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Biomedical subjects

S Lerman

Publications and source records attributed to S Lerman.

At least 19 recordsLinked to original sources

In vivo MRI and fluorescence studies on the ocular lens.

During the past two decades progress in biophysical technology has made it possible to monitor aging and pre-cataractous as well as cataractous changes in the ocular lens in vivo as well as in vitro. Because they are non-invasive these techniques can be performed in vivo and utilized as screening methods to detect and predict eventual lens opacification, and they should also provide increasingly important information to help clarify the cataractogenic process. Three such biophysical approaches can now be employed in vivo; these include lens fluorescence, light scattering measurements and magnetic resonance imaging (MRI) T2 analyses (1-27). We have utilized two of these methods (fluorescence spectroscopy and MRI measurements of lens water [T2] phases) to delineate normal age-related and pre-cataractous changes in a series of human subjects and in patients with early lens opacities. The parameters employed for these studies were based on data accumulated from in vitro experiments on human lenses and in vivo and in vitro data from animal experiments (2, 6-8, 18, 19, 22, 25-27).

Adult

Assessing the biostability of intraocular lenses.

This manuscript represents an attempt to evaluate the methods used to assess the biostability of IOLs, in particular their leaching characteristics, the effects of laser pitting, their tensile strength and the effects of UV irradiation on long term implantation of IOLs. The literature relating to these topics during the last two decades has been reviewed and experimental study protocols are presented.

Animals

Ocular side effects of accutane therapy.

The recent interest in treating acne with one of the retinoid drugs has been accompanied by a wide variety of ocular side effects involving the eyelids, cornea, lens, optic nerve and retina. In one group of patients being evaluated for possible efficacy of a retinoic acid analogue in treating psoriasis, several patients complained of difficulty driving at night due to decreased dark adaptation which we were able to document. Fortunately, most of the above side effects tend to disappear within months after the drug is discontinued. However, we have recently seen two cases of dry eye syndrome associated with Accutane therapy that have persisted for more than two years. In addition, scattered reports have appeared regarding cataracts in young patients (teens to early 40's) which developed during, and/or after Accutane treatment. We have examined lens matter derived from two such patients who had extracapsular cataract extractions. Their lens proteins showed an elevation in UV absorptivity (between 330-390 nm) compared with matched control material (derived from Eye Bank specimens) and HPLC analyses demonstrated an abnormal peak in their profiles which was similar to one present in control samples incubated with retinoic acid and was not present in lens protein samples derived from cataracts not associated with Accutance therapy. These observations demonstrate that some of the Accutane induced ocular side affects are not reversible when the drug is stopped, and patients on such therapy should be carefully monitored.

Acne Vulgaris

Cutaneous and ocular ramifications of ultraviolet radiation.

In this article,the uses of photobiologic techniques such as ultraviolet B radiation and PUVA are discussed, as is a general review of their potential acute and chronic side effects. The authors then focus, in more extensive detail, on the potential acute and chronic ocular toxicity associated with these modalities.

Cataract

In vivo non-invasive studies on the human lens.

Progress in biophysical technology now permits us to monitor aging and precataractous changes in the human ocular lens in vivo as well as in vitro. We are employing two noninvasive techniques to measure changes in lens fluorescence and in one lens water compartment (T2) utilizing Scheimpflug lens fluorescence densitography and magnetic resonance imaging. These studies demonstrate age-related changes in the normal lens as reflected by enhanced fluorescence and longer T2 values. Precataractous changes can also be detected with this approach.

Adult

Phototoxicity involving the ocular lens: in vivo and in vitro studies.

Our laboratory has demonstrated the cataractogenic potential of UV radiation and several photosensitizing drugs in laboratory animals and in humans. We have utilized lens fluorescence measurements (which we have demonstrated to be a reliable marker for pre-cataractous and early cataractous changes), NMR pulse relaxation techniques, and our recently developed magnetic resonance imaging method to measure lens T2 values in the normal and UV exposed Degus lens (in vivo and in vitro) to detect pre-cataractous changes in the lens. These approaches will permit us to employ two parameters (increased non-tryptophan fluorescence and a decrease in T2 values) to monitor for such changes months before the lens opacities become manifest by conventional slit lamp examinations.

Animals

Fluorescence polarization and circular dichroism studies on aging human lens proteins.

The tryptophan residues within the alpha, beta and gamma crystallins (derived from normal human lenses ranging in age from the 1st through the 7th decade) were examined by fluorescence polarization (FP) and near UV circular dichroism (CD) techniques. These experiments demonstrate an age-related difference mainly in the gamma crystallin fraction in which the polarization and CD data demonstrate changes in the old gamma (7th decade) compared with the young gamma fraction (1st-3rd decade). Young gamma has the highest stability and is one of the most compact of the lens crystallins, as reflected by the FP and CD studies, and these parameters decrease significantly in the old gamma fraction. The loss of one of the gamma fractions as the lens ages may also be correlated with these age-related changes. There were no significant aging changes in the beta crystallins, while the alpha crystallins demonstrated a moderate FP change with age.

Adolescent

Reversible lactose malabsorption and intolerance in Graves' disease.

Ten patients with untreated Graves' disease underwent tests to determine lactose absorption, liquid gastric emptying, and oral cecal transit time. To determine the influence of thyroid hormone status on lactose absorption, eight of these same patients had repeat studies when rendered euthyroid. Two of these eight patients also underwent studies while transiently hypothyroid. Motility studies were also evaluated in a group of 11 control subjects. Lactose malabsorption occurred in nine patients with Graves' disease. In seven patients who repeated these studies, lactose malabsorption normalized in three, symptoms induced by lactose improved in two and were unchanged in two. However, these latter two patients appeared to have improved symptoms in the transient hypothyroid state. Liquid gastric emptying was significantly faster in untreated patients than controls and treated self-same patients. Transit time was significantly faster in untreated patients than when they were rendered euthyroid. There may be a relationship between altered lactose absorption states and changes in intestinal motility in patients with Graves' disease.

Adult

NMR & fluorescence studies on human and animal lenses.

Our laboratory has demonstrated the potential of non-invasive biophysical methods in studying cataractogenesis. Initially these studies involved in vitro spectroscopic assays (UV, fluorescence and phosphorescence) on excised lenses or lens matter. In addition, we performed NMR pulse relaxation studies on extracted lenses which demonstrated an age-related increase in the T1 and T2 values of the normal lens. The in vitro fluorescence and NMR data suggested potential parameters for monitoring human and animal lenses in vivo. We then developed in vivo lens fluorescence densitography utilizing the Scheimpflug camera and have recently employed our Magnetic Resonance Imaging (MRI) method (using specially constructed small coils) to measure the moderately bound lens water compartment (T2) in vivo. Both of these in vivo methods correlate with our in vitro data and they demonstrate age-related changes in the normal lens; - i.e. - a progressive increase in fluorescence intensity and longer T2 values. Indices have been developed which permit us to detect abnormal lens fluorescence and changes in the moderately bound lens water (T2) compared with normal values for each specific age group by decade. These 2 non-invasive biophysical techniques can detect pre-cataractous changes in the living clear lens, months to years before any type of opacity becomes manifest with the conventional slit lamp method. The MRI technique can be performed in less than 20 minutes and the lens fluorescence method requires 4-6 minutes; thus they provide a rapid and objective in vivo measure of the status of the living lens as well as a method for evaluating anti-cataract drug efficacy.

Adolescent

Parathyroid cyst: diagnosis and treatment of an unusual surgical problem.

A case of parathyroid cyst is reported in which the diagnosis was suggested when watery, clear fluid was aspirated from a mass found in the anterior region of the neck of a 34-year-old woman on routine medical examination. The diagnosis was confirmed by measurement of the parathormone content in the cyst fluid and by histologic examination of the cyst wall. Although rare, parathyroid cyst should be considered in the differential diagnosis of cysts in the anterior compartment of the neck. Surgery has been the usual treatment of such cysts, but several reports have been published in which repeated aspiration resulted in the disappearance of the cyst. If conservative treatment of a parathyroid cyst is unsuccessful, the cyst should be removed surgically.

Adult

Biophysical methods to monitor lens aging and pre-cataractous changes in vivo.

When monitoring for drug induced lenticular side effects and/or anti-cataract drug efficacy, it would be advantageous to detect such effects prior to the onset of a cataract. Our MRI technique can detect precataractous changes in the lens water compartments (T2 values) months to years before opacities become manifest. The in vivo human and animal studies correlate well with in vitro NMR pulse relaxation data on such lenses. The MRI technique requires 2-4 minutes per eye and provides excellent pictures of the globe as well as T2 values. These data correlate well with our in vivo lens fluorescence technique thereby providing two parameters capable of evaluating potential drug induced changes in the lens well before the cataract becomes manifest.

Adult

NMR pulse relaxation studies on the normal aging and cataractous lens.

Proton NMR pulse relaxation experiments have been performed in this and other laboratories mainly on animal lenses and some human lenses. In order to evaluate T1 and T2 analyses as a potentially useful (non-invasive) parameter in delineating lenticular changes in normal aging human rabbit lenses, and in human cataracts, we performed a series of pulse relaxation studies on human eye bank lenses 10 to 93 yr of age, on fresh intact human cataracts and on normal rabbit lenses. Additional spectroscopic studies (fluorescence and 31P-NMR) were also performed on the lenses in order to correlate these parameters with the data relating to 'water phases' in the lens. These experiments demonstrate a potential additional parameter for evaluating 'molecular' changes in the aging and cataractous lens.

Adolescent

Photographic and spectroscopic correlations of human cataracts.

Intracapsular cataracts obtained within 3 h after surgical extraction were photographed with the CCRG technique and immediately subjected to fluorescence spectroscopy followed by 31P- and 13C-nuclear magnetic resonance (NMR) spectroscopy. Fluorescence spectroscopy demonstrates an excellent correlation between nontryptophan fluorescence intensities and lens color. An interesting correlation was also observed between the degree of light scatter as determined by the 290-nm excitation peak for intrinsic lens tryptophan fluorescence and the CCRG (photographic) appearance of these cataractous lenses. Based on 100 cataracts analyzed, there is a strong correlation between this kind of light scattering measurement and the type and degree of lens opacification. A similar correlation is evident with the 31P-NMR organophosphate profiles in the lenses in which the sugar phosphate levels are elevated only in diabetic patients with cataracts ('diabetic cataracts'). Aside from fluorescence and 31P-NMR spectroscopy, selected lenses were also incubated with 5.5 nM 13C-glucose as soon as they were obtained, and the foregoing spectroscopy was performed, followed by 13C-NMR analyses to detect and monitor for sorbitol accumulation in young versus old normal lenses and in diabetic cataracts. These studies clearly demonstrate a direct correlation between nontryptophan-fluorescent chromophore levels, light scattering (determined by tryptophan excitation peaks), lens age and cataract type. In addition, the organophosphate profiles clearly delineate the diabetic cataracts, and the 13C-NMR spectra correlate well with the age-related decrease in aldose reductase activity.

Aged