Standardization of radiograph readings during bowel management week.

INTRODUCTION: During "bowel management week," abdominal radiographs are used to monitor the amount and location of stool. A radiologist familiar with the treatment plan can provide an improved interpretation. The goal of this paper is to standardize the radiological reports during a bowel management week. METHODS: We saw 744 patients during bowel management week from May 2016 until March 2023. Diagnosis included: anorectal malformation (397), idiopathic constipation (180), Hirschsprung disease (89), and spina bifida (78). Laxatives were the treatment for 51% of patients, and 49% received enemas. Characteristic radiographs were selected for each treatment group for a proposed reading standardization. RESULTS: When the stool is visualized, it is crucial to report its location. Having a contrast enema helps with the correct interpretation of the colonic anatomy. It is also essential to always compare the amount of stool with the radiograph from the previous day to determine if there is an increase or decrease in stool. Examples of radiographs are shown to guide the use of the preferred proposed terminology. CONCLUSION: Providing information regarding which treatment modality the patient is receiving and stating that a patient is on a bowel management week treatment is crucial for the radiologist to provide adequate interpretation. The radiologist must be familiar with the treatment goals and purpose of the daily radiograph.

Incidence of medullary thyroid carcinoma and Hirschsprung disease based on the cosmos database.

PURPOSE: Multiple endocrine neoplasia Type 2A (MEN2A) can occur with Hirschsprung disease (HD) due to mutation in the RET proto-oncogene, with the majority developing medullary thyroid carcinoma (MTC). Given the comorbidity, many parents have contacted us to share concerns and unfortunate experiences about the prevalence rates of MEN2A/MTC in patients with HD. The aim is to determine the prevalence rate of patients with HD and MEN2A or medullary thyroid carcinoma, respectively. METHODS: This is a cross-sectional study of the COSMOS database from January 01, 2017, to March 08, 2023. The database was searched for patients diagnosed with MEN2A, MTC, and HD. IRB exemption was provided (COMIRB #23-0526). RESULTS: The database contained 183,993,122 patients from 198 contributing organizations. The prevalence of HD and MEN2A was 0.00002%, and for HD and MTC was 0.000009%. One in 66 patients (1.5%) with MEN2A also had HD. One in 319 patients (0.3%) in the HD group had MEN2A. One in 839 patients (0.1%) within the HD population had MTC. CONCLUSION: The prevalence of MTC and HD or MEN2A and HD in the study population was low. Considering that almost all MEN2A patients have a positive family history, this data does not support the general genetic testing of HD patients.

Do adult patients with congenital colorectal conditions know their diagnosis?

PURPOSE: Limited research exists about the knowledge that adult patients have about their congenital colorectal diagnosis. METHODS: This was an IRB approved, prospective study of patients in the Adult Colorectal Research Registry who completed surveys between October 2019 and March 2022. Surveys were administered through REDCap after patients consented to being contacted for research purposes. Patients provided demographic data, which was linked to surgical records, and the diagnoses provided by patients were compared with diagnoses recorded by the original surgeons. RESULTS: One hundred and thirty-one questionnaires were collected, 115 patients had anorectal malformations (ARM) and 16 had Hirschsprung disease (HD). Seven patients who had ARM were unaware that they had an ARM or HD. The type of ARM recorded by the surgeon was unavailable for comparison with the patient's reported diagnosis in four cases. Of the 111 remaining patients with ARM, only 32 of them (29%) knew what their own type of anomaly was. Female patients recalled their diagnosis more often than male patients (42.4% vs 13.5%). All 16 participants with HD correctly identified their diagnosis severity as HD with or without total colonic aganglionosis. CONCLUSION: The results of this study demonstrate patient's limited understanding of their type of ARM and highlight the urgent need to enhance communication and education strategies, such as issuing patients with medical diagnosis identification cards. It is critical for clinicians to better communicate with patients to ensure that they and their relatives truly understand their precise diagnosis. Adequately informed patients can better advocate for themselves, adhere to treatments and precautionary recommendations and navigate the complexities of transitional care. Consequently they can more effectively manage their lifelong complications.

[Cystic fibrosis and computed tomography of the lungs]. / Computertomographie der Lunge bei Mukoviszidose.

With its high detail of morphological changes in lung parenchyma and airways as well as the possibilities for three-dimensional reconstruction, computed tomography (CT) represents a solid tool for the diagnosis and follow-up in patients suffering from cystic fibrosis (CF). Guidelines for standardized CT image acquisition in CF patients are still missing. In the mostly younger CF patients, an important issue is the well-considered use of radiation in CT imaging. The use of intravenous contrast agent is mainly restricted to acute emergency diagnostics. Typical morphological findings in CF lung disease are bronchiectasis, mucus plugging, or signs of decreased ventilation (air trapping) which can be detected with CT even in early stages. Various scoring systems that have become established over time are used to grade disease severity and for structured follow-up, e.g., in clinical research studies. With the technical development of CT, a number of postprocessing software tools were developed to help clinical reporting and overcome interreader differences for a standardized quantification. As an imaging modality free of ionizing radiation, magnetic resonance imaging (MRI) is becoming increasingly important in the diagnosis and follow-up of CF patients and is already frequently a substitute for CT for long-term follow-up at numerous specialized centers.

Tethered cord in children with anorectal malformations with emphasis on rectobladder neck fistula.

PURPOSE: To find the incidence of tethered cord (TC) in patients with anorectal malformations (ARM) and to determine the relationship between bowel/urinary control and TC in a subset of patients with rectobladder neck fistula (RBNF). METHODS: The database of a tertiary medical center was retrospectively collected for all patients treated for ARM from 1980 to 2012. All patients with TC and RBNF were identified. RESULTS: Among 790 patients, who underwent screening for TC, 285(36%) were diagnosed with TC. Eleven of 37 screened patients with RBNF were diagnosed with TC. The median follow-up period was 49 months (range 2-222 months). TC was diagnosed in 3/18(16.6%) patients with sacral ratio (SR) ≥ 0.7; 4/12(33.3%) with SR 0.41-0.69; and 4/7(57.1%) patients with SR 0-0.4. The association of TC in RBNF patients had a negative influence in the prognosis for bowel and urinary control. CONCLUSION: The incidence of TC among patients with ARM is 36%. Incidence of TC among patients with RBNF correlates with SR value and is higher with lower SR. Patients with RBNF and TC have dismal prognosis for bowel control, unrelated to their SR status. Many unresolved questions related to the management of ARM patients with asymptomatic TC still remain.

Postnatal cytomegalovirus infection and pulmonary vascular disease in extremely premature infants: A case series.

BACKGROUND: Pulmonary vascular disease (PVD) is a major determinant of both morbidity and mortality in extremely low birth weight infants. It is biologically plausible that postnatal cytomegalovirus (pCMV) infection may lead to PVD in premature infants secondary to pneumonitis or via derangement of pulmonary vascular development directly through endothelial dysfunction. Uncertainty remains, however, regarding thresholds for intervention in premature infants with cardiorespiratory instability and presumed CMV infection likely secondary to the limited understanding of the natural history of the disease. METHODS/RESULTS: We describe four cases of premature infants with clinical and echocardiography features of PVD, in the setting of postnatally acquired CMV. All patients had atypical PVD trajectories, refractory to vasodilator treatment, which improved after initiation of CMV treatment. CONCLUSION: We highlight the need to consider postnatally acquired CMV infection in patients with PVD non-responsive to standard pulmonary vasodilator therapies or disease severity which is out of proportion of the usual clinical trajectory. Treatment of extremely premature infants with CMV-associated PVD may have positive impact on cardiorespiratory health, although duration of therapy remains uncertain.

Deep phenotyping of the unselected COPSAC2010 birth cohort study.

BACKGROUND: We hypothesize that perinatal exposures, in particular the human microbiome and maternal nutrition during pregnancy, interact with the genetic predisposition to cause an abnormal immune modulation in early life towards a trajectory to chronic inflammatory diseases such as asthma and others. OBJECTIVE: The aim of this study is to explore these interactions by conducting a longitudinal study in an unselected cohort of pregnant women and their offspring with emphasis on deep clinical phenotyping, exposure assessment, and biobanking. Exposure assessments focus on the human microbiome. Nutritional intervention during pregnancy in randomized controlled trials are included in the study to prevent disease and to be able to establish causal relationships. METHODS: Pregnant women from eastern Denmark were invited during 2008-2010 to a novel unselected 'COPSAC2010 ' cohort. The women visited the clinic during pregnancy weeks 24 and 36. Their children were followed at the clinic with deep phenotyping and collection of biological samples at nine regular visits until the age of 3 and at acute symptoms. Randomized controlled trials of high-dose vitamin D and fish oil supplements were conducted during pregnancy, and a trial of azithromycin for acute lung symptoms was conducted in the children with recurrent wheeze. RESULTS: Seven hundred and thirty-eight mothers were recruited from week 24 of gestation, and 700 of their children were included in the birth cohort. The cohort has an over-representation of atopic parents. The participant satisfaction was high and the adherence equally high with 685 children (98%) attending the 1 year clinic visit and 667 children (95%) attending the 2 year clinic visit. CONCLUSIONS: The COPSAC2010 birth cohort study provides longitudinal clinical follow-up with highly specific end-points, exposure assessments, and biobanking. The cohort has a high adherence rate promising strong data to elucidate the interaction between genomics and the exposome in perinatal life leading to lifestyle-related chronic inflammatory disorders such as asthma.

Impact of early screening echocardiography and targeted PDA treatment on neonatal outcomes in "22-23" week and "24-26" infants.

The hemodynamically significant patent ductus arteriosus (hsPDA) is a controversial topic in neonatology, particularly among neonates at the earliest gestational ages of 22+0-23+6 weeks. There is little, to no data on the natural history or impact of the PDA in extremely preterm babies. In addition, these high-risk patients have typically been excluded from randomized clinical trials of PDA treatment. In this work, we present the impact of early hemodynamic screening (HS) of a cohort of patients born 22+0-23+6 weeks gestation who either were diagnosed with hsPDA or died in the first postnatal week as compared to a historical control (HC) cohort. We also report a comparator population of 24+0-26+6 weeks gestation. All patients in the HS epoch were evaluated between 12-18h postnatal age and treated based on disease physiology whereas the HC patients underwent echocardiography at the discretion of the clinical team. We demonstrate a two-fold reduction in the composite primary outcome of death prior to 36 weeks or severe BPD and report a lower incidence of severe intraventricular hemorrhage (n=5, 7% vs n=27, 27%), necrotizing enterocolitis (n=1, 1% vs n=11, 11%) and first-week vasopressor use (n=7, 11% vs n=40, 39%) in the HS cohort. HS was also associated with an increase in survival free of severe morbidity from the already high rate of 50% to 73% among neonates <24 weeks gestation. We present a biophysiological rationale behind the potential modulator role of hsPDA on these outcomes and review the physiology relevant to neonates born at these extremely preterm gestations. These data highlight the need for further interrogation of the biological impact of hsPDA and impact of early echocardiography directed therapy in infants born less than 24 weeks gestation.

[Serotonin receptor 1A-modulated dephosphorylation of glycine receptor α3: a new molecular mechanism of breathing control for compensation of opioid-induced respiratory depression without loss of analgesia]. / Die von Serotoninrezeptor 1A modulierte Dephosphorylierung des Glyzinrezeptors α3: Ein neuer molekularer Mechanismus der Atmungskontrolle zur Kompensation opioidinduzierter Atemdepression ohne Verlust der Analgesie.

To control the breathing rhythm the medullary respiratory network generates periodic salvo activities for inspiration, post-inspiration and expiration. These are under permanent modulatory control by serotonergic neurons of the raphe which governs the degree of phosphorylation of the inhibitory glycine receptor α3. The specific activation of serotonin receptor type 1A (5-HTR(1A)), which is strongly expressed in the respiratory neurons, functions via inhibition of adenylate cyclase and the resulting reduction of the intracellular cAMP level and a gradual dephosphorylation of the glycine receptor type α3 (GlyRα3). This 5-HTR(1A)-GlyRα3 signal pathway is independent of the µ-opioidergic transduction pathway and via a synaptic inhibition caused by an increase in GlyRα3 stimulates a disinhibition of some target neurons not only from excitatory but also from inhibitory neurons. Our physiological investigations show that this 5-HTR(1A)-GlyRα3 modulation allows treatment of respiratory depression due to opioids without affecting the desired analgesic effects of opioids. The molecular mechanism presented here opens new pharmacological possibilities to treat opioid-induced respiratory depression and respiratory disorders due to disturbed inhibitory synaptic transmission, such as hyperekplexia.

Which techniques are relevant in the surgical management of the nasal tip?

In this article, we give an overview of safe and consistent techniques for nasal tip surgery. A change in the morphology of the tip has an impact on the profile of the face. A knowledge of facial proportions is therefore important when performing rhinoplastic surgery. We prefer an external approach because it provides the best overview and because the possibility of bimanual working makes manipulation of the lower lateral cartilages easier. The techniques described here can be used to alter the nasal tip in a controllable way.

Corundum, rutile, periclase, and CaO in Ca,Al-rich inclusions from carbonaceous chondrites.

Four calcium,aluminum-rich inclusions from four carbonaceous chondrites-Allende, Acfer 082, Acfer 086, and Acfer 094-were studied by transmission electron microscopy. All inclusions contained at least two of the oxides periclase (MgO), rutile (TiO2), calcium oxide (CaO), and corundum (Al2O3). The oxides (50 to 200 nanometers in size) were found inside and at grain boundaries of the constituent minerals of the inclusions. Determining how these oxides formed may provide insight about condensation processes in the early solar nebula and the origin of refractory inclusions in chondrites. Formation of these oxides by exsolution is considered unlikely. An origin by kinetically controlled condensation appears more probable.

The fetal programming of food preferences: current clinical and experimental evidence.

Increased energy consumption is one of the major factors implicated in the epidemic of obesity. There is compelling evidence, both clinical and experimental, that fetal paucity of nutrients may have programming effects on feeding preferences and behaviors that can contribute to the development of diseases. Clinical studies in different age groups show that individuals born small for their gestational age (SGA) have preferences towards highly caloric foods such as carbohydrates and fats. Some studies have also shown altered eating behaviors in SGA children. Despite an apparent discrepancy in different age groups, all studies seem to converge to an increased intake of palatable foods in SGA individuals. Small nutrient imbalances across lifespan increase the risk of noncommunicable diseases in adult life. Homeostatic factors such as altered responses to leptin and insulin and alterations in neuropeptides associated with appetite and satiety are likely involved. Imbalances between homeostatic and hedonic signaling are another proposed mechanism, with the mesocorticolimbic dopaminergic pathway having differential reward and pleasure responses when facing palatable foods. Early exposure to undernutrition also programs hypothalamic-pituitary-adrenal axis, with SGA having higher levels of cortisol in different ages, leading to chronic hyperactivity of this neuroendocrine axis. This review summarizes the clinical and experimental evidence related to fetal programming of feeding preferences by SGA.

Emerging functions for neuropeptide Y5 receptors.

The Y5 subtype of neuropeptide Y (NPY) receptors has raised considerable interest as a mediator of NPY-stimulated food intake, but with the advent of recent data, this hypothesis has come into question. Moreover, Y5 receptor-selective drugs might not be specific for food intake because additional functions in the central and peripheral nervous systems, including endogenous anti-epileptic activity, attenuation of morphine withdrawal symptoms, enhancement of diuresis and natriuresis, lowering of blood glucose and reduction of acetylcholine release in the ileum, have recently been reported to occur via Y5-like receptors. Given that mRNA for the cloned Y5 receptor is apparently restricted to the CNS, Angela Bischoff and Martin Michel discuss the possible existence of additional NPY receptor subtypes with Y5-like recognition features and their presence in peripheral tissues.

Myelin and glial membrane structures in the optic nerve of normal and jimpy mouse. A freeze-etching study.

In order to investigate the myelin and the glial cell membranes in the optic nerve of the mutant mouse "Jimpy," the method of freeze-etching was applied. The compact myelin lamellae and the first two glial membranes of the mutant, as compared to the normal mouse, show several abnormalities: absence of intramembraneous particles on the P-face, myelin lamellae separated by cytoplasmic layers, vesicular protrusions forming irregular invaginations, and elevations and tight junctions with a discontinuous, zigzag course. Some of these characteristics were found in the membrane of the oligodendroglia cell of the pathological animal, as well. The astrocytic membranes of both normal and Jimpy mice contain two types of gap junctions. The occurrence of one type seems to be increased in the mutant. Freeze-fractured internodal regions of the axolemma are not significantly different from those of normal animals.

Neuropeptide Y lowers blood glucose in anaesthetized rats via a Y5 receptor subtype.

We have investigated the receptor subtype mediating effects of neuropeptide Y (NPY) on blood glucose concentrations. In anaesthetized rats a 120 min i.v. infusion of 2 microg/kg/min NPY lowered blood glucose by 26 mg/dl. This was mimicked by the same dose of peptide YY (PYY), NPY2-36, PYY3-36 and [Leu31,Pro34]NPY but not by NPY13-36, PYY13-36 or rat or human pancreatic polypeptide. The effects of NPY and [Leu31,Pro34]NPY were not inhibited by 10 microg/kg/min BIBP 3226. Neither treatment significantly altered plasma insulin concentrations. We conclude that NPY lowers blood glucose concentrations via a Y5 receptor subtype, i.e. a subtype which has also been implicated in stimulation of food intake.

The antiemetic activity of high-dose alizapride and high-dose metoclopramide in patients receiving cancer chemotherapy: a prospective, randomized, double-blind trial.

Alizapride is a new substituted benzamide with suggested superior antiemetic efficacy to and fewer side effects than metoclopramide. High-dose alizapride (4 mg/kg X five doses) was compared with high-dose metoclopramide (2 mg/kg X five doses) in a prospective, randomized, double-blind trial in 62 evaluable patients undergoing strongly emetic cancer chemotherapy. Patients receiving metoclopramide experienced significantly fewer vomiting episodes than patients receiving alizapride (median of three episodes vs. eight episodes; P less than 0.001). Metoclopramide was more effective in decreasing the volume of emesis than was alizapride (median of 100 ml vs. 360 ml; P less than 0.02). Seventy-two percent of the patients receiving alizapride and 57% of those receiving metoclopramide experienced side effects. High-dose metoclopramide is an effective antiemetic in patients receiving cancer chemotherapy. Alizapride is less effective and has more side effects than metoclopramide. We do not recommend the further use of alizapride.

A combined blockade of glycine and calcium-dependent potassium channels abolishes the respiratory rhythm.

In order to test whether glycinergic inhibition is essential for the in vivo respiratory rhythm, we analysed the discharge properties of neurones in the medullary respiratory network after blockade of glycine receptors in the in situ perfused brainstem preparation of mature wild type and oscillator mice with a deficient glycine receptor. In wild type mice, selective blockade of glycine receptors with low concentrations of strychnine (0.03-0.3 microM) provoked considerable changes in neuronal discharge characteristics: The cycle phase relationship of inspiratory, post-inspiratory and expiratory specific patterns of membrane potential changes was altered profoundly. Inspiratory, post-inspiratory and expiratory neurones developed a propensity for fast voltage oscillations that were accompanied by multiple burst discharges. These burst discharges were followed by "after-burst" hyperpolarisations that were capable of triggering secondary burst discharges. Blockade of glycine receptors and the "big" Ca2+-dependent K+-conductance by charybdotoxin (3.3 nM) resulted in loss of the respiratory rhythm, whilst only tonic discharge activity remained. In contrast, rhythmic activity was only weakened, but preserved after the "small" Ca2+-dependent activated K+ conductance was blocked with apamin (8 nM). Also low concentrations of pentobarbital sodium (6 mg/kg) abolished rhythmic respiratory activity after blockade of glycine receptors in the wild type mice and in glycine receptor deficient oscillator mice. The data imply that failure of glycine receptors provokes enhanced bursting behaviour of respiratory neurones, whilst the additional blockade of BKCa channels by charybdotoxin or with pentobarbital abolishes the respiratory rhythm.

Receptor subtypes Y1 and Y5 are involved in the renal effects of neuropeptide Y.

1. Systemic infusion of neuropeptide Y (NPY) reduces renal blood flow and can concomitantly increase diuresis, natriuresis and calciuresis in anaesthetized rats. The present study was designed to investigate whether the apparently contradictory NPY effects on renal blood flow and urine formation and composition are mediated by distinct NPY receptor subtypes. 2. NPY and its analogues, peptide YY (PYY), [Leu31, Pro34]NPY and NPY13-36, were infused in incremental doses of 0.3, 1 and 3 micrograms kg-1 min-1 for 45 min each and the results compared to those obtained in vehicle-infused rats. Renal blood flow was monitored in 1-5 min intervals, while urine excretion and composition were determined in 15 min collection periods. Plasma renin activity and aldosterone concentrations were measured at the end of the final infusion period. 3. Relative to vehicle NPY, PYY and [Leu31, Pro34]NPY dose-dependently reduced renal blood flow and increased diuresis, natriuresis and calciuresis with roughly similar potency; NPY13-36 slightly but significantly increased renal blood flow but had no effect on diuresis, natriuresis and calciuresis. None of the peptides significantly affected endogenous creatinine clearance or kaliuresis. 4. Plasma renin activity was significantly reduced by PYY. Quantitatively similar reductions were observed with NPY and [Leu31, Pro34]NPY but failed to reach statistical significance with the given number of experiments. NPY13-36 did not reduce plasma renin activity. None of the peptides significantly affected plasma aldosterone concentrations. 5. In another series of experiments infusion of PYY3-36 (2 micrograms kg-1 min-1 for 120 min) did not reduce renal blood flow but significantly enhanced diuresis and natriuresis to a similar extent as the NPY 2 micrograms kg-1 min-1. 6. In a final series of experiments the Y1-selective antagonist, BIBP 3226 (1 or 10 micrograms kg-1 min-1) dose-dependently antagonized reductions of renal blood flow elicited by bolus injections of NPY (0.1-30 micrograms kg-1). BIBP 3226 (10 micrograms kg-1 min-1) also inhibited the effects of a 120 min infusion of NPY (2 micrograms kg-1 min-1) on renal blood flow but had only minor inhibitory effects on enhancements of diuresis and did not significantly affect enhancements of natriuresis. 7. We conclude that NPY reduces renal blood via a classical Y1 subtype of NPY receptor. In contrast enhancements of diuresis, natriuresis and calciuresis occur via a distinct subtype which resembles the receptor that mediates NPY-induced enhancement of food intake.