Nil per os except medications order in the dysphagic patient.

OBJECTIVES: To demonstrate why the 'nil per os except medications' order is contraindicated prior to dysphagia testing and to recommend ways to prevent aspiration of medications in the dysphagic population. METHODS: A 71-year-old male deemed at-risk for aspiration due to coughing when drinking thin liquids was made nil per os except medications and referred for dysphagia testing. Swallowing was analyzed objectively with trans-nasal fiberoptic endoscopic evaluation of swallowing. RESULTS: Aspiration on the initial 5 cc puree bolus swallow trial elicited a cough reflex. A 325 mg, 1 cm diameter, enteric coated aspirin pill emerged from the trachea, progressed through the glottis and remained transiently in the laryngeal vestibule before lodging, along with pudding residue, in a mucosal fold of the left vallecula. Neither volitional coughing nor single 5 cc water bolus swallows dislodged the pill. Otolaryngology was called and removed the pill trans-orally under direct visualization with a Kelly clamp. The pill maintained both its enteric coating and integrity for a total of 7.5 h after being aspirated. CONCLUSION: The nil per os except medications order is contraindicated in the dysphagic population. When aspiration is suspected, nil per os including medications is recommended until dysphagia testing determines what form of medication can be swallowed safely.

Safe initiation of oral diets in hospitalized patients based on passing a 3-ounce (90 cc) water swallow challenge protocol.

BACKGROUND: Safe and timely oral alimentation is crucial for optimum patient care. OBJECTIVE: To determine the short-term success of recommending specific oral diets, including drinking thin liquids, to acute care hospitalized patients at risk for dysphagia based on passing a 3-ounce water swallow challenge protocol. DESIGN: Prospective single group consecutively referred case series. SETTING: Large, urban, tertiary care, teaching hospital. PARTICIPANTS: 1000 hospitalized patients. INTERVENTION: 3-ounce (90 cc) water swallow challenge protocol. MEASUREMENTS: Specific diet recommendations and volume (in cc) of liquid ingested at the next day's meal 12-24 h after passing a 3-ounce challenge protocol were accessed electronically from oral intake information entered on each participant's daily care logs. Eating and drinking success, clinically evident aspiration events and compliance with ordering the recommended diet were recorded. Care providers were blinded to the study's purpose. RESULTS: Of 1000 patients, 907 met the inclusion criteria of stable medical, surgical or neurological conditions 12-24 h after passing a 3-ounce water swallow challenge protocol. All 907 were both eating and drinking thin liquids successfully and without overt signs of dysphagia. Median volume of liquid ingested was 340 cc [interquartile range (IQR), 240-460]. Specific diet recommendations were followed with 100% accuracy. CONCLUSION: A 3-ounce water swallow challenge protocol successfully identified patients who can be safely advanced to an oral diet without subsequent identification of overt signs of aspiration within 12-24 h of testing. Importantly, when a clinical 3-ounce challenge protocol administered by a trained provider is passed, specific diet recommendations, including drinking thin liquids, can be made safely and without the need for additional instrumental dysphagia testing.

Studies in organic archaeometry VII--differentiation of wood and bark pitches by pyrolysis capillary gas chromatography (PY-CGC).

Tars and pitches were prepared from wood and bark of various deciduous trees and conifers and analysed with the intention to distinguish between various starting materials. All this was done before the background of an archaeometrical problem: to provide a basis for the chemical identification of those pitches which are frequently found in archaeological excavations. Intending to extend the already existing possibilities for such analyses the present paper is dealing with the application of pyrolysis coupled with capillary gas chromatography and by subsequent chemometric studies. It could be shown that by this technique indeed not only tars and pitches prepared from deciduous trees and from conifers could clearly be differentiated, but that even respective species could be identified. Thus a fundament is provided for future studies aiming to identify the starting material of real archaeological finds by a novel method which requires by far less quantities of sample material as compared to the methods hitherto used by us.

The patient's perspective and rheumatoid arthritis disease activity indexes.

BACKGROUND: Monitoring disease activity in rheumatoid arthritis (RA) patients by composite indexes is regarded as obligatory when following the recent recommendations for therapy. Whether these recommendations and the patient's perspective are in congruence is a crucial question with respect to the patient's compliance. The aim of the study was to obtain information on the patient's perspective with respect to the disease activity indexes used most often. METHODS: Two hundred and seven RA patients (157 female, 50 male; mean age 59.03 yr, 17-86 yr) were enrolled in this cross-sectional evaluation. The patients' satisfaction [PATSAT (Austrian school mark system) 1 = excellent to 5 = unsatisfactory] and the patients' attitude to therapy (PATATT 1 = reduction, 2 = no change, 3 = increase) were assessed and related to the 28-joint Disease Activity Score (DAS28), the Simplified Disease Activity Index (SDAI) and the Modified Health Assessment Questionnaire (M-HAQ). Statistical evaluation was carried out by applying the Mann-Whitney U test, calculating chi2 and ANOVA. RESULTS: According to the DAS28 and the M-HAQ, patients were at a moderately active disease stage and had low functional deficiency. PATSAT was significantly correlated to the disease activity indexes (all PS < or = 0.002). The mean DAS28 (2.56) at PATSAT 1 was within the remission range, whereas at PATSAT 5 a mean of 5.52 indicated highly active disease. PATATT was found to be related to PATSAT, but did not completely parallel it. Reduction of therapy was intended at a mean DAS28 of 2.87, whereas a request for an increase did not occur before a mean DAS28 of 4.92. CONCLUSION: The patients' therapeutic attitudes are somewhat in line with their satisfaction, which mirrors disease activity to a great extent, though not with the common therapeutic recommendations. The DAS28 proved to be superior to both other indexes taking account of the patient's perspective. These results may provide guidance in patient care and education as well as therapeutic strategies.

[Interdisciplinary endoscopic outpatient management of connatal dacryocystoceles]. / Ambulante endoskopische Therapie der Dakryozystozele des Neugeborenen.

Dacryocystocele may represent a rare type of connatal stenosis of the lacrimal duct. If conservative measures fail and in case of secondary inflammation, probing or regular surgery is usually recommended. We report on 15 neonates suffering from 18 connatal dacryocystoceles which were presented to the clinic of ophthalmology at the 16th (6 - 44) day of life. There was a definite female preponderance (65 %). Conservative treatment (external massage, at times i. v. antibiotic therapy) had proven to be ineffective. The neonates were subjected to outpatient nasal endoscopy and the ballooning cyst of the inferior nasal meatus was managed by endoscopic marsupialization in 14 cases applying local anesthesia. Two nasal cysts had to be operated on in general anesthesia due to obstructing local anatomy which obviated endoscopical microsurgery. Three additional dacryocystoceles have been detected incidentally in 2 neonates being subjected to surgery in general anesthesia for choanal atresia and lacrimal probing respectively. The corresponding dacryocystoceles were managed by concomitant endonasal microsurgery. We advocate interdisciplinary (ophthalmological and rhinological) outpatient examination in all neonates with suspected dacryocystoceles. Diagnosis is based on palpation, probing and nasal endoscopy applying local anesthesia together with mucosal decongestion. Microsurgical marsupialization immediately follows and will lead to persisting relief of symptoms.

Embryonic lethality caused by apoptosis during gastrulation in mice lacking the gene of the ADP-ribosylation factor-related protein 1.

ADP-ribosylation factor (ARF)-related protein 1 (ARFRP1) is a membrane-associated GTPase with significant similarity to the family of ARFs. We have recently shown that ARFRP1 interacts with the Sec7 domain of the ARF-specific guanine nucleotide exchange factor Sec7-1/cytohesin and inhibits the ARF/Sec7-dependent activation of phospholipase D in a GTP-dependent manner. In order to further analyze the function of ARFRP1, we cloned the mouse Arfrp1 gene and generated Arfrp1 null-mutant mice by gene targeting in embryonic stem cells. Heterozygous Arfrp1 mutants developed normally, whereas homozygosity for the mutant allele led to embryonic lethality. Cultured homozygous Arfrp1 null-mutant blastocysts were indistinguishable from wild-type blastocysts. In vivo, they implanted and formed egg cylinder stage embryos that appeared normal until day 5. Between embryonic days 6 and 7, however, apoptotic cell death of epiblast cells occurred in the embryonic ectoderm during gastrulation, as was shown by histological analysis combined with terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling. Epiblast cells that would normally differentiate to mesodermal cells detached from the ectodermal cell layer and were dispersed into the proamniotic cavity. In contrast, the development of extraembryonic structures appeared unaffected. Our results demonstrate that ARFRP1 is necessary for early embryonic development during gastrulation.

Effect of tracheotomy tube occlusion on upper esophageal sphincter and pharyngeal pressures in aspirating and nonaspirating patients.

The biomechanics of the pharyngeal swallow in patients with a tracheotomy tube were investigated with manometry. Upper esophageal sphincter (UES) and pharyngeal pressure recordings were made with and without occlusion of the tracheotomy tube. Criteria for selection were ability to tolerate tracheotomy tube occlusion for both 5 minutes prior to and during the first manometric analysis, absence of surgery to the upper aerodigestive tract other than tracheotomy, and no history of oropharyngeal cancer or stroke. Aspiration was determined objectively by fiberoptic endoscopic evaluation of swallowing (FEES) immediately prior to manometric recording. Eleven adult individuals with tracheotomy participated; 7 swallowed successfully and 4 exhibited aspiration on FEES. The results indicated no significant effect of tracheotomy tube occlusion on UES or pharngeal pressures in either aspirating or nonaspirating patients. It was concluded that the biomechanics of the swallow as determined by UES and pharyngeal manometric pressure measurements were not changed significantly by tracheotomy tube occlusion in aspirating or nonaspirating patients. These results support previous observations that subjects either aspirated or swallowed successfully regardless of tracheotomy tube occlusion status.

Use of arterial oxygen saturation, heart rate, and blood pressure as indirect objective physiologic markers to predict aspiration.

If an indirect bedside variable can reliably predict whether an objective instrumental dysphagia evaluation is needed, time and money can be saved without compromising patient care. To date, the search for a reliable indirect subjective marker of aspiration has not been successful. However, research on indirect objective markers of aspiration is alluring. The purpose of the present study was to investigate changes, if any, in the physiologic parameters of arterial oxygen saturation (SpO(2)), heart rate, and blood pressure during simultaneous objective confirmation of aspiration status with Fiberoptic Endoscopic Evaluation of Swallowing (FEES). Sixty adult subjects were divided into 4 groups of 15. Group 1 did not require supplemental oxygen and did not aspirate. Group 2 did not require supplemental oxygen and exhibited aspiration. Group 3 required supplemental oxygen and did not aspirate. Group 4 required supplemental oxygen and exhibited aspiration. Simultaneous SpO(2), heart rate, and blood pressure measurements were collected at 1-min intervals, i.e., pre-FEES baseline for 5 min; during FEES; and post-FEES for 5 min. Results indicated no significant differences in SpO(2) levels based on aspiration status or oxygen requirements for any of the 4 groups. A consistent pattern of higher heart rate values during FEES and continuing for 5 min post-FEES was observed for all 4 groups. A consistent pattern of higher blood pressure values during FEES and then lower blood pressure values post-FEES was observed for all 4 groups. It was concluded that the use of changes in SpO(2), heart rate, or blood pressure values as indirect objective markers of aspiration was not supported.

Fiberoptic endoscopic evaluation of swallowing in the pediatric population.

OBJECTIVE: To investigate the diagnostic and rehabilitative usefulness of routine fiberoptic endoscopic evaluation of swallowing (FEES) in the pediatric population. STUDY DESIGN: Prospective, consecutive, blinded. PATIENTS AND METHODS: Thirty pediatric inpatients from a large, urban, tertiary care teaching hospital participated. Their ages ranged from 11 days to 20 years (mean, 10 years and 4 months). In a random fashion, seven subjects were assessed with both videofluoroscopic evaluation of swallowing (VFES) and FEES and 23 subjects were assessed solely with FEES. Diagnosis of dysphagia was determined by spillage, residue, laryngeal penetration, and aspiration. Rehabilitative strategies, e.g., positioning and modification of bolus consistencies, were based on diagnostic findings. RESULTS: There was 100% agreement between the blinded diagnostic results and implementation of rehabilitative strategies for subjects randomly assigned to receive both VFES and FEES and for subjects who received solely FEES. Of the 23 subjects assessed solely with FEES, 13 of 23 (57%) exhibited normal swallowing and 10 of 23 (43%) exhibited dysphagia. The feeding recommendation for 4 of 10 subjects with dysphagia (40%) was for a non-oral diet because of aspiration. FEES allowed for specific feeding recommendations (i.e., bolus consistency modifications, positioning, and feeding strategies) to reduce aspiration risk in 6 of 10 subjects with dysphagia (60%). CONCLUSION: FEES can be used routinely to diagnose and treat pediatric dysphagia in the acute care setting.

Investigation of the causal relationship between tracheotomy and aspiration in the acute care setting.

OBJECTIVE: To investigate the causal relationship, if any, between tracheotomy and incidence of aspiration in the acute care setting. STUDY DESIGN: Prospective, consecutive. PATIENTS AND METHODS: Twenty adult patients evaluated between February 1997 and October 1999 participated. Criteria for inclusion were a dysphagia evaluation before tracheotomy, subsequent tracheotomy and placement of a tracheotomy tube, and then a repeat dysphagia evaluation after tracheotomy prior to decannulation. This permitted the causal relationship between tracheotomy and incidence of aspiration to be investigated. Differences between duration of tracheotomy placement and age were analyzed with the Student t test and for non-parametric nominal data the chi2 test was applied. RESULTS: No causal relationship between tracheotomy and aspiration was exhibited, as 19 of 20 (95%) subjects exhibited the same aspiration status before and after tracheotomy. All 12 (100%) subjects who aspirated before tracheotomy also aspirated after tracheotomy and 7 of 8 (88%) subjects who did not aspirate before tracheotomy also did not aspirate after tracheotomy (P > .05). In addition, no significant differences were observed between aspiration status and days since tracheotomy or age (P > .05). CONCLUSION: In the acute care setting, no causal relationship between tracheotomy and aspiration status was exhibited.

Specificity determinants of substrate recognition by the protein kinase DYRK1A.

DYRK1A is a dual-specificity protein kinase that is thought to be involved in brain development. We identified a single phosphorylated amino acid residue in the DYRK substrate histone H3 (threonine 45) by mass spectrometry, phosphoamino acid analysis, and protein sequencing. Exchange of threonine 45 for alanine abolished phosphorylation of histone H3 by DYRK1A and by the related kinases DYRK1B, DYRK2, and DYRK3 but not by CLK3. In order to define the consensus sequence for the substrate specificity of DYRK1A, a library of 300 peptides was designed in variation of the H3 phosphorylation site. Evaluation of the phosphate incorporation into these peptides identified DYRK1A as a proline-directed kinase with a phosphorylation consensus sequence (RPX(S/T)P) similar to that of ERK2 (PX(S/T)P). A peptide designed after the optimal substrate sequence (DYRKtide) was efficiently phosphorylated by DYRK1A (K(m) = 35 microM) but not by ERK2. Both ERK2 and DYRK1A phosphorylated myelin basic protein, whereas only ERK2, but not DYRK1A, phosphorylated the mitogen-activated protein kinase substrate ELK-1. This marked difference in substrate specificity between DYRK1A and ERK2 can be explained by the requirement for an arginine at the P -3 site of DYRK substrates and its presumed interaction with aspartate 247 conserved in all DYRKs.

Effect of a one-way tracheotomy speaking valve on the incidence of aspiration in previously aspirating patients with tracheotomy.

The purpose of the present study was to investigate the incidence of aspiration in previously aspirating patients with tracheotomy after use of a one-way tracheotomy tube speaking valve. Twenty consecutive inpatients from the acute care setting of a large urban tertiary care teaching hospital were included. All subjects had objective documentation of aspiration by a fiberoptic endoscopic evaluation of swallowing prior to placement of a one-way tracheotomy speaking valve, from 2 to 7 days of valve use with intelligible speech production, and no surgery to the upper aerodigestive tract except tracheotomy. Results indicated that incidence of aspiration was not affected by use of a one-way tracheotomy speaking valve. These results are in agreement with previous observations that subjects either aspirated or swallowed successfully regardless of tracheotomy tube occlusion status. Also, no significant differences were found between aspiration status and time since tracheotomy, time off ventilator, or duration of valve use. It was concluded that use of a one-way speaking valve provided mostly nondeglutitive benefits and should not be considered to promote successful swallowing for patients with tracheotomy in the acute care setting.

Cloning and characterization of DYRK1B, a novel member of the DYRK family of protein kinases.

The DYRK1A gene on human chromosome 21 encodes a protein kinase presumed to be involved in the pathogenesis of mental retardation in Down's syndrome. Here we describe a highly similar homolog, DYRK1B, which is, in contrast to DYRK1A, predominately expressed in muscle and testis. The human DYRK1B gene was mapped to chromosome 19 (19q12-13.11) by radiation hybrid analysis. The amino acid sequences of DYRK1A and DYRK1B are 84% identical in the N-terminus and the catalytic domain but show no extended sequence similarity in the C-terminal region. DYRK1B contains all motifs characteristic for the DYRK family of protein kinases. In addition, the sequence comprises a bipartite nuclear localization motif. A green fluorescent protein (GFP) fusion protein of DYRK1B was found mainly in the nucleus of transfected COS-7 cells. These data suggest that DYRK1B is a muscle- and testis-specific isoform of DYRK1A and is involved in the regulation of nuclear functions.

Alpha-galactosidase of Bifidobacterium adolescentis DSM 20083.

Bifidobacterium adolescentis was grown anaerobically in medium enriched with alpha-D-galactosides. alpha-Galactosidase (EC 3.2.1. 22) was released from the cells by ultrasonic treatment and purified 36-fold by ultrafiltration, ammonium-sulphate precipitation, anion-exchange chromatography, and size-exclusion chromatography. Two protein bands were consistantly observed after sodium-dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE). Electrophoretically homogeneous alpha-galactosidase was only obtained by electroelution. The enzyme had an apparent molecular mass of 344 kDa and 79 kDa as judged by size-exclusion chromatography and SDS-PAGE, respectively. Activity-staining after nondenaturing SDS-PAGE indicated an apparent molecular mass of 145 kDa. Thus, a tetrameric structure of the protein is suggested. The alpha-galactosidase showed optimal activity at pH 5.5 and 55 degrees C. Lower pH values and higher temperatures rapidly inactivated alpha-galactosidase. The enzyme hydrolyzed specifically alpha-galactosidic linkages, and alpha-(1-3)-linkages were hydrolyzed at a higher rate compared to alpha-(1-6)-linkages. Hydrolysis of galactosides followed normal saturation kinetics; KM-values for p-nitrophenyl-alpha-galactopyranoside (p-NPG) and raffinose were calculated with 0.957 mM and 4.12 mM, respectively.

Fiberoptic endoscopic evaluation of swallowing in patients with acute traumatic brain injury.

Dysphagia and aspiration in intensive care unit patients with acute traumatic brain injury (TBI) is a frequent and potentially life-threatening problem. Any diagnostic technique used with this population, therefore, must be able to be performed in a timely and efficient manner while providing objective information on the nature of the swallowing problem. The purpose of the present study was to investigate the utility of using the fiberoptic endoscopic evaluation of swallowing (FEES) technique to diagnosis pharyngeal stage dysphagia and determine aspiration status in patients who presented with acute TBI. A total of 47 subjects were assessed with FEES. Thirty of 47 (64%) subjects swallowed successfully and were able to take an oral diet: 2 of 30 (7%) thickened liquids and purée consistencies, 8 of 30 (27%) a soft diet, and 20 of 30 (67%) a regular diet. Seventeen of 47 (36%) subjects exhibited pharyngeal stage dysphagia with aspiration and were not permitted an oral diet based on objective results provided by FEES. Of the 17 subjects who aspirated, 9 of 17 (53%) exhibited silent aspiration. Younger subjects (mean age 34 years, 3 months) aspirated significantly less often than older subjects (mean age 51 years, 8 months). No significant age difference was observed for gender or between overt and silent aspirators. It was concluded that FEES is an objective and sensitive tool that can be used successfully to diagnose pharyngeal stage dysphagia, determine aspiration status, and make recommendations for oral or nonoral feeding in patients with acute TBI.

Serial fiberoptic endoscopic swallowing evaluations in the management of patients with dysphagia.

OBJECTIVE: To determine whether serial fiberoptic endoscopic evaluation of swallowing (FEES) can be used successfully and efficiently in deciding to change a patient's feeding status from nonoral (NPO) to oral (PO) with no adverse health outcome. DESIGN: A prospective, consecutive, cohort study. SETTING: Inpatient population of a tertiary-care university teaching hospital. SUBJECTS: Thirty-two adults were recruited from a cohort of 400 consecutive subjects who participated in a previous dysphagia study. INTERVENTION: Serial FEES was performed 3 to 6 times in each subject to detect objectively pharyngeal phase dysphagia, aspiration, and aspiration risk and to provide information for recommendations regarding oral feeding status and therapeutic intervention. The number of FEES was based on the subject's medical status, evidence of dysphagia, and clinical judgement. MAIN OUTCOME MEASURES: Identification of pharyngeal phase dysphagia, aspiration, and aspiration risk, and recommendations for initial feeding status, when to resume oral feeding, and what bolus consistencies to use for optimal swallowing success. RESULTS: In all subjects, serial FEES detected pharyngeal phase dysphagia, aspiration, and aspiration risk and enabled determination of initial feeding status (NPO or PO), when to resume successful oral feeding, and what bolus consistencies to use for optimal swallowing success. Specifically, 15 of 32 (47%) subjects received FEES 3 to 5 times within only 6 to 22 days. Timely serial FEES allowed 22 of 32 (69%) subjects to resume an oral diet as early and safely as possible. CONCLUSIONS: No subject who resumed an oral diet based on results of FEES developed an aspiration pneumonia. Serial FEES, therefore, enabled feeding status to be successful and efficiently changed from NPO to PO with no adverse health outcome. FEES was an efficient procedure with regard to appointment scheduling, transportation, patient issues, and personnel requirements.

Fiberoptic endoscopic documentation of the high incidence of aspiration following extubation in critically ill trauma patients.

The purpose of this study was to investigate the incidence of aspiration following extubation in critically ill trauma patients. This prospective pilot study included 20 consecutive trauma patients who required orotracheal intubation for at least 48 hours. All subjects underwent a bedside transnasal fiberoptic endoscopic evaluation of swallowing at 24 +/- 2 hr after extubation to determine objectively aspiration status. Aspiration was defined as the entry of a blue dyed material into the airway below the level of the true vocal folds, with silent aspiration occurring in the absence of any external behavioral signs such as coughing or choking. Aspiration was identified in 9 of 20 (45%) subjects and 4 of these 9 (44%) were silent aspirators. Therefore, silent aspiration occurred in 20% of the study population. Eight of the 9 (89%) aspirating subjects resumed an oral diet from 2-10 days (mean, 5 days) following extubation. All subjects had no evidence of pulmonary complications. It was concluded that trauma patients after orotracheal intubation and prolonged mechanical ventilation have an increased risk of aspiration. An objective assessment of dysphagia to identify aspiration may reduce the likelihood of pulmonary complications after extubation.

Tracheotomy tube occlusion status and aspiration in early postsurgical head and neck cancer patients.

The purpose of the present study was to investigate tracheotomy tube occlusion status and prevalence of aspiration utilizing videofluoroscopy. A prospective study was done of 16 consecutive, early, postsurgical head and neck cancer patients with tracheotomy. Selection criteria included the ability to tolerate tracheotomy tube occlusion prior to and during the modified barium swallow procedure, oral and/or pharyngeal surgical resection, no history of neurological disease or stroke, and medical clearance to begin oral feeding. There was 100% agreement among the independent reviewers on ratings of the presence or absence of aspiration. It was found that occlusion status of the tracheotomy tube did not influence the prevalence of aspiration in the immediate postoperative period. No trends were observed when comparing bolus consistency, type of tracheotomy tube, or presence/absence of a nasogastric tube and the ratings of aspiration.