Dynamical Generation of Elementary Fermion Mass: First Lattice Evidence.

Using lattice simulations we demonstrate from first principles the existence of a nonperturbative mechanism for elementary particle mass generation in models with gauge fields, fermions, and scalars, if an exact invariance forbids power divergent fermion masses and fermionic chiral symmetries broken at UV scale are maximally restored. We show that in the Nambu-Goldstone phase a fermion mass term, unrelated to the Yukawa operator, is dynamically generated. In models with electroweak interactions weak boson masses are also generated, opening new scenarios for beyond the standard model physics.

Retinoblastoma and mental retardation microdeletion syndrome: clinical characterization and molecular dissection using array CGH.

We describe three patients with retinoblastoma, dysmorphic features and developmental delay. Patients 1 and 2 have high and broad forehead, deeply grooved philtrum, thick anteverted lobes and thick helix. Patient 1 also has dolicocephaly, sacral pit/dimple and toe crowding; patient 2 shows intrauterine growth retardation and short fifth toe. Both patients have partial agenesis of corpus callosum. Patient 3 has growth retardation, microcephaly, thick lower lip and micrognathia. Using array-comparative genomic hybridization (CGH), we identified a 13q14 de novo deletion in patients 1 and 2, while patient 3 had a 7q11.21 maternally inherited deletion, probably not related to the disease. Our results confirm that a distinct facial phenotype is related to a 13q14 deletion. Patients with retinoblastoma and malformations without a peculiar facial phenotype may have a different deletion syndrome or a casual association of mental retardation and retinoblastoma. Using array-CGH, we defined a critical region for mental retardation and dysmorphic features. We compared this deletion with a smaller one in a patient with retinoblastoma (case 4) and identified two distinct critical regions, containing 30 genes. Four genes appear to be good functional candidates for the neurological phenotype: NUFIP1 (nuclear fragile X mental retardation protein 1), HTR2A (serotonin receptor 2A), PCDH8 (prothocaderin 8) and PCDH17 (prothocaderin 17).

Primary open angle glaucoma in a case of mitochondrial encephalomyopathy (Kearns-Sayre syndrome).

PURPOSE: Kearns-Sayre syndrome is characterized by chronic progressive external ophthalmoplegia, tapetoretinal degeneration and severe generalized myopathy. METHODS AND RESULTS: We report on a 82-year-old male patient with Kearns-Sayre syndrome with open angle glaucoma. DISCUSSION: Reports of primary open angle glaucoma with Kearns-Sayre syndrome are very rare, but it is difficult to believe that this association is merely coincidental.

Adult-onset primary glaucoma and molecular genetics: a review.

PURPOSE: To evaluate recent molecular genetic studies focused on localizing and identifying the genes involved in adult-onset primary glaucoma, characterizing the gene products, and investigating the molecular mechanisms implicated in the pathophysiology of the disease. METHODS: Several studies have aimed at understanding gene expression and protein processing and attempting to correlate the mutations identified in the involved genes, particularly the TIGR/MYOC gene, with the overall spectrum of the disease, ranging from juvenile glaucoma to typical late-onset primary open-angle glaucoma. Genetic research remains essential until highly specific and sensitive tests have been developed (plausible disease-causing sequence variations, polymorphisms). RESULTS: The most effective method for detecting glaucoma clinically is the study of optic nerve and visual field damage, as well as intraocular pressure. In subjects at high risk, in members of families with a strong history of inherited glaucoma, and in families with a MYOC-positive test, the result may represent a marker to assess presymptomatic diagnosis and may be useful as a prognostic marker. CONCLUSIONS: OPTN seems to have a role confined to the pathogenesis of normotensive glaucoma with a few exceptions. Presently, the introduction of the expensive and time-consuming OPTN gene test in the current diagnosis of familial glaucoma is not justified.

Metachronous tumor development in unilateral retinoblastoma.

PURPOSE: A series of 205 retinoblastoma (RB) patients referred to the Department of Ophthalmology at the University of Siena (Italy) was evaluated in order to assess the proportion of unilateral cases later developing tumors in the companion eye ("metachronous" bilateral retinobastoma) (MBRB). METHODS: The total number of unilaterally affected patients developing tumors in the fellow eye was recorded and the risk factors assessed for the development of asynchronous bilateral retinoblastoma, i.e., family history, tumor multifocality and early age at diagnosis. RESULTS: Only two out of 133 (1.5%) unilateral retinoblastoma patients in our series could be considered affected by MBRB. CONCLUSIONS: The incidence of MBRB in our series was negligible (1.5% of all unilateral cases) compared to other reports. None of the reported risk factors for the development of tumors in the fellow eye was relevant in the present series. Although close follow-up of some unilateral cases is still recommended, thorough examination of the fellow eye, to search for lesions in the peripheral retina, is essential in all cases of unilateral RB. MBRB may be a distinctive clinical entity with specific clinical, genetic and prognostic features. However, all these aspects need to be better investigated in larger series.

Loss of heterozygosity on the long arm of chromosome 11 in orbital embryonal rhabdomyosarcoma (OERMS): a microsatellite study of seven cases.

OBJECTIVES. To investigate, by means of microsatellite analysis, regions of chromosome 11 involved in the genesis of embryonal rhabdomyosarcoma (ERMS) localized to the orbit. METHODS. Microsatellite analysis was carried out on seven cases of orbital ERMS by comparing the electrophoretic migration patterns of PCR-amplified microsatellites of chromosome 11 from both constitutional (blood) and tumor genotypes. Five of the tumors analyzed were samples frozen at the time of surgery, and two were paraffin embedded. RESULTS. Overall, microsatellites D11S1396 (11q13.1-q22.3) and D11S976 (11q) showed loss of heterozygosity (LOH) in all tumor samples, thus indicating the presence, on the long arm of chromosome 11, of one or more tumor suppressor genes with a possible role in the genesis of the disease. CONCLUSION. While the role of genes on the short arm of chromosome 11 in the genesis of ERMS is well established, much less is known of the possible involvement of tumor suppressor genes on the long arm of the same chromosome. This is the first report showing the possible involvement of tumor suppressor genes in this portion of the chromosome in ERMS localized to the orbit.

Design and implementation of a relational database used in the management of patients with retinoblastoma.

Clinical data are most useful in the management of patients with complex medical problems if they are accurate, reliable, and easily accessible by physicians and the medical community at large. Furthermore, the data are most valuable when they can be shared among cooperating institutions. We describe a computer system which exhibits a uniform taxonomy, an integrated on-line dictionary of clinical terms, a coherent temporal layout, and persistent spatial integrity with regard to the values of the variables. The system is user friendly and provides real time data access which can be retrieved by structured query language or may be programmed to be used as part of an international network in the management of patients with retinoblastoma, a malignant and potentially fatal tumor of childhood. Furthermore, because of its design flexibility, this system provides for potential application to other ophthalmic disorders, such as malignant uveal melanoma, and other areas of medicine as well.

Phantom eye: features and prevalence. The predisposing role of headache.

We prospectively evaluated the frequency, time-course and predisposing factors of phantom eye syndrome in 53 patients who underwent surgical eye amputation to cure ocular cancer. Before surgery, patients were classified as Group I (n = 25) if they had no history of headache or Group II (n = 28) if they were headache sufferers. Three clinical patterns were distinguished: phantom pain, non-painful phantom phenomena and photopsias. Their symptoms developed 7 days to 6 months after surgery, with peak incidence after 6 months (photopsia 43%; phantom pain 28%; non-painful phantom phenomena 62%). Phantom eye syndrome was more common in headache sufferers than in non-headache subjects. Headache sufferers were more prone to phantom pain, but more so to non-painful phenomena and photopsias. These findings are in accord with our previous results indicating that primary headache sufferers are prone to phantom tooth pain.

The polymerase chain reaction (PCR) in the routine genetic characterization of retinoblastoma: a tool for the clinical laboratory.

The Polymerase Chain Reaction (PCR) is a highly innovative technique which allows for the generation of large amounts of DNA starting from minute quantities obtained from the blood or tissue of a patient. With the increasing knowledge concerning the structure of the human genome and the potential to amplify specific segments of DNA by the PCR technique, the molecular genetic characterization of many ocular disorders has been greatly facilitated. This is particularly true of retinoblastoma (RB) where the causative gene, RB1, gene has been identified and characterized. Using PCR technique, specific sequences of the RB1 gene can be amplified and analyzed to precisely define the genetic mutation in an affected individual. In addition, this technique can also be applied in order to characterize the genetic defect within the tumor itself. In this report we illustrate the use of the PCR technique in the genetic characterization of the RB1 gene and its application to the study of RB. These techniques are applicable even in a small clinical laboratory and can be extended to a number of ophthalmic disorders.

Healon GV versus Healon in demanding cataract surgery.

This study compared how well two sodium hyaluronate viscoelastics maintained the anterior chamber during cataract surgery in eyes at risk for high vitreous pressure. Patients were divided into two groups based on the sodium hyaluronate used: Healon or Healon GV. Qualitative data were obtained with a digital slide gauge attached to the operating microscope. After capsulorhexis, mean anterior chamber depth (distance of the corneal apex to the iris plane) was significantly greater in the Healon GV group (P = .0012). Subjective intraoperative evaluation by surgeons also favored Healon GV. There was no difference between the groups in postoperative inflammation, corneal edema, intraocular pressure, or visual acuity. Therefore, although the two viscoelastics are equally safe, Healon GV maintains the anterior chamber better during cataract surgery.

Butterfly-shaped macular dystrophy. Longitudinal case study of two siblings.

Two brothers with butterfly-shaped macular dystrophy (BSMD) are reported. The anatomical and functional data were analyzed in 11 family members. Progressive photoreceptor dysfunction, supported by ERG abnormalities, was documented in both patients. The progression of the disease was observed over a period of seven years. The present observations emphasize that BSMD, at least in some cases, can be a chronic progressive disorder with secondary involvement of the photoreceptors.

Non-conventional ultrasonography (power spectrum analysis) in the management of retinoblastoma.

The differential diagnosis among the diseases that may simulate retinoblastoma is supported by several techniques; however, none of them can give an undeniable answer. In the authors' opinion the tissue characterization by power spectrum analysis of the radiofrequency ultrasound data may play an important role in the backscattered signal spectrum while being sensitive to the spectral shift trend. In order to evaluate the patterns of regression of quiescence of retinoblastoma foci after conservative treatment the authors try to create a model of tissue characterization that provides information not available in conventional A & B scan ultrasonography about cell type, vascularization and necrosis.

Cosmetic possibilities and problems in eyelid neurofibromas.

Neurofibromatosis type 1 (NF1) is an inherited systemic disease with frequent ocular involvement. A typical alteration observed in NF1 is the eyelid plexiform neurofibroma, often associated with facial homolateral hypertrophy. In such cases, surgical cosmetic results are rather unsatisfactory, since plexiform neurofibromas classically show a non-capsulated mass, with a marked tendency to local recurrence. The techniques for a cosmetic attempt are discussed on the basis of a personal series of eyelid reconstructions in NF1. The results can be considered satisfactory in some cases, when the orbital shape is preserved and the eyelid structure has not been excessively altered by the neurofibroma; in all other cases, the cosmetic outcome is inferior to the patient's and parents' expectations. The serious problem of recurrence is however a limitation to cosmetic surgery in eyelid neurofibromas.

Radical orbital resections.

The authors describe the techniques for subtotal, total and radical orbital exenteration. The aspects of primary and late reconstructive surgery are also discussed, with special reference to Frezzotti's personal technique for temporalis muscle transplantation after subtotal exenteration.

Italian register for retinoblastoma. Pros and cons of a retrospective statistical study.

In an attempt to verify some of the current conflicting results concerning the impact of relevant prognostic factors in the retinoblastoma therapy, the authors took into consideration, for statistical analysis, the series of 459 cases included in the Italian Registry for retrospective study of retinoblastoma. Although this series appears large enough, problems related to the continuously changing approaches to the disease and the consequent lack of standardization often make it difficult to draw significant conclusions. Hence, while historical (retrospective) analysis often allows the manipulation of a great number of data, particularly in the case of relatively rare diseases, prospective randomized controlled trials are strongly recommended to standardize definitely the relevant prognostic criteria. These and other problems related to retrospective analysis are discussed in detail.

Recurrent and new tumours during conservative treatment of bilateral retinoblastoma.

Conservative treatment of retinoblastoma is a combination of different therapeutic modalities: radiotherapy, photocoagulation, cryocoagulation, chemotherapy. The choice of the most suitable treatment depends on the stage of the disease. The evaluation of the regression and quiescence of tumoral foci after radiotherapy, Xenon photocoagulation or cryocoagulation is based on a purely subjective examination of the ophthalmoscopic aspects which are common to various types of treatment. Frequently, degenerative changes of the tumour mass are difficult to differentiate from actual recurrence. Recurrences generally start at the edge of the scar or within the scar, while new retinal tumours are observed far from the original tumour, sometimes near the ora serrata. The authors discuss the regression patterns and the ophthalmoscopic and clinical aspects of recurrent and new tumours and report their personal experience on the therapeutic approach.

Pathogenesis of posterior capsular opacification. Part II: Histopathological and in vitro culture findings.

The most interesting sources of information about the pathogenesis of posterior capsular opacification seem to be histopathological studies and in vitro tissue cultures. Since our surgical technique is extracapsular cataract extraction, the explants we used for tissue culture consisted of the anterior capsule epithelial sheet without the equatorial germinative zone. We successfully overcame several problems by using the autologous plasma clot culture method. This medium, considered the optimal one for this type of culture, allowed us to study the heterogeneous behavior of the epithelial cells in culture. Using the plasma clot culture method, we were able to demonstrate in vitro fibroblastic transformation of the epithelial cells. Histopathological findings of particular cases of posterior capsule opacification and immunohistochemistry of the human lens are also reported.

Pathogenesis of posterior capsular opacification. Part I. Epidemiological and clinico-statistical data.

We examined 895 eyes having extracapsular cataract surgery; 403 had an intraocular lens (IOL) implanted and 492 did not. The incidence of posterior capsular opacification was 7.69% in the eyes with an IOL and 14.23% in the eyes without an IOL. If we exclude complicated cataracts from the cases that did not have an IOL, the incidence of posterior capsular opacification decreases to 9.06%. Various models of implanted IOLs showed different incidences of posterior capsular opacification: For J-looped lenses the incidence was 11.02%; for Frezzotti-Caporossi lenses, 7.35%. The follow-up was too short for soft lenses. The Frezzotti-Caporossi lens can be inserted with the convex side either anterior or posterior. A statistical evaluation shows that the reverse optic or posterior convex orientation in the bag caused a lower incidence of posterior capsular opacification (3.01%).

Retinoblastoma. Analysis of 75 cases and proposal for a new model of oncogenesis and tumor growth kinetics.

A series of 75 retinoblastoma patients were analyzed at the Institute of Ophthalmology, Siena, and a mathematical model for the 'nodule to cancer' transformation applied to it. The authors obtained data in disagreement with Knudson's 'two hit' hypothesis but fitting an alternative model of oncogenesis. This model is based on probabilistic arguments and a possible pattern of tumor growth and evolution is given in detail.