Effects of tranexamic acid on human nasal ciliary beat frequency.

BACKGROUND: Patients with recurrent epistaxis, particularly due to hereditary hemorrhagic telangiectasia (HHT) are recommended to apply topical tranexamic acid (TXA) to reduce bleeding events. Those patients may suffer ciliary dysfunction due to TXA's effects on ciliary beating frequency (CBF) and their consequences. METHODOLOGY/PRINCIPAL: Human nasal epithelial cells were harvested with a nasal brush in 30 healthy subjects. We investigated the CBF in RPMI medium using high-frequency video microscopy. TXA was added to the cells in various concentrations ranging from 2 to 5%, including the therapeutic concentration (2%) and a control (0%). RESULTS: CBF in the control condition was 6.1 ± 1.6 Hz. TXA reduces CBF in a time and concentration dependent manner, to, e.g. 4.3 ± 1.2 Hz with 2% TXA and 3.3 ± 0.9 Hz with 5% TXA after 16-20 min. The differences in CBF were statistically significant for all concentrations of TXA. CONCLUSIONS: TXA has the potential to significantly impair nasal epithelial function. Therefore, frequent or regular topical nasal application of TXA should be done under close monitoring of nasal function, especially in patients with co-morbidities like chronic rhinosinusitis.

[Prophylaxis of venous thromboembolic events in head and neck surgery]. / Die Prophylaxe venöser Thromboembolien bei Kopf­Hals­Operationen.

BACKGROUND: Application of perioperative thrombosis prophylaxis in head and neck surgery lacks consistent standards in Germany. Due to sparse data, the latest German S3 guideline concerning prophylaxis of thromboembolic events recommends a restrictive handling of anticoagulants in head and neck surgery, with few specific recommendations. OBJECTIVE: The aim of this paper is to provide concrete clinical recommendations based on a systematic literature review and the S3 guidelines. MATERIALS AND METHODS: A keyword-based literature search was performed and the German S3 guideline "Prophylaxis of Venous Thromboembolic Events" was used to state the current level of evidence and provide a clinical algorithm. RESULTS: Eight additional cohort studies dealing with the incidence of thromboembolic events in head and neck surgery were identified. There were no randomized controlled trials. In the proposed algorithm, a classification of dispositional (patient history) and expositional (operation time) risk into three groups enables preoperative risk evaluation indicating the individual demand for prophylaxis. In short operations without major tissue traumatization, routine drug-based thrombosis prophylaxis is not necessary, provided no third-grade risk factors (earlier thromboembolic event, coagulopathy, or malignant disease) are present. Low molecular weight heparins should be used as anticoagulants for drug-based prophylaxis. CONCLUSION: Prophylaxis of thromboembolic events in head and neck surgery is of high clinical relevance but there is currently limited evidence regarding its implementation. This paper is based on a systematic literature review and provides a clinical algorithm for head and neck surgeons.

[Hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) as an example of a rare disease relevant for oto-rhino-laryngology]. / Hereditäre hämorrhagische Teleangiektasie (Morbus Rendu-Osler-Weber) als Beispiel einer seltenen Erkrankung des HNO-Fachgebietes.

Diagnosis and treatment of rare diseases are difficult. Hereditary hemorrhagic telangiectasia (HHT, Rendu-Osler-Weber disorder) is a relatively common rare disease. Because epistaxis is the most frequent manifestation of this disease, affected individuals often approach otorhinolaryngologists first. The latter ones often have a key position for early diagnosis and screening for visceral involvement which can prevent life-threatening complications. Treatment of epistaxis can improve quality of life of affected persons. Diagnosis and treatment of rare diseases can be complex and it can be very helpful to use information resources to ensure a correct management. Various possibilities to access these resources are presented in general and in relation to HHT.

International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia.

BACKGROUND: HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults. OBJECTIVE: The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease. METHODS: The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches. RESULTS: The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.

An association of migraine with hereditary haemorrhagic telangiectasia independently of pulmonary right-to-left shunts.

Hereditary haemorrhagic telangiectasia (HHT) is a genetic disorder characterized by epistaxis, telangiectasia and visceral vascular manifestations. It is associated with migraine with aura due to pulmonary arteriovenous malformations (pAVMs). The aim of the study was to evaluate headache prevalence in 106 consecutive HHT patients (67 female, 39 male, age 53.5 +/- 14.5 years) and age- and gender-matched controls. An extensive clinical work-up was performed and headache prevalence was determined. Lifetime prevalence of migraine was higher in HHT patients (39.6%) than in controls (19.8%) [P < 0.001, chi(2) = 12.17, odds ratio (OR) 3.0; 95% confidence interval 1.6 < OR < 5.7]. A positive association was confirmed between HHT patients with pAVMs and migraine with aura (38.5% vs. 10%). Furthermore, HHT patients without pAVMs had a higher prevalence of migraine without aura (11.5% vs. 26.3%; chi(2) = 11.85; d.f. = 2; P = 0.003). We speculate that pathophysiological mechanisms, including dysfunction of the transforming growth factor-beta pathways and resulting vascular changes, contribute to the higher prevalence of migraine without aura in HHT patients without pAVMs.

Treatment of recurrent epistaxis in HHT.

No optimal treatment modality is currently available for the treatment of recurrent epistaxis in HHT. In this review, different therapeutic concepts are discussed together with their pathophysiologic background. Patients often profess a preventive effect for nasal ointments and use packings which can be self-administered in the case of bleeding. An effective first-line treatment for physicians is the endonasal laser coagulation or argon plasma coagulation. A second line surgical procedure is septodermoplasty according to Saunders which can provide long-lasting relief if performed correctly. There have been reports on antifibrinolytic agents and hormones, but their efficacy has yet to be determined.

Mutation analysis in hereditary haemorrhagic telangiectasia in Germany reveals 11 novel ENG and 12 novel ACVRL1/ALK1 mutations.

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal-dominant disease characterized by recurrent epistaxis, mucocutaneous telangiectasias and visceral arteriovenous malformations. Mutations in endoglin (ENG) and activin A receptor type II-like kinase 1 (ACVRL1 or ALK1) have been found in patients with HHT. We have screened a total of 51 unselected German index cases with the suspected diagnosis of HHT. We identified 30 different mutations in 32 cases (62.7%) by direct sequencing. Among these mutations, 11 of 13 ENG mutations and 12 of 17 ACVRL1 mutations were not previously reported in the literature. Two of the ACVRL1 mutations were each shared by two families. An analysis of the genotype-phenotype correlation is consistent with a more common frequency of pulmonary arteriovenous malformations in patients with ENG mutations than in patients with ACVRL1 mutations in our collective.

Ultrasound-guided mechanical intraductal stone fragmentation and removal for sialolithiasis: a new technique.

BACKGROUND: Not all patients with sialolithiasis can be treated successfully by established minimally invasive techniques. METHODS: A forceps was used under sonographic control to fragment and retrieve salivary calculi in five cases refractory to established minimal invasive approaches. RESULTS: One patient with a sialolithiasis of the Stenon duct, two patients with a stone in the hilum region of the submandibular gland, and one patient with a sialolith in the sublingual gland were cured by this technique. For another patient, only a part of the stone in the hilum region of the submandibular gland could be removed. No relevant side effects occurred. CONCLUSIONS: To the authors' knowledge, this is the first report of a new, simple, and inexpensive minimally invasive technique that proved to be at least partially successful in the treatment of sialolithiasis in cases refractory to other therapies. The technique also seems to be suitable as a primary treatment approach.

[The use of lipid containing nasal ointment for allergic rhinitis--a therapeutic option? A bicentric, prospective, open, randomised, controlled clinical study]. / Die Anwendung lipidhaltiger Nasensalbe bei allergischer Rhinitis--eine Therapieoption? Eine bizentrische, prospektive, offene, randomisierte, kontrollierte klinische Studie.

BACKGROUND: Some 10-20% of the population suffer from allergic rhinitis. A recently discussed and interesting, albeit disputed therapy option is the use of a lipid-based nasal ointment. METHOD: To test the efficacy of this nasal ointment as an adjuvant therapy for allergic rhinitis, a two-centre, prospective, open, randomized, controlled clinical study was carried out. RESULT: In the study, 17 patients using the test agent were compared with 16 who did not. For the group using the test agent, before and after comparisons showed a significant (about 40%) improvement in the medium, relative total range of symptoms (Wilcoxon-Mann-Whitney U-test, P<0.01) based on the individual parameters of sneezing attacks, nasal itching, nasal secretion and nasal obstruction. In the control group, non-use of the test agent meant that the total range of symptoms remained unchanged. No side effects were recorded. CONCLUSION: The test agent used in our study contains a lipid fraction, in this case in the form of high purity, long chain hydrocarbons. By local application, a significant improvement of the total symptomatology was shown. The mechanism has not been clarified. Owing to the efficacy and low risk of side effects, this seems to be a promising adjuvant therapy for allergic rhinitis. The probetoric use of this nasal ointment as a supportive therapeutic option should be reviewed in further clinical studies.

[Hereditary hemorrhagic telangiectasia. A rare treatable cause of stroke]. / Hereditäre hämorrhagische Teleangiektasie. Seltene Insultursache mit Behandlungsoption.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease of the vascular connective tissue. Pulmonary arteriovenous and cerebral vascular malformations are risk factors for serious neurological complications such as paradoxical embolism and intracranial hematomas. We describe two patients with HHT and pulmonary arteriovenous malformations suffering from stroke caused by paradoxical embolism. In both cases, fistulas were successfully treated by embolisation and no further cerebral ischemic events occurred. In ischemic strokes of unknown origin, HHT should be considered as a possible diagnosis with effective treatment options.

[Rendu-Osler-Weber syndrome--a complex systemic disease]. / Teleangiektasien--Epistaxis--vaskuläre Malformationen. Morbus Osler--die Suche nach der tickenden Zeitbombe.

Hereditary hemorrhagic teleangiectasia (HHT or Rendu-Osler-Weber Syndrome) is an inherited autosomal dominant disorder of the vascular connective tissue. The resulting vascular malformations can occur in virtually any organ. Nosebleeds can massively impact on the quality of life of those afflicted. However, visceral manifestations are likely to be more serious, and may be comparable with a "ticking time bomb". Most commonly affected are the vascular systems of the lungs, liver, brain and gastrointestinal tract. Screening is recommended--at least with regard to the lungs. Difficult constellations of this complex condition may be successfully managed by an interdisciplinary approach.

Visceral manifestations in hereditary haemorrhagic telangiectasia type 2.

Hereditary haemorrhagic telangiectasia (HHT) is a genetic vascular disorder characterised by epistaxis, telangiectases, and visceral manifestations. The two known disease types, HHT1 and HHT2, are caused by mutations in the endoglin (ENG) and ALK-1 genes, respectively. A higher frequency of pulmonary arteriovenous malformations (AVMs) has been reported for HHT1 while HHT2 is thought to be associated with a lower penetrance and milder disease manifestations. In this study, we present 10 families with an ALK-1 genotype. Visceral manifestations were detected in 24 (26%) of the 93 HHT2 patients from nine of the families and included gastrointestinal bleeding (14%), intrahepatic shunts (6%), and AVMs in the lung (4%) and brain (3%). Gastrointestinal bleeding, the most frequent visceral manifestation, was reported in six of the 10 families, mostly in patients over the age of 50. These patients also had frequent epistaxis and suffered from anaemia, often requiring blood transfusions. The identification of ALK-1 mutations in subjects with a suspected diagnosis and without clinical signs of HHT argue in favour of a molecular diagnosis. We also analysed the data published on 44 families with HHT2 and conclude that visceral manifestations occur in 26 of these families and affect 30% of HHT2 patients. This is considered an underestimate given incomplete and variable screening for lung, brain, and/or liver involvement in different clinical centres. These findings, however, stress the need for an early diagnosis of HHT that can be useful for the early control of associated visceral involvement.

[Telemedicine: interaction between clinic and general practice]. / Telemedizin: Interaktionen zwischen Klinik und Praxis.

BACKGROUND: The rapid development of information and communication technologies has led to a change of many practical aspects of professional and private life. These technologies also influence interactions between hospitals and outpatient units. METHODS: This paper provides an overview over current telemedical developments with effects on interactions between in- and outpatient units. RESULTS AND CONCLUSIONS: Probably the most important application of telemedicine in Germany is not distant patient care but an improved communication structure between different health care providers. Candidates for first routine applications are electronic medical reports and teleconsultations. The widespread use of telemedicine will be accompanied by an increased standardisation in medicine.

[Hereditary telangiectasia, recurrent laryngeal nerve paralysis, tumor in the neck area. When you need the expertise of an ENT specialist]. / Hereditäre Teleangiektasie, Recurrenslähmung, Tumor im Halsbereich. Wann Sie die Expertise des HNO-Spezialisten brauchen.

Numerous internal diseases can express themselves in the form of ENT manifestations. Epistaxis is one of the most common emergencies seen by the ENT specialist. Possible underlying systemic etiologies may be hypertension, systemic anticoagulation or even rare entities such as hereditary hemorrhagic telangiectasia. Internal-medical conditions underlying hoarseness are usually injuries to the recurrent nerve with lesions of the thyroid gland and mediastinum being prominent. Modern electrophysiological techniques permit early prognostication of the chances of healing a vocal cord paresis. A number of surgical procedures for improving vocal problems in the treatment of irreversible paresis are available. Unclear cervical swellings prompt a wide range of possible differential diagnoses that differ dramatically in terms of both treatment and outcome. For this reason, a rational, interdisciplinary diagnostic work-up is essential. In light of the risk of delaying the diagnosis and worsening the outcome, uncritical primary sampling of such tissue must be avoided.

[Hereditary hemorrhagic telangiectasia (Osler's disease). An interdisciplinary challenge]. / Hereditäre hämorrhagische Teleangiektasie (Morbus Osler). Eine interdisziplinäre Herausforderung.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT or Rendu-Osler-Weber disease) is an autosomal dominant inherited disease of the fibrovascular tissue. More than 90% of patients have recurrent nosebleeds. Therefore, ENT physicians often have a key position for diagnosis and management of the disease. Epistaxis can severely reduce the quality of life, but visceral lesions are also life threatening. METHODS: This paper provides a review of the literature about the disease, its diagnosis, preventive measures, and therapy of the different manifestations. RESULTS AND CONCLUSIONS: Physicians should be especially aware of gastrointestinal telangiectases, arteriovenous malformations (AVM) of the lungs, liver, and brain. A screening is recommended at least for pulmonary AVM.

[Results of an in vitro study and initial clinical application of a combined Ho:YAG-/Nd:YAG laser]. / Ergebnisse einer In-vitro-Studie und erster klinischer Anwendung eines kombinierten Ho:YAG-/Nd:YAG-Lasers.

BACKGROUND AND OBJECTIVE: A combined Ho:YAG/Nd:YAG laser produces light with properties similar to the beams of the mainly coagulating Nd:YAG laser and the cutting CO2 laser alone. PATIENTS/METHODS: The combined laser was tested in vitro on pig tissue. Additionally, we used this new combined tool for enoral operations. RESULTS: An effect of the pulsed Ho:YAG laser was explosive-like tissue disruption and sprinkling of fragments. Simultaneous use of the Nd:YAG laser resulted in an enlarged zone of coagulation. Clinically, the laser-assisted intervention was inferior to the classic operational methods. CONCLUSIONS: Comparing the established CO2 laser and the Ho:YAG laser, the latter showed only the advantage of delivery via a flexible fiber. Sprinkling of tissue fragments and wide incisions are oncologically problematic. We conclude that this new tool is of minor value for otorhinolaryngologists and head and neck surgeons.

In vitro tissue effects of a combined Ho:YAG/Nd:YAG laser: sprinkling of tissue fragments by Ho:YAG laser light may be problematic for oncological interventions.

BACKGROUND AND OBJECTIVE: Surgery of soft tissue, for example, of the tongue or the liver, requires a cutting and coagulating device. Therefore, a combined Ho:YAG/Nd:YAG laser providing the laser beam of both systems together in one bare fiber seems to be useful. STUDY DESIGN/MATERIALS AND METHODS: We studied the effect of such a laser system in vitro on tongues of pigs. RESULTS: Combined application of both lasers results in vitro in a thicker coagulation zone in soft tissue (tongue). Tissue fragments possibly containing vital cells are sprinkled by the pulsed energy of the Ho:YAG laser up to a distance of 20 cm. CONCLUSION: Using the pulsed Ho:YAG laser for oncologic interventions seems to be problematic. Combined laser effect in vivo may result in better hemostasis.

[Nd:YAG laser therapy of recurrent epistaxis in hereditary hemorrhagic telangiectasia]. / Nd:YAG-Lasertherapie der rezidivierenden Epistaxis bei hereditärer hämorrhagischer Teleangiektasie.

BACKGROUND: Epistaxis is the leading symptom of hereditary hemorrhagic teleangiectasia (HHT). Over the last years several laser systems have been used for therapy. Only a few studies have published results of Nd:YAG laser therapy evaluating a larger number of patients. PATIENTS AND METHODS: From 1987 through 1996, forty-one patients with HHT were treated with a Nd:YAG laser due to recurrent epistaxis at the Department of Otorhinolaryngology of Kiel University. Thirty-two patients were followed-up over a period of at least 24 months. A centripetal technique was used for endonasal laser light application (15-25 Watts; 0.1-0.5 s), i.e., the laser light was applied from the periphery towards the center of the angiodysplasia. Intensive preoperative and postoperative nasal care with ointments was performed. RESULTS: Bleeding frequency and intensity decreased in 30 (94%) patients. Duration of the therapeutical success differed individually and varied from seven weeks to 14 months. Repeated laser therapy was necessary in 27 of 32 patients. CONCLUSION: The Nd:YAG laser is a suitable tool in the treatment of epistaxis in HHT. This procedure is less traumatic, less painful, and can be repeated multiple times. Nd:YAG laser therapy and other therapeutic options cannot obtain a lasting cure of Rendu-Osler-Weber syndrome. However, in the vast majority of cases recurrent nasal bleeding as the dominant symptom can be reduced in frequency as well as in intensity.