bluuebunny/crossref_metadata_2025 huggingface dataset:
Triage by HPV‐DNA testing: is it useful in women with persistent minor smear abnormalities?
Authors: Pisal Narendra , Sindos Michael , Chow Carl , Singer Albert
Published: May 2003

Background.  This study was carried out to evaluate the efficacy of HPV‐DNA (Human Papilloma Virus) testing as a triage strategy for persistent borderline and mild cytological abnormalities.

Methods.  A prospective cross‐sectional study involving 321 women registered between January and December 2001 with two smears showing borderline or mild dyskaryosis, taken 6 months apart. This study was undertaken in a colposcopy unit in a large district general hospital in central London.

Results.  Three hundred and twenty‐one women referred with persistent borderline and mild dyskaryosis were recruited in this study. HPV‐DNA testing was positive in 194 women (60.4%). Histology of colposcopically directed biopsy showed CIN2/3 in 57 women (18%). Fifty‐one of these 57 women were detected by HPV‐DNA testing (sensitivity for high‐grade disease 89.5%). Specificity for high‐grade disease was 45.8%. Negative predictive value was 95.3%. Women with a positive HPV‐DNA result had a 7.2 times higher risk of having a high‐grade cervical cancer precursor lesion.

Conclusion.  Negative predictive value of HPV‐DNA testing for high‐grade cervical lesion is very high. Hence, it can be used as a triage strategy for persistent borderline changes and mild dyskaryosis.
Maternal serum interleukin‐6, interleukin‐8, tumor necrosis factor‐α and interferon‐γ in preterm labor
Authors: Bahar Ahmed M. , Ghalib Hashim W. , Moosa Riyad A. , Zaki Zaki M. S. , Thomas Chet , Nabri Osman A.
Published: May 2003

Background.  To find out whether preterm labor is associated with raised maternal serum concentrations of interleukin (IL)‐6, IL‐8, tumor necrosis factor alpha (TNF‐α) and interferon gamma (IFN‐γ) and whether the measurement of these cytokines can be used to detect early intrauterine infection in preterm labor.

Methods.  Cross‐sectional study: 77 women in preterm labor, 47 controls of healthy preterm women not in labor and 19 women in term labor. The serum cytokines levels were measured by enzyme‐linked immunosorbent assay (ELISA). The newborns of women who were in labor were followed up for evidence of infection. Differences between groups were tested using analysis of variance, Student's t‐test and χ2‐test.

Results.  There was no significant difference in the concentration of all the cytokines measured between the different groups. No statistical difference was found in the concentration of the cytokines between women in preterm labor with ruptured membranes and those with intact membranes. There was also no difference found in the concentration of cytokines between women whose newborns had positive bacterial culture and those with negative culture. There was a positive correlation between the concentrations of IL‐6, IL‐8 and TNF‐α.

Conclusion.  Serum levels of interleukin‐6, interleukin‐8 and tumor necrosis factor‐α were not increased in preterm labor compared to normal control women. There is doubt regarding the usefulness of maternal serum measurement of these cytokines for the detection of early fetal infection in preterm labor, but this needs further evaluation.
Probability analysis for diagnosis of endometrial hyperplasia and cancer in postmenopausal bleeding: an approach for a rational diagnostic workup
Authors: Bachmann Lucas M. , Ter Riet Gerben , Clark T. Justin , Gupta Janesh K. , Khan Khalid S.
Published: May 2003

Objective.  To develop an analytical approach to estimate the probability of endometrial hyperplasia and cancer in women with postmenopausal bleeding, using a combination of patient history and tests.

Methods.  A prospectively collected database of 428 postmenopausal women investigated for abnormal uterine bleeding in an outpatient rapid access clinic was used. The probability of disease was estimated using multivariable logistic regression models considering a combination of age and the use of hormone replacement therapy (HRT) and tests (ultrasound and hysteroscopy) in keeping with the actual clinical process.

Results.  The prevalence or prior probability of endometrial cancer in the sample studied was 4.4%. Hysteroscopy alone performed better than ultrasound alone. In all patients, a negative hysteroscopy reduced the probability of cancer to 1.3%. In women less than 60 years of age who use HRT, a negative hysteroscopy further reduced this probability to 0.1%. Overall, a positive hysteroscopy raised the probability of cancer to 38.9%. However, in women over 60 years of age not using HRT, a positive hysteroscopy increased this probability to 59.4%. Combining ultrasound results with hysteroscopy did not meaningfully alter the diagnostic probability.

Conclusion.  The combination of information obtained from patient history and tests allows generation of specific disease probabilities in postmenopausal bleeding. This type of multivariable analysis puts diagnostic information gained from history and other tests into a perspective that reflects actual clinical practice.
A systematic review of transvaginal ultrasonography, sonohysterography and hysteroscopy for the investigation of abnormal uterine bleeding in premenopausal women
Authors: Farquhar Cynthia , Ekeroma Alec , Furness Susan , Arroll Bruce
Published: May 2003

Background.  To determine the accuracy of transvaginal ultrasonography, sonohysterography and diagnostic hysteroscopy for the investigation of abnormal uterine bleeding in premenopausal women.

Design.  Systematic review of common diagnostic imaging tests.

Data sources.  Relevant papers were identified through electronic searching of MEDLINE (1980 to July 2001) and EMBASE (1980 to July 2001) and manual searching of a bibliography of primary and review articles.

Review methods.  Studies were selected if accuracy of transvaginal ultrasonography, sonohysterography and diagnostic hysteroscopy was compared with a reference standard and included data that could be abstracted into a two‐by‐two table in order to calculate sensitivity and specificity. Quality assessment and data extraction were performed by at least two independent reviewers. Diagnostic accuracy was determined by calculating positive and negative likelihood ratios for all intrauterine pathologies, submucous fibroids and endometrial hyperplasia.

Results.  Nineteen studies met the inclusion criteria. Statistically significant heterogenenity was present between the likelihood ratios for studies of transvaginal ultrasound. A positive test result with sonohysterography diagnosed submucous fibroids with a pooled likelihood ratio of 29.7 (17.8, 49.6). A positive test result with hysteroscopy diagnosed submucous fibroids with a pooled likelihood ratio of 29.4 (13.4, 65.3), and any intrauterine pathology with a pooled likelihood ratio of 7.7 (4.3, 13.7). A negative test result with hysteroscopy for diagnosing any intrauterine pathology had a pooled likelihood ratio of 0.07 (0.04, 0.15).

Conclusion.  Although there was considerable variability present between the studies, all three diagnostic tests were moderately accurate in detecting intrauterine pathology. However, sonohysterography and hysteroscopy performed better than transvaginal ultrasound in detecting submucous fibroids.
A sporadic case of von Hippel‐Lindau disease with a secondary maculopathy as the presenting sign
Authors: Kreusel Klaus‐Martin , Bechrakis Nikolaos E. , Neumann Hartmut P. H. , Foerster Michael H.
Published: May 2003

A 36‐year‐old male presented with a drop in visual acuity in his left eye to 0.1. Ophthalmoscopy of the affected eye revealed dense, macular, lipid exudates at the posterior pole (Fig. 1) and a single peripheral capillary retinal haemangioma with only moderately enlarged draining vessels (Fig. 2). Retinal findings in the right eye were unremarkable. As the patient had reported headache, magnetic resonance tomography (MRT) of the brain was performed. This showed a single infratentorial haemangioblastoma (Fig. 3) with a solid (arrow) and cystic (arrow) component, thus allowing for a clinical diagnosis of von Hippel‐Lindau disease (VHL) (Neumann 1987). However, the subject's family history was negative for this autosomal‐dominant, multi‐tumour syndrome. Molecular genetic analysis of the VHL gene (3p25–26) by sscp (Latif et al. 1993) detected a mutation (477 C/G) in the patient's DNA (Fig. 4, lane 2), but not in his mother's or sister's DNA (Fig. 4, lanes 3 and 4; wild‐type DNA: lane 1). Although a positive family history is present in the majority of VHL cases, the disease can also present sporadically due to a de novo mutation (Richards et al. 1995; Kreusel et al. 2000). Ruthenium‐106 brachytherapy of the haemangioma (Kreusel et al. 1998) induced complete regression to a choroido‐retinal scar (Fig. 5). During 5 years of follow‐up according to current screening recommendations (Maher et al. 1990), no further haemangioma or other new VHL lesions were detected in the patient.

Fundus photograph of the posterior pole of the left eye. Abundant lipid exudates are present, resembling pronounced stellate retinopathy. There is only discrete enlargement of the inferior temporal artery and vein.

image

In the temporal inferior periphery a capillary retinal hemangioma surrounded by retinal hemorrhage is present. The feeder vessels are only moderately enlarged.

image

Magnetic resonance image of the patients brain showing an infratentorial hemangioblastoma with a solid (arrow) and cystic (arrow) component. The lesion was removed surgically.

image

Single‐strand polymorphism (SSCP) analysis of exon 1 of the VHL gene after amplification by polymerase chain reaction (PCR) and labelling. The patients blot (lane 2) showed an additional band (arrow) not present in the wild type DNA (lane 1) or the blot of his mother (lane 3) or sister (lane 4). Sequencing revealed an exchange of cytosine for guanine at nucleotide 477.

image

Fundus view after ruthenium‐106‐brachytherapy. The hemangioma shows complete regression.

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Type 1 diabetes patients with severe non‐proliferative retinopathy may benefit from panretinal photocoagulation
Authors: Lövestam‐Adrian Monica , Agardh Carl‐David , Torffvit Ole , Agardh Elisabet
Published: May 2003

Purpose:  To examine whether panretinal photocoagulation for severe non‐proliferative retinopathy in type 1 diabetes patients could halt the progression of retinopathy with subsequent vitreous haemorrhages and visual impairment.

Methods:  During a 10‐year follow‐up study period of 344 type 1 diabetes patients, 81 subjects went through panretinal photocoagulation. Forty patients were treated for severe non‐proliferative retinopathy (age at onset of diabetes 14 ± 8 years, diabetes duration 18 + 10 years) and 41 for proliferative retinopathy (age at onset 15 ± 10 years, diabetes duration 22 + 13 years). One randomly selected eye per patient forms the basis for the study. Metabolic control, systolic and diastolic blood pressure, serum creatinine and urinary albumin levels were measured and analysed yearly during the follow‐up period.

Results:  A total of 35% (14/40) of eyes treated for severe non‐proliferative retinopathy developed neovascularizations during a mean time of 2.9 ± 1.5 years. Vitreous haemorrhages were more frequent in eyes with proliferative retinopathy at treatment than in eyes with severe non‐proliferative retinopathy (12/41 versus 2/40; p = 0.007). The number of vitrectomies due to vitreous haemorrhages in eyes treated for severe non‐proliferative retinopathy tended to be lower (1/40 versus 6/41; p = 0.052). Before photocoagulation, visual acuity (VA) was similar in eyes with severe non‐proliferative retinopathy and in those with proliferative retinopathy (1.0, 0.4–1.0 versus 1.0, 0.1–1.0; median and range). Visual impairment and blindness tended to develop more often in eyes treated for proliferative retinopathy compared to those treated for severe non‐proliferative retinopathy (10/40 versus 4/40; p = 0.056). Eyes with neovascularizations at follow‐up were more often visually impaired (VA < 0.5) than eyes without neovascularizations (15/55 versus 1/26; p = 0.016).

Conclusion:  In type 1 diabetes, panretinal photocoagulation may be beneficial even at the severe non‐proliferative retinopathy stage in terms of preventing vitreous haemorrhage, subsequent vitrectomy and visual impairment.
Longterm results of one‐site phacotrabeculectomy
Authors: Cagini Carlo , Murdolo Paola , Gallai Raffaella
Published: May 2003

Purpose:  To evaluate results of one‐site phacotrabeculectomy and intraocular lens (IOL) implantation.

Methods:  A retrospective study of a consecutive series of 62 eyes with cataract and glaucoma, which underwent primary one‐site phacotrabeculectomy with IOL implantation. Mean follow‐up time was 28 ± 12.3 months (range 12–46 months).

Results:  Preoperative mean intraocular pressure (IOP) (25.1 ± 8.6 mmHg) dropped significantly, to 16.4 ± 1.3 mmHg 1 year after surgery (p < 0.01). Mean logMAR best corrected visual acuity (VA) improved significantly from 0.74 ± 0.49 to 0.22 ± 0.28 (p < 0.01). The most common complications were fibrinous exudation (10%) and choroidal detachment (6%). In two eyes (3%) we successfully performed scleral flap revision to achieve IOP control.

Conclusion:  One‐site combined surgery was a safe and effective procedure with good IOP control and visual rehabilitation.
Visual prognosis in immunocompetent patients with herpes zoster ophthalmicus
Authors: Zaal M. J. W. , Völker‐Dieben H. J. , D'Amaro J.
Published: May 2003

Purpose:  To determine the normal spectrum of ocular complications and associated visual outcome in patients with herpes zoster ophthalmicus.

Methods:  This prospective observational cohort study included 73 immunocompetent adults with herpes zoster ophthalmicus, referred by their general practitioners within 7 days of skin rash onset. The follow‐up period was 6 months. All patients received a 7–14‐day course of systemic aciclovir treatment combined with longterm application of a lubricating ophthalmic ointment as long as the corneal epithelium was affected. Topical corticosteroids were strictly avoided in the acute phase of ocular disease. Acquired visual loss scores at 1, 2 and 6 months were based on best corrected visual acuity (BCVA) level and evaluation of the ophthalmological history and findings.

Results:  Ophthalmic herpes zoster led to a variety of transient inflammatory reactions within the anterior eye segment of the involved side in 46 patients (63%), but did not seriously compromise their ultimate visual outcome. Mild to moderate visual loss, with corrected VA between 0.3 and 0.8, was found in 17 patients at 1 month (23%), in 10 patients at 2 months (14%) and in seven patients at 6 months follow‐up (10%). None of the patients developed visual loss with a corrected VA of less than 0.3.

Conclusion:  Functional vision was retained in all ophthalmic zoster patients referred to the ophthalmologist in the acute phase of the disease by vigorous antiviral treatment and adequate prevention of corneal exposure.
Capillary haemangioma of the eyelids and orbit: a clinical review of the safety and efficacy of intralesional steroid
Authors: O'Keefe Michael , Lanigan Bernadette , Byrne Sinead A.
Published: May 2003

Purpose:  To describe the presenting features, investigations, treatment and outcome of a series of patients with capillary haemangioma of the eyelids and orbit.

Methods:  A retrospective analysis of 21 patients, presenting between the years 1985 and 2000. Effectiveness of treatment was determined by final visual acuity and cosmetic result.

Results:  Lesions were more common in females and the upper eyelid was a definite site of predilection. A total of 87.5% of lesions presented within 6 weeks of birth. Intralesional steroid injections were received by 79% of patients. Amblyopia was a definite complication. No local or systemic complications were associated with intralesional steroid injection. Surgery and laser treatment were reserved for persistent lesions.

Conclusion:  Early recognition and prompt treatment with intralesional steroid prevents early occlusion amblyopia, but follow‐up and management of refractive amblyopia with glasses and patching is necessary in the longer term. In this series, intralesional steroid proved to be a safe effective treatment.
Eales' disease in Inuit: Report of four cases
Authors: Moldow Birgitte , La Cour Morten
Published: May 2003

Purpose:  To report four cases of Eales' disease in Inuit from Greenland diagnosed within a 6.5‐year period. There are no previous reports on Eales' disease among Greenlanders.

Methods:  Four younger Inuit, three males and one female, were diagnosed with Eales' disease based on fundus changes and exclusion of possible differential diagnoses. Several studies point to a possible relation between Eales' disease and tuberculosis (TB); examination of possible exposure to TB was part of the clinical investigation.

Results:  Retinal changes made panretinal laser photocoagulation necessary in all cases. Four eyes in three patients were vitrectomized. Three patients received oral corticosteroid treatment. The final visual outcome was relatively good, with a visual acuity below 6/60 (3/36) in only one vitrectomized eye. All patients had been exposed to TB.

Conclusion:  Eales' disease seems to be rather common in the small population of Inuit (56 000) in Greenland. Attention is required to ensure diagnosis and appropriate treatment, including laser photocoagulation, leading to a reasonably good prognosis.
Predicted corneal visual acuity in keratoconus as determined by ray tracing
Authors: Uçakhan Ömür Ö.
Published: May 2003

Purpose:  To evaluate the optical quality of the central anterior corneal surface in normal eyes and in eyes with keratoconus, and to investigate the accuracy of the predicted corneal visual acuity (PCVA) index as determined by ray tracing analysis.

Methods:  Twenty keratoconus eyes with contact lens‐corrected visual acuity (VA) of 20/20 or better (11 patients, group A) and 20 eyes of 15 normal subjects (group B) were evaluated. After a detailed eye examination including measurement of pupil diameter, keratometry, topography and pachymetry, each subject eye was evaluated using ray tracing analysis with the Technomed C‐scan colour ellipsoid topometer, using basic software (Technomed GmbH, Baesweiler, Germany). The PCVA was determined for each patient, and the results were analysed comparatively using two‐sample t‐test, regression analysis and Pearson correlation analysis.

Results:  The average best spectacle‐corrected VA was measured as 0.2 ± 0.2 logMAR (20/32) in group A and −0.1 ± 0.1 logMAR (20/16) in group B. The average PCVA measurements derived from ray tracing analysis for 3.0 mm, 3.5 mm and 4.0 mm pupil diameters were 0.06 ± 0.12 logMAR, 0.14 ± 0.13 logMAR and 0.21 ± 0.17 logMAR, respectively, in group A, and −0.14 ± 0.08 logMAR,−0.11 ± 0.09 logMAR and −0.09 ± 0.11 logMAR, respectively, in group B. There was good correlation between best corrected VA and PCVA in both groups for all pupil diameters measured (p < 0.007).

Conclusion:  Predicted corneal visual acuity as determined by ray tracing analysis is useful for estimating best spectacle‐corrected VA in normal corneas and the effect of irregular corneal astigmatism on VA in eyes with mild to moderate keratoconus. Further studies are required to evaluate the efficacy of ray tracing in evaluation of aberrations of the optical system of the eye.
Oculometric features of hyperopia in children with accommodative refractive esotropia
Authors: Uretmen Onder , Pamukçu Kemal , Kose Süheyla , Egrilmez Sait
Published: May 2003

Purpose:  To determine the nature of hyperopia in children with accommodative refractive esotropia (ARE) by evaluating the relationships between corneal radius (CR), axial length (AL), age and equivalent spherical refraction (SEQ).

Methods:  A total of 112 children with ARE were included in the study. The children underwent an overall ophthalmic examination including cycloplegic refraction, keratometry and ultrasonic AL measurement.

Results:  Statistical analysis revealed a strong relationship between AL and SEQ (p < 0.001). A significant correlation was also found between AL and CR (p < 0.001). The relationship between AL and age was weak but statistically significant (p = 0.02). Multiple regression analysis, using SEQ as the dependent variable and CR, AL and age as independent variables, revealed that AL accounts for 43.5% of the variance, and the combination of CR and AL accounts for 60.9% of the variance.

Conclusion:  Hyperopia is predominantly axial in nature in children with ARE. However, other refractive components are also involved in producing hyperopic refractive errors.
Characterization of vasomotion in porcine retinal arterioles
Authors: Hessellund Anders , Jeppesen Peter , Aalkjaer Christian , Bek Toke
Published: May 2003

Purpose:  To characterize vasomotion in porcine retinal arterioles in vitro using isobaric (pressure myograph) and isometric (wire myograph) methods.

Methods:  Pressure myograph: 208 small porcine retinal arterioles (outer diameter 68 ± 4 μm) were studied under isobaric conditions in a double‐barrelled pipette system. Diameter changes of the arterioles were registered by video recordings. Wire myograph: 60 large porcine retinal arterioles (inner diameter 147 ± 1.6 μm) were studied under isometric conditions in a small vessel myograph for force measurements.

Results:  The rates of success in initiating vasomotion were 7.2% using the pressure myograph and 43% using the wire myograph (p < 0.001). The small vessels studied under isobaric conditions oscillated with a frequency of 0.014 Hz and the episodes lasted 6.0 ± 1.0 min, whereas the large vessels under isometric conditions oscillated with a significantly faster frequency of 0.043 Hz and lasted 32.1 ± 4.9 min (p = 0.026).

Conclusion:  Retinal vasomotion can be studied in vitro using both pressure myograph and wire myograph techniques. The wire myograph is superior to the pressure myograph in initiating and maintaining vasomotion in vitro.
A conservative blepharoplasty may be a means of alleviating dry eye symptoms
Authors: Floegel Ingrid , Horwath‐Winter Jutta , Muellner Klaus , Haller‐Schober Eva‐Maria
Published: May 2003

Purpose:  Patients with dermatochalasis often complain of dry eye symptoms. In a prospective study, the influence of upper eyelid blepharoplasty on dry eye symptoms, tear film parameters and ocular surface morphology was evaluated.

Methods:  Patients with upper eyelid dermatochalasis were studied before and 3 months after upper eyelid blepharoplasty. Changes in ocular symptoms and physical examinations such as tear film break‐up time, Schirmer test without local anaesthesia, impression cytology of the bulbar conjunctiva and inflammatory reaction were recorded.

Results:  Subjective dry eye symptoms were found in 11 patients (46%) preoperatively and in five patients (21%) postoperatively. Objective dry eye signs were present in eight patients (33%) before blepharoplasty and in nine patients (38%) 3 months postoperatively. Morphological findings did not change within the observation period. The inflammatory reaction shown by impression cytology decreased postoperatively.

Conclusion:  Blepharochalasis may be associated with dry eye. Blepharoplasty might be a means of alleviating dry eye symptoms. The reason for this subjective alleviation might be due to reduced inflammatory reaction, changes in blink mechanism or the fact that patients are more confident about their appearance.
Efficacy and safety of timolol maleate/latanoprost fixed combination versus timolol maleate and brimonidine given twice daily
Authors: Stewart William C. , Stewart Jeanette A. , Day Douglas , Sharpe Elizabeth D.
Published: May 2003

Purpose:  To evaluate the efficacy and safety of the timolol maleate/latanoprost fixed combination (TLFC) given once each evening versus brimonidine and timolol solution given twice daily as concomitant therapy in primary open‐angle glaucoma or ocular hypertension patients.

Methods:  Qualified subjects were begun on timolol alone twice daily for 1 month and then randomized to either TLFC or brimonidine and timolol concomitant therapy for 6 weeks. Patients were then switched to the other treatment regimen. Intraocular pressures (IOPs) were measured every 2 hours between 08 : 00 and 20 : 00 hours at baseline and at the end of periods 1 and 2.

Results:  This study found that in 32 subjects the IOP diurnal curve on timolol alone (20.9 ± 2.8 mmHg) decreased to 17.9 ± 3.2 mmHg when patients were treated with TLFC and to 19.0 ± 2.4 mmHg when patients were treated with brimonidine and timolol (p = 0.02). Intraocular pressures at individual time‐points were statistically similar between the groups at the 08 : 00 trough and 2 and 4 hours after dosing. However, beyond 4 hours after dosing, TLFC‐treated subjects demonstrated a trend towards lower IOPs at each 2‐hour time‐point that was not statistically significant after a Bonferroni correction (p ≤ 0.05). The incidence of both solicited and unsolicited side‐effects was similar between groups.

Conclusion:  This study suggests that TLFC given in the evening reduces the mean daytime diurnal IOP more than brimonidine and timolol given concomitantly twice daily.
Ocular complications and visual outcome in juvenile chronic arthritis: a 25‐year follow‐up study
Authors: Zak Marek , Fledelius Hans , Pedersen Freddy Karup
Published: May 2003

Objective:  Assessment of longterm ophthalmic outcome in juvenile chronic arthritis (JCA) with emphasis on visual acuity and identification of disease‐related parameters associated with rheumatic eye affection.

Material:  Sixty‐five adults (52 females, 13 males) with a history of or still active JCA were assessed an average of 26.7 years after disease onset.

Methods:  Cross‐sectional, longterm, follow‐up study including complete ophthalmological and rheumatological examinations.

Results:  Evidence of ocular complications was found in 13 subjects (20%): 10 had had recurrent iritis, two band keratopathy, and one diplopia due to rheumatoid eye muscle involvement. The three single eyes with poor sight (<0.1) were all in the complication subgroup. Binocularly, all but one patient scored at least 6/9 as best corrected visual acuity; one, however, had severe glaucoma‐impaired visual fields. The refractive range was −8.12 to +6.0 D. There were no cases of keratoconjunctivitis sicca. Iritis was associated with early disease onset (p = 0.02), longer disease duration (p = 0.02) and a positive antinuclear antibodies (ANA) (p = 0.02).

Conclusion:  Ophthalmic complications were recorded in 20% of the study group, primarily in ANA positive patients with pauciarticular onset JCA. In addition to the two patients with severely affected bilateral visual status (3%), one of the 65 patients had acquired unilateral blindness. Half of the complications were late in that they were first recorded after the age of 16 years. Otherwise, the findings were in keeping with other studies of visual prognosis using non‐selected series.
Lymphoid tumours of the ocular adnexa: a morphologic and genotypic study of 15 cases
Authors: Sigurdardottir Margret , Sigurdsson Haraldur , Barkardottir Rosa Björk , Kristjansdottir Sigrun , Agnarsson Bjarni A.
Published: May 2003

Purpose:  To examine all lymphoproliferative lesions of the ocular adnexa diagnosed in Iceland during 1983–2000 and to determine whether polymerase chain reaction (PCR) methods to determine clonality are helpful in characterizing these lesions.

Methods:  All patients diagnosed with lymphoproliferative lesions in the ocular adnexa in the years 1983–2000 were included in the study. Polymerase chain reaction studies for clonality were performed on these lesions.

Results:  Fifteen cases were identified. Seven were classified as inflammatory pseudotumour, one as lymphoid hyperplasia, four as atypical lymphoid hyperplasia and three as lymphoma. Of 12 cases examined by PCR, three were monoclonal for B‐cells (one lymphoma, one inflammatory pseudotumour and one atypical lymphoid hyperplasia) while the remaining lesions (including two lymphomas) appeared polyclonal.

Conclusion:  The results of this study suggest that analysis of clonality by PCR methods may be of limited use in classifying lymphoproliferative lesions of the ocular adnexa as benign or malignant. These results underscore the importance of using several techniques when determining clonality.
Factor V Leiden and prothrombin gene G20210A mutations in ocular Behçet disease
Authors: Batioğlu Figen , Atmaca Leyla S. , Karabulut Halil Gürhan , Beyza Sayin Derya
Published: May 2003

Purpose:  To investigate genetic prothrombotic factors (factor V Leiden and prothrombin gene G20210A mutations) and their relation with retinal vascular occlusions in ocular Behçet disease.

Methods:  Thirty Behçet patients were prospectively recruited into the study. Their mean age was 34.2 ± 8.3 years. All patients underwent complete ophthalmic examination and fluorescein angiography. Of the 30 patients, 15 (16 eyes) had retinal vascular occlusion. Patients were tested for the presence of factor V Leiden and prothrombin gene G20210A mutations by polymerase chain reaction. The results were compared with the frequencies of factor V Leiden in 285 and prothrombin gene G20210A mutation in 182 healthy members of the Turkish population.

Results:  The prevalence of factor V Leiden mutation was significantly higher in ocular Behçet patients (12/30, 40%), compared with healthy control subjects (28/285, 9.8%) (p < 0.001). Of the 12 Behçet patients with factor V Leiden mutation, eight had retinal vascular occlusion. The prevalence of factor V Leiden was 53.3% (8/15) of the 15 patients with retinal vascular occlusion and 26.7% (4/15) of the remaining 15 patients without vascular occlusion. Prothrombin gene mutation was detected in none of Behçet patients compared with 2.7% (5/182) of the control group.

Conclusion:  These data suggest that factor V Leiden may be an additional risk factor in ocular Behçet disease, whereas factor II mutations do not seem to be relevant.
Effects of thick Tenon's capsule on primary trabeculectomy with mitomycin‐C
Authors: Akarsu Cengiz , Önol Merih , Hasanrei̇soglu Berati
Published: May 2003

Purpose:  To investigate the effects of thick Tenon's capsule on primary trabeculectomy with adjunctive mitomycin‐C.

Methods:  In this prospective interventional case series of 45 consecutive uncomplicated glaucoma patients, 45 eyes with thick Tenon's capsule underwent primary trabeculectomy with intraoperative mitomycin‐C (0.4 mg/ml for 3 min). Success was defined as intraocular pressure (IOP) ≤ 21 mmHg with (qualified) or without (complete) medications.

Results:  The mean follow‐up period was 22.55 months. The mean preoperative IOP and number of medications were 28.91 ± 7.06 mmHg and 1.68 ± 0.73, respectively. The postoperative IOPs and the number of medications at all intervals were significantly lower than preoperative levels (p < 0.01 for each interval). The mean IOP was 11.03 ± 3.93 mmHg (12.17 ± 4.98 mmHg) at 24 months (12 months). Kaplan‐Meier survival analysis revealed a qualified success rate of 93.1% (95.6%) after 24 months (12 months). During follow‐up of the 45 eyes, 38 (84.4%) developed avascular thin‐walled bleb, seven eyes (15.6%) had hypotony (IOP < 6 mmHg), 14 eyes (31.1%) had a shallow anterior chamber, and one eye (2.2%) had endophthalmitis.

Conclusions:  The use of mitomycin‐C is associated with high success rates and good IOP control even in the presence of thick Tenon's capsule. However, thick Tenon's capsule does not seem to eliminate the development of complications in eyes undergoing primary trabeculectomy with mitomycin‐C.
Measuring visual field progression in the Early Manifest Glaucoma Trial
Authors: Heijl Anders , Leske M. Cristina , Bengtsson Boel , Bengtsson Bo , Hussein Mohamed ,   EMGT Group
Published: May 2003

Aims:  The Early Manifest Glaucoma Trial (EMGT) (316 eligible eyes) has used a new set of criteria to define visual field progression in glaucoma. This paper provides estimates of the amount of visual field worsening required to reach the EMGT definition of definite perimetric progression.

Methods:  In the 148 eyes that reached definite progression, we first determined changes between baseline and the time of definite EMGT progression, both for mean deviation (MD) and for number of highly (p < 0.5%) significantly depressed test points in pattern deviation probability maps. Second, we studied whether such changes depended on baseline MD, intraocular pressure (IOP), age and time to progression, all of which are factors that affect the rate of field progression.

Results:  In eyes reaching progression, the mean change in MD from baseline was −1.93 dB (SE ± 0.20) and the mean change in number of significant points was +4.85 (SE ± 0.35). These changes did not show linear dependency on baseline MD, IOP or time to progression.

Conclusions:  The average amount of field deterioration needed to reach EMGT visual field progression has been measured and expressed in more conventional units (i.e. a loss of about − 2dB in MD and an increase in about five highly significant points). These estimates will facilitate the clinical interpretation of the results of EMGT.
Frequency doubling technology and high‐pass resolution perimetry in glaucoma and ocular hypertension
Authors: Kalaboukhova Lada , Lindblom Bertil
Published: May 2003

Purpose:  To study the correlation between frequency doubling technology perimetry (FDT) and high‐pass resolution perimetry (HRP) in eyes with primary open‐angle glaucoma, suspect glaucoma, ocular hypertension, and in normal eyes.

Patients and Methods:  Ninety‐four patients (162 eyes) were studied. Visual fields were assessed by HRP, FDT screening C‐20–5 and FDT threshold C‐20 programs. In eyes with a discrepancy between the test results, a comprehensive clinical examination was performed, including optic disc photography and Heidelberg retinal tomography (HRT).

Results:  There was a strong correlation between HRP global deviation and the FDT mean deviation (for FDT threshold C‐20 test), and between HRP score and FDT score (for FDT screening C‐20–5 ). The correlation coefficients were r = −0.83 and r = 0.77, respectively. In all, 75 eyes (46.3%) had normal HRP and FDT screening results, while 67 eyes (41.4%) showed abnormal results in both tests. In 12 eyes (7.4%) HRP was within normal limits while FDT screening was abnormal. Seven of these eyes were judged to have glaucoma; three of them had converted from ocular hypertension to glaucoma. In eight eyes (4.9%) HRP was abnormal while FDT screening was normal. Three of these were judged to have glaucoma. Thus, the sensitivity and specificity of the FDT screening test for the detection of glaucoma were 91.7% and 87.8%, respectively.

Conclusion:  There was a strong correlation between FDT threshold C‐20, FDT screening C‐20–5 and HRP test results. Frequency doubling technology perimetry C‐20–5 represents a good screening test for the detection of optic nerve damage in open‐angle glaucoma.
Relationship between optic nerve head microcirculation and visual field loss in glaucoma
Authors: Yaoeda Kiyoshi , Shirakashi Motohiro , Fukushima Atsushi , Funaki Shigeo , Funaki Haruko , Abe Haruki , Tanabe Naohito
Published: May 2003

Purpose:  To study the relationship between optic nerve head blood flow velocity and visual field loss in patients with primary open‐angle glaucoma (POAG) and normal tension glaucoma (NTG).

Methods:  This study included 44 eyes of 44 patients with POAG and 44 eyes of 44 patients with NTG. To evaluate optic nerve head blood flow velocity, the square blur rate (SBR) was measured by means of laser speckle flowgraphy. The correlation between SBR and Humphrey visual field indices was evaluated with linear regression analysis.

Results:  In the NTG group, the average SBR at the superior and inferior temporal neuroretinal rim was positively correlated with mean deviation (MD) (r = 0.349, p = 0.020). The SBR at the superior or inferior temporal neuroretinal rim was positively correlated with the sum of the total deviations in the corresponding hemifields (r = 0.299, p = 0.049; r = 0.354, p = 0.019, respectively). The correlations between SBR and MD did not differ statistically between the NTG and POAG groups; however, no significant correlation between SBR and visual field indices was observed in the POAG group.

Conclusion:  These results suggested that the change in the circulation of the optic nerve head may be related to visual field damage in the NTG group but may be less involved in visual field damage in the POAG group.
Topical medication interferes with face‐down positioning after macular hole surgery
Authors: Krohn Jørgen
Published: May 2003

Purpose:  To investigate whether different procedures of topical medication interfere with postoperative face‐down positioning and thereby influence the anatomical success rate of macular hole surgery.

Methods:  A total of 39 consecutive eyes with macular holes were operated with vitrectomy and fluid‐gas exchange, followed by face‐down positioning for 1 week. Postoperatively, the procedures for topical medication differed between two consecutive groups of patients. In the first group (16 patients), a conventional postoperative regimen of topical antibiotics and steroids was administered as eye drops six times daily. In the second group (23 patients), topical medication was administered as ointments once daily, while the patients kept their heads straight forwards and looked slightly downwards.

Results:  The macular hole closed successfully in 10 (62.5%) of the 16 eyes in the eye drop group, and in 21 (91.3%) of the 23 eyes in the ointment group (p < 0.05).

Conclusion:  The present study indicates that frequent postoperative administration of eye drops reduces the success rate of macular hole surgery. To prevent patients from looking upwards during the instillation of topical antibiotics and steroids, the use of ointments is recommended.
Amniotic membrane as support for human retinal pigment epithelium (RPE) cell growth
Authors: Capeáns Carmen , Piñeiro Antonio , Pardo María , Sueiro‐López Catalina , Blanco María José , Domínguez Fernando , Sánchez‐Salorio Manuel
Published: May 2003

Purpose:  The aim of this work was to culture human retinal pigment epithelium (hRPE) cells over human amniotic membrane (hAM). Human AM was studied for its viability as an adequate support for transplantation of an hRPE cell monolayer with preserved cell polarity to the subretinal space.

Methods:  Human AM was obtained from pregnant women during caesarean section. The hAM was sectioned and the pieces were fixed to culture dishes. Human RPE cells were cultured from adult corneal donors and were seeded over hAM. Phase‐contrast photographs were obtained. Selected specimens were processed by transmission electronic microscopy (TEM).

Results:  The attachment and growth of hRPE cells over hAM was observed. Human RPE cells constituted tight colonies that maintained epithelial phenotype. Using TEM, we identified a monolayer of hRPE cells, with cuboidal to spheroidal morphology. These cells showed integration with the substrate and cell−cell contacts were detected.

Conclusion:  Amniotic membrane may be a suitable substrate for hRPE growth. Further studies are required in order to determine the viability of hRPE on hAM in the subretinal space.
The Enteric Nervous System II: Gastrointestinal Functions
Authors: Hansen Mark Berner
Published: May 2003

Abstract: The enteric nervous system is involved in most of the physiological and pathophysiological processes in the gastrointestinal tract. This Minireview is part two of three and describes the role of the enteric nervous system in gastrointestinal functions (motility, exocrine and endocrine secretions, blood flow, and immune processes) in health and some disease states. In this context, the functional importance of the enteric nervous system for food intake, the gall bladder, and pancreas will be addressed. In specific, dysmotility, diarrhoea, constipation, non‐occlusive intestinal ischaemia (intestinal angina), inflammation, cholelithiasis, cholecystitis, postcholecystectomy syndrome, and pancreatitis can be treated with neuroactive pharmacological agents. For example, serotonin receptor type four agonists can be used for the treatment of constipation, while nitric oxide synthesis inhibitors can be employed for the treatment of intestinal angina.
Neuroprotective Effects of Currently Used Antidotes in Tabun‐Poisoned Rats
Authors: Kassa Jiří , Krejèová Gabriela
Published: May 2003

Abstract: The neuroprotective effects of antidotes (atropine, pralidoxime/atropine, obidoxime/atropine and HI‐6/atropine mixtures) on rats poisoned with tabun at a lethal dose (220 μg/kg intramuscularly; 100% of LD50 value) were studied. The tabun‐induced neurotoxicity was monitored using a functional observational battery and an automatic measurement of motor activity. The neurotoxicity of tabun was monitored at 24 hr and 7 days after tabun challenge. The results indicate that atropine alone is not able to protect the rats from the lethal effects of tabun. Three non‐treated tabun‐poisoned rats and one tabun‐poisoned rat treated with atropine alone died within 24 hr. On the other hand, atropine combined with all tested oximes allows all tabun‐poisoned rats to survive at least 7 days following tabun challenge. Obidoxime combined with atropine seems to be the most effective antidotal treatment for the elimination of tabun‐induced neurotoxicity in the case of lethal poisoning among tested antidotal mixtures. The antidotal mixture consisting of atropine and HI‐6 is significantly less effective than the combination of atropine with obidoxime in the elimination of tabun‐induced neurotoxicity in rats at 24 hr following tabun challenge. Pralidoxime in combination with atropine appears to be practically ineffective to decrease tabun‐induced neurotoxicity at 24 hours as well as 7 days following tabun poisoning. Due to its neuroprotective effects, obidoxime seems to be the most effective and most suitable oxime for the antidotal treatment of acute tabun exposure among currently used oximes. Thus, the replacement of obidoxime by a more effective acetylcholinesterase reactivator for soman poisoning, the oxime HI‐6, can to a small extent diminish the neuroprotective efficacy of antidotal treatment in the case of acute tabun poisonings.
Analysis of Adenosine Vascular Effect in Isolated Rat Aorta: Possible Role of Na+/K+‐ATPase
Authors: Grbović Leposava , Radenković Miroslav
Published: May 2003

Abstract: The present experiments were undertaken in order to examine the effect of adenosine in isolated rat aorta, to investigate the possible role of intact endothelium and endothelial relaxing factors in this action and to determine which population of adenosine receptors is involved in rat aorta response to adenosine. Adenosine (0.1–300 μM) produced concentration‐dependent (intact rings: pD2=4.39±0.09) and endothelium‐independent (denuded rings: pD2=4.52±0.12) relaxation of isolated rat aorta. In the presence of high concentration of K+ (100 mM) adenosine‐evoked relaxation was significantly reduced (maximal relaxation in denuded rings: control – 92.1±9.8 versus K+– 54.4±5.0). Similar results were obtained after incubation of ouabain (100 μM) or glibenclamide (1 μM). In K+‐free solution, K+ (1–10 mM)‐induced rat aorta relaxant response was significantly inhibited by ouabain (100 μM). Application of indomethacin (10 μM), NG‐nitro‐L‐arginine (10 μM) or tetraethylammonium (500 μM) did not alter the adenosine‐elicited effect in rat aorta. 8‐(3‐Chlorostyril)‐caffeine (0.3–3 μM), a selective A2A‐receptor antagonist, significantly reduced adenosine‐induced relaxation of rat aorta in a concentration‐dependent manner (pKB=6.57). Conversely, 1,3‐dipropyl‐8‐cyclopentylxanthine (10 nM), an A1‐receptor antagonist, did not affect adenosine‐evoked dilatation. These results indicate that in isolated rat aorta, adenosine produces endothelium‐independent relaxation, which is most probably dependent upon activation of smooth muscle Na+/K+‐ATPase, and opening of ATP‐sensitive K+ channels, to a smaller extent. According to receptor analysis, vasorelaxant action of adenosine in rat aorta is partly induced by activation of smooth muscle adenosine A2A receptors.
Catechol‐O‐methyltransferase Inhibition in Erythrocytes and Liver by BIA 3‐202 (1‐[3,4‐dibydroxy‐5‐nitrophenyl]‐2‐phenyl‐ethanone)
Authors: Soares‐da‐Silva Patrício , Vieira‐Coelho Maria A. , Parada António
Published: May 2003

Abstract: The present study evaluated the relationship between the degree of catechol‐O‐methyltransferase (COMT) inhibition in erythrocytes and liver by BIA 3‐202 (1‐[3,4‐dihydroxy‐5‐nitrophenyl]‐2‐phenyl‐ethanone) and determined its effects upon the O‐methylation of L‐DOPA in rats orally treated with L‐DOPA plus benserazide. The soluble form of COMT (S‐COMT) in erythrocytes was endowed with the same affinity as liver S‐COMT for the substrate adrenaline. BIA 3‐202 inhibited erythrocytes and liver S‐COMT with ED50's of 1.9 (0.7, 3.1) and 1.9 (0.5, 3.2) (95% confidence limits) mg kg−1, respectively. BIA 3‐202 reduced the L‐DOPA‐induced rise of 3‐O‐methyl‐L‐DOPA in the peripheral circulation, striatal dialysate levels and striatum, and increased dopamine striatal levels. In BIA 3‐202‐treated rats the increase in L‐DOPA in peripheral blood and striatal dialysates was significantly greater than in vehicle‐treated rats. It is concluded that S‐COMT activity in erythrocytes may provide important information on the pharmacodynamic profile of COMT inhibitors. The novel COMT inhibitor BIA 3‐202 is a potent COMT inhibitor that enhances the availability of L‐DOPA to the brain by reducing its O‐methylation, which may prove beneficial in patients with Parkinson's disease treated with L‐DOPA.
Comparative Pharmacokinetics and Pharmacodynamics of Intravenous and Oral Nefopam in Healthy Volunteers*
Authors: Aymard Guy , Warot Dominique , Démolis Pierre , Giudicelli Jean François , Lechat Philippe , Le Guern Marie Emmanuelle , Alquier Christine , Diquet Bertrand
Published: May 2003

Abstract: To determine the pharmacokinetic, subjective effects of a single 20 mg dose of nefopam administered either intravenously or orally in healthy volunteers, twenty‐four healthy Caucasian men received 20 mg nefopam orally+placebo intravenous infusion and placebo orally+intravenous infusion of 20 mg nefopam with one week interval, in a double‐blind, double‐dummy cross‐over study. Nefopam and desmethyl‐nefopam plasma concentrations were measured by HPLC with UV detection up to 48 hr after drug administration. Self‐rating questionnaires (Mood and vigilance Visual Analogue Scales, Addiction Research Centre Inventory) and drug safety were investigated. The F value (bioavailability) of the parent drug was 0.36±0.13. The AUCoral/AUCiv ratio of nefopam+desmethyl‐nefopam was 0.62±0.23. The half–life of nefopam was similar whether administered orally (5.1±1.3 hr) or intravenously (5.1±0.6 hr). The half‐life of desmethyl‐nefopam was two to three times longer than that of the parent molecule (orally: 10.6±3.0 versus 5.1±1.3 hr, P<10−4 and intravenously: 15.0±2.4 versus 5.1±0.6 hr, P<10−4). As assessed by the Addiction Research Centre Inventory, no evidence of abuse liability in healthy, drug‐naive volunteers was observed. On visual analogue scales, volunteers rated themselves as more drowsy, less alert, less energetic and less anxious after oral compared to intravenous administration. The AUC0→24 hr of anxiety and energy parameters were not different after oral and intravenous administration: 90±142 versus 35±84 (P=0.27) and 66±74 versus 46±54 mm.hr (P=0.36), respectively. The AUC0→24 hr of drowsiness and alertness parameters were significantly greater after oral than after intravenous administration: 68±65 versus 27±30 (P=0.005) and 54±63 versus 28±48 mm.hr (P=0.03), respectively. A clockwise hysteresis loop was observed for drowsiness in 16 out of 24 volunteers after oral administration. The results suggest that in healthy volunteers desmethyl‐nefopam may contribute to the pharmacodynamic effects of single dose nefopam solution administered orally. This study shows a rather low bioavailability of nefopam given in intravenous solution when administered orally. Nevertheless, when the main metabolite desmethyl‐nefopam is taken into account, the ratio of the areas under the curves is almost doubled.