Search PubMedSearch

Biomedical subjects

S Lerman

Publications and source records attributed to S Lerman.

At least 73 records · Page 4Linked to original sources

Ocular phototoxicity and psoralen plus ultraviolet radiation (320-400 nm) therapy: an experimental and clinical evaluation.

The increase in fluorescent chromophores within the human ocular lens is age related, leading to an increasingly yellow core (nucleus) that presumably results from UV radiation exposure. In approximately 10% of our population this process progresses more rapidly, resulting in the formation of the brown (nuclear) cataract. Some lenticular discoloration may be beneficial, since it enables the mature lens to filter UV and short-wavelength visible radiation, thus protecting the retina from potential photodamage. Aphakic primate retinas can be irreversibly damaged by exposure to approximately 5 mW.cm-2 long-wavelength UV (greater than 325 nm) radiation. Photosensitized damage to the lens and retina with psoralen plus UV radiation (320-400 nm) (PUVA) has been demonstrated in experimental animals, and cataracts have recently been reported in patients given PUVA therapy. A new method to screen patients for lens damage is by enhanced fluorescence measurements. This method, UV slit-lamp densitography, permits detection of lenticular photodamage at a molecular level, years before visible opacities become manifest by conventional slit-lamp examination. This procedure has also demonstrated a significantly lower level of lens fluorescence (hence decreased filtering capacity) in patients with retinal degenerative diseases, suggesting UV photodamage as a factor in the progression and perhaps pathogenesis of these conditions.

Aging

Clinical evaluation of direct and photosensitized ultraviolet radiation damage to the lens.

We are reporting a new, objective, and quantitative method for monitoring age-related molecular changes in the human ocular lens in vivo, as expressed by increases in at least two (nontryptophan) fluorescence wavelengths. These fluorescence wavelengths appear to be caused by photochemically induced changes in the lens, and they reflect the ultraviolet (UV) filtering capacity of the patients' ocular lenses. These data correlate with previously reported in vitro lens fluorescence changes that are associated with the aging process. This method will also detect alterations in lenticular fluorescence caused by photosensitized as well as direct UV radiation damage.

Adolescent

Nuclear magnetic resonance analyses of the cold cataract: whole lens studies.

Pulse nuclear magnetic resonance (NMR) magnetization decay studies were performed on normal and cold cataractous rat lenses. Computer analyses of the decay curves have been interpreted to reflect two types of water within the lens that do not exchange rapidly. Upon lowering the temperature in the presence and absence of 5% acrylamide (a known agent that prevents the cold cataract phenomenon), significant differences in the relaxation rates of one water fraction were noted. 2H (NMR) spectra on young rabbit and human lenses showed temperature-related linewidth changes, which are significantly diminished in lenses incubated in acrylamide. 31P spectra also showed similar inorganic phosphate linewidth changes and also reflected progressive alterations in the metabolic state of these lenses. These studies demonstrate the potential of NMR methods for monitoring physicochemical parameters in the normal and cataractous mammalian lens.

Acrylamide

Psoralen--long-wave ultraviolet therapy and human cataractogenesis.

Cataract formation associated with psoralen--long-wave ultraviolet (P-UVA) therapy has been documented in experimental animals. Presumptive P-UVA cataracts in humans have also been reported recently. Cataracts from two patients on P-UVA therapy were subjected to high-resolution phosphorescence spectroscopy. The lens homogenates from these two patients showed phosphorescence peaks identical (in shape and lifetime) with the previously reported 8-methoxypsoralen lens protein photoproduct seen in P-UVA-treated cataractous rat lenses. The data provide objective proof that these phototherapeutic drugs can generate specific P-UVA photoproducts in human lenses. Similar photoproducts have previously been demonstrated in experimental (rat) P-UVA cataracts.

Adult

[PUVA treatment and the problem of ocular damage (author's transl)].

Recently, psoriasis has been shown to respond favorably to PUVA treatment, i.e., local or systemic therapy with a photosensitizer (e.g., 8-methoxypsoralen) and subsequent long UV irradiation. The possibility of this treatment damaging the eye is discussed in the light of various experimental results. As toxic changes only occur when photosensitizer and UVA act jointly, the eyes of PUVA-treated patients must be shielded from any ultraviolet exposure by UV-absorbing protective glasses with side shields. Such glasses should have no significant absorption in the visible range. The new Spectra Shield process enables lenses to be coated in such a way that virtually no UV or IR radiation is transmitted.

Eye Protective Devices

Hyperthyroidism and polycythemia vera with chronic urticaria and angioedema.

Of 154 patients with chronic urticaria, six manifested concomitant hyperthyroidism and four polycythemia vera. Investigations of serum IgE, immune complex quantitation, complement and skin biopsies failed to elucidate a causal relationship. Polycythemia vera and hyperthyroidism should be considered as possible associations in the evaluation of chronic urticaria.

Angioedema

Potential ocular complications from PUVA therapy and their prevention.

During the last decade psoralens have become increasingly popular in treating psoriasis. The well-known photosensitizing action of these drugs has led to increasing concern regarding potential ocular complications, particularly in patients receiving prolonged psoralen therapy. We have demonstrated that this drug can be found in lenses of rats injected (intraperitoneally) with 4-8 mg/kg of 8-methoxypsoralen (8-MOP) and that its presence can lead to a photosensitized enhancement of lenticular fluorescence. Our experiments suggest one mechanism regarding the photosensitizing properties of 8-MOP within the ocular lens. Photo-addition products are generated with certain amino acid residues in the lens proteins which may result in the permanent retention of this compound within the ocular lens. We have recently shown that free 8-MOP can also be detected in human lenses for at least 12 hr following oral ingestion. Since the free 8-MOP tends to diffuse out of the lens during this period of time (as long as photic stimulation is prevented) it may be possible to prevent these photochemical reactions if the patient avoid exposure to ambient light for 12-24 hr immediately following ingestion of the drug. It may also be possible to protect these patients with special glasses which are capable of reflecting all UV radiation (up to 400 nm) while completely transmitting the visible radiation (400-750 nm).

Adult

Potential ocular complications of psoralen-UV-A therapy.

During the last decade, psoralens have become increasingly popular in treating psoriasis. The well known photosensitizing action of these drugs has led to concern regarding potential ocular complications, particularly in patients receiving prolonged psoralen therapy. We have demonstrated that this drug can be found in humans and rat lenses and that its presence can lead to a photosensitized enhancement of lenticular fluorescence and phosphorescence. At higher doses, cataracts will develop in experimental animals. We have demonstrated that photoaddition products are generated with certain aromatic amino acid residues in the lens proteins (particularly tryptophan) as well as with the pyrimidine bases of DNA, resulting in the permanent retention of this compound within the ocular lens. Free 8-MOP can also be detected in human lenses for at least 12 h following oral ingestion. When the lens is kept in the dark, the free 8-MOP diffuses out within 12--24 hr. Thus it is possible to prevent photochemical reactions by avoiding exposure to ambient light for 12--24 h following ingestion of the drug. Special glasses, capable of reflecting all UV radiation (up to 400 nm) while completely transmitting the visible radiation (400--750 nm), may also protect the patient.

Animals