Evidence of large-scale chronic eutrophication in the Great Barrier Reef: quantification of chlorophyll a thresholds for sustaining coral reef communities.

Long-term monitoring data show that hard coral cover on the Great Barrier Reef (GBR) has reduced by >70 % over the past century. Although authorities and many marine scientists were in denial for many years, it is now widely accepted that this reduction is largely attributable to the chronic state of eutrophication that exists throughout most of the GBR. Some reefs in the far northern GBR where the annual mean chlorophyll a (Chl a) is in the lower range of the proposed Eutrophication Threshold Concentration for Chl a (~0.2-0.3 mg m⁻³) show little or no evidence of degradation over the past century. However, the available evidence suggests that coral diseases and the crown-of-thorns starfish will proliferate in such waters and hence the mandated eutrophication Trigger values for Chl a (~0.4-0.45 mg m⁻³) will need to be decreased to ~0.2 mg m⁻³ for sustaining coral reef communities.

Analysis of satellite imagery using a simple algorithm supports evidence that Trichodesmium supplies a significant new nitrogen load to the GBR lagoon.

This work supports previous studies in the Great Barrier Reef lagoon that show the new nitrogen (N) load introduced by Trichodesmium is similar to or greater than that from riverine discharges. However, the current management programs aimed at improving the chronic eutrophic state of the GBR ignore the N load from Trichodesmium. These programs also ignore the evidence that Trichodesmium blooms could promote the bioavailability of heavy metals and be a source of toxins in the ciguatera food chain. Further work is urgently required to better quantify the potential impacts of Trichodesmium and develop management plans to reduce those impacts. A simple algorithm that uses MODIS imagery is developed for not only monitoring the spatial extent of Trichodesmium blooms but also for quantifying the concentration of those blooms. The algorithm is based on the readily available MODIS L2 data. A management plan that includes the harvesting of Trichodesmium is outlined.

The GALA trial: will it influence clinical practice?

The General Anesthesia vs. Local Anesthesia for Carotid Surgery (GALA) trial did not show a difference in 30-day postoperative stroke, myocardial infarction and death rates between patients undergoing carotid endarterectomy (CEA) under local vs. general anesthesia. The present article discusses some limitations of the GALA trial. Firstly, the expected stroke and death rates following CEA is so low, that it was unlikely that the GALA trial would show any significant difference between local and general anesthesia. Secondly, preoperative statin use was not recorded. Thirdly, intraoperative shunt usa ge rates (a possible parameter for the development of stroke) varied considerably between the 2 groups (43% vs. 14%, for general vs. local anesthesia, respectively; P < .0001), as well as between UK and non-UK surgeons who always (73.6% vs. 20.8%, respectively; P < .0001), never (4.2% vs. 26%, respectively; P < .0002), or selectively (22.2% vs. 53.2%, respectively; P < .0001) used a shunt. Furthermore, no information was provided regarding the type of shunts used; for example, atraumatic shunts may be associated with lower perioperative stroke rates. These limitations could influence the interpretation of the results of the GALA trial. Due to lack of differences between the 2 groups and the presence of the above limitations, it seems likely that this trial will have little effect on clinical practice.

The antithrombotic effect of dextran-40 in man is due to enhanced fibrinolysis in vivo.

BACKGROUND: Dextran-40 is effective in reducing postoperative Doppler-detectable embolization in patients undergoing carotid endarterectomy (CEA). Dextrans are thought to have antithrombotic and antiplatelet effects. The mode of action is unclear. In rats, dextran blocks uptake of tissue plasminogen activator (tPA) by mannose-binding receptors. Because this would have the effect of enhancing endogenous fibrinolysis, we explored this effect of dextran-40 on fibrinolysis in man. METHODS: Twenty patients undergoing endovascular stenting for abdominal aortic aneurysm were randomized to receive 100 mL of 10% dextran-40 or saline, over 1 hour, during their operation in addition to heparin. Blood samples were taken preoperatively, intraoperatively (immediately after operative procedure), and 24 hours postoperatively. Thrombi were formed in a Chandler loop and used to assess endogenous fibrinolysis over 24 hours, measured as the fall in thrombus weight, and the release of fluorescently labelled fibrinogen from the thrombus. Plasma samples were analyzed for markers of fibrinolysis; plasmin-antiplasmin (PAP), PAI-1, and t-PA, and for functional von Willebrand factor (vWF). Platelet response to thrombin and other agonists was measured by flow cytometry. RESULTS: Thrombi formed ex vivo from the intraoperative blood samples from the dextran-treated patients exhibited significantly greater fibrinolysis vs preoperative samples, seen both as a significantly greater percentage reduction in thrombus weight (from 34.7% to 70.6% reduction) and as an 175% increase in the release of fluorescence (P < .05). Fibrinolysis returned to baseline levels the next day. No change was seen in the saline-treated group. Plasma levels of PAP and PAI-1 increased significantly postoperatively in the dextran-treated group vs the saline group (P < .05). The postoperative level of functional VWF was significantly lower in the dextran-treated group vs controls. A specific reduction occurred in the platelet response to thrombin, but not to other agonists, in the intraoperative samples from the dextran-treated group (11.1% vs 37.1%; P = .022), which was not seen in the controls. CONCLUSIONS: These data are consistent with a rise in plasmin due to dextran blockade of tPA uptake in vivo, leading to enhanced fibrinolysis, cleavage of vWF and of the platelet protease-activated receptor-1 (PAR-1) thrombin receptor. This suggests that dextran exerts a combined therapeutic effect, enhancing endogenous fibrinolysis, whilst also reducing platelet adhesion to vWF and platelet activation by thrombin. The proven antithrombotic efficacy of low-dose dextran in carotid surgery may be applicable to wider therapeutic use.

Treatment of asymptomatic carotid disease with stenting: con.

The landmark trials of the 1980s established a powerful precedent for demanding that "evidence" rather than "intuitive reasoning" should determine practice regarding management of patients with carotid disease. Accordingly, for our opponents to succeed in this debate, they must first demonstrate that there is little remaining confusion regarding the optimal management of asymptomatic carotid disease and then provide compelling evidence that it is now reasonable to offer carotid angioplasty with stenting without the protection of randomized trials. It is our contention that neither can be demonstrated and that the motion cannot be sustained.

Matrix metalloproteinase-8 and -9 are increased at the site of abdominal aortic aneurysm rupture.

BACKGROUND: Abdominal aortic aneurysm (AAA) expansion is characterized by extracellular matrix degradation and widespread inflammation. In contrast, the processes that characterize AAA rupture are not well understood. The aim of this study was to investigate the proteolytic and cellular activity of ruptured AAA, focusing on matrix metalloproteinases (MMPs) and their inhibitors (TIMPs). METHODS AND RESULTS: Anterior aneurysm wall biopsies were taken from 55 nonruptured and 21 ruptured AAAs. A further biopsy from the site of rupture was taken from 12 of the ruptured AAAs. MMP-1, -2, -3, -8, -9, and -13, as well as TIMP-1 and -2, were quantified in each biopsy with ELISA. A comparison of anterior aneurysm biopsies showed no difference in MMP or TIMP concentrations between nonruptured and ruptured AAA. In a comparison of ruptured AAA biopsies, MMP-8 and -9 levels were significantly elevated in the 12 rupture site biopsies compared with their 12 paired anterior wall biopsies, whereas other MMPs and TIMPs showed no difference (MMP-8, P<0.001; MMP-9, P=0.01). MMP-8 and -9 expression was mediated by native mesenchymal cells and was independent of the inflammatory infiltrate. CONCLUSIONS: A localized increase in MMP-8 and -9, mediated by native mesenchymal cells, presents a potential pathway for collagen breakdown and AAA rupture.

Repair of ruptured abdominal aortic aneurysms by endovascular techniques.

Emergency EVR for ruptured AAA is now technically feasible, and several reports with small numbers have appeared in the literature from major centers suggesting that the results may be the same as or better than seen with open repair. The immediate priority is avoidance of over-resuscitation together with the rapid transfer of the patient to CT and then to the operating theater. Because of the learning curve involved, these cases should be attempted only by major centers that have extensive elective endovascular experience. The requirement for 24-hour availability of surgeons and radiologists trained in endovascular techniques places an enormous strain on vascular and radiologic staff and is achievable only in major centers with large teams of doctors. These issues raise important questions about the delivery of vascular services and whether all cases of ruptured aortic aneurysm should be transferred to major vascular centers. The operating theater staff and other support persons need training in endovascular techniques and in rapid deployment of an aortic occlusion balloon. A wide selection of devices, guidewires, and catheters must be immediately available in the operating theater. The ideal way to establish the role of EVR for ruptured AAA would be a randomized trial, but there might be logistic difficulties in recruiting sufficient numbers in major vascular centers, particularly as screening for AAA becomes more common and reduces the number of cases. There also are ethical issues as to whether these patients can give informed consent for involvement in such a trial. The alternative is for major centers to continue to develop their endovascular programs, to do more cases, and to compare the results with historical controls undergoing open repair.

Reevaluation of ENCORE: support for the eutrophication threshold model for coral reefs.

The results from the multimillion dollar Enrichment of Nutrients on Coral Reefs Experiment (ENCORE) on One Tree Island Reef (OTIR) suggest that increased nutrient loads to coral reefs will have little or no effect on the algal growth rates and, hence, on the associated effects that increased algal growth might have on the functioning and stability of coral reefs. However, a comparison of the concentrations of nutrients within the OTIR lagoon with the proposed nutrient threshold concentrations (NTC) for coral reefs suggests that all sites, including the control sites, were saturated with nutrients during ENCORE, and, hence, one would not expect to get any differences between treatments in the algal-growth related measurements. Thus, ENCORE results provide strong support for the proposed NTCs and support the ecological principle that algal productivity and, consequently, the functioning of coral reefs are sensitive to small changes in the background concentrations of nutrients. The principal conclusion of ENCORE, namely that the addition of nutrients did not cause the "pristine" OTIR to convert from coral communities to algal dominated reefs, is contrary to the fact that there was prolific macroalgal growth on the walls and crests of the experimental microatolls by the end of ENCORE.

Prospective, randomized, double-blind trial investigating the effect of doxycycline on matrix metalloproteinase expression within atherosclerotic carotid plaques.

BACKGROUND AND PURPOSE: Elevated levels of matrix metalloproteinases (MMPs), particularly MMP-1 and MMP-9, have been implicated in plaque rupture. It has been suggested that inhibition of MMPs may stabilize vulnerable atherosclerotic plaques and improve clinical outcome. The aim of the study was to investigate the ability of doxycycline, a nonspecific MMP inhibitor, to reduce MMP concentration in carotid atheroma. METHODS: The study design was a prospective, double-blind randomized trial. One hundred patients requiring carotid endarterectomy were randomized to receive 200 mg/d doxycycline or placebo for 2 to 8 weeks before surgery. During endarterectomy, carotid plaques were retrieved. The concentrations of MMPs and doxycycline were determined in the atherosclerotic tissue by enzyme-linked immunosorbent assay and high-performance liquid chromatography, respectively. Clinical events were recorded, as was the rate of preoperative embolization (transcranial Doppler). RESULTS: Analysis of endarterectomized specimens demonstrated a mean doxycycline concentration of 6.0 micro g/g wet weight in treated patients. Administration of doxycycline significantly reduced the concentration of MMP-1 in carotid plaques from a mean of 14.8 to 10.3 ng/100g wet weight (P=0.038). This difference was due to decreased MMP-1 transcript (P<0.001). There was no difference in any other MMP (MMP-2, -3, or -9) or tissue inhibitor of matrix metalloproteinases-1 or -2. CONCLUSIONS: Doxycycline penetrated atherosclerotic plaques with acceptable tissue levels. This resulted in a reduction in MMP-1 concentration because of decreased expression.

Comparison of levels of matrix metalloproteinases, tissue inhibitor of metalloproteinases, interleukins, and tissue necrosis factor in carotid endarterectomy specimens from patients on versus not on statins preoperatively.

We performed an observational study on 137 patients undergoing carotid endarterectomy (CEA). Patients on statins were less likely to have had symptoms in the 4 weeks before CEA (p = 0.0049) and were less likely to have spontaneous cerebral embolization detected by transcranial Doppler (p = 0.0459). Carotid plaques retrieved at CEA from patients taking statins revealed significantly lower concentrations of matrix metalloproteinase-1 (p = 0.0176), matrix metalloproteinase-9 (p = 0.0018), and interleukin-6 (p = 0.0005).

Evaluation of level 1 care facilities for vascular patients.

BACKGROUND: A surgical acute care unit (SACU) was established within our hospital to specifically provide level 1 care to surgical patients. We assess the impact that this has had on outcome in vascular patients. METHODS: All patients undergoing carotid endarterectomy (CEA) and elective abdominal aortic aneurysm repair (AAA) during the first year of SACU were included in the present study. A control group was compiled from patients undergoing the same two procedures in the year preceding the opening of the SACU. Data were collected on admission time, time spent in critical care, outcome and operative cancellations. RESULTS: During the first year of the SACU there were 28 CEA and 42 AAA repairs performed. In the control group there were 18 CEA and 34 AAA repairs performed. There were no significant differences in death rate or length of hospital stay between the two groups for either AAA repair or CEA. CEA patients in the study group had a significantly reduced level 2 stay (P < 0.001 Mann-Whitney U-test), with 71% of patients being admitted directly to the level 1 facility from theatre. There were less CEA cancelled because of critical care bed shortages among the cases (n = 0) compared to the control group (n = 2), although this did not reach statistical significance (P = 0.15 Fisher's exact test). CONCLUSIONS: Designated level 1 care has reduced the need for the postoperative admission of CEA patients to level 2 care facilities. It has had no discernible impact on admission time or mortality, but might reduce the number of cancelled operations caused by a lack of level 2 beds.

An investigation into the cause of distal endoleaks: role of displacement force on the distal end of a stent-graft.

PURPOSE: To investigate if the forces developed by pulsatile flow on a stent-graft and dimensional changes of the graft material might contribute to distal endoleak and stent-graft kinking. METHODS: An in vitro experimental model was used to measure the peak displacement force developed by pulsatile flow pressure on the distal end of a stent-graft. Polytetrafluoroethylene (PTFE) graft material (110 mm long, 22 mm in diameter) was evaluated in a flow circuit, with water as the circulating liquid. In addition, the effect of internal pressure on PTFE graft dimensions was measured under nonpulsatile conditions in 3 configurations (1 bifurcated and 2 straight). RESULTS: Pressure in the PTFE graft did not cause a change in graft diameter but did increase the length of the graft. The mean load required to prevent retrograde displacement was 208.5+/-2.5 g. Peak retrograde displacement force developed on the distal end of the stent-graft by the pressure of pulsatile flow was strongly associated with the systolic phase of the cardiac cycle. CONCLUSIONS: The distal end of the stent-graft is subject to a retrograde displacement force by the pressure of pulsatile arterial flow. In addition, pressure inside the PTFE graft causes its length to increase. Both of these factors may be important in the development of late complications of stent-grafting.

Early rupture of a partially treated abdominal aortic aneurysm: another endovascular lesson.

PURPOSE: To report early rupture of a partially treated abdominal aortic aneurysm. CASE REPORT: A 76-year-old man with a 6.4-cm abdominal aortic aneurysm had the main body of a bifurcated graft inserted into the aneurysm. However, it was not possible to cannulate the short cuff of the graft to deploy the contralateral limb, probably due to a proximal aortic stenosis compressing the stent-graft. The plan was for the patient to return on another date for a further attempt at recannulation; however, shortly after the patient was discharged, the aneurysm ruptured, necessitating conventional open repair, which the patient survived. CONCLUSIONS: Every effort should be made to complete endovascular treatment of abdominal aortic aneurysms at a single session.

Clinical outcome of primary infrainguinal subintimal angioplasty in diabetic patients with critical lower limb ischemia.

PURPOSE: To evaluate the clinical outcome of subintimal angioplasty in diabetic patients with critical limb ischemia (CLI) compared to nondiabetics irrespective of the patency status of the treated arteries. METHODS: The records of 99 consecutive patients (53 men; median age 78.5 years, range 42-92) suffering from CLI who underwent primary infrainguinal subintimal angioplasty in 112 limbs within a 6-month period were studied retrospectively. A third of the patients (n=33) were diabetic. The technical success, perioperative morbidity/mortality, and clinical success were compared between the diabetic and nondiabetic patients. Kaplan-Meier life-table analysis was used to analyze clinical success, limb salvage, and survival for both groups. RESULTS: The overall technical success was 89% (81% in diabetics, 93% in nondiabetics, p=0.05). Perioperative morbidity was 8% (16.7% in diabetics, 3.9% in nondiabetics, p=0.03). The perioperative mortality was zero. The clinical success at 12, 24, and 36 months was 74%, 72%, and 65% in nondiabetics and 69%, 63%, and 54% in diabetics, respectively (p=0.17). The limb salvage rate at 36 months was 88% overall (90% in nondiabetics, 82% among diabetics, p=0.20). The 36-month survival rate was 61% in nondiabetics and 57% in diabetics (p=0.29). CONCLUSIONS: In terms of clinical outcome, infrainguinal subintimal angioplasty is almost equally effective in diabetics as in nondiabetics suffering from CLI.

Long-term results of endovascular AAA repair using a homemade aortomonoiliac PTFE device.

PURPOSE: To assess the long-term results of a homemade aortomonoiliac polytetrafluoroethylene (PTFE) device used for endovascular abdominal aortic aneurysm (AAA) repair. METHODS: A vascular audit database was interrogated to identify 58 consecutive AAA patients (all men; median age 73 years, range 56-88) who underwent aortomonoiliac stent-graft repair. AAAs were eligible for endovascular treatment if the infrarenal neck was > or = 15 mm long and < or = 28 mm in diameter. RESULTS: Nine (15.5%) procedures failed, 8 during the procedure and 1 on the 7th postoperative day; 8(13.8%) patients were converted, but one was unfit for surgery. There was one intraprocedural stroke, and 3 (5.2%) patients died within 30 days. The primary success rate (no conversion or mortality) was 79.3%. Over a median follow-up of 45 months (range 23-80), there were 3 (5.2%) graft occlusions, 1 kink requiring stent implantation, and 1 expanding sac without identifiable endoleak. There were 11 (19.0%) endoleaks in 10 patients, 9 type I leaks (2 proximal) and 1 type II. One patient with a distal type I endoleak (treated) also exhibited a type III leak at 2 years, but the sac size had not increased. There was a 40% incidence of bilateral buttock claudication, which was serious in only 1 patient. The long-term survival rate by Kaplan-Meier life-table analysis was 57% at 4 years. CONCLUSIONS: Implantation of an aortomonoiliac PTFE device can be achieved with good primary success, and the stent-graft seems durable over the long term. Proximal type I endoleaks are rare, but distal endoleaks from the contralateral common iliac artery can be solved by using a different covered stent.

A Coculture Model of Intrahepatic Islet Transplantation: Activation of Kupffer Cells by Islets and Acinar Tissue.

Clinical and experimental studies of intrahepatic islet transplantation have allowed histological and systemic observations to be made, but the location of the transplanted islets makes it difficult to assess direct effects on the cells of the liver. An in vitro coculture model of Kupffer cells with islets or pancreatic acinar tissue is described, using porcine tissue and measuring the secretion of thromboxane B2, prostaglandin E2, 6-keto-prostaglandin F1α, and prostaglandin F2α as an indicator of Kupffer cell stimulation. The results have demonstrated activation of Kupffer cells in the presence of acinar or islet tissue, both when the cells were in direct contact and when separated by a membrane. This indicated that the stimulation was due to a soluble factor or factors, and was confirmed by the culture of Kupffer cells with acinar conditioned medium. The degree of stimulation was much greater with acinar tissue than with islets. In subsequent experiments, aprotinin, an enzyme activation inhibitor, was added to the cocultures in an attempt to reduce Kupffer cell activation. This had no effect, possibly due to the fact that the endogenous pancreatic enzymes may already be activated during digestion of the pancreas. Aprotinin alone caused an increase in secretion of eicosanoids from Kupffer cells. The high response to acinar tissue is of particular relevance to islet autotransplantation in which unpurified pancreatic digest is often transplanted. The clinical effectiveness of aprotinin in the light of these results is discussed. In conclusion, although unable to mimic the complex situation following intrahepatic islet transplantation, the coculture model described here allows the opportunity to assess the events relating to specific cell types, and will provide the scope to undertake more detailed studies on the mechanisms involved. The same model could be applied to the coculture of pancreatic tissue with hepatocytes to determine any effects on the normal function of hepatocytes.

Patients' thromboembolic potential after carotid endarterectomy is related to the platelets' sensitivity to adenosine diphosphate.

UNLABELLED: Background and purpose Postoperative microemboli in patients undergoing carotid endarterectomy are a significant risk factor for stroke. These emboli can be detected by intraoperative transcranial Doppler monitoring. They are not linked to technical error and are variable between patients. As it is known that platelets play a key role in arterial thrombosis, it was hypothesized that a patient's risk of postoperative carotid thrombosis was linked to the individual's platelet response to physiologic agonists. METHODS: Blood samples from 120 patients undergoing carotid endarterectomy were analyzed before surgery. Platelet aggregation was measured in response to adenosine diphosphate (ADP) (0.5 to 4 micromol/L), collagen (10 to 50 mg/mL), and arachidonic acid (3 or 6 micromol/L), and fibrinogen binding to GPIIb-IIIa was measured by whole blood flow cytometry in response to ADP (0.1 to 10 micromol/L) and thrombin (0.02 to 0.16 micro/mL). Patients underwent intraoperative transcranial Doppler monitoring for 3 hours after surgery, and platelet functional data of those who had >25 emboli in this period (n = 22) were compared with the data of those with <25 emboli (n = 88). RESULTS: The platelet response to ADP was significantly higher in the patients with >25 emboli, as measured both by aggregometry (P =.0012) and by flow cytometry (P <.0001). Platelet aggregation with collagen was also significantly higher in this group (P =.0018), but the response to thrombin was not statistically different in the two groups. In addition, there was no difference in the response to arachidonic acid between the groups. CONCLUSION: The platelet response to ADP may be linked to clinical outcome, and thus, specific ADP receptor inhibitors may be appropriate for this group of patients.