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Biomedical subjects

M D Tharp

Publications and source records attributed to M D Tharp.

At least 19 recordsLinked to original sources
PubMed1998

Clobetasol propionate emollient 0.05% in the treatment of atopic dermatitis.

A 4-week, double-blind, randomized clinical trial, comparing the efficacy and safety of clobetasol propionate emollient cream 0.05% and its vehicle, was conducted at four private dermatology clinics in 81 non-hospitalized patients (> or = 12 years old) with moderate-to-severe atopic dermatitis covering 2% or more of their body surface. All patients had at least one lesion 2 cm or more in diameter. Three signs/symptoms of target lesions (erythema, pruritus, and induration/papulation) were scored by investigators on a scale of 0-3 (in 0.5-point increments; 0 = absent, 1 = mild, 2 = moderate, and 3 = severe); the total of the three scores had to be > or = 6 for patients to qualify for study entry. Patients were excluded if they were immunocompromised, pregnant, or nursing; had skin atrophy, telangiectasia or striae in skin areas to be treated; or had received topical treatments for atopic dermatitis within 1 week prestudy, intramuscular triamcinolone within 6 weeks prestudy, or long-term systemic corticosteroid usage within 6 months prestudy. Patients were randomized in a 1:1 ratio to receive either clobetasol propionate emollient 0.05% twice daily (n = 41), or the emollient vehicle twice daily (n = 40), for 4 weeks. A fingertip unit, equaling approximately 0.5 g in males and 0.43 g in females (enough to cover approximately 2% of the body), was used to measure and apply a thin film of study drug to the affected areas. The efficacy was evaluated by investigators and patients on days 4, 8, 15, and 29 after initiation of therapy, and 2 weeks after the end of treatment (day 43). Investigators performed a physician's gross assessment based on the percentage improvement of the target lesion. They also rated changes from baseline in mean severity scores for six individual signs/symptoms (erythema, pruritus, induration/papulation, lichenification, erosion/oozing/crusting, and scaling/dryness) and for total signs/symptoms according to the severity scoring system described above. Patients rated their response to treatment as excellent, good, fair, poor, or worse. Laboratory assessments were made on days 15, 29, and (if necessary) day 43.

Administration, Topical↗
PubMed1996

IgG anti-50 kd lymphocyte membrane peptide antibody in patients with Sézary syndrome.

BACKGROUND: Recent evidence suggests that as cutaneous T-cell lymphoma progresses, cell-mediated immunity is reduced and humoral responses are augmented. OBJECTIVE: The present study was designed to compare the IgG response in Sézary syndrome with that in mycosis fungoides. METHODS: The IgG antilymphocyte response was studied in six patients with Sézary syndrome and in 11 patients with mycosis fungoides by means of immunoblot analysis, enzyme-linked immunosorbent assay, immunohistochemistry, and flow cytometry. RESULTS: An IgG antilymphocyte response to a 50 kd peptide was seen in five of the six patients with Sézary syndrome; however, none of the 11 patients with mycosis fungoides expressed this response. CONCLUSIONS: An enhanced IgG immune response to 50 kd lymphocyte peptide may be helpful in identifying disease progression in patients with cutaneous T-cell lymphoma.

Adult↗
PubMed1996

Immune-associated cells in basal cell carcinomas of skin.

Increased numbers of mast cells (MCs) and lymphocytes infiltrating in basal cell carcinomas (BCCs) have been observed. The presence of these infiltrating cells has been considered a sign of an immunologic anti-tumor response in the host, but the relationship of these two cell populations has not been examined. To elucidate this possible relationship, 30 non-ulcerated BCCs were analyzed. Frozen sections of the tumors were stained with monoclonal antibodies for Langerhans' cells, lymphocyte subsets and natural killer cells. Fluorescein isothiocynate (FITC)-avidin as well as anti-tryptase and anti-CD45RO monoclonal antibodies were used on formalin-fixed, paraffin-embedded sections for mast cell and T cell identification, respectively. B cells and natural killer cells were rarely observed in these tumors. MCs and T cells were quantified by direct enumeration and expressed as number of cells per high power field (hpf). FITC-avidin and anti-tryptase antibodies were equivalent in their ability to identify MCs. MC content in BCCs ranged from 1.0 to 31 cells/hpf. The number of T cells ranged from 0 to 50 cells/hpf with helper/suppressor cell ratios of 0.2 to 10. There was no correlation between helper/suppressor ratios and mast cell numbers; however, an inverse relationship was observed between the numbers of T cells and the number of mast cells in these tumors. These studies indicate that T cells and MCs are the primary immune cell populations responding to BCCs, and that decreased numbers of T cells are associated with more aggressive tumors.

Basal Cell Carcinoma↗
PubMed1996

A comparison of twice-daily and once-daily administration of fluticasone propionate cream, 0.05%, in the treatment of eczema.

This multicenter, double-blind, randomized, parallel, four-week, vehicle-controlled study compared the efficacy and safety of once- and twice-daily application of fluticasone propionate cream, 0.05%, over a twenty-eight-day treatment period in 238 patients with moderate-to-severe eczema. Clinical evaluations, which included the physician's gross assessment, the severity of signs and symptoms, and the patient's subjective evaluation, were conducted at baseline and at weekly intervals following initiation of treatment. Both fluticasone QD and BID were found to be superior to vehicle at each evaluation. Application of fluticasone BID was found to be superior to once-daily application at day 22 based on the physician's gross assessment, and at days 15 and 22 based on the patient's subjective assessment. There were, however, no statistically significant differences between QD and BID application at day 8 and at the end of the twenty-eight-day treatment period. The results of this study suggest that QD application may be recommended for the treatment of moderate-to-severe eczema in most patients. As always, treatment effectiveness should be monitored periodically and BID application may be necessary to maximize therapeutic benefits in some patients.

Administration, Topical↗
PubMed1996

Cetirizine: a new therapeutic alternative for chronic urticaria.

Chronic urticaria represents a cutaneous reaction pattern that may last for slightly more than six weeks to more than five years. Treatment of patients with chronic urticaria can be a problem for both physician and patient because of the significant side effects that may be caused by first-generation H1 antihistamines or long-term corticosteroid therapy. Newer antihistamines represent a major advance for the treatment of patients with chronic urticaria. Of this group, cetirizine appears to offer some distinct pharmacokinetic and pharmacodynamic advantages. An open-label multicenter trial of 217 patients with chronic idiopathic urticaria demonstrated that cetirizine was effective, rapid in onset, and well tolerated. Thus, cetirizine was shown to be an attractive alternative treatment for patients with chronic idiopathic urticaria.

Adolescent↗
PubMed1996

Chronic urticaria: pathophysiology and treatment approaches.

Urticaria, a cutaneous reaction pattern, varies clinically and histopathologically. The origin of acute urticaria can be detected in some cases; in patients with chronic urticaria, however, the cause is rarely identified. Thus, most patients with chronic urticaria are considered to have idiopathic disease. The dermal mast cell and its mediators may play a central role in chronic idiopathic urticaria. Other inflammatory cells, including lymphocytes and polymorphonuclear cells, have also been implicated. Treatment is based on identification of the inflammatory cells within skin lesions and blockage of the effects of histamine in the skin. Urticaria in which a lymphocyte-predominant infiltrate is seen often responds to one or more H1 antihistamines. Recently, a new generation of nonsedating or mildly sedating H1 antihistamines has proved useful in the management of these cases. Antihistamine use alone may be unsuccessful in urticaria in which polymorphonuclear neutrophils predominate; frequently, the addition of agents that alter polymorphonuclear neutrophil function, such as colchicine or dapsone, is required. During the introduction of antihistamine and anti-polymorphonuclear neutrophil therapy, a simultaneous brief course of systemic corticosteroid therapy may be necessary, but the extended use of systemic corticosteroids should be avoided because of significant adverse effects. As the pathophysiologic mechanisms responsible for chronic urticaria are better defined, more effective therapeutic agents should become available.

Chronic Disease↗
PubMed1995

Cetirizine and astemizole therapy for chronic idiopathic urticaria: a double-blind, placebo-controlled, comparative trial.

BACKGROUND: Cetirizine and astemizole have been shown to be safe and effective in the treatment of patients with chronic idiopathic urticaria. Cetirizine brings about clinical benefit more rapidly. OBJECTIVE: The purpose of this study was to compare the efficacy of single daily doses of cetirizine and astemizole in relieving the symptoms of chronic idiopathic urticaria, with particular emphasis on the commencement of action. METHODS: Patients with chronic idiopathic urticaria were randomly assigned to relieve either 10 mg of cetirizine, 10 mg of astemizole, or placebo for 4 weeks in a multicenter double-blind trial. Patients rated symptom severity each night, and investigators rated symptoms weekly. RESULTS: One hundred eighty-seven patients were enrolled in the trial; 180 were included in the safety analysis and 177 were included in at least one efficacy analysis. Both cetirizine and astemizole were significantly superior to placebo in relieving symptoms of chronic idiopathic urticaria. Both patients' and investigators' ratings indicated that cetirizine acted more rapidly. Both active treatments were well tolerated, and the incidence of somnolence did not differ statistically between cetirizine (14.5%) and astemizole (10.3%). CONCLUSION: Both cetirizine and astemizole provide effective relief of the symptoms of chronic idiopathic urticaria with similar side-effect profiles. However, clinical benefit occurs significantly more rapidly with cetirizine.

Adult↗
PubMed1994

A role for mast cells in the progression of Duchenne muscular dystrophy? Correlations in dystrophin-deficient humans, dogs, and mice.

Dystrophin deficiency has been shown to be the underlying cause of Duchenne muscular dystrophy. Although dystrophin-deficient homologous animal models have been identified (dog, mouse, and cat), the clinical expression of the biochemical defect is species-specific. Thus, while the genetics and biochemistry of Duchenne dystrophy is understood, the pathophysiological cascade leading to muscle weakness in only humans and dogs remains obscure. To begin to dissect the pathophysiology at the histological level, we undertook a systematic study of mast cells in normal and dystrophin-deficient muscle. Mast cells have been implicated in the development of fibrosis in other disorders, and progressive fibrosis has been hypothesized to mediate the failure of muscle regeneration in human and dog dystrophin deficiency. Our results show a strong correlation between mast cell content and localization, and the clinico-histopathological progression in humans, dogs and mice. The mast cell increases were disease specific: other dystrophic myopathies with normal dystrophin generally did not show substantial increases in mast cell content or degranulation. Our data suggest that mast cell accumulation and degranulation may cause the grouped necrosis characteristic of dystrophin deficiency in all species.

Animals↗
PubMed1994

Rat mast cell protease I alters cell metabolism.

Rat connective tissue mast cells are known to store significant amounts of mast cell protease I (RMCP I), which suppresses normal cell growth and mediates cytotoxicity against tumor cell lines, including the fibrosarcoma cell line FL. To better define its effects on FL cells, RMCP I was added to FL cultures for 30 min. Analysis of de novo nuclear protein synthesis revealed that RMCP I suppressed the expression of three proteins (41, 46, and 69 kD) and enhanced the expression of two other proteins (25 and 32 kD). Treatment of FL cells with diisopropylfluorophosphate (DFP)-inactivated RMCP I proved that these effects were largely independent of the protease catalytic site. Western blot hybridization, using a monoclonal antibody to phosphotyrosine-containing proteins, revealed that RMCP I inhibited phosphorylation of a nuclear and a cytoplasmic 81-kD tyrosylprotein. Inhibition of nuclear tyrosine kinase activity by RMCP I appeared to be catalytic site dependent, whereas cytoplasmic tyrosine kinase inhibition was independent of RMCP I proteolytic activity. Biotinylated RMCP I was used to identify potential surface-binding proteins. Three specific binding complexes (130, 150, and 210 kD) were detected. The binding of biotinylated RMCP I to these surface proteins was inhibited by excess unlabeled RMCP I, but not by trypsin or chymotrypsin. We speculate that the binding proteins may be critical in initiating RMCP I-induced metabolic changes on FL cells. The ability of RMCP I to alter the metabolism of cells suggests that it may have an important role in regulating their functions.

Animals↗
PubMed1993

Mast cell and myofibroblast in wound healing.

Growing evidence in the literature indicates that mast cells are integrally involved in the process of dermal wound repair. They are resident cells of the normal dermis and have several cytokines stored in their granules that are stimulatory to fibroblasts. They also contain serine proteases that may be involved in remodeling of the extracellular matrix during healing. Mast cells are found in increased numbers in acute wounds and in certain chronic fibrotic diseases. Their influence on fibroblast growth and collagen production may be an important element in fibrosis. The effects of mast cell mediators on dermal fibroblasts are currently being explored by our laboratory and others. Myofibroblasts are implicated in the phenomenon of wound contraction. These phenotypically altered fibroblasts express some features of smooth muscle cells, notably actin filaments, and are abundant in granulation tissue. It has been proposed that they are responsible for wound contraction and possibly certain types of contracture. However, this hypothesis has been challenged by studies demonstrating the presence of myofibroblasts in wounds that do not contract, or the process of contraction in vitro in the absence of myofibroblasts. At this time the issue remains open to debate and further research.

Fibroblasts↗
PubMed1991

Growth of human basal cell carcinomas transplanted to C57/Balb/C bgJ/bgJ nu/nu (beige-nude) mice.

The purpose of this study was to measure growth parameters of transplanted basal cell carcinoma (BCC) to beige-nude mice during a 4-month observation time. Forty male beige-nude mice were transplanted with human BCC with our reported subcutaneous implantation technique. Initial volume and wet weight were determined for each tumor. The tumors were measured every 2 weeks by calipers with a final volume determined at 120 days, at which time the tumors were harvested, weighed, and processed for routine histology. Thirty-two tumor sites were positive for persistent tumor at harvest. Tumor volumes declined by an average of 51% and average tumor weight by 33%. There were increased numbers of mast cells surrounding the BCC tumor lobules. These results indicate that BCC can survive for 120 days in the beige-nude mouse.

Animals↗
PubMed1990

IgE and immediate hypersensitivity.

Tissue mast cells play a central role in immediate hypersensitivity reactions. The clinical manifestations of these reactions appear to be dependent, in large part, on the anatomic location of the stimulated mast cells and the type of mediators released. In vivo and in vitro studies indicate that the tissues in which mast cells reside may greatly influence their biochemical composition, expression of surface receptors, and response to potential stimuli. Although all human mast cells in different organs store similar concentrations of histamine, heparin, and tryptase, cutaneous mast cells appear to be the predominant source of mast cell-derived chymase. Furthermore, at the time of stimulation, human skin mast cells predominantly form PGD2, whereas lung and intestinal mast cells generate LTB4, LTC4, and PGD2. Functional studies indicate that human cutaneous mast cells differ from human lung, heart, and intestinal mast cells. Skin mast cells are responsive to a variety of immunologic and nonimmunologic stimuli in vitro, whereas human pulmonary, cardiac, and intestinal mast cells are relatively refractory to many of these stimulatory signals. Taken together, these observations indicate that mast cells may assume different, and possibly specialized, functions within a specific tissue. Such site-to-site variation potentially could have important clinical significance, to the extent that information gained from mast cells in one organ may not be applicable to a mast cell population in a different tissue. Furthermore, these differences among human mast cells may not be confined to their biochemical composition and responses to various stimuli, but also may extend to the effectiveness of different anti-allergic preparations. Therefore, these observations underscore the importance of continued detailed investigation of human mast cells from different anatomic sites.

Humans↗