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1.
Nat Rev Immunol ; 12(8): 607-14, 2012 07 20.
Article in English | MEDLINE | ID: mdl-22814509

ABSTRACT

Given the limitations of antiretroviral therapy and recent advances in our understanding of HIV persistence during effective treatment, there is a growing recognition that a cure for HIV infection is both needed and feasible. The International AIDS Society convened a group of international experts to develop a scientific strategy for research towards an HIV cure. Several priorities for basic, translational and clinical research were identified. This Opinion article summarizes the group's recommended key goals for the international community.


Subject(s)
Antiretroviral Therapy, Highly Active/methods , HIV Infections/drug therapy , HIV/physiology , HIV Infections/virology , Humans , Virus Latency/drug effects , Virus Replication/drug effects
2.
J Reconstr Microsurg ; 28(3): 149-54, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22131106

ABSTRACT

Free flap monitoring is essential to the early detection of compromise thereby increasing the chance of successful salvage surgery. Many alternatives to classical clinical monitoring have been proposed. This study seeks to investigate a relatively new monitoring technology: near infrared spectroscopy (NIRS). Patients were recruited prospectively to the study from a single center. During the research period, 10 patients underwent reconstruction with a free deep inferior epigastric perforator flap (DIEP). Measurements of flap perfusion were taken using NIRS in the preoperative and intraoperative phases and postoperatively for 72 hours. NIRS showed characteristic changes in all cases which returned to theater for pedicle compromise. In these cases, NIRS identified pedicle compromise prior to clinical identification. There were no false-positives. NIRS accurately identified all compromised flaps in our study. In most cases, there was an evidence of changes in oxygen saturation on NIRS prior to clinical observation. Further research, ideally double blind randomized control trials with large sample groups would be required to definitively establish NIRS as an ideal flap monitoring modality.


Subject(s)
Epigastric Arteries/transplantation , Mammaplasty/methods , Spectroscopy, Near-Infrared/methods , Surgical Flaps/blood supply , Tissue Survival , Abdominal Muscles/blood supply , Abdominal Muscles/transplantation , Adult , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Cohort Studies , Epigastric Arteries/surgery , Female , Follow-Up Studies , Graft Rejection/prevention & control , Humans , Mammaplasty/adverse effects , Mastectomy/adverse effects , Mastectomy/methods , Microcirculation/physiology , Middle Aged , Monitoring, Physiologic/instrumentation , Monitoring, Physiologic/methods , Oxygen Consumption/physiology , Postoperative Care/methods , Prospective Studies , Reproducibility of Results , Sensitivity and Specificity , Statistics, Nonparametric , United Kingdom
3.
PLoS One ; 6(3): e14759, 2011 Mar 14.
Article in English | MEDLINE | ID: mdl-21423727

ABSTRACT

BACKGROUND: Ventilator-associated pneumonia is the most prevalent acquired infection of patients on intensive care units and is associated with considerable morbidity and mortality. Evidence suggests that an improved understanding of the composition of the biofilm communities that form on endotracheal tubes may result in the development of improved preventative strategies for ventilator-associated pneumonia. METHODOLOGY/PRINCIPAL FINDINGS: The aim of this study was to characterise microbial biofilms on the inner luminal surface of extubated endotracheal tubes from ICU patients using PCR and molecular profiling. Twenty-four endotracheal tubes were obtained from twenty mechanically ventilated patients. Denaturing gradient gel electrophoresis (DGGE) profiling of 16S rRNA gene amplicons was used to assess the diversity of the bacterial population, together with species specific PCR of key marker oral microorganisms and a quantitative assessment of culturable aerobic bacteria. Analysis of culturable aerobic bacteria revealed a range of colonisation from no growth to 2.1×10(8) colony forming units (cfu)/cm(2) of endotracheal tube (mean 1.4×10(7) cfu/cm(2)). PCR targeting of specific bacterial species detected the oral bacteria Streptococcus mutans (n = 5) and Porphyromonas gingivalis (n = 5). DGGE profiling of the endotracheal biofilms revealed complex banding patterns containing between 3 and 22 (mean 6) bands per tube, thus demonstrating the marked complexity of the constituent biofilms. Significant inter-patient diversity was evident. The number of DGGE bands detected was not related to total viable microbial counts or the duration of intubation. CONCLUSIONS/SIGNIFICANCE: Molecular profiling using DGGE demonstrated considerable biofilm compositional complexity and inter-patient diversity and provides a rapid method for the further study of biofilm composition in longitudinal and interventional studies. The presence of oral microorganisms in endotracheal tube biofilms suggests that these may be important in biofilm development and may provide a therapeutic target for the prevention of ventilator-associated pneumonia.


Subject(s)
Bacteria/growth & development , Bacteria/genetics , Biofilms , Intubation, Intratracheal/adverse effects , Pneumonia, Ventilator-Associated/microbiology , Adult , Aged , Algorithms , Cluster Analysis , DNA, Bacterial/genetics , Denaturing Gradient Gel Electrophoresis , Female , Humans , Male , Middle Aged , Polymerase Chain Reaction , Porphyromonas gingivalis/genetics , RNA, Ribosomal, 16S/genetics , Species Specificity , Templates, Genetic , Young Adult
4.
J Plast Reconstr Aesthet Surg ; 62(5): 589-94, 2009 May.
Article in English | MEDLINE | ID: mdl-19233756

ABSTRACT

A syndrome now known as Ehlers-Danlos, comprising laxity and fragility of the skin associated with hypermobility of the large joints, was published in 1892 by Tschernogobow. Ehlers-Danlos type VIIA is an extremely rare form of the syndrome. While the UK-based Ehlers-Danlos Support Group recommends that the surgical management of patients with Ehlers-Danlos VIIA should be carried out in conjunction with a plastic surgeon, there is nothing in the plastic surgery literature regarding this syndrome. The management of patients suffering from Ehlers-Danlos VIIA is highly complex, as a result of the breadth of genetic and phenotypic presentations, and resulting complications. We present a review of the literature regarding this syndrome and, in particular, the surgical problems that may be encountered. A case report outlining our experience of successfully managing this condition is also presented.


Subject(s)
Ehlers-Danlos Syndrome/surgery , Plastic Surgery Procedures/methods , Child, Preschool , Cicatrix/pathology , Dermatologic Surgical Procedures , Ehlers-Danlos Syndrome/genetics , Ehlers-Danlos Syndrome/pathology , Humans , Male , Scoliosis/surgery , Skin/pathology , Wound Healing
6.
J Virol ; 78(18): 9740-9, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15331707

ABSTRACT

Interleukin-7 (IL-7) regulates T-cell homeostasis, and its availability is augmented in lymphopenic hosts. Naive CD8+ T cells transferred to lymphopenic mice acquire a memory-like phenotype, raising the possibility that IL-7 is the biological mediator of this effect. Here, we provide direct evidence that IL-7 induces the acquisition of memory-cell markers not only in CD8+ T cells but also in CD4+ T-cell subsets in immune-competent Indian rhesus macaques. The increase of these memory-like populations was dependent on the dose of the cytokine, and these cells were found in the blood as well as secondary lymphoid organs. Memory-like CD4+ and CD8+ T cells acquired the ability to secrete tumor necrosis factor alpha and, to a lesser extent, gamma interferon following stimulation with a cognate antigen. The phenotypic change observed in naive T cells was promptly reversed after discontinuation of IL-7. Importantly, IL-7 induced cycling of both CD4+ and CD8+ central memory and effector memory T cells, demonstrating its contribution to the maintenance of the entire T-cell pool. Thus, IL-7 may be of benefit in the treatment of iatrogenic or virus-induced T-cell depletion.


Subject(s)
CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/drug effects , Interleukin-7/pharmacology , Animals , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Cell Division/drug effects , Immunologic Memory , Ki-67 Antigen/biosynthesis , Kinetics , Lymph Nodes/cytology , Lymph Nodes/drug effects , Lymph Nodes/immunology , Lymphopenia/drug therapy , Lymphopenia/immunology , Lymphopenia/pathology , Macaca mulatta , Phenotype , Recombinant Proteins/pharmacology , Tumor Necrosis Factor-alpha/biosynthesis
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