Beta2 integrin/ICAM-1 adhesion molecule interactions in cutaneous inflammation and tumor promotion

The beta2 integrin (CD 18/CD 11 a, b, c) family of proteins mediate adherence of leukocytes to vascular endothelium and the associated ligand, intercellular adhesion molecule-1 (ICAM-1; CD 54), interacts with beta2 integrin proteins to allow transendothelial migration of leukocytes into sites of inflammation. The present study examines the function of these proteins in a murine model of acute cutaneous inflammation induced following topical application of 12-O- tetradecanoylphorbol-13-acetate (TPA) to the dorsal epidermis of SENCAR mice and in a model of skin multistage carcinogenesis. At 24 h following topical application of TPA to the dorsal epidermis of mice, dermal leukocytes expressed higher levels of beta2 integrin protein compared with the lower levels of beta2 integrin protein expression by peripheral blood leukocytes. ICAM-1 protein was localized to epidermal keratinocytes and vascular endothelium in TPA-treated skin and to proliferating papilloma cells. Intravenous (i.v.) injection of either 50 microg anti-beta2 integrin antibody alone or in combination with anti-ICAM-1 antibody significantly inhibited both TPA-stimulated neutrophil infiltration into the dermis (P < 0.001) and myeloperoxidase (MPO) activity (P < 0.03 anti-beta2 integrin antibody; P < 0.01 anti- beta2 integrin + ICAM-1 adhesion molecule antibodies), but had no effect on TPA-induced epidermal hyperplasia. In addition, injection of either anti-ICAM-1 adhesion molecule antibody alone (P < 0.004) or in combination with anti-beta2 integrin antibody (P < 0.001) significantly inhibited TPA-induced production of 7,8-dihydroxy-2'-deoxyguanosine (8- OHdG) immunoreactive proteins by epidermal keratinocytes. Beta2 integrin/ICAM-1 adhesion molecules work in concert to regulate migration, retention and functional activation of leukocytes within the dermis during TPA-induced skin inflammation and within stromal tissue of papillomas that form during multi-stage carcinogenesis. Agents that inhibit these receptor/ligand interactions may be useful in defining the roles of specific cell populations in cutaneous inflammation and multistage carcinogenesis and may also have potential as anti-promoting and anti-progression agents.      

Facteurs associés aux perdus de vue des patients sous traitement antirétroviral dans un centre de traitement ambulatoire du VIH à Conakry,Guinée

Background

Late or inadequate therapeutic management increases the risk of mortality associated with HIV/AIDS. The aim of this study was to analyze the proportion and factors associated with loss of follow-up in HIV patients who receiving antiretroviral therapy at Conakry.

Antibodies to diphtheria, tetanus and pertussis in infants before and after immunization with DTP (Triple Antigen) vaccine

Objective : To determine antibody levels to the Australian manufactured combined diphtheria, tetanus and pertussis (DTP) vaccine (Triple Antigen, CSL Ltd) in infante before and after their primary immunization course.
Methodology : Serosurvey (antibody prevalence study) in two groups: infants aged 5-9 weeks who had not received any immunizations ( n = 25), and infants aged 7-10 months who had received two ( n = 25) or three immunizations ( n = 57) with DTP, sampled from infants attending the Royal Children's Hospital, Melbourne, either as inpatients or outpatients between February and April 1993. The immunization history for each infant was determined from hospital records, the parent-held child health record, or the local council or family doctor who immunized the infant.
Results : Enzyme immunoassay (EIA) of antibodies to diphtheria and tetanus showed all infants to have adequate protective levels after two or three vaccinations (£0.01 IU/mL). All subjects who had received all three DTP vaccinations had detectable antibody to at least one pertussis antigen. Antibodies to the pertussis antigens filamentous haemagglutinin and pertussigen (pertussis toxin) were comparable to levels determined for whole cell pertussis vaccines used elsewhere in the world. EIA-determined antibodies to pertussis agglutinogen type 2 and agglutinogen type 3 showed substantially higher geometric mean titres when results for pre-immunization and post-immunization subjects were compared.
Conclusions : These data show that the Australian manufactured DTP vaccine has immunogenic properties similar to those of vaccines used elsewhere, and that antibody concentrations following immunization are at levels consistent with efficacy.     

Hilar masses: evaluation with CT-guided biopsy after negative bronchoscopic examination

Computed tomography (CT)-guided biopsies of 20 patients with hilar masses were performed after non-diagnostic bronchoscopic examination. Bronchoscopy included washings, brushings, routine biopsy, and, in many cases, transbronchial biopsy. In all but one case (95%), biopsy with a 22-gauge needle permitted a cytologic diagnosis of malignancy. In 14 of the 19 cases (74%), a diagnosis of primary lung carcinoma involving the hili was made, and in the remaining five of the 19 (26%), metastatic hilar adenopathy from an extrathoracic primary tumor was identified. A pneumothorax rate consistent with our average rate for CT-guided biopsies (25%) was obtained, and only one patient required chest tube placement. In this series, CT-guided biopsies of hilar masses were more consistently successful in obtaining tissue for diagnosis than were bronchoscopic biopsies. Transthoracic needle aspiration biopsy may be the preferred initial diagnostic procedure in many patients with hilar masses.     

Risk to Tourists Posed by Wild Mammals in South Africa

BACKGROUND: One of South Africa's principal tourist attractions is the opportunity to encounter Africa's large mammals in the wild. Attacks by these mammals can be exceptionally newsworthy with potentially deleterious effects on tourism. Little is known about the risk of injury and death caused by wild mammals to visitors to South Africa's nature reserves. The aim of this study was to determine the incidence of fatal and nonfatal attacks on tourists by wild mammals in South Africa and to ascertain avoidable factors, if any. METHODS: Commercial press records covering all South African Newspapers archived at the Independent Newspapers' central library were systematically reviewed for a 10-year period, January 1988 to December 1997 inclusive, to identify all deaths and injuries to domestic and international tourists resulting from encounters with wild mammals in South Africa. All of these incidents were analyzed to ascertain avoidable factors. RESULTS: During the review period seven tourists, including two students from Thailand and a German traveler, were killed by wild mammals in South Africa. Three of the four deaths ascribed to lions resulted from tourists carelessly approaching prides on foot in lion reserves. A judicial inquiry found that the management of a KwaZulu-Natal Reserve was culpable for the remaining death. Tourist ignorance of animal behavior and flagrant disregard of rules contributed to the two fatalities involving hippopotami. The unusual behavior manifested by the bull elephant responsible for the final death, resulted from discomfort caused by a dental problem to this pachyderm. During the same period there were 14 nonfatal attacks on tourists, including five by hippo, three by buffalo, two by rhino, and one each by a lion, leopard, zebra and musth elephant. Only the latter occurred while the visitor was in a motor vehicle. Tourist ethological naivete and failure to determine the experience of trail guides prior to travel, resulted in inadvertent agonistic behavior, unnecessary risk-taking and avoidable injury. CONCLUSIONS: This retrospective study has shown that attacks on tourists by wild mammals in South Africa are an uncommon cause of injury and death. Sensible precautions to minimize this risk include remaining in a secure motor vehicle or adequately fenced precincts while in the vicinity of large mammals, rigidly observing nature reserve instructions, never approaching animals that appear ill, malnourished, displaying aggressive behavior traits or female wild mammals with young, and demanding adequately trained and experienced game rangers when embarking on walking trails. Any behavior that might be construed as antagonistic and which could provoke an attack by large mammals should be avoided (e.g., driving directly at a lion). Visitors need to be informed of classic signs of aggression, in particular in elephants, which will allow timely avoidance measures to be taken. The risk-enhancing effect of excessive alcohol intake is undesirable in the game reserve setting, as is driving at high speed after dusk in areas where hippos graze. Local advice on personal safety in wildlife reserves and the credentials of trail guides should be obtained from lodge or reserve management, tourism authorities or the travel industry prior to travel to game reserves.