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TOPIC: GERD (Gastro Esophageal Reflux Disease)
What role if any do you think surgery plays in the treatment of GERD?
If it were more cost-effective, do you feel it would play a greater role as opposed to life-long Proton Pump Inhibitors (PPI’s)?
For background, you should refer to GASTRO Electronic Highlights Bulletin #1: “Cost-effectiveness of omeprazole vs. fundoplication in the long-term treatment of reflux esophagitis”; or April Supplement of Gastroenterology, Abstract A 19
RESPONSE 1: GERD should be as good a topic as any to start with.
What role if any do you think surgery plays in the treatment of GERD?
Over the past few years, we’ve seen a rapidly shrinking role of surgery in severe GERD. Although I am a surgeon, and often have patients referred to me for surgery by physicians who have been trying to control symptoms with medication, I find that I’m becoming increasingly reluctant to operate unless I’m convinced about failure of medical therapy. I often suspect patient compliance, especially during chronic therapy. Continue reading GASTRO-EHLB: GERD Discussion Threads
A debate was conducted that begged the question “Should Lipid Lowering Drugs Play a Major Role in the Treatment of Hypertension?” The proponent was John LaRosa,MD who made the following point: Hyperlipidemia promotes atherogenesis; The single most important risk factor for the development of plaques is a cholesterol level above 150mg/dL; The addition of hypertension increases the risk by a four-fold measure; The association of both risk factors are probably related to hyperinsulinemia but not necessarily causally; If cholesterol levels are lowered, blood pressure lowering usually follows suit and this could be a passive phenomenon. Finally, lowering cholesterol has been shown to lower the incidence of stroke and coronary artery disease. The question was then modified to ask, not whether hypercholesterolemia should be treated, but how to treat it. The point was made that treatment does not necessarily mean drug therapy. Continue reading Metabolic issues and treatment of hypertension
A thesis was presented based on data accumulated over 30 years that examined the relation between the incidence of stroke as a marker for hypertension and economic class. The data show that the incidence of hypertension is not random but rather related to education. There is an inverse relationship between the level of education and the incidence of hypertension in whites and nonwhites but more pronounced in blacks and more so in female than male blacks. The incidence was linearly increased in darker skinned people and in low socioeconomic class than higher class. After stratification, all effects were more related to social status.
The HDFP trial conducted in the 1970′s on 150,000 people with geographic heterogeneity showed that the prevalence of hypertension was related to educational level. Yet, blacks had a higher prevalence at every educational level. Prognosis and mortality was also found to be related to educational achievement. For African-American men, the lower the educational achievement the higher the stroke mortality. Although there is an absolute decline in the incidence of stroke since 1972, the gradient persists. A similar disparity exists for black women as compared to white. Continue reading The role of socioeconomic status in hypertension
Incubation of monocyte/macrophages with even very high concentrations of native low- density lipoproteins (LDL) fails to lead to cholesterol accumulation, yet LDL is the ultimate source of the cholesterol accumulation in monocyte-derived foam cells. This apparent paradox has been resolved by the demonstration that a number of modifications of LDL result in forms that are taken up more rapidly by the macrophage. The best studied of these modifications is oxidation. There is a large body of evidence from animal studies showing that oxidative modification occurs in vivo. Furthermore, inhibition of oxidative modification in animal models slows the progression of early lesions. Epidemiologic studies show a negative correlation between intake of antioxidant vitamins and risk of coronary artery disease (CAD). However, we do not know whether this reflects a causal relationship. Clinical intervention studies are already in progress, but results are 5 to 10 years away. Other modifications of LDL that increase its uptake by monocyte/macrophages include self- aggregation and complexing with autoantibodies. These and other modifications may be as important as oxidative modification. However, research in these areas has not progressed to the point of intervention in animal models, let alone in humans. Continue reading The pathobiology of atherosclerosis (2)
The genesis of atherosclerosis begins with the development of the fatty streak. A fibrous plaque is formed, leading to calcification, then rupture, thrombosis, and myocardial infarction. The site of plaque rupture is usually at the shoulder of lesions that have monocyte- macrophages characteristic of chronic inflammatory reactions. But what causes the chronic inflammatory reaction in the artery wall? Using state-of-the-art ultrastructural techniques, the Atherosclerosis Research Unit at the University of California, Los Angeles, demonstrated that normal low-density lipoproteins (LDL) are trapped in a matrix of fibers and fibrils in the artery wall. Here, the lipids in LDL are exposed to the oxidative wastes of the artery wall cells. Oxidation of the LDL phospholipids produces biologically active molecules that cause the expression of high levels of binding molecules on the endothelium. Continue reading The pathobiology of atherosclerosis
This morning’s speakers focused on guidelines and strategies that can be used to provide the most effective hypertensive treatment based on current knowledge of the pathophysiology of the disease and the benefits of available therapies.
Dr. Black referred to some of the controversy that has surrounded the recent fifth report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure, commonly referred to as JNC-V (Arch Int Med 1993; 153: 154-183). The report states that the goal of therapy “is to prevent morbidity and mortality associated with high blood pressure and to control blood pressure by the least intrusive means possible.” Therefore, the clinician should individualize therapy since what is obtrusive to one patient may be acceptable to another. JNC-V moves away from a rigid treatment algorithm, giving practitioners more latitude in selecting optimal therapy. Continue reading Sunrise seminar series individualization of treatment for hypertension
Participants in this symposium reviewed the subject of chronobiology and demonstrated how blood pressure and other physiologic functions change normally throughout the day, reviewed the pathogenesis of acute myocardial infarction and discussed the role of plaque rupture in leading to acute coronary syndromes, and reviewed the efficacy and therapeutic profile of drugs designed to be most active when blood pressure is normally higher.
Medical chronobiology is the application of rhythms in medicine. Rhythms are paced by master clocks in the brain and synchronized by environmental and societal time cues. Circadian rhythms influence the findings of diagnostic tests and the occurrence and treatment of disease. For example, angina worsens during sleep, and hemorrhagic stroke tends to occur in the evening. Chronotherapeutics is the scheduling of medications to account for rhythm dependencies in drug kinetics or dynamics and the pathophysiology of disease processes. Continue reading The emerging role of chronotherapeutics in managing hypertension
The afternoon session began with a philosophical discussion on the need for social protection of society; on the balance between the allocation of resources and the need for profitability. As an example, there is new evidence for the polymorphism of the RAAS. Yet, government may not be interested in pursuing research in this area. There is evidence that industry can no longer support clinical research and that government will have to fill the breech. However, there is concern that statistical studies will be used for cost containment purposes rather than for intellectual pursuit. Continue reading Angiotensin II: impact of basic sciences on clinical practice
This session focused on the important aspects of various groups of patients that might present with hypertension. Dr. Materson began by reviewing the results of the VA Cooperative Study Group on Antihypertensive Agents, which were published in 1993 and 1994. Key information about the relative effectiveness of antihypertensive agents in whites and blacks was obtained from this study. For example, whites responded significantly better to treatment with nadolol than a thiazide, whereas the opposite was observed for blacks. Whites responded better to captopril than blacks, but this difference was abolished when a diuretic was added to the regimen. Continue reading Hypertension in special populations
A statistical summary of several large studies showed that reducing systolic blood pressure mitigates target organ damage and that the effect is virtually linear. Lowering diastolic blood pressure was also correlated with reduced target organ damage. However, a J-curve effect appeared in patients with ischemic heart disease so that lowering diastolic BP below 80mm Hg appeared to increase the risk of coronary events. The benefits of lowering blood pressure was seen in cerebrovascular, cardiovascular and renal markers for disease progression.
Simultaneous recording of blood pressure and ECG over 24 hours showed that ischemic events appeared 20 minutes subsequent to a rise of systolic blood pressure of 20 mmHg or more, suggesting that ischemia is due to elevated blood pressure and not vice versa. Twenty-four hour blood pressure monitoring also showed a wide variability between day and nighttime blood pressure of as much as 30mm Hg with a morning surge that is correlated with cardiovascular events. Continue reading Effect of ace inhibition on progression of cardiovascular diseases
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