Kimberly S. Ephgrave

Depressive Symptoms in Medical Students and Residents: A Multischool Study

Background This multisite, anonymous study assessed depressive symptoms and suicidal ideation in medical trainees (medical students and residents). Method In 2003–2004, the authors surveyed medical trainees at six sites. Surveys included content from the Center for Epidemiologic Studies–Depression scale (CES-D) and the Primary Care Evaluation of Mental Disorders (PRIME-MD) (measures for depression), as well as demographic content. Rates of reported major and minor depression and of suicidal ideation were calculated. Responses were compared by level of training, gender, and ethnicity. Results More than 2,000 medical students and residents responded, for an overall response rate of 89%. Based on categorical levels from the CES-D, 12% had probable major depression and 9.2% had probable mild/moderate depression. There were significant differences in depression by trainee level, with a higher rate among medical students; and gender, with higher rates among women (&khgr;2 = 10.42, df = 2, and P = .005 and &khgr;2 = 22.1, df = 2, and P < .001, respectively). Nearly 6% reported suicidal ideation, with differences by trainee level, with a higher rate among medical students; and ethnicity, with the highest rate among black/African American respondents and the lowest among Caucasian respondents (&khgr;2 = 5.19, df = 1, and P = .023 and &khgr;2 = 10.42, df = 3, and P = .015, respectively). Conclusions Depression remains a significant issue for medical trainees. This study highlights the importance of ongoing mental health assessment, treatment, and education for medical trainees.

Enteral nutrients prevent stress ulceration and increase intragastric volume

Tube feedings and intragastric glucose prevent stress ulceration by unknown mechanisms. We tested the hypothesis that glucose protects the gastric mucosa by direct repletion of glycogen stores. We compared the effects of enteral glucose with enteral lipids in the rat restraint model. The rats were given equal volumes of 0.9% saline, 20% lipids, or 25% glucose during a 4-h period of restraint stress. The effects of each treatment on gastric residual volume and luminal pH, as well as on stress lesion formation were measured. Both enteral nutrients significantly reduced the number of mucosal lesions compared to saline. In conjunction with their protective effect, both nutrients significantly increased both gastric residual volume and luminal pH. As stress-induced prolonged gastric contractions are related to mucosal injury in this model, the nutrient solutions may have been protective in part because they increased gastric volume and prevented mechanical trauma to the mucosa. We conclude that tube feedings do not prevent stress ulceration by glucoses repletion of local glycogen stores, as lipids and glucose were equally effective. Both increased intragastric volume and increased intraluminal pH associated with administration of enteral nutrients may contribute to their protection of the gastric mucosa from stress ulceration.

Effects of endotoxin on regulation of intestinal smooth muscle nitric oxide synthase and intestinal transit

BACKGROUND The disrupted intestinal transit during endotoxemia may be mediated by nitric oxide (NO). We hypothesized that the isoforms of nitric oxide synthase (NOS) are up-regulated in intestinal smooth muscle during endotoxemia and that the scavenging of NO will normalize transit. METHODS Rats were given Escherichia coli lipopolysaccharide (LPS) 10 mg/kg intravenously and were killed 4 hours later. To determine the activity of NOS isoforms in the jejunum and ileum, the conversion of tritiated L-arginine to tritiated L-citrulline was measured. Western immunoblots were performed by incubating the extracted protein with specific polyclonal antibodies. To determine intestinal transit, rats were divided into 4 groups: 0.9% sodium chloride 1 mL/h intravenously for 5 hours, LPS 10 mg/kg intravenous bolus plus 1 mL/h 0.9% sodium chloride intravenously, LPS plus oxyhemoglobin 0.5 g/kg/h intravenously, and oxyhemoglobin 0.5 g/kg/h intravenously. RESULTS LPS increased the constitutive and inducible NOS enzyme activities in the jejunum and ileum. Western blots demonstrated that LPS up-regulates both the NOS1 and NOS2 isoforms in jejunal and ileal smooth muscle. Oxyhemoglobin alone increased intestinal transit compared with controls, whereas endotoxemia increased intestinal transit, which was ameliorated with infusions of oxyhemoglobin. CONCLUSIONS NO may play a major role in mediating the rapid intestinal transit induced by endotoxemia.

Liver dysfunction and energy source: results of a randomized clinical trial.

Controversy still exists regarding the role of the carbohydrate:fat ratio on liver function abnormalities associated with the administration of total parenteral nutrition (TPN). We designed a prospective clinical trail comparing standard carbohydrate-based TPN (8.5% amino acids, 50% dextrose, 7.5% of total calories from lipids) with an isocaloric lipid-based TPN (8.5% amino acids, 30% dextrose, 40% of total calories from lipids) in 43 patients exclusively receiving TPN > or = 2 weeks. Energy needs were calculated as basal energy expenditure x 1.5. The mean daily calorie intake for patients who obtained carbohydrate-based TPN (CHO) was 2227 kcal, whereas the lipid-based TPN (LIP-CHO) group achieved a mean of 2310 kcal. Patients with preexisting liver disease were excluded. There was no significant difference in age or diagnosis between the groups. We monitored total bilirubin, direct bilirubin, alkaline phosphatase, gamma-glutamyl transferase, lactic dehydrogenase, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase. Initial liver-associated tests did not vary significantly between groups. Group mean values after 2 weeks of TPN were significantly different for total bilirubin (1.5 mg/dL in the CHO group compared with 0.7 in the LIP-CHO group, p < .05) and direct bilirubin (0.8 mg/dL in the CHO group compared with 0.3 mg/dL in the mixed substrate group, p < .05). Differences in mean values between groups were also noted for serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, and lactic dehydrogenase. In conclusion, this prospective trial reveals that the use of a balanced energy source TPN solution prevents the abnormalities in liver-associated tests commonly associated with TPN.(ABSTRACT TRUNCATED AT 250 WORDS)

Pathophysiology of adynamic ileus

We hypothesized that the inhibitoryneurotransmitters nitric oxide (NO) and vasoactiveintestinal peptide (VIP) may play a role in thedisrupted gastrointestinal motility of endotoxemia.Strain gauge transducers on the stomach and small intestine of dogsdetermined interdigestive gastrointestinal motility.Tissue levels of NO synthase and VIP and serum levels ofnitrite/nitrate (NO2-/NO3-) and VIP weremeasured. Following completion of the baseline studies,dogs were given a single dose of E. colilipopolysaccharide, 200 μg/kg intravenously, and thestudies were repeated for the next three days. Following endotoxin bolus, the migrating motor complex(MMC) was delayed for two days while serum VIP wasincreased on postendotoxin day 1 and serumNO2-/NO3-was increased on postendotoxin day 2. There were nochanges in gut smooth muscle levels of NO synthase orVIP. We conclude that a single, sublethal dose ofendotoxin results in prolongation of the MMC withdistinct but independent increases in serum levels ofVIP and NO2-/NO3-

Effect of endotoxin on opossum gallbladder motility: a model of acalculous cholecystitis.

ObjectiveTo determine whether endotoxin causes histologic changes in the gallbladder consistent with acalculous cholecystitis, and to determine the effects of endotoxin on gallbladder motility. Summary Background DataAcute acalculous cholecystitis is frequently seen in critically ill, septic patients, after prolonged fasting and gallbladder stasis. The pathogenesis of acalculous cholecystitis is unknown; however, previous studies have suggested that ischemia may play a role. MethodsAdult opossums received Escherichia coli lipopolysaccharide. The gallbladder was removed for histologic examination or for physiologic studies 4 hours to 2 weeks later. For histologic examination, gallbladder strips underwent standard hematoxylin-and-eosin processing. For physiologic studies, they were mounted in a tissue bath to determine responses to cholecystokinin octapeptide or electrical field stimulation. ResultsIntravenous endotoxin at a dose of 0.005 mg/kg resulted in disrupted mucosal surfaces and areas of hemorrhage; higher doses of endotoxin resulted in coagulation necrosis, hemorrhage, areas of fibrin deposition, and extensive mucosal loss, consistent with an acute ischemic insult. Endotoxin abolished the contractile response to cholecystokinin octapeptide in gallbladder strips 4 hours after endotoxin administration. The 0.005-mg/kg dose of endotoxin decreased the contractile response to cholecystokinin octapeptide for up to 96 hours after endotoxin administration and decreased the contractile response to electrical field stimulation for 48 hours after administration. Inhibition of nitric oxide synthase reversed the decreased contractile response to cholecystokinin octapeptide. ConclusionsEndotoxin causes an ischemic insult to the gallbladder similar to that seen in acalculous cholecystitis. Also, endotoxin may lead to gallbladder stasis by decreasing gallbladder contractile responses to hormonal and neural stimuli.

Stress ulcers: current understanding of pathogenesis and prophylaxis

Stress-related gastrointestinal bleeding is known to occur in approximately 25 percent of untreated seriously ill patients, but with appropriate prophylaxis is largely preventable. Since the treatment of stress bleeding is generally unsatisfactory and has a high mortality, routine prophylaxis should be instituted for susceptible patients. Multiple mechanisms contribute to stress ulcer formation, the most important of which appear to be mucosal ischemia and the inability to control back-diffused hydrogen. Antacids and histamine2-blocking agents are presently the cornerstone of effective prophylaxis, but because they have been implicated as contributors to nosocomial pneumonias due to bacterial overgrowth in the stomach, investigation is ongoing into such alternative prophylactic agents as sucralfate and prostaglandins that do not alter the normal gastric acidity. This article presents a review of the literature on the development and prevention of stress ulcer disease.

Captopril decreases stress ulceration without affecting gastric perfusion during canine hemorrhagic shock

The renin-angiotensin axis has recently been called the source of disproportionate splanchnic vasoconstriction during shock, and blocking this axis decreased gastric stress ulceration during swine cardiogenic shock. The present study tested whether the angiotensin converting enzyme inhibitor captopril would prevent stress ulceration when given after the onset of canine hemorrhagic shock, and whether any detrimental effects would result from enhancing splanchnic perfusion with captopril during hemorrhagic shock. We found that captopril treatment was associated with a decrease in gastric mucosal injury and with a marked decrease in systemic acidosis. Captopril enhanced blood flow to the small intestine, pancreas, liver, and spleen, but not flow to the stomach, during shock. Following the reinfusion of shed blood, the captopril-treated animals had decreased mean blood pressures and increased heart rates compared with untreated animals. We found captopril alleviated the stress ulceration produced by canine hemorrhagic shock, but concluded that the likely mechanism was alleviating systemic acidosis through enhanced perfusion of other viscera rather than a specific enhancement of gastric perfusion.

Effect of endotoxin on canine colonic motility and transit

Diarrhea is a common problem in patients who have episodes of sepsis and are beingfed enterally. Endotoxemia results in gastrointestinal motor dysfunction characterized by slowed gastric emptying and rapid intestinal transit; however, the effect of endotoxin on colonic motility is unknown. The aim of our study was to determine the effects of a single sublethal dose of endotoxin on colonic motility and transit. Seven dogs underwent construction of a 50 cm colonic Thiry-Vella fistula. Five manometry catheters were sewn into the colonic lumen at 8 cm intervals along the fistula. Following recovery, the fistula was perfused with an isotonic solution at 2.9 ml/min, and fasting and postprandial colonic motility was determined. Liquid transit was assessed by bolus ofa nonabsorbable marker instilled into the proximal end of the Thiry-Vella fistula. Recordings of gastrointestinal contractile activity were made digitally to determine contractile frequencies and motility indexes. Following completion of the baseline studies, each dog was given a single dose ofE. coli lipopolysaccharide, 200 γg/kg intravenously, and studies were repeated daily for the next 3 days. Endotoxin doubled the fasting colonic contractile frequency on postendotoxin day 1 and also increased motility indexes on that same day. Fasting motility indexes and contractile activity were decreased on postendotoxin days 2 and 3. The postprandial frequency of contractions and motility indexes were decreased on postendotoxin day 3. Fasting colonic liquid transit was rapid on postendotoxin day 1, whereas postprandial liquid transit was rapid on both postendotoxin days 1 and 2. Endotoxin temporarily speeds liquid transit and increases both the frequency and strength of colonic contractions. These effects may contribute to the diarrhea that occurs during episodes of sepsis.

Presentation of pancreatic pseudocysts: Implications for timing of surgical intervention

A review of 115 patients with pancreatic pseudocysts treated surgically between 1976 and 1984 showed four patterns of presentation: pseudocyst alone, pseudocyst and acute pancreatitis, acute pancreatitis alone, or neither apparent on hospital admission. These patterns of presentation were associated with differences in the clinical course and ultimate surgical outcome of each group of patients. Emergency procedures greatly increased the morbidity and mortality of surgery for pseudocysts. A preoperative delay for pseudocyst maturation was expected to decrease the morbidity and mortality of elective pseudocyst drainage, but no benefit was found either for the series as a whole or for any subgroup. We conclude that an arbitrary preoperative delay for pseudocyst maturation (in the absence of acute pancreatitis) exposes patients to the risks of preoperative complications, increases the expense of care for pancreatic pseudocysts, and fails to improve surgical outcome.