Confirmation of translocated gastrointestinal bacteria in a neonatal model.

PURPOSE: The hypothesis that enteric bacteria translocate from the gastrointestinal (GI) tract to extraintestinal sites has been extensively studied. However, definitive evidence that spontaneous bacterial translocation and dissemination from the GI tract to extraintestinal sites occur in a neonatal model has been lacking. The aim of this study was to confirm this phenomenon by tracking enterally administered, plasmid-labeled bacteria to extraintestinal sites. MATERIALS AND METHODS: Escherichia coli 07:K1 (E. coli K1) with and without a nontransferable, ampicillin resistance plasmid (pGEM-7) were used in this study. Newborn New Zealand white rabbit pups were separated into three treatment groups: transformed E. coli K1 (E. coli K1 + pGEM-7, n = 20), nontransformed E. coli K1 (n = 12), and control pups (no bacteria, n = 7). Pups were enterally fed 10% Formulac solution supplemented with a suspension of bacteria respective to their group. After the pups fed twice daily for 2 days, representative tissue specimens from the small bowel (SB), mesenteric lymph nodes (MLNs), spleen (SPL), and liver (LIV) were aseptically harvested and tested for culture growth in ampicillin-supplemented medium. RESULTS: Positive growths of plasmid-induced ampicillin-resistant bacteria were detected in tissue specimens harvested from rabbits fed transformed E. coli K1, but were not detected in the other groups. CONCLUSION: This experiment demonstrated conclusively that transformed E. coli K1 fed to healthy rabbit pups spontaneously translocated from the intestinal lumen and subsequently disseminated to the mesenteric lymph nodes, spleen, and liver.     

Mesenteric lymph is responsible for post-hemorrhagic shock systemic neutrophil priming.

BACKGROUND: Hemorrhagic shock-induced splanchnic hypoperfusion has been implicated as a priming event in the two event model of multiple organ failure (MOF). We have previously shown that early postinjury neutrophil (PMN) priming identifies the injured patient at risk for MOF. Recent in vitro studies have demonstrated that postshock mesenteric lymph primes isolated human neutrophils. We hypothesize that lymphatic diversion before hemorrhagic shock abrogates systemic PMN priming and subsequent lung injury. METHODS: Sprague-Dawley rats (n >or= 5 per group) underwent hemorrhagic shock (MAP 40 mm Hg x 30 min) and resuscitation (shed blood + 2x crystalloid) with and without mesenteric lymphatic duct diversion. Sham animals underwent anesthesia and laparotomy. Whole blood was taken 2 hours after resuscitation, heparinized, and incubated for 5 min at 37 degrees C. Surface expression of CD11b (a marker for PMN priming) was determined by flow-cytometry compared with isotype controls. In addition, lung myeloperoxidase (MPO) was measured for PMN sequestration, and Evans blue lung leak was assessed in the bronchoalveolar lavage fluid in sham, and shock +/- lymph diversion animals. RESULTS: Hemorrhagic shock resulted in increased surface expression of PMN CD11b relative to sham (23.8 +/- 6.7 vs. 9.9 +/- 0.6). Mesenteric lymphatic diversion before hemorrhagic shock abrogated this effect (8.0 +/- 2.6). Lung PMN accumulation, as assessed by MPO, was greater in the lungs of nondiverted (113 +/- 14 MPO/mg lung) versus sham (55 +/- 4 MPO/mg lung, p < 0.05); lymph diversion reduced lung PMNs to control levels (71 +/- 6.5 MPO/mg lung, p < 0.05). Evans blue lung leak was 1.6 times sham in the hemorrhagic shock group; this was returned to sham levels after lymph diversion (p < 0.05). CONCLUSION: Post-hemorrhagic shock mesenteric lymph primes circulating PMNs, promotes lung PMN accumulation, and provokes acute lung injury. Lymphatic diversion abrogates these pathologic events. These observations further implicate the central role of mesenteric lymph in hemorrhagic shock-induced lung injury. Characterizing the PMN priming agents could provide insight into the pathogenesis of postinjury MOF and ultimately new therapeutic strategies.     

Fluid resuscitation with deferoxamine prevents systemic burn-induced oxidant injury.

We studied the effect of deferoxamine (DFO) infused after burns on hemodynamic stability as well as local and systemic inflammation and oxidant-induced lipid peroxidation. Eighteen anesthetized sheep were given a 40% of total body surface burn and fluid resuscitated to restore oxygen delivery (DO2) and filling pressures to baseline values. Animals were resuscitated with lactated Ringer's (LR) alone or LR plus 1,500 ml of a 5% hetastarch complexed with DFO (8 mg/ml). Animals were killed 6 hours postburn. The sheep resuscitated with LR and LR plus hetastarch demonstrated significant lung inflammation and significant increases in lung and liver malondialdehyde (MDA) from controls of 47 +/- 6 and 110 +/- 7 nMol/gm to 63 +/- 13 and 202 +/- 59 for LR and 67 +/- 4 and 211 +/- 9 for LR + hetastarch, respectively. The group resuscitated with hetastarch alone required 15% less fluid. VO2 returned to baseline values in both groups by 2 hours. Resuscitation with the 5% hetastarch-DFO decreased total fluids by 30% over LR and prevented the increase in lung and liver MDA. In addition, postburn VO2 increased by 25% above baseline values. Burn tissue edema, measured as protein-rich lymph flow, was significantly increased with the administration of DFO compared with the other groups. We conclude that DFO used for burn resuscitation prevents systemic lipid peroxidation and decreases the vascular leak in nonburn tissues while also increasing O2 utilization. Resuscitation with hetastarch-DFO may accentuate burn tissue edema, possibly by increased perfusion of burn tissue.     

Morbidity of pelvic lymphadenectomy.

A retrospective review of 100 patients undergoing pelvic lymphadenectomy alone or with additional surgery was done to assess the morbidity and to help identify factors contributing to a high wound morbidity. Major wound morbidity occurred in 8 per cent of patients, while 16 per cent had minor wound problems. Factors contributing to wound morbidity included urinary tract infection, altered metabolic states, and the use of wound drains. Other morbid events are tabulated.     

V-N plasty for the release of severe postburn contractures.

The authors describe a technique for the release of severe postburn contractures of the web spaces by using all the available tissues in the web space as local flaps to avoid using skin grafts or distant flaps. We rely on the central part of the web to raise the main triangular flaps that may be used to create a functional web space. We called it the V-N plasty.     

AUC-guided dosing of tacrolimus prevents progressive systemic overexposure in renal transplant recipients

BACKGROUND: Tacrolimus has a narrow therapeutic window, and bioavailability is known to vary considerably between renal transplant recipients. Most centers still rely on measurement of trough levels, but there are conflicting reports on the correlation between tacrolimus trough levels and systemic exposure, as measured by the area-under-the-concentration-over-time curve (AUC((0-12h))). METHODS: We developed and validated a two-compartmental population-based pharmacokinetic model with Bayesian estimation of tacrolimus systemic exposure. Subsequently, we used this model to apply prospectively AUC-guided dosing of tacrolimus in 15 consecutive renal transplant recipients. The main objective was to study intrapatient variability in the course of time. RESULTS: Bayesian forecasting with a two-point sampling strategy, a trough level, and a second sample obtained between two and four hours post-dose significantly improved the squared correlation with the AUC((0-12h)) (r(2)= 0.94). Compared with trough level monitoring only, this approach reduced the 95%-prediction interval by 50%. The Bayesian approach proved to be feasible in clinical practice, and provided accurate information about systemic tacrolimus exposure in individual patients. In the AUC-guided dosing cohort the apparent clearance of tacrolimus decreased gradually over time, which was not reflected in corresponding trough levels. CONCLUSION: This simple, flexible method provides the opportunity to tailor immunosuppression, and should help minimize tacrolimus-related toxicity, such as nephrotoxicity and post-transplant diabetes mellitus.     

Intrarenal redistribution of blood flow in the early postburn period.

We interpret the findings of the present study and other studies reported here to indicate that alterations of renal outer to inner cortical blood flow distribution develop in the early postburn period. These alterations are similar to those observed by other investigators in animals subjected to various other traumatic events. Such flow redistributions were observed in both untreated animals and those receiving intravenous fluid resuscitation. Sharp reductions in urinary chloride and sodium concentrations observed in conjunction with these blood flow shifts may be a reflection of the relatively greater perfusion of juxtamedullary nephrons, which are alleged to have greater salt-retaining characteristics than their outer cortical counterparts.     

Three-field lymphadenectomy and pattern of lymph node spread in T3 adenocarcinoma of the distal esophagus and the gastro-esophageal junction

Objective: Lymph node metastasis in carcinoma of the esophagus and the gastro-esophageal junction is often underestimated by clinical staging. It is the aim of this study to provide support to the fact that three-field lymphadenectomy leads to a better pathological staging also in adenocarcinoma. Methods: The pattern of lymph node metastasis in adenocarcinoma of the gastro-esophageal junction (GEJ) and the distal esophagus was charted in a prospective way by using a database. An analysis was performed with regard to lymphatic spread in T₃, N⁺ adenocarcinomas of the distal esophagus and the GEJ junction, which were treated with a radical resection including a three-field lymphadenectomy. Out of 324 patients with adenocarcinoma of the esophagus and GEJ, we selected a group of 37 patients with an adenocarcinoma T₃, N⁺ of the distal (n=17) or GEJ junction (n=20), treated with a radical resection and three-field lymphadenectomy (>25 lymph nodes resected). Results: In total, 2240 lymph nodes were removed, with a mean of 59.5 per patient. In the GEJ group the ratio of positive nodes was 15.9, in the distal 1/3 group this ratio was 12.7%. Abdominal lymph nodes were positive in all GEJ tumors and in 70% of the distal third carcinomas. Thoracic lymph nodes were positive in 40% of GEJ tumors, and 70.6% of the distal group. Cervical lymph nodes were positive in 20% of the GEJ tumors and in 35.3% of the distal tumors. In six patients only right-sided cervical nodes were affected. Three patients in the GEJ group had positive lymph nodes in the neck without any involvement of thoracic lymph nodes. Conclusions: (1) Three-field lymphadenectomy improves accuracy of staging. (2) Cervical nodes are frequently involved. (3) Especially in tumors of the GEJ there is an important skipping phenomenon, i.e. positive lymph nodes in the neck in the absence of involvement of thoracic nodes. (4) Clinical staging remains deficient in regard to lymph node metastasis, especially cervical nodes. (5) The frequent unforeseen involvement of cervical lymph nodes in adenocarcinoma of the distal esophagus and GEJ tumors makes the interpretation of results of induction chemoradiotherapy questionable. (6) For the same reason, cervical lymph nodes should be included in the radiation field in case of induction chemoradiotherapy. (7) The similar pattern of lymph node involvement suggests similar oncological behavior of adenocarcinoma of the distal esophagus and the GEJ, questioning the actual TNM classification of these tumors as gastric carcinomas.     

Mortality and morbidity rates, postoperative course, quality of life, and prognosis after extended radical lymphadenectomy for esophageal cancer. Comparison of three-field lymphadenectomy with two-field lymphadenectomy.

PURPOSE: The authors evaluated the efficacy of extended radical (three-field) lymphadenectomy for esophageal cancer compared with less radical (two-field) lymphadenectomy. STUDY SUBJECTS AND ANALYTIC METHODS: The mortality and morbidity rates, postoperative courses, and survival rates were compared between 63 patients who underwent three-field lymph node dissection and 65 who underwent two-field lymph node dissection at Kurume University Hospital from 1986 to 1991. Long-term quality of life after surgery was compared between 37 patients who underwent three-field dissection and 35 who underwent two-field dissection from 1980 to 1991. RESULTS: Three-field dissection resulted in better survival for patients with positive lymph node metastasis from a carcinoma in the upper thoracic or midthoracic esophagus compared with two-field dissection. The mortality rates, postoperative courses and quality of life were the same for both procedures. CONCLUSIONS: Three-field dissection is preferred for upper thoracic or midthoracic esophageal cancer because of improved survival, acceptable mortality and morbidity rates, and good postoperative course and quality of life.     

Orbicularis oculi myocutaneous flap in reconstruction of postburn lower eyelid ectropion.

The management of postburn lower eyelid ectropion is difficult, since the contraction of the skin graft may give rise to secondary deformities especially around the lateral 1/3 of the lower eyelid. In this paper, the results of reconstruction in lower eyelid ectropion with a laterally based orbicularis oculi myocutaneous flap from the upper eyelid in 7 young patients are presented. Satisfactory function and cosmesis were obtained in the evaluation of the patients up to 40 months follow-up. The method proved versatile as the donor scar was well-hidden in the supratarsal fold and the temporally based myocutaneous flap provided additional support to the lower eyelid by exerting an upward pull against the gravity. It is concluded that usage of this flap in postburn ectropion cases is worthwhile to avoid any recurrences. reserved.     

Mechanism of prevention of postburn hypermetabolism and catabolism by early enteral feeding.

This study was performed to investigate the mechanism whereby immediate enteral feeding after burn injury reduces postburn hypermetabolism and hypercatabolism. Fifty-seven burned guinea pigs (30% TBSA) were divided into three groups: A (N = 19), given 175 kcal/kg/day beginning 2 hours after burn; B (N = 20), given 175 kcal/kg/day with an initial 72-hour adaptation period; and C (N = 18), given 200 kcal/kg/day with the same adaptation period as B. Resting metabolic expenditure (RME) on PBD 13 was lowest in group A (109% of preburn level), compared with group B (144%, p less than 0.001) and group C (137%, p less than 0.01). On PBD 1, group A had the greatest jejunal mucosal weight and thickness (p less than 0.001), and mucosal weight had negative correlations with plasma cortisol (r = 0.829, p less than 0.001) and glucagon (r = 0.888, p less than 0.001). Two weeks after burn, urinary vanillyl mandelic acid (VMA) excretion, plasma cortisol, and glucagon were lowest in group A (p less than 0.05 to p less than 0.01). These hormones also significantly correlated with RME (p less than 0.01 to p less than 0.001). These findings suggest that immediate postburn enteral feeding can prevent hypermetabolism via preservation of gut mucosal integrity and prevention of excessive secretion of catabolic hormones.