Early diagnosis of anastomotic leakage after colorectal surgery by the Dutch leakage score, serum procalcitonin and serum C-reactive protein: study protocol of a prospective multicentre observational study by the Italian ColoRectal Anastomotic Leakage (iC.

BACKGROUND: Anastomotic leakage (AL) is a dreaded major complication after colorectal surgery. There is no uniform definition of anastomotic dehiscence and leak. Over the years many risk factors have been identified (distance of anastomosis from anal verge, gender, BMI, ASA score) but none of these allows an early diagnosis of AL. The DUtch LeaKage (DULK) score, C reactive protein (CRP) and procalcitonin (PCT) have been identified as early predictors for anastomotic leakage starting from postoperative day (POD) 2-3. The study was designed to prospectively evaluate AL rates after colorectal resections, in order to give a definite answer to the need for clear risk factors, and testing the diagnostic yeld of DULK score and of laboratory markers. Methods and analysis. A prospective enrollment for all patients undergoing elective colorectal surgery with anastomosis carried out from September 2017 to September 2018 in 19 Italian surgical centers. OUTCOME MEASURES: preoperative risk factors of anastomotic leakage; operative parameters; leukocyte count, serum CRP, serum PCT and DULK score assessment on POD 2 and 3. Primary endpoint is AL; secondary endpoints are minor and major complications according to Clavien-Dindo classification; morbidity and mortality rates; readmission and reoperation rates, length of postoperative hospital stay (Retrospectively registered at ClinicalTrials.gov Identifier: NCT03560180, on June 18, 2018). Ethics. The ethics committee of the "Comitato Etico Regionale delle Marche - C.E.R.M." reviewed and approved this study protocol on September 7, 2017 (protocol no. 2017-0244-AS). All the participating centers submitted the protocol and obtained authorization from the local Institutional Review Board.

Laparoscopic Deloyers procedure for tension-free anastomosis after extended left colectomy: technique and results.

BACKGROUND: The Deloyers procedure, which includes inversion of the right colon around the axis of the ileocolic vessels, can be used to achieve a well vascularized, tension-free colorectal anastomosis after extended left colectomy. The aim of this study is to report our technique and outcome in a series of ten consecutive patients who underwent right colonic transposition by laparoscopic approach. METHODS: Charts were retrospectively reviewed to analyze postoperative outcome and bowel function. A video was recorded to demonstrate the procedure. RESULTS: Conversion was required in one (10%) patient due to extensive adhesions. No intraoperative complications were recorded. Anastomotic leakage occurred in one (10%) case and was managed with peritoneal lavage and ileostomy. Six months after surgery, all patients reported a median number of 2.5 (range 2-3) bowel movements per day with solid stool consistency. Neither anastomotic stricture nor bowel ischemia was found at 1-year endoscopic follow-up. CONCLUSION: Our experience shows that laparoscopic right colonic transposition is a safe and feasible procedure and provides good functional outcomes.

Electrical and ultraviolet characterization of 4H-SiC Schottky photodiodes.

Fabrication and electrical and optical characterization of 4H-SiC Schottky UV photodetectors with nickel silicide interdigitated contacts is reported. Dark capacitance and current measurements as a function of applied voltage over the temperature range 20 °C - 120 °C are presented. The results show consistent performance among devices. Their leakage current density, at the highest investigated temperature (120 °C), is in the range of nA/cm(2) at high internal electric field. Properties such as barrier height and ideality factor are also computed as a function of temperature. The responsivities of the diodes as functions of applied voltage were measured using a UV spectrophotometer in the wavelength range 200 nm - 380 nm and compared with theoretically calculated values. The devices had a mean peak responsivity of 0.093 A/W at 270 nm and -15 V reverse bias.

Single-layer versus double-layer closure of the enterotomy in laparoscopic right hemicolectomy with intracorporeal anastomosis: a single-center study.

BACKGROUND: The aim of our study was to evaluate the short-term outcomes of totally laparoscopic right colectomy, in particular to compare the incidence of leakage of the ileocolic anastomosis after either single-layer (SL) or double-layer (DL) enterotomy closure. METHODS: From March 2010 to July 2014, 162 patients underwent laparoscopic right colectomy with intracorporeal ileocolic anastomosis. The enterotomy was closed with either SL (77 patients) or DL technique (85 patients). Short-term outcomes in both groups were retrospectively analyzed. RESULTS: Median time to perform the ileocolic anastomosis was similar in the two groups (17 min in SL versus 20 min in DL, p = 0.109). DL closure was associated with a significantly lower incidence of anastomotic leakage (1.2 % in DL vs 7.8 % in SL, p = 0.044). Shorter hospital stay was also observed in the DL group. CONCLUSIONS: Adoption of DL closure of the enterotomy resulted in significantly improved outcome. We strongly recommend a double-layer closure technique when performing an intracorporeal enterocolic anastomosis.

Surgical treatment of thymoma: personal experience.

INTRODUCTION: Thymomas (THs) are rare epithelial tumors of the thymus gland. In this study we report our personal experience in the management and surgical treatment of THs. CASE REPORTS: We report two clinical cases treated with combined therapy (surgery followed by adjuvant therapy). RESULTS: Total transternal thymectomy was performed in both patients. The post-operative course was uneventful. The patients received adjuvant radiotherapy and chemotherapy. No relapse has been observed during follow-up. DISCUSSION: THs are usually slowly growing tumors with similar incidence in both sexes. They occur through a wide age range, with a peak in the fifth and sixth decades. Distinctive features reminiscent of the normal thymus make the pathologic diagnosis of THs easy in most cases. Malignant behaviour is indicated by microscopic or macroscopic invasion of the tumor capsule or surrounding organs or by the presence of metastases. Although there is no standardized staging system for thymoma, the one proposed by Masaoka is commonly employed. Total thymectomy is the procedure of choice, even for encapsulated tumors, with carefully exploration of the mediastinum for evidence of ectopic thymic tissue or local invasion. CONCLUSIONS: Despite an indolent course and a cytologically bland appearance, all thymic tumors can manifest a malignant behavior. Surgery continues to be the mainstay of treatment, and the ability to achieve complete resection seems to be the most important prognostic factor. Multimodality treatment involving postoperative chemotherapy and radiotherapy appears to increase the rate of complete resection and improves survival in advanced THs.

Bilateral lung and liver hydatid cysts. Case report.

Introduction. Synchronous occurrence of pulmonary and hepatic hydatid cysts is an uncommon manifestation of hydatid disease that is observed in less than 10% of cases. We report a rare case of bilateral lung (with bronchial fistula) and liver cyst, surgically treated after medical therapy. Case report. A 44-year-old housewife reporting fever, anorexia and fatigue that had been present for the previous 20 days received diagnosis of bilateral lung and liver hydatid cyst. Because of the dimensions of right lung cyst and the successive bronchial fistolization, we proceeded to three-stage operation of two thoracotomies and a laparotomy to control the risk of further rupture. After surgery, all post-operatives were uneventful. Complete resolution of the therapy with no evidence of recurrence at 2 years follow-up. Conclusion. We emphasize the need to search for additional hydatids in patients who present with either pulmonary or liver hydatids. The simultaneous treatment of liver and lung should be reserved to patients in good conditions; in all other cases, especially when one cyst is more symptomatic than the others or has more risk of rupture, we prefer to treat single cyst.

Sinonasal inverted papilloma: 84 patients treated by endoscopy and proposal for a new classification.

AIM: To suggest a new classification system for sinonasal papilloma based on a critical analysis of surgical indications and results obtained. METHODS: We analysed surgical data from 84 cases of sinonasal papilloma treated endoscopically. RESULTS: In 58 males and 26 females, between 25 and 85 years, the ethmoid sinus (63 cases), the maxillary sinus (43), and the nasal fossa (22) were mostly involved. No case of endocranial extension or carcinoma was reported. Complications were reported in 15.4% of patients, as well as 5 recurrences (5.9%). Median follow up was 39,5 months. To categorise the tumour for the most appropriate surgical treatment, we propose a classification based on 6 main categories that depend on the location, origin and extension of the tumour. CONCLUSION: The classification that we propose presents advantages for prognosis and surgical indication in comparison with other classifications.

Non-recurrent laryngeal nerve coexisting with ipsilateral recurrent nerve: personal experience and literature review.

INTRODUCTION: Non-recurrence and variations in ascending course of the recurrent laryngeal nerve (RLN) represent a risk factor for nerve injuries during thyroid surgery. Non-recurrent laryngeal nerve (NRLN) coexisting to recurrent nerve branch is a rare anatomic anomaly. It could be a cause of nerve injuries during thyroidectomy. A systematic intraoperative nerve identification may allow an effectiveness prevention of iatrogenic injuries. CASE REPORT: We report one case of a young woman underwent to total thyroidectomy (TT) for papillary thyroid carcinoma (PTC) where we found a rare variation of the right inferior laryngeal nerve anatomy. We identified both right laryngeal nerve structures before completing thyroidectomy avoiding possible nerve damage. The postoperative course was without complications. DISCUSSION: Iatrogenic injury of RLN is one of the most serious complication in thyroid surgery. Several risk factors favouring this complication were found as the presence of anatomic variations of the inferior laryngeal nerve. Identification of a normal caliber recurrent nerve can allow the surgeon to complete the thyroid excision; diversely, in case of a smaller caliber nerve in the usual recurrent course, a careful dissection should be continued to demonstrate a possible merger with ipsilateral non-recurrent nerve. CONCLUSIONS: The aim of this paper is to report a rare case of NRLN associated to a smaller caliber branch of RNL. We emphasize that careful dissection and intimate knowledge of normal and anomaly anatomy allow for avoidance of nerve injury during surgery in the neck.

[Endoscopic rubber band ligation in treatment of esophageal varices bleeding. Personal experience]. / La legatura elastica nel trattamento endoscopico della emorragia da rottura di varici esofagee. Esperienza di un singolo centro.

INTRODUCTION: Bleeding esophageal varices is the most serious complication of the portal hypertension, and the greater cause of dead (25% of the patients). The survival after esophageal varices bleeding depends in wide part from the swiftness and effectiveness of hemostasis and from the degree of functional liver reserve. Aim of our manuscript is to report our experience about hemostasis bleeding esophageal varices with endoscopic rubber band ligation. PATIENTS AND METHODS: From January 1999 to January 2008 we performed 302 esofagogastroduodenoscopy (EGDS) for esophageal varices bleeding (M: F ratio = 1.4:1, mean age 56.4 years, 62% of cases with HCV-related cirrhosis, 29% alcoholic cirrhosis and 9% cryptogenic cirrhosis; 20% suffered from chronic renal failure, 15% diabetes mellitus, 10% hepatocellular carcinoma on cirrhosis, 5% systemic encephalopathy and 1% AIDS). RESULTS; All patients were treated within 6 hours after the first reported episode of haematemesis and all received beta-blocker therapy after the episode. In the first phase of our experience were used rechargeable elastic ligator and then multibyte, even in combination with polidocanol sclerotherapy (8%) or injection of cyanoacrylate (5%). The best results were achieved with band ligation, in terms of primitive haemostasis, rebleeding, (3%), intraoperative mortality (1%) and 6 weeks mortality (1%). CONCLUSION: To date, no single method applicable to all patients with bleeding esophageal varices, but endoscopic rubber band ligation is currently considered the first-line treatment of proper multidisciplinary approach to the patient, both during the acute event than prevention of rebleeding, because it is an effective, safe and repeatable, in experienced hands.

Exposure-response effects of inhaled sulfur mustard in a large porcine model: a 6-h study.

CONTEXT: Inhalation of sulfur mustard (HD) vapor can cause life-threatening lung injury for which there is no specific treatment. A reproducible, characterized in vivo model is required to investigate novel therapies targeting HD-induced lung injury. MATERIALS AND METHODS: Anesthetized, spontaneously breathing large white pigs (~50 kg) were exposed directly to the lung to HD vapor at 60, 100, or 150 µg/kg, or to air, for ~10 min, and monitored for 6 h. Cardiovascular and respiratory parameters were recorded. Blood and bronchoalveolar lavage fluid (BALF) were collected to allow blood gas analysis, hematology, and to assay for lung inflammatory cells and mediators. Urine was collected and analyzed for HD metabolites. Histopathology samples were taken postmortem (PM). RESULTS: Air-exposed animals maintained normal lung physiology whilst lying supine and spontaneously breathing. There was a statistically significant increase in shunt fraction across all three HD-exposed groups when compared with air controls at 3-6 h post-exposure. Animals were increasingly hypoxemic with respiratory acidosis. The monosulfoxide ß-lyase metabolite of HD (1-methylsulfinyl-2-[2(methylthio)ethylsulfonyl)ethane], MSMTESE), was detected in urine from 2 h post-exposure. Pathological examination revealed necrosis and erosion of the tracheal epithelium in medium and high HD-exposed groups. CONCLUSION: These findings are consistent with those seen in the early stages of acute lung injury (ALI).

Acute onset of esophageal duplication cyst in adult. Case report.

INTRODUCTION: Esophageal duplication (ED) cyst is unusual congenital disorder of the foregut, accounting for 10% to 15% of duplications of all foregut cysts. We report a case of esophageal duplication with acute clinical presentation, treated successfully with surgical resection. CASE REPORT: 46-year-old man with acute dysphagia and gastroesophageal reflux of 2 weeks duration, showed submucosal bulging mass in the posterior wall of the middle third of oesophagus, fluid-filled cystic structure, dyshomogeneous, low-attenuation mass with smooth borders compatible with an hemorrhagic esophageal duplication cyst. With the suspect of acute presentation of a complicated esophageal cyst, the patient underwent surgery by right posterolateral thoracotomy. A gastrografin esophagogram was performed on third postoperative day and showed no leaks. DISCUSSION: Up to 80% of the esophageal duplication cysts are diagnosed in childhood and the majority of young patients develop symptoms, while symptomatic cyst into adult life is very rare (<7%). Acute onset is generally due to complications, i.e. intracystic hemorrhage, perforation, and infection, especially of the cyst with esophageal communication. Complete surgical excision by thoracotomy or thoracoscopy is the therapy of choice even if the patient is asymptomatic because of the risk of complications such as aspiration and bleeding. CONCLUSIONS: The diagnosis and treatment of esophageal cysts is still evolving. The pathological diagnosis of oesophageal duplication requires the presence of the Ladd and Gross criteria. The infrequent acute onset doesn't modify the management and the surgical resection is the procedure of choice. The future of the treatment of esophageal cysts lies in the advancement of minimally invasive operative techniques.

When traditions become dangerous: Intestinal perforation from unusual foreign body-Case report and short literature review.

Gastrointestinal perforation (GI) is a common cause of acute abdomen in the emergency department that needs a prompt surgery intervention. Nowadays, CT examinations represent the method of choice to image patients with acute abdominal pain in emergency. GI perforations by foreign bodies ingested is rare and only <1% of ingested foreign bodies are believed to cause perforation of GI. MDCT is to be considered the best imaging method for identifying foreign bodies, the perforation site and the surgical treatment to be planned reliably. We presente a case of 70-year-old lady presented to our Emergency Department with acute abdominal pain.

Enhanced recovery pathways in colorectal surgery: a consensus paper by the Associazione Chirurghi Ospedalieri Italiani (ACOI) and the PeriOperative Italian Society (POIS).

Enhanced Recovery After Surgery (ERAS) pathway is a multi-disciplinary, patient-centered protocol relying on the implementation of the best evidence-based perioperative practice. In the field of colorectal surgery, the application of ERAS programs is associated with up to 50% reduction of morbidity rates and up to 2.5 days reduction of postoperative hospital stay. However, widespread adoption of ERAS pathways is still yet to come, mainly because of the lack of proper information and communication. Purpose of this paper is to support the diffusion of ERAS pathways through a critical review of the existing evidence by members of the two national societies dealing with ERAS pathways in Italy, the PeriOperative Italian Society (POIS) and the Associazione Italiana Chirurghi Ospedalieri (ACOI), showing the results of a consensus development conference held at Matera, Italy, during the national ACOI Congress on June 10, 2019.

Exposure to noise during continuous positive airway pressure: influence of interfaces and delivery systems.

BACKGROUND: We measured noise intensity and perceived noisiness during continuous positive airway pressure (CPAP) performed with two interfaces (face-mask, helmet) and four delivery systems. METHODS: Eight healthy volunteers received CPAP in random order with: two systems provided with a flow generator using the Venturi effect and a mechanical expiratory valve (A: Venturi, Starmed; B: Whisperflow-2, Caradyne Ltd); one 'free-flow' system provided with high flow O(2) and air flowmeters, an inspiratory gas reservoir, and a water valve (C: CF800, Drägerwerk, AG); and a standard mechanical ventilator (Servoventilator 300, Siemens-Elema). Systems A, B, and C were tested with a face-mask and a helmet at a CPAP value of 10 cm H(2)O; the mechanical ventilator was only tested with the face mask. Noise intensity was measured with a sound-level meter. After each test, participants scored noisiness on a visual analog scale (VAS). RESULTS: The noise levels measured ranged from 57+/-11 dBA (mechanical ventilator plus mask) to 93+/-1 and 94+/-2 dBA (systems A and B plus helmet) and were significantly affected by CPAP systems (A and B noisier than C and D) and interfaces (helmet CPAP noisier than mask CPAP). Subjective evaluation showed that systems A and B plus helmet were perceived as noisier than system C plus mask or helmet. CONCLUSIONS: Maximum noise levels observed in this study may potentially cause patient discomfort. Less noisy CPAP systems (not using Venturi effect) and interfaces (facial mask better than helmet) should be preferred, particularly for long or nocturnal treatments.

Preliminary studies of sulphur mustard-induced lung injury in the terminally anesthetized pig: exposure system and methodology.

ABSTRACT Although normally regarded as a vesicant, inhalation of sulphur mustard (HD) vapor can cause life-threatening lung injury for which there is no specific treatment. Novel therapies for HD-induced lung injury are best investigated in an in vivo model that allows monitoring of a range of physiological variables. HD vapor was generated using two customized thermostatically controlled glass flasks in parallel. The vapor was passed into a carrier flow of air (81 L. min(-1)) and down a length of glass exposure tube (1.75 m). A pig was connected to the midpoint of the exposure tube via a polytetrafluoroethylene-lined endotracheal tube, Fleisch pneumotachograph, and sample port. HD vapor concentrations (40-122.8 mg. m(-3)) up-and downstream of the point of exposure were obtained by sampling onto Porapak absorption tubes with subsequent analysis by gas chromatography-flame photometric detection. Real-time estimates of vapor concentration were determined using a photo-ionization detector. Lung function indices (respiratory volumes, lung compliance, and airway resistance) were measured online throughout. Trial runs with methylsalicylate (MS) and animal exposures with HD demonstrated that the exposure system rapidly reached the desired concentration within 1 min and maintained stable output throughout exposure, and that the MS/HD concentration decayed rapidly to zero when switched off. A system is described that allows reproducible exposure of HD vapor to the lung of anesthetized white pigs. The system has proved to be robust and reliable and will be a valuable tool in assessing potential future therapies against HD-induced lung injury in the pig. Crown Copyright (c) 2007 Dstl.

Use of balloon catheter dilation and steroid-eluting stent in light and severe rhinosinusitis of frontal sinus: a multicenter retrospective randomized study.

OBJECTIVE: Frontal sinus surgery has an increased rate of re-stenosis, if compared to other sinuses. It depends mainly on recurrent inflammation and abnormal scarring at the frontal recess and its reduction represents one of the keys to therapeutic success. Balloon catheter dilation (BCD) and implantable sinus stents/spacers represent strategies to improve sinus ventilation respecting the integrity of mucosa and reducing abnormal post-surgical scarring. The purpose of this study was to evaluate the effectiveness, safety and correct indication about the use of BCD and a non-absorbable stent (Relieva Stratus™ MicroFlow spacer) in the management of chronic rhinosinusitis (CRS) of the frontal sinus. PATIENTS AND METHODS: In this multicentric retrospective study we included a population of 76 frontal sinuses with non-polypoid CRS. 41 frontal sinuses were treated with BCD alone and 35 frontal sinuses with BCD + Spacer. We analyzed both radiological (Lund-McKay CT scoring modified by Zinreich) and symptomatological results (SNOT-20 questionnaire) before surgery and after 12 months, dividing our population in two main groups: group "L" (light/mild frontal CRS) and group "S" (moderate/severe frontal CRS). RESULTS: Our results confirm a good safety and effectiveness of BCD in the management of frontal CRS and show a good safety but a not significative effectiveness of Relieva Stratus™ MicroFlow spacer when added to BCD in the management of light and severe frontal chronic rhinosinusitis. CONCLUSIONS: BCD is an acclared option in the management of frontal CRS and in the near future, utilization of stents/spacers could become a new and effective weapon in the management of rhinosinusitis, both like an adjunct to standard therapies, and in patient populations where the use of systemic drugs is contraindicated.

Use of balloon catheter dilation vs. traditional endoscopic sinus surgery in management of light and severe chronic rhinosinusitis of the frontal sinus: a multicenter prospective randomized study.

OBJECTIVE: Chronic rhinosinusitis (CRS) of the frontal sinus is a complex pathological condition and many surgical techniques were described to treat this area endoscopically, like traditional endoscopic sinus surgery (ESS) and balloon catheter dilation (BCD). PATIENTS AND METHODS: We designed a multicenter prospective randomized study to assess the validity and safety of BCD vs. ESS in symptomatological chronic rhinosinusitis of the frontal sinus enrolling a population of 102 adult patients (64 men and 38 women; overall 148 frontal sinuses studied) with non-polypoid CRS. For a better evaluation of the disease, in our study we decided to analyze both radiological (Lund-McKay CT scoring modified by Zinreich) and symptomatological results (SNOT-20 questionnaire). We divided the population affected in two groups, one with light/mild frontal CRS and the other with moderate/severe frontal CRS, basing on radiological findings at Lund-MacKay modified by Zinreich score. Every group was divided in two subgroups, in one we used BCD and in the other we used traditional ESS. RESULTS: The current literature does not support the suggestion that indications for BCD and ESS are identical, and additional research is needed to determine the role for BCD in specific patient populations. The results showed a not statistically significative difference between BCD and conventional ESS of the frontal sinus in patients with light/mild CRS and in patients with moderate/severe CRS at Lund-Mackay modified by Zinreich score. The same not statistically significative difference was observed comparing the results of SNOT-20 questionnaire in the group of light/mild frontal chronic rhinosinusitis. However, we noticed a statistically significant better outcome of SNOT-20 score in patients with moderate/severe chronic rhinosinusitis that underwent BCD of frontal sinus compared to ESS. CONCLUSIONS: BCD and ESS are two alternative weapons in the baggage of every endoscopic surgeon, even because they present similar outcomes, safeness and effectiveness both in light/mild and moderate/severe chronic rhinosinusitis of the frontal sinus. An interesting result of our study was the statistically significant better outcome of SNOT-20 score in patients that underwent BCD of frontal sinus for a moderate/severe CRS, compared to those that underwent a traditional ESS.

Workshop summary: phosgene-induced pulmonary toxicity revisited: appraisal of early and late markers of pulmonary injury from animal models with emphasis on human significance.

A workshop was held February 14, 2007, in Arlington, VA, under the auspices of the Phosgene Panel of the American Chemistry Council. The objective of this workshop was to convene inhalation toxicologists and medical experts from academia, industry and regulatory authorities to critically discuss past and recent inhalation studies of phosgene in controlled animal models. This included presentations addressing the benefits and limitations of rodent (mice, rats) and nonrodent (dogs) species to study concentration x time (C x t) relationships of acute and chronic types of pulmonary changes. Toxicological endpoints focused on the primary pulmonary effects associated with the acute inhalation exposure to phosgene gas and responses secondary to injury. A consensus was reached that the phosgene-induced increased pulmonary extravasation of fluid and protein can suitably be probed by bronchoalveolar lavage (BAL) techniques. BAL fluid analyses rank among the most sensitive methods to detect phosgene-induced noncardiogenic, pulmonary high-permeability edema following acute inhalation exposure. Maximum protein concentrations in BAL fluid occurred within 1 day after exposure, typically followed by a latency period up to about 15 h, which is reciprocal to the C x t exposure relationship. The C x t relationship was constant over a wide range of concentrations and single exposure durations. Following intermittent, repeated exposures of fixed duration, increased tolerance to recurrent exposures occurred. For such exposure regimens, chronic effects appear to be clearly dependent on the concentration rather than the cumulative concentration x time relationship. The threshold C x t product based on an increased BAL fluid protein following single exposure was essentially identical to the respective C x t product following subchronic exposure of rats based on increased pulmonary collagen and influx of inflammatory cells. Thus, the chronic outcome appears to be contingent upon the acute pulmonary threshold dose. Exposure concentrations high enough to elicit an increased acute extravasation of plasma constituents into the alveolus may also be associated with surfactant dysfunction, intra-alveolar accumulation of fibrin and collagen, and increased recruitment and activation of inflammatory cells. Although the exact mechanisms of toxicity have not yet been completely elucidated, consensus was reached that the acute pulmonary toxicity of phosgene gas is consistent with a simple, irritant mode of action at the site of its initial deposition/retention. The acute concentration x time mortality relationship of phosgene gas in rats is extremely steep, which is typical for a local, directly acting pulmonary irritant gas. Due to the high lipophilicity of phosgene gas, it efficiently penetrates the lower respiratory tract. Indeed, more recent published evidence from animals or humans has not revealed appreciable irritant responses in central and upper airways, unless exposure was to almost lethal concentrations. The comparison of acute inhalation studies in rats and dogs with focus on changes in BAL fluid constituents demonstrates that dogs are approximately three to four times less susceptible to phosgene than rats under methodologically similar conditions. There are data to suggest that the dog may be useful particularly for the study of mechanisms associated with the acute extravasation of plasma constituents because of its size and general morphology and physiology of the lung as well as its oronasal breathing patterns. However, the study of the long-term sequelae of acute effects is experimentally markedly more demanding in dogs as compared to rats, precluding the dog model to be applied on a routine base. The striking similarity of threshold concentrations from single exposure (increased protein in BAL fluid) and repeated-exposure 3-mo inhalation studies (increased pulmonary collagen deposition) in rats supports the notion that chronic changes depend on acute threshold mechanisms.

A simple method for accurate endotracheal placement of an intubation tube in Guinea pigs to assess lung injury following chemical exposure.

ABSTRACT Guinea pigs are considered as the animal model of choice for toxicology and medical countermeasure studies against chemical warfare agents (CWAs) and toxic organophosphate pesticides because of the low levels of carboxylesterase compared to rats and mice. However, it is difficult to intubate guinea pigs without damaging the larynx to perform CWA inhalation experiments. We describe an easy technique of intubation of guinea pigs for accurate endotracheal placement of the intubation tube. The technique involves a speculum made by cutting the medium-size ear speculum in the midline leaving behind the intact circular connector to the otoscope. Guinea pigs were anesthetized with Telazol/meditomidine, the tongue was pulled using blunt forceps, and an otoscope attached with the specially prepared speculum was inserted gently. Insertion of the speculum raises the epiglottis and restrains the movements of vocal cord, which allows smooth insertion of the metal stylet-reinforced intubation tube. Accurate endotracheal placement of the intubation tube was achieved by measuring the length from the tracheal bifurcation to vocal cord and vocal cord to the upper front teeth. The average length of the trachea in guinea pigs (275 +/- 25 g) was 5.5 +/- 0.2 cm and the distance from the vocal cord to the front teeth was typically 3 cm. Coinciding an intubation tube marked at 6 cm with the upper front teeth accurately places the intubation tube 2.5 cm above the tracheal bifurcation. This simple method of intubation does not disturb the natural flora of the mouth and causes minimum laryngeal damage. It is rapid and reliable, and will be very valuable in inhalation exposure to chemical/biological warfare agents or toxic chemicals to assess respiratory toxicity and develop medical countermeasures.

Mechanism of hyperoxia-induced pulmonary vascular paralysis: effect of antioxidant pretreatment.

We designed experiments using isolated rabbit lungs to determine the effect of hyperoxia on the pulmonary vasoconstriction caused by the infusion of the lipid peroxide tert-butyl hydroperoxide (t-bu-OOH), which produces vasoconstriction by stimulating the pulmonary synthesis of thromboxane. Exposure to 48-60 h of 100% O2 at 1 ATA markedly reduced the increase in pulmonary artery pressure caused by t-bu-OOH infusion. We also investigated whether the mechanism for the attenuated vasoconstriction was due to altered production of arachidonate mediators or oxidant-induced damage to the contractile mechanism. In addition to infusing t-bu-OOH, which selectively stimulates thromboxane production, we also infused Intralipid, an esterified fatty acid emulsion that stimulates production of both thromboxane and prostacyclin. These experiments were done to study the effect of hyperoxia on prostacyclin synthesis. To determine if antioxidant therapy would prevent the changes in mediator production and vascular reactivity caused by hyperoxia, we pretreated animals with the antioxidants butylated hydroxyanisole (BHA) or vitamin E. The lack of vascular reactivity to t-bu-OOH was not due to a decrease in thromboxane synthesis or an increase in prostacyclin synthesis. Hyperoxia did not affect thromboxane synthesis during basal conditions or after stimulation of synthesis by t-bu-OOH. 100% O2 also did not effect the basal synthesis of prostacyclin by the lung. Hyperoxia did, however, markedly reduce prostacyclin synthesis when it was stimulated by Intralipid infusion. Antioxidant pretreatment did not reverse the inhibition of prostacyclin synthesis but did prevent the loss of vascular reactivity caused by hyperoxia. Thus hyperoxia causes vascular paralysis through oxidant-induced injury to the pulmonary vasculature.