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G Richard

Publications and source records attributed to G Richard.

At least 91 records · Page 5Linked to original sources
PubMed1999

[Immunohistochemical characterisation of surgically excised choroidal neovascularisation in age-related macular degeneration].

AIM: The objective of the study was to gather further information about the pathogenesis of choroidal neovascularisations (CNV), which is still not clearly understood, and to establish criteria for making decisions on a appropriate therapy. Immunohistochemical characteristation should allow a more comprehensive evaluation of cellular components of the membranes and their functional role. PATIENTS AND METHODS: In 29 patients (16 women, 13 men) with age-related macular degeneration ranging in age from 46 to 91 years (mean age, 76.4 years), CNV were excised by pars-plana vitrectomy. Sections were stained with hematoxylin-eosin (HE) and periodic acid-Schiff (PAS) and examined by light microscopy. For the immunohistochemical characterisation of the surgical specimens the following anti-genetic determinants were used: glial fibrillary acid protein (GFAP) for glial cells, synaptophysin for neuronal cells, neuron-specific enolase (NSE) for neuronal and neuroectodermal cells, CD 31 for endothelial cells and pancytokeratin (KL1) for cells of the retinal pigment epithelium (RPE). Cells undergoing apoptosis were labeled with the TUNEL technique. RESULTS: 22 (76%) surgical specimens showed TUNEL positive cells in the connective tissue, vascular endothelium and retinal pigment epithelium. Positive immunostaining of neuronal antigenetic determinants was found for glial fibrillary acid protein in 22 patients (76%), for synaptophysin in 28 patients (97%) and for neuron-specific enolase in 21 patients (72%) CNV. The epithelial marker KL1 was positive in 28 patients (97%) and the endothelial marker CD 31 in 20 patients (69%). CONCLUSION: The immunohistochemical analyses of CNV showed that in the majority of cases during the excision of choroidal neovascularizations in addition to scar tissue and connective tissue also parts of the native retinal pigment epithelium and of the neurosensory retina are removed which is only partly visible with standard staining techniques. These findings suggest that the mostly not satisfying postoperative results are partly due to the damage of neuronal cells and a partial loss of the retinal pigment epithelium. Apoptosis as a regulating mechanism in choroidal neovascularization. The variable appearence of apoptosis suggests that it is possibly related to the degree of activity of CNV.

Aged↗
PubMed1999

Alpha/beta- and gamma/delta TCR(+) lymphocyte infiltration in necrotising choroidal melanomas.

AIM: To detect specific tumour infiltrating T cells (TIL) carrying antigen specific MHC-I restricted receptor genes on necrotising and non-necrotising malignant melanomas and to correlate the findings with clinical data. METHODS: alpha/beta- and gamma/delta- TIL were determined by immunohistochemical staining in melanomas of patients with known follow up of more than 10 years. An antigen retrieval method was used to determine variable genes delta1 and gamma1 on TCR(+) cells by an anti-TCR Vdelta1 and anti-CrgammaM1, and of Valpha and Vbeta TCR(+) by an anti-pan-TCR(+) alpha/beta antibody. RESULTS: Intratumoral TIL were present in 86 of 113 (76.1%) necrotising melanomas (NMM) v 21 of 100 (21%) in non-necrotising melanomas (MM); of these, Valpha/beta- TCR(+) cells were present in 52 of 74 (70.3%) TIL harbouring NMM v four of 21 (19%) MM; Vgamma1 in 29 of 74 (39.2%) NMM v two of 21 (10%) MM; and Vdelta1 in 39 of 74 (52.7%) NMM v three of 21 (14%) MM. Extratumoral lymphocytic infiltration was seen in 86 (76.1%) NMM including Valpha/beta TCR(+) cells in 10 (11.6%) cases, v five (5%) MM cases with no Valpha/beta TCR(+) cells detected. Vgamma1 and Vdelta1 TCR(+) cells were not found in extratumoral infiltrates. CONCLUSIONS: In NMM, the median survival was 69.3 (range 6-237) months, 19 of 74 patients (25.7%) survived 5 years, and mortality was associated with advanced stage (p<0.001), patient age (p<0.023), and extent of necrosis (p<0.048). Survival was increased with evidence of Vgamma1 and Vdelta1 TCR(+) cells (p<0.026).

Adult↗
PubMed1999

[Conus venoms: a source of toxins which interact with membrane- potential-dependent sodium channels].

Marine snails of the genus Conus, as they are carnivorous predators, have a venom apparatus used to capture their prey. The toxins contained in the venoms of Conidae, called conotoxins, are of a particular high degree of diversity and represent powerful tools in the neuroscience field. Indeed, these toxins specifically bind with a high affinity to receptors and ionic channels. Therefore, they provide original pharmacological tools which receive increasing investigation both to identify and study some functions of the nervous systems and to characterize new types and closely related subtypes of receptors or ionic channels. The voltage-gated sodium channel, because of its fundamental role in cell membrane excitability, is the specific target of a large number of animal and vegetal toxins. Actually, at least seven toxin receptor sites have been identified on this channel-protein. These toxins, and in particular conotoxins, are used to precise the role of different types and/or closely related subtypes of sodium channels in the peripheral and central nervous systems. The focus of the present review is to summarize our current knowledge of the consequences of physiological interactions between different conotoxin families and sodium channels.

Action Potentials↗
PubMed1998

Rapid categorization of natural images by rhesus monkeys.

Two rhesus macaques were tested on a categorization task in which they had to classify previously unseen photographs flashed for only 80 ms. One monkey was trained to respond to the presence of an animal, the second to the presence of food. Although the monkeys were not quite as accurate as humans tested on the same material, they nevertheless performed this very challenging visual task remarkably well. Furthermore, their reaction times were considerably shorter than even the fastest human subject. Such data, combined with the detailed knowledge of the monkey's visual system, provide a severe challenge to current theories of visual processing. They also argue that this form of rapid visual categorization is fundamentally similar in both monkeys and humans.

Animals↗
PubMed1998

[Intraocular pseudotumor in an AIDS patient. Block excision, differential diagnosis, histology].

BACKGROUND: Intraocular pseudotumors are a rare event in Aids patients and often pose diagnostic problems. CASE REPORT: A 37-year-old patient who had had HIV seroconversion for 7 years was seen to developed progressively growing, multiple, disseminated, subretinal lesions OD > OS, accompanied by exudative retinal detachment and iritis. Since all etiological laboratory diagnostic efforts to detect an infectious, noninfectious and neoplastic systemic lesion failed, a diagnostic and curative therapeutic chorioretinal excisional biopsy specimen of the largest of the tumors (3 x 3 x 2 mm) was taken. The histological work-up demonstrated granulation tissue similar to an intraocular pseudotumor without signs of infection, malignancy or reactive lymphoid hyperplasia. This finding resulted in systemic corticosteroid treatment with complete resolution of the lesions in both eyes and no recurrences. CONCLUSIONS: An invasive diagnostic procedure in patients suffering from lesions of unknown cause resulting in the institution of an appropriate medical treatment may be beneficial for the integrity and vision of the respective eye.

Adult↗
PubMed1998

[Necrotizing keratitis in chronic polyarthritis. Combined immunosuppressive and surgical therapy].

INTRODUCTION: Areactive forms of keratitis in patients with seropositive rheumatoid arthritis are inflammations threatening the visual acuity and integrity of the eye. They commonly occur in a rheumatologically inactive interval and have a poor prognosis. A retrospective evaluation of medicamentous and surgical strategies for a curative therapy with optical rehabilitation is necessary to optimise the treatment of patients with necrotic sclerokeratitis. PATIENTS AND METHODS: A total of 27 eyes of 22 patients (14 women and 8 men, ranging in age at the time of operation from 40 to 88 years; mean 68.7 years) with seropositive rheumatoid arthritis and secondary Sjögren's syndrome were reviewed retrospectively. There were 17 eyes with necrotic keratitis and 9 eyes with necrotic sclerokeratitis. In one eye, necrotic sclerokeratitis with bacterial transmigrating keratitis and hypopyon occurred. OPERATIONS: In 8 cases we performed a perforating mini-keratoplasty, in 16 cases a tectonic and optical perforating keratoplasty, in 3 cases a tectonic sclerokeratoplasty, in 9 patients a combined keratoplasty and cataract extraction with posterior chamber lens implantation and in 1 case a partial conjunctival plasty. Follow-up ranged from 7 months to 4 years (average 2.8 years). RESULTS: In all eyes, a sufficient tectonic and primary curative effect was achieved only under cyclophosphamide immunosuppression. In 3 cases, a rekeratoplasty had to be performed because of recurrent keratitis after changing the systemic cyclophosphamide therapy to methotrexate, glucocorticosteroids or non-steroid antiphlogistic agents. Visual acuity outcome was depending on the eccentricity of the keratoplasty and earlier affections of the eye. Postoperatively, the visual acuity improved in 23 eyes. In 3 cases, no change of visual acuity was achieved. Visual acuity deteriorated in one case from counting fingers to hand motions. Peri- and postoperative complications during the follow-up period were corneal infiltration around sutures in 4 eyes, graft rejecting reactions in 3 cases, and sicca syndrome in 6 cases. CONCLUSIONS: The intensive cooperation of ophthalmologists and rheumatologists enables the successful treatment of apparently hopeless situations in necrotic sclerokeratitis in patients with seropositive rheumatoid arthritis. The rate of complications under an immunosuppressive therapy with cyclophosphamide was found at average 2.8 years follow-up to be low. The indication for the combined therapy depends on the ophthalmological findings; rheumatologists and ophthalmologists should decide on the appropriate dosage for the systemic cyclophosphamide therapy. Topical glucocorticosteroid therapy alone is contra-indicated.

Adult↗
PubMed1998

Limitations of imaging choroidal tumors in vivo by optical coherence tomography.

BACKGROUND: Optical coherence tomography (OCT) produces two-dimensional cross-sectional images with a longitudinal resolution of 10 microns. Its capacity for imaging retinal structure has been shown in a variety of diseases. There are no reports on its capacity and limitations in imaging choriocapillary and choroidal structures. METHODS: Twenty-two patients with the diagnosis of malignant melanoma of the choroid were submitted to OCT. We used a prototype and a commercial device, both with an 850-nm superluminescent diode with a band-width of 30 nm (reported longitudinal resolution 10 microns). The images were evaluated for retinal thickness, changes in retinal pigment epithelium, subretinal fluid accumulation and changes in choriocapillary or choroidal reflectivity. RESULTS: Retinal edema and detachment found on biomicroscopic examination for fluorescein angiography was detected by OCT in all such cases. In 2 of 22 cases small retinal detachments were detected only by OCT. Tumor extension through the retinal pigment epithelium was not seen in this series, either by biomicroscopy or by OCT. The pattern of choroidal or choriocapillary reflectivity was nonspecifically lower than that of normal choroid, but did not yield any additional information about tumor histology. When normal retina was present, the OCT appearance of a malignant melanoma resembled that of normal choroid. CONCLUSION: OCT may provide information about the retinal structure overlying prominent tumors and the extent of adjacent retinal detachment. In its present state of development, OCT is of little value in the differential diagnosis of choroidal tumors. Its potential value for the follow-up of shallow tumors needs further investigation.

Adult↗
PubMed1998

Functional defects of Cx26 resulting from a heterozygous missense mutation in a family with dominant deaf-mutism and palmoplantar keratoderma.

Mutations in GJB2 encoding the gap junction protein connexin-26 (Cx26) have been established as the basis of autosomal recessive non-syndromic hearing loss. The involvement of GJB2 in autosomal dominant deafness has also been proposed, although the putative mutation identified in one family with both deafness and palmoplantar keratoderma has recently been suggested to be merely a non-disease associated polymorphism. We have observed a similar phenotype in an Egyptian family that segregated with a heterozygous missense mutation of GJB2, leading to a non-conservative amino acid substitution (R75W). The deleterious dominant-negative effect of R75W on gap channel function was subsequently demonstrated in the paired oocyte expression system. Not only was R75W alone incapable of inducing electrical conductance between adjacent cells, but it almost completely suppressed the activity of co-expressed wildtype protein. The Cx26 mutant W77R, which has been implicated in autosomal recessive deafness, also failed to form functional gap channels by itself but did not significantly interfere with the function of wildtype Cx26. These data provide compelling evidence for the serious functional consequences of Cx26 mutations in dominant and recessive deafness.

Amino Acid Sequence↗
PubMed1998

Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis.

Erythrokeratodermia variabilis (EKV, OMIM 133200) is an autosomal dominant genodermatosis with considerable intra- and interfamilial variability. It has a disfiguring phenotype characterized by the independent occurrence of two morphologic features: transient figurate red patches and localized or generalized hyperkeratosis. Both features can be triggered by external factors such as trauma to the skin. After initial linkage to the RH locus on 1p, EKV was mapped to an interval of 2.6 cM on 1p34-p35, and a candidate gene (GJA4) encoding the gap junction protein alpha-4 (connexin 31, Cx31) was excluded by sequence analysis. Evidence in mouse suggesting that the EKV region harbours a cluster of epidermally expressed connexin genes led us to characterize the human homologues of GJB3 (encoding Cx31) and GJB5 (encoding Cx31.1). GJB3, GJB5 and GJA4 were localized to a 1.1-Mb YAC in the candidate interval. We detected heterozygous missense mutations in GJB3 in four EKV families leading to substitution of a conserved glycine by charged residues (G12R and G12D), or change of a cysteine (C86S). These mutations are predicted to interfere with normal Cx31 structure and function, possibly due to a dominant inhibitory effect. Our results implicate Cx31 in the pathogenesis of EKV, and provide evidence that intercellular communication mediated by Cx31 is crucial for epidermal differentiation and response to external factors.

Amino Acid Sequence↗
PubMed1998

[Type I lattice corneal dystrophy. Clinical and molecular genetic study of a large family].

BACKGROUND: Lattice corneal dystrophy type I is one of the frequent forms of stromal dystrophies following autosomal dominant inheritance. The beta-IG-h3 gene encoding keratoepithelin on the long arm of chromosome 5 has recently been described as disease gene for lattice corneal dystrophy type I as well as for three other corneal dystrophies with autosomal dominant pattern of inheritance. PATIENTS AND METHODS: Ten family members in three generations of a large family with autosomal dominant lattice corneal dystrophy were analyzed clinically by slit-lamp biomicroscopy. Mutation analysis in the beta-IG-h3 gene was carried out at the mRNA level by RT-PCR and cDNA sequencing. RESULTS: A heterozygous single-base substitution (417C-->T) in exon 4 of the beta-IG-h3 gene was detected predicting the replacement of arginine-124 by cysteine. Analysis of 10 family members showed perfect cosegregation of the mutation and lattice corneal dystrophy type I. The investigation excluded this mutation in one family member previously classified as potentially affected. CONCLUSIONS: The investigation confirmed autosomal dominant inheritance with complete penetrance in the family described. The mutation 417C-->T has already been found earlier in another family of different geographic origin. These results suggest a mutation hot spot at position 417. In addition, no evidence of genetic heterogeneity of lattice corneal dystrophy type I was detected. Molecular genetic analysis (in conjunction with genetic counselling) therefore may be useful in routine diagnostics as the confirmation of the diagnosis by histological examination is possible only after keratoplasty. The common pathomechanism in lattice corneal dystrophy type I may facilitate development of new therapeutic concepts; the easy accessibility of the target organ may provide new possibilities e.g. for gene therapy.

Adult↗
PubMed1998

[Recurrent pterygium over 15 years: epibulbar cartilaginous findings].

BACKGROUND: Epibulbar and extraocular cartilage bearing tumors in adults are extremely rare. PATIENT: A nasally located pterygium in a 24-year-old patient was excised and recurred over the ensuing 15 years six times requiring local excisions, and each time a histological diagnosis of pterygium was made. Only a curative excision including a biopsy of the insertion of the m. rectus medialis and a sclerokeratoplasty revealed the tumor to bear cartilage histologically in an unusual place. A Ruthenium-106 brachytherapy was followed by a triple procedure for visual rehabilitation, and no further recurrences were observed. CONCLUSION: The differential diagnosis of a cartilaginous tumor most likely a choristoma growing in an unusual localisation should be considered in adults suffering from recurrent pterygia without known physical risk factors, and a curative excision be performed. Further treatment options depend on the appearance of the tumor.

Adult↗
PubMed1998

[Immunohistochemical markers for cytoplasmic antigens in acquired melanosis, malignant melanomas, and nevi of the conjunctiva].

BACKGROUND: Benign and malignant melanocytic lesions of the conjunctiva are difficult to differentiate histologically. At present in the ophthalmologic literature there is not known a high specific and simply applicable histological feature (tumor marker) of differentiation to identify melanocytic lesions of the conjunctiva. METHODS: In this study 55 nevi, 15 primary acquired melanoses (stage Ia) and 54 melanomas of the conjunctiva were examined retrospectively immunhistochemically by antibodies vs. S-100 protein, and the melanoma-associated antigens HMB-45 and NKI/C3 using the labelled avidin-biotin method. 45 patients (25 female, 20 male) with malignant melanomas of the conjunctiva have been followed up clinically. RESULTS: S-100, HMB-45 and NKI/C3 are highly significant markers to identify malignant melanomas of the conjunctiva (sensitivity: S-100: 96.4%, HMB-45: 96.3%, NKI/C3: 98.1%), whereas markers in acquired melanoses (sensitivity: 93.3%, 78.6% and 92.9%), and nevi (sensitivity: 92.9% 40.7%, 98.2%) are not. Positive tumor markers do not correlate with local recurrences or metastasis. The localization of malignant melanomas and the lymphocytic infiltration are not prognostically significant. The only significant risk factor (p = 0.0485) predicting the development of recurrence or metastasis is tumor thickness > 1.5 mm. CONCLUSIONS: The tumor markers S-100, HMB-45 and NKI/C3 cannot differentiate reliably between benign and malignant melanocytic lesions of the conjunctiva, and positive tumor markers do not correlate with local recurrences or metastasis. The only significant risk factor (p = 0.0485) predicting the development of metastasis is tumor thickness (> 1.5 mm).

Adult↗
PubMed1998

[Clinical and histopathological aspects of 113 necrotizing malignant melanomas of the choroid. 1. Clinical and histological features of necrotizing choroidal melanomas].

BACKGROUND: Tumor necrosis may reflect a destructive immune reaction. Systematic and statistically significant comparative clinico-histopathologic studies have not yet been reported. PATIENTS AND METHODS: 113 necrotizing choroidal melanomas (NCM) recruited from 701 enucleated globes 1967-1988 were resectioned, stained and compared to 100 choroidal melanomas without necrosis (CM), and data of 74 patients with a follow-up of more than 10 years were evaluated. RESULTS: Statistically significant characteristics of NCM were: patient age < 60 yrs. for NCM 27.4%, CM 46%; patient age in men for NCM was 64 yrs on average (CM: 58 yrs.), in women for NCM 67 yrs. (CM: 59 yrs.). Time elapsed between first symptoms and enucleation was < 12 months in 15.9% of NCM (89% for CM), and > 12 months in 23.9% of NCM (11% in CM). Mixed or epitheloid cell tumors was seen in 54.9% of NCM and 49% of CM, spindle cell tumors in 36.3% of NCM and 51% in CM. Advanced tumor stages T3 and T4 were present in 45.1% resp. 36.3% of NCM compared to 37% resp. 16% in CM. Scleral invasion was documented in 67.3% of NCM and 37% of CM, extrascleral dissemination in 43% of NCM and 16% of CM. Secondary glaucomas were seen in 62.2% of NCM and 6% CM, a penetration through Bruch's membrane in 61.0% of NCM and 46% of CM. Intratumoral hemorrhage was noted in 68.14% of NCM and 24% of CM, extratumoral bleeding in 23.9% of NCM and 0% CM. Inflammatory reactions in tumors were observed in 96.7% of NCM harboring > 30% necrosis compared to 5% in CM, and extratumoral in 94.5% of NCM and 0% of CM. Intraocular extratumoral necrosis was seen in 23.9% of NCM and 0% of CM. There were no significant differences in the degree of pigmentation of the 90.3% pigmented NCM or of the 94% pigmented CM, neither in the tumor localization, being constantly behind the equator in 87% of cases. Survival of patients with NCM patients was 5 years and 9 months on average (5-year mortality rate 41.9%), and 74.3% were deceased from metastatic spread. CONCLUSIONS: Significant clinical and histopathological differences between necrotizing and non-necrotizing malignant melanomas of the choroid can be identified. The inflammatory reaction of NCM must be further elucidated, particularly with respect to the nature of tumor-infiltrating lymphocytes.

Adult↗
PubMed1998

[Clinical and histopathological aspects of 113 necrotizing malignant melanomas of the choroid. 2. Immunogenetic characterization of T-cell receptor-positive tumor-infiltrating lymphocytes and survival of patients with necrotizing melanomas of the choroid].

BACKGROUND: T-cell receptor (TCR) gene analysis of tumor infiltrating lymphocytes (TIL) has been recognized to play a pivotal role in the immunosurveillance of solid neoplasms. PATIENTS AND METHODS: Therefore, 113 necrotizing choroidal melanomas (NMM) were compared to 100 non-necrotizing melanomas (MM) histologically and immunohistochemically. RESULTS: NMM showed TIL more frequently (76.11% vs. 21%, p < 0.001). V alpha/V beta- (70.3% of NMM) and V gamma 1- (39.2% of NMM) and V delta 1- (52.7% of NMM) TCR+ cells were distributed focal or diffuse, and correlated with tumor volume, diameter, and scleral invasion. 74.33% of NMM patients had died after 240 months (5 year survival: 58.1%). Mortality was not significantly associated with TIL (p < 0.33) or V alpha/V beta-TCR+ cells (p < 0.2), however, survival was significantly increased with evidence of V gamma 1- and V delta 1-TCR+ cells (p < 0.026). CONCLUSIONS: V alpha/V beta-, V gamma 1- and V delta 1-TCR+ tumor infiltrating lymphocytes can be demonstrated in choroidal melanomas. This is a basis for functional studies providing a rationale for the evaluation of immunotherapeutic modalities.

Adult↗
PubMed1998

Endothelial cell loss secondary to two different phacoemulsification techniques.

BACKGROUND AND OBJECTIVE: The endothelial cell count after phacoemulsification serves as a sensitive indicator for the level of corneal damage caused by different phacoemulsification techniques. PATIENTS AND METHODS: In a prospective and randomized study, the "Reversed Tip and Snip" technique and the "Divide and Conquer" technique were performed in groups of 30 patients each. The corneal endothelial cell count was measured preoperatively as well as 4 weeks and 3 months postoperatively. RESULTS: The endothelial cell count showed significant (P < .001) reduction by approximately 10% after the "Reversed Tip and Snip" technique and by approximately 15% (P < .001) after the "Divide and Conquer" technique. The latter produced a significantly (P < .001) greater cell loss. CONCLUSIONS: The "Reversed Tip and Snip" phacoemulsification technique produces less endothelial cell loss than the "Divide and Conquer" technique.

Aged↗