Short nasal respiratory cilia and impaired mucociliary function

Summary A 48-year-old man was examined because of anosmia. He was otherwise healthy except for mild arterial hypertension. He had stopped smoking 20 years ago. Previously he had been exposed to sulfuric acid gases for 3 years in his work. Clinical examination revealed no findings to explain his anosmia. The patient was fertile, indicating normal sperm/cilia motility. Nasal mucociliary function was examined by radioactive tracer and found to be markedly and constantly impaired. Ciliary ultrastructure in cross-sections was normal. However, in longitudinal sections the length of the cilia varied from 0.6 m to 3.9 gm. The mean length of the cilia from the cell membrane to the tip was 2.5 ± 0.9 gm, in contrast to normal ciliary length of 5–7 m. These findings represent a new structural defect among the various known ciliary abnormalities. Offprint requests to: M. Rautiainen     

Long-term follow-up of the clinical relevance of short outer dynein arms in human nasal cilia

Clinical significance of short outer dynein arms was examined in a long-term follow-up study of 76 patients with various respiratory symptoms. Clinical evaluations, nasal mucociliary transport rate (NMTR) measurement and transmission electron microscopy were performed. Follow-up examinations took place 5–11 years later. In the initial examination four patients and on follow-up seven patients were found to have short outer dynein arms in their nasal mucosal biopsies. Short dynein arms were associated with a slow NMTR, poorly coordinated ciliary beat direction, and clinical symptoms of perennial rhinitis and recurrent sinusitis. Short dynein arms were found to be a significant histologic finding and probably represent a variant of primary ciliary dyskinesia. In some cases short outer dynein arms may be a reversible finding with improving clinical symptoms. It is obvious that at least part of dynein defects are acquired. Received: 23 December 1997 / Accepted: 15 May 1998     

Comparison of Chondroitin Sulfate and Hyaluronic Acid Doped Conductive Polypyrrole Films for Adipose Stem Cells

Polypyrrole (PPy) is a conductive polymer that has aroused interest due to its biocompatibility with several cell types and high tailorability as an electroconductive scaffold coating. This study compares the effect of hyaluronic acid (HA) and chondroitin sulfate (CS) doped PPy films on human adipose stem cells (hASCs) under electrical stimulation. The PPy films were synthetized electrochemically. The surface morphology of PPy–HA and PPy–CS was characterized by an atomic force microscope. A pulsed biphasic electric current (BEC) was applied via PPy films non-stimulated samples acting as controls. Viability, attachment, proliferation and osteogenic differentiation of hASCs were evaluated by live/dead staining, DNA content, Alkaline phosphatase activity and mineralization assays. Human ASCs grew as a homogenous cell sheet on PPy–CS surfaces, whereas on PPy–HA cells clustered into small spherical structures. PPy–CS supported hASC proliferation significantly better than PPy–HA at the 7 day time point. Both substrates equally triggered early osteogenic differentiation of hASCs, although mineralization was significantly induced on PPy–CS compared to PPy–HA under BEC. These differences may be due to different surface morphologies originating from the CS and HA dopants. Our results suggest that PPy–CS in particular is a potential osteogenic scaffold coating for bone tissue engineering.     

Mucociliary function of the eustachian tube in the eustachian tube dysfunction

Background: Most of the tests to evaluate the eustachian tube (ET) function are focused on the ventilation function of the ET.

Aim: Here we evaluate mucociliary function of the ET in patients with ET dysfunction.

Materials and methods: Ten patients with ET dysfunction were enrolled into the study. Six patients had chronic tympanic membrane retraction and four patients had chronic middle ear effusion (MEE). All patients had intact tympanic membranes. Tympanometry and clinical examinations were done to all patients. Mucociliary function was evaluated with technetium labeled albumin and blue dye. Tympanometry and clinical examinations were done to six patients with chronic tympanic membrane retraction and four patients with chronic middle ear effusion (MEE). Mucociliary function of the ET was evaluated with technetium labeled albumin and blue dye placed into middle ear through an intact tympanic membrane and followed from nasopharynx ET orifice (blue dye) and with gamma camera (technetium).

Results: Blue dye was observed in tubal orifice in six (6 of 10) patients during 30?min observation. Five of those patients (5 of 6) had tympanic membrane retraction and one patient (1 of 6) had MEE. Tracer activity decreased from middle ear in six (6 of 10) patients. Four of those patients had tympanic membrane retraction and two had MEE.

Conclusion: Mucociliary function of the ET seems to be better in patients with tympanic membrane retraction than patients with middle ear effusion.

Significance: Mucociliary function of the ET is an important function for middle ear aeration, blue dye test is easily available to be used also in clinical practice.     

In situ hybridization detection of human herpesvirus 6 in brain tissue from fatal encephalitis

A 23-month-old girl died after 2 days' illness with rash, fever, and convulsions. Neuropathologic findings were consistent with viral hemorrhagic encephalitis in pontine tegmentum and medial thalamic areas. Human herpesvirus 6 (HHV-6) DNA was detected in pontine nuclei by in situ hybridization. In addition, polymerase chain reaction for HHV-6 of serum and paraffin-embedded pontine tissue was positive, and serology indicated an acute primary infection. This is the first case showing HHV-6 DNA in the brain cells of an immunocompetent patient with acute encephalitis.     

Comprehensive characterization of HNPCC-related colorectal cancers reveals striking molecular features in families with no germline mismatch repair gene mutations

A considerable fraction of families with HNPCC shows no germline mismatch repair (MMR) gene mutations. We previously detected 'hidden' MMR gene defects in 42% of such families, leaving the remaining 58% 'truly' mutation negative. Here, we characterized 50 colorectal carcinomas and five adenomas arising in HNPCC families; 24 truly MMR gene mutation negative and 31 MMR gene mutation positive. Among 31 tumors from MMR gene mutation positive families, 25 (81%) had active Wnt signaling as indicated by aberrant beta-catenin localization with or without CTNNB1 mutations, compared to only 7/18 tumors from MMR gene mutation negative families (39%; P=0.005). CGH studies revealed stable profiles in 9/16 (56%) of MMR gene mutation negative tumors, which was significantly associated with membranous beta-catenin (P=0.005). Tumors with membranous beta-catenin from the MMR gene mutation negative group also showed low frequency of TP53 mutations compared to those with nuclear beta-catenin. Thus, a majority of the MMR gene mutation negative cases exhibited a novel molecular pattern characterized by the paucity of changes in common pathways to colorectal carcinogenesis. This feature distinguishes the MMR gene mutation negative families from both HNPCC families linked to MMR defects and sporadic cases, suggesting the involvement of novel predisposition genes and pathways in such families.     

Trophic transfer of cyanobacterial toxins from zooplankton to planktivores: consequences for pike larvae and mysid shrimps

The aim of this study was to evaluate the potentially harmful effects of zooplankton preexposed to cyanobacteria on two planktivorous animals: a fish larva (pike, Esox lucius) and a mysid shrimp (Neomysis integer). The planktivores were fed zooplankton from a natural community that had been preexposed to cell-free extract or to purified toxin (nodularin) of the cyanobacterium Nodularia spumigena, and the growth, feeding, and pellet production of the planktivores, as well as the toxin content of the pellets, were measured. In addition, radiolabeled nodularin ((3)H-dihydronodularin) was used in separate experiments to measure the vector transfer of nodularin from zooplankton to their predators. During 11-day exposures, dissolved nodularin was transferred to pike larvae and N. integer via zooplankton at very low rates of accumulation. Treatment with N. spumigena extract decreased the ingestion and feces production rates of pike larvae. With purified nodularin alone, no such effect could be observed. No effect on molting cycle length, fecal pellet production, C:N ratio, or growth of N. integer was detected. The results suggest that dissolved cyanobacterial toxins released during bloom decay can have a negative impact on feeding and, hence, on the growth of fish larvae via zooplankton, even without direct contact between cyanobacteria and the fish.     

Effects of premium discount on workers' compensation claims in agriculture in Finland

BACKGROUND: The objective of this study was to measure changes in injury claim rates after a premium discount program was implemented in the Finnish farmers' workers' compensation insurance. We focused on measures that could indicate whether the changes occurred in the true underlying injury rate, or only in claims reporting. METHODS: Monthly injury claim rates were constructed at seven disability duration levels from January 1990 to December 2003. We conducted interrupted time series analyses to measure changes in the injury claim rates after the premium discount was implemented on July 1, 1997. Three additional policy change indicators were included in the analyses. RESULTS: The overall injury claim rate decreased 10.2%. Decreases occurred at four severity levels (measured by compensated disability days): 0 days (16.3%), 1-6 days (14.1%), 7-13 days (19.5%), and 14-29 days (8.4%). No changes were observed at higher severity levels. Minor injuries had a seasonal pattern with higher rates in summer months while severe injuries did not have a seasonal pattern. CONCLUSIONS: The premium discount decreased the overall claim rate. Decreases were observed in all categories up to 29 disability days. This pattern suggests that under-reporting contributes to the decrease but may not be the only factor. The value of the premium discount is lower than the value of a lost-time claim, so there was no financial reason to under-report lost-time injuries. Under-reporting would be expected to be greatest in the 0 day category, but that was not the case. These observations suggest that in addition to under-reporting, the premium discount may also have some preventive effect.