Money well spent: a comparison of hospital operating margin for laparoscopic and open colectomies.

BACKGROUND: Cost analysis after laparoscopic colectomy has been examined, although reports evaluating the effects of laparoscopy on hospital operating margin are lacking. We compared several cost/revenue measures, including hospital operating margin, between open and laparoscopic colectomies at an academic center. METHODS: Our cost-accounting database was queried for laparoscopic partial (LPC) and total colectomies (LTC), and open partial (OPC) and total colectomies (OTC) to analyze net revenue, total costs, and total hospital operating margin over a 4-year period. Laparoscopic and open colectomy cases were compared, with mean operating margin as the primary outcome. RESULTS: From July, 2002 through May, 2006, 842 patients were included for analysis with 138 undergoing laparoscopic colectomy. Net revenue was higher in the LTC group compared with open (US dollars 30,300 vs US dollars 26,800 [P = .02]), and lower in the LPC group (US dollars 15,300 vs US dollars 21,300 open [P < .0001]). Total costs were reduced in both the LPC and LTC groups compared with open [US dollars 11,700 vs US dollars 17,600 [P < .0001] and US dollars 18,000 vs US dollars 19,400 [P = .0019], respectively). LPC resulted in a similar HOM (US dollars 3,602) compared with OPC (US dollars 3,647; P = .35). LTC resulted in a higher HOM (US dollars 12,300) compared with OTC (US dollars 7,400; P = .02). CONCLUSIONS: LTC generates a significantly higher hospital operating margin than an OTC, although the margins are similar for LPC and OPC.

Transport properties of alveolar epithelium measured by molecular hetastarch absorption in isolated rat lungs.

To evaluate the transport properties of the alveolar epithelium, we instilled hetastarch (Het; 6%, 10 ml, 1 - 1 x 10(4) kDa) into the trachea of isolated rat lungs and then measured the molecular distribution of Het that entered the lung perfusate from the air space over 6 h. Het transport was driven by either diffusion or an oncotic gradient. Perfusate Het had a unique, bimodal molecular weight distribution, consisting of a narrow low-molecular-weight peak at 10-15 kDa (range, 5-46 kDa) and a broad high-molecular-weight band (range 46-2,000 kDa; highest at 288 kDa). We modeled the low-molecular-weight transport as (passive) restricted diffusion or osmotic flow through a small-pore system and the high-molecular-weight transport as passive transport through a large-pore system. The equivalent small-pore radius was 5.0 nm, with a distribution of 150 pores per alveolus. The equivalent large-pore radius was 17.0 nm, with a distribution of one pore per seven alveoli. The small-pore fluid conductivity (2 x 10(-5) ml. h(-1). cm(-2). mmHg(-1)) was 10-fold larger than that of the large-pore conductivity.

Results of multiple diagnostic tests for Mycobacterium avium subsp. paratuberculosis in patients with inflammatory bowel disease and in controls.

Mycobacterium avium subsp. paratuberculosis has been incriminated as a cause of Crohn's disease (CD); however, studies to date have been relatively small and generally only used a single diagnostic assay. The objective of the study was to reexamine the association of M. avium subsp. paratuberculosis and CD using multiple diagnostic tests. Five methods were used to detect M. avium subsp. paratuberculosis infections in 439 inflammatory bowel disease (IBD) patients and 324 control subjects in the United States and Denmark. Most assays were adaptations of diagnostic tests for this infection performed routinely on animals. PCR for IS900, a genetic element unique to M. avium subsp. paratuberculosis, was positive significantly more often on resected bowel and lymph node tissues from CD patients (19.0%) and ulcerative colitis (UC) patients (26.2%) than from controls (6. 3%) (P < 0.05). Positive IS900 PCR results occurred more often in U. S. than in Danish IBD patients, 32.0 versus 13.3% (P = 0.025). The majority of Danish patients were bacillus Calmette-Guérin (Mycobacterium bovis BCG) vaccinated (CD, 77.5%; UC, 86.6%; controls, 83.0%) whereas none of the U.S. patients with IBD and only 2% of U. S. controls were vaccinated. Among Danish IBD patients, positive PCR findings were four times more common among subjects who were not BCG vaccinated (33.3%) than among BCG vaccinates (8.8%, P = 0.02). Culture of the same tissues tested by PCR using modified BACTEC 12B medium failed to grow M. avium subsp. paratuberculosis from patients or controls. U.S. CD patients had the highest serological evidence (enzyme-linked immunosorbent assay [ELISA] for serum antibodies) of M. avium subsp. paratuberculosis infection (20.7% of patients positive) which was higher than for all UC patients studied (6.1%) or healthy controls (3.8%, P < 0.005). Among Danish patients alone, however, no significant differences in rates of ELISA-positive results among CD, UC, or control patients were found. For 181 study subjects, both IS900 PCR and ELISA were performed. Although 11 were ELISA positive and 36 were PCR positive, in no instance was a patient positive by both tests, suggesting that these states are mutually exclusive. Evaluation of cytokine-mediated immune responses of IBD patients was complicated by the influence of immunosuppressive therapy given most IBD patients. Gamma interferon (IFN-gamma) release by peripheral blood leukocytes after M. avium purified protein derivative PPD antigen stimulation showed significantly lower responses in CD patients than in UC patients or controls in both U.S. (by ex vivo assay) and Danish (by in vitro assay) populations (P < 0.05). Interleukin-5 responses were not different among CD, UC, or control groups. Collectively, the PCR, ELISA, and IFN-gamma tests for M. avium subsp. paratuberculosis together with the unexpected observation that BCG vaccination influenced M. avium subsp. paratuberculosis detection, lead us to conclude that M. avium subsp. paratuberculosis, or some similarly fastidious mycobacterial species, infects at least a subset of IBD patients. Whether the infection is primary (causal) or secondary, it may contribute to the etiopathogenesis of IBD.

Acellular hemoglobin solution enters compressed lung capillaries more readily than red blood cells.

High lung inflation pressures compress alveolar septal capillaries, impede red cell transit, and interfere with oxygenation. However, recently introduced acellular hemoglobin solutions may enter compressed lung capillaries more easily than red blood cells. To test this hypothesis, we perfused isolated rat lungs with fluorescently labeled diaspirin cross-linked hemoglobin (DCLHb; 10%) and/ or autologous red cells (hematocrit, 20). Septal capillaries were compressed by setting lung inflation pressure above vascular pressures (zone 1). Examination by confocal microscopy showed that DCLHb was distributed throughout alveolar septa. Furthermore, this distribution was not affected by adding red blood cells to the perfusate. We estimated the maximum acellular hemoglobin mass within septa to be equivalent to that of 15 red blood cells. By comparison, we found an average of 2.7 +/- 4.6 red cells per septum in zone 1. These values increased to 30.4 +/- 25.8 and 50.4 +/- 22.1 cells per septum in zones 2 and 3, respectively. We conclude that perfusion in zone 1 with a 10% acellular hemoglobin solution may increase the hemoglobin concentration per septum up to fivefold compared with red cell perfusion.

Pulmonary capillary sieving of hetastarch is not altered by LPS-induced sepsis.

BACKGROUND: Gram-negative lipopolysaccharide (LPS) has been demonstrated to increase pulmonary capillary permeability as judged by the increased flow of protein-rich lymph from the lungs of sheep infused with LPS. This finding suggests that LPS-injured pulmonary capillaries might be less restrictive than uninjured capillaries to the filtration of large hetastarch molecules. Hetastarch has a broad molecular mass spectrum (35-1,500 kilodaltons (kDa)), and one way to test the restrictiveness of pulmonary capillaries is to measure the size of the largest hetastarch molecules that cross the microvascular barrier and enter the lymph. To evaluate the effects of LPS, we compared hetastarch molecular distributions in the lung lymph of normal and LPS-injured sheep. METHODS: Adult sheep (38.2 +/- 0.8 kg) were surgically prepared for the collection of lung lymph, with study initiation after a 5- to 7-day recovery period. Hetastarch (6%) was infused (10 mL/kg) 24 hours before study to allow for stabilization of the hetastarch molecular distribution. On the day of study, LPS (Escherichia coli lipopolysaccharide, 2 microg/kg; n = 6) was infused, and plasma and lymph samples were collected for 12 hours. An additional group of animals not infused with LPS (n = 6) served as controls. Hetastarch molecular distributions in plasma and lymph were measured by using high performance size exclusion chromatography. RESULTS: In control sheep, the largest hetastarch molecules in lymph averaged 861 +/- 18 kDa (mean +/- SEM) (plasma, 1,065 +/- 18 kDa). In LPS-treated sheep, the largest hetastarch molecules in lymph averaged 845 +/- 19 kDa (not significant vs. normal) (plasma, 1,025 +/- 14 kDa). Hetastarch concentrations in plasma and lung lymph of normal sheep, respectively, were 0.61 +/- 0.05% and 0.34 +/- 0.07%. In LPS-treated sheep, hetastarch concentrations in plasma and lymph were 0.56 +/- 0.08 (not significant vs. normal) and 0.29 +/- 0.07, respectively (p < or = 0.05). Lymph concentrations were lower after LPS because of increased lymph flows (19.9 +/- 5.4 mL/30 min, compared with 3.6 +/- 0.8 mL/30 min in normal sheep). CONCLUSION: Our results suggest that LPS does not alter the diameter of the largest pores perforating the walls of pulmonary capillaries. Rather, the number of these pores in the capillary wall appears to be increased. This increase would explain why lymph flows rise after LPS with little change in the lymph protein concentration. Our results are also consistent with a filtration model in which capillaries are assumed to be perforated by small pores (protein reflection coefficient = 1) as well as large pores (protein reflection coefficient = 0).

Filtration of diaspirin crosslinked hemoglobin into lung and soft tissue lymph.

Diaspirin crosslinked hemoglobin (DCHb) is a new blood substitute manufactured from human blood. To evaluate its microvascular filtration properties, we infused DCLHb into unanesthetized sheep (10%, 20 ml/kg) and measured the flow and composition of lung and soft tissue lymph. For comparison, we also infused human serum albumin (HSA; 10%, 20 ml/kg). DCLHb raised systemic and pulmonary arterial pressures from baseline values of 83 +/- 7 and 13 +/- 2 mm Hg, respectively, to peak values of 113 +/- 9 and 26 +/- 3 mm Hg (p < 0.05 versus baseline). These increases were significantly greater than those associated with HSA, which raised systemic and pulmonary arterial pressures from baseline values of 86 +/- 4 and 13 +/- 2 mm Hg, respectively, to peak values of 97 +/- 3 and 21 +/- 7 mm Hg (p <= 0.05 versus baseline and versus DCLHb). These differences reflect the known pressor properties of DCLHb. Accordingly, DCLHb raised lung and soft tissue lymph flows to peak values of 12.2 +/- 3.8 and 1.6 +/- 0.7 ml/30 min, respectively, while HSA raised lung and soft tissue lymph flows to peak values of 7.5 +/- 4.8 and 4.6 +/- 1.9 ml/30 min, respectively (p <= 0.05 versus DCLHb). The half-times of DCLHb equilibration from plasma into lung and soft tissue lymph of 1. 0 +/- 0.3 and 2.1 +/- 1.1 h, respectively, were significantly faster than HSA equilibration half-times of 3.1 +/- 0.2 and 3.8 +/- 0.9 h. Filtration differences between DCLHb and HSA appear to be due to the pressor properties DCLHb.

Physiologic evaluation and surgical management of failed ileoanal pouch.

BACKGROUND: Following proctocolectomy and ileal pouch-anal anastomosis, a small percentage of patients will have poor functional results attributable to pouchitis or anastomotic or septic complications. Additionally, functional failures can occur secondary to limited pouch capacity and compliance. We present five such patients managed with operative conversion to W-ileal pouch-anal anastomosis and examined physiologic parameters important for improving functional results. METHODS: Five female patients (mean age, 30 (range, 24-39) years) with poorly functioning J-ileal pouch-anal anastomoses were referred for evaluation with symptoms of high stool frequency and incontinence problems. Three had severe nocturnal incontinence, and the remaining two patients experienced minor nocturnal incontinence. Preoperative and postoperative evaluation included barium pouch studies, flexible sigmoidoscopy, anal manometry, evacuation volume, and pouch compliance. Pouch-to-anal pressure gradients were calculated. To improve reservoir capacity and compliance, all five patients underwent conversion to W-ileal pouch-anal anastomoses. RESULTS: Twenty-four hour and nocturnal stool frequencies decreased from 13.8+/-1.7 and 3+/-1.3 to 5.8+/-0.3 and 0.3+/-0.2 postconversion (P < 0.05). Mean pouch evacuation volume increased from 83+/-27 to 290+/-29 ml postoperatively (P < 0.05). Pouch compliance increased from 2.7+/-0.5 mmHg/ml to 7.7+/-0.6 mmHg/ml postconversion (P < 0.05). Improvement in postconversion stool frequency correlated with an increase in pouch evacuation volume (r=-0.87). All patients reported improved day and nocturnal continence, despite no significant change between preoperative and postoperative anal manometric pressures. Improved continence correlated with a significant widening of the pouch-to-anal pressure gradients, which increased from 5 to 25 mmHg at 150 ml following pouch conversion. CONCLUSIONS: Poorly functioning ileal reservoirs secondary to limited capacity and compliance can be successfully managed with conversion to W-ileal pouch-anal anastomosis. The increased pouch capacity is associated with improvement in compliance and widening of the pouch-to-anal pressure gradients, providing excellent functional results.

Pneumocystis carinii pneumonia postrestorative proctocolectomy for ulcerative colitis: a role for perioperative prophylaxis in the cyclosporine era? Report of a case and review of the literature.

PURPOSE: Medical management of severe ulcerative colitis has used cyclosporine with increasing frequency as an adjuvant to systemic steroids and mercaptopurine. However, the effects of combined management with cyclosporine and prednisone may lead to significant immune compromise and adversely affect operative morbidity in the event urgent surgery is required. METHODS: A case is reported of a 43-year-old white male who presented with severe ulcerative colitis. The patient had been initially treated with prednisone and cyclosporine for six weeks before surgical intervention. The intractability of his ulcerative colitis caused the patient to present to surgery, where he underwent restorative proctocolectomy. RESULTS: On initial presentation, the patient manifested systemic signs of severe ulcerative colitis with hypoalbuminemia, anemia, and weight loss, despite continuous prednisone and cyclosporine management. Before surgical intervention, a chest x-ray and the patient's respiratory status were normal. A total abdominal colectomy with ileal pouch reconstruction and temporary loop ileostomy were performed without incident. On the fifth postoperative day, the patient developed respiratory failure, which was subsequently diagnosed as Pneumocystis carinii pneumonia. Although ventilator support and both aggressive medical and surgical management eventually resulted in successful outcome, significant perioperative morbidity occurred. CONCLUSIONS: In the era of aggressive medical management for ulcerative colitis with both steroids and cyclosporine, the complications of immunosuppression may be significant, including opportunistic pneumonia. Prophylaxis against P. carinii pneumonia with sulfa antibiotics should be considered, especially in patients for whom proctocolectomy is a potential end point.

Neoplasia in ileal pouch mucosa after total proctocolectomy for juvenile polyposis: report of a case.

PURPOSE: Patients treated with restorative proctocolectomy for familial adenomatous polyposis or ulcerative colitis occasionally develop disease in the ileal pouch similar to that originally present in the colon. We investigated the possibility of analogous involvement in the ileal pouch of juvenile polyposis patients. METHODS: Endoscopic surveillance for neoplasia throughout the gastrointestinal tract was performed, with retrieval of all polypectomy specimens for histologic classification using the criteria of Morson. RESULTS: Multiple large juvenile polyps were found in the ileal pouch of one patient less than 10 years after restorative proctocolectomy for hereditary juvenile polyposis. The pouch was much more severely affected than the proximal ileum, small intestine, or stomach. Although most polyps had a completely benign histologic appearance, three had moderate to severe dysplasia. DISCUSSION: Mucosal changes induced by bacteria or stasis of luminal contents may promote manifestation in the ileal pouch of the disease phenotype usually more evident in the colon. Patients with severe or generalized juvenile polyposis should be considered for periodic endoscopic surveillance of the ileal pouch beginning several years after restorative proctocolectomy.

Molecular distribution of hetastarch in plasma and lung lymph of unanesthetized sheep.

We used high performance size exclusion chromatography (HPSEC) to measure concentrations and molecular masses of hetastarch (Het) in plasma and lung lymph of unanesthetized sheep. Our goal was to assess the osmotic effectiveness of Het in the pulmonary circulation as judged by its exclusion from lung lymph. Sheep (n = 5) received 35 ml/kg of Het (6%) over 90 min. At the end of the infusion, Het concentrations in plasma reached a peak value of 2.9 +/- 0.1% (mean +/- SD). Lymph concentrations reached a peak value of 1.3 +/- 0.3% at 4.5 h. Het molecular masses in plasma averaged 650 +/- 36 kD at 90 min, but ranged from 31 to 2,942 +/- 187 kD. Masses in lung lymph averaged 373 +/- 71 kD, and ranged from 19 +/- 2 to 1,693 +/- 514 kD (p < or = 0.05 vs. plasma). Het contributed 6.7 +/- 1.5 mm Hg to the plasma macromolecular osmotic pressure, and 3.7 +/- 1.8 mm Hg to the lymph osmotic pressure. Despite the fact that Het has the largest molecular mass of any of the current macromolecular plasma volume expanders, we found that it filtered readily into lymph, raising the lymph osmotic pressure. These findings suggest that the rationale for the osmotic performance of such solutions may need to be reconsidered.

Resuscitation from hemorrhagic shock with diaspirin cross-linked hemoglobin, blood, or hetastarch.

BACKGROUND: An oxygen-transporting hemoglobin solution should be more effective than a nonhemoglobin solution for resuscitation from hemorrhagic shock. A way to evaluate this effectiveness is to determine whether a hemoglobin solution can reverse the base deficit accumulated during hemorrhage at a faster rate than a nonhemoglobin solution. Using this criterion, we compared the resuscitative powers of autologous blood, hetastarch (Het), and diaspirin cross-linked hemoglobin (DCLHb). METHODS: Fifteen sedated, spontaneously breathing sheep (37.5 +/- 10.2 kg) were bled until base deficits fell to -5 to -10 mEq/L, and plasma lactate concentrations rose to 6 to 9 mg/L. The animals were resuscitated with autologous blood (n = 5), Het (n = 5), or DCLHb (n = 5) (3.5-4.0 mL/kg every 15 minutes) until base deficits returned to prehemorrhage baseline. RESULTS: Exsanguination to target base deficits required removal of an average of 41.4 +/- 5.5 mL blood/kg (estimated total blood volume, 80 mL/kg). Resuscitation required 18 +/- 3, 38 +/- 2 (different from blood), and 35 +/- 1 (different from blood) mL/kg of autologous blood, Het and DCLHb, respectively, over periods of 78 +/- 8, 163 +/- 10 (different from blood), and 129 +/- 9 minutes (different from blood and different from Het (p < or = 0.05)). Based on regression analysis, autologous blood, Het, and DCLHb corrected the base deficit at rates of, respectively, 0.074 (different from Het (p < or = 0.05)), 0.016, and 0.056 (different from Het (P < or = 0.05)) mEq/L/min. CONCLUSIONS: Based on the rate of base deficit correction and the volume of solution required, autologous blood was the most effective resuscitation solution. However, DCLHb was more effective than Het. DCLHb may be an attractive alternative to blood for resuscitation from hemorrhagic shock.

Lung lymph oncotic pressure may not modulate pulmonary vascular filtration in sheep.

We tested the hypothesis that plasma oncotic pressure alone, not the plasma-to-lymph oncotic pressure difference, modulates pulmonary transvascular fluid filtration. To do this we measured lung lymph flow after raising left atrial pressure (by inflating a balloon) in sheep that were receiving a continuous (32 h) infusion of dextran 40. For comparison, we also raised left atrial pressure elevation, plasma oncotic pressures in dextran and control sheep, respectively, were 39.5 +/- 4.5 and 17.7 +/- 2.2 mm Hg; plasma-to-lymph oncotic pressure gradients, respectively, were 4.4 +/- 0.6 and 4.4 +/- 0.6 mm Hg. Left atrial pressure elevation during dextran infusion increased lung lymph flow by a factor of 2.4 +/- 0.4, compared with a factor of 4.2 +/- 2.3 in control sheep. Thus, left atrial pressure elevation increased lymph flow less in dextran-treated animals than in control animals, even though the plasma-to-lymph oncotic pressure gradients were equal. This suggests that plasma oncotic pressure alone may be a more important determinant of pulmonary transvascular fluid filtration than the plasma-to-lymph oncotic pressure difference.

Thoracic versus lumbar epidural anesthesia's effect on pain control and ileus resolution after restorative proctocolectomy.

BACKGROUND: Epidural anesthesia as a perioperative adjunct has been shown to provide superior pain control and has been implicated in more rapid ileus resolution after major abdominal surgery, possibly through a sympatholytic mechanism. Studies suggest that the vertebral level of epidural administration influences these parameters. METHODS: One hundred seventy-nine patients (120 male, 59 female; average age, 36 years) underwent restorative proctocolectomy for ulcerative colitis or familial polyposis between 1989 and 1995. Patients were grouped according to type of anesthesia. Group THO (n = 53) received thoracic (T6 to T10) epidurals. Group LUM (n = 51) received lumbar (L2 to L4) epidurals, and group PCA (n = 75) received patient-controlled intravenous narcotic analgesia. Patients were compared for complications, perioperative risk factors, postoperative pain, and ileus resolution. RESULTS: Epidural narcotics, alone or combined with local anesthetics, were administered for an average of 2 (LUM) to 4 (THO) days without significant complications. Infrequent problems related to the epidural catheters included self-limited headaches or back pain (four) and site infections (two). Epidural failure, as measured by conversion to PCA for inadequate pain control, was not significantly greater for LUM (25%) than THO (23%). Average pain scores, rated daily on a visual analog scale, were significantly higher (indicating more pain) for PCA patients (4.2) during postoperative days 1 through 5 than for LUM (3.5) (p < 0.05) and for THO (2.4) (p < 0.05). Ileus resolution, as determined by stool output and return of bowel sounds, was significantly faster in THO than in LUM or PCA (p < 0.05). Resolution of ileus was not significantly different between PCA and LUM (p > 0.05). CONCLUSIONS: Thoracic epidural analgesia has distinct advantages over both lumbar epidural or traditional patient-controlled analgesia in shortening parameters measuring postoperative ileus and in reducing surgical pain. The procedure is safe and associated with low morbidity. Thoracic epidural anesthesia is also economically justifiable and may prove to impact significantly on future postoperative management by reducing length of hospitalization. Our data and those of others are most striking in these regards for patients with thoracic catheters, indicating the importance of vertebral level in epidural drug administration.

Pulmonary vascular filtration of starch-based macromolecules: effects on lung fluid balance.

BACKGROUND: Pulmonary edema is a complication of critical care fluid management that may be restricted by the use of oncotically effective resuscitation fluids. Potentially beneficial oncotic properties of starch-based plasma volume expanders such as hetastarch (Het), pentafraction (Pen), and Dextran-70 (Dex) may be compromised by their broad range of molecular masses, some of which are small enough to filter from the circulation. Leakage of these molecules into the pulmonary interstitium may limit their oncotic effectiveness and enhance fluid filtration. We measured the filtration of these three resuscitation solutions into lung lymph to evaluate their oncotic contribution to pulmonary edema formation. MATERIALS AND METHODS: Unanesthetized euvolemic adult sheep, prepared with chronic lung lymph fistulae, underwent plasma volume expansion with Het (n = 6), Pen (n = 6), or Dex (n = 6 ) (6%, 35 ml/kg/90 min). Oncotic effectiveness was determined by measuring plasma and lymph oncotic pressures and the oncotic pressures contributed by each starch. Pulmonary hydrostatic pressures and lung lymph flows (Q(L)) were also measured. Results are expressed as means +/- SEM. Comparisons were made by two-factor analysis of variance. RESULTS: Dex contributed 9.0 +/- 0.9 mmHg to the plasma oncotic pressure, significantly more than Het and Pen (5.3 +/- 0.6, 6.5 +/- 0.6 mmHg, respectively). However, Dex filtration also contributed 6.1 +/- 0.5 mmHg to the lymph oncotic pressure, compared to 3.1 +/- 0.3 and 4.7 +/- 0.5 mmHg for Het and Pen, respectively (P < or = 0.05). Dex, Het, and Pen raised Q(L) over baseline by 7.7 +/- 1.5, 4.3 +/- 1.0, and 3.2 +/- 0.7 ml/30 min, respectively (P < or = 0.05). Dex increased Q(L) significantly more than Het or Pen. CONCLUSIONS: Pen and Het demonstrated greater oncotic effectiveness because of restricted plasma-to-lymph macromolecular filtration and limited transvascular fluid flux. By comparison, Dex filtered rapidly and increased transvascular fluid filtration. Pen appears to possess filtration properties that optimize critical care fluid management compared to currently available colloid solutions such as Het and Dex.

Effects of University of Wisconsin and Euro-Collins solutions on interstitial pulmonary edema in isolated rat lungs.

Macromolecules are present in lung preservation solutions to limit liquid filtration out of the pulmonary circulation and minimize pulmonary edema. We tested the effectiveness of these molecules by measuring interstitial edema in rat lungs perfused with macromolecular solutions (University of Wisconsin [UW] solution and Euro-Collins solution supplemented with modified pentastarch [pentafraction, PEN]) or with solutions that lacked macromolecules (UW solution with PEN and Euro-Collins solution.) The lungs were inflated with air and perfused with one of the test solutions, then rapidly frozen and prepared for histological analysis. From tissue sections, we measured cross-sectional areas of pulmonary arteries and veins, and also measured cross-sectional areas of the interstitial spaces surrounding arteries and veins. We then calculated the interstitium-to-vessel cross-sectional area ratio. In lungs perfused with macromolecular solutions these ratios were 0.09+/-0.15 and 0.53+/-0.56 (mean +/- SD) for UW solution and Euro-Collins solutions solution with PEN, respectively (P

Does plasma protein depletion increase lung liquid conductance?

Lung liquid conductance (Kf) is calculated as the quotient of lung lymph flow divided by net filtration pressure (Pnf), where Pnf is the balance of osmotic and hydrostatic pressures in the lung microcirculation. In protein depletion, lymph flow rises with little change in Pnf, suggesting that calculated Kf also rises. However, several previous reports have concluded that protein depletion causes little change in Kf, leaving open the question of how lung lymph flow can rise in protein depletion with little change in Pnf. To address this, we measured Kf in sheep following two kinds of protein depletion: batch plasmapheresis (BP; n = 5) and thoracic duct drainage (TD; n = 5). Both methods lowered plasma protein concentrations by 30%, and raised lung lymph flows by 55%. Lung microvascular hydrostatic pressures and plasma-to-lymph osmotic pressure gradients both changed by 1 to 2 mm Hg. With BP, calculated Kf rose from 0.26 +/- 0.09 at baseline to 0.50 +/- 0.20 on Day 1, and to 0.39 +/- 0.27 ml/mm Hg/30 min on Day 2 (p < or = 0.05). With TD, calculated Kf rose from 0.28 +/- 0.13 at baseline to 0.43 +/- 0.19 on Day 1, and to 0.43 +/- 0.19 ml/mm Hg/30 min on Day 2 (p < or = 0.05). Calculated Kf rose because filtration increased even though the hydrostatic and osmotic driving forces responsible for filtration changed little. This is puzzling because it suggests that lymph flow rose with little or no change in the forces affecting filtration. Our findings contradict several previous reports that concluded that protein depletion produces little or no change in calculated Kf.

Interleukin-2 does not sequester activated lymphocytes into lung lymph of sheep.

PURPOSE OF STUDY: Interleukin-2 (IL-2) is a potent activator of lymphocytes, but its effectiveness as an anti-cancer agent is compromised by several adverse side effects including pulmonary edema. One explanation for the pulmonary toxicity of IL-2 is that activated lymphocytes directly induce the pulmonary vascular endothelium to become more leaky. METHODS: To test this hypothesis the number of total lymphocytes, gamma delta T cells, and CD2-positive cells (alpha beta T cells and natural killer cells) in peripheral blood and lung lymph of sheep were compared before and after IL-2 infusion. Hemodynamic and lymph dynamic changes were also evaluated. RESULTS: IL-2 decreased mean aortic pressure, increased cardiac output, lowered systemic vascular resistance, and doubled lung lymph flow (P < or = 0.05), but had no effect on plasma or lymph oncotic pressure. The lymph protein concentration and the lymph-to-plasma protein concentration ratio were not different after IL-2 infusion. IL-2 had no effect on the number of total lymphocytes, gamma delta T cells, or CD2-positive cells in the peripheral blood. In contrast, the number of total lymphocytes, gamma delta T cells, and CD2-positive cells in lung lymph decreased significantly (P < or = 0.05). CONCLUSIONS: The lymphocyte populations decreased more than could be explained by the increase in lymph flow, demonstrating that lung lymphocytes were not reduced simply by dilution. These results imply that the pulmonary edema associated with IL-2 is not caused by activated lymphocytes.

Relationships between sclerosing cholangitis, inflammatory bowel disease, and cancer in patients undergoing liver transplantation.

BACKGROUND: Liver transplantation has emerged as the definitive treatment for primary sclerosing cholangitis (PSC). Its relationships to inflammatory bowel disease and cholangiocarcinoma were evaluated in this series. METHODS: Fifty-three liver transplantations were performed in 41 patients with PSC at the University of Wisconsin from 1986 through 1994. Fourteen of the patients underwent colectomies for inflammatory bowel disease, eight before transplantation and six after transplantation. Five patients had cholangiocarcinoma on the hepatectomy specimen, and another two had been diagnosed before transplantation. RESULTS: Patient survival for PSC without cholangiocarcinoma was 85% and 62% at 2 and 9 years, respectively. No patient with PSC and cholangiocarcinoma has survived 2 years, although two patients were free of disease 11 and 20 months after transplantation. Despite maintenance immunosuppression seven patients with liver transplants had reactivation of inflammatory bowel disease and colon carcinoma developed in three after liver transplantation. CONCLUSIONS: Liver transplantation should be performed early in the course of PSC to avoid the lethal complications of cholangiocarcinoma. Careful colonoscopic follow-up is necessary in patients undergoing transplantation for PSC because immunosuppressive therapy does not necessarily cause inflammatory bowel disease to be quiescent, nor does it reduce the risk of colon carcinoma developing.

Management of paraesophageal hernia with a selective approach to antireflux surgery.

BACKGROUND: The role of an antireflux procedure in the management of paraesophageal hernia is controversial. To address this issue, we reviewed our experience with selective use of antireflux procedures in patients with pure paraesophageal hernia (type II; n = 26) and those with a partial sliding component (type III; n = 11). PATIENTS AND METHODS: Surgical repair was performed on diagnosis in all 37 patients. Competency of the lower esophageal sphincter was evaluated on the basis of reflux symptoms, and objectively, with endoscopy in 21 patients and 24-hour esophageal pH studies in 17 patients. Repair included an antireflux procedure in 11 patients, as indicated by reflux disease. RESULTS: Preoperatively, 80% of both type II and type III patients reported obstructive symptoms. Reflux symptoms were present in 27% of patients--19% of type II and 45% of type III patients. Endoscopy revealed esophagitis in 5 cases, and 24-hour pH studies indicated significant reflux in 3 of 17 patients. There were no operative deaths and 1 recurrence. Symptoms improved in 92% of patients after surgery. Medically manageable reflux was identified in 2 patients. CONCLUSIONS: Frequent obstructive symptoms and the potential for gastric volvulus indicate elective repair of paraesophageal hernia on diagnosis. Significant gastroesophageal reflux is less common, especially in type II patients, and excellent symptomatic results are obtained with selective application of an antireflux procedure.

Abnormal rectal mucosa of the anal transitional zone in ulcerative colitis.

OBJECTIVE: To determine the frequency of atypia and active ulcerative colitis (UC) in rectal mucosa within the anal transitional zone (ATZ). DESIGN: Surgeons identified ATZ tissues from restorative proctocolectomy specimens for determination by surgical pathologists of specific histopathologic features in rectal mucosa of the ATZ. SETTING: Surgical referral center for restorative proctocolectomy. PATIENTS: Ninety-four patients with symptomatic UC underwent restorative proctocolectomy between January 1991 and December 1994. INTERVENTIONS: Specific histopathologic features of active UC in the ATZ were evaluated by a single reviewer who did not know the clinicopathologic details of individual study patients. MAIN OUTCOME MEASUREMENTS: Presence and coexistence of rectal mucosal dysplasia (high or low grade), mucosa classified as indefinite for dysplasia, and acute UC (crypt abscess or cryptitis) in the ATZ. RESULTS: Of 94 ATZ tissue specimens, acute intracryptic inflammation was present in 60 rectal mucosa specimens (64%). In 29 (48%) of these 60 specimens, inflammation was neither widespread nor intense. Rectal mucosal dysplasia (low grade but not high grade) was present in 15 (16%) of 94 ATZs specimens. Inflammation elsewhere in the rectal mucosa accompanied dysplasia in 11 (73%) of 15 ATZ specimens. Rectal mucosa classified as indefinite for dysplasia was present in 24 (26%) of 94 ATZ specimens and coexisted with inflammation in 15 (63%) of these 24. Thus, rectal mucosal atypia was present in 39 (41%) of 94 ATZ specimens, and in 26 (67%) of these 39, abnormal rectal mucosa coexisted with acute inflammation. CONCLUSIONS: Rectal mucosa in the ATZ can exhibit active UC and/or atypia. Long-term monitoring is advisable if the ATZ is preserved during restorative proctocolectomy.