Evolutionary Rates of Bumblebee Genomes Are Faster at Lower Elevations.

The importance of climate in determining biodiversity patterns has been well documented. However, the relationship between climate and rates of genetic evolution remains controversial. Latitude and elevation have been associated with rates of change in genetic markers such as cytochrome b. What is not known, however, is the strength of such associations and whether patterns found among these genes apply across entire genomes. Here, using bumblebee genetic data from seven subgenera of Bombus, we demonstrate that all species occupying warmer elevations have undergone faster genome-wide evolution than those in the same subgenera occupying cooler elevations. Our findings point to a critical biogeographic role in the relative rates of whole species evolution, potentially influencing global biodiversity patterns.

Sequencing and analysis of genes involved in the biosynthesis of a vancomycin group antibiotic.

BACKGROUND: The emergence of resistance to vancomycin, the drug of choice against methicillin-resistant Staphylococcus aureus, in enterococci has increased the need for new antibiotics. As chemical modification of the antibiotic structure is not trivial, we have initiated studies towards enzymatic modification by sequencing the DNA coding for the biosynthesis of chloroeremomycin (also known as A82846B and LY264826). RESULTS: Analysis of 72 kilobases of genomic DNA from Amycolatopsis orientalis, the organism that produces chloroeremomycin, revealed the presence of 39 putative genes, including those coding for the biosynthesis of the antibiotic. Translation and subsequent comparison with known proteins in public databases identified enzymes responsible for the biosynthesis of the heptapeptide backbone and 4-epi-vancosamine, as well as those for chlorination and oxidation reactions involved in the biosynthesis of chloroeremomycin. CONCLUSIONS: The genes responsible for the biosynthesis of chloroeremomycin have been identified, and selective expression of these genes could lead to the synthesis of new potent glycopeptide antibiotics.

Vascular surgical society of great britain and ireland: transcranial doppler-directed dextran therapy in the prevention of postoperative carotid thrombosis

BACKGROUND: Evidence suggests that embolization precedes carotid thrombosis, a previously unpredictable event complicating 2-3 per cent of all carotid endarterectomies. It was hypothesized that dextran 40 therapy might prevent progression to complete thrombosis in high-risk patients. METHODS: Between October 1995 and July 1998, 400 consecutive patients were monitored following carotid endarterectomy using transcranial Doppler ultrasonography. Those with sustained embolization (more than 25 in 10 min) or those with emboli that distorted the middle cerebral artery waveform were commenced on an incremental dextran 40 infusion. RESULTS: Two hundred and sixteen patients (54 per cent) had one or more emboli detected (96 per cent within 2 h of flow restoration) but only 15 (4 per cent) required dextran therapy. Embolization ceased in each case although the dextran dose had to be adjusted in four. In one of the latter patients, embolization recurred on day 5 but was again controlled with high-dose dextran. Overall, the death and any stroke rate was 2 per cent and no patient suffered a stroke due to carotid thrombosis. CONCLUSION: A few patients develop sustained embolization following carotid endarterectomy which, in previous studies, has been shown to be highly predictive of carotid thrombosis. The authors' experience to date suggests that dextran can stop this phase of embolization and prevent progression to complete carotid thrombosis. However, the dose of dextran has to be adjusted in 25 per cent of patients (i.e. blind administration of dextran may not be effective) and, very rarely, embolization may recur later.

Can cerebrovascular reactivity be assessed without measuring blood pressure in patients with carotid artery disease? .

BACKGROUND AND PURPOSE: Conventional methods of assessing cerebrovascular reactivity (CVR) omit the influence of blood pressure (BP). This study demonstrates the significant influence of BP during the assessment of CVR in patients with carotid artery disease. METHODS: In 56 subjects the CVR was bilaterally assessed by measurement of cerebral blood flow velocity change in response to inhalation of 5% CO2 in air while BP was continuously monitored. Three methods of calculating the CVR were used: the conventional ratio between relative cerebral blood flow velocity and end-tidal CO2, simple linear regression, and multiple linear regression analysis (MLRA). The clinical significance of the difference in CVR indices was evaluated. The Bland-Altman test was applied to quantify the comparability and bias between measurements. The magnitude and significance of a change in BP during the CVR assessment were calculated in conjunction with an estimate of the velocity change attributed to the BP. The statistical significance of the data segment length on the variability and magnitude of the CVR index was computed. RESULTS: The value of the CVR index was reduced by 20% and 6% in comparison to the conventional ratio approach when MLRA and linear regression were applied, respectively. With the use of MLRA, in 96% of cases the value of the BP coefficient was statistically significant, and in four patients the increase in velocity was primarily attributed to the increase in BP. CONCLUSIONS: The influence of BP is significant and requires consideration when the CVR index is calculated in patients with carotid artery disease.

Control of emboli in patients with recurrent or crescendo transient ischaemic attacks using preoperative transcranial Doppler-directed Dextran therapy.

BACKGROUND: Transcranial Doppler (TCD)-directed Dextran 40 treatment after carotid endarterectomy reduces the rate of early postoperative thrombosis. This study assessed the efficacy of intravenous Dextran 40 at controlling symptoms and emboli before elective carotid endarterectomy in patients with recurrent or crescendo transient ischaemic attacks (TIAs). METHODS: In a prospective study, patients with more than 70 per cent internal carotid artery stenosis who had two or more symptomatic episodes within 30 days and TCD-detected microemboli were studied. Dextran 40 was commenced at 20 ml/h and TCD was repeated to reassess the rate of embolization. The infusion was increased in 20-ml/h increments until symptoms and emboli were controlled. The patient then had carotid surgery on the next elective list. RESULTS: Nineteen patients with internal carotid stenosis greater than 70 per cent, recurrent symptoms and TCD-detected emboli were studied. All patients had symptoms and emboli controlled with Dextran 40. One patient with both unstable angina (awaiting urgent operation) and crescendo TIAs died from a myocardial infarct before undergoing operation. Of the 18 patients who had an operation, one suffered a non-disabling stroke on the third postoperative day. CONCLUSION: TCD-directed Dextran 40 offers a safe approach to high-risk patients before elective carotid endarterectomy, and warrants further study.

Quality control during endovascular aneurysm repair: monitoring aneurysmal sac pressure and superficial femoral artery flow velocity.

PURPOSE: To use intraoperative aneurysmal sac pressure measurement and flow monitoring of the superficial femoral artery (SFA) to ensure complete exclusion of the aneurysm from the circulation. METHODS: A 5F catheter was positioned in the aneurysmal sac of 15 consecutive patients undergoing endovascular aortomonoiliac aneurysm repair between February and September 1997. The catheter was connected to an external pressure transducer allowing pressure monitoring throughout the operation and for 24 hours postprocedurally. Flow velocity was monitored in the contralateral SFA by insonation with a 2-MHz Doppler ultrasound probe. RESULTS: No technical defect was observed in the deployment of 10 endografts, which demonstrated marked reduction in sac pressure and good flow in the lower limb. The mean aneurysm pressure dropped from 123 to 57 mmHg after graft insertion. In 5 cases, monitoring detected problems during the endograft procedure. In 3, incomplete stent deployment was detected by a failure of sac pressure to fall following stent inflation and by the presence of flow in the contralateral femoral artery. In the other 2 cases, a distal endoleak was detected by direct injection of contrast into the sac. CONCLUSIONS: Measuring aneurysm pressure in combination with SFA Doppler flow monitoring can detect complications of endovascular aneurysm repair.

Prevention of postoperative thrombotic stroke after carotid endarterectomy: the role of transcranial Doppler ultrasound.

PURPOSE: To determine the incidence of particulate embolization after carotid endarterectomy (CEA), the effect of dextran-40 infusion in patients with sustained postoperative embolization, and the impact of transcranial Doppler (TCD) monitoring plus adjuvant dextran therapy on the rate of postoperative carotid thrombosis. METHODS: Prospective study in 100 patients who underwent CEA with 6-hour postoperative monitoring using a TCD that was modified to allow automatic, intermittent recording from the ipsilateral middle cerebral artery waveform (10 minute sample every 30 minutes). An incremental dextran-40 infusion was commenced if 25 or more emboli were detected in any 10-minute period. RESULTS: Overall, 48% of patients had one or more emboli detected in the postoperative period, particularly in the first 2 hours. However, sustained embolization that required Dextran therapy developed in only five patients. In each case, the rate of embolization rapidly diminished. CONCLUSIONS: A small proportion of patients have sustained embolization after CEA, which in previous studies has been shown to be highly predictive of thrombotic stroke. Intervention with dextran reduced and subsequently stopped all the emboli in those in whom it was used and contributed to a 0% perioperative morbidity and mortality rate in this series.

A policy of quality control assessment helps to reduce the risk of intraoperative stroke during carotid endarterectomy.

OBJECTIVES: A pilot study in our unit suggested that a combination of transcranial Doppler (TCD) plus completion angioscopy reduced incidence of intra-operative stroke (i.e. patients recovering from anaesthesia with a new deficit) during carotid endarterectomy (CEA). The aim of the current study was to see whether routine implementation of this policy was both feasible and associated with a continued reduction in the rate of intraoperative stroke (IOS). MATERIALS AND METHODS: Prospective study in 252 consecutive patients undergoing carotid endarterectomy between March 1995 and December 1996. RESULTS: Continuous TCD monitoring was possible in 229 patients (91%), while 238 patients (94%) underwent angioscopic examination. Overall, angioscopy identified an intimal flap requiring correction in six patients (2.5%), whilst intraluminal thrombus was removed in a further six patients (2.5%). No patient in this series recovered from anaesthesia with an IOS, but the rate of postoperative stroke was 2.8%. CONCLUSIONS: Our policy of TCD plus angioscopy has continued to contribute towards a sustained reduction in the risk of IOS following CEA, but requires access to reliable equipment and technical support. However, a policy of intraoperative quality control assessment may not necessarily alter the rate of postoperative stroke.

Randomized study of carotid angioplasty and stenting versus carotid endarterectomy: a stopped trial.

BACKGROUND: Carotid angioplasty (CA) has been suggested to be a safer and more cost-effective alternative to carotid endarterectomy (CEA) in the management of symptomatic severe internal carotid artery (ICA) disease. METHODS: The study was conducted as a prospective consecutive randomized trial of CEA versus CA for symptomatic severe ICA disease in a university teaching hospital. All patients were assessed before and after surgery by a neurologist. The study consisted of 23 patients with focal carotid territory symptoms and severe ICA stenosis (> 70%) who were randomized to either CEA or CA. However, only 17 had received their allocated treatment before trial suspension. CEA with patching or CA with stenting were used as interventions. The main outcome measures were death or disabling or nondisabling stroke within 30 days. RESULTS: All 10 CEA operations proceeded without complication, but 5 of the 7 patients who underwent CA had a stroke (P=.0034), 3 of which were disabling at 30 days. CONCLUSIONS: After referral, the Data Monitoring Committee invoked the stopping rule and the trial was suspended. The investigators and the Ethics Committee subsequently concluded that the trial could not be restarted--even in an amended format-primarily because of problems with informed consent. We review many of the ethical dilemmas encountered in the performance of this study. If future trials do suggest a selected role for CA, it is essential that both the inclusion and the exclusion criteria are fully documented.

Work-load generated by the establishment of a non-heart beating kidney transplant programme.

The work-load generated by a non-heart-beating donor (NHBD) kidney transplant programme over a 3-year period is reported. A total of 73 referrals were made, 64 from the Accident department and 9 from the wards. Organ procurement was performed in 24 cases (33%) and resulted in the retrieval of 44 kidneys. Reasons for failure to achieve organ procurement were; refused consent (n = 13; 18%), relatives unavailable to ask for consent (n = 9; 12%), technical problems with catheter insertion or perfusion (n = 10; 14%), transplant staff unavailable (n = 1; 1%), long asystolic period (n = 8; 11%) and donor unsuitable for other reasons (n = 8; 11%). Of the 44 kidneys retrieved, 30 were transplanted locally, 8 were transplanted at other United Kingdom centres and 6 were discarded. Locally transplanted NHBD kidneys represented 21% of the total transplant programme during the time period under study. We conclude that NHBD kidneys are a good source of additional organs for transplantation, but only one-third of referrals result in a successful procurement procedure. Moreover, the setting up of a successful programme is labour-intensive and requires a highly committed staff.

Reducing the risk of carotid surgery: a 7-year audit of the role of monitoring and quality control assessment.

BACKGROUND AND PURPOSE: The current risk of stroke after carotid endarterectomy may be worse than reported in the international trials. Because studies have suggested that most operative strokes follow surgeon error, the aim of the current study was to audit the impact of introducing a strategy of perioperative monitoring and quality control assessment on outcome. METHODS: A total of 500 patients underwent carotid endarterectomy with intraoperative transcranial Doppler scan monitoring, completion angioscopy, and 3 hours of postoperative transcranial Doppler scan monitoring. The last of these guided selective dextran therapy in patients with high rates of postoperative embolization, which in previous series has been shown to be highly predictive of progression to thromboembolic stroke. RESULTS: Intimal flaps were repaired in 3% of patients and luminal thrombus removed in 4% of patients. The rate of intraoperative stroke was 0.2%. A total of 313 patients had more than one embolus detected postoperatively (96% within 2 hours of flow restoration), but only 22 patients had sustained embolization requiring dextran. Embolization ceased in all but one patient receiving dextran, although the dose had to be increased in seven patients (36%). One patient was unable to receive adequate dextran therapy because of severe cardiac failure. Overall, the 30-day death/stroke rate was 2.2%, no patient had a perioperative stroke because of carotid thrombosis, and the rate of ipsilateral embolic stroke was 0.8%. Most complications resulted from cardiac pathology or intracranial hemorrhage. CONCLUSIONS: A program of monitoring and quality control assessment has been associated with a 60% decrease in the operative risk in comparison with that observed before implementation of the protocol.

Transcranial Doppler-directed Dextran-40 therapy is a cost-effective method of preventing carotid thrombosis after carotid endarterectomy.

OBJECTIVES: perioperative stroke reduces the clinical effectiveness of carotid endarterectomy (CEA). Postoperative thrombotic stroke may be reduced in incidence by the use of transcranial Doppler-directed Dextran-40 therapy. This programme requires the purchase of additional equipment and employment of more staff. This study examined whether this additional financial outlay was cost-effective in terms of saving expenditure by preventing postoperative thrombotic stroke. MATERIALS AND METHODS: data was collected prospectively on a series of 600 consecutive CEAs. The costs of the monitoring programme were analysed over 1- and 5-year periods. Formulae were derived allowing other units to calculate whether this technique will be cost-effective for them. RESULTS: after the introduction of TCD monitoring the postoperative thrombotic stroke rate fell from 2.7% to 0% (8 strokes prevented). Our local unit cost for the treatment of stroke was 25,702 pounds. After allowing for the additional costs of the monitoring programme, we calculate that postoperative TCD has saved 171,393 pounds. CONCLUSIONS: postoperative TCD monitoring is a clinically effective and also cost-effective method of reducing the stroke rate associated with CEA. For units performing more than 50 CEAs per year who experience occasional postoperative carotid thrombosis, its introduction should be considered.

Transcranial Doppler directed dextran therapy in the prevention of carotid thrombosis: three hour monitoring is as effective as six hours.

BACKGROUND: Six hours' monitoring by transcranial Doppler (TCD) has been successful in directing Dextran therapy in patients at high risk of thrombotic stroke after carotid endarterectomy (CEA). OBJECTIVES: Is 3 h of routine monitoring as effective as 6 h in the prevention of early postoperative thrombotic stroke? DESIGN: Prospective, consecutive study in all patients with an accessible cranial window. METHODS: One hundred and sixty-six patients undergoing CEA underwent 3 h of postoperative monitoring by TCD. Any patient with > 25 emboli detected in any 10 min period or those with emboli that distorted the arterial waveform were commenced on an incremental infusion of dextran 40. RESULTS: The majority of patients destined to embolise will do so within the first 2 postoperative hours. Dextran therapy was instituted in nine patients (5%) and rapidly controlled this phase of embolisation although the dose had to be increased in three (33%). No patient suffered a postoperative carotid thrombosis but one suffered a minor stroke on day 5 and was found to have profuse embolisation on TCD; high dose dextran therapy was again instituted, the embolus count rate fell rapidly and he made a good recovery thereafter. Overall, the death and disabling stroke rate was 1.2% and the death/any stroke rate was 2.4%. CONCLUSION: Three hours of postoperative TCD monitoring is as effective as 6 h in the prevention of postoperative carotid thrombosis.

Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.