Different patterns of extracellular matrix protein expression in the convexity and the concavity of the dilated aorta with bicuspid aortic valve: preliminary results

OBJECTIVE: This study aimed to assess extracellular matrix protein expression patterns at the convexity (right anterolateral wall) and the concavity of the dilated ascending aorta in patients with bicuspid aortic valve disease. METHODS: Aortic wall specimens were retrieved from the convexity and the concavity in 27 bicuspid aortic valve patients (12 with stenosis and 15 with regurgitation) and 6 heart donors (controls). Morphometry, immunohistochemistry, Western blot, and polymerase chain reaction were performed, focusing on matrix proteins involved in vascular remodeling. RESULTS: Type I and III collagens were significantly decreased in bicuspid-associated dilated aortas versus controls (P < .001), particularly at the convexity (P < .05 vs concavity). Expression of messenger RNA for collagens was lower than normal only in the regurgitant subgroup. At immunohistochemistry, proteins whose overproduction has been demonstrated in response to abnormal wall stress, such as tenascin and fibronectin, were more expressed in the convexity than in the concavity, especially in the stenosis subgroup. Tenascin, which is produced by smooth muscle cells in the synthetic phenotype, was nearly undetectable in controls. Fewer smooth muscle cells (stenosis, P = .017; regurgitation, P = .008) and more severe elastic fiber fragmentation (P = .029 and P < .001) were observed in the convexity versus the concavity. CONCLUSIONS: In bicuspid-associated aortic dilations, an asymmetric pattern of matrix protein expression was found that was consistent with the asymmetry in wall-stress distribution reported previously. Differences exist between patients with stenosis and those with regurgitation in terms of protein expression and content in the aortic wall. Further studies could clarify the relations between these findings and the pathogenesis of aortic dilatation in bicuspid aortic valve patients.     

Colitis cystica profunda of the rectum: report of a case and review of the literature

Colitis cystica profunda is a rare intestinal lesion. Because of its clinical expression (rectorrhagia, mucorrhea and abdominal pain) and the way it appears to current imaging techniques this disease presents features which can be associated with colon neoplasm. Its diagnosis has to be confirmed histologically, and its etiology remains unclear. The following is a case report of colitis cystica profunda recurring 20 years after a first episode in a white woman, who had had an anterior resection of the sigmoid colon and upper rectum to deal with a colitis cystica profunda-induced stenosis of the sigmoid colon and at 41 underwent the transanal removal of a polypoid lesion. A review of 20 cases in the literature showed that colitis cystica profunda has a predilection for the male and generally affects the medial and lower rectum and the sigmoid colon. The literature also confirmed the association with ulcerative rectocolitis, Crohn's disease and rectal prolapse. The type of treatment varies from surgical, medical, and endoscopic to no treatment at all.     

Future biomarkers for detection of ischemia and risk stratification in acute coronary syndrome

BACKGROUND: Evaluation of patients who present to the hospital with a complaint of chest pain or other signs or symptoms suggestive of acute coronary syndrome (ACS) is time-consuming, expensive, and problematic. Recent investigations have indicated that increases in biomarkers upstream from biomarkers of necrosis (cardiac troponins I and T), such as inflammatory cytokines, cellular adhesion molecules, acute-phase reactants, plaque destabilization and rupture biomarkers, biomarkers of ischemia, and biomarkers of myocardial stretch may provide earlier assessment of overall patient risk and aid in identifying patients with higher risk of an adverse event. APPROACH AND CONTENT: The purpose of this review is to provide an overview of the pathophysiology and clinical and analytical characteristics of several biomarkers that may have potential clinical utility to identify ACS patients. These biomarkers (myeloperoxidase, metalloproteinase-9, soluble CD40 ligand, pregnancy-associated plasma protein A, choline, ischemia-modified albumin, unbound free fatty acids, glycogen phosphorylase isoenzyme BB, and placental growth factor) have demonstrated promise and need to be more thoroughly evaluated for commercial development for implementation into routine clinical and laboratory practice. SUMMARY: Specifications that have been addressed for cardiac troponins and natriuretic peptides will need to be addressed with the same scrutiny for the biomarkers discussed in this review. They include validating analytical imprecision and detection limits, calibrator characterization, assay specificity and standardization, pre-analytical issues, and appropriate reference interval studies. Crossing boundaries from research to clinical application will require replication in multiple settings and experimental evidence supporting a pathophysiologic role and, ideally, interventional trials demonstrating that monitoring single or multiple biomarkers improves outcomes.     

Abnormalities of cardiovascular neural control and reduced orthostatic tolerance in patients with primary fibromyalgia

OBJECTIVE: Fibromyalgia (FM) is a syndrome characterized by widespread musculoskeletal pain. Symptoms of orthostatic intolerance may also be present, suggesting underlying abnormalities of cardiovascular neural regulation. We tested the hypothesis that FM is characterized by sympathetic overactivity and alterations in cardiovascular autonomic response to gravitational stimulus. METHODS: Sixteen patients with primary FM and 16 healthy controls underwent electrocardiography examination, finger blood pressure, respiration, and muscle sympathetic nerve activity (MSNA) recordings at rest and during stepwise tilt test, up to 75 degrees . The autonomic profile was assessed by MSNA, plasma catecholamine, and spectral indices of cardiac sympathetic (LFRR in normalized units, NU) and vagal (HFRR both in absolute and NU) modulation and of sympathetic vasomotor control (LFSAP) computed by spectrum analysis of RR and systolic arterial pressure (SAP) variability. Arterial baroreflex function was evaluated by the SAP/RR spontaneous-sequences technique, the index a, and the gain of MSNA/diastolic pressure relationship during stepwise tilt test. RESULTS: At rest, patients showed higher values of heart rate, MSNA, LFRR NU, LF/HF, LFSAP, and reduced HFRR than controls. During tilt test, lack of increase of MSNA, less decrease of HFRR, and excessive rate (44%) of syncope were found in patients, suggesting reduced capability to enhance the sympathetic activity to vessels and withdraw the vagal modulation to sino-atrial node. Baroreflex function was similar in both groups. CONCLUSION: Patients with FM have an overall enhancement of cardiovascular sympathetic activity while recumbent. Lack of increased sympathetic discharge to vessels and decreased cardiac vagal activity characterize their autonomic profile during tilt test, and might account for the excessive rate of syncope.     

Insulin resistance causes impaired vasodilation and hypofibrinolysis in young women with polycystic ovary syndrome

INTRODUCTION: Insulin resistance, a novel cardiovascular risk factor, is often associated with increased plasminogen activator inhibitor-1 levels and impaired vasodilation. Insulin infusion in the forearm induces plasminogen activator inhibitor-1 and tissue plasminogen activator expression and endothelium-dependent vasodilation in normal subjects. The present study explores the relationship between insulin-induced vasodilatory and fibrinolytic properties of the endothelium in women with polycystic ovary syndrome, frequently affected by insulin resistance and early atherosclerosis. MATERIALS AND METHODS: Metabolic, hormonal and fibrinolytic parameters were evaluated in 64 patients with polycystic ovary syndrome (19 insulin-resistant and 45 insulin-sensitive) and in 25 controls. In 16 women with polycystic ovary syndrome, 8 insulin-resistant and 8 insulin-sensitive, blood flow, plasminogen activator inhibitor-1 and tissue plasminogen activator expression were evaluated during insulin infusion into the forearm. RESULTS: Elevated basal plasminogen activator inhibitor-1 levels were found in women with polycystic ovary syndrome, correlating directly with insulin levels. Plasminogen activator inhibitor-1 expression increased during insulin infusion in all women with polycystic ovary syndrome, but was delayed and sustained in insulin-resistant patients (p<0.01). Vasodilatory response to insulin was blunted (p<0.01) and tissue plasminogen activator expression abolished in insulin-resistant patients (p<0.01). CONCLUSION: Our study demonstrates that women with polycystic ovary syndrome and insulin resistance show a blunted endothelial-dependent vasodilation. The impaired endothelial release of tissue-plasminogen activator and the sustained plasminogen activator inhibitor-1 release during insulin infusion suggest a hypofibrinolytic state in PCOS patients with insulin resistance. This hemodynamic and fibrinolytic derangement may contribute to the pathogenesis of early atherosclerosis in insulin resistance.     

Leveling of prostate cancer mortality in Western Europe

BACKGROUND: Mortality from prostate cancer (CaP) has increased throughout Europe until the early 1990s. Trends in 24 European countries, the European Union (EU), six selected Central and Eastern European countries, and the Russian Federation have been updated to 1999. METHODS: Cancer death certification data for CaP were abstracted from the World Health Organization database. RESULTS: In the EU, the peak rate (15.7/100,000) was reached in 1993, followed by a leveling off and a decline to 14.1/100,000 in 1999. Age-standardized analysis for each subsequent age group of men aged 50 or over showed larger absolute falls in the elderly. CaP rates were lower in Central and Eastern European countries providing data, but showed a rise from 9.7/100,000 in 1980 to 11.3 in 1996, and leveled off thereafter. Rates were originally lower, but the rises larger in the Russian Federation (from 5.1/100,000 in 1980 to 8.1/100,000 in 1999). In the late 1990s, there was a threefold difference between the highest rates of 22/100,000 in Norway and those of 7.7 in Russia or 7.3 in Ukraine. Such a difference was, however, restricted to the elderly, since at age 35-64 the Russian rate (6.7/100,000) was the same as that of Norway, and only Greece and Italy had appreciably lower rates. CONCLUSION: The pattern of trends in CaP rates observed across Europe is consistent with a favorable role of improved diagnosis, but mainly of advancements of therapy (including more widespread adoption of radical prostatectomy and androgen blockage) on CaP mortality in Western Europe.     

Body weight, diet and water intake in preventing stone disease

Nutrition plays a major role in the pathogenesis of the most widespread forms of nephrolithiasis, i.e. calcium (calcium oxalate and phosphate) and uric acid stone disease. For this reason, dietary measures are the first level of intervention in primary prevention, as well as in secondary prevention of recurrences. An unbalanced diet or particular sensitivity to various foods in stone formers can lead to urinary alterations such as hypercalciuria, hyperoxaluria, hyperuricosuria, hypocitraturia and an excessively acid urinary pH. Over the course of time, these conditions contribute to the formation or recurrence of kidney stones, due to the effect they exert on the lithogenous salt profile. The fundamental aspects of the nutritional approach to the treatment of idiopathic nephrolithiasis are body weight, diet and water intake. This paper will present data resulting from our own investigations and the most significant evidence in literature.     

The sensitive innervation of the ostrich nasal mucosa

The sensitive innervation of the ostrich's nasal mucosa, through impregnative gold chloride methods, was investigated. The autonomy innervation, constituted by ganglion cells placed along the course of nerve trunks was particularly represented in the respiratory tract of the nasal cavity. The somatic nerve component, composed by free and capsulated endings, was especially distributed in the vestibular district. The nerve corpuscles were morphologically classified as Pacini, Pacini-like, Golgi-Mazzoni and Herbst. Further investigations must be expected to attribute an effective functional role particularly to this last nerve component.