Restraint-induced stress ulcer. I. Hypothalamic,urinary, and adrenal biochemical studies

The purpose of these experiments was to study the incidence of stress ulcers in restrained rats and to correlate it with hypothalamic and adrenal cortical and medullary activity, with and without vagotomy. A total of 217 adult rats were used, grouped into 56 sets, and distributed at random in 5 experimental groups. Restraint was followed by a 79% incidence of ulceration in the glandular portion of the gastric mucosa. Vagotomy made these worse (p<0.01). Hypothalamic levels of catecholamines and serotonin showed no significant changes. Urinary measurements revealed decreased excretion of 17-ketosteroids (p<0.001), increased excretion of uropepsinogen (p<0.01), and no significant changes in vanillylmandelic acid among the rats submitted to immobilization. In the adrenal glands of stressed animals, there was a decreased level of catecholamines (p<0.01) and no significant changes in corticosteroid content (17-ketosteroids). These results suggest that hypothalamic stimulation and the participation of the adrenal glands are not essential factors in the pathogenesis of restraint-induced experimental stress ulcer.     

Bedside Percutaneous Tracheostomy: Prospective Evaluation of a Modification of the Current Technique in 100 Patients

Percutaneous dilatational tracheostomy (PDT) is being increasingly used. Concerns have been raised as to its safety, especially when it is done at the bedside. A prospective evaluation was conducted of 100 consecutive, unselected critically ill patients with PDT. The mean intensive care unit (ICU) stay before PDT was 12 days. One surgeon performed PDT alone (5 cases) or assisted residents (95 cases) in all operations; 84 were performed at the ICU bedside. Only the first six patients were taken to the operating room solely for tracheostomy. A modified technique was used: (1) the endotracheal tube was left in place during sequential dilations; (2) dilators were inserted in a 60-degree cephalad orientation to the skin and directed caudally after penetration of the anterior tracheal wall; (3) a digit was inserted through the tracheal opening to guide withdrawal of the endotracheal tube to the level of the vocal cords; and (4) size 8 tracheostomy cannulas were inserted over 28F dilators. The average time from skin incision to insertion of the tracheostomy tube was 12 minutes (< 10 minutes, 41 patients; 10 to 15 minutes, 37 patients; > 15 minutes, 22 patients). Sixty-five percent had unfavorable anatomic conditions due to spinal precautions or diffuse neck edema. Postoperative complications occurred in four patients; surgical emphysema after tracheal lacerations in three, cannula dislodgment in one. All complications were successfully managed without an operation by tube exchange (n= 3) or observation (n= 1); there was no procedure-related mortality. Forty patients were available for long-term follow-up (6–18 months after tracheostomy) by telephone; one had persistent hoarseness without respiratory difficulty. We concluded that bedside PDT is safe and easy to teach when performed with a technique that ensures correct instrumentation.     

Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy.

PURPOSE: To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. PATIENTS AND METHODS: Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 microg/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. RESULTS: Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. CONCLUSION: ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.     

Impact of declines in nutritional status on outcomes in adult patients hospitalized for more than 7 days

OBJECTIVE: To assess the association between changes in nutritional status in hospitalized patients and the occurrence of infections, complications, length of stay in hospital, and hospital charges. DESIGN: A prospective observational study with a retrospective component was conducted over a 7-month interval at a university hospital. SUBJECTS: A total of 404 adults (> or = 18 years old) admitted to the inpatient service for more than 7 days who were not pregnant or lactating and not a psychiatric patient were included. MAIN OUTCOME MEASURES: Major outcome variables included changes in nutritional status as assessed by subjective global assessment (SGA) at hospital admission and discharge, length of stay, hospital charges, complications, and infections. STATISTICAL ANALYSIS PERFORMED: Analysis of variance with a Tukey adjustment for multiple comparisons was used to examine the impact of changes in nutritional status between nutrition change categories for continuous variables (charges and length of stay). Discrete variables were assessed using chi 2 analysis. Logistic regression was used to calculate odds ratios with 95% confidence intervals for the development of complications and infections when compared with the reference group. RESULTS: Compared with the reference group (normally nourished at admission and discharge), patients who declined nutritionally, regardless of nutritional status at admission, had significantly higher hospital charges ($28,631 +/- 1,835 vs $45,762 +/- 4,021). Odds of complications were significantly greater for patients who declined nutritionally, regardless of nutritional status at admission, compared with the reference group. APPLICATIONS/CONCLUSIONS: Declines in patients' nutritional status while they are hospitalized, regardless of their nutritional status at admission, were associated with significantly higher hospital charges and a higher likelihood of complications. Practicing clinicians should make reducing declines in patients' nutritional status a priority regardless of patients' nutritional status at admission.     

Epidemiology and clonality of methicillin-resistant and methicillin-susceptible Staphylococcus aureus causing bacteremia in a tertiary-care hospital in Spain.

OBJECTIVES: To describe the relative proportions of nosocomial and community-onset Staphylococcus aureus bacteremia at our institution and the epidemiologic characteristics and clonal diversity of S. aureus isolates, as determined by pulsed-field gel electrophoresis (PFGE) and antimicrobial resistance patterns. DESIGN: Retrospective cohort study of all cases of S. aureus bacteremia between October 2001 and October 2002. SETTING: A 1300-bed, tertiary-care hospital. RESULTS: One hundred sixty-two unique episodes of S. aureus bacteremia were identified. Forty-three cases (26.5%) were caused by methicillin-resistant S. aureus (MRSA). Most cases of S. aureus bacteremia, whether MRSA or methicillin susceptible (MSSA), were nosocomial in origin (77.2%) or were otherwise associated with the healthcare system (16%). Only 11 (6.8%) of the cases (all MSSA) were strictly community acquired. Thirty-five unique macrorestriction patterns were identified among the 154 isolates that were typed by PFGE. Four major genotypes were defined among the isolates of MRSA, with 36 (85.7%) represented by a single PFGE type. Of the isolates within this major clone, all (100%) were ciprofloxacin resistant and 77.8% were erythromycin resistant. In contrast, the 112 isolates of MSSA comprised 31 different PFGE types, 3 of which represented 42.9% of all MSSA isolates and were associated with both nosocomial and community-onset bacteremia. CONCLUSIONS: Most cases of S. aureus bacteremia in our healthcare region are nosocomial in origin or are acquired through contact with the healthcare system and are thus potentially preventable. To preclude dissemination of pathogenic clones, it is therefore necessary to redouble preventive measures in both the hospital and the community.     

Morphine-induced suppression of saccharin intake is correlated with elevated corticosterone levels

Rats suppress intake of a saccharin conditioned stimulus (CS) when paired with a drug of abuse. This phenomenon, however, is not uniform across all subjects and is greater following exposure to stress and in animals that more readily self-administer drugs of abuse. The present study was designed to examine these individual differences in intake suppression following seven saccharin-morphine pairings. Plasma corticosterone also was evaluated both before and after conditioning in order to determine whether the magnitude of CS suppression is, or is not, related to circulating corticosterone levels. The findings indicated that, while all rats were exposed to the same number of saccharin-morphine pairings, only half of these animals actually suppressed intake of the saccharin CS. Moreover, the results showed that greater suppression of CS intake was associated with higher corticosterone levels at test (r=-0.84, P<0.0001). Taken together, the results demonstrate that individual differences affect not only the reduction in CS intake following taste-drug pairings, but also the associated cue-induced elevation in circulating corticosterone.     

Treatment of osteoarthritis of the knee with valgus deformity by means of varus osteotomy

Nineteen cases of osteoarthritis of the knee with valgus deformity in 17 patients were treated by femoral supracondylar varus osteotomy (17 cases) or by high tibial varus osteotomy (2 cases) over the last 15 years. Fixation was performed using a 95 degrees AO blade-plate in 13 of the femoral osteotomies and a straight plate in the other four. The mean follow-up time was 6.5 years. The valgus deformity was idiopathic in 14 cases, secondary to rheumatoid arthritis in 2 cases and to tibial valgus in one case. The Hospital for Special Surgery (HSS) score was used to evaluate the clinical results: nearly 75% were excellent or good. The causes related to poor results are analyzed regarding indication and surgical technique. It appears that varus osteotomy is an effective procedure for the treatment of osteoarthritis of the knee with valgus deformity, above all in order to alleviate pain, although the operation requires precision, and correct selection of patients is of prime importance.     

Approach to the management of complex hepatic injuries

BACKGROUND: Complex hepatic injuries American Association for the Surgery of Trauma Organ Injury Scale grades IV and V incur high mortality rate ranging from 40 to 80%, respectively. The objective of this study is to assess the clinical experience with an aggressive approach to the management of these, the most complex of hepatic injuries. METHODS: This is a retrospective 6-year study (1992-1997) at an American College of Surgeons urban Level I trauma center of patients sustaining complex hepatic injuries whose interventions included surgery, angiographic embolization, endoscopic retrograde cholangiopancreatography plus biliary stenting and percutaneous computed tomographic-guided drainage. The main outcome measure was survival. RESULTS: A total of 22 patients sustaining complex hepatic injuries; mean age of 26 years (range, 10-52 years), mean Revised Trauma Scale score of 9.9, mean Injury Severity Score of 32 (range, 16-75), American Association for the Surgery of Trauma - Organ Injury Scale grade IV (13 cases); grade V (9 cases). Mean estimated blood loss was 4,600 mL; mean number of units of blood transfused was 15. The patients underwent the following interventions: surgery (n = 22), re-operated (n = 13), mean number of operations 1.6 (range, 1-4), extensive hepatotomy and hepatorrhaphy (n = 17), nonanatomic resection (n = 7), formal hepatectomy (n = 4), packing (n = 10), direct approach to hepatic veins (n = 3); angiographic embolization (n = 15); endoscopic retrograde cholangiopancreatography and stenting (n = 5); computed tomographic guided drainage (n = 6). Mean length of stay in the intensive care unit was 21 days (range, 2-134 days), mean hospital length of stay was 40 days (range, 2-147 days). Overall mortality rate was 14% (3 of 22 cases), hepatic mortality rate was 9% (2 of 22 cases), mortality rate by injury grade was 8% grade IV (1 of 13 cases) and 22% grade V (2 of 9 cases). CONCLUSION: In this select patient population, improvements in mortality rates can be achieved with an aggressive approach to the management of complex hepatic injuries, including surgery, early packing, angiographic embolization, endoscopic retrograde cholangiopancreatography and stenting of biliary leaks, and drainage of hepatic abscesses.