Regression of advanced atherosclerosis in swine: chemical studies

Advanced complicated atherosclerosis was produced in the abdominal aortas of swine by a combination of mechanical injury and of a four-month high-cholesterol, high-fat diet. After discontinuation of the atherogenic diet, the animals were given swine mash for 14 months; subsequent chemical studies showed that regression of lesions had occurred, as delineated by decreased levels of DNA and DNA synthesis, total and esterified cholesterol, and phospholipid but no change in the levels of free cholesterol and triglycerides. The rate of DNA synthesis, but not that of total protein synthesis, had decreased. Collagen content had increased. By all criteria studied, the regressed lesions did not differ greatly from the abdominal aortic tissue of animals that had received only a mash diet for 18 months after mechanical injury. These findings, if extrapolated to man, would make the prognosis for possible regression of atherosclerosis under strictly controlled dietary regimens excellent.     

Regression of advanced atherosclerosis in swine

Advanced complicated atherosclerosis was produced in the abdominal aorta of swine by a combination of mechanical injury and high-cholesterol, high-fat diet for four months. After removal of the high-cholesterol diet and placing the animal on swine mash for 14 months, there was a significant (P less than .005) decrease in size of lesions with remodeling of the intima toward a smooth surface. Sudanophilia had virtually disappeared and atheromas were almost absent in the regression group, as were thrombosis and hemorrhage in plaques. Cell proliferation, as judged by the number of labeled cells in autoradiography, was less pronounced in this group. There was no decrease in the numbers of segments showing calcification; however, the size of the calcified areas was smaller in the regression group than in the base line. The data suggest that advanced atherosclerosis is susceptible to regression on removal of the atherosclerotic stimulus.     

Cholesterol & atherosclerosis: a controversy resolved

We should regard the so-called cholesterol "controversy" as resolved. Elevated cholesterol levels cause coronary disease and probably are an essential ingredient for the development of atherosclerosis. Elevated cholesterol levels should be a cause for concern. From a public health point of view, the ultimate treatment of atherosclerosis will depend on major changes in the lifestyles of populations in developed countries, including a shift to diets that are largely vegetarian, as well as the elimination of tobacco use, an increase in regular exercise, and a reduction in the propensity of to increase weight, particularly with age. For patients at high risk for coronary events, including those with other coronary risk factors and with clinically established coronary disease, cholesterol lowering is absolutely essential. In the majority of cases, it will require not only dietary change but also cholesterol-lowering medication. Taken together, these public health and medical measures can massively reduce, if not eliminate, the burden of atherosclerosis that currently plaques developed countries and now threatens the developing world.     

Homocysteine: a new risk factor for atherosclerosis

The accumulating evidence for the role of homocysteine as a risk factor for atherosclerosis is persuasive. A high plasma homocysteine concentration induces pathologic changes in the arterial wall and thus is strongly associated with an increased risk of atherosclerosis, manifested as cardiovascular, cerebrovascular and peripheral vascular events. Studies are being conducted to determine whether lowering homocysteine levels prevents occlusive events. At present, testing for elevated homocysteine concentrations should be considered in patients with premature atherosclerosis or a strong family history of atherosclerosis, since hyperhomocysteinemia is a common risk factor in these patients. Treatment of hyperhomocysteinemia is straightforward and associated with minimal risk. This disorder is usually correctable with vitamin supplements containing folic acid.     

Watanabe rabbits with heritable hypercholesterolaemia: a model of atherosclerosis

Many factors play important roles in the development of atherosclerotic lesions. The leading risk factor for atherosclerosis is familial hypercholesterolaemia (FH). FH is a genetic disease characterized by a deficiency of receptors for low density lipoprotein (LDL) on the plasmalemma of endothelial cells, a high level of serum LDL, and early development of atherosclerosis and skin xanthoma. Watanabe and colleagues have developed a line of rabbits with unprovoked hypercholesterolaemia, increased blood level of LDL, pronounced atherosclerosis and skin xanthoma. These Watanabe Heritable Hyperlipidaemic (WHHL) rabbits possess an inheritable mutation of one gene, similar to that in human FH. The morphogenesis of atherosclerosis in patients with FH is characterized by multifocal deposit of lipids in the stromal cells of thymus, spleen, skin, interstitial and parenchymatous cells of kidneys and the presence of some single foam cells in aorta. The manifestation of atherosclerotic lesions in WHHL rabbits increases progressively with age but the presence of atherosclerotic lesions in newborn WHHL rabbits suggest that the process may commence in utero. Moreover, the main mass of plasma cholesterol in WHHL rabbits is first found in LDL and to a lesser degree in lipoproteins of intermediate density. This is contrary to diet-induced atherosclerosis in rabbits where the main mass of serum cholesterol is found in very low density beta-lipoproteins. Thus the distribution of cholesterol among lipoprotein fractions differs from that in WHHL rabbits. Atherosclerotic damage of arteries in WHHL rabbits goes through several stages. During the progression of intimal damage, lipid and foam cell deposits are found in the internal surface together with developing plaques and increased content of lipids in the tunica media. Calcification often follows this process. The main factors initiating atherosclerosis in WHHL rabbits are adhesion of leukocytes and platelets to endothelial cells and the accumulation of lipids in the aortic wall. The deposits of lipids in macrophages and intimal smooth muscle cells in WHHL rabbits occurs mostly at the expense of cytoplasmic neutral lipid particles with some accumulation in lysosomes. Hypertension as a risk factor increases the area of atherosclerotic damage in all arterial vessels in WHHL rabbits, particularly in the thoracic and abdominal aorta. Morphogenesis of the development of atherosclerosis in WHHL and diet-induced atherosclerosis in rabbits was similar, but differs from rats with heritable hypercholesterolaemia. Damage or loss of endothelial cells can predispose the atherosclerotic vessels to vasospasm and can leave vessels unprotected against vasoconstrictor stimuli. The development of the WHHL model has not only given insight into the mechanisms of development of familial hypercholesterolaemia but has also provided a model for assessing various therapeutic approaches for the prevention and treatment of atherosclerosis.     

Myocarditis: a review

BACKGROUND AND OBJECTIVES: Although pediatric sedation (PS) is widely used in emergency departments (ED), the practice of PS in general community hospital (GH) ED has not been described. We surveyed PS practice patterns in pediatric hospitals (CH) and GH and compared frequency and usage between the two groups. METHODS: All CH (n = 115) and 400 randomly selected GH were surveyed. Alcohol and drug detoxification, psychiatric, chronic care, rehabilitation, and specialty facilities were excluded. Data were collected on hospital type (pediatric or community), location (urban, suburban, rural), annual visits, academic affiliation (presence of an emergency medicine residency or pediatric emergency medicine fellowship in the hospital), and sedation agents used. RESULTS: Of 515 hospitals surveyed, 238 responded [84/115 CH (73%), 154/400 GH (39%)] yielding an overall response rate of 46%. Of the responding CH the majority were urban [57 (68%) were urban, 15 (18%) suburban, and 12 (14%) rural]. GH were more evenly distributed by location [44/153 (29%) were urban, 49/153 (32%) suburban, and 60/153 (39%) rural]. Eight (5%) GH had emergency medicine residencies, while 39 (46%) CH had pediatric emergency medicine fellowships. The mean annual pediatric volume was 38,000 for CH and 6500 for GH. For the four specified clinical scenarios, representing the most common ED procedures using sedation (laceration repair, fracture reduction, radiologic imaging), GH performed significantly fewer sedations than CH when matched for pediatric volume. PS was less frequently used among rural GH compared to suburban (P < 0.01) and urban GH (P < 0.01). Midazolam was listed as the most frequently used drug in all three geographic locations for both CH and GH. CH listed fentanyl as a second agent, while GH preferred meperidine. Fentanyl and ketamine were listed as preferred agents only in CH. For cranial computerized tomography, chloral hydrate was listed as the drug of choice by both CH and GH. Both CH and GH listed "relief of pain and anxiety" as the first and "agitation control" as the second most common reason for using sedation. CH and GH listed "the risks outweigh the benefits" as the primary reason and "ED too busy/takes too much time" as the secondary reason for not using sedation. CONCLUSIONS: GH performed fewer sedations than did CH when matched for pediatric volume in all geographic locations and for the most common ED procedures using sedation. Since 1989, sedation patterns have shifted in CH to include the short-acting agents, while GH (with the exception of midazolam) continue to prefer the long-acting agents. Midazolam is now the most frequently used sedation agent for ED procedures in both CH and GH.     

Hysteroscopy: a review

3 chemicals were selected for mutagenicity testing from a priority list, based on production volume and available mutagenicity data. Propargyl alcohol (PA), 2-nitroaniline (2NA), and 5-methyl-1H-benzo-triazole (MBT) were selected for testing using the approach recommended in the Health Protection Branch Genotoxicity Guidelines. The battery of tests included the Salmonella/mammalian microsome mutation assay, the in vitro chromosomal aberration assay, and the bone-marrow micronucleus assay. The results indicate that 2 of the 3 chemicals, PA and 2NA, were clastogenic in vitro. Both PA and 2NA induced chromosomal aberrations in CHO cells in vitro with and without metabolic activation, while none induced reverse mutations detectable with the Salmonella/mammalian microsome assay. Because PA and 2NA were found to be in vitro clastogens, they also were tested in the mouse bone-marrow micronucleus assay. 2NA induced a small increase in micronuclei in males but not females. PA did not induce an increase in micronuclei.     

Teleradiology: a review

The Biographical Personality Interview (BPI) was applied to 179 subjects (158 psychiatric patients and 21 probands from the general population); 100 patients and 20 healthy controls served as a validation sample; the others had been interviewed during the training period or did not meet the inclusion criteria for the validation of the BPI. The acceptance of the interview was high, the inter-rater reliability of the ratings of premorbid personality structures ("types") varied between 0.81 and 0.88 per type. Concurrent validity of the typological constructs as assessed by means of the BPI was inferred from the intercorrelations of type scores and correlations of these scores with questionnaire data and proved to be adequate. Clinical validity of the assessment was indicated by statistically significant differences between diagnostic groups. Problems and further developments of the instrument and its application are discussed.     

Lipoprotein(a): a link between thrombosis and atherosclerosis?

Lipoprotein(a) (Lp(a)) represents a class of plasma lipoproteins similar to low-density lipoprotein (LDL), but containing an unique apolipoprotein(a) with striking homology to plasminogen. Plasma Lp(a) is inherited as a quantitative genetic trait, with a continuous distribution in Caucasian populations (< 10-2000 mg/l), where high levels are associated with an increased risk of atherosclerotic disease. The physiological role of Lp(a) is unknown, and the metabolism is obscure. Plasma Lp(a) is apparently resistent to diets and drug therapy, and LDL-apheresis is currently the most effective way of reducing plasma Lp(a). However, clinical benefits of lowering plasma Lp(a) have not been demonstrated, and specific therapeutic goals cannot be recommended at present. The structural similarity between apo(a) and plasminogen has generated several experimental observations indicating a prothombogenic and proatherogenic role of Lp(a), but the exact pathophysiological mechanisms have not been determined.     

Moxonidine: a review

Moxonidine is an imidazoline compound which acts on I1 imidazoline 'receptors' in the central nervous system to reduce blood pressure. This novel mechanism of action is claimed to lead to fewer adverse effects than the older centrally-acting agents such as clonidine. In this review we examine the drug's pharmacology, clinical pharmacokinetics, efficacy as an antihypertensive agent including comparative studies with pre-existing drugs, and adverse effect profile. With a growing number of effective antihypertensive agents already available to the clinician, it is not yet clear whether moxonidine represents a significant advance in hypertension management.     

Noma: a review

Cancrum oris or noma is a condition not well known in western Europe and North America. It is, however, a relatively common cause of mortality and disability in children of undeveloped areas of Africa, Asia, and South America. This paper describes the experience at Galmi Hospital, in the sub-Saharan region of South Africa in the Niger Republic, with 50 operative patients out of a group of 300 who were referred. An extensive review of the literature is presented describing the epidemiological impact of the disease, the characteristics of the lesions, the pathogenesis, symptoms, sequelae, differential diagnosis, and preoperative preparation. Additionally, we review approaches to anesthesia, methods of reconstruction, and the most common causes of complications and mortality. Numerous photographs illustrating the devastating consequences of this problem are presented.     

Regression to the Mean: More than a Statistic.

This article looks at Galton's regression to the mean (R to M) from several traditionally unrelated but interwoven venues: (1) as a law of trait heredity; (2) as a statistical artifact infiltrating careless research designs; (3) as an illustration of cognitive bias. Hereditarians argue for the first of these, disputed by biogeneticists, who view R to M as a mere correlate of generational traits (e.g., IQ) decline. Research designers busy themselves with the second perspective, but to explain the concept, cavalierly adduce various organismic states that sum as "error variance" Research on subjective probability finds R to M in unexpected places. Across these contexts, the weight of argument falls on R to M's confounding rather than causal role in vexing data analysis. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Homocysteine, a risk factor of atherosclerosis

Homocysteine is a sulphurated amino acid which, at high plasma concentrations, predisposes to thrombosis and induces focal arteriosclerosis. These characteristics have been established both in patients with homocystinuria, a genetic disease in which homocysteine accumulates in the blood, and in animals submitted to intravenous infusions of this amino acid. Many recent publications have addressed the problem of whether mild increases in plasma homocysteine predisposed to the development of the usual forms of atherosclerosis. Transverse epidemiological studies have established a correlation between homocysteine levels and atherosclerosis at all its vascular localisations, coronary, carotid and lower limb. Multivariate analysis in several prospective studies have shown plasma homocysteine to be an independent risk factor for cerebrovascular accidents and myocardial infarction. Causes of mild increases in plasma homocysteine are usually dietetic deficiencies in folic acid, vitamin B6 or B12, or genetic by mutation of the methylene-tetrahydrofolate reductase. Renal failure is also associated with a high risk in plasma homocysteine levels. However, the toxicity of homocysteine to the arterial wall at slightly elevated concentration remains speculative.     

Pharmacology of diminazene: a review

Chemotherapy for trypanosomiasis in domestic livestock depends on only a few compounds, of which several are chemically closely related. Of these compounds, the most widely used therapeutic agent in cattle, sheep and goats is diminazene aceturate. Diminazene was first described in 1955. Subsequently, a substantial body of data has been generated on various pharmacological aspects of the compound. In this review, we consider the current status of knowledge concerning the therapeutic spectrum of diminazene, resistance to diminazene in trypanosomes, and combination therapeutic regimens in which diminazene has been administered together with other compounds. Analytical techniques for diminazene, the pharmacokinetics of diminazene, data concerning diminazene's toxicity, and the different molecular mechanisms by which diminazene may exhibit trypanocidal action are also considered.     

Viruses and atherosclerosis: do they play a pathogenic role?

PURPOSE: To evaluate the results of interstitial radiotherapy of anorectal tumors. PATIENTS AND METHODS: From 1972 to 1993, one of the authors treated 45 patients by an interstitial implant for anorectal tumors. Of these, 33 patients suffered from primary tumors, 19 from squamous carcinoma, 2 from basaloid carcinoma of the anus and the other 12 from primary adenocarcinoma of the rectum. Of 12 patients treated for local recurrence, 10 had adenocarcinoma and 2 squamous cell carcinoma. Of the 33 patients with primary tumors, 27 received a course of external-beam radiotherapy before the implant. The median follow-up was 35 months. RESULTS: Local response depended on the tumor volume treated. All 21 anal tumors showed complete response, 5 patients developed local recurrence and 4 distant metastases: 3 died from their disease. Of 12 rectal adenocarcinomas, 9 responded completely, 4 patients developed local recurrence and 4 distant metastases; 6 died from active disease. In the last group of 12 patients who were treated for recurrent tumors, 7 responded completely. One patient developed local recurrence and 9 distant metastases, only 4 are alive. CONCLUSIONS: A combination of external-beam and interstitial radiotherapy is a relatively simple, non-mutilating, but well-tolerated and very effective method of treatment for early carcinoma of the lower rectum and anus.     

Thyroid cancer: a review

Thyroid cancer is a rare and complex disease. The thyroid contains various cell types from which distinct diseases arise. These malignancies range from indolent to extremely aggressive. Diagnosis includes attention to risk factors, family history, and subjective reports. The most valuable tool for diagnosis is the fine-needle aspiration. Primary treatment is surgery with postoperative hormone therapy. Radiation and chemotherapy serve palliative and adjuvant roles in advanced, recurrent, or metastatic disease. Nurses make a significant contribution to patient understanding and successful treatment outcome.     

Mastoiditis: a case-based review

The ultrasound (US) scans of eleven patients with histologically proven xanthogranulomatous cholecystitis have been reviewed. The thickness of the gallbladder (GB) wall, echogenicity of the thickened GB wall, the presence of intramural nodules, gallstones, pericholecystic fluid, loss of wall definition with the liver, and intrahepatic ductal dilatation were specifically assessed by two radiologists. The range of thickness of the GB wall was 3-20mm (mean, 11.2 mm). Thickening was diffuse in nine cases and focal in two. The thickened GB wall, excluding intramural nodules, was echogenic in seven, isoechoic in three and hypoechoic in one, compared with hepatic echogenicity. Intramural nodules were found in eight cases. These were discrete, oval or flat, and of low echogenicity. These ranged in size from 6 to 12 mm (mean, 10.5 mm). Gallstones were present in six cases and there was intrahepatic duct dilatation in two of these. Definition between the liver and the GB was obliterated in seven cases. One case of GB perforation, confirmed at operation, demonstrated pre-operatively a GB wall defect and connection with the surrounding pericholecystic fluid. Pericholecystic fluid was absent in the other 10 cases. Xanthogranulomatous cholecystitis presents ultrasonically as GB wall thickening, and the majority of cases in this series also demonstrated intramural hypoechoic nodules. These findings can be helpful in the diagnosis of xanthogranulomatous cholecystitis.