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Biomedical subjects

D Kaufman

Publications and source records attributed to D Kaufman.

At least 91 records · Page 5Linked to original sources

Formative evaluation of a multimedia CAL program in an ophthalmology clerkship.

The use of computer-aided learning (CAL) in medical education has grown considerably in recent years. CAL has a number of attractive educational features, and computer simulations have been shown to improve learning in health professions education. This paper describes the formative evaluation of a multimedia CAL simulation used in a third year ophthalmology clerkship. The CAL program combines the use of a Macintosh computer with a mannequin head, housing two motor driven camera diaphragms which simulate pupil response. This allows students to practice the "swinging flashlight test", an important clinical exam commonly used to detect visual dysfunction. Five questions are addressed in this study and the formative evaluation process is described. The highly positive results are then presented, with suggestions given for improvement followed by implications for future development.

Clinical Clerkship↗

The catecholic metal sequestering agent 1,2-dihydroxybenzene-3,5-disulfonate confers protection against oxidative cell damage.

Tiron (1,2-dihydroxybenzene-3,5-disulfonate), a nontoxic chelator of a variety of metals, is used to alleviate acute metal overload in animals. It is also oxidized to the EPR-detectable semiquinone radical by various biologically relevant oxidants, such as .OH, O2-., alkyl, and alkoxyl radicals. Since Tiron reacts with potentially toxic intracellular species and is also a metal chelator, we evaluated its protective effects in V79 cells subjected to various types of oxidative damage and attempted to distinguish the protection due to direct detoxification of intracellular radicals from that resulting from chelation of redox-active transition metals. We found that Tiron protects Chinese hamster V79 cells against both O2.(-)-induced (and H2O2 via dismutation of O2.-) and H2O2-induced cytotoxicity as measured by clonogenic assays. In experiments where Tiron was incubated with V79 cells and rinsed prior to exposure to HX/XO or H2O2, cytoprotection was observed, indicating that it protects against intracellular oxidative damage. On the other hand, Tiron did not protect V79 cells against the damage caused by ionizing radiation under aerobic conditions, which is predominantly mediated by H., .OH, and hydrated electrons in a metal-independent fashion. We demonstrate also that in in vitro studies, Tiron protects supercoiled DNA from metal-mediated superoxide-dependent strand breaks. We conclude that Tiron is a potentially useful protecting agent against the lethal effects of oxidative stress and suggest that it offers protection by chelating redox-active transition metal ions, in contrast to earlier reports where the protection by this compound in cellular systems subjected to oxidative damage has been interpreted as due to radical scavenging alone.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗

Nitroxide-mediated protection against X-ray- and neocarzinostatin-induced DNA damage.

The stable free radical Tempol (4-hydroxy-2,2,6,6-tetramethyl-piperidinyloxy) has been shown to protect against X-ray-induced cytotoxicity and hydrogen peroxide- or xanthine oxidase-induced cytotoxicity and mutagenicity. The ability of Tempol to protect against X-ray- or neocarzinostatin (NCS)-induced mutagenicity or DNA double-strand breaks (dsb) was studied in Chinese hamster cells. Tempol (50 mM) provided a protection factor of 2.7 against X-ray-induced mutagenicity in Chinese hamster ovary (CHO) AS52 cells, with a protection factor against cytotoxicity of 3.5. Using the field inversion gel electrophoresis technique of measuring DNA dsb, 50 mM Tempol provides a threefold reduction in DNA damage at an X-ray dose of 40 Gy. For NCS-induced damage, Tempol increased survival from 9% to 80% at 60 ng/mL NCS and reduced mutation induction by a factor of approximately 3. DNA dsb were reduced by a factor of approximately 7 at 500 ng/mL NCS. Tempol is representative of a class of stable nitroxide free radical compounds that have superoxide dismutase-mimetic activity, can oxidize metal ions such as ferrous iron that are complexed to DNA, and may also detoxify radiation-induced organoperoxide radicals by competitive scvenging. The NCS chromophore is reduced by sulfhydryls to an active form. Electron spin resonance (ESR) spectroscopy shows that 2-mercaptoethanol-activated NCS reacts with Tempol 3.5 times faster than does unactivated NCS. Thus, Tempol appears to inactivate the NCS chromophore before a substantial amount of DNA damage occurs.

Animals↗

Hodgkin's disease.

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Hodgkin Disease↗

A clinical and cytological study of vitamin A deficiency in Kiribati.

Vitamin A status was assessed clinically and by conjunctival impression cytology in a selected group under seven years of age in the Republic of Kiribati. A total of 230 children were studied. Of 185 with readable histology, 14.6% were clinically and histologically abnormal; 19.5% were clinically abnormal but histologically normal; and 15.7% were clinically normal and histologically abnormal. The remainder (50.3%) were clinically and histologically normal. There was a significant correlation between clinical disease and histology (P < 0.001). The prevalence of the disease in males was 45.8% and 26.3% in females. The risk of deficiency appeared to increase with advancing age. There was no significant difference between the two villages studied.

Child↗

Inhibition of oxygen-dependent radiation-induced damage by the nitroxide superoxide dismutase mimic, tempol.

Stable nitroxide radicals have been previously shown to function as superoxide dismutase (SOD)2 mimics and to protect mammalian cells against superoxide and hydrogen peroxide-mediated oxidative stress. These unique characteristics suggested that nitroxides, such as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (Tempol), might protect mammalian cells against ionizing radiation. Treating Chinese hamster cells under aerobic conditions with 5, 10, 50, and 100 mM Tempol 10 min prior to X-rays resulted in radiation protection factors of 1.25, 1.30, 2.1, and 2.5, respectively. However, the reduced form of Tempol afforded no protection. Tempol treatment under hypoxic conditions did not provide radioprotection. Aerobic X-ray protection by Tempol could not be attributed to the induction of intracellular hypoxia, increase in intracellular glutathione, or induction of intracellular SOD mRNA. Tempol thus represents a new class of non-thiol-containing radiation protectors, which may be useful in elucidating the mechanism(s) of radiation-induced cellular damage and may have broad applications in protecting against oxidative stress.

Animals↗

Probucol treatment in hypercholesterolemic patients: effects on lipoprotein composition, HDL particle size, and cholesteryl ester transfer.

Despite probucol's capacity to induce regression of tendinous xanthomata and reduce whole plasma and LDL cholesterol (LDL-C) in patients with hypercholesterolemia, its therapeutic use in the United States has been limited because of concern about its HDL-lowering effects. To assess the possibility that probucol might facilitate mobilization of tissue cholesterol in the presence of low HDL levels as a consequence of favorable changes in lipoprotein composition and function, we have analyzed lipoproteins and studied cholesteryl ester transfer (CET) in hypercholesterolemic patients before and after treatment. Prior to treatment, the free cholesterol (FC)/lecithin (L) ratio in plasma, a new index of cardiovascular risk, and the mass of cholesteryl ester transferred from HDL to the apo B-containing lipoproteins (CET) both were significantly increased (P less than 0.001). As previously shown, plasma cholesterol, LDL-C, HDL-C, HDL2, and apolipoproteins A-I, A-II, and B all fell significantly following probucol treatment. The FC/L ratio in plasma (P less than 0.01) and HDL2 (P less than 0.01) both fell significantly also, as did the sphingomyelin/lecithin ratio in VLDL + LDL (P less than 0.001) which is typically increased in untreated patients with hypercholesterolemia. Nondenaturing gradient gel electrophoresis in 6 patients revealed that the quantitative changes in HDL were associated with a redistribution of particles characterized by a decrease in the prevalence of the largest (HDL2b) and a relative increase in the number of the smallest (HDL3b) particles. Moreover, CET following probucol therapy returned to levels which were indistinguishable from those of normolipidemic controls. These results indicate that untreated patients with hypercholesterolemia have abnormalities in (1) lipoprotein composition which have been shown to retard the movement of cholesterol from tissues to HDL, and in (2) CET which is accelerated and can potentially lead to the formation in plasma of atherogenic CE-enriched apo B-containing lipoproteins. Probucol's capacity to reverse these specific alterations suggests that it may have beneficial effects on cholesterol transport in patients with hypercholesterolemia.

Adult↗

Methylene chloride: report of five exposures and two deaths.

Five patients presented to the emergency department (ED) following exposure in an enclosed space to methylene chloride (dichloromethane), used for removing paint. Two workers and three rescuers were involved. Two rescuers complained only of dizziness and mild nausea, and were subsequently discharged from the ED. One rescuer was asymptomatic. Worker no. 1 arrived in cardiac arrest and eventually died in the ED despite resuscitation efforts. Worker no. 2 also presented to the ED in cardiac arrest, and was successfully resuscitated to pulse and blood pressure. However, he never regained consciousness or spontaneous respirations, and died on the fourth day. Of interest is that worker no. 2's carboxyhemoglobin level increased from 2% to 8% over the 9 hours following admission, despite administration of 40% to 50% oxygen by endotracheal tube. Among the conclusions that can be drawn are (1) the cause of death in these patients was not carbon monoxide poisoning, but solvent-induced narcosis; (2) carboxyhemoglobin levels may continue to rise following cessation of exposure, despite administration of high flow oxygen; (3) rescuers can easily become victims if proper protective clothing and respirators are not worn.

Adult↗

A new in vitro approach to determine acquired tolerance in long-term kidney allograft recipients.

Previous studies indicate some kidney allograft recipients treated with total lymphoid irradiation, cyclosporine, or conventional immunosuppressive therapy demonstrate specific proliferative unresponsiveness in mixed lymphocyte culture (MLC) to donor cells at various times posttransplant. To investigate possible donor-specific hyporeactivity, we have studied 3 patients treated with TLI whose grafts have survived longer than 10 years; 2 patients given the same immunosuppressive protocol but without TLI whose grafts have survived longer than 10 years; and 27 CsA-treated living-related donor and cadaver-allograft recipients 1 year posttransplant. We confirmed previous observations of hyporeactivity of some patients' cells to stimulation by donor cells. In addition, we identified hyporeactivity to stimulation by homozygous typing cells (HTCs) defining the HLA-Dw specificities of the donor cells for all 3 of the 3 TLI patients, 1 of the 2 non-TLI patients, and 9 of the 27 patients 1 year posttransplant. The LRD recipients with donor-specific hyporeactivity as defined by the HTC analysis demonstrated fewer rejection episodes (25% vs. 57%) and lower mean creatinine levels (1.18 vs 1.78 mg/dL) than patients without donor-specific hyporeactivity. These studies demonstrate the feasibility of monitoring the immune status of allograft recipients posttransplant by means of HTC analysis, eliminating the need for pretransplant specimens. This approach provides a possible means to assess which patients may have acquired donor-specific hyporeactivity to their kidney allograft and thus may require less immunosuppression.

Clone Cells↗