Platelet-activating factor: an endogenous mediator for bowel necrosis in endotoxemia

We have developed a model of isochemic bowel necrosis in the rat by injecting platelet-activating factor (PAF) or PAF in combination with bacterial endotoxin. PAF causes profound hypotension, and it has been suggested that it is released during endotoxin shock. Because ischemic bowel necrosis is often associated with shock or infection, it is possible that PAF is the endogenous mediator that causes shock and bowel necrosis during sepsis. In this study, we have demonstrated that: 1) normal intestine contained a small amount of PAF; 2) necrotic lesions of the intestine could be induced by endotoxin injection; 3) PAF production in the bowel is markedly increased in animals treated with endotoxin; 4) pretreatment of the animal with PAF antagonists prevent endotoxin-induced necrosis; 5) isolated, buffer-perfused small intestine produced a small quantity of PAF in response to endotoxin injection. Therefore, we conclude that PAF is a likely endogenous mediator in endotoxemia, which causes bowel necrosis and shock.     

Acid-fast bacilli in fine needle aspiration smears from tuberculous lymph nodes. Where to look for them

OBJECTIVE: To analyze where acid-fast bacilli (AFB) are most often seen in smears prepared from tuberculous lymph nodes. STUDY DESIGN: Patients referred for fine needle aspiration cytology for evaluation of lymphadenopathy between March 1994 and June 1998 were analyzed. Only those cases clinically and therapeutically proven to be tuberculous were included in the study. RESULTS: Of 783 cases analyzed, 213 (27.2%) were tuberculous. Aspirates obtained were of three types: blood-mixed particles, caseous material and pus. Five cytologic pictures were seen: epithelioid cell granulomas alone or with coexistent necrosis, AFB or both, and necrosis with AFB. AFB were most often seen in purulent aspirates, followed by caseous and least often in blood-mixed particles. Granulomas were most often seen when the aspirate was blood-mixed particles, followed by caseous and, least often, pus. CONCLUSION: AFB detection should be carried out on all suspected tuberculous patients. The relationship between the presence of granuloma and of AFB is inverse. The chance of finding AFB is highest in patients presenting with a cold abscess and yielding pus on aspiration followed by patients who yield caseous material on aspiration.     

Management of necrotizing pancreatitis.

A comprehensive management plan is presented for patients with severe acute pancreatitis. These patients may have pancreatic or peripancreatic necrosis or pancreatic fluid collections. Multiple organ failure often develops in patients with severe pancreatitis. We therefore recommend that all patients with acute pancreatitis be evaluated for pancreatic anatomy and function. If a patient is seriously ill, a computed tomographic (CT) scan with vascular enhancement should be done. Meanwhile, vigorous fluid replacement is necessary using Swan-Ganz monitoring. Patients with necrosis do not need surgical intervention unless the clinical course or CT scan-guided aspiration shows infection. The objective of an operation should be to remove all infected tissue and fluid. A preoperative CT scan with vascular enhancement should be used as a guide during the operation to ensure that all foci of infected necrosis or fluid are eliminated. We have found that open packing and irrigation with sodium oxychlorosene are helpful in patients with extensive necrosis or those who become infected early after the onset of symptoms. In all, 40% to 50% of patients treated by closed drainage will require reoperation because of incomplete debridement. Persistent sepsis is an indication for reoperation.     

The early management of flap necrosis in breast reconstruction

Flap necrosis is a potential complication of any type of breast reconstruction. Of 302 breast reconstructions performed by the author at the University of Texas M.D. Anderson Cancer Center, some degree of flap necrosis occurred in 59 (19.5 percent). Small areas of flap necrosis can be managed with simple observation, but secondary healing may not be complete for months. Early and aggressive excision of the ischemic tissue with immediate primary closure often can achieve rapid primary healing. In addition, early revision and reshaping of the breast may, in selected patients, permit achievement of a significantly better final result. This is true not only for TRAM and latissimus dorsi flaps, but also for the mastectomy flap necrosis sometimes encountered in immediate reconstruction with simple implants or tissue expanders.     

Necrosis in field beans (Vicia faba) induced by interactions between bean leaf roll, pea early-browning and pea enation mosaic viruses

Mixed infections with two or three viruses - bean leaf roll (BLRV), pea early-browning (PEBV) and pea enation mosaic (PEMV) - were detected in plants showing leaf curling, stunting and necrosis in a crop of field beans grown for seed in 1980. In glasshouse tests, field bean plants infected with any one of these viruses showed no necrosis, and plants infected with PEBV and PEMV together showed symptoms of PEMV only. However, mixed infection with BLRV and PEMV almost invariably induced severe stunting and leaf necrosis, and infection with BLRV and PEBV often induced both leaf and stem necrosis and sometimes caused early death. Thus it seems that the necrotic symptoms seen in the field were induced by interactions between BLRV and the other viruses. No transmission of PEBV was detected through seed harvested from the crop, but up to 5% transmission was detected through seed from experimentally-infected plants. The infected seedlings were symptomless.     

Early observations of pancreatic ultrastructure during hemorrhagic necrosis in the rat with closed duodenal pouch]

Many problems are still unanswered in the pathogenesis of acute clinical and experimental pancreatic necrosis. A new technique which can be performed in the rat seems a suitable model for reflux pancreatic necrosis without artificial pressure changes in the ductal system. A closed duodenal loop is obtained with ligation proximal and distal to Vater's ampulla and a gastroenteroanastomosis is associated to avoid intestinal obstruction. All the rats die with hemorrhagic pancreatic necrosis in 36 hours. After 12 hours from the operation ductal and acinar lumina are enlarged. In the centroacinar and intercalated duct cells some lysosomes and mitochondria with clear matrix and reduced cristae are detected. Intercellular junctions in ducts and acini have normal morphology. In the basal cytoplasm of acinar cells some prominent autophagic vacuoles are detectable. After 24 hours in the acinar cells autophagic vacuoles are greatly increased and basal cytoplasmic degeneration often occurs, with plasmalemma and basal lamina interruptions. Intercellular junctions are apparently unaffected until cell necrosis sets in. In blood capillaries endothelial cells are swollen, fibrin thrombosis, hemorrhage and leucocyte infiltration are often detectable. As lysosomal activity occurs also in different kinds of experimental pancreatic necrosis, it could be a common pathogenetic factor, responsible for hydrolytic enzyme activation and for vascular damage in the early stages of hemorrhagic pancreatic necrosis.     

Myospherulosis. Fine needle aspiration cytologic findings in 19 cases

An analysis was made of 19 cases of myospherulosis seen on fine needle aspirates of mammary and subcutaneous tissue masses. Myospherulosis, best seen with the Papanicolaou stain, appeared as 4 microns to 7 microns spherules that were homogeneously smooth or contained one or more internal dense bodies. The spherules were dispersed singly or aggregated into sac-like structures. Myospherulosis accompanied 16 benign and 3 malignant conditions. In two aspirates, myospherulosis was seen simultaneously with breast carcinoma; in another, fat necrosis with myospherulosis masked an underlying breast malignancy. In 10 of the 12 aspirates from patients with previous tissue trauma, it accompanied evidence of fat necrosis and mesenchymal repair; in 4 aspirates, no other underlying condition was apparent. These findings indicate that myospherulosis is not an uncommon finding in fine needle aspirates of fatty sites; it often accompanies fat necrosis and mesenchymal repair. The presence of myospherulosis in aspirates of clinically suspicious masses does not exclude an underlying malignancy.     

Genetic evidence in the mouse solidifies the calcium hypothesis of myofiber death in muscular dystrophy

Muscular dystrophy (MD) refers to a clinically and genetically heterogeneous group of degenerative muscle disorders characterized by progressive muscle wasting and often premature death. Although the primary defect underlying most forms of MD typically results from a loss of sarcolemmal integrity, the secondary molecular mechanisms leading to muscle degeneration and myofiber necrosis is debated. One hypothesis suggests that elevated or dysregulated cytosolic calcium is the common transducing event, resulting in myofiber necrosis in MD. Previous measurements of resting calcium levels in myofibers from dystrophic animal models or humans produced equivocal results. However, recent studies in genetically altered mouse models have largely solidified the calcium hypothesis of MD, such that models with artificially elevated calcium in skeletal muscle manifest fulminant dystrophic-like disease, whereas models with enhanced calcium clearance or inhibited calcium influx are resistant to myofiber death and MD. Here, we will review the field and the recent cadre of data from genetically altered mouse models, which we propose have collectively mostly proven the hypothesis that calcium is the primary effector of myofiber necrosis in MD. This new consensus on calcium should guide future selection of drugs to be evaluated in clinical trials as well as gene therapy-based approaches.     

Energy supply and the shape of death in neurons and lymphoid cells

Apoptosis and necrosis are considered as conceptually distinct forms of cell death. Nevertheless, there is increasing evidence that classical apoptosis and necrosis represent only the extreme ends of a wide range of possible morphological and biochemical deaths. The two classical types of demise can occur simultaneously in tissues or cell cultures exposed to the same stimulus, and often the intensity of the same initial insult decides the prevalence of either apoptosis or necrosis. This suggests that, while some early events may be common to both types of cell death, a downstream controller may be required to direct cells towards the organised execution of apoptosis. We have recently shown that intracellular energy levels and mitochondrial function are rapidly compromised in necrosis, but not in apoptosis of neuronal cells. Then, we went on to show that pre-emptying human T cells of ATP switches the type of demise caused by two classic apoptotic triggers (staurosporin and CD95 stimulation) from apoptosis to necrosis. Conditions of controlled intracellular ATP depletion, which was obtained by blocking mitochondrial and/or glycolytic ATP generation, were used in combination with repletion of the cytosolic ATP pool with glucose to redirect the death program towards apoptosis or necrosis. At least two distinct steps, the typical nuclear degradation, and the expression of annexin V-recognisable determinants on the cell surface require sufficient ATP generation. This suggests that some upstream regulators of cell death may be common to both types of cell demise, whereas yet unknown downstream processes decide its shape and the implications for the neighbouring tissue.     

Scintigraphie myocardique et séquelles de myocardite : présentation d’un cas clinique

Acute and subacute myocarditis are well-defined pathological entities but it is often difficult to identify them because their clinical expression is variable and the diagnosis is histological showing myocardial inflammation associated with degeneration and/or necrosis. Often symptoms are similar to those of acute pericarditis with “chest-crushing” pain that mimics myocardial infarction and prompts practitioners to request angiography, especially when there are cardiovascular risk factors. We report the case of a 61-year-old patient with neither cardiac history nor cardiovascular risk factor who consulted for a long and self-limited atypical chest pain with normal clinical examination and electrocardiogram. Myocardial perfusion scintigraphy showed a non-reversible photopenic area suspected of being a nontransmural necrosis or an artifact. The discovery of inferolateral hypokinesis of left ventricle on echocardiography led to perform a coronary angiography which was finally normal. Cardiac MRI allowed to diagnose scars of a previous episode of myocarditis.     

Tumor necrosis factor-alpha induces the phosphorylation of 28kDa stress proteins in endothelial cells: possible role in protection against cytotoxicity?

Tumor necrosis factor-alpha has been shown to rapidly increase the phosphorylation of three 28 kDa proteins in bovine aortic endothelial cells but not in L929 cells. Tumor necrosis factor-alpha induces the necrosis of the latter cells but not of the former. Arsenite enhanced the phosphorylation of the same 28kDa proteins as tumor necrosis factor-alpha in the endothelial cells. As stress proteins often play a protective role, we suggest that the phosphorylation of these proteins in endothelial cells may be responsible for the resistance of these cells to tumor necrosis factor-alpha.     

Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and nonsmokers

Smoking results in impaired wound healing and poor surgical results. In this retrospective study, we compared outcomes in 155 smokers, 76 ex-smokers, and 517 nonsmokers who received postmastectomy breast reconstructions during a 10-year period. Ex-smokers were defined as those who had quit smoking at least 3 weeks before surgery. Transverse rectus abdominis musculocutaneous (TRAM) flap surgery was performed significantly less often in smokers (24.5 percent) than in ex-smokers (30.3 percent) or nonsmokers (39.1 percent) (p < 0.001). Tissue expansion followed by implant was performed in 112 smokers (72.3 percent), 50 (65.8 percent) ex-smokers, and 304 nonsmokers (58.8 percent) (p = 0.002). The overall complication rate in smokers was 39.4 percent, compared with 25 percent in ex-smokers and 25.9 percent in nonsmokers, which is statistically significant (p = 0.002). Mastectomy flap necrosis developed in 12 smokers (7.7 percent), 2 ex-smokers (2.6 percent), and 8 nonsmokers (1.5 percent) (p < 0.001). Among patients receiving TR4AM flaps, fat necrosis developed in 10 smokers (26.3 percent), 2 ex-smokers (8.7 percent), and 17 nonsmokers (8.4 percent). Abdominal wall necrosis was more common in smokers (7.9 percent) than in ex-smokers (4.3 percent) or nonsmokers (1.0 percent). In this large series, tissue expansion was performed more often in smokers than was autogenous reconstruction. Complications were significantly more frequent in smokers. Mastectomy flap necrosis was significantly more frequent in smokers, regardless of the type of reconstruction. Breast reconstruction should be done with caution in smokers. Ex-smokers had complication rates similar to those of nonsmokers. Smokers undergoing reconstruction should be strongly urged to stop smoking at least 3 weeks before their surgery.     

Metabolism and toxicity of anacrotine, a pyrrolizidine alkaloid, in rats

The effects of anacrotine, a pyrrolizidine alkaloid (PA) which has the structure of senecionine with an additional 6-hydroxy group, have been investigated in weanling male rats. When anacrotine was given i.p. (100 mg/kg), pyrrolic metabolites reached a peak level in the liver during the first 0.5 h, then fell rapidly to a lower level which subsequently declined more slowly. Pyrrolic metabolites accumulated in the lungs during the first hour to a level which then remained relatively steady for at least 4 h. The lung level of pyrrolic metabolites after 2 h was about 39% of the liver level, compared with 16% in rats given senecionine. Anacrotine caused acute centrilobular necrosis and congestion of the liver when 125 mg/kg or more was given i.p., but oral doses (up to 180 mg/kg) caused relatively little liver necrosis. Enlarged hepatocytes developed during ensuing weeks, but these were moderate compared with the bizarre giant cells often associated with pyrrolizidine intoxication. In contrast, anacrotine produced much more severe lung damage than most other pyrrolizidine alkaloids. The lungs were affected by i.p. or oral doses well below those needed to produce acute liver damage. Pulmonary congestion and oedema, extensive necrosis of the pulmonary endothelium, and thickening of alveolar septae, developed within 2 days after dosing. After single i.p. doses of 60 mg/kg or more progressive consolidation of lung tissue often led to death after 2-5 weeks. Hearts showed myocardial necrosis of the right ventricular wall. Dehydroanacrotine, the putative reactive pyrrolic metabolite of anacrotine, given i.v. to rats, caused dose-related chronic lung and heart damage identical to that produced by anacrotine, but after lower doses (6-27 mg/kg); larger amounts caused acute lung damage. It is suggested that the severe lung damage in animals given anacrotine is due to dehydroanacrotine, formed in the liver. This metabolite is more stable than the pyrrolic derivatives of most other pyrrolizidine alkaloids, and it is thus able to reach the lungs in relatively large amounts.     

Parasite development and visceral pathology in Galba truncatula co-infected with Fasciola hepatica and Paramphistomum daubneyi

Histological investigations in Galba truncatula naturally or experimentally co-infected with Fasciola hepatica and Paramphistomum daubneyi were carried out to study parasite development and the responses of the digestive gland and kidney of snails, as larval forms of these digeneans often use these two sites for their growth within the snail's body. The number of live rediae per snail ranged from 2.4 to 4.2 for the dominating parasite (it developed in the digestive gland) and was less than 2.0 for the other species. When the dominating species was F. hepatica, most snails harboured cercariae-containing rediae; if this parasite was P. daubneyi, procercariae-containing rediae with or without free procercariae were observed in most snails. In contrast, most rediae of the other species were immature. The pathology caused by the dominating species in the digestive gland was greater than that recorded in the kidney, where the other parasite was generally located. The most frequent tissue lesions in the digestive gland were generalized epithelial necrosis and epithelial reconstitution. In the kidney, multifocal epithelial necrosis was frequently observed, particularly when P. daubneyi was the dominating species. The frequencies of lesions in the digestive gland agreed with percentages reported by our team in other snails mono-infected with F. hepatica or P. daubneyi. In contrast, multifocal necrosis in the kidney was clearly greater in the present study and this finding might be explained by assuming that a sufficient number of free larvae within the snail would be necessary for the development of epithelial necrosis in the whole kidney.     

Partial cecal necrosis treated by laparoscopic partial cecal resection

Acute colonic ischemia is the common cause of colitis in elderly population. However, isolated ischemic necrosis of cecum is rare entity, often associated with variety of conditions. Here we present a case of a 73-year old woman with a past history of hypertension presented with clinical symptoms of right lower quadrant abdominal pain and tenderness localized to the right lower quadrant, guarding and rebound tenderness. With diagnosis of acute appendicitis, the patient underwent laparoscopy where the cecal partial necrosis was discovered. Necrotic area of cecum was excised using two endoscopic cutters and laparoscopic appendectomy was performed. Pathologist report showed thrombosis of vessels and necrosis of entire cecal wall. The patient completely recovered without any surgical complications. This is the first case of partial cecum necrosis laparoscopicaly managed and with a partial cecal resection only.     

Reactions of Pinus sylvestris (Scots Pine) Root Tissues to the Presence of Mutualistic, Saprotrophic and Necrotrophic Micro-organisms

Using Scots pine seedlings as experimental hosts, the general reactions and recognition patterns of living conifer tissues challenged in vitro with either parasitic, saprotrophic, epiphytic or mutualistic microbial species were investigated. Three distinct reaction and recognition patterns were observed. In one, a necrosis type of browning reaction occurred that restricted vascular penetration of the seedlings when inoculated with a saprotroph (Marasmius androsaceus) or a mycorrhizal-associated bacterium (Pseudomonas fluorescens). The second pattern, a kind of necrosis in which the host defence system was ultimately ineffective, was typically observed in seedlings challenged with the S or P types of the root rot fungus (Heterobasidion annosum), the fine root parasite (Fusarium avenaceum) or the saprotrophic wood decay fungus (Phlebia gigantea). The third type, described as non-recognition, was observed on seedlings showing no necrosis and was particularly common with seedlings inoculated with either mycorrhizal fungi (Suillus granulatus, Piloderma croceum) or saprotrophs (Trichoderma aureoviride, Coriolus versicolor), or an unidentified rod-shaped bacterial isolate. Since necrosis is often linked to rapid accumulation of H₂O₂, increases in peroxidase activity were determined. Only seedlings challenged with the S-type of H. annosum had a systemic increase in peroxidase levels of needles, shoot and roots. Similarly, only H. annosum, F. avenaceum, P. gigantea and the Pseudomonas bacterium caused a two- to four-fold increase in the peroxidase level of inoculated roots, results suggesting that a relationship exists between the degree of necrosis and the ratio of peroxidase induction. But the higher levels of peroxidase activity was not correlated with increased resistance to disease development.     

Veinal necrosis induced by turnip mosaic virus infection in Arabidopsis is a form of defense response accompanying HR-like cell death

In the pathosystems of Turnip mosaic virus (TuMV) with Brassicaceae crops, various symptoms, including mosaic and necrosis, are observed. We previously reported a necrosis-inducing factor TuNI in Arabidopsis thaliana, a model species. In this study, we show that the necrotic symptom induced by TuNI, observed along the veins, was actually a form of defense response accompanying a hypersensitive reaction (HR)-like cell death in the veinal area. The virus is often localized in the necrotic region. The necrotic response is associated with the production of H2O2, accumulation of salicylic acid (SA), emission of ethylene, and subsequent expression of defense-related genes. Additionally, this HR-like cell death is eased or erased by a shading treatment. These features are similar to the HR-associated resistance reaction to pathogens. However, unlike HR, two phytohormones--SA and ethylene--are involved in the necrosis induction, and both SA- and ethylene-dependent pathogenesis-related genes are activated. We concluded that the veinal necrosis induced by TuMV is regulated by a complex and unique network of at least two signaling pathways, which differs from the signal transduction for the known HR-associated resistance.