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Biomedical subjects

L Edwards

Publications and source records attributed to L Edwards.

At least 37 records · Page 2Linked to original sources

The effect of an intralesional sustained-release formulation of interferon alfa-2b on basal cell carcinomas.

Intralesional interferon alfa-2b has been proven effective in the treatment of basal cell carcinomas. Because nine injections over a 3-week period have been necessary to produce clinically significant cure rates, a sustained-release protamine zinc chelate interferon formulation has been developed. In this study, 65 basal cell carcinomas were treated in one of two dosing schedules with intralesional sustained release interferon alfa-2b (10 million IU per injection). Thirty-three patients received a single injection and 32 patients received one injection per week for 3 weeks. At study week 16, 80% of evaluable tumors treated with three injections and 52% treated with one injection were cured histologically. Two patients discontinued injections because of side effects. A sustained-release protamine zinc preparation of interferon alfa-2b shows promise as a practical, effective, and cosmetically elegant treatment for basal cell carcinoma.

Adult

Effect of oral isotretinoin on dysplastic nevi.

We previously reported a favorable histologic response of dysplastic nevi to topical tretinoin in three patients. To investigate the anticancer and cancer preventive effects of retinoids we have examined the effect of systemic isotretinoin on dysplastic nevi. After confirmatory baseline biopsies, eleven patients with the dysplastic nevus syndrome were treated with oral isotretinoin, 40 mg twice a day for 4 months. At completion of therapy, at least three previously identified and photographed clinically typical dysplastic nevi were rephotographed and removed for histologic evaluation. Eight patients completed the full course of medication. There were no clinical changes in the dysplastic nevi in these patients. Posttherapy biopsy specimens in six volunteers revealed most of the remaining lesions to be dysplastic nevi. The majority of lesions biopsied in two subjects showed normal, benign nevi only. This proportion of clinically typical dysplastic nevi that prove to be normal nevi histologically (28%) is not significantly different from that reported by others. Oral isotretinoin does not appear to have a significant biologic effect on the clinical or histologic appearance of dysplastic nevi in the treatment schedule employed.

Administration, Oral

Vulvar lichen planus.

The clinical presentation of lichen planus of the vulva spans a spectrum from subtle, fine, reticulate papules to severe erosive disease accompanied by scarring and loss of the normal vulvar architecture. The end result may mimic other diseases. Because cutaneous lichen planus is usually absent and oral disease may be asymptomatic, the diagnosis can be easily missed unless the clinician has a high index of suspicion. Although treatment for vulvar lichen planus is suboptimal, a correct diagnosis may end the patient's search for an answer and help to prevent unnecessary procedures and therapies.

Adult

How would you like to have an orchidectomy for advanced prostatic cancer?

One hundred thirteen patients were randomized for the study. There was no significant difference between the groups for response or survival. The incidence of side effects related to the reduction of testosterone was similar in both groups. Disease "flare" was seen in three patients treated with long-acting D-Trp-6 LH-RH. All symptoms resolved by the end of 8 weeks. There was less psychological morbidity in the D-Trp-6 LH-RH group but the difference did not reach statistical significance. Our results indicate that long-acting D-Trp-6 LH-RH offers a safe and effective alternative to surgical orchidectomy.

Antineoplastic Agents

168 double J (pigtail) ureteric catheter insertions: a retrospective review.

The medical records of 116 patients who had 168 ureteric double J (pigtail) catheters inserted over a 6-year period between 1981 and 1987 were reviewed. Eighty-five patients had pigtails inserted for benign conditions and 31 for malignant disease. The pigtail catheters were inserted cystoscopically in 88 patients, percutaneously in 7 patients and by open surgery in 21 patients. Of 168 pigtail catheters used, 147 were soft (silicone, multilength) and 21 hard (polyurethane). No mortality was attributable to the use of these catheters but certain complications were commonly encountered. Loin discomfort occurred after 32 (19%) insertions; 27 of 147 (18%) soft catheters and 5 of 21 (24%) hard catheters. Trigonal irritation, confirmed cystoscopically was reported in 26 of 147 (18%) insertions of soft catheters and in 6 of the 21 (29%) with hard catheters (chi 2, P = 0.37). Urinary tract infection (confirmed by urine microscopy and culture) occurred after 46 (31%) soft catheter insertions and after 13 of 21 (61%) hard catheter insertions (chi 2 test, P = 0.01). Stent migration occurred in five patients and obstruction in two. Pigtail catheters are safe ureteric stents which are easy to insert and their use is supported by this study. The complications of associated infection, trigonal irritation and loin discomfort are relatively common and still occur even with soft catheters. Careful monitoring of all patients with pigtail catheters in position is recommended.

Adult

Pharmacokinetics and metabolism of retinol administered at a chemopreventive level to normal subjects.

Thirteen subjects between the ages of 50 years and 70 years were administered a daily 25,000 IU dose of retinol for 9 months. Two subjects experienced mild skin dryness, headaches, and/or alopecia. There were no significant changes in serum chemistries. High performance liquid chromatography assays for plasma retinol revealed no evidence of drug accumulation; however, there was a significant increase in the plasma concentration-versus-time curve for retinyl palmitate concentrations between the first and subsequent sampling days (P = 0.009). The mean skin retinol and retinyl palmitate concentrations in 7 retinol-treated subjects (131.7 and 15.9 ng/g, respectively) were not significantly different from those observed in 13 age-matched controls (118.9 and 25.5 ng/gm, respectively).

Adipose Tissue

Desquamative vaginitis: lichen planus in disguise.

A principal cause of desquamative vaginitis is erosive lichen planus. We report five cases to illustrate the classic oral and vaginal findings, describe the histology, and relate the therapeutic response of the disease. Early recognition of the disorder and prompt use of corticosteroids and vaginal dilators may prevent the common sequelae of adhesion formation and vaginal stenosis.

Administration, Topical

Competition of milrinone, a non-iodinated cardiac inotropic agent, with thyroid hormone for binding sites on human serum prealbumin (TBPA).

Milrinone [2-methyl-5-cyano-(3,4'-bipyridin)-6(1H)-one] is a positive cardiac inotropic agent recently shown to have thyromimetic activity in vitro in a rabbit myocardial membrane Ca2+-ATPase system [K. M. Mylotte et al., Proc. natn. Acad. Sci. U.S.A. 82, 7974 (1985)]. In the present studies, milrinone was examined for activity as an inhibitor of iodothyronine binding by human serum thyroid hormone transport proteins, thyroxine-binding globulin (TBG), prealbumin (TBPA) and albumin. Polyacrylamide gel electrophoresis at pH 9.0 of sera equilibrated with [125I]thyroxine showed that milrinone competed with L-thyroxine (T4) for binding sites on TBPA (10 and 100 microM milrinone caused 61 and 73% reductions, respectively, in T4 binding to TBPA, P less than 0.01); T4 displaced from TBPA was bound by TBG and albumin. Comparable reductions in T4 binding to TBPA were observed in electrophoretic studies conducted at pH 7.4. Binding of triiodo-L-thyronine (T3) to TBPA was electrophoretically confirmed and shown to be decreased in the presence of milrinone. Electrophoresis of purified TBPA also demonstrated that [14C]milrinone co-migrated with this transport protein and that milrinone displaced tracer T4 from TBPA. Amrinone, the 2-H-5-NH2 analog of milrinone, had less than 5% of the activity of milrinone as an inhibitor of T4 binding in electrophoretic studies. Scatchard analysis of T4 and milrinone binding to purified TBPA, measured by equilibrium dialysis, showed two classes of binding sites, with association constants, respectively, of 6.1 X 10(7) M-1 and 1.6 X 10(6) M-1 for T4, and 1.7 X 10(6) M-1 and 8.9 X 10(2) M-1 for milrinone. Computer graphic modeling of the binding of milrinone to the T4 site in the crystal structure of TBPA showed that milrinone best occupied this site when the substituted bipyridine ring overlapped the phenolic ring of T4. In this orientation the 5-cyano group, which has an electronegativity similar to that of iodine, occupied the same volume as the 5'-iodine of T4. The 5-amino group of amrinone lacks these characteristics. In this orientation, the keto function of milrinone overlapped the T4 4'-hydroxyl and could participate in similar intermolecular interactions. Thus, milrinone, a non-iodinated bipyridine, and thyroid hormone share structural and biochemical homologies and compete for the same binding site on TBPA.

Amrinone

Scalp distribution of visual evoked potentials to foveal pattern and luminance stimuli.

Scalp potentials elicited by pattern reversal, pattern onset, and flash stimulation have been studied in normal subjects by means of a 16-channel brain mapping system. In two groups of experiments the topography of the major positive component in each response was compared with 4 degrees full- and lateral half-field stimuli and, for more detailed exploration of the pattern components by M-scaled stimuli selected to activate 1 cm2-patches of striate cortex and associated extrastriate re-projections. The 4 degrees stimuli were found to elicit scalp distributions for the pattern reversal P100 and the pattern onset C1 consistent with striate and extrastriate visual cortical origins respectively. Data on the flash P2 component suggest that stimulation was not localized accurately; this may have been due to lateral spread of neural activity in the retina. Predictably, the M-scaled stimuli showed extensive inter- and intraindividual variations depending on stimulus type and location relative to fixation. The manner in which, in some subjects, the region of maximal activity on the map appears to migrate with change of stimulus position possibly reflects local retinotopic order in visual evoked potential generator areas. However, data are neither extensive nor detailed enough to be conclusive.

Adult

Orchiectomy versus long-acting D-Trp-6-LHRH in advanced prostatic cancer.

One hundred and four patients were randomised for the study. Fifty-five were entered into the D-Trp-6-LHRH group and 49 into the orchiectomy group. All pre-treatment patient characteristics were similar and testosterone levels at 1 month or later were in the castrate range in both groups. Forty-six patients (83%) in the D-Trp-6-LHRH group and 40 (82%) in the orchiectomy group had a partial remission or stable disease at 3 months or later. There was no significant difference between the groups for response or survival. Three patients in the D-Trp-6-LHRH group had a disease "flare" in the first 10 days of treatment. The flare symptoms resolved by the end of 4 to 8 weeks. The incidence of flushing, decreased libido and impotence was similar in both groups. Although there was less psychological morbidity in the D-Trp-6-LHRH group the difference did not reach statistical significance. Our results indicate that long-acting D-Trp-6-LHRH offers a safe and highly effective alternative to orchiectomy.

Clinical Trials as Topic

Donor age-dependent decline in response of human red cell Ca2+-ATPase activity to thyroid hormone in vitro.

The effect of increasing donor age on the susceptibility of human red blood cell Ca2+-ATPase activity to stimulation in vitro by thyroid hormone was studied in 26 normal subjects, aged 15-81 yr. Basal enzyme activity (no added thyroid hormone) was unaffected by donor age. Group analysis, young (less than or equal to 50 yr) vs. elderly (greater than 60 yr old), revealed a 23% decrease in responsiveness of the enzyme to L-T4 (P less than 0.001). Regression analysis confirmed an age-dependent decline in thyroid hormone stimulability of Ca2+-ATPase [r = -0.42 (T4 effect) and -0.38 (T3 effect); P less than 0.01]. Red cell membrane Na,K-ATPase activity was not affected by donor age. Plasma T4 and T3 concentrations in these normal subjects also did not change with age. Possible contributions of the following mechanisms to this age-correlated change in enzyme activity were examined: altered responsiveness to calmodulin of membrane Ca2+-ATPase; membrane content of endogenous calmodulin, endogenous plasma T4 and T3 concentrations, and plasma glucose concentrations. Calmodulin responsiveness is required for iodothyronine action on the enzyme, but the calmodulin responsiveness of cells from elderly donors was not significantly different from that of cells from younger donors (P greater than 0.10). There was no relationship between membrane immunoassayable calmodulin and donor age or membrane calmodulin and Ca2+-ATPase activity. There were positive correlations between donor plasma T4 level and basal enzyme activity (P less than 0.05) and between donor plasma T3 concentration and hormone-responsive Ca2+-ATPase (P less than 0.01), but these did not contribute to the age effect. Plasma glucose previously was found to modulate red cell Ca2+-ATPase activity, but did not correlate with decreased hormone responsiveness of the enzyme in elderly donors. In conclusion, we found that the susceptibility of human red cell Ca2+-ATPase to in vitro thyroid hormone stimulation declined significantly with advancing donor age. Several possible calmodulin-dependent mechanisms for this age-dependent change were excluded, and thus, we postulate that the altered hormone sensitivity of the enzyme is membrane phospholipid mediated.

Adolescent

Complementary components and local variations of the pattern electroretinogram.

Pattern electroretinograms have been presumed to arise from a combination of luminance and pattern detection activities. Since the responses at low spatial frequencies are linearly related to contrast and contain negligible pattern specific components, it is proposed that a retinal illuminance response for higher spatial frequencies can be computed from the optical transfer function of the eye. These computed responses are subtracted from pattern electroretinograms to reveal a pattern-specific response with a marked bandpass characteristic. The peak spatial frequency of the bandpass curve declines with increasing peripheral angle. For central vision, the peak amplitude of the pattern-specific response is larger than the retinal illuminance response, but, in the peripheral retina, the two responses are found to be almost equal. The possible origins of these signals are discussed, and it is concluded that the technique provides a method of obtaining separated illuminance and pattern responses from retinal regions having different properties of spatial selectivity.

Electroretinography