Calcium channel blockers and the incidence of breast and prostate cancer: A meta-analysis.

WHAT IS KNOWN AND OBJECTIVE: Breast cancer (BCa) and prostate cancer (PCa), both hormone-dependent cancers, are the second leading cause of death in both women and men, respectively. Calcium channel blockers (CCBs) have been thought to increase the risk of cancer by inhibiting calcium signal-mediated apoptosis, but the evidence for this association remains inconclusive. We have reviewed pertinent literature and pooled data to establish a consensus on the relationship of CCB use and the incidence of these two cancers. METHODS: PubMed was used to conduct a search for English articles from inception to April 2016. Relevant data including study design, number of total participants and CCB users, total cases of BCa and PCa, age (mean and/or range), follow-up period and statistical outcomes were retrieved. Quality assessment was carried out using Newcastle Ottawa system, with the selection of high-quality studies. Summary effects were obtained using random- and mixed-effects models, followed by sensitivity analysis, and testing for publication bias. RESULTS AND DISCUSSION: This meta-analysis includes 11 relevant studies for BCa and 6 for PCa. The odds ratio (OR) association between BCa and CCB use was 1.14 (95%CI: 1.02, 1.27, P = .02). The OR association between PCa and CCB use was 1.12 (95%CI .94-1.35, P = .21). WHAT IS NEW AND CONCLUSION: Although a statistically significant association between CCB use and incidence of BCa does exist, the limitations of the individual studies restrict the clinical application of this relationship. Our meta-regression model does newly identify a 9-year latency period of CCB use and a significantly increased risk of BCa. No significant association exists between CCB use and the incidence of PCa. Our meta-regression shows CCB may have a protective effect upon PCa incidence among older populations.

Short-term outcomes of inguinal hernia repair in octogenarians and nonagenarians.

BACKGROUND: The objective of this study is to report the 30-day outcomes following inguinal hernia repair in octogenarians (80-89 years of age) and nonagenarians (≥90 years) using a large, prospective, multi-institutional database and to identify the individual risk factors associated with increased morbidity and mortality. STUDY DESIGN: Patients aged 80 and above undergoing inguinal hernia repair were identified from the American College of Surgeons' National Surgical Quality Improvement Program (2007-2008). Univariate analysis was performed using chi square, Fisher's exact test and t test. Multivariate logistic regression analysis was carried out to assess factors associated with increased postoperative complications and mortality. RESULTS: Of 2,377 patients above 80 years of age, 226 (9.5 %) were nonagenarians. Men accounted for 81.4 % (1,936) of patients. There were significantly more female patients in the nonagenarian group (29.2 vs. 17.4 %, p < 0.0001). Laparoscopic repair was performed in 210 (9.9 %) patients. Emergency repair was more frequent in nonagenarians than octogenarians (12 vs. 4.4 %, p < 0.0001). The 30-day overall complication rate was significantly increased in nonagenarians compared to octogenarians (6.1 vs. 3.2 %, p = 0.03). Mortality is increased tenfold in elective inguinal hernia repair in nonagenarians compared to octogenarians (3 vs. 0.3 %, p < 0.0005). On multivariate analysis, preoperative variables found to be significantly associated with morbidity included totally dependent functional status, congestive heart failure and emergent nature of procedure, while higher age, emergency repair and open wound are associated with increased mortality. CONCLUSIONS: Elective inguinal hernia repair can be safely performed in octogenarians with low morbidity and mortality but is increased in nonagenarians. More vigilant postoperative care is required after emergent hernia repairs due to the increased risk of morbidity and mortality, and effort should be made to electively repair inguinal hernias early in this elderly population.

Sites of conditional essential fatty acid deficiency in end stage liver disease.

BACKGROUND: End stage liver disease (ESLD) is a devastating illness. Its protean manifestations involve many different aspects of disturbed hepatic function. One consequence of ESLD is a decrease in plasma levels of very long chain polyunsaturated fatty acids (VL-PUFAs), particularly arachidonic acid (AA) and docosahexaenoic acid (DHA), the former important for eicosanoid metabolism and the latter for retinal and brain membrane structure. The purpose of this study was to define the VL-PUFA changes in liver disease by comparing plasma and tissue levels of VL-PUFAs in controls to patients with ESLD. METHODS: Fatty acid profiles from plasma, red blood cell (RBC) membranes, muscle, liver, and fat tissue from ESLD patients undergoing liver transplants were measured and compared with control patients undergoing elective liver resection. RESULTS: Fatty acid profiles from plasma and RBC membranes showed significant decreases in AA and DHA levels in patients with ESLD compared with controls. However, there were no significant differences in tissue fatty acid composition between ESLD patients and controls. CONCLUSIONS: ESLD affects the liver's ability to maintain circulating levels of AA and DHA, and thereby presumably RBC membrane levels. However, solid tissues appear not to be affected by ESLD. Although the mechanism for these changes remains to be defined, it is consistent with hepatic impairment of elongation and desaturation to produce VL-PUFA for transport. The present results also suggest that dietary interventions to include preformed VL-PUFA rather than their precursors, linoleic and alpha linolenic acid, would be needed to normalize plasma VL-PUFA levels in patients with ESLD.

Increased survival after cecal ligation and puncture in mice consuming diets enriched with sesame seed oil.

OBJECTIVES: Lignans that present in the nonfat portion of sesame seed oil (SSO) can inhibit delta-5 desaturase activity, resulting in an increase in the accumulation of dihomo-gamma-linolenic acid and, subsequently, decrease the production of proinflammatory dienoic eicosanoids with a concomitant increase in the secretion of less inflammatory monoenoic eicosanoids. DESIGN: Female Balb/c mice were fed diets supplemented with 5wt% SSO or a physical mixture of oils (control) whose fatty acid composition resembled that of SSO for 3 wks. MEASUREMENTS AND MAIN RESULTS: During a 4-day observation period after cecal ligation and puncture, only 20% of the controls and as many as 65% in the SSO group survived. Furthermore, the levels of cytokines and dienoic eicosanoids produced in response to an intraperitoneal injection of a nonlethal dose (50 microg/mouse) of endotoxin were measured in both groups. The interleukin (IL)-10 levels were markedly higher in mice fed SSO diets compared with the controls. However, the plasma concentrations of prostaglandin E1 + 2, tumor necrosis factor-alpha, IL-6, and IL-12 did not differ significantly between the two groups of mice. CONCLUSIONS: Because the fatty acid composition is almost similar between the two diets, sesamin, sesamol and other lignans in SSO appear to be responsible for an increase in survival after cecal ligation and puncture and also for an increase in the IL-10 levels in response to a nonlethal dose of endotoxin in mice.

Fat depot origin affects fatty acid handling in cultured rat and human preadipocytes.

Regional differences in free fatty acid (FFA) handling contribute to diseases associated with particular fat distributions. As cultured rat preadipocytes became differentiated, FFA transfer into preadipocytes increased and was more rapid in single perirenal than in epididymal cells matched for lipid content. Uptake by human omental preadipocytes was greater than uptake by abdominal subcutaneous preadipocytes. Adipose-specific fatty acid binding protein (aP2) and keratinocyte lipid binding protein abundance was higher in differentiated rat perirenal than in epididymal preadipocytes. This interdepot difference in preadipocyte aP2 expression was reflected in fat tissue in older animals. Carnitine palmitoyltransferase 1 activity increased during differentiation and was higher in perirenal than in epididymal preadipocytes, particularly the muscle isoform. Long-chain acyl-CoA levels were higher in perirenal than in epididymal preadipocytes and isolated fat cells. These data are consistent with interdepot differences in fatty acid flux ensuing from differences in fatty acid binding proteins and enzymes of fat metabolism. Heterogeneity among depots results, in part, from distinct intrinsic characteristics of adipose cells. Different depots are effectively separate miniorgans.

Fetal tissue engineering: diaphragmatic replacement.

BACKGROUND/PURPOSE: Prosthetic repair of congenital diaphragmatic hernia has been associated with high complication rates. This study was aimed at applying fetal tissue engineering to diaphragmatic replacement. METHODS: Fetal lambs underwent harvest of skeletal muscle specimens. Once expanded in vitro, fetal myoblasts were suspended in a collagen hydrogel submitted to controlled radial tension. The construct was then placed in a bioreactor. After birth, all animals underwent creation of 2 diaphragmatic defects. One defect was repaired with the autologous-engineered construct placed in between 2 acellular supporting membranes and the other with an identical construct but without any cells. Each animal was its own control (graft, n = 10). Animals were killed at different time-points postimplantation for histologic examination. Statistical analysis was by analysis of variance (ANOVA). RESULTS: Fetal myoblasts expanded up to twice as fast as neonatal cells. Hydrogel-based radial tension enhanced construct architecture by eliciting cell organization within the scaffold. No eventration was present in 4 of 5 engineered constructs but in 0 of 5 acellular grafts (P<.05). At harvest, engineered constructs were thick and histologically resembled normal skeletal muscle, whereas acellular grafts were thin, floppy, and showed low cell density with increased fibrosis. CONCLUSIONS: Unlike acellular grafts, engineered cellular diaphragmatic constructs are anatomically and histologically similar to normal muscle. Fetal tissue engineering may be a viable alternative for diaphragmatic replacement.

Hypocaloric total parenteral nutrition: effectiveness in prevention of hyperglycemia and infectious complications--a randomized clinical trial.

OBJECTIVE: To determine whether the frequency rate of hyperglycemia and infectious complications can be reduced by an underfeeding strategy in patients requiring total parenteral nutrition (TPN), without deleterious effects on nitrogen balance. DESIGN: Prospective, randomized, controlled nonblinded trial. SETTING: A university-affiliated teaching hospital with a dedicated TPN service. PATIENTS: TPN was initiated in 40 adult patients and continued for > or =5 days. INTERVENTION: Two different TPN feeding strategies were compared: hypocaloric feeding (1 L containing 70 g protein and 1000 kcal) and standard weight-based regimen, begun in similar amounts initially, but advanced in increments toward 25 kcal and 1.5 g protein/kg dry (or adjusted ideal) weight. MEASUREMENTS AND MAIN RESULTS: We evaluated the frequency rate of hyperglycemia, average blood glucose, numbers and types of infections while receiving nutritional support and nitrogen balance after 5 days of TPN. There were significant differences between the quantities of calories, dextrose, fat, and protein provided to the two groups. However, average blood glucose, frequency rate of hyperglycemia, and infection rates (from intravenous catheter, pneumonia, and wound/abdominal collection) were similar in each group. The control group showed a trend toward a higher insulin requirement. Nitrogen balance, only available as a subset, was significantly more negative in the hypocaloric group. CONCLUSIONS: Provision of TPN to a goal of 25 kcal/kg was not associated with more hyperglycemia or infections than a deliberate underfeeding strategy. A regimen of 1.5 g/kg protein in conjunction with 25 kcal/kg did, however, provide significant nutritional benefit in terms of nitrogen balance in comparison with hypocaloric TPN.

Effects of sesamin-supplemented dietary fat emulsions on the ex vivo production of lipopolysaccharide-induced prostanoids and tumor necrosis factor alpha in rats.

BACKGROUND: Sesamin, a nonfat constituent of sesame oil, inhibits Delta(5)-desaturase activity, resulting in accumulation of dihomo-gamma-linolenic acid (DGLA), which displaces arachidonic acid (AA) and consequently decreases the formation of proinflammatory 2-series prostaglandins. OBJECTIVE: We sought to determine whether dietary supplementation with sesamin augments the antiinflammatory effects of dietary linseed oil in rats. DESIGN: We investigated the effects of continuous tube feedings of emulsions containing safflower oil or linseed oil with sesamin (SO+ and LO+) or without sesamin (SO and LO) on liver fatty acid composition and on endotoxin-induced production of prostaglandin E(2), 6-keto-prostaglandin F(1alpha), and tumor necrosis factor alpha (TNF-alpha) by whole blood from rats (n = 6 per diet group). RESULTS: We found a significant accumulation of DGLA only in the liver phospholipids of animals fed SO+ and LO+ (1.8 +/- 0.2 and 1.4 +/- 0.3 mol%, respectively), which suggests that sesamin inhibited Delta(5)-desaturation of n-6 fatty acids. These changes were associated with significant reductions in plasma prostaglandin E(2) concentrations in animals fed SO+ compared with those fed SO (P: < 0. 05). Despite a significant reduction in tissue AA content in the LO group, the prostaglandin E(2) concentrations did not differ significantly from those of the SO group. Plasma concentrations of TNF-alpha were significantly lower (P: < 0.05) in the animals fed LO+ than in those fed SO (199 +/- 48 and 488 +/- 121 ng/L, respectively). CONCLUSION: These data indicate that in rats, tube feedings of diets containing sesamin exerted antiinflammatory effects that were augmented by concurrent consumption of linseed oil.

Enabling sutureless vascular bypass grafting with the exovascular sleeve anastomosis.

PURPOSE: We describe a technique for end-to-end sleeve anastomosis that may enable minimally invasive bypass grafting and characterize the tensile strength, stenosis rate, durability, and healing of the anastomosis. METHOD: An anastomotic device assembly consisting of a cable tie-type band with mobile teeth elements is mounted on the outer surface of a polytetrafluoroethylene graft. The graft is drawn over the artery resulting in a sleeve of vessel within the graft. As the band is tightened over an intraluminal obturator, the independently mobile anchoring teeth are driven through the graft into the artery. The tensile strength of the anastomosis was compared with sutured anastomosis during in vitro studies using cadaveric human femoral arteries. For in vivo studies on pigs and goats, we used a proximal exovascular sleeve anastomosis along with a distal sutured aortic anastomosis. Survival animals were studied by angiogram postoperatively and at the time of explantation. RESULTS: In vitro studies showed no difference in maximal tensile strength between sutured and exovascular anastomoses (10.5 +/- 2.7 lb vs 10.2 +/- 3.0 lb, P =.83). However, loss of continuous graft to artery interface occurred at lower loads in the sutured anastomoses (6.5 +/- 0.6 lb, P <.05). In total, all 24 pigs tested in nonsurvival or survival settings sustained a successful and leakproof anastomosis. Of the 13 nonsurvival cases, maximal epinephrine-induced hypertension sustained over 15 minutes (peak systolic blood pressure > 210-250 mm Hg) was tolerated without leakage in a subgroup of five animals (100%). All 11 survival pigs had no pseudoaneurysms or stenosis relative to sutured control anastomoses at 6 week explantation (8.2 +/- 1.25 mm vs 8.5 +/- 1.6 mm, P =.21). The three long-term survival goats had no pseudoaneurysm or stenosis after 40 weeks. Histologic examination confirmed healing of the aorta to graft with minimal neointimal hyperplasia. CONCLUSION: Exovascular sutureless anastomosis appears comparable to sutured anastomosis in stenosis rate, healing, and durability, with some advantages in tensile strength and rapidity of application.

Biology of heterotrimeric G-protein signaling.

The G proteins are components of a complex membrane signaling system designed to modulate extracellular signals as they are transmitted into the cell. The principal components are the receptor, the G proteins including the alpha, beta, gamma subunits and the effector. Associated with these molecules are several molecular processes by which the signal is transmitted, and regulated including desensitization. Molecules such as arrestin, the RGS (regulators of the G-protein signaling) as well as downstream kinases associated with cyclic AMP are key to regulating the G protein signal. Membrane lipids are key for both anchoring this signal system to the plasma membrane but also in defining the signaling process. Through understanding the biology of the signal system, a number of diseases have been linked to dysfunction of the G protein system. It is clear that this important membrane signal system will become the target for more intense investigation and pharmacologic manipulation to treat critical illness.

Interventions to improve cardiopulmonary hemodynamics during laparoscopy in a porcine sepsis model.

BACKGROUND: Laparoscopy is increasingly used in severely ill and acutely septic patients. In animals undergoing laparoscopy, the hemodynamic response to sepsis is blunted. Specific interventions to augment the hemodynamic potential may make laparoscopic intervention a safer alternative in septic patients. We compared different interventions to improve hemodynamic performance during exploratory laparoscopy in a porcine endotoxic shock model. STUDY DESIGN: Domestic pigs (n = 12) received intravenous lipopolysaccharide injection and underwent surgical abdominal exploration using either laparoscopy or conventional laparotomy. For comparison, pigs exposed to endotoxin underwent laparoscopy with these interventions: intravenous infusions of prostacyclin (n = 5) or indomethacin (n = 4), intravenous crystalloid resuscitation (n = 5), pulmonary hyperventilation (n = 4), or abdominal insufflation with air (n = 5). Hemodynamic measurements and blood gas analyses were obtained using Swan-Ganz and arterial catheters. RESULTS: Septic animals treated with prostacyclin undergoing laparoscopy had a higher cardiac index (CI, p < 0.01), stroke volume (SV; p < 0.001) and oxygen delivery (p < 0.05) than the untreated group. Likewise, treatment with indomethacin was associated with a higher CI (p < 0.001), SV (p < 0.005), and oxygen delivery (p < 0.005) compared with the untreated group. These effects may be secondary to a decreased pulmonary vascular resistance, demonstrated in the animals that received either prostacyclin (p < 0.05) or indomethacin (p < 0.05). In addition, animals given aggressive fluid resuscitation had a significantly higher CI (p < 0.05) and SV (p < 0.001) than those with normal fluid resuscitation during laparoscopy. Manipulation of arterial pH by insufflation of the abdomen with air to create the pneumoperitoneum, or by aggressively hyperventilating the animals, did not improve CI. CONCLUSIONS: Adverse effects of laparoscopy on cardiovascular hemodynamics in the septic state may be mediated by increased pulmonary vascular resistance, diminished venous return, or both. Specific interventions to reverse these variables may ameliorate hemodynamic changes seen.

Effect of short-term enteral feeding with eicosapentaenoic and gamma-linolenic acids on alveolar macrophage eicosanoid synthesis and bactericidal function in rats.

OBJECTIVES: Because vasoactive eicosanoids derived from arachidonic acid present in immune cell phospholipids promote lung inflammation in critically ill patients, novel experimental diets containing eicosapentaenoic acid from fish oil and gamma-linolenic acid from borage oil have been designed to limit arachidonic acid metabolism. However, excess dietary eicosapentaenoic acid impairs superoxide formation and bacterial killing by immune cells. The present study determined whether short-term enteral feeding with diets enriched with either eicosapentaenoic acid alone or in combination with gamma-linolenic acid would modulate alveolar macrophage eicosanoid synthesis without compromising bactericidal function. DESIGN: Prospective, randomized, controlled, blinded study. SETTING: University medical center. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Rats underwent surgical placement of a gastroduodenal feeding catheter and were randomly assigned to receive one of three high-fat (55.2% of total calories), low-carbohydrate diets containing isocaloric amounts of lipids for 4 days. The control diet was enriched with linoleic acid, whereas the two test diets were low in linoleic acid and enriched with either 5 mole % eicosapentaenoic acid alone or in combination with 5 mole % gamma-linolenic acid. Alveolar macrophages were then procured to assess phospholipid fatty acid composition, eicosanoid synthesis after stimulation with endotoxin, superoxide formation and phagocytosis by flow cytometry, and killing of Staphylococcus aureus MEASUREMENTS AND MAIN RESULTS: Alveolar macrophage levels of arachidonic acid were significantly (p < .01) lower and levels of eicosapentaenoic and dihomo-gamma-linolenic acids were higher after feeding the eicosapentaenoic and gamma-linolenic acid diet vs. the linoleic acid diet. Ratios of thromboxane B2,/B3, leukotriene B4/B5, and prostaglandin E2/E1 were reduced in the macrophages from rats given either the eicosapentaenoic acid or eicosapentaenoic acid with gamma-linolenic acid diet compared with ratios from rats given the linoleic acid diet. Macrophages from rats given the eicosapentaenoic with gamma-linolenic acid diet released 35% or 24% more prostaglandin E1 than macrophages from rats given either the linoleic acid or the eicosapentaenoic acid diet, respectively. Macrophage superoxide generation, phagocytosis of opsonized zymosan, and killing of S. aureus were similar irrespective of dietary treatment. CONCLUSION: Short-term enteral feeding with an eicosapentaenoic acid-enriched or eicosapentaenoic with gamma-linolenic acid-enriched diet rapidly modulated the fatty acid composition of alveolar macrophage phospholipids, promoted a shift toward formation of less inflammatory eicosanoids by stimulated macrophages, but did not impair alveolar macrophage bactericidal function relative to responses observed after feeding a linoleic acid diet.

Effects of laparoscopic vs laparotomy treatment of E. coli peritonitis on hemodynamic responses in a porcine model.

BACKGROUND: Laparoscopic surgery is being used now for increasingly diverse clinical applications, including diagnosis and treatment of appendicitis and bacterial peritonitis. However, some concerns and controversies exist regarding the effectiveness of laparoscopic irrigation of the abdominal cavity compared with that achieved during laparotomy. Of no less importance is concern that establishing a CO(2) pneumoperitoneum in patients with cardiopulmonary insufficiency or endotoxemic shock may compromise hemodynamic function. The objective of this randomized, controlled study was to determine the effects of laparoscopic versus laparotomy intervention on hemodynamic and outcome measurements using a porcine model of Escherichia coli peritonitis. METHODS: For this study, 24 specific pathogen-free Hanford pigs underwent surgical placement of carotid, Swan-Ganz, and peritoneal catheters. After a 24-h recovery period, one subset of pigs (n = 12) received a bolus infusion of 9 x 10(8) CFU/kg E. coli intraperitoneally (septic) and intravenous fluid resuscitation. The remaining 12 pigs were not challenged with E. coli (control). Twenty-four hours later, all 24 pigs underwent either laparoscopic or open peritoneal irrigation with saline, then were reevaluated 48 h after surgical intervention. Standard cardiopulmonary, hematologic, and bacteriologic assessments were obtained both perioperatively and 48 h after surgical intervention. RESULTS: Pigs given E. coli exhibited significantly elevated heart rates and core temperatures and decreased O(2) saturation during the initial 6 h. Within 24 h, these pigs exhibited respiratory alkalosis, altered blood leukocyte profiles, and E. coli-infected peritoneal fluid. Random blood samples from the septic pigs tested negative for E. coli. Mean pulmonary artery and capillary wedge pressures were lower (p < 0.05) in septic than in control pigs before and after surgical intervention. Septic pigs that underwent laparoscopy had significantly lower (p < 0.05) arterial pH and higher arterial pCO(2) levels than septic pigs after laparotomy. Other cardiopulmonary responses were similar irrespective of the surgical modality used. One of six septic pigs from each surgical group still had E. coli growth in its peritoneal fluid 48 h after surgical intervention. CONCLUSION: Laparoscopic intervention demonstrated effectiveness equal to that of laparotomy for treating acute E. coli peritonitis in pigs without septic shock.

Priming of the neutrophil respiratory burst is species-dependent and involves MAP kinase activation.

BACKGROUND: Priming of the neutrophil respiratory burst has been implicated in the pathogenesis of multi-system organ failure (MSOF) after sepsis and trauma. The intracellular signal transduction pathways that mediate priming are unclear. METHODS: Human, porcine, rabbit, rat, and mouse neutrophils were assayed by luminol-dependent chemiluminescence in whole blood and purified neutrophil preparations. Multiple priming agents and agonists were studied, as was inhibition of priming by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580 and the Mek 1/2 inhibitor PD98059. RESULTS: Priming by tumor necrosis factor alpha (TNF-alpha), interleukin-8 (IL-8), and granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly inhibited by SB203580, whereas platelet-activating factor (PAF) priming was unaffected. Neither TNF-alpha nor PAF primed polymorphonuclear neutrophils (PMNs) within whole blood for N-formyl-methionyl-leucyl-phenylalanine (f-MLP) activation, in contrast to activation by complement-opsonized zymosan (OPZ) or low-dose phorbolmyristate acetate (PMA). Both TNF-alpha and PAF, however, primed purified neutrophils for f-MLP activation. In contrast to human and porcine PMNs, rabbit, rat, and mouse PMNs could not be primed by TNF-alpha or PAF, regardless of the final agonist. CONCLUSIONS: Priming of the PMN respiratory burst proceeds through multiple signaling pathways, depending on the particular priming agent and agonist pair. Differences in priming between PMNs in whole blood and purified preparations may be physiologically significant. There is a pronounced species dependency in the ability to prime the neutrophil respiratory burst.

Incidence, prognosis, and etiology of end-stage liver disease in patients receiving home total parenteral nutrition.

BACKGROUND: Elevations in liver function tests have been reported in patients receiving total parenteral nutrition (TPN). The clinical aspects of end-stage liver disease (ESLD) associated with the prolonged use of home TPN have not been fully clarified. In previous series patients with duodenocolostomies appeared to be at higher risk than persons with some jejunum or ileum remaining in situ. METHODS: The records of 42 patients treated with home TPN for more than 1 year were examined. This constituted 283 person-years of home TPN. Patients with duodenocolostomies were examined as a separate group on the basis of the literature experience. RESULTS: Six of 42 patients who received chronic home TPN had ESLD with 100% subsequent mortality, at an average of 10.8 +/- 7.1 months after the initial bilirubin elevation. Thirteen of 42 patients had superior mesenteric artery or vein thrombosis (SMT) leading to duodenocolostomy. In 8 of these 13 patients with SMT and underlying inflammatory or malignant disorder, 2 had ESLD. The remaining 5 SMT patients who had only minimal liver enzyme elevation over 13.6 +/- 6.7 (range 3 to 19) years of home TPN were significantly younger (36 +/- 7 years vs 64 +/- 13 years) and did not have underlying inflammation either by clinical diagnosis or as reflected in the high normal serum albumin level (> or = 4.0 g/dL). Despite their extreme short bowel syndrome and long exposure to home TPN, ESLD did not develop. CONCLUSIONS: Approximately 15% of patients who receive prolonged TPN have ESLD with a high rate of morbidity and mortality. The combination of chronic inflammation and the short bowel syndrome appears to be necessary for the development of ESLD with prolonged home TPN.

Plasma lipid changes after supplementation with beta-glucan fiber from yeast.

BACKGROUND: Dietary fiber has been shown to improve blood lipids. OBJECTIVE: The purpose of this study was to evaluate the effect on serum lipids of a yeast-derived beta-glucan fiber in 15 free-living, obese, hypercholesterolemic men. DESIGN: After a 3-wk period in which subjects ate their usual diet, 15 g fiber/d was added to the diet for 8 wk and then stopped for 4 wk. Plasma lipids were measured weekly during baseline and at week 7 and 8 of fiber consumption, and again at week 12. RESULTS: Compared with baseline, fiber consumption significantly reduced plasma total cholesterol (by 8% at week 7 and 6% at week 8; P < 0.05 using Bonferroni correction); week 12 values did not differ from baseline. No significant differences were noted between baseline LDL cholesterol and values at weeks 7, 8, or 12 when comparing individual groups by using Bonferroni correction, even though the overall one-way analysis of variance with repeated measures was highly significant (P < 0.001). LDL-cholesterol concentrations did decline by 8% at week 8 compared with baseline. There was a significant effect of diet on plasma HDL-cholesterol concentrations (P < 0.005 by one-way ANOVA with repeated measures). However, a group difference was observed only between baseline and week 12 (16% increase; P < 0.05 by Bonferroni correction). Triacylglycerol concentrations did not change. CONCLUSIONS: The yeast-derived beta-glucan fiber significantly lowered total cholesterol concentrations and was well tolerated; HDL-cholesterol concentrations rose, but only 4 wk after the fiber was stopped.

Nutritional management of hypoglycemia.

PURPOSE: People with type 1 diabetes who follow an intensive management program have an increased risk of hypoglycemia, particularly overnight. New strategies for the nutritional management of hypoglycemia are essential. METHODS: The unique properties of foods that affect blood glucose are reviewed, with special attention to a new medical food bar designed to reduce the incidence of nocturnal hypoglycemia. RESULTS: All carbohydrate-containing foods affect blood glucose, but each causes a different rise in concentration. Consuming a variety of conventional foods with different glycemic indices can help control hypoglycemia. A new medical food bar that provides a sequential triphasic release of glucose from sucrose, protein, and uncooked cornstarch can help control blood glucose levels. CONCLUSIONS: Hypoglycemia can be avoided by consuming foods with varying glycemic indices. A new medical food bar that provides sequential release of glucose into the bloodstream may also help control blood glucose levels.

Conditionally essential fatty acid deficiencies in end-stage liver disease.

Patients with end-stage liver disease (ESLD) manifest a wide variety of functional abnormalities that lead eventually to their death. Such patients also often have low levels of long-chain polyunsaturated fatty acids (PUFA) of carbon length 20 or greater in plasma total lipids, triacylglycerols, cholesterol esters, and phospholipids. We hypothesize that, due to hepatic damage, there is an impairment in de novo synthesis of very long-chain (20-22) carbon PUFA from their essential fatty acid 18 carbon dietary precursors that normally takes place principally in the liver. This results in a "conditional" essential fatty acid deficiency that may, in fact, be responsible for some of the pathophysiologic effects in ESLD. We propose that direct supplementation with very long-chain PUFA will provide a unique advantage in the correction of this "conditional" essential fatty acid deficiency in patients with ESLD and lead to improvements in their clinical condition.

Acute exercise induces GLUT4 translocation in skeletal muscle of normal human subjects and subjects with type 2 diabetes.

Total GLUT4 content in skeletal muscle from individuals with type 2 diabetes is normal; however, recent studies have demonstrated that translocation of GLUT4 to the plasma membrane is decreased in response to insulin stimulation. It is not known whether physical exercise stimulates GLUT4 translocation in skeletal muscle of individuals with type 2 diabetes. Five subjects (two men, three women) with type 2 diabetes and five normal control subjects (5 men), as determined by a standard 75-g oral glucose tolerance test, were recruited to determine whether an acute bout of cycle exercise activates the translocation of GLUT4 to the plasma membrane in skeletal muscle. Each subject had two open biopsies of vastus lateralis muscle; one at rest and one 3-6 weeks later from the opposite leg after 45-60 min of cycle exercise at 60-70% of VO2max. Skeletal muscle plasma membranes were prepared by subcellular fractionation, and GLUT4 content was determined by Western blotting. Plasma membrane GLUT4 increased in each subject in response to exercise. The mean increase in plasma membrane GLUT4 for the subjects with type 2 diabetes was 74 +/-20% above resting values, and for the normal subjects the increase was 71+/-18% above resting values. Although plasma membrane GLUT4 content was approximately 32% lower at rest and after exercise in the muscle of the subjects with type 2 diabetes, the differences were not statistically significant. We conclude that in contrast to the previously reported defect in insulin-stimulated GLUT4 translocation in skeletal muscle of individuals with type 2 diabetes, a single bout of exercise results in the translocation of GLUT4 to the plasma membrane in skeletal muscle of individuals with type 2 diabetes. These data provide the first direct evidence that GLUT4 translocation is an important cellular mechanism through which exercise enhances skeletal muscle glucose uptake in individuals with type 2 diabetes.

Effect of beta-glucan from oats and yeast on serum lipids.

Heart disease is the leading cause of death in the U.S. One way to reduce the risk of developing the disease is to lower serum cholesterol levels by making dietary changes. In addition to reducing intake of total fat, saturated fat, and dietary cholesterol, serum cholesterol can be further reduced by added fiber, especially from sources rich in beta-glucan. In this review, two sources of beta-glucan are described; one source is oats and the other yeast. Their chemical structures and physical properties are compared, and their effect on serum lipid levels is described. Oat beta-glucans are found in various breakfast cereals and snacks. Usually, several servings of these products are required to meet the Food and Drug Administration's claim of reducing the risk of heart disease. The yeast-derived fiber is a more concentrated source of beta-glucan than the oat product. It is currently being tested in a wide variety of food products.