Effect of long-term calcitonin administration on steroid-induced osteoporosis after cardiac transplantation.

BACKGROUND: Early, rapid bone loss and fractures after cardiac transplantation are well-documented complications of steroid administration; therefore, we undertook this study on the effects of long-term calcitonin on steroid-induced osteoporosis. METHODS: Twenty-three heart transplant recipients on maintenance immunosuppression with cyclosporine, mycophenolate mofetil and prednisone were retrospectively studied. All patients received long-term prophylactic treatment with elemental calcium and vitamin D. Twelve (52.2%) patients also received long-term intranasal salmon calcitonin, whereas 11 (47.8%) received none. Bone mineral density and vertebral fractures were assessed at yearly intervals. Statistical comparisons between each group's bone loss during the first year and in the early (1 to 3 years), intermediate (4 to 6 years) and late (7+ years) post-transplantation periods were done. RESULTS: Lumbar spine bone loss was significant during the early follow-up period in the group not receiving calcitonin (0.744 +/- 0.114 g/cm(2) vs 0.978 +/- 0.094 g/cm(2) [p = 0.002]). The calcitonin group showed bone mineral density (BMD) levels within normal average values throughout the study period. BMD increased in the no-calcitonin group during the intermediate (4 to 6 years) and late (7+ years) follow-up periods, with values approaching normal average and no significant difference between the 2 groups (0.988 +/- 0.184 g/cm(2) vs 0.982 +/- 0.088 g/cm(2) [p = 0.944] and 0.89 +/- 0.09 g/cm(2) vs 1.048 +/- 0.239 g/cm(2) [p = 0.474], respectively). CONCLUSIONS: Prophylactic treatment with intranasal salmon calcitonin prevents rapid bone loss associated with high-dose steroids early after cardiac transplantation. Long-term administration does not seem warranted in re-establishing BMD.     

Regulation of the small GTPase RhoA by syndecan-4 and integrins in focal adhesion formation

Introduction The transmembrane heparan sulfate proteoglycan, syndecan‐4, and integrins are important receptors for focal adhesion (FA) formation on fibronectin (FN) substrates. The small GTPase RhoA is also known to regulate FA and stress fiber formation. It has been suggested that syndecan‐4 and integrins co‐operatively regulate the assembly of FA in a Rho‐dependent manner, but the mechanism is unclear. Here, we examined the function of RhoA and the Rho effector kinases ROCKs in syndecan‐4 signalling on the process of FA formation and the possible mechanism by which syndecan‐4 may regulate RhoA activity. Methods Primary rat embryonic fibroblasts (REFs) were seeded on FN or ‘RGD’‐containing integrin‐binding domain of FN and lysed at various time points. The amount of active form of RhoA in each lysate was analysed by pull‐down experiments. Results and discussion The relative activities of RhoA showed one peak in the process of FA formation on FN, whereas no peak was obtained on the integrin‐binding domain. The one peak of RhoA activity on integrin‐binding domain was restored by addition of heparin‐binding domain into medium. These results suggested that a signal through syndecan‐4 link to the Rho pathway. Both ROCK‐I and ‐II isozymes were present in REF cell lysates and each could be specifically immunoprecipitated. The ROCK kinase activities in immunoprecipitates were analysed using GST‐myosin light chain as a substrate. The amount of ROCK‐I and ‐II activities changed through the adhesion process on FN and appeared to be independently regulated. Therefore, one or both ROCKs may be downstream of a syndecan‐4‐mediated signalling response through RhoA. The core protein of syndecan‐4 can directly bind to and activate PKC‐α. We found that PKC‐α could phosphorylate Rho‐Guanine Nucleotide Dissociation Inhibitor (GDI) in vitro. It has been suggested that PKC‐α‐mediated phosphorylation of Rho GDI stimulates GDI dissociation, thereby resulting in Rho activation. It is possible that syndecan‐4 regulates Rho/ROCK pathway through PKC‐α activation on the process of FA formation.     

Competing causes of death and second primary tumors in patients with locoregionally advanced head and neck cancer treated with chemoradiotherapy.

PURPOSE: The purpose of this retrospective analysis was to evaluate the emergence of second primary malignancies and the contribution of different causes of death to the outcome of patients with locoregionally advanced head and cancer receiving primary chemoradiotherapy. EXPERIMENTAL DESIGN: We studied 324 patients with stage IV squamous cell head and neck cancer who were enrolled on five consecutive multicenter Phase II studies of concurrent chemoradiotherapy. All of the regimens included concurrent 5-fluorouracil and hydroxyurea on an alternate week schedule with radiotherapy, either alone (FHX) or with cisplatin (C-FHX) or paclitaxel (T-FHX). The cumulative incidence of second primary tumors or death from any cause was estimated using methods of competing risk analysis. RESULTS: Median follow-up of surviving patients was 5.2 years (2-10.6 years). The 5-year overall survival and progression-free survival of the cohort were 46% and 65%, respectively. Causes of death and median time of occurrence were as follows: disease (n = 88; 1.5 years), treatment-associated acute or late complications (n = 30; 4 months), second primary tumors (n = 18; 3.5 years), comorbidities (n = 41; 1.9 years), and unknown (n = 20; 5.1 years). Predominant causes of death from comorbidities were cardiac and respiratory illnesses. Twenty-six patients (8%) developed a second primary tumor at a median time of 2.8 years (4 months to 10 years). The cumulative incidence of second primary tumors was 5%, 7%, and 13% at 3, 5, and 10 years, respectively. The most frequent site of second primaries was the lung (n = 13), followed by the esophagus (n = 3) and head and neck (n = 2) CONCLUSIONS: Patients with locoregionally advanced head and neck cancer treated with concurrent chemoradiotherapy are potentially curable but face significant risks of mortality from causes other than disease progression. Ameliorating toxicity, and implementing secondary screening and chemoprevention strategies are major goals in the management of head and neck cancer.     

Biomechanical diagnosis of keratoconus: evaluation of the keratoconus match index and the keratoconus match probability

Purpose:  To evaluate the diagnostic capacity of the Ocular Response Analyser’s keratoconus match index (KMI) and keratoconus match probability (KMP) classification in a sample of keratoconus (KC) patients. Methods: Keratoconus match index and KMP from 114 KC eyes, randomly selected from 114 patients with bilateral keratoconus (KCG), were compared with the corresponding ones from 109 normal eyes (CG). Keratoconus match index’s predictive accuracy was assessed by receiver operating curves (ROC). Keratoconus match probability level of agreement was evaluated at the different KC stages of the Amsler–Krumeich classification. Correlations were estimated with topographic keratoconus classification (TKC), keratoconus index (KI), index of surface variance (ISV), vertical asymmetry (IVA), height asymmetry (IHA), height decentration (IHD), minimal radius (Rmin), central corneal thickness (CCT), thinnest corneal thickness (TCT) mean keratometry (Km) and intraocular pressure (IOPg). Results: Mean KMI in KCG and CG was 0.20 ± 0.38 and 0.98 ± 0.25, respectively (p < 0.01). Significant KMI differences (p < 0.01) were detected in different KC groups [range: 0.62 ± 0.38 (KC 1), ?0.62 ± 0.04 (KC 4)]. Significant correlation was detected between KC staging and KMI (r = ?0.56, p < 0.0001). Keratoconus match probability identified 22.03% of the CG eyes as suspect. Moreover, KMP identified 7.01% and 23.68% of the KCG eyes as normal and suspect, respectively. Receiver operating curves analysis for KMI parameter indicated a predictive accuracy of 97.7% (cut‐off point: 0.512, sensitivity: 91.18%, specificity: 94.34%). Conclusions: Keratoconus match index seems to be a reliable index in keratoconus diagnosis and staging. Keratoconus match probability identifies a significant percentage of topographically defined KC and CG eyes as suspect. Diagnostic capacity of these novel indexes needs to be further explored.     

Magnetic Metal Oxide-Based Photocatalysts with Integrated Silver for Water Treatment

In this review, the most recent advances in the field of magnetic composite photocatalysts with integrated plasmonic silver (Ag) is presented, with an overview of their synthesis techniques, properties and photocatalytic pollutant removal applications. Magnetic attributes combined with plasmonic properties in these composites result in enhancements for light absorption, charge-pair generation-separation-transfer and photocatalytic efficiency with the additional advantage of their facile magnetic separation from water solutions after treatment, neutralizing the issue of silver’s inherent toxicity. A detailed overview of the currently utilized synthesis methods and techniques for the preparation of magnetic silver-integrated composites is presented. Furthermore, an extended critical review of the most recent pollutant removal applications of these composites via green photocatalysis technology is presented. From this survey, the potential of magnetic composites integrated with plasmonic metals is highlighted for light-induced water treatment and purification. Highlights: (1) Perspective of magnetic properties combined with plasmon metal attributes; (2) Overview of recent methods for magnetic silver-integrated composite synthesis; (3) Critical view of recent applications for photocatalytic pollutant removal.     

Intravenous Tobramycin and Metronidazole as an Adjunct to Corticosteroids in Acute, Severe Ulcerative Colitis

Objectives : The aim of this study was to evaluate the role of metronidazole and tobramycin as an adjunct to corticosteroids in acute, severe ulcerative colitis. Methods : Thirty-nine consecutive patients with severe ulcerative colitis were randomized on admission to the hospital to receive intravenously either metronidazole (O.5g tid ) and tobramycin (4 mg/kg tid ) (n = 19), or placebo (n = 20). In addition, they were given parenteral nutrition, intravenous hydrocortisone (100 mg qid ) and hy-drocortisone enemas (100 mg bid). All patients were assessed after 10 days of continuous treatment, or at any time a severe complication occurred. Results : Twelve of 19 patients (63.15%) treated with antibiotics and 13/20 patients (65%) with placebo showed substantial improvement. Seven patients in each group did not improve (n = 9), or developed complications (n = 5) and underwent emergency colectomy without perioper-ative deaths or late deaths. Conclusions : These results do not support the routine use of intravenous tobramycin and metronidazole in the treatment of severe ulcerative colitis.     

Outbreak Caused by an Ertapenem-Resistant,CTX-M-15-Producing Klebsiella pneumoniae Sequence Type 101 Clone Carrying an OmpK36 Porin Variant

Although numerous studies have documented outbreaks of carbapenem-resistant Klebsiella pneumoniae (CRKP) possessing various carbapenemases, reports on outbreaks due to CRKP possessing extended-spectrum β-lactamases (ESBLs) and/or AmpCs with porin lesions have been limited. Here, we describe an outbreak caused by an ertapenem-resistant, CTX-M-15-producing clonal K. pneumoniae strain expressing an OmpK36 porin variant. From May 2012 to November 2012, 37 ertapenem-resistant K. pneumoniae isolates phenotypically negative for carbapenemase production were recovered from 19 patients hospitalized in the intensive care unit of a Greek hospital. The isolates were either susceptible or intermediate to other carbapenems and resistant to all remaining β-lactams but cefotetan. Phenotypic and molecular analysis revealed the presence in all isolates of the bla_CTX-M-15 gene on a conjugative 100-kb plasmid, disruption in the expression of the ompK35 gene, and the production of an Ompk36 porin variant. The index case was a patient admitted from another hospital. Active surveillance upon admission and on a weekly basis was immediately initiated; environmental samples were also periodically tested. Molecular typing showed that all clinical isolates as well as two ertapenem-resistant environmental K. pneumoniae isolates belonged to the same clonal type and were assigned to multilocus sequence typing (MLST) sequence type 101 (ST101). As all colonized/infected patients were hospitalized during overlapping periods, cross-infection was considered the main route for the dissemination of the outbreak strain. Despite reinforcement of infection control measures and active surveillance, the outbreak lasted approximately 7 months. Identification of hidden carriers upon admission and by screening on a weekly basis was found valuable for early recognition and subsequent successful management of the outbreak.     

A fatal case of Ludwig's angina and mediastinitis caused by an unusual microorganism, Gemella morbillorum

We present a case of Ludwig's angina in a 48-y-old immunocompetent male caused by an unusual pathogen, Gemella morbillorum. The infection was complicated with mediastinitis and despite aggressive management of the disease the patient died after 12 d of hospitalization. This is the first reported case of Ludwig's angina caused by G. morbillorum and emphasizes that the disease remains a potentially lethal infection.