[Anesthesiological aspects in patients with epidermolysis bullosa]. / Anästhesiologische Aspekte bei Patienten mit Epidermolysis bullosa.

Epidermolysis bullosa causes blistering due to altered structural proteins of the dermoepidermal junction, resulting in scarring and strictures of the skin and mucous membranes. Affected individuals typically require frequent surgical interventions due to burdensome symptoms and complications of the disease. The anesthesiological management of these patients is inherently challenging. This review article summarizes the relevant features of this patient cohort and provides practical recommendations for care.

Cholelithiasis in adult bearded dragons: retrospective study of nine adult bearded dragons (Pogona vitticeps) with cholelithiasis between 2013 and 2015 in southern Germany.

With an increased number of pet reptiles, many diseases occur due to nutritional disorders. Between 2013 and 2015, irregular gallbladder contents (sludge/choleliths) in adult bearded dragons (Pogona vitticeps) were recorded in many of the routinely conducted necropsies at the reptile rescue station in Munich (Auffangstation für Reptilien, München e.V., Munich, Germany). Nine animals, six from the rescue station and three from an associated veterinary practice (Tierärztliche Praxis für Exoten, Augsburg, Germany), were studied. Gallbladder contents from all animals were analysed at the Institute for Clinical Chemistry in Zurich, Switzerland. In three of nine animals, one cholelith composed of 100% calcium carbonate (CaCO3 ) was detected and it precipitated either as pure calcite or as a calcite:vaterite combination. In the remaining six animals, analyses suggested a protein-based material. The detection of choleliths/sludge was not anticipated at necropsy or surgery in eight of nine animals. The diet of the six animals from the rescue station was retrospectively described as mainly insects, whereas the diet of the three animals from the veterinary practice also contained little plant matter. Fed insect species were mealworm larva (Tenebrio molitor), house cricket (Acheta domestica), migratory locust (Locusta migratoria) and zophobas larva (Zophobas morio), all high in protein and fat. In other species, a nidus must be present for CaCO3 to precipitate. As a protein-based sludge was detected in six gallbladders, it is possible that a high-protein diet could lead to such a nidus and subsequently to cholelith formation. Cholelithiasis seems to be a rising problem in adult bearded dragons and is likely underdiagnosed, as many choleliths were found at necropsy. This rise in cholelithiasis may correlate with an unnatural high-protein, high-fat insect-based diet instead of a balanced plant-based diet.

Randomized crossover study assessing oropharyngeal leak pressure and fiber optic positioning : Laryngeal Mask Airway Supreme™ versus Laryngeal Tube LTS II™ size 2 in non-paralyzed anesthetized children.

BACKGROUND: As there are currently no data available comparing the practicability of the laryngeal mask airway (LMA) Supreme™ size 2 versus the laryngeal tube LTS II™ size 2 in children, this trial was conducted to quantify the differences between these two airway devices concerning leak pressure and fiber optic-controlled positioning in non-paralyzed, anesthetized pediatric patients. METHODS: A total of 56 children aged 1-6 years and weighing between 11 and 23 kg were enrolled in the study. Anesthesia was intravenously induced according to local standards using fentanyl and propofol. After induction of anesthesia both airway devices were inserted consecutively in accordance with the randomization protocol. RESULTS: The mean oropharyngeal leak pressure was significantly higher for the LTS II™ (33±8 cmH2O) than for the LMA Supreme™ (21±7 cmH2O, p < 0.0001). Fiber optic position monitoring was better when the LMA Supreme™ was used (p  < 0.001). The first attempt success rates for insertion (55Supreme LMA vs. 43LTSII, p < 0.001), the insertion time (25 s Supreme LMA vs. 34 s LTSII, p < 0.04) and the frequency of bloodstaining (0Supreme LMA vs 4LTSII, p < 0.04) for the initially used device were better for the LMA Supreme™ than the laryngeal tube LTS II™. CONCLUSION: We conclude that oropharyngeal leak pressure, fiber optic position, first attempt insertion success rate and bloodstaining differed between the LMA Supreme™ and the LTS II™ in children.

Bleeding risk, physical functioning and non-use of anticoagulation among patients with stroke and atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is common among people with stroke. Anticoagulation medications can be used to manage the deleterious impact of AF after stroke, however, may not be prescribed due to concerns about post-stroke falls and decreased functioning. Thus, the purpose of this study was to identify, among people with stroke and AF, predictors of anticoagulation prescription at hospital discharge. METHODS: This is a secondary analysis of a retrospective cohort study of data retrieved via medical records, including National Institutes of Health Stroke Scale score, Functional Independence Measure (FIM) motor score (motor or physical function), ambulation on second day of hospitalization, Morse Falls Scale (fall risk) and HAS-BLED score (Hypertension; Abnormal renal and liver function; Stroke; Bleeding; Labile INRs; Elderly >65; and Drugs or alcohol). Data analyses included bivariate comparisons between people with and without anticoagulation at discharge. Logistic-regression modeling was used to assess predictors of discharge anticoagulation. RESULTS: There were 334 subjects included in the analyses, whose average age was 75 years old. Anticoagulation was prescribed at discharge for 235 (70%) of patients. In the adjusted regression analyses, only the FIM motor score (adjusted OR = 1.015, 95% CI 1.001-1.028) and the HAS-BLED score (adjusted OR = 0.36, 95% CI 0.22-0.58) were significantly associated with anticoagulation prescription at discharge. CONCLUSION: It appears that in this sample, post-stroke anticoagulation decisions appear to be made based on clinical factors associated with bleed risk and motor deficits or physical functioning. However, opportunities may exist for improving clinician documentation of specific reasoning for non-anticoagulation prescription.

Comparison of reliability in anatomical landmark identification using two-dimensional digital cephalometrics and three-dimensional cone beam computed tomography in vivo.

OBJECTIVES: To compare reliability for landmark identification on patient images from three-dimensional (3D) cone beam CT (CBCT) and digital two-dimensional (2D) lateral cephalograms. METHODS: Ten lateral cephalometric digital radiographs and their corresponding CBCT images were randomly selected. 27 observers digitally identified 27 landmarks in both modes. The x- and y-coordinates for each landmark, indicating the horizontal and vertical positions, were analysed for interobserver reliability by comparing each measurement to the best estimate of the true value. Intraobserver reliability was also assessed. Linear models and intraclass correlation coefficients (ICCs) were used for analyses. RESULTS: For interobserver reliability, the following locations were farther from the best estimate for 2D than 3D: x-location in subspinale (A-point), anterior tip of the nasal spine (ANS), L1 lingual gingival border and L1 root; y-location in porion, ramus point and orbitale; x- and y-locations in basion, condylion, midramus, sigmoid notch and U6 occlusal. 3D y-locations were farther in the gonion, L1 tip, sella and U1 tip. For intraobserver reliability, 2D locations were farther in y-locations in orbitale and sigmoid notch, and both x- and y-locations in basion. 3D locations were farther in the x-location in U1 labial gingival border and y-locations in L1 tip, L6 occlusal, menton and sella. For intraobserver ICCs, greater variations in 2D than 3D included: A-point, ANS, midramus, orbitale, ramus point, sigmoid notch and U1 root. CONCLUSIONS: 3D imaging, as in CBCT, allows for overall improved interobserver and intraobserver reliability in certain landmarks in vivo when compared with two-dimensional images.

Ex-Utero Intrapartum Treatment (EXIT) in a giant case of Congenital Cystic Adenomatoid Malformation (CCAM) of the lung.

Congenital Cystic Adenomatoid Malformations (CCAM) of the lung are a relatively rare anomaly. The majority of cases do not require any antenatal or perinatal interventions. However, selected cases need special and intensified management. This article discusses a case of a CCAM of the left pulmonary lobe covering 2/3 to 3/4 of the thoracic volume, causing mediastinal shift and hydrops. The enormous size required the planning of an EXIT (Ex Utero-Intrapartum Treatment) procedure, which was performed when the trial of intraoperative ventilation of the lungs was unsuccessful. A thoracotomy and resection of the left upper lobe were performed with the fetus on feto-placental circulation. After resection and closure of the thoracotomy, improvement of lung ventilation allowed the delivery of the child. The child and mother were discharged in a healthy condition. We conclude that the EXIT procedure is a feasible and potentially life-saving method for select cases of prenatally detected CCAM.

Knowledge and use of fluoride among Indiana dental professionals.

OBJECTIVES: This study assessed the knowledge of Indiana dentists and dental hygienists about fluoride's predominant mode of action and their protocols for the use of fluoride for dental caries prevention. METHODS: In 2000, questionnaires were mailed to 6,681 Indiana dentists and hygienists prior to the 2001 release of recommendations for the use of fluoride by the US Centers for Disease Control and Prevention. In 2005, the questionnaires were again sent to Indiana dental professionals to assess changes in knowledge and protocols. In addition, a 10 percent sample of Illinois dentists and hygienists were surveyed to determine the similarity of Indiana and Illinois responses. RESULTS: Questionnaires were anonymously completed and returned. In 2000, a minority of Indiana health professionals (17 percent) correctly identified that remineralization was fluoride's predominant mode of action. There was a significant increase in Indiana respondents correctly identifying this predominant mode of action between 2000 and 2005 (17 percent versus 25 percent, respectively, P < 0.0001). Fourteen percent of Illinois respondents answered correctly in 2005. Preeruptive incorporation of fluoride into enamel was the most frequently cited incorrect response (IN 2000, 79 percent; IN 2005, 71 percent; IL 2005, 82 percent). Some protocols for use of fluoride products reflected inadequate understanding of fluoride's predominant posteruptive mode of action. CONCLUSIONS: The majority of dental professionals surveyed were unaware of the current understanding of fluoride's predominant posteruptive mode of action through remineralization of incipient carious lesions. Additional research is indicated to assess fluoride knowledge and protocols of dental professionals nationwide. Educational efforts are needed to promote the appropriate use of fluoride.

Density value means in the evaluation of external apical root resorption: an in vitro study for early detection in orthodontic case simulations.

OBJECTIVES: The purpose of this study was to develop an alternative diagnostic tool for the early detection of external apical root resorption (EARR). METHODS: Mandibular incisors (n=36) with and without simulated EARR lesions were used. 18 teeth with facial and proximal windows, each with a range of 2 sizes, were placed in 6 N hydrochloric acid (HCl) baths for 10 min. A sample of the acid solution was analysed for calcium concentration by atomic absorption spectrophotometry. Incisors were imaged at 80 degrees, 90 degrees and 100 degrees under 3 test conditions (bracketed, non-bracketed and with subtraction registration templates (SRTs)). The images were reconstructed and subtracted to determine the accuracy and sensitivity of the method. Quantified histograms for each subtracted image were constructed. RESULTS: At either an angle of 80 degrees or 100 degrees, the bracketed group had the largest mean standard deviation of the subtraction histograms while the SRT group had the smallest. Density values as a function of total calcium removed were plotted indicating a linear relationship between subtraction density units and calcium loss. CONCLUSION: The use of the SRTs was significantly more accurate than the use of the brackets alone for digital subtraction radiography reconstructions. This model shows promise for detecting EARR prior to a noticeable decrease in root length. It may be useful for early detection of resorptive lesions during routine orthodontic treatment.

NKP608: a selective NK-1 receptor antagonist with anxiolytic-like effects in the social interaction and social exploration test in rats.

NKP608 is a non-peptidic derivative of 4-aminopiperidine which acts as a selective, specific and potent antagonist at the neurokinin-1 (NK-1) receptor both in vitro and in vivo. In vitro, the binding of NKP608 to bovine retina was characterized by an IC50 of 2.6+/-0.4 nM, whereas the compound's affinity to other receptor binding sites, including NK-2 and NK-3, was much lower. Species differences in IC(50) values with NKP608 were less pronounced than with previously described NK-1 receptor antagonists, being 13+/-2 and 27+/-2 nM in gerbil midbrain and rat striatum, respectively. In vivo, using the hind foot thumping model in gerbils, NKP608 exhibited a potent NK-1 antagonistic activity following oral administration (ID(50)=0.23 mg/kg; 2 h pretreatment), supporting a central activity of NKP608. The compound had a long duration of action with an ID(50) value of 0. 15 mg/kg p.o. and 0.38 mg/kg p.o. following a pretreatment of 5 and 24 h, respectively. Following a subchronic administration for 7 consecutive days (once daily) there was no evidence for the development of tolerance or accumulation. In the social interaction test performed in a highly illuminated, unfamiliar test arena, NKP608 specifically increased the time the two rats spent in social contact, and there was no concomitant increase in parameters reflecting general activity, i.e. ambulation (number of square entries) or the number of rearings. Active social time was maximally increased at a dose range of 0.01-1 mg/kg p.o. NKP608, the effect being weaker or absent at both lower (0.001 mg/kg p.o.) and higher (10 mg/kg p.o.) doses. A comparable bell-shaped dose-response relation was seen in the social exploration test in rats. In this modified resident/intruder paradigm, maximal increase in social contact of the intruder rat directed towards the resident rat was seen at a similar dose range (0.03-3 mg/kg p.o.) The effects observed following an acute oral administration of NKP608 were comparable to those seen following a treatment with the well-known benzodiazepine, chlordiazepoxide, in both these tests. These findings indicate that NKP608 exhibits an anxiolytic-like effect and that this effect, as concluded from the observed antagonism of the hind foot thumping induced by i.c.v. administration of the NK-1 receptor agonist SPOMe, is centrally mediated. This makes this compound a potentially promising candidate for treating anxiety-related disorders in humans.

N-phosphonoalkyl-5-aminomethylquinoxaline-2,3-diones: in vivo active AMPA and NMDA(glycine) antagonists.

N-Substituted 5-aminomethylquinoxalinediones containing carboxy or phosphonic acids yield potent and selective AMPA and/or NMDA (glycine-binding site) antagonists. Phosphonic acid derivatives are particularly water-soluble and display potent anticonvulsant effects in the electroshock-induced convulsion assay in mice.

The potency of the novel tachykinin receptor antagonist CGP49823 at rat and gerbil motoneurones in vitro.

The novel tachykinin receptor antagonist CGP49823 ((2R,4S)-2-benzyl-1-(3,5-dimethylbenzoyl)-4-(quinolin-4-y lmethylamino)piperidine) has been compared with three other selective non-peptide tachykinin NK1 receptor antagonists. The drugs were tested as antagonists of the depolarization of spinal motoneurones induced by bath application of the selective tachykinin NK1 receptor agonist septide-(6-11) (300 nM) for 120 s at 15 min intervals. The antagonists were bath applied and the depolarizations were recorded from lumbar ventral roots of 7 to 12 day old rat and gerbil hemisected spinal cords in vitro. The gerbil preparation is considered to model the human species variant of the tachykinin NK1 receptor. With the exception of SR140333 ((S)-1-[2-[3-(3,4-dichlorophenyl)-1-[[3-(1-methylethoxy)phenyl]ace tyl]-3-piperidinyl]ethyl]-4-phenyl-1-azoniabicyclo[2.2.2]octane chloride), the antagonists were approximately thirty-fold more potent on gerbil preparations. The respective mean IC50 values from gerbil preparations produced by CP96345 ((2S-cis)-2-(diphenylmethyl)-N-[(2-methoxyphenyl)methyl]-1-azabicy clo[2.2.2]octan-3-amine), CGP49823, SR140333 and CP99994 ((2S-cis)-N-[(2-methoxyphenyl)methyl]-2-phenyl-3-piperidinamine) were, in microM +/- S.E. (n) 0.10 +/- 0.02 (6), 0.22 +/- 0.03 (6), 0.30 +/- 0.10 (5) and 0.38 +/- 0.02 (5) and the corresponding values from the rat preparations were 3.7 +/- 0.4 (5), 7.8 + 1.3 (5), 1.06 +/- 0.16 (6) and 10.5 +/- 2.2 (7). Dominance of tachykinin NK1 receptor activity in the measured responses was confirmed by low potency of the tachykinin NK2-selective antagonist SR48968 ((S)-N-methyl-N[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl] benzamide) which yielded an IC50 value of 12.0 +/- 2.8 (5) on gerbil preparations and produced less than 50% depression of septide-induced depolarization of rat motoneurones at the highest concentration (100 microM) tested.

5-Aminomethylquinoxaline-2,3-diones, Part III: Arylamide derivatives as highly potent and selective glycine-site NMDA receptor antagonists.

A series of quinoxaline-2,3-diones with very high affinity to the glycine site of the NMDA receptor has been discovered. In contrast to the 7-nitro derivatives, the most potent 7-bromo substituted compounds were highly selective for the glycine site. Although none of the described compounds were active in the electroshock model in mice, 1a displayed significant protection in the quinolinic acid-induced excitotoxicity model in vivo.

5-Aminomethylquinoxaline-2,3-diones. Part II: N-aryl derivatives as novel NMDA/glycine and AMPA antagonists.

Potent antagonists at the glycine-binding site of NMDA receptors, as well as dual antagonists acting also at AMPA receptors have been identified in a series of 5-arylaminomethylquinoxaline-2,3-diones. A study of the structure-activity relationship of these compounds is reported here.

Visual loss in cryptococcal meningitis.

Optic neuropathy with visual loss is a well-known complication of chronic elevated intracranial pressure. The association of visual loss with cryptococcal meningitis may reflect the intracranial hypertension often seen in this condition. However, the generally poor results of optic nerve sheath fenestration and analysis of autopsy cases have led to the suggestion that direct invasion of the visual system by organisms may be the more common mechanism of visual loss. We describe a patient with severe visual loss from cryptococcal meningitis in whom organisms were demonstrated in the optic nerve sheath obtained at the time of fenestration. This is the first report to demonstrate this finding in a living patient.

Betaxolol in chronic obstructive pulmonary disease.

We evaluated the effect of betaxolol on the pulmonary function tests of nine patients with glaucoma and chronic obstructive pulmonary disease (COPD) requiring beta-blocker therapy. The results of pre-treatment pulmonary function tests were compared to results after two weeks of betaxolol therapy. The mean ratio of forced expiratory volume in one second (FEV-1) to forced vital capacity (FVC) was 59.33 +/- 13.30%. After two weeks of betaxolol therapy, the resulting mean FEV-1/FVC was 57.89 +/- 13.89%, a statistically insignificant difference (P greater than 0.05). The mean FEV-1 was 1.94 +/- 0.83 liters, compared to 1.91 +/- 0.78 liters after two weeks of betaxolol. The mean FVC was 3.19 +/- 0.91 liters, compared to 3.23 +/- 0.89 liters after two weeks of betaxolol. These differences were, also, not statistically significant (P greater than 0.05). This prospective study supports previous reports suggesting that betaxolol has potential advantages for those patients at risk for developing pulmonary side effects from beta-blocker therapy. This report represents the largest single-center series of patients who have been studied in this fashion.