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Biomedical subjects

A D Singh

Publications and source records attributed to A D Singh.

At least 19 recordsLinked to original sources
PubMed1998

Treatment of retinoblastoma vitreous base seeding.

OBJECTIVE: The purpose of the study is to describe results of a new treatment for retinoblastoma vitreous base seeding. DESIGN: The study design was a retrospective review of patients treated at an ocular oncology referral center. PARTICIPANTS: Five eyes of five patients with vitreous base seeding that occurred after previous external beam radiation therapy were treated between October 1987 and December 1994. INTERVENTION: A customized plaque made from iridium-192/platinum wire was placed to deliver 4000 cGy to the tumor apex along its entire length and systemic chemotherapy (consisting of carboplatin, vincristine, and etoposide) was given. MAIN OUTCOME MEASURES: Eye preservation and tumor control were measured. RESULTS: Vitreous base seeding was controlled completely and the eye preserved in four of the five treated eyes with an average follow-up of 26.2 months. CONCLUSIONS: The combination of a customized iridium-192 plaque and systemic chemotherapy is an effective means of treating vitreous base seeding of retinoblastoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Lifetime prevalence of uveal melanoma in white patients with oculo(dermal) melanocytosis.

OBJECTIVE: In the white population, an association between oculo(dermal) melanocytosis (ODM) and uveal melanoma is well recognized. However, the lifetime prevalence of uveal melanoma in the ODM population is not known. This study was designed to determine the lifetime prevalence of uveal melanoma among patients with ocular melanocytosis. DESIGN: Fifty-six white patients manifesting ODM with uveal melanoma formed the basis of the study. MAIN OUTCOME MEASURES: Published prevalence rates of ODM and uveal melanoma were used for calculations using Bayes' theorem. RESULTS: The lifetime prevalence of uveal melanoma in white patients with ODM is estimated to be 2.6 x 10(-3). The median age at diagnosis of uveal melanoma in the ODM population was similar to a randomly selected population (60.5 years and 62.5 years, respectively). In the vast majority of patients (90%) with ODM-associated uveal melanoma, the uveal melanoma was diagnosed between the ages of 31 years and 80 years. CONCLUSIONS: One of about 400 patients with ODM followed for life is estimated to develop uveal melanoma. Excessive melanocytes in the uveal tract in ODM may provide the biologic basis for susceptibility to the development of uveal melanoma. Patients with ODM should be monitored ophthalmoscopically, especially during the susceptible period, for the development of uveal melanoma. The authors suggest that a national registry of ODM patients be created and prospective data collected to better assess the risk of developing uveal melanoma.

Adolescent↗
PubMed1998

Cartridge cracks during foldable intraocular lens insertion.

PURPOSE: To assess the incidence of cartridge cracks during foldable intraocular lens (IOL) insertion and to determine factors that play a role in the development of these cracks. SETTING: Leesburg Regional Ambulatory Surgical Care Center, Leesburg, Florida, USA. METHODS: Small incision cataract surgery was performed in 350 consecutive cases. A foldable silicone IOL (Allergan Medical Optics SI-40) was inserted in all cases using the Unfolder cartridge and 3 viscoelastic agents: sodium hyaluronate (Healon, Vitrax) and sodium chondroitin sulfate-sodium hyaluronate (Viscoat). RESULTS: Cartridge cracks occurred in 52 eyes (14.86%). Almost all cracks (98.1%) occurred in cases in which Healon was used to load the IOL. In each case of a cracked cartridge, there was evidence of the plunger overriding the optic edge. CONCLUSIONS: We recommend the use of chondroitin-based viscoelastic agents to load the SI-40 foldable IOL to minimize the risk of cartridge cracks. Modifications in the design of the IOL inserter may eliminate the problem of cartridge cracks.

Chondroitin Sulfates↗
PubMed1997

Anti-interleukin 5 strategies as a potential treatment for asthma.

A paradigm shift, championed largely by cellular immunologists, has redefined asthma as an immune mediated phenomenon characterised by an interleukin 5 (IL-5) driven eosinophilic bronchitis. This change in emphasis has provoked intense interest in the possibility that inhibitors of IL-5 production, or antagonists of its activity, will provide a new generation of anti-asthma drugs.

Asthma↗
PubMed1996

Familial uveal melanoma. Clinical observations on 56 patients.

OBJECTIVE: To study the clinical profile and kindreds of patients with familial uveal melanoma (FUM). DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: Medical charts of 4500 patients with uveal melanoma were reviewed for family history of uveal melanoma. The clinical profile of these patients and their kindreds were studied to determine the incidence of FUM and pattern of inheritance. The association of FUM to cutaneous melanoma, familial atypical mole and melanoma syndrome, and other nonmelanocytic cancers was analyzed using statistical methods. RESULTS: Of 4500 patients with uveal melanoma, 56 patients in 27 families (0.6%) had a family history of uveal melanoma. The uveal melanoma in all 56 familial patients was unilateral. In 17 cases (63%), the second affected relative was a first-degree relative. In the remainder, the second affected relative was a second- (22%) and third-degree (15%) relative. In 25 families (93%) only two members were affected, and in two families (7%) three members had uveal melanoma. Patients with FUM were four times as likely to have a second primary malignant neoplasm than were people in the general population. However, no evidence was seem that unaffected kindreds of patients with FUM were at higher risk of having a second primary malignant neoplasm. CONCLUSIONS: Familial involvement in uveal melanoma is rare. Familial uveal melanoma most often (63%) affects first-degree relatives, rarely affects more than two persons in a family, and may be associated with a generalized inherited predisposition to cancer. Further genetic studies are necessary to fully characterize FUM syndrome.

Adult↗
PubMed1996

Familial uveal melanoma, III. Is the occurrence of familial uveal melanoma coincidental?.

OBJECTIVE: To ascertain whether the familial occurrence of uveal melanoma was coincidental in kindreds in which 1 first-degree relative of the proband had also been affected with primary uveal melanoma. PATIENTS: In a series of 4500 patients with primary uveal melanoma, 17 kindreds were identified in which a first-degree relative of the proband had also been affected with primary uveal melanoma. DESIGN: In the 17 families in which a first-degree relative of the proband had been affected, primary uveal melanoma was classified as familial. In the remaining 4483 families, primary uveal melanoma was classified as sporadic. The expected number of affected first-degree relatives of probands for a family was estimated, assuming an incidence rate of 6 cases per million population per year in each type of family. RESULTS: The expected number of affected first-degree relatives was calculated to be 0.81, with an SE of 0.08, compared with 17 observed affected first-degree relatives (P < .001). CONCLUSION: Our study provides strong statistical evidence that occurrence of familial uveal melanoma is not coincidental.

Adolescent↗
PubMed1996

Bilateral primary uveal melanoma. Bad luck or bad genes?

BACKGROUND: The occurrence of bilateral primary uveal melanoma has been assumed to be a rare, random event . Bilaterality of a primary cancer is suggestive of an inherited cancer predisposition. The authors therefore evaluated patients with bilateral primary uveal melanoma for such cancer predisposition. METHODS: The charts of 4500 patients with uveal melanoma were reviewed for the presence of bilaterality. The clinical profile of patients with bilateral primary uveal melanoma was studied. The presence of ocular melanocytosis, familial atypical mole and melanoma syndrome, neurofibromatosis type 1, cutaneous melanoma, familial uveal melanoma, Li-Fraumeni syndrome, and second primary cancers also was investigated. RESULTS: Of 4500 patients with primary uveal melanoma, 8 (0.18%) were identified to have bilateral primary uveal melanoma. Using the annual incidence rate (Shammas and Watzke) and normal approximation to the binomial, the expected number of patients with primary bilateral uveal melanoma in the authors' series was calculated to be less than one person. Observation of eight patients with bilateral primary uveal melanoma represented greater than expected occurrence (P<0.0001). The mean age at diagnosis in the first eye was 56 years. The interval between the diagnosis of uveal melanoma in the two eyes ranged from 2 to 32 years (median, 10.5 years). Two patients had bilateral ocular melanocytosis. Ocular melanocytosis was more common (2/8, 25%) in patients with bilateral uveal melanoma compared with those with unilateral uveal melanoma (60/4492, 1.3%). This difference was statistically significant (P = 0.001). No relation to familial atypical mole and melanoma syndrome, cutaneous melanoma, neurofibromatosis type 1, familial uveal melanoma, second primary cancers, or Li-Fraumenni syndrome was observed. CONCLUSIONS: Bilateral primary uveal melanoma occurs more frequently than expected by chance, and may be associated with ocular melanocytosis. In the authors' series, there was no clinical evidence of an inherited genetic predisposition for bilateral primary uveal melanoma. Unidentified germ-line mutations may be involved in pathogenesis of bilateral uveal melanoma.

Adult↗
PubMed1996

Diagnosis and treatment of uveal melanoma.

Most malignant melanomas in the ocular region arise in the uveal tract (iris, ciliary body, and choroid). Uveal melanoma generally has characteristic clinical features and the diagnosis can usually be made by an experienced ophthalmologist using slit lamp biomicroscopy or indirect ophthalmoscopy. Ancillary studies such as fluorescein angiography, ultrasonography, magnetic resonance imaging, and fine needle biopsy can occasionally be used to establish the diagnosis in atypical cases. Today, most affected patients are managed by specialists in ocular oncology. The management of uveal melanoma has been the subject of considerable controversy. Iris melanoma can usually be excised without enucleation of the affected eye. With regard to posterior uveal melanoma (ciliary body and choroid), enucleation of the affected eye was once the undisputed method of treatment. More recently, however, removal of the eye is performed less often and alternatives to enucleation have gained popularity. Several years ago, laser photocoagulation and plaque brachytherapy were the most popular alternatives to enucleation. Now, techniques of local tumor excision and transpupillary thermotherapy are gaining popularity in selected cases. Even more recently, various combinations of these methods have been judiciously used in many instances. The selected method of treatment in a given case depends on a number of complex clinical factors. Philosophies regarding the management of these lesions continue to change. This review covers the current diagnosis and management of uveal melanoma with emphasis on methods of management.

Brachytherapy↗
PubMed1996

Genetic aspects of uveal melanoma: a brief review.

Uveal melanoma usually occurs sporadically in the absence of obvious genetic predisposing factors. However, in rare patients, there is a suggestion that there may be genetic predisposition. Rare occurrences of familial uveal melanoma are believed to be inherited in an autosomal dominant mode. There are a few clinical conditions that can predispose to or be associated with uveal melanoma, including ocular melanocytosis, neurofibromatosis type I, and familial atypical mole and melanoma syndrome. Nonrandom cytogenetic changes in uveal melanoma are characterized by monosomy 3, trisomy 8, and structural or numerical abnormalities of chromosome 6. Alterations of chromosome 9p are less frequently observed. CDKN2 gene, a cutaneous melanoma predisposition gene, is probably not a uveal melanoma predisposition gene as evidenced by the lack of somatic mutations involving this gene in uveal melanoma samples and the absence of germline mutations in familial uveal melanoma patients. Transgenic mouse models developed using a tyrosinase promoter tagged with a mutated ras gene or SV40-Tag oncoprotein develop retinal pigment epithelium tumors that resemble uveal melanoma. We propose that uveal melanoma cases be categorized on genetic basis according to a new classification system. This classification scheme will help to identify and uniformly categorize uveal melanoma patients with genetic predisposition. Such patients offer unique opportunities for studying the genetic aspects of uveal melanoma and, therefore, appropriate tissue samples should be obtained from them for molecular genetic studies. Further studies are needed to fully understand the genetic aspects of uveal melanoma.

Animals↗
PubMed1995

Melanoma-associated retinopathy.

PURPOSE/METHODS: A 64-year-old man with a history of maxillary antrum melanoma had abrupt-onset night blindness and photopsia. RESULTS/CONCLUSIONS: Ophthalmologic examination and electroretinogram suggested melanoma-associated retinopathy. Serum produced a weak but specific labeling of human bipolar cells by indirect immunofluorescence. Complete excision of melanoma may have contributed to low levels of circulating autoantibodies. The identity of the retinal bipolar antigen recognized by melanoma-associated retinopathy autoantibodies is needed for more accurate diagnosis.

Electroretinography↗
PubMed1995

Treatment of non-resectable malignant iris tumours with custom designed plaque radiotherapy.

BACKGROUND: Plaque radiotherapy is the most common method of managing posterior uveal melanoma but its use for iris melanoma and iris metastases has not yet been evaluated. METHODS: Fourteen patients with non-resectable iris melanoma and four with iris metastasis were treated with plaque radiotherapy. The tumour response to treatment and the local side effects of the radioactive plaque were evaluated. RESULTS: In the iris melanoma group over a mean follow up of 26 (range 6-75) months, the tumour regressed in 13 of the 14 patients (93%) and recurred as diffuse seeding in one patient (7%). Despite large doses of radiation given transcorneally, the cornea developed epitheliopathy, abrasion, and oedema in only one case each. The major radiation side effects were localised iris vasculopathy without glaucoma in two cases, posterior synechiae in five cases, and cataract in six cases. In the iris metastasis group, tumour regression was observed in all four patients (100%) and radiation side effects were not evident over the relatively short mean follow up period of 8 (range 4-9) months. All of the 14 patients with irradiated iris melanoma have remained systemically healthy without metastasis while three of the four patients with irradiated iris metastases have died of metastases from the primary neoplasm. CONCLUSION: Custom designed plaque radiotherapy appears to be an effective alternative method of controlling non-resectable diffuse iris melanoma and solitary iris metastasis and has relatively few side effects.

Brachytherapy↗
PubMed1995

Uveal melanoma and familial atypical mole and melanoma (FAM-M) syndrome.

We conducted this study to determine whether occurrence of primary uveal melanoma in the setting of familial atypical mole and melanoma (F A M-M) syndrome (an autosomal dominant cutaneous preneoplastic syndrome) follows a pattern of a hereditary cancer predisposition syndrome. A retrospective review of 4600 consecutive patients with primary uveal melanoma revealed eight patients with biopsy-proven F A M-M syndrome. The clinical profile of these patients was studied and their kindreds analyzed. In patients with F A M-M syndrome, the uveal melanoma occurred at a relatively young age (mean 40 years; range 10-52 years). The diagnosis of F A M-M syndrome preceded or followed the diagnosis of uveal melanoma by as much as 10 years. None of the patients had an associated nonmelanocytic malignancy. Three of the eight patients had a positive family history of melanoma (cutaneous melanoma (2) and uveal melanoma (1). The authors conclude that the occurrence of primary uveal melanoma in the setting of F A M-M syndrome does not follow a clear pattern of a hereditary cancer predisposition syndrome.

Adult↗
PubMed1994

Rarity of somatic and germline mutations of the cyclin-dependent kinase 4 inhibitor gene, CDK4I, in melanoma.

Evidence from cytogenetics, multipoint linkage analyses of familial melanoma, and loss of heterozygosity studies of familial and sporadic melanomas support localization of a melanoma susceptibility or tumor suppressor gene at chromosomal region 9p21-23. Recently, the inhibitor of cyclin-dependent kinase 4 (CDK4I; also known as p16INK4, multiple tumor suppressor 1, or CDKN2 gene) has been mapped to 9p21 and shown to be mutated or deleted in a large fraction of cell lines derived from many tumor types, including melanoma, suggesting that this gene could be a melanoma suppressor gene. In order to test for somatic mutations in the CDK4I gene in tumors, DNAs from 30 surgically resected melanomas of both cutaneous and uveal origins were sequenced. No mutations were detected in the coding region of the CDK4I gene, while mutations or deletions were detected in 60% (9 of 15) of the cultured melanoma cell line DNAs. Among presumptive familial cases, nine of which were members of families with one or two other documented melanoma cases, no germline mutations were detected by sequence analysis. A deletion in the second exon of the CDK4I gene was found in one germline allele of a familial melanoma patient from a family with eight affected first degree relatives. These results not only support the suggestion that the CDK4I gene is a familial malignant melanoma gene, they also suggest the presence of another suppressor gene locus within 9p21 which is the target of loss of heterozygosity in sporadic melanomas.

Base Sequence↗
PubMed1994

Use of the hydroxyapatite ocular implant in the pediatric population.

OBJECTIVES: There is always a hesitancy to use an ocular implant after enucleation in children, especially in cases of eyes enucleated for retinoblastoma. DESIGN AND SETTING: In this prospective study, we report our experience of 60 consecutive cases in which we used the hydroxyapatite ocular implant after enucleation in children younger than age 10 years. RESULTS: The mean age at the time of enucleation and hydroxyapatite placement was 27 months (range, 1 to 108 months). The histopathologic diagnoses after enucleation included retinoblastoma in 51 patients, endophthalmitis in two patients, persistent hyperplastic primary vitreous in two patients, neovascular glaucoma resulting from Coats' disease in one patient, uveal melanoma in two patients, undifferentiated intraocular neoplasm in one patient, and blind painful traumatized eye in one patient. After a mean follow-up of 19 months (range, 6 to 36 months), two cases of conjunctival erosion and five cases of conjunctival thinning were recorded. These problems were associated with a flat posterior prosthesis vault in all seven cases. There were no cases of orbital cellulitis, implant extrusion, or implant migration. All children showed good small-degree prosthesis motility despite the lack of peg placement. Only one older child underwent drilling and peg placement and she had excellent small- and large-degree prosthesis motility. We generally postpone the drilling and peg placement stage and tedious prosthesis revision in children until they are able to fully cooperate with the ocularist. CONCLUSIONS: The hydroxyapatite ocular implant is well tolerated and provides good prosthesis motility in children with few complications. It is critical for the ocularist to fit the prosthesis comfortably with a high posterior vault.

Child↗