Katja Technau-Ihling

Essential role of endothelial nitric oxide synthase for mobilization of stem and progenitor cells

Endothelial nitric oxide synthase (eNOS) is essential for neovascularization. Here we show that the impaired neovascularization in mice lacking eNOS is related to a defect in progenitor cell mobilization. Mice deficient in eNOS (Nos3−/−) show reduced vascular endothelial growth factor (VEGF)-induced mobilization of endothelial progenitor cells (EPCs) and increased mortality after myelosuppression. Intravenous infusion of wild-type progenitor cells, but not bone marrow transplantation, rescued the defective neovascularization of Nos3−/− mice in a model of hind-limb ischemia, suggesting that progenitor mobilization from the bone marrow is impaired in Nos3−/− mice. Mechanistically, matrix metalloproteinase-9 (MMP-9), which is required for stem cell mobilization, was reduced in the bone marrow of Nos3−/− mice. These findings indicate that eNOS expressed by bone marrow stromal cells influences recruitment of stem and progenitor cells. This may contribute to impaired regeneration processes in ischemic heart disease patients, who are characterized by a reduced systemic NO bioactivity.

Role of Cat-Scratch Disease in Lymphadenopathy in the Head and Neck

Bartonella henselae is the causative agent of cat-scratch disease (CSD), which usually manifests as acute regional lymphadenopathy. The causes of cervical lymphadenopathy, with special regard to CSD, were investigated in a study of 454 patients who presented with unclear masses in the head and neck from January 1997 through January 2001. Sixty-one patients (13.4%) experienced CSD; 54 (11.9%) had primary lymphadenopathy due to other infectious agents, and 41 (9.0%) had lymphadenopathy that occurred in association with primary infections of other organs. For 171 patients (37.7%), the cause of the cervical lymph node enlargement could not be found. B. henselae DNA was detected in extirpated lymph nodes only during the first 6 weeks of lymphadenopathy, which indicates that the results of polymerase chain reaction strongly depend on the duration of illness. CSD should be included in the differential diagnosis of adenopathy in the otorhinolaryngologic patient population, to avoid unnecessary treatment.

Spectrum and Management of Deep Neck Space Infections: An 8-Year Experience of 234 Cases

OBJECTIVE: To study the clinical course and outcome of deep neck infections (DNI), with special emphasis on microbiology and histopathology. STUDY DESIGN: Two hundred thirty-four patients with DNIs were included in this study. Patients with peritonsillar or dental infections, infections arising from salivary glands, as well as subjects with abscesses caused by neck trauma were excluded. METHODS: Clinical analysis of all patients with DNIs who were treated between January 1, 1997 and May 31, 2005 in a single center. RESULTS: In 13 patients, the DNI was the first manifestation of a malignant tumor. In 17 cases, the DNI was associated with cat-scratch disease (CSD). Six patients suffered from tuberculosis, and in another 7, an infected lateral cleft cyst was found. In 176 patients, the origin of DNI remained unclear. CONCLUSIONS: Our results demonstrate that CSD, tuberculosis, and malignant tumors must be considered as possible causes of DNIs. The current study represents one of the largest series of DNIs in the modern medical literature.

Cat-scratch disease: Otolaryngologic manifestations and management

OBJECTIVE: The bacteria Bartonella henselae has been known as the principal causative agent of cat-scratch disease (CSD) since 1992. It is an important cause of infectious lymphadenopathies in the head and neck. Nevertheless, CSD often remains unrecognized in cases of cervicofacial lymph node enlargement. STUDY DESIGN: Between January 1997 and May 2003, we conducted a prospective clinical study including 721 patients with primarily unclear masses in the head and neck. RESULTS: CSD was diagnosed by serology and molecular investigations in 99 patients (13.7%; median age 33 years). Cervicofacial lymphadenopathy was the most common manifestation. Atypical manifestation of CSD including Parinauds oculoglandular syndrome, swelling of the parotid gland and erythema nodosum were diagnosed in 8.1%, 8.1%, and 2.0% of cases, respectively. CONCLUSIONS: Our results demonstrate that CSD is a major cause of enlarged cervicofacial lymph nodes and should therefore be included in the differential diagnosis of lymphadenopathy in the head and neck region.

ULTRASOUND-GUIDED CORE-NEEDLE BIOPSY IN THE DIAGNOSIS OF HEAD AND NECK MASSES: INDICATIONS, TECHNIQUE, AND RESULTS

Unclear cervicofacial masses are common presentations that often require tissue sampling to guide therapy. While open biopsy is invasive, fine‐needle aspiration cytology includes a high rate of nondiagnostic samples.

Evidence that wild-type p53 in neuroblastoma cells is in a conformation refractory to integration into the transcriptional complex

Neuroblastoma (NB) cells reportedly accumulate wild-type p53 exclusively in the cytoplasm. However, immunofluorescence assays with five different antibodies showed that p53 accumulates in the nucleus of up to 10% of NB cells. PAb1801 detected cytoplasmic ‘punctate structures’ which were also found in p53-null cells, rendering this antibody unsuitable for p53 detection. A comparison of DO-1 and PAb1801 staining in NB tissue sections confirmed the results obtained with NB cells. Nuclear accumulation of p53 was induced in NB cells using substances which disturb p53s tertiary structure at its zinc finger motif, or by treatment with mitomycin C. Constitutive nuclear accumulation was observed in an SK-N-SH variant, AW-1, which has a point mutation in p53 at Cys176>Ser, disturbing the same motif. Even though p53 showed DNA-binding capability after mitomycin C treatment of NB cells, the target gene products MDM2 and p21WAF1,CIP1,SDI1 were not synthesized and no p53 transactivating activity measured in a reporter gene assay. Therefore we suggest that p53 in NB cells might be predominantly in a conformation refractory to integration into the transcriptional complex, resulting in at least partial transcriptional inactivity, hyperactive nuclear export and resistance to degradation by exogenously expressed MDM2.

Influenza A virus infection of mice induces nuclear accumulation of the tumorsuppressor protein p53 in the lung

Summary. To investigate whether the tumor suppressor p53 protein, an indicator of DNA damage and cell stress, accumulates in the course of influenza-virus-induced murine pneumonia at the site of inflammation, female BALB/c mice were infected each with 5 × 104 infectious units of influenza virus A, strain Puerto Rico (PR) 8, by instillation into the nose and the pharynx. Two days later the mice became sick. Three and 6 days after infection the lungs of sacrificed infected and uninfected mice were examined. We assessed the presence and localisation of inflammation, the expression of influenza viral and p53 protein, as well as of the WAF1/Cip1/SDI gene product p21. Further, the appearance of nitrotyrosine, as an indicator of the formation of peroxynitrite, and eventually of apoptotic cells was examined. No significant nuclear p53 accumulation was found in influenza virus-infected murine cells in vitro. The results show, that in the course of influenza A virus-mediated murine pneumonia inflammatory bystander cells may cause activation of the tumor suppressor protein p53, due to oxidative stress and DNA damage, with ensuing p53-dependent upregulation of p21. Apoptosis is then mainly due to these indirect processes, with possible involvement of p53.

Deep Neck Abscess Masquerading Hypopharyngeal Carcinoma

rhinolaryngology at the University Clinic of Freiburg in December 1998 for surgical treatment of a bacterial neck abscess. During the previous 3 months he had reported several small, painless neck masses with a self-healing tendency. At the time of presentation, he had an increasing painful swelling at the left side of his neck that had showed no improvement for 3 days. Moreover, he reported a fever up to 38.6°C (measured at the axilla), odynophagia, and mild dysphagia. He was a management consultant and had smoked about 40 cigarettes per day for 25 years. Furthermore, he regularly consumed 2 to 4 beers per day. Until presentation, he had been healthy except for primary hypercholesteremia, which was treated medically with simvastatin. Otolaryngologic examination showed trismus and an inflammatory and fluctuating induration on the left side of the neck as large as a tennis ball. Transnasal fiberoptic laryngoscopy revealed medial displacement of the lateral pharyngeal wall with soft tissue edema. Blood examination showed a leukocytosis of 18,700/μL. All other clinical findings were unremarkable. Ultrasonographic scans demonstrated a hypoechoic and heterogeneous deep abscess between the left sternocleidomastoid muscle and the common carotid artery. Surgical drainage of the abscess was performed the same day with the patient under general anesthesia. During surgery a great deal of purulent exudate was drained. Extensive tissue necrosis was debrided. Biopsy specimens for pathologic investigation and smears for bacteriologic culture were taken. The wound was closed with active suction drainage. The microbiologic results indicated an infection with large quantities of Streptococcus intermedius and Streptococcus equisimilis. The patient was treated with oral cefuroxime for 14 days. His fever resolved after surgery, but the odynophagia persisted. Deep neck abscess masquerading hypopharyngeal carcinoma

Value and Utility of Minimal-invasive Automatic Cutting-needle Biopsy as a Diagnostic Technique in the Head and Neck

BACKGROUND Lymphadenopathies and unclear masses in the head and neck often require tissue sampling to establish a diagnosis and to guide therapy. Open biopsy and lymph node excision is invasive and may entail general anaesthesia. Fine needle aspiration cytology is minimal-invasive and widely used but includes a high rate of non diagnostic samples and false negative results. Cutting needle biopsy is an established technique outside the head and neck but has found little attention among otorhinolaryngologists up to now. PATIENTS AND METHODS Between April 2003 and May 2007 we performed a total of 307 cutting-needle biopsies in 143 patients with unclear cervicofacial masses, using side-notch-needles with a diameter of 12-16 Gauge. RESULTS High-quality tissue cores without crushing artefacts for histopathological studies were obtained without complications from all patients. The target tissue was obtained in 132 of 143 patients, in these cases the sensitivity and accuracy rate for the diagnosis of malignant lesions was 98.9% and 99.2%, respectively. CONCLUSIONS Ultrasound-guided Cutting-needle biopsy in the head and neck is a safe and reliable biopsy tool with an excellent diagnostic efficacy, which can be performed as an outpatient procedure with low expenditure of time and manpower. Performing the procedure requires substantiated experience in topographic head and neck anatomy as well as sonography of this body region.

Spectrum and management of deep neck space infections: Seven year prospective study

Objectives: Antibiotics have reduced the prevalence and improved the outcome of deep neck space infections; however, they continue to be associated with high rates of morbidity and mortality. It is essential for the otolaryngologist to understand the etiology and pathogenesis of those infections in order to induce the necessary diagnostic steps and the appropriate therapy as soon as possible. Methods: Between January 1997 and December 2003, we conducted a prospective clinical study including 189 patients with deep neck space infections. Dental abscesses as well as abscesses evolving from tonsillitis or infections of the large salivary glands were not included in this study. Results: The median age was 44 years (1–90 years) and there were 104 male and 85 female patients, respectively. We performed a surgical drainage in 86.2% of subjects. The bacteria most commonly involved included streptococci (n = 48), anaerobes (n = 37) and staphylococci (n = 26). We found 15 abscesses to be caused by Bartonella henselae (cat-scratch disease) and another 7 by Mycobacterium tuberculosis. In 10 cases, the deep neck space abscess represented the first manifestation of a malignant head and neck tumor. Conclusions: Ensuring a secure airway is the first priority in the management of a deep neck space infection. Surgical intervention is indicated in most cases. However, abscesses caused by B henselae or M tuberculosis may be managed with antibiotic therapy alone. The indication for a simultaneous panendoscopy should be regarded generously, especially in patients with the well-known risk factors for head and neck carcinomas.