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Biomedical subjects

R Camp

Publications and source records attributed to R Camp.

At least 19 recordsLinked to original sources

The role of interleukins 1, 6 and 8 as lymphocyte attractants in the photodermatoses polymorphic light eruption and chronic actinic dermatitis.

The two photodermatoses, polymorphic light eruption (PLE) and chronic actinic dermatitis (CAD), are characterized by lymphocyte-rich inflammatory infiltrates, the pathogeneses of which are not fully understood. We have therefore studied suction blister fluid (SBF) samples from patients with these conditions before and at two time points after the induction of experimental lesions by means of a solar simulator; this SBF was then tested for the presence of selected cytokines known to induce peripheral blood lymphocyte (PBL) migration in vitro. A specific EL-4 NOB-1 bioassay was used to detect interleukin (IL)-1 activity, which has already been noted in normal skin and this was found in pre-irradiation control samples as well as 1-3 h and 24 h post-irradiation in both patient groups, but at levels not significantly different from those of controls. Use of a B9 cell proliferation assay showed no detectable IL-6-like activity pre-irradiation, but there was substantial activity in samples at both post-irradiation time points in both patient groups. Further, in other experiments, retained SBF samples were tested in an in vitro PBL migration assay in the presence and absence of neutralizing antibodies against IL-1 alpha, IL-1 beta, IL-6 and IL-8; considerable PBL attractant activity was noted in the pre-irradiation SBF from both patient groups; a finding consistent with previous reports of such activity in samples from normal skin, and at least in CAD patients, a proportion of this activity appeared to be due to IL-1, pre-incubation of SBF with neutralizing antibodies against IL-1 alpha and IL-1 beta reducing the effect significantly. Substantial PBL attractant activity was present also in the SBF from 1-3 h and 24 h post-irradiation samples in both patient groups and again, IL-1 neutralizing antibodies reduced this in the 1-3 h and 24 h CAD samples. In addition, neutralizing antibodies against IL-6 and IL-8 reduced the activity in the 24 h PLE samples significantly and although not fully conclusive in the case of IL-1, these data suggest that IL-6, IL-8 and possibly IL-1 may be involved in the induction of PBL infiltrates, and perhaps other events, in both PLE and CAD.

Adult↗

Association of cocaine and methamphetamine use with giant gastroduodenal ulcers.

OBJECTIVES: Giant gastric and duodenal ulcers (>2-3 cm in greatest dimension) are reported to have higher rates of complication and mortality and to be associated with increasing age, renal failure, and use of nonsteroidal antiinflammatory drugs (NSAIDs). This study investigated the outcome and associations of gastric and duodenal ulcers >2.5 cm compared to ulcers of lesser size. METHODS: Records from all patients with gastric and duodenal ulcers >0.5 cm diagnosed by upper endoscopy between January 1994 and September 1995 were studied for evidence of concurrent use of aspirin, NSAIDs, methamphetamine, and cocaine, as well as for transfusion requirements, length of hospital stay, mortality, surgery, rebleeding, Helicobacter pylori infection, and malignancy. RESULTS: A logistic regression analysis of the 220 patients identified revealed that recent methamphetamine and/or cocaine use was significantly predictive of giant ulcer formation (p = 0.0002) with an odds ratio of 9.66. Also significant was younger age (p = 0.026) and aspirin or NSAID use (p = 0.046). H. pylori infection was significant only for giant gastric ulcers (p = 0.031). Ulcer size did not predict mortality, rate of rebleeding, requirement for surgery, transfusion requirements, or length of hospital stay. However, giant gastric ulcers were significantly more likely to be malignant (p = 0.002). CONCLUSIONS: Giant gastric and duodenal ulcers were strongly associated with stimulant abuse. They were also associated with younger age and use of aspirin or NSAIDs. Additionally, giant gastric ulcers were associated with malignancy and H. pylori infection. Ulcer size did not predict rate of complications or outcome.

Adolescent↗

Cytokines induce lymphocyte migration in vitro by direct, receptor-specific mechanisms.

Several cytokines have been found to induce human peripheral blood lymphocyte (PBL) migration in vitro. The mechanisms involved are unclear, therefore experiments were carried out to determine whether PBL migration in response to selected cytokines is due to a direct effect, or to the generation of nonspecific secondary mediators, and whether migration is receptor specific. Purified human PBL were incubated with the lymphocyte chemotactic cytokines interleukin (IL)-1 alpha and IL-8, followed after 30-60 min by addition of specific neutralizing monoclonal antibody. Supernatants of these mixtures were shown by subsequent assay to be devoid of PBL attractant activity, whereas positive control supernatants containing no antibody induced dilution-related migration. Addition of antibody to the high affinity IL-2 receptor abolished the potent attractant effect of IL-2 on PBL, but had little effect on responses to IL-1 alpha and IL-8. These results demonstrate that the in vitro locomotor responses of human PBL to selected cytokines are due to direct, receptor-specific effects and are not dependent upon the generation of secondary mediator(s).

Antibodies, Monoclonal↗

Topically applied verapamil hydrochloride inhibits tuberculin-induced delayed-type hypersensitivity reactions in human skin.

Calcium channel antagonists have been reported to possess inhibitory effects on lymphocyte migration and activation in vitro, and on cell-mediated immune reactions in the skin of experimental animals. We have therefore studied the effects of topically applied 8% (w/v) verapamil hydrochloride in propylene glycol on tuberculin-induced delayed-type hypersensitivity reactions in the skin of normal human volunteers. There was significant inhibition of the tuberculin reactions by the verapamil preparation compared to vehicle controls, as determined by forearm skin fold thickness measurement and assessment of the density of mononuclear cell infiltrates in skin biopsies. The precise mechanism of action of verapamil hydrochloride remains unclear, but could include effects on T-cell migration and activation, on antigen-presenting cells, and/or on other cells. The potential for the use of topical calcium channel antagonist preparations in inflammatory skin diseases warrants further study.

Administration, Topical↗

A prospective, randomized, blinded trial of cytological yield with disposable cytology brushes in upper gastrointestinal tract lesions.

Brush cytology is an important technique in the diagnosis of upper gastrointestinal tract lesions. Optimum cytological yields depend on cellularity (a measure of the amount of epithelial cellular material) and preservation (a measure of artifact induced by desiccation). We sought to determine the cytological yield of four disposable cytology brushes. Seventy-eight patients were studied, with a total of 80 disposable cytology brushes from four different manufacturers (Wilson-Cook, Microvasive, Mill-Rose, and Hobbs). Cellularity and preservation were assessed in a blinded fashion by experienced cytotechnologists. There was no significant difference in cellularity between the different non-disposable brushes. However, the Wilson Cook disposable cytology brush was significantly superior to the other disposable cytology brushes (P < 0.05) with regard to preservation. Its unique design features (longer head and more acutely angled bristles) may account for the better results.

Cytological Techniques↗

Induction of in vitro human lymphocyte migration by interleukin 3, interleukin 4, and interleukin 6.

The effects of interleukin 3 (IL 3), IL 4, IL 6, and interferon-gamma (IFN-gamma) on lymphocyte migration have been investigated and compared with those of transforming growth factor-beta 1 (TGF-beta 1), granulocyte colony stimulating factor (GCSF), and macrophage colony stimulating factor (MCSF). Potent, temperature-dependent stimulation of lymphocyte migration was obtained in response to IL 3 and IL 4 (ED50 less than 10(-11) M and less than 10(-13) M, respectively) and this migration was abolished in the presence of 3 micrograms ml-1 cytochalasin B. IL 6 and IFN-gamma were less active (ED50 greater than or equal to 10(-9) M and greater than or equal to 10(-8) M, respectively), maximal migration in response to IFN-gamma being only 30% above background as compared with approximately 250% for IL 3 and IL 4. TGF-beta 1, GCSF, and MCSF failed to stimulate lymphocyte migration in doses similar to those used for IL 3, IL 4, and IL 6. The presence of antisera to IL 3, IL 4, and IL 6 specifically inhibited lymphocyte migration induced by the corresponding cytokines (IC50 values being 1/10,000, greater than 1/30,000, and greater than 1/30,000 dilution of antibody, respectively). Cross-desensitization experiments using IL 3 and IL 4 demonstrated that neither IL 3 nor IL 4 were able to stimulate dose-related lymphocyte migration in cells preincubated with IL 3. Cells preincubated with IL 4 were only stimulated by a supraoptimal concentration of IL 4 (10(-11) M). The induction of lymphocyte migration by IL 3, IL 4, and IL 6 therefore appears to be a specific and potentially important effect of these cytokines. Cross-desensitization of lymphocytes by IL 3 and IL 4 raises the possibility that the induction of lymphocyte migration by these cytokines may occur through a common postreceptor signal transduction mechanism.

Chemotaxis, Leukocyte↗

Potent inflammatory properties in human skin of interleukin-1 alpha-like material isolated from normal skin.

Recombinant human interleukin 1 (IL-1) possesses potent inflammatory properties in both animal and human skin. However, IL-1-like material has been isolated from normal epidermal samples. In view of the uncertainty concerning the structure and biologic properties of human epidermal IL-1, heel stratum corneum, and chamber fluid samples from normal skin have been purified by successive reversed phase and anion exchange high-performance liquid chromatography (HPLC), and aliquots of each HPLC fraction tested for IL-1 activity in an EL-4 NOB-1 assay and for inflammatory activity by intradermal injection of autologous material. The results consistently indicated the presence of inflammatory quantities of IL-1 alpha-like material, which induced persistent erythema lasting at least 24 h, associated in 4-h biopsies with mixed dermal leukocyte infiltrates containing increased numbers of neutrophils, monocytes, and T helper cells. Biologically active quantities of IL-1 beta were not recovered following HPLC purification in most experiments. Analysis of heel stratum corneum extract also showed that the majority of the dilution-related IL-1 activity detected in the EL-4 NOB-1 bioassay was neutralized by IL-1 alpha but not IL-1 beta antiserum. These findings suggest that IL-1 alpha-like material is present in inflammatory amounts in normal human epidermis, and its release may represent a primary inflammatory mechanism in human skin.

Adult↗

Value of pharmacy services: perceptions of consumers, physicians, and third party prescription plan administrators.

A study of patients, physicians, and third party prescription plan administrators was conducted to identify those pharmacy services they believe are important and valuable and to determine whether third party plan administrators would reimburse pharmacists for such services. Patient and physician focus groups indicated that both wanted personalized services related to medications. Physicians believe that pharmacists are talking to patients about their medications, whereas patients want more drug information but report that pharmacists are not always providing such information. A mail survey of 41 third party prescription plan administrators indicated they believe that pharmacy services are important to consumers and that pharmacists are already providing most of the services identified. One-third of the third party administrators said their companies would consider implementing a structured pharmacist incentive plan to improve enrollee satisfaction. Those whose companies would not most often gave "increased cost" as the reason. No clear relationship was shown between number or type of services and the incentive value offered. Providing administrators with evidence that enhanced pharmacy services will increase overall program cost savings may lead to implementation of pharmacy incentives.

Attitude of Health Personnel↗

The perivascular cell populations in human skin after topical application of leukotriene B4.

Fifteen timed biopsies of human skin were performed after application of 100 nanograms of leukotriene B4 in a Finnchamber for six hours. The number of inflammatory cells were counted per high power perivascular field and compared to three control biopsies. At 24 hours a peak of neutrophiles was observed and subsequently lymphocytes predominated. Eosinophils were never prominent. This pattern of successive cell populations has been described in inflammatory and whealing skin disease.

Administration, Topical↗

Production of intraepidermal microabscesses by topical application of leukotriene B4.

Leukotriene B4 is a highly potent leukocyte chemotactic compound. It has been identified in chamber fluid and scale from psoriatic skin lesions, in which epidermal neutrophil infiltration is reported to be one of the earliest pathologic events. The ability of leukotriene B4 to reproduce the inflammatory events of psoriasis, by topical application to the skin of normal human volunteers, was thus studied. Persistent visible inflammatory reactions were elicited by application of amounts of leukotriene B4 as low as 5 ng, and the maximum diameters of the reactions were dose-related up to at least 500 ng. The visible reactions appeared 12-24 h after initial application of leukotriene B4, and persisted for several days, leaving brownish pigmentation and scaling at 7 days. Histologic examination showed intraepidermal neutrophil microabscesses at 24 h, but these had resolved by 48 h. A mixed, perivascular neutrophil and mononuclear cell infiltrate was seen in the dermis at 24 h, becoming predominantly mononuclear after 24 h. Nonspecific chemical irritant contact dermatitis was excluded by the absence of reactions to high doses of two chemically similar metabolites of arachidonic acid which lack significant in vitro chemokinetic activity. These experiments provide further evidence for the role of leukotriene B4 in the pathogenesis of psoriasis, and may lead to the development of an experimental model of the inflammatory events in psoriasis, and of a simple in vivo test of neutrophil function.

Abscess↗

The release of leukotriene B4-like material in biologically active amounts from the lesional skin of patients with psoriasis.

The 5,12-dihydroxy metabolite of arachidonic acid, leukotriene B4, is a highly potent neutrophil chemoattractant. In view of the characteristic epidermal neutrophil infiltrate in psoriasis, the presence of leukotriene B4 in samples from untreated lesional and uninvolved skin has been sought. Chambers were fixed to abraded skin and filled with phosphate-buffered saline (PBS). After 35 min, the fluid was removed, and acidic lipids were extracted and subjected to high-performance liquid chromatography (HPLC). Extracts were purified by both straight- and reversed-phase HPLC, and assay of evaporated fractions by an agarose microdroplet chemokinesis technique indicated the presence of leukotriene B4-like material. No significant leukotriene B4-like activity was found in samples from uninvolved skin. Subsequent experiments using a modification of the initial skin chamber method indicated that leukotriene B4 was being released from deeper layers of lesional skin and not only from superficial scale. Monohydroxy-eicosatetraenoic acid-like activity was also seen in lesional samples as determined by straight-phase HPLC and chemokinesis assay. These findings and the proinflammatory properties of these compounds in human skin suggest that they may play a role in the pathogenesis of the psoriatic neutrophil infiltrate.

Chemotaxis, Leukocyte↗

Novel prostaglandin dehydrogenase in rat skin.

Present evidence suggests that skin is an important organ of prostaglandin metabolism. To clarify its role, the basic kinetics of 15-hydroxyprostaglandin dehydrogenase (PGDH) from rat skin were investigated with either NAD+ of NADP+ as co-substrate. Prostaglandin F2 alpha (PGF2 alpha) and prostaglandin E2 (PGE2) were used as substrates and preliminary studies were made of the inhibitory effects of the reduced co-substrates NADH and NADPH. A radiochemical assay was used in which [3H]PGF2 alpha or [14C]PGE2 were incubated with high-speed supernatant of rat skin homogenates. The substrate and products were then extracted by solvent partition, separated by t.l.c. and quantified by liquid-scintillation counting. At linear reaction rates and at an NAD+ concentration of 10 mM the mean apparent Km for PGF2 alpha was 24 microM with a mean apparent Vmax. of 9.8 nmol/s per litre of reaction mixture. For PGE2 the mean apparent Km was 8 microM, with a mean apparent Vmax, of 2.7 nmol/s per litre of reaction mixture. With NADP+ as a co-substrate at a concentration of 5 mM a mean apparent Km of 23 microM was obtained for PGF2 alpha with a mean apparent Vmax. of 5.2 nmol/s per litre. For PGE2 values of 7.5 microM and 3.0 nmol/s per litre were obtained respectively. These results show that skin contains NAD+- and NADP+-dependent PGDH. An important finding was that the NADP+-linked enzyme gave Km values for PGE2 that were considerably lower than those reported for NADP+-linked PGDH from other tissues. Furthermore, preliminary inhibition studies with the NAD+-linked PGDH system indicate that this enzyme is not only inhibited by NADH, but also by NADPH, a property not previously reported for NAD+-linked PGDH derived from other tissues.

Animals↗