p38 MAPK regulates group IIa phospholipase A2 expression in interleukin-1beta -stimulated rat neonatal cardiomyocytes.

Group IIa phospholipase A(2) (GIIa PLA(2)) is released by some cells in response to interleukin-1beta. The purpose of this study was to determine whether interleukin-1beta would stimulate the synthesis and release of GIIa PLA(2) from cardiomyocytes, and to define the role of p38 MAPK and cytosolic PLA(2) in the regulation of this process. Whereas GIIa PLA(2) mRNA was not identified in untreated cells, exposure to interleukin-1beta resulted in the sustained expression of GIIa PLA(2) mRNA. Interleukin-1beta also stimulated a progressive increase in cellular and extracellular GIIa PLA(2) protein levels and increased extracellular PLA(2) activity 70-fold. In addition, interleukin-1beta stimulated the p38 MAPK-dependent activation of the downstream MAPK-activated protein kinase, MAPKAP-K2. Treatment with the p38 MAPK inhibitor, SB202190, decreased interleukin-1beta stimulated MAPKAP-K2 activity, GIIa PLA(2) mRNA expression, GIIa PLA(2) protein synthesis, and the release of extracellular PLA(2) activity. Infection with an adenovirus encoding a constitutively active form of MKK6, MKK6(Glu), which selectively phosphorylates p38 MAPK, induced cellular GIIa PLA(2) protein synthesis and the release of GIIa PLA(2) and increased extracellular PLA(2) activity 3-fold. In contrast, infection with an adenovirus encoding a phosphorylation-resistant MKK6, MKK6(A), did not result in GIIa PLA(2) protein synthesis or release by unstimulated cardiomyocytes. In addition, infection with an adenovirus encoding MKK6(A) abrogated GIIa PLA(2) protein synthesis and release by interleukin-1beta-stimulated cells. These results provide direct evidence that p38 MAPK activation was necessary for interleukin-1beta-induced synthesis and release of GIIa PLA(2) by cardiomyocytes.

Hemorrhage-induced alpha-adrenergic signaling results in myocardial TNF-alpha expression and contractile dysfunction.

Hemorrhagic shock (HS), secondary to major blood loss, frequently precedes multiple organ dysfunction and is accompanied by a surge in circulating catecholamine levels. Expression of the cardiodepressant cytokine, tumor necrosis factor-alpha (TNF-alpha), has been observed in the heart after HS and resuscitation (HS/R) and alpha(1)-adrenergic blockade prevented translocation of the nuclear transcription factor, NF-kappa B, to the nucleus. We hypothesized that alpha(1)-adrenergic stimulation induces myocardial TNF-alpha expression, which results in depressed cardiac function after HS/R. The role of alpha(1)-adrenergic stimulation in myocardial TNF-alpha expression and depressed cardiac function after HS/R was assessed by treatment with the alpha(1)-adrenergic inhibitor, prazosin hydrochloride (1 mg/kg ip), for 1 h before the onset of hemorrhage. In addition, TNF-alpha was neutralized with a specific antibody (600 microl/kg iv) 5 min before hemorrhage. HS was induced by the withdrawal of blood to a mean blood pressure of 50 mmHg for 1 h. Contractile function was measured with the use of a Langendorff apparatus 2 h after the end of HS. HS/R led to significant decreases in left ventricular developed tension and in the maximal rate of pressure increase over time during both contraction and relaxation. Myocardial expression of TNF-alpha measured by enzyme-linked immunosorbent assay increased significantly after 30 min of hemorrhage and peaked after 60 min of HS and 45 min of resuscitation. Depression in cardiac function after HS/R was reversed by 85% in hearts from rats treated with a TNF-alpha neutralizing antibody and by 90% in hearts from rats treated with prazosin hydrochloride. We conclude that HS activates a alpha(1)-adrenergic pathway, resulting in TNF-alpha expression in the heart and depressed myocardial contractile function.

Role of TNF-alpha in myocardial dysfunction after hemorrhagic shock and lower-torso ischemia.

Ruptured abdominal aortic aneurysm (RAAA) repair, a combination of hemorrhagic shock and lower-torso ischemia, is associated with a 50-70% mortality. Myocardial dysfunction may contribute to the high rate of mortality after aneurysm repair. We attempted to determine whether RAAA repair results in cardiac dysfunction mediated by tumor necrosis factor-alpha (TNF-alpha). We modeled aortic rupture and repair in the rat by inducing hemorrhagic shock to a mean blood pressure of 50 mmHg for 1 h, followed by supramesenteric clamping of the aorta for 45 min. After 90 min of reperfusion, cardiac contractile function was assessed with a Langendorff preparation. Myocardial TNF-alpha, ATP and creatine phosphate (CP) levels, and markers of oxidant stress (F(2)-isoprostanes) were measured. Cardiac function in the combined shock and clamp rats was significantly depressed compared with sham-operated control rats but was similar to that noted in animals subjected to shock alone. Myocardial TNF-alpha concentrations increased 10-fold in the combined shock and clamp rats compared with sham rats, although there was no difference in myocardial ATP, CP, or F(2)-isoprostanes. TNF-alpha neutralization improved cardiac function by 50% in the combined shock and clamp rats. Hemorrhagic shock is the primary insult inducing cardiac dysfunction in this model of RAAA repair. An improvement in cardiac contractile function after immunoneutralization of TNF-alpha indicates that TNF-alpha mediates a significant portion of the myocardial dysfunction in this model.

Massive upper gastrointestinal haemorrhage due to direct visceral erosion of splenic artery aneurysm.

Six male patients (age group: 30-60 years) with aneurysm of the splenic artery presented with massive upper gastrointestinal tract hemorrhage. Five patients presented with hematemesis and one with melena. Chronic pancreatitis was noted in all the patients, four of whom were chronic alcoholics. Endoscopy was not useful in diagnosis. Bleeding through the Ampulla of Vater was seen in the patient with melena. Angiography was diagnostic in all. Pancreatic resection including the aneurysm(2), and bipolar ligation with underrunning of the aneurysm (3) were the operative procedures. Distal pancreatectomy with pancreatogastrostomy was carried out in the patient with hemosuccus pancreaticus. If endoscopy is inconclusive, angiography and early intervention is recommended to reduce the high mortality associated with conservative management.

Gastric lipoma presenting as obstruction and hematemesis.

A rare case of gastric lipoma presented to us with hematemesis and symptoms of obstruction. On oesophagoduodenoscopy, a mass projecting in the lumen of stomach was found. Barium meal examination revealed a mass in the antral region suggestive of malignancy. The diagnosis of lipoma was suspected only after exploration. It was confirmed following incision through the serosa. The lipoma was enucleated without any damage to mucosa.

Primary extrapancreatic gastrinoma.

Extrapancreatic gastrinoma is a rare clinical entity encountered in surgical practice. A patient was referred to us who had a history of recurring symptoms of peptic ulcer disease and ulcer perforation located at an unusual site. Serum gastrin levels were abnormally high. Scopy revealed multiple ulcers in the antrum and duodenum. A mass superior to the head of the pancreas was detected on USG, which later on found to be a separate mass on CT scan. The tumour was excised and confirmed on histopathology. Results of conservative surgery were found to be satisfactory.

Calvarial bone grafts for augmentation rhinoplasty.

A large variety of graft materials have been used for augmentation rhinoplasty. To date there has been no graft material which can be regarded as completely satisfactory. The modern trend is to prefer autologous material to new biological material. The membranous bones of the calvarium are extremely suitable for augmenting moderate to severe saddle nose deformities. Calvarial bone grafts can be harvested easily, with minimum donor site morbidity and disfigurement. Our experience with calvarial bone grafts for augmentation rhinoplasty is presented.

Tuberculous otitis media presenting as complications: report of 18 cases.

Tuberculous otitis media is a rare but treatable disease; delay in its diagnosis usually leads to complications. In the last 15 years we have come across 18 cases of tuberculous otitis media, which presented various intra- and extracranial complications. In the past, tuberculous otitis media had always been considered a discrete disease, but it is possible that tuberculosis may coexist or secondarily affect an already discharging ear. The following discussion illustrates the complications and clinical problems encountered in tuberculous otitis media.