Treatment of cholera-like diarrhoea with oral rehydration.

Cholera diarrhoea remains a major global health problem that has caused seven pandemics. The pathogenesis of cholera is attributable to the production of cholera toxin by the causative pathogen, Vibrio cholerae. The toxin causes increased production of cyclic adenosine monophosphate and this results in massive water and electrolyte secretion into the intestinal lumen. These changes manifest clinically as the painless defecation of voluminous stools that resemble 'rice water', leading to severe dehydration. The cornerstone in the management of cholera diarrhoea is the use of oral rehydration solutions (ORS) to replace the water and electrolytes lost as stools. The World Health Organization recommends the use of ORS of 'reduced osmolarity' for the treatment of acute non-cholera diarrhoea and the use of rice-based ORS for the management of cholera diarrhoea. Although several attempts have been made to improve ORS, studies to evaluate some of the modifications, which include the addition of amylase-resistant starch, the use of amino acids (such as glycine, alanine and glutamine) as sodium cotransporters, and zinc-supplemented ORS, are still needed.

A new central venous catheter cap: decreased microbial growth and risk for catheter-related bloodstream infection.

OBJECTIVE: Catheter-related blood stream infection (CRBI) is a major cause of morbidity and mortality, and is a source of significant healthcare expenditures in patients that require central venous catheters for intravenous nutrition, chemotherapy, and other products. The source of many catheter-related infections is contamination of the catheter hub. Herein an antimicrobial catheter cap, the AB Cap is described. METHODS: The AB Cap device is a catheter cleaning device designed to keep needleless luer valves clean by encapsulating them in a cleaning solution. This device was evaluated using an in vitro model of hub contamination with Staphylococcus aureus, Staphylococcus epidermidis (S. epidermidis), Klebsiella pneumonia (K. pneumonia), Pseudomonas aeruginosa, Escherichia coli and Candida albicans (C. albicans). Following hub contamination on days 1, 3, 5 and 7, saline was infused through the AB Cap and effluent collected from the efferent end. The effluent fluid was cultured for the index organisms, and allowed to incubate in culture for up to 7 days. Negative control caps were not contaminated and positive controls lacked cleaning solution and were contaminated. RESULTS: Microbial growth developed for all index organisms, and generally within 1 day of culture growth following the first day of contamination (day 1) in effluent from all positive controls, while no growth occurred in effluent from negative controls. No growth of any organism occurred in any of the test items after the first day of contamination. Growth of three organisms was detected in two of the three test AB Caps following contamination day 3, after 1-4 days of incubation. All organisms could be cultured in the effluent from two of the three test items at contamination day 5, generally by the second day of incubation. One test item remained free of growth for the entire test period except for one organism. By day 7, this particular test item grew an additional organism and the testing was concluded. All positive growth test items remained positive on subsequent inoculations during culture of newly obtained effluent with the exception of test item A, from which effluent following inoculation on day 3 showed growth of S. epidermidis and K. pneumonia, but no growth for these organisms from effluent obtained on inoculation day 5. In addition, effluent from test item C showed growth of C. albicans from inoculation day 5, but no growth from effluent obtained on inoculation day 7. The growth of S. epidermidis from effluent of test item A from the day 3 inoculation, and C. albicans from effluent of test items B and C did not occur until day 4 of incubation, suggesting a very small amount of contamination. CONCLUSION: An antimicrobial catheter cap is not a complete substitute for a proper catheter cleaning technique and other anti-infection precautions. However, we describe a unique catheter cap that significantly decreased the likelihood of a catheter-related infection from a non-cleaned cap in an in vitro model.

Total parenteral nutrition: challenges and practice in the cirrhotic patient.

Patients with cirrhosis develop metabolic derangements of protein, carbohydrate, and lipid metabolism. Malnutrition is commonplace and is associated with morbidity and mortality. Specific nutrient deficiencies may occur and enteral or parenteral nutritional support may improve outcome in appropriately selected patients. Parenteral nutrition itself has been associated with hepatic dysfunction, although the preponderance of evidence suggests that hepatic dysfunction is more a function of the underlying disorder and malabsorption. Intravenously infused organic nutrients may be metabolized differently than the same nutrient consumed enterally. The pathophysiology of total parenteral nutrition-associated liver disease is discussed as well as potential management options.

Double blind, placebo controlled trial of the remission inducing and steroid sparing properties of an ICAM-1 antisense oligodeoxynucleotide, alicaforsen (ISIS 2302), in active steroid dependent Crohn's disease.

BACKGROUND AND AIMS: To evaluate the safety and efficacy of the intercellular adhesion molecule 1 (ICAM-1) antisense phosphorothioate oligonucleotide alicaforsen (ISIS 2302) in Crohn's disease. METHODS: Active (Crohn's disease activity index (CDAI) 200-350), steroid dependent (prednisone 10-40 mg) Crohn's patients were randomised into three treatment groups: placebo versus ISIS 2302 (2 mg/kg intravenously three times a week) for two or four weeks. Patients were treated in months 1 and 3, with steroid withdrawal attempted by week 10. The primary end point (steroid free remission) was a CDAI <150 off steroids at the end of week 14. RESULTS: A total of 299 patients were enrolled, with a mean baseline CDAI of 276 and steroid dose of 23 mg/day. Rates of steroid free remission were equivalent for the two and four week ISIS 2302 groups (20.2% and 21.2%) and the placebo group (18.8%). At week 14, steroid withdrawal was successful in more ISIS 2302 patients compared with placebo treated patients (78% v 64%; p=0.032). Steroid free remission was highly correlated with exposure (p=0.0064). Other clinical responses were correlated with exposure, with significant results versus placebo being observed in the highest area under the curve subgroup. CDAI scores decreased by 136 (112) at week 14 versus 52 (107) for placebo (p=0.027) and inflammatory bowel disease score questionnaire improved by 43 (31) versus 15 (36) for placebo (p=0.027). CONCLUSIONS: Although the primary outcomes failed to demonstrate efficacy, pharmacodynamic modelling suggests that alicaforsen (ISIS 2302) may be an effective therapy for steroid dependent Crohn's disease.

Nutritional and metabolic considerations in the etiology of nonalcoholic steatohepatitis.

The aim of this study was to determine if a relationship exists between nonalcoholic steatohepatitis (NASH) and serum levels of free fatty acids, choline deficiency, or celiac disease. Forty-seven patients with liver biopsy proven NASH were enrolled. Total serum free fatty acids and anti-endomysial antibodies were determined in all patients, while plasma free and phospholipid-bound choline were determined in 29 patients. Total serum free fatty acid concentration correlated significantly with female gender and serum albumin concentration. Patients with severe fibrosis on liver biopsy had significantly greater serum concentration of free fatty acids than patients without severe fibrosis. Plasma free and phospholipid-bound choline levels were normal and no significant correlation was found between the concentration of plasma free or phospholipid bound choline, and the severity of liver damage. Only one of the 47 patients with NASH had a positive titer for the anti-endomysial antibody. In conclusion, increased serum concentrations of free fatty acids were found in NASH and were associated with development of more severe liver disease. Neither choline deficiency nor celiac sprue by anti-endomysial antibody testing was associated with NASH.

Side effects of corticosteroid therapy.

BACKGROUND: Corticosteroids have been used for the treatment of inflammatory bowel disease since the late 1940s. Upwards of 80% of patients may respond acutely to treatment with these medications, although 20% or more may be refractory and others become dependent on corticosteroid use to suppress disease activity. Side effects in the acute situation are relatively minor, although significant side effects (e.g., psychosis) have been encountered; the long-term use of corticosteroids is more problematic. This creates a milieu for the potential for serious and irreversible problems. These side effects are discussed in detail. The side effects from corticosteroids emulate from exogenous hypercortisolism, which is similar to the clinical syndrome of Cushing's disease. STUDY: PubMed search for years 1966-2000, author's personal manuscript/abstract files, and citations of known references. CONCLUSION: Short-term corticosteroid use is associated with generally mild side effects, including cutaneous effects, electrolyte abnormalities, hypertension, hyperglycemia, pancreatitis, hematologic, immunologic, and neuropsychologic effects, although occasionally, clinically significant side effects may occur. Long-term corticosteroid use may be associated with more serious sequel, including osteoporosis, aseptic joint necrosis, adrenal insufficiency, gastrointestinal, hepatic, and ophthalmologic effects, hyperlipidemia, growth suppression, and possible congenital malformations.

Hyperbaric oxygen therapy for severe ulcerative colitis.

Hyperbaric oxygen therapy has been used to successfully treat perineal Crohn's disease. We describe the first successful use of hyperbaric oxygen therapy in the treatment of ulcerative colitis, refractory to conventional therapies. Therapy consisted of 30 courses of 100% oxygen at a pressure of 2.0 atm absolute. Clinical remission was achieved on the basis of the Truelove-Witts and disease activity index scores. Corticosteroids were successfully tapered off once remission was achieved.

Choline deficiency causes reversible hepatic abnormalities in patients receiving parenteral nutrition: proof of a human choline requirement: a placebo-controlled trial.

BACKGROUND: Previous studies have shown that plasma free choline concentrations are significantly decreased in many long-term home total parenteral nutrition (TPN) patients. Furthermore, low choline status has been associated with both hepatic morphologic and hepatic aminotransferase abnormalities. A preliminary pilot study suggested choline-supplemented TPN may be useful in reversal of these hepatic abnormalities. METHODS: Fifteen patients (10 M, 5 F) who had required TPN for > or =80% of their nutritional needs were randomized to receive their usual TPN (n = 8), or TPN to which 2 g choline chloride had been added (n = 7) for 24 weeks. Baseline demographic data were similar between groups. Patients had CT scans of the liver and spleen, and blood for plasma free and phospholipid-bound choline, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, gamma glutamyl transferase (GGT), bilirubin, serum lipids, complete blood count (CBC), and chemistry profile obtained at baseline, and weeks 2, 4, 6, 12, 16, 20, 24, and 34. CT scans were analyzed for Hounsfield unit (HU) densities. RESULTS: There were no significant differences in any measured parameters after 2 weeks. However, at 4 weeks, a significant difference in liver HU between groups was observed (13.3+/-5.0 HU [choline] vs 5.8+/-5.2 HU [placebo], p = .04). This significant trend continued through week 24. Recurrent hepatic steatosis and decreased HU were observed at week 34, 10 weeks after choline supplementation had been discontinued. A significant increase in the liver-spleen differential HU was also observed in the choline group (10.6+/-6.2 HU [choline] vs 1.3+/-3.3 HU [placebo], p = .01). Serum ALT decreased significantly (p = .01 to .05) in the choline group vs placebo at weeks 6,12, 20, and 24. Serum AST was significantly decreased in the choline group by week 24 (p = .02). The serum alkaline phosphatase was significantly reduced in the choline group at weeks 2, 12, 20, 24, and 34 (p = .02 to 0.07). Total bilirubin was normal in these patients and remained unchanged during the study. Serum GGT tended to decrease more in the choline group, but the greater decrease was not statistically significant. CONCLUSIONS: Choline deficiency is a significant contributor to the development of TPN-associated liver disease. The data suggest choline is a required nutrient for long-term home TPN patients.

Glutamine: commercially essential or conditionally essential? A critical appraisal of the human data.

Glutamine is a nonessential amino acid that can be synthesized from glutamate and glutamic acid by glutamate-ammonia ligase. Glutamine is an important fuel source for the small intestine. It was proposed that glutamine is necessary for the maintenance of normal intestinal morphology and function in the absence of luminal nutrients. However, intestinal morphologic and functional changes related to enteral fasting and parenteral nutrition are less significant in humans than in animal models and may not be clinically significant. Therefore, it is unclear whether glutamine is necessary for the preservation of normal intestinal morphology and function in humans during parenteral nutrition. It was suggested that both glutamine-supplemented parenteral nutrition and enteral diets may pre-vent bacterial translocation via the preservation and augmentation of small bowel villus morphology, intestinal permeability, and intestinal immune function. However, it is unclear whether clinically relevant bacterial translocation even occurs in humans, much less whether there is any value in the prevention of such occurrences. Results of the therapeutic use of glutamine in humans at nonphysiologic doses indicate limited efficacy. Although glutamine is generally recognized to be safe on the basis of relatively small studies, side effects in patients receiving home parenteral nutrition and in those with liver-function abnormalities have been described. Therefore, on the basis of currently available clinical data, it is inappropriate to recommend glutamine for therapeutic use in any condition.

Organ heavy-metal accumulation during parenteral nutrition is associated with pathologic abnormalities in rats.

OBJECTIVES: Metabolic bone disease, hepatic abnormalities, splenic insufficiency, and nephropathy have been associated with long-term total parenteral nutrition (TPN). We determined the heavy-metal contamination in TPN solutions and investigated whether it was associated with organ deposition and pathologic organ damage. METHODS: Five representative TPN solutions (two adult standard solutions, one renal solution, and one standard pediatric solution to reflect clinical practice) and 28 TPN components were analyzed with inductively coupled plasma mass spectrometry. Twenty-six male Fisher 344 rats were assigned to two groups (chow/NaCl = 8 and TPN = 18). TPN or NaCl was infused at a rate of 50 mL/d. After 14 d, serum, femurs, spine, liver, kidneys, brain, spleen, and testes were analyzed for heavy-metal deposition by using inductively coupled plasma mass spectrometry. Tissues were fixed in formalin, sectioned, and stained with hematoxylin and eosin, periodic acid Schiff, and Masson's trichrome stain. Kidneys were fixed in gluteraldehyde for ultrastructural examination with scanning electron microscopy. RESULTS: The predominant sources of contaminants in TPN were amino acids (Al, As, Cr, Ge, Pb, Sn), dextrose (As, Ba, Cr, Sn), Ca gluconate (Al), K2PO4 (Al), lipid emulsion (As, Sn), and vitamins (As). Significant variations in the level of contamination depended on TPN formulation and brand of constituents. In the kidney, Pb, Cr, and Mn concentrations were greater than in controls, although there was no correlation with serum creatinine. Hepatic Cr and Pb concentrations were greater in TPN rats, although there was no correlation with serum aspartate aminotransferase or total bilirubin. Splenic Ba, Cr, Ge, Pb, Mn, and Sn concentrations were greater in TPN rats. Only serum Cr concentration was significantly correlated with splenic concentration (r = 0.46, P = 0.04). Brain and serum Ba concentrations were significantly correlated (r = 0.60, P = 0.007). No significant correlations were observed between any other metal in serum and that metal's respective organ concentration. No increase in heavy-metal accumulation was seen in the femur, spine, or testis. There were no significant depositions of As, Cd, Hg, St, or V in any of the organs examined. Serum Al and Cr concentrations were significantly increased in TPN rats, although there was no correlation with tissue concentrations. No significant increases in heavy-metal concentrations in tissue or plasma were observed for any of the other metals measurable by inductively coupled plasma mass spectrometry. Histologically in the TPN group, 50% of the rats had mild to moderate hepatic steatosis and 33% to 50% developed renal morphologic abnormalities; brains and spleens remained histologically normal. CONCLUSIONS: We found significant heavy-metal contamination of TPN solutions, and this contamination can lead to organ deposition and subsequent histologic abnormalities.

Complications of long-term home total parenteral nutrition: their identification, prevention and treatment.

The purpose of this review is to describe the most common complications of home total parenteral nutrition, their identification, treatment and prevention. Data sources were manuscripts and abstracts published in the English literature since 1968. Studies were selected for summarization in this review on the basis of clinical relevance to the practicing clinician. Home total parenteral nutrition is a relatively safe, life-saving method for nutrient delivery in patients with compromised gastrointestinal function. However, numerous complications, with associated morbidity and mortality, involving the delivery system and the gastrointestinal, renal, and skeletal systems may develop. Catheter-related complications are often preventable and treatable when they occur, although renal and bone abnormalities have elusive etiologies.

Verbal and visual memory improve after choline supplementation in long-term total parenteral nutrition: a pilot study.

BACKGROUND: Previous investigations have demonstrated that choline deficiency, manifested in low plasma-free choline concentration and hepatic injury, may develop in patients who require long-term total parenteral nutrition (TPN). Preliminary studies have suggested lecithin or choline supplementation might lead to improved visual memory in the elderly and reverse abnormal neuropsychological development in children. We sought to determine if choline-supplemented TPN would lead to improvement in neuropsychological test scores in a group of adult, choline-deficient outpatients receiving TPN. METHODS: Eleven subjects (8 males, 3 females) who received nightly TPN for more than 80% of their nutritional needs for at least 12 weeks before entry in the study were enrolled. Exclusion criteria included active drug abuse, mental retardation, cerebral vascular accident, head trauma, hemodialysis or peritoneal dialysis, (prothrombin time [PT] >2x control), or acquired immune deficiency syndrome (AIDS). Patients were randomly assigned to receive their usual TPN regimen (n = 6, aged 34.0 +/- 12.6 years) over a 12-hour nightly infusion or their usual TPN regimen plus choline chloride (2 g) (n = 5, aged 37.3 +/- 7.3 years). The following neuropsychological tests were administered at baseline and after 24 weeks of choline supplementation (or placebo): Weschler Adult Intelligence Scale-Revised (WAIS-R, intellectual functioning), Weschler Memory Scale-Revised (WMS-R, two subtests, verbal and visual memory), Rey-Osterrieth Complex Figure Test (visuospatial functioning and perceptual organization), Controlled Oral Word Association Test (verbal fluency), Grooved Pegboard (manual dexterity and motor speed), California Verbal Learning Test (CVLT, rote verbal learning ability), and Trail Making Parts A & B (visual scanning, psychomotor speed and set shifting). Scores were reported in terms of standard scores including z scores and percentile ranks. Mean absolute changes in raw scores were compared between groups using the Wilcoxon rank sum test, where p values < .05 constituted statistical significance. RESULTS: Significant improvements were found in the delayed visual recall of the WMS-R (7.0 +/- 2.7 vs -.33 +/- 5.7, p = .028), and borderline improvements in the List B subset of the CVLT (1.0 +/- 0.8 vs -2.0 +/- 2.4, p = .06) and the Trails A test (-3.8 +/- 8.1 vs 3.7 +/- 4.5 seconds, p = .067). No other statistically significant changes were seen. CONCLUSIONS: This pilot study indicates both verbal and visual memory may be impaired in patients who require long-term TPN and both may be improved with choline supplementation.

Plasma choline in normal newborns, infants, toddlers, and in very-low-birth-weight neonates requiring total parenteral nutrition.

Choline deficiency is associated with hepatic abnormalities in adult volunteers and patients administered total parenteral nutrition (TPN). Preliminary investigation has suggested that plasma-free choline concentration (PFCh) is greater in neonatal animals, including humans, than in adults. The aims of this study were to determine the normal PFCh and phospholipid-bound choline concentration (PPLBCh) for newborns, infants, and toddlers and to determine the change during TPN. We also sought to determine the degree of fetal choline extraction, the relation between maternal and newborn plasma choline concentrations, and the relation between plasma choline status and normal newborn length, weight, and gestational age. Blood samples were obtained from 104 full-term newborns in two centers (Ben Taub and Maimonides), 25 mothers, 21 normal infants aged 20.3 +/- 11.8 wk, 12 normal infants aged 62.4 +/- 3.9 wk, and 14 preterm infants (gestational age = 28.9 +/- 2.2 wk) who required TPN. The vein PFChs were 28.1 +/- 13.0 nmol/mL (Ben Taub) and 68.1 +/- 16.9 nmol/mL (Maimonides). The artery PFChs were 27.1 +/- 13.0 nmol/mL (Ben Taub) and 57.9 +/- 11.6 nmol/mL (Maimonides). The vein PPLChs were 1004.7 +/- 246.6 nmol/mL (Ben Taub) and 1121.2 +/- 289.6 nmol/mL (Maimonides). The artery PPLChs were 1065.7 +/- 469.3 nmol/mL (Ben Taub) and 1106.9 +/- 285.8 nmol/mL (Maimonides). The vein-minus-artery differences for PFCh were 1.0 +/- 9.7 nmol/mL (Ben Taub) and 10.2 +/- 10.9 nmol/mL (Maimonides). The vein-minus-artery differences for PPLCh were -51.9 +/- 398.2 nmol/mL (Ben Taub General Hospital, Houston, Texas) and 14.4 +/- 254.3 nmol/mL (Maimonides, New York, New York). Maternal venous PFCh was 8.4 +/- 3.1 nmol/mL. Maternal venous PPLCh was 2592.1 +/- 584.0 nmol/mL (range = 1227.8-3729.0). Maternal venous PFCh correlated with newborn arterial PFCh (r = 0.53, P < 0.05) but not with newborn venous PFCh. No correlation was seen between maternal venous and newborn PPLCh. No significant differences were seen in PPLCh or choline extraction in Ben Taub versus Maimonides patients, although PFCh was significantly greater in the newborns from Maimonides (P < 0.05). The mean venous PFCh and PPLCh in the preterm infants before beginning TPN was 21.2 +/- 6.3 and 1366.8 +/- 339.1 nmol/mL, respectively. Just before initiation of tube feeding (4.0 +/- 2.7 d after TPN had been started), mean venous PFCh and PPLCh was 18.4 +/- 5.3 and 2251.8 +/- 686.9 nmol/mL, respectively. When TPN was discontinued and tube feeding increased to goal, after 10.8 +/- 10.4 d, venous PFCh and PPLCh was 22.6 +/- 8.7 and 2072.5 +/- 540.6 nmol/mL, respectively. Venous PFCh and PPLCh was 13.4 +/- 2.5 and 1827.5 +/- 327.0 nmol/mL, respectively in the older infant group. In conclusion, newborn PFCh is significantly greater than PFCh in adults but falls to adult levels within the first year of life. Low maternal PFCh may be associated with low newborn PFCh. Normal newborn plasma choline status has no bearing on intrauterine growth, although the role of maternal choline deficiency in underweight newborns is unknown. Newborn PPLCh is substantially below that of adults, which suggests its use in membrane synthesis during growth.

Metabolic bone disease in IBD.

A substantial number of patients with inflammatory bowel disease (IBD) will manifest extra-intestinal complications. Metabolic bone disease and arthropathies are among the most debilitating of these. Decreased bone mineral density and increased fracture risk may occur in relation to the underlying disease itself or result from vitamin, mineral, and hormonal deficiencies; medications used to treat the underlying disease; lifestyle; and perhaps other factors. In many cases, the factors remain unidentified. Options for the treating clinician include correction of these deficiencies, treatment of the underlying disease, and use of medication to promote bone formation and decrease bone resorption.