The Yin-Yang of tumor-associated macrophages in neoplastic progression and immune surveillance

Summary: An intrinsic (oncogene-driven) pathway and an extrinsic (microenvironment-driven) pathway connect inflammatory reactions and cancer. M2-polarized tumor-associated macrophages and the related myeloid-derived suppressor cells are key prototypic components of smoldering inflammation driving neoplastic progression. However, mononuclear phagocytes can exert anti-tumor activity by killing tumor cells and eliciting tissue disruptive reactions (M1), a likely scenario in the early phases of carcinogenesis of immunogenic tumors and following therapeutic intervention. Shifting the macrophage balance represents a viable therapeutic target. Herein, the 'macrophage balance' is discussed in the context of the apparent paradox of tumor promotion by innate immunity-driven inflammation and the seemingly opposed tumor surveillance by adaptive immune responses.     

Priorities for antibiotic resistance surveillance in Europe

Antibiotic resistance is an increasing global problem. Surveillance studies are needed to monitor resistance development, to guide local empirical therapy, and to implement timely and adequate countermeasures. To achieve this, surveillance studies must have standardised methodologies, be longitudinal, and cover a sufficiently large and representative population. However, many fall short of these requirements that define good surveillance studies. Moreover, current efforts are dispersed among many, mostly small, initiatives with different objectives. These studies must be tailored to the various reservoirs of antibiotic-resistant bacteria, such as hospitalised patients, nursing homes, the community, animals and food. Two studies that could serve as examples of tailored programmes are the European Antimicrobial Resistance Surveillance System (EARSS), which collects resistance data during the diagnosis of hospitalised patients, and the DANMAP programme, which collects data in the veterinary sector. As already noted by the WHO, genetic studies that include both the typing of isolates and the characterisation of resistance determinants are necessary to understand fully the spread and development of antibiotic resistance.     

Population-based laboratory surveillance for tribe Proteeae isolates in a large Canadian health region

The tribe Proteeae comprises the genera Proteus, Morganella and Providencia. Few studies have specifically investigated the epidemiology of infections caused by the Proteeae, and none has been conducted in a large non-selected population. The present study was a population-based laboratory surveillance in the Calgary Health Region (population 1.2 million), Canada during 2000-2005 that aimed to define the incidence, demographical risk-factors for acquisition and antimicrobial susceptibilities of Proteeae isolates. In total, 5047 patients were identified from whom Proteeae isolates were obtained (an annual incidence of 75.9/100 000), with females and the elderly being at highest risk. Incidence rates were 64.8, 7.7 and 3.4/100,000/year for the genera Proteus, Morganella and Providencia, respectively. Overall, 85% of infections were community-onset, and the overall rate of bacteraemic disease was 2.0/100,000. Compared with other species, Proteus mirabilis occurred at a much higher frequency, especially among females, and was less likely to be isolated from hospital-onset infections or to be part of a polymicrobial infection. Among isolates from community-onset infections, Providencia spp. were less likely to be from outpatients and more likely to be from nursing home residents. There were low overall rates of resistance to ciprofloxacin (4%) and gentamicin (5%), with Prot. mirabilis generally being the most susceptible. Members of the Proteeae were isolated frequently in both the community and hospital settings, but were infrequent causes of invasive disease. The occurrence, demographical risk-factors and microbiology of Proteeae isolates varied according to the individual species.     

An influenza A(H3) reassortant was epidemic in Australia and New Zealand in 2003

During 2003, Australia and New Zealand experienced substantial outbreaks of influenza. The strain responsible was an A(H3N2) influenza virus described as A/Fujian/411/2002-like, which had circulated as a minor variant in the previous Northern Hemisphere (NH) winter, mainly in Korea and Japan. Early in the year the isolates were very similar to those that had been previously isolated in the NH, however, a reassortant strain emerged early in the New Zealand winter, followed by the appearance of similar viruses in Australia and other regional areas. While the hemagglutinin HA1 sequence of these viruses demonstrated only minor differences from the A/Fujian/411/2002 reference strain, the neuraminidase gene was clearly different from that of other recently circulating H3 viruses and most closely matched an earlier reference strain A/Chile/6416/2001. Three internal genes (NS, NP, M) in the reassortant viruses were also more closely related to the A/Chile/6416/2001 lineage. This reassortant A(H3) virus predominated in Australia and New Zealand in 2003 was also seen in Brazil and Malaysia during 2003 and was widespread in the United States and Europe during their 2003-04 winter. Interestingly most of the strains of A(H3) that were isolated at the beginning of the 2004 winter in Australia, did not have this earlier A/Chile/6416/2001-like neuraminidase but had a neuraminidase that was similar to that of the reference strain A/Fujian/411/2002. This was suggestive of the re-introduction of influenza A(H3) from other countries, however, there was still low level circulation of the reassortant virus in 2004 with isolates detected in Australia and Singapore.     

Autonomous histopathological regression of primary tumours associated with specific immune responses to cancer antigens

Spontaneous histopathological regression of cancer has been reported. The involvement of the immune system in such regression has been advocated, leading to the theory of immunological surveillance against cancer. A prediction of this theory is that common tumour antigens can be recognized upon repeated exposure by cell-mediated immunity, which leads to tumour regression and the subsequent appearance of tumour antigen-loss variants. However, no direct evidence has been provided in non-viral-induced experimental animal models of primary malignancy or in human primary cancer. This study examined two groups of melanoma patients where histopathological regression of the primary tumour was observed. Many of the 23 patients with multiple (> or =3) primary melanomas showed significant regression of their last melanoma (median 33%, mean 40) compared with matched melanomas from patients with a single primary melanoma (median 0%, mean 12) (p=0.0080), or compared with their first primary melanoma (p=0.0013). Regression was consistent with an 'immunization effect' seen in murine tumour transplantation studies, where inoculation with > or =3 asynchronous tumours induces transplantation rejection on subsequent challenge. A significant decrease in the expression of the melanoma common tumour antigen MART-1 in the last primary tumour from multiple melanoma patients (median 8%, mean 24) versus matched single melanoma patients (median 79%, mean 68) (p=0.0041) and in the last versus first tumour in multiple primary patients was found (p=0.0083). Metastases from 17 patients whose primary skin melanomas had completely regressed (occult primary melanoma) also showed significant MART-1 loss (median 0%, mean 11) compared with matched metastases from patients with non-regressing primary melanoma (median 51%, mean 50) (p=0.0013). MART-1 antigen-loss variants observed in the multiple primary and occult primary patients correlated with the presence of peripheral blood MART-1-specific cytotoxic T lymphocytes (CTLs) (p=0.03). No similar effects were observed with two other melanoma antigens, gp100 and CD63. Thus, in two groups of human melanoma patients, evidence is provided for histopathological tumour regression associated with cancer immune surveillance.     

Characterisation of macrolide-non-susceptible Streptococcus pneumoniae colonising children attending day-care centres in Athens, Greece during 2000 and 2003

Nasopharyngeal Streptococcus pneumoniae isolates colonising young children are representative of isolates causing clinical disease. This study determined the frequency of macrolide-non-susceptible pneumococci, as well as their phenotypic and genotypic characteristics, among pneumococci collected during two cross-sectional surveillance studies of the nasopharynx of 2847 children attending day-care centres in the Athens metropolitan area during 2000 and 2003. In total, 227 macrolide-non-susceptible pneumococcal isolates were studied. Increases in macrolide non-susceptibility, from 23% to 30.3% (p <0.05), and in macrolide and penicillin co-resistance, from 3.4% to 48.6% (p <0.001), were identified during the study period. The M resistance phenotype, associated with the presence of the mef(A)/(E) gene, predominated in both surveys, and isolates carrying both mef(A)/(E) and erm(AM) were identified, for the first time in Greece, among the isolates from the 2003 survey. Pulsed-field gel electrophoresis analysis of the isolates from the 2000 survey indicated the spread of a macrolide- and penicillin-resistant clone among day-care centres. The serogroups identified most commonly in the study were 19F, 6A, 6B, 14 and 23F, suggesting that the theoretical protection of the seven-valent conjugate vaccine against macrolide-non-susceptible isolates was c. 85% during both study periods.     

广州市白云区1991—2007年艾滋病疫情监测

目的总结广州市白云区艾滋病流行特征，评估监测效能，为下一步防治工作的深入开展提供依据。方法运用SAS统计软件对广州市艾滋病疫情数据库中白云区属的病例进行相关描述性统计分析。结果截至2007年底，白云区共发现病例1136例，男女比为3．5：1；年龄以15-49岁为主（94．01％）。传播途径以静脉吸毒为主（61．10％），流动人口占疫情的大部分（71．48％）。性传播（x^2=12．009，P=0．001）和职业人群（x^2=44．935，P=0．001）随年份比例增加；常规监测发现病例日趋增加（x^2=5．533，P=0．019）。结论白云区已进入疫情的快速增长期，疫情主要侵袭青壮年男性，吸毒人群和无业人士所占比例较大。由于白云区在经济和生活上的一些特点，流动人口的疫情负担较重，且传播途径向多元化发展。加大监测力度包括高危人群干预专项和监测效能，将有助于迅速准确的掌握疫情。     

血管内介入治疗脑动静脉畸形

目的 探讨血管内栓塞治疗脑动静脉畸形(AVM)的临床效果和安全性．方法 应用血管内栓塞治疗脑AVMll例，栓塞剂为NBCA，栓塞后3例行手术切除，3例行γ-刀治疗．结果 1例完全栓塞，5例栓塞70％—90％，3例栓塞50％—70％，2例栓塞小于50％．生活、工作完全正常治愈5例，症状明显改善4例，症状无改善2例．结论 血管内栓塞治疗脑AVM的方法是相对安全的，可治愈部分脑AVM，对于大型、重要功能区的脑AVM，血管内栓塞联合手术或放疗可提高治愈率，降低致残率和死亡率．     

Child illness, the parenting alliance, and parenting stress

Assessed relationship between children's minor illnesses during the first 3 years of life and parenting stress in the 4th year. Also examined whether a good parenting alliance would compensate for or moderate this relationship. Parents of 56 3- to 4-year-olds completed parenting alliance and stress questionnaires. Child morbidity, assessed from medical records, was directly related to mothers' but not fathers' feelings of stress. The parenting alliance was more strongly related to parenting stress for fathers than for mothers. However, child morbidity and parenting alliance interacted in predicting child-related paternal stresses. While fathers in a poor alliance reported more stress, stress was unrelated to their children's illnesses; for fathers in a moderate to strong alliance, illness and stress were positively correlated. Even minor child illnesses appear to be a source of stress for parents.