Course and therapy of intoxication with imidazoline derivate naphazoline

OBJECTIVE: Imidazoline derivatives like naphazoline have a firm place in diagnostics and therapy of otorhinolaryngology because of their vasoconstrictive and decongestive properties. Their alpha-adrenergic potential could induce not only local but also systemic side effects like hypertension and tachycardia which can increase a life-threatening intoxication. Signs of imidazoline intoxication are excessive systolic and diastolic hypertension and hypotension, bradycardia with arrhythmia, respiratory depression, excitation or severe CNS depression. PATIENTS: The typical course of an intoxication and its sufficient therapy is reported by means of two cases of intraoperative application of naphazoline for hemostasis. RESULTS: In case of overdosage or intoxication, symptomatic drug therapy with intravenous administration of 5 mg phentolamine for adults and 1 mg phentolamine for infants has to be done. Phentolamine, an alpha-adrenoceptor antagonist, acting against peripheral and central side effects has to be used because no specific antidote is available. CONCLUSIONS: Especially pediatric otorhinolaryngologists have to know about symptoms and therapy of an intoxication after application of naphazoline. Particularly with children, a narrow therapeutic to toxic window can be observed in this frequently used drug.     

Plattenepithelkarzinome des oberen Aerodigestivtraktes

The capsular rupture and subsequent extranodal spread of lymph node metastases is of crucial and well established prognostic value in patients with squamous cell carcinomas of the upper aerodigestive tract. Besides the basic histologic definition of the extranodal spread (i.e. contact of the metastasis with perinodal fatty tissue), there is no agreement on the morphologic extent of transcapsular spread. As a measure of improvement, a histologic evaluation differentiating between seven gradual types of metastatic nodal affection was applied. The histologic scheme considers intranodal growth, infiltration of the capsule, the presence of desmoplasia and especially the rupture of the capsule and the subsequent extranodal spread of the metastasis. As extranodal spread is an easily reproducible and reliably significant prognostic criterion, it should be included in the current TNM classification, e.g., by an addition of the index R+ (lymph node metastasis with capsular rupture) or R- (lymph node metastasis without capsular rupture) to the N category.     

Possible linkage of schizophrenia and bipolar affective disorder to chromosome 3q29: a follow-up

The present linkage study is a follow-up within the chromosome 3q29 region in schizophrenia and bipolar affective disorder families, based on our recently published genome scan, resulting in evidence for linkage of both disorders to this region (marker D3S1265: NPL [non parametric lod] score Z_all=3.74, P=0.003). Using the same family sample (five pedigrees with schizophrenic index patients and three pedigrees with index bipolar disorder patients N=86; 50 of them were available for genotyping), genotyping of eight additional markers close to D3S1265 was done. Five of those new markers (three centromeric and two telomeric of D3S1265) spanning 4.14 cM (centiMorgan) could be used for statistical analyses (“new markers”). Moreover, marker D3S1265, genotyped within the published genome scan, was used for additional calculations. Linkage analysis was performed using the GENEHUNTER program version 2.1r3. Within newly genotyped markers the highest NPL score Z_all observed was 1.93296 with the telomeric SNP (single nucleotide polymorphism) rs1835669, corresponding to P=0.032166. Statistical analysis including D3S1265, located in between the newly genotyped markers, resulted in a peak NPL score Z_all=4.00179 with marker D3S1265, that is P=0.000128. Doing subset analyses of the bipolar disorder and schizophrenia families separately with new markers and D3S1265, linkage signals arose substantially from bipolar disorder families, with contribution from schizophrenia families, too. The results of our follow-up study support our previous linkage finding of schizophrenia and bipolar affective disorder to chromosome 3q29.     

Different gender-associated genotype risks of Wegener's granulomatosis and microscopic polyangiitis

Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA) are systemic small vessel vasculitides associated with ANCA (AAV). Predominant Th1 and Th2 cytokine patterns have been reported for WG and MPA, respectively. Consequently, genotypes suppressing Th1 responses or augmenting Th2 responses may be more frequent in MPA than in WG. Transforming growth beta1 (TGF-beta1) and interleukin-10 (IL-10) genes may modify the course of vasculitis. Therefore, we investigated associations between genotype frequencies of functional polymorphisms of these cytokine genes and clinical manifestations in AAV. One hundred sixty-one AAV patients and 153 healthy blood donors were genotyped for the biallelic polymorphism in codon 25 of the TGF-beta1 gene and the biallelic polymorphism at position -1082 of the IL-10 gene. No difference was found for TGF-beta1 codon 25 polymorphism between control and patient groups. In contrast, a significant shift toward the homozygous AA genotype of the IL-10 (-1082) polymorphism was found in WG (25%, p<0.005) and MPA patients (39%; p<0.00001) compared to controls (10.5%). Furthermore, in MPA the AA homozygous genotype was significantly more frequent in females (62.5%) compared to males (20%, p<0.05). A contribution of the TGF-beta1 codon 25 polymorphism to the susceptibility-defining genetic backgrounds of AAV appears unlikely. In contrast, our findings suggest a role of the enhanced IL-10 (-1082) PM in WG and MPA with a significant gender difference in MPA.     

Influence of number of surfaces and observers on statistical power in a multiobserver ROC radiographic caries detection study

The aim of the study was to evaluate the influence of the number of surfaces (N(SURF)) and the number of observers (N(OBS)) on the statistical power of a study comparing the diagnostic accuracies of radiographic systems used for approximal caries lesion detection. A data set consisting of 338 surfaces examined by 10 independent observers using four radiographic systems was available. The presence of a caries lesion was assessed from a 5-point confidence scale. The true lesion diagnosis was established by histological validation. ROC curve areas (A(z)s) were used to express the diagnostic accuracy of the observers with the radiographic systems. Assuming that the A(z)s were tested by a two-way analysis of variance, we performed a simulation study in order to evaluate how the power of this statistical analysis depended on N(SURF) and N(OBS). As a measure of the statistical power we used the standard error of the difference between the expected A(z)s of two systems. The simulations were made with N(SURF) in the range from 25 to 338 and N(OBS) from 2 to 10. The simulations showed that the power increased as a function of the total number of evaluations per system (N(SURF) x N(OBS)), but how this number was attained in relation to the number of surfaces and observers had only marginal influence on the power. Thus, from a statistical point of view it may be concluded, provided that data are analyzed by a two-way analysis of variance, that study designs for comparing the accuracy of several systems can be composed freely in relation to the number of surfaces and observers as long as the total number of evaluations per system are identical.     

Neue Aspekte zur Mechanik der Tuba auditiva

The aim of the present article is to describe the mechanical components of the auditory tube and the role of these components in auditory tube function. Particular attention will be given to those aspects which have not been sufficiently dealt with in the past, such as the role of the isthmus region, the function of the lateral mucosal folds, the significance of the of the surfactant proteins and the pathophysiology of the patulous auditory tube. Special attention is given to the tensor veli palatini muscle and its physiology. Because of its isometric contraction, the function of this muscle depends on so-called hypomochlia changing the direction of its force. In the context of this article, the three hypomochlia involved are the pterygoid hamulus, Ostmann's fatty tissue and the medial pterygoid muscle. The so-called "Eppendorf-maneuver" is depicted for the first time.     

Cardiopulmonary resuscitation after near drowning and hypothermia: restoration of spontaneous circulation after vasopressin

Recent animal data have challenged the common clinical practice to avoid vasopressor drugs during hypothermic cardiopulmonary resuscitation (CPR) when core temperature is below 30 degrees C. In this report, we describe the case of a 19-year-old-female patient with prolonged, hypothermic, out-of-hospital cardiopulmonary arrest after near drowning (core temperature, 27 degrees C) in whom cardiocirculatory arrest persisted despite 2 mg of intravenous epinephrine; but, immediate return of spontaneous circulation occurred after a single dose (40 IU) of intravenous vasopressin. The patient was subsequently admitted to a hospital with stable haemodynamics, and was successfully rewarmed with convective rewarming, but died of multiorgan failure 15 h later. To the best of our knowledge, this is the first report about the use of vasopressin during hypothermic CPR in humans. This case report adds to the growing evidence that vasopressors may be useful to restore spontaneous circulation in hypothermic cardiac arrest patients prior to rewarming, thus avoiding prolonged mechanical CPR efforts, or usage of extracorporeal circulation. It may also support previous experience that the combination of both epinephrine and vasopressin may be necessary to achieve the vasopressor response needed for restoration of spontaneous circulation, especially after asphyxial cardiac arrest or during prolonged CPR efforts.     

Management of vasodilatory shock: defining the role of arginine vasopressin

The rationale for an arginine vasopressin (argipressin) infusion was put forward after it was discovered that patients in shock states might have an endogenous arginine vasopressin deficiency. Subsequently, several investigations impressively demonstrated that arginine vasopressin can successfully stabilise haemodynamics even in advanced vasodilatory shock. We report on physiological and pharmacological aspects of arginine vasopressin, and summarise current clinical knowledge on employing a continuous arginine vasopressin infusion in critically ill patients with catecholamine-resistant vasodilatory shock of different aetiologies. In view of presented experimental evidence and current clinical experience, a continuous arginine vasopressin infusion of approximately 2 to approximately 6 IU/h can be considered as a supplemental strategy to vasopressor catecholamines in order to preserve cardiocirculatory homeostasis in patients with advanced vasodilatory shock. Because data on adverse effects are still limited, arginine vasopressin should be reserved for patients in whom adequate haemodynamic stabilisation cannot be achieved with conventional vasopressor therapy or who have obvious adverse effects of catecholamines that result in further significant haemodynamic deterioration. For the same reasons, arginine vasopressin should not be used as a single, alternative vasopressor agent instead of catecholamine vasopressors. Future prospective studies will be necessary to define the exact role of arginine vasopressin in the therapy of vasodilatory shock.