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Aim: Temperature control is a complex bundled intervention; the synergistic impact of each individual component is ill defined and underreported. Resultantly, the influence of parameter optimization on temperature control's overall neuroprotective effect remains poorly understood. To characterize variability in temperature control parameters and barriers to short pre-induction and induction times, we surveyed sites enrolling in an ongoing multicenter clinical trial., Methods: This was a cross-sectional, survey study evaluating temperature control practices within the Influence of Cooling duration on Efficacy in Cardiac Arrest Patients (ICECAP) trial (NCT04217551). A 23-question web-based survey (Qualtrics) was distributed to the site principal investigators by email. Respondents were asked about site practices pertaining to the use of temperature control, including the request to upload individual institutional protocols. Open-ended responses were analyzed qualitatively by categorizing responses into identified themes. To complement survey level data, records pertaining to the quality of temperature control were extracted from the ICECAP trial database., Results: The survey response rate was 75% (n = 51) including 23.5% (n = 12) survey respondents who uploaded institutional protocols. Most sites reported having institutional protocols for temperature control (n = 41; 80%), including 62.5% (n = 32) who had separate protocols for initiation of temperature control in the emergency department (ED). Fewer sites had protocols specific to sedation or neuromuscular blockade (NMB) management (n = 35, 68.6%). Use of NMB during temperature control induction was variable; 61.7% (n = 29) of sites induced paralysis less than 20% of the time. While most institutional protocols (n = 11, 83.3%) commented on the importance of early initiation of temperature control, this was incongruent with the largest reported barrier, which was clinical nihilism regarding the importance of early temperature control initiation (n = 30, 62.5%). Within the ICECAP trial database, 1 in 2 patients were treated with NMB however, use of NMB and time to initiation of temperature control device varied widely between sites., Conclusion: Amongst ICECAP trial sites, there was significant variability in resources, methods, and barriers for early temperature control initiation. Defining and standardizing high-quality temperature control must be prioritized, as it may impact the interpretation of past and current clinical trial findings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ‘The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The following conflicts of interest should be reported: SY, RC, RR: support from NIH for ICECAP DCC work scope, PK, RG, RS, WM: support from NIH for ICECAP CCC work scope. Multiple authors are supported by the following grants: UG3HL145269, UH3HL145269, U24HL145272, U24NS100659, U24NS100655 from the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Neurological Disorders and Stroke (NINDS). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.’., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established., Methods: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures., Discussion: In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms., Trial Registration: ClinicalTrials.gov NCT04217551. Registered on 30 December 2019., (© 2024. The Author(s).)

Background: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the United States. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established., Methods: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 hours of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 hours will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient reported quality of life measures., Discussion: In-vitro and in-vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms., Trial Registration: ClinicalTrials.gov (NCT04217551, 2019-12-30)., Competing Interests: Competing interests {28} B Abella: Funding: NIH, DOD, Neuroptics, Becton Dickinson; equity: VOC Health, Neuroptics, MDAlly, volunteer: AHA T Aufderheide: Unrestricted research grant from ZOLL Medical, Inc. S Berry: Part owner of Berry Consultants K Broglio: Owns stock in AstraZeneca NIH (K23HL157610) and Hyper ne (SAFE MRI study) S Cho: NIH (K23HL157610) and Hyper ne (SAFE MRI study) R Lewis: I am the Senior Medical Scientist at Berry Consultants, LLC, a statistical consulting firm that specializes in the design, conduct, and analysis of Bayesian adaptive clinical trials. Berry Consultants contributed to the statistical design of the trial reported here. All other authors declare that they have no competing interests.

Intestinal ischemia-reperfusion injury (IRI) is associated with a myriad of conditions in both veterinary and human medicine. Intestinal IRI conditions, such as gastric dilatation volvulus (GDV), mesenteric torsion, and colic, are observed in animals such as dogs and horses. An initial interruption of blood flow causes tissues to become ischemic. Although necessary to salvage viable tissue, subsequent reperfusion can induce further injury. The main mechanism responsible for IRI is free radical formation upon reperfusion and reintroduction of oxygen into damaged tissue, but there are many other components involved. The resulting local and systemic effects often impart a poor prognosis. Intestinal IRI has been the subject of extensive research over the past 50 years. An in vivo rodent model in which the base of the superior mesenteric artery (SMA) is temporarily ligated is currently the most common method used to study intestinal IRI. Here, we describe a model of intestinal IRI utilizing isoflurane anesthesia in 21% O2 medical air that yields reproducible injury, as demonstrated by consistent histopathology of the small intestines. Tissue injury was also assessed in the colon, liver, and kidneys.

Background:  There is need for validated outcome measures for postthrombotic syndrome (PTS) following pediatric venous thromboembolism (VTE), with a focus on quality of life (QoL)., Aims:  This article assesses reliability and validity of two PTS and two QoL scales for children following lower extremity VTE., Methods:  Pediatric patients following lower extremity VTE were recruited from three thrombosis clinics. The Manco-Johnson (MJ) and the modified Villalta (MV) PTS scales were compared with each other and with the generic pediatric health-related QoL, PedsQL, and a newly developed pediatric venous-specific QoL, the Peds-VEINES-QOL., Results:  Eighty children following VTE and 60 healthy control children were enrolled. Internal consistency measured by Cronbach's α was high for the two QoL scales, and moderate for the two PTS scales. Inter-rater reliability using intraclass correlation coefficients was moderate to high for the MJ, MV, and Peds-VEINES-QOL, and moderate for the PedsQL. Evidence of high internal consistency by Cronbach's α coefficients, and moderate to high interitem correlations support the premise that a single construct was measured by each instrument. Correlations between the four instruments indicate convergent validity., Conclusion:  The MJ and MV scales detect similar outcomes in children following VTE. As used, the MJ is slightly more sensitive to QoL because a positive diagnosis requires pain which is the leading factor in reduced QoL following deep vein thrombosis. When using the MV, a requirement for pain or abnormal use to diagnose PTS would make the MV a better predictor of QoL., Competing Interests: N.A.G. has received consultant fees and/or honoraria for roles in clinical trial Steering Committees and Data and Safety Monitoring Committees, from the Academic Research Organization CPC Clinical Research as well as pharmaceutical companies (Daiici Sankyo, Inc., Novartis, Chiesi). The remaining authors report no conflicts of interest., (Thieme. All rights reserved.)

The Wilmot Cancer Institute launched the Tobacco Dependence Treatment Program in 2015. Formal program evaluation consisted of 324 patients who presented for at least one visit to assess quit rates. The secondary aim was to ascertain the effectiveness of guideline recommendations that four or more visits would be beneficial in an outpatient oncology tobacco treatment program to promote success in smoking cessation. The first 32 months of program data revealed that there were significantly improved quit rates for those who were seen for four or more visits compared to those seen for three or fewer visits.

Purpose: This study aimed to examine the impact of group-based central venous catheter education (CVC) on the knowledge, skill and comfort of caregivers, length of stay (LOS) related to initial CVC placement and 30-day return hospital visit for central line associated blood stream infections (CLABSI)., Design and Methods: This pilot study employed a pretest-posttest design comparing retrospective data collected before implementation of the group-based education (GLAD Model). Data were collected from children's caregivers before and after taking the educational class through use of the Comfort Survey, and collected though the electronic medical record. The data were analyzed using SPSS 24, repeated measures analysis of variance, and t-test., Results: Pre-post difference with the Comfort Survey indicated significant increase (M = 0.49, SD = 0.79), t(92) = 6.05, p = 0.001, d = -0.62) for skill, knowledge and comfort for the pre- and the post 2 (1 month after) and 3 (2 months after). After GLAD Model implementation, LOS related to initial CVC placement during retrospective review declined from 29.7 days to 27.7 and 30-day return hospital visit declined from twelve to zero. Our results suggest that use of the GLAD Model educational program might be effective in improving caregiver knowledge, skill and comfort as well as LOS and 30-day return hospital visit., Conclusion: This study suggests that group-based, education with use of the GLAD Model should to be considered as an effective educational intervention in providing caregivers CVC education. This may help care for their child at home while enhancing their hospital experience and decreasing unplanned hospital visits., (Copyright © 2018. Published by Elsevier Inc.)

Intrabone (IB) hematopoietic cell transplantation (HCT) of umbilical cord blood in humans remains experimental and the technique has not been optimized. It is unknown whether hematopoietic progenitor cells (HPCs) injected IB are initially retained in the marrow or rapidly enter into the venous circulation before homing to the marrow. To develop an IB-injection technique that maximizes HPC marrow-retention, we tracked radiolabeled human HPCs following IB-injection into swine. We developed a method to radionuclide-label HPCs using a long-lived positron emitter (89) Zr and protamine sulfate that resulted in cellular-retention of low-dose radioactivity. This approach achieved radioactivity levels sufficient for detection by positron emission tomography with both high sensitivity and spatial resolution when fused with computed tomography. We found that conditions utilized in pilot IB-HCT clinical trials conducted by others led to both rapid drainage into the central venous circulation and cellular extravasation into surrounding muscle and soft tissues. By optimizing the needle design, using continuous real-time intra-marrow pressure monitoring, and by reducing the infusion-volume and infusion-rate, we overcame this limitation and achieved high retention of HPCs in the marrow. This method of IB cellular delivery is readily applicable in the clinic and could be utilized in future investigational IB-HCT trials aimed at maximizing marrow retention of HPCs., (Published 2015. This article is a U.S. Government work and is in the public domain in the USA.)

Lipoprotein (a) is a risk factor for adult cardiovascular events, in which the apolipoprotein (a) component is thought to promote atherogenesis and impair fibrinolysis. We investigated whether elevated plasma lipoprotein (a) concentration and small predominant apolipoprotein (a) isoform size (number of kringle-4 domains) are risk factors for childhood arterial ischemic stroke and correlate with plasma fibrinolytic function. Patients who had had an arterial ischemic stroke in childhood (29 days - <21 years at onset; n=43) and healthy controls (n=127) were recruited for plasma sampling and laboratory determinations. Cases were followed for recurrence in a prospective cohort study. The median lipoprotein (a) concentration did not differ between groups [cases: median 18.0 nmol/L (7.5 mg/dL) and observed range 0.9-259 nmol/L (0.38-108.0 mg/dL), controls: 20.4 nmol/L (8.5 mg/dL) and 0.2-282 nmol/L (0.08-117.5 mg/dL); P=0.62]. While odds of incident stroke were not significantly increased, risks of recurrent arterial ischemic stroke were each more than ten-times increased for lipoprotein(a) >90(th) percentile of race-specific reference values and apolipoprotein (a) <10(th) percentiles [odds ratio=14.0 (95% confidence interval: 1.0-184), P=0.05 and odds ratio=12.8 (1.61-101), P=0.02]. Statistically significant but weak correlations were observed between euglobulin lysis time and both lipoprotein (a) level (r=0.18, P=0.03) and apolipoprotein (a) size (r= -0.26, P=0.002). In conclusion, elevated lipoprotein (a) and small apolipoprotein (a) potently increase the risk of recurrent arterial ischemic stroke in children, with a mechanism only partially attributable to impaired fibrinolysis. Collaborative studies are warranted to investigate these findings further and, more broadly, to establish key risk factors for incident and recurrent arterial ischemic stroke in children.

Using the Manco-Johnson instrument in a derivation cohort of 107 children with or without a central venous catheter, upper extremity physical findings of post-thrombotic syndrome were absent, and the pain score was 0 in all but one child. Interrater reliability in an independent validation cohort (n = 38) of children with or without upper extremity deep venous thrombosis was 97%-100%., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Important predictors of adverse outcomes of thrombosis in children, including postthrombotic syndrome (PTS), have recently been identified. Given this knowledge and the encouraging preliminary pediatric experience with systemic thrombolysis, we sought to retrospectively analyze our institutional experience with a thrombolytic regimen versus standard anticoagulation for acute, occlusive deep venous thrombosis (DVT) of the proximal lower extremities in children in whom plasma factor VIII activity and/or D-dimer concentration were elevated at diagnosis, from within a longitudinal pediatric cohort. Nine children who underwent the thrombolytic regimen and 13 who received standard anticoagulation alone were followed from time of diagnosis with serial clinical evaluation and standardized PTS outcome assessments conducted in uniform fashion. The thrombolytic regimen was associated with a markedly decreased odds of PTS at 18 to 24 months compared with standard anticoagulation alone, which persisted after adjustment for significant covariates of age and lag time to therapy (odds ratio [OR] = 0.018, 95% confidence interval [CI] = < 0.001-0.483; P = .02). Major bleeding developed in 1 child, clinically judged as not directly related to thrombolysis for DVT. These findings suggest that the use of a thrombolysis regimen may safely and substantially reduce the risk of PTS in children with occlusive lower-extremity acute DVT, providing the basis for a future clinical trial.

Objective: Lemierre's syndrome, or jugular vein thrombosis (JVT) associated with anaerobic infection of the head and neck and frequently complicated by septic pulmonary embolism (PE), has historically been described as a disease of young adults. In recent years, an increasing number of case reports of childhood Lemierre's syndrome have been published, focusing mostly on the clinical and laboratory findings at disease presentation and the outcomes of infection. Given the potentially life-threatening thromboembolic complications of this disorder, we reviewed our single-institutional experience with pediatric Lemierre's and Lemierre's-like syndromes (LALLS) from within the context of a larger cohort study of thrombosis in children., Methods: Children who were aged from birth to 21 years and had received a diagnosis of JVT and Lemierre's syndrome at the Children's Hospital (Denver, CO) between 2001 and 2005 were identified for inclusion. Case designation of LALLS required all the following: (1) radiologic confirmation of JVT, (2) clinical diagnosis of pharyngitis or other febrile illness, and (3) intraoperative evidence of loculated infection in the head and neck region or radiologic demonstration of bilateral pulmonary infiltrates. Isolation of a causative organism by microbiologic culture of blood, tissue, or purulent fluid was also a necessary diagnostic criterion among patients who had not been treated with antibiotics before culture. A designation of classic Lemierre's syndrome was reserved for documented cases of anaerobic infection. Children in whom JVT was associated with the presence of an ipsilateral central venous catheter were excluded from the analysis. Analysis included information on underlying medical conditions, microbiologic and radiologic findings, and comprehensive hypercoagulability testing results from the time of diagnosis, as well as antimicrobial and anticoagulant therapies administered. In addition, clinical outcomes were evaluated via serial follow-up and included bleeding complications, thrombus resolution on serial radiologic studies, symptomatic recurrent venous thromboembolism (VTE), and mortality., Results: From January 2001 to January 2005, 9 children with LALLS were identified. Median age was 15 years (range: 2.5-20 years). Clinical presentation was consistent with septic PE in 5 cases and septic shock in 2. Thrombophilia was present in 100% (7 of 7) of children tested, consisting principally of antiphospholipid antibodies and elevated factor VIII activity. Anticoagulation was given in 89% (8 of 9), for a median duration of 3 months (range: 7 weeks-1 year). After a median follow-up time of 1 year, all children had survived without recurrent VTE or anticoagulant-associated major hemorrhage. JVT failed to resolve at 3 to 6 months in 38% of anticoagulated children., Conclusions: Our experience suggests that LALLS is an emerging pediatric concern with serious acute (eg, septic PE) and chronic (eg, persistent vascular occlusion) complications. Septic JVT may not be uniquely anaerobic, and the inflammatory prothrombotic state is often characterized by antiphospholipid antibodies and elevated factor VIII levels. Early diagnosis and aggressive antimicrobial and antithrombotic therapies in LALLS may be necessary for optimal long-term outcomes.

Background: Elevated levels of plasma factor VIII and D-dimer predict recurrent venous thromboembolism in adults. We sought to determine whether an elevation of factor VIII, D-dimer, or both at diagnosis and persistence of the laboratory abnormality after three to six months of anticoagulant therapy correlate with poor outcomes of thrombosis in children., Methods: We evaluated levels of factor VIII and D-dimer and additional components of an extensive laboratory thrombophilia (i.e., hypercoagulability) panel at the time of diagnosis in 144 children with a radiologically confirmed acute thrombotic event. All patients were treated initially with heparin and then with either warfarin or low-molecular-weight heparin for at least three to six months, according to the current standard of care. Patients were examined at follow-up visits 3, 6, and 12 months after diagnosis and then annually, at which times testing was repeated in children with previously abnormal factor VIII and D-dimer test results and a uniform evaluation for the post-thrombotic syndrome was performed., Results: Among 82 children for whom complete data were available regarding laboratory test results at diagnosis and thrombotic outcomes during follow-up, 67 percent had factor VIII levels above the cutoff value of 150 IU per deciliter, D-dimer levels above 500 ng per milliliter, or both at diagnosis, and at least one of the two laboratory values was persistently elevated in 43 percent of the 75 patients in whom testing was performed after three to six months of anticoagulant therapy. Fifty-one percent of the 82 patients had a poor outcome (i.e., a lack of thrombus resolution, recurrent thrombosis, or the post-thrombotic syndrome) during a median follow-up of 12 months (range, 3 months to 5 years). Elevated levels of factor VIII, D-dimer, or both at diagnosis were highly predictive of a poor outcome (odds ratio, 6.1; P=0.008), as was the persistence of at least one laboratory abnormality at three to six months (odds ratio, 4.7; P=0.002). The combination of a factor VIII level above 150 IU per deciliter and a D-dimer level above 500 ng per milliliter at diagnosis was 91 percent specific for a poor outcome, and after three to six months of standard anticoagulation, the combination was 88 percent specific., Conclusions: Elevated levels of plasma factor VIII, D-dimer, or both at diagnosis and a persistent elevation of at least one of these factors after standard-duration anticoagulant therapy predict a poor outcome in children with thrombosis., (Copyright 2004 Massachusetts Medical Society)

Background: Delayed ischemic preconditioning promotes cardioprotection via genomic reprogramming. We hypothesize that molecular regulation of mitochondrial energetics is integral to this cardioprotective program., Methods and Results: Preconditioning was induced by use of 3 episodes of 3-minute coronary artery occlusion separated by 5 minutes of reperfusion. Twenty-four hours later, infarct size was reduced by 58% after preconditioning compared with sham-operated controls (P<0.001). Cardiac mitochondria were isolated from sham and preconditioned rat hearts. Mitochondrial respiration and ATP production were similar between the groups; however, preconditioned mitochondria exhibit modest hyperpolarization of the inner mitochondrial membrane potential (> or =22% versus control, P<0.001). After 35-minute anoxia and reoxygenation, preconditioned mitochondria demonstrated a 191+/-12% improvement in ADP-sensitive respiration (P=0.002) with preservation of electron-transfer-chain (ETC) activity versus controls. This augmented mitochondrial recovery was eradicated when preconditioning was abolished by the antioxidant 2-mercaptopropionyl glycine (2-MPG). These biochemical modulations appear to be regulated at the genomic level in that the expression of genes encoding rate-controlling complexes in the ETC was significantly upregulated in preconditioned myocardium, with a concordant induction of steady-state protein levels of cytochrome oxidase, cytochrome c, and adenine nucleotide translocase-1. 2-MPG abolished preconditioning induction of these transcripts. Moreover, transcripts of nuclear regulatory peptides known to orchestrate mitochondrial biogenesis, nuclear respiratory factor-1 and peroxisome-proliferator-activated receptor gamma coactivator 1alpha, were significantly induced in preconditioned myocardium., Conclusions: Delayed preconditioned mitochondria display increased tolerance against anoxia-reoxygenation in association with modifications in mitochondrial bioenergetics, with concordant genomic induction of a mitochondrial energetic gene regulatory program. This program appears to be mediated by reactive oxygen species signaling.

Severe genetic protein C deficiency is rare and is associated with severe, often fatal thrombosis. The authors report the use of recombinant activated protein C (APC) to treat an episode of purpura fulminans (PF) in a teenage girl with severe protein C deficiency who had developed anaphylaxis to fresh-frozen plasma that was given in the past to treat recurrent episodes of PF. Concomitant with an infusion of APC, 20 microg/kg/h for 10 hours, a d-dimer level that was markedly positive (6,450 ng/mL) prior to the onset of PF decreased to 847 ng/mL following the APC. The teenager was treated with heparin along with warfarin for four days until the INR was more than 3.5 and the d-dimer level was less than 230 ng/mL. At the end of the APC infusion all skin lesions of PF were resolved. There were no adverse reactions to APC. APC was safe and effective for treatment of PF in severe genetic protein C deficiency.

Using microsurgical techniques, biomedical researchers are able to perform procedures that would otherwise be impossible on small laboratory animals. The authors provide a primer on learning microsurgical technique, from correct posture and hand position, to understanding lenses and proper handling of surgical needles and suture material.

Microsurgery requires specialized instruments and very fine suture material. The authors describe microsurgical instruments and suturing materials available for small animal microsurgery.

The manometric, ultrastructural, radiographic, and physiological consequences of retrograde biliary infusion were determined in normostatic and cholestatic mice. Intraluminal biliary pressure changed as a function of infusion volume, rate, and viscosity. Higher rates of constant infusion resulted in higher peak intraluminal biliary pressures. The pattern of pressure changes observed was consistent with biliary ductular and/or canalicular filling followed by leakage at a threshold pressure. Retrograde infusion with significant elevations in pressure led to paracellular leakage of lanthanum chloride, radiopaque dye, and [(14)C]sucrose with rapid systemic redistribution via sinusoidal and subsequent hepatic venous drainage. Chronic extrahepatic bile duct obstruction resulted in significantly smaller peak intrabiliary pressures and lower levels of paracellular leakage. These findings indicate that under both normostatic and cholestatic conditions elevated intrabiliary volumes/pressures result in an acute pressure-dependent physical opening of tight junctions, permitting the movement of infusate from the intrabiliary space into the subepithelial tissue compartment. Control of intraluminal pressure may potentially permit the selective delivery of macromolecules >18-20 A in diameter to specific histological compartments.

We describe a 30-year-old man who presented with a tangled knot of worms that he "passed per rectum." The worms were identified as Paragordius varius. This is an uncommon pseudoparasite that is ingested from contaminated food or water. Identifying characteristics and the life cycle of Gordian worms are briefly discussed. Identification of this worm is important to distinguish it from true parasitic worms.

Sixty-five fly maggots were retrieved from the nasal cavity of an unconscious 64-year-old man who had been admitted 18 days earlier with diabetic hyperosmolar coma. The larvae were identified as Cochliomyia macellaria, an organism commonly associated with myiasis in the United States. The clinical time sequence indicates that this infection was acquired in the hospital. This incident provides further evidence that immobile and debilitated patients are at risk to acquire myiasis.