Cold liver preservation in the University of Wisconsin solution (UW) followed by reperfusion alters hepatic parenchyma and stroma. In this study we demonstrated the benefit of adding S-nitrosoglutathione (GSNO) to the UW solution before cold storage, as an effective Nitric Oxide (NO) donor to prevent hepatic injury. Wistar adult rat livers were stored in UW solution (4 degrees C-48Hs) and then reperfused 60 minutes in the isolated perfused rat liver model (IPRL). Normal untreated livers and perfused livers, but not preserved were used as controls. Parenchymal damages were evaluated with Hematoxylin-Eosin stain and an inmunohistochemistry assay for albumin was used as functional test. To study the stroma, collagen type III and I networks were analyzed using Picro-sirius Red stain and Gordon Sweets' method for reticulin. After 48 Hs of cold preservation in UW solution livers showed few rounded endothelial cells inside sinusoidal lumen and extended areas of cell vacuolation. Albumin distribution was evident only around central veins and middle zones of the hepatic lobule. Collagens III and I networks were disorganized. When preserved with the addition of 100 microM GSNO and then reperfused, the hepatic morphology, in general, was conserved showing little vacuolation, fewer endothelial cells inside sinusoids and good albumin distribution around central veins and middle zones. The stroma had organized networks of collagen III and I. We concluded that the addition of 100 microM GSNO as a NO donor, can improve UW solution properties to preserve rat liver by maintaining the hepatic morphology and avoiding hepatic injury post cold preservation/reperfusion.
A little more than 100 years ago Halsted pioneered a surgical approach that led, for the first time, to the cure of breast cancer in some patients. Veronesi's contribution was to offer the same possibility while considerably reducing the mutilation that went with cure. This article reviews the development of the conservative surgical approach in breast cancer and synoptically presents the results of large-scale clinical trials conducted by Veronesi's group in Milan in the 1970s and 1980s to demonstrate the efficacy of quadrantectomy, radiotherapy and axillary dissection (QUART) as conservative treatment for small size breast cancer. These studies set in motion the world-wide trend to conservative surgery in all forms of cancer. The article goes on to describe the surgical procedures of quadrantectomy and complete axillary dissection as developed by Veronesi, and outlines new indications for, and developments of this established conservative technique.
BACKGROUND:Fibroproliferative disorders, which include hypertrophic scars and keloids, represent deviations from the normal process of wound healing. The fibrogenic cytokines have been associated with excessive scarring. It has been proposed that placing silicone in contact with hypertrophic scars may prove to be an effective form of treatment. This may be a result of downregulating fibroblasts and/or decreasing the fibrogenic cytokines. An in vitro model to study wound contraction is a fibroblast populated collagen lattice (FPCL). This study used FPCL as a method to study the effect of silicone sheeting on hypertrophic scar fibroblasts.METHODS:Fibroblast cultures were obtained and collagen lattices were prepared. Silicone sheeting was placed over the collagen matrix versus Saran wrap used as a treatment control. The amount of gel contraction was measured every 24 hours for five days. The supernatant obtained from the culture medium following completion of the FPCL portion of the experiment was then used in an immunoassay for TGFbeta2.RESULTS:A statistically significant decrease in amount of FPCL contraction occurred between three of the four brands of silicone sheets used compared to untreated control or Saran wrap treated FPCL. The immunoassay for TGFbeta2 showed a statistically significant decrease with all four types of silicone sheeting.CONCLUSION:FPCLs populated with burn hypertrophic scar fibroblasts exposed to silicone sheeting have decreased contraction compared to an unexposed control and Saran wrap treated control. In addition, TGFbeta2 is downregulated in the silicone exposed group. It appears that silicone sheeting may act by downregulating fibroblasts and decreasing fibrogenic cytokines.
BACKGROUND:The Ileo-Pouch-Anal-Anastomosis (IPAA) is the standard restorative procedure for Ulcerative Colitis and Familial Adenomatous Polyposis (FAP). IPAA may lead to considerable losses of fluids, especially in association with a protective loop ileostomy.AIM:The aim of this study was to investigate adrenal mechanisms in the regulation of volume homeostasis immediately after IPAA and protective ileostomy.METHODS:For that purpose, 20 patients out of our patient population with elective IPAA with ileostomy participated in this study between 1993 and 1997. In all patients, routine laboratory tests and gluco- and minealocorticoid hormone measurements were performed preoperatively and 10 days after operation.RESULTS:These blood analyses indicated functional hyperaldosteronism immediately after IPAA. Significantly elevated levels of Aldosterone (36.4 +/- 25.1 ng/dl) and 18-OH-Corticosterone ( 173 +/- 11.3 ng/dl) were found. Among hormones with glucocorticoid effects, blood levels of Cortisol (10.4 +/- 4.8 microg/dl) were significantly elevated, while 11-Desoxycortiosterone (13.9 +/- 8.4 ng/dl) and Corticosterone (0.8 +/- 0.6 microg/dl) were not significantly elevated. Serum electrolytes remained unchanged.CONCLUSIONS:Our results indicate that hormones with mineralocorticoid effects play a predominant role in the compensation of ileostomy losses after IPAA.
BACKGROUND:Elevated intraabdominal pressure (IAP) is observed in various clinical situations, the most common of which are severe abdominal trauma and laparoscopic surgery. Extreme pressures may lead to Abdominal Compartment Syndrome (ACS), but even with lower pressures adverse effects are apparent. The cardiovascular system, the respiratory system, the kidneys and the visceral circulation are all affected, but the exact physiological mechanism is not well defined.AIMS:To discuss possible mechanisms which explain the observed hemodynamic effects of increased IAP.METHODS:Large animal model observations and review of current literature regarding the correlation between IAP and intracranial pressure (ICP).RESULTS:It was shown that the elevation of abdominal pressure leads to elevation of ICP. Transfer of pressure through the central venous system or by the cerebrospinal fluid (CSF) has been proposed as an explanation. In response to elevated ICP, various stress hormones are secreted by the central nervous system, including vasoconstricting agents such as vasopressin and catecholamines. It is hypothesized that the central nervous system is the link between the increased abdominal pressure and its adverse hemodynamic effects. This may be a protective mechanism of the brain, aimed to increase the mean arterial pressure when the ICP is elevated, in order to preserve the cerebral perfusion pressure.CONCLUSION:ICP is elevated in response to IAP elevation, and may be responsible for its adverse hemodynamic effects. Antagonists to vasopressin may have a role in the treatment of this condition.
BACKGROUND AND OBJECTIVE:Bariatric surgery has included a large number of operative procedures, some of which have become extinct and others, such as gastric restrictive procedures, which continue to be performed. While these operative procedures play an important role in the management of obesity, they are associated with significant failure rates. This study was performed to evaluate the results of operations performed on patients to revise failed gastric restrictive procedures.METHODS:During the past 15 years operative revision of gastric restrictive procedures was performed on 65 patients. The demographic, operative, and postoperative information has been prospectively collected. The patients were divided into 20 non-obese patients who weighed less than 250 pounds (range 90-247 pounds) and 45 obese patients weighing more than 250 pounds (range 256-527 pounds). The primary indications for operation on the non-obese patients were intragastric foreign body, gastric fistula, gastroesophageal reflux, and non emptying gastric pouch. The obese patients underwent revision for gastroesophageal reflux and failure to maintain weight loss. The obese patients frequently had obesity associated health problems including sleep apnea (N = 5), hypertension (N = 6), diabetes (N = 5) and ventral hernia (N = 30). The operative procedures in the non-obese patients consisted of revision of a gastroplasty in two patients, conversion of a gastroplasty to a gastric bypass in 12 patients and revision of a gastric bypass in eight patients. In the obese patient group, eight patients underwent revision of a gastroplasty, 19 patients had a gastroplasty converted to a gastric bypass and 14 patients underwent revision of a gastric bypass. The mean +/- SEM length of follow-up was 57 +/- 8 months.RESULTS:There were two postoperative deaths, one from a pulmonary embolus and one from unknown cause. There was no significant difference regarding the results of the various operations to revise gastric restrictive procedures on the weight of the non-obese patients at long-term follow-up. When obese patients underwent revision of a gastric bypass procedure, they lost 69 +/- 9 pounds which was significantly less than the 82 +/- 12 pounds lost by the patients who underwent revision of a gastroplasty. Conversion of gastroplasty operations to gastric bypass operations in obese patients resulted in the loss of 110 +/- 7 pounds at long-term follow-up.CONCLUSIONS:Revision of gastric restrictive procedures can be performed with durable control of obesity; however, revision of gastric bypass restrictive procedures in obese patients produced the least benefit.
BACKGROUND:Postoperative pain remains the most dreaded part of haemorrhoidectomy in the minds of both patients and doctors. It may delay patient discharge, recovery, and return to work. Glyceryl trinitrate has been used successfully in the treatment of anal fissures. We investigated its topical use in the management of pain after haemorrhoidectomy.METHOD:Twenty patients were entered into a double-blind trial and randomised into two groups. Group A (n = 10) applied glyceryl trinitrate ointment (0.2% twice daily) to the perianal area following surgery, and Group B applied a placebo ointment. They applied the ointment for up to 42 days after surgery, or until they felt it necessary to stop the treatment. Patients scored their daily anal pain using a visual analogue scale. Six weeks after surgery, patients were reviewed by an independent observer.RESULTS:The total pain score was calculated for each patient. The median score for Group A was 50.65; the median score for Group B was 73.50. There was no significant difference in pain scores between both groups, even when aberrant results were ignored. 20% of patients in each group complained that the ointment caused headache.CONCLUSION:The results suggest that topical glyceryl trinitrate ointment may not significantly reduce postoperative pain following haemorrhoidectomy. Meta-analysis would provide a more definitive answer.
The aim of this retrospective study was to investigate the accuracy of using preoperative data for the prediction of conversion from laparoscopic to open cholecystectomy in patients operated on for acute calculous cholecystitis. Laparoscopic cholecystectomy was scheduled in eighty-nine of 184 consecutive patients with acute calculous cholecystitis who underwent urgent or early cholecystectomy without bile duct exploration in our department between 1991 and 1998. The correlation between 11 preoperative clinical, laboratory and ultrasonographic variables, and the rate of conversion to open cholecystectomy was studied. Among the 11 variables tested, age and leukocyte count were independent factors of predictive significance. These two factors were used for constructing an additive prognostic index for conversion to open cholecystectomy. Thus, three groups of patients could be identified having a 10%, 30-70% or over 88% risk of conversion. Logistic regression analysis permits accurate preoperative identification of unsuccessful laparoscopic cholecystectomy in patients with acute calculous cholecystitis.
AIM:To evaluate the effects of Teicoplanin and/or Granulocyte-Colony Stimulating Factor (G-CSF) on survival in an experimental model of MRSA pneumonia.MATERIAL AND METHOD:Seventy five Swiss Albino mice weighing 35 gr (32-43) were used. 50 microl of clinical isolate of MRSA (3 x 10(8) CFU/ml in saline solution) was administered by tracheal puncture to neutropenic mice. Neutropenia was achieved by using Cyclophosphamide 200 mg per kg intraperitoneally. The groups were consisted of tracheal puncture control in neutropenic mice (group 1) (n = 15), pneumonia in neutropenic mice (group II) (n = 15), Teicoplanin therapy for pneumonia in neutropenic mice (group III) (n = 15), G-CSF therapy for pneumonia in neutropenic mice (group IV) (n = 15), Teicoplanin and G-CSF combined therapy for pneumonia in neutropenic mice (group V) (n = 15). Differences in the survival rates within 72 hours among the groups, microbiological analysis of various tissue samples were accomplished and white blood cell counts were obtained. Kaplan-Meier statistics was used for survival analysis. Subgroup comparisons were done by using Breslow statistics.RESULTS:Teicoplanin therapy increased the survival rate (p = 0.0001) whereas G-CSF therapy did not in comparison to other groups. Teicoplanin and G-CSF combination therapy improved survival rate when compared with groups II, III, IV (p = 0.0001, p = 0.003, p = 0.0001, respectively).CONCLUSION:Teicoplanin and G-CSF combination therapy seems effective in reducing mortality rates in MRSA pneumonia in an experimental setting. Further animal and clinical studies must be done to achieve success in the treatment of nosocomial MRSA pneumonia.
Cold liver preservation in the University of Wisconsin solution (UW) followed by reperfusion alters hepatic parenchyma and extra cellular matrix. In this study we analyzed the benefit of adding either 500 μM Sodium Nitroprusside (NPNa) or 100 μM S-nitrosoglutathione (GSNO) as Nitric Oxide (NO) donors to the UW solution to prevent hepatic injury. Wistar adult rat livers were stored in UW solution (0°C) for 48Hs and reperfused (60 minutes) in the isolated perfused rat liver model (IPRL). Untreated livers were used as normal controls. Livers perfused but not preserved were used as controls of reperfusion. Parenchyma damages were evaluated by Hematoxylin-Eosin stain. Picrosirius Red and Gordon-Sweets stains were used for collagen and reticulin networks, respectively. An inmunohistochemistry assay for albumin was used as functional test. Cold preservation step was followed by swollen hepatocytes with “light empty halos” surrounding the nucleus, conserved hepatocyte cords and many rounded endothelial cells. The addition of NPNa or GSNO into UW solution, avoid these alterations. Livers preserved for 48 Hs and then reperfused showed extended areas of vacuolation around central veins, and many endothelial cells were rounded and located inside sinusoidal lumens. The collagen network was disorganized while the reticulin one was less altered. Albumin was distributed preferentially in pericentral areas. On the contrary, livers preserved in presence of NPNa or GSNO did not show vacuolation and both collagen and reticulin networks were unchanged. Albumin was more homogeneously distributed in both groups. In conclusion, the addition of 500 μ NPNa or 100 μ GSNO as a NO donor, improves UW solution properties to preserve rat livers by maintaining the hepatic morphology and avoiding hepatic injury post-cold preservation/reperfusion.
BACKGROUND:Of major interest for a better molecular understanding of pancreatic cancer is the EGF receptor family. While HER-1 (EGF-receptor) and HER-2 have been extensively studied, little is known about the clinical significance of HER-3 and especially HER-4 expression.METHODS:We investigated the expression of HER-1, HER-2, HER-3 and HER-4 in 11 pancreatic cancer cell lines using FACS-analysis and determined expression and overexpression of these receptors in 24 pancreatic cancer specimens. Therefore, we used two different immunostaining techniques: a highly sensitive streptavidin-biotin method showed receptor expression while an approximatly 10-fold less sensitive indirect immunperoxidase technique determined receptor-overexpression.RESULTS:HER-1 and HER-2 were expressed by all 11 pancreatic cancer cell lines, HER-3 was found in 82% and HER-4 in 54% of the cell lines. Low levels of HER-1, HER-2 and HER-3 were detected in all tumor samples but overexpression was only found in 33%, 25% and 50% of the cases, respectively. HER-4 was expressed by 37% of the tumor specimens but overexpression was seen in one patient only. HER-1 and HER-2 overexpression increased in parallel with the tumor stage and R0-resected tumors showed significantly less often overexpression compared to R1/R2 resected tumors (p < 0.05). In contrast, 54% of the R0-resected vs. 18% of the R1/R2 resected tumors showed HER-4 expression (p = 0.07) and HER-4 was exclusively found in non-metastatic tumors (p = 0.0149).CONCLUSION:Our data indicate that HER-1 and HER-2 overexpression contributes to a more aggressive phenotype. In contrast, the lack of HER-4 expression might increase the metastatic capacity of pancreatic cancer cells.
BACKGROUND:The objective of this study was to determine the effects of a continuous infusion of the phosphodiesterase inhibitor enoximone on mucosal villus blood flow in a normotensive model of endotoxemia.METHODS:Twenty-four anesthetized and ventilated rats underwent laparotomy and a ileal portion was exteriorized and opened by an antimesenteric incision. The ileal segment was fixed on a plexiglass stage with the mucosal surface upward. Microcirculatory parameters were assessed by intravital videomicroscopy. The animals were randomly assigned to receive one of three treatments: infusion of Escherichia coli lipopolysaccharides (LPS, 2 mg/kg/h) without phosphodiesterase inhibitor pretreatment (LPS group); or infusion of LPS with enoximone pretreatment (10 microg x kg(-1) x min(-1), start 30 min before LPS infusion, enoximone group), or infusion of an eqivalent volume of NaCl 0.9% (control group). Macrohemodynamic parameters (MAP, HR) and microhemodynamic parameters of ileal mucosa (mean diameter of central arterioles = DA, and mean erythrocyte velocity within the arterioles = VE) were measured 30 min before and at 0, 60, and 120 min after induction of endotoxemia. Mucosal villus blood flow was calculated from DA and VE.RESULTS:In this normotensive endotoxemia model MAP remained stable in the control and the LPS group but significantly decreased in the enoximone group. The endotoxin-induced decrease of VE and DE of central arterioles of mucosal villi could be prevented. Thus, mucosal villus blood flow did not decrease compared to the LPS group.CONCLUSIONS:Our results indicate that enoximone during an early stage of sepsis contributes to systemic hypotension but prevents mucosal hypoperfusion.
BACKGROUND Transthoracic endoscopic sympathectomy (TES) has been already a standard method for the treatment of primary hyperhidrosis. There are rare reports about possibly encountered problems during TES. Therefore, we present our experience in treating palmar and axillary hyperhidrosis and discuss the resoluble methods of potential problems during and after TES. PATIENTS AND METHODS From June 1994 to October 1999, there were 2200 patients with palmar or axillary hyperhidrosis underwent TES. There are 926 males and 1274 females. Their mean age was 23.4 years old (range: 5-65). All except 12 patients were placed in half-sitting position under single or double-lumen intubation anesthesia. Either a 6-mm or 8-mm, 0degrees thoracoscope, (Karl Storz, Germany) was used to perform sympathectomy thru 0.8 cm incisions below each axilla. Ablation of T2 ganglion was performed in treating patients with palmar hyperhidrosis. Ablation of T3 and T4 ganglia was performed for patients with axillary hyperhidrosis. All except 22 patients were discharged 4 hours after TES, and returned to their activities within one week. RESULT Successful sympathectomy were achieved up to 2178 patients (99%), but the rates of incidental unusual findings and possibly encountered problems during TES were 5.6% and 7.1% alternatively. Surgical complications included pneumothorax (10 patients, 0.45%), Hemothorax (2 patients, 0.09%) segmental atelectasis (12 patients, 0.55%), mild wound infection (3 patients, 0.14%) and compensatory sweating (1936 patients, 88%). There was no surgical mortality case. But pleural adhesion (54 patients, 2.45%), repeat sympathectomy (27 patients, 1.23%), obscured upper sympathetic trunk by adipose tissue (22 patients, 1%), medially located sympathetic trunk (18 patients, 0.81%), great vessels overriding or close to the sympathetic trunk (15 patients, 0.68%), aberrant vessels (3 patients, 0.14%), transient bradycardia (3 patients, 0.14%) and re-expansion pulmonary edema (1 patient, 0.05%) might occur during TES. CONCLUSION Potential complications may happen during and after TES. But nearly all endoscopic sympathectomy could be achieved if surgeons acknowledge possible anatomic variation and has ability to overcome pleural adhesions.
BACKGROUND AND OBJECTIVE:CAP37, also known as heparin-binding protein (HBP), is neutrophil-derived protein with multifunctional properties that include monocyte chemotaxis and the enhancement of LPS-induced tumor necrosis factor (TNF-alpha), IL-1, IL-6, and PGE2production from isolated monocytes, which suggest a generalized effect on LPS-induced monocyte activation. In this study, we tested whether HBP amplifies the release of other LPS-responsive cytokines from isolated human monocytes.METHODS:Freshly isolated monocytes from 5 healthy donors were stimulated for 24 h with saline, LPS (10 ng/ml), HBP (10 microg/ml), or a combination of LPS + HBP. Cytokine levels in the supernate were measured with ELISA. ANOVA and Fisher's posthoc test were used to determine significance (p < 0.05). Differential display was used to assess cellular mRNA levels.RESULTS:HBP alone induced the production of IL-8, macrophage inhibitory protein MIP-1alpha, and TNF-alpha. HBP increased the LPS-induced production of IL-8, MIP-1alpha, TNF-alpha, IL-1beta, but HBP did not increase the significant LPS-induced release of IL-10, monocyte chemoattractant protein MCP-1, and IL- 12. Differential display demonstrated that HBP induced an mRNA pattern that was different from the mRNA pattern induced by saline, LPS, or HBP + LPS, indicating multiple and different gene activation.CONCLUSIONS:We conclude that HBP is not a general amplificator of LPS-induced monocyte activation but rather a molecule that targets the production of a distinct set of mediators including pro-inflammatory cytokines such as TNF-alpha and IL-1beta, but not the anti-inflammatory cytokine IL-10, nor IL-12 and MCP-1. The exact intracellular signaling pathways remain unknown but include mechanisms that alter gene transcription.
BACKGROUND:Generalized purulent peritonitis is characterized by an early exposure of the immune system to a large number of bacterial antigens. The hypothesis that intravenous IgG treatment may improve the outcome of severe experimental peritonitis was studied.METHODS:Peritonitis was induced in rats by cecal ligation and perforation. Continuous intravenous fluid infusion, broad-spectrum antibiotics, and twenty-four hours treated forty rats after the induction of the disease they were re-operated and the perforated cecum was excised. Twenty of these animals received in addition specific rat IgG in two intravenous infusions (0.4 gr./kg), two and twenty four hours after the induction of peritonitis.RESULTS:Elevated WBC counts and mild metabolic acidosis was found one day after the induction of peritonitis. IgG treatment was associated with lower WBC counts in the following days and with higher pH than in the control group (p < 0.05 for both parameters). All peritoneal cultures and 90% of blood cultures were positive 24 hours after the initial operation. These rates decreased in the following days and in the IgG treatment rats the peritoneal cavity and blood were sterile earlier than in the control animals (p < 0.05). Serum IgG was depleted in the control animals within 48 hours after the induction of peritonitis, while in the IgG treated animals its levels were remarkably elevated. IgG administration significantly improved the survival, which was 70% in the IgG treatment rats as compared to 40% in the control rats.CONCLUSION:These results indicate that intravenous IgG has beneficial effects on severe experimental peritonitis.
Urachal Adenocarcinoma is a rare tumour that predominantly affects men between the ages of 50-60; it presents late and is therefore associated with a poor prognosis. We discuss the presentation, investigation, treatment and prognosis of this uncommon tumour.
Following severe trauma and surgical injury, nutritional support via the enteral route has been shown to lead to increased survival and decreased complications when compared to the parenteral route. We hypothesized that the route of nutrient delivery may affect cutaneous wound healing following severe traumatic insult. Forty-six Sprague Dawley rats underwent bilateral closed femoral fractures, central venous catheterization, gastrostomy placement and dorsal skin incision with placement of polyvinyl alcohol sponges into subcutaneous pockets. Identical nutritional infusates of 25% dextrose, 4.25% amino acids, and vitamins were given, half the animals receiving the infusion via the gastrostomy (ENT) and the other half via the venous catheter (TPN). Animals were sacrificed on post-operative days 5, 7, or 10. Wound breaking strength (WBS, g) and sponge granuloma hydroxyproline content (OHP- a measure of wound collagen deposition, microg/ 100mg sponge) were measured. There were no significant nutritional differences between the two feeding groups. On days 5 and 7, WBS was significantly higher in the ENT group (58.0 +/- 3.1 g vs 48.9 +/- 2.6 g, p < 0.05, and 123 +/- 19 g vs 87.6 +/- 4.2 g, p < 0.05 vs TPN respectively). Sponge OHP content on day 5 was significantly higher in the ENT group (101 +/- 3 vs 86.7+/-5.8 microg/100 sponge, p < 0.05). These data demonstrate that the enteral feeding route imparts a benefit to early post-traumatic wound healing s compared to parenteral feeding.
