The decline of butterflies in Europe: Problems,significance, and possible solutions

We review changes in the status of butterflies in Europe, focusing on long-running population data available for the United Kingdom, the Netherlands, and Belgium, based on standardized monitoring transects. In the United Kingdom, 8% of resident species have become extinct, and since 1976 overall numbers declined by around 50%. In the Netherlands, 20% of species have become extinct, and since 1990 overall numbers in the country declined by 50%. Distribution trends showed that butterfly distributions began decreasing long ago, and between 1890 and 1940, distributions declined by 80%. In Flanders (Belgium), 20 butterflies have become extinct (29%), and between 1992 and 2007 overall numbers declined by around 30%. A European Grassland Butterfly Indicator from 16 European countries shows there has been a 39% decline of grassland butterflies since 1990. The 2010 Red List of European butterflies listed 38 of the 482 European species (8%) as threatened and 44 species (10%) as near threatened (note that 47 species were not assessed). A country level analysis indicates that the average Red List rating is highest in central and mid-Western Europe and lowest in the far north of Europe and around the Mediterranean. The causes of the decline of butterflies are thought to be similar in most countries, mainly habitat loss and degradation and chemical pollution. Climate change is allowing many species to spread northward while bringing new threats to susceptible species. We describe examples of possible conservation solutions and a summary of policy changes needed to conserve butterflies and other insects.     

Effectiveness of diclofenac versus paracetamol in knee osteoarthritis: a randomised controlled trial in primary care

Background

The effectiveness of diclofenac versus paracetamol in primary care patients with pain caused by knee osteoarthritis is unclear.

Aim

To assess the effectiveness of diclofenac compared with paracetamol over a period of 2, 4, and 12 weeks in patients with knee osteoarthritis.

Design and setting

Randomised controlled trial in general practice.

Method

There were 104 patients included in the study, they were aged ≥45 years consulting their GP with knee pain caused by knee osteoarthritis. Patients were randomly allocated to diclofenac (n = 52) or paracetamol (n = 52) for at least 2 weeks. Primary outcomes were daily knee pain severity, and knee pain and function measured with the Knee Injury and Osteoarthritis Outcome Score (KOOS).

Results

Over a period of 2- and 4-weeks follow-up, no significant difference in daily knee pain was found between the patient groups: estimated differences of 0.5 (95% CI = −0.2 to 1.3) and −0.2 (95% CI = −1.0 to 0.7), respectively. Over the 12-weeks follow-up, no significant differences were found between both groups for KOOS pain: estimated difference of −2.8 (95% CI = −10.7 to 5.1) and KOOS function of −2.7 (−10.6 to 5.0).

Conclusion

Over a period of 2- and 4-weeks follow-up no significant difference in daily measured knee pain severity was found between primary care patients with knee osteoarthritis taking paracetamol or diclofenac. Also, over a period of 12-weeks follow-up no significant differences were found regarding KOOS pain and KOOS function between both groups. Patients more frequently reported minor adverse events after taking diclofenac (64%) than paracetamol (46%).     

Differential effects of nitric oxide on erythroid and myeloid colony growth from CD34+ human bone marrow cells

Nitric oxide (NO) is a reactive molecule with numerous physiologic and pathophysiologic roles affecting the nervous, cardiovascular, and immune systems. In previous work, we have demonstrated that NO inhibits the growth and induces the monocytic differentiation of cells of the HL- 60 cell line. We have also demonstrated that NO inhibits the growth of acute nonlymphocytic leukemia cells freshly isolated from untreated patients and increases monocytic differentiation antigens in some. In the present work, we studied the effect of NO on the growth and differentiation of normal human bone marrow cells in vitro. Mononuclear cells isolated from human bone marrow were cultured in semisolid media and treated with the NO-donating agents sodium nitroprusside (SNP) or S- nitroso-acetyl penicillamine (SNAP) (0.25 to 1 mmol/L). Both agents decreased colony-forming unit-erythroid (CFU-E) and colony-forming unit- granulocyte macrophage (CFU-GM) formation by 34% to 100%. When CD34+ cells were examined, we noted that these cells responded to SNP and SNAP differently than did the mononuclear cells. At a concentration range of 0.25 to 1 mmol/L, SNP inhibited the growth of CFU-E by 30% to 75%. However, at the same concentration range, SNP increased the number of CFU-GM by up to 94%. At concentrations of 0.25 to 1 mmol/L, SNAP inhibited the growth of CFU-E by 33% to 100%. At a concentration of 0.25 mmol/L, SNAP did not affect CFU-GM. At higher concentrations, SNAP inhibited the growth of CFU-GM. Although SNP increased intracellular levels of cGMP in bone marrow cells, increasing cGMP in cells by addition of 8-Br-cGMP (a membrane permeable cGMP analogue) did not reproduce the observed NO effects on bone marrow colonies. These results demonstrate that NO can influence the growth and differentiation of normal human bone marrow cells. NO (generated in the bone marrow microenvironment) may play an important role modulating the growth and differentiation of bone marrow cells in vivo.     

Characterizing the PK/PD relationship for inhibition of capsaicin-induced dermal vasodilatation by MK-3207, an oral calcitonin gene related peptide receptor antagonist

Aims

Calcitonin gene related peptide (CGRP) receptor antagonists are effective acute migraine treatments. A capsaicin-induced dermal vasodilatation (CIDV) model has been developed to provide target-engagement information in healthy volunteers. In the model, CGRP release is provoked after dermal capsaicin application, by activating transient receptor potential vanilloid-type-1 (TRPV1) receptors at peripheral sensory nerves. Laser Doppler imaging is used to quantify CIDV and subsequent inhibition by CGRP receptor antagonists. We sought to evaluate a CGRP receptor antagonist, MK-3207, in the biomarker model and to assess the predictability of the CIDV response to migraine clinical efficacy.

Methods

An integrated population pharmacokinetic/pharmacodynamic (PK/PD) model was developed to describe the exposure−response relationship for CIDV inhibition by CGRP and TRPV1 receptor antagonists. MK-3207 dose−response predictions were made based on estimated potency from the PK/PD model and mean plasma concentrations observed at the doses investigated.

Results

The results suggested that a 20 mg dose of MK-3207 (EC₅₀ of 1.59 nm) would be required to attain the peripheral CIDV response at a target level that was shown previously to correlate with 2 h clinical efficacy based on phase 3 telcagepant clinical data, and that a plateau of the dose−response would be reached around 40–100 mg. These predictions provided a quantitative rationale for dose selection in a phase 2 clinical trial of MK-3207 and helped with interpretation of the efficacy results from the trial.

Conclusions

The integrated CIDV PK/PD model provides a useful platform for characterization of PK/PD relationships and predictions of dose−response relationships to aid in future development of CGRP and TRPV1 receptor antagonists.     

Interleukin-10 promoter polymorphisms in rheumatoid arthritis and Felty's syndrome

OBJECTIVE: To examine whether promoter polymorphisms associated with variation in interleukin-10 (IL-10) production are relevant to the development of rheumatoid arthritis (RA) or Felty's syndrome (FS). METHODS: DNA was obtained from 44 FS patients, 117 RA patients and 295 controls. The promoter region between -533 and - 1120 was amplified by polymerase chain reaction, and polymorphisms detected by restriction enzyme digest or sequence-specific oligonucleotide probing. RESULTS: We found no significant difference in allele or haplotype frequencies between the groups. CONCLUSION: There is no association between FS or RA and these recently identified IL-10 promoter polymorphisms. Other genetic or environmental factors could explain the alterations in IL-10 levels seen in these conditions.      

Bioelectrical impedance analysis and other hydration parameters as risk factors for delirium in rural nursing home residents

BACKGROUND: The study investigators conducted a vigorous screening protocol for delirium in rural long-term care (LTC) facilities for a period of 28 days focusing on Bioelectrical Impedance Analysis (BIA) and other hydration parameters as risk factors. METHODS: A two-stage cluster sampling procedure was used to randomly select participants (n = 313) from 13 LTC facilities located in southeastern Iowa, stratified on facility bed size. BIA was used to estimate intracellular water (ICW), extracellular water (ECW), and total body water (TBW) on four occasions--baseline and follow-up days 7, 14, and 28. Volume estimates were calculated as a percent of body weight (%WT). Serum electrolytes and hematology were also measured. Delirium was measured with four strict criteria: a NEECHAM Confusion Scale score < 25, Vigilance "A" score > 2, a Mini-Mental Status Examination < baseline, and a positive Confusion Assessment Method score. RESULTS: There were n = 69 delirium cases (22.0%). Blood urea nitrogen/creatinine ratios greater than 21:1 (odds ratio = 1.76, 95% confidence interval 1.02-3.06). No significant risk for delirium was associated with ICW, ECW, or TBW as a percent of body weight. CONCLUSIONS: Some changes were observed with a slight decrease in ICW between day 7 and day 14 of follow-up that tended to follow an increase in delirium events, but in general the BIA measures did not predict delirium events.     

A review of cervical spine injury associated with maxillofacial trauma at a UK tertiary referral centre

IntroductionThe aim of this study was to determine the incidence and patterns of cervical spine injury (CSI) associated with maxillofacial fractures at a UK trauma centre.MethodsA retrospective analysis was conducted of 714 maxillofacial fracture patients presenting to a single trauma centre between 2006 and 2012.ResultsOf the 714 maxillofacial fracture patients, 2.2% had associated CSI including a fracture, cord contusion or disc herniation. In comparison, 1.0% of patients without maxillofacial trauma sustained a CSI (odds ratio: 2.2, p=0.01). The majority (88%) of CSI cases of were caused by a road traffic accident (RTA) with the remainder due to falls. While 8.8% of RTA related maxillofacial trauma patients sustained a CSI, only 2.0% of fall related patients did (p=0.03, not significant). Most (70%) of the CSIs occurred at C1/C2 or C6/C7 levels. Overall, 455, 220 and 39 patients suffered non-mandibular, isolated mandibular and mixed mandibular/non-mandibular fractures respectively. Their respective incidences of CSI were 1.5%, 1.8% and 12.8% (p=0.005, significant). Twelve patients with concomitant CSI had their maxillofacial fractures treated within twenty-four hours and all were treated within four days.ConclusionsThe presence of maxillofacial trauma mandates exclusion and prompt management of cervical spine injury, particularly in RTA and trauma cases involving combined facial fracture patterns. This approach will facilitate management of maxillofacial fractures within an optimum time period.     

Alloimmunization to platelets in heavily transfused patients with sickle cell disease

Bone marrow transplantation (BMT) is now an option for some patients with sickle cell disease (SCD). Many SCD patients are multiply transfused with red blood cells (RBCs), and may be immunized to alloantigens other than erythrocyte antigens. Because platelet refractoriness is a significant complication during BMT, we wished to determine the prevalence of alloimmunization to platelets in transfused SCD patients. Sera collected from 47 transfused and 14 untransfused SCD patients were screened for HLA and platelet-specific antibodies. Transfusion and RBC antibody histories were reviewed. A subset of the patients were rescreened 1 year later. Eighty-five percent of patients with at least 50 RBC transfusions (22 of 26), 48% of patients with less than 50 transfusions (10 of 21), and none of 14 untransfused patients demonstrated platelet alloimmunization (P < .05). Platelet alloimmunization was more prevalent than RBC alloimmunization (20% to 30%). Half of the platelet reactivity was chloroquine-elutable. Eighteen of 22 patients (82%) on chronic RBC transfusion remained platelet-alloimmunized 11 to 22 months after initial testing. In summary, 85% of heavily transfused SCD patients are alloimmunized to HLA and/or platelet-specific antigens. These patients may be refractory to platelet transfusion, a condition that would increase their risk during BMT. Leukodepletion in the transfusion support of SCD patients should be considered to prevent platelet alloimmunization.     

The effect of lithium on growth factor production in long-term bone marrow cultures

We have previously reported that lithium chloride (LiCl) stimulates the production of granulocyte-macrophage colony-forming cells (GM-CFC), pluripotent stem cells (CFU-S), and differentiated granulocytes, macrophages and megakaryocytes in murine Dexter marrow cultures and that this effect appears to be mediated indirectly by a radioresistant adherent marrow cell. In this study we have established that exposure of murine Dexter cultures to LiCl (4 mEq/L) causes an increase of colony-forming cell megakaryocytes (CFU-meg) over 1 to 6 weeks of culture in both supernatant (188% to 611%) and stromal phases (123% to 246%). Moreover, we have shown that lithium treatment of either irradiated (1,100 rad) or unirradiated stromal cells increased production of activities stimulating formation of megakaryocyte, granulocyte, macrophage, and mixed lineage colonies and proliferation of the factor-dependent cell line, FDC-P1. This FDC-P1 stimulatory activity was completely blocked by an antibody to purified recombinant granulocyte-macrophage colony stimulating factor (rGM-CSF). The baseline or lithium-induced--stromal-derived bone marrow colony stimulating activity was partially blocked by the antibody to rGM-CSF and by an antibody to purified colony stimulating factor I (CSF-1); the two antibodies combined resulted in greater than 90% inhibition of the lithium-induced marrow stimulatory activity. In addition, radioimmunoassay (RIA) showed that although CSF-1 was detectable in supernatants of these cultures, exposure to lithium did not increase CSF-1 levels. These data indicate that Dexter stromal cells produce CSF- 1 and GM-CSF and that lithium appears to exert its stimulatory effects on in vitro myelopoiesis by inducing production of GM-CSF.