Riste Saat

Basement membrane collagen type IV expression by human mesenchymal stem cells during adipogenic differentiation

During adipogenic differentiation human mesenchymal stem cells (hMSC) produce collagen type IV. In immunofluorescence staining differentiating hMSCs started to express collagen type IV when Oil Red O‐positive fat droplets appeared intracellularly. Quantitative real time‐polymerase chain reaction confirmed progressive increase of collagen type IV α1 and α2 mRNA levels over time, 18.6‐ and 12.2‐fold by day 28, respectively, whereas the copy numbers of α3–α6 mRNAs remained rather stable and low. Type IV collagen was in confocal laser scanning microscopy seen around adipocytes, where also laminins and nidogen were found, suggesting pericellular deposition of all key components of the fully developed basement membrane. Immunofluorescence staining of matrix metalloproteinase‐2 (MMP‐2, 72 kD type IV collagenase, gelatinase A) and MMP‐9 (92 kD type IV collagenase, gelatinase B) disclosed only faint staining of MSCs, but MMP‐9 was strongly induced during adipogenesis, whereas MSC supernatants disclosed in zymography pro‐MMP‐2 and faint pro‐MMP‐9 bands, which increased over time, with partial conversion of pro‐MMP‐2 to its active 62 kD form. Differentiation was associated with increasing membrane type 1‐MMP/MMP‐14 and tissue inhibitor of metalloproteinase‐2 (TIMP‐2) staining, which may enable participation of type IV collagenases in basement membrane remodelling via ternary MT1‐MMP/TIMP‐2/MMP‐2 or −9 complexes, focalizing the fully active enzyme to the cell surface. MMP‐9, which increased more in immunofluorescence staining, was perhaps preferentially bound to cell surface and/or remodelling adipocyte basement membrane. These results suggest that upon MSC‐adipocyte differentiation collagen type IV synthesis and remodelling become necessary when intracellular accumulation of fat necessitates a dynamically supporting and instructive, partly denatured adipogenic pericellular type IV collagen scaffold.

MR Imaging Features of Acute Mastoiditis and Their Clinical Relevance

BACKGROUND AND PURPOSE: MR imaging is often used for detecting intracranial complications of acute mastoiditis, whereas the intratemporal appearance of mastoiditis has been overlooked. The aim of this study was to assess the imaging features caused by acute mastoiditis in MR imaging and their clinical relevance. MATERIALS AND METHODS: Medical records and MR imaging findings of 31 patients with acute mastoiditis (21 adults, 10 children) were analyzed retrospectively. The degree of opacification in the temporal bone, signal and enhancement characteristics, bone destruction, and the presence of complications were correlated with clinical history and outcome data, with pediatric and adult patients compared. RESULTS: Most patients had ≥50% of the tympanic cavity and 100% of the mastoid antrum and air cells opacified. Compared with CSF, they also showed intramastoid signal changes in T1 spin-echo, T2 TSE, CISS, and DWI sequences; and intramastoid, outer periosteal, and perimastoid dural enhancement. The most common complications in MR imaging were intratemporal abscess (23%), subperiosteal abscess (19%), and labyrinth involvement (16%). Children had a significantly higher prevalence of total opacification of the tympanic cavity (80% versus 19%) and mastoid air cells (90% versus 21%), intense intramastoid enhancement (90% versus 33%), outer cortical bone destruction (70% versus 10%), subperiosteal abscess (50% versus 5%), and perimastoid meningeal enhancement (80% versus 33%). CONCLUSIONS: Acute mastoiditis causes several intra- and extratemporal changes on MR imaging. Total opacification of the tympanic cavity and the mastoid, intense intramastoid enhancement, perimastoid dural enhancement, bone erosion, and extracranial complications are more frequent in children.

Bacteriology in relation to clinical findings and treatment of acute mastoiditis in children.

OBJECTIVE We assessed clinical, radiological, laboratory and microbiological findings in children with acute mastoiditis in order to improve the diagnostics and treatment of these patients. We also investigated whether different pathogens cause different clinical findings of mastoiditis. METHODS A retrospective review of the medical records of all children aged 0-16 years treated as in-ward patients for acute mastoiditis at Helsinki University Central Hospital, Department of Otorhinolaryngology, between 2003 and 2012. RESULTS Fifty-six patients met the inclusion criteria. The incidence of mastoiditis was 1.88/100000/year. The most common pathogens were Streptococcus pneumoniae (38%), Streptococcus pyogenes (11%) and Pseudomonas aeruginosa (11%). Of S. pneumoniae, 48% had reduced susceptibility (intermediate or resistant) for the common antimicrobials; this was clearly overrepresented relative to the background population (p<0.001). Otalgia and retroauricular symptoms were common in the patients with S. pneumoniae. Otorrhoea was less common (p=0.03) in these patients relative to the other pathogens. Patients with S. pneumoniae had more destruction of the mastoid septa (p=0.05) than patients with any of the other pathogens. Mastoidectomy was performed in 34% of all cases, it was most common (60%) in the patients with S. pneumoniae with reduced susceptibility. The patients with S. pyogenes had less otalgia and seemed to have less retroauricular symptoms relative to other pathogens. P. aeruginosa especially affected children with tympanostomy tubes, caused otorrhoea in all patients and caused a milder form of disease with less retroauricular swelling (p=0.04) than the other pathogens, and there was no need for mastoidectomies. The younger children (<2 years) had less otorrhoea and more retroauricular symptoms of infection than the older patients. No significant differences emerged in outcome of the patient groups. CONCLUSIONS The clinical findings of acute mastoiditis differ according to the causative pathogen. S. pneumoniae, especially strains with reduced susceptibility, causes severe symptoms and leads to mastoidectomy more often than the other pathogens. S. pyogenes causes less otalgia than the other pathogens. P. aeruginosa particularly affects children with tympanostomy tubes and causes a less aggressive form of disease.

Intracranial abscesses over the last four decades; changes in aetiology, diagnostics, treatment and outcome

Abstract Background The development of modern medicine has resulted in changes in the predisposing conditions, clinical picture, treatment and results of treatment of intracranial abscesses. This study sought to evaluate these changes in a hospital district. Methods A retrospective analysis of the clinical data of all patients treated due to intracranial abscesses at a tertiary referral centre, between 1970–2012. Results The total number of intracranial abscesses was 166. The incidence of intracranial abscesses was 0.33/100 000/year (2000–2012). The most common predisposing conditions were infection of the ear-, nose- and throat region (22%), odontogenic infection (15%) and cardiac anomaly (13%). Lately (2000–2012), infections of the ear-, nose- and throat region (15%) and cardiac anomalies (5%) have become less common, whereas odontogenic infections (32%) have become more common. The most common pathogens belong to Streptococcus spp (42%), Fusobacteriae (14%), Actinomycetales (8%) and Staphylococcus spp (8%). Most patients (66%) experienced a favourable recovery; the proportion of patients with favourable outcome enabling return to prior occupation rose over time, from 12% in 1970–1989 to 24% in 1990–2012. Conclusions The predisposing conditions for intracranial abscesses have changed markedly within the study period. Odontogenic infections have become a common predisposing condition, whereas infections of the ear-, nose- and throat region and cardiac malformations are nowadays less common as predisposing conditions compared to at the beginning of the study period. The proportion of patients with favourable outcome enabling return to prior occupation seems to have increased with time.

Boron Neutron Capture Therapy in the Treatment of Recurrent Laryngeal Cancer.

PURPOSE To investigate the safety and efficacy of boron neutron capture therapy (BNCT) as a larynx-preserving treatment option for patients with recurrent laryngeal cancer. METHODS AND MATERIALS Six patients with locally recurrent squamous cell laryngeal carcinoma and 3 patients with persistent laryngeal cancer after prior treatment were treated with BNCT at the FiR1 facility (Espoo, Finland) in 2006 to 2012. The patients had received prior radiation therapy with or without concomitant chemotherapy to a cumulative median dose of 66 Gy. The median tumor diameter was 2.9 cm (range, 1.4-10.9 cm) before BNCT. Boron neutron capture therapy was offered on a compassionate basis to patients who either refused laryngectomy (n=7) or had an inoperable tumor (n=2). Boronophenylalanine-fructose (400 mg/kg) was used as the boron carrier and was infused over 2 hours intravenously before neutron irradiation. RESULTS Six patients received BNCT once and 3 twice. The estimated average gross tumor volume dose ranged from 22 to 38 Gy (W) (mean; 29 Gy [W]). Six of the 8 evaluable patients responded to BNCT; 2 achieved complete and 4 partial response. One patient died early and was not evaluable for response. Most common side effects were stomatitis, fatigue, and oral pain. No life-threatening or grade 4 toxicity was observed. The median time to progression within the target volume was 6.6 months, and the median overall survival time 13.3 months after BNCT. One patient with complete response is alive and disease-free with a functioning larynx 60 months after BNCT. CONCLUSIONS Boron neutron capture therapy given after prior external beam radiation therapy is well tolerated. Most patients responded to BNCT, but long-term survival with larynx preservation was infrequent owing to cancer progression. Selected patients with recurrent laryngeal cancer may benefit from BNCT.

Children hospitalized due to acute otitis media: How does this condition differ from acute mastoiditis?

OBJECTIVES To evaluate the clinical picture and microbiological findings of children hospitalized due to acute otitis media and to analyze how it differs from acute mastoiditis. METHODS A retrospective review of the medical records of all children (0-16 years) hospitalized due to acute otitis media in the Department of Otorhinolaryngology at the Helsinki University Hospital, between 2003 and 2012. Comparison with previously published data of children with acute mastoiditis (n=56) from the same institute and period of time. RESULTS The most common pathogens in the children hospitalized due to acute otitis media (n=44) were Streptococcus pneumoniae (18%), Pseudomonas aeruginosa (16%), Streptococcus pyogenes (14%), and Staphylococcus aureus (14%). One of the most common pathogens of out-patient acute otitis media, Haemophilus influenzae, was absent. Otorrhea was common in infections caused by S. pyogenes and otorrhea via tympanostomy tube in infections caused by P. aeruginosa. In children under 2 years-of-age, the most common pathogens were S. pneumoniae (43%), Moraxella catarrhalis (14%), and S. aureus (7%). S. pyogenes and P. aeruginosa were only found in children over 2 years-of-age. Previous health problems, bilateral infections, and facial nerve paresis were more common in children hospitalized due to acute otitis media, compared with acute mastoiditis, but they also demonstrated lower CRP values and shorter duration of hospital stay. The number of performed tympanostomies and mastoidectomies was also comparatively smaller in the children hospitalized due to acute otitis media. S. aureus was more common and S. pneumoniae, especially its resistant strains, was less common in the children hospitalized due to acute otitis media than acute mastoiditis. CONCLUSIONS Acute otitis media requiring hospitalization and acute mastoiditis compose a continuum of complicated acute otitis media that differs from common out-patient acute otitis media. The bacteriology of children hospitalized due to acute otitis media resembled more the bacteriology of acute mastoiditis than that of out-patient acute otitis media. The children hospitalized due to acute otitis media needed less surgical treatment and a shorter hospitalization than those hospitalized due to acute mastoiditis.

Submandibular gland cancer: Specific features and treatment considerations

In the absence of unified treatment protocol, we evaluated the management and outcomes of submandibular gland cancers in an unselected patient series.

Multidisciplinary Approach to Management of Temporal Bone Giant Cell Tumor.

Background Giant cell tumors (GCTs) are rare osseous tumors that rarely appear in the skull. Methods We review the clinical course of a 28-year-old previously healthy woman with a complicated GCT. Results The reviewed patient presented with a middle cranial fossa tumor acutely complicated by reactive mastoiditis. Left tympanomastoidectomy was performed for drainage of the mastoiditis and for biopsies of the tumor. Due to the challenging tumor location, the patient was treated with denosumab, a fully humanized monoclonal antibody against receptor activator of nuclear factor kappa-B ligand, for 7 months, which resulted in significant preoperative tumor shrinkage. Extensive temporal craniotomy and resection of the tumor followed utilizing a temporomandibular joint total endoprosthesis for reconstruction. A recurrence of the tumor was detected on computed tomography at 19 months after surgery and treated with transtemporal tumor resection, parotidectomy, and mandible re-reconstruction. Conclusion A multidisciplinary approach resulted in a good functional result and, finally, an eradication of the challengingly located middle cranial fossa tumor.

Severe Acute Otitis Media and Acute Mastoiditis in Adults.

OBJECTIVE To evaluate and compare clinical and microbiological findings in adults hospitalized for acute otitis media (AOM) or mastoid infections (acute or latent). MATERIALS AND METHODS We retrospectively reviewed the medical records of all adults (≥17 years old) hospitalized (between 2003 and 2012) at a tertiary referral center for acute mastoid infections or AOM not responding to outpatient medical treatment. RESULTS Of the 160 patients in the study sample, 19% had an infection caused by S. pyogenes, 14% by S. pneumoniae, and 11% by P. aeruginosa. AOM was the most common infection (38%), whereas 33% had acute mastoiditis (AM), 18% had latent mastoiditis (LM), and 13% AM of a chronically infected ear (AMc). In contrast to the other infections, P. aeruginosa (30%) and S. aureus (25%) were most common in AMc. Otorrhea (83%), tympanic membrane perforation (57%), and hearing problems (83%) were common in S. pyogenes infections. Patients with S. pneumoniae had longer lengths of hospitalization than those with other bacterial infections (7 vs. 4 days). Otorrhea (94%) and retroauricular symptoms were more common in P. aeruginosa infections. Hearing symptoms were common (67%) but fever (32%) and retroauricular symptoms were uncommon in AOM. Fever (44%) and mastoid tenderness (65%) were common in AM. Patients with LM underwent the most mastoidectomies (54%). Prior medical conditions, retroauricular symptoms, otorrhea (90%), and post-infection problems were common in AMc. CONCLUSION The bacteriological etiology of hospitalized AOM more closely resembled those of LM and AM than that of AMc. Adults hospitalized for AOM or AM required fewer mastoidectomies than those hospitalized for LM or AMc.

Otogenic Intracranial Abscesses, Our Experience Over the Last Four Decades

OBJECTIVE To evaluate the predisposing factors for otogenic intracranial abscesses, assess their changes over time, and analyze how they differ from those due to other causes. MATERIALS AND METHODS The medical records of all patients treated for otogenic intracranial abscesses, between 1970 and 2012 at a tertiary referral center, were retrospectively analyzed. The analysis included patient demographics, clinical characteristics, causative pathogens, treatments, outcomes, and comparisons of otogenic and non-otogenic intracranial abscesses. RESULTS Of all intracranial abscesses, 11% (n=18) were otogenic. In the 1970s, otogenic infections were a common predisposing factor for intracranial abscess; but within our study period, the incidence of otogenic intracranial abscesses decreased. Most (94%) otogenic cases were due to chronic suppurative otitis media and 78% were associated with cholesteatoma. Most patients (94%) had ear symptoms. The most common presenting symptoms were discharge from the infected ear (50%), headache (39%), neurological symptoms (28%), and fever (17%). The most common pathogens belonged to Streptococcus spp. (33%), Gram-negative enteric bacteria (22%), and Bacteroides spp. (11%). Neurosurgery was performed on all patients, 69% of which were prior to a later ear surgery. Surgery of the affected ear was performed on 14 patients (78%). A favorable recovery was typical (78%); however, one patient died. CONCLUSION Otogenic intracranial abscesses were most commonly due to a chronic ear infection with cholesteatoma. Ear symptoms and Gram-negative enteric bacteria were more common among patients with otogenic than non-otogenic intracranial abscesses.