Medical Report


ARTERIOSCLEROSIS, a generic term for thickening and hardening of the arterial wall, is responsible for the majority of deaths in the United States and most westernized societies. One type of arteriosclerosis is atherosclerosis, the disorder of the large arteries that underlies most coronary artery disease, aortic aneurysm, and arterial disease of the lower extremities and also plays a major role in cerebrovascular disease. Atherosclerosis is by far the leading cause of death in the United States, both above and below age 65 and in both sexes.

In order to understand the pathogenesis of atherosclerosis, it would be better for us to overview the structure of the normal artery.

A. STRUCTURE The normal artery wall consists of three layers : the intima, the media, and the adventitia.
Intima: A single continuous layer of endothelial cells lines the lumen of all arteries. The intima is delimited on its outer aspect by a perforated tube of elastic tissue, the internal elastic lamina. This tube of elastic tissue is particularly prominent in the large elastic arteries and the medium-caliber muscular arteries, and it disappears in capillaries. The endothelia cells are attached to one another by a series of junctional complexes and are also attached, apparently somewhat tenuously, to an underlying mesh work of loose connective tissue, the basal lamina. These lining endothelial cells normally form a barrier that controls the entry of substances from the blood into the artery wall.
Media: The media consists of only one cell type, the smooth muscle cell, arranged in either a single layer or multiple lamellae. These cells are surrounded by small amounts of collagen and elastic fibers, which they elaborate, and usually take the pattern of diagonal concentric spirals through the vessel wall. The smooth-muscle cell appears to be the major connective tissue-forming cell of the artery wall, producing collagen, elastic fibers, and proteoglycans. In this sense it is analogous to the fibroblast in skin, the osteoblast in bone, and chondroblast in cartilage. The media is bounded on the luminal side by the internal elastic lamina and on the abluminal side by a less continuous sheet of elastic tissue, the external elastic lamina and on the abluminal side by a less continuous sheet of elastic tissue, the external elastic lamina.
Adventitia: The outermost layer of the artery is the adventitia, which is delimited on the luminal aspect by the external elastic lamina. This external coat consists of a loose interwoven admixture of collagen bundles, elastic fibers, smooth-muscle cells, and fibroblasts. This layer also contains the vasa vasorum and nerves.

ATHEROSCLEROSIS, involves primarily the intimal layer and occurs most commonly in the abdominal aorta and its large renal and lower extremity branches, the coronary arteries, and the cerebral vasculature. The lesions on the arterial wall are commonly classified as 1.early lesions (initial lesions and fatty streaks), 2.intermediate lesions, 3.fibrous plaques, and 4. complicated lesions.
1& 2. Initial (fatty streak) and intermediate lesions are focal, small and non obstructive. Initial lesions may be detectable only chemically or microscopically, consist of lipid deposition in intimal macrophages (macrophage foam cells), and represent the first changes that have been found to evolve into lesions associated with clinical disease. Fatty streaks are visible to the naked eye on the endothelial surface of the aorta and coronary arteries as yellowish or whitish patches, streaks, or dots on the intimal surface. They are still small and non obstructive and contain a large accumulation of lipid filled smooth muscle cells and macrophages (foam cells) and fibrous tissue in focal areas of the intima. The lipid is mainly cholesterol oleate and is mainly intracellular.
3. Fibrous plaques are palpably elevated areas of the intimal thickening and represent the most characteristic lesion of advancing atherosclerosis. These atheromatous lesions first appear in the abdominal aorta, coronary arteries, and carotid arteries in the third decade and increase progressively with age. Typically, the fibrous plaque is firm, elevated, and dome-shaped, with an opaque glistering surface that bulges into the lumen. It consists of a central core of extracellular lipid (with cholesterol crystals) and necrotic cell debris covered by a fibromuscular layer or cap containing large numbers of smooth muscle cells, macrophages, and collagen. Thus the plaque is much thicker than is normal intima. Although the lipid, like that of fatty streaks, is mainly cholesterol ester, the principal esterified fatty acid is linoleic rather than oleic, reflecting its largely extracellular distribution. Thus plaque cholesterol ester composition differs from fatty streaks but resembles plasma lipoproteins.
4. The complicated lesion is a calcified fibrous plaque containing various degrees of necrosis, thrombosis, and ulceration. These are the lesions frequently associated with symptoms. With increasing necrosis the arterial wall progressively weakens, and rupture of the intima can occur, causing aneurysm and hemorrhage. Arterial emboli can form when fragments of plaque dislodge into the lumen. Stenosis and impaired organ function result from gradual occlusion as plaques thicken and thrombi form.

A generally accepted theory for the pathogenesis of atherosclerosis consistent with a variety of experimental evidence is the reaction to injury hypothesis. According to this idea, the endothelial cells lining the intima are exposed to repeated or continuing insults to their integrity. The injury to the endothelium may be subtle or gross, resulting in a loss of the ability of the cells to function normally and act as a permeability barrier. In the extreme, the cells may desquamate. Examples of types of injury to the endothelium include metabolic injury, as in chronic hypercholesterolemia or homocysteinemia, mechanical stress associated with hypertension, and immunologic injury, as may be seen after cardiac or renal transplantation. Dysfunctional endothelial cells at susceptible sites in the arterial tree would lead to exposure of the subendothelial tissue to increased concentrations of plasma constituents. This may trigger a sequence of events including monocyte and platelet adherence, migration of monocytes into the intima to become macrophages, platelet aggregation and formation of microthrombi, and release of platelet and macrophage secretory products including growth factors and cytokines (such as platelet derived growth factor, interleukin 1, colony stimulating factors), in conjunction with plasma constituents, including lipoproteins and hormones such as insulin. This could stimulate the proliferation of intimal smooth muscle cells at these sites of injury. These proliferating smooth muscle cells would deposit a connective tissue matrix and accumulate lipid, some of which are in the form of lipid protein complexes characteristic of oxidized lipoproteins. These cells are also capable of modifying lipoproteins in situ, favoring their uptake by scavenger receptors. Endothelial cells and macrophages can elaborate a chemoattractant protein sustains accumulation of monocyte derived macrophages. Adherence of monocytes to altered endothelial cells and their migration into the arterial wall to become resident macrophages may be the earliest cellular abnormality in atherogenesis. Thus repeated or chronic injury could lead to a slowly progressing lesion involving a gradual increase in intimal smooth muscle cells, macrophages, connective tissue, and lipid. Areas where the shearing stress on endothelial cells is increased, such as branch points or bifurcation of vessels, would be at greatest risk. As the lesion progress and the intima becomes thicker, blood flow over the sites will be altered and will potentially place the lining endothelial cells at even greater risk for further injury, leading to an inexorable cycle of events culminating in the complicated lesion. However, a single or a few injurious episodes may lead to a proliferative response that could regress, in contrast to continued or chronic injury. This hypothesis of reaction to injury thus is consistent with the known intimal thickening observed during normal aging, would explain how many of the etiologic factors implicated in atherogenesis might enhance lesion formation, might explain how inhibitors of platelet aggregation could interfere with lesion formation, and could elucidate how treatment targeted at risk factor reduction can interrupt progression or even produce regression of atheromatous lesions. Other theories of atherogenesis are not mutually exclusive.

The monoclonal hypothesis suggests, on the basis of single isoenzyme types found in lesions, that the intimal proliferative lesions result from the multiplication of single, individual smooth muscle cells, as do benign tumors. In this manner, mitogenic, and possibly mutagenic factors that might stimulate smooth muscle cells proliferation would act on single cells. Focal clonal senescence may explain how intrinsic aging processes contribute to atherosclerosis. According to this hypothesis, the intimal smooth muscle cell that proliferate to form an atheroma are normally under feedback control by mitosis inhibitors formed by the smooth muscle cells in the contiguous media, and this cells die and are not adequately replaced. This is consistent with the observation that cultured human arterial medial smooth muscle cells, like fibroblasts, show a decline in their ability to replicate as a function of donor age. The lysosomal theory suggests that altered lysosomal function might contribute to atherogenesis. Since lysosomal enzymes can accomplish the generalized degradation of cellular components required for continuing renewal, this system has been implicated in cellular aging and the accumulation of lipofuscin. It has been suggested that increased deposition of cholesterol esters in arterial smooth muscle cells may be related in part to a relative deficiency in the activity of lysosomal cholesterol ester hydrolase. Consonant with this idea, some patients with the rare cholesterol ester storage disease caused by a defect in lysosomal cholesterol ester hydrolase may have accelerated atherosclerosis.

The majority of people below age 65 afflicted with atherosclerosis have one or more identifiable risk factors other than aging. The risk factor concept implies that a person with at least one risk factor is more likely to develop a clinical atherosclerotic event and is likely to do so earlier than a person with no risk factors. The most potent factors for development atherosclerosis are, (1).hyperlipidemia, (2) hypertension and (3) cigarette smoking. Risk factors also vary in terms of their potential reversibility with current techniques of preventive management. Thus age, gender, and genetic factors are currently considered to be irreversible risk factors, whereas continually emerging evidence suggests that elimination of cigarette smoking and treatment of hypertension reverses the high risk for atherosclerosis attributable to those factors

Before dealing with the Hyperlipidemia it is more convenient for us to overlook some general rules of lipid transport. As we know we have 4 major groups of lipoproteins, a) The chylomicrons, b) Very Low Density Lipoproteins, c) The Low Density Lipoproteins, and d) The High Density Lipoproteins . The TG are transported via chylomicrons or VLDL. The chylomicrons transport exogenous lipids (diet) from the intestines and the VLDL transport endogenous lipids from the liver to most tissues for oxidation and to adipose tissue for storage. The formation of chylomicrons and VLDL occurs even in the fasting state, their lipids originating mainly from bile and intestinal secretions. The remnant (VLDL) and Chylomicron remnant are about half the diameter of the parent and in terms of the percentage composition become relatively enriched in cholesterol and cholesterol esters because of the loss of TG. For the CE transport we have the LDL and the HDL lipoproteins. The HDL (Good cholesterol) is synthesized and secreted from both liver and intestine. However nascent HDL from intestine does not contain apolipoprotein C or E but only A. Thus, apo C and Apo E are synthesized in the liver and transferred to intestinal HDL. The major function of HDL is to act as a repository for apolipoproteins C and E that are required in the metabolism of chylomicrons and VLDL Both hypercholesterolemia and hypertriglyceridemia appear to be important risk factors for atherosclerosis. While there is no absolute quantitative definition of hyperlipidemia, statistical definitions, based on the upper 5 or 10 percent of the distribution of the plasma lipid levels within population, are often used. Such definitions are likely to detect affected individuals from families with one of the familial hyperlipidemias or having hyperlipidemia associated with other diseases or drugs; they also are useful for prediction of emergence of premature atherosclerosis and institution of preventive measures. However, these upper limits of normality are too high for defining those cholesterol and triglyceride levels that are correlated with increasing risk ischemic heart diseases in whole population. The increases in cholesterol are associated mainly with a rise in LDL concentrations; the increase in triglyceride are associated with a rise in VLDL and remnants of their catabolism (mainly intermediate density lipoproteins IDL). Accumulation of cholesterol in the circulation may in part be secondary to excessive production of triglyceride rich lipoproteins. Particle size of LDL (small, dense LDL or LDL subclass phenotype pattern B) has been implicated as a risk factor for ischemic heart disease. LDL pattern B may be inherited as a dominant genetic trait and is also associated with high TG and low HDL cholesterol levels. HYPERCHOLESTEROLEMIA. The levels of serum cholesterol are directly correlated with the incidence of ischemic heart disease. Men with cholesterol levels above 6 mmol/L (240 mg/dL) had more than a threefold increased risk of ischemic heart disease death compared with a men with cholesterol levels below about 5 mmol/L (200 mg/dL). There is a continuous exponential gradient of risk as the cholesterol level ascends. These data are supported by comparisons of the prevalence of ischemic heart disease and cholesterol (or LDL) in many other populations. The relationship of triglycerides and VLDL to ischemic heart diseases is confounded by a rise in cholesterol and VLDL increases.

Treatment Management Treatment always includes dietary management and drug therapy is added if necessary.
DIET: The first step in treatment of primary hyperlipidemia is attention to diet. All patients with mild to moderate hyperlipidemia should first be brought to normal weight if they exceed it and then be maintained on a diet emphasizing decreases in intake of saturated fat and cholesterol. If hypertriglyceridemia is present, alcohol intake should be limited or eliminated. A single dietary approach to all forms of hyper lipidemia, including reduced intake of calories, cholesterol (to less than 300mg/d), and saturated fat (to less than 10 percent of total calories), is appropriate for most patients. The degree of dietary modification would be proportional to the degree and nature of the hyperlipidemia. In practice, such a modification translates into limitation of animal fats and substitution of vegetable oils, fish, and carbohydrates. Increased physical activity is often a useful adjunct to dietary management. The maximum effect of such a regimen will be observed within 3 months after body weight has stabilized.

This often needs to be added for the management of the familial hyperlipidemias and for patients with a positive family history of atherosclerosis. Drug therapy is recommended for any adult patient whose LDL cholesterol level remains greater than 4.9 mmol/L (190 mg/dL) or greater than 4.1 mmol/L (160 mg/dL) in the presence of two or more risk factors after an adequate trial of at least 3 months of diet therapy alone. A more aggressive approach is recommended for patients with clinically manifest of ischemic heart disease, with a suggested LDL cholesterol level of 3.4 mmol/L (130 mg/dL) or greater for initiation of drug therapy. A decision to start drug therapy should be made only after careful evaluation, since it usually commits patients to lifelong treatment. Continued follow up Drug therapy can reduce fat absorption from the intestine (resins), modify hepatic synthesis (HMG-CoA reductase inhibitors) or release of lipoproteins (niacin), increase peripheral clearance of lipoproteins (gemfibrozil group), and possibly exert other effects (probucol). These drugs are given orally. The amin classes of drugs used clinically are: bile acid binding RESINES,FIBRATES,HMG-CoA reductase inhibitors,NIACIN (nicotinic acid). Other drugs that are sometimes used include PROBUCOL and fish oils.

RESINS Mechanism and Effects:. Bile acid binding resins (cholestyramine and colestipol) are large nonabsorbable polymers that bind bile acids and similar steroids in the intestine. Neomycin, though not a resin, also causes a reduction in bile acid reabsorption. By preventing absorption of dietary cholesterol and reducing reabsorption of bile acids secreted by the liver, these agents greatly enhance the diversion of hepatic cholesterol synthesis to new bile acids, thereby reducing the availability of cholesterol for the production of plasma lipids. A compensatory increase in high affinity LDL receptors often occurs in the liver. Resins are minimally absorbed and have no systemic toxicity. Adverse effects include bloating, constipation, and impaired absorption of some cationic or neutral drugs. Neomycin is rarely used because it is associated with a higher incidence of adverse effects than are the resins. HMG-CoA reductase inhibitors Mechanism and effects:. Lovastatin (mevinolin) and simvastatin are pro drug lactones. Pravastatin and fluvastatin are active as given. In the body, the active drugs are structural analogues that competitively inhibit mevalonate synthesis by HMG-CoA reductase, a process essential for cholesterol biosynthesis in the liver. The liver compensates by increasing the number of high-affinity LDL receptors and this results in increased clearance of VLDL remnants (IDL) and LDL from the blood. After administration of this drug mild elevations of serum transaminase are common but are not often associated with hepatic damage. Patients with preexisting liver disease my have more severe reactions. An increase in creatine kinase (released from skeletal muscle) is noted in about 10% of patients; in a few, severe muscle pain and even rhabdomyolysis may occur. Progression of cataracts was reported in a few patients in early studies but has not been found in more extensive trials.
NIACIN (NICOTINIC ACID) Mechanism and Effects:. Niacin (but not nicotimide) reduces the secretion of VLDL from the liver, possibly by inhibiting hepatic synthesis of apolipoproteins. Consequently, LDL formation is reduced. Increased clearance of VLDL by lipoprotein lipase in the periphery has also been demonstrated. In addition, the levels of HDL may increase. Finally, niacin decreases circulating fibrinogen and increases tissue plasminogen activator. After administration cutaneous flushing is a common adverse effect. Aspirin may reduce the intensity of this flushing, suggesting that it is mediated by prostaglandin release. Tolerance usually develops within few days. Pruritus and other skin conditions are reported. Moderate elevations of liver enzymes may occur.
GEMFIBROZIL AND RELATED DRUGS (fibrates) Mechanism and Effects:. Gemfibrozil, fenofibrate, and clofibrate cause a decrease in VLDL levels through a peripheral effect. This effect is probably stimulation of lipoprotein lipase, resulting in an increase in the clearance of triglyceride rich lipoproteins. Cholesterol biosynthesis in the liver is secondarily reduced. There may be an increase in HDL levels. After administration of the drugs, nausea is the most common adverse effect will all members of this subgroup. Skin rashes are common with gemfibrozil. Myalgia is reported in patients taking clofibrate; an antiplatelet effect may cause an interaction between this drug and anticoagulants. Most importantly, clofibrate has been associated with an increase in the incidence of gastrointestinal and hepatobiliary neoplasms.
PROBUCOL Mechanism and Effects:. Probucol reduces LDL cholesterol levels by an unknown mechanism. Unfortunately, this drug often reduces HDL level as well, which limits its usefulness. However, some evidence suggests that the drug may inhibit atherogenesis by other mechanisms in addition to its effect on plasma lipids, possibly by an antioxidant effect. Probucol distributes into adipose tissue and has a very long half life. It is particularly important drug in treatment of homozygous familial hypercholesterolemia, because the drug's actions do not require functioning hepatic LDL receptors. Drugs available for treatment of the hyperlipidemias Drugs available Major lipoprotein decreased Mechanism Daily dose Common side effects Fibric acid derivates

High blood pressure is an important risk factor for atherosclerosis. The risk increases progressively with increasing blood pressure. A mechanical stress on endothelial cells may develop and alteration in the endothelial permeability. In industrialized populations, blood pressure appears to increase inexorably with age. The age associated blood pressure increase might be related to physical activity or dietary factors, particularly sodium and total caloric content. Hypertension appears to increase atherosclerosis throughout the age span. Conversely, the risk for atherosclerosis appears diminished by therapeutic reduction of blood pressure. Recent intervention studies have shown convincingly that reduction of diastolic levels that had been greater than 105 mmHg significantly reduces the incidence of strokes, ischemic heart disease, and congestive heart failure in men. A recent trial of treatment of isolated systolic hypertension in otherwise healthy elderly subjects showed that reduction of blood pressure substantially reduced both ischemic heart disease and stroke.

Treatment Management

The strategies for treating high blood pressure are based on the determinants of arterial pressure. These strategies include reduction of blood volume, sympathetic tone, vascular smooth muscle tone, and angiotensin concentration. Because of the baroreceptor reflex, the compensatory homeostatic responses to these drugs may be significant. Thus the compensatory responses can be counteracted with B-blockers or reserpine (for tachycardia) and diuretics or ACE inhibitors (for salt and water retention). Diuretics (Thiazide) reduce blood pressure initially by facilitating renal excretion of sodium and water, thereby reducing blood volume and cardiac output. Angiotensin inhibitors (Captopril) reduce blood pressure by preventing the renin angiotensin mechanism from acting on the vascular smooth muscle, adrenal cortex, kidney, and brainstem. Adrenergic blockers interfere with the transmission of the neurohumoral facilitators (e.g. norepinephrine) of vasoconstriction and cardiac stimulation. Hypertension is usually managed with both pharmacologic and A non pharmacologic methods. A dietary modification include the sodium (Na) restriction to 2g/day, to increase potassium intake, to restrict saturated fat intake, and to adjust calorie intake as required to maintain optimum weight.

(3) CIGARETTE SMOKING Not only is cigarette smoking one of the more potent risk factors for atherosclerosis, it is also one of the factors that when reduced or eliminated clearly decreases the risk of developing atherosclerosis. Smokers dying of causes other than ischemic heart diseases have been found at autopsy to have more coronary atherosclerosis than nonsmokers. Those who stop smoking show a prompt decline in risk and may reach the risk level of nonsmokers as early as after 1 year of abstention. D. MECHANISMS OF ATHEROGENESIS

The development of atherosclerosis accelerates in approximate quantitative relation to the degree of hyperlipidemia. A long established theory suggests that the higher the circulating levels of lipoprotein, the more likely they are to gain entrance to the arterial wall. By an acceleration of the usual transendothelial transport, large concentrations of lipoproteins within the arterial wall could overwhelm the ability of smooth muscle cells and monocyte derived macrophages to metabolize them. Lipoproteins have been immunologically identified in atheroma, and in humans there is a close relationship between plasma cholesterol and arterial lipoprotein cholesterol concentration. HDL may be protective in relation to their ability to promote cholesterol efflux from artery wall cells. Chemically modified or oxidized lipoproteins, possibly produced in hyperlipidemic disorders, could gain access to the scavanger arterial wall macrophages, leading to formation of foam cells. On the other hand, the Diabetes could provide a unique contribution to atherogenesis. Although the fundamental genetic abnormality in either type of human diabetes mellitus remains unknown, it has been suggested that genetic diabetes in humans imparts a primary cellular abnormality intrinsic to all cells, resulting in a decreased life span of individual cells, which in turn results in increased cell turnover in tissues. If arterial endothelial and smooth muscle cells are intrinsically defective in diabetes, accelerated atherogenesis can be readily postulated on the basis of any one of the current theories of pathogenesis The effect of chronic smoke inhalation from cigarettes could result in repetitive toxic injury to endothelial cells, thereby accelerating atherogenesis. Hypoxia stimulates proliferation of cultured human arterial smooth muscle cells; thus, since cegarette smoking is associated with high levels of carboxyhemoglobin and low oxygen delivery to tissues, another mechanism for atherogenesis is suggested. Hypoxia could produce diminished lysosomal enzyme degradative ability, as evidenced by impaired degradation of LDL by smooth muscle cells causing LDL derived cholesterol to accumulate in the cells. Consistent with this suggestion is the fact that aortic lesions that resemble atheroma have been produced in experimental animals by systemic hypoxia, and lipid accumulation in the arterial wall.


Although premature ischemic heart disease is overall the most costly and common complication of atherosclerosis, preoccupation with ischemic heart disease should not obscure the fact that angina pectoris and myocardial infarction are expressions of late stage atherosclerotic lesions. Factors precipitating these clinical events may be independent of those leading to initiation of plaque formation or its progression to a complicated lesion. Steps taken to prevent recurrence of myocardial infarction or fatal arrhythmia, termed secondary prevention, will not necessarily be the same as those taken to delay or prevent formation of atherosclerosis (primary prevention). Thus prevention of atherosclerosis, rather than treatment, is the goal. Although an effective program has not been established with certainty, enough is known to act as a guide both in identification of those with a higher risk and in development of conservative measures that probably will reduce that risk. Thus prevention currently is equated with risk factor reduction. The decline of American death rates from premature ischemic heart diseases coincides with two trends in health practices. One is the increasing recognition of the importance of detecting and attempting to correct some of the risk factors correlated with atherosclerosis. The other is a greater awareness of the dietary sources of cholesterol and saturated fats and a tendency of the public to restrict their intake somewhat. Whether these trends are causally related to the decline in death rate is not known. While a rigorous approach to changes in life style for the general population may be debatable, it is desirable to continue finding and helping those most susceptible to early atherosclerosis. The physician's role in risk factor reduction involves treatment of hypertension and hyperlipidemia and advice regarding diet, body weight, smoking, and exercise. Drug treatment of hyperlipidemia should be limited to those individuals at high risk who do not respond adequately to dietary management.


Atherosclerosis is a form of arteriosclerosis in which the thickening and hardening of the vessel walls are caused by soft deposits of intraarterial fat and fibrin that harden over time. It has long been recognized that lipid deposition is an early event in atherogenesis and occurs when influx and deposition of cholesterol into the arterial wall exceed efflux. The lesions of atherosclerosis occur primarily within tunica intima and include the fatty streak, fibrous plaque, and the advanced or complicated lesion. Atherosclerotic lesions generally cause no symptoms until 60% or more of the tissue's blood supply is occluded. If plaque formation occurs slowly, collateral arteries may develop to supply tissue. Treatment of atherosclerosis is always focused first on dietary modification. Fat intake should be reduced to less than 30% of daily calorie consumption, with no more than 10% saturated fats, no more than 10% polyunsaturated fats, and 10% to 15% monounsaturated fats and daily cholesterol intake must be reduced to 250 to 300 mg. Drugs that decrease lipidemia are prescribed only if serum lipoproteins are not reduced by a reasonable trial of dietary modification or if lipids levels are dangerously elevated in an individual who will require a considerable time for significant dietary change and weight reduction.

References : Pharmacology H.P. Rang M.M. Dale J.M. Ritter Pharmacology Bertram G. Katzung Anthony J. Trevor Pathophysiology Kathryn L. McCance Sue E. Huether Physiology Berne & Levy Harper's Biochemistry Robert L. Murray Daryl K. Granner Peter A. Mayes Victor W. Rodwell