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A Berson

Publications and source records attributed to A Berson.

At least 19 recordsLinked to original sources
PubMed1999

Diode-light transillumination for ophthalmic plaque localization around juxtapapillary choroidal melanomas.

PURPOSE: An evaluation of plaque-mounted diode-light transillumination (DLT) for localization of episcleral plaques beneath juxtapapillary tumors. METHODS AND MATERIALS: Two patients scheduled for radiotherapy for juxtapapillary melanomas were offered DLT as an additional method of ophthalmic plaque localization. Plaques were constructed by affixing 4 non-heat producing, light-emitting diodes with their apertures flush with the episcleral outer surface of the plaque's rim. Bio-implantable epoxy was used to encapsulate the electronic components. Then the plaques were loaded with 103Pd seeds. After the eye-plaques were sewn to the episclera covering the base of the intraocular tumors; the diode-lights were illuminated, viewed and recorded. Photodocumentation of the relative position of the 4 lights around tumor's base was obtained in both cases. RESULTS: Digital images of plaque-mounted diode retro-transillumination were obtained. No evidence of diode-light toxicity was noted. Both tumors were found to be covered by the ophthalmic plaques. CONCLUSION: Juxtapapillary tumors are often difficult or impossible to visualize with standard transillumination techniques and have been associated with poor local control rates. We have developed plaque-mounted DLT in an effort to improve ophthalmic plaque localization. Retrobulbar transillumination was viewed by indirect ophthalmoscopy and recorded with video-imaging. This technique provides unique photographic documentation of episcleral plaque localization beneath juxtapapillary tumors.

Choroid Neoplasms↗
PubMed1999

Decrease in hepatic cytochrome P450 after interleukin-2 immunotherapy.

Interleukin-2 (IL-2) has been shown to decrease cytochrome P450 (CYP) mRNAs and proteins in cultured rat hepatocytes, and IL-2 administration decreases CYPs in rats. Although high doses of IL-2 are administered to cancer patients, the effect on human CYPs has not yet been determined. Patients with hepatic metastases from colon or rectum carcinomas were randomly allocated to various daily doses of human recombinant IL-2 (from 0 to 12.10(6) units/m(2)). IL-2 was infused from day 7 to day 3 before hepatectomy and the conservation of a non-tumorous liver fragment in liquid nitrogen. Hepatic CYPs and monooxygenase activities were not significantly decreased in 5 patients receiving daily doses of 3 or 6 10(6) IL-2 units/m2, compared to 7 patients who did not receive IL-2. In contrast, in 6 patients receiving daily doses of 9 or 12 x 10(6) IL-2 units/m2, the mean values for immunoreactive CYP1A2, CYP2C, CYP2E1, and CYP3A4 were 37, 45, 60 and 39%, respectively, of those in controls; total CYP was significantly decreased by 34%, methoxyresorufin O-demethylation by 62%, and erythromycin N-demethylation by 50%. These observations suggest that high doses of IL-2 may decrease total CYP and monooxygenase activities in man.

Adenocarcinoma↗
PubMed1999

Ophthalmic plaque radiotherapy for age-related macular degeneration associated with subretinal neovascularization.

PURPOSE: To evaluate ophthalmic plaque radiotherapy for the treatment of subretinal neovascularization associated with age-related macular degeneration. METHODS: In a prospective phase I clinical trial, we treated 23 patients (23 eyes) with ophthalmic plaque radiotherapy for subfoveal exudative macular degeneration. Palladium 103 ophthalmic plaque brachytherapy was delivered to a retinal apex dose of 1,250 to 2,362 cGy (rad). Early Treatment Diabetic Retinopathy Study type visual acuity determinations, ophthalmic examinations, and angiography were performed before and after treatment. Clinical evaluations were performed in a nonrandomized and unmasked fashion. RESULTS: Patients were followed up for a mean (+/-SD) of 19 +/- 10.7 months (range, 3 to 37 months). Six months after radiation therapy, three (16%) of 19 eyes had lost 3 or more lines of best-corrected visual acuity; 12 months after radiation therapy, four eyes (31% of 13 eyes), and 24 months after radiation therapy, only two (22% of nine eyes) lost 3 or more lines of visual acuity. No eye suffered sudden irreversible loss of central vision. No radiation retinopathy, optic neuropathy, or cataract could be attributed to radiotherapy within this follow-up period. CONCLUSION: Ophthalmic plaque radiotherapy can be used to treat neovascular age-related macular degeneration. In contrast to external beam radiotherapy, ophthalmic plaque radiotherapy is a unilateral treatment, which allows a larger dose to be delivered to the macula with less irradiation of normal ocular structures. We have found no sight-limiting complications at the doses, dose rates, and follow-up evaluated in this study.

Aged↗
PubMed1999

An alcoholic binge causes massive degradation of hepatic mitochondrial DNA in mice.

BACKGROUND & AIMS: Ethanol causes oxidative stress in the hepatic mitochondria of experimental animals and mitochondrial DNA deletions in alcoholics. We postulated that ethanol intoxication may cause mitochondrial DNA strand breaks. METHODS: Effects of an intragastric dose of ethanol (5 g/kg) on hepatic mitochondrial DNA levels, structure, and synthesis were determined by slot blot hybridization, Southern blot hybridization, and in vivo [3H]thymidine incorporation, respectively. RESULTS: Two hours after ethanol administration, ethane exhalation (an index of lipid peroxidation) increased by 133%, although hepatic lipids were unchanged. Mitochondrial DNA was depleted by 51%. Its supercoiled form disappeared, whereas linearized forms increased. Long polymerase chain reaction evidenced lesions blocking polymerase progress on the mitochondrial genome. Mitochondrial transcripts decreased. Subsequently, [3H]thymidine incorporation into mitochondrial DNA increased, and mitochondrial DNA levels were restored. In contrast, nuclear DNA was not fragmented and its [3H]thymidine incorporation was unchanged. Liver ultrastructure only showed inconstant mitochondrial lesions. Ethanol-induced mitochondrial DNA depletion was prevented by 4-methylpyrazole, an inhibitor of ethanol metabolism, and attenuated by melatonin, an antioxidant. CONCLUSIONS: After an alcoholic binge, ethanol metabolism causes oxidative stress and hepatic mitochondrial DNA degradation in mice. DNA strand breaks may be involved in the development of mitochondrial DNA deletions in alcoholics.

Alcohol Drinking↗
PubMed1999

Palladium-103 plaque radiotherapy for choroidal melanoma: results of a 7-year study.

OBJECTIVE: To describe the first clinical experience with palladium-103 (103Pd) ophthalmic plaque radiotherapy for choroidal melanoma. DESIGN: Phase-I (nonrandomized) clinical trial. PARTICIPANTS: Eighty patients with uveal melanomas were diagnosed by clinical examination, found to be negative for metastatic disease, and offered 103Pd radioactive plaque treatment. Nine patients were concurrently treated with microwave hyperthermia. INTERVENTION: Palladium-103 ophthalmic plaque radiotherapy was employed for each patient. Eye plaques were sewn to the episclera to cover the base of the intraocular tumor, radiation was continuously delivered over 5 to 7 days, and then the plaques were removed. A mean apical dose of 81 Gy was delivered. MAIN OUTCOME MEASURES: The authors evaluated the ease of use of 103Pd seeds within standard gold eye plaques. Patient-related outcomes were control of tumor growth, change in visual acuity, the development of radiation damage (retinopathy, optic neuropathy, and cataract), and metastatic disease. RESULTS: From September 1990 to December 1997, 80 patients were treated with 103Pd and followed for an average of 38 months. Two patients were lost to follow-up. During this time, the authors found that 103Pd seeds were equivalent to iodine-125 (125I) with respect to plaque manufacture and ease of dosimetric calculations. Two patients in this series were treated for tumor recurrence after 125I plaque radiotherapy. They both failed secondary 103Pd treatment and were enucleated. When 103Pd was used as a primary treatment, it controlled the growth of 75 of 78 tumors (96%). Overall, there have been six enucleations: three failures of primary treatment, two failures of retreatment, and one for neovascular glaucoma. Visual acuity evaluations at the 36-month follow-up visit (including the enucleated patients) revealed that 38% of eyes had decreased 3 or more lines of vision, and 77% were 20/200 or better. CONCLUSION: Palladium-103 plaque radiotherapy can be used to treat uveal melanomas. Compared with 125I, computerized dosimetry suggests a more favorable dose distribution with 103Pd. Treatment of most patients resulted in tumor shrinkage and preservation of functional vision. The authors have noted no complications that might preclude the use of 103Pd ophthalmic plaque radiotherapy for choroidal melanoma.

Brachytherapy↗
PubMed1999

Mesalazine (5-aminosalicylic acid) induced chronic hepatitis.

BACKGROUND: Treatment of ulcerative colitis or Crohn's disease with sulphasalazine causes several adverse effects, including hepatitis. Sulphasalazine is cleaved by colonic bacteria into 5-aminosalicylic acid and sulphapyridine. Received wisdom was that 5-aminosalicylic acid was topically active, whereas sulphapyridine was absorbed and caused immunoallergic side effects. Mesalazine, a slow release formulation of 5-aminosalicylic acid, was expected to be a safe alternative. However, several cases of acute hepatitis have been reported. CASE REPORT: A 65 year old man had increased liver enzymes, anti-nuclear and anti-smooth muscle autoantibodies and IgG levels, and lesions of chronic hepatitis after 21 months of mesalazine treatment. Although liver dysfunction had been identified eight months earlier, simvastatin rather than mesalazine had been withdrawn, without any improvement. In contrast, liver enzyme and IgG levels became normal and autoantibodies disappeared after discontinuation of mesalazine administration. CONCLUSION: Contrary to initial expectations, mesalazine can cause most of the sulphasalazine induced adverse effects, and hepatic side effects may be almost as frequent. When liver dysfunction occurs, mesalazine administration should be discontinued to avoid the development of chronic hepatitis and liver fibrosis.

Aged↗
PubMed1999

Interleukin-2 overexpresses c-myc and down-regulates cytochrome P-450 in rat hepatocytes.

The interaction of interleukin-2 (IL-2) with its receptor (IL-2R) decreases cytochrome P-450 (CYP) expression in rat hepatocytes. Because IL-2 increases c-Myc in lymphocytes and because c-myc overexpression represses several genes, we postulated that the IL-2/IL-2R interaction may increase c-Myc and thereby down-regulate CYP in hepatocytes. Cultured rat hepatocytes were exposed for 24 h to IL-2 (350 U/ml) and other agents. IL-2 increased c-myc mRNA and protein but decreased total CYP and the mRNAs and proteins of CYP2C11 and CYP3A. The IL-2-mediated c-myc overexpression and CYP down-regulation were prevented by 1) genistein (a tyrosine kinase inhibitor that blocks the initial transduction of the IL-2R signal), 2) retinoic acid, butyric acid, or dimethyl sulfoxide (three agents that block c-myc transcription), or 3) an antisense c-myc oligonucleotide (which may cause rapid degradation of the c-myc transcript). It is concluded that IL-2 causes the overexpression of c-myc and the down-regulation of CYPs in rat hepatocytes. Block of c-myc overexpression, at three different levels with five different agents, prevents CYP down-regulation, suggesting that c-myc overexpression may directly or indirectly repress CYP in hepatocytes.

Animals↗
PubMed1998

Three-dimensional ultrasonography of choroidal melanoma: localization of radioactive eye plaques.

OBJECTIVE: To evaluate the use of 3-dimensional (3D) ultrasonography for the localization of episcleral eye plaques during the treatment of choroidal melanomas. METHODS: A series of 13 patients with choroidal melanoma were treated with radioactive palladium 103 seeds affixed into gold eye plaques. During surgery, 3D ultrasonography was performed with a commercially available system to evaluate the relative position of radioactive plaques secured beneath their intraocular tumors. This system consists of an automated, rotating, handheld, B-scan ultrasonographic probe operating at 10 MHz, a personal computer, and 3D imaging software. RESULTS: We measured the margins of the plaque extending beyond the tumor and the distance between the radioactive seeds and the tumor apex. We also evaluated the relationship between the plaque edge, the episclera, and the tumor's edges. While the plaques were well centered over the tumor in all cases, the plaque margins around the tumor were found to be variably sized. When comparing measurements taken at the time of plaque insertion with those taken at the time of plaque removal, we noted changes in the apical tumor height and in plaque centration. In the 1 patient with a juxtapapillary tumor, the posterior margin of the plaque was found to be displaced away from the sclera, or "tilted." CONCLUSIONS: Three-dimensional ultrasonography offers a new method for ophthalmic plaque localization. Unique perspectives can be visualized through the use of computer-aided 3D reconstructions that permit the assessment of the relative position of the plaque to the optic nerve and the measurement of the distance between the in vivo radioactive seed and the tumor apex. Our experience suggests that when compared with 2-dimensional ultrasonography, 3D ultrasonography offers new capabilities that can be used to improve plaque placement and radiation dose calculations.

Brachytherapy↗
PubMed1998

Long-term mechanical circulatory support system reliability recommendation: American Society for Artificial Internal Organs and The Society of Thoracic Surgeons: long-term mechanical circulatory support system reliability recommendation.

Jointly developed by members of the American Society for Artificial Internal Organs and the Society of Thoracic Surgeons along with staff from the Food and Drug Administration, the National Heart, Lung and Blood Institute and other experts, this recommendation describes the reliability considerations and goals for Investigational Device Exemption and Premarket Approval submissions for long-term, mechanical circulatory support systems. The recommendation includes a definition of system failure, a discussion of an appropriate reliability model, a suggested in vitro reliability test plan, reliability considerations for animal implantation tests, in vitro and animal in vivo performance goals, the qualification of design changes during the Investigational Device Exemption clinical trial, the development of a Failure Modes Effects and Criticality Analysis, and the reliability information for surgeons and patient candidates. The document will be periodically reviewed to assess its timeliness and appropriateness within five years.

Animals↗
PubMed1998

Steatohepatitis-inducing drugs cause mitochondrial dysfunction and lipid peroxidation in rat hepatocytes.

BACKGROUND & AIMS: 4,4'-Diethylaminoethoxyhexestrol (DEAEH), amiodarone, and perhexiline cause steatohepatitis in humans. The mechanisms of these effects are unknown for DEAEH and have not been completely elucidated for amiodarone and perhexiline. The aim of this study was to determine these mechanisms. METHODS: Rat liver mitochondria, cultured rat hepatocytes, or rats were treated with these drugs, and the effects on mitochondrial respiration, beta-oxidation, reactive oxygen species formation, and lipid peroxidation were determined. RESULTS: DEAEH accumulated in mitochondria and inhibited carnitine palmitoyl transferase I and acyl-coenzyme A dehydrogenases; it decreased beta-oxidation and caused lipid deposits in hepatocytes. DEAEH also inhibited mitochondrial respiration and decreased adenosine triphosphate (ATP) levels in hepatocytes. DEAEH, amiodarone, and perhexiline augmented the mitochondrial formation of reactive oxygen species and caused lipid peroxidation in rats. CONCLUSIONS: Like amiodarone and perhexiline, DEAEH accumulates in mitochondria, where it inhibits both beta-oxidation (causing steatosis) and respiration. Inhibition of respiration decreases ATP and also increases the mitochondrial formation of reactive oxygen species. The latter oxidize fat deposits, causing lipid peroxidation. We suggest that ATP depletion and lipid peroxidation may cause cell death and that lipid peroxidation products may account, in part, for other steatohepatitis lesions.

Animals↗
PubMed1997

MMAC1/PTEN mutations in primary tumor specimens and tumor cell lines.

A candidate tumor suppressor gene, MMAC1/PTEN, located in human chromosome band 10q23, was recently identified based on sequence alterations observed in several glioma, breast, prostate, and kidney tumor specimens or cell lines. To further investigate the mutational profile of this gene in human cancers, we examined a large set of human tumor specimens and cancer cell lines of many types for 10q23 allelic losses and MMAC1 sequence alterations. Loss of heterozygosity (LOH) at the MMAC1 locus was observed in approximately one-half of the samples examined, consistent with the high frequency of 10q allelic loss reported for many cancers. Of 124 tumor specimens exhibiting LOH that have been screened for MMAC1 alterations to date, we have detected variants in 13 (approximately 10%) of these primary tumors; the highest frequency of variants was found in glioblastoma specimens (approximately 23%). Novel alterations identified in this gene include a missense variant in a melanoma sample and a splicing variant and a nonsense mutation in pediatric glioblastomas. Of 76 tumor cell lines prescreened for probable LOH, microsequence alterations of MMAC1 were detected in 12 (approximately 16%) of the lines, including those derived from astrocytoma, leukemia, and melanoma tumors, as well as bladder, breast, lung, prostate, submaxillary gland, and testis carcinomas. In addition, in this set of tumor cell lines, we detected 11 (approximately 14%) homozygous deletions that eliminated coding portions of MMAC1, a class of abnormality not detected by our methods in primary tumors. These data support the occurrence of inactivating MMAC1 alterations in multiple human cancer types. In addition, we report the discovery of a putative pseudogene of MMAC1 localized on chromosome 9.

Brain Neoplasms↗
PubMed1997

Palliation of AIDS-related primary lymphoma of the brain: observations from a multi-institutional database.

PURPOSE: To catalogue the presenting symptoms of patients with AIDS who are presumed to have primary central nervous system lymphoma (PCNSL). To document the palliative efficacy of cranial irradiation (RT) relative to the endpoints of complete and overall response for the respective symptoms. METHODS: An analysis of 163 patients with AIDS-related PCNSL who were evaluated at nine urban hospitals was performed. These patients were treated for PCNSL after the establishment of a tissue diagnosis or on a presumptive basis after failing empiric treatment for toxoplasmosis. All patients were treated between 1983 and 1995 with radiotherapy (median dose-fractionation scheme = 3 Gy x 10) and steroids (>90% dexamethasone). Because multiple fractionation schemes were used, prescriptions were converted to biologically effective doses according to the formula, Gy10 = Total Dose x (1 + fractional dose/alpha-beta); using an alpha-beta value of 10. RESULTS: The overall palliative response rate for the entire group was 53%. In univariate analysis, trends were present associating complete response rates with higher performance status (KPS > or = 70 vs. KPS < or = 60 = 17% vs. 5%), female gender (women vs. men = 29% vs. 8%), and the delivery of higher biologically effective doses (BED) of RT (Gy10 > 39 vs. < or = 39 = 20% vs. 5%). In multivariate analysis of factors predicting complete response, both higher KPS and higher BED retained independent significance. A separate univariate analysis identified high performance status (KPS > or = 70 vs. KPS < or = 60 = 71% vs. 47%), and young age (< or = 35 vs. > 35 = 61% vs. 40%) as factors significantly correlating with the endpoint of the overall response. In multivariate analysis, high performance status and the delivery of higher biologically effective doses of irradiation correlated significantly with higher overall response rates. CONCLUSION: Most AIDS patients who develop symptoms from primary lymphoma of the brain can achieve some palliation from a management program that includes cranial irradiation. Young patients with excellent performance status are most likely to respond to treatment. The delivery of higher biologically effective doses of irradiation also may increase the probability of achieving a palliative response.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Renoprotective effects of the 21-aminosteroid U74389G in ischemia-reperfusion injury and cold storage preservation.

Free radical mediated lipid peroxidation (LPO) has been implicated in the pathogenesis of ischemic-reperfusion injury (IRI). To address the renoprotective effect(s) of LPO inhibition, the efficacy of the 21 aminosteroid U74389G was evaluated in three IRI models. In Model 1 51 unilateral nephrectomized rats that underwent 60 min of warm ischemia followed by a 72-hr reperfusion interval were treated with the test vehicle only, or 3, 6, or 12 mg/kg of U74389G intravenously, 5 min pre- or postischemia. In Model 2 Sprague-Dawley rats underwent sham operation (n=9), or 45 min of warm ischemia and 10 min of reperfusion with U74389G (6 mg/kg; n=10) or test vehicle only (n=10) administered intravenously over 10 min beginning 5 min prior to clamp release. After reperfusion, LPO was determined by assay of snap frozen tissue for thiobarbituric acid (TBA) concentrations (nmol/g tissue weight). In Model 3 domestic lean maid pigs (14-18 kg) underwent left nephrectomy with 30 min of warm ischemia, Collins C-4 flush, and 24 hr of cold storage preservation. Heterotopic autotransplantation and immediate contralateral nephrectomy was then performed in Group A-nonischemic controls (n=4), Group B-ischemic controls (n=5), and Group C-U74389G (6 mg/kg) administered preischemia and at autotransplantation (n=5). In Model 1 maximal renoprotection was demonstrated with the 6 mg/kg dose of U74389G administered after ischemia (ischemic control 72-hr serum creatinine (Cr) = 8.01+/-1.1 mg% vs. 3.32+/-0.96 mg%; ischemic control creatinine clearance = 0.069+/-0.03 ml/min vs. 0.206+/-0.04 ml/min; P<0.05). In Model 2 TBA levels were significantly lower in U74389G treated animals (88.5+/-10.0 vs. ischemic controls = 296.8+/-81.4; P=0.02). In Model 3 graft survivals were 100%, 0%, and 60% respectively. Peak Cr and BUN (mg%) were significantly greater in Group C vs. Group A, (Group A Cr = 8.59+/-0.63 vs. Group C = 12.8+/-1.01; Group A BUN = 64.1+/-2.73 vs. Group C = 104.9+/-12.21)--however, by day 10, thee were no significant differences in renal function: (Group A Cr = 2.15+/-0.3 vs. Group C = 2.10+/-0.06; Group A BUN = 27.0+/-6.0 vs. Group C = 31.1+/-6.4). These results support the beneficial effects of LPO inhibitors in models of ischemia-reperfusion, as well as preservation/transplantation, and suggest that this renoprotection correlates with decreased membrane lipid peroxidation.

Animals↗
PubMed1997

Multiple hepatic mitochondrial DNA deletions suggest premature oxidative aging in alcoholic patients.

BACKGROUND/AIMS: A 4977-base pair deletion has been detected in the hepatic mitochondrial DNA of alcoholic patients with microvesicular steatosis, a lesion ascribed to impaired mitochondrial beta-oxidation. However, only a single deletion had been looked for in this previous study, and it could not be determined whether the deletion was preexisting or acquired. Alcohol abuse increases the formation of reactive oxygen species in hepatic mitochondria. If this effect accelerates the oxidative aging of mitochondrial DNA, several other mutations would be expected. METHODS: The mtDNA region extending from nucleotide 8167 to nucleotide 14246 was screened for the presence of large mitochondrial DNA deletions in 58 alcoholic patients and 67 age-matched non-alcoholic controls. Hepatic DNA was subjected to polymerase chain reactions that amplified non-deleted and deleted mitochondrial DNA, respectively, and the boundaries of the mitochondrial DNA deletions were sequenced. RESULTS: Only 3% of the non-alcoholic controls carried a mitochondrial DNA deletion, whereas 24% of all alcoholic patients and 85% of the 13 alcoholic patients with microvesicular steatosis exhibited either single or multiple 4977, 5385, 5039 and 5556-base pair mitochondrial DNA deletions. No deletion(s) were observed, however, in 13 patients with microvesicular steatosis due to other causes. CONCLUSIONS: Diverse mitochondrial DNA rearrangements are observed in alcoholic patients with microvesicular steatosis. We suggest that alcohol abuse leads to premature oxidative aging of mitochondrial DNA. Hypothetically, oxidative damage to mitochondrial constituents (DNA, proteins and lipids) may favor microvesicular fat deposition.

Adult↗