Characteristics of sudden death in hemodialysis patients.

Hemodialysis (HD) is an intermittent procedure during which large fluid and electrolyte shifts occur. We hypothesized that sudden death occurrences in HD patients are related to the timing of HD, and that they occur more frequently in the 12 h period starting with dialysis and in the 12 h period at the end of the dialysis-free weekend interval. In a retrospective study, 228 patient deaths were screened to determine if they met the criteria for sudden death. Information was obtained from clinic charts, dialysis center records, and interview of witnesses of the death event. There were 80 HD patients who met the criteria for sudden death. A bimodal distribution of death occurrences was present, with a 1.7-fold increased death risk occurring in the 12 h period starting with the dialysis procedure and a threefold increased risk of death in the 12 h before HD at the end of the weekend interval (P=0.011). Patients with sudden death had a high prevalence of congestive heart failure and coronary artery disease. Only 40% of patients experiencing sudden death were receiving beta-blockers, and the prior monthly serum potassium value was less than 4 mEq/l in 25%. Sudden death is temporally related to the HD procedure. Every other day HD could be beneficial in preventing sudden death. Careful attention to the usage of beta-blockers and to the maintenance of normal serum potassium values is indicated in HD patients at risk for sudden death.

Regulation of pancreatic amylase and lipase gene expression by diet and insulin in diabetic rats.

Although insulin has been proposed to mediate the dietary regulation of pancreatic amylase, its interaction with diet in the regulation of amylase and lipase is not well understood and was examined in diabetic rats fed diets high in carbohydrate (HC), protein (HP), or fat (HF) and treated with insulin. Diabetes, independent of diet, decreased amylase content (97%; P < 0.0001) and mRNA (90%; P < 0.0001), but insulin only restored amylase content and mRNA to respective dietary control values. Diabetes, independent of diet, also increased lipase mRNA 1.6-fold (P < 0.004) but interacted (P < 0.0003) with diet on lipase content, resulting in opposite effects in HC- (increased 202%) and HF-diabetic rats (decreased 40%). Insulin partially restored lipase content and mRNA to respective dietary control values. Diet, independent of diabetes, regulated amylase content (P < 0.0001) and mRNA (P < 0.0003), which were three- to fourfold greater in HC- than in HF-fed rats, and lipase content (P < 0.001) and mRNA [rat pancreatic lipase 1 (rPL-1), P < 0.04; rPL-3, P < 0.0001], which were 1.8-fold greater in HF- than in HC- or HP-fed rats. Insulin failed to stimulate maximal amylase gene expression in HP- or HF-fed diabetic rats, suggesting that it is necessary, but not sufficient, for this dietary regulation. Differential regulation of lipase activity and mRNA by diet and insulin raises the possibility that lipase gene expression is regulated by a complex interaction of diet and insulin.

Amount and type of dietary fat regulate pancreatic lipase gene expression in rats.

Both amount and type of dietary triglycerides regulate pancreatic lipase, but the mechanism is not fully understood. This study investigated the effects of type (safflower oil and lard) and amount [low (50 g/kg diet) or moderate (174 g/kg diet)] of fat on rat pancreatic lipase (rPL) activity and mRNA levels. Polyunsaturated safflower oil resulted in 80% greater lipase activity compared with the saturated lard at moderate levels, whereas safflower oil resulted in 50% lower lipase activity compared with lard at low levels. The rPL-3 mRNA levels were greater in rats fed the moderate safflower oil diet (163%) or the moderate lard diet (212%) than in those fed the respective low fat diets and were 45% greater in those fed safflower oil than in those fed lard. The rPL-1 mRNA levels were greater in rats fed moderate safflower oil (50%) or lard (135%) than in those fed the respective low fat diet, but these levels were not affected by type of fat, in contrast to rPL-3 mRNA levels. The amount of fat independent of its type regulates pancreatic lipase pre-translationally, because increasing dietary saturated or polyunsaturated fat resulted in parallel changes in rPL-3 and rPL-1 mRNA levels. However, type of fat may regulate pancreatic lipase at other levels such as translational or post-translational, because the 212% increase in rPL-3 mRNA in rats fed the moderate lard diet compared with the low lard diet did not result in greater pancreatic lipase activity.

Effects of secretin and caerulein on pancreatic digestive enzymes in cultured rat acinar cells.

Caerulein is proposed to regulate the synthesis of pancreatic proteases and amylase. Similarly, secretin is implicated in the regulation of pancreatic lipase synthesis. Evidence of these regulations is predominantly from in vivo studies. We therefore examined the effects of caerulein and secretin directly on acinar cells to eliminate possible interactions with other regulatory factors. Cellular and media enzyme activities and relative synthesis were measured after 24 h of hormonal treatment. Cells were incubated with [14C]-amino acids and then subjected to two-dimensional gel electrophoresis to separate individual acinar proteins for subsequent determination of incorporated radioactivity and relative synthesis. In general, all enzyme activities decreased (33%; p < 0.02) over time in culture and medium enzyme activities increased (370%; p < 0.00001) in all treatment groups. Caerulein further decreased cellular content of all enzymes (p < 0.002) and increased media amylase and lipase activities (p < 0.02). Caerulein, however, significantly increased the relative synthesis of trypsin (28%) and tended to increase that of chymotrypsin (25%; p < 0.06), which supports its proposed role in protease regulation. Secretin, on the other hand, did not significantly affect the cellular or medium activities or the relative synthesis of any pancreatic enzyme evaluated. Therefore, this study does not support the proposed role of secretin in lipase regulation.

Ontogenic differences in the inhibition of gastric acid secretion by epidermal growth factor.

Gastric secretions were studied in rats by pyloric ligation in vivo. The effects of epidermal growth factor (EGF) administered s.c. on gastric secretion were evaluated at different stages of development (8, 14, 20 and 30 postnatal days). The rates of fluid, protein and acid outputs were very low in developing rats but increased in maturing rats. The rate of acid output in 8- day-old rats (3.83 +/- 1.16) was not different from that in 14-day-old rats (4.84 +/- 0.99), whereas the rate of acid output in 20-day-old rats was 11-fold greater than that in 14-day-old rats, and it was 21-fold greater in 30-day-old rats. Subcutaneous administration of 30 micrograms/kg b.wt. of EGF significantly suppressed the gastric secretion of fluid, protein and acid in 20- and 30-day-old rats. In 30-day-old rats, acid output was 85% lower at 1 hr after EGF administration and in 20-day-old rats it was 85% lower at 2 hr and 50% lower at 3 hr. Interestingly, EGF had no effect on basal gastric secretions in 8- and 14-day-old rats; EGF also had no effect on the gastric acid output that was stimulated by pentagastrin administration in 14-day-old rats. In 20-day-old rats, inhibitory effects of EGF lasted for 3 hr before gastric secretions rebounded to normal levels, but inhibition lasted for only 1 hr in 30-day-old rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Involving nursing staff in research. A non-traditional approach.

The staggering complexity of issues that affect nursing service requires the participation of nurses at all practice levels in the continuing development of the knowledge and practice of nursing. The authors describe a practical application of a nursing research and development method in which nursing values are integrated with elements of non-traditional research approaches.

The internal cardioverter defibrillator: patient-family teaching.

The ICD has proved to be a valuable therapeutic adjunct for patients at risk for sudden cardiac death. Careful attention to details associated with patient and family teaching assures a smooth adaptation to what may seem an overwhelming circumstance for patients and family members.

Effects of secretin and caerulein on enzymes of cultured pancreatic acinar cells.

We examined the effects of secretin (0 to 200 nM) and caerulein (0 to 100 nM) on rat pancreatic acinar cells cultured 0 to 48 h in serum-free medium. The effects of 100 nM secretin with 1 nM caerulein were also studied because secretin may potentiate the effects of caerulein. Cellular and media (secreted) lipase and amylase were analyzed as were cellular DNA and protein content. Cellular lipase and amylase activities significantly decreased (P less than 0.0001) over time in all treatment groups, whereas media amylase and lipase significantly increased (P less than 0.0001). Neither secretin nor caerulein affected cellular lipase or media amylase. However, secretin significantly increased (P less than 0.04) and caerulein tended to increase (P less than 0.08) media lipase in a dose-dependent manner. At 12 h, 10 nM secretin maximally increased media lipase (58%) suggesting that cultured acinar cells remain responsive to secretin in vitro. Caerulein, at all concentrations, significantly decreased (P less than 0.001) cellular amylase but exhibited a dose-dependent effect only at 24 h when 100 nM caerulein maximally decreased cellular amylase (34%). Secretin (100 nM) did not alter these effects of caerulein. These results support the proposed role of caerulein in the regulation of amylase but not a direct role of secretin in the regulation of lipase.

Effects of diet and ketones on rat pancreatic lipase in cultured acinar cells.

The activity, synthesis rate and mRNA level of pancreatic lipase increase with dietary fat intake. Ketones, intermediates of lipid metabolism, have been proposed to mediate this change. Therefore, we investigated their direct effect on cultured pancreatic acinar cells and examined their possible interactive effects with glucose and dietary fat. beta-Hydroxybutyrate (0.01 to 2 mmol/L) did not affect lipase activity in cells isolated from rats fed a commercial nonpurified (NP) diet and cultured in high glucose (HG, 27.8 mmol/L) or low glucose (LG, 6.9 mmol/L) medium. The effects of ketones were also examined in acinar cells isolated from rats fed purified high fat (HF, 67% of energy from fat) or low fat (LF, 11% of energy from fat) diet. Cellular lipase was significantly higher in cells from HF-fed rats at both 24 and 48 h (264% and 145% of LF values, respectively; P less than 0.0001). beta-Hydroxybutyrate significantly increased (P less than 0.04) lipase activity in LF cells at 48 h but did not affect lipase activity in HF cells. These studies suggest that ketones may be involved in the regulation of pancreatic lipase in rats fed a LF diet, but their role is complex and interactive with dietary carbohydrate and fat.

Effects of dietary manganese deficiency on rat pancreatic amylase mRNA levels.

Manganese deficiency is associated with increased pancreatic amylase activity in rats. The present study investigated whether this increase in amylase activity is associated with increased pancreatic amylase messenger RNA (mRNA) levels. Weanling rats were fed a high carbohydrate diet containing either 40 micrograms Mn/g (control) or 0.5 microgram Mn/g (deficient) for 4 to 8 wk. Mn deficiency was confirmed by determining hepatic Mn content, which was significantly lower in Mn-deficient rats than in controls. Pancreatic RNA from both groups of rats was hybridized with 32P-labeled complementary DNAs for amylase and trypsinogen. Amylase mRNA levels were increased in rats fed Mn-deficient diets for both 4 wk (200%) and 8 wk (250%) when compared with respective control levels. In contrast, Mn deficiency was not associated with alterations in trypsinogen mRNA levels. Serum levels of insulin and corticosterone, hormones known to increase pancreatic amylase mRNA, were not affected by Mn deficiency. These observations suggest that Mn may participate in the regulation of amylase gene expression in a manner that is independent of insulin and corticosterone.

Adaptation of the exocrine pancreas to diet.

Pancreatic adaptation represents dietary regulation of gene expression; dietary substrates alter the synthesis and mRNA levels of their respective digestive enzymes. The mechanisms whereby mRNA levels change are not understood, but they must be elucidated. Although the changes in synthesis of proteases, amylase, and lipase parallel the changes in their mRNA levels in response to respective substrates, the concomitant changes in the synthesis of the other enzymes can be discordant with mRNA levels. The evidence supports a pretranslational mechanism of the adaptation of proteases, amylase, and lipase to their respective substrates and suggests potential translational mechanisms of other enzymes in these adaptations. Changes in synthesis occur within hours after a dietary change, but whether mRNA levels also change so early is unknown. Rapid, adaptive changes may occur by a different mechanism from later adaptation, possibly by translational control or nuclear transport. The differential effects of acute and chronic caerulein administration support the possibility of multiple mechanisms of regulation by a single effector. The mediators of pancreatic adaptations have not yet been identified, except for adaptation to dietary protein. CCK appears to mediate protease adaptation through the feedback regulation of its release by dietary protein. Available evidence supports a role of insulin and glucose in the adaptation to carbohydrate and a role of secretin and ketones in the adaptation to dietary fat. Elucidation of the mediators of pancreatic adaptation to carbohydrate and fat and their mechanisms is needed.

Effect of diet on triolein absorption in weanling rats.

To determine the effect of altered dietary fat intake on the rate of fat absorption in the intact animal, we fed male weanling rats either a high fat-low carbohydrate (HF-LC) (calories: 67% fat, 10% carbohydrate, 20% protein) or low fat-high carbohydrate (LF-HC) (calories: 10% fat, 67% carbohydrate, 20% protein) diet for 8 days. Absorption of [14C]triolein was estimated by determining 1) 14CO2 expiration in breath, 2) intestinal triglyceride output using Triton WR-1339, an inhibitor of lipoprotein lipase, and 3) quantitating the disappearance of labeled triolein from the gastrointestinal tract. Changes in the activity of pancreatic lipase and amylase confirmed the adaptation to altered fat and carbohydrate intake. Animals fed the HF-LC diet exhibited approximately twofold greater triolein disappearance, oxidation, and intestinal triglyceride output compared with animals fed LF-HC. There was also a highly significant linear relationship between 14CO2 excretion and intestinal triglyceride output in both diet groups. These data show that high dietary fat content markedly enhances in vivo fat absorption in the weanling rat.

Synthesis of amylase by cultured rat pancreatic acinar cells: effects of antecedent diet.

Amylase synthesis in cultured pancreatic acinar cells was determined using an affinity adsorbent, alpha-glucohydrolase inhibitor--Sepharose 4B. This adsorbent exhibited a consistent binding capacity and was specific for amylase. To assess the effects of antecedent diet on amylase synthesis during culture, acinar cells from rats fed high fat (HF) or high carbohydrate (HC) diets for 7 d were cultured for 1-48 h in serum-free medium. Amylase activity remained significantly higher in cells from rats fed the HC diet than in cells from rats fed the HF diet through 24 h in culture, despite an overall decrease with time in culture. The relative synthesis of amylase [([3H]phenylalanine amylase/[3H]phenylalanine total protein) x 100] was also significantly higher in cells from HC-fed rats than in cells from HF-fed rats at isolation and remained higher during culture. The results demonstrate that these cultured acinar cells synthesize amylase in vitro and that the effect of diet on amylase activity and relative synthesis persists during culture.

Effect of diet on intestinal and pancreatic enzyme activities in the pig.

Intestinal and pancreatic enzyme activities are known to respond to changes in dietary composition. Studies in rats and humans suggest that adaptive mechanisms differ between species in response to altered intakes of carbohydrate and fat. Because of increased use of the pig in the study of human nutrition, we compared the responses of pancreatic enzymes and intestinal disaccharidases in groups of 7- to 10-week-old pigs fed either high-carbohydrate/low-fat (70 cal% starch, 25% protein, 5% fat) or low-carbohydrate/high-fat (5, 25, 70%, respectively) diets for 7 and 30 days. No changes were observed in the activities for lactase, trypsin, or chymotrypsin or in the tissue protein concentrations, regardless of diet duration. High-carbohydrate/low-fat intake resulted in higher specific activities of sucrase, maltase, and amylase for both periods studied. Low-carbohydrate/high-fat intake resulted in higher specific activities of pancreatic lipase for both periods studied. The response of the intestinal disaccharidases differs from that observed previously in rodents but resembles the response reported in humans. Conversely, amylase and lipase responded similarly to the pattern in the rat. These data support the continued use of the pig as a suitable model in the study of adaptation to altered intakes of carbohydrate and fat.

Effects of reserpine treatment on dietary adaptation of the rat exocrine pancreas.

Chronic reserpine treatment (500 micrograms/kg) of the rat results in generalized exocrinopathy, impaired pancreatic secretion, and decreased pancreatic amylase. These characteristics are similar to those in cystic fibrosis and are the basis for use of this experimental model for cystic fibrosis. Pancreatic enzymes adapt to diet, but it is not known whether chronic reserpine treatment affects this response. Due to the malnutrition induced by this treatment, another dose of reserpine was required that would alter pancreatic function but not induce malnutrition in order to evaluate dietary adaptation. Male rats (100-120 g) were injected subcutaneously daily for 7 days with 1) no injection (control); 2) 1.0 ml/kg vehicle or sham (pair fed-sham); or 3) reserpine: 500, 50, or 5 micrograms/kg. Food consumption was comparable among control and reserpine-treated (50 and 5 micrograms/kg) rats and significantly greater (200%) than pair fed-sham and 500 micrograms/kg reserpine-treated rats. Pancreatic amylase, however, was significantly lower in all reserpine-treated rats (500 micrograms/kg, 74%; 50 micrograms/kg, 56%; 5 micrograms/kg, 52%) than in control rats. To evaluate dietary adaptation, control and reserpine-treated (5 micrograms/kg) rats were fed high carbohydrate, high fat or high protein diets. Both groups adapted to these diets with the greatest amylase, lipase, and trypsin activities in high carbohydrate-, high fat-, and high protein-fed rats, respectively. Reserpine-treated rats fed high carbohydrate, however, had significantly lower (64%) amylase activity than high carbohydrate-fed control rats. Although reserpine-treated rats can adapt pancreatic enzymes to diet, the adaptation of amylase to carbohydrate is impaired.

Effects of epidermal growth factor, insulin and insulin-like growth factor I on rat pancreatic acinar cells cultured in serum-free medium.

The effects of epidermal growth factor (EGF), insulin, and insulin-like growth factor I (IGF-I) were examined alone and in combination on rat pancreatic acinar cells cultured 48 h in serum free medium. IGF-I at a concentration of 2.7 nM maintained viability of cultured acinar cells comparably to EGF. In contrast, insulin was less effective in maintaining acinar viability, even at high concentrations (170nM). There were no additive or interactive effects of these growth factors on acinar viability. EGF significantly increased [3H]-phenylalanine incorporation into acinar protein and the specific activity of phenylalanine-acylated transfer RNA (tRNAphe), but did not change the apparent rate of protein synthesis when compared with insulin of IGF-I. EGF with insulin, IGF-I, or both resulted in significantly lower specific activities of tRNAphe when compared to EGF alone, but all had comparable rates of total phe-incorporation. Acinar cells readily degraded insulin, but not EGF or IGF-I. These results demonstrate some specificity in the acinar requirement for growth factors (EGF = IGF-I greater than insulin) in maintaining viability in culture.

Effects of manganese deficiency and dietary composition on rat pancreatic enzyme content.

Recent studies show that manganese (Mn) deficiency increases pancreatic amylase content. Pancreatic adaptation to dietary composition also alters enzyme content. The present study investigated whether Mn deficiency alters pancreatic adaptation to diet. Weanling rats that were fed for 6 wk a high carbohydrate (HC) diet with less than 1 mg Mn/kg diet (Mn deficient) or 40 mg Mn/kg diet (control) were divided into three control and deficient dietary subgroups: 1) HC, 2) high protein (HP) or 3) high fat (HF). Rats were then fed these diets for 10 d. Body weights and food consumption were comparable among the groups. Pancreatic and hepatic Mn contents were significantly lower in Mn-deficient rats than in respective controls. Digestive enzymes adapted to diet in both control and Mn-deficient rats with the greatest amylase, lipase and trypsin activities in HC, HF and HP rats, respectively. Mn deficiency resulted in significantly greater amylase activity in HC and HP groups and lipase activity in only the HF group than in respective controls. These data suggest that Mn participates in the regulation of pancreatic amylase content and in the adaptive response of pancreatic lipase to dietary fat.