Maija Hytönen

Adenoviral VEGF-C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes

Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are important regulators of blood and lymphatic vessel growth and vascular permeability. The VEGF‐C/VEGFR‐3 signaling pathway is crucial for lymphangiogenesis, and heterozygous inactivating missense mutations of the VEGFR‐3 gene are associated with hereditary lymphedema. However, VEGF‐C can have potent effects on blood vessels because its receptor VEGFR‐3 is expressed in certain blood vessels and because the fully processed form of VEGF‐C also binds to the VEGFR‐2 of blood vessels. To characterize the in vivo effects of VEGF‐C on blood and lymphatic vessels, we have overexpressed VEGF‐C via adenovirus‐and adeno‐associated virus‐mediated transfection in the skin and respiratory tract of athymic nude mice. This resulted in dose‐dependent enlargement and tortuosity of veins, which, along with the collecting lymphatic vessels were found to express VEGFR‐2. Expression of angiopoietin 1 blocked the increased leakiness of the blood vessels induced by VEGF‐C whereas vessel enlargement and lymphangiogenesis were not affected. However, angiogenic sprouting of new blood vessels was not observed in response to AdVEGF‐C or AAV‐VEGF‐C. These results show that virally produced VEGF‐C induces blood vessel changes, including vascular leak, but its angiogenic potency is much reduced compared with VEGF in normal skin.—Saaristo, A., Veikkola, T., Enholm, B. Hytönen, M., Arola, J., Pajusola, K., Turunen, P., Jeltsch, M., Karkkainen, M. J., Kerjaschki, D., Bueler, H., Ylä‐Herttuala, S., Alitalo, K. Adenoviral VEGF‐C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes. FASEB J. 16, 1041–1049 (2002)

Nasal polyposis: clinical course during 20 years

BACKGROUND The etiology of nasal polyposis is mainly unknown although it has been connected with many clinical conditions. The long-term clinical course of nasal polyposis is largely unknown, because long-term followup studies on the recurrence of nasal polyposis have rarely been reported. OBJECTIVE The aim of the study was to find out the clinical course of nasal polyposis over a long period of time. PATIENTS AND METHODS Our report describes a 20-year follow-up study of 41 patients with nasal polyps. These patients had surgery for nasal polyp disease 20 years previously and they were initially grouped according to occurrence of (1) acetylsalicylic acid (ASA) intolerance, (2) atopic allergy (AT), and (3) intrinsic allergy-like disease (INTR). Patients were now re-examined, sinus computed tomography (CT) scanning was made, and a biopsy from polyp or from mucosa of the middle turbinate was taken. RESULTS Anterior rhinoscopy revealed polyps in 35 of 41 patients. Thus nasal polyposis was still active in 85% of patients after 20 years. Mucosal changes in paranasal sinuses were found in every patient. Anosmia or hyposmia was found in 61% (25/41) of the patients. Eight patients had had 11 or more surgical operations during the 20-year period. Of these, 88% (7/8) belonged to the ASA group. Bronchial asthma was found in all ASA intolerance patients (11/11), and in 36% (4/11) of AT and in 16% (3/19) of INTR patients, respectively. CONCLUSION Because of the high recurrence tendency and insidious symptoms of nasal polyposis, patients will require followup for the rest of their lives.

Submucosal bipolar radiofrequency thermal ablation of inferior turbinates: A long-term follow-up with subjective and objective assessment

Objective To assess the efficacy and morbidity of bipolar radiofrequency thermal ablation of the inferior turbinates in patients with nasal obstruction caused by turbinate hypertrophy.

Vascular Endothelial Growth Factor-C and Its Receptor VEGFR-3 in the Nasal Mucosa and in Nasopharyngeal Tumors

Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are important regulators of blood and lymphatic vessel growth and vascular permeability. Both blood and lymphatic vessels of the upper respiratory tract play important roles in pathological conditions, such as infections and tumors. Here we have studied the expression of VEGF-C and its receptor VEGFR-3 in the upper respiratory system by Northern blot analysis and immunohistochemistry of human tissues, and in situ mRNA hybridization of developing mouse embryos and beta-galactosidase staining of mouse embryos having a LacZ marker gene in the VEGFR-3 gene locus. The results demonstrate expression of VEGF-C and VEGFR-3 in the developing and adult nasal respiratory epithelium and in the nasal vascular plexus, respectively. Unlike in most other tissues, in the nasal mucosa VEGFR-3 is expressed in both blood and lymphatic vessels. Expression of VEGF-C was also detected in nasal and nasopharyngeal tumor islands, which were surrounded by VEGFR-3-positive angiogenic blood vessels. These results suggest that VEGF-C and VEGFR-3 have a role in the development of the nasal submucosal vascular plexus and in its normal function and that they are associated with angiogenesis in nasal and nasopharyngeal tumors.

Complications of Acute Sinusitis in Children

Acute sinusitis is often a mild, self-limiting disease. However, in some cases, especially among children, sinusitis may become a severe, even life-threatening, disease. To examine the nature of complications of acute sinusitis, we studied the cases of children treated at the Helsinki University ENT Hospital, because of a complication caused by acute sinusitis from January 1997 to September 1998. There were 12 children (4 girls, 8 boys), whose ages ranged from 16 months to 16 years. One child had an epidural abscess, one got meningitis and cavernous sinus thrombosis, five had orbital cellulitis, one of whom lost her vision permanently in one eye, and five had preseptal cellulitis. All the children were treated with intravenous antibiotics and all, except the youngest, were treated with a direct sinus puncture. An operation (intranasal antrostomy, orbital drainage, functional endoscopic sinus surgery or adenoidectomy) was performed on six patients. In the majority of children, acute sinusitis is a mild self-limiting disease. However, severe complications still exist. When a complication of sinusitis is suspected, it is of utmost importance that the child be sent immediately to a hospital for proper diagnosis and treatment.Acute sinusitis is often a mild, self-limiting disease. However, in some cases, especially among children, sinusitis may become a severe, even life-threatening, disease. To examine the nature of complications of acute sinusitis, we studied the cases of children treated at the Helsinki University ENT Hospital, because of a complication caused by acute sinusitis from January 1997 to September 1998. There were 12 children (4 girls, 8 boys), whose ages ranged from 16 months to 16 years. One child had an epidural abscess, one got meningitis and cavernous sinus thrombosis, five had orbital cellulitis, one of whom lost her vision permanently in one eye, and five had preseptal cellulitis. All the children were treated with intravenous antibiotics and all, except the youngest, were treated with a direct sinus puncture. An operation (intranasal antrostomy, orbital drainage, functional endoscopic sinus surgery or adenoidectomy) was performed on six patients. In the majority of children, acute sinusitis is a mild self-limiting disease. However, severe complications still exist. When a complication of sinusitis is suspected, it is of utmost importance that the child be sent immediately to a hospital for proper diagnosis and treatment.

Nasal obstruction and sleep-disordered breathing: the effect of supine body position on nasal measurements in snorers.

Objective --Nasal obstruction is considered to be a potential etiological factor in sleep-disordered breathing. However, a significant correlation between nasal measurements and obstructive sleep apnea has not been demonstrated so far. The aim of this study was to investigate the relationships between nasal resistance, nasal volumes and selected sleep parameters using nasal measurements performed in both seated and supine positions. We also investigated whether snoring patients in our clinical sample showed increased positional or decongestive nasal mucosal changes. Material and Methods --Forty-one snoring men on a waiting list for correction of nasal obstruction underwent polysomnography, anterior rhinomanometry and acoustic rhinometry. Nineteen non-snoring control subjects were also recruited. Nasal measurements were performed in a seated position, after lying down in a supine position and, after decongestion of nasal mucosa, in a seated position again. Results --In the overall patient group, nasal volume at a distance 2-4 cm from the nares in the supine position correlated inversely with apnea-hypopnea index (AHI) ( r = m 0.32, p <0.05) and oxygen desaturation index (ODI) ( r = m 0.49, p <0.05). In the non-obese patients, total nasal resistance measured in a supine position correlated with AHI ( r =0.50, p <0.05) and ODI ( r =0.58, p <0.05) and supine nasal volumes were also inversely correlated with ODI. No significant correlations were found between baseline nasal measurements performed in a seated position and sleep parameters. Postural or decongestive changes in nasal measurements were not increased in snoring patients compared with control subjects. Conclusion --The relationship found between nasal measurements and sleep parameters suggests that nasal obstruction does augment airway collapse.

Radiofrequency thermal ablation for patients with nasal symptoms: a systematic review of effectiveness and complications

Radiofrequency ablation (RFA) is a relatively new method for the reduction of submucosal tissue. The method has gained increasing popularity in the treatment of snoring, tonsillar hypertrophy, tongue base hypertrophy, and nasal obstruction secondary to non-allergic or allergic rhinitis. We present a systematic literature review of current knowledge on the effectiveness, and complications of nasal radiofrequency thermal ablation (RFA) in the treatment of nasal obstruction. We performed a computerized literature search using several databases to select articles dealing with RFA treatment in the field of otorhinolaryngology. Selected articles were independently appraised by at least two of the authors. Thirty-five articles met the inclusion criteria. Twenty-six articles were reports on uncontrolled patient series. Of the nine included randomized controlled trials only one reported a double-blind comparison. Most of the studies reported an improvement in subjective symptoms after treatment and the number of serious side effects was small. However, the only placebo-controlled trial did not show effectiveness. Nasal-RFA appears to be a safe operative procedure and may reduce inferior turbinate submucosal tissue volume in patients having chronic nasal obstruction and who fail to respond to medical treatment. Based on current knowledge, RFA alters the nasal mucosa only slightly and causes only minor discomfort and risk of side effects for the patient. However, most of the published studies on nasal-RFA are observational and have a relatively short follow-up. Consequently, there is an urgent need for well-planned, double-blind, placebo-controlled randomized trials on nasal-RFA treatment.

Radiofrequency ablation treatment of soft palate for patients with snoring: A systematic review of effectiveness and adverse effects†

To assess the effectiveness and adverse effects of radiofrequency ablation (RFA) of soft palate (SP) in snoring.

Postoperative infection following nasal septoplasty.

This retrospective study evaluates the incidence and spectrum of infectious complications in 100 consecutive adult nasal septoplasty patients. A total of 12 patients (mean age 40 years; age range 24-55 years) suffered from postoperative infection, and 3/12 had received prophylactic antibiotics. Patients presented with abscess formation ( n =7), submucosal swelling and flush ( n =4) and haematoma and high fever ( n =1). None of the patients had life-threatening complications, such as meningitis, endocarditis or septic/toxic shock. After surgical drainage, antibiotic treatment was given orally or intravenously. The mean hospitalization time was 3.6 days. To assess the clinical outcome, 8/12 patients were re-examined about 1.8 years after the operation. They all had an improved rhinological status. Septoplasty had been successful in relieving nasal obstruction in seven (88%) patients. Staphylococcus aureus was isolated from the nasal mucosa in three (38%) patients, which is in line with previous findings in healthy nasal septoplasty patients. The use of antimicrobial prophylaxis in septal surgery will be discussed.

Vascular permeability factor/vascular endothelial growth factor in nasal polyps

Although the aetiology of polyps is still, for the most part, unknown, the disease is known to involve tissue oedema. Vascular permeability/vascular endothelial growth factor (VPF/VEGF) is a major inducer of angiogenesis and capillary permeability. This study investigated VPF/VEGF expression in biopsies of nasal polyps from 39 patients and in healthy nasal mucosa from 10 patients by immunohistochemical staining. Staining for VPF/VEGF in the mucosal surface and in the glandular epithelium of nasal polyps was weaker than in normal controls. In two patients, strong staining for VPF/VEGF was found in a granular pattern in mast cells, while the mast cells in other polyposis patients appeared to be largely degranulated. VPF/VEGF was not seen in the mast cells of control patients. Although expression of VPF/VEGF was not increased in the epithelium of the nasal polyps, VPF/VEGF secreted from mast cells may take part in nasal polyp formation.Although the aetiology of polyps is still, for the most part, unknown, the disease is known to involve tissue oedema. Vascular permeability/vascular endothelial growth factor (VPF/VEGF) is a major inducer of angiogenesis and capillary permeability. This study investigated VPF/VEGF expression in biopsies of nasal polyps from 39 patients and in healthy nasal mucosa from 10 patients by immunohistochemical staining. Staining for VPF/VEGF in the mucosal surface and in the glandular epithelium of nasal polyps was weaker than in normal controls. In two patients, strong staining for VPF/VEGF was found in a granular pattern in mast cells, while the mast cells in other polyposis patients appeared to be largely degranulated. VPF/VEGF was not seen in the mast cells of control patients. Although expression of VPF/VEGF was not increased in the epithelium of the nasal polyps, VPF/VEGF secreted from mast cells may take part in nasal polyp formation.