Widespread skin and soft-tissue infections due to two methicillin-resistant Staphylococcus aureus strains harboring the genes for Panton-Valentine leucocidin

Infections caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) are emerging as a major public health problem. CA-MRSA has been associated previously with skin and soft-tissue infection (SSTI) and with carriage of staphylococcal cassette chromosome mec (SCCmec) type IV and the Panton-Valentine leucocidin (PVL) virulence factor. To assess the clonal distribution of PVL-carrying strains and the association with SSTI in the San Francisco Bay area, we surveyed six collections of S. aureus isolates-671 isolates in all-collected between 1997 and 2002 originating from inpatient and outpatient clinical specimens and from a community-based sampling. Isolates were genotyped by pulsed-field gel electrophoresis, multilocus restriction fragment typing, and multilocus sequence typing and assayed for the PVL virulence factor. The S. aureus populations showed a high proportion of PVL-carrying strains, with frequencies ranging up to 70% in MRSA isolated from jail inmate patients and 69% in MRSA from patients receiving surgical treatment at an outpatient clinic specializing in treating SSTIs. PVL-carrying isolates were identified in nine clonal groups, but 88.5% of the PVL-carrying MRSA isolates belonged to only two clonal groups. These two clonal groups carried the SCCmec type IV resistance determinant and were more likely than other clonal groups to be recovered from SSTI sites than from other sites (P < 0.0001). There is evidence of clonal replacement over the period from 1999 to 2002, with one of these two clonal groups being supplanted by the other.     

Postnatal development and lymphocyte production of jejunal and ileal Peyer's patches in normal and gnotobiotic pigs.

The development of the number, size, structure and proliferative capacity of Peyer's patches (PP) in the jejunum and ileum has been studied during the early postnatal period of conventional and germ-free pigs. A mean of 15 discrete PP in the jejunum and upper ileum (jejPP) were counted at birth, and the number increased only gradually. A continuous PP is located in the terminal ileum (ileal PP). The length of both jejPP and ileal PP increased with age due to the increase in follicle size and in the number of follicles in the ileal PP. In older pigs, only the ileal PP regressed to small scattered follicles. In germ-free piglets at 39 and 59 days of age, longer PP were found than in normal new-born piglets, but they were significantly shorter than in age-matched controls. Lymphocyte production was studied by the metaphase-arrest technique using vincristine. Lymphocyte production in follicles increased dramatically with age, while in other compartments, such as the inter-follicular and dome area, a low age-independent production of lymphocytes was found. There were no differences in lymphocytopoiesis between jejPP and ileal PP. The present data show major differences in the development, structure and function of PP in pigs in comparison to other species. These species-specific aspects are important for future studies on the immunological function of PP.     

An Immunohistochemical Study of the Pathology of Fatal Malaria: Evidence for Widespread Endothelial Activation and a Potential Role for Intercellular Adhesion Molecule-1 in Cerebral Sequestration

The sequestration of parasitized erythrocytes in the microvasculature of vital organs is central to the pathogenesis of severe Plasmodium falciparum malaria. This process is mediated by specific interactions between parasite adherence ligands and host receptors on vascular endothelium such as intercellular adhesion molecule-1 (ICAM-1) and CD36. Using immunohistochemistry we have examined the distribution of putative sequestration receptors in different organs from fatal cases of P.falciparum malaria and noninfected controls. Receptor expression and parasite sequestration in the brain were quantified and correlated. Fatal malaria was associated with widespread induction of endothelial activation markers, with significantly higher levels of ICAM-1 and E-selectin expression on vessels in the brain. In contrast, cerebral endothelial CD36 and thrombospondin staining were sparse, with no evidence for increased expression in malaria. There was highly significant co-localization of sequestration with the expression of ICAM-1, CD36, and E-selectin in cerebral vessels but no cellular inflammatory response. These results suggest that these receptors have a role in sequestration in vivo and indicate that systemic endothelial activation is a feature of fatal malaria.     

Comorbidity of asthma and anxiety and depression in Puerto Rican children

Studies have reported that childhood asthma is associated with internalizing disorders, but most of these studies have used global measures of depressive and anxiety symptoms. The Diagnostic Interview Schedule for Children was administered to a group of 1891 youth ages 4 to 17 and their caregivers in Puerto Rico to determine DSM-IV symptoms and diagnoses. Asthma diagnosis and having had an asthma attack were assessed by parental report. A diagnosis of asthma was associated with having any depressive disorder and one symptom of separation anxiety. An asthma attack was associated with any depressive disorder and any anxiety disorder and, more specifically, with separation anxiety disorder, major depressive disorder, and symptoms of depression, separation anxiety, and generalized anxiety. Possible explanations for the findings are discussed.     

A randomised controlled trial to test the feasibility of a collaborative care model for the management of depression in older people

BACKGROUND: Depression is the most common mental health disorder in people aged over 65 years. Late-life depression is associated with chronic illness and disability. AIM: To investigate the feasibility of a collaborative care model for depression in older people in a primary care setting. DESIGN OF STUDY: Randomised controlled trial with 16-weeks follow up. SETTING: A primary care trust in Manchester. METHOD: Participants were 105 people aged 60 years or older who scored 5 or more on the Geriatric Depression Scale; 53 were randomly allocated to an intervention group and 52 to a usual care group. The intervention group received care managed by a community psychiatric nurse who delivered an intervention comprising a facilitated self-help programme with close liaison with primary care professionals and old-age psychiatry according to a defined protocol. The usual care group received usual GP care. A nested qualitative study explored the views of the health professionals and patients regarding the acceptability and effectiveness of the intervention. RESULTS: The main outcome measure was recovery from depression. Patients in the intervention group were less likely to suffer from major depressive disorder at follow up compared with usual care (0.32, 95% confidence = interval = 0.11 to 0.93, P = 0.036). The qualitative component of the study demonstrated the acceptability of the intervention to patients. CONCLUSION: A model of collaborative care for older people with depression, used in a primary care setting with a facilitated self-help intervention is more effective than usual GP care. This study demonstrates that the implementation of a collaborative care model is feasible in UK primary care and that the intervention is effective and acceptable to patients.     

Subpopulations of motor and sensory neurons respond differently to brain-derived neurotrophic factor depending on the presence of the skeletal muscle.

The aim of our study was to assess the ability of brain-derived neurotrophic factor (BDNF) to rescue motor and sensory neurons from programmed cell death. It is clearly demonstrated that the administration of a single injection of a putative neurotrophic factor to mouse embryos in utero on embryonic day (E) 14.5 is sufficient to significantly reduce the death of motor neurons when assessed on E18.5. However, the trophic requirements of somatic neurons have not been unequivocally determined in a mammalian species in vivo. Indeed, the unexpectedly high numbers of surviving neurons observed in neurotrophin and tyrosine kinase receptor knockout mice are probably the consequence of functional redundancy between the neurotrophins and their receptors. We studied spinal cord and facial motor nucleus neurons and proprioceptive neurons in the dorsal root ganglion and mesencephalic nucleus. The action of BDNF was assessed in wild-type fetuses to gain insight into its ability to rescue neurons from naturally occurring programmed cell death. In addition, we used Myf5(-/-):MyoD(-/-) embryos, which completely lack skeletal musculature, to assess the ability of BDNF to rescue neurons from excessively occurring programmed cell death. We found that BDNF differentially rescued neurons from naturally vs. excessively occurring cell death and that its ability to do so varied among neuronal subpopulations.     

Nasal mucosal gene expression in patients with allergic rhinitis with and without nasal polyps

BACKGROUND: Nasal polyps are a common problem that is difficult to diagnose and treat, in part because the cause of nasal polyposis is unknown. Although information on the pathogenesis of polyposis is lacking, there are reports suggesting that a genetic predisposition underlies this disorder. OBJECTIVE: We sought to better understand the basis of nasal polyposis associated with allergic rhinitis. We hypothesize that the expression of unique genes is associated with the nasal polyposis phenotype. METHODS: We examined 12000 human genes transcribed in the nasal mucosa of patients with allergic rhinitis with and without nasal polyps. Biopsy specimens of the mucosa of patients with and without polyps were obtained after the patients refrained from the use of topical or systemic steroid therapy for 2 weeks. RESULTS: Thirty-four genes were differentially expressed between the patient groups, including those for inflammatory molecules and putative growth factors. The greatest differential expression identified by the array analysis was for a group of genes associated with neoplasia, including mammaglobin, a gene transcribed 12-fold higher in patients with polyps compared with control patients with rhinitis alone. Quantitative RT-PCR confirmed this differential expression and documented that the number of mammaglobin mRNA copies is actually 64-fold greater in tissues of patients with polyps versus control patients. The specificity of mammaglobin protein expression was evaluated by means of immunohistochemistry, which showed specific staining in nasal polyp mucosal goblet cells only in patients with polyps. CONCLUSION: These data suggest that nasal polyposis involves deregulated cell growth, using gene activation in some ways similar to a neoplasm. In addition, mammaglobin, a gene of unknown function associated with breast neoplasia, might be related to polyp growth.     

Histological studies of the elimination of Leishmania enriettii from skin lesions in the guinea-pig.

Nineteen guinea-pigs were each inoculated intradermally with 10(6) amastigotes of Leishmania enriettii, and the development of the lesions was followed from Weeks 4 to 10 with a view to elucidating the histological mechanisms involved with the elimination of parasites. Electron microscopic observations were made in 1 animal. Extensive necrosis of the parasite-laden macrophages was observed in 7 out of 7 animals at 4 and 5 weeks. In the ulcerated core of the lesion at 4 weeks no intact macrophages could be identified. Very many amastigotes were extracellular. Others were present in the cytoplasm of residual macrophages the cell walls of which had disintegrated. Necrosis was less marked at 8 weeks and absent in the resolving lesions at 10 weeks. Signs of stimulation or maturation of macrophages were only apparent when parasites were few. At 4 weeks macrophages were almost all of the non-stimulated form, but cytological evidence of activation became progressively more definite and widespread from 5 to 8 weeks, starting at the periphery of the lesion. Ultrastructural observations of amastigotes suggested that there might be more than one mechanism of degradation. It appeared that the majority of parasites were released through necrosis and discharged through the ulcer, and that intracellular degradation of the remaining parasites was important mainly in the later phase before resolution. The first phase was associated mainly with plasma-cell production, the second mainly with lymphocytes.