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Biomedical subjects

D M Albert

Publications and source records attributed to D M Albert.

At least 73 records · Page 4Linked to original sources
PubMed1996

Antineoplastic effect of 1,25-dihydroxy-16-ene-23-yne-vitamin D3 analogue in transgenic mice with retinoblastoma.

OBJECTIVE: To evaluate the in vivo efficacy and clinical toxic effects of the 1,25-dihydroxy-16-ene-23-yne-vitamin D3 analogue in beta-luteinizing hormone-Tag (LH beta-Tag) transgenic mice with heritable retinoblastoma. METHODS: Forty-two mice (8-10 weeks old), randomly assigned to experimental (n = 21) or control (n = 21) groups, received intraperitoneal injections of 0.05 microgram of 1,25-dihydroxy-16-ene-23-yne-D3 in 0.5-mL mineral oil vehicle (experimental group) or 0.5 mL of mineral oil vehicle (control group) for 5 weeks. One experimental and 3 control animals died of injection-related trauma. Eyes were enucleated 1 week after treatment and were examined histologically in a masked fashion. RESULTS: All experimental and control animals showed evidence of tumor. The tumors in the experimental mice showed a significantly smaller cross-sectional area (0.88 +/- 0.08 mm2) compared with that in the control mice (1.12 +/- 0.12 mm2) (P = .02). All mice completed the treatment and showed no clinical evidence of toxic effects. CONCLUSIONS: Tumors in transgenic mice with retinoblastoma treated with 1,25(OH)2-16-ene-23-yne-D3 showed a 21% smaller cross-sectional area compared with that in the control mice, without producing clinically apparent toxic effects. This compound may be useful as adjunctive therapy in the treatment of retinoblastoma.

Animals↗
PubMed1996

Edward Jackson in 1896: a man and his specialty at a crossroads. LIII Edward Jackson Memorial Lecture: Part 1.

PURPOSE: To review the life of Dr. Edward Jackson and his contributions to American medicine and ophthalmology, using as a reference point 1896, the year of the founding of the American Academy of Ophthalmology. METHODS: Review of published materials by and about Edward Jackson and other historical materials to evaluate Dr. Jackson's contributions to and the status of American ophthalmology during the late nineteenth and early twentieth centuries. RESULTS: Eighteen ninety-six was a seminal year for Dr. Jackson. He assumed a leadership role in American ophthalmology and medicine while overcoming personal tragedy and the difficult transition from being part of the Eastern establishment to becoming "a great champion of the West." CONCLUSION: The issues and events of 1896, and their evolution and repercussions in subsequent decades, confirm that Edward Jackson was a major figure in shaping modern American ophthalmology.

History, 19th Century↗
PubMed1996

Nasal lipomas presenting as part of a syndromic diagnosis.

An important part of the initial assessment of children presenting with congenital nasal masses is to exclude an intracranial extension using either magnetic resonance imaging (MRI) or computed tomography (CT) imaging. We present three patients with such lesions in which unusual radiological findings were noted as part of the investigations.

Female↗
PubMed1996

Frequency of ocular metastases in patients dying of cancer in eye bank populations.

AIMS: To examine the frequency of intraocular metastases in patients who had died of cancer, in an eye bank and necropsy population sample. METHODS: The first group included 302 cancer cases received from the Wisconsin Eye Bank between 1988 and 1993. In the second group, ocular pathology records at the Wilmer Institute from 1976 to 1980 were analysed for ocular metastases in necropsy subjects dying of cancer. Nonocular cancer was the cause of death in 741 cases; among these, 510 were attributed to carcinomas. RESULTS: In the Wisconsin Eye Bank group, three cases (1%) had gross metastases. Out of 255 carcinoma cases, one (0.4%) had gross metastases. In the Wilmer Institute group, gross metastases were observed in 35 (4.7%) cases. Of the 510 patients dying of carcinomas, six (1.2%) had macroscopic metastases. Ocular metastases were detected histopathologically in 93 of 741 (12.6%) of cases. CONCLUSION: Even though it is difficult to assess the true frequency of ocular metastases in patients dying of cancer, the answer to this question was attempted by determining the frequency of ocular metastasis in patients who died of cancer and who donated their eyes to the Wisconsin Eye Bank or had postmortem examination at the Johns Hopkins Hospital. Microscopic metastases were found in 12.6% of cases. The frequency of gross metastases has decreased over the past 12 years from 4.7% to 1% (p value = 0.005) owing to improved treatment of leukaemia; however, the frequency of macroscopic metastases due to carcinomas has not changed (p value = 0.38).

Autopsy↗
PubMed1996

Trilateral tumors in four different lines of transgenic mice expressing SV40 T-antigen.

PURPOSE: A line of transgenic mice containing the simian virus (SV) 40 T-antigen (T-ag) gene driven by the beta-luteinizing hormone (BLH) promoter developed bilateral retinoblastoma and primitive neuroectodermal tumors (PNET) of the midbrain. Midbrain tumors arose from the subependymal layer of the cerebral aqueduct. Bilateral ocular and brain tumors ("trilateral") were found in three other SV40 T-ag transgenic murine lines containing different promoters (murine interphotoreceptor retinoid-binding protein (IRBP), human IRBP, and alpha A-crystallin). To gain insight into the regulatory mechanisms involved in central nervous system tumorigenesis, the authors examined brain tumors from four lines of SV40 T-ag mice with different promoters. METHODS: Formalin-fixed brain tumors were examined from four lines of transgenic mice containing different promoters linked to the protein coding region of the enhancerless SV40 T-ag oncogene. Transgenes contained the following promoters: BLH, mouse 1.8-kb IRBP, human 1.3-kb IRBP, and alpha A-crystallin. RESULTS: Mice with a 1.8-kb IRBP promoter develop retinal photoreceptor and pineal tumors. Intracranial tumors arising from the subependymal layer of the third ventricle also were observed. Mice with a 1.3-kb IRBP promoter exhibit bilateral retinal PNET and PNET originating from the subependymal layer of the third ventricle. Mice with the alpha A-crystallin promoter exhibit bilateral lens tumors and PNET of the midbrain. CONCLUSIONS: Ocular tumors in these mice may be ascribed to the promoter-driven, tissue-specific expression of SV40 T-ag. The common finding of PNET arising from the subependymal layer of the diencephalon is unlikely to be promoter related. These findings indicate that a regulatory region specific to the subependymal layer of the cerebral aqueduct and third ventricle resides in the structural region of the SV40 T-ag gene.

Animals↗
PubMed1995

Post-operative morbidity following paediatric tonsillectomy; a comparison of bipolar diathermy dissection and blunt dissection.

In a prospective study of 76 children aged between 18 months and 13 years, 40 children underwent tonsillectomy using the traditional blunt dissection technique with bipolar diathermy to establish haemostasis while 36 children underwent tonsillectomy where bipolar diathermy alone was used to dissect out the tonsils. Blood loss was significantly reduced in the diathermy dissection group (10.5 ml +/- 2.05, diathermy dissection, 33.56 ml +/- 1.95, blunt dissection, P < 0.05). More analgesia was required in the diathermy dissection group prior to hospital discharge (P = 0.01). The diathermy dissection group took a significantly longer period of time to re-establish a normal diet (7.07 days +/- 0.44, diathermy dissection, 5.15 days +/- 0.36, blunt dissection, P = 0.001). Fifteen percent of children in the blunt dissection group and 31% in the diathermy dissection group were taken to the general practitioner between days 3-10 because of sore throat, poor oral intake or otalgia. Twenty two point four percent of children overall were prescribed antibiotics. This recently described technique of bipolar diathermy dissection could be a useful technique in selected cases such as the very small or those with a bleeding diathesis but is associated with increased postoperative morbidity and requires good postoperative analgesia.

Acetaminophen↗
PubMed1995

Vitamin D inhibits angiogenesis in transgenic murine retinoblastoma.

PURPOSE: Vitamin D compounds have been shown to inhibit tumor growth in a transgenic retinoblastoma murine model. The mechanism of action has not been defined clearly, although an antiangiogenic action has been proposed. METHODS: Transgenic retinoblastoma mice received high (0.05 microgram) and low (0.025 microgram) doses of vitamin D3 by intraperitoneal injection 5 times per week for 5 weeks. Control animals were injected with mineral oil vehicle alone. At 5 months of age, the animals were killed and eyes were enucleated and processed for light microscopy. Paraffin-embedded sections were stained with an immunoperoxidase stain (GS-1) specific for mammalian vascular endothelium. Sections were graded by a single masked reviewer, and intraobserver reliability was assessed. Mean vessel counts were made for each group. RESULTS: The high-dose group had the lowest mean vessel count (8.5), followed by the low-dose group (10.1). The control group had the highest mean vessel count (14.1). Vitamin D-treated animals (high- and low-dose groups combined) had significantly fewer vessels P = 0.001) than untreated controls. CONCLUSIONS: These results support the hypothesis that inhibition of angiogenesis is a mechanism of action for vitamin D in the transgenic retinoblastoma mouse model.

Animals↗
PubMed1994

Extensive contribution of Rb-deficient cells to adult chimeric mice with limited histopathological consequences.

Homozygosity for a mutation in the Rb tumor suppressor gene causes mid-gestation embryonic lethality in the mouse. Using a two-step targeting protocol, we have constructed Rb homozygous mutant mouse embryonic stem cells and used them to create chimeric animals partially composed of Rb-deficient cells. Analysis of these chimeras demonstrates widespread contribution of the mutant cells to adult tissues, including the retina and mature erythrocytes. Despite the presence of large numbers of Rb-deficient cells in most tissues of these mice, they are remarkably normal but do exhibit certain histological defects including cataracts, hyperplasia of the adrenal medulla, and enlarged cells in the cerebellum and the liver. Like animals heterozygous for the Rb mutation, the chimeras develop tumors of the intermediate lobe of the pituitary, and the rate of pituitary tumorigenesis is greatly accelerated.

Adrenal Glands↗
PubMed1994

Apoptosis or retinoblastoma: alternative fates of photoreceptors expressing the HPV-16 E7 gene in the presence or absence of p53.

A transgenic mouse model for retinoblastoma was produced previously by directing SV40 T antigen expression to retinal photoreceptor cells using the promoter of the interstitial retinol-binding protein (IRBP) gene. This gene becomes active prior to the terminal differentiation of photoreceptors. Because T antigen-transforming activity is attributable, at least in part, to the inactivation of the retinoblastoma (pRb) and p53 tumor suppressor proteins, we addressed the role of p53 in the development of retinoblastoma in mice. Transgenic mice expressing HPV-16 E7 under the control of the IRBP promoter were generated to inactivate pRb in photoreceptors while leaving p53 intact. Rather than developing retinoblastomas, the retinas of these mice degenerate due to photoreceptor cell death at a time in development when photoreceptors are normally undergoing terminal differentiation. The dying cells exhibit the histological and ultrastructural features of apoptosis and contain fragmented DNA. p53 is required for the induction of apoptosis in this model, because mice expressing E7 in a p53 nullizygous background develop retinal tumors instead of undergoing retinal degeneration.

Animals↗
PubMed1994

Otitis externa in Langerhans' cell histiocytosis--the successful use of topical nitrogen mustard.

Otitis externa is a common symptom of Langerhans' cell histiocytosis, and occurs in half of all children with the disease. Previous treatment regima have been either unsuccessful, or associated with undesirable side-effects. This study describes the successful use of topical 20% nitrogen mustard ear drops in the management of five children who had Langerhans' cell histiocytosis with otitis externa. All of them had previously been resistant to other forms of treatment. The children were aged between 6 months and 6 years. The otitis externa fee period to date is up to 5 years. Topical nitrogen mustard ear drops are rapidly effective, can be administered at home, have not caused any adverse effects, and are of long-term benefit.

Administration, Topical↗
PubMed1994

Histopathologic features of the floppy eyelid syndrome. Involvement of tarsal elastin.

PURPOSE: Patients with the floppy eyelid syndrome have chronic papillary conjunctivitis with easily everted upper eyelids and a soft, pliant upper tarsus. The purpose of this study is to describe the clinical features and the histopathologic correlate in a group of patients with floppy eyelid syndrome. METHODS: The authors examined eight patients with floppy eyelid syndrome, four of whom underwent surgical management with horizontal eyelid shortening. Eyelid tissue from these patients was examined using light microscopy, electron microscopy, and immunohistochemistry and compared with controls with unrelated eyelid or orbital disorders. RESULTS: Clinical findings included obesity or eye rubbing, lash ptosis, and, less commonly, blepharoptosis. Two patients had documented sleep apnea with abnormal sleep electroencephalogram. Light microscopy of the surgical specimens showed chronic conjunctival inflammation, papillary conjunctivitis, and meibomian gland abnormalities, including granuloma formation. Verhoeff's modified elastin stain demonstrated a marked decrease in the amount of elastin fibers in tarsus from patients with floppy eyelid syndrome compared with controls. Immunohistochemical staining for elastin also showed a marked decrease of tarsal elastin in floppy eyelid patients compared with controls. In contrast, immunohistochemical stains showed that the distribution of collagen types I and III was similar between patients with floppy eyelid syndrome and controls. Electron microscopy demonstrated that tarsal collagen was comparable in patients and controls, and that there was a reduced amount of tarsal elastin in floppy eyelid syndrome compared with controls. CONCLUSIONS: These findings demonstrate that tarsal elastin is decreased in the floppy eyelid syndrome, which may contribute to the laxity of the tarsus in this disorder.

Adult↗
PubMed1994

Cooperative tumorigenic effects of germline mutations in Rb and p53.

The tumour suppressor genes Rb and p53 are mutated in several types of human cancer, and many tumour types carry mutations in both genes. To study how these genes normally function, we and others have created mouse strains with Rb and p53 mutations. Here we describe the phenotypic effects of combined germline mutations in these two tumour suppressor genes. Mice mutant for both genes have reduced viability and exhibit novel pathology including pinealoblastomas, islet cell tumours, bronchial epithelial hyperplasia and retinal dysplasia. These data indicate that mutations in Rb and p53 can cooperate in the transformation of certain cell types in the mouse.

Adenoma, Islet Cell↗