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Biomedical subjects

M Crane

Publications and source records attributed to M Crane.

At least 37 records · Page 2Linked to original sources
PubMed2002

Renal flares are common in patients with severe proliferative lupus nephritis treated with pulse immunosuppressive therapy: long-term followup of a cohort of 145 patients participating in randomized controlled studies.

OBJECTIVE: Immunosuppressive agents have become the standard of therapy for proliferative lupus nephritis, but some patients may relapse after discontinuing treatment. We reviewed the cases of renal flares in a cohort of patients who participated in 2 randomized controlled clinical trials at the National Institutes of Health and explored the prevalence, outcome, and predictive factors of renal flares. METHODS: Data were obtained on 145 patients treated with pulse cyclophosphamide, pulse methylprednisolone, or the combination of both. Patients had not received immunosuppressive therapy for at least 6 months and had experienced complete or partial response according to defined criteria. Renal flares were classified as either proteinuric or nephritic based on changes in urinary protein and sediment. Most patients who experienced a flare received additional immunosuppressive therapy. RESULTS: Seventy-three patients had a complete response, and 19 had partial response/stabilization. Forty-one of these patients (45%) experienced renal flares (nephritic in 33, proteinuric in 8) after a mean followup of 117 months; 31 of them received additional immunosuppressive therapy. The median time to renal flare was 36 months in the complete responders and 18 months in the partial responders. Eleven of the 41 patients (27%) progressed to end-stage renal disease (ESRD); 9 had nephritic flares (all severe except for 1) and 2 had proteinuric flares (1 in each responder group). Compared with patients who had a complete response, those with a partial response were more likely to experience a flare, to have a severe nephritic flare, or to progress to ESRD. Low C4 at the time of response and African American ethnicity were significant independent risk factors for renal flare, by multivariate Cox proportional hazards analysis. CONCLUSION: Nephritic flares are common in patients with proliferative lupus nephritis, even in those with a complete response to therapy, but they do not necessarily result in loss of renal function if treated with additional immunosuppressive agents. Renal flares are an important feature of the natural history of lupus nephritis and provide an opportunity for additional preventive strategies, as well as measures of efficacy in future therapeutic trials.

Adult↗
PubMed2002

Toxicity of cadmium and zinc to encystment of Notocotylus attenuatus (Trematoda: Notocotylidae) cercariae.

The toxicity of cadmium, zinc, and cadmium/zinc mixtures at concentration ranging from 100 to 10,000 microg/L was investigated against the encystment strategy of free-living metacercarial stages of the parasitic fluke Notocotylus attenuatus. Exposure of encysting cercariae caused a reduction in encystment by all metals at concentrations of 1000 microg/L or higher. The formation of cyst associations was reduced in all metal-polluted test solutions. In addition, there was an increase in the number of floating metacercariae (cysts formed when not in contact with any surface) at low metal concentrations. The effects of metal toxicity to encystment strategy and its influence on transmission to the target host are briefly discussed.

Animals↗
PubMed2002

Toxicity of cadmium and zinc mixtures to Diplostomum spathaceum (Trematoda: Diplostomidae) cercarial survival.

The toxicity of cadmium and zinc mixtures at concentrations ranging from 0.1 to 10,000 microg/L was investigated against the survival of the free-living cercarial stage of the parasitic fluke Diplostomum spathaceum. Cercariae were exposed to metal mixtures of equal concentration, metal mixtures of unequal concentration, and low-dose pretreatment followed by high-dose exposure mixtures. Under all exposures cercarial survival was increased compared to that achieved with single metals. At exposures with metal mixture of equal concentration in the range 0.1-100 microg/L survival was increased compared to that achieved by controls. The mechanism of metal toxicity and their effects on cercarial survival are discussed.

Animals↗
PubMed2002

Species sensitivity distributions: data and model choice.

Species sensitivity distributions (SSDs) are increasingly incorporated into ecological risk assessment procedures. Although these new techniques offer a more transparent approach to risk assessment they demand more and superior quality data. Issues of data quantity and quality are especially important for marine datasets that tend to be smaller (and have fewer standard test methods) when compared with freshwater data. An additional source of uncertainty when using SSDs is appropriate selection from the range of methods used in their construction. We show through examples the influence of data quantity, data quality, and choice of model. We then show how regulatory decisions may be affected by these factors.

Decision Making↗
PubMed2002

The comparison of rapid bioassays for the assessment of urban groundwater quality.

Groundwater is a complex mixture of chemicals that is naturally variable. Current legislation in the UK requires that groundwater quality and the degree of contamination are assessed using chemical methods. Such methods do not consider the synergistic or antagonistic interactions that may affect the bioavailability and toxicity of pollutants in the environment. Bioassays are a method for assessing the toxic impact of whole groundwater samples on the environment. Three rapid bioassays, Eclox, Microtox and ToxAlert, and a Daphnia magna 48-h immobilisation test were used to assess groundwater quality from sites with a wide range of historical uses. Eclox responses indicated that the test was very sensitive to changes in groundwater chemistry; 77% of the results had a percentage inhibition greater than 90%. ToxAlert, although suitable for monitoring changes in water quality under laboratory conditions, produced highly variable results due to fluctuations in temperature and the chemical composition of the samples. Microtox produced replicable results that correlated with those from D. magna tests.

Ammonia↗
PubMed2002

Toxicity of cadmium and zinc to cercarial tail loss in Diplostomum spathaceum (Trematoda: Diplostomidae).

The effect of cadmium and zinc at concentrations ranging from 0.1 to 10,000 microg/l on tail loss in cercariae of Diplostomum spathaceum was investigated at 3 temperatures (12, 20 and 25 degrees C) and 3 levels of water hardness (distilled water, soft water and hard water). Increasing tail loss over time was found to be linked with a parallel decrease in cercarial survival in controls. Exposure to the heavy metals induced, especially at high concentrations, a change in the relationship between cercarial tail loss and survival, causing either stimulation or inhibition of tail loss dependent on the individual toxic exposure. Under most environmental conditions the rate of tail loss over time was reduced by increasing metal concentrations. Inhibition of tail loss occurred in a limited number of both control and metal-exposed cercariae, with a number of low metal concentrations inducing greater inhibition than in controls. Stimulation of tail loss causing an increased tail loss rate above controls also occurred at certain high metal concentrations. Increasing water hardness and decreasing water temperature caused a reduced tail loss rate over time in both control and metal-exposed cercariae. However, with decreasing temperature a reduced rate of tail loss over time in metal-exposed cercariae compared to controls occurred at some low metal concentrations. When tail loss was compared against cercarial death of the experimental population toxic exposure induced changes in the parallel relationship of these parameters, dependent on individual metal concentration, water temperature and hardness. Differences in the relative effects of cadmium and zinc on cercariae were dependent on the environmental conditions of exposure. Both metals showed limited effects during the period of maximum cercarial infectivity (0-5 h). The mechanisms and importance of metal toxicity to cercarial tail loss are discussed.

Animals↗
PubMed2002

Toxic effects of cadmium and zinc on the transmission of Echinoparyphium recurvatum cercariae.

The toxicity of cadmium, zinc and Cd/Zn mixtures to the transmission of Echinoparyphium recurvatum (Digenea: Echinostomatidae) cercariae into the snail second intermediate hosts was investigated at concentrations ranging from 100 microg l-1 to 10 000 microg l-1 in both soft and hard water. A differential response in the infectivity of metal-exposed cercariae into Lymnaea peregra and Physa fontinalis was demonstrated which was dependent on the snail species being infected. Exposure of L. peregra, P. fontinalis, and L. stagnalis to heavy metals caused a differing susceptibility to E. recurvatum cercariae depending on the snail species being exposed. The mechanism and effects of metal toxicity, together with the importance of the parasite/host strain on cercarial transmission are discussed.

Animals↗
PubMed2002

Differences in immunocontraceptive responses in white-tailed deer (Odocoileus virginianus) and goats (Capra hircus).

Thirteen deer (Odocoileus virginianus) and three goats (Capra hircus) were given an initial immunization of 300 microg porcine zona pellucida (PZP) combined with 50 mg synthetic trehalose dicorynomycolate ml(-1) (STDCM) in drakeol i.m. in the semitendinosus and semimembranosus muscles. This immunization was followed by two booster injections of 300 microg PZP, 2 weeks apart. The vaccinations were made from the same purified batch of PZP and lot of adjuvant. All the doses were made at the same time and injected on the same day. The immune response was quantified by measuring serum anti-PZP IgG antibody concentration by ELISA. The results showed that the mean serum IgG concentration of the deer increased from 0.000 +/- 0.003 to 0.083 +/- 0.023 absorbance units, whereas in the goats the mean IgG concentration increase was from 0.044 +/- 0.019 to 1.245 +/- 0.774 absorbance units. Both the goats and deer showed a significant increase in IgG concentration (P < 0.05) after the final booster injection compared with preimmune serum. The final goat IgG concentration was significantly (P < 0.05) higher than that of the deer. If PZP and Freund's adjuvant are administered to deer, immunocontraception is achieved, but the IgG concentration in the deer in this study did not appear to be compatible with immunocontraception.

Animals↗
PubMed2001

IL-10 improves skin disease and modulates endothelial activation and leukocyte effector function in patients with psoriatic arthritis.

Psoriatic arthritis (PsA) provides an ideal disease model in which to investigate the bioactivities of potentially therapeutic cytokines at multiple sites of tissue inflammation. We investigated the effects of IL-10, an antiinflammatory cytokine, given s.c. for 28 days in a double-blind, placebo-controlled study in PsA patients. Synovial/skin biopsies, peripheral blood leukocytes, articular magnetic resonance images, and clinical disease activity scores were obtained sequentially. Modest, but significant clinical improvement in skin, but not articular disease activity scores with only minor adverse effects was observed. Type 1, but not type 2 T cell cytokine production in vitro was suppressed in human rIL-10 compared with placebo recipients. Similarly, monokine production in vitro was reduced, whereas serum soluble TNFRII levels were elevated, indicating suppression of monocyte function. Decreased T cell and macrophage infiltration in synovial tissues was accompanied by reduced P-selectin expression. Moreover, suppressed synovial enhancement on magnetic resonance imaging and reduced alpha(v)beta(3) integrin expression on von Willebrand factor(+) vessels were observed. Together these data demonstrate that a short course of IL-10 modulates immune responses in vivo via diverse effects on endothelial activation, and leukocyte recruitment and effector function. Such biological changes may result in clinically meaningful improvement in disease activity.

Adult↗
PubMed2001

Combination therapy with pulse cyclophosphamide plus pulse methylprednisolone improves long-term renal outcome without adding toxicity in patients with lupus nephritis.

BACKGROUND: Controlled trials in lupus nephritis have demonstrated that cyclophosphamide therapy is superior to corticosteroid therapy alone. The long-term effectiveness and side-effect profiles of pulse immunosuppressive regimens warrant further study. OBJECTIVE: To define the long-term risk and benefit of monthly treatment with boluses of methylprednisolone, cyclophosphamide, or both. DESIGN: Extended follow-up (median, 11 years) of a randomized, controlled trial. SETTING: U.S. government research hospital. PATIENTS: 82 patients with proliferative lupus nephritis. MEASUREMENTS: Rates of treatment failure (defined as need for supplemental immunosuppressive therapy or doubling of serum creatinine concentration, or death) and adverse events. RESULTS: In an intention-to-treat survival analysis, the likelihood of treatment failure was significantly lower in the cyclophosphamide (P = 0.04) and combination therapy (P = 0.002) groups than in the methylprednisolone group. Combination therapy and cyclophosphamide therapy alone did not differ statistically in terms of effectiveness or adverse events. Of patients who completed the protocol (n = 65), the proportion of patients who had doubling of serum creatinine concentration was significantly lower in the combination group than in the cyclophosphamide group (relative risk, 0.095 [95% CI, 0.01 to 0.842]). CONCLUSION: With extended follow-up, pulse cyclophosphamide continued to show superior efficacy over pulse methylprednisolone alone for treatment of lupus nephritis. The combination of pulse cyclophosphamide and methylprednisolone appears to provide additional benefit over pulse cyclophosphamide alone and does not confer additional risk for adverse events.

Adult↗