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Biomedical subjects

D M Albert

Publications and source records attributed to D M Albert.

At least 55 records · Page 3Linked to original sources
PubMed1997

Treatment of spontaneously arising retinoblastoma tumors in transgenic mice with an attenuated herpes simplex virus mutant.

The use of viruses to treat tumors has received renewed interest with the availability of genetically defined attenuated mutants. Herpes simplex virus (HSV) type 1 in particular has been shown to be effective for tumors of neuronal origin. However, the model systems used for these studies rely on the use of explanted tumor cells in immunodeficient animals. We have used a recently developed transgenic mouse model, wherein mice spontaneously develop retinoblastomas, to determine if a mutant HSV has a therapeutic effect against an endogenously arising tumor in an immunocompetent host. The injection of 1 x 10(6) PFU of the neuroattenuated HSV-1/HSV-2 recombinant RE6 into the vitreous of transgenic mice resulted in a significant inhibition of tumor growth compared to injection of medium alone (P = 0.0063). Immunohistochemical analysis of viral antigen showed that viral replication was restricted to focal areas of the tumors and the retinal pigment epithelium. Viral growth was not significantly different in the eyes of transgene-positive and transgene-negative mice, suggesting that enhanced replication in tumor cells may not explain the effects. Tumor cells in the treated eyes were significantly less differentiated than those in the untreated eyes (P = 0.04), suggesting that the virus may replicate better in certain cell types in the tumors. Although the injection of RE6 resulted in a difference in tumor size, the treatment did not result in the elimination of tumors in any of the mice improvements in the efficacy of tumor control are needed if this therapy is to be of use.

Animals↗
PubMed1997

Comparison of transillumination and histologic slide measurements of choroidal melanoma.

OBJECTIVE: To compare transillumination and histologic slide measurements of choroidal melanomas in 479 eyes randomized to enucleation in the Collaborative Ocular Melanoma Study. DESIGN: Transillumination defects were measured during gross examination of enucleated eyes. Tumor basal diameter and height were measured on histologic slides and each tumor was assigned to 1 of 8 distinct shape categories. Comparison of the transillumination and histologic slide measurements revealed 3 categories of difference: underestimation (transillumination measurement more than 4 mm smaller than the histologic slide measurement), overestimation (transillumination measurement more than 4 mm larger than the histologic slide measurement), and agreement within 4 mm. RESULTS: There was good correlation between transillumination and histologic slide estimates of largest basal diameter, particularly when the basal diameter was 16 mm or less. Measurement discrepancies were related to the shape of the tumors but not to the presence of subretinal fluid or fixation. CONCLUSION: Agreement was high between measurements of transillumination defect and histologic sections.

Brachytherapy↗
PubMed1997

Retinoblastoma in a dog.

OBJECTIVE: To describe and classify a retinal tumor found in a dog that histologically resembles human retinoblastoma and to discuss the molecular mechanisms of retinal oncogenesis. METHODS: A dog eye with a retinal tumor was examined histologically. Studies including immunocytochemical analysis for retinal S-antigen and glial fibrillary acidic protein, enzyme histochemical analysis for carbonic anhydrase, and nick-end DNA labeling were used to characterize the tumor. Normal retina from another dog and other tumors from dogs, including 2 ciliary body medulloepitheliomas and a brain medulloepithelioma, were examined as controls. RESULTS: The retinal tumor disclosed characteristics typical of human retinoblastoma, including Flexner-Wintersteiner rosettes. It showed strong immunoreactivity with S-antigen and glial fibrillary acidic protein. Carbonic anhydrase activity also could be shown in the tumor. Apoptosis was found to be the predominant method of cell death as shown by nick-end DNA labeling. In contrast to the other tumors examined, this tumor contained areas with retinal photoreceptor and glial differentiation. CONCLUSIONS: The histopathologic findings and differential staining characteristics in this retinal tumor are compatible with retinoblastoma, making this, to our knowledge, the first documented case of spontaneous retinoblastoma in an animal.

Animals↗
PubMed1997

Clear cell differentiation in choroidal melanoma. COMS report no. 8. Collaborative Ocular Melanoma Study Group.

OBJECTIVE: To describe 2 enucleated eyes of patients enrolled in the Collaborative Ocular Melanoma Study that contained primary choroidal melanoma with clear cell features. METHODS: During a 9-year period, 1493 eyes enucleated as part of the Collaborative Ocular Melanoma Study routinely processed for histologic examination were evaluated by the pathology review committee (H.E.G, D.M.A, and W.R.G). Two eyes with unusual variants of choroidal melanoma were identified and immunostained for S100 protein and HMB 45. Portions of the tumors were processed for electron microscopic examination. RESULTS: Results of electron microscopic examination of both tumors displayed malignant melanoma (mixed cell type with many malignant cells with clear cytoplasm). The cytoplasm of the clear cells stained with periodic acid-Schiff and failed to stain when pretreated with diastase. Results of immunohistochemical stains in both tumors were positive for S100 protein and HMB 45 in the tumor cells. Results of electron microscopic examination showed that the cytoplasm of the clear cells contained scattered glycogen granules, premelanosomes, and melanosomes. CONCLUSION: These cases represent a clear cell variant of malignant melanoma of the choroid. This tumor should not be confused with metastatic clear cell carcinoma to the choroid.

Aged↗
PubMed1997

Histopathologic study of eyes after iodine I 125 episcleral plaque irradiation for uveal melanoma.

OBJECTIVES: To describe the histopathologic findings attributable to irradiation in eyes with uveal malignant melanoma treated with iodine I 125 brachytherapy and to compare these findings with those reviewed in a previous study that compared histopathologic findings in eyes enucleated after proton beam teletherapy with those seen in eyes in a nonirradiated control group. METHODS: The slides from 22 eyes with uveal melanoma that had undergone enucleation after the administration of 125I brachytherapy were studied. The histopathologic features of the tumor and the retina were graded. Results were compared with findings from a previously reported group of 47 proton beam-treated eyes and its control group. RESULTS: Patient age, time between irradiation and enucleation, and ciliary body involvement were similar for the 125I brachytherapy-treated group and the proton beam-treated group and its control group. This allows comparison of the histopathologic findings. Comparing the 125I brachytherapy- and proton beam-treated groups, most histopathologic features were similar with nominally statistically significant differences only for cell type, number of mitotic figures, and fibrous metaplasia of the retinal pigment epithelium adjacent to the tumor. CONCLUSIONS: Irradiation of uveal melanoma induces changes in the tumor and in the surrounding retina. Brachytherapy and charged particle therapy are the 2 principal methods of irradiation. This study demonstrates that similar changes are produced by 125I plaque irradiation and proton beam irradiation.

Adult↗
PubMed1997

The herpes simplex virus type 1 ribonucleotide reductase is required for acute retinal disease.

We have used a herpes simplex virus type 1 (HSV-1) ribonucleotide reductase (RR) null mutant (ICP6 delta) to determine if the HSV-1 RR is required for acute retinal disease. Injection of the ICP6 delta mutant into the vitreous induced mild transient signs of infection (vitreal infiltrate, retinal inflammation, and changes in retinal cytology). In contrast, the parental KOS and a revertant virus (ICP6 delta + 3.1) in which the RR gene had been restored, caused severe retinitis. Injection of media alone also induced mild transient signs of disease. Two months after infection, ICP6 delta injected eyes could not be distinguished from normal eyes. Repeated injection of ICP6 delta (3 times, 2 weeks apart) resulted in vitreal infiltrate near the site of injection but the retina did not appear damaged. The mutant, ICP6 delta, grew to peak titers 1 x 10(3) to 1 x 10(5)-fold lower and cleared faster than KOS or ICP6 delta + 3.1 in the injected eyes suggesting that the reduced virulence was due to reduced ability of the virus to grow. These results show that the viral RR is required for acute retinal disease.

Acute Disease↗
PubMed1997

The ocular melanoma story. LIII Edward Jackson Memorial Lecture: Part II.

PURPOSE: To trace the evolution and status of our knowledge of choroidal melanoma with regard to the nature, cause, and treatment of this tumor. METHODS: Historical materials beginning with Georg Bartisch's contributions in 1583 through to the Collaborative Ocular Melanoma Study and recent basic research are reviewed. RESULTS: Many individuals have made important contributions to our knowledge about this tumor. Basic information, however, regarding the natural history of the tumor, the most effective treatment, and its cause is lacking. CONCLUSION: The Collaborative Ocular Melanoma Study will provide important information regarding the choice of treatment between enucleation and radiotherapy as well as natural history information, quality of life, and definitive pathology findings. Definitive treatment of choroidal melanoma will depend on knowledge of the genetic defects that cause the tumor. Within the next 25 years, it is predicted that genetic defects will be determined and tumor samples will be obtained using small-needle aspiration and DNA probes located on microchips. In addition, treatment will then be based on drugs designed to inhibit molecules related to the genetic defect in the tumor.

Choroid Neoplasms↗
PubMed1997

The color of the human eye: a review of morphologic correlates and of some conditions that affect iridial pigmentation.

Iris color can be affected by a variety of ocular disorders. It is suspected that iris color may not remain constant throughout life. These observations have drawn attention to the morphologic correlates of iris color and its regulation. Differences in the iris color of normal eyes are the result of variable amounts of melanin pigment granules within a constant number of melanocytes in the superficial stroma of the iris. These melanocytes seem to reach their genetically determined amount of melanin in early childhood, and their melanin content usually remains constant in adulthood. Diseases such as Horner's syndrome and Fuchs' heterochromic iridocyclitis affect iris color, resulting in a decrease of iris pigmentation. Evidence suggests that melanin content of some melanocytes is subject to adrenergic regulation even past childhood. Application of the prostaglandin analogue latanoprost, on the other hand, leads to an increase in iris pigmentation in some patients. Studies with cultured dermal and uveal melanocytes, as well as with uveal melanoma cells, however, show no increase in cell proliferation when treated with latanoprost in vitro. The mechanisms by which latanoprost affects regulation of iris pigmentation requires further investigation.

Cell Count↗
PubMed1997

Surgical aspects of paediatric cochlear implantation.

Cochlear implantation in the paediatric population is now an accepted method of rehabilitating profoundly or totally deaf children. The problems of cochlear implantation in children with other significant medical problems are examined. A retrospective review of the records of the first 45 children implanted at our centre was carried out. The review focused on surgical factors and outcome in addition to variations in technique which have occurred since the programme began. Congenital hearing loss was the most common indication for implantation. Fifteen children (33 per cent) had other medical problems. Three cases of flap breakdown (two occurring after direct trauma to the package bed) and one case of a misplaced electrode requiring re-implantation accounted for the only major complications to date. Minor complications included hypertrophic scar formation and post-operative wound infection. All children were using their implants at the time of this review, but two have subsequently been explanted. Cochlear implantation of children with multiple medical problems requires acceptance of a slightly higher risk of complications.

Adolescent↗
PubMed1997

Surgical experience with bone-anchored hearing aids in children.

Titanium osseointegrated implants for bone-anchored hearing aids (BAHAs) have been in use since 1977. A series of 32 children who received implantation since 1990 is reported. The report focuses on the surgical aspects of BAHAs, predisposing factors, and prevention of complications in an unusual pediatric population. The records of 32 children who had undergone two-stage implantation of a BAHA were retrospectively reviewed. The majority of the patients had craniofacial abnormalities. Of the 32 implantees, 29 use their BAHA at present. Five children failed to achieve osseointegration, and eight patients have had revision surgery for lost abutments, trauma, or chronic skin problems. There were no differences between preimplantation and postimplantation bone or air conduction thresholds. The pediatric BAHA carries with it a unique set of challenges and problems but can be successfully implanted and maintained.

Adolescent↗
PubMed1997

Recessive epidermolysis bullosa simplex associated with plectin mutations: infantile respiratory complications in two unrelated cases.

Plectin is a 500 kDa protein involved in cytoskeleton-plasma membrane attachment with a wide tissue distribution including cutaneous and airway epithelia, muscle and neuronal tissue. Recently, mutations in the gene encoding plectin (PLEC1) have been implicated in the pathogenesis of an autosomal recessive variant of epidermolysis bullosa simplex in which cutaneous blistering starting in the neonatal period is associated with muscular dystrophy in later life. In this study, we report two unrelated patients, both of consanguineous parentage, who presented with cutaneous blistering and a hoarse cry from birth. Both experienced inspiratory stridor and respiratory distress, necessitating emergency tracheostomy in one case. Immunoreactivity to monoclonal antibodies against plectin was absent or markedly reduced in skin biopsies from both patients. Electron microscopy revealed a low intraepidermal plane of cleavage and hypoplastic hemidesmosomes with a reduced association with keratin intermediate filaments. Direct sequencing of PLEC1 in each case demonstrated two novel homozygous frameshift deletion mutations, 5069del19 and 5905del2, which both create downstream premature termination codons. Although currently neither patient has symptoms of muscle disease, the identification of mutations in PLEC1 may be predictive for the future development of muscular dystrophy. Recessive epidermolysis bullosa simplex resulting from abnormalities in plectin should be considered in the differential diagnosis blistering, hoarseness and stridor in infancy.

Child, Preschool↗
PubMed1996

Otitis media with effusion in paediatric cochlear implantees: the role of peri-implant grommet insertion.

INTRODUCTION: Otitis media with effusion (OME) is a common disease coincident with the need for cochlear implantation in 44% of the 45 children (mean = 4.8 years) currently implanted at our centre. Our suspicion that peri-implant effusion contributed to complications generated our interest in studying this issue. METHOD: Retrospective review of patient records was carried out with the focus on clinical and audiological evidence of OME before, during and after implantation. Operative records were reviewed to determine any effect OME had on the procedure and postoperative complications. RESULTS: Of our 45 implanted patients, 10 males and 10 female had OME prior to or after implantation. Pre-implant, 19 children had OME diagnosed and 11 received grommets (6 had multiple sets). Peri-implantation, 11 children had OME. These children with peri-implant effusions had 2 of 3 major, 2 of 2 intermediate and 1 of 2 minor complications. Children with peri-implant effusions also accounted for 3 of 4 cases in which there were bothersome middle ear effusions or granulation tissue at operation. The 6 children in whom grommets were placed within two months of cochlear implantation accounted for only one case of effusion at implantation and their courses were complicated only by a keloid in one child and a late flap disruption in another. SUMMARY: Insertion of grommets prior to cochlear implantation in children with peri-implant OME may provide some protection against intra-operative and some post-operative complications. Our management policy in patients with OME now aims at placing grommets such that they are in and patent at the time of implantation.

Child↗
PubMed1996

Melanocytes and iris color. Light microscopic findings.

OBJECTIVE: To systematically evaluate morphologic differences in iris stroma that contribute to clinically perceptible differences in iris color, using immunohistochemical identification of stromal melanocytes and fluorescence microscopy. METHODS: Paraffin-embedded sections from 51 human irides were stained with S100a and fluorescein isothiocyanate. Cells were counted and scored as melanocytes or other. Melanocyte number, proportion, and density were determined for light-colored (blue), medium-colored (hazel) and dark-colored (brown) irides and compared. RESULTS: No statistically significant difference was observed for mean total cellularity or mean melanocyte number among the three color groups. Mean total stromal cell count was 1177 +/- 259 (mean +/- SEM), and mean melanocyte number was 778 +/- 196 per 5-micrometer section. In human irides, 65.9% of the iris stroma is composed of melanocytes. Melanocyte density (number of cells per square millimeter) is not related to iris color. CONCLUSION: The number of melanocytes, the proportion of melanocytes, and iris stromal cellularity are not major contributors to iris color.

Aged↗
PubMed1996

Melanocytes and iris color. Electron microscopic findings.

OBJECTIVE: To quantitatively associate iris color with melanocyte pigment content. METHODS: Autopsy eyes were classified as uniform-blue, uniform-hazel, or uniform-brown or showing a darker peripupillary ring. Using electron microscopic images and computerized image analysis, area, number, and size of mature melanosomes within the perinuclear cytoplasmic area only or within perinuclear and peripheral cytoplasmic areas of the superficial stromal melanocytes combined were measured. RESULTS: Average melanosomal area per perinuclear cytoplasmic area (AMAC) and average number of melanosomes per perinuclear area (AMNC) significantly differed across iris color groups (overall P<.001). This result reflects the large difference between blue-uniform and all other color groups. A marginally significant (nominal) trend from blue-ring through brown-ring was also detected (P=.06 for AMAC and P=.07 for AMNC). The average perinuclear cytoplasmic area was larger in the central iris zone (within 1 mm around the pupillary margin) than in the intermediate iris zone (between 1 and 2 mm around the pupillary margin) (P=.002), but AMAC and AMNC did not significantly differ between zones. The average melanosome size did not differ significantly across color groups (P=.11). CONCLUSION: Differences in iris colors are at least partially attributed to variable AMNC and AMAC within superficial melanocytes.

Aged↗
PubMed1996

Neonatal hepatoblastoma metastatic to the choroid and iris.

A newborn boy was diagnosed with hepatoblastoma after a systemic workup was prompted because of abnormal-appearing eyes. Radiological examination revealed mass lesions involving the liver, brain, eyes, and ribs. A liver biopsy was performed before death and results showed hepatoblastoma, an unusual solid tumor of childhood. At autopsy, hepatoblastoma was also found histopathologically in the irides and choroid of both eyes. No previous report of hepatoblastoma metastatic to the eye could be found in the medical literature. In addition, we believe this is the first report in a child of a solid tumor metastatic to the choroid and iris, and of a solid tumor metastatic to the iris that is confirmed histopathologically.

Biopsy↗
PubMed1996

Radiation therapy and ferromagnetic hyperthermia in the treatment of murine transgenic retinoblastoma.

BACKGROUND: Combined modality therapy for childhood retinoblastoma holds the potential of decreasing treatment-related morbidity while maintaining excellent tumor control rates. OBJECTIVE: To evaluate the efficacy of external beam radiation therapy (EBRT), ferromagnetic hyperthermia (FMH), and the combination of both modalities in the control of ocular tumors in a transgenic murine model of retinoblastoma. METHODS: One hundred sixty-six mouse eyes from 4-week-old animals transgenically positive for simian virus 40 large T antigen were treated with a total dose of 10, 15, 20, 30, 40, 45, or 50 Gy of EBRT in 5-Gy fractions twice daily, with 48 degrees C or 54 degrees C FMH for 20 minutes, or with combined EBRT at 10 or 30 Gy and 48 degrees C or 54 degrees C FMH for 20 minutes. Serial histologic sections, obtained 8 weeks after treatment, were examined for the presence of tumor. RESULTS: The tumor control dose for 50% of eyes (TCD50) treated with EBRT occurred at 27.6 Gy. Ferromagnetic hyperthermia at 48 degrees C cured 30% (6/20) of eyes, while 54 degrees C FMH resulted in a 100% (20/20) cure rate. Combined treatment with 48 degrees C FMH and EBRT exhibited a TCD50 at 3.3 Gy. The thermal enhancement ratio was 8.4. Ferromagnetic hyperthermia at 54 degrees C exhibited tumor cure in all animals, but 25% of eyes were lost owing to secondary treatment complications. CONCLUSIONS: This represents the first documentation of tumor control via EBRT, ocular FMH, and a combination of these treatment modalities in this murine transgenic retinoblastoma model. The extent of treatment synergy in this model suggests that combined treatment application may allow a reduction in total ocular and periocular radiation dose while maintaining excellent local tumor control.

Animals↗