幽门螺杆菌毒力基因分型和宿主遗传多态性与胃病关系研究进展

幽门螺杆菌(Helicobacter pylori)感染能导致慢性胃炎、消化性溃疡、胃粘膜相关的淋巴样组织(Mu-cosa-associated lymphoid tissue,MALT)淋巴瘤和胃腺癌等疾病的发生。1994年世界卫生组织国际癌症研究中心(IARC)将H.pylori列为胃癌第一级因子。H.pylori感染引起的不同临床结局主要与H.pylori致病因子和宿主遗传易感性有关,大部分重大疾病发生在特定的细菌毒力因子(如cagA,vacA)与易感宿主遗传背景共同存在时。文章综述了H.pylori菌株的毒力基因的分型和宿主的遗传多态性对胃病发生的影响。     

Anaerobic Balanoposthitis: Two Cases and Review of the Literature

Anaerobic balanoposthitis is an infection of the glans penis and prepuce caused by anaerobic Gram-negative rods. It is characterized by intense inflammation and edema of the prepuce, superficial ulcers on the glans penis, foul-smelling subpreputial discharge, and bilateral inguinal lymphadenopathy. Infection tends to be locally destructive with severe tenderness of the penis and can result in considerable necrosis and tissue damage. The presence of a tight foreskin and sub-optimal hygienic practices seem to be a prerequisite for this condition to develop. Anaerobic Gram-negative rods belonging to the genus Bacteroides are the most commonly incriminated in the pathogenesis. Possible modes of transmission include contact with infected mucosal surfaces, such as during sexual intercourse, contamination by colonized saliva, or extension from the perirectal area. We report the first two cases of anaerobic balanoposthitis in HIV-positive patients and review the literature. Both patients had a previous history of sexually transmitted diseases and practiced sub-optimal hygiene. In both cases response to therapy was complete within 48–72 h.     

Levofloxacin (Tavanic) in the treatment of corneal ulcers]

The main clinical forms of cornea ulcers were systematized and high efficacy of levofloxacin in the treatment of bacterial ulcer of the cornea was shown. In the treatment of several bacterial affections of the eye the systemic use of levofloxacin should be combined with local antibiotic therapy. Combination of levofloxacin with ophthalmic drops of lomefloxacin (okacin) or ofloxacin (floxal) proved to be efficient.     

Bacteriæmia and Oral Sepsis: (Section of Odontology)

Transient streptococcal bacteri?mias are a frequent sequel to dental extractions especially when the mouth is the seat of severe chronic gum infection. Bacteria may also gain admission to the blood-stream in such cases irrespective of operative procedures and probably as the result, in many instances, of minor degrees of gum injury such as is produced by biting on a loose tooth. Acute apical infections do not appear to be especially associated with blood infection of this kind, the focus of infection here apparently being effectively "walled off" by the associated inflammatory reaction.Of the two factors, infection and trauma, involved in the production of these post-operative bacteri?mias, infection appears to be the more important since, when it is marked, very slight degrees of gum injury are sufficient to produce blood-stream invasion. In the complete absence, however, of the type of trauma induced by the "rocking" of a tooth during its removal, extraction may be accomplished without producing a heavy bacterial shower in the blood.Usually these transient bacteri?mias produce no permanent ill-effect, but there is some evidence that, occurring in subjects with abnormal heart valves, they may lead to subacute infective endocarditis. Thirteen cases are reported where the valvular infection appeared to result from a post-operative dental bacteri?mia.Prevention of such bacteri?mias may be achieved by the reduction or elimination of infection and trauma. Complete elimination of the gum infection is difficult although preliminary treatment of the gum margin by some measure such as cauterization may lessen it and lead to a reduction of the post-operative bacterial shower. Similarly, by manipulating an infected tooth as little as possible during its extraction the incidence or degree of blood infection may be decreased.     

Clinical spectrum of invasive candidiasis in critically ill non-neutropenic patients

Invasive Candida spp. infections in non-neutropenic critically ill patients admitted to intensive care units can be classified as focal and systemic. Both types of infection usually occur after episodes of candidemia, although some focal infections may be of exogenous development, like those occurring after trauma or be device-related.The clinical spectrum of invasive Candida spp. infections includes focal urinary tract, abdominal, ocular, respiratory tract, renal and hepato-biliary infections, as well as systemic infections like candidemia and acute systemic candidiasis with multiorgan involvement after hematogenous seeding. Candida spp. isolates in "significant" samples, like synovial fluid, cerebrospinal fluid and blood cultures, represent true infection. However, the diagnosis of invasive infection based on "non-significant" samples, like surgical drains and digestive tract exudates, requires additional criteria. The total number of isolates from different sites, the presence of risk factors, the clinical host response, as well as severity of illness need to be taken into account for the diagnosis of invasive candidiasis. The clinical signs of systemic infection due to Candida spp. are completely non-specific and cannot be differentiated from bacterial peritonitis, urinary tract infection or bacteremia. These infections may be associated with signs of sepsis,severe sepsis, septic shock or multiorgan dysfunction. In the future clinical multicentre observational and interventional studies are necessary to reach agreement on clinical definitions and classification of invasive Candida spp. infections in critically ill non-immunocompromised patients.     

The status of corticosteroid therapy in dermatology

Therapy with systemic corticosteroids, despite attendant serious risks, is mandatory in diseases such as pemphigus, acute disseminated lupus erythematosus and some cases of exfoliative dermatitis that are ordinarily fatal, for in such cases life may be prolonged and the patients made comfortable. If no contraindications exist, therapy with corticosteroids is desirable, for diseases of short duration-contact dermatitis, serum sickness reactions and drug eruptions of all kinds-provided the causative factors have been removed and the reactions are causing severe distress.On the basis of encouraging reports in the literature corticosteroid therapy may be instituted with justification for a group of unrelated, intractable and discomforting diseases such as maddening pruritus ani, sclerema neonatorum, dermatomyositis, certain cases of sarcoidosis, berylliosis, Behcet's syndrome, universal calcinosis, Reiter's disease and ulcers of sickle-cell anemia. One must always bear in mind the well-defined contraindications to corticosteroid therapy and the hazards of its use, particularly if therapy is to be prolonged. Results from topical hydrocortisone therapy are particularly pleasing in chronic eczematous otitis externa and especially when it is combined with an antibiotic drug. Results are excellent also in nuchal eczema, dermatitis of the eyelids and in pruritus ani. More often than not, hydrocortisone ointment and lotions benefit more than do other standard remedies such diseases as atopic eczema, contact dermatitis, lichen simplex-chronicus and eczematized phases of conditions such as psoriasis and superficial mycotic infections. Preparations containing a combination of hydrocortisone and an antibiotic are more useful than hydrocortisone alone. When used with discrimination, with full attention to the selection of cases and proper concentration in the correct vehicle, hydrocortisone preparations in combination with antibiotics are excellent antieczematous agents.     

Mitochondrial protection by the thioredoxin-2 and glutathione systems in an in vitro endothelial model of sepsis

The Streptococcus pyogenes cysteine protease SpeB (streptococcal pyrogenic exotoxin B) is important for the invasive potential of the bacteria, but its production is down-regulated following systemic infection. This prompted us to investigate if SpeB potentiated the host immune response after systemic spreading. Addition of SpeB to human plasma increased plasma-mediated bacterial killing and prolonged coagulation time through the intrinsic pathway of coagulation. This effect was independent of the enzymatic activity of SpeB and was mediated by a non-covalent medium-affinity binding and modification of the serpin A1AT (α-1 antitrypsin). Consequently, addition of A1AT to plasma increased bacterial survival. Sequestration of A1AT by SpeB led to enhanced contact system activation, supported by increased bacterial growth in prekallikrein deficient plasma. In a mouse model of systemic infection, administration of SpeB reduced significantly bacterial dissemination. The findings reveal an additional layer of complexity to host-microbe interactions that may be of benefit in the treatment of severe bacterial infections.     

Non-Diabetic Hyperglycemia Exacerbates Disease Severity in Mycobacterium tuberculosis Infected Guinea Pigs

Hyperglycemia, the diagnostic feature of diabetes also occurs in non-diabetics associated with chronic inflammation and systemic insulin resistance. Since the increased risk of active TB in diabetics has been linked to the severity and duration of hyperglycemia, we investigated what effect diet-induced hyperglycemia had on the severity of Mycobacterium tuberculosis (Mtb) infection in non-diabetic guinea pigs. Post-prandial hyperglycemia was induced in guinea pigs on normal chow by feeding a 40% sucrose solution daily or water as a carrier control. Sucrose feeding was initiated on the day of aerosol exposure to the H37Rv strain of Mtb and continued for 30 or 60 days of infection. Despite more severe hyperglycemia in sucrose-fed animals on day 30, there was no significant difference in lung bacterial or lesion burden until day 60. However the higher spleen and lymph node bacterial and lesion burden at day 30 indicated earlier and more severe extrapulmonary TB in sucrose-fed animals. In both sucrose- and water-fed animals, serum free fatty acids, important mediators of insulin resistance, were increased by day 30 and remained elevated until day 60 of infection. Hyperglycemia mediated by Mtb infection resulted in accumulation of advanced glycation end products (AGEs) in lung granulomas, which was exacerbated by sucrose feeding. However, tissue and serum AGEs were elevated in both sucrose and water-fed guinea pigs by day 60. These data indicate that Mtb infection alone induces insulin resistance and chronic hyperglycemia, which is exacerbated by sucrose feeding. Moreover, Mtb infection alone resulted in the accumulation tissue and serum AGEs, which are also central to the pathogenesis of diabetes and diabetic complications. The exacerbation of insulin resistance and hyperglycemia by Mtb infection alone may explain why TB is more severe in diabetics with poorly controlled hyperglycemia compared to non-diabetics and patients with properly controlled blood glucose levels.     

Why Children with Severe Bacterial Infection Die: A Population–Based Study of Determinants and Consequences of Suboptimal Care with a Special Emphasis on Methodological Issues

Introduction

Suboptimal care is frequent in the management of severe bacterial infection. We aimed to evaluate the consequences of suboptimal care in the early management of severe bacterial infection in children and study the determinants.

Methods

A previously reported population-based confidential enquiry included all children (3 months- 16 years) who died of severe bacterial infection in a French area during a 7-year period. Here, we compared the optimality of the management of these cases to that of pediatric patients who survived a severe bacterial infection during the same period for 6 types of care: seeking medical care by parents, evaluation of sepsis signs and detection of severe disease by a physician, timing and dosage of antibiotic therapy, and timing and dosage of saline bolus. Two independent experts blinded to outcome and final diagnosis evaluated the optimality of these care types. The effect of suboptimal care on survival was analyzed by a logistic regression adjusted on confounding factors identified by a causal diagram. Determinants of suboptimal care were analyzed by multivariate multilevel logistic regression.

Results

Suboptimal care was significantly more frequent during early management of the 21 children who died as compared with the 93 survivors: 24% vs 13% (p = 0.003). The most frequent suboptimal care types were delay to seek medical care (20%), under-evaluation of severity by the physician (20%) and delayed antibiotic therapy (24%). Young age (under 1 year) was independently associated with higher risk of suboptimal care, whereas being under the care of a paediatric emergency specialist or a mobile medical unit as compared with a general practitioner was associated with reduced risk.

Conclusions

Suboptimal care in the early management of severe bacterial infection had a global independent negative effect on survival. Suboptimal care may be avoided by better training of primary care physicians in the specifics of pediatric medicine.     

Biology,role and therapeutic potential of circulating histones in acute inflammatory disorders

Histones are positively charged nuclear proteins that facilitate packaging of DNA into nucleosomes common to all eukaryotic cells. Upon cell injury or cell signalling processes, histones are released passively through cell necrosis or actively from immune cells as part of extracellular traps. Extracellular histones function as microbicidal proteins and are pro‐thrombotic, limiting spread of infection or isolating areas of injury to allow for immune cell infiltration, clearance of infection and initiation of tissue regeneration and repair. Histone toxicity, however, is not specific to microbes and contributes to tissue and end‐organ injury, which in cases of systemic inflammation may lead to organ failure and death. This review details the processes of histones release in acute inflammation, the mechanisms of histone‐related tissue toxicity and current and future strategies for therapy targeting histones in acute inflammatory diseases.     

How to diagnose and treat fungal infections in chronic prostatitis

Epidemiologic changes that include immune-compromised patients and drug-resistant fungi have caused an increase in nosocomial infections by Candida albicans and non-albicans Candida species. Other fungi, aspergilla and Cryptococcus (environmental contaminants), are opportunistic invaders of the immune-compromised (transplant, HIV) patients. The environmental fungi Coccidioides immitis (dry arid areas), Histoplasma capsulatum (Avian-infested areas), and Blastomyces dermatitidis (aquatic areas) can cause infections in immune-competent and immune-deficient patients. Each fungus can cause changes in the prostate that mimic bacterial infection, benign prostatic hypertrophy, or neoplasm. Diagnosis can be established by urine cultures or needle biopsy of the prostate. Prostate surgery for carcinoma or benign enlargement may detect latent fungal infection. Different fungal species can have divergent clinical manifestations and require different treatment. In some cases, asymptomatic, localized, fungal prostatitis can be cured by removal of the infected gland. Symptomatic and disseminated infection may require prostatectomy and systemic antifungal therapy.     

Human cytomegalovirus end-organ disease is associated with high or low systemic viral load in preemptively treated solid-organ transplant recipients

Human cytomegalovirus (HCMV) end-organ disease in solid-organ transplant recipients (SOTR) may be associated with either high or low HCMV load in blood. In transplantation Centers where the preemptive therapy approach is adopted, antiviral therapy of systemic HCMV infections is initiated upon reaching pre-determined cut-off levels of viral DNA in blood, whereas no guidelines are provided for local end-organ infection/disease. In the latter case, clinicians often start antiviral treatment without defining the etiology of local symptoms. Here, we describe 14 cases of SOTR, in which a documented HCMV end-organ disease was observed. Nine patients had a systemic viral load lower than the cut-off for preemptive therapy and were treated based on viral load of local HCMV disease. The remaining five patients had a systemic viral load greater than the preemptive therapy cut-off and were efficiently treated for both the systemic and the local HCMV disease. Thus, HCMV infection in the post-transplant period must be monitored virologically both in blood and locally. End-organ disease in preemptively treated patients, seems to be associated with lack of development (primary HCMV infection) or reconstitution (reactivated infection) of HCMV-specific CD4+ and CD8+ T-cell immunity or with its functional impairment.     

Systemic Candidiasis,A Diagnostic Challenge

The serious and increasing problem of deep-seated Candida infection and the difficulties encountered in diagnosis of this entity prompted review of all well-documented cases of systemic candidiasis in a 39-month period at Stanford Medical Center. In only 19 of the 40. cases (47.5 percent) was the diagnosis suspected premortem; in 15 (37.5 percent) of these, the diagnosis was established. Thirty-three (82.5 percent) of the 40 patients died, and in 12 (39.4 percent) of them Candida infection was considered to be the primary cause of death or a major contributing factor. The seven survivors were treated either by specific chemotherapy or drainage of abscesses and empyema cavities. When the data were assessed in relation to underlying diseases and other possible predisposing factors, surgery was implicated in 50 percent of the total. In a study to define the prevalence of Candida in the saliva of patients with severe underlying illnesses receiving antibiotics or immunosuppressive therapy at the Stanford Medical Center, a significantly higher prevalence was noted in the multiple therapeutic modality group than in controls.In a review of reported data on methods for serological diagnosis of systemic candidiasis, only the precipitin and agglutinin methods appear promising.     

Bacterial colonization and healing of gastric ulcers: the effects of epidermal growth factor

Experimental gastric ulcers are rapidly colonized by various bacteria, resulting in significantly impaired healing. Epidermal growth factor (EGF) is capable of preventing bacterial colonization of the healthy intestinal mucosa. In this study, we examined the possibility that EGF accelerates gastric ulcer healing by reducing bacterial colonization of the ulcer. Gastric ulcers were induced by serosal application of acetic acid. The effect of daily administration of EGF on ulcer healing and bacterial colonization was assessed and compared with the effect of daily treatment with broad-spectrum antibiotics. EGF administration reduced colonization levels and accelerated ulcer healing as effectively as the antibiotic treatment. EGF was without effect on acid secretion or neutrophil infiltration into the ulcer. Bacterial growth was not inhibited in the presence of EGF in vitro. These results demonstrate that EGF reduces bacterial colonization during an established infection of a compromised mucosal surface. This effect may contribute to the ability of EGF to accelerate gastric ulcer healing. This effect is acid independent and not due to an anti-inflammatory effect or to direct bactericidal actions.     

Can dead bacterial cells be defined and are genes expressed after cell death?

There is a paucity of knowledge on gene expression in dead bacterial cells. Why would this knowledge be useful? The cells are dead. However, the time duration of gene expression following cell death is often unknown, and possibly in the order of minutes. In addition, it is a challenge to determine if bacterial cells are dead, or viable but non-culturable (VBNC), and what is an agreed upon correct definition of dead bacteria. Cells in the bacterial population or community may die at different rates or times and this complicates both the viability and gene expression analysis. In this article, the definition of dead bacterial cells is discussed and its significance in continued gene expression in cells following death. The definition of living and dead has implications for possible, completely, synthetic bacterial cells that may be capable of growth and division.     

Use of antibiotics in the management of postirradiation wound infection and sepsis

Ionizing gamma irradiation depresses the host defenses and enhances the susceptibility of the immunocompromised host to local and systemic infection due to endogenous or exogenous microorganisms. Trauma and wounding act synergistically and decrease the survival after exposure to irradiation. The current antimicrobial agents suitable for controlling serious infections and their use in post irradiation local and systemic infection with and without trauma are discussed. The experience gained in managing immunocompromised patients following chemotherapy is reviewed. Empiric single agent or combination agent therapy should be directed at the eradication of potential gram-negative as well as gram-positive pathogens. The most important organisms known to cause these infections are Pseudomonas sp. and Enterobacteriaceae. Management of intra-abdominal infections following trauma should include early surgical correlation and antimicrobials directed against the Bacteroides fragilis group and Enterobacteriaceae. Staphylococcus aureus and Streptococcus pyogenes cause most skin and soft tissue infections following trauma. Chemoprophylaxis of enteric sources of systemic infection can be achieved by antimicrobials that selectively inhibit the Enterobacteriaceae sp. and preserve the anaerobic flora. The management of infection in the injured and irradiated host includes supportive and restorative therapy. Supportive therapy includes débridement and cleansing of wounds, fluids, immunoglobulin, and antimicrobials. Restorative therapy includes definite surgery repair and replenishment of the immune system by use of immunomodulators, growth factors, and bone marrow transplantation. Further studies are needed to examine the usefulness of presently available drugs and experimental agents in the irradiated and traumatized host.     

Effect of CD14 blockade in rabbits with Escherichia coli pneumonia and sepsis

CD14, a pattern recognition receptor found on myeloid cells, is a critical component of the innate immune system that mediates local and systemic host responses to Gram-negative and Gram-positive bacterial products. Previous studies in normal animals have tested the effect of CD14 blockade on the systemic response to i.v. LPS. The goals of the study were to determine whether CD14 blockade protected against the deleterious systemic response associated with Escherichia coli pneumonia and to determine whether this strategy affected the pulmonary response to tissue infection. Rabbits were pretreated with either anti-CD14 mAb or isotype control mAb at 2.5 mg/kg. E. coli (1 x 109 CFU) was inoculated into the lungs, and the animals were observed for either 4 or 24 h. The blockade of CD14 improved the mean arterial blood pressure (p = 0.001) and decreased the i.v. fluid requirements (p = 0.01). Although this therapy protected the vascular compartment, rabbits treated with anti-CD14 mAb had increased bacterial burdens in the bronchoalveolar lavage fluid recovered from the instilled lung (p = 0.005) and widened alveolar-arterial oxygen difference. Blockade of CD14 prevents the deleterious systemic responses that occur in sepsis; however, other measures are necessary to control bacterial proliferation at the primary site of infection.     

PSEUDOMONAS AERUGINOSA INFECTIONS OF THE EYE

Pseudomonas aeruginosa seldom invades the body except in persons or in organs lacking natural defenses, and usually the infection is chronic rather than acute, evoking little systemic response. When introduced into the cornea, however, as in penetration by a foreign body or in contaminated medicines, it acts with extreme virulence, in many cases causing blindness and even necessitating enucleation.Although many attempts at control of Ps. aeruginosa, even with powerful antibiotics, have been unsuccessful, polymyxin B appeared to have good effect and was tested in experimental infection of the cornea in rabbits.It was demonstrated by preliminary studies in vitro that polymyxin B was effective against nine strains of Ps. aeruginosa which on inoculation caused rapidly progressive ulcers in the corneas of rabbits.A strain of proved virulence was introduced into both eyes of each of 18 rabbits. The left eyes only were treated with subconjunctival injections at 48-hour intervals of a solution of polymyxin B, to which epinephrine was added as a vasoconstrictor to prevent rapid dispersion. The right eyes remained untreated as controls.In five of the six rabbits treated immediately after inoculation, the treated eyes remained clear, while moderate infiltration developed in the sixth. In the six rabbits not treated for 24 hours after inoculation, ulcers developed but remained localized during therapy. In those not treated for 48 hours after inoculation, ulcers developed before treatment began but did not spread as rapidly as in the controls.Hyaluronidase was added to the preparation for half the rabbits in each group but had no perceptible beneficial effect.     

Apoptosis Is Essential for Neutrophil Functional Shutdown and Determines Tissue Damage in Experimental Pneumococcal Meningitis

During acute bacterial infections such as meningitis, neutrophils enter the tissue where they combat the infection before they undergo apoptosis and are taken up by macrophages. Neutrophils show pro-inflammatory activity and may contribute to tissue damage. In pneumococcal meningitis, neuronal damage despite adequate chemotherapy is a frequent clinical finding. This damage may be due to excessive neutrophil activity. We here show that transgenic expression of Bcl-2 in haematopoietic cells blocks the resolution of inflammation following antibiotic therapy in a mouse model of pneumococcal meningitis. The persistence of neutrophil brain infiltrates was accompanied by high levels of IL-1β and G-CSF as well as reduced levels of anti-inflammatory TGF-β. Significantly, Bcl-2-transgenic mice developed more severe disease that was dependent on neutrophils, characterized by pronounced vasogenic edema, vasculitis, brain haemorrhages and higher clinical scores. In vitro analysis of neutrophils demonstrated that apoptosis inhibition completely preserves neutrophil effector function and prevents internalization by macrophages. The inhibitor of cyclin-dependent kinases, roscovitine induced apoptosis in neutrophils in vitro and in vivo. In wild type mice treated with antibiotics, roscovitine significantly improved the resolution of the inflammation after pneumococcal infection and accelerated recovery. These results indicate that apoptosis is essential to turn off activated neutrophils and show that inflammatory activity and disease severity in a pyogenic infection can be modulated by targeting the apoptotic pathway in neutrophils.