Targeting the networks that underpin contiguous immunity in asthma and chronic obstructive pulmonary disease

Recent advances in the field of innate immunity have driven an important reappraisal of the role of these processes in airway disease. Various strands of evidence indicate that resident cells, such as macrophages and epithelial cells, have central importance in the initiation of inflammation. Macrophage activation has the potential to regulate not just typical aspects of innate immunity but also, via a variety of intricate cell-cell networks, adaptive responses and responses characterized by Th2-type cytokine production. In turn, such adaptive immune processes modify the phenotype and function of the innate immune system. Cooperative responses between monocytic cells and tissue cells are likely to be crucial to the generation of effective inflammatory responses, and a realization of the importance of these networks is providing a new way of identifying antiinflammatory therapies. Importantly, the repeated cycles of allergic and nonallergic inflammation that comprise chronic human airway disease are not necessarily well described by current terminology, and we propose and describe a concept of contiguous immunity, in which continual bidirectional cross-talk between innate and adaptive immunity describes disease processes more accurately.     

Reference values of diffusing capacity of non-smoking Chinese in Hong Kong

BACKGROUND AND OBJECTIVE: This study was conducted to define normal reference values and lower limits of normal (LLN) for single-breath carbon monoxide diffusing capacity (DLco) and DLco per unit of alveolar volume (Kco) for Chinese adults in Hong Kong. METHODS: Healthy non-smoking men and women aged 18-80 years were recruited by random digit dialing. DLco and Kco were measured according to American Thoracic Society standards. Reference equations were obtained by multiple linear regression; LLN were derived by distribution-free method for estimation of age-related centiles. RESULTS: Tests from 568 subjects (259 men, 309 women) were analysed. DLco declined with age in both genders, and increased with height and the interaction term of height and age in men and women, respectively. Considering Hb values did not improve the reference equations. Kco declined with age and increased with weight in both genders, while height and its interaction term with age were additional determinants in women. The reference DLco was lower than some Caucasian values, and was only explained partially by a smaller body size and alveolar volume in Chinese. The distribution-free method yielded better overall approximation to the fifth percentile compared with the traditional method of determining LLN. CONCLUSIONS: The equations for reference values and LLN of diffusing capacity derived in this study are of clinical relevance to Chinese subjects.     

Microgeographical and tribal variations in water contact and Schistosoma mansoni exposure within a Ugandan fishing community

OBJECTIVE: To explore patterns of water contact and Schistosoma mansoni exposure by age, sex, tribe and space within a single village. METHODS: For 10 months, we systematically observed water contacts made by the 800 inhabitants of a small Ugandan fishing village. In order to estimate cercarial exposure, times spent in water were weighted by snail infection levels, time of day and degree of immersion. RESULTS: There were marked differences in water contact patterns between the two main tribes, which inhabited geographically distinct ends of the village resulting in geographically distinct spatial patterns of water contact. The distributions of the intermediate hosts, Biomphalaria sudanica and Biomphalaria stanleyi, also appeared to differ over small distances. This led to quite different exposure patterns between the two tribes, particularly amongst females. CONCLUSIONS: Schistosoma mansoni exposure can vary markedly within a single village. Such non-homogenous patterns of exposure are likely to have wider implications for schistosomiasis control programmes and research studies.     

Adherence to Antiretroviral Therapy Assessed by Unannounced Pill Counts Conducted by Telephone

BACKGROUND: Unannounced pill counts conducted in patients' homes is a valid objective method for monitoring medication adherence that is unfortunately costly and often impractical. Conducting unannounced pill counts by telephone may be a viable alternative for objectively assessing medication adherence. PURPOSE: To test an unannounced pill count assessment of adherence conducted by telephone. METHODS: HIV-positive men and women (N = 77) in Atlanta GA completed an unannounced telephone-based pill count immediately followed by a pill count conducted in an unannounced home visit. RESULTS: A high degree of concordance was observed between phone and home-based number of pills counted (Intraclass correlation, ICC = .997, 95% CI .995-.998, P < .001) and percent of pills taken (ICC = .990, 95% CI .986-.992, P < .001). Concordance between adherence above/below 90% and phone/home counts was 95%, Kappa coefficient = .995. Concordance between pill counts was not influenced by participant education or health literacy and was maintained when the data were censored to remove higher levels of adherence. Analyses of discordant pill counts found the most common source of error resulted from overcounted doses in pillboxes on the telephone. CONCLUSIONS: Unannounced phone-based pill counts offer an economically and logistically feasible objective method for monitoring medication adherence.     

Shock induced by spontaneous rupture of a giant thymoma

Spontaneous bleeding of thymoma is a very rare event. We report the case of a 73-year-old woman who was referred to our hospital for acute onset of chest pain followed by shock. Chest computed tomographic scanning showed a huge mediastinal tumor with abundant left pleural effusion and contralateral shift of the mediastinum. Emergency surgical treatment was carried out through a clamshell incision. At the opening of the left pleura 1,600 mL of fresh blood was found, originating from a rupture of the tumor's capsular veins. The lesion was completely resected, en-bloc with a wide pericardial excision. The postoperative course was uneventful. The pathology report classified the lesion as thymoma AB.     

Nonneoplastic signet-ring cells in the gallbladder and uterine cervix. A potential source of overdiagnosis

We describe 3 cases of nonneoplastic signet-ring cell change in ulcerated mucosa, 2 of them in the gallbladder and 1 in an endocervical polyp. In the gallbladder cases, there were focal collections of signet-ring cells both on the mucosal surface and within the lumen of tubules, whereas in the endocervical polyp, the signet-ring cell aggregates were entirely confined to the mucosal surface. In all 3 cases, the signet-ring cells were positive for Mayer's mucicarmine and immunoreactive for keratin AE1/AE3. The lack of nuclear atypicality, the arrangement in superficial and intraluminal nests, and the admixture with histiocytes and other inflammatory cells are in keeping with the interpretation that the signet-ring cells are disrupted mucosal goblet cells exhibiting hyperplastic and degenerative changes. A review of the literature disclosed only other 2 previously reported cases of benign signet-ring cell changes in the gallbladder and none--to the best of our knowledge--in an endocervical polyp. Awareness of this phenomenon is of importance to avoid a potential overdiagnosis of signet-ring cell adenocarcinoma.     

mda-7/IL-24, novel anticancer cytokine: focus on bystander antitumor, radiosensitization and antiangiogenic properties and overview of the phase I clinical experience (Review)

Subtraction hybridization applied to a 'differentiation therapy' model of cancer employing human melanoma cells resulted in the cloning of melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24). Initial studies confirm an inverse correlation between mda-7 expression and melanoma development and progression. Forced expression of mda-7 by means of a plasmid or via a replication incompetent adenovirus (Ad.mda-7) promotes growth suppression and induces apoptosis in a broad array of human cancers. In contrast, mda-7 does not induce growth suppressive or toxic effects in normal cells. Based on structure (containing an IL-10 signature motif), secretion by cells (including subsets of T-cells) and location on chromosome 1q (in an area containing IL-10-family genes), mda-7 has now been renamed mda-7/IL-24. Studies by several laboratories have uncovered many of mda-7/IL-24's unique properties, including cancer-specific apoptosis-induction, cell cycle regulation, an ability to inhibit angiogenesis, potent 'bystander antitumor activity' and a capacity to enhance the sensitivity of tumor cells to radiation, chemotherapy and monoclonal antibody therapy. Moreover, based on its profound cancer tropism, substantiated by in vivo human xenograft studies in nude mice, mda-7/IL-24 (administered as Ad.mda-7) was evaluated in a phase I clinical trial in patients with melanomas and solid cancers. These studies document that mda-7/IL-24 is well tolerated and demonstrates evidence of significant clinical activity. In these contexts, mda-7/IL-24 represents a unique cytokine gene with potential for therapy of human cancers. The present review focuses on three unique properties of mda-7/IL-24, namely its potent 'bystander antitumor activity', ability to sensitize tumor cells to radiation, and its antiangiogenesis properties. Additionally, an overview of the phase I clinical trial is provided. These studies affirm that mda-7/IL-24 has promise for the management of diverse cancers.