Manual therapy and eccentric exercise in the management of Achilles tendinopathy

Chronic Achilles tendinopathy (AT) is an overuse condition seen among runners. Eccentric exercise can decrease pain and improve function for those with chronic degenerative tendon changes; however, some individuals have continued pain requiring additional intervention. While joint mobilization and manipulation has not been studied in the management in Achilles tendinopathy, other chronic tendon dysfunction, such as lateral epicondylalgia, has responded well to manual therapy (MT). Three runners were seen in physical therapy (PT) for chronic AT. They were prescribed eccentric loading exercises and calf stretching. Joint mobilization and manipulation was implemented to improve foot and ankle mobility, decrease pain, and improve function. Immediate within-session changes in pain, heel raise repetitions, and pressure pain thresholds (PPT) were noted following joint-directed MT in each patient. Each patient improved in self-reported function on the Achilles tendon specific Victorian Institute for Sport Assessment questionnaire (VISA-A), pain levels, PPT, joint mobility, ankle motion, and single-leg heel raises at discharge and 9-month follow-up. The addition of MT directed at local and remote sites may enhance the rehabilitation of patients with AT. Further research is necessary to determine the efficacy of adding joint mobilization to standard care for AT.

Level of Evidence: Case series. Therapy, Level 4.     

Influenza and Bacterial Superinfection: Illuminating the Immunologic Mechanisms of Disease

Seasonal influenza virus infection presents a major strain on the health care system. Influenza virus infection has pandemic potential, which was repeatedly observed during the last century. Severe disease may occur in the young, in the elderly, in those with preexisting lung disease, and in previously healthy individuals. A common cause of severe influenza pathogenesis is superinfection with bacterial pathogens, namely, Staphylococcus aureus and Streptococcus pneumoniae. A great deal of recent research has focused on the immune pathways involved in influenza-induced susceptibility to secondary bacterial pneumonia. Both innate and adaptive antibacterial host defenses are impaired in the context of preceding influenza virus infection. The goal of this minireview is to highlight these findings and synthesize these data into a shared central theme of pathogenesis.     

Non‐muscle invasive bladder cancer and bacillus Calmette‐Guerin treatment: a review of the literature

Bladder cancer is the second most common urological cancer in the UK, with over 10 000 cases diagnosed annually. With 80% of urothelial bladder cancers being non‐muscle invasive, it is important to understand the treatments available. This review aims to identify and review the literature regarding bacillus Calmette‐Guerin (BCG) treatment. An integrative‐based review was conducted to generate a broad overview of the existing knowledge for BCG treatment. An open search of online databases was conducted to identify articles published in English from the earliest date available to September 2013, using key terms related to BCG. A significant number of articles were identified. To narrow the results and identify the most relevant articles, the search terms were cross‐referenced. The resulting articles were then reviewed using the critical appraisal skills programme framework. The tools provided by CASP give a systematic, transparent and rigorous approach to the quality assessment of research studies. The research articles were then categorized under the following headings: side effects, including local, systemic and age; quality of life; and attrition. The major conclusion from this literature review is that BCG treatment, when given through an induction and maintenance regime, significantly reduces the risk of progression and recurrence. However, there are potential side effects which the patient and the nurse need to be aware. This review also highlighted that there is a lack of research from the UK and that there is a paucity of research showing why patients withdraw from BCG treatment     

Sudden Onset Vision Loss in an 8‐year‐old Female with McCune–Albright Syndrome

Abstract: We describe a case of an 8‐year‐old girl with large irregular café au lait macules on the right cheek and right lower extremity presenting with sudden onset vision loss and found to have polyostotic fibrous dysplasia on imaging. The classic triad of McCune–Albright syndrome is discussed along with the importance of recognition in patients with partial presentation. This case also highlights a rare and potentially devastating neurologic complication of McCune–Albright syndrome, as well as the need for early diagnosis and continual surveillance in these patients.     

Immune and functional role of nitric oxide in a mouse model of respiratory syncytial virus infection

BACKGROUND: Respiratory syncytial virus (RSV) infection of respiratory epithelial cell cultures increases expression of inducible nitric oxide synthase (iNOS). The present study was designed to evaluate both the effect of RSV infection on expression of iNOS and the role of NO in the host responses to RSV infection in vivo. METHODS: RSV infection was performed by nasal inoculation of BALB/c mice (6-8 weeks old). Total cell and differential counts were measured in bronchoalveolar lavage (BAL) fluid. Lung nitrates were measured in BAL fluid by use of the Greiss reaction, and cytokines were measured by enzyme-linked immunosorbent assay. Lung hyperresponsiveness to methacholine was measured by use of a Buxco unrestrained whole-body plethysmograph. RESULTS: RSV infection increased levels of lung nitrites, levels of iNOS protein and activity, and levels of iNOS mRNA. RSV infection resulted in recruitment of neutrophils and lymphocytes into the lungs, enhanced levels of interferon (IFN)-gamma, and increased airway hyperresponsiveness (AHR). Treatment with iNOS inhibitors (2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine and N-nitro-L-arginine methyl ester) increased RSV titers in the lungs yet reduced lung inflammation and RSV-induced AHR. Inhibition of iNOS activity with either agent did not significantly alter levels of IFN-gamma or interleukin-4 in the lungs. CONCLUSIONS: The results of the present study suggest that RSV-induced production of NO participates in complex host responses and may mediate important aspects of the clinical disease.     

Haematological reconstitution following high dose and supralethal chemo-radiotherapy using stored, non-cryopreserved autologous bone marrow

S ummary . Eighteen patients with small cell carcinoma of the lung received high dose cyclophosphamide (180–200 mg/kg) intensification following five pulses of 'CHOP' chemotherapy (cyclophosphamide 750 mg/m² i.v., adriamycin 50 mg/m² i.v., vincristine 1·4 mg/m² i.v., prednisolone 40 mg orally for 5 d). They received infusions of autologous bone marrow which had been stored at 4°C for 34 h. Pancytopenia was predictable in onset and its duration acceptable. Recovery of neutrophils to greater than 1·0 × 10⁹/l was achieved in 17·5 ± 0·9 d (mean ± SEM) and platelets to greater than 100 × 10⁹/l in 17·5 ± 0·8 d. Four patients with acute myeloid leukaemia in complete remission received intensification with the supralethal combination of cyclophosphamide and total body irradiation followed by infusion of autologous marrow which had been stored at 4°C for 54 h. Haematological reconstitution in these patients was acceptable but slower (greater than 1·0 × 10⁹/l neutrophils between days 26 and 40; greater than 20 × 10⁹/l platelets between days 23 and 77). Except in one case, normal peripheral counts were attained in all patients.
It is concluded that bone marrow stored at 4°C for up to 54 h is a simple and practical source of viable stem cells which have the capacity for acceptable haematological reconstitution.     

Tissue-specific roles of Axin2 in the inhibition and activation of Wnt signaling in the mouse embryo

Axin proteins are key negative regulators of the canonical Wnt signal transduction pathway. Although Axin2 null mice are viable, we identified an unusual ENU-induced recessive allele of Axin2, canp, that causes midgestation lethality in homozygotes. We show that the Axin2(canp) mutation is a V26D substitution in an invariant N-terminal sequence motif and that the Axin2(canp) protein is more stable than wild type. As predicted for an increased level of a negative regulator, the Axin2(canp) mutation leads to decreased Wnt signaling in most tissues, and this can account for most of the morphological phenotypes of Axin2(canp) mutants. In contrast, there is a paradoxical increase in canonical Wnt activity in the late primitive streak of all Axin2(canp) mutant embryos that is associated with the formation of an ectopic tail in some mutants. Treatment of wild-type embryos with an inhibitor of Tankyrase that stabilizes Axin proteins also causes inhibition of Wnt signaling in anterior regions of the embryo and a gain of Wnt signaling in the primitive streak. The results indicate that although increased stability of Axin2 leads to a loss of canonical Wnt signaling in most tissues, stabilized Axin2 enhances Wnt pathway activity in a specific progenitor population in the late primitive streak.     

Infant formula alters surfactant protein A (SP-A) and SP-B expression in pulmonary epithelial cells

Surfactant proteins A (SP-A) and SP-B are critical in the ability of pulmonary surfactant to reduce alveolar surface tension and provide innate immunity. Aspiration of infant milk formula can lead to lung dysfunction, but direct effects of aspirated formula on surfactant protein expression in pulmonary cells have not been described. The hypothesis that infant formula alters surfactant protein homeostasis was tested in vitro by assessing surfactant protein gene expression in cultured pulmonary epithelial cell lines expressing SP-A and SP-B that were transiently exposed (6 hr) to infant formula. Steady-state levels of SP-A protein and mRNA and SP-B mRNA in human bronchiolar (NCI-H441) and mouse alveolar (MLE15) epithelial cells were reduced in a dose-dependent manner 18 hr after exposure to infant formula. SP-A mRNA levels remained reduced 42 hr after exposure, but SP-B mRNA levels increased 10-fold. Neither soy formula nor non-fat dry milk affected steady-state SP-A and SP-B mRNA levels; suggesting a role of a component of infant formula derived from cow milk. These results indicate that infant formula has a direct, dose-dependent effect to reduce surfactant protein gene expression. Ultimately, milk aspiration may potentially result in a reduced capacity of the lung to defend against environmental insults.