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Biomedical subjects

E C Gomez

Publications and source records attributed to E C Gomez.

At least 19 recordsLinked to original sources

Neurotropic melanoma. A case report and review of the literature.

Neurotropic melanoma is a rare tumor with a biphasic growth pattern associated with a change in morphology from melanocytic features toward Schwann cell features. The tumor thereby develops a capacity for infiltrating nerves which may result in clinically evident cranial neuropathies, most commonly of the fifth and seventh cranial nerves. The histology of this lesion is difficult to interpret; it often erroneously appears fibrous in origin and may be considered to be benign. Despite this benign appearance histologically, the tumor behaves aggressively with multiple local recurrences and possible CNS invasion by either direct perineural growth or distant metastases. We review the literature of neurotropic melanomas and report a 46th case which describes a typical course with neural invasion. Although a rare cause of cranial neuropathies, the neurologist should consider this entity in the differential diagnosis and the history of a recurrent skin lesion of the face should be sought whenever examining such a patient.

Adult↗

Quantitative in vitro assessment of phototoxicity by a fibroblast-neutral red assay.

We have adapted the neutral red uptake assay for quantitative assessment of injury to fibroblast cultures by potential phototoxins. Tetracycline derivatives, quinolone derivatives, and chlorpromazine were used as model compounds for development of the assay. Human fibroblasts were incubated with potential phototoxins, the cell cultures irradiated with UV, and the capacity for neutral red uptake determined. Demeclocycline and doxycycline, two known photosensitizers, showed a 94% and 95% decrease of neutral red uptake, respectively, indicating photo-induced cytotoxicity. Minocycline, a non-photosensitizing tetracycline derivative, showed no decrease in uptake. Tetracycline, a weak phototoxin, showed minor (10%) decrease at equivalent concentrations (20 micrograms/ml). Microscopic observation of neutral red uptake and cell damage paralleled the spectrophotometric findings. Chlorpromazine, a non-tetracycline phototoxin, showed 91% decrease. An additional group of phototoxic drugs, quinolone antibacterials, were studied. Nalidixic acid, ofloxacin, ciprofloxacin, and norfloxacin all demonstrated phototoxicity, with nalidixic acid showing the greatest decrease in neutral red uptake. This methodology may provide a useful rapid method to quantify phototoxic potential of new drugs or suspected phototoxins.

Cells, Cultured↗

Efficacy of tolciclate solution in patients with tinea pedis.

Forty patients with tinea pedis were treated for six weeks in a double-blind study with a tolciclate or placebo solution. The tolciclate solution demonstrated moderate efficacy compared with placebo. The finding of positive KOH preparations in a significant number of tolciclate-treated patients with persistently negative cultures suggests that the vehicle used (polyethylene glycol-400) may not provide adequate penetration of this effective antifungal agent. No adverse effects were noted.

Administration, Cutaneous↗

The aging skin.

The anatomic, biochemical, and physical changes occurring in the skin with aging are reviewed and discussed. An attempt is made to distinguish between changes resulting from accumulated injury from environmental factors and the changes of aging per se.

Adolescent↗

Excess granulation tissue responses associated with isotretinoin therapy.

Multiple polypoid projections of granulation tissue developed in two patients receiving isotretinoin for acne. Histological study of the lesions revealed increased amounts of non-sulphated acid mucopolysaccharides in the ground substance of the granulation tissue stroma. Complete resolution occurred following curettage with or without chemical cautery. The role of isotretinoin in the development of these lesions is discussed.

Acne Vulgaris↗

In-vitro testosterone metabolism in the mouse preputial gland: intercellular co-operation and changes with cell maturation.

In-vitro [14C]testosterone metabolism was investigated in isolated cells of adult male mouse preputial sebaceous glands. Labelled steroids were extracted and chromatographed after a 2-h incubation, and were identified as 5 alpha-dihydrotestosterone, androstenedione, 5 alpha-androstane-3,17-dione, 5 alpha-androstane-3 alpha,17 beta-diol and 5 alpha-androstane-3 beta,17 beta-diol, androsterone and 3-epiandrosterone. In cells separated according to state of maturity (lipid content) by isopycnic centrifugation in a metrizamide gradient, maximal testosterone metabolism occurred in large, nearly mature cells. In this population, mean hydroxysteroid 5 alpha-reductase and 17 beta-hydroxysteroid dehydrogenase activities were 3.8 and 2.3 nmol/10(6) cells per 2h respectively, more than 100-fold greater than in the densest population, comprised of undifferentiated and early differentiating cells. It was also found that the profile of testosterone metabolites was dependent on the proportion of the label metabolized. The metabolite index (MI), i.e. the average number of enzymatic steps undergone per molecule of metabolite, increased with increasing substrate utilization. Metrizamide showed reversible, non-specific inhibition of testosterone metabolism and reduction of the MI. Thus, it was postulated that testosterone is metabolized sequentially by different cells, with metrizamide inhibiting cellular uptake and intercellular substrate transport. This suggested that most of the metabolites would be found in the medium, rather than in the cellular compartment. Further, in incubations run without cell disaggregation, efficient substrate cycling among cells should result in a high MI, independent of metrizamide concentration and substrate utilization. These predictions were all confirmed, providing strong evidence that testosterone metabolism is a co-operative effort among several cells in this tissue.

Animals↗

Generalized staphylococcal scalded skin syndrome in an anephric boy undergoing hemodialysis.

Generalized staphylococcal scalded skin syndrome (SSSS) is a toxin-related epidermolytic disease that predominantly affects previously healthy infants and children younger than 5 years. In contrast, the majority of the reported adult cases have been associated with underlying diseases, suggesting that immunosuppression and renal insufficiency are important predisposing conditions for this age group. We report herein a case of adult-type SSSS in an anephric 10-year-old boy. Patients undergoing hemodialysis who have chronic renal failure may be uniquely predisposed to the SSSS by virtue of their decreased glomerular filtration rate, associated uremic immunodeficiency, and a high incidence of Staphylococcus aureus bacteremia.

Animals↗

Actions of isotretinoin and etretinate on the pilosebaceous unit.

Isotretinoin administered subcutaneously to male hamsters results in marked involution of the sebaceous glands of the flank organ without discernible effort on the other androgen-dependent structures, pigmented hair follicles, and dermal melanocytes. Treatment of androgen-stimulated female hamsters with isotretinoin prevented the androgen-induced growth of the sebaceous glands but not the formation of large pigmented hairs and dermal pigment cells. Etretinate, in comparable dosage, did not show the inhibitor effect on sebaceous gland growth. The hamster flank organ seems a promising system for assessment of the sebaceous gland inhibitory activity of retinoids and may be predictive for therapeutic activity in acne.

Animals↗

Ultrasonic assessment of cutaneous atrophy caused by intradermal corticosteroids.

A noninvasive technique of pulsed ultrasound was used to determine the long-term changes in skin thickness resulting from intradermal injections of triamcinolone acetonide (TA). Injections of 0.1 ml of either saline or a suspension containing 5 mg/ml or 10 mg/ml of TA were made at selected sites on the forearms of two human volunteers. The corticosteroid-treated sites showed a maximal decrease of 30% to 40% of the original skin thickness at 4 to 8 weeks after a single injection. A transient thinning was observed at control sites injected with saline. A greater degree of thinning was seen at the site injected with 10 mg/ml of TA as compared to the site injected with 5 mg/ml of TA. The thinning at the corticosteroid injection sites persisted at least 18 weeks after the single corticosteroid injection but had approached normal thickness values by 44 weeks following treatment. Pulsed ultrasound may be useful as a noninvasive technique for monitoring the effects of intradermally injected corticosteroids on human skin thickness and may also be useful in assessing intrinsic atrophogenic potentials of different corticosteroid molecules in human skin and the duration of action of various injectable formulations of a corticosteroid.

Atrophy↗

Differential effect of 13-cis-retinoic acid and an aromatic retinoid (Ro 10-9359) on the sebaceous glands of the hamster flank organ.

The effect of subcutaneously administered 13-cis-retinoic acid and an aromatic retinoid (Ro 10-9359) on the sebaceous glands of the hamster flank organ were compared. As previously reported, 13-cis-retinoic acid caused a marked diminution of sebaceous gland size without affecting other androgen dependent structures. The aromatic retinoid derivative showed no effect upon any of the flank organ components. Studies utilizing androgen stimulated female confirmed our previous finding that 13-cis-retinoic acid prevented the growth of sebaceous glands without affecting the development of dermal pigmentation or large pigmented hair follicles. The aromatic retinoid derivative showed slight, if any, effect upon sebaceous gland size and no effect upon pigmentation or pigmented follicle development. The findings with this model system suggest that any efficacy of Ro 10-9359 in the treatment of acne would be by some mode other than the inhibition of sebum production.

Animals↗

Effect of topical diflumidone on ultraviolet-light-induced erythema.

The relative topical efficacy of indomethacin and diflumidone, a novel non-steroidal antiinflammatory drug, for the suppression of ultraviolet-light (290-320 nm region; UVB)-induced erythema has been compared in a randomized, double-blind, placebo-controlled study in man. During the early phases of erythema development (3-6 h) following the administration of 3 minimal erythema doses (MED) of UVB, a single topical application of diflumidone and of indomethacin were found to be equal in their ability to inhibit the development of erythema compared to untreated or placebo-treated sites. At 24 h after application, the indomethacin-treated sites had significantly less erythema than did the diflumidone-treated sites. Pigmentation of test sites at 5 and 14 days following irradiation was indistinguishable at the diflumidone, placebo, or untreated sites, but relatively less pigment developed at the indomethacin-treated sites.

Administration, Topical↗

Effect of 13-cis-retinoic acid on the hamster flank organ.

Administration of 13-cis-retinoic acid subcutaneously to mature male hamsters produced a marked decrease in the size of the sebaceous glands of the flank organ, without diminution of other hormonally dependent structures of the flank organs. Subcutaneous administration of 13-cis-retinoic acid to female hamsters treated simultaneously with injections of testosterone enanthate prevented the androgen-induced growth of the flank organ sebaceous glands but did not prevent the growth of other hormonally dependent structures such as the dermal pigment cells and large pigmented hair follicles. The sebaceous gland progressively decreased during 3 weeks of treatment and the effect persisted at least 3 weeks after cessation of treatment but was completely reversed by 6 mos after treatment. In vitro studies of testosterone metabolism by hamster flank organ indicated the lack of inhibition of 5 alpha-reduction by 13-cis-retinoic acid. It seems likely that systemically administered 13-cis-retinoic acid, unlike antiandrogens, exerts a specific extrahormonal effect on the sebaceous glands of the hamster flank organ without affecting other androgen dependent cells.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

Efficacy of mycophenolic acid for the treatment of psoriasis.

The efficacy of orally administered mycophenolic acid (MPA), an inhibitor of guanosine monophosphate (GMP) synthesis, for the treatment of psoriasis, was studied in a double-blind fashion. Of twenty-one patients completing the study period, ten of eleven patients treated with MPA had a greater than 25% decrease in severity score compared with only two of ten patients treated with placebo. The placebo group had a slight increase in severity score compared to almost 50% reduction in the average severity score of the MPA-treated group. After termination of the double-blind portion of the study, the placebo group was treated with MPA and showed a 60% decrease in severity score. Adverse effects encountered included anorexia, nausea, vomiting, and diarrhea. One patient had an uncomplicated episode of herpes zoster. Other than a mild decrease hemoglobin, no hematologic toxicity was noted.

Adult↗

Cutaneous involvement by IgD myeloma.

Multiple, firm, nontender, violaceous, cutaneous and subcutaneous nodules of the abdomen and thighs developed in a 53-year-old man with proven IgD myeloma. A biopsy specimen showed dermal infiltration by large atypical undifferentiated cells similar to those previously found on bone marrow aspiration. Despite intermittent improvement with radiotherapy and chemotherapy, the patient died and an autopsy showed multiple osteolytic lesions and massive involvement with tumors that encased the pelvic organs, infiltrated and replaced portions of the psoas muscles, infiltrated the kidneys and intestines, and replaced the bone marrow by small and intermediate-sized malignant lymphoid cells. IgD myeloma is a rare hematologic malignancy that occurs at a younger age than other forms of myeloma, has a high incidence of involvement of soft tissues, and is a particularly dedifferentiated and vicious form of myeloma.

Humans↗

Cutaneous beta-glucuronidase: cleavage of mycophenolic acid by preparations of mouse skin.

Mycophenolic acid, a new chemotherapeutic agent for the treatment of psoriasis, is known to be rapidly conjugated on absorption and to circulate largely in the form of its glucuronide conjugate. Since this metabolite does not readily penetrate intact cells and is cleaved by the enzyme beta-glucuronidase to yield free mycophenolic acid, the ability of preparations of mouse skin to cleave mycophenolic glucuronide was studied. The time course of mycophenolic acid liberation by such preparations and the dependence upon the amount of enzyme preparation were demonstrated. Preparations of mouse skin and mouse liver, kidney, spleen, lung, heart and small intestine were assayed for beta-glucuronidase activity using p-nitrophenyl-beta-D-glucuronide as substrate. Skin yielded preparations with higher beta-glucuronidase activity per/mg protein than any of the other organs tested. When expressed on the basis of beta-glucuronidase activity recovered per milligram of tissue DNA, skin, liver and kidney showed higher levels than the other organs tested.

Animals↗

Topical halcinonide and betamethasone valerate effects on plasma cortisol: acute and subacute usage studies.

The effect of topical application of halcinonide cream and betamethasone valerate cream on plasma cortisol was studied in an acute usage study as well as a subacute study, which more closely approximated common clinical usage. In the acute study, halcinonide cream caused a marked decrease in plasma cortisol, both with and without occlusion, in patients with extensive psoriasis, but only with occlusion in normal subjects. Betamethasone valerate cream decreased plasma cortisol levels in patients with extensive psoriasis when applied with occlusion and, to a lesser extent, without occlusion. In a double-blind subacute usage study without occlusion, two of 23 patients treated with halcinonide cream showed decreased plasma cortisol levels during the treatment period, while none of the 21 patients treated with betamethasone valerate cream showed such decreases. Three patients in the halcinonide group developed striae. Clinical response to halcinonide was superior to that with betamethasone valerate cream, but a similar number of patients were resistant to treatment with each medication.

Administration, Topical↗

Induction of glycosuria and hyperglycemia by topical corticosteroid therapy.

A patient with psoriasis is described who had an abnormal response to the glucose tolerance test without other evidence of diabetes and then developed postprandial hyperglycemia and glycosuria during a period of topical administration of a corticosteroid cream, halcinonide cream 0.1%, under occlusion. A second patient with a similar glucose tolerance test result showed postprandial hyperglycemia when treated similarly with betamethasone valerate cream 0.1%. Two additional patients with midly abnormal responses to glucose tolerance tests showed no evidence of altered glucose metabolism when treated with halcinonide cream in a similar manner.

Administration, Topical↗