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Biomedical subjects

Benjamin Miller

Publications and source records attributed to Benjamin Miller.

At least 19 recordsLinked to original sources
PubMed2007

Evaluation of intravitreal kenalog toxicity in humans.

OBJECTIVE: To evaluate possible functional toxicity of intravitreal Kenalog (commercial triamcinolone acetonide) in patients' retinas. DESIGN: Observational case series. PARTICIPANTS: Thirty-two phakic eyes of 16 patients who had nonproliferative diabetic retinopathy and bilateral macular edema refractory to laser therapy, which had no other eye disorder and no previous ophthalmic operation. INTERVENTION: Kenalog (4 mg/0.1 ml) was injected intravitreally to one eye, whereas the second eye served as the control. The experimental eye was chosen as the eye with worse visual acuity (VA). MAIN OUTCOME MEASURES: Deterioration of electroretinogram parameters of the study eye measured at 3 months of follow-up when compared with the electroretinogram responses of the fellow, control eye and when compared with electroretinogram responses obtained before injection. Visual acuity, intraocular pressure (IOP), and eventual complications were assessed. No improvement or deterioration of VA or any increase in IOP was regarded as a secondary outcome. RESULTS: Average maximal response amplitude ratios of the dark-adapted b-wave (treated/control eyes) of the electroretinogram were 0.93 before (P = 0.221) and 0.94 (P = 0.387) 3 months after Kenalog injection. Average ratios of the light-adapted b-wave amplitude (treated/control eyes) of the electroretinogram were 1.04 (P = 0.702) before and 0.86 (P = 0.138) 3 months after Kenalog injection. No significant differences (P>0.05) were found between the electroretinogram parameters obtained from all eyes before and 3 months after Kenalog injection. Average VAs in the treated eyes were 1.08, 0.8, and 1.0 logarithm of the minimum angle of resolution units before and 2 and 4 months after injection, respectively. Temporary elevation of IOP was found in 4 treated eyes of 4 patients (25%). CONCLUSIONS: No electroretinographic evidence of a retinotoxic effect of intravitreal Kenalog was found in our patients.

Adult↗
PubMed2007

Retinal capillary basement membrane thickness in diabetic mice genetically modified at the haptoglobin locus.

BACKGROUND: Individuals with diabetes mellitus (DM) homozygous for the haptoglobin (Hp) 1 allele are at decreased risk of retinopathy as compared to DM individuals with the Hp 2 allele. We sought to recapitulate these findings in DM mice genetically modified at the Hp locus. METHODS: An early morphological characteristic of the microangiopathy seen in diabetic retinal disease is retinal capillary basement membrane (RCBM) thickening. RCBM thickness as assessed by electron microscopy was performed on a total of 12 eyes taken from three mice in each of the four study groups (three eyes from C57Bl/6 Hp 1 and C57Bl/6 Hp 2 mice with and without streptozotocin-induced diabetes). RESULTS: The non-parametric Kruskal-Wallis ANOVA test demonstrated that there was a highly significant difference between the four groups of mice (P < 0.0001). Mann-Whitney tests for specific pair-wise comparisons demonstrated that there was no significant difference in the RCBM thickness between Hp 1 and Hp 2 mice (p = 0.70) or between DM Hp 1 and non-DM Hp 1 mice (p = 0.42). However, induction of diabetes resulted in a marked increase in RCBM thickness in Hp 2 mice compared to non-DM Hp 2 mice (p = 0.0004) and compared to DM Hp 1 mice (p = 0.0005). CONCLUSIONS: A highly significant increase in RCBM thickness was observed in DM mice with the Hp 2 genotype. These data provide important support for association studies done in humans showing an increased prevalence of diabetic retinopathy in individuals with the Hp 2 genotype.

Animals↗
PubMed2006

Haptoglobin genotype is a regulator of reverse cholesterol transport in diabetes in vitro and in vivo.

Two common alleles exist at the haptoglobin (Hp) locus, and the Hp2 allele is associated with an increased incidence of cardiovascular disease, specifically in diabetes mellitus (DM). Oxidative stress is increased in Hp2 mice and humans with DM. Oxidative modification of the apolipoprotein A-I inhibits reverse cholesterol transport. We sought to test the hypothesis that reverse cholesterol transport is impaired in Hp2 DM mice and humans. In vitro, using serum from non-DM and DM individuals, we measured cholesterol efflux from (3)H-cholesterol-labeled macrophages. In vivo, we injected (3)H-cholesterol-loaded macrophages intraperitoneally into non-DM and DM mice with the Hp1-1 or Hp2-2 genotype and monitored (3)H-tracer levels in plasma, liver, and feces. In vitro, in DM individuals only, we observed significantly decreased cholesterol efflux from macrophages incubated with serum from Hp2-1 or Hp2-2 as compared with Hp1-1 individuals (P<0.01). The interaction between Hp type and DM was recapitulated using purified Hp and glycated Hb. In vivo, DM mice loaded with (3)H-cholesterol-labeled macrophages had a 40% reduction in (3)H-cholesterol in plasma, liver, and feces as compared with non-DM mice (P<0.01). The reduction in reverse cholesterol transport associated with DM was significantly greater in Hp2-2 mice as compared with Hp1-1 mice (54% versus 25% in plasma; 52% versus 27% in liver; 57% versus 32% in feces; P<0.03). reverse cholesterol transport is decreased in Hp2-2 DM. This may explain in part the increased atherosclerotic burden found in Hp2-2 DM individuals.

Alleles↗
PubMed2006

Hypotrichosis with juvenile macular dystrophy: clinical and electrophysiological assessment of visual function.

PURPOSE: To evaluate retinal function in subjects suffering from hypotrichosis with juvenile macular dystrophy (HJMD). DESIGN: Retrospective case-control study. PARTICIPANTS: Sixteen HJMD patients belonging to 2 genetic groups and 20 control subjects. METHODS: The HJMD patients underwent clinical ophthalmological examination and electrophysiological testing for a period of as many as 14 years. The electroretinogram (ERG), electro-oculogram (EOG), and visual evoked potential (VEP) were recorded serially to assess visual function and to follow possible progression of the disease. MAIN OUTCOME MEASURES: Amplitudes and implicit times of ERG and VEP, and Arden ratio of EOG. RESULTS: Fundus examination revealed pigmentary abnormalities with atrophic changes at the posterior pole extending to regions beyond the macular area. A slow and time-dependent decline in visual acuity was noted. The ERG responses were subnormal in amplitude. The ERG deficit was similar for light- and dark-adapted responses. There was a gradual but consistent decrease in the ERGs with time. The EOG measurements were within the normal range. Pattern reversal VEPs were very subnormal, even in patients with mild deterioration of visual acuity. The flash VEPs were of slightly subnormal amplitudes and implicit times in the upper limit of the normal range. CONCLUSIONS: The fundus pictures and electrophysiological tests were consistent with retinal involvement extending beyond the macular region. Follow-up of visual acuity and ERG testing indicated a slowly progressing retinal disorder affecting cone-mediated vision as well as rod-mediated vision. Therefore, we suggest that a more appropriate name for this syndrome is hypotrichosis with cone-rod dystrophy.

Adolescent↗
PubMed2006

Epiphora (excessive tearing) and other ocular manifestations related to weekly docetaxel: underestimated dose-limiting toxicity.

PURPOSE: Epiphora due to canalicular stenosis is a recently described side effect of weekly docetaxel. We prospectively evaluated the incidence of this complication and other ocular manifestations in patients treated at our medical center. PATIENTS AND METHODS: Twenty-one consecutive patients (breast cancer: 14; metastatic non-small cell lung cancer: 6; metastatic nasopharyngeal carcinoma: 1) (female/male: 14/7; age range: 34-78 yr) were treated with weekly docetaxel (35 mg/m2/wk iv for 6 wk, cycles repeated every 49 d). A standard questionnaire regarding epiphora was completed before each dose of docetaxel. Patients who complained of excessive tearing underwent a thorough ophthalmologic evaluation before receiving the next dose. RESULTS: Epiphora due to stenosis of the lacrimal puncti and canaliculi developed in seven (33%) patients following a cumulative dose of 208-645 mg/m2 (median: 400 mg/m2). Two patients developed complete canalicular stenosis requiring surgery. Epiphora was accompanied by madarosis and ectodermalization of the palpebral and bulbar conjunctiva, complete in five patients. Treatment was discontinued due to epiphora in two (10%) patients. After a median follow-up of 11 mo, four patients still had epiphora. CONCLUSION: Epiphora due to canalicular stenosis is a frequent complication of weekly docetaxel and might be dose limiting. Irreversible damage requiring surgical intervention may develop despite close monitoring.

Adult↗
PubMed2005

[Upper lid frontalis suspension as a treatment for essential blepharospasm].

BACKGROUND: Essential blepharospasm is a progressive disease of unknown etiology causing a significant decline in the quality of life of patients suffering from the disease. Currently used treatment for this condition is repeated injections of Botulinum toxin. Some of the patients' therapeutic response to Botox injections is insufficient, and some develop ocular complications. GOALS AND METHODS: This report presents our experience with sling frontalis suspension for essential blepharospasm in 4 patients with follow-up periods of six months to 2 years. A literature review is presented and discussed. RESULTS: A treatment trial with Botox injections was attempted in all four patients. Three of the patients showed insufficient treatment response. Three of the patients developed side effects of recurrent episodes of upper lid ptosis following injections. In all four patients that underwent operations significant reduction of blepharospasm was observed. In two of the patients Botulinum toxin could be discontinued, in one patient treatment intensity could be reduced, and in three--treatment complications were prevented. All four patients reported a high degree of satisfaction from treatment results. CONCLUSIONS: Our results indicate that sling frontalis suspension for essential blepharospasm is a safe and efficient treatment for essential blephrospasm with a high degree of patient satisfaction. Further large-scale studies are needed to substantiate our results.

Aged↗
PubMed2005

[Oxygen effect on ocular lens].

BACKGROUND: Cataract is the leading cause of preventable blindness worldwide. Clinical observations and laboratory results have shown that oxygen has a possible toxic role in cataract formation. AIM: The aim of the present study was to demonstrate, measure and characterize the damage caused to bovine lenses in organ culture as a result of their exposure to hyperbaric oxygen pressure. MATERIALS AND METHODS: Twenty bovine lenses exposed to hyperbaric pressure were compared to 20 control lenses. Lenses were kept in an organ culture for 14 days. Each day the focusing ability of the exposed lenses was compared to controls. The comparison was based on the amount to which the focus point of each measured ray diverged from the focus point of the lens. Lenses were also examined under the microscope and morphologic changes in study lenses were compared to controls. RESULTS: A statistically significant difference in focusing ability between the study and control lenses was observed. The difference became larger during the incubation period indicating an accumulation of damage. The damage resulted from the peripheral but not the central part of the lenses. The morphologic changes observed under the microscope matched the damage profile of the focusing ability. CONCLUSIONS: Oxygen has a possible role in cataract formation. The effect of oxygen is cumulative. The route of damage formation follows the diffusion of oxygen into the lens.

Animals↗
PubMed2004

Syndromic surveillance for influenzalike illness in ambulatory care network.

Conventional disease surveillance mechanisms that rely on passive reporting may be too slow and insensitive to rapidly detect a large-scale infectious disease outbreak; the reporting time from a patient's initial symptoms to specific disease diagnosis takes days to weeks. To meet this need, new surveillance methods are being developed. Referred to as nontraditional or syndromic surveillance, these new systems typically rely on prediagnostic data to rapidly detect infectious disease outbreaks, such as those caused by bioterrorism. Using data from a large health maintenance organization, we discuss the development, implementation, and evaluation of a time-series syndromic surveillance detection algorithm for influenzalike illness in Minnesota.

Ambulatory Care↗
PubMed2003

NADPH diaphorase activity in the rat retina during the early stages of experimental diabetes.

BACKGROUND: Nitric oxide (NO) plays an important physiological role in inter-cellular communication, but when produced in excess it can become toxic. Our goal was to evaluate possible involvement of NO in the development of retinopathy in diabetic rats. METHODS: Diabetes was induced in male albino rats by intravenous injection of streptozotocin. Some of the normal and diabetic rats were raised with added L-arginine to increase in vivo NO synthesis, or with added L-NAME to inhibit the rate of in vivo NO synthesis. NADPH diaphorase histochemistry was conducted on retinal whole mounts and transverse sections at different time intervals after induction of diabetes. The electroretinogram (ERG) was recorded to assess retinal function. RESULTS: After 6 weeks of diabetes, NADPH diaphorase amacrine cells in the diabetic retinas appeared abnormal in their morphology and the degree of staining was decreased in their processes. In contrast, NADPH diaphorase activity was augmented in Müller cells. Supplementing the rats' diet with L-arginine for 10 weeks slightly reduced NADPH diaphorase activity in amacrine cell in normal rats but had no effect on the diabetic rats. Adding L-NAME for 10 weeks did not alter NADPH diaphorase histochemistry in either normal or diabetic rats. The ERG responses were reduced by L-arginine supplementation in normal and diabetic rats, and were unaffected by adding L-NAME to the drinking water. CONCLUSIONS: Our findings are consistent with the hypothesis that high glucose levels are deleterious to the rat retina and that excessive synthesis of NO may contribute to the development of diabetic retinopathy.

Animals↗
PubMed2003

Haptoglobin phenotype in age-related macular degeneration patients.

PURPOSE: To investigate a possible role of the haptoglobin phenotype in the development of exudative age-related macular degeneration (AMD) in human subjects. DESIGN: Prospective, observational, comparative population study. METHODS: The study was carried out in an institutional setting. All patients referred because of exudative AMD in one eye during an 18-month period were included in the study group. A group of patients treated for other ocular diseases and not having AMD in either eye served as control. Haptoglobin phenotype was determined from a blood sample drawn from each patient in both the study and control groups. The main outcome measure was the distribution of the haptoglobin phenotype in the study and control group. RESULTS: One hundred eighty-five participants were included in the study. Ninety-eight had exudative AMD, and 87 were AMD-free. The difference between the study and control groups in distribution of the haptoglobin phenotype was found to be statistically insignificant. CONCLUSIONS: Our results suggest that the haptoglobin phenotype has no effect on the prevalence of exudative AMD.

Aged↗
PubMed2003

Phenotypic diversity and mutation spectrum in hypotrichosis with juvenile macular dystrophy.

Hypotrichosis with juvenile macular dystrophy is a rare autosomal recessive disorder characterized by abnormal growth of scalp hair during infancy, and by the later occurrence of macular degeneration leading to blindness during the first to third decade of life. Hypotrichosis with juvenile macular dystrophy was recently shown to result from mutations in CDH3 encoding P-cadherin. In this study, we assessed 27 individuals, including nine patients, belonging to five families in an attempt to characterize further the CDH3 mutation spectrum and delineate possible phenotype-genotype correlations. Deleterious biallelic mutations, predicted to lead to the translation of a dysfunctional protein, were found in all affected individuals. Four of these mutations are novel. Affected individuals of two large separate apparently unrelated families of Arab Israeli origin were found to carry the same homozygous mis-sense mutation (R503H) in exon 11 of the CDH3 gene. This mutation, which alters a Ca2+-binding site in the fourth extracellular domain of P-cadherin, was previously described in a third unrelated Arab Israeli family. Using haplotype analysis for a series of polymorphic markers encompassing the CDH3 gene, we obtained evidence suggesting a founder effect for R503H in the Arab Israeli population. We also compared the dermatologic and ophthalmologic features of 22 hypotrichosis with juvenile macular dystrophy patients with known recessive mutations in CDH3. Whereas hair paucity and macular degeneration were found in all patients, we noticed significant interfamilial and intrafamilial differences in hair morphology, associated skin findings as well as severity and age of onset of visual disability. Altogether, our results obtained in a series of families of various ethnic origins firmly establish mutations in CDH3 as the proximal cause of hypotrichosis with juvenile macular dystrophy and demonstrate genetic homogeneity as well as phenotypic heterogeneity in this disorder.

Cadherins↗
PubMed2003

Posterior lamellar gold-weight extrusion.

We report a case of a man who had undergone gold eyelid loading for lagophthalmos 22 years earlier. During examination for a complaint of foreign body sensation in the operated eye, the gold weight was found under the palpebral conjunctiva. Although extrusion of a gold weight through the skin anteriorly is well recognized, posterior extrusion has not been previously reported. Although such an extrusion involves tarsal plate erosion, the patient's complaints in this case were minor, probably due to the chronic nature of the process. This finding should serve to draw the attention of surgeons using gold eyelid loading to the possible, albeit rare, complication of posterior extrusion.

Eyelid Diseases↗
PubMed2003

Lenticular oxygen toxicity.

PURPOSE: To investigate the possible toxic effect of oxygen on lenses in an organ culture. METHODS: Bovine lenses were exposed to four different combinations of ambient pressure and oxygen concentration in an organ culture throughout a 7-day period. Lens transparency, histology, enzymatic activities, and photomicrographs were compared in study and control groups. RESULTS: No differences were observed between study and control lenses in all measured parameters in a group subjected to a single exposure of 100% oxygen under increased (i.e., hyperbaric) ambient conditions and a group exposed repeatedly to high ambient pressure and normal oxygen partial pressure. Decreased lenticular transparency and enzymatic activities along with structural changes were observed in lenses exposed repeatedly to 100% oxygen concentration under both normal and increased ambient pressures. The observed changes were oxygen-load-dependent: the higher the oxygen partial pressure and the longer the time of exposure, the more severe the changes observed. Optical and structural changes in the lens occurred in a centripetal orientation: the greater the oxygen load, the more central the damage. CONCLUSIONS: High oxygen load has a toxic effect on bovine lenses in organ culture. These effects appear to be cumulative: the higher the oxygen partial pressure and the greater the number of exposures, the more severe the changes observed in the lenses. Changes marking toxicity follow the route of oxygen diffusion into the lens, from the periphery to the center. Cautious interpretation of the results may indicate a role of oxygen (and/or its derivatives) in human cataract formation.

Animals↗
PubMed2003

[Presumed Candida tropicalis endophthalmitis following anterior resection].

We present a case of a 75 years old patient who developed a presumed Candida Tropicalis endophthalmitis after an anterior resection for rectal carcinoma. The pathogen was identified in blood cultures but not in vitreal cultures. Systemic anti fungal treatment brought no ocular improvement. After having a vitrectomy and intravitreal antifungal agent injection gradual improvement up to full resolution took place. To the best of our knowledge, this is the first report of a post surgical candida tropicalis endophthalmitis in a non-neutropenic patient. We suggest special attention to ophthalmic complaints in patients with systemic candidemia and prompt treatment according to ocular findings.

Aged↗
PubMed2002

Acetazolamide for central serous retinopathy.

OBJECTIVE: To find out whether acetazolamide has a beneficial effect in the treatment of central serous retinopathy (CSR). DESIGN: Prospective, nonrandomized, comparative trial. PARTICIPANTS: Fifteen acetazolamide-treated and 7 untreated (control) CSR patients who completed at least 24 months of follow-up. METHODS: Patients in the treatment group were given systemic acetazolamide according to a standard protocol. Main outcome measures were compared between treatment and control groups using Student's t test and the Mann-Whitney U test for statistical analysis. MAIN OUTCOME MEASURES: Time until subjective visual improvement, time until full clinical resolution, and rate of recurrences. RESULTS: Mean times to both subjective visual improvement and clinical resolution of the attack were shorter in the study group than in the control group. Recurrence rate did not differ between the study and control groups. CONCLUSIONS: Acetazolamide treatment for CSR shortens the time for subjective and objective clinical resolution, but has no effect on either final visual acuity or recurrence rate of the disease.

Acetazolamide↗