Biomedical subjects
Publications and source records attributed to J S Dover.
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Graft-vs-host disease can develop in immunosuppressed individuals who receive blood-product transfusions that contain immunocompetent lymphocytes. We report two cases of fatal transfusion-associated graft-vs-host disease that developed in patients with Hodgkin's disease who were undergoing therapy. We review all cases of this entity in patients with malignancies, represented predominantly by patients with hematologic malignancies. The groups at risk for development of transfusion-associated graft-vs-host disease, the clinical presentation and course, and methods of diagnosis are summarized. Prevention of this highly fatal condition is possible by irradiation of blood products given to patients at risk, but problems remain in determining the groups that warrant such measures. Dermatologists need to have heightened awareness of this entity to facilitate more complete diagnosis and allow establishment of effective standards of care.
Tattoo treatment with Q-switched ruby laser pulses (694 nm, 40 to 80 nanoseconds) was studied by clinical assessment and light and electron microscopy. Fifty-seven blue-black tattoos or portions thereof (35 amateur and 22 professional) were irradiated with 1.5 to 8.0 J/cm2 at a mean interval of 3 weeks. Substantial lightening or total clearing occurred in 18 (78%) of 23 amateur tattoos and 3 (23%) of 13 professional tattoos in which the protocol was completed. Response was related to exposure dose. Scarring occurred in one case, and persistent confettilike hypopigmentation was frequent. Optimal fluence was 4 to 8 J/cm2. Clinicohistologic correlation was poor. Q-switched ruby laser pulses can provide an effective treatment for tattoos.
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We examined 20 punch biopsies taken from five patients at varying intervals following CO2 laser-induced thermal injury. The regenerating epidermis was studied with monoclonal antibodies AE1 and AE3 (directed against low and high molecular weight keratins), and involucrin, a protein found within the cellular envelope of the most mature keratinocytes. Twenty-four hours following thermal damage, there was extensive spillage of keratins and involucrin into the papillary dermis and disarray of all constituents of the necrotic keratinocytes. Early ingrowth of basaloid keratinocytes weakly expressed AE1. By 1 week, keratinocytes expressed AE1 in varying intensities throughout the epidermis. AE3 was present in its normal distribution, staining all but the most basaloid keratinocytes. Involucrin stained cells deep within the epidermis. Six weeks following the initial injury, the staining pattern within the epidermis had returned to normal. Thus, it appears that the regenerating epidermis produces low molecular weight keratins in cells at all levels and forms premature cellular envelopes, perhaps as a protective measure, before expression of these constituents reverts to the normal pattern. These findings suggest that keratinocyte differentiation in wound-healing following laser-induced thermal injury is similar to that seen in other types of injury. Observed clinical differences may be attributable to differences in keratinocyte proliferative or migratory capabilities.
The skin of black and albino guinea pigs was irradiated with single, 750 nsec-long laser pulses at 435, 488, 530, and 560 nm in order to determine an action spectrum for the gross threshold response of immediate epidermal whitening. In addition, the immediate and delayed gross and histologic changes induced at, above, and below the threshold radiant exposures at all four wavelengths were studied. The action spectrum in the black guinea pigs was consistent with the reported absorption spectrum of DOPA-melanin. Histologically, there was epidermal damage immediately after radiant exposures at and above threshold at all four wavelengths. In addition, radiant exposures greater than threshold caused an immediate decrease in stainable epidermal pigment that was most marked at 435 and 488 nm. The healing response was also wavelength- and dose-dependent. Seven days after above-threshold exposures, there was little epidermal pigment in the 435 nm specimens. As wavelength increased, there was progressively more pigment, and in the 560 nm specimens, the epidermal pigment was equivalent to that seen in nonirradiated black guinea pig control specimens. Seven days after subthreshold radiant exposures, there was increased epidermal pigmentation and melanocytes at all four wavelengths. This was the most pronounced in the 435 nm specimens. There was no observable epidermal damage in albino guinea pig skin.
The adverse effects and therapeutic benefits of heat, specifically infrared radiation, on skin have received little attention. In this review we discuss the evidence indicating that heat and infrared radiation are not totally harmless, but that they may be involved in both photoaging and photocarcinogenesis. We also review the clinical syndrome thought to be caused by infrared radiation and the therapeutic uses of both local heat and infrared radiation.
A prospective, randomized, double-blind, placebo-controlled trial was performed to assess the effect of a potent topical corticosteroid cream used in conjunction with ultraviolet B (UVB) phototherapy on psoriasis with respect to time to clearing and duration of remission after clearing. Of the 53 outpatients who received suberythemogenic UVB phototherapy three times per week, 24 applied the topical corticosteroid and 29 applied the placebo cream twice daily until clearing was achieved. Nine patients in each group failed to comply with the protocol. Although there was a trend toward a slightly more rapid response in the topical corticosteroid-treated group, there was no significant difference in patients' early response to therapy, number of treatments, and UVB dose required to achieve clearing. Patients in the topical corticosteroid-treated group remained in remission longer than did patients in the control group (183 vs 116 days). Life-table analysis predicts that 62% of emollient-treated patients flare within 6 months of clearing compared with only 42% of topical corticosteroid-treated patients (p less than 0.1). For most patients with psoriasis who receive UVB therapy in an outpatient setting, the use of potent topical corticosteroids appears to produce, at most, a modest beneficial effect.
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Exposure of skin to nanosecond-domain laser pulses affects the pigmentary system by a process called selective photothermolysis, in which melanosomes and pigmented cells are preferentially altered. Due to the broad absorption spectrum of melanin, this effect may occur with wavelengths that penetrate to vastly different depths within tissue, potentially producing different biologic responses. The effects of single near-ultraviolet (355 nm), visible (532 nm), and near infrared (1064 nm) pulses of 10-12 nsec duration were determined in guinea pig skin using gross, histologic, and electron microscopic observations. Threshold response in pigmented skin was a transient immediate ash-white discoloration, requiring 0.11, 0.20, and 1.0 J/cm2, at 355, 532, and 1064 nm, respectively. At each wavelength, melanosomes were ruptured within keratinocytes and melanocytes, with cytoplasmic and nuclear alterations. Delayed epidermal depigmentation occurred, followed by gradual repigmentation. Deep follicular cells were altered only at 532 and 1064 nm, which produced permanent leukotrichia. The action spectrum for threshold response was consistent with mechanisms implied by selective photothermolysis. These data may be useful for consideration of treatment for cutaneous pigmentation abnormalities or unwanted follicular pigmentation, or both.
Serum albumin is one of the most common parameters used in evaluating nutritional status. Three of the popular methods available for measuring serum albumin are serum protein electrophoresis and the two dye binding methods: BCG and BCP. BCG is currently the most popular method because of its simplicity, rapidity, and cost. Although electrophoretic methods are considered more accurate, BCP has shown to correlate well with electrophoresis in most cases. BCG often overestimates serum albumin levels, although its specificity can be improved by minimizing contact time with the serum sample. The average difference between BCG methods and other methods is usually 0.5-0.6 g/dL. From a quantitative standpoint, some might consider the difference in specificity of BCG versus the other two methods to be insignificant; however, from a qualitative standpoint, the difference could easily alter the interpretation of nutritional assessment parameters. Because of differences in analytical methods, serum albumin measurements should be interpreted in the context of the assay being used and the accepted normal range for that laboratory. Likewise, published studies, especially those that stratify degrees of malnutrition and/or risk of complications based on specific serum albumin levels, should specify the assay methodology utilized.
Q-switched ruby laser pulses cause selective damage to cutaneous pigmented cells. Repair of this selective damage has not been well described. Therefore, using epilated pigmented and albino guinea pig skin, we studied the acute injury and tissue repair caused by 40-ns, Q-switched ruby laser pulses. Gross observation and light and electron microscopy were performed. No specific changes were evident in the albino guinea pigs. In pigmented animals, with radiant exposures of 0.4 J/cm2 or greater, white spots confined to the 2.5-mm exposure sites developed immediately and faded over 20 minutes. Delayed depigmentation occurred at seven to ten days, followed by full repigmentation by four to eight weeks. Regrowing hairs in sites irradiated at and above 0.4 J/cm2 remained white for at least four months. Histologically, vacuolation of pigment-laden cells was seen immediately in the epidermis and the follicular epithelium at exposures of 0.3 J/cm2 and greater. Melanosomal disruption was seen immediately by electron microscopy at and above 0.3 J/cm2. Over the next seven days, epidermal necrosis was followed by regeneration of a depigmented epidermis. By four months, melanosomes and melanin pigmentation had returned; however, hair follicles remained depigmented and devoid of melanocytes. This study demonstrates that selective melanosomal disruption caused by Q-switched ruby laser pulses leads to transient cutaneous depigmentation and persistent follicular depigmentation. Potential exists for selective treatment of pigmented epidermal and dermal lesions with this modality.
Reed et al described the clinical and light-microscopic findings of palisaded encapsulated neuromas in 1972, but few cases have been reported since. We have studied 81 consecutive tumors. Clinically, these were solitary, asymptomatic, 2- to 6-mm, flesh-colored papules, usually located on the face of middle-aged patients. The correct diagnosis was rarely made; the lesion was most often mistaken for a basal cell epithelioma, melanocytic nevus, or other benign tumor. Light microscopy revealed single or multiple encapsulated dermal lobules composed of interlacing Schwann cells. Variable numbers of fine axons and myelin sheath remnants were present. Palisading of nuclei was not a prominent feature. Electron microscopy demonstrated substantial numbers of class C fibers (mostly nonmyelinated) only partially enveloped by Schwann cell cytoplasm. Pathologically, palisaded encapsulated neuromas are distinctive true neuromas resembling those seen in the multiple mucosal neuroma syndrome. Electron-microscopic findings are similar to those seen in peripheral nerve regeneration, suggesting that palisaded encapsulated neuromas may be traumatic in origin, and could represent regeneration following local minor injury to the skin.
We studied 44 patients with delayed pressure urticaria. The mean age at onset of the disease was 33 years (range, 5 to 63 years) and the mean duration of disease was 9 years (range, 1 to 40 years). After pressure stimulus, the mean onset of whealing occurred in 3 1/2 hours, the mean peak swelling occurred after 10 hours, and the mean lesion duration was 36 hours. Two thirds of patients had generalized flulike symptoms. Sixty percent had disabling nonremitting delayed pressure urticaria. Sixty-two percent had coexistent chronic idiopathic urticaria, and 27% had angioedema. Delayed pressure urticaria was confirmed by pressure tests with either a calibrated dermographometer or suspended weights. More than 50% of patients tested also had delayed dermographism. A double-blind, controlled, crossover trial of indomethacin therapy in 14 patients revealed no significant subjective improvement or reduction in area of induced wheals. We conclude: (1) The diagnosis of delayed pressure urticaria can be easily made by dermographometer testing. (2) Delayed dermographism may be the same entity as delayed pressure urticaria induced by a different method of pressure application. (3) Systemic corticosteroids remain the only known effective treatment for disabling delayed pressure urticaria.
We describe seven patients, four female and three male, who developed intense pruritus on sun-exposed skin without visible change. The clinical features resembled those of polymorphic light eruption (PLE) without rash. Four patients also occasionally developed typical PLE upon sun exposure, but sun-induced pruritus alone occurred most frequently. No patient was taking any drug therapy. One patient developed similar pruritus following solar simulated irradiation, and one following PUVA therapy. All other laboratory investigations were negative. Treatment with low dose UVB phototherapy or PUVA therapy was effective. The condition, which we have called polymorphic light eruption sine eruptione (PLESE), appears to be a variant of PLE not previously reported.