Antimicrobial Photodynamic Therapy (aPDT) for decontamination of high-speed handpieces: A comparative study.

BACKGROUND: Cross-transmission is a major concern in dental offices. Various disinfection methods have been frequently used to reduce its incidence. Standard procedures include decontamination and sterilization. Traditional decontamination methods include: Alcohol 70 % and chlorhexidine digluconate, however, antimicrobial photodynamic therapy (aPDT) could be added as an option. The objective was to evaluate the effectiveness of aPDT on decontamination of high-speed handpieces, contaminated by Staphylococcus aureus (SA) and Escherichia coli (EC), and compare it to autoclave sterilized and to conventional chemical decontamination methods. METHODS: Sterilized, SA and EC contaminated high-speed handpieces were divided in 7 groups: G1- sterilized in an autoclave. G2- contaminated untreated control. G3- contaminated and decontaminated using Alcohol 70 %. G4- contaminated and decontaminated using chlorhexidine digluconate 2%. G5- contaminated and laser treated. G6- contaminated and photosensitizer treated. G7- contaminated and photodynamic therapy. RESULTS: The groups G3, G4, G7 did not show bacterial growth, G5 and G6 showed bacterial growth similar to G2. The study did not find SA or EC sensible to laser irradiation only, differently from some authors and did not consider biofilm in our experiments. CONCLUSION: Our experiment showed that, laser and photosensitizer isolated were not effective to inhibit Staphylococcus aureus (SA) and Escherichia coli (EC) growth, but when associated in aPDT technique, can be compared to chemical disinfection agents that are traditionally used and effective against this pathogen.

One hundred questions of importance to the conservation of global biological diversity.

We identified 100 scientific questions that, if answered, would have the greatest impact on conservation practice and policy. Representatives from 21 international organizations, regional sections and working groups of the Society for Conservation Biology, and 12 academics, from all continents except Antarctica, compiled 2291 questions of relevance to conservation of biological diversity worldwide. The questions were gathered from 761 individuals through workshops, email requests, and discussions. Voting by email to short-list questions, followed by a 2-day workshop, was used to derive the final list of 100 questions. Most of the final questions were derived through a process of modification and combination as the workshop progressed. The questions are divided into 12 sections: ecosystem functions and services, climate change, technological change, protected areas, ecosystem management and restoration, terrestrial ecosystems, marine ecosystems, freshwater ecosystems, species management, organizational systems and processes, societal context and change, and impacts of conservation interventions. We anticipate that these questions will help identify new directions for researchers and assist funders in directing funds.

Global biodiversity conservation priorities.

The location of and threats to biodiversity are distributed unevenly, so prioritization is essential to minimize biodiversity loss. To address this need, biodiversity conservation organizations have proposed nine templates of global priorities over the past decade. Here, we review the concepts, methods, results, impacts, and challenges of these prioritizations of conservation practice within the theoretical irreplaceability/vulnerability framework of systematic conservation planning. Most of the templates prioritize highly irreplaceable regions; some are reactive (prioritizing high vulnerability), and others are proactive (prioritizing low vulnerability). We hope this synthesis improves understanding of these prioritization approaches and that it results in more efficient allocation of geographically flexible conservation funding.

Wilderness and biodiversity conservation.

Human pressure threatens many species and ecosystems, so conservation efforts necessarily prioritize saving them. However, conservation should clearly be proactive wherever possible. In this article, we assess the biodiversity conservation value, and specifically the irreplaceability in terms of species endemism, of those of the planet's ecosystems that remain intact. We find that 24 wilderness areas, all > or = 1 million hectares, are > or = 70% intact and have human densities of less than or equal to five people per km2. This wilderness covers 44% of all land but is inhabited by only 3% of people. Given this sparse population, wilderness conservation is cost-effective, especially if ecosystem service value is incorporated. Soberingly, however, most wilderness is not speciose: only 18% of plants and 10% of terrestrial vertebrates are endemic to individual wildernesses, the majority restricted to Amazonia, Congo, New Guinea, the Miombo-Mopane woodlands, and the North American deserts. Global conservation strategy must target these five wildernesses while continuing to prioritize threatened biodiversity hotspots.

Effectiveness of parks in protecting tropical biodiversity.

We assessed the impacts of anthropogenic threats on 93 protected areas in 22 tropical countries to test the hypothesis that parks are an effective means to protect tropical biodiversity. We found that the majority of parks are successful at stopping land clearing, and to a lesser degree effective at mitigating logging, hunting, fire, and grazing. Park effectiveness correlates with basic management activities such as enforcement, boundary demarcation, and direct compensation to local communities, suggesting that even modest increases in funding would directly increase the ability of parks to protect tropical biodiversity.

Biodiversity hotspots for conservation priorities.

Conservationists are far from able to assist all species under threat, if only for lack of funding. This places a premium on priorities: how can we support the most species at the least cost? One way is to identify 'biodiversity hotspots' where exceptional concentrations of endemic species are undergoing exceptional loss of habitat. As many as 44% of all species of vascular plants and 35% of all species in four vertebrate groups are confined to 25 hotspots comprising only 1.4% of the land surface of the Earth. This opens the way for a 'silver bullet' strategy on the part of conservation planners, focusing on these hotspots in proportion to their share of the world's species at risk.

Strategies to reduce side effects of interleukin-2: evaluation of the antihypotensive agent NG-monomethyl-L-arginine.

PURPOSE: The clinical utility of high-dose intravenous recombinant interleukin (IL)-2 therapy is limited by severe toxicity including hypotension, fever, chills, pulmonary edema, and oliguria Hypotension has been previously shown to result from excessive vascular relaxation due to overproduction of the endogenous vasodilator nitric oxide. Nitric oxide production can be decreased by administration of the competitive enzyme inhibitor NG-monomethyl-L-arginine (NMA). A clinical trial to investigate the dose-dependent effects of NMA on blood pressure was undertaken in patients with metastatic renal cell carcinoma. PATIENTS AND METHODS: Patients with metastatic renal cell carcinoma receiving a 5-day continuous infusion of IL-2 (18 million IU/m2/d) who developed hypotension were treated with increasing doses of NMA, ranging from 3 to 36 mg/kg. RESULTS: Twenty-three patients received a total of 61 courses of IL-2; 18 of these patients developed hypotension and received NMA. Antihypotensive activity was observed at all dose levels, and the duration of the effect varied directly with the dose of NMA. At the higher dose levels tested (12 to 36 mg/kg), increased pulmonary vascular resistance and decreased cardiac output were observed. Patients experiencing a significant decrease in cardiac output received dobutamine (2.5 to 10 microg/kg/min). Pulmonary capillary wedge pressure was unaffected by administration of NMA. One patient treated at 24 mg/kg (bolus) experienced a major motor seizure, but no neurologic disorders were observed in other patients treated with NMA doses of 24 to 36 mg/kg. No other adverse events involving hepatic, renal, or hematologic systems were attributed to NMA. Three patients received NMA by an initial bolus followed by a continuous infusion. Similar antihypotensive effects were noted, and these patients were able to complete a full 5-day course of IL-2. CONCLUSION: The antihypotensive effects of NMA appear to be optimal at a dose of 24 mg/kg, with maintenance doses of 8 mg/kg every 4 to 6 hours. At this dose level, blood pressure was restored, and IL-2-associated vasodilatation was fully reversed. Coincident with the reversal of hypotension, the state of high cardiac output was also reversed by NMA administration. These results suggest that NMA may be effective for alleviating the hypotensive effects of high-dose IL-2 therapy in cancer patients.

Phase II trial of liposome-encapsulated doxorubicin, cyclophosphamide, and fluorouracil as first-line therapy in patients with metastatic breast cancer.

PURPOSE: To determine the efficacy and safety profile, including the risk for cardiac toxicity, of liposome-encapsulated doxorubicin (TLC D-99), fluorouracil (5-FU), and cyclophosphamide as first-line chemotherapy in patients with metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-one women were registered in this phase II study. All patients had measurable disease and no previous chemotherapy for MBC. Treatment consisted of TLC D-99 60 mg/m2 and cyclophosphamide 500 mg/m2 on day 1 and 5-FU 500 mg/m2 on days 1 and 8 every 3 weeks. Serial cardiac monitoring, including endomyocardial biopsies, was performed. RESULTS: The overall response rate was 73% (95% confidence interval, 57% to 86%). The median duration of response was 11.2 months, the median time to treatment failure was 8.1 months, and the median overall survival duration was 19.4 months. The median number of cycles per patient was 10. The median cumulative dose of TLC D-99 was 528 mg/m2. Ten patients required hospitalization for febrile neutropenia. Nausea/vomiting, stomatitis, and fatigue higher than grade 2 occurred in 12%, 15%, and 41% of patients, respectively. Twenty-one patients reached a cumulative doxorubicin dose greater than 500 mg/m2. Three patients (7%) were withdrawn from the study due to protocol-defined cardiac toxicity, two because of a decrease in left ventricular ejection fraction to < or = 40%, and one because her endomyocardial biopsy result was grade 1.5. One patient had congestive heart failure that was probably nonanthracycline related. CONCLUSION: This chemotherapy regimen, including TLC D-99, was highly active against MBC and associated with low cardiac toxicity despite high cumulative doses of doxorubicin.

Fine-needle aspiration cytology of mediastinal non-Hodgkin's nonlymphoblastic lymphoma.

BACKGROUND: The histologic features of primary mediastinal non-Hodgkin's nonlymphoblastic lymphoma (NHL) are well described in the surgical pathology literature. However, the fine-needle aspiration (FNA) cytology of these lesions has not been characterized thoroughly. METHODS: FNA material from 12 patients with primary mediastinal NHL was reviewed. The series was comprised of 7 men and 5 women with a mean age of 42 years (age range, 26-65 years). All 12 patients underwent a mediastinal FNA as the initial step in their diagnostic evaluation. In some cases, flow cytometry or immunocytochemical studies were performed on the FNA material to render a definitive diagnosis. RESULTS: On the basis of the cytomorphologic findings and ancillary studies performed on the FNA material, a diagnosis of malignant lymphoma (five cases), consistent with/suspicious for malignant lymphoma (four cases), or nondiagnostic/negative for lymphoma (three cases) was rendered for each case. In general, a definitive diagnosis of malignancy was established when there was cytomorphologic evidence of lymphoma and a monoclonal lymphoid population could be demonstrated by immunocytochemistry. Eleven of the 12 primary mediastinal non-Hodgkin's lymphomas were large cell lymphomas (LCL), and 1 was a composite lymphoma (LCL and Hodgkin's disease). In three of the LCL cases the neoplastic cells exhibited prominent nuclear hyperlobation in association with sclerosis. CONCLUSIONS: A diagnosis of primary mediastinal NHL can be established with a high degree of accuracy on the basis of FNA cytology. The FNA cytomorphology of primary mediastinal NHL correlates with the spectrum of morphologic diversity associated with this entity in the surgical pathology literature.

Phase II trial of docetaxel: a new, highly effective antineoplastic agent in the management of patients with anthracycline-resistant metastatic breast cancer.

PURPOSE: To determine the efficacy (objective response rate and duration of response and survival) and toxicity of docetaxel in patients with strictly defined anthracycline-resistant metastatic breast cancer (MBC). PATIENTS AND METHODS: Thirty-five patients with bidimensionally measurable MBC who had progressive disease while receiving anthracycline-containing chemotherapy were registered onto the phase II trial. Docetaxel was administered at a dose of 100 mg/m2 over 1 hour every 21 days. RESULTS: Thirty-four patients were assessable for disease response; 18 (53%; 95% confidence interval [CI], 35% to 70%) achieved a partial response. The median times to disease progression and survival duration were 7.5 and 13.5 months, respectively, for responding patients. The median overall survival duration was 9 months. Two hundred eight cycles (median, five) of docetaxel were administered. Neutropenia with less than 500 cells/microL developed in 31 of 35 patients; it was complicated by fever in 30 (14%) of 208 cycles and in 18 (51%) of 35 patients, including one treatment-related death. Fluid retention was seen in 15 (43%) of 35 patients, including pleural effusions in 11 patients (31%). Moderate skin toxicity, asthenia, and myalgia were observed in 16%, 58%, and 37% of cycles, respectively. CONCLUSION: Docetaxel has the highest reported antitumor activity in anthracycline-resistant MBC. High objective response rates were seen in patients with visceral-dominant involvement, multiple metastatic sites, or extensive previous therapy. Docetaxel is associated with severe but reversible neutropenia, asthenia, and cumulative dose-related fluid retention. Dexamethasone decreased the frequency and severity of skin toxicity and appeared to ameliorate fluid retention.

NG-methyl-L-arginine, an inhibitor of nitric oxide synthase, reverses interleukin-2-induced hypotension.

OBJECTIVE: To evaluate the role of NG-methyl-L-arginine as a modulator of the hyperdynamic shock induced by the administration of interleukin-2 (IL-2). DESIGN: A prospective, pilot clinical study. SETTING: Intensive care unit of a tertiary care center. PATIENTS: Three sequential patients with metastatic renal cell carcinoma who developed hypotension during their first course of treatment with high-dose IL-2 (18 x 10(6) IU/m2/day by continuous infusion for 5 days). INTERVENTIONS: Upon developing hypotension during their subsequent therapy with IL-2, patients were administered 12 mg/kg of NG-methyl-L-arginine. Thereafter, a dose of 4 mg/kg was given every 4 hrs, as needed, to maintain the systolic blood pressure above 100 mm Hg. MEASUREMENTS AND MAIN RESULTS: Invasive hemodynamic monitoring was instituted before the initiation of treatment with IL-2. Differences noted before, and 15 mins after, the administration of NG-methyl-L-arginine were analyzed using the paired t-test. NG-methyl-L-arginine (12 mg/kg) induced a significant antihypotensive effect (mean blood pressure increased from 87 +/- 4 to 121 +/- 7 mm Hg), accompanied by an increase of the systemic vascular resistance (549 +/- 51 to 860 +/- 167 dyne.sec/cm5) and pulmonary vascular resistance (81 +/- 16 to 117 +/- 29 dyne.sec/cm5). A decrease in the cardiac index was also documented (4.5 +/- 0.5 to 3.6 +/- 0.3 L/min/m2). No significant changes in pulmonary artery occlusion and central venous pressures were observed. Maintenance doses of 4 mg/kg of NG-methyl-L-arginine induced similar hemodynamic results, although the duration of the antihypotensive effect of NG-methyl-L-arginine decreased with sequential doses. CONCLUSIONS: The hemodynamic effects induced by IL-2 administration are reversed by NG-methyl-L-arginine, a nitric oxide synthesis inhibitor. These results provide evidence for the biological activity of NG-methyl-L-arginine when administered alone to hypotensive patients. While no adverse effects were observed in this preliminary study, issues of toxicity and effectiveness need to be defined further in formal clinical trials. NG-methyl-L-arginine may play a therapeutic role in the modulation of the extreme vasodilation induced by cytokine administration or in septic shock.

Acute myositis and dermatitis as the initial presentation of sarcoidosis.

We report a case of a patient who presented with symptoms of acute debilitating proximal muscle weakness, which mimicked acute polymyositis, accompanied by a hypopigmented papular rash. The histology of the skin and muscle demonstrated sarcoidosis. A review of the literature of acute sarcoid myositis and the various other myopathies of sarcoidosis is presented.

Habitat, density and group size of primates in a Brazilian tropical forest.

Habitats, population densities and group sizes of 5 primate species (Callithrix flaviceps, Callicebus personatus personatus, Cebus apella nigritus, Alouatta fusca clamitans, and Brachyteles arachnoides) were estimated, using the method of repeated transect sampling, in an area of montane pluvial forest in eastern Brazil (Atlantic forest). A. fusca and C. apella had the highest densities in terms of groups and individuals per square kilometer, respectively, while B. arachnoides was least abundant. The highest primate densities were observed in areas of secondary vegetation. Both group sizes and population densities for the 5 species were generally lower at the Reserva Biologica Augusto Ruschi than those reported in other areas of Atlantic forest. Hunting pressure and the different carrying capacity of the habitat are suggested as possible causes for the low number of sightings registered for these species.