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R C Lowe

Publications and source records attributed to R C Lowe.

15 recordsLinked to original sources

Pharmacological therapy for the treatment of esophageal varices.

Portal hypertension is a common complication of hepatic cirrhosis, and is responsible for much of the mortality and morbidity associated with advanced liver disease. Esophageal varices are a common occurrence, and esophageal variceal hemorrhage carries a high mortality. Endoscopic therapies have proven effective in treating active bleeding and preventing recurrence, but several pharmacological agents are useful adjuncts to endoscopy in both acute bleeding and in the primary and secondary prophylaxis of variceal hemorrhage. In acute hemorrhage, vasoconstricting agents such as vasopressin, terlipressin, somatostatin, and octreotide have been demonstrated to add benefit to endoscopic therapy. Secondary prophylaxis includes endoscopic therapy to eradicate varices, usually combined with oral beta-blockers. Primary prophylaxis is typically used in patients with medium or large varices, and consists of oral beta-blockers, at times combined with oral nitrates. This paper the reviews the pharmacological principles behind these therapies, and the clinical trial data that has led to their widespread use.

Acute Disease↗

The pharmacological management of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders, and the pharmacological management of GERD is a topic of intense interest given the sizeable yearly expenditure for antireflux therapies. GERD is primarily a motor disorder of the esophagus, yet pharmacological approaches directed at altering esophageal motility have been only partially effective. Antisecretory therapy is the mainstay of treatment for GERD. Both H2 receptor antagonists (H2RA) and proton pump inhibitors (PPIs) are effective in the treatment of GERD, but PPI therapy is clearly superior in the treatment of severe disease and in the healing of erosive esophagitis. A treatment schema for GERD based on presenting symptoms is outlined, promoting a stepwise approach to the appropriate use of antisecretory therapy.

Antacids↗

Pharmacologic therapy for portal hypertension.

Pharmacologic therapy for portal hypertension is effective in the treatment and prevention of hemorrhage from esophagogastric varices. Acute hemorrhage from varices can be treated with intravenous agents such as somatostatin or terlipressin, either alone or in combination with endoscopic sclerotherapy or band ligation. Intravenous octreotide has not shown effectiveness as monotherapy, but it appears to be beneficial when combined with endoscopic treatment. The prevention of rebleeding after initial hemorrhage is best accomplished with non-selective beta blockers, endoscopic band ligation of varices, or a combination of endoscopic and pharmacologic therapies. The addition of oral nitrates may further decrease rebleeding rates, but more data from randomized trials are needed. Beta blockers are currently the only agents recommended for the primary prevention of variceal hemorrhage.

Acute Disease↗

Primary prophylaxis of variceal hemorrhage.

Figure 3 shows an algorithm for the primary prevention of variceal hemorrhage. Pharmacologic therapy is the current standard of treatment for the primary prophylaxis of esophageal variceal bleeding. Patients with medium or large varices should be treated with a nonselective beta-blocker with the dose titrated to achieve a 25% decrement in resting heart rate or a heart rate of 55 to 60 bpm. The development of symptoms will, of course, limit the dose used. As discussed previously, these therapeutic endpoints are not well correlated with decreases in portal pressure. Measurement of the HVPG before therapy and after 3 months of therapy provides a rational approach to drug dosing. If the HVPG decreases by 20% or to less than 12 mm Hg, the medication dose will be effective in preventing hemorrhage. If, however, the HVPG is not appropriately lowered, a long-acting nitrate may be added. Patients with small varices should be observed, with endoscopic examinations every 2 years to assess progression of variceal size. Endoscopic therapy is not indicated for the primary prevention of variceal bleeding.

Adrenergic beta-Antagonists↗

Training intensity, blood lipids, and apolipoproteins in men with high cholesterol.

Twenty-six hypercholesterolemic men (mean cholesterol, 258 mg/dl; age, 47 yr; weight, 81.9 kg) completed 24 wk of cycle ergometer training (3 days/wk, 350 kcal/session) at either high (n = 12) or moderate (n = 14) intensity (80 and 50% maximal O2 uptake, respectively, randomly assigned) to test the influence of training intensity on blood lipid and apolipoprotein (apo) concentrations. All physiological, lipid, and apo measurements were completed at 0, 8, 16, and 24 wk. Lipid data were analyzed via two x four repeated-measures analysis of variance (alpha = 0.0031). Training produced a significant decrease in body weight and increase in maximal O2 uptake. No interactions between intensity and weeks of training were noted for any lipid or apo variable, and no between-group differences were significant before or throughout training. Therefore, intensity did not affect the training response. Regardless of intensity, apo AI and apo B fell 9 and 13%, respectively, by week 16 and remained lower through week 24 (P < 0.0003). Total cholesterol fell transiently (-5.5%) by week 16 (P < 0.0021) but returned to initial levels by week 24. Triglyceride, low-density-lipoprotein cholesterol, and high-density-lipoprotein (HDL) cholesterol did not change with training. In contrast, HDL2 cholesterol rose 79% above initial levels by week 8 and 82% above initial levels by week 24 (P < 0.0018); HDL3 cholesterol fell 8 and 13% over the same training intervals (P < 0.0026). These data show that changes in blood lipid and apo concentrations that accompany training in hypercholesterolemic men are not influenced by exercise intensity when caloric expenditure is held constant.

Adult↗

Effects of training and a single session of exercise on lipids and apolipoproteins in hypercholesterolemic men.

To differentiate between transient (acute) and training (chronic) effects of exercise at two different intensities on blood lipids and apolipoproteins (apo), 26 hypercholesterolemic men (cholesterol = 258 mg/dl, age = 47 yr, weight = 81.9 kg) trained three times per week for 24 wk, 350 kcal/session at high (80% maximal O2 uptake, n = 12) or moderate (50% maximal O2 uptake, n = 14) intensity. Serum lipid and apolipoprotein (apo) concentrations (plasma volume adjusted) were measured before and immediately, 24, and 48 h after exercise on four different occasions corresponding to 0, 8, 16, and 24 wk of training. Data were analyzed using three-way repeated-measures multivariate analysis of variance followed by analysis of variance and Duncan's procedures (alpha = 0.05). A transient 6% rise in low-density-lipoprotein cholesterol measured before training at the 24-h time point was no longer evident after training. Triglycerides fell and total cholesterol, high-density-lipoprotein cholesterol (HDL-C), HDL3-C, apo A-I, and apo B rose 24-48 h after exercise regardless of training or intensity. Total cholesterol, HDL3-C, apo A-I, and apo B were lower and HDL2-C was higher after training than before training. Thus exercise training and a single session of exercise exert distinct and interactive effects on lipids and apolipoproteins. These results support the practice of training at least every other day to obtain optimal exercise benefits.

Adult↗

Changes in serum lipids and apolipoproteins after exercise in men with high cholesterol: influence of intensity.

The purpose of this study was to characterize the short-term changes in blood lipid and apolipoprotein concentrations in healthy hypercholesterolemic men after high-intensity [80% maximal O2 uptake (VO2max); n = 20] or moderate-intensity (50% VO2max; n = 19) cycle ergometer exercise balanced for caloric expenditure (350 kcal). The men's age, height, weight, %fat, and VO2max were 46 +/- 2 yr, 173 +/- 7 cm, 82.7 +/- 2.2 kg, 28 +/- 1%, and 31.1 +/- 1.0 ml O2.kg-1.min-1, respectively. Blood samples were drawn before exercise, immediately after exercise, then 24 and 48 h later, and concentrations of all variables were adjusted for changes in plasma volume. Significant changes (P < 0.0016) were as follows: total and low-density lipoprotein cholesterol fell by 4% immediately after exercise and then rose by 5-8% by 48 h. Triglycerides were 18 and 15% lower at 24 and 48 h, respectively. HDL-cholesterol, high-density lipoprotein3-cholesterol, and apolipoprotein B rose 8-9% by 24 h and remained elevated. High-density lipoprotein2-cholesterol rose by 27% by 48 h after exercise, but this change was not significant. Apolipoprotein A-I did not change with exercise. The response patterns were not affected by exercise intensity. These data show that a single session of exercise performed by untrained hypercholesterolemic men alters blood lipid and apolipoprotein concentrations. Furthermore, the postexercise response patterns are not influenced by exercise intensity, as long as caloric expenditure is held constant.

Adult↗

Oxygen consumption and cardiac response of short-leg and long-leg prosthetic ambulation in a patient with bilateral above-knee amputation: comparisons with able-bodied men.

This study measured oxygen uptake (VO2), minute ventilation (VE), and heart rate (HR) in a bilateral above-knee (AK) amputee and in three able-bodied controls during progressive treadmill exercise. Walking conditions for the amputee included using bilateral short-leg (SL) and long-leg (LL) prostheses. A progressive treadmill protocol to maximal capacity was used for the amputee and duplicated by the control subjects. An automated system was used to measure VO2, VE, and HR throughout exercise. Data analysis was restricted to the use of parameter averages and percentages to describe differences between experimental conditions. Maximal VO2 for the amputee averaged 23.3mL/kg-1/min-1 with the LL and 22.8mL/kg-1/min-1 with the SL prostheses, a negligible difference between conditions; however, exercise duration was 27% longer when using the SL prostheses. In addition, when averaged over the first four stages of exercise, VO2, VE, and HR were 24%, 32%, and 14% higher, respectively, when the LL prostheses were used. Treadmill walking by unimpaired controls averaged 47% and 79% more economical than walking with the SL or LL prostheses, respectively. These results demonstrate that the use of currently available AK prostheses requires significant energy expenditure, which limits their use to only the most physically fit individuals.

Adult↗

Substrate usage during prolonged exercise following a preexercise meal.

The effect of a high-carbohydrate meal 4 h before 105 min of exercise at 70% of maximal O2 uptake was determined in seven endurance-trained cyclists and compared with exercise following a 16-h fast. The preexercise meal produced a transient elevation of plasma insulin and blood glucose, which returned to fasting basal levels prior to the initiation of exercise. The meal also resulted in a 42% elevation (P less than 0.05) of glycogen within the vastus lateralis at the beginning of exercise. The 1st h of exercise when subjects were fed was characterized by a 13-25% decline (P less than 0.05) in blood glucose concentration, a suppression of the normal increase in plasma free fatty acids and blood glycerol, and a 45% (P less than 0.05) greater rate of carbohydrate oxidation compared with exercise when subjects were fasted. After 105 min of exercise, there were no significant differences when subjects were fed or fasted regarding blood glucose levels, rate of carbohydrate oxidation, or muscle glycogen concentration. The greater muscle glycogen utilization (97 +/- 18 vs. 64 +/- 8 mmol glucosyl units X kg-1; P less than 0.05) and carbohydrate oxidation when subjects were fed appeared to be derived from the glycogen synthesized following the meal. These results indicate that preexercise feedings alter substrate availability despite a return of plasma insulin to fasting levels prior to exercise and that these effects persist until the 2nd h of exercise.

Bicycling↗

Hemispheric lateralization of event-related potentials in a cued reaction-time task.

Subjects were tested in a cued reaction-time task wherein warning stimuli (S1) of 5-letter words or dot patterns inter-mixed across trials were briefly presented. After 2 sec a second stimulus (S2) of th same category as the S1 appeared and the subject pressed a key with the left or right hand. The right key was pressed if S2 was a synonym of S1 or if the second dot pattern was the same as the first. The left key was pressed for antonyms or different patterns. It was predicted that CNVs would be larger over the left than right hemisphere on word trials and vice-versa on pattern trials in accordance with speculations concerning hemispheric specialization. The CNV was lateralized as expected, most prominently on pattern trials. In addition a negative transient evoked by S2, and a late negative post-imperative slow wave were similarly lateralized. P300 waves were very large and largest to the S2 when it differed from S1. Factor analysis confirmed these results and indicated, in addition, that P300 was larger in the hemisphere least relevant to the task.

Adult↗