Effects of selective phosphodiesterase inhibitors on platelet-activating factor- and antigen-induced airway hyperreactivity, eosinophil accumulation, and microvascular leakage in guinea pigs

There is currently interest in the potential use of selective inhibitors of cyclic nucleotide phosphodiesterases (PDE) in the treatment of asthma. In this study we examined the effects of three selective PDE inhibitors, milrinone (PDE III), rolipram (PDE IV) and zaprinast (PDE V), on the broncoconstriction produced by antigen and histamine, the airway hyperreactivity and microvascular leakage after aerosol exposure to platelet-activating factor (PAF) and antigen, and the antigen-induced eosinophil infiltration in guinea-pig lung. Inhaled rolipram (0.01–10 mg ml^–1) inhibited dose dependently the bronchospasm produced by aerosol antigen (5 mg ml^–1) an anaesthetised, ventilated guinea-pigs. Rolipram (10 mg ml^–1) produced maximal inhibition of antigen-induced bronchoconstriction but only partial inhibition of the response to aerosol histamine (1 mg ml^–1). Milrinone and zaprinast (each 10 mg ml^–1) showed weak, or no, inhibitory effects against bronchoconstriction produced by aerosol antigen or histamine. Pretreatment with rolipram (10 mg kg^–1, i.p.) prevented airway hyperreactivity to histamine which develops 24 h after exposure of conscious guinea-pigs to aerosol PAF (500 g ml^–1) or antigen (5 mg ml^–1). The pulmonary eosinophil infiltration obtained with 24 h of antigen-exposure was inhibited by rolipram. In contrast, milrinone and zaprinast (each 10 mg kg^–1, i.p.) failed to reduce either the airway hyperreactivity of the eosinophil accumulation in these animals. Rolipram (1–10 mg ml^–1) reduced the extravasation of Evans blue after aerosol PAF (500 g ml^–1) at all airway levels while a lower dose (0.1 mg ml^–1) was only effective at intrapulmonary airways. Rolipram (0.01–1 mg ml^–1) markedly reduced airway extravasation produced by inhaled antigen (5 mg ml^–1). Zaprinast (1–10 mg ml^–1) was also effective against airway microvascular leakage produced by aerosol PAF or antigen while milrinone (10 mg ml^–1) had no antiexudative effect. These data support previous suggestions that pharmacological inhibition of PDE IV results in anti-spasmogenic and anti-inflammatory effects in the airways and may be useful in the treatment of asthma.     

Left pancreatectomy with preservation of the spleen without its pedicle. Apropos of 13 cases]

Overwhelming post splenectomy infections in childhood were first described by King and Shumaker in 1952. This septic risk, although a matter of controversy, also exists in adults. Thus, splenic conservation must become a surgical concern in left pancreas resections for benign or traumatic diseases. The authors report their experience with a simplified procedure in which the splenic pedicle is resected "en bloc" with the left pancreas. This technique has been employed in thirteen patients, in whom spleen could be preserved in twelve, without operative mortality and a low morbidity rate.     

Gastrointestinal motility of patients with Roux-en-Y reconstruction

The electromyographic activity of the gastrointestinal tract was studied in 28 patients undergoing gastric, biliary, and pancreatic operations with reconstruction of the gastrointestinal tract with a Roux-en-Y limb. The Roux-en-Y limb was constructed 1 to 5 years before the study in 8 patients (chronic Roux-en-Y) and at the operation in which the electrodes were implanted in 20 patients (recent Roux-en-Y). All four phases of the migrating motor complex (MMC) were identified in the gastrointestinal tract, including in the Roux-en-Y limb. The duration of the MMC was 82.4 ± 22.3 min in the patients with chronic Roux-en-Y and 89.0 ± 25.1 min in the patients with recent Roux-en-Y. Food ingestion converted the MMC to the fed pattern in the entire gastrointestinal tract, including the Roux-en-Y limb in 16 (76.2%) of 21 recordings of the patients with chronic Roux-en-Y and in 27 (84.4%) of 32 recordings of the patients with recent Roux-en-Y. The duration of the fed pattern was 170 ± 34 min in the patients with chronic Roux-en-Y and 154 ± 26 min in the patients with recent Roux-en-Y. The findings of this study indicate that the electromyographic activity of the Roux-en-Y limb is normal during both fasting and fed states, even many years after the construction of the Roux-en-Y.

---

Resumen Se estudió la motilidad electromiográphica del tracto gastrointestinal de 28 pacientes sometidos a operaciones gástricas, biliares y pancreáticas con reconstrucción de tipo Roux-en-Y. El asa de Roux-en-Y fue construida 1–5 años antes del estudio en un grupo de ocho pacientes (Roux-en-Y crónica) y en otro grupo de 20 lose electrodos fueron implantados durante la operación (Roux-en-Y reciente). Se identificaron las cuatro fases del complejo motormigratorio en el tracto gastrointestinal, incluso en el asa de Roux-en-Y. La duración del CMM fue 82.4 ± 22.3 min en los pacientes con Roux-en-Y crónica y 89.0 ± 25.1 min en los pacientes con Roux-en-Y reciente. Con la ingesta de alimento se substituyó el CMM por el patrón postalimentación en la totalidad del tracto gastrointestinal incluso en el asa de Roux-en-Y, en 16 de los 21 registros (76.2%) de los pacientes con Roux-en-Y crónica y en 27 de los 32 registros (84.4%) de los pacientes con Roux-en-Y reciente. La duración del patrón postalimentacón fue 170 ± 34 min en los pacientes con Roux-en-Y crónica y 154 ± 26 min en los pacientes con Roux-en-Y reciente. Los hallazgos en este estudio indican que la actividad electromiográphica del asa de Roux-en-Y es normal durante las fases de ayuno o de alimentación, aún transcurridos muchos años de la confección del Roux-en-Y.

---

Résumé L'activité électromyographique de l'intestin grêle a été étudiée chez 28 patients ayant eu des interventions portant sur le l'estomac, les voies biliaires ou le pancréas et comportant une reconstruction avec une anse en Y. Chez huit de ces patients, l'intervention initiale pendant laquelle cette anse en Y avait été mopntée, datait de 1 à 5 ans (anse en Y dite chronique). Chez les 20 autres patients, les électrodes pour mesurer l'activité électrique ont été placées pendant l'intervention initiale (anse en Y dite récente). Les quatre phases du complexe moteur migrateur (CMM) ont été identifiées sur l'intestin et sur l'anse en Y. La durée du CMM a été de 82.4 ± 22.3 min chez les patients ayant une anse en Y chronique, et de 89.0 ± 25.1 min chez les patients ayant une anse en Y récente. Pendant l'alimentation, la courbe d'activité dite d'alimentation a remplacé les CMM dans le tube intestinal en entier, y compris l'anse en Y chez 16 des 21 enregistrements (76.2%) des patients ayant une anse en Y chronique et chez 27 des 32 (84.4%) enregistrements des patients ayant une anse en Y récente. La durée des courbes dites d'alimentation a été de 170 ± 34 min chez les patients avec une anse en Y chronique et de 154 ± 26 min chez les patients avec une anse en Y récente. Les résultats de cette étude indiquent que l'activité électromyographique des anses en Y est normale pendant le jeûne et pendant l'alimentation, et ce même plusieurs années après la confection d'une anse en Y.

     

CLINICO-PATHOLOGIC CONFERENCE: 12-YEAR-OLD GIRL WITH FATIGUE, ANEMIA, WEIGHT LOSS, ABDOMINAL DISTENTION, AND OCCASIONAL NAUSEA AND VOMITING

A clinicopathologic case is presented. The patient was a 12-year-old white girl with a history of fatigue and dizziness, occasional nausea and vomiting, and anemia, who showed abdominal distention, especially in the epigastrium. An epigastric mass was palpable. Gastroscopy was done, and surgery followed. Pertinent laboratory findings are presented, and clinical discussion follows. The pathology is then presented and discussed.     

Failure of Nonoperative Management of Isolated Superior Mesenteric Artery Dissection

A case of isolated dissection of the superior mesenteric artery is presented here. This rare condition was confirmed angiographically in a 46-year-old man with persistent abdominal pain. He was treated initially with anticoagulation alone. One year later, he developed recurrent symptoms and had radiologic documentation of progression of the condition. Operative repair was performed and recovery was uneventful. This case demonstrates a failure of the nonoperative approach to this rare condition and suggests that disease progression may be inevitable. Early surgical correction may ease operative management.     

Summary of findings from the evaluation of a pilot medically supervised safer injecting facility

In many cities, infectious disease and overdose epidemics are occurring among illicit injection drug users (IDUs). To reduce these concerns, Vancouver opened a supervised safer injecting facility in September 2003. Within the facility, people inject pre-obtained illicit drugs under the supervision of medical staff. The program was granted a legal exemption by the Canadian government on the condition that a 3-year scientific evaluation of its impacts be conducted. In this review, we summarize the findings from evaluations in those 3 years, including characteristics of IDUs at the facility, public injection drug use and publicly discarded syringes, HIV risk behaviour, use of addiction treatment services and other community resources, and drug-related crime rates. Vancouver's safer injecting facility has been associated with an array of community and public health benefits without evidence of adverse impacts. These findings should be useful to other cities considering supervised injecting facilities and to governments considering regulating their use.     

Methylamine but not mafenide mimics insulin-like activity of the semicarbazide-sensitive amine oxidase-substrate benzylamine on glucose tolerance and on human adipocyte metabolism

It has been reported that benzylamine reduces blood glucose in rabbits, stimulates hexose uptake, and inhibits lipolysis in mouse, rabbit, and human adipocytes. In the presence of vanadate, benzylamine is also able to improve glucose disposal in normoglycaemic and diabetic rats. Such insulin-mimicking properties are the consequence of hydrogen peroxide production during benzylamine oxidation by semicarbazide-sensitive amine oxidase (SSAO). The aim of the study was to determine whether other SSAO-substrates could share such potential antidiabetic properties. Thus, mafenide, a synthetic antimicrobial sulfonamide structurally related to benzylamine, and which has been recently reported to interact with SSAO, was tested in the above mentioned models, in parallel with methylamine, a proposed endogenous SSAO-substrate. All tested amines stimulated glucose uptake and inhibited lipolysis in rat and mouse fat cells. Methylamine and benzylamine, but not mafenide, reduced the hyperglycaemic response during a glucose tolerance test in rabbits while the three amines tested were devoid of insulin-releasing activity under both in vivo and in vitro conditions. In human adipocytes, mafenide did not stimulate glucose transport since it was not a high-affinity substrate for SSAO and generated less hydrogen peroxide than benzylamine or methylamine. Therefore, mafenide could not be considered as an antidiabetic drug despite being oxidized and exhibiting insulin-mimicking effects in rat and mouse adipocytes. By contrast, the endogenous substrate methylamine improved glucose utilization in all in vitro and in vivo models, leading to consider novel SSAO substrates as drugs with potential anti-hyperglycaemic properties.     

Transvaginal repair of vesicovaginal fistula: surgical techniques to improve access and successful vaginal closure

This video demonstrates surgical techniques to improve closure of high vesicovaginal fistula using the vaginal approach and the Latzko procedure.