Immunohistochemical localization of protein 3-nitrotyrosine and S-nitrosocysteine in a murine model of inhaled nitric oxide therapy.

Inhaled nitric oxide (INO) therapy is currently used clinically to selectively dilate the pulmonary vasculature and to help treat persistent pulmonary hypertension and bronchopulmonary dysplasia in the neonate. However, in the presence of oxygen or superoxide, nitric oxide forms potentially harmful reactive nitrogen species. Using an experimental mice model, we examined the effects of concurrent hyperoxia and INO on protein tyrosine nitration and cysteine S-nitrosylation in pulmonary tissue. Data showed enhanced 3-nitrotyrosine staining within the airway epithelium and alveolar interstitium of mice lungs treated with hyperoxia, which did not increase significantly with INO administration. Within the alveolar interstitium, 3-nitrotyrosine staining was localized to macrophages. S-Nitrosocysteine staining in airway epithelium was significantly enhanced with INO administration regardless of oxygen content. These data suggest that the formation of protein S-nitrosocysteine is the major protein modification during administration of INO.

Complete biliary avulsion from blunt compression injury.

The liver is the solid organ most commonly injured as a result of blunt abdominal trauma. Complete avulsion of the common hepatic duct is a rare and devastating type of hepatobiliary trauma. Here the authors report the case of a 7-year-old child who had complete biliary disruption as a result of an abdominal crush injury that was not diagnosed correctly preoperatively. The intraoperative diagnosis and treatment of this injury is discussed.

The efficacy of diagnostic laparoscopic ultrasound.

Precise staging of malignant disease is required to define the optimum therapeutic strategy. In spite of technical advances, the sensitivity of conventional imaging techniques is usually limited to defining lesions of at least 1 cm in size. Laparoscopy is a sensitive technique that is very valuable for visual inspection of the abdominal cavity and the identification of small surface lesions. However, non-superficial lesions may escape detection due to the lack of tactile sensitivity. As an adjunct to laparoscopy, this study, utilizing a young swine model, has analyzed the detectability of intra-abdominal lymph nodes by laparoscopic ultrasound (LU). Lymph nodes in and around the hepatoduodenal ligament, examined and measured by LU, were resected by subsequent open laparotomy in eight young, mixed-breed swine. The numbers and sizes of lymph nodes detected by LU and resected at laparotomy were compared and analyzed statistically. Forty-six lymph nodes were resected by laparotomy, while LU failed to detect 3 small nodes (sensitivity, 43/46 = 93.5%). The sizes of lymph nodes in the LU group correlated strongly with the sizes actually measured in the laparotomy group (r = 0.936, P < 0.001). Twenty-six small lymph nodes, which conventional extracorporeal imaging might have failed to diagnose, were detected accurately by LU (r = 0.877, P < 0.001). This new technology may not only be effective for staging intra-abdominal malignant disease, but adds the benefit of obtaining tissue samples under direct vision using minimally invasive techniques.

Differential effects of hyperoxia on the inducible and constitutive isoforms of nitric oxide synthase in the lung.

Hyperoxia is commonly used in the treatment of newborn respiratory distress. Although essential and life saving, oxygen therapy can result in the development of lung injury. Oxygen toxicity is associated with the production of reactive oxidant species. Nitric oxide (NO) is an oxidant formed by the catalysis of L-arginine when acted upon by the enzyme nitric oxide synthase (NOS). We studied the differential effects of prolonged normobaric hyperoxia (FIO2 = .95, for 3, 4, and 5 days) on the two major NOS enzymes, constitutive endothelial cell NOS (ecNOS) and inducible NOS (iNOS). Hyperoxia led to a significant lung injury, as measured by pulmonary compliance studies. Hyperoxia did not increase serum NO production, measured as the concentration of nitrite and nitrate. However, hyperoxia did result in a small but significant increase in NO production in the bronchoalveolar lavage fluid, as measured by the products of nitrite and nitrate concentration. This increase in NO was not associated with an induction of whole lung iNOS, as measured by the conversion of L-[3H]arginine to L-[3H]citrulline or by Northern blot analysis. Hyperoxia significantly decreased ecNOS activity as measured by the conversion of L-[3H]arginine to L-[3H]citrulline. In addition, administration of the NOS inhibitor NG-nitro-L-arginine methyl ester worsened the injury, as measured by lung compliance and survival. Further studies need to be performed to determine whether this decrease in ecNOS activity during hyperoxia plays a role in the pathogenesis of hyperoxia-related lung injury.

Evaluation of operative stress and peritoneal macrophage function in minimally invasive operations.

BACKGROUND: Laparoscopic operative procedures have decreased postoperative pain and the length of hospitalization. In addition, evidence supports a physiologic benefit from laparoscopic surgery. By analyzing several parameters of peritoneal macrophage function, we report a comparison of the magnitude of postoperative stress between two types of minimally invasive access techniques contrasted with an open laparotomy, in a murine model. STUDY DESIGN: Immature male A/J mice were exposed to pneumoperitoneum using carbon dioxide, gasless suspension, or laparotomy. Peritoneal macrophages were then harvested, and the number and viability of the macrophages from each group of mice were compared. Last, as a marker of postoperative stress, the in vitro production of nitric oxide and tumor necrosis factor alpha by these macrophages was determined. RESULTS: The number of peritoneal macrophages and the viability of the macrophages in the laparotomy group were significantly decreased 4 hours after operation compared with the minimally invasive and control groups. In addition, macrophage production of tumor necrosis factor alpha and nitric oxide, two markers of macrophage stress, 24 hours after operation was significantly increased in the laparotomy group compared with animals serving as controls. Gasless suspension and pneumoperitoneum decreased the number of macrophages to a lesser degree than did open laparotomy and did not affect macrophage viability. Moreover, gasless suspension and pneumoperitoneum did not lead to an increase in tumor necrosis factor alpha or nitric oxide production by peritoneal macrophages. CONCLUSIONS: Postoperative stress, assessed by a decrease in macrophage viability and an increase in cytotoxic cytokine production, is maximized after laparotomy compared with stress in murine hosts that underwent minimally invasive treatment. These data provide basic scientific evidence for the possible physiologic benefit of minimally invasive techniques.

Decreased pulmonary compliance is an early indicator of pulmonary oxygen injury.

Pulmonary oxygen injury is classified by the development of tissue and alveolar edema, surfactant dysfunction, lung inflammation, and decreased pulmonary compliance. In neonates prolonged oxygen therapy is associated with the development of bronchopulmonary dysplasia. Recombinant DNA technology makes it possible to experimentally explore the role of specific proteins in the development of pulmonary oxygen injury. However, in vivo experiments require sensitive ways of identifying pulmonary oxygen injury early in its development. We therefore compared the sensitivities of several experimental assays used to assess pulmonary injury. We found that changes in pulmonary compliance were the most sensitive and showed significant differences after 72 hr of exposure to normobaric hyperoxia (FiO2 = 0.95), which correlated with a small change in the histology of the mice lungs. The concentration of protein in the bronchoalveolar lavage fluid was less sensitive and did not differ significantly until after 96 hr of exposure. The survival in hyperoxia also did not worsen until after 96 hr. The lung wet/ dry weight ratios was the least sensitive assay and did not increase until after 5 days of exposure to normobaric hyperoxia. We conclude that a decrease in pulmonary compliance is an early indicator of pulmonary oxygen injury and may be a better way to study the mechanisms and mediators of pulmonary oxygen injury.

Pancreatic trauma in children: mechanisms of injury.

BACKGROUND: Pancreatic trauma occurs in up to 10% of all cases of blunt pediatric trauma. Here we attempted to identify markers of pancreatic injury in children and to assess our current diagnostic approach to pancreatic injury. METHOD: We performed a retrospective chart review of all patients with a pancreatic injury admitted to a Level I pediatric trauma center between January of 1980 and September of 1994. RESULTS: In all, 26 children were included. All pancreatic injuries were due to blunt trauma. Handlebar injuries were the most common mechanism of injury and resulted in a unique pattern of isolated pancreatic trauma, often complicated by the development of a pseudocyst. Computed tomographic scans, performed with intravenous and oral contrast and done in the acute setting, were 85% sensitive for diagnosing a pancreatic injury. CONCLUSIONS: Double contrast computed tomographic scan is a more sensitive test than ultrasound in diagnosing pancreatic injury. The constellation of abdominal pain, an elevated serum amylase and a handlebar mechanism of injury warrants hospitalization and a double contrast abdominal computed tomographic scan.

Low-level expression and limited role for the inducible isoform of nitric oxide synthase in the vascular hyporeactivity and mortality associated with cecal ligation and puncture in the rat.

Expression of the inducible isoform of nitric oxide synthase (iNOS) contributes to the hypotension and vascular hyporeactivity in various models of shock induced by bacterial lipopolysaccharide (LPS). However, the role of iNOS in response to shock caused by live bacteria is more controversial. In the present study, we investigated the role of iNOS in a rat model of cecal ligation and puncture (CLP). CLP resulted in increased plasma nitrite/nitrate levels (up to 59 microM at 24 h) and increased pulmonary iNOS activity (up to 71 fmoles/mg/min at 12 h) and caused a significant vascular hyporeactivity at 18 h. The degree of NO production and iNOS induction was approximately 30% of that observed several hours after administration of LPS in the same species, and the degree of vascular hyporeactivity was less than that observed after LPS injection. Selective inhibition of iNOS with mercaptoethylguanidine (MEG) reduced plasma nitrite/nitrate levels, but did not prevent the development of vascular hyporeactivity, and did not improve survival in this model of CLP. Thus, CLP-induced sepsis causes low-level induction of iNOS, but factors other than iNOS are the crucial determinants of the vascular failure and mortality in this model.

Selective inhibition of the inducible isoform of nitric oxide synthase prevents pulmonary transvascular flux during acute endotoxemia.

The inducible isoform of nitric oxide synthase (iNOS) is expressed in various organs, including the lung, during systemic endotoxemia. Overproduction of nitric oxide (NO) by iNOS contributes significantly to the vascular failure and end-organ damage in endotoxemia. Using selective pharmacological inhibitors of iNOS, the purpose of this study was to define the role of iNOS in a rat model of endotoxin-induced pulmonary transvascular flux (TVF). Lung TVF was assessed by a method of Evans Blue permeability index (PI). Bacterial lipopolysaccharide (LPS) (15 mg/kg intraperitoneally [IP]) significantly increased pulmonary iNOS activity and serum levels of nitrite/nitrate (NO2/NO3). This was accompanied by a significant elevation of the PI 5 hours after injection. Selective iNOS inhibition with either S-methyl isothiourea (SMT; 5 mg/kg IP) or aminoguanidine (AG; 20 mg/kg IP), administered 2 hours after LPS injection, significantly prevented the increase in PI associated with LPS injection. Similarly, inhibition of the induction of iNOS with dexamethasone (10 mg/kg IP), given 3 hours before LPS, also inhibited the increase in PI. All three treatments significantly prevented the increase in both lung iNOS activity and serum NO2/NO3 associated with endotoxemia. In conclusion, the overproduction of NO generated by iNOS during systemic endotoxemia causes a vascular leak in the lung. Thus, it is speculated that selective inhibition of iNOS may be beneficial in preventing the development of acute respiratory failure in sepsis.

Primary extrarenal Wilms' tumor in the inguinal canal: case report and review of the literature.

Inguinal and scrotal Wilms' tumors are extremely rare; only 15 cases have been reported to date. The authors report a case of inguinal Wilms' tumor (stage III), which occurred in a previously healthy 3 1/2-year-old boy who was staged and treated according to currently accepted National Wilms' Tumor Study III criteria. The exact embryological origin of this tumor has not been determined. However, there is evidence that the origin is more primitive than that of intrarenal Wilms' tumor.

Spontaneous recanalization of the pancreatic duct: case report and review.

An eight-year-old boy received a grade 3 pancreatic injury as a result of a bicycle handlebar accident. Endoscopic retrograde cholangiopancreatography (ERCP) showed a proximal pancreatic duct transection. At laparotomy, a complete transection of the gland and duct was visualized; however, only debridement and external fistulization were performed. Follow-up ERCP performed 3 months postoperatively showed recanalization of the pancreatic duct without further operative intervention. At 1-year follow-up, the patient is pain free and tolerating a regular diet.

Nitric oxide: an overview.

Nitric oxide (NO), a paracrine-acting gas enzymatically synthesized from L-arginine, is a unique biologic mediator that has been implicated in a myriad of physiologic and pathophysiologic states. It is an important regulator of vascular tone and may be the mediator of the hemodynamic changes involved in sepsis and cirrhosis. In addition, there is increasing evidence that NO is involved in coagulation, immune function, inhibitory innervation of the gastrointestinal tract, protection of gastrointestinal mucosa, and the hepatotoxicity of cirrhosis. It has already been speculated that NO may represent a point of control or intervention in a number of disease states. The purpose of this paper is to provide the surgeon with a broad overview of the scientific and clinical aspects of this important molecule.

Specialization and referral among the n'anga (traditional healers) of Zimbabwe.

PIP: Traditional medicine is the source of primary care for most Zimbabweans. N'angas (traditional healers) are consulted for their political and religious powers along with their healing powers. The Zimbabwe National Traditional Healers Association was formed and is officially recognized by the government and has a constitution along with departments of education and research. Each member pays annual dues. Herbal remedies are used. Most n'angas say they are possessed by a healing spirit which they invoke while treating the patient. These n'angas practice specialization--the extent to which the n'angas claim expertise, outside of which they will refer a patient to others. The referral and specialization practices of a select group of n'angas in and around the capital, Harare are studied. 30 n'angas from 7 suburbs of harare were interviewed personally at their place of practice in 1987. All 30 claimed to specialize in the treatment of certain illnesses. They specialized in spiritual, not just medical, problems. The n'angus referred to other n'angas for either or both of 2 reasons: 1) most referred patients for whom their treatment had failed; and 2) patients were referred for suffering an illness which that certain n'anga could not cure, usually because their healing spirit did not give them the cure. There were some things that the n'angas would only send to western medical practitioners and hospitals. These were mostly accidents or emergencies. "Abnormal illnesses" were never referred to Western practitioners and hospitals. "Abnormal illnesses" were caused by evil spirits such as "ngozi." The n'angas were divided over what to do about the acquired immunodeficiency syndrome (AIDS). 1 n'anga sand that he was so good at curing AIDS that he was flown to America to treat a patient. Others would send AIDS patients to hospitals. Most all Zimbabwe natives are descended from Shona and Ndebele cultures.^ieng