Monoclonal antibodies to the spike protein of feline infectious peritonitis virus mediate antibody-dependent enhancement of infection of feline macrophages.

Antibody-dependent enhancement of virus infection is a process whereby virus-antibody complexes initiate infection of cells via Fc receptor-mediated endocytosis. We sought to investigate antibody-dependent enhancement of feline infectious peritonitis virus infection of primary feline peritoneal macrophages in vitro. Enhancement of infection was assessed, after indirect immunofluorescent-antibody labelling of infected cells, by determining the ratio between the number of cells infected in the presence and absence of virus-specific antibody. Infection enhancement was initially demonstrated by using heat-inactivated, virus-specific feline antiserum. Functional compatibility between murine immunoglobulin molecules and feline Fc receptors was demonstrated by using murine anti-sheep erythrocyte serum and an antibody-coated sheep erythrocyte phagocytosis assay. Thirty-seven murine monoclonal antibodies specific for the nucleocapsid, membrane, or spike proteins of feline infectious peritonitis virus or transmissible gastroenteritis virus were assayed for their ability to enhance the infectivity of feline infectious peritonitis virus. Infection enhancement was mediated by a subset of spike protein-specific monoclonal antibodies. A distinct correlation was seen between the ability of a monoclonal antibody to cause virus neutralization in a routine cell culture neutralization assay and its ability to mediate infection enhancement of macrophages. Infection enhancement was shown to be Fc receptor mediated by blockade of antibody-Fc receptor interaction using staphylococcal protein A. Our results are consistent with the hypothesis that antibody-dependent enhancement of feline infectious peritonitis virus infectivity is mediated by antibody directed against specific sites on the spike protein.     

Examinations of cell mediated immunity in diffuse peritonitis]

Phagocytic index and rosette test E have been determined in 50 patients, including 15 with diffuse peritonitis and the noncomplicated diffuse peritonitis, 20 patients with septic complications, and 15 patients who underwent abdominal surgery. It was found, that phagocytic index is decreased in all patients after abdominal surgery. The most marked decrease of this index was found in patients with complicated peritonitis. It still decreases in the course of peritonitis and increases in the reference group. The marked decrease in the number of T-cells was observed in complicated peritonitis during the whole period of follow-up while it normalizes in case of noncomplicated peritonitis as in the reference group. Using the tests under study it was possible to assess cell-mediated immunity which is depressed in peritonitis. The tests enable also the prediction of septic complications of peritonitis.     

氨曲南联合恩替卡韦对肝硬化原发性腹膜炎患者血清甲状腺激素水平及临床疗效的影响

目的:探讨氨曲南联合恩替卡韦对乙肝肝硬化原发性腹膜炎患者血清甲状腺激素水平及临床疗效的影响。方法:选择于我院就诊的乙肝肝硬化原发性腹膜炎患者60例,根据电脑生成的随机数字表将所有患者随机分为实验组和对照组,每组各30例,对照组患者给予氨曲南进行治疗,实验组患者在对照组的基础上联合应用恩替卡韦进行治疗。比较治疗前后两组患者血清甲状腺激素、中性粒细胞比例、血白细胞及腹水细胞水平,并对治疗前后两组患者的体重、腹围及24 h尿量进行记录。结果:与治疗前相比,两组患者血清TSH水平、体重、腹围均降低,FT3、FT4、T3、T4水平及24 h尿量升高(P0.05);与对照组相比,实验组患者血清TSH水平、体重、腹围较低,FT3、FT4、T3、T4水平及24h尿量较高(P0.05);临床总有效率较高(P0.05)。结论:氨曲南联合恩替卡韦对乙肝肝硬化原发性腹膜炎具有较好的临床疗效,推测其机制与改善甲状腺激素水平,降低炎症反应有关。     

Intra-Abdominal Candidiasis: The Importance of Early Source Control and Antifungal Treatment

Intra-abdominal candidiasis (IAC) is poorly understood compared to candidemia. We described the clinical characteristics, microbiology, treatment and outcomes of IAC, and identified risk factors for mortality. We performed a retrospective study of adults diagnosed with IAC at our center in 2012–2013. Risk factors for mortality were evaluated using multivariable logistic regression. We identified 163 patients with IAC, compared to 161 with candidemia. Types of IAC were intra-abdominal abscesses (55%), secondary peritonitis (33%), primary peritonitis (5%), infected pancreatic necrosis (5%), and cholecystitis/cholangitis (3%). Eighty-three percent and 66% of secondary peritonitis and abscesses, respectively, stemmed from gastrointestinal (GI) tract sources. C. albicans (56%) and C. glabrata (24%) were the most common species. Bacterial co-infections and candidemia occurred in 67% and 6% of patients, respectively. Seventy-two percent of patients underwent an early source control intervention (within 5 days) and 72% received early antifungal treatment. 100-day mortality was 28%, and highest with primary (88%) or secondary (40%) peritonitis. Younger age, abscesses and early source control were independent predictors of survival. Younger age, abscesses and early antifungal treatment were independently associated with survival for IAC stemming from GI tract sources. Infectious diseases (ID) consultations were obtained in only 48% of patients. Consulted patients were significantly more likely to receive antifungal treatment. IAC is a common disease associated with heterogeneous manifestations, which result in poor outcomes. All patients should undergo source control interventions and receive antifungal treatment promptly. It is important for the ID community to become more engaged in treating IAC.     

Emergency Resection in Treatment of Diverticular Disease of Colon Complicated by Peritonitis

Of a consecutive series of 25 patients with peritonitis secondary to colonic diverticular disease all, except one with faecal peritonitis, underwent some form of emergency resection.All the three patients with faecal peritonitis died, but the 22 with purulent peritonitis survived. The average duration of the emergency admission of the 22 survivors was 25.4 days, and in nine (41%) of them intestinal continuity had been restored by the end of that admission.Thus some form of emergency resection is the operation of choice in patients with spreading peritonitis due to diverticular disease of the sigmoid colon.     

Primary microcephaly in two children born to mothers with complicated appendicitis or late appendectomy during pregnancy

BACKGROUND: The possible association between maternal appendicitis/appendectomy during pregnancy and congenital abnormalities in the offspring was studied. CASES: Two cases with primary microcephaly were born to mothers who had complicated appendicitis owing to the delay of appendectomy resulting in abscess/peritonitis associated with septicemia and fever in the second trimester of pregnancy. CONCLUSIONS: Delay in surgical intervention of appendicitis in pregnancy can result in maternal morbidity that may be associated with primary microcephaly in the offspring. Birth Defects Research (Part A), 2009. © 2009 Wiley‐Liss, Inc.     

Alterations of the composition and metabolism of pulmonary surfactant phospholipids induced by experimental peritonitis in rats

Pulmonary complications often accompany the development of acute peritonitis. In this study, we analyzed the alterations of alveolar surfactant phospholipids in rats with experimentally induced peritonitis. The results showed a reduction of almost all phospholipid fractions in pulmonary surfactant of experimental animals. The most abundant alveolar phospholipids-phosphatidylcholine and phosphatidylglycerol were reduced significantly in surfactant of rats with experimental peritonitis. In addition, analysis of the fatty acid composition of these two phospholipids revealed marked differences between experimental and control animals. The activity of phospholipase A2, which is localized in the hydrophyllic phase of alveolar surfactant, was higher in rats with experimental peritonitis compared to sham-operated ones. Also, a weak acyl-CoA:lysophospholipid acyltransferase activity was detected in alveolar surfactant of rats with experimental peritonitis, whereas in control animals this activity was not detectable. The lipid-transfer activity was quite similar in pulmonary surfactant of control and experimental rats. The total number of cells and the percentage of neutrophils were strongly increased in broncho-alveolar lavage fluid from rats with peritonitis. Thus, our results showed that the development of peritonitis was accompanied by pulmonary pathophysiological processes that involved alterations of the phospholipid and fatty acid composition of alveolar surfactant. We suggest that the increased populations of inflammatory cells, which basically participate in internalization and secretion of surfactant components, contributed to the observed alterations of alveolar phospholipids. These studies would be useful for clarification of the pathogenic mechanisms underlying the occurrence of pulmonary disorders that accompany acute inflammatory conditions, such as peritonitis and sepsis.     

The ultrastructure of the peritoneal membrane in chronically dialysed rats with spontaneous peritonitis: preliminary observations

In this paper we describe ultrastructure of the peritoneal membrane from single peritoneal biopsies collected from chronically dialysed rats with spontaneous peritonitis. The results were compared with those obtained in chronically dialysed animals without peritonitis. In rats with peritonitis, peritoneum was much thicker than in peritonitis-free animals. The increased thickness of the peritoneum during peritonitis was due to infiltration of the submesothelial tissue with oedematous fluid and to the presence of huge amount of cells in the stroma. The connective tissue cells were accumulated just underneath the peritoneal surface. In deeper parts of the interstitium, infiltrating acute inflammatory cells were present (lymphocytes, polymorphonuclear cells: neutrophils and eosinophils). Inversely, the increased thickness of the peritoneum in peritonitis-free animals was mainly due to enhanced amounts of collagen. Additionally, in rats with peritonitis, the surface was often denuded of mesothelial cells. The damaged mesothelial cells that detached from the peritoneal surface were also found. In conclusion, the morphological changes observed in rats with peritonitis are similar to those reported in humans, thus the model of peritonitis in dialysed rats can be used for the study of peritoneal remodeling during peritoneal dialysis complicated by peritonitis.     

Delineation of the role of Toll-like receptor signaling during peritonitis by a gradually growing pathogenic Escherichia coli

In a mouse model of Escherichia coli sepsis characterized by a primary peritoneal infection with 10(4) E. coli and a gradually growing bacterial load, we here show that the early cytokine response and antibacterial defense are dominated by TLR4 via a cooperative action of MyD88 and Trif. Although MyD88(-/-) mice succumbed earlier than WT mice in this E. coli peritonitis model, Trif(-/-) mice displayed a small but significant survival advantage. Despite a large early deficit in antimicrobial defense, TLR4(-/-) mice showed an unaltered survival with normal neutrophil attraction to the peritoneal cavity and normal or even elevated late cytokine release. TLR2 compensated for the lack of TLR4 because TLR2(-/-)/TLR4(-/-) mice did show decreased neutrophil attraction and increased mortality compared with WT mice. Nearly normal early peritoneal TNFα production and lack of early counterregulating systemic levels of the chemoattractant KC were associated with normal peritoneal neutrophil attraction in TLR4(-/-) mice. Late stage increased TNF, IL-1β, IFN-β, and typical IFN-γ production in TLR4(-/-) mice prompted us to evaluate expression of the negative feedback regulator SOCS-1. Lack of early hepatic SOCS-1 expression in TLR4(-/-) mice explained the late innate production of IFN-γ by the liver in TLR4(-/-) mice in this low dose E. coli peritonitis model. In contrast, early TLR4-induced IFN-γ production is described as a hallmark in high dose E. coli peritonitis models. The present study displays how the kinetics of pro- and anti-inflammatory mechanisms are regulated by TLRs during peritonitis by a gradually growing E. coli load and how these kinetics may affect outcome.     

冰醋酸致小鼠实验性腹膜炎模型的研究

目的研究建立小鼠实验性腹膜炎模型,探讨建立一种简便、易行、效果稳定、便于获取实验数据的实验方法。方法小鼠腹腔分别注射2%冰醋酸生理盐水溶液0.1 ml(高浓度组)、1%冰醋酸生理盐水溶液0.2 ml(低浓度组),观察小鼠一般情况及腹腔解剖情况,进行血细菌培养;肝、回肠组织病理学观察;比色法测定肝、回肠LDH活性和MDA含量。结果注射不同浓度和剂量的冰醋酸,均表现出腹膜炎临床征象,高浓度组的小鼠模型病程快、死亡率高,血细菌培养有大量G-杆菌;低浓度组的小鼠模型,经21 d可自愈,无死亡。组织病理学观察,肝和回肠有病理改变。结论高浓度组的小鼠腹膜炎模型可作为急性腹膜炎的实验研究模型,低浓度组的小鼠腹膜炎模型,可作为研究实验性腹膜炎自愈过程机体抗损伤机制的实验模型。     

A study of small bowel tumors; with special emphasis on clinical aspects

Ninety-eight patients with 100 different tumors of the small bowel were studied. There were more malignant than benign tumors. Adenocarcinoma was the commonest lesion and the ileum the most frequent anatomical site of all tumors. Except for carcinoid tumors, the lesions were observed more often in male than in female patients. The average age of patients in this series was higher than that reported in most other series. Loss of weight, and abdominal pain were the most constant symptoms. Clinical syndromes of anemia and bleeding, small bowel obstruction, biliary obstruction, perforation with peritonitis, abdominal tumor, melanosis with small bowel polyposis, and cutaneous von Recklinghausen's disease with small bowel neurofibromatosis were encountered either alone or in combination. In the group operated upon, a resection of the involved segment with end-to-end anastomosis was done when feasible. None of the patients operated upon before 1946 lived as much as five years after operation. The most common causes of death were extension of the primary tumor and metastasis, peritonitis due to perforation, associated bronchopneumonia, and hemorrhage.     

Candida Parapsilosis peritonitis in patients on CAPD

Twenty-four episodes of C. parapsilosis peritonitis in 23 patients on continuous ambulatory peritoneal dialysis (CAPD) over 6 years were reviewed. Clinical manifestations and laboratory findings were similar to those of other pathogens. All started treatment with intravenous amphotericin B. In six cases it was attempted to maintain a peritoneal catheter in situ, but removal became essential to relieve fungal peritonitis. Of the patients who developed peritonitis, 15 episodes (62.5%) continued the CAPD program. Nine cases could not resume CAPD because of death in 4, patient preference in 2, and abdominal adhesion in 3. Antifungal treatment alone was ineffective in most cases. It was found that peritonitis developing after gram negative bacterial peritonitis and the use of fluconazole after catheter removal were associated with CAPD discontinuation. It was suggested that C. parapsilosis peritonitis in CAPD patients should be treated with rapid catheter removal, particularly those with fungal peritonitis who had prior gram negative peritonitis. This revised version was published online in June 2006 with corrections to the Cover Date.     

Peritonitis prevented in continuous ambulatory peritoneal dialysis by using the Hong Kong connection.

Based on the hypothesis that air contamination is an important cause of peritonitis in continuous ambulatory peritoneal dialysis, a simple and cheap connection system was developed whereby a clear polyethylene bag containing an antiseptic gauze was used as a sterilising chamber, effectively enclosing the connection procedure. Seven modifications to the connection technique were introduced over 32 months in 28 patients during 27.9 patient years of experience. The overall rate of peritonitis was 0.6 episode/patient year, but after a final modification at the beginning of the third year the rate fell to 0.17, without a single case of peritonitis occurring attributable to a connection failure in 11.5 patient years. These findings show that in patients receiving continuous ambulatory peritoneal dialysis peritonitis may be prevented by enclosing the connection process and sterilising the introduced air and tubing ends.     

Peritoneal macrophages from patients on continuous ambulatory peritoneal dialysis show a differential secretion of prostanoids and interleukin-1 beta.

In vitro secretion of the prostanoids PGE2 and PGI2 and of the cytokine IL-1 beta by peritoneal macrophages obtained from CAPD patients during episodes of peritonitis and infection free periods, was determined, after culturing with or without 5 micrograms/ml of LPS. The release of PGE2 and PGI2 as measured by its stable metabolite 6-keto-PGF alpha was determined in 10 episodes of peritonitis and 10 infection free periods. IL-1 beta release was determined in 14 episodes of peritonitis and 20 infection free periods. PGI2 release from macrophages declined sharply during peritonitis both in the absence and presence of LPS in the culture medium (p less than 0.005). A tendency to decreased PGE2 release was found during peritonitis, when macrophages were cultured in the absence of LPS. In the presence of LPS, the same amounts of PGE2 were released during peritonitis and during an infection free period. On the other hand, peritoneal macrophages released significantly more IL-1 beta during peritonitis as compared to an infection free period, provided that the cells were in vitro stimulated with LPS. In view of the interregulatory effects between prostanoids and macrophage cytokines in their production, these findings may indicate that the impaired release of PGI2 during peritonitis has allowed the macrophages to secrete more IL-1 beta after in vitro stimulation with LPS. This implies that PGI2 and PGE2 may play a distinct role in the regulation of cytokine secretion by these cells.     

A STUDY OF SMALL BOWEL TUMORS—With Special Emphasis on Clinical Aspects

Ninety-eight patients with 100 different tumors of the small bowel were studied. There were more malignant than benign tumors. Adenocarcinoma was the commonest lesion and the ileum the most frequent anatomical site of all tumors. Except for carcinoid tumors, the lesions were observed more often in male than in female patients. The average age of patients in this series was higher than that reported in most other series. Loss of weight, and abdominal pain were the most constant symptoms. Clinical syndromes of anemia and bleeding, small bowel obstruction, biliary obstruction, perforation with peritonitis, abdominal tumor, melanosis with small bowel polyposis, and cutaneous von Recklinghausen''s disease with small bowel neurofibromatosis were encountered either alone or in combination.In the group operated upon, a resection of the involved segment with end-to-end anastomosis was done when feasible. None of the patients operated upon before 1946 lived as much as five years after operation. The most common causes of death were extension of the primary tumor and metastasis, peritonitis due to perforation, associated bronchopneumonia, and hemorrhage.     

Seeking clarity within cloudy effluents: differentiating fungal from bacterial peritonitis in peritoneal dialysis patients

Background

Fungal peritonitis is a serious complication of peritoneal dialysis (PD) therapy with the majority of patients ceasing PD permanently. The aims of this study were to identify risk factors and clinical associations that may discriminate between fungal from bacterial peritonitis.

Methods

We retrospectively identified episodes of fungal peritonitis from 2001–2010 in PD patients at Liverpool and Westmead Hospitals (Australia). Fungal peritonitis cases were matched in a 1∶2 ratio with patients with bacterial peritonitis from each institution''s dialysis registry, occurring closest in time to the fungal episode. Patient demographic, clinical and outcome data were obtained from the medical records.

Results

Thirty-nine episodes of fungal peritonitis (rate of 0.02 episodes per patient-year of dialysis) were matched with 78 episodes of bacterial peritonitis. Candida species were the commonest pathogens (35/39; 90% episodes) with Candida albicans (37%), Candida parapsilosis (32%) and Candida glabrata (13%) the most frequently isolated species. Compared to bacterial peritonitis, fungal peritonitis patients had received PD for significantly longer (1133 vs. 775 catheter-days; p = 0.016), were more likely to have had previous episodes of bacterial peritonitis (51% vs. 10%; p = 0.01), and to have received prior antibacterial therapy (51% vs. 10%; p = 0.01). Patients with fungal peritonitis were less likely to have fever and abdominal pain on presentation, but had higher rates of PD catheter removal (79% vs. 22%; p<0.005), and permanent transfer to haemodialysis (87% vs. 24%; p<0.005). Hospital length of stay was significantly longer in patients with fungal peritonitis (26.1 days vs. 12.6 days; p = 0.017), but the all-cause 30-day mortality rate was similar in both groups. Fluconazole was a suitable empiric antifungal agent; with no Candida resistance detected.

Conclusion

Prompt recognition of clinical risk factors, initiation of antifungal therapy and removal of PD catheters are key considerations in optimising outcomes.     

Possibilities of restoration of the regional lymphatic channel by the use of sorbents in the treatment of experimental generalized purulent peritonitis]

Regional lymphatic bed in local application of mineral sorbent SUMS-2p in 80 white noninbred rats with experimental generalized purulent peritonitis is studied with the use of indirect intravital lympho-roentgenography. The correlation between lympho-dynamics and generalized purulent peritonitis stage was observed. It is shown that the peritoneo-sorption with the mineral sorbent SUMS-2p led to early restoration of lympho-drainage.     

Experimental and clinical study of nitazol as an antibacterial drug in the complex treatment of peritonitis

Antibacterial properties of the Soviet drug nitazol which is a derivative of imidazole were studied. It was shown that nitazol in a dose of 4-8 micrograms/ml was highly active against gram-negative nonsporulating anaerobes, gram-positive anaerobic cocci and spore-forming Clostridia spp. Unlike metronidazole, it was efficient against both standard and clinical strains of facultative anaerobes such as E. coli, S. aureus and Klebsiella spp. isolated from patients with peritonitis and being poly-resistant to antibiotics. It was found in vitro that the antibacterial effect of nitazol was higher when it was used in combination with some antibiotics. It was demonstrated on experimental models of peritonitis caused by Staphylococcus spp. and E. coli in mice that nitazol used alone or in combination with gentamicin had a favourable effect on the animal survival and lifespan. The combination of nitazol with gentamicin was applied in the combined treatment of appendicular peritonitis in 80 children and its high therapeutic efficacy was stated. Nitazol is useful as an antibacterial drug in the combined treatment of children with purulent peritonitis.     

Factors affecting development of peritonitis in continuous ambulatory peritoneal dialysis.

A questionnaire based survey in patients receiving continuous ambulatory peritoneal dialysis showed that there was an increased incidence of upper respiratory tract symptoms (suggestive of viral illness) in the 14 days before the development of peritonitis. No other factors were identified that might distinguish patients who develop peritonitis. The possibility that viral infections predispose to peritonitis by altering host defence mechanisms in patients receiving this form of renal replacement therapy warrants further study.     

Effect of intravascular laser irradiation of blood on the status of the adrenergic and cholinergic structures of the small intestine in experimental peritonitis

In the experiment performed on 60 mongrel dogs the effect of intravascular laser radiation of blood (ILRB) to adrenergic and cholinergic fibers of the small intestine has been studied at treatment of experimental generalized suppurative peritonitis. At treatment of the experimental peritonitis by means of traditional method only one month after its termination a positive reaction to acetylcholinesterase (AChE) is noted, structural organization of cholinergic fibers corresponds to the norm, and density of their plexuses increases. Application of ILRB at treatment of the experimental peritonitis facilitates to increasing density of the cholinergic fibers already on the 21st day after termination of the treatment; their AChE increases essentially, their structural organization corresponds to the norm. In cytoplasm of neurons of the muscular-intestinal plexus a positive reaction to AChE is revealed; this demonstrates their increased functional activity. The small intestine adrenergic apparatus at peritonitis undergoes less manifested structural-chemical alterations. After termination of treatment by means of traditional methods it corresponds to the norm on the 7th day, and after ILBR treatment----on the 3d day. Thus, application of ILBR in treatment of the experimental peritonitis enhances the development of regenerative processes in adrenal and cholinergic structures of the small intestine, facilitates a more manifested demonstration of compensatory-reparative possibilities of the organism.