In a double-blind randomized trial, the hemodynamic events following the administration of propranolol (n = 51) or a placebo (n = 51) were prospectively studied in cirrhotic patients with esophageal ...varices. The hepatic venous pressure gradient, heart rate, and variceal size were determined at the baseline and 3, 12, and 24 months after the beginning of therapy. Baseline values were similar in both groups. At 3 months, the hepatic venous pressure gradient decreased significantly in propranolol-treated patients (from 18.1 +/- 4.2 to 15.7 +/- 3.4 mm Hg; P less than 0.05) but not in patients receiving the placebo (19.6 +/- 6.8 to 17.5 +/- 5.3 mm Hg; NS). At subsequent time intervals this gradient decreased significantly from the baseline value in both groups. Heart rate decreased significantly in the propranolol-treated group at all times (P less than 0.001). Variceal hemorrhage occurred in 13 patients (11 placebo-, 2 propranolol-treated; P less than 0.01), all of whom had a hepatic venous pressure gradient greater than 12 mm Hg. In 21 patients (14 propranolol-, 7 placebo-treated) the hepatic venous pressure gradient decreased to less than or equal to 12 mm Hg; none of them bled from esophageal varices, and their mortality rate also decreased. Because most of the bleeding events occurred during the first year (10 placebo-, 1 propranolol-treated; P less than 0.01), propranolol seems to have its protective effect during the period associated with the largest reduction in the hepatic venous pressure gradient. Because a reduction in the hepatic venous pressure gradient to less than 12 mm Hg protects from variceal bleeding and increases the rate of survival, this should be the aim of the pharmacological therapy of portal hypertension.
In an operator-blind design, we used an echo-Doppler duplex system to examine superior mesenteric artery and portal vein hemodynamics on two consecutive mornings in 12 fasting cirrhotic patients and ...12 matched controls, randomized to a standardized 355 kcal mixed-liquid meal vs. water. Cross-sectional area and mean velocity were recorded from the portal vein and superior mesenteric artery at 30 min intervals, from 0 min to 150 min after ingestion. Flows were calculated. Pulsatility index, an index related to vascular resistance, was obtained for the mesenteric artery. Baseline flows did not differ between cirrhotic patients and control patients, but pulsatility index was reduced in the cirrhotic subjects. Maximal postprandial hyperemia was attained at 30 min. Cirrhotic patients showed a blunted hyperemic response to food. In normal controls, portal vein area increased significantly after the meal from 30 min to 150 min, whereas in cirrhotic patients a significant difference occurred only at 30 min. Pulsatility index in both groups was significantly reduced after eating, and this reduction persisted up to 150 min. No changes after ingestion of water were observed. Echo-Doppler was very sensitive in detecting postprandial splanchnic hemodynamic changes and differences between cirrhotic patients and normal subjects. Mesenteric artery pulsatility index was more sensitive than flow in detecting baseline hemodynamic differences. In cirrhotic patients, portal postprandial hyperemia was mainly related to the increase in mean velocity.
Restenosis, the major limitation of balloon angioplasty, is the result of intimai hyperplasia after the procedure. Lovastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) inhibitor, may ...influence intimai hyperplasia by lowering serum cholesterol and by blocking deoxyribonucleic acid (DNA) synthesis. To determine whether lovastatin reduces intimai hyperplasia, a prospective, randomized blinded study was performed in 60 atherosclerotic New Zealand White male rabbits. Atherosclerosis was produced by air desiccation injury followed by a 28 day diet of 2% cholesterol and 6% peanut oil that was terminated before balloon angioplasty was performed. Angioplasty could not be performed in 14 rabbits with bilateral femoral artery occlusion, and in one rabbit the procedure was a technical failure.
Forty-five rabbits underwent balloon angioplasty performed with use of a 2.5-mm balloon inflated to 10 atm for three l min dilations at 1 min intervals. Seven rabbits died during the procedure. Thirty-eight rabbits were randomized to either a lovastatin group (6 mg/kg body weight per day) or a control group. Angioplasty was performed on all patent vessels (n = 54); the procedure was bilateral in 16 rabbits and unilateral in 22. Fifteen lovastatin-treated and 15 control rabbits survived 39 days after angioplasty and were then killed. Angiograms, obtained before and 10 nin and 39 days after balloon angioplasty, were read with use of electronic calipers by two observers who had no knowledge of treatment data. After the rabbits were killed, vessels were pressure perfused using a standardized protocol to maintain in vivo dimensions for minded quantitative histologic analysis.
After balloon angioplasty, total cholesterol decreased 36 ± 13% (mean ± SEM) in the lovastatin group (p < 0.05) and 26 ± 15% in the control group (p < 0.05, one-sided ttest). The percent decrease in angiographic luminal diameter from 10 min to 34 days after angioplasty was less in the lovastatin group (n = 22) than in the control group (n = 23) (reader 1:13 ± 11% versus 47 ± 8%, p < 0.05; reader 2:17 ± 8% versus 47 ± 8%, p < 0.01). Intimal thickness was 0.16 ± 0.02 mm in the lovastatin group and 0.30 ± 0.04 mm in the control group (p < 0.01). Thus, lovastatin reduced intimal hyperplasia after balloon angioplasty of the femoral artery in the hypercholesterolemic atherosclerotic rabbit. Its effect in patients undergoing coronary angioplasty should be evaluated.
Our goal was to test the hypothesis that children who exhibit bed-wetting during childhood were less likely to be breastfed during infancy compared with normal controls.
A case-control study was ...conducted in a pediatric continence center and a general pediatric practice. Cases (n = 55) were recruited from the continence center and defined as children 5 to 13 years of age who experienced lifetime involuntary voiding of urine during nighttime sleep at least 2 times a week in the absence of defects of the central nervous system or urinary tract. Age- and gender-matched controls (n = 117) who did not exhibit bed-wetting were enrolled from a general pediatric practice. Infant feeding practices were measured as breastfeeding (yes/no) and, for those who were breastfeed, by the duration of breastfeeding and the time of formula supplementation.
Among the case subjects, 45.5% were breastfed, whereas among the controls 81.2% were breastfed. The controls reported higher household incomes than the case subjects, and their mean family size (number of children) was slightly lower. After adjusting for race, income, and family size, the odds ratio was 0.283, indicating that case subjects were significantly less likely than controls to be breastfeed. Among all the study subjects who were breastfed, controls were breastfed for a significantly longer period than case subjects (an average of 3 months longer). Although breastfed controls were less likely to be supplemented with formula than breastfed case subjects, this difference was not statistically significant.
Breastfeeding longer than 3 months may protect against bed-wetting during childhood. Breast milk supplemented with formula did not make a difference in the rate of enuresis.
Toxicity study of pegaspargase ETTINGER, Lawrence J; LERNER, Emanuel D; MANGLANI, Mamta V
Indian pediatrics,
06/2000, Letnik:
37, Številka:
6
Journal Article
We have studied both the distribution and incidence of colorectal cancer using the Connecticut Tumor Registry, the oldest tumor registry in the United States. During the time period 1973 to 1985, ...left‐sided colon cancers accounted for 63% of the cancers, right‐sided cancers 33%, and cancers with unspecified sites 4%. Indeed, this pattern of distribution has remained constant for 25 years. For the period 1935 to 1985, we calculated the sex‐specific, age‐adjusted (normalized to the 1970 U.S. Census) incidence. Age‐adjusted incidence of rectal cancer has remained stable for 50 years: for men, 22.8 cases/100,000/year, and for women, 13.9 cases/100,000/ year. During these 50 years, the age‐adjusted incidence of cecal carcinoma for men has increased from 3.6 to 16.7 cases/100,000/year, while for women, it has increased from 4.9 to 14.2 cases/100,000/year. Sigmoid carcinoma for men has increased from 8.8 to 18.7 cases/100,000/year, and for women, it has increased from 7.7 to 12.8 cases/100,000/year. the incidence of colon cancer at each site has been and continues to be increasing at a constant rate. Age‐adjusted incidence for all colorectal cancers has increased from 35.2 to 70.2 cases/100,000/year for men and from 32.1 to 49.2 cases/100,000/year for women. Thus, distribution of colorectal cancers by site in Connecticut has remained stable for 25 years. More importantly, however, the age‐adjusted incidence of colon cancer has continued to increase for 50 years, whereas that of rectal cancer has remained relatively stable.
The effect of octreotide, a long-acting synthetic analog of somatostatin, on fasting and postprandial splanchnic hemodynamics was investigated in cirrhotic patients. Splanchnic hemodynamics were ...assessed using an echo-Doppler duplex system in a prospective, double-blind, placebo-controlled, crossover study performed on 2 separate days, 1 week apart, in 30 cirrhotic patients. Measurements of portal vein (PV) cross-sectional area (PVA) and mean velocity (PV-V), and of superior mesenteric artery (SMA) mean velocity (SMA-V) and pulsatility index (SMA-PI) (an index of vascular resistance) were performed at baseline, 30 minutes after octreotide (200 μg subcutaneously) or placebo administration, and 30 and 60 minutes after the ingestion of a liquid meal. In the fasted state, octreotide induced a significant decrease in PV-V (−7%) and in SMA-V (−10%) and an increase in PI (+16%). On the day of placebo administration, meal ingestion induced a significant increase in PV-V (+21%) and in SMA-V (+43%) and a decrease in PI (−21%). In contrast, meal ingestion on octreotide day induced significantly smaller increases in PV-V (+10%) and in SMAV (+18%) and a significantly smaller decrease in PI (−10%). Octreotide, although producing a mild reduction in PV-V and SMA-V in the fasted state, markedly blunts postprandial splanchnic hyperemia in cirrhotic patients.
Delayed gastric emptying of liquids and/or solids was hypothesized as a mechanism which could increase the volume of gastroduodenal contents and could contribute to the pathogenesis of ...gastroesophageal reflux. Gastric emptying of an isotope-labeled mixed solid-liquid meal was compared in a study of 20 age-matched gastroesophageal reflux patients and 20 normal subjects whose sex distribution and weight were similar; and also in a study of 100 reflux patients and 26 normals. The 20 GER patients emptied isotope from the stomach at a slower rate than age-matched normals at 30 min (p < 0.10); 60 min (p < 0.05, one-tailed t-test); and 90 min (p < 0.05). Using the range established from 26 normal subjects for percent of isotope remaining in the stomach after 90 min (mean +/- 2 SD), 53% of the 100 reflux patients evaluated were within the "normal" range of the controls; 41% had delayed gastric emptying exceeding the upper limit of isotope retention; and 6% emptied isotope rapidly. The means for LES pressure, age, and weight among the slow and "normal" emptying reflux esophagitis patients were similar. Based on the composition of the test meal, it is hypothesized that motor functions of the stomach may be abnormal in a high percentage (41%) of GER patients. The results also suggest a rationale for employing agents which enhance gastric emptying in the therapeutic approach to gastroesophageal reflux.
Most studies testing vasoactive agents in portal-hypertensive rats have been performed in young animals. To assess age-related changes in hemodynamic responses to adrenergic stimuli, we examined (a) ...responsiveness to norepinephrine (0.14 to 12.0 micrograms.kg-1.min-1) in young (3-mo-old) and aged (9-mo-old) sham-operated and portal-hypertensive rats and (b) response to propranolol (2 and 10 mg.kg-1 body wt), nitroglycerin (3.6 mg.kg-1.min-1) or saline solution in aged portal-hypertensive rats. Aged rats exhibited significantly (p < 0.05) smaller responses to norepinephrine with regard to increases in mean arterial pressure and superior mesenteric arterial vascular resistance, irrespective of portal hypertension. Portal hypertension alone potentiated this reduced response in aged animals and was associated with cardiovascular hyporesponsiveness to norepinephrine in young rats. Portal pressure was significantly (p < 0.05) lower in aged sham-operated rats than in young sham-operated rats over a wide range of norepinephrine doses. Portal-hypertensive aged rats showed significantly (p < 0.05) lower heart rates. Furthermore, systemic and splanchnic cardiovascular responses to propranolol and nitroglycerin mediated by the sympathetic nervous system were decreased or negligible in aged rats, compromising the portal-hypotensive effects of these drugs. In summary, aged rats express diminished cardiovascular responsiveness to adrenergic stimuli. Therefore age should be considered an important factor in studies evaluating pharmacological agents for the treatment of portal hypertension.
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