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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In spite of all that has been discussed, there are no hard data documenting what influences a couple's decision to have more children after the birth of a child with a genetic disorder. It is likely that recurrence risk does not play a major role. The difference between a 25 per cent and a 50 per cent recurrence risk with each pregnancy probably does not have a great deal of personal significance. However, the burden of a disease is something to which every couple can relate. They know how the disease has affected the living situation of their family, and that is very meaningful. Because genetic counseling services are not standardized and the prediction of the outcome of these services is so difficult to quantify, third parties have not been very agreeable to pay for genetic counseling. I think it is important, however, to realize that the standardization of procedures may be less important than the emotional support given to a couple during the difficult time after they have been informed that their child has a genetic disease.
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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.
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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.
We decided to examine whether the mechanism for production of granulation tissue during moist wound healing under a vapor-permeable membrane (VPM) is related to a fibroblast growth-promoting substance in the wound fluid beneath the VPM. The experimental design utilized growth curves performed on synchronized fibroblast cultures derived from 2 normal infants. Cell counts were performed at days 1, 4, 7, and 11 (saturation density). VPM fluid (MWF, moist wound-healing fluid) from 7 different patients was used to supplement growth medium (GM) in the test growth curves. Both 2% MWF alone and 2% MWF plus 2% human serum (2 + 2) were evaluated for each patient. Control curves were conducted using GM supplemented with 2%, 4%, and 10% human serum (HS). When 2% MWF alone was added to culture medium, all cells lifted off the surface of the flask within 4-7 days. If (2 + 2) was used to supplement the medium, detachment did not occur. At days 4, 7, and 11, (2 + 2) flasks had significantly greater cell densities than did flasks supplemented with either 2% or 4% HS alone (p less than 0.001). At days 4 and 7, (2 + 2) cell counts were the same as 10% HS cell counts (p = 0.99). By day 11, (2 + 2) cell counts exceeded those of 10% HS (p less than 0.01). We conclude that the fluid that collects under the specific VPM used in this study when added to HS causes synergistic stimulation of fibroblast cell division and an altered pattern of fibroblast growth.
A patient was seen with several congenital anomalies and bilateral branchial cleft sinuses that clinically resembled inflammatory linear verrucous epidermal nevi. This unusual condition most likely represented a cutaneous reaction to residual branchial remnants and prior surgical therapy.
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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.