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Biomedical subjects

Stephen J D O'Keefe

Publications and source records attributed to Stephen J D O'Keefe.

16 recordsLinked to original sources
PubMed2007

Why do African Americans get more colon cancer than Native Africans?

The incidence of colorectal cancer (CRC) is dramatically higher in African Americans (AAs) than in Native Africans (NAs) (60:100,000 vs. <1:100,000) and slightly higher than in Caucasian Americans (CAs). To explore whether the difference could be explained by interactions between diet and colonic bacterial flora, we compared randomly selected samples of healthy 50- to 65-y-old AAs (n = 17) with NAs (n = 18) and CAs (n = 17). Diet was measured by 3-d recall, and colonic metabolism by breath hydrogen and methane responses to oral lactulose. Fecal samples were cultured for 7-alpha dehydroxylating bacteria and Lactobacillus plantarum. Colonoscopic mucosal biopsies were taken to measure proliferation rates. In comparison with NAs, AAs consumed more (P < 0.01) protein (94 +/- 9.3 vs. 58 +/- 4.1 g/d) and fat (114 +/- 11.2 vs. 38 +/- 3.0 g/d), meat, saturated fat, and cholesterol. However, they also consumed more (P < 0.05) calcium, vitamin A, and vitamin C, and fiber intake was the same. Breath hydrogen was higher (P < 0.0001) and methane lower in AAs, and fecal colony counts of 7-alpha dehydroxylating bacteria were higher and of Lactobacilli were lower. Colonic crypt cell proliferation rates were dramatically higher in AAs (21.8 +/- 1.1% vs. 3.2 +/- 0.8% labeling, P < 0.0001). In conclusion, the higher CRC risk and mucosal proliferation rates in AAs than in NAs were associated with higher dietary intakes of animal products and higher colonic populations of potentially toxic hydrogen and secondary bile-salt-producing bacteria. This supports our hypothesis that CRC risk is determined by interactions between the external (dietary) and internal (bacterial) environments.

Africa↗
PubMed2006

Small bowel transplantation.

Until very recently, outcomes from small bowel transplantation (SBTx) lagged behind those in liver, heart, and kidney transplantation because of the magnitude of the immunologic burden; the strong expression of histocompatibility antigens; and the contamination in grafts by bacterial organisms. With novel techniques of immune-induction therapies, such as recipient "preconditioning" with lymphocyte reduction, followed by the more subtle use of immunosuppression-based single-agent tacrolimus, graft and host 1-year survival is now over 90% in the most active US centers, a finding that parallels the outcomes in liver and kidney transplantation. In contrast to the alternative therapy for permanent intestinal failure, home total parenteral nutrition (TPN), SBTx improves quality of life and restores digestive and absorptive function, making patients nutritionally autonomous. With survival beyond 1 to 3 years, the procedure is cost-effective. Current results support expansion of the indications for SBTx from use as salvage therapy for patients with TPN failure to preemptive therapy for patients at risk of developing TPN failure.

Aged↗
PubMed2006

Short bowel syndrome and intestinal failure: consensus definitions and overview.

Short bowel syndrome (SBS)-associated intestinal failure is a highly disabling condition that impairs quality of life and social integration. Although the condition is not uniformly fatal, it might lead to serious, life-threatening complications. The basic goals of medical treatment are to maintain fluid, electrolyte, and nutrient balances and to make appropriate modifications in disease management to avoid side effects. Various definitions have been proposed for SBS and intestinal failure within the medical literature, but many focus on different aspects of the conditions, leading to confusion. In the past, identifying the cause of intestinal failure was of little consequence, because all patients were managed on total parenteral nutrition at home. However, with the recent development of medical therapies such as recombinant growth hormone, octreotide, and glucagon-like peptide-2 analogues and with improvements in small bowel transplantation, many patients can be made nutritionally autonomous. To evaluate the relative efficacy of these therapies, there is now a need to develop consensus definitions so that patients can be properly categorized before therapy. To this end, a group of experts on the subject was convened to develop the following new definitions: "Intestinal failure results from obstruction, dysmotility, surgical resection, congenital defect, or disease-associated loss of absorption and is characterized by the inability to maintain protein-energy, fluid, electrolyte, or micronutrient balance." "Short-bowel syndrome results from surgical resection, congenital defect, or disease-associated loss of absorption and is characterized by the inability to maintain protein-energy, fluid, electrolyte, or micronutrient balances when on a conventionally accepted, normal diet."

Humans↗
PubMed2006

Treatment of intestinal failure: home parenteral nutrition.

Intestinal failure can result from surgical resection, obstruction, dysmotility, congenital deficiencies or disease-associated loss of absorption. Before the development of intravenous feeding in the late 1960s, the condition was fatal, but by the 1990s approximately 40,000 patients were being successfully managed on long-term home parenteral nutrition (HPN) annually in the US. Survival on HPN depends on the nature of the underlying medical condition: over 80% of Crohn's disease patients survive for 5 years, but only 20% of cancer patients survive for 1 year. Although a patient's nutritional status is easy to maintain, there are serious long-term complications that arise from bypassing the gut and infusing nutrients directly into the systemic circulation. Catheter sepsis occurs about once per year (range 0-12 times). Abnormalities in liver function tests are common, but end-stage liver disease is rare. Central venous thrombosis develops in nearly all patients after 5 years. Although approximately 80% of patients on HPN are completely rehabilitated at home, their quality of life is impaired by the perpetual dependence on nocturnal intravenous infusions (every 8-12 h). In conclusion, HPN has allowed patients with previously fatal intestinal failure to survive and lead relatively normal lives at home, but their quality of life remains impaired by the dependence on intravenous infusions and complications that progress with time.

Clinical Trials as Topic↗
PubMed2006

Candidacy for intestinal transplantation.

A recent report from the American Small Bowel Transplant Registry (2003) has highlighted the significant progressive increase in graft and host survival to over 80% at 1 yr, suggesting that a new era has dawned, and that soon transplantation may offer an attractive alternative to any patient with permanent intestinal failure. In order to investigate the potential candidacy for small bowel transplantation in Western Europe, 854 home long-term parenteral nutrition (TPN) patients and their physicians were surveyed in nine countries. Their results demonstrated that only a small proportion of patients were considered candidates, but that candidacy was higher in the pediatric population (34% vs 16%, respectively). Despite the general acceptance in the United States that the development of the complication of liver failure in home TPN patients is an indication for urgent transplantation, "immediate candidacy" was only made by physicians in 36% of such adults and 43% of such children. This study reveals that there remains reluctance in Europe to refer patients for transplantation, even when life-threatening complications have developed. Further investigations need to be performed to determine whether this was because of inaccessibility to a transplant center or unfamiliarity with the procedure and its outcomes.

Adolescent↗
PubMed2005

Trypsin secretion and turnover in patients with acute pancreatitis.

Studies in humans have shown that pancreatic enzyme secretion is reduced during acute pancreatitis. It is not known, however, whether the reduction is due to impaired synthesis or disruption of the secretory pathway. The rate of secretion and turnover of trypsin was measured in 12 patients with acute pancreatitis of variable etiology and severity (median Ranson's score 2.5, range 0-5, 4 with severe necrotizing disease) and eight healthy volunteers by 4-h primed/continuous intravenous infusions of 1-(13)C-labeled l-leucine, and collection of pancreatic secretions by duodenal perfusion and sampling. Trypsin secretion was reduced from 476 +/- 73 to 153 +/- 60 U/h (means +/- SE, P = 0.005) in acute pancreatitis, with the greatest reductions being observed in patients with necrotizing disease (32 +/- 7 U/h, P = 0.003). The time for newly labeled trypsin to first appear in digestive juice was not, however, delayed in pancreatitis patients (87.2 +/- 11.1 vs. 94.7 +/- 4.9 min); on the contrary, there was an early appearance of newly labeled trypsin at 30 min in patients with severe necrotizing pancreatitis (P < 0.05). Calculated zymogen pool turnover was unchanged, but pool size was decreased (P = 0.01). Despite low rates of luminal secretion, trypsin continues to be synthesized in patients with acute pancreatitis. Our findings could be explained by post-Golgi leakage of enzymes from acinar cells or by loss of synthetic function in some cells with preservation in others.

Adolescent↗
PubMed2005

Enteral feeding without pancreatic stimulation.

OBJECTIVE: All forms of commonly practiced enteral feeding techniques stimulate pancreatic secretion, and only intravenous feeding avoids it. In this study, we explored the possibility of more distal enteral infusions of tube feeds to see whether activation of the ileal brake mechanism can result in enteral feeding without pancreatic stimulation, with particular reference to trypsin, because the avoidance of trypsin stimulation may optimize enteral feeding in acute pancreatitis. METHODS: The pancreatic secretory responses to feeding were studied in 36 healthy volunteers by standard double-lumen duodenal perfusion/aspiration techniques over 6 hours. Subjects were assigned to no feeding (n = 7), duodenal feeding with a polymeric diet (n = 7) or low-fat elemental diet (n = 6), mid-distal jejunal feeding (n = 11), or intravenous feeding (n = 5). All diets provided 40 kcal/kg ideal body weight/d and 1.5 g protein/kg ideal body weight/d. Plasma gut peptide responses were monitored in 15 subjects. RESULTS: In comparison with basal fasting trypsin secretion rates (mean = 134 [standard error = 22] U/h), duodenal feeding with the polymeric and elemental formulae stimulated trypsin secretion (mean = 408 [standard error = 51] U/h; P < 0.001), whereas intravenous feeding (mean = 171 [standard error = 34] U/h) and mid-distal jejunal (mean = 119 [standard error = 16] U/h) did not. Stimulation was associated with an increase in plasma cholecystokinin, whereas distal jejunal feeding resulted in an increase in plasma glucagon-like peptide-1 and peptide YY concentrations. CONCLUSIONS: Our results suggest that enteral feeding can be given without stimulating pancreatic trypsin secretion provided it is delivered into the mid-distal jejunum. The mechanism may involve activation of the ileal brake mechanism.

Adult↗
PubMed2004

Differential effect of saturated and polyunsaturated fatty acids on hepatic glucose metabolism in humans.

Prolonged infusions of lipid and heparin that achieve high physiological free fatty acid (FFA) concentrations inhibit hepatic (and peripheral) insulin sensitivity in humans. These infusions are composed largely of polyunsaturated fatty acids (PUFA; linoleic and linolenic). It is not known whether fatty acid composition per se affects hepatic glucose metabolism in humans. To address this issue, we examined the impact of enteral infusions of either palm oil (48% palmitic, 35% oleic, and 8% linoleic acids) or safflower oil (6% palmitic, 12% oleic, 74% linoleic acids) in 14 obese nondiabetic subjects. (2)H(2)O was administered to determine the contribution of gluconeogenesis to endogenous glucose production (EGP), and a primed continuous infusion of [6,6-(2)H]glucose was administered to assess glucose appearance. As a result of the lipid infusions, plasma FFA concentrations increased significantly in both the palm oil (507.5 +/- 47.4 to 939.3 +/- 61.3 micromol/l, P < 0.01) and safflower oil (588.2.0 +/- 43.0 to 857.8 +/- 68.7 micromol/l, P < 0.01) groups after 4 h. EGP was similar at baseline (12.4 +/- 1.8 vs. 11.2 +/- 1.0 micromol x kg FFM(-1) x min(-1)). During a somatostatin-insulin clamp, the glucose infusion rate was significantly lower (AUC glucose infusion rate 195.8 +/- 50.7 vs. 377.8 +/- 38.0 micromol/kg FFM, P < 0.01), and rates of EGP were significantly higher (10.7 +/- 1.4 vs. 6.5 +/- 1.5 micromol x kg FFM(-1) x min(-1), P < 0.01) after palm oil compared with safflower oil, respectively. Baseline rates of gluconeogenesis and glycogenolysis were also similar. However, after lipid infusion, rates of glycogenolysis were suppressed by safflower oil but not by palm oil. Thus these studies demonstrate, for the first time in humans, a differential effect of saturated fatty acids and PUFA on hepatic glucose metabolism.

Adult↗
PubMed2004

Nutritional support in acute pancreatitis.

Acute pancreatitis is one of the most catabolic of critical illnesses, and its clinical course is often prolonged. Consequently, the need for interventional nutritional support is great. Because of fears that feeding might exacerbate the tryptic autodigestion and disease process, total parenteral nutrition was used exclusively until recent years, when it was recognized that the complications of hyperglycemia and sepsis outweighed nutritional benefits. In clinical practice, enteral feeding has proven superior because it avoids these complications and maintains gut function, but enteral feeding needs to be given in a form that minimizes pancreatic stimulation. This review discusses the advances in our understanding of the pathophysiology of the disease, the results of recent clinical trials of nutritional support, and the challenges that remain in optimizing nutritional management.

Acute Disease↗
PubMed2004

Severe acute pancreatitis: nutritional management in the ICU.

Patients with acute pancreatitis have elevated nutritional needs due to increased energy expenditure and catabolism. It is a clinical challenge to provide adequate nutrition to these patients while maintaining gut function, preventing pancreatic stimulation, and minimizing the risk of septic and metabolic complications associated with nutritional support. We present the case of a patient who had severe acute pancreatitis and was initially given total parenteral nutrition. After a period of initial improvement, he developed hyperglycemia, bacteremia, and sepsis. Parenteral nutrition was discontinued and infection was treated with antibiotics. Subsequent nutritional support consisted of enteral feeding with an elemental diet infused via a nasojejunal feeding tube. His condition improved gradually and he made a full recovery. This case illustrates the difficulties encountered while managing a case of severe acute pancreatitis and provides an evidence based approach to the nutritional management of severe acute pancreatitis in the intensive care unit setting.

Journal Article↗
PubMed2003

Physiological effects of enteral and parenteral feeding on pancreaticobiliary secretion in humans.

In the nutritional management of digestive disorders, it is important to know the relative secretory and metabolic responses to enteral and parenteral feeding. Twenty-seven healthy volunteers were studied while receiving either oral drinks or duodenal infusions of a complex formula diet, duodenal or intravenous infusions of elemental (protein as free amino acids, low fat) formulae, or saline. Pancreaticobiliary secretory responses were measured by nasoduodenal polyethylene glycol perfusion and aspiration, while monitoring blood hormone and nutrient levels. Diets were matched for protein (1.5 g x kg(-1) x d(-1)) and energy (40 kcal x kg(-1) x d(-1)). Compared with placebo, all oroenteral diets stimulated amylase, lipase, trypsin, and bile acid secretion and increased plasma concentrations of gastrin and cholecystokinin, whereas intravenous feeding did not. The complex formula produced a similar response whether given as drinks or duodenal infusions. Changing the duodenal formula to elemental reduced enzyme secretion by 50%, independently of CCK. Higher increases in plasma insulin, glucose, and amino acids were noted with intravenous feeding. Delivering food directly to the intestine by a feeding tube does not reduce pancreaticobiliary secretion. Enteral "elemental" formulae diminish, but only intravenous feeding avoids pancreatic stimulation. Intravenous administration impairs metabolic clearance.

Adult↗
PubMed2003

Nutrition in the management of necrotizing pancreatitis.

Comparative trials have shown that enteral feeding (EN) is better than total parenteral nutrition (TPN) in acute pancreatitis. However, the following case report of a 64-year-old man with necrotizing pancreatitis suggests that EN may cause complications in patients with ductular damage. In the second week, this patient with acute pancreatitis developed >50% pancreatic necrosis, resulting in gastroduodenal obstruction and pain, leading to the use of TPN. A trial of EN delivered past the obstruction was associated with increased abdominal pain, leukocytosis, and pancreatic fluid accumulation. Measurement of the pancreatic response to feeding showed a 90% reduction in enzyme secretion compared to healthy volunteers, but no change in the uptake of stable isotope labeled amino acids into secreted trypsin. This suggests that enzymes were being synthesized by the remaining pancreatic tissue, but that some of the secretions were leaking into the inflammatory mass. Symptoms resolved after reinstitution of TPN and bowel rest. A further trial of EN was successful when the tube was advanced to the distal jejunum to avoid pancreatic stimulation. After 3 weeks of home EN, he was readmitted for surgical evacuation of an infected fluid collection. Although enteral feeding is generally better than TPN in the nutritional management of acute pancreatitis, there may be a subgroup of patients with ductular damage due to necrotizing disease in whom TPN and pancreatic rest may be safer.

Disease Management↗
PubMed2002

Hypocaloric jejunal feeding is better than total parenteral nutrition in acute pancreatitis: results of a randomized comparative study.

OBJECTIVES: The aims of this study were to define the indications for, and to evaluate the cost-effectiveness of, nutritional support in patients with acute pancreatitis. METHODS: All admissions during the 12-month period from January through December 2000, were entered into a common management protocol consisting of an initial 48-h fast with i.v. fluids and analgesics. After 48 h, those patients who were improving were restarted on oral feeding (group O). The remaining patients were randomized to receive nasojejunal (group EN) or parenteral feeding (group TPN). The randomization study was continued until 50 patients had been accrued. Outcomes in the three groups were compared with respect to length of hospital stay, duration of feeding, complications, and hospital costs. RESULTS: A total of 156 admissions were evaluated in the first 12 months. Of these, 87% patients had mild disease, 10% moderate, and 3% severe; 62% were related to alcohol abuse, 18% gallstones, and 8% idiosyncratic drug reactions. Of the patients, 75% improved on 48 h bowel rest and i.v. fluids, and were discharged within 4 days. The remainder were randomized to jejunal elemental (n = 26) or parenteral (n = 27) feeding. Duration of feeding was shorter with EN (6.7 vs 10.8 days, p < 0.05) and nutrition costs were lower, representing an average cost saving of $2362.00 per patient fed. EN was less effective in meeting estimated nutritional requirements (54 vs 88%, p < 0.0001), but metabolic (p < 0.003) and septic complications (p = 0.01) were lower. Subgroup analysis of patients with severe disease showed similar findings. CONCLUSION: Despite concerns that metabolic expenditure is increased and that food-stimulated pancreatic secretion might exacerbate the disease process, hypocaloric enteral feeding seems to be safer and less expensive than parenteral feeding and bowel rest in patients with acute pancreatitis.

Acute Disease↗
PubMedDate not supplied

Nutrition support during acute pancreatitis.

Studies have shown that protein catabolism increases by 80% and energy expenditure by 20% in acute pancreatitis, indicating that nutritional requirements are elevated. Other studies have associated the resolution of negative nitrogen balance by nutrition support with improved outcome. Consequently, the need for effective nutrition is one cornerstone of management of acute pancreatitis. Concerns that feeding may exacerbate the disease process by stimulating the synthesis of proteolytic enzymes in the acinar cell and perpetuating autolysis has led to the widespread use of total parenteral nutrition (TPN) and bowel rest. Unfortunately, the use of TPN in clinical practice has been associated with major metabolic and infective complications, possibly because 1). patients with acute pancreatitis are intolerant of glucose due to coexistent pancreatic endocrine dysfunction and 2). the disease causes immune suppression. This has led to the search for alternatives. Based on physiologic studies, infusion of nutrients into the distal jejunum bypasses the stimulatory effect of feeding on pancreatic secretion. Many controlled trials have compared TPN with jejunal feeding. No study has shown that jejunal feeding exacerbates the disease. Further, jejunal feeding is associated with fewer infectious and metabolic complications. These observations and the fact that enteral feeding is one-tenth the cost of TPN has resulted in the general acceptance of jejunal feeding as the preferred mode for maintaining nutrition in patients with acute pancreatitis.

Acute Disease↗
PubMedDate not supplied

Transnasal endoscopic placement of feeding tubes in the intensive care unit.

BACKGROUND: There is an increasing demand for enteral feeding in intensive care unit (ICU) patients. However, gastroparesis is common, and jejunal placement with gastric decompression leads to delays in feeding. In an attempt to minimize delays, we describe our technique and results with transnasal endoscopic placement of double-lumen gastric aspiration, jejunal feeding tubes (DLFT). METHODS: Fifty-one consecutive ICU patients referred for nutrition support were studied; 29% had respiratory failure, 28% acute head injury, and 33% acute pancreatitis. A 5.8-mm ultraslim video endoscope was used to place a guidewire through the nose terminating beyond the Ligament of Treitz. After withdrawal of the endoscope, a DLFT was passed over the wire. Final position of the tube was checked and adjusted under direct vision by reendoscopy though the opposite nasal passage. RESULTS: Initial placement of the guidewire and DLFT was successful in 46 of 51 patients. Massive gastric dilatation and acute pancreatitis complicated by duodenal compression impeded full duodenoscopy in 5 patients, necessitating fluoroscopy for correct guidewire deployment. In confirming correct tube placement, there was near perfect concordance between reendoscopy and x-ray (45/46). Previously unrecognized upper gastrointestinal tract pathology was detected in most patients, with acute gastritis in 47, superficial gastric ulceration in 24, and erosive esophagitis in 5. CONCLUSIONS: Transnasal endoscopic placement of feeding tubes in the ICU is quick, effective, and minimally disruptive of intensive therapy. In addition, it can reveal unrecognized pathology, which potentially could lead to improvements in overall medical care.

Acute Disease↗