Intravascular Sites Research Articles

Bioinspired molecular communications system for targeted drug delivery with IoBNT-based sustainable biocyber interface

This paper presents a sustainable biocyber interface approach for an intelligent targeted drug delivery system (TDDS). The proposed approach employs a bioinspired molecular communications (MC) system in which molecules are used as information carriers and a multi-input multi-output (MIMO) Forster resonance energy transfer (FRET) nanorelay to efficiently transfer therapeutic drugs from extravascular (outside blood vessels) to intravascular (within blood vessels) sites that are targeting diseased tissue. The proposed approach consists of a number of bio-nano things (BNTs) implanted inside the human intra-body nanonetwork near the diseased site. The communication among BNTs is accomplished by a sequential multistep FRET, and the nanonetwork is controlled by the Internet of Bio-Nano Thing (IoBNT) paradigm sustained by an uplink/downlink biocyber interface. The bit error rate (BER) and molecular channel capacity are utilized to evaluate the performance of the proposed approach. In addition, a Markov model decision in terms of the number of nanomachines is presented to calculate the successful probability of drug delivery and the average delay time. The numerical results show how effective the suggested method is at transmitting therapeutic medication information with an attainable bit-rate error.

The influence of subclavian ansae stimulation on cardiac hemodynamics and electrophysiology in atrial fibrillation- exploring a novel target for neuromodulation in atrial fibrillation (SAS-AF study)

Abstract Background Sympathetic nervous system activation plays a significant role in arrhythmia development and maintenance.Neuromodulation techniques such as stellate ganglion block and sympathectomy, are limited by off-target side effects and complex targeting.The Subclavian Ansae (SA,a nerve cord encircling the subclavian artery) may be an intravascular site allowing specific targeting of the cardiac afferent sympathetic system.Preclinical studies have revealed increased sympathetic tone upon selective SA stimulation. Objective We sought to define for the first time in Humans the functional anatomy and physiology of Subclavian Ansae via a percutaneous approach. Methods A prior cadaveric study defined the anatomical course of the subclavian ansae, encircling the subclavian arteries and connecting the middle cervical ganglia to inferior cervical ganglia/stellate.Patients undergoing catheter ablation for paroxysmal atrial fibrillation(pAF) under general anesthesia were prospectively recruited for the study. Subclavian Ansae stimulation (SAS) was performed on the left and/or the right (L/SAS ± R/SAS) within the subclavian artery using the TactiCath Ablation Catheter introduced via a femoral arterial sheath. Stimulation parameters included up to 70 V output, 10 Hz frequency, and pulse width of 2-4ms for 20-30s. Test pulses ensured no cardiac capture during stimulation. Participants discontinued antiarrhythmic agents at least 4-5 half-lives prior to the procedure. Invasive arterial blood pressure(BP), heart rate (HR), and electrophysiological parameters were recorded in response to selective stimulation. An increase of ten percent or more in either arterial blood pressure(BP) or heart rate(HR) from the initial baseline measurements was deemed a positive response. Results 15 patients (62±11 years, 9 males, pAF duration 51±24 months) underwent the simulation protocol prior to their clinical AF ablation procedure. A positive hemodynamic response was observed in nine patients, and among them, arrhythmia was inducible in 3 patients (atrial fibrillation in 2 patients and repeated runs of atrial ectopy in 1 patient) in response to SAS. Mean sinus cycle length(CL) decreased(chronotropic) after stimulation,particularly with a significant change observed in response to R/SAS. Additionally,L/SAS led to a notable increase in mean systolic (SBP) and diastolic(DBP) blood pressure (inotropic). While the mean right atrial effective refractory period (ERP) did not significantly decrease after stimulation, there was a demonstrable difference in interatrial conduction time(dromotropy). Six patients, including the initial 3 subjected to low-energy stimulation (up to 12V), did not exhibit an adrenergic response. Conclusion This study represents the first successful application of selective SAS in humans. A heterogeneity in electrophysiological modulation by SAS exists, including laterality.The SA is a potential important target for targeted autonomic neuromodulation therapy

Fibrin-associated EBV-positive Large B-Cell Lymphoma: An Indolent Neoplasm With Features Distinct From Diffuse Large B-Cell Lymphoma Associated With Chronic Inflammation.

Incidental cases of localized fibrin-associated Epstein-Barr virus (EBV)+ large B-cell proliferations have been described at unusual anatomic sites and have been included in the category of diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI) in the WHO Classification. We describe 12 cases and review the literature to define their clinicopathologic spectrum and compare features with typical cases of DLBCL-CI. Median age was 55.5 years with a M:F ratio of 3. In all 12 cases, the lymphoma was an incidental microscopic finding involving atrial myxomas (n=3), thrombi associated with endovascular grafts (n=3), chronic hematomas (n=2), and pseudocysts (n=4). All cases tested were nongerminal center B-cell origin, type III EBV latency, and were negative for MYC rearrangements and alternative lengthening of telomeres by FISH. Most showed high CD30, Ki67, and PD-L1, and low to moderate MYC and p53 expression. Among 11 patients with detailed follow-up, 6 were treated surgically, 3 with cardiac or vascular lesions had persistent/recurrent disease at intravascular sites, and 4 died of causes not directly attributable to lymphoma. Reports of previously published fibrin-associated cases showed similar features, whereas traditional DLBCL-CI cases with a mass lesion had significantly higher lymphoma-associated mortality. Fibrin-associated EBV+ large B-cell lymphoma is clinicopathologically distinct from DLBCL-CI, warranting separate classification. Most cases, particularly those associated with pseudocysts, behave indolently with the potential for cure by surgery alone and may represent a form of EBV+ lymphoproliferative disease rather than lymphoma. However, primary cardiac or vascular disease may have a higher risk of recurrence despite systemic chemotherapy.

Diffuse Gastric Carcinoma Undergoes Characteristic Phenotypic Changes in the Intravascular Environment: Evidence for a Reversal of the Epithelial-Mesenchymal Transition in Lymphovascular Metastasis.

This article reports differences between the properties of extravascular carcinoma, which generally forms the vast bulk of a tumor, and those of intravascular carcinoma, at both primary and metastatic lymph node sites. In a morphological and immunohistochemical study of 19 diffuse gastric adenocarcinomas, we report that in comparison to extravascular carcinoma, the intravascular tumor compartment showed frequent and profound phenotypic change, including increased tumor cell cohesion, differentiation and cadherin/catenin expression. For example, greatest cohesion was seen at the intravascular site in 78% ( P = .00006) of primary cancers and in 84% ( P = .000015) of their lymph node metastases. Pan cadherin showed a statistically significant increase at the intravascular metastatic site ( P = .031). We suggest that this change from an extravascular isolated cell phenotype to an intravascular cohesive phenotype represents reversal of the epithelial to mesenchymal transition. Since this proposed reversal of epithelial to mesenchymal transition in intravascular carcinoma is frequently conspicuous in routine histological sections of many types of cancer, as our previous publications have indicated, this process is likely to have widespread significance for the biology of metastasis.

Automated Tube Voltage Selection for Radiation Dose Reduction in CT Angiography Using Different Contrast Media Concentrations and a Constant Iodine Delivery Rate.

The purpose of this study was to systematically investigate radiation dose reduction using automated tube voltage selection during CT angiography (CTA) and to evaluate the impact of contrast medium (CM) injection protocols on dose reduction. A circulation phantom containing the thoracic and abdominal vasculature was used. Four different concentrations of CM (iopromide 300 and 370 mg I/mL and iomeprol 350 and 400 mg I/mL) were administered while maintaining an identical iodine delivery rate (1.8 g I/s) and total iodine load (20.0 g). Three different scanning protocols for CTA of the thoracoabdominal aorta were used: protocol A, no dose modulation; protocol B, automated tube current modulation (CARE Dose4D); and protocol C, automated tube voltage selection (CARE kV). The dose-length product was recorded to calculate the effective dose. Attenuation values (in Hounsfield units), image noise levels, and signal-to-noise ratios (SNRs) in six predefined intravascular sites (three thoracic and three abdominal) were measured by two readers. All values were analyzed using the Kruskal-Wallis test and two-way ANOVA. There was a significant reduction in the effective dose (in millisieverts) for protocols B (mean ± SD, 2.03 ± 0.1 mSv) and C (1.00 ± 0.0 mSv) compared with protocol A (4.34 ± 0.0 mSv). The dose was reduced by 53% for protocol B and by 77% for protocol C. No significant differences were found in the effective dose among the different CM injection protocols within the scanning protocols; all p values were > 0.05. The attenuation values and SNRs were comparable among all the different CM injection protocols; all p values were > 0.05. A large radiation dose reduction (77%) can be achieved using automated tube voltage selection independent of the CM injection protocol.

Porous scaffolds support extrahepatic human islet transplantation, engraftment, and function in mice.

Islet transplantation as a therapy or cure for type 1 diabetes has significant promise but has been limited by islet mass requirements and long-term graft failure. The intrahepatic and intravascular site may be responsible for significant loss of transplanted islets. Nonencapsulating biomaterial scaffolds provide a strategy for architecturally defining and modulating extrahepatic sites beyond the endogenous milieu to enhance islet survival and function. We utilized scaffolds to transplant human islets into the intraperitoneal fat of immunodeficient mice. A smaller human islet mass than previously reported reversed murine diabetes and restored glycemic control at human blood glucose levels. Graft function was highly dependent on the islet number transplanted and directly correlated to islet viability, as determined by the ATP-to-DNA ratio. Islets engrafted and revascularized in host tissue, and glucose tolerance testing indicated performance equivalent to healthy mice. Addition of extracellular matrix, specifically collagen IV, to scaffold surfaces improved graft function compared to serum-supplemented media. Porous scaffolds can facilitate efficient human islet transplantation and provide a platform for modulating the islet microenvironment, in ways not possible with current clinical strategies, to enhance islet engraftment and function.

The Treacherous Clot: Arterial Line External Haematoma in a Patient with HIT While Receiving Lepirudin

Heparin-induced thrombocytopenia is known to produce thrombotic events in addition to bleeding. A large external haematoma developed around the radial arterial line site in a patient with proven HIT while receiving lepirudin. The haematoma masqueraded as continued bleeding and delayed starting renal replacement therapy. This case emphasised the importance of close visual examination of intravascular catheter sites for any evidence of thrombosis.

Pivotal role of endogenous tachykinins and the NK 1 receptor in mediating leukocyte accumulation, in the absence of oedema formation, in response to TNFα in the cutaneous microvasculature

Tachykinins including substance P (SP) are well known to play a role in influencing oedema formation and leukocyte accumulation during tissue insult and inflammation. Cutaneous inflammatory models to characterize a TNFα-dependent mechanism where endogenous SP act via the NK 1 receptor to promote leukocyte accumulation in the absence of oedema formation were used. We found that TNFα induced dose-dependent leukocyte accumulation at 4 h, which returned towards basal levels at 8 h in NK 1 +/+ mice. This response was absent in both the NK 1 +/+ mice treated with an NK 1 receptor antagonist and NK 1 −/− mice. At the highest dose IL-6 induced a significant accumulation in NK 1 +/+ and NK 1 −/− mice but IL-12 was ineffective. SP induced skin oedema but none of the cytokines did. Either co-injection of SP with low dose of TNFα (0.3 pmol/site) or SP previously injected (30 min) to TNFα evoked a significant increase in MPO activity when compared with that induced by the cytokine alone. In contrast, SP injected i.d. 3.5 h after TNFα failed to produce additive response. Control, but not capsaicin-pretreated rats (to deplete sensory nerves), exhibited a marked increase in MPO activity in response to TNFα. Histological analysis showed that TNFα caused tissue infiltrate of leukocytes in NK 1 +/+ mice, whilst leukocytes accumulated at intravascular sites in NK 1 −/− mice, but did not appear to emigrate, suggesting a defect in trans-endothelial migration. Interestingly, monocytes in addition to neutrophils accumulated 4 h post TNFα injection. In conclusion, the NK 1 receptor plays a functional role in mediating leukocyte accumulation independently of the historically important NK 1 mediated oedema formation. It seems that TNFα directly activates sensory nerve in addition to its chemoattractant activity. The NK 1 receptor agonist influences the accumulation of monocytes in addition to that of PMN by 4 h, thus revealing an important influence of the NK 1 receptor on TNFα mediated events in mouse skin.

Myocardial damage during percutaneous interventions for non-ST-elevation acute coronary syndromes

The prognostic significance and pathophysiological mechanisms underlying elevations in cardiac enzymes in patients with non-ST-segment elevation acute coronary syndromes (ACS) post-percutaneous coronary intervention (PCI) is a matter of debate. The few available data, derived mainly from sub-analyses of large randomized trials and from small prospective observational studies, suggest that patients with ACS who undergo PCI have an increased risk for procedural myocardial damage which, in turn, is associated with an adverse clinical outcome. Although the pathophysiology of post-PCI myocardial damage is multifactorial, the embolization of debris or calcified plaque material, or exposure of thrombogenic material at intravascular sites seems to play a key role, as shown by mechanistic studies that demonstrate a close relationship between post-procedural enzyme release and abnormal tissue perfusion. Several pre-procedural treatment strategies using antithrombotic therapies have evolved in an attempt to lower the rate of myocardial damage related to the performance of PCI in ACS patients. Major trials that evaluated the use of glycoprotein (GP) IIb/IIIa inhibitors during PCI in patients with ACS have suggested that maximum benefit is obtained in patients with increased troponin levels and in patients undergoing PCI, reducing the incidence of cardiac enzyme release after the procedure. However, a number of lingering unsolved issues concerning which agent should be used and the most appropriate timing and dosage remain to be explored. Mechanistic and clinical findings suggest that an early invasive strategy with upstream GP IIb/IIIa inhibitors may yield more favourable outcomes than downstream strategies.

Embryonic Mouse STO Cell–Derived Xenografts Express Hepatocytic Functions in the Livers of Nonimmunosuppressed Adult Rats

Cells derived from embryonic mouse STO cell lines differentiate into hepatocytes when transplanted into the livers of nonimmunosuppressed dipeptidylpeptidase IV (DPPIV)-negative F344 rats. Within 1 day after intrasplenic injection, donor cells moved rapidly into the liver and were found in intravascular and perivascular sites; by 1 month, they were intrasinusoidal and also integrated into hepatic plates with approximately 2% efficiency and formed conjoint bile canaliculi. Neither donor cell proliferation nor host inflammatory responses were observed during this time. Detection of intrahepatic mouse COX1 mitochondrial DNA and mouse albumin mRNA in recipient rats indicated survival and differentiation of donor cells for at least 3 months. Mouse COX1 targets were also detected intrahepatically 4-9 weeks after STO cell injection into nonimmunosuppressed wild-type rats. In contrast to STO-transplanted rats, mouse DNA or RNA was not detectable in untreated or mock-transplanted rats or in rats injected with donor cell DNA. In cultured STO donor cells, DPPIV and glucose-6-phosphatase activities were observed in small clusters; in contrast, mouse major histocompatibility complex class I H-2Kq, H-2Dq, and H-2Lq and class II I-Aq markers were undetectable in vitro before or after interferon gamma treatment. Together with H-2K allele typing, which confirmed the Swiss mouse origin of the donor cells, these observations indicate that mouse-derived STO cell lines can differentiate along hepatocytic lineage and engraft into rat liver across major histocompatibility barriers.

Postoperative Bleeding After Coronary Artery Bypass Surgery with Cardiopulmonary Bypass

In Response: We thank Dr. Belcher for his comments regarding our study (1). We would like to make only a few minor clarifications in response. Our objective was to determine whether the technique as described was effective in a large and homogenous group presumed at high-risk for bleeding and transfusion. We did not address mechanisms of effect in detail. We agree that platelets would already be concentrated at intravascular sites of vessel wall damage. The topical application of autologous platelet gel to raw surfaces and wound edges was intended as an extravascular mechanical sealant along the lines of “tissue glue” rather than an attempt to correct for a local platelet deficiency. We noted in our introduction that the efficacy of this aspect of the technique had not been reported, but it was part of our established practice at the time (based on reports in conference proceedings (2) and personal communications), and was quick, easy, and safe to do. Recent publications in the orthopedic (3) and cosmetic (4) surgery literature support use of topical autologous platelet gel and fibrin glue to arrest capillary bleeding from bone and under skin flaps. Autologous platelet gel has also been reported to contain platelet-derived growth factor that may enhance wound healing. Dr. Belcher lists several reasons for platelet dysfunction after cardiopulmonary bypass, all of which we recognized and attempted to prevent or minimize by our pheresis protocol. Therapeutic quantities of platelets were sequestered before heparinization and reinfused only after protamine reversal thus avoiding (in the sequestrate) the heparin and bypass induced plasma change(s) referred to by Dr. Belcher. The degree to which these plasma changes persist in the patient (if they do) after bypass and heparin reversal remains unquantified and deserving of further research. Autologous platelets prepared by whole blood centrifugation and stored for several hours before reinfusion exhibit less activation and greater responsiveness than allogeneic platelets (5). Our study of reoperative CABG patients showed only that therapeutic yield plateletpheresis did not improve the two clinical outcomes we measured. Mean chest tube drainage was close to obligate loss volumes in both groups, making further reduction unlikely. Allogeneic PRBC transfusion was also very low, averaging 1.2–1.5 units per patient. Up to 55% of patients in both groups received some allogeneic exposure, but this includes those patients receiving platelets and fresh frozen plasma as treatment for postoperative bleeding. Low rates of preoperative aspirin exposure, routine antifibrinolytic use, and minimal exposure of blood to nonbiologic surfaces are likely to have contributed to our low control group rates, and thus made a treatment difference less likely. We performed only routine measurements of hemostasis (platelet counts, INR, APTT—we did not measure bleeding times) perioperatively, and patients were transfused with platelets only if clinically bleeding with a count < 100 × 109/L. We stand by our conclusion that while the technique was not beneficial in our unit, it may have a place in other institutions where baseline blood loss and transfusion rates are higher than ours. We agree with Dr. Belcher that platelet transfusions should be restricted to bleeding patients with significant thrombocytopenia, and not administered routinely after cardiopulmonary bypass surgery. Paul Wajon, FANZCA John Gibson, FANZCA

The influence of cardiac output distribution on the tissue/plasma drug concentration ratio.

In pharmacokinetics, it is currently assumed that blood and interstitial spaces belong to the central compartment, when the solute is quickly equilibrated between both fluids. Taking into account that the same extracellular fluid dissolves the drug either in the plasma or in the interstitium, both drug concentrations (intra and intravascular) should be identical. However, this equality may not exist when there is a dissimilar distribution of blood flow among the organs. A closed, two-zone, three-compartment model was mathematically investigated. Compartment 1 was intravascular, and compartments 2 and 3 were extravascular. The fluid within the compartment 1 was supposed to be pushed by a pump, and to be distributed towards two different zones. One of these zones was in contact with the compartment 2, and the other with compartment 3. The drug could be exchanged between the compartments 1 and 2 or 1 and 3, by mean of first-order kinetics (k12, k21, k13, k31). It was assumed a very fast flow that assured instantaneous homogeinity of drug concentration in compartment 1. Pressure was kept constant, so an increase in the pump output distribution towards one zone is compensated by a decrease towards the other zone. At time infinite the drug concentration (C) ratio between compartments yielded: C2/C1 = k12.sigma.V1/(k21.V2) and C3/C1 = k13.(1-sigma).V1/(k31.V3), being sigma: the pump output fraction served to the zone where compartment 2 was located, and Vi: the volumes of compartments. So, at the equilibrium the concentrations are not necessarily identical between the extravascular and intravascular sites. In conclusion, as the cardiac output distribution changes due to circadian rythms and cardiovascular active drug administration, current therapeutic drug monitoring and bioequivalence studies using plasma as biologic fluid would be controversial issues.

Ventricular rate control during atrial fibrillation by cardiac parasympathetic nerve stimulation: a transvenous approach

OBJECTIVESTo identify intravascular sites for continuous, stable parasympathetic stimulation (PS) in order to control the ventricular rate during atrial fibrillation (AF).BACKGROUNDVentricular rate control during AF in patients with congestive heart failure is a significant clinical problem because many drugs that slow the ventricular rate may depress ventricular function and cause hypotension. Parasympathetic stimulation can exert negative dromotropic effects without significantly affecting the ventricles.METHODSIn 22 dogs, PS was performed using rectangular stimuli (0.05 ms duration, 20 Hz) delivered through a catheter with an expandable electrode-basket at its end. The catheter was positioned either in the superior vena cava (SVC, n = 6), coronary sinus (CS, n = 10) or right pulmonary artery (RPA, n = 6). The basket was then expanded to obtain long-term catheter stability. Atrial fibrillation was induced and maintained by rapid atrial pacing.RESULTSNonfluoroscopic (SVC) and fluoroscopic (CS/RPA) identification of effective intravascular PS sites was achieved within 3 to 10 min. The ventricular rate slowing effect during AF started and ceased immediately after on-offset of PS, respectively, and could be maintained over 20 h. In the SVC, at least a 50% increase of ventricular rate (R-R) intervals occurred at 22 ± 11 V (331 ± 139 ms to 653 ± 286 ms, p < 0.001), in the CS at 16 ± 10 V (312 ± 102 ms vs. 561 ± 172 ms, p < 0.001) and in the RPA at 18 ± 7 V (307 ± 62 ms to 681 ± 151 ms, p < 0.001). Parasympathetic stimulation did not change ventricular refractory periods.CONCLUSIONSIntravascular PS results in a significant ventricular rate slowing during AF in dogs. This may be beneficial in patients with AF and rapid ventricular response since many drugs that decrease atrioventricular conduction have negative inotropic effects which could worsen concomitant congestive heart failure.

Cardioprotection with a novel adenosine regulating agent mediated by intravascular adenosine

Adenosine is cardioprotective in models of myocardial stunning and infarction, but the precise compartment within the heart in which adenosine elicits its cardioprotective effects has not been determined. The goals of the present study were to (i) investigate the effects of a novel adenosine regulating agent, GP531 (5-amino-1-β- d-(5-benzylamino-5-deoxyribofuranosyl)imidazole-4-carboxamide), on post-ischemic myocardial function, and (ii) examine the contribution of endogenous adenosine in the intravascular and interstitial compartments in mediating the beneficial effects. Pigs were instrumented for measurement of myocardial segment shortening, and for sampling of coronary venous blood and myocardial interstitial fluid for determination of adenosine concentration. Myocardial dysfunction was induced by 4×8 min coronary occlusions, and recovery of regional function was monitored for 2 h. In control pigs, function recovered to 24±2% of baseline after 2 h. Treatment with GP531 improved functional recovery to 55±3%. GP531-mediated cardioprotection was prevented by adenosine receptor blockade with 8-sulfophenyltheophylline (23±2%). GP531 did not affect basal adenosine levels, but caused a 2-fold greater increase in vascular adenosine concentration with ischemia (54.6±10.6 vs. 28.1±8.0 μM in controls, P<0.05). In contrast, the interstitial adenosine concentration was not significantly different in treated vs. untreated control pigs (9.4±3.9 vs. 15.0±1.3 μM in controls). These data indicate that (1) GP531 improves recovery of myocardial function following ischemia-reperfusion injury via an adenosine receptor-dependent mechanism, and (2) the cardioprotection is associated with increased intravascular, but not interstitial, adenosine concentration during ischemia. Therefore, we conclude that cardioprotection elicited by GP531-enhanced endogenous adenosine is dependent on an intravascular site of action. © 1997 Elsevier Science B.V. All rights reserved.

Intravascular site care: are critical care nurses practicing according to written protocols?

Objective: To observe and describe site care for intravascular devices, to identify internurse variations in site care, and to compare written protocols for site care with actual practice in one geographic area. Design: Observational, descriptive study. Setting: Adult critical care units in one community, and one university teaching hospital in the Washington, D.C., metropolitan area. Sample: Direct observation of 86 central and 30 peripheral site care episodes. Results: A total of 116 site care episodes were observed on five critical care units. There were wide variations between units from the same hospital in gloving practices and use of aseptic technique. Significant differences across both hospitals, as well as between individual units, were noted for a number of other practices including: time since last site care, use of ointment and skin adhesive, type of dressing used, and duration of care. In both hospitals, compliance with all steps of the written protocol was similar—23.2% and 23.3%. Compliance with documentation requirements ranged from 53.3% to 85.7%, and was significantly different between the two hospitals with regard to recording the dressing change and whether the dressing label and chart agreed. Conclusions: Intravascular site care varies significantly among critical care units within the same institution, as well as between different hospitals, and varies from written protocol. Standardized, well-defined site care protocols and education of staff, along with quality improvement surveillance systems are needed to ensure consistent quality intravascular site care.

Intravascular site care: Are critical care nurses practicing according to written protocols?

To observe and describe site care for intravascular devices, to identify internurse variations in site care, and to compare written protocols for site care with actual practice in one geographic area. Observational, descriptive study. Adult critical care units in one community, and one university teaching hospital in the Washington, D.C., metropolitan area. Direct observation of 86 central and 30 peripheral site care episodes. A total of 116 site care episodes were observed on five critical care units. There were wide variations between units from the same hospital in gloving practices and use of aseptic technique. Significant differences across both hospitals, as well as between individual units, were noted for a number of other practices including: time since last site care, use of ointment and skin adhesive, type of dressing used, and duration of care. In both hospitals, compliance with all steps of the written protocol was similar-23.2% and 23.3%. Compliance with documentation requirements ranged from 53.3% to 85.7%, and was significantly different between the two hospitals with regard to recording the dressing change and whether the dressing label and chart agreed. Intravascular site care varies significantly among critical care units within the same institution, as well as between different hospitals, and varies from written protocol. Standardized, well-defined site care protocols and education of staff, along with quality improvement surveillance systems are needed to ensure consistent quality intravascular site care.

Deferoxamine reduces early metabolic failure associated with severe cerebral ischemic acidosis in dogs.

Postischemic metabolic injury may be mediated by acidosis and tissue bicarbonate depletion, with consequent-iron mobilization and oxygen radical formation during reperfusion. We have previously shown that reducing intracellular pH to below 5.7 and bicarbonate ion to below 1 to 2 mmol/L during hyperglycemic ischemia produces a profound secondary deterioration of brain ATP and cerebral blood flow during reperfusion. This study tested the hypothesis that pretreatment with free deferoxamine ameliorates metabolic decay and delayed hypoperfusion after global hyperglycemic ischemia. In addition, deferoxamine conjugated to a high-molecular-weight starch was administered to determine the importance of an intravascular site of action. Iron-loaded deferoxamine was used to determine whether the iron chelation properties of deferoxamine are important to postischemic viability as distinguished from the agent's significant radical scavenging potential. Cerebral ATP, phosphocreatine, and pH were measured by 31P magnetic resonance spectroscopy in anesthetized dogs. Tissue bicarbonate concentration was calculated from the Henderson-Hasselbalch equation. Incomplete cerebral ischemia was produced by intracranial pressure elevation for 30 minutes with plasma glucose at 540 +/- 15 mg/dL. Free deferoxamine, saline vehicle, hydroxyethyl starch-conjugated deferoxamine, hydroxyethyl starch vehicle, and deferoxamine loaded with equimolar ferric chloride were administered intravenously in five groups of dogs. The dose of deferoxamine was 50 mg/kg before ischemia, 50 mg/kg at the onset of reperfusion, and 50 mg/kg over the 180-minute reperfusion period. Ischemic hemispheric blood flow (mean, 6 to 8 mL/min per 100 g), intracellular pH (5.7 to 6.0), and bicarbonate levels (1 to 2 mmol/L) were similar in all groups. During reperfusion, cerebral pH and bicarbonate recovered only in the free-deferoxamine group. Both ATP and phosphocreatine initially increased in all groups, but recovery was sustained only in the free-deferoxamine group. Secondary losses of energy phosphates and cerebral oxygen consumption were observed in all other groups, accompanied by progressive reduction of perfusion. These data support the hypothesis that iron catalyzed oxygen radical production plays an important role in acidosis-mediated mechanisms of ischemic brain injury. The results with free and iron-loaded deferoxamine suggest that iron scavenging is an important, but not necessarily the principal, component of this mechanism. The poor recovery seen with conjugated deferoxamine indicates that the beneficial action of deferoxamine is not localized within the intravascular compartment.

Ampicillin-resistant enterococcal species in an acute-care hospital

A prospective review of all enterococcal isolates for 13 months showed that 9.0% were resistant to ampicillin (MIC, greater than or equal to 16 micrograms/ml; zone diameter, less than 15 mm), as determined by the Vitek system, disk diffusion, microdilution MIC testing, and macrodilution MIC testing. All were beta-lactamase negative. A total of 19 and 3 resistant isolates were from urine and intravascular sites, respectively. Ampicillin-resistant enterococci appear to be a growing clinical problem.

Optimized ultrasound imaging catheters for use in the vascular system

Clinical experience with 6 and 9 Fr ultrasound imaging catheters (UICs) reveals that several transducer and catheter tip varieties are needed for optimum imaging of diseased intravascular sites. Our UIC design has combined established catheter design and very high frequency ultrasound imaging technology to create a versatile, user configured system for intravascular ultrasound imaging. Optimum use requires proper strategic selection of transducer and catheter sizes, frequencies of operation, and interventional accessories.

Candida parapsilosis fungemia associated with parenteral nutrition and contaminated blood pressure transducers.

During the period September 1983 through May 1985, Candida parapsilosis was isolated from intravascular sites (blood or vascular catheter tips) in 12 patients at a pediatric hospital. Of 205 patients with cultures of any site positive for Candida species, 32 (16%) had cultures positive for C. parapsilosis. In contrast, of 23 patients with intravascular cultures positive for Candida species, 12 (51%) had cultures positive for C. parapsilosis (P less than 0.001, Fisher's exact test). The 12 patients with intravascular cultures positive for C. parapsilosis were more likely to have received central venous nutrition therapy (10 of 12 versus 7 of 23; P less than 0.01, Mantel-Haenzel chi-square test) and had a longer duration of exposure to blood pressure transducers (P less than 0.08, paired t test) than the 23 ward- and age-matched controls. C. parapsilosis was isolated from 11 (32%) of 34 in-use and stored blood pressure transducers. After ethylene oxide sterilization of blood pressure transducers was begun, in-use pressure transducers showed no growth of C. parapsilosis. This study emphasizes the role of C. parapsilosis as a nosocomial pathogen associated with invasive devices and parenteral nutrition; it also emphasizes the importance of adhering to recommended procedures for sterilizing blood pressure transducers.