bluuebunny/crossref_metadata_2025 huggingface dataset:
Latanoprost: Experience of 2‐year treatment in Scandinavia
Authors: Alm Albert , Widengård Ingmar
Published: March 2003

Purpose: The aim of the study was to assess efficacy and side effects of latanoprost during two years of treatment.

Methods: The study was a randomized, parallel group, double‐masked, multicenter comparison between latanoprost and timolol in patients with open angle glaucoma or ocular hypertension, followed by an open‐label 18‐month extension during which all patients were treated with latanoprost.

Results: Latanoprost caused a marked and sustained reduction of the intraocular pressure (IOP). IOP was reduced from baseline levels 25.1±3.5 mm Hg (mean±SD) in 183 patients initially randomized to treatment with latanoprost to 17.4±2.9 mm Hg (n=66) after 24 months of treatment. For patients initially randomized to treatment with timolol the corresponding figures were 24.3±2.3 mm Hg (n=72) and 17.4±2.6 (n=41) mm Hg after 18 months of treatment with latanoprost. Two patients were withdrawn because of uncontrolled IOP and 11 patients required additional timolol treatment to maintain an adequate IOP control. Patients initially treated with timolol and switched to latanoprost had a further reduction of the IOP of 1.0 mm Hg after 6 months of treatment with latanoprost (p<0.005). 46 patients were withdrawn from the study, mostly due to increased iris pigmentation or an iris color with known high risk of developing increased pigmentation. 22 patients developed increased pigmentation of the iris. The follow‐up revealed no previously unknown ocular or systemic side effects.

Conclusion: Once daily applications of latanoprost cause a marked and sustained reduction of the IOP. The only clinically significant side effect noted was the increased pigmentation of the iris, most frequently seen in irides with a mixture of brown and blue/gray or green colors. No systemic side effect was observed.
NGF administered by microdialysis into rabbit vitreous
Authors: Waga Janina , Ehinger Berndt
Published: March 2003

Purpose: Microdialysis has been used in eye research for almost a decade. We have previously developed and used it mainly for chronic experiments and here it is used in acute experiments. It is highly suitable for both administration and withdrawal of substances from the eye, as it only permits molecules to cross the intraocular membrane without any net fluid movement in or out of the eye.

Methods: We have here investigated the ability of 125I labeled NGF (nerve growth factor) to cross a previously implanted high permeability membrane of a new type (polyether sulphone, PES, cutoff at 100 000 daltons) in the rabbit vitreous. It was perfused for different time periods with a solution containing NGF. The radioactivity of the entire vitreous was then counted.

Results: The results show detectable levels (up to 10−11M) of the substance after the perfusions.

Conclusion: We conclude that microdialysis with PES membranes is a possible method for the intraocular administration of NGF.
The 30‐Hz flicker cone ERG for monitoring the early course of central retinal vein occlusion
Authors: Larsson Jörgen , Bauer Birgitta , Andréasson Sten
Published: March 2003

Purpose: Investigation of the full‐field ERG (electoretinography) within 24 hours after the onset of symptoms in central retinal vein occlusion, and repeated examination within the following days and weeks.

Methods: Seven patients with central retinal vein occlusion were examined with full‐field ERG within less than 24 hours after the onset of their symptoms and every second to third day during the first 3 weeks. They were then followed for a period of time of six months.

Results: The amplitudes as well as the implicit times in the 30 Hz flicker ERG changed considerably within the first three weeks. In the three patients who developed rubeosis, the cone b‐wave implicit times as well as the amplitudes were altered considerably. In the patients that did not develop rubeosis, the cone b‐wave implicit times as well as the amplitudes in the 30 Hz flicker ERG were more stable.

Conclusion: The full‐field cone ERG reflects the retinal function and the ERG parameters change considerably during the first weeks after the onset of the central retinal vein occlusion. The 30 Hz flicker ERG gives important information concerning the early development of the disease. The optimal time to do a predictive ERG could be after three weeks.
Mohs' micrographic surgery for basal cell carcinomas on the eyelids and medial canthal areaI
Authors: Lindgren Gun , Lindblom Bertil , Bratel Annika Ternesten , Mölne Lena , Larkö Olle
Published: March 2003

Purpose: To analyse the characteristics of eyelid basal cell carcinomas excised using Mohs' micrographic technique.

Methods: Sixty‐six eyelid basal cell carcinomas were excised using Mohs' micrographic technique. The tumours were classified into four subtypes; morpheiform, intermediate, nodular/micronodular and superficial. Data on previous treatment of the tumours were retrieved.

Results: Thirty‐two tumours (48%) were primary, 8 tumours (12%) were incompletely excised using conventional excision surgery and 26 tumours (39%) were recurrent. Nineteen of the 26 (73%) recurrent tumours and 14 of the 32 (44%) primary tumours were nodular/micronodular. To achieve radical excision, superficial tumours needed an average of 2.0, nodular/micronodular 2.5, intermediate 2.0 and morpheiform tumours 2.9 excisions.

Conclusions: Eyelid basal cell carcinomas with ill‐defined borders or recurrent tumours are well suited for Mohs' micrographic surgery. The extensions of the tumours are difficult to determine even in some less aggressive subtypes such as superficial and nodular/micronodular basal cell carcinomas.
Magnetic resonance imaging of a non‐pigmented adenoma of the ciliary epithelium
Authors: Nakazawa Toru , Abe, Toshiaki , Sato Yumi , Yuda Fumiaki , Omura Makoto , Tamai Makoto
Published: March 2003

Purpose: A non‐pigmented adenoma of the ciliary epithelium is rare. No good documentation has been reported in which magnetic resonance imaging (MRI), histological examination, and immunohistological evaluation have all been conducted. We showed how this tumor differed from ciliary body melanoma.

Methods: We evaluated the ciliary body tumor by MRI, histological examination, and immunohistochemical examination. The data was compared with previously reported cases.

Result: The tumor was classified as an adenoma of the non‐pigmented ciliary epithelium with extracellular pools of hyaluronidase‐sensitive mucopolysaccharide. The MRI appearance of the vitreous in our patient showed hyperintensity on T1, isointensity on T2 and marked enhancement with gadolinium. None of 3 other reported patients exhibited the same signals.

Conclusion: MRI appearance is most variable in adenomas and no microscopical diagnosis can be based on that. Our patient showed isointensity on T2 with marked enhancement by gadolinium when compared to malignant melanoma.
Quantitative anomaloscopy and optical coherence tomography scanning in central serous chorioretinopathy
Authors: Bek Toke , Kandi Maria
Published: March 2003

Background: Dyschromatopsia is a prominent sign in a variety of central retinal diseases, such as central serous chorioretinopathy (CSC). The changes in colour vision may be due to either optical or neuronal factors in the diseased retina. The relative contribution from the two causes is unknown, but may be elucidated by obtaining knowledge of the anatomical derangement in the diseased retina in CSC.

Methods: Twenty‐six normal persons had their colour vision tested using the Tomey anomaloscope. The calculation of setting range (SR) and central mean point (CMP) for Rayleigh match and Moreland match was optimized, and normal ranges for these values were defined. Subsequently 24 patients with CSC were examined by anomaloscopy and optical coherence tomography scanning, and the measures of colour vision were related to the anatomical changes observed on the scans.

Results: The algorithm for calculating SR and CMP which is integrated into the Tomey anomaloscope could be considerably improved to increase sensitivity and reproducibility of these measures. Fifteen patients had abnormal colour vision. Nine patients had pseudo‐protanomaly, seven patients had pseudo‐tritanomaly, and three patients had abnormalities in both matches. There was no relation between these colour vision abnormalities and the anatomical derangement as seen by OCT in the diseased central retina.

Conclusion: The findings argue against the notion that the density of retinal cell nuclei, the orientation of photoreceptors, or the size of the central serous detachment are related to the colour vision abnormalities in CSC. The question of whether these abnormalities are due to optical or neuronal factors remains open.
Detection of changes of the optic disc in glaucomatous eyes: Clinical examination and image analysis with the Topcon Imagenet system
Authors: Azuara‐Blanco Augusto , Katz L. Jay , Spaeth George L. , Nicholl Jamie , Lanzl Ines M.
Published: March 2003

Purpose: This study was designed to evaluate the clinical agreement in the detection of optic disc changes and the ability of computerized image analysis to detect glaucomatous deterioration of the optic disc.

Methods: Pairs of stereophotographs of 35 glaucomatous optic discs taken 5 years apart and of 5 glaucomatous discs photographed twice on the same day. Two glaucoma specialists examined the pairs of stereophotographs (35 cases and 5 controls) in a masked manner and judged whether the optic disc showed changes in the optic disc compatible with progression of glaucomatous damage. The stereophotographs of the five optic discs photographed twice on the same day (which by definition did not change) and of five cases judged to have deteriorated by both glaucoma specialists were analyzed by computerized image analysis with the Topcon ImageNet system. Intra‐ and inter‐observer agreement in the detection of optic disc changes (evaluated using kappa statistic), and changes in the rim area to disc area ratio (evaluated using descriptive statistics and paired t‐test).

Results: Intra‐observer agreement had a kappa value of 0.75 for observer 1 and 0.60 for the observer 2. Inter‐observer agreement between the glaucoma specialists had a kappa value of 0.60. The image analyzer did not discriminate between controls and cases with clinically apparent glaucomatous change of the optic disc.

Conclusion: Clinical agreement in detecting changes in the optic disc was moderate to substantial. Computerized image analysis with the Topcon ImageNet system appeared not to be useful in detecting glaucomatous changes of the optic disc.
A Forced Choice Comfort Study of Olopatadine Hydrochloride 0.1% versus Ketotifen Fumarate 0.05%
Authors: Artal Maria Natalia , Luna José Domingo , Discepola Marino
Published: March 2003

Purpose: To compare the ocular comfort of two ophthalmic anti‐allergic agents: olopatadine hydrochloride 0.1% and ketotifen fumarate 0.05%.

Subjects and Methods: In a double‐masked, multi‐centered, randomized trial, 80 subjects were asked to make a ‘forced choice’ based on ocular comfort between one drop of olopatadine hydrochloride 0.1% instilled in one eye and one drop of ketotifen fumarate 0.05% instilled in the contralateral eye. At one site, the incidence of adverse reactions was also reported.

Results: All subjects (100%) selected olopatadine as the more comfortable formulation. One site (n=35) reported a 49% incidence of moderate burning and a 49% incidence of mild burning after ketotifen instillation. One subject (2% of population) at this site experienced no ocular discomfort with ketotifen. There were no reports of discomfort associated with olopatadine instillation.

Conclusion: Olopatadine is a more comfortable ophthalmic preparation than ketotifen.
Latanoprost versus combined therapy with timolol plus dorzolamide: IOP‐lowering effect in open‐angle glaucoma
Authors: Polo V. , Larrosa J. M. , Gomez M. L. , Pablo L. , Honrubia F. M.
Published: March 2003

ABSTRACT. Purpose: To compare the effect on intraocular pressure of latanoprost versus timolol plus dorzolamide in open‐angle glaucoma.

Methods: Thirty‐five patients with open‐angle glaucoma were randomized, 18 to latanoprost once daily and 17 to timolol plus dorzolamide twice daily. Intraocular pressure and ocular side effects were recorded at baseline, and after 2 weeks and 3 months of treatment.

Results: Latanoprost reduced the intraocular pressure 1.09 and 1.58 mm Hg more than timolol plus dorzolamide after 2 weeks and 3 months of treatment, respectively. These differences were statistically significant (p<0.05) at the end of the study. After 3 months of treatment, 32.3% of the eyes in the latanoprost group reduced the intraocular pressure in 30% or more with respect to baseline, while 15.6% of the eyes in the timolol plus dorzolamide group achieved this reduction.

Conclusions: Latanoprost administered once daily reduced the intraocular pressure at least as well as timolol plus dorzolamide twice daily in patients with open‐angle glaucoma.
Recurrent episcleritis associated with brucellosis
Authors: Güngör Kıvanç , Bekir Necdet A. , Namıduru Mustafa
Published: March 2003

ABSTRACT. Purpose: To document the clinical course and the treatment of episcleritis associated with brucellosis.

Methods: Three consecutive cases of patients with recurrent episcleritis associated with brucellosis were evaluated through clinical and laboratory data including serology (tube agglutination), blood culture, and synovial fluid culture.

Results: All the patients had ingested contaminated milk and/or fresh cheese. The diagnosis of brucellosis was confirmed by high antibody titer, positive blood culture, negative synovial fluid culture and unresponsive condition to the previous nonspecific therapy for episcleritis and reactive arthritis. The patients responded well to the therapy with doxycycline and rifampicin.

Conclusion: We proposed that recurrent episcleritis had a co‐occurence with reactive arthritis in the course of the brucellosis, and that it responded well to the antibrucellar antibiotics rather than to steroids. This also implies that brucellosis as a rule is an underlying triggering infection associated with reactive arthritis.
Retinoblastoma with an unusual presentation in a child with polydactyly. Clinical associations and genetic implications
Authors: Tsinopoulos I. , Papadopoulou V. , Papandroudis A. , Stangos N.
Published: March 2003

ABSTRACT. Retinoblastoma is the most common intraocular malignancy of childhood. It may rarely present with white spots on the iris and pseudohypopyon. We report a case of an 11‐month old child with polydactyly with this presentation of retinoblastoma. There was no positive family history of the disease. Investigations included anterior segment examination under anaesthesia, fundoscopy with scleral indentation, A‐ and B‐scan ultrasound and MRI examination of the head. This was a Reese Ellsworth group 5 retinoblastoma with an indication for enucleation. Pathology reports of the enucleated globe showed choroidal and ciliary body invasion. Therefore, subsequent chemotherapy treatment was undertaken. The retinoblastoma gene is located in the long arm of chromosome 13. Almost all familial and bilateral cases carry the abnormal gene. In unilateral isolated retinoblastomas – as in our case – most patients do not have a germinal mutation, however, only DNA analysis can safely exclude that. We also discuss possible factors having a link to both polydactyly and retinoblastoma.
Strabismus and binocular function in children with Down syndrome. A population‐based, longitudinal study
Authors: Haugen Olav H. , Høvding Gunnar
Published: March 2003

ABSTRACT. Purpose: We have performed a population‐based, longitudinal study on strabismus in children with Down syndrome. The aims of the study were to examine the frequency and type of strabismus, the age at onset, and the binocular potential.

Methods: An unselected population of 60 children with Down syndrome born 1988–1999 was followed with repeated examinations. Mean follow‐up time was 55±23 months (range 24–115). The alignment of the eyes was examined using Hirschberg corneal reflex test and cover test for near fixation. To evaluate binocular function, Titmus House Fly Test and Lang’s stereo test were used.

Results: Twenty‐five patients (42%) had strabismus (21 esotropias, two exodeviations and two vertical deviations). Only one case of infantile esotropia was found, the other esotropias were acquired forms. The mean age at “onset” (e.g. when strabismus was first noticed) was 54±35 months. In the acquired esotropia group (n=20), 15 (75%) were associated with hypermetropia (mean spherical equivalent +4.3±1.7 D). Seventeen of the strabismic patients had an accommodation weakness. Eleven of the strabismus patients gave a clearly positive response to one or both stereotests.

Conclusions: The majority of the Down syndrome children with strabismus have an acquired esotropia and hence a potential for binocularity. Hypermetropia and accommodation weakness are probably important factors in esotropia in Down syndrome patients.
Randomised controlled trial of ketorolac in the management of korneal abrasions
Authors: Goyal Raina , Shankar Jai , Fone David L. , Hughes David S.
Published: March 2003

ABSTRACT. Purpose: To evaluate the role of topical non‐steroidal anti‐inflammatory agents (NSAIDs) in the management of corneal abrasions with respect to symptoms and healing.

Methods: The study was designed as a prospective, single center, randomised, placebo controlled, double‐blinded trial. Eighty‐eight consecutive patients with non‐infective, non‐contact lens related traumatic or foreign body removal related corneal abrasions were recruited to this study. They were randomised into two groups. Both groups were given a single instillation of Gutt. cyclopentolate 0.5% followed by chloramphenicol eye ointment four times a day until the following day. In addition, the treatment group received topical Ketorolac trometamol 0.5% ophthalmic solution while the control group received placebo Liquifilm tears. Patients were assessed at presentation and about twenty‐four hours later for subjective symptoms, abrasion size and any associated complications.

Results: There was no statistical difference in the two groups at base line and twenty‐four hour follow‐up when assessed for five subjective symptoms of pain, photophobia, grittiness, watering and blurring of vision. However, those receiving topical ketorolac required significantly less additional oral analgesics (p=0.001). There was no difference in the rate of healing.

Conclusion: Use of topical ketorolac may be a useful adjunct in the management of corneal abrasions.
Comparative study of vitrectomy for dropped nucleus with and without the use of perfluorocarbon liquid. Clinical, electrophysiological and visual field outcomes
Authors: Verma Lalit , Gogoi Madhurjya , Tewari Hem Kumar , Kumar Atul , Talwar Dinesh
Published: March 2003

ABSTRACT. Purpose: To compare pars plana vitrectomy for dropped nucleus with and without perfluorocarbon liquid.

Methods: 24 eyes with dropped nucleus were randomized to undergo PPV with perfluorodecalin, (study, n=12) and without it (control, n=12). Visual acuity, IOP, visual evoked response and electroretinography were noted at study entry and up to 3 months after PPV. Humphrey perimetry was done at 3 months.

Results: Final visual acuity was >20/60 in 75% of study eyes and 41.6% of controls. The two groups were statistically comparable with regard to the above parameters before PPV and during follow‐up. The timing of vitrectomy did not significantly influence the final visual acuity. A higher rate of complications was seen in the control group.

Conclusions: Perfluorodecalin facilitated the procedure and possibly minimized complications, and was found to be safe for intraoperative use in terms of recovery of visual acuity, stable ERG and VER, and normal visual fields.
Refractive error and glaucoma
Authors: Grødum Kirsti , Heijl Anders , Bengtsson Bo
Published: March 2003

Purpose: To study the association between refractive error, glaucoma damage and IOP in a large population.

Methods: We examined 32,918 citizens of the city of Malmö, Sweden, 57–79 years of age, searching for individuals with undetected glaucoma. Refraction was measured with autorefractors. Glaucoma damage was defined as reproducible visual field defects with the Humphrey Full Threshold 24–2 program.

Results: Glaucoma prevalence was clearly associated with refractive state, increasing gradually with increasing myopia. This was seen both in males and females and persisted over the full age range. Glaucoma was significantly more common in myopic than in hyperopic eyes with low IOP readings (p=0.024). The overrepresentation of glaucoma in myopic eyes declined with increasing IOP and no relationship was observed in eyes with IOP ≥31 mmHg.

Conclusion: In this large population, the prevalence of glaucoma increased with increasing myopia. The association between myopia and glaucoma was strong at lower IOP levels, and weakened gradually with increasing IOP. Our findings indicate that myopia is an important risk factor for glaucoma and particularly for normal tension glaucoma.
Octreotide reduces ischaemia‐reperfusion injury in the retina
Authors: Celiker U. , Ilhan N. , Ozercan I. , Demir T. , Celiker H.
Published: March 2003

Purpose:  To investigate the role of octreotide on retinal lipid peroxidation and histopathological changes during ischaemia/reperfusion (I/R).

Methods:  Three groups of seven pigmented guinea pigs each were formed. These represented a control group, an ischaemia group and an ischaemia/octreotide group. One eye of each animal was selected for histopathological evaluation and the other for biochemical assay. Bilateral pressure‐induced retinal ischaemia was instigated for 90 min and was followed by 24 hours of reperfusion. Animals in the ischaemia/octreotide and ischaemia groups received either 10 µg/kg of octreotide or saline, repeated five times at 6‐hourly intervals, with the first dose administered 15 min prior to the ischaemic insult. Retinal malondialdehyde (MDA) levels and the thickness of the retinal layers were measured. These were compared with equivalent measurements of the control group.

Results:  The mean MDA level increased in the ischaemia group (p < 0.01) but not in the octreotide group (p > 0.05). Significant increases in the thickness of the overall retina (p < 0.01), inner retina (p < 0.05) ganglion cell layer (p < 0.01) inner plexiform layer (p < 0.01) and inner nuclear layer (p < 0.01) were observed in the ischaemia group. No significant difference in thickness was found in any of the layers in the ischaemia/octreotide group.

Conclusion:  Octreotide reduces the increases in retinal MDA levels and retinal thickness observed during I/R.
Progression of retinal nerve fibre layer damage in betaxolol‐ and timolol‐treated glaucoma patients
Authors: Vainio‐Jylhä Elina , Vuori Marja‐Liisa , Nummelin Kari
Published: March 2003

Purpose:  It has been suggested that there are differences between selective and non‐selective beta‐blocking agents in their ability to protect glaucomatous eyes. The purpose of this study was to follow glaucoma patients treated with either betaxolol 0.5% or timolol 0.25% ophthalmic solutions and to compare the rate and degree of progression in retinal nerve fibre layer (RNFL) defects between the groups.

Methods:  A total of 64 patients were prospectively recruited in a double‐masked study and randomly divided into two treatment groups. Retinal nerve fibre layer photographs were analysed. The incidence and total amount of progression in each group were recorded. The rate of impairment was demonstrated using Kaplan Meier survival curves.

Results:  The analysis included 27 patients treated with betaxolol and 28 patients treated with timolol. Of these, 30% of betaxolol‐treated patients and 46% of timolol‐treated patients had RNFL damage progression (p = 0.20). The total amount or rate of progression did not differ significantly between the two groups. There was no significant difference in intraocular pressure (IOP) levels between the groups (p = 0.68) during follow‐up. The degree of RNFL deterioration did not correlate to the amount of IOP reduction.

Conclusion:  The group treated with betaxolol 0.5% and the group treated with timolol 0.25% did not differ significantly in RNFL damage progression.
Expression of 5′‐nucleotidase and alkaline phosphatase in human aqueous drainage channels
Authors: Krohn Jørgen , Rødahl Eyvind
Published: March 2003

Purpose:  Lymphatic vessels and blood vessels can be distinguished histochemically by their expression of 5′‐nucleotidase and alkaline phosphatase. The aim of this study was to compare the expression of these enzymes in human aqueous drainage channels with that seen in lymphatics and blood vessels.

Methods:
  Histological sections from the angular regions of human eyes were prepared both by enzyme histochemical and immunohistochemical methods to analyse 5′‐nucleotidase and alkaline phosphatase expression. In some of these eyes, Indian ink‐stained gelatine was injected into Schlemm's canal and the suprachoroidal space to facilitate the identification of aqueous drainage routes.

Results:  There was no expression of 5′‐nucleotidase in the endothelium of aqueous drainage channels. Ocular blood vessels were characterized by strong expression of alkaline phosphatase, whereas the cellular lining of Schlemm's canal, the collector channels, the aqueous veins and a scleral channel from the suprachoroidal space showed significantly weaker expression or no expression at all.

Conclusion:  The study failed to show a histochemical similarity between lymphatics and human aqueous drainage channels, as no expression of 5′‐nucleotidase could be found in any part of the aqueous outflow pathway. The endothelium of aqueous drainage channels also differed from normal blood vessels by a much weaker expression of alkaline phosphatase. This makes a histochemical distinction between aqueous veins and scleral veins possible.
GDx in glaucoma
Authors: Miglior S.
Published: March 2003

The purpose of this paper is to review the clinical applications of GDx in the diagnosis and follow‐up of glaucoma. The limits and potential of GDx technology are discussed.
Influence of secondary colonizers and human plasma on the adherence of Porphyromonas gingivalis in vitro
Authors: Sato Masaru , Nagayama Motohiko , Yamaguchi Ryozo , Fujiwara Shuu , Takeuchi Hiroshi
Published: March 2003

The influence of secondary colonizers (Fusobacterium nucleatum and Actinomyces naeslundii) and the effect of human plasma on the adherence of Porphyromonas gingivalis were investigated. Hydroxyapatite (HAP) discs coated with Streptococcus sanguis were immersed in a 3H‐labeled bacterial cell suspension of F. nucleatum or A. naeslundii and then in a 14C‐labeled P. gingivalis cell suspension. Bacterial cells on the discs were pyrolysed to quantify the radioisotopes released. The cell numbers of secondary colonizers on the discs increased with immersion time and this, in turn, resulted in significantly elevated adherence of P. gingivalis. These two secondary colonizers had very similar positive effects on the adherence of P. gingivalis. Human plasma significantly inhibited the adherence of P. gingivalis and secondary colonizers to S. sanguis‐coated HAP discs. Adherence of P. gingivalis and A. naeslundii was strongly inhibited by plasma, while that of F. nucleatum was affected the least. Treatment with plasma, after immersion of streptococcal‐coated discs in individual cell suspension of secondary colonizers, also reduced subsequent adherence of P. gingivalis. The rate of decrease was much smaller in F. nucleatum. These results indicate that both F. nucleatum and A. naeslundii enhance the adherence of P. gingivalis, and that the former may play a more important role in the establishment of P. gingivalis in dental plaque where plasma‐derived components are present.
Prion diseases. An overview
Authors: Dalsgaard Niels Jørn
Published: March 2003

Prion disease is the new designation of a group of spongiform encephalopathies, all invariably fatal, which show similar clinical and neuropathological changes. They comprise a range of distinct diseases in both animals and man, and spontaneous, hereditary and transmissible forms are recognized. Until the sudden occurrence in the mid‐1980s of an epizootic of a formerly unknown disease, popularly named ‘mad cow disease’, in cattle in the UK, very little attention had been paid to these rather obscure diseases. Concurrently it was asserted that the disease‐causing agent appeared to be a ubiquitous mammalian brain constituent, and the disease mechanism a conformational change of its structure. These events have not only led to a new understanding of these extraordinary diseases, but have also provided insight into both neurodegeneration and disease mechanisms at the molecular level. Moreover, in 1997 the prion concept earned its originator the second Nobel price for medicine within this scientific field. In this introduction and overview of prion diseases, historical and philosophical perspectives are presented along with descriptions of the diseases in both animals and man. Epidemiology, genetics and transmissibility are also covered.
Early and late pathogenesis of natural scrapie infection in sheep
Authors: Van Keulen L. J. M. , Vromans M. E. W. , Van Zijderveld F. G.
Published: March 2003

The pathogenesis of scrapie infection was studied in sheep carrying the PrPVRQ/PrPVRQgenotype, which is associated with a high susceptibility for natural scrapie. The sheep were killed at sequential time points during a scrapie infection covering both the early and late stages of scrapie pathogenesis. Various lymphoid and neural tissues were collected and immunohistochemically examined for the presence of the scrapie‐associated prion protein PrPSc, a marker for scrapie infectivity. The first stage of scrapie infection consisted of invasion of the palatine tonsil and Peyer's patches of the caudal jejunum and ileum, the so‐called gut‐associated lymphoid tissues (GALT). At the same time, PrPScwas detected in the medial retropharyngeal lymph nodes draining the palatine tonsil and the mesenteric lymph nodes draining the jejunal and ileal Peyer's patches. From these initial sites of scrapie replication, the scrapie agent disseminated to other non‐GALT‐related lymphoid tissues. Neuroinvasion started in the enteric nervous system followed by retrograde spread of the scrapie agent via efferent parasympathetic and sympathetic nerve fibres innervating the gut, to the dorsal motor nucleus of the vagus in the medulla oblongata and the intermediolateral column of the thoracic spinal cord segments T8–T10, respectively.
Clinical diagnosis and differential diagnosis of CJD and vCJD
Authors: Zerr Inga , Poser Sigrid
Published: March 2003

The most widely distributed form of transmissible spongiform encephalopathy, sporadic Creutzfeldt‐Jakob disease, typically affects patients in their sixties. Rapidly progressive dementia is usually followed by focal neurological signs and typically myoclonus. The disease duration in sporadic CJD is shorter than in variant CJD (6 months and 14 months, respectively). The clinical diagnosis in sporadic CJD is supported by the detection of periodic sharp and slow wave complexes in the electroencephalogram, hyperintense signals in basal ganglia on magnetic resonance imaging and elevated levels of neuronal proteins in the cerebrospinal fluid (such as 14‐3‐3). In contrast to the sporadic form, hyperintense signals in the posterior thalamus (``pulvinar sign'') are seen in variant CJD. Following recent developments in diagnostic premortem techniques, clinical criteria for probable sporadic and probable variant CJD were established. Clinicopathological studies on sporadic CJD revealed different phenotypes which are characterized by neuropathological lesion profile, clinical syndrome, codon 129 genotype and type of proteinase K‐resistant core of the prion protein. Alzheimer's disease and Lewy body dementia are the most frequent differential diagnoses in sporadic CJD in elderly patients, whereas chronic inflammatory disorders of the central nervous system have to be considered in younger patients.
Sequence analysis of measles virus strains collected during the pre‐ and early‐vaccination era in Denmark reveals a considerable diversity of ancient strains
Authors: Christensen L. Siig , Schöller Susanne , Schierup Mikkel H. , Vestergaard B. Faber , Mordhorst Carl H.
Published: March 2003

A total of 199 serum samples from patients with measles collected in Denmark, Greenland and the Faroe Islands from 1964 to 1983 were analysed by PCR. Measles virus (MV) RNA could be detected in 38 (19%) of the samples and a total of 18 strains were subjected to partial sequence analysis of the hemagglutinin gene. The strains exhibited a considerable genomic diversity, which is at odds with the assumption that one genome type prevailed among globally circulating MV strains prior to the advent of live‐attenuated vaccines. Our data indicate that the similarity of the various vaccine strains is attributed to their having originated from the same primary isolate. Consequently, it is implied that a small number of clinical manifestations of MV worldwide from which strains similar to the vaccine strain were identified were vaccine related rather than being caused by members of a persistently circulating ancient genome type. The Danish pre‐ and early‐vaccination era MV strains seem to change the evolutionary spectrum of genome types A, C2 and E into one coherent group, suggesting that the genome types of MV strains circulating in the world at present do not represent far ranging evolutionary lineages but merely members of an evolutionary continuum of pre‐vaccination era MV strains which by chance or due to an improved capability survived the worldwide partial herd immunity accomplished through vaccination.
Expression of HGF/SF and Met protein is associated with genetic alterations of VHL gene in primary renal cell carcinomas
Authors: Oh Ro Ra , Park Jik Young , Lee Jong Heun , Shin Min Sun , Kim Hong Sug , Lee Sang Kyu , Kim Young Sil , Lee Sug Hyung , Lee Sie Nae , Yang Young Mok , Yoo Nam Jin , Lee Jung Young , Park Won Sang
Published: March 2003

We analyzed the genetic alterations of VHL, HGF/SF, and Met genes and the expression pattern of HGF/SF and Met protein in 26 renal cell carcinomas (RCCs). We found five mutations of the VHL gene and frequent LOH (50%) only in non‐papillary clear cell RCC. We found six cases in which the CpG island of VHL was methylated. In addition, one missense mutation of the HGF/SF gene was detected in clear cell RCC. HGF/SF and Met protein were expressed in 84.6% and 80.7% of RCCs, respectively. All of the cases with the genetic alterations of VHL or HGF/SF demonstrated strong expression of HGF/SF and Met protein in RCC cells. Statistically, genetic alterations of VHL and HGF/SF were significantly correlated with HGF/SF and Met expression (Fisher's exact test, p=0.022 and p=0.0070). Thus, these results strongly suggest that the expression of HGF/SF and Met protein is closely associated with the genetic alterations of VHL and HGF/SF in primary RCCs.
No immunosuppressive effect of transfected annexin II
Authors: Hansen Torbjørn
Published: March 2003

Annexin II (AXII) was reported to suppress lymphoproliferation and immunoglobulin production. To investigate this further, the AXII‐negative human B‐lymphoma cell line Raji was transfected with AXII followed by transfection with p11. Stable transfectants were generated. In vitro immunological effects of Raji, Raji‐AXII and Raji‐AXII‐p11 were compared by using irradiated cells as stimulators for PBM in mixed lymphocyte reactions or by adding the supernatants to lymphoproliferation or ELISPOT cultures. None of the assays provided evidence of significant immunosuppression by AXII. Thus, expression of AXII or AXII plus p11 does not by itself give a cell immunosuppressive ability.
Uncoupling activation‐induced modulation of CD16 and CD69 in CD56+ cells during AIDS
Authors: Barboza José M. , Salmen Siham , Cova José A. , Albarrán Benibelks , Goncalves Loredana , Borges Lérida , Hernández Manuel , Berrueta Lisbeth
Published: March 2003

The immune system of HIV+ patients is chronically activated, which has been associated with a detrimental effect on both innate and acquired immunity during AIDS. We analyzed the expression and modulation of the triggering markers CD69 and CD16 in CD56+ cells from 18 asymptomatic HIV+ individuals and 8 AIDS patients, compared with 21 seronegative subjects. We observed a diminished PMA‐induced CD16 downregulation in AIDS patients (p<0.01), associated with low numbers of CD4+ cells (p<0.02). Furthermore, an enhanced unstimulated expression of CD69 in asymptomatic HIV+ patients (p<0.05) was shown. AIDS patients could not efficiently upregulate PHA‐dependent CD69 expression (p<0.05), which correlated with low CD4+ counts (p< 0.05). These abnormalities in CD16 and CD69 modulation were recorded in patients under highly active antiretroviral therapy (HAART). Our results demonstrate an altered modulation of two functionally relevant receptors in CD56+ cells from AIDS patients, contributing to our understanding of the immunopathogeny of NK cell dysfunction during disease progression.
Myocarditis and sudden infant death syndrome
Authors: Råsten‐Almqvist Petra , Eksborg Staffan , Rajs Jovan
Published: March 2003

This is a retrospective survey of findings of myocarditis in 437 infants under the age of 1 year who died suddenly and unexpectedly between 1982 and 1999, and were investigated at the Department of Forensic Medicine in Stockholm, Sweden. Myocarditis was diagnosed in 69/410 infants who died naturally (16.8%) and in 2/27 violent deaths (7.4%). In 43/410 natural deaths (10.5%) the myocarditis was an isolated finding and the only explanation for cause of death and in 26 (6.3%) there were additional possible causes of death. The myocarditis was acute in 45/69 and chronic in 24/69 natural deaths, and was found to occur as early as at a few weeks of age. No specific risk factors were found when reviewing critical time of year, age, gender, previous symptoms, sleeping position, aspiration of gastric contents and environmental factors in infant deaths with finding of myocarditis compared to 313 deaths due to sudden infant death syndrome. Myocarditis was found in 13 of 37 deaths where cultures for cytomegalovirus were positive. More than 50% of the foci of the isolated myocarditis were located in the upper part of the interventricular septum and the adjacent part of the right atrium, areas including parts of the conduction system. This localisation is significant for the cause of death when comparing deaths with myocarditis as an isolated finding to deaths with other possible causes.
Nodal marginal zone B‐ceil lymphoma resembling plasmacytoma arising from a plasma cell variant of localized Castleman's disease
Authors: Kojima MASARU , Nakamura SHIGEO , Shimizu KAZUHIKO , Suda YOSHIO , Kasuga YOSHIO , Sugihara SHIRO , Sakata NORIYUKI , Masawa NOBUHIDE
Published: March 2003

Nodal marginal zone B‐cell lymphoma (NMZBL) occasionally represents prominent plasma cell differentiation. Recently, primary lymph node plasmacytoma has been suggested to represent an extremely plasmacytic differentiation of NMZBL. We here report a case of NMZBL showing histological features resembling plasmacytoma arising from a plasma cell variant of localized Castleman's disease (PCLCD). The patient was a 69‐year‐old Japanese female with a 20‐year history of a right inguinal mass. Histologically, a prominent proliferation of plasma cells occupied the interfollicular area of the central portion of the lymph node, whereas centrocyte‐like (CCL) cells were the main cellular component in the peripheral portion of the lymph node. Although most of the plasma cells were mature ‘Marshalko‐type’, occasional atypical forms with enlarged nuclei were also present. The majority of the lymphoid follicles had atrophic or regressive germinal centers. A few lymphoid follicles were colonized by CCL cells. Immunohistochemistry study revealed that both plasma cells and some CCL cells had a monotypic intracytoplasmic lambda light chain. When monoclonal plasma cell infiltration is observed in PCLCD, the light chains are mostly restricted to the lambda chain. This case suggests that some plasma cell‐containing tumors arising from PCLCD may represent a variant of NMZBL.
P53 autoantibodies in sera from Danish ovarian cancer patients and their correlation with clinical data and prognosis
Authors: HØGdall ESTRID VS. , HØGdall CLAUS K. , Blaakaer JAN , Heegaard NIELS H. H. , Glud EVA , Christensen LISE , Bock JOHANNES E. , NØRgaard‐Pedersen BENT , Wiik ALLAN , Kjaer SUSANNE K.
Published: March 2003

Thep53 gene, a tumour suppressor gene located on the short arm of chromosome 17 (17pl3), is frequently mutated in various human tumours. Accumulation ofp53 protein in neoplastic cells and its relea se following tumour necrosis can lead to development of circulating autoantibodies (AAb) againstp53. Earlier studies of ovarian cancer (OC) patients reported different frequencies ofp53 AAb and conclusions regarding the clinical and prognostic value of these AAb have not been in agreement. We therefore analysed for the presence ofp53 AAb in a total of 227 preoperative serum samples from 193 OC patients and 34 patients with ovarian borderline tumours, and, in addition, serum samples from 86 healthy controls. An enzyme‐linked immunosorbent assay (ELISA) was used to measure serum IgG antibodies against p53. Thep53 protein used in the assay was produced as a hexahistidine‐tagged fusion protein by baculovirus‐infectedSpodoptera frugiperdacells. Cut‐off values forp53 AAb were evaluated, and correlations ofp53 AAb with clinical‐, biochemical data and survival were examined. We found a low sensitivity forp53 AAb alone, and no major additional effect of the detection rate of CA125 was found. No significant associations were found betweenp53 AAb and clinical stage, age, histological subtype and radicality after primary surgery. In contrast, we found significantly elevated CA125 levels inp53 AAb‐positive patients compared to lower CA125 levels inp53 AAb‐negative patients (p=0.003). No significant differences were found betweenp53 AAb‐positive andp53 AAb‐negative patients in the univariate and multivariate survival analyses. In conclusion, in a screening study for OC serump53 AAb levels are of no diagnostic value, even if combined with the tumour marker CA125. The presence of increased serump53 AAb in patients with diagnosed OC could not be correlated with any clinical data and preoperative serump53 AAb status had no evident value.
Mutations in gyrA, gyrB, parC, and parE in quinolone‐resistant strains of Neisseria gonorrhoeae
Authors: Lindbäck Emma , Rahman Motiur , Jalal Shah , Wretlind Bengt
Published: March 2003

Mutations in the genes for the subunits GyrA and ParC of the target enzymes DNA gyrase and topoisomerase IV are important mechanisms of resistance in quinolone‐resistant bacteria, including Neisseria gonorrhoeae. The target enzymes also consist of the subunits GyrB and ParE, respectively, though their role in quinolone‐resistance has not been fully investigated. We sequenced the quinolone‐resistance‐determining regions (QRDR) of gyrA, gyrB, parC, and parE in 25 ciprofloxacin‐resistant strains from Bangladesh (MIC 4→32 mg/l) and 5 susceptible strains of N. gonorrhoeae. All the resistant strains had three or four mutations. Two of these were at positions 91 and 95 of gyrA. Fourteen strains had an additional mutation in parC at position 91, and 17 strains had an additional mutation in parE in position 439. No alterations were found in gyrB. The five susceptible strains had identical DNA sequences. Data indicate that the mutations detected in the QRDR of gyrA and parC may be important in the development of quinolone resistance. According to transformation experiments we assume that the alteration in parE is not related to a high degree of quinolone resistance. There was no correlation between ciprofloxacin MICs and pattern or number of mutations in the target genes.
Periodontal tissues and their counterparts around endosseous implants
Authors: Listgarten M. A. , Lang N. P. , Schroeder H. E. , Schroeder A.
Published: March 2003

New technology coupled with a better understanding of tissue biology has played a key role in restoring the somewhat tarnished image of implant dentistry, Thanks to carefully conducted longitudinal studies, it has now become clear that the replacement of missing teeth by artificial implants integrated into the living tissues of the jaws is a predictable procedure, as long as certain guidelines are followed in the manufacture of the implant, its placement, its eventual functional loading, and its maintenance. Yet, functional success for a natural tooth is dependent on a number of anatomic, physiologic, and environmental considerations which differ in some important respects from those that insure the functional success of an implant. In this paper, we review the anatomic features of the natural dentition with emphasis on the periodontal tissues, and contrast these characteristics with those that exist around well‐integrated endosseous implants.
Healing‐in of root analogue titanium implants placed in extraction sockets. An experimental study in the beagle dog.
Authors: Hämmerle C. H. F. , Schmid J. , Olah A. J. , Lang N. P.
Published: March 2003

The aim of this study was to test whether healing of extensive transosseous defects in the calvaria can successfully be achieved using guided bone regeneration. The results demonstrated complete osseous bridging of the skull defect in the test specimen. In the control specimen, fibrous connective tissue occupied the area of the skull defect.
ITI implants in combination with bone grafts: design and biomechanical aspects
Authors: Sutter F. , Weingart D. , Mundwiler U. , Sutter F. J. , Asikainen P.
Published: March 2003

In this article we describe the implantation of ITI implants in combination with bone grafts. Two different cases were considered: the augmentation of an atrophic maxilla or mandible where the transplant was fixed by means of ITI implants and the implantation into free transplants fixed by means of the THORP reconstruction plate system. These indications require 2‐stage procedures with submerged implants and transplants during the healing period. For this new applications, standard ITI implants were combined with specially developed new transgingival units of high manufacturing precision. The new design resulted in a maximum tightening moment of 4.0 N.m versus 1.25 N.m achievable with a conventional 2‐mm screw. Dynamic testing showed that, for the range of tightening moments of 0.25 N.m up to 1.0 N.m, the loosening moment after 2,000,000 cycles remained approximately 10% above the tightening moment. For the clinical application a tightening moment of 0.35–0.5 N.rn is recommended. The special design and the high precision of the extension parts results in a tight adaptation between the primary implant and the extension parts, which may be important for microbiological reasons.