Combined Superficial and Deep Serratus Plane Block With Bupivacaine, Dexamethasone, and Clonidine in the Treatment of a Patient With Postmastectomy Pain Syndrome: A Case Report.

Postmastectomy pain syndrome poses a significant treatment challenge. We present the case of a 42-year-old woman who presented to our pain clinic with a 16-month history of postmastectomy pain. We performed a combined superficial and deep serratus plane block using bupivacaine, dexamethasone, and clonidine. At 1-month follow-up, the patient had 100% pain relief. At 2-month follow-up, her pain was 5/10. The block was repeated with the same drugs at 3 months with similar pain relief. This case illustrates the utility of a combined superficial and deep serratus plane block in postmastectomy pain syndrome with a possible benefit from added dexamethasone and clonidine.

Characterization of Mycobacterium tuberculosis-Specific Cells Using MHC Class II Tetramers Reveals Phenotypic Differences Related to HIV Infection and Tuberculosis Disease.

A major challenge for the development of an effective vaccine against tuberculosis (TB) is that the attributes of protective CD4+ T cell responses are still elusive for human TB. Infection with HIV type 1 is a major risk factor for TB, and a better understanding of HIV-induced alterations of Mycobacterium tuberculosis-specific CD4+ T cells that leads to failed host resistance may provide insight into protective T cell immunity to TB. A total of 86 participants from a TB-endemic setting, either HIV-infected or uninfected and with latent or active TB (aTB), were screened using M.tuberculosis-specific MHC class II tetramers. We examined the phenotype as well as function of ex vivo M. tuberculosis-specific tetramer+CD4+ T cells using flow cytometry. The numbers of M. tuberculosis-specific tetramer+CD4+ T cells were relatively well maintained in HIV-infected persons with aTB, despite severe immunodeficiency. However, although HIV-uninfected persons with latent TB infection exhibited ex vivo M. tuberculosis-specific CD4+ T cells predominantly of a CXCR3+CCR6+CCR4- (Th1*) phenotype, aTB or HIV infection was associated with a contraction of this subset. Nevertheless, in individuals with aTB and/or HIV infection, circulating ex vivo M. tuberculosis-specific CD4+ T cells did not display defects in exhaustion or polyfunctionality compared with healthy HIV-uninfected individuals with latent TB infection. Collectively, these data suggest that increased susceptibility to TB disease could be related to a loss of circulating Th1* CD4+ T cells rather than major changes in the number or function of circulating CD4+ T cells.

HIV Skews the Lineage-Defining Transcriptional Profile of Mycobacterium tuberculosis-Specific CD4+ T Cells.

HIV-infected persons are at greater risk of developing tuberculosis (TB) even before profound CD4 loss occurs, suggesting that HIV alters CD4(+) T cell functions capable of containing bacterial replication. An effective immune response to Mycobacterium tuberculosis most likely relies on the development of a balanced CD4 response, in which distinct CD4(+) Th subsets act in synergy to control the infection. To define the diversity of M. tuberculosis-specific CD4(+) Th subsets and determine whether HIV infection impacts such responses, the expression of lineage-defining transcription factors T-bet, Gata3, RORγt, and Foxp3 was measured in M. tuberculosis-specific CD4(+) T cells in HIV-uninfected (n = 20) and HIV-infected individuals (n = 20) with latent TB infection. Our results show that, upon 5-d restimulation in vitro, M. tuberculosis-specific CD4(+) T cells from healthy individuals have the ability to exhibit a broad spectrum of Th subsets, defined by specific patterns of transcription factor coexpression. These transcription factor profiles were skewed in HIV-infected individuals where the proportion of T-bet(high)Foxp3(+) M. tuberculosis-specific CD4(+) T cells was significantly decreased (p = 0.002) compared with HIV-uninfected individuals, a change that correlated inversely with HIV viral load (p = 0.0007) and plasma TNF-α (p = 0.027). Our data demonstrate an important balance in Th subset diversity defined by lineage-defining transcription factor coexpression profiles that is disrupted by HIV infection and suggest a role for HIV in impairing TB immunity by altering the equilibrium of M. tuberculosis-specific CD4(+) Th subsets.

Evaluating potential T-cell epitope peptides for detecting HIV-specific T cell responses in a highly diverse HIV-1 epidemic from Cameroon.

HIV genetic diversity is a major obstacle for vaccine development. To define whether potential T-cell epitope (PTE) peptide usage improves the detection of T cell responses in a highly diverse HIV-1 epidemic, we compared the magnitude, breadth and depth of group M PTE peptide responses to consensus M peptides in Gag and Nef proteins. Gag PTE responses were detected at a higher magnitude, more Nef PTE responses were detected at a cohort (but not individual) level and depth was detected in both Gag and Nef responses.

T regulatory cells control susceptibility to invasive pneumococcal pneumonia in mice.

Streptococcus pneumoniae is an important human pathogen responsible for a spectrum of diseases including pneumonia. Immunological and pro-inflammatory processes induced in the lung during pneumococcal infection are well documented, but little is known about the role played by immunoregulatory cells and cytokines in the control of such responses. We demonstrate considerable differences in the immunomodulatory cytokine transforming growth factor (TGF)-ß between the pneumococcal pneumonia resistant BALB/c and susceptible CBA/Ca mouse strains. Immunohistochemistry and flow cytometry reveal higher levels of TGF-ß protein in BALB/c lungs during pneumococcal pneumonia that correlates with a rapid rise in lung Foxp3(+)Helios(+) T regulatory cells. These cells have protective functions during pneumococcal pneumonia, because blocking their induction with an inhibitor of TGF-ß impairs BALB/c resistance to infection and aids bacterial dissemination from lungs. Conversely, adoptive transfer of T regulatory cells to CBA/Ca mice, prior to infection, prolongs survival and decreases bacterial dissemination from lungs to blood. Importantly, strong T regulatory cell responses also correlate with disease-resistance in outbred MF1 mice, confirming the importance of immunoregulatory cells in controlling protective responses to the pneumococcus. This study provides exciting new evidence for the importance of immunomodulation during pulmonary pneumococcal infection and suggests that TGF-ß signalling is a potential target for immunotherapy or drug design.

Molecular analysis of ceruloplasmin in a South African cohort presenting with oesophageal cancer.

Oesophageal cancer (OC) is a disease characterized by the development of malignant tumors in the epithelial cells lining the oesophagus. It demonstrates marked ethnic variation, with squamous cell carcinoma (SCC) being more prevalent in the Black population and adenocarcinoma (ADC) occurring more often in Caucasians. The etiology of this complex disease has been attributed to a variety of factors, including an excess of iron (resulting in increased tumourigenesis), oesophageal injury and inflammation (due in part to Barrett's oesophagus and smoking among others). The aim of this study was to determine if genetic variations identified in the ceruloplasmin (CP) gene (implicated in iron homeostasis) contribute to OC pathogenesis or susceptibility. The study cohort consisted of 96 unrelated OC patients from the Black Xhosa-speaking South African population and 88 population-matched control individuals. The promoter and coding regions of the CP gene were analyzed for DNA sequence variation using heteroduplex single-strand conformation polymorphism (HEX-SSCP) analysis, restriction fragment length polymorphism (RFLP) analysis and semi-automated bidirectional DNA sequencing analysis. Fourteen previously described and four novel variants were identified. Statistically significant associations were revealed for two of the novel variants with OC in this study and could, therefore, potentially contribute to disease susceptibility. In silico analysis of the region of the promoter spanning the identified variants sought to identify putative transcription factor binding sites (TFBSs) that could possibly regulate the expression of CP. To our knowledge, this is the first study to examine CP with respect to OC in the Black South African population.