Classification of the external auditory canal cholesteatoma

OBJECTIVES/HYPOTHESIS: The external auditory canal cholesteatoma (EACC) is a rare disease in the field of otolaryngology. Only 1 in 1,000 new otologic patients present with this entity, which was first described by Toynbee. The aim of this article is to classify EACC by different histopathologic and clinical findings of patients presenting to the Department of Otolaryngology at the University of Mannheim, Germany. METHODS: From 2000 to 2004, 17 patients presented to our clinic with EACC. The cholesteatoma were treated surgically, and the specimens were investigated histologically. Clinical findings were also recorded. We classified four stages: stage I with hyperplasia of the canal epithelium, stage II including periosteitis, Stage III including a defective bony canal, and stage IV showing an erosion of adjacent anatomic structure. RESULTS: Eight patients presented with stage II, five patients with stage III, three with stage I, and only one patient presented with erosion of the mastoid cells, which was determined as stage IV. CONCLUSION: In summary, our classification serves to describe the different histopathologic and clinical stages of EACC.     

Diacylglycerol-containing docosahexaenoic acid in acyl chain modulates airway smooth muscle tone

We synthesized and assessed the role of a diacylglycerol (DAG)-containing docosahexaenoic acid (DHA), that is, 1-stearoyl-2-docosahexaenoyl-sn-glycerol (SDHG), in the contraction of guinea pig airway smooth muscle (ASM). We compared its action with 1-stearoyl-2-arachidonoyl-sn-glycerol (SAG) and 1,2-dioctanoyl-sn-glycerol (1,2-DiC8), a stable DAG analog. The three DAGs (SAG, SDHG, and 1,2-DiC8) induced reversible concentration-dependent contraction of ASM. SDHG induced higher guinea pig ASM contraction than did SAG and 1,2-DiC8. The effects of SDHG were blocked, to different extents, by nifedipine (L-type Ca2+ channel blocker). By employing GF-109203X (protein kinase C [PKC] inhibitor) and lanthanum (La3+), a nonselective cation channel blocker, we observed that SDHG evoked ASM contractile response via PKC-dependent and PKC-independent (but Ca2+-dependent) pathways. Interestingly, SAG exerted its action only by increasing [Ca2+]i and did not require PKC activation. To probe the implication of calcium mobilization, we employed thapsigargin (TG), which also induced ASM contraction in a calcium-dependent manner. SDHG and 1,2-DiC8, in a PKC-dependent manner, induced the phosphorylation of CPI-17 (myosin light chain phosphatase inhibitor of 17 kD). Furthermore, SAG and TG failed to phosphorylate CPI-17 in ASM cells. Our results suggest that different DAG species, produced during a dietary supplementation with fatty acids, could modulate the reactivity of airway smooth muscles in a PKC-dependent and -independent manner, and hence, may play a critical role in health and disease.     

Effect of subcutaneous insulin on intestinal adaptation in a rat model of short bowel syndrome

Insulin has been shown to influence intestinal structure and absorptive function. The purpose of the present study was to evaluate the effects of parenteral insulin on structural intestinal adaptation, cell proliferation, and apoptosis in a rat model of short bowel syndrome (SBS). Male Sprague-Dawley rats were divided into three experimental groups: sham rats underwent bowel transection and reanastomosis, SBS rats underwent a 75% small bowel resection, and SBS-INS rats underwent a 75% small bowel resection and were treated with insulin given subcutaneously at a dose of 1 U/kg, twice daily, from day 3 through day 14. Parameters of intestinal adaptation, enterocyte proliferation, and enterocyte apoptosis were determined on day 15 following operation. SBS rats demonstrated a significant increase in jejunal and ileal bowel and mucosal weight, villus height and crypt depth, and cell proliferation index compared with the sham group. SBS-INS animals demonstrated higher jejunal and ileal bowel and mucosal weights, jejunal and ileal mucosal DNA and protein, and jejunal and ileal crypt depth compared with SBS animals. SBS-INS rats also had a greater cell proliferation index in both jejunum and ileum and a trend toward a decrease in enterocyte apoptotic index in jejunum and ileum compared with the SBS untreated group. In conclusion, parenteral insulin stimulates structural intestinal adaptation in a rat model of SBS. Increased cell proliferation is the main mechanism responsible for increased cell mass.     

Expression von Zell-Zell-Adhäsionsproteinen im Gehörgangscholesteatom

BACKGROUND: External auditory canal cholesteatoma (EACC) is a rare entity in otolaryngology, which is histomorphologically identical with middle ear cholesteatoma. The cause of EACCt is, however, still not clear. The aim of this study was to describe the expression of beta-catenin, MMP-2, and MMP-9 in EACC matrix compared to the normal auditory meatal skin (AMS). METHODS: Thirteen specimens were obtained during surgical procedure. EACC and AMS specimens were immunostained with antibodies for beta-catenin, MMP-2, and MMP-9. RESULTS: Only the basal layers of the EACC specimens were positive for beta-catenin. The suprabasal layers showed diminished or negative immunostaining for beta-catenin. In all layers, AMS was homogeneously positive for beta-catenin. In contrast, the immunostaining for the gelatinases was equally increased in all layers of EACC, whereas AMS was weekly positive. CONCLUSION: The reduced immunoreactivity for beta-catenin may have been present because of the lessened cell-cell adhesion in the suprabasal layers of EACC. The increased expression of the metalloproteinases might point at an increased lack of integrity of EACC matrix. Recent studies revealed a balance between disintegrating and stabilising factors in normal tissue, which is disturbed in inflamed and neoplastic tissue. In EACC matrix, an imbalance of these factors, represented by reduced beta-catenin and increased gelatinase expression, is possible. Increased desquamation, the accumulation of keratin debris, and loss of tissue-stability support our findings.     

Granular cell tumor--a rare, benign respiratory tract neoplasm in the material of the Institute of Tuberculosis and Lung Diseases

The granular cell tumor (GCT) is a nodule that arises most commonly in the skin, the breast or the tongue. The vast majority are benign. Approximately 6-10% of granular cell tumors have been reported in the lower respiratory tract. The clinical, pathological and immunohistochemical findings of eleven cases are described in our material consisted of 6 males and 5 females aged from 35 to 58 years (median, 46 years). The GCT were solitary lesions in all our patients. The tumors were located in trachea (6 cases) and in bronchus (5 cases). They were found during bronchoscopy performed because of symptoms of pneumonia, lung cancer and hemoptysis or dyspnea alone. Diameter of the tumors ranged from 0.2-2.5 cm (median 1.2 cm). Six tumors were surgically excised and 5 were endoscopically removed. Pulmonary GCT behave in a benign fashion. It was observed that tumors of less than 8 mm were more amenable to endoscopic removal and larger tumors were more likely to infiltrate through the bronchial wall. Histologically, the GCT showed submucosal infiltrates of round or oval cells with abundant granular cytoplasm. The tumors cells were positive for S-100 protein, neuron specific enolase, CD68 and vimentin. Our immunohistochemical results are consistent with this concept.     

Effects of verteporfin therapy on central visual field function

PURPOSE: To evaluate the effect of photodynamic therapy with verteporfin on the maintenance of central visual field function. DESIGN: Randomized controlled clinical trial. PARTICIPANTS: Forty-six consecutive patients with subfoveal choroidal neovascularization (CNV) caused by age-related macular degeneration including a classic component were randomly assigned. Thirty-three participants received standard verteporfin therapy, and 13 received placebo and laser treatment. METHODS: The trial was performed as a single-center, double-masked study. Patients were examined before therapy and continuously in 3-month intervals during 2 years of follow-up. A scanning laser ophthalmoscope (SLO) was used to perform macular microperimetry. Absolute and relative scotomas were documented at each visit, and size was measured in square millimeters. MAIN OUTCOME MEASURES: The change in size of central scotoma in the verteporfin group compared with the placebo group. RESULTS: An absolute scotoma was seen in 88%, and a relative scotoma was seen in 100% of eyes before therapy. Absolute defects were associated with the classic CNV component localized angiographically. In the verteporfin group, the absolute scotoma grew from 2.5 mm(2) at baseline to a final size of 7.3 mm(2) at month 24. In the placebo group, the mean lesion size of the absolute scotoma enlarged from an initial size of 2.7 mm(2) to 31.5 mm(2) after 24 months. The relative scotoma increased from 7.9 mm(2) at baseline to 20.8 mm(2) at month 24 in the verteporfin group, whereas a progression from 8.5 mm(2) initially to 48.3 mm(2) at the final presentation was measured in the placebo group. Statistical analysis showed that both the mean absolute and relative scotoma sizes were significantly smaller in the verteporfin group than the placebo group for all intervals from 6 to 24 months (P<0.001). CONCLUSIONS: Documentation of macular function with SLO perimetry demonstrated a significant benefit of verteporfin therapy for the preservation of the central visual field. Absolute and relative scotoma sizes remained smaller after therapy. This may influence reading ability and visual rehabilitation.     

Animal models of inflammatory bowel disease

In inflammatory bowel disease (IBD), experimental models have proven to be important tools for detecting potential therapeutic agents and for investigating the mechanisms of pathogenesis. This review is intended to cover recent advances in basic IBD model applications. The use of more than 20 animal models has allowed the detection of numerous protective pharmacological agents, including a number of immunomodulatory agents that have entered the therapeutic armamentarium. The models have been classified into five main categories based on the methods of induction: gene knockout (KO), transgenic, chemical, adoptive transfer, and spontaneous (each with subcategories).     

Fitz-Hugh-Curtis syndrome after laparoscopic tubal ligation. A case report

BACKGROUND: Minimally invasive techniques are being used throughout all fields of surgery. With the increasing use and complexity of these cases, new complications will also develop. Fitz-Hugh-Curtis syndrome is an uncommon finding from the spread of infection in pelvic inflammatory disease, causing perihepatitis. CASE: A 29-year-old woman presented 2 weeks after an apparently uneventful laparoscopic tubal ligation with a complaint of right upper quadrant pain. She also had elevated liver function tests but normal ultrasound of the gallbladder. Eventually an intravenous pyelogram showed a bladder injury. Computed tomography revealed fluid in the pelvis and enhancement around the liver. During surgery, intense inflammation with multiple adhesions throughout the peritoneal cavity and around the liver were found. CONCLUSION: The findings were similar to the perihepatitis that occurs when Fitz-Hugh-Curtis syndrome complicates pelvic inflammatory disease. The unusual presentation in this patient made diagnosis very difficult and should remind physicians that unusual complications must be considered as technology evolves and spreads throughout all surgical fields.     

Autophagocytosis of the apical membrane in microvillus inclusion disease

BACKGROUNDS: Microvillus inclusion disease (MID) is a disorder with the clinical signs of intractable diarrhoea in the newborn and infancy. The typical pathological features of the disease are well known whereas the pathophysiology is still unclear. AIM: This study was performed to define possible alterations of the cytoskeleton and exocytic as well as endocytic pathways within enterocytes in MID. PATIENTS: Four patients with MID were studied. Three had a congenital onset of diarrhoea and one patient had a late onset form. METHODS: Thin frozen sections of small bowel biopsies of patients were labelled by antibodies against the cytoskeleton and the brush border enzyme sucrase-isomaltase. The binding sites of the primary antibodies were visualised by immunogold particles in the electron microscope. Biopsies were labelled in organ culture to analyse the biosynthetic and endocytic pathways within the enterocytes. RESULTS: Labelling with antibodies against actin and villin did not differ significantly in control and patient biopsies. Biosynthetic labelling revealed normal intracellular processing and transport of the brush border enzyme sucrase-isomaltase. Secretory granules in crypt epithelial cells were positive for sucrase-isomaltase, differing in its labelling density between patients. Patient biopsies showed microvillus inclusion bodies which endocytosed cationised ferritin within five minutes after uptake as well as ovalbumin after incubation for 10 minutes. These microvillus inclusion bodies correspond to early endosomes because they lack lysosome associated membrane proteins. Late endosomes and lysosomes containing sucrase-isomaltase did not reveal microvillus-like structures. CONCLUSION: Microvillus inclusion bodies in MID originate from autophagocytosis of the apical membrane of enterocytes with engulfing of microvilli.