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Kenneth A Kudsk

Publications and source records attributed to Kenneth A Kudsk.

At least 19 recordsLinked to original sources
PubMed2006

Parenteral nutrition impairs gut-associated lymphoid tissue and mucosal immunity by reducing lymphotoxin Beta receptor expression.

OBJECTIVE: To determine the effects of parenteral nutrition (PN) on LTbetaR in gut-associated lymphoid tissue (GALT), particularly the intestine and Peyer's patches (PP). SUMMARY BACKGROUND DATA: Lack of enteral stimulation with PN impairs mucosal immunity and reduces IgA levels through depression of GALT cytokines (IL-4 and IL-10) and GALT specific adhesion molecules. We have shown that each is critical to intact mucosal immunity through effects on lymphocyte homing, IgA production, and resistance to antibacterial and antiviral immunity. IgA is the principal specific immunologic mucosal defense. LTbetaR stimulation controls production of IL-4, the adhesion molecule MAdCAM-1, and other key components of GALT, all of which are important in increasing IgA levels and maintaining mucosal defenses. METHODS: Experiment 1: LTbetaR expression in intestine and PP was analyzed by Western blot after 5 days of chow, a complex enteral diet (CED), or PN. Diets were isocaloric and isonitrogenous except for chow. Experiment 2: After completing pilot experiments to determine the appropriate dose of the LTbetaR agonistic antibody, mice received chow, PN + 5 mug of anti-LTbetaR mAb (2 times/d, i.v.) or PN + isotype control antibody. PP lymphocytes and intestinal IgA levels were measured after 2 days. RESULTS: Lack of enteral stimulation with PN significantly decreased LTbetaR expression in intestine and PP compared with chow and CED. LTbetaR stimulation with an agonistic anti-LTbetaR mAb significantly increased PP lymphocyte counts and intestinal IgA in PN fed-mice. CONCLUSIONS: LTbetaR expression is critical for GALT control mechanisms and intact mucosal immunity. PN reduces LTbetaR expression, PP lymphocytes, and intestinal IgA production. Exogenous LTbetaR stimulation reverses PN-induced depression of gut mucosal immunity.

Animals↗
PubMed2006

Immunonutrition in surgery and critical care.

The benefits of specialty supplemented enteral diets administered to critically ill and critically injured patients and those undergoing major surgical procedures have been documented in a number of randomized prospective studies. It is unclear which nutrient or combination of nutrients causes the beneficial effects, but there are significant reductions in infectious complications depending upon the patient populations studied. It is imperative that the data be interpreted in the context of individual patient risk since specialty formulas appear most beneficial in patients at risk of subsequent complications or in those with significant pre-existing malnutrition. Although controversy exists regarding the use of specialty supplemented enteral diets in critically ill patients, they have been administered safely with minimal risk of adverse outcome in malnourished patients and in the critically ill and critically injured.

Amino Acids, Branched-Chain↗
PubMed2005

Treatment of electrolyte disorders in adult patients in the intensive care unit.

PURPOSE: The treatment of electrolyte disorders in adult patients in the intensive care unit (ICU), including guidelines for correcting specific electrolyte disorders, is reviewed. SUMMARY: Electrolytes are involved in many metabolic and homeostatic functions. Electrolyte disorders are common in adult patients in the ICU and have been associated with increased morbidity and mortality, as has the improper treatment of electrolyte disorders. A limited number of prospective, randomized, controlled studies have been conducted evaluating the optimal treatment of electrolyte disorders. Recommendations for treatment of electrolyte disorders in adult patients in the ICU are provided based on these studies, as well as case reports, expert opinion, and clinical experience. The etiologies of and treatments for hyponatremia hypotonic and hypernatremia (hypovolemic, isovolemic, and hypervolemic), hypokalemia and hyperkalemia, hypophosphatemia and hyperphosphatemia, hypocalcemia and hypercalcemia, and hypomagnesemia and hypermagnesemia are discussed, and equations for determining the proper dosages for adult patients in the ICU are provided. Treatment is often empirical, based on published literature, expert recommendations, and the patient's response to the initial treatment. Actual electrolyte correction requires individual adjustment based on the patient's clinical condition and response to therapy. Clinicians should be knowledgeable about electrolyte homeostasis and the underlying pathophysiology of electrolyte disorders in order to provide the optimal therapy to patients. CONCLUSION: Treatment of electrolyte disorders is often empirical, based on published literature, expert opinion and recommendations, and patient's response to the initial treatment. Clinicians should be knowledgeable about electrolyte homeostasis and the underlying pathophysiology of electrolyte disorders to provide optimal therapy for patients.

Adult↗
PubMed2005

l-selectin and alpha4beta7 integrin, but not ICAM-1, regulate lymphocyte distribution in gut-associated lymphoid tissue of mice.

BACKGROUND: Adhesion molecules on lymphocytes ( l -selectin and alpha4beta7) and endothelium (MAdCAM-1 and ICAM-1) direct lymphocytes into the gut-associated lymphoid tissue (GALT) of mice. Parenteral nutrition and MAdCAM-1 blockade reduce GALT cell mass. This study examined the effects on GALT cell mass of blockade of l -selectin, alpha4beta7, and ICAM-1 with saturating doses of monoclonal antibodies. METHODS: In experiment 1, l -selectin and alpha4beta7 expression were measured by flow cytometry in chow-fed mice. In experiment 2, 49 mice randomly received chow, parenteral nutrition, chow + intravenous (IV) anti-CD62L, chow + IV anti-LPAM-1, or chow + IV isotype control antibody. After 4 days, lymphocyte yields in GALT and respiratory and intestinal IgA levels were measured. In experiment 3, 27 mice randomly received chow, parenteral nutrition, chow + IV anti-ICAM-1 monoclonal antibody, or chow + IV isotype control antibody for 5 days. Lymphocyte counts and IgA levels were determined as in experiment 2. RESULTS: Some 80% of all circulating lymphocytes were positive for l -selectin and alpha4beta7. Lymphocyte counts in the Peyer's patches, lamina propria, and intraepithelial space were lower in the l -selectin and alpha4beta7 blockade groups (3.1, 1.8, and 0.9 x 10(6) and 2.1, 1.9, and 0.7 x 10(6) , respectively) than in the chow group (5.9, 3.0, and 1.7 x 10(6) ; P < .02 vs the l -selectin group and P <.001 vs the alpha4beta7 group) and similar to the levels in the parenteral group. Respiratory and intestinal IgA levels are maintained in all groups except the parenteral group ( P <.04 vs the chow group). ICAM-1 blockade did not influence cell counts or IgA levels. CONCLUSION: Most circulating lymphocytes have GALT homing potential. Their distribution into GALT is hindered by blockade of l -selectin or alpha4beta7, but not by ICAM-1.

Animals↗
PubMed2004

Higher calorie prescription improves nutrient delivery during the first 5 days of enteral nutrition.

AIMS: It is unclear whether prescribing a higher amount of calories by enteral nutrition (EN) increases actual delivery. This prospective controlled study aimed at comparing the progression of EN of two study populations with different levels of calorie prescriptions, during the first 5 days of EN. METHODS: The daily calorie prescription of group 1 (n=346) was 25 and 20 kcal/kg body weight for women <60 and > or =60 years, respectively, and 30 and 25 kcal/kg body weight for men <60 and > or =60 years, respectively. The prescription of group 2 (n=148) was 5 kcal/kg body weight higher than in group 1. Calorie intakes were expressed as percentage of resting energy expenditure (REE) and protein intakes as percentage of requirements estimated as 1.2 g/kg body weight/day. Patients were classified as <60 and > or =60 years and as medical or surgical patients. Statistical analysis was performed with ANOVA for repeated measures. RESULTS: Calorie and protein deliveries increased in both groups independently of age and ward categories (P< or =0.0001). Group 2 showed faster progressions of calorie and protein intakes than group 1 in patients altogether (P< or =0.002), > or =60 years (P< or =0.01) and in surgical patients (P< or =0.02). Differences of calorie and protein intakes between day 1 and day 5 were significantly higher in group 2 than group 1 for patients altogether (75+/-61 vs. 56+/-54% of REE; 41+/-30 vs. 31+/-/-27% of protein requirements), those over 60 years (76+/-67 of REE vs. 52+/-59 of protein requirements) and surgical patients (81+/-52 vs. 58+/-57% of REE; 44+/-27 vs. 33+/-29% of protein requirements). CONCLUSIONS: Increasing the levels of EN prescriptions improved calorie and protein deliveries. While the mean energy delivery over 5 days was sufficient to cover requirements, the protein delivery by EN was insufficient, despite our nutritional support team.

Analysis of Variance↗
PubMed2004

Health Insurance Portability Accountability Act (HIPAA) regulations: effect on medical record research.

OBJECTIVE: To evaluate the effect of impending HIPAA regulations on Applications for Exemptions from Institutional Review Board (IRB) approval. SUMMARY BACKGROUND DATA: HIPAA was implemented to reduce potential for misuse of personal information and restricts access to medical records by insurers, employers, and clinical researchers. We hypothesized that HIPAA regulations adversely impact medical records research. METHODS: The UW-Madison Human Subjects Committee database was accessed to evaluate success and delays in processing Applications for Exemption between September 1999 and March 2003. The number of protocols submitted, number of required revisions, and number considered nonexempt (requiring full IRB review) were determined. RESULTS: Prior to 2000, applications for medical records research were rare (11 applications in 1999-2000). In anticipation of the implementation of HIPAA regulations, a new application process was instituted in 2001. During that year, 92 of 103 were approved by an expedited process with few requiring full IRB approval. In 2002 to 2003, submissions increased to 199 and approval without revision dropped to 59% (P < 0.0001) as the number requiring revision (25%) and full IRB approval (16%) increased significantly (P < 0.0001 and P < 0.05, respectively). Of the 31 requiring full IRB approval, 7 were pursued while 24 (77%) were abandoned. CONCLUSION: HIPAA appears to inhibit medical record and database research. Ethical considerations in healthcare research are paramount, but current HIPAA implementation strategies increase workload for HSC and researchers, and increase the dropout rate for proposed studies when investigators are unable or unwilling to meet the regulatory requirements. It is unclear whether or to what degree the new requirements add to protection of privacy. Studies designed to investigate the costs and effects on quantity and/or quality of research should be prospectively implemented.

Biomedical Research↗
PubMed2003

Management of complex perineal injuries.

A retrospective study of 25 patients with severe soft tissue injuries to the perineum from the last 14 years was performed to determine the most appropriate management strategy for these problematic wounds. There were 20 (80%) men and 5 (20%) women with an average age of 29 years. Six (24%) patients died of exsanguination from their pelvic injuries within the first few hours of presentation. The remaining 19 patients were taken to the operating room for sigmoidoscopy, diverting colostomy, distal rectal washout, and radical debridement and irrigation of any devitalized tissue. Enteral access by jejunostomy was obtained in six patients. Most patients underwent daily debridement and pulsatile irrigation for at least three days, but usually longer, until the treating surgeon deemed the wound to be clean. None of the patients managed in this fashion developed pelvic sepsis. However, pelvic sepsis did occur in all four patients who did not receive early mandatory daily debridement. Total parenteral nutrition was required in eight patients because there were significant delays in the ability of these patients to resume oral intake. In most previously published series in which daily debridement was not performed, a pelvic sepsis rate of 40% to 80% was reported. Therefore, to optimize the clinical course and recovery from these complex wounds, we conclude that mandatory daily debridement with pulsatile irrigation should be instituted in conjunction with sigmoidoscopy, diversion of the fecal stream, distal rectal irrigation, enteral access, and initial radical debridement of devitalized tissue.

Adolescent↗
PubMed2003

Effect of route and type of nutrition on intestine-derived inflammatory responses.

BACKGROUND: Immunological links between the gastrointestinal (GI) tract and respiratory tract has been postulated in the development and maintenance of mucosal immunity. Route and type of nutrition affects mucosal immunity by reducing cell populations within the Peyer's patches of the small intestine and lamina propria as well as altering cytokine profiles within these sites. In addition to the mucosal affects, these alternations in cytokines (decreases in interleukin-4 and interleukin-10) also appear to influence the vascular endothelium of the GI tract. DATA SOURCES: This review examines the laboratory data regarding cytokine profile within the gut, endothelial adhesion molecule expression within the intestinal and extraintestinal organs, and the effect of these alterations on neutrophil accumulation and organ responses to gut ischemia/reperfusion. It also describes the effect of a specific nutrient, glutamine, on the starved gut. CONCLUSIONS: Changes induced by failure to feed the GI tract affects GI vascularity increasing expression of proinflammatory adhesion molecules. These adhesion molecules attract neutrophils and prime them for subsequent ischemic events. Lack of feeding the gastrointestinal tract acts as a "first hit" and increases the inflammatory response to a secondary insult in the lungs, liver, and GI tract. The addition of the specific nutrient, glutamine, reverses many of these defects and favorably influences the proinflammatory effects of gut starvation.

Cytokines↗
PubMed2003

Interactions between the enteric nervous system and the immune system: role of neuropeptides and nutrition.

Neuropeptidergic synthesis occurs in enteric nerves and immune cells of the gut-associated lymphoid tissue. Lymphocytes, macrophages, mast cells, and intestinal epithelial cells are capable of responding to these neuropeptides. Neuropeptides generate proliferative or antiproliferative responses of mucosal lymphocytes and intestinal epithelial cells, affect cytokine production and immunoglobulin synthesis by immune cells, and control secretion of water and electrolytes. Some neuropeptides, particularly cholecystokinin, gastrin-releasing peptide, and neurotensin, appear promising to maintain mucosal immunity in patients who cannot receive enteral feeding during critical illness or after GI tract loss. Exogenous administration of neuropeptides to preserve normal immune defenses represents a potential new field of pharmacotherapeutics against bacterial invasion.

B-Lymphocytes↗
PubMed2003

Glutamine improves impaired cellular exudation and polymorphonuclear neutrophil phagocytosis induced by total parenteral nutrition after glycogen-induced murine peritonitis.

Clinical and laboratory evidence shows that enteral feeding significantly reduces pneumonia and intra-abdominal abscess formation after celiotomy for severe trauma. Supplementation of total parenteral nutrition (TPN) with glutamine (GLN) supports impaired immunity induced by TPN in several animal and human studies. This work investigates the peritoneal cellular response and polymorphonuclear neutrophil (PMN) bactericidal function after mouse chemical peritonitis after TPN with and without GLN. Thirty-three mice received chow, TPN, or 2% GLN-supplemented TPN (GLN-TPN) for 5 days. All mice then received 2 mL of a 1% glycogen solution intraperitoneally to induce cell exudation, and peritoneal exudative cells (PECs) were recovered 4 h later. Total and differential PEC numbers, as well as PMN phagocytosis, reactive oxygen intermediate production (ROI), CD11b (integrin aM chain) expression, and CD16/32 (Fcgamma II/III receptor) expression were measured. PMN, macrophage, and lymphocyte cell numbers were significantly lower with TPN than with chow or GLN-TPN groups, with no differences between chow and GLN-TPN. TPN significantly lowered peritoneal PMN phagocytosis compared with chow (P < 0.05) and approached significance with GLN-TPN (P = 0.06). There were no significant differences in ROI production or CD11b and CD16/32 expression on peritoneal PMN. GLN supplementation improved the reduction in cell exudation and PMN phagocytosis induced by TPN after chemical peritonitis.

Animals↗
PubMed2003

Controversy of immunonutrition for surgical critical-illness patients.

Specific nutrients such as arginine, glutamine, dietary nucleotides, and omega-3 fatty acids have been shown to influence infectious morbidity, antibiotic use, and hospital length of stay. The combination of these nutrients into one enteral formulation has become known as immune-enhancing diets. Consensus guidelines developed by a number of clinical investigators and published in 2001 concluded that immune-enhancing diets were beneficial in moderate to severely malnourished patients undergoing elective gastrointestinal surgery and patients sustaining severe blunt and penetrating torso trauma. The purpose of this article is to review data published between February 1, 2001, and January 31, 2003, to determine whether new studies substantiated or refuted the current recommendations for the use of immune-enhancing diets in surgical, critically injured, and critically ill patients. Results confirmed the benefits of preoperative administration of immune-enhancing diets in surgical patients but also demonstrated that postoperative administration offered no advantages. Decreased infectious complications were also observed in critically ill patients receiving immune-enhancing diets. Accumulating evidence supports the use of immune-enhancing diets in these specific patient populations.

Arginine↗
PubMed2003

Route of nutrition influences generation of antibody-forming cells and initial defense to an active viral infection in the upper respiratory tract.

OBJECTIVE: To assess whether lack of enteral feeding significantly impairs generation of specific immune responses to an acute viral infection. SUMMARY BACKGROUND DATA: Parenteral feeding provides adequate nutrients to meet metabolic needs, but lack of enteral stimulation creates a defect in mucosal immunity characterized by loss of IgA-mediated defenses in the respiratory tract. METHODS: The enzyme-linked Immunospot (ELISPOT) assay was used to determine accumulation of immunologic cells in the nasal passages after diet manipulation. Viral shedding and nasal IgA levels were measured in additional groups of mice. RESULTS: After determining the time course of antibody-forming cells (AFCs) via ELISPOT to an active infection with the A/PR8 influenza virus, a significant reduction was found in total AFCs, IgA-producing AFCs, and IgG-producing AFCs over the course of a 13-day experiment with significant depression in viral-specific respiratory IgA levels. Eight days following an active infection, seven of nine total parenteral nutrition-fed animals continued to have viral shedding in the nasal passages compared to one of nine chow-fed mice and one of six animals fed a complex enteral diet. CONCLUSIONS: Lack of enteral stimulation significantly impairs the generation of IgA-mediated mucosal immunity.

Animals↗
PubMed2003

Enteral feeding preserves mucosal immunity despite in vivo MAdCAM-1 blockade of lymphocyte homing.

OBJECTIVE: To determine the influence of route of nutrition on gut mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) expression and the effect of MAdCAM-1 blockade on gut-associated lymphoid tissue (GALT) lymphocyte populations and established respiratory antibacterial immunity. SUMMARY BACKGROUND DATA: Lymphocytes, sensitized to antigens in Peyer's patches, migrate via mesenteric lymph nodes and home to intestinal lamina propria. MAdCAM-1 located on endothelial cells regulates this trafficking. Experimentally, parenteral nutrition (PN) decreases GALT cell mass and mucosal immunity when compared with enteral feeding. METHODS: In experiment 1, MAdCAM-1 expression was quantified in 32 mice after 4 days of feeding chow, a complex diet, intragastric (IG)-PN, or PN. In experiment 2, MAdCAM-1 was measured in 102 mice 0, 4, 8, 12, 24, 48, or 72 hours after starting PN and at 0, 4, 8, 12, 24, or 48 hours after reinstituting chow following 5 days of PN. In experiment 3, 56 mice received chow, PN, chow + MECA-367 (anti-MAdCAM-1 mAb), or chow + Isotype control Ab (IsoAb) for 5 days, followed by Peyer's patches, lamina propria, and intraepithelial lymphocyte yield with respiratory and intestinal IgA levels. In experiment 4, 10 days after Pseudomonas immunization, mice received chow + MECA-367 or chow + IsoAb for 4 days followed by 1.2 x 108 Pseudomonas intratracheally. RESULTS: Diet and route affect MAdCAM-1 expression (chow > complex diet > IG-PN > PN). Decreased MAdCAM-1 expression occurred within hours of starting PN in Peyer's patches, but not mesenteric lymph nodes or the intestine, and recovered quickly with enteral refeeding. MAdCAM-1 blockade reduced all GALT populations. Blockade had little effect on IgA levels and partially impaired the late response of established respiratory immunity. CONCLUSIONS: Enteral feeding affects MAdCAM-1 expression. Complete MAdCAM-1 blockade reduces GALT lymphocytes to PN levels, but the chow feeding stimulus preserves IgA and early antibacterial resistance, implying the existence of non-MAdCAM-1 mechanisms to preserve mucosal immunity.

Animals↗