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Purpose of review The COVID-19 pandemic has had unprecedented global effects, yet the rapid emergence of telehealth across the globe has allowed healthcare professionals to connect virtually with patients and families while following safe social distancing guidelines. Telehealth has been used relatively well in patients from remote regions with limited access to subspecialty healthcare providers. This article discusses novel ways of using telehealth during the current pandemic and measures that would need to be taken to sustain telehealth and teleconsultations. Recent findings Telehealth has expanded to outpatient pediatric cardiology clinics across the globe during the pandemic. Technological advancements in video conferencing and the abundance of readily available wearable devices have allowed cardiologists to establish a preliminary diagnosis and set forth a treatment plan. Additional support by insurance providers and relaxation of mandatory regulations by the government have allowed telehealth to succeed during the pandemic. Although many subdisciplines within pediatric cardiology can be easily adapted into a sustainable telehealth model, some unique patient interactions, such as fetal cardiology, exercise physiology, and echocardiograms cannot be done remotely. The field of telehealth medicine with HIPAA-compliant programs and both insurance and government support should remain in our armamentarium of available resources for all patients and families. Summary Although not unique to pediatric cardiology, telehealth has emerged as an avenue to perform an initial evaluation and even establish a care pathway for patients. It is well recognized that telehealth visits will not supplant all patient--physician interactions but is a very acceptable first step in the majority of cases and can often steer the patient to subsequently undergo more selective and streamlined care.

Purpose of review The purpose of this review is to explore the paradigm shift in healthcare delivery that will need to take place over the next few years away from an emphasis on supply-driven health care to better quality transparent-driven health care whose focus is on the consumer's best interest. Recent findings The current healthcare system is fragmented and costs continue to rise. The best way to contain costs is to improve quality to the consumer, the patient. Physicians and hospitals need to align in a team-based approach that allows physicians to understand current costs and how to strive toward a focus on healthcare outcomes. Pediatric cardiology is a unique discipline that cares for patients with complex congenital conditions that will span their lifetime and also involves not just cardiology but surgery, intensive care, anesthesia, nursing, and a host of inpatient and ambulatory services. Understanding what matters to the patient and his/her family and presenting quality outcomes in a transparent fashion will gradually allow a shift to take place away from physician visits, tests ordered, and procedures performed. This can only be achieved with physicians, given the appropriate tools to understand costs, value, and outcomes and models where the hospitals and physicians are aligned. Summary The transformation to a value-based healthcare system is beginning and pediatric cardiologists need to be educated, given the appropriate resources, receive appropriate feedback, and patients need to be part of the solution so that care providers can understand what matters most to them.

Background: Despite safety concerns, many young patients with implantable cardioverter-defibrillators (ICDs) participate in sports. We undertook a prospective, multinational registry to determine the incidence of serious adverse events because of sports participation. The primary end points were death or resuscitated arrest during sports or injury during sports because of arrhythmia or shock. Secondary end points included system malfunction and incidence of ventricular arrhythmias requiring multiple shocks for termination. Methods: Athletes with ICDs aged ≤21 years were included in this post hoc subanalysis of the ICD Sports Registry. Data on sports and clinical outcomes were obtained by phone interview and medical records review. ICD shocks and clinical details of lead malfunction were classified by 2 electrophysiologists. Results: A total of 129 young athletes participating in competitive (n=117) or dangerous (n=12) sports were enrolled. The mean age was 16 years (range, 10–21; 40% female; 92% white). The most common diagnoses were long QT syndrome (n=49), hypertrophic cardiomyopathy (n=30), and congenital heart disease (n=16). The most common sports were basketball and soccer, including 79 varsity/junior varsity high school and college athletes. During a median follow-up of 42 months, 35 athletes (27%) received 38 shocks. There were no occurrences of death, arrest, or injury related to arrhythmia, during sports. There was 1 ventricular tachycardia/ventricular fibrillation storm during competition. Freedom from lead malfunction was 92.3% at 5 years and 79.6% at 10 years. Conclusions: Although shocks related to competition/practice are not uncommon, there were no serious adverse sequelae. Lead malfunction rates were similar to previously reported in unselected pediatric ICD populations. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00637754.

Background: Component separation techniques (CSTs) have allowed for midline fascial reapproximation in large midline ventral hernias. In certain cases, however, fascial apposition is not feasible, resulting in a bridged repair that is suboptimal. Previous estimates on myofascial advancement are based on hernia location and do not take into account variability between patients. Examination of preoperative computed tomography (CT) may provide insight into these variabilities and may allow for prediction of abdominal closure with CST. Study Design: A retrospective review was conducted of patients who underwent abdominal wall reconstruction from 2007 to 2012 with CST. Preoperative CT was obtained, and specific parameters were analyzed using image analysis software. Logistic regression was used to predict ideal operative closure. Multivariate analyses were adjusted for age and sex. An a priori value was set at P G 0.05. Results: Fifty-four patients met the criteria and had preoperative CT available for analysis. Forty-eight patients had fascial reapproximation achieved, whereas 6 patients had a bridged repair. Age, sex, weight, and body mass index were similar between groups (P 9 0.05). Significant differences were seen between groups in 3 variables: transverse defect size (19.8 vs 10 cm, P G 0.05), defect area (420 vs 184.2 cm 2 , P G 0.05), and percent abdominal wall defect (18.9% vs 10.6%, P G 0.05). Conclusions: Preoperative determination of abdominal wall defect ratios and hernia defect areas may represent a more accurate method to predict abdominal wall closure after CST. Predicting midline approximation after CST is critical because outcomes after bridged repair can result in higher recurrence rates.

Background— Implantable cardioverter-defibrillator (ICD) therapy in children and congenital heart disease patients is hampered by poor long-term lead survival. Lead extraction is technically difficult and carries substantial morbidity. We sought to determine the outcomes of ICD leads in pediatric and congenital heart disease patients. Methods and Results— The Pediatric Lead Extractability and Survival Evaluation (PLEASE) is a 24-center international registry. Pediatric and congenital heart disease patients with ICD lead implantations from 2005 to 2010 were eligible. Study subjects comprised 878 ICD patients (44% congenital heart disease). Mean±SD age at implantation was 18.6±9.8 years. Of the 965 total leads, 54% were thin (≤7F), of which 57% were Fidelis, and 23% were coated with expanded polytetrafluoroethylene. There were 139 ICD lead failures (14%) in 132 patients (15%) at a mean lead age of 2.0±1.4 years, causing shocks in 53 patients (40%). Independent predictors of lead failure included younger implantation age and Fidelis leads. Actuarial analysis showed an incremental risk of lead failure with younger age at implantation: 18 years ( P =0.015). The actuarial yearly failure rate was 2.3% for non-Fidelis and 9.1% for Fidelis leads. Extraction was performed on 143 leads (80% thin, 7% expanded polytetrafluoroethylene coated), with lead age as the only independent predictor for advanced extraction techniques. There were 6 major extraction complications (4%) but no procedural mortality. Conclusions— This study demonstrates that ICD leads in children and congenital heart disease patients have an age-related suboptimal performance, further compounded by a high failure rate of Fidelis leads. Advanced extraction techniques were common and correlated with older lead age. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00335036.

Background— Cardiac rhythm devices are increasingly used in the pediatric population, although their impact on quality of life (QOL) is poorly understood. The purpose of this study was to compare (QOL) scores among pediatric device patients, healthy controls, and congenital heart disease (CHD) patients and determine the key drivers of QOL in pediatric device patients. Methods and Results— Multicenter, cross-sectional study at 8 pediatric centers of subjects aged 8 to 18 years with either a pacemaker or defibrillator was carried out. Patient–parent pairs completed the Pediatric Quality of Life Inventory and Pediatric Cardiac Quality of Life Inventory. QOL outcomes in device patients were compared with healthy controls and patients with various forms of CHD. Structural equation modeling was used to test for differences in Pediatric Cardiac Quality of Life Inventory scores among (1) device type, (2) presence of CHD, and (3) hypothesized key drivers of QOL. One hundred seventy-three patient–parent pairs (40 defibrillators/133 pacemakers) were included. Compared with healthy controls, patients with devices and their parents reported significantly lower Pediatric Quality of Life Inventory scoring. Similarly, compared with patients with mild forms of CHD, parents and patients with devices reported significantly lower Pediatric Cardiac Quality of Life Inventory scores and were similar to patients with more severe CHD. Key drivers of patient QOL were presence of implantable cardioverter-defibrillator and CHD. For patients, self-perception was a key driver of lower QOL, whereas for parents behavioral issues were associated with lower QOL. Conclusions— Patient QOL is significantly affected by the presence of cardiac rhythm devices. Whether these effects can be mitigated through the use of psychotherapy needs to be assessed.

The aim is to review pathophysiological mechanisms and treatment of nocturnal asthma.Physiologic changes accompanying sleep, as well as the nocturnal phase of circadian rhythms, may have an adverse effect on asthma control. Chronotherapeutic principles, which consider circadian variation in relevant biologic rhythms, may improve asthma outcomes. Administration of long-acting bronchodilators and inhaled corticosteroids which achieve maximum efficacy at night may improve nocturnal asthma. Comorbid conditions that may contribute to nocturnal asthma should be considered. The prevalence of obstructive sleep apnea is greater in a cohort of patients with severe asthma than in moderate asthma and in BMI and age matched nonasthmatic controls, suggesting a link between these diseases. A large trial concluded that esomeprazole did not improve asthma control even with comorbid acid reflux, questioning the importance of acid reflux in asthma. The role of polymorphisms of the β2-adrenergic receptor and their relationship with nocturnal asthma remain controversial.Sleep is a time of vulnerability to respiratory compromise, especially in asthma patients experiencing nocturnal exacerbations. This asthma phenotype is associated with poorer control, reduced sleep quality, daytime somnolence and increased morbidity and mortality. Nocturnal asthma is a common but under-recognized problem.

The occurrence of sudden cardiac death in asymptomatic children is a rare but feared event. Ventricular pre-excitation (referred to as Wolff–Parkinson–White syndrome when associated with symptoms of supraventricular tachycardia) is one of the underlying causes of such events, with the mechanism of sudden death attributed to rapid antegrade conduction of atrial tachycardias via the accessory pathway resulting in ventricular fibrillation. Although estimates of the lifetime risk of mortality secondary to this ECG pattern vary somewhat, most suggest this risk to be in the range of 1:1000 pts/yr.1–3 Patient factors suggested to be associated with an increased risk for sudden cardiac death include inducibility of tachycardia, male sex, presence of multiple accessory pathways and, most importantly, the capacity of the accessory pathway to perform rapidly.1,3–5 Most patients whose initial presentation was a life-threatening event have an accessory pathway capable of conducting at cycle lengths faster than 220 to 250 ms.1,3,6,7 Article see p 218 It is disconcerting that studies have identified previously asymptomatic children with ventricular pre-excitation whose initial and only symptom was ventricular fibrillation.1,6,8 Although it would seem reasonable to assume that patients with symptoms of tachycardia were somehow at higher risk for these potentially lethal complications, the risk profiles of symptomatic and asymptomatic patients may in fact be similar.9 Asymptomatic patients in the past have been incidentally discovered, but increasingly they are identified as a result of ECG screening before sports participation or medication prescription. It is estimated that more than half of adolescents with ventricular pre-excitation are asymptomatic.2,10 Catheter ablation seems to be effective at eliminating the risk of sudden cardiac death in patients with ventricular pre-excitation, and it has become widely available as …

The field of traumatic brain injury has evolved since the time of the Civil War in response to the needs of patients with injuries and disabilities resulting from war. The Department of Veterans Affairs and the Defense and Veterans Brain Injury Center have been in the forefront of the development of the interdisciplinary approach to the rehabilitation of soldiers with traumatic brain injury, particularly those injured from the recent conflicts in Iraq and Afghanistan. The objectives of this literature review are to examine how the casualties resulting from major wars in the past led to the establishment of the current model of evaluation and treatment of traumatic brain injury and to review how the field has expanded in response to the growing cohort of military service members and veterans with TBI.

In general, there is no reason to evaluate either liver function tests or a urinalysis in asymptomatic athletes. However, at times they are ordered inadvertently, and when abnormal, the provider faces a quandary - ignore or evaluate them. Up to 20% of the liver function tests and urinalyses can be abnormal in the asymptomatic healthy athlete. The key concept for the provider is to quickly, accurately, and economically identify results that are normal variants from those that may be a prelude to a pathologic process. This article will discuss the most common etiologies of these abnormal laboratory tests as well as provide a framework to the follow-up evaluation. Our goal is to aid clinicians in keeping their athletes participating in their sports while at the same time not missing any significant illnesses.

Ethanol-induced liver injury is characterized by increased formation of reactive oxygen species (ROS) and inflammatory cytokines, resulting in the development of hepatic steatosis, injury, and cell death by necrosis and apoptosis. Thioredoxin (Trx), a potent antioxidant and antiinflammatory molecule with antiapoptotic properties, protects animals from a number of inflammatory diseases. However, the effects of ethanol on Trx or its role in ethanol-induced liver injury are not known. Female C57BL/6 mice were allowed ad libitum access to a Lieber-deCarli ethanol diet with 5.4% of calories as ethanol for 2 days to acclimate them to the diet, followed by 2 days with 32.4% of calories as ethanol or pair-fed control diet. Hepatic Trx-1 was decreased by ethanol feeding; daily supplementation with recombinant human Trx (rhTrx) prevented this ethanol-induced decrease. Therefore, we tested the hypothesis that administration of rhTrx during ethanol exposure would attenuate ethanol-induced oxidative stress, inflammatory cytokine production, and apoptosis. Mice were treated with a daily intraperitoneal injection of either 5 g/kg of rhTrx or phosphate-buffered saline (PBS). Conclusion: Ethanol feeding increased accumulation of hepatic 4-hydroxynonenal protein adducts, expression of hepatic tumor necrosis factor α, and resulted in hepatic steatosis and increased plasma aspartate aminotransferase and alanine aminotransferase. In ethanol-fed mice, treatment with rhTrx reduced 4-hydroxynonenal adduct accumulation, inflammatory cytokine expression, decreased hepatic triglyceride, and improved liver enzyme profiles. Ethanol feeding also increased transferase-mediated dUTP-biotin nick-end labeling-positive cells, caspase-3 activity, and cytokeratin-18 staining in the liver. rhTrx treatment prevented these increases. In summary, rhTrx attenuated ethanol-induced increases in markers of oxidative stress, inflammatory cytokine expression, and apoptosis. (HEPATOLOGY 2009.)

Identification of microsatellite unstable (MSI-H) colorectal cancers (CRCs) is important not only for the identification of hereditary nonpolyposis colorectal cancer syndrome but also because MSI-H CRCs have a better prognosis and may respond differently to 5-fluorouracil-based chemotherapy. We present 2 nearly equivalent logistic regression models for clinical use that predict microsatellite instability based on the review of 1649 CRCs from patients of all ages collected in a population-based case control study in northern Israel. One hundred ninety-eight of these 1649 tumors demonstrated a high degree of microsatellite instability (12%). Multivariate analysis found that2 tumor-infiltrating lymphocyte (TIL) cells per high-powered field, the lack of dirty necrosis, the presence of a Crohn-like reaction, right-sided location, any mucinous differentiation (mucinous or focally mucinous) and well or poor differentiation, and age less than 50 were all independent predictors of MSI-H. We developed 2 logistic regression models that differ only by the statistical approach used to analyze the number of TIL cells per high-powered field, where the slightly more accurate (and complex) model uses the log of the total number of TIL cells. The simpler clinical model uses a cut-off of 2TIL cells per high-powered field. The accuracy of both models is high, with an 85.4% versus 85.0% probability of correctly classifying tumors as MSI-H. By employing the simpler model, pathologists can predict the likelihood of microsatellite instability by compiling the MSI probability score (Table 4 and Fig. 1) from simple histologic and clinical data available during sign-out. Our model shows that approximately 43% of CRCs have a MSI probability score of 1 or less and hence have little likelihood (3%) of being MSI-H. Although this model is not perfect in predicting microsatellite instability, its use could improve the efficiency of expensive diagnostic testing.

A hematopoietic stem cell transplant recipient developed abdominal pain, pneumatosis intestinalis, hepatitis, pancreatitis, and inappropriate antidiuretic hormone secretion. Blood for varicella-zoster virus (VZV) DNA polymerase chain reaction was positive. She was treated with acyclovir and subsequently developed VZV antigen-positive zoster. Detection of VZV DNA in blood may be useful for early diagnosis in immunocompromised hosts who present with zoster without skin lesions.

Introduction… 316 General Evaluation… 316 Syncope in the Patient With a Normal Evaluation… 318 Syncope in the Patient With Coronary Artery Disease… 319 Nonischemic Dilated Cardiomyopathy… 320 Syncope in Other Forms of Structural Heart Disease… 320 Syncope Resulting From Inherited Cardiac Ion Channel Abnormalities… 321 Evaluation of the Pediatric Patient With Syncope… 321 Special Considerations in the Elderly… 323 Neurological Evaluation… 323 Conclusions… 324 Syncope, a transient loss of consciousness, is a common clinical problem. The most common causes of syncope are cardiovascular in origin and are associated with a high rate of mortality in patients with underlying heart disease, transient myocardial ischemia, and other less common cardiac abnormalities.1 The primary purpose of the evaluation of the patient with syncope is to determine whether the patient is at increased risk for death. This involves identifying patients with underlying heart disease, myocardial ischemia, Wolff-Parkinson-White syndrome, and potentially life-threatening genetic diseases such as long-QT syndrome (LQTS), Brugada syndrome, and catecholaminergic polymorphic ventricular tachycardia. If these diagnoses can be excluded, the goal then becomes identification of the cause of syncope in an attempt to improve the quality of the patient’s life and to prevent injury to the patient or others. The purpose of this statement is to summarize the data that direct the evaluation of the patient with syncope (Figure 1). Figure 1. Flow chart for the diagnostic approach to the patient with syncope. In the general population, the most common cause of syncope is neurocardiogenic, followed by primary arrhythmias. Other names for neurocardiogenic syncope include neurally mediated, vasodepressor, and vasovagal syncope. The causes of syncope are highly age dependent.2 Pediatric and young patients are most likely to have neurocardiogenic syncope, conversion reactions (psychiatric causes), and primary arrhythmic causes such as the LQTS and Wolff-Parkinson-White syndrome. In middle age, neurocardiogenic syncope …

Objectives a) To determine whether decreased sarcoplasmic calcium release channel (CRC) activity is a mechanism by which myocardial contractility is reduced in endotoxemia; b) to determine whether nitric oxide modulates CRC activity in endotoxemia; and c) to examine two nitric oxide signaling pathways in relation to CRC function in endotoxemia. Design Randomized, prospective using a rat model of endotoxemia. Setting : Research laboratory. Subjects Sprague-Dawley rats. Interventions Endotoxemia was induced by lipopolysaccharide administration. The effects of nitric oxide were studied using the highly selective inducible nitric oxide synthase inhibitor N-(3-(aminomethyl)benzyl)acetamidine dihydrochloride (1400W) and the specific guanylyl cyclase inhibitor 1-H (1, 2, 4)oxadiazolo[4,3-a]quinoxalin-1-one (ODQ). Measurements and main results We assessed myocardial contractility, myocardial nitric oxide content, and guanosine-3',5' (cyclic) phosphate (cGMP) content. We determined CRC activity by calcium release and ryanodine binding assays. We followed these variables at four time points through the course of endotoxemia. We found that myocardial contractility and CRC activity were decreased in late but not in early endotoxemia. Furthermore, inducible nitric oxide synthase inhibition with 1400W restored contractility and CRC activity in late endotoxemia but paradoxically worsened these variables in early endotoxemia. Through the use of the guanylyl cyclase inhibitor ODQ, we demonstrate that nitric oxide acts through cGMP-mediated mechanisms in early and late endotoxemia. We investigated cGMP-independent pathways by assessing the oxidative status of the CRC. We found that in late endotoxemia, nitric oxide decreased the number of free thiols, demonstrating that nitric oxide also acts through cGMP-independent pathways. Conclusions Nitric oxide has a dual effect on the CRC in endotoxemia. At low concentrations, as measured in early endotoxemia, nitric oxide stabilizes the CRC through cGMP-mediated mechanisms. In late endotoxemia, high nitric oxide concentrations decrease channel activity through both cGMP-dependent and cGMP-independent mechanisms.

The purpose of this report is to summarize existing literature with respect to carotid artery blowout and to present an up-to-date algorithm for its management that incorporates recent advances with respect to its diagnosis and treatment.Although once thought as one entity, carotid blowout is now considered to be a syndrome with clinical manifestations ranging from acute hemorrhage to asymptomatic exposure of a carotid artery. As a result, carotid blowout syndrome can present as one of three separate entities: threatened, impending, and acute carotid blowout. In recent years newer approaches to management have centered around the use of diagnostic angiography followed by definitive therapy with either carotid occlusion by coils, detachable balloons, or endovascular stents. Overall morbidity of management has decreased.Interventional radiologic techniques have revolutionized the treatment of carotid blowout syndrome, allowing more accurate diagnosis and lower treatment morbidity.

A "super scan" pattern detected on bone scintigraphy usually indicates either metabolic bone disease or diffuse metastases. We report a rare case of a 45-year-old man with recurrent episodes of syncope of 10 years' duration in whom bone scintigraphy showed a super scan with an axial skeleton distribution of uptake. Bone marrow biopsy established the diagnosis of systemic mastocytosis. The few reports in the literature of super scans associated with systemic mastocytosis showed diffuse axial and appendicular increased uptake. The present case shows a super scan involving the axial skeleton, which led to the diagnosis of systemic mastocytosis.

The phenotypic markers of colorectal carcinomas with microsatellite instability have been widely studied and include mucinous or poor differentiation, prominent host response, a circumscribed growth pattern, histologic heterogeneity, and right-sided location. As part of a population-based case-control study of colorectal cancer in northern Israel, we reviewed the pathology and microsatellite status of 528 consecutively diagnosed colorectal cancers. Phenotypic analysis was performed by one pathologist (J.K.G.) and included assessment of grade, mucinous histology (50%, or focal), histologic heterogeneity, growth pattern, necrosis, and host response. Microsatellite status was determined on microdissected portions of formalin-fixed, paraffin-embedded tissue using a panel of 5 NCI consensus primers. Fifty-two of 528 colorectal carcinomas were microsatellite unstable (9.85%). Multivariate analysis found that2 tumor infiltrating lymphocytes per high power field (p0.0001), the lack of dirty necrosis (p = 0.0054), a Crohn's-like host response (p = 0.0064), right-sided location (p = 0.032), well or poor differentiation (p = 0.037), and any mucinous differentiation (p = 0.039) were independent predictors of microsatellite instability. Tumor infiltrating lymphocytes were the single best histologic predictor of microsatellite instability. The absence of dirty necrosis and the presence of well-differentiated tumors and tumors with only focal mucinous differentiation were also important markers for microsatellite instability that have not been emphasized previously. The combination of2 tumor infiltrating lymphocytes per high power field and/or any mucinous differentiation and/or the absence of dirty necrosis identified all MSI-H tumors in this study.

Objectives: To determine the time course for myocardial production of nitric oxide, peroxynitrite, and glutathione, to determine the activities of the myocardial antioxidant enzymes glutathione peroxidase, superoxide dismutase, and glutathione reductase throughout endotoxemia and into recovery, and to correlate the levels of these variables to left ventricular contractility in endotoxemia. Design: Rats were treated with lipopolysaccharide. Endotoxemic hearts were examined at baseline, 4, 16, 24, and 48 hrs after lipopolysaccharide. Saline time-control groups were treated identically. Setting: A pulmonary research laboratory of a university teaching hospital. Measurements and Main Results: Lipopolysaccharide administration resulted in decreased contractility at 16 hrs as assessed by the isolated papillary muscle technique. Contractility recovered by 24 hrs. Myocardial glutathione content initially increased, but it was decreased from baseline by 16 hrs, as was glutathione peroxidase activity. Both superoxide dismutase and glutathione reductase activities were increased early (4 hrs) and remained elevated throughout the course of the experiment. Myocardial nitric oxide content (assessed by the chemiluminescence technique) was increased by 4 hrs and was markedly elevated by 16 hrs. Nitric oxide levels remained elevated despite recovery of contractility at 24 hrs. Similarly, peroxynitrite (assessed by measurement of 3-nitrotyrosine by high-pressure liquid chromatography) was elevated at 16 hrs and remained elevated despite normalization of contractility at 24 and 48 hrs. Conclusions: Myocardial dysfunction in endotoxemia correlates mainly with decreased glutathione content and glutathione peroxidase activity rather than nitric oxide or peroxynitrite formation. These data indicate that lipopolysaccharide-induced myocardial dysfunction is not solely caused by elevated myocardial nitric oxide levels but rather caused by the sum of complex interactions between various oxygen- and nitrogen-derived radicals.

The compatibility of different dental materials (root canal sealer and composite core build-up restoratives) is an important factor for a successful restoration. The aim of this in vitro study was to determine the effects on compressive and diametral tensile strength of a classical chemical cure composite resin (Henry Schein Composite Anterior-Posterior dental restorative) when in contact with either eugenol or an epoxy-resin (EZ-Fill) in a variety of situations: (a) eugenol or epoxy-resin added during mixing of a composite resin before curing; (b) vapor exposure to cured samples; and (c) specimens placed directly in eugenol or epoxy-resin (after curing). Compressive strengths and diametral tensile strengths were tested for each group. Only the addition of eugenol during mixing with the composite resin (directly before curing) resulted in specimens that were unable to be tested, because they did not achieve a full cure or hardness. For all other groups, there were no significant differences with respect to either compressive strength (p = 0.17) or diametral tensile strength (p = 0.39). Group 1 (mixed directly with eugenol) was found to be statistically different from groups 2 through 7.

Reconstruction of laryngotracheal stenosis continues to be a significant challenge. Many authors using a variety of techniques have reported success rates as high as 90%. Preoperative investigation, staging, and postoperative management have all seen advances based on animal or clinical studies. Unf

Background —The purpose of this study was to evaluate the long-term outcome of all pediatric epicardial pacing leads. Methods and Results —All epicardial leads and 1239 outpatient visits between January 1, 1983, and June 30, 2000, were retrospectively reviewed. Pacing and sensing thresholds were reviewed at implant, at 1 month, and at subsequent 6-month intervals. Lead failure was defined as the need for replacement or abandonment due to pacing or sensing problems, lead fracture, or phrenic/muscle stimulation. A total of 123 patients underwent 207 epicardial lead (60 atrial/147 ventricular, 40% steroid) implantations (median age at implant was 4.1 years [range 1 day to 21 years]). Congenital heart disease was present in 103 (84%) of the patients. Epicardial leads were followed for 29 months (range 1 to 207 months). The 1-, 2-, and 5-year lead survival was 96%, 90%, and 74%, respectively. Compared with conventional epicardial leads, both atrial and ventricular steroid leads had better stimulation thresholds 1 month after implantation; however, only ventricular steroid leads had improved chronic pacing thresholds (at 2 years: for steroid leads, 1.9 μJ [from 0.26 to 16 μJ]; for nonsteroid leads, 4.7 μJ [from 0.6 to 25 μJ]; P P Conclusions —Steroid epicardial leads demonstrated relatively stable acute and chronic pacing and sensing thresholds. In this evaluation of >200 epicardial leads, lead survival was good, with steroid-eluting leads demonstrating results similar to those found with historical conventional endocardial leads.

OBJECTIVE To compare the cardiopulmonary and peripheral circulatory effects of the nonselective nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME) to the more selective inducible NOS inhibitor S-methylisothiourea (SMT) and to phenylephrine (PE) in endotoxic and normal swine. DESIGN Prospective, randomized, unblinded study. SETTING Research laboratory of academic medical center. SUBJECTS Nonanesthetized, sedated, mechanically ventilated, minimally invasive swine model. INTERVENTIONS Animals received either lipopolysaccharide (LPS, LPS groups) or equivalent volume of saline (normal groups). LPS animals were further randomized into four groups when mean arterial pressure (MAP) had dropped to

PURPOSE: Pelvic recurrence of rectal cancer is an ominous event for the patient and a formidable challenge to the managing surgeon. We reviewed the results of abdominosacral resection to manage these patients and correlated outcome (survival and recurrence) with known prognostic factors. METHODS: An abdominosacral resection was performed on 61 patients with pelvic recurrence (53 with curative intent and 6 for palliation; 2 had extended pelvic resection). Of the 53 patients (32 males; average age, 59 years) previous resection included abdominoperineal resection in 27 patients, abdominoperineal resection plus hepatic lobectomy in 2 patients, low anterior resection in 19 patients, plus trisegmentectomy in 1 patient, and advanced primary cancers in 4 patients. Initial primary stage was Dukes B (64 percent) and Dukes C (36 percent). All had been irradiated (3,000–6,500 in 50 patients, 8,300 and 11,000 in 2 patients, and unknown dose in 3 patients). Preoperative carcinoembryonic antigen was elevated (>5 ng/ml) in 54 percent. Extent of resection: high sacral resection S-1–S-2 was done in 32 patients, midsacrum in 14 patients, and low S-4–S-5 in 6 patients. Twenty-eight patients (60 percent) required partial or complete bladder resection with or without adjacent viscera, and all had internal iliac and obturator node dissection. RESULTS: There were four postoperative (within 60 days) deaths, 8 percent in curative groups (5.4 percent overall). Major complications included prolonged intubation (20 percent), sepsis (34 percent), posterior wound infection or flap separation (38 percent). The survival rate in the curative group (49 postoperative survivors) was 31 percent at five years, with 13 patients surviving beyond five years. Seven of these patients survived from 5 to 21 years, whereas six patients recurred again and died within 5.5 to 7.5 years after abdominosacral resection. Disease-free survival rate at five years was 23 percent. Recent reconstruction with large composite myocutaneous gluteal flaps in 5 patients permitted complete sacral wound coverage, resulting in earlier ambulation and reduced hospital stay. CONCLUSIONS: Abdominosacral resection permits removal of pelvic recurrence of rectal cancer that is fixed to the sacrum and is associated with long-term survival in 31 percent of patients. Recent technical advances have improved the short-term outcome and have made the procedure more feasible for surgical teams familiar with these techniques.

In the traditional medical model, the physician, acting in the best interests of the patient, assumes full responsibility for delivering information, making decisions about treatment, and providing care. This model is not suitable for chronic care or preventive health maintenance. Recent alternatives to this model include participatory decision-making and family-centered care, clinical approaches in which the patient and family share the responsibility for decision-making with the physician. Research has demonstrated that patients and families vary in their willingness to make decisions about care. The Adaptive Practice model describes how compassionate and effective medical practice ranges from traditional hierarchical relationships to full patient or family control, depending on the situation. Four different clinical approaches-directing, teaching, collaborating, and supporting-result from variations in the direction of leadership and in the degree of interaction in the situation. Each approach is suitable for specific situations. For example, directing is appropriate in emergencies or crises. Supporting is appropriate when families are both knowledgeable and motivated to make decisions that affect their quality of life. Sensitive physicians assess the situation, negotiate an approach suitable to the family's and patient's needs at the time, and adjust their approach as the partnership evolves. The Adaptive Practice model provides a structure for analyzing clinical situations, choosing clinical approaches, and understanding problems in physician-family relationships when they arise. J Dev Behav Pediatr 20:111-116, 1999. Index terms: family-centered care, doctor-patient communication, family, chronic illness, disabilities, children with special health care needs, participatory decision-making.

OBJECTIVES Scorpion envenomation may be accompanied by metabolic acidosis even in the absence of hypoxia and cardiovascular derangement. We tested the hypothesis that venom causes ischemia of the gastrointestinal tract rather than failure of delivery of oxygen to the periphery. DESIGN Repeated measures, prospective study in experimental animals. SETTING University-affiliated hospital research laboratory. INTERVENTIONS In ten spontaneously breathing, intubated, sedated pigs, purified dried venom (Leiurus quinquestriatus), 0.05 mg/kg, was administered intravenously. Measurements were obtained before (baseline), and 5, 15, 30, 60, 120, 180, and 240 mins after injection. MEASUREMENTS AND MAIN RESULTS Variables measured included: mean arterial pressure (MAP), heart rate (HR), mean pulmonary arterial pressure, pulmonary artery occlusion pressure, cardiac output, stroke volume, right ventricular ejection fraction (rapid thermistor), left ventricular dimensions (echocardiography), arterial gas tensions, lactate and catecholamine concentrations, gastric interstitial mucosal pH (tonometry), as well as systemic and pulmonary vascular resistances. Within 5 mins after venom injection, there was a hyperdynamic state accompanied by significantly increased MAP (97 +/- 18 to 136 +/- 47 mm Hg, p < .0003), HR (70 +/- 12 to 121 +/- 24 beats/min, p < .00006), and cardiac output (1.88 +/- 0.35 to 2.95 +/- 0.53 L/min, p < .0003), with no change in stroke volume, or pulmonary artery occlusion pressure. Right ventricular ejection fraction increased from 38.1 +/- 4.3 to 48.6 +/- 9.0% (p < .0009) by 15 mins. No change in left ventricular function was observed. There were significant decreases in systemic vascular resistance and pulmonary vascular resistance following envenomation. Arterial and gastric mucosal pH significantly decreased from 7.40 +/- 0.04 to 7.25 +/- 0.07 (p < .0001) for arterial pH, and 7.33 +/- 0.08 to 7.17 +/- 0.13 (p < .00001) for gastric mucosal pH by 30 mins after envenomation. The decrease in arterial pH was not sufficient to account for the change in gastric mucosal pH, indicating gastric mucosal ischemia. Arterial lactate increased from 2.6 +/- 1.4 to 7.4 +/- 1.9 (p < .05 x 10(-8)). There were significant increases in serum epinephrine and norepinephrine values by 5 mins. All hemodynamic variables and catecholamine concentrations returned to baseline by 4 hrs. However, there was persistent arterial and gastric mucosal acidosis and increased lactate concentrations even at 4 hrs. Oxygen delivery remained normal or supernormal for 4 hrs following envenomation. However, despite this finding, systemic and gastric mucosal pH changes indicate impaired gastrointestinal oxygen delivery. CONCLUSIONS Despite increased peripheral oxygen delivery, scorpion envenomation was associated with evidence of ischemia of the gastrointestinal tract. This association could be due to shunting of blood from metabolically active areas, possibly associated with massive catecholamine release, or a direct toxic effect of the venom on regional oxygen transport at the cellular level.

AIM: Prostate specific antigen (PSA) is a widely utilized screening marker for prostate cancer. Its performance in detecting prostate cancer is enhanced with the 5α-reductase inhibitor (5aRI) dutasteride. We evaluated if PSA density velocity (PSADV) further improved the ability to predict prostate cancer risk on repeat biopsy utilizing the REDUCE trial data in order to avoid unnecessary biopsies. MATERIALS AND METHODS: The REDUCE study randomized 8 231 men aged 50 to 75 years with a PSA between 2.5 and 10 ng/ mL and a previously benign prostate biopsy. Prostate volume, PSA and biopsy results at 24 months were available for 1 074 subjects. PSADV, defined as the change in PSA density divided by the number of days between PSA measurements (ng/mL/cc/day), was calculated and compared between the placebo and treatment groups and further stratified by prostate biopsy results. Statistical significance was after prostate cancer diagnosis or final biopsy) PSADV, defined as the change in PSA density divided by the number of days between PSA measurements (ng/ml/cc/day), was calculated and compared between the placebo and treatment groups and further stratified by prostate biopsy results. Statistical significance was calculated using the Wilcoxon rank sum test performed at the significance level of 0.05.

This in vitro study measured the time required to instrument and shape canals by conventional reamers and files compared with a newly introduced reamer and file system. This experiment was divided into four groups with 10 block samples for each group. The results of instrumentation time demonstrate that the noninterrupted flat-sided design (EZ-Fill SafeSider reamers) produced the fastest times for comparably shaped canals because of reduced engagement of the instrument with the walls of the canal compared with conventional instruments. The conventional designs for both reamers and files result in increased instrumentation time compared with their EZ-Fill SafeSider counterparts.

The prevention of cholesterol gallstone formation by three bile acid analogs, sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24- sulfonate, sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulfonate and sodium 3 alpha,6 alpha-dihydroxy-5 beta-cholane-24-sulfonate, was examined in a hamster model of cholesterol cholelithiasis. Sodium taurochenodeoxycholate, sodium tauroursodeoxycholate and sodium taurohyodeoxycholate were studied simultaneously for comparison. Gallstones and cholesterol crystals were induced in 14 of 15 hamsters fed a bile acid-free, semipurified lithogenic diet containing 0.3% cholesterol and 4% butterfat for 6 wk. The addition of 0.1% sodium taurochenodeoxycholate and sodium tauroursodeoxycholate to the lithogenic diet had little effect on the formation of gallstones or biliary cholesterol crystals. In contrast, sodium 3 alpha,7 alpha-hydroxy-5 beta-cholane-24- sulfonate and sodium 3 alpha,7 beta-dihydroxy-5 beta-cholane-24-sulfonate, when fed at the same dose, prevented cholesterol gallstone formation significantly. Sodium taurohyodeoxycholate and sodium 3 alpha,6 alpha-dihydroxy-5 beta-cholane- 24-sulfonate inhibited cholesterol gallstone formation effectively. The cholesterol saturation index of bile was greater than 1.00 in all groups, with the exception of the group fed sodium 3 alpha,7 alpha-dihydroxy-5 beta-cholane-24-sulfonate. Liver and serum cholesterol levels tended to be lower in most of the groups that were fed bile acids. This effect was most pronounced in the animals receiving sodium taurohyodeoxycholate. At the end of the experiment, the administered sulfonate analogs were detected in gallbladder bile.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of various concentrations of platelets and plasma on in vitro t-PA-induced fibrinolysis were investigated. At t-PA levels between 30 and 70 ng/ml, fibrinolysis proceeded faster in platelet-rich plasma (PRP) than in platelet-poor plasma (PPP). When PRP was serially diluted with PPP and the rate of fibrinolysis compared to PPP, higher platelet counts (up to 300 x 10(9)/l) were associated with increased enhancement of lysis. However, lysis was inhibited when platelets were added to plasma diluted with buffer. Thus, platelets enhance fibrinolysis in undiluted plasma but inhibit lysis in diluted plasma. This is probably because platelets provide a catalytic surface for fibrinolysis but also release inhibitors of fibrinolysis. In undiluted plasma, there would be sufficient fibrinogen and plasminogen to overcome the effect of the platelet inhibitors, but in diluted systems, the inhibitors would predominate, retarding fibrinolysis.

Although previous ultrasonographic studies did monitor ventricular enlargement successfully in experimentally-induced models of feline hydrocephalus, the resolution of neuroanatomic detail was relatively poor after placement of a ventriculoperitoneal (VP) shunt because the skull had ossified over the coronal sutures. Therefore, the present study employed magnetic resonance imaging to follow the progression of ventriculomegaly more accurately, as well as to evaluate the compensatory effects of VP shunting. Hydrocephalus was induced in kittens between 7 and 10 days old by injection of kaolin into the cisterna magna. Age-matched controls received similar injections of saline. At 9 to 14 days after the kaolin injection, the hydrocephalic animals received VP shunts. Anesthetized kittens were scanned at various intervals before and after shunt placement and were killed for morphological correlation. The features observed on the magnetic resonance imaging scans were consistent with the gross morphological changes that accompanied ventricular enlargement. The lateral ventricle began to enlarge as early as 1 day after the kaolin injection, and within 3 days, both the occipital and temporal horns, along with the 4th ventricle, showed signs of moderate dilatation. By 5 days, a bilateral communication had been established through the septum pellucidum. Continued expansion of the ventricular system occurred from 6 to 20 days after injection, to the point where the cerebral cortex was reduced to less than 25% of its original thickness. The internal capsule was stretched and edematous, the caudate nucleus was compressed ventrolaterally, and the cerebellar hemispheres were eroded and/or compressed. Animals in which shunts were successfully placed demonstrated a dramatic improvement in behavior, and a reduction of about 50% in the size of the lateral ventricles within 2 days. In some cases, the lateral ventricles became slit-like within 1 week. When they were killed, about half of the animals that received shunts exhibited mild to moderate ventriculomegaly. These results indicate that magnetic resonance imaging is an excellent method for visualizing the morphological changes associated with this animal model, that these alterations occur soon after the onset of hydrocephalus, and that VP shunting can successfully reduce ventriculomegaly.

The effect of dietary administration of four different amino acid (N-acyl) conjugates of ursodeoxycholic acid on biliary bile acid composition, liver tests and hepatic morphology by light microscopy was examined in the rabbit. Each group of four to five rabbits received a chow diet supplemented with a single conjugate of ursodeoxycholic acid ursodeoxycholylglycine, ursodeoxycholyl-sarcosine, ursodeoxycholyltaurine or ursodeoxycholyl-N-methyltaurine for 3 wks at a dose of 50 mg/kg/day; a control group received chow alone. After 3 wks of feeding, animals receiving ursodeoxycholyl-glycine or ursodeoxycholyl-taurine had hepatotoxicity associated with abnormal liver tests. Lithocholic acid made up 11% ± 2.7% of biliary bile acids in the ursodeoxycholyl-glycine and 10% ± 2.2% in the ursodeoxycholyl-taurine group. In contrast, animals receiving ursodeoxycholyl-sarcosine or ursodeoxycholyl-N-methyltaurine had neither hepatotoxicity nor abnormal liver tests and the proportion of lithocholic acid in biliary bile acids increased much less. Complementary studies showed that ursodeoxycholyl-sarcosine and ursodeoxycholyl-N-methyltaurine were not biotransformed during hepatic transport and were resistant to deconjugation and dehydroxylation in the rabbit. These experiments indicate that the N-methyl amino acid conjugates of ursodeoxycholic acid are nontoxic in the rabbit and resist deconjugation and dehydroxylation. Such resistance decreases formation of lithocholic acid in the colon, thus reducing its accumulation and consequent induction of hepatotoxicity.(HEPATOLOGY 1990;11:989-996.).

Dermatofibrosarcoma protuberans is an uncommon skin tumor with a high potential for local recurrence if not adequately excised. There are only two reports in the literature describing dermatofibrosarcoma protuberans that enlarged considerably during pregnancy. On the other hand, the new development or enlargement of dermatofibromas in pregnancy is well documented. We present 2 additional patients in whom a dermatofibrosarcoma protuberans appeared and grew rapidly during pregnancy. Immunohistochemical studies were negative for estrogen and progesterone receptors. The possible pathophysiology and surgical management are presented and discussed.

Several herpesviruses have been reported to reactivate in non-immunocompromised patients in the intensive care unit (ICU) including herpes simplex virus (HSV), human herpesvirus 6, and cytomegalovirus (CMV). Shedding of HSV has been associated with reduced survival in non-immunocompromised patients on ventilators in some studies [1]; however, at present it is not known whether this is due to a general impairment in host defense mechanisms that occurs in patients in the ICU or whether the virus is a direct cause of morbidity and mortality. Human herpesvirus 6 has also been reported to reactivate in non-immunocompromised patients admitted to the ICU; however, the virus was not been associated with increased severity of disease or mortality in these patients [2].

A 28-year-old man was examined because of a mass in the right side of his neck. A thyroid scan with Tc-99m pertechnetate showed an area of decreased activity in the right lower lobe that corresponded to the palpable nodule. Because the fine-needle aspiration did not provide satisfactory specimens, the patient underwent surgery. The nodule was firmly attached to the right lobe and both were excised. A histologic analysis revealed that the cystic mass was consistent with an echinococcal cyst. Thyroid involvement by hydatid cysts, especially as a primary site, is very uncommon.

The purpose of this in vitro study was to determine the cytotoxicity of two root canal sealing materials (AH26 and AH-Plus). This cytotoxicity test (agar diffusion test) was conducted based on the procedures described in the International Organization for Standardization. The biological reactivity of a mammalian monolayer, L929 mouse fibroblast cells, in response to the tested agents was determined. After the 48-h observation period, the cell cultures exposed to the test articles discs for AH26 and AH-Plus exhibited severe reactivity (grade 4). The positive control article exhibited moderate reactivity (grade 3). No signs of reactivity (grade 0) were noted for the negative control article or the negative control discs. The tested samples of AH26 and AH-Plus are considered cytotoxic and do not meet the requirement of the agar diffusion test. Similar cytotoxicity results have been found in the literature for AH26 and other root canal sealing cements.