Apoptosis imaging: anti-cancer agents in medicinal chemistry.

There is a rapid expansion in the number of new anti-cancer drugs with remarkably different mechanisms of action that can augment traditional chemotherapy. As these agents are often used in combination with traditional chemotherapy testing the effects of these novel agents has proven difficult requiring large sample sizes to detect relatively small differences in patient survival. Despite the wide variety of mechanisms, most new drugs are thought to ultimately induce apoptosis of tumor cells or their supportive vasculature.

Quantitative ultrasound renal parenchymal area correlates with renal volume and identifies reflux nephropathy.

Purpose: Studies show that renal volume on magnetic resonance imaging correlates with differential function and is decreased in children with vesicoureteral reflux diagnosed after urinary tract infection. We examined the correlation between ultrasound renal parenchymal area and magnetic resonance imaging volume to determine whether quantitative ultrasound renal parenchymal area might be a reliable, less costly and less invasive substitute for renal magnetic resonance imaging volume.

Materials And Methods: To determine the correlation of ultrasound renal parenchymal area with magnetic resonance imaging, we identified 82 children with primary vesicoureteral reflux who underwent renal magnetic resonance imaging and ultrasound.

Imaging the molecular signatures of apoptosis and injury with radiolabeled annexin V.

Annexin V is a ubiquitous intracellular protein in humans that has a variety of intriguing characteristics, including a nanomolar affinity for the membrane-bound constitutive anionic phospholipid known as phosphatidylserine (PS). PS is selectively expressed on the surface of apoptotic or physiologically stressed cells. As such, radiolabeled forms of annexin V have been used in both animal models and human Phase I and Phase II trials to determine if this tracer can be employed as an early surrogate marker of therapeutic efficacy in NSCLC and non-Hodgkin's lymphoma.

Developing a systems approach to prevent meconium aspiration syndrome: lessons learned from multinational studies.

Passage of fetal bowel movement (meconium) is common (in about one out of six births), and in some the staining of the amniotic fluid is a sign of fetal distress. Inhalation of meconium (aspiration syndrome, in upto one out of five to eight such births) just before or at birth may be preventable by a coordinated approach by well-trained and informed birth attendants. Respiratory failure secondary to meconium aspiration syndrome (MAS) remains a major cause of morbidity and mortality in the neonatal population.

Monitoring of treatment-induced apoptosis in oncology with PET and SPECT.

The early assessment of a solid tumor's response to conventional or new drug therapy to complement or replace current RECIST (or other clinical) criteria remains an elusive goal. The work horse PET tracer (18)F-FDG, may represent the most immediate method to track individual tumor response to therapy for many types of cancer. Newer radiotracers such as radiolabeled annexin V, have also shown the ability to selectively localize to tumor cells undergoing apoptosis (programmed cell death) in response to successful treatment in vivo.

Posttraumatic stress disorder following traumatic injury: narratives as unconscious indicators of psychopathology.

Current conventional assessment methodologies used to diagnose posttraumatic stress disorder (PTSD) rely heavily on symptom counts obtained from clinical interviews or self-report questionnaires. Such measures may underestimate the impact of traumatic events, particularly in individuals who deny or repress emotional distress. This case report illustrates the use of two methods of narrative analysis to assess unconscious representations of PTSD.

In vivo imaging of apoptosis.

Despite over a decade of intense investigation there is still no routine method for the clinical imaging of apoptosis in oncologic patients. There have been multiple tracers proposed but none as of yet has received FDA approval. Radiolabeled annexin V is one of the few radiotracers that has been widely used in Phase II trials and is still under development.

In vivo detection of apoptosis.

After several decades of debate, it is now widely acknowledged that apoptosis, also known as programmed cell death, is central to homoeostasis and normal development and physiology in all multicellular organisms, including humans. The dysregulation of apoptosis can lead to the destruction of normal tissues in a variety of disorders, including autoimmune and neurodegenerative diseases (too much apoptosis) or the growth of tumors (too little apoptosis). In addition, effective therapy of tumors requires the iatrogenic induction of programmed cell death by radiation, chemotherapy, or both.

Free radicals, antioxidants in disease and health.

Free radicals and oxidants play a dual role as both toxic and beneficial compounds, since they can be either harmful or helpful to the body. They are produced either from normal cell metabolisms in situ or from external sources (pollution, cigarette smoke, radiation, medication). When an overload of free radicals cannot gradually be destroyed, their accumulation in the body generates a phenomenon called oxidative stress.

Rorschach correlates of adolescent self-mutilation.

The present study examined various Rorschach variables of aggression, dysphoric affect, and disordered thinking in relation to self-mutilation in samples of self-mutilating (SM; n=16) and nonself-mutilating (N-SM; n=26) adolescent inpatients. Categorical comparisons indicated that SM patients had significantly higher mean scores for Aggressive Past (AgPast), but not for Aggressive Content (AgC), Aggressive Movement (AG), Morbid Content (MOR), Inanimate Movement (m), Sum Shading (SumY), and the Perceptual-Thinking Index (PTI), than N-SM patients. Additionally, logistic regression results suggested that PTI and AgPast were the most robust predictors of group membership.

Outcomes of transplantation in children with primary hepatic malignancy.

HBL and HCC are the most common hepatic malignancies in children. The role of OLT in children with HCC is still a matter of debate. The aim of this study was to review our experience of OLT for HCC.

Nuclear medicine applications in molecular imaging: 2007 update.

This review examines several classes of radiolabeled agents, including analogs localizing in somatostatin, benzodiazepine and dopamine receptors; analogs of progesterone and estrogen; and agents localizing in lesions with hypoxia. It concludes the status of agents advocated for detecting angiogenesis and inflammation. The current clinical status of these agents, and their potential roles in diagnosis and treatment are discussed.

The use of inhaled nitric oxide in the premature infant with respiratory distress syndrome.

The identification of the biologic properties of nitric oxide (NO) is one of the key scientific discoveries of the century, but its potential for treating human disease is yet to be fully realized. NO has a basic role in regulating vascular tone of the pulmonary circulation, and recent animal models have suggested a more wide reaching influence on perinatal lung development. In animal models, NO has effects on lung growth, angiogenesis, airway smooth muscle proliferation, vascular remodeling, surfactant function, inflammation, and pulmonary mechanics.

Chiral drugs: an overview.

About more than half of the drugs currently in use are chiral compounds and near 90% of the last ones are marketed as racemates consisting of an equimolar mixture of two enantiomers. Although they have the same chemical structure, most isomers of chiral drugs exhibit marked differences in biological activities such as pharmacology, toxicology, pharmacokinetics, metabolism etc. Some mechanisms of these properties are also explained.

Kernicterus in late preterm infants cared for as term healthy infants.

Objective: To compare the clinical profile and health care experiences related to management of newborn jaundice and hyperbilirubinemia in preterm infants (<37(0/7) weeks gestation) who are cared for as term infants (> or =37(0/7) weeks) and develop acute and/or chronic posticteric sequelae.

Methods: Retrospective study of a convenient sample of term and near term infants voluntarily reported to the Pilot Kernicterus Registry (1992-2003). Study infants were required to meet the clinical definitions for acute bilirubin encephalopathy (moderate or advanced severity) and/or the classical signs of kernicterus.

Anthracyclines cause endothelial injury in pediatric cancer patients: a pilot study.

Purpose: The vascular endothelium plays a central role in the regulation of arterial vasomotor tone, releasing nitric oxide for vasodilation. Endothelial-dependent vasodilation can be assessed in vivo, using high resolution ultrasound to measure changes in diameter of the brachial artery. Animal studies have demonstrated that anthracyclines can damage the endothelium and impair the vasodilatory response of arteries; however, there are no comparable data in humans.

Underdiagnosis of pediatric obesity and underscreening for fatty liver disease and metabolic syndrome by pediatricians and pediatric subspecialists.

Objectives: To evaluate how often general pediatricians, pediatric endocrinologists, and gastroenterologists diagnose children as overweight and how often interventions are provided, including nutritional counseling and screening for nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome.

Study Design: The study was a retrospective chart review of outpatient visits at 2 academic hospitals.

Results: A total of 2256 patient visits were analyzed, including 715 visits by overweight children.

Brain stem glioma: two case studies.

The paths taken by each family in coming to terms with the dismal prognosis associated with brain stem glioma can be quite different. The case studies of 2 school-age girls diagnosed with a brain stem glioma within weeks of each other are presented. The multi-disciplinary team response to each family was individualized at each stage of diagnosis, treatment, and end-of-life care, as expected.

Hospital staff and family perspectives regarding quality of pediatric palliative care.

Background: Development of a pediatric palliative care program was preceded by a needs assessment that included a staff survey and family interviews regarding improving pediatric palliative care.

Methods: Four hundred forty-six staff members and community physicians responded to a written survey regarding comfort and expertise in delivering end of life care. Sixty-eight family members of 44 deceased children were interviewed regarding treatment, transition to palliative care, and bereavement follow-up contact.

Recent advances in the imaging of programmed cell death.

A deficiency or an excess of programmed cell death (apoptosis) is an integral component of autoimmune disorders, organ and bone marrow transplant rejection, and cancer. A technique to image programmed cell death would be useful in the development of drugs to treat these and others diseases, and to monitor the effectiveness of therapy. The most widely studied agent for the in vivo study of apoptosis is radiolabeled annexin V, an endogenous protein labeled with technectium-99m, now undergoing clinical trials in both Europe and the United States.

Hyperhomocysteinemia in pediatric and young adult renal transplant recipients.

Hyperhomocysteinemia (HHcy) has been recently identified as an important and reversible cardiovascular risk factor in adult and pediatric renal transplant recipients. A retrospective cross-sectional analysis of 70 pediatric and young adult renal transplant recipients was performed to determine the prevalence, and important clinical and laboratory correlates of HHcy. Total homocysteine concentration, free and protein bound, was determined by fluorescence polarization immunoassay using an IMX analyzer.

Development of radiocontrast agents for vascular imaging: progress to date.

The revolution in molecular imaging techniques is profoundly changing the understanding of the pathophysiology and treatment of atherosclerosis. With these rapid changes there is an increasing demand for development of sensitive and well tolerated novel imaging agents that can be rapidly translated from small animal models into patients with atherosclerosis. Nuclear medicine and positron emission tomography techniques have the ability to detect and serially monitor a variety of biologic and pathophysiologic processes usually with tracer quantities of radiolabeled peptides, drugs, and other molecules at dosages free of pharmacologic adverse effects unlike the current generation of intravenous agents required for magnetic resonance imaging (MRI) and computed axial tomography (CT) scanning.