Cleaning Symbiosis of Caribbean Reef Fish: Analysis of Biological Factors That Affect Cleaning Frequency

Cleaning symbiosis is an important mutualistic relationship for both cleaner and client fish on the coral reef. Until recently, factors affecting the frequency of cleaning stations surrounding the reef have remained unstudied. The purpose of this study was to determine which factors affected cleaning stations in the South Water Caye Marine Reserve (Belize), with particular focus on the role played by parasites. Cleaning stations were observed for a 2-week period, and analyses were made to compare depth, cleaner and client species, and time of day to frequency of cleaning observed. Parrotfish and Surgeonfish were observed most frequently at cleaning stations (48.31% and 21.47%, respectively), which implied that fish known to have more parasites were cleaned most often. There was a negative relationship between encounters of cleaning per session and time of day, which supported the hypothesis that cleaning occurred more often in the morning, likely due to high parasite levels. Even though the parasites were not studied directly, there was strong evidence that parasites play an important role in the ecology of Caribbean coral reefs

“How to Do It”

Pulmonary vein stenosis (PVS) is often progressive and severe. Surgical and percutaneous angioplasty are acutely successful; however, restenosis is common and many patients require multiple reinterventions. We perform intraoperative “hybrid” stent placement to deliver larger, stronger stents. Hybrid stent placement is well described for pulmonary arterial stenosis (PAS). The PAS data demonstrate that smaller stents are associated with rapid in-stent restenosis. Data from PVS in adults demonstrate superior outcomes with larger stents. Hybrid stent placement requires a strong collaborative effort between congenital heart surgeons and interventional cardiologists. </jats:p

Potential of ancestral sylvatic dengue-2 viruses to re-emerge

AbstractDengue viruses (DENV) are the most important arboviral pathogens in tropical and subtropical regions throughout the world. DENV transmission includes both a sylvatic, enzootic cycle between nonhuman primates and arboreal mosquitoes of the genus Aedes, and an urban, endemic/epidemic cycle between Aedes aegypti, a mosquito with larval development in peridomestic water containers, and human reservoir hosts. All 4 serotypes of endemic DENV evolved independently from ancestral sylvatic viruses and have become both ecologically and evolutionarily distinct; this process may have involved adaptation to (i) peridomestic mosquito vectors and/or (ii) human reservoir hosts. To test the latter hypothesis, we assessed the ability of sylvatic and endemic DENV-2 strains, representing major genotypes from Southeast Asia, West Africa and the Americas, to replicate in two surrogate human model hosts: monocyte-derived, human dendritic cells (moDCs), and mice engrafted with human hepatoma cells. Although the various DENV-2 strains showed significant inter-strain variation in mean replication titers in both models, no overall difference between sylvatic and endemic strains was detected in either model. Our findings suggest that emergence of endemic DENV strains from ancestral sylvatic strains may not have required adaptation to replicate more efficiently in human reservoir hosts, implying that the potential for re-emergence of sylvatic dengue strains into the endemic cycle is high. The shared replication profiles of the American endemic and sylvatic strains suggest that American strains have maintained or regained the ancestral phenotype

Formal DNA Hydrolysis by Mono- and Dinuclear Iron Complexes

The complexes CpFe(CO)2Ph and [CpFe(CO)2]2 cleave DNA in the presence of H2O2 or organic peroxides to give products resulting from the formal hydrolysis of the phosphodiester groups

Phase II Study of 2-Weekly CHOP+Rituximab Followed by Yttrium-90 Ibritumomab Tiuxetan (Zevalin) In Patients with Previously Untreated Diffuse Large B Cell Lymphoma (DLBCL): Final Analysis

Abstract Abstract 3947 Background: Dose dense CHOP (CHOP-14), the addition of rituximab to CHOP-21 and consolidation with radioimmunotherapy following CHOP chemotherapy have all been shown to improve the outcome of DLBCL. We report the results of final analysis of a phase II clinical trial using a combination of the above with dose dense CHOP+R, every 2 weeks, followed by radioimmunotherapy consolidation in untreated DLBCL patients. Patients and Methods: Patients with previously untreated DLBCL with measurable disease, age &gt;18 years, performance status 0–2, and adequate marrow, liver and kidney function were eligible. Those with transformed lymphoma were excluded. Patients received standard CHOP along with rituximab 375mg/m2 IV on day 1, repeated every two weeks for 6 cycles, followed by Zevalin consolidation 6–8 weeks later. Results: 20 patients were enrolled. The median age was 60 years (range 33–81 years). 8 patients were men and all patients had an ECOG performance status of 0 or 1. 4 (20%) had stage II, 11 (55%) stage III and 5 (25%) stage IV disease. The majority of patients had an IPI of 2 (40%) or 3 (55%). 14 patients (70%) had extra-nodal disease. 18 patients completed 6 cycles of CHOP+R, 16 of whom went onto Zevalin consolidation. Of the 2 patients who did not complete 6 cycles of CHOP+R, one patient with multiple lung masses could not tolerate further therapy and the other withdrew consent after 5 cycles. Of the 2 patients who completed 6 cycles of chemotherapy but did not receive Zevalin, one was excluded due to abnormal biodistribution on dosimetry with Zevalin and the other because of organizing pneumonia. Following CHOP+R alone in patients who received 4 or more cycles (n=20), ORR was 100% with a 75% CR (n=15) and a 25% PR (n=5). All 4 patients who stopped treatment with dose dense CHOP+R remained in CR. With Zevalin, 3 patients converted from PR to CR, maintaining an ORR of 100% (n=20) with an improved CR of 90% and a PR of 10%. The most common grade 3/4 toxicity with Zevalin was neutropenia in 8 patients (n=50%) with no cases of neutropenic fever. At a median follow-up of 42.4 months, median PFS and OS were not reached. 3 patients relapsed (15%), all of whom had extra-nodal disease, 2 had an IPI of 3, and 2 had bulky disease. All relapses were retreated with one patient now in CR and 2 deceased. One other patient died of organizing pneumonia, in CR at the time of death. To date, 17 patients remain alive, all in CR. Conclusion: Consolidation with Zevalin radioimmunotherapy following dose dense CHOP+R therapy converts PRs to CRs and maintains durable responses with acceptable toxicity in patients with untreated DLBCL. Disclosures: Off Label Use: Chemotherapy with R-CHOP every 21 days is the standard of care for DLBCL in the front-line setting. We are administering R-CHOP every 14 days for dose intensification followed by zevalin (radioimmunotherapy) consolidation for untreated DLBCL. This regimen is off-label. Gregory:Amgen: Consultancy; Astellas: Research Funding; Celgene: Research Funding; Cephalon: Research Funding, Speakers Bureau; Genentech (Roche): Consultancy, Research Funding, Speakers Bureau; Glaxo-Smith-Kline: Research Funding; Immunomedics: Research Funding; NCIC CTG: Research Funding; Novartis: Consultancy, Research Funding; Onyx (Proteolix): Research Funding; Spectrum Pharmaceuticals: Consultancy. </jats:sec

Immune Ablation Using Cyclophosphamide without Stem Cell Rescue for Intractable Multiple Sclerosis and Its Variants

Abstract Background: Multiple sclerosis (MS) is the most common progressively disabling neurologic disease of young adults worldwide. MS is a cytotoxic T Cell mediated disease with autoimmune-driven destruction occurring most actively in the early stages. Immune suppression with high dose steroids, cyclophosphamide (CTX), cladribine, and mitoxantrone has demonstrated benefit in intractable, more progressive or frequently relapsing patients, both on clinical and MRI parameters. In particular, non-ablative doses of CTX appear to stabilize progressive MS for one year or longer and were most effective earlier in the course of the disease. In aggressive MS deletion of cytotoxic T cells through immune ablation may offer a more durable remission than standard immune suppression. Due to aldehyde dehydrogenase mediated resistance of CD34+ cells to CTX, hematopoietic reconstitution without hematopoietic stem cell rescue is possible and could eliminate the need for stem cell mobilization which has been associated with disease flare and potential re-infusion of T-cells. Objective: To assess the safety and efficacy of immunoablation using CTX without hematologic stem cell rescue for intractable relapsing progressive multiple sclerosis failing standard immune modulation or immune suppression. Patients and Methods: Eight patients (median age = 29, range 24–37, men = 2, women = 6) between January 2005 and July 2008 underwent immunoablation with high dose CTX (HD-CTX) at 50 mg per kg per day intravenously for four consecutive days. Adequate hydration and forced diuresis were implemented to prevent hemorrhagic cystitis. G-CSF was started 6 days after the last dose of chemotherapy at 5 mcg/kg per day until the absolute neutrophil count was &amp;gt; 1000 per UL for two consecutive days. Red cell transfusions were administered to maintain hemoglobin of &amp;gt; 8 gm/dl and platelet transfusions were given to patients with &amp;lt; 10 Th/ul or to patients with active bleeding regardless of their platelet count. Clinical, laboratory, and MRI monitoring was scheduled at 3–6 month intervals over 24 months. Results: Eight patients have been treated with HD-CTX since 2005 and six of these patients have been monitored for more than 2 years. Hematologic complications included grade 4 neutropenia in all patients (duration 9–18 days), grade 4 thrombocytopenia in all patients (duration 3–13 days in 5 patients; 3 patients were discharged prior to platelet recovery), and grade 3 anemia in 6 patients (duration 1–9 days). All 8 patients required platelet transfusion (mean = 3.85 units, range 1–13 units) and 7 patients required PRBC transfusion (mean = 1.625 units, range 0–4 units). Non-hematologic grade 3 or 4 complications included grade 3 neutropenic fever in 7 patients, grade 3 hematuria in 2 patients and CTX-induced cardiotoxity with troponin elevation and infective endocarditis in 1 patient. 1 pt had a dystonic reaction to compazine. All patients have demonstrated improvements ranging from halting progression of MS clinically and radiologically to dramatic reductions of neurologic deficits, except in two patients whose disease reprogressed after 20 months of stability. One of these two patients demonstrated only subclinical disease activity on brain MRI without clinical correlates whereas the other experienced two milder clinical exacerbations. The latter has begun therapy with natalizumab, and the same has been recommended for the former. Given the refractory nature of these patients’ MS prior to therapy, the absence of further disease activity has been remarkable. Conclusions: Immunoablation with HD-CTX without stem cell rescue in patients with intractable MS represents a reasonable treatment option. These patients had significant improvements ranging from amelioration to stabilization of the disease course as well as reduction of disabilities. HD-CTX was tolerable with acceptable side effects and full hematologic recovery without the use of stem cell rescue. This is particularly important in patients with MS because of the associated disease flare and potential re-infusion of T-cells with stem cell mobilization. More data is needed and this clinical trial continues to accrue patients.</jats:p