MMTV-Wnt-1转基因小鼠作为高发乳腺癌动物模型的观察

目的　观察MMTV Wnt 1转基因小鼠的乳腺癌发病情况及病理学变化规律。方法　观察MMTV Wnt 1转基因小鼠肿瘤发生情况 ,并采用原位移植将瘤组织置于裸鼠皮下 ,通过组织病理学切片来观察MMTV Wnt 1阳性转基因小鼠和移植鼠的病理学变化。结果　MMTV Wnt 1转基因小鼠最早从 7周龄开始出现乳腺瘤 ,发瘤鼠剖检可见脾、肝有不同程度的肿大 ,其他器官无明显病变 ;病理组织学检查发现发瘤鼠各脏器有不同程度的病变 ,但未出现肿瘤转移。将瘤组织移植裸鼠后 ,肿瘤可在裸鼠皮下生长 ,移植肿瘤病理学形态与原发瘤一致 ,未出现转移。结论　实验结果验证MMTV Wnt 1转基因小鼠可稳定自发乳腺肿瘤 ,可作为研究乳腺癌的良好的动物模型     

Clearance and persistence of hepatitis C virus in a Tunisian population: association with HLA class I and class II

Human leukocyte antigens (HLAs) of class I and class II are reported to influence the outcome of hepatitis C virus (HCV) infection. The aim of this study was to assess the role of HLA class I and class II in influencing spontaneous viral clearance or persistence in HCV-infected patients. HLA class I (A and B) typing was performed by lymphocytotoxicity test and HLA class II (DRB1) was determined by low-resolution PCR-SSP (polymerase chain reaction amplification with sequence-specific primers) for 99 subjects (48 men and 51 women). Of these, 75 had chronic infection and 24 had viral clearance. No significant differences were observed between individuals with spontaneous viral clearance or chronic HCV infection for age, sex, source of infection, and risk factors. HLAB-w35 and HLA-DRB1*08 occurred more frequently in those with viral clearance (21.7 and 16.6%, respectively) compared with those with chronic infection (5.5 and 2.6%; p < 0.04 and p < 0.01, respectively). DRB1*15 occurred more often in those with chronic infection (29.3%) compared with those with viral clearance (16.66%), but the difference did not reach statistical significance. These results support the hypothesis that specific HLA class I and class II alleles might influence the clearance or persistence of HCV infection. Both Bw35 and DRB1*08 are associated with clearance of circulating HCV whereas DRB1*15 appears to predispose to progression of liver disease in Tunisian patients. Taken together, our results and those previously reported suggest that HLA associations with the outcome of hepatitis C viremia vary in relation to the ethnicity of the population studied. Further prospective studies of larger cohorts of HCV-infected subjects are needed to evaluate, in different populations, the role of specific HLA class I and class II alleles in the outcome of HCV infection.     

Psoas abscess of the adult: study of 38 cases

OBJECTIVE: Our aim is to report the clinical aspects, the etiologies, the treatment and the evolution of the psoas abscess in the adult. METHODS: Our retrospective study concerns 38 cases of psoas abscesses collected in the Department of Infectious Diseases of Sfax (Tunisia), over a period of 16 years (January 1990 - December 2005). RESULTS: The average age is 44 years (extremes: 16-76 years). The sex-ratio is 1.4. Six patients were diabetics and one had a chronic renal injury at the stage of hemodialysis. The clinical manifestations were: a fever (76.4%), an abdomino-pelvic ache (84.2%) and a psoitis (34.2%). All patients had a biologic inflammatory syndrome with a hyperleucocytosis in 28 cases. The abscess was one-sided in 29 cases and bilateral in 9 cases. After microbiological study and/or histological study, pathogens were identified in 31 patients, they were Staphylococcus aureus (10 cases), Staphylococcus lugdunensis (1 case), Streptococci (3 cases), Escherichia coli (2 cases), Bacteroides fragilis (1 case), Actinomyces (2 cases), Brucella (3 cases), Mycobacterium tuberculosis (8 cases) and Candida glabrata (1 case). The psoas abscess was primary in 10 cases and secondary in 28 cases. All the patients received an antibiotherapy or an antifungal therapy adapted to the micro-organism in cause, with a drainage of the abscess in 25 cases (surgical in 9 cases and percutaneous in 16 cases). The evolution was favourable in 36 cases. One patient presented recurrences and one patient died. CONCLUSION: The psoas abscess of the adult is characterized by a polymorphe clinical presentation. Germs in cause are very variable.     

Weak D in the Tunisian population

BackgroundMore than 90 weak D types have been discovered to date. As there are no published data on the frequencies of weak D types in the Tunisian population, the aim of this study was to determine the composition of weak D alleles in our population.ResultsAmong the D+ donor cohort, weak D type 4 was the most prevalent allele (n=33, 1.2%) followed by weak D type 2 (n=6, 0.17%), weak D type 1 (n=4, 0.11%), and weak D type 5 (n=1, 0.28%) and weak D type 11 (n=1, 0.28%). RHD sequencing identified a weak D type 4.0 allele in all 19 samples tested. Among the D− pool, comprising 223 samples, we detected one sample with weak D type 4.0 associated with a C+c+E−e+ phenotype which had been missed by routine serological methods.DiscussionWeak D type 4.0 appears to be the most prevalent weak D in our population. However, all samples must be sequenced in order to determine the exact subtype of weak D type 4, since weak D type 4.2 has considerable clinical importance, being associated with anti-D alloimmunisation. One case of weak D type 4 associated with dCe in trans had been missed by serology, so quality control of serological tests should be developed in our country.     

Chronic lymphocytic leukemia revealed by a branulomatous zosteriform eruption

A 70-year-old woman presented with an atypical erythematopapular zosteriform eruption of 3 weeks' duration. The patient had no history of previous vesicular eruption. She developed a painful burning sensation on the neck. Clinical examination revealed a cluster of small erythematous firm papules and plaques in a zosteriform distribution on the left ear, face, neck, and shoulder (Figure 1A). The lesions were unilateral and did not cross the midline. Multiple cervical and axillary lymph nodes were palpable. Laboratory tests revealed an increase in white blood cells of 25,000/mm3, with 17,910/mm3 lymphocytes and a normal range of hemoglobin, platelets, creatinine, and liver enzymes. Erythrocyte sedimentation rate was 87 mm. Blood smear results showed small, morphologically mature lymphocyte cells. In immune phenotyping, lymphocyte cells co-express CD5 and B-cell-surface antigens CD19 and CD23, as well as a restriction of kappa immunoglobulin light chains. The cells were CD22-, CD79b-, CD38-, CD10-, CD25- and FMC7-. Computed thoracoabominal tomography revealed cervical, mediastinal, abdominal, and pelvic adenopathy confirming the diagnosis of B-cell chronic lymphocytic leukemia (B-CLL) stage B. Histology of a skin biopsy from a papule showed a dense nodular granulomatous infiltrate in the dermis (Figure 2A). The infiltrate contained epithelioid and giant cells surrounded by lymphocytes and plasma cells. Small monomorphic lymphocytes without mitotic figures predominated (Figure 2B). The epidermis was irregularly thickened. Immunohistology revealed a polymorphous infiltrate with a phenotype of reactive T lymphocytes (CD3, CD5 positive) (Figure 2C), B lymphocytes (CD20 positive) (Figure 2D). Epithelioid and giant cells were positive for CD68 (Figure 2E). A latent herpes zoster infection with granulomatous reaction at the site ofzoster lesions was highly suspected as the patient reported a unilateral burning sensation without a history of vesicular zosteriform eruption. She received treatment with intravenous acyclovir 10 mg/kg every 8 hours. The papular lesions resolved markedly (60%) on macular plaques at the end of the treatment. Following topical treatment with corticosteroids, the lesions healed completely within 4 weeks (Figure 1B). Concerning leukemia, our patient was monitored without therapy by the hematologist.     

Acid-base status is an important factor for inflammation,but don’t forget CO2!

Zampieri and colleagues used sophisticated statistical methods to create a picture of acid-base pattern and inflammation relationship in a clinical context. The observed independent relationship between acidosis and albumin concentration and inflammatory pattern opens up a new area for research. It has become clear that, in addition to the characterization of mediators, receptors, and cellular phenotypes, the inflammatory response has to be interpreted in light of acid-base status, albumin concentration, and probably also carbon dioxide level.Until now, the interplay between acid-base status and inflammation has received little attention, especially in a clinical context. The article by Zampieri and colleagues [1] in a previous issue of Critical Care is a pioneering study analyzing the relationship between acidosis variables, inflammatory mediators, and end-organ failures (acute kidney injury and shock). Since the metabolic and inflammatory reactions are simultaneous, the demonstration of interplay that is more than a simultaneous modification remains a difficult challenge. Because of this, the authors used three different statistical methods to separate the confounding factors. First, they developed a generalized linear model using the measured mediator as a dependent variable and components of acid-base status as variables. Second, they performed a multivariate adaptive regression with splines in order to evaluate the association of selected cytokines and acid-base components. Third, they performed a principal component analysis using Simplified Acute Physiology Score 3 as a way of quantifying illness severity in order to assess the independent association of acid-base variables and cytokine levels. The authors found that, in 87 prospective unselected patients, the level of strong anion gap (SIG) was positively associated with TNFα and IL-6, IL-8, and IL-10. A negative association was found between albumin level and TNFα and IL-6, IL-7, IL-8, and IL-10 and IFNγ. The conclusion drawn from these results opens up a new route for research to understand the mechanisms that link acid-base variables, albumin level, and immunological activation.Such a topic is important and clinically relevant since plasma and interstitial fluid constitute the microenvironment for immune and tissue cells. Acid-base and albumin characteristics may then interfere with the cell response to different signals such as endotoxin. In addition, both fluid resuscitation and capillary leak may largely influence the composition of the cell microenvironment, especially when a crystalloid such as saline or a balanced crystalloid such as Ringer’s lactate is used. The role of surrounding cell pH could be seen as a result of metabolic acidosis and carbon dioxide (CO₂) level, an aspect that was not investigated in the study [2,3]. Given the picture presented in this article, some approaches might be tested to clarify the mechanisms involved in immune modifications induced by acid-base changes. First, immune cells should be drawn from septic patients that have been incubated in the septic plasma or drawn after replacement of septic plasma by healthy plasma; both acid-base conditions or albumin concentration can then be modified to test their impact on immune cells phenotype. This might help to clarify how the pH, the SIG, and albumin concentration change the immune cell phenotypes. Second, similar experiments with healthy cells incubated in plasma from acutely injured patients could be performed to demonstrate the role of physicochemical plasma patterns. Mediators and cell functions then could be evaluated in different acid-base conditions. Until now, few data on alkalosis have been reported in terms of immunity, and the essential information comes from acidosis situations. One author of the study was part of a group [4] that showed that metabolic acidosis induced by hydrochloric acid and lactic acidosis added to culture media of RAW 264.7 cells have opposite effects: hydrochloric acid at a pH of 7 seems essentially pro-inflammatory (nitric oxide level, IL-6/IL-10 ratio, NF-κB DNA binding), whereas lactic acidosis is essentially anti-inflammatory. A group with the same author, using a rat model, confirmed these results in terms of systemic cytokines [5]. In that study, the authors found a positive relationship between SIG and IL-6, IL-8, and IL-10 and TNFα, which was independent of illness severity. Even though albumin was not administered in the presented cohort, it can be discussed in light of immune effects. The authors observed a negative correlation between albumin level and IL-6, IL-8, IL-10, monocyte chemoattractant protein-1 and IFNγ. In addition to its complex effects, albumin was shown to be immunosuppressive for peripheral blood monocytes (IFNγ and TNFα) and also for T lymphocyte clone [6], which confirmed the presented results. Except for specific indications, albumin is not recommended for use in fluid resuscitation, especially after the recent negative results of a randomized clinical trial [7]. Third, the role of hypo- or hypercarbia has to be investigated since elevated CO₂ was shown to modulate mammalian inflammatory and innate immune responses in vitro and in vivo [3], independently of extra- and intra-cellular pH. During a sterile insult of inflammation stimulation, hypercapnia may be of benefit but would be deleterious in the setting of infection due to host immunosuppression. The underlying mechanism implicates the NF-κB signaling pathway as an important hub of CO₂ sensitivity [3,8]. This, in combination with the ability of elevated CO₂ to enhance bacterial and fungal virulence and survival, suggests that hypercapnia may predispose humans to infections or worsen outcomes [3]. Understanding the involved molecular signaling pathways will be of great importance in the identification of new approaches to control infection and inflammation in the clinical setting.