Pupillometric assessment of dysautonomia in pediatric bowel and bladder dysfunction: a pilot study.

Bowel and bladder dysfunction (BBD) refers to a heterogeneous group of voiding disorders, accounting for an estimated 40% of pediatric urology visits. Symptoms of BBD include enuresis, urgency, and urinary retention, often accompanied by constipation. The aim of this pilot study was to explore whether a pupillary response can be characterized for BBD, by examining the pupillary light reflex (PLR) before and after voiding among patients with BBD. A total of 28 patients aged from 7 to 21 years were recruited from the Wetting, Infections, and Stooling Help clinic at Children's National Medical Center. An infrared pupilometer was used to assess the PLR. Both baseline static and dynamic pupillometry assessments were obtained before and after voiding. Measurements were also taken after 5 min in the supine position, followed by 5 min standing to induce an orthostatic stressor. Visual inspection of the graphed data revealed a characteristic shape in 11 of 28 patients with voiding symptoms. In these 11 patients, the redilation arm of the PLR shows a 'notch,' or a brief reconstriction of the pupil before resting pupil size is reestablished (figure). This feature of the PLR has not been seen in previous and parallel studies using pupillometry to evaluate other populations. The results of this study suggest that a subset of patients with BBD may have a significant perturbation of autonomic regulation, identifiable through analysis of the PLR. To our knowledge, this 'notch' during redilation has not been previously described or seen in other patient populations and may represent a distinctive and readily identifiable physiologic marker of disease. These results are broadly aligned with results of other studies that have examined ANS activity in patients with BBD, although further study is needed to confirm the results of this pilot study and to assess relative contributions of sympathetic and parasympathetic function in producing pupillary abnormalities. This study has several limitations, including the small sample size, the absence of data on severity and duration of symptoms, and the absence of a control group of patients without any voiding symptoms. A simple tool for diagnosing BBD and for monitoring response to treatment could significantly improve the quality of treatment for one of the most common pediatric urologic complaints. Given the heterogeneity of symptoms under the BBD umbrella, pupillometric data could guide selection of treatment options, as well as assess adequacy of response to pharmacologic therapy.

Application of the systematic "DAmP" approach to create a partially defective C. albicans mutant.

An understanding of gene function often relies upon creating multiple kinds of alleles. Functional analysis in Candida albicans, a major fungal pathogen, has generally included characterization of mutant strains with insertion or deletion alleles and over-expression alleles. Here we use in C. albicans another type of allele that has been employed effectively in the model yeast Saccharomyces cerevisiae, a "Decreased Abundance by mRNA Perturbation" (DAmP) allele (Yan et al., 2008). DAmP alleles are created systematically through replacement of 30 noncoding regions with nonfunctional heterologous sequences, and thus are broadly applicable. We used a DAmP allele to probe the function of Sun41, a surface protein with roles in cell wall integrity, cell-cell adherence, hyphal formation, and biofilm formation that has been suggested as a possible therapeutic target (Firon et al., 2007; Hiller et al., 2007; Norice et al., 2007). A SUN41-DAmP allele results in approximately 10-fold reduced levels of SUN41 RNA, and yields intermediate phenotypes in most assays. We report that a sun41Δ/Δ mutant is defective in biofilm formation in vivo, and that the SUN41-DAmP allele complements that defect. This finding argues that Sun41 may not be an ideal therapeutic target for biofilm inhibition, since a 90% decrease in activity has little effect on biofilm formation in vivo. We anticipate that DAmP alleles of C. albicans genes will be informative for analysis of other prospective drug targets, including essential genes.

Unintended changes in cognition, mood, and behavior arising from cell-based interventions for neurological conditions: ethical challenges.

The prospect of using cell-based interventions (CBIs) to treat neurological conditions raises several important ethical and policy questions. In this target article, we focus on issues related to the unique constellation of traits that characterize CBIs targeted at the central nervous system. In particular, there is at least a theoretical prospect that these cells will alter the recipients' cognition, mood, and behavior-brain functions that are central to our concept of the self. The potential for such changes, although perhaps remote, is cause for concern and careful ethical analysis. Both to enable better informed consent in the future and as an end in itself, we argue that early human trials of CBIs for neurological conditions must monitor subjects for changes in cognition, mood, and behavior; further, we recommend concrete steps for that monitoring. Such steps will help better characterize the potential risks and benefits of CBIs as they are tested and potentially used for treatment.

Cell-based interventions for neurologic conditions: ethical challenges for early human trials.

BACKGROUND: Attempts to translate basic stem cell research into treatments for neurologic diseases and injury are well under way. With a clinical trial for one such treatment approved and in progress in the United States, and additional proposals under review, we must begin to address the ethical issues raised by such early forays into human clinical trials for cell-based interventions for neurologic conditions. METHODS: An interdisciplinary working group composed of experts in neuroscience, cell biology, bioethics, law, and transplantation, along with leading disease researchers, was convened twice over 2 years to identify and deliberate on the scientific and ethical issues raised by the transition from preclinical to clinical research of cell-based interventions for neurologic conditions. RESULTS: While the relevant ethical issues are in many respects standard challenges of human subjects research, they are heightened in complexity by the novelty of the science, the focus on the CNS, and the political climate in which the science is proceeding. CONCLUSIONS: Distinctive challenges confronting US scientists, administrators, institutional review boards, stem cell research oversight committees, and others who will need to make decisions about work involving stem cells and their derivatives and evaluate the ethics of early human trials include evaluating the risks, safety, and benefits of these trials, determining and evaluating cell line provenance, and determining inclusion criteria, informed consent, and the ethics of conducting early human trials in the public spotlight. Further study and deliberation by stakeholders is required to move toward professional and institutional policies and practices governing this research.

The effect of intranasal fentanyl on the emergence characteristics after sevoflurane anesthesia in children undergoing surgery for bilateral myringotomy tube placement.

UNLABELLED: Children undergoing placement of bilateral myringotomy tubes (BMT) often exhibit pain-related behavior (agitation) in the postanesthesia care unit. We compared the emergence and recovery profiles of pediatric patients who received sevoflurane with or without supplementary intranasal fentanyl for BMT surgery. By using a prospective, double-blinded design, 150 children 6 mo to 5 yr of age, scheduled for routine BMT surgery, were anesthetized with sevoflurane (2%-3%) in a 60% N(2)O/O(2) gas mixture. Patients were randomized to receive equal volumes of intranasal saline (Control), 1 microg/kg fentanyl or 2 microg/kg fentanyl. A blinded observer evaluated each patient using a previously described 4-point agitation scale and the Steward recovery scale. Response to parental presence was observed after a score of six (full recovery) was achieved on the Steward recovery scale. There were no significant differences among the three groups regarding age, weight, surgeon, duration of anesthesia, or ear condition. Recovery times and emergence characteristic scores were not statistically different. Agitation scores were significantly reduced in the 2-microg/kg Fentanyl group as compared with the Control group (P = 0.012). Fentanyl 2 microg/kg is recommended to reduce the incidence of agitation seen in these patients. IMPLICATIONS: We examined the use of nasally administered fentanyl for the relief of agitation or discomfort after placement of bilateral myringotomy tubes in 150 children ages 6 mo to 5 yr using a prospective, double-blinded design. Fentanyl 2 microg/kg was found to reduce the incidence of agitation in these patients.

The predictive value of indium-111 leukocyte scans in the diagnosis of infected total hip, knee, or resection arthroplasties.

To evaluate the usefulness of the indium-111 scan in detecting actually or potentially infected total hip, knee, and resection arthroplasties, 153 scans were performed on 143 patients who underwent reoperation for a loose or painful total joint arthroplasty or a resection arthroplasty between 1990 and 1996. Scans were interpreted as infected, not infected, or equivocal by an experienced nuclear medicine radiologist. Patients were considered to be infected if they met any 2 of the following criteria: i) positive intraoperative cultures, ii) final permanent histologic section indicating acute inflammation, and iii) intraoperative findings of gross purulence within the joint. Twenty-six patients (17%) met the infection criteria at the time of reoperation. Indium scans were found to have a 77% sensitivity, 86% specificity, 54% and 95% positive and negative predictive values, and 84% accuracy for the prediction of infection. Of 6 equivocal scans, none were infected. The results of this study suggest limited indications for the use of the indium-111 scan in the evaluation of painful hip, knee, or resection arthroplasties. A negative indium scan may be helpful in suggesting the absence of infection in cases in which the diagnosis is not otherwise evident.

Involving family members in cancer care: focus group considerations of patients and oncological providers.

Family members are an integral part of a patient's cancer care from the moment the diagnosis is delivered to the conclusion of treatment. Family members bring with them a range of emotional reactions, interpersonal dynamics and expectations for the care the patient receives. This study is part of a multi-institutional project to continue to improve the process of cancer care. In this study, 19 focus groups (11 patient and 8 provider) were conducted concerning issues related to doctor-patient communication in eight cancer centers in the United States. The content of the conversations was analyzed and thematic categories emerged that highlight the various strengths and difficulties associated with family involvement. The focus groups' comments support the need for explicit conversations between professional caregivers, patients and their loved ones, in order to negotiate the expectations and needs of each team member. Implications for clinical practice and strategies for working with family members are offered.

A randomized, double-blinded study of remifentanil versus fentanyl for tonsillectomy and adenoidectomy surgery in pediatric ambulatory surgical patients.

UNLABELLED: We compared, in a double-blinded manner, the anesthetic maintenance and recovery properties of remifentanil with a clinically comparable fentanyl-based anesthetic technique in pediatric ambulatory surgical patients. Anesthesia was induced with either halothane or sevoflurane and nitrous oxide and oxygen. Patients were randomized (computer generated) to receive either remifentanil or fentanyl in a blinded syringe with nitrous oxide and oxygen in one of four possibilities: halothane/remifentanil, halothane/fentanyl, sevoflurane/remifentanil or sevoflurane/fentanyl. In patients receiving remifentanil, a placebo bolus was administered, and a continuous infusion (0.25 microg. kg(-1). min(-1)) was begun. In patients receiving fentanyl, a bolus (2 microg/kg) was administered followed by a placebo continuous infusion. The time from discontinuation of the anesthetic to extubation, discharge from the postanesthesia care unit (PACU), and discharge to home, as well as pain scores, were assessed by a blinded nurse observer. Systolic blood pressure and heart rate were noted at selected times, and adverse events were recorded. Remifentanil provided faster extubation times and higher pain-discomfort scores. PACU and hospital discharge times were similar. There were no statistical differences among the groups for adverse events. There were statistically, but not clinically, significant differences in hemodynamic variables. We noted that continuous infusions of remifentanil were intraoperatively as effective as bolus fentanyl. Although patients could be tracheally extubated earlier with remifentanil, this did not translate to earlier PACU or hospital discharge times. In addition, remifentanil was associated with higher postoperative pain scores. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children. IMPLICATIONS: This is a study designed to examine the efficacy and safety of a short-acting opioid, remifentanil, when used in pediatric patients. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children.

The epidural dorsomedian septum as a possible cause for unilateral anaesthesia in an infant.

Unilateral epidural anaesthesia occurring in an infant is reported. An epidurogram revealed the presence of a midline structure suggestive of the dorsomedian septum. Epidural anatomy is reviewed and implications for threading epidural catheters in infants are discussed.

Heart rate variability at rest and during mental stress in patients with coronary artery disease: differences in patients with high and low depression scores.

This study tested the hypothesis that coronary artery disease (CAD) patients with high depressed mood scores differ in sympatho-vagal balance during mental stress compared to patients with low depressed mood scores. Using electrocardiographic monitoring, heart variability data from spectral analysis and hemodynamic parameters were obtained prior to and during mental stress from 34 men and 7 women. A public speaking task was used as the mental stressor. Patients were grouped by a median split of their Minnesota Multiphasic Personality Inventory-Depression score. During mental stress, patients with higher depression scores had greater changes in peak heart rate (p < .05) and low frequency to high frequency power ratio (p < 0.05) than patients with lower scores suggesting a shift toward more sympathetic activity during mental stress. These findings may be related to the reported relation between depression and survival risk in patients with CAD.

Heart rate variability in patients with coronary artery disease: differences in patients with higher and lower depression scores.

OBJECTIVE: This study tested the hypothesis that coronary artery disease patients with higher depression scores have lower heart rate variability during daily life. METHOD: Thirty-three men and nine women, ranging in age from 46 to 79, with coronary artery disease and exercise-induced ischemia were studied. The standard deviation of normal R-R intervals (SDNN) and average heart rate were obtained from 24-hour ambulatory electrocardiographic monitoring. Patients were grouped by a median split of the Minnesota Multiphasic Personality Inventory (MMPI-D) score. RESULTS: SDNN was lower (p = .009) and average heart rate was higher (p = .003) in patients with higher depression scores. These relationships remained substantially unaltered after statistically adjusting for the only demographic/clinical factor that varied between the groups: gender. CONCLUSIONS: In comparison to the lower depression score group, those with higher depression scores had lower heart rate variability during daily life. These findings may be related to the reported relationship between depression and survival risk in patients with coronary artery disease.

A guideline for the design of a four-wheeled walker.

More people use assistive technology devices to compensate for mobility impairments than for any other general type of impairment. Increasing numbers of people with mobility or balance problems use walkers with four wheels. Four-wheeled walkers are often outfitted with seats to make it possible to travel longer distances with intermediate resting periods. The dangers of sitting on a parked walker are well known. Many physiotherapists tell walker users to park the walker against a wall to prevent injury in case the user forgets to apply the brakes or the brakes fail. To design a safer walker that can be used for sitting, the demands placed on it must be measured. With these data, three modes of walker instability must be considered: first, the brakes may hold but the wheels may slide along the ground; second, the entire walker may tip over; and third, the brakes may fail to hold the wheels in place, and they may begin to roll. Mathematical models can be constructed to simulate how different walker designs will perform. By this process, design improvements can be made for existing walkers, and future walker designs can also be proposed.

Relationship among depression scores, beta-endorphin, and angina pectoris during exercise in patients with coronary artery disease.

OBJECTIVES: To determine the relationship between depression scores and (1) anginal indices during exercise including time to onset of angina, duration of angina, and severity of angina and (2) beta-endorphin at rest and in response to exercise. DESIGN: Prospective clinical trial. SETTING: Tertiary-care university hospital. PATIENTS: Fifty-eight patients with documented coronary artery disease and exercise-induced ischemia. OUTCOME MEASURES: Anginal indices during exercise (time to onset of angina, duration of angina, severity of angina); hemodynamic measures (systolic blood pressure, heart rate, rate pressure product) at rest, at onset of angina and at peak exercise; and plasma beta-endorphin levels at rest and immediately after exercise. RESULTS: Twenty-two of 58 patients had typical angina and electrocardiographic change indicating myocardial ischemia during exercise. There was a positive correlation between depression scores and duration of angina and a negative correlation between depression scores and time to onset of angina. Among patients with angina during exercise, systolic blood pressure increased to a greater extent in patients with high depression scores. Patients with high depression scores had higher resting beta-endorphin levels. CONCLUSIONS: Patients with depressed mood had greater perception of anginal pain than nondepressed patients, which cannot be explained by differences in the severity of ischemia. Possible mechanisms include an alteration in beta-endorphin regulation or differences in baroreceptor stimulation.

Tarsal tunnel syndrome.

The diagnosis of tarsal tunnel syndrome can be difficult to make. Clinical findings may be varied and symptoms are commonly vague and diffuse. MR imaging, with its excellent soft tissue contrast and ability to demonstrate musculotendinous and neurovascular structures, clearly demonstrates the anatomy of the tarsal tunnel and its contents and the presence and extent of lesions causing this syndrome.

Identification of epidural neoplasm. Radiography and bone scintigraphy in the symptomatic and asymptomatic spine.

Early identification and treatment of epidural neoplasm, before the development of significant neurologic deficits, provides the best opportunity for a favorable outcome. Among the many patients with symptoms, signs, or scintigraphic or radiographic findings suggesting possible epidural disease, a small proportion will have the lesion. The selection of patients for definitive imaging of the epidural space should be based on a determination of the risk of this complication. In this study, the medical records, plain spinal radiographs, bone scintigraphs and myelograms of 43 patients were analyzed retrospectively to assess the risk of epidural disease associated with specific clinical, radiographic, and scintigraphic findings. Cervical, thoracic, and lumbosacral spinal segments were evaluated independently. Symptomatic segments (SS) (N = 41), defined by focal pain or neurologic dysfunction, were distinguished from asymptomatic segments (AS). At SS, epidural disease was found at 86% and 8% of abnormal and normal spinal radiographs, respectively (P less than 0.001), and at 69% and 0% of abnormal and normal scintigrams, respectively (P less than 0.001), whereas at AS epidural disease occurred in 43% and 3% of abnormal and normal spinal radiographs, respectively (P less than 0.001), and 14% and 7% of abnormal and normal scintigrams, respectively (P = NS). Vertebral collapse was highly predictive of an epidural lesion. Epidural disease occurred in 12% of SS and 0% of AS with an abnormal scintigram and normal radiograph, 86% of SS and 45% of AS with abnormalities on both scintigram and radiograph, and at two AS when both were normal. Decision analysis applied to these data yielded a specific conditional probability of epidural disease for each combination of clinical, scintigraphic, and radiographic findings. These data provide a basis for the selection of patients for additional evaluation of the epidural space before neurologic deficits develop.

Red blood cell labeling with technetium-99m. Effect of radiopaque contrast agents.

Radiographic contrast agents have been reported in the literature to interfere significantly with red blood cell (RBC) labeling in vivo by Tc-99m. Moreover, in the presence of contrast agents, red cells have been known to undergo significant morphologic changes. These observations led to the current RBC labeling study in patients (N = 25) undergoing procedures with the administration of contrast media. Before and after contrast administration, blood samples were drawn from each patient into vacutainer tubes containing heparin and RBC labeling was performed using 1-ml aliquots of these samples following the Brookhaven National Laboratory protocol. The differences in average percentage labeling yield with and without contrast media were not significant. In vivo labeling in hypertensive rats with administration of contrast media up to 600 mg likewise consistently gave high labeling yields at all concentrations. Purported alterations in cell labeling attributed to contrast agents are not reflected in these studies, and other pathophysiologic factors need to be identified to substantiate the previous reports. In vitro study offers a potentially useful and simple method to delineate effects of various agents on cell labeling.

Diazepam in a patient with chronic schizophrenia complicated by agoraphobia.

A case of chronic schizophrenia complicated by agoraphobia expressed as an exacerbation of negative symptoms is presented. The patient responded to diazepam combined with behavior therapy. The need to recognize treatable factors contributing to negative symptoms of schizophrenia is discussed.