PCB congener analysis. Received: 17 January 2002/Accepted: 29 July 2002     

Pathology of pituitary tumors

Pituitary adenomas are benign neoplasms originating in adenohypophysial cells. They represent the most common neoplasm of the sellar region, comprising approximately 15% of all primary intracranial tumors. Depending on the studies of unselected adult autopsy material, their frequency as an incidental finding varies between 5% and 20%. The first part of this article summarizes the immunohistochemistry of nontumorous human adenohypophysis. In the second part, the classification of pituitary tumors is discussed, followed by the immunohistochemical and electron microscopic findings of pituitary adenomas and pituitary carcinomas.     

Juxtaposition of an ectopic corticotroph adenoma of the sphenoid sinus with orthotopic intrasellar corticotroph hyperplasia in a patient with Cushing disease. Case report

Ectopic pituitary adenomas (EPAs) are rare and their association with orthotopic corticotroph hyperplasia has not been published. The case of a 30-year-old woman with clinical and biochemical evidence of Cushing disease (CD) is reported. A magnetic resonance image obtained preoperatively revealed asymmetrical inhomogeneity of the pituitary gland, which was suggestive of localized adenoma. It also showed what was thought to be a small sphenoid polyp. Postoperatively the latter lesion was found to be an ectopic corticotroph adenoma. The pituitary gland, which was free from any tumor, exhibited diffuse unilateral corticotroph hyperplasia. Clinical, radiological, laboratory, and histopathological findings are presented. A review of the literature and a discussion of possible causes of this unique association between the ectopic corticotroph adenoma and the pituitary hyperplasia are provided.