Robert G. Martindale

Structure and function of ATA3, a new subtype of amino acid transport system A, primarily expressed in the liver and skeletal muscle.

To date, two different transporters that are capable of transporting alpha-(methylamino)isobutyric acid, the specific substrate for amino acid transport system A, have been cloned. These two transporters are known as ATA1 and ATA2. We have cloned a third transporter that is able to transport the system A-specific substrate. This new transporter, cloned from rat skeletal muscle and designated rATA3, consists of 547 amino acids and has a high degree of homology to rat ATA1 (47% identity) and rat ATA2 (57% identity). rATA3 mRNA is present only in the liver and skeletal muscle. When expressed in Xenopus laevis oocytes, rATA3 mediates the transport of alpha-[(14)C](methylamino)isobutyric acid and [(3)H]alanine. With the two-microelectrode voltage clamp technique, we have shown that exposure of rATA3-expressing oocytes to neutral, short-chain aliphatic amino acids induces inward currents. The amino acid-induced current is Na(+)-dependent and pH-dependent. Analysis of the currents with alanine as the substrate has shown that the K(0. 5) for alanine (i.e., concentration of the amino acid yielding half-maximal current) is 4.2+/-0.1 mM and that the Na(+):alanine stoichiometry is 1:1.

Glutamine and the gastrointestinal tract.

The amino acid glutamine has become one of the most intensively studied nutrients in the field of nutrition and metabolic support. A variety of studies in cell culture systems, animal models of gut mucosal atrophy, injury/repair and adaptation and a limited number of clinical trials demonstrate trophic and cytoprotective effects of glutamine in small bowel and colonic mucosal cells. Although the routine clinical use of glutamine-enriched parenteral and enteral nutrient solutions remains controversial, available data demonstrate both the safety and metabolic and clinical efficacy of glutamine treatment in selected patient groups. Basic investigations are elucidating underlying mechanisms of glutamine action in intestinal cells. These will inform preclinical and clinical investigations designed to determine glutamine efficacy in selected gastrointestinal disorders. Emerging clinical trials will further define the utility of adjunctive glutamine supplementation as a component of specialized nutrition support in gastrointestinal disease.

Prebiotics and Synbiotics in Clinical Medicine

Pharmaceutical medicine has thus far been unable to stop the increasing global morbidity and mortality both in acute and chronic diseases. Typically, medical practice has focused on reducing the aggressor with treatments such as antibiotics; little interest has been given to efforts to increase the individuals resistance to disease. The increased morbidity has occurred in parallel to a deviation from a large consumption of fresh fruits, vegetables, and tubers rich in live lactic acid bacteria (LAB), plant fibers, and natural antioxidants to an industry-produced diet rich in fat and refined sugar but containing little fiber, antioxidants, and LAB. Plant fiber/prebiotics, plant-derived antioxidants, and LAB/probiotics are known to have the potential to reinforce the immune system of the body and increase resistance to disease. However, this depends on the type of fiber, antioxidant, and strain or combination of strain used. At this stage, only about 10% of the LAB studied have proven strong immunosupportive effects. Similarly, only a few plants contain what has been called superantioxidants, antioxidants 10 or more times stronger than vitamin C and E. Increasing evidence suggests that combining several probiotic bacteria into multistrain probiotics will achieve stronger effects than single-strain probiotics. And combining probiotics and prebiotics into synbiotics will further enhance the immunosupportive effects. There is little evidence that a single-strain-based superprobiotic/magic LAB will ever be found. Instead, combining several specific and defined probiotics and several key plant fibers into multistrain/multifiber synbiotics appears to be the most promising alternative. Some edge-cutting effects from using multistrain and multifiber compositions are reported both from animal and controlled clinical studies.

'Push' versus 'pull' Percutaneous endoscopic gastrostomy tube placement in patients with advanced head and neck cancer

Objectives/Hypothesis: Percutaneous endoscopic gastrostomy tube (PEG) placement by means of the “pull” method has been reported to result in a significantly higher complication rate when compared with “push” PEG placement. These findings have led to a renewed interest in the push, or Russell introducer, method of PEG placement at the authors institution when PEG is required before definitive treatment of advanced head and neck cancer. The authors sought to determine whether the push method of PEG placement is associated with a lower incidence of complications in this patient population. Study Design: Nonrandomized, retrospective patient analysis. Methods: The medical records of all patients presenting to the Medical College of Georgia (Augusta, GA) who received a diagnosis of squamous cell carcinoma of the head and neck between 1999 to 2001 were retrospectively reviewed. Patients who required PEG placement as part of their treatment comprised the study population. Results: The push PEG technique was used in 29 patients, and the pull technique was used in 50 patients. There was a statistically significant difference in the complication rate between the two techniques. Patients who underwent placement by means of the pull technique had an overall complication rate of 30% (15 of 50) versus a 0% (0 of 29) complication rate in patients undergoing the push technique (P = .0006, Fishers Exact test). Conclusion: The push PEG technique appears to have a significantly lower risk of complications compared with the pull technique in patients with advanced head and neck cancer. The authors recommend considering the use of the push method when PEG placement is required.

Bedside placement of small bowel feeding tubes in hospitalized patients: A new role for the dietitian

OBJECTIVEnThe benefits of enteral nutrition when compared with parenteral nutrition are well established. However, provision of enteral nutrition may not occur for several reasons, including lack of optimal feeding access. Gastric feeding is easier to initiate, but many hospitalized patients are intolerant to gastric feeding, although they can tolerate small bowel feeding. Many institutions rely on costly methods for placing small bowel feeding tubes. Our goal was to evaluate the effectiveness of a hospital-developed protocol for bedside-blind placement of postpyloric feeding tubes.nnnMETHODSnThe Surgical Nutrition Service established a protocol for bedside placement of small bowel feeding tubes. The protocol uses a 10- or 12-French, 110-cm stylet containing the feeding tube; 10 mg of intravenous metoclopramide; gradual tube advancement followed by air injection and auscultation; and an abdominal radiograph for tube position confirmation. In a prospective manner, consults received by the surgical nutrition dietitian for feeding tube placements were followed consecutively for a 10-mo period. The registered dietitian recorded the number of radiograph examinations, the final tube position, and the time it took to achieve tube placement.nnnRESULTSnBecause all consults were included, feeding tube placements occurred in surgical and medical patients in the intensive care unit and on the ward. Of the 135 tube placements performed, 129 (95%) were successfully placed postpylorically, with 84% (114 of 135) placed at or beyond D3. Average time for tube placement was 28 min (10 to 90 min). One radiograph was required for 92% of the placements; eight of 135 (6%) required two radiographs. No acute complications were associated with the tube placements.nnnCONCLUSIONSnHospitalized patients can receive timely enteral feeding with a cost-effective feeding tube placement protocol. The protocol is easy to implement and can be taught to appropriate medical team members through proper training and certification.

Is the use of specialized nutritional formulations a cost-effective strategy? A national database evaluation.

BACKGROUNDnWe apply currently published clinical outcomes data to length of stay and hospital cost to determine the potential economic benefit associated with the use of specialized nutritional formulations in elective surgical, trauma, and medical patients. Although the use of immune-modulating formulations has repeatedly shown favorable clinical outcomes, including decreased complications (both infectious and noninfectious), length of stay (both ICU and total days), and ventilator days, the cost-effectiveness of nutritional modulation of the immune response in a US-based population has not previously been explored.nnnMETHODSnData for the current study were obtained from a large national database with 126 member hospitals and data from over 1 million patients. Data extracted from the database included patient type (surgical, medical, and trauma) and subservice, whether the hospital stay was complicated or uncomplicated (as determined by diagnosis-related groups and International Classification of Diseases, Ninth Revision coding), mean length of stay, mean cost, and incremental cost per complication experienced. The clinical outcomes measures from 3 major peer-reviewed studies were then applied to the cost data in order to determine the cost savings associated with the use of specialized nutritional formulations in each of the patient populations. Additionally, cost data were segmented by region of the United States (New England, mid-Atlantic, South, Midwest, Southwest, and West) and by primary focus of the health care facility (academic, indigent care, large community) to enable more meaningful cost comparisons.nnnRESULTSnFor the medical patient population, according to the published rate of 51% decrease in risk of infectious complications and a decreased length of hospital stay of 9.7 days, net cost savings (after accounting for the increased costs of administering immune modulating formula) is

Differential influence of cAMP on the expression of the three subtypes (ATA1, ATA2, and ATA3) of the amino acid transport system A.

2066. The same calculations were done for surgical and trauma patients, with

Probiotics: A Practical Review of Their Role in Specific Clinical Scenarios

688 and

The gastrointestinal tract in critical illness

308 net cost savings per patient, respectively. These figures assume a base infection rate of 5%. Expected cost savings vary markedly for deviations in base infection rate and slightly for differences in facility type or region of the country.nnnCONCLUSIONSnThis study demonstrates that specialized nutritional formulations are a cost-effective way for hospitals to improve clinical outcomes while reducing resource consumption and total cost. These benefits are observable in all patient types, all facility types, and all regions of the United States.

The gastrointestinal tract in critical illness: nutritional implications.

Treatment of HepG2 cells with forskolin led to 60–100% stimulation of system A activity, measured as the Na+‐dependent uptake of α‐(methylamino)isobutyric acid. The stimulation was reproducible with cholera toxin and dibutyryl cAMP, and inhibitable by H7, a non‐specific protein kinase inhibitor. The stimulatory effect was eliminated by cycloheximide and actinomycin D. The forskolin effect was associated with an increase in the maximal velocity of the transport system, with no change in substrate affinity. These cells express three different subtypes of system A (ATA1, ATA2, and ATA3). Treatment with forskolin increased the steady‐state levels of ATA1 and ATA2 mRNAs, but decreased that of ATA3 mRNA.