Biomedical subjects
Publications and source records attributed to J C Alper.
We describe a patient with Sezary syndrome and seronegative symmetric polyarthritis. Detailed analysis of the synovial membrane, including T lymphocyte subset delineation, demonstrated that malignant synovial infiltration was the direct cause of arthritis in this patient.
Previous studies have suggested oral 5-fluorouracil (5-FU) is unpredictably and erratically absorbed. We studied oral pharmacokinetics of 5-FU in 16 patients (aged 34-71 years) with severe recalcitrant psoriasis. Each patient received repeated single oral doses of 5-FU, each separated by 1 week. Doses were ascending (300, 600, 900, 1,200 mg/m2), and after the first 3 patients, doses were started at 600 mg/m2 and increased. Multiple blood samples were obtained after each 5-FU dose and plasma 5-FU concentration determined by HPLC. Response was determined by clinical assessment of skin thickening, redness, and scaling on upper and lower body and quantified as percent improvement. Among all patients total dose and total area under the plasma 5-FU concentration-time curve (AUC) was significantly related (r = 0.65; p less than 0.01). In contrast no relationship between either total 5-FU dose and response (r = -0.07) or AUC and response (r = -0.08) was identified. With each individual patient, total 5-FU dose and response were well correlated in 11 of 14 patients (r = 0.96, 0.92, 0.92, 0.97, 0.78, 0.85, 0.71, 0.89, 0.96, 0.76, 0.94) and less well related in 3 of 14 (r = 0.57, 0.51, 0.15). Similarly, cumulative 5-FU AUC and response were well correlated in 11 of 14 patients (r = 0.91, 0.84, 0.83, 0.91, 0.77, 0.86, 0.75, 0.93, 0.99, 0.74, 0.89) and less well related in the same 3 patients (r = 0.61, 0.40, 0.03). The relationship of the 5-FU dose and AUC was nonlinear with normalized dose: AUC 1.0 at the lowest dose for each patient, at 1.5 dose AUC was 3.4 times baseline, at 2.0 dose AUC was 5.3 times baseline, and at 3.0 dose AUC was 36 times baseline. In patients with recalcitrant psoriasis 5-FU is consistently absorbed into the systemic circulation with extent of absorption increased with increasing dose in a nonlinear manner. Evaluation of both total 5-FU dose and total 5-FU AUC indicates a clear within-patient dose and AUC:response relationship.
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This article presents a detailed discussion of six genetic disorders with major cutaneous manifestations that might commonly be seen by the dermatologist or pediatrician. These include neurofibromatosis, tuberous sclerosis, xeroderma pigmentosum, incontinentia pigmenti, incontinentia pigmenti achromians, and Down's syndrome. The appearance of each disease at birth is described, and all manifestations of each entity are discussed in detail. Disorders with different inheritance patterns were chosen so that important genetic principles could be elucidated. The article concludes with a general discussion of genetic counseling, which draws upon the six genetic diseases for specific examples of important concepts.
In an effort to improve clinical response and reduce systemic toxicity, nine patients with recalcitrant psoriasis were treated with rational combinations of chemotherapeutic agents. Five patients received methotrexate by injection, 7.5 or 10 mg, followed 1 hour later by intravenous 5-fluorouracil, 170 to 562 mg/m2, on a weekly schedule. Four patients received oral triacetyl-azauridine, 2 to 4 gm daily, in combination with intravenous 5-fluorouracil, 225 to 600 mg/m2, administered every week. Three patients experienced greater than 75% clearing of disease, five patients experienced greater than 50% clearing, and only one patient failed to respond. Response rates did not differ between the two treatment groups. Adverse effects of these therapies were mild and infrequent. We conclude that 5-fluorouracil in combination with either methotrexate or triacetyl-azauridine is a relatively safe and effective alternative for the therapy of patients with severe psoriasis.
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Metabolic pathways and toxic effects of long-term selenium exposure in animal models and humans have both similarities and significant differences. In animal models the target organ is the liver, in which chronic cirrhosis develops. In man the target organ appears to be the lung, which manifests acute "rose cold," or, as in our patient, a chronic granulomatous hypersensitivity. Our data indicate not only a different target organ than would have been predicted from animal models, but also a difference in the distribution of selenium in human tissues. Long-term use of selenium favors production of dimethylselenide, which is excreted by the lungs and should be considered a pulmonary toxin. The ramifications of these findings may require a change in the monitoring techniques of long-term industrial exposure and mandate a close follow-up of selenium as a health fad.
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Two patients had an unusual ichthyosiform dermatosis, neurosensory deafness, and vascularizing keratitis. There was no family history of the disorder and no consanguinity. A squamous cell carcinoma of the tongue developed in one child. The association of such an eruption and deafness in previously reported cases is reviewed.
A patient with a congenital claw-like lesion of the finger was studied to determine the nature of the tissue. A variety of biochemical techniques and histological examinations indicated that the lesion was an example of rudimentary polydactyly covered with stratum corneum rather than an accessory nail.