Viral cultures, cycle threshold values and viral load estimation for assessing SARS-CoV-2 infectiousness in haematopoietic stem cell and solid organ transplant patients: a systematic review.

BACKGROUND: Solid organ and haematopoietic stem cell transplant recipients are more vulnerable to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) than non-transplant recipients due to immunosuppression, and may pose a continued transmission risk, especially within hospital settings. Detailed case reports including symptoms, viral load and infectiousness, defined by the presence of replication-competent viruses in culture, provide an opportunity to examine the relationship between clinical course, burden and contagiousness, and provide guidance on release from isolation. OBJECTIVES: To investigate the relationship between serial SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) cycle threshold (Ct) value or cycle of quantification value, or other measures of viral burden and the likelihood and duration of the presence of infectious virus based on viral culture, including the influence of age, sex, underlying pathologies, degree of immunosuppression, and/or vaccination on this relationship, in transplant recipients. METHODS: LitCovid, medRxiv, Google Scholar and the World Health Organization COVID-19 database were searched from 1st November 2019 to 26th October 2022. Studies reporting relevant data (results from serial RT-PCR testing and viral culture data from the same respiratory samples) for transplant recipients with SARS-CoV-2 infection were included in this systematic review: Methodological quality was assessed using five criteria, and the data were synthesized narratively and graphically. RESULTS: Thirteen case reports and case series reporting on 41 transplant recipients (22 renal, five cardiac, one bone marrow, two liver, one bilateral lung and 10 blood stem cell) were included in this review. A relationship was observed between proxies of viral burden and likelihood of shedding replication-competent SARS-CoV-2. Three individuals shed replication-competent viruses for >100 days after symptom onset. Lack of standardization of testing and reporting platforms precludes establishing a definitive viral burden cut-off. However, the majority of transplant recipients stopped shedding replication-competent viruses when the Ct value was >30 despite differences across platforms. CONCLUSIONS: Viral burden is a reasonable proxy for infectivity when considered within the context of the clinical status of each patient. Standardized study design and reporting are essential to standardize guidance based on an increasing evidence base.

Freshwater fish gill ion transport: August Krogh to morpholinos and microprobes.

August Krogh proposed that freshwater fishes (and other freshwater animals) maintain body NaCl homoeostasis by extracting these ions from the environment via separate Na(+) /NH(4)(+) and Cl(-) /HCO(3)(-) exchangers in the gill epithelium. Subsequent data from other laboratories suggested that Na(+) uptake was more probably coupled to H(+) secretion via a vesicular proton pump (V-ATPase) electrically coupled to a Na(+) channel. However, despite uncertainty about electrochemical gradients, evidence has accrued that epithelial Na(+) /H(+) exchange indeed may be an alternative pathway for Na(+) uptake. The specific pathways for Na(+) uptake may be species and environment specific. An apical Cl(-) /HCO(3)(-) exchanger is generally accepted for most species (some species do not extract Cl(-) from freshwater), but the relative roles of anion exchanger-like (SLC4A1) vs. pendrin-like (SLC26Z4) exchangers are unknown, and also may be species specific. Most recently, data have supported the presence of an apical Na(+) + Cl(-) cotransporter (NCC-type), despite thermodynamic uncertainty. Ammonia extrusion may be via NH(3) diffusing through the paracellular junctions or NH(4) (+) substitution on both basolateral and apical ionic exchangers (Na(+) + K(+) -ATPase; Na(+) + K(+) + Cl(-) - cotransporter; and Na(+) /H(+) exchanger), but recent evidence suggests that Rhesus-glycoproteins mediate both basolateral and apical movement of ammonia.

Immunolocalization of Na+/K+-ATPase and Na+/K+/2Cl- cotransporter in the tubular epithelia of sea snake salt glands.

The sublingual salt gland is the primary site of salt excretion in sea snakes; however, little is known about the mechanisms mediating ion excretion. Na(+)/K(+)-ATPase (NKA) and Na(+)/K(+)/2Cl(-) cotransporter (NKCC) are two proteins known to regulate membrane potential and drive salt secretion in most vertebrate secretory cells. We hypothesized that NKA and NKCC would localize to the basolateral membranes of the principal cells comprising the tubular epithelia of sea snake salt glands. Although there is evidence of NKA activity in salt glands from several species of sea snake, the localization of NKA and NKCC and other potential ion transporters remains unstudied. Using histology and immunohistochemistry, we localized NKA and NKCC in salt glands from three species of laticaudine sea snake: Laticauda semifasciata, L. laticaudata, and L. colubrina. Antibody specificity was confirmed using Western blots. The compound tubular glands of all three species were found to be composed of serous secretory epithelia, and NKA and NKCC were abundant in the basolateral membranes. These results are consistent with the morphology of secretory epithelia found in the rectal salt glands of marine elasmobranchs, the nasal glands of marine birds and the gills of teleost fishes, suggesting a similar function in regulating ion secretion.

Phototherapy promotes cell migration in the presence of hydroxyurea.

Phototherapy has been shown to cause an increase in cell proliferation and migration. This study focused on viability (trypan blue), proliferation [sodium 3'-(1-(phenylaminocarbonyl)-3,4-tetrazolium)-bis(4-methoxy-6-nitro)-benzene sulphonic acid hydrate (XTT) and adenosine triphosphate (ATP)] and migration of WS1 cells following irradiation in the presence of hydroxyurea (HU), which is an inhibitor of proliferation. Wounded cells were irradiated on days 1 and 4 with a fluence of 5 J/cm(2) with a helium-neon (He-Ne) laser at 632.8 nm. After a repair time of 24 h, cellular responses were assessed. Wounded irradiated cells without HU showed an increase in cell viability and proliferation, which was confirmed by complete wound closure by day 4. Although wounded irradiated cells treated with 5 mM HU showed incomplete wound closure, these cells showed increased migration compared with that of control cells. This study showed that laser irradiation using an He-Ne laser with a fluence of 5 J/cm(2) stimulates cell viability. The HU results confirmed that laser irradiation promotes cell migration and proliferation.

Identifying the high-risk patient with clinically relevant embolisation after carotid endarterectomy.

OBJECTIVES: Sustained embolisation after carotid endarterectomy (CEA) predicts an increased risk of stroke due to post-operative carotid thrombosis (POCT). Progression towards stroke can be prevented by transcranial Doppler (TCD) directed intravenous Dextran therapy. However, TCD monitoring is extremely labour intensive. The aim of this study was to see whether a small cohort of high-risk patients could be identified following a 30-min period of monitoring in the Recovery Area of the operating theatre so as to reduce the overall burden of monitoring for the majority of patients. METHODS: Retrospective audit of prospectively acquired data in 821 patients with an accessible temporal window who had undergone 3h of TCD monitoring after CEA. Patients with >25 emboli in any 10 min period or large emboli distorting the waveform received Dextran. RESULTS: Group 1: 694 patients (85%) with

An automatic selections method for cerebral blood flow autoregulation signals from neonates

Interpretation and quantification of cerebral blood flow autoregulation can be carreid out from step responses to arterial blood pressure changes estimated with various identification methods. However estimates usually need to be visually inspected to rejected some that are not physiologically acceptable...

Deterioration in carotid baroreflex during carotid endarterectomy.

OBJECTIVE: Blood pressure instability after carotid endarterectomy (CEA) has been associated with a disturbance of the baroreflex control mechanism caused by the surgery in the carotid sinus region. The purpose of this study was to determine if a deterioration in carotid baroreceptors occurs during the surgery. METHOD: Heart rate (HR) and blood pressure (BP) were recorded continuously in 60 patients undergoing CEA as well as preoperatively and postoperatively at 2 days and 6 weeks. The baroreflex sensitivity was determined by cross-spectral analysis of HR and systolic blood pressure (SBP). During the surgery, three tests were used to assess the baroreflex response. The first test simulated a sudden fall in systemic blood pressure by clamping the common carotid artery. The second test simulated a rise in systemic blood pressure by applying pressure by using a rubbing action on the luminal surface of the carotid sinus region. The rub test was performed twice, once with the atheromatous plaque in situ and once when the plaque had been removed. The third test is clamp removal and restoration of blood flow through the carotid sinus. RESULTS: Carotid cross-clamping increased mean +/- standard error of the mean SBP from 117 +/- 3 mm Hg before clamping to 125 +/- 3 mm Hg (P <.05) at 30 beats after clamping. The first rub test with the plaque in situ decreased SBP from 121 +/- 3 mm Hg to 117 +/- 3 mm Hg (P <.01) at 10 beats after the rub test, indicating a functioning baroreceptor reflex. The second rub test increased SBP from 126 +/- 3 mm Hg to 128 +/- 3 mm Hg (P <.05). SBP dropped (P <.01) when unclamping suggesting a selective alteration of the baroreflex sensitivity. The baroreflex sensitivity was significantly reduced 2 days postoperatively when compared to preoperative values (P <.05). CONCLUSIONS: These findings suggest that the act of plaque removal could be associated with a partial disruption of baroreceptor mechanism in the carotid artery. This could affect type I baroreceptors.

Immunochemical analysis of the vacuolar proton-ATPase B-subunit in the gills of a euryhaline stingray (Dasyatis sabina): effects of salinity and relation to Na(+)/K(+)-ATPase.

In the gills of freshwater teleost fishes, vacuolar proton-ATPase (V-H(+)-ATPase) is found on the apical membrane of pavement and chloride (Na(+)/K(+)-ATPase-rich) cells, and is an important transporter for energizing Na(+) uptake and H(+) excretion. In the gills of elasmobranch fishes, the V-H(+)-ATPase has not been extensively studied and its expression in freshwater individuals has not been examined. The goals of this study were to examine the effects of environmental salinity on the expression of V-H(+)-ATPase in the gills of an elasmobranch (the Atlantic stingray, Dasyatis sabina) and determine if V-H(+)-ATPase and Na(+)/K(+)-ATPase are expressed in the same cells. We found that gills from freshwater stingrays had the highest relative abundance of V-H(+)-ATPase and greatest number of V-H(+)-ATPase-rich cells, using immunoblotting and immunohistochemistry, respectively. When freshwater animals were acclimated to sea water for 1 week, V-H(+)-ATPase abundance and the number of V-H(+)-ATPase-rich cells decreased significantly. Atlantic stingrays from seawater environments were characterized by the lowest expression of V-H(+)-ATPase and least number of V-H(+)-ATPase-rich cells. In contrast to teleost fishes, localization of V-H(+)-ATPase in freshwater stingray gills was not found in pavement cells and occurred on the basolateral membrane in cells that are presumably rich in mitochondria. In freshwater stingrays acclimated to sea water and seawater stingrays, V-H(+)-ATPase localization appeared qualitatively to be stronger in the cytoplasm, which may suggest the transporter was stored in vesicles. Using a double-immunolabeling technique, we found that V-H(+)-ATPase and Na(+)/K(+)-ATPase occurred in distinct cells, which suggests there may be two types of mitochondrion-rich cells in the elasmobranch gill epithelium. Based on these findings, we propose a unique model of NaCl and acid-base regulation where the V-H(+)-ATPase-rich cells and Na(+)/K(+)-ATPase-rich cells are the sites of Cl(-) uptake/HCO(3)(-) excretion and Na(+) uptake/H(+) excretion, respectively.

Interposition flaps in transabdominal vesicovaginal fistula repairs: are they really necessary?

Objectives. To evaluate the use of interposition flaps in repairing vesicovaginal fistulas (VVFs) of benign and malignant etiologies. Interposition flaps are not routinely used in the repair of VVFs when the surrounding tissues appear healthy and well-vascularized, such as in a benign etiology.Methods. We retrospectively reviewed the charts of 37 women (mean age 49.1 years) at our institution who underwent transabdominal repair of their VVF by urologic surgeons between August 1978 and June 1999. The preoperative and postoperative medical records were reviewed.Results. Of the 37 VVFs repaired transabdominally, 29 had a benign etiology (25 related to gynecologic procedures) and 8 a malignant etiology (all related to gynecologic neoplasia). Of the 29 benign VVFs, an interposition flap was used in 10 repairs with all 10 successful (100%). The remaining 19 benign VVF repairs were performed without using a flap, with 12 successful (63%). Of the 8 malignant fistulas, an interposition flap was used in 2 repairs with both successful (100%). The remaining 6 malignant VVF repairs were performed without a flap, with 4 successful (67%).Conclusions. The results of our study indicate a higher success rate for transabdominal VVF repairs performed with an interposition flap (100% success rate at our institution). This observation holds true regardless of the appearance of healthy surrounding tissue or, more importantly, a benign or malignant etiology. We recommend interposition flaps in transabdominal repairs of VVFs, even in the cases of benign fistulas with well-preserved surrounding tissue.

Effects of environmental salinity on Na(+)/K(+)-ATPase in the gills and rectal gland of a euryhaline elasmobranch (Dasyatis sabina).

Changes in Na(+)/K(+)-ATPase activity and abundance associated with environmental salinity were investigated in the gills and rectal gland of the Atlantic stingray Dasyatis sabina. Using a ouabain-specific ATPase assay and western blotting, we found that stingrays from fresh water had the highest activity and highest relative abundance of Na(+)/K(+)-ATPase in the gills. Using immunohistochemistry, we also found that gills from freshwater stingrays had the greatest number of Na(+)/K(+)-ATPase-rich cells. When freshwater stingrays were acclimated to sea water for 1 week, the activity and abundance of Na(+)/K(+)-ATPase and the number of Na(+)/K(+)-ATPase-rich cells decreased in the gills. In seawater stingrays, the branchial activity and abundance of Na(+)/K(+)-ATPase and the number of Na(+)/K(+)-ATPase-rich cells were further reduced. In rectal glands, the activity and abundance of Na(+)/K(+)-ATPase were lower in freshwater animals than in seawater-acclimated and seawater stingrays, both of which had equivalent levels. These findings suggest that salinity-associated changes in gill and rectal gland Na(+)/K(+)-ATPase activity are due to changes in the abundance of Na(+)/K(+)-ATPase. We conclude that the gills may be important for active ion uptake in fresh water, while the rectal gland is important for active NaCl excretion in sea water. The results from this study are the first to demonstrate an effect of environmental salinity on Na(+)/K(+)-ATPase expression in the gills and rectal gland of an elasmobranch.

A comparison of colour duplex ultrasonography, papaverine testing and common femoral Doppler waveform analysis for assessment of the aortoiliac arteries.

OBJECTIVE: to study the "accuracy" of aortoiliac colour duplex ultrasonography. DESIGN: prospective study. SETTING: vascular laboratory, University Hospital. METHODS: a total of 25 aortoiliac stenoses were studied in 23 patients. For each iliac segment, colour duplex ultrasound, papaverine testing, hyperaemic common femoral Doppler waveform analysis and hyperaemic testing using a thigh pressure cuff were performed. A velocity ratio of two was used to indicate a significant 50% diameter-reducing stenosis, but the velocity differences across stenoses as well as various characteristics of the hyyperaemic common femoral waveform were also studied. Retrospective receiver-operator characteristics and Kappa values were used for analysis. RESULTS: the Kappa agreement between ultrasonography and papaverine testing was 0.12 using peak systolic velocity ratios and 0.8 using hyperaemic peak systolic velocity differences. Hyperaemic common femoral pulsatility (PI) and resistance index (RI) both gained a Kappa level of 0.60. The reactive hyperaemia produced by a thigh cuff was more pronounced than that produced by papaverine. CONCLUSION: although the velocity ratio did not appear to perform well against the papaverine test, its apparent over-sensitivity calls into question the sensitivity of papaverine testing itself. The hyperaemic velocity difference at the stenosis or the hyperaemic PI or RI at common femoral level appear useful, non-invasive indicators of significant aortoiliac arterial disease.

Activation of MeIQ (2-amino-3,4-dimethylimidazo- [4,5-f]quinoline) by sequence variants of recombinant human cytochrome P450 1A2.

Understanding the relationships between the sequences and catalytic activities of P450 enzymes that catalyze the bioactivation of mutagens and carcinogens is an important goal in mutation research. Escherichia coli strain DJ4309 expresses recombinant human P450 1A2 and activates promutagens such as MeIQ (2-amino-3, 4-dimethylimidazo[4,5-f]quinoline), as measured by induction of reverse mutations detected as lacZ(+) colonies on minimal lactose (ML) plates. Pools of P450 1A2 mutants were constructed by polymerase chain reaction (PCR) mutagenesis of putative substrate recognition sites (SRSs). Cultures of individual clones were patched onto MeIQ/ML plates and the growth of revertant microcolonies within each patch was inspected after 2 days of incubation. Beginning with a pool of several thousand clones, we identified 25 distinct P450 1A2 SRS variants with altered activities. In this study, the MeIQ dose-responses of all the variants are reported. The implications of the results are considered with reference to published models of the protein's structure.

The complete genome sequence of shope (rabbit) fibroma virus.

We have determined the complete DNA sequence of the Leporipoxvirus Shope fibroma virus (SFV). The SFV genome spans 159.8 kb and encodes 165 putative genes of which 13 are duplicated in the 12.4-kb terminal inverted repeats. Although most SFV genes have homologs encoded by other Chordopoxvirinae, the SFV genome lacks a key gene required for the production of extracellular enveloped virus. SFV also encodes only the smaller ribonucleotide reductase subunit and has a limited nucleotide biosynthetic capacity. SFV preserves the Chordopoxvirinae gene order from S012L near the left end of the chromosome through to S142R (homologs of vaccinia F2L and B1R, respectively). The unique right end of SFV appears to be genetically unstable because when the sequence is compared with that of myxoma virus, five myxoma homologs have been deleted (C. Cameron, S. Hota-Mitchell, L. Chen, J. Barrett, J.-X. Cao, C. Macaulay, D. Willer, D. Evans, and G. McFadden, 1999, Virology 264, 298-318). Most other differences between these two Leporipoxviruses are located in the telomeres. Leporipoxviruses encode several genes not found in other poxviruses including four small hydrophobic proteins of unknown function (S023R, S119L, S125R, and S132L), an alpha 2, 3-sialyltransferase (S143R), a protein belonging to the Ig-like protein superfamily (S141R), and a protein resembling the DNA-binding domain of proteins belonging to the HIN-200 protein family S013L). SFV also encodes a type II DNA photolyase (S127L). Melanoplus sanguinipes entomopoxvirus encodes a similar protein, but SFV is the first mammalian virus potentially capable of photoreactivating ultraviolet DNA damage.

DNA binding and aggregation properties of the vaccinia virus I3L gene product.

The vaccinia virus I3L gene encodes a single-stranded DNA-binding protein which may play a role in viral replication and genetic recombination. We have purified native and recombinant forms of gpI3L and characterized both the DNA-binding reaction and the structural properties of DNA-protein complexes. The purified proteins displayed anomalous electrophoretic properties in the presence of sodium dodecyl sulfate, behaving as if they were 4-kDa larger than the true mass. Agarose gel shift analysis was used to monitor the formation of complexes composed of single-stranded DNA plus gpI3L protein. These experiments detected two different DNA binding modes whose formation was dependent upon the protein density. The transition between the two binding modes occurred at a nucleotide to protein ratio of about 31 nucleotides per gpI3L monomer. S1 nuclease protection assay revealed that at saturating protein densities, each gpI3L monomer occludes 9.5 +/- 2.5 nucleotides. In the presence of magnesium, gpI3L promoted the formation of large DNA aggregates from which double-stranded DNA was excluded. Electron microscopy showed that, in the absence of magnesium and at low protein densities, gpI3L forms beaded structures on DNA. At high protein density the complexes display a smoother and less compacted morphology. In the presence of magnesium the complexes contained long fibrous and tangled arrays. These results suggest that gpI3L can form octameric complexes on DNA much like those formed by Escherichia coli single-stranded DNA protein. Moreover, the capacity to aggregate DNA may provide an environment in which hybrid DNA formation could occur during DNA replication.

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.

Shope fibroma virus DNA topoisomerase catalyses holliday junction resolution and hairpin formation in vitro.

The telomeres of poxviral chromosomes comprise covalently closed hairpin structures bearing mismatched bases. These hairpins are formed as concatemeric replication intermediates and are processed into mature, unit-length genomes. The structural transitions and enzymes involved in telomere resolution are poorly understood. Here we show that the type I topoisomerase of Shope fibroma virus (SFV) can promote a recombination reaction which converts cloned SFV replication intermediates into hairpin-ended molecules resembling mature poxviral telomeres. Recombinant SFV topoisomerase linearised a palindromic plasmid bearing 1.5 kb of DNA encoding the SFV concatemer junction, at a site near the centre of inverted-repeat symmetry. Most of these linear reaction products bore hairpin tips as judged by denaturing gel electrophoresis. The resolution reaction required palindromic SFV DNA sequences and was inhibited by compounds which block branch migration (MgCl2) or poxviral topoisomerases. The resolution reaction was also slow, needed substantial quantities of topoisomerase, and required that the palindrome be extruded in a cruciform configuration. DNA cleavage experiments identified a pair of suitably oriented topoisomerase recognition sites, 90 bases from the centre of the cloned SFV terminal inverted repeat, which may mark the resolution site. These data suggest a resolution scheme in which branch migration of a Holliday junction through a site occupied by covalently bound topoisomerase molecules, could lead to telomere resolution.

DNA ligase gene disruptions can depress viral growth and replication in poxvirus-infected cells.

Poxvirus-encoded DNA ligases are assumed to play a role in viral DNA replication; however mutational inactivation of vaccinia ligase has not been reported to affect viral growth rates in culture. This communication re-examines this surprising aspect of poxviral biology using both Shope fibroma virus (SFV) and vaccinia virus. SFV and vaccinia ligase deficiencies create essentially identical phenotypes. In particular, ligase-deficient SFV strains are mildly UV sensitive and etoposide resistant, phenotypes previously shown to characterize ligase-deficient vaccinia strains. Moreover, we find that ligase mutations can inhibit the growth of both SFV and vaccinia virus in vitro. The poor growth observed in the absence of a viral ligase is correlated with a two- to tenfold reduction in viral and extragenomic DNA synthesis. This phenotype is host dependent. No differences in viral growth or DNA yield were seen when vaccinia strains were cultured on rabbit (SIRC) cells, but ligase deficiencies reduced growth and DNA yields when vaccinia was plated on BSC-40 cells or SFV on SIRC cells. Despite these replicative defects, mutational inactivation of SFV ligase produced no detectable increase in the number of viral DNA breaks and had no effect on virus-catalyzed extragenomic DNA recombination or UV repair. We conclude that poxviral ligases do play a role in viral DNA replication, but the replicative defect is obscured in some cell lines.

Experience with transcranial Doppler monitoring reduces the incidence of particulate embolization during carotid endarterectomy.

BACKGROUND: The aim of this study was to investigate whether the introduction of routine transcranial Doppler (TCD) ultrasonography during carotid endarterectomy reduces the incidence of microembolization by altering operative technique. METHODS: The number and nature of microemboli detected during the first 75 consecutive carotid endarterectomies performed with TCD monitoring during 1992-1993 (group 1) were compared with those in a similar series of 75 consecutive patients undergoing carotid endarterectomy in 1995 (group 2), after substantial experience (210 patients) with TCD monitoring. Emboli were classified as either particulate or gaseous. RESULTS: In patients with evidence of particulate emboli during the dissection phase of the operation, the total number of particulate emboli fell significantly in patients in group 2 (P = 0.019). Similarly, in patients in whom microembolization was detected on immediate opening of the shunt, the total number of microemboli also fell significantly in group 2 (P = 0.003). Overall, the median (95 per cent confidence interval) number of particulate emboli detected during the entire procedure fell significantly from 21 (16-29) in group 1 to 9 (7-14) in group 2 (P = 0.0008). CONCLUSIONS: TCD monitoring plays an important role in the training and quality control of carotid endarterectomy and helps significantly to reduce the amount of microembolization.

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.