M.C. Richir

Glycemic Control Modulates Arginine and Asymmetrical-Dimethylarginine Levels during Critical Illness by Preserving Dimethylarginine-Dimethylaminohydrolase Activity

In the context of the hypercatabolic response to stress, critically ill patients reveal hyperglycemia and elevated levels of asymmetrical-dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthases. Both hyperglycemia and elevated ADMA levels predict increased morbidity and mortality. Tight glycemic control by intensive insulin therapy lowers circulating ADMA levels, and improves morbidity and mortality. Methylarginines are released from proteins during catabolism. ADMA is predominantly cleared by the enzyme dimethylarginine-dimethylaminohydrolase (DDAH) in different tissues, whereas its symmetrical isoform (SDMA) is cleared via the kidneys. Therefore, glycemic control or glycemia-independent actions of insulin on protein breakdown and/or on DDAH activity resulting in augmented ADMA levels may explain part of the clinical benefit of intensive insulin therapy. Therefore, we investigated in our animal model of prolonged critical illness the relative impact of maintaining normoglycemia and of glycemia-independent action of insulin over 7 d in a four-arm design on plasma and tissue levels of ADMA and SDMA, on proteolysis as revealed by surrogate parameters as changes of body weight, plasma urea to creatinine ratio, and plasma levels of SDMA, and on tissue DDAH activity. We found that ADMA levels remained normal in the two normoglycemic groups and increased in hyperglycemic groups. SDMA levels in the investigated tissues remained largely unaffected. The urea to creatinine ratio indicated reduced proteolysis in all but normoglycemic/normal insulin animals. DDAH activity deteriorated in hyperglycemic compared with normoglycemic groups. Insulin did not affect this finding independent of glycemic control action. Conclusively, maintenance of normoglycemia and not glycemia-independent actions of insulin maintained physiological ADMA plasma and tissue levels by preserving physiological DDAH activity.

Learning in student-run clinics: a systematic review.

Student‐run clinics (SRCs) have existed for many years and may provide the most realistic setting for context‐based learning and legitimate early clinical experiences with responsibility for patient care. We reviewed the literature on student outcomes of participation in SRCs.

Antioxidant-enriched enteral nutrition and immuno-inflammatory response after major gastrointestinal tract surgery

Major surgery induces an immuno-inflammatory response accompanied by oxidative stress that may impair cellular function and delay recovery. The objective of the study was to investigate the effect of an enteral supplement, containing glutamine and antioxidants, on circulating levels of immuno-inflammatory markers after major gastrointestinal tract surgery. Patients (n 21) undergoing major gastrointestinal tract surgery were randomised in a single-centre, open-label study. The effects on circulating levels of immuno-inflammatory markers were determined on the day before surgery and on days 1, 3, 5 and 7 after surgery. Major gastrointestinal surgery increased IL-6, TNF receptor 55/60 (TNF-R55) and C-reactive protein (CRP). Surgery reduced human leucocyte antigen-DR (HLA-DR) expression on monocytes. CRP decrease was more pronounced in the first 7 d in the treatment group compared with the control group. In the treatment group, from the moment Module AOX was administered on day 1 after surgery, TNF receptor 75/80 (TNF-R75) level decreased until the third post-operative day and then stabilised, whereas in the control group the TNF-R75 level continued to increase. The results of the present pilot study suggest that enteral nutrition enriched with glutamine and antioxidants possibly moderates the immuno-inflammatory response (CRP, TNF-R75) after surgery.

Pharmacology and Therapeutics Education in the European Union Needs Harmonization and Modernization: A Cross‐sectional Survey Among 185 Medical Schools in 27 Countries

Effective teaching in pharmacology and clinical pharmacology and therapeutics (CPT) is necessary to make medical students competent prescribers. However, the current structure, delivery, and assessment of CPT education in the European Union (EU) is unknown. We sent an online questionnaire to teachers with overall responsibility for CPT education in EU medical schools. Questions focused on undergraduate teaching and assessment of CPT, and students preparedness for prescribing. In all, 185 medical schools (64%) from 27 EU countries responded. Traditional learning methods were mainly used. The majority of respondents did not provide students with the opportunity to practice real‐life prescribing and believed that their students were not well prepared for prescribing. There is a marked difference in the quality and quantity of CPT education within and between EU countries, suggesting that there is considerable scope for improvement. A collaborative approach should be adopted to harmonize and modernize the undergraduate CPT education across the EU.

Hypertaurinemia in Bile Duct–Ligated Rats After Surgery: The Effect of Gut Endotoxin Restriction on Organ Fluxes and Oxidative Status

Surgery in obstructive jaundice is associated with complications related to gut-derived endotoxemia. The organs involved in these complications, including liver, kidneys, and gut, are important in the metabolism of taurine, which is implicated in bile acid conjugation and has antioxidative effects. Taurine organ metabolism and liver oxidative status were studied in bile duct-ligated rats (BDL) after laparotomy. Oral cholestyramine treatment inhibits gut-derived endotoxemia and was used to evaluate the role of endotoxin. In BDL rats, postoperative plasma taurine levels were higher compared with SHAM (p < .0001). Cholestyramine treatment reduced plasma taurine in BDL rats (p < .005), but levels remained higher compared with SHAM groups (p < .0001). In contrast to a liver uptake of taurine in SHAM rats, a release from livers of BDL rats was found (p < .005). Cholestyramine treatment in BDL rats resulted in a liver uptake of taurine (p < .05 vs BDL). A higher uptake of taurine by the kidneys was found in both BDL animals after surgery and SHAM controls (p < .005); however, cholestyramine had no effect. A release of taurine from the gut was found in the SHAM groups, which was reversed in both BDL groups (p < .01). Cholestyramine lowered the elevated levels of hepatic enzymes in BDL rats (ALT and AST: p < .05). Total liver glutathione levels were lower in BDL rats (p < .0001) compared with SHAM groups, and cholestyramine significantly attenuated this decrease (p < .01). Liver malondialdehyde levels were higher in BDL rats compared with SHAM (p < .01), whereas cholestyramine completely prevented this increase in lipid peroxidation (p < .0001). Hypertaurinemia in BDL rats after surgery is most likely explained by reduced bile acid conjugation and hepatocellular leakage. Cholestyramine treatment reduced hepatocellular damage by inhibiting gut-derived endotoxemia, and reversed the release of taurine from the jaundiced liver into an uptake and consequently lowered plasma taurine levels. This uptake may contribute to the improved antioxidant status in cholestyramine-treated BDL rats.

A Delphi study among internal medicine clinicians to determine which therapeutic information is essential to record in a medical record

Several studies have demonstrated that using a template for recording general and diagnostic information in the medical record (MR) improves the completeness of MR documentation, communication between doctors, and performance of doctors. However, little is known about how therapeutic information should be structured in the MR. The aim of this study was to investigate which specific therapeutic information registrars and consultants in internal medicine consider essential to record in the MR. Therefore, we carried out a 2‐round Internet Delphi study. Fifty‐nine items were assessed on a 5‐point scale; an item was considered important if ≥80% of the respondents awarded it a score of 4 or 5. In total, 26 registrars and 30 consultants in internal medicine completed both rounds of the study. Overall, they considered it essential to include information about 11 items in the MR. Subgroup analyses revealed that the registrars considered 8 additional items essential, whereas the consultants considered 1 additional item essential to record. Study findings can be used as a starting point to develop a structured section of the MR for therapeutic information for both paper and electronic MRs. This section should contain at least 11 items considered essential by registrars and clinical consultants in internal medicine.

The Prognostic Value of Severe Malnutrition in the Development of Nonthyroidal Illness in Head and Neck Cancer Patients

BACKGROUNDnThyroid hormone metabolism is modulated by starvation and overfeeding but also by dietary composition. Unfortunately, little is known about the effect of malnutrition on disease-induced nonthyroidal illness (NTI). In this study, we investigated whether the degree of NTI after surgery differed between severely malnourished and well-fed patients with head and neck cancer.nnnMETHODSnPlasma levels of the thyroid hormones 3,5-triiodothyronine (T(3)), reverse T(3) (rT(3)), free T(4) (FT(4)), and thyrotropin (TSH) were measured on the first day before the operation and on the first, fourth, and seventh day after the operation in 16 malnourished patients who were admitted for intentional curative surgery of T1-T4 carcinomas of the head and neck. Six well-fed head and neck cancer patients eligible for surgical treatment served as a control group.nnnRESULTSnIn the malnourished group, rT(3) showed a significant increase, whereas T(3) and FT(4) decreased significantly due to the operation. TSH showed no significant change. During the postoperative course, it took 7 days until rT(3) and 4 days until T(3) and FT(4) were restored to their preoperative value. In contrast, well-fed patients did not develop NTI.nnnCONCLUSIONSnThis study shows that peri- and postoperative rT(3), T(3), and FT(4) levels change significantly in malnourished patients compared with well-fed patients. Therefore, it can be concluded that nutrition status of patients undergoing major head and neck surgery should be optimized in order to prevent the development of NTI.

Clarifying learning experiences in student-run clinics: a qualitative study

BackgroundStudent-run clinics (SRCs) are outpatient clinics run and organized by undergraduate medical students. While these clinics offer participating students multiple learning opportunities, little is known about how participation in an SRC contributes to learning and how this learning is influenced.MethodsIn this qualitative clarification study, we conducted semi-structured interviews with a purposive sample of 20 students and student-coordinators participating in our learner-centred SRC (LC-SRC), to gain in-depth insight into their experiences and learning. These interviews were analysed using Glaser’s approach to grounded theory.ResultsAnalysis revealed that responsibility, authenticity, and collaboration described how SRC participation contribute to learning. Responsibility encompassed the responsibility students had for their patients and the responsibility that the student coordinators had for the students. Authenticity reflected the context and tasks in the LC-SRC. Collaboration covered collaboration with other students, with student coordinators, and with clinical supervisors. These three themes are interrelated, and together enhanced motivation and promoted patient-centred learning in both the LC-SRC and the regular curriculum.ConclusionsLearning in an LC-SRC is highly dependent on students’ feelings of responsibility for real authentic tasks and is stimulated by extensive collaboration with fellow students and supervising doctors.

30 Medicatie toedienen

De WHO Guide to Good Prescribing beschrijft het rationeel voorschrijven van medicatie in de vorm van een stappenplan.1,2 In tabel 30.1 wordt dit 6-stappenplan als checklist weergegeven en hieronder kort beschreven. In verschillende Nederlandse boeken is dit verder uitgewerkt.3,4

O016 ARGININE/ADMA IS A PREDICTOR FOR CARDIAC OUPUT IN SEPTIC SHOCK PATIENTS

Rationale: Critical illness may impair liver mitochondrial function. We hypothesised that i.v. glutamine reverses hepatic mitochondrial dysfunction in critically-ill adults. Methods: After ethics approval, 43 critically-ill adults were randomised to receive 0.5 (n = 16), 0.3 (n = 14) or 0 g/kg/d (n = 13) i.v. alanyl-glutamine as a standalone infusion. A [1-13C]methionine breath test was performed by administering 2mg/kg [1-13C]methionine and measuring breath CO2/CO2 ratio every 15min for 3h. The test was performed at ICU admission and repeated on d5 or day of discharge from ICU, if sooner. 8 Healthy adults were tested as controls. [1-13C]methionine oxidation, reflecting hepatic mitochondrial function, was calculated as cumulative percentage dose recovered (CPDR) over 3h. Data (mean±SEM) are compared by one-way ANOVA or paired or unpaired t-tests as appropriate. Results: At ICU admission, patients had a significantly lower CPDR than controls (34.7±3.4 vs. 59.8±6.0, p = 0.005, reflecting impaired liver mitochondrial function). At d5/ICU discharge, patients who did not receive glutamine had a significantly lower CPDR compared with healthy controls (Table; p < 0.05). At d5/ICU discharge, patients receiving 0.5 g/kg/d alanyl-glutamine had a significant improvement in CPDR compared with baseline (p < 0.05), and a significantly higher CPDR than patients receiving 0 g/kd/d (Table, p < 0.05), such that their CPDR was similar to controls. Patients receiving 0.3 g/kg/d had a CPDR intermediate between the placebo group and the 0.3 g/kg/d group.