The role of the 148 Asp/Glu polymorphism of the APE1 gene in the development and progression of primary open angle glaucoma development in the Polish population.

Glaucoma is an ocular disorder that is characterized by progressive degeneration of the optic nerve and loss of visual field (VF). Recent data have suggested that the level of oxidative DNA damage in human trabecular meshwork is significantly increased in glaucomatous patients as compared to controls. It was also noted that progressive loss of visual field may by connected with elevated levels of oxidative DNA lesions. This hypothesis may suggest the role of an inefficient base excision repair pathway in primary open angle glaucoma (POAG) pathogenesis. The aim of the study was to evaluate the association of the 148 Asp/Glu APE1 gene polymorphism with the risk of POAG development. One hundred fifty patients with POAG and 190 controls were enrolled in our study. Gene polymorphisms were analyzed by PCR-CTPP. We did not observe a statistically significant difference between the frequencies of alleles and genotypes of the 148 Asp/Glu APE1 gene polymorphism in POAG patients and controls. However, the presented study indicated that 148 Asp/Glu of the APE1 gene was associated with decreased risk of progression of POAG with reference to the parameter VF. We suggest that the 148 Asp/Glu APE1 gene polymorphism may decrease the risk of POAG progression.

Menière's disease as a manifestation of vestibular ganglionitis.

OBJECTIVE: To present morphologic evidence of viral-induced vestibular nerve pathology in Menière's Disease (MD). MATERIAL STUDIED: Twelve temporal bones (TB) from 8 patients with the clinical symptoms of MD. RESULTS: There was endolymphatic hydrops (EH) and perilymphatic fibrosis in 10 of the 12 TB from MD patients. Of the 10 TB with EH of the pars inferior, 3 also contained outpouchings in the pars superior (utricle and canals), and 3 showed apical spiral ganglion cell loss. Focal vestibular nerve axonal degeneration was observed in all but one TB. CONCLUSION: Morphologic changes in TB of patients with MD, and clinical observations in patients with recurrent vestibulopathy, support the concept that the pathologic mechanism responsible for auditory and vestibular symptoms in MD may be reactivation of a latent viral vestibular ganglionitis.

[The attempt to identify mutations in TIGR gene in Polish patients with primary open angle glaucoma]. / Próba identyfikacji mutacji w genie TIGR w polskiej populacji chorych na jaskre pierwotna otwartego kata.

PURPOSE: The case work presents studies on the identification of the most frequent TIGR mutations in Polish population with primary open angle glaucoma. The TIGR gene was identified in a GLC1A locus on chromosome 1 (1q) in a family with juvenile primary open angle glaucoma. The gene encodes TIGR protein (trabecular meshwork inducible gluco-corticoid response protein)--trabecular meshwork glucoprotein. MATERIAL AND METHODS: Ophthalmologic examination was performed in twenty subjects with juvenile primary open angle glaucoma. The blood samples were taken for DNA analyses. RESULTS: Neither any mutations nor polymorphic changes in TIGR gene were found. CONCLUSION: Our studies have not identified any mutations in exon 3 of TIGR gene. We cannot exclude, however, that mutations are localised in other exons or regulatory region of examined gene. The questions how many genes, how many mutations of these genes and how often they contribute to glaucoma in general population are still open? These are important questions to answer in order to get closer to understanding extremely complicated aetiology of glaucoma.

[Genetic studies on primary open angle glaucoma]. / Badania genetyczne rodzin w jaskrze pierwotnej otwartego kata.

Case work presents the newest studies on molecular genetics in primary open angle glaucoma. The molecular genetics in all types of glaucoma have been a subject of investigations for the last few years. As a result, two loci (GLC3A and GLC3B) have been identified for primary congenital glaucoma, one locus (GLC1A) for juvenile primary open angle glaucoma and further two loci (GLC1B and GLC1C) for adult-onset primary open angle glaucoma. The gene TIGR (trabecular meshwork inducible glucocorticoid response protein) localised in GLC1A was described last year for the first time, thereafter there were trials on mutations within this gene conducted successfully. In this review there are studies presenting the mapping of the first five GLC loci and identification of mutations.

Adult spontaneous cerebrospinal fluid otorrhea: diagnosis and management.

OBJECTIVE: To describe demographic, radiologic, and surgical features in adult patients with spontaneous cerebrospinal fluid otorrhea (SCSFO). STUDIED: Review was made of office and hospital charts of 21 patients with SCSFO and 2 patients with spontaneous CSF rhinorrhea, all of which were repaired successfully from 1989 to 1998. METHOD: Radiologic examples of the structure responsible for SCSFO and rhinorrhea are used to illustrate the changes essential for diagnosis. RESULTS: The responsible lesion for SCSFO and rhinorrhea in the adult are arachnoid granulations (AG) or villi, which do not reach a venous lumen and are aberrantly distributed in areas of the anterior, middle, and posterior cranial fossae that are in proximity to the middle ear/mastoid space, ethmoid, and sphenoid sinuses. The ages of the 21 patients ranged from 38 to 83 years (mean 63 years) with all but one older than 50 years. The sex ratio was 14 women to 7 men; the CSF leak was right sided in 13 and left sided in 8 patients. Eighteen of the SCSF leaks were located in the middle cranial fossa surface of the temporal bone (TB) while two were on the posterior fossa border of the TB. The middle fossa leaks were managed by craniotomy and repair with fascia, whereas the posterior fossa defects were obliterated by adipose tissue inserted through an intact canal wall mastoidectomy. The most common radiologic finding on computerized tomography (CT) was a soft tissue mass adjacent to a tegmen bone defect. The posterior fossa AG created an erosion of cortical and trabecular bone in the mastoid compartment. Spontaneous CSF rhinorrhea in two patients also radiologically appeared as soft tissue mass adjacent to bone erosion in the sphenoid and ethmoid sinuses. These also represent aberrant AGs, which are responsible for CSF rhinorrhea in later life. CONCLUSIONS: The demographic, radiologic, and pathologic findings in this series of 21 TB and 2 paranasal sinus SCSF leaks support the concept that the responsible lesions are AGs that are aberrantly located adjacent to pneumatized parts of the skull. Because these AGs enlarge with age, they may erode through the bony confines of the TB and sinuses and present as SCSFO or rhinorrhea in middle and old age.

Evidence for laryngeal paralysis in cricoarytenoid joint arthritis.

OBJECTIVE/HYPOTHESIS: To demonstrate denervation atrophy of laryngeal muscles in a case of gout involving the cricoarytenoid joint. METHODS: The posterior cricoarytenoid (PCA) and arytenoideus (A) muscles from a 72-year-old man with extensive gout were compared with those from a normal adult larynx (age and sex unknown) using stereologic techniques for changes in muscle composition and fiber diameter. RESULTS: The PCA and A muscles in the gout specimen contained changes Indicative of muscle degeneration. In the PCA the volume fraction (VF) of intact muscle was 0.30, of degenerating muscle 0.13, and of fat 0.16. A normal PCA had a VF for intact muscle of 0.64 and 0 for degenerating muscle and fat. Similar changes were seen in the gout A muscle but were not measured. Muscle fiber diameters in the gout PCA (1,024 fibers) showed a significantly higher atrophy and hypertrophy factor than the normal PCA (1,255 fibers). The variability coefficient in the gout PCA (487) was almost double that in the normal PCA (290). Although muscle fiber diameters were not measured in the A muscle in gout, variability in fiber size was seen. CONCLUSIONS: The pattern and magnitude of muscle fiber degeneration in the PCA and A muscles from a larynx with gout fixation of the cricoarytenoid joint indicate neural degeneration. Since similar changes were not found in the thyroarytenoid (TA) and lateral cricoarytenoid (LCA), the neuropathy is selective for the posterior branch of the recurrent laryngeal nerve. This neuropathy is likely responsible for vocal cord adduction (stridor) and incomplete closure of the posterior commissure (aspiration) associated with acute cricoarytenoid arthritis. In chronic cricoarytenoid joint arthritis, ankylosis of the joint space maintains the adducted cord position.

Pseudoepitheliomatous hyperplasia versus squamous cell carcinoma of the external auditory canal.

Four case reports are presented to demonstrate the clinical and histopathologic similarity of pseudoepitheliomatous hyperplasia (PH) to squamous cell carcinoma (SCC) in the external auditory canal (EAC). In all four cases the original report of SCC on a biopsy specimen of an EAC lesion was corrected on review to PH. In one patient conservative management resulted in resolution of the EAC lesion. A second patient underwent radiation therapy and partial temporal bone resection with no SCC found in the surgical specimen. A third patient's ear canal had healed with conservative treatment and repeated biopsy revealed no malignancy. After a 6-year symptom-free interval, she developed invasive SCC with bone involvement that required surgery and radiation treatment. A fourth patient underwent a sleeve resection of the skin of the EAC that proved to be PH, and no evidence of SCC was found. A thoughtful clinical history, careful physical examination, response to conservative treatment, and close communication with the pathologist should be exercised in the evaluation of EAC lesions.

Cricoarytenoid joint mobility after chronic vocal cord paralysis.

Eleven whole organ laryngeal specimens (10 human and 1 dog) with a history of long-standing (6 months to 17 years) paralysis were studied histopathologically for changes in the cricoarytenoid (CA) joints and the intrinsic laryngeal musculature. In 9 cases the paralysis was unilateral and in 2 bilateral. No evidence of CA joint ankylosis (fibrous/osseous obliteration of joint space or degeneration of articular surfaces) was seen in the specimens. The absence of CA joint ankylosis permits the efficacy of thyroplasty medialization procedures.

Comparison of labyrinthectomy and vestibular neurectomy in the control of vertigo.

One hundred twenty-six patients who were treated with labyrinthectomy (81 patients) or vestibular neurectomy (45) between the years 1979 and 1994 were reviewed. The cause for vertigo in 124 of the 126 patients was Meniere's disease (89 patients), labyrinthitis (15), delayed endolymphatic hydrops (8), vestibular neuritis (7), and failed labyrinthectomy (5). In the remaining 2 patients, a normal labyrinth was sacrificed to fistulize a petrous apex cyst. Both procedures were equally effective in relieving vertigo (labyrinthectomy 98.8%; neurectomy 97.8%), but the length of hospitalization, length of disability before return to work, and cost were twice as great with vestibular neurectomy than with labyrinthectomy. More patients exhibited prolonged ataxia following neurectomy (5 patients) than after labyrinthectomy (2). Vestibular neurectomy was associated with several complications: reversible facial paresis (15 patients), meningitis (1), cerebrospinal fluid leak (1), and epidural hematoma (1). Labyrinthectomy was complicated by postoperative hyponatremia in 1 patient. Selective vestibular neurectomy preserved hearing in 32 (82%) of 39 patients. Criteria for recommending either ablation procedure are discussed. The incidence of sequential involvement of the contralateral ear was 1.5%.

Effect of singular neurectomy on the caloric response.

PURPOSE: This study was performed to determine the contribution of the posterior semicircular canal to the vestibulo-ocular responses (VOR) from caloric stimulation of the labyrinth. MATERIALS AND METHODS: Seven consecutive patients with disabling benign paroxysmal positional vertigo, which was treated with singular neurectomy, were tested before and after surgery with bithermal stimulation of the operated and nonoperated ears. RESULTS: There was a significant (P = .0156) decrease in the VOR from stimulation of the operated ear following singular neurectomy. The nonoperated ear showed a variety of changes that may have resulted from compensatory mechanisms and/or utricular dysfunction. CONCLUSIONS: We conclude that the posterior canal together with the lateral and superior canals are responsible for the VOR following caloric stimulation of the labyrinth.

Synthesis and characterization of iodixanol.

Iodixanol (Visipaque) is a new nonionic roentgen contrast medium intended for general use. Visipaque is a pharmaceutical formulation of iodixanol which is isotonic and iso-osmotic with blood. Two synthetic routes from 5-nitro-isophthalic acid to iodixanol are described. The chemical structure is confirmed spectroscopical data ((1)H-NMR, (13)C-NMR, FAB-MS, UV, IR and Raman). Chromotographic characteristics are related to the isomerism of iodixanol.

Singular neurectomy in the management of paroxysmal positional vertigo.

Paroxysmal positional vertigo is one of the common causes of episodic vertigo seen in neurotologic practice. It is thought to be caused by high specific gravity deposits in the cupula (cupulolithiasis) or membranous posterior semicircular canal (canalithesis) as a result of trauma, aging, viral insult, or surgical insult to the inner ear. The vast majority (90%) of patients undergo spontaneous resolution or cure by positioning maneuvers designed to dislodge the otoconial debris. The very small number of patients with disabling chronic paroxysmal positional vertigo (more than 1 year duration) can be effectively relieved of the positional vertigo (95%) by selective transection of the nerve supply to the posterior canal sense organ (singular neurectomy) through a tympanotomy approach using local anesthesia. The risk of sensorineural hearing loss is 3%.

Cochlear pathology in presbycusis.

A survey of the temporal bone collection at the Massachusetts Eye and Ear Infirmary reveals 21 cases that meet the criterion for the clinical diagnosis of presbycusis. It is evident that the previously advanced concept of four predominant pathologic types of presbycusis is valid, these being sensory, neural, strial, and cochlear conductive. An abrupt high-tone loss signals sensory presbycusis, a flat threshold pattern is indicative of strial presbycusis, and loss of word discrimination is characteristic of neural presbycusis. When the increments of threshold loss present a gradually decreasing linear distribution pattern on the audiometric scale and have no pathologic correlate, it is speculated that the hearing loss is caused by alterations in the physical characteristics of the cochlear duct, and the loss is identified as cochlear conductive presbycusis. It is clear that many individual cases do not separate into a specific type but have mixtures of these pathologic types and are termed mixed presbycusis. About 25% of all cases of presbycusis show none of the above characteristics and are classified as indeterminate presbycusis.

Preparation of white cell-reduced platelet concentrates from whole blood during component preparation.

This article introduces a new method of component preparation that is capable of producing white cell (WBC)-reduced platelet concentrates (PCs) from whole blood. Whole blood is separated into packed red cells (RBCs) and platelet-rich plasma (PRP) by centrifugation, and the PRP is expressed through a newly designed WBC removal filter into the platelet storage bag. The filtered PRP is then centrifuged and yields WBC-reduced PCs and plasma for freezing as fresh-frozen plasma (FFP). The method uses standard triple-pack blood bags and centrifugation protocols. Fifteen WBC-reduced PCs prepared with this technique had an average volume of 56.7 mL, an average Day 5 platelet content of 8.6 x 10(10) per unit, and an average Day 5 WBC content of 0.83 +/- 0.7 x 10(4) per unit (0.14 WBCs/microL). This represents WBC removal equal to at least 99.9 percent (3 log10) of the WBCs found in standard PCs prepared in our laboratory by an identical centrifugation protocol. Paired studies documented a 4.5-percent platelet loss by filtration. Filtration had no effect on the plasma prepared for FFP as measured by prothrombin time; activated partial thromboplastin time; factors I, V, VIII:C, and VIII:von Willebrand factor; antithrombin-III; albumin; globulin; or total protein. This method holds promise as a simple and highly effective technique for the production of WBC-reduced PCs by filtration during component preparation.