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Biomedical subjects

C H Kirkpatrick

Publications and source records attributed to C H Kirkpatrick.

At least 73 records · Page 4Linked to original sources
PubMed1983

Long-term therapy of chronic mucocutaneous candidiasis with ketoconazole: experience with twenty-one patients.

Our experience in the treatment of chronic mucocutaneous candidiasis with ketoconazole is reviewed. Of 21 patients, 15 have evidence of deficient cellular immunity and eight have endocrine abnormalities. Six patients had concurrent dermatophytosis or chromomycosis. All patients responded to treatment. Mucosal lesions improved in 6.7 +/- 0.5 days and cutaneous lesions responded to 22.7 +/- 5.1 days. The responses by infected nails were more variable (mean response time 92.4 +/- 14.4 days). Concurrent dermatophytoses did not prolong response times. Adverse effects were infrequent: one patient had drug-induced hepatitis and two patients became hypertensive. The relationship of hypertension to ketoconazole treatment is unclear. One patient was able to remain in remission after treatment was discontinued. Two patients had relapses while on treatment. Candida albicans isolated from these patients was highly resistant to ketoconazole in vitro. We conclude that ketoconazole is an effective and well-tolerated drug for the treatment of the infectious component of chronic mucocutaneous candidiasis.

Adolescent↗
PubMed1983

Human tonsillar IgE biosynthesis in vitro. I. Enhancement of IgE and IgG synthesis in the presence of pokeweed mitogen by T-cell irradiation.

A study of the events regulating human IgE biosynthesis in vitro was undertaken with tonsillar lymphocytes. IgG synthesis was also studied to evaluate the specificity of our observations. T-cell irradiation significantly enhanced synthesis of IgE by pokeweed mitogen (PWM)-stimulated B cells from 12 of 18 donors and IgG in all 18 donors. This enhancement was the result of de novo immunoglobulin synthesis, since the amount of IgE and IgG spontaneously released from lysed and lysed-and-cultured mononuclear cells was significantly less than that detected in the cell cultures, and the augmentation was completely ablated by the treatment of the cells with cycloheximide or mitomycin C. Enhancement was also dependent on the presence of PWM; T-cell irradiation did not enhance IgE synthesis in unstimulated cultures. Moreover, this enhancement was also observed in the co-cultures of B cells and allogeneic irradiated T cells. These observations suggest that radiosensitive T cells exert a suppressive activity that contributes to regulation of human IgE and IgG synthesis and that the suppressor function as well as the helper function can overcome allogeneic disparities.

Adolescent↗
PubMed1983

Treatment of fungal infections in the bones and joints with ketoconazole.

Seven patients with fungal infections in the bones and joints were treated with ketoconazole. One patient had aspergillosis, two had sporotrichosis, and four had coccidioidomycosis. All of the organisms that were tested demonstrated in vitro sensitivity to ketoconazole. Patients were treated with 200-600 mg of oral ketoconazole per day for a minimum of six months. Initially four of seven patients responded to therapy, but only one was cured. The other three patients did not respond. Treatment failure may be due to poor penetration of ketoconazole into bone. Ketoconazole will not cure fungal osteomyelitis, but it may be useful in conjunction with surgical debridement. Chronic suppressive therapy with ketoconazole is well tolerated but may not prevent metastatic fungal infection.

Adult↗
PubMed1983

Acquired immunodeficiency syndrome in a patient with hemophilia.

A patient with hemophilia A developed T-cell deficiency characterized by infection with several opportunistic pathogens. Immunologic investigation showed cutaneous anergy, lymphocyte unresponsiveness to mitogens and antigens, an abnormal ratio of T-helper and T-suppressor cells with absolute lymphopenia and elevated IgA. The clinical and immunologic characteristics of this patient fit the recently described syndrome of opportunistic infections or Kaposi's sarcoma in patients with acquired T-cell deficiency; however, this patient does not have any of the associated underlying risk factors such as homosexuality, intravenous drug or amyl nitrite use, or positive serologic tests for syphilis. We conclude that the patient's acquired T-cell deficiency can be explained by exposure to a virus or other transmissible agent during factor VIII transfusions.

Acquired Immunodeficiency Syndrome↗
PubMed1982

Interstitial and hemorrhagic pneumonitis induced by mycobacterial trehalose dimycolate.

Intraperitoneal injections of cord factor (trehalose dimycolate, TDM) provides a model for interstitial and hemorrhagic lung disease that is produced by a chemically defined substance. A single injection of 10 micrograms of TDM, in light mineral oil or hexadecane, into C57BL/6 mice produces interstitial and hemorrhagic pneumonitis. Following injection of TDM the pulmonary lesions increase gradually and become maximal by the seventh to ninth day, at which time 70% of the mice show both gross hemorrhages and dense mononuclear infiltrates; an additional 20% of the mice show only microscopic lesions. From day 14 onward the incidence and severity of the lesions decrease, and by day 28 the lungs are normal by both gross and light-microscopy examination. Only 5% of the mice succumb. Except for peritonitis other organs are not affected. Doses of 3.3 and 10 micrograms of TDM are equally effective in producing the lesions, but a dose of 1.0 microgram of TDM causes only mild interstitial inflammation and lesser doses do not induce lesions. A single subcutaneous injection of 10 micrograms of TDM causes lesions in only 20% of mice. Vehicle-injected mice do not develop lesions. Electron microscopy revealed that the majority of the infiltrating cells are monocytes and macrophages and that extensive interstitial damage is produced. The mechanism of the effects of TDM are unknown and is currently under study. Our preliminary data suggests that the phenomenon is dependent upon T-lymphocytes.

Animals↗
PubMed1981

Murine transfer factor. I. Description of the model and evidence for specificity.

A model for studying transfer of delayed-type sensitivity to mice with cellfree materials is described. The results with a particulate antigen (Candida) and 4 soluble protein antigens (PPD, ferritin, cytochrome c, and horseradish peroxidase) suggest that the phenomenon is antigen specific. Identical preparations from the spleens of insensitive donors were not active. This murine model should facilitate characterization of the immunologic and chemical properties of transfer factor.

Animals↗
PubMed1980

Dermatophytosis in patients with chronic mucocutaneous candidiasis.

We review the association of concurrent dermatophytic infections in patients with chronic mucocutaneous candidiasis and add twelve new patients to the seventeen previously reported ones. In sixty patients with chronic mucocutaneous candidiasis studied at the National Institutes of Health (NIH), twelve (20%) also had significant local or diffuse dermatophytosis. A comparison between candidiasis patients with and without dermatophytosis revealed no significant differences in their distribution within the various clinical syndromes of chronic mucocutaneous candidiasis nor in the immunologic responses that were tested. Failure to recognize coexistent dermatophytosis in candidiasis patients may lead to unsatisfactory responses to treatment.

Adult↗
PubMed1980

Comparison of antibody responses in chronic mucocutaneous candidiasis and tinea versicolor.

Antibody titers against Candida albicans and Pityrosporum orbiculare, the presumed etiologic agent of tinea versicolor, were determined in normal subjects, and in patients with tinea versicolor or chronic mucocutaneous candidiasis. Whereas antibody against both organisms was found in low titer in normal subjects, a majority of patients with each infection had elevated antibody titers against the infecting organism. Patients infected with one organism did not have elevated titers against the other, and titers against one did not correlate with titers against the other. Therefore, these studies indicate that both of the superficial infections are capable of inducing a significant humoral immune response and that actual infection with the organism rather than mere colonization is required for production of the elevated antibody titers.

Agglutination Tests↗
PubMed1980

Transfer factor.

The understanding of passive transfer of cell mediated-immune responses with transfer factor and other cell free materials has progressed to the point that investigators are seeking the chemical identity of the molecule(s) that are responsible for these effects and are working on their mechanisms of action. In addition, clinical trials are underway that should clarify the potential for use of transfer factor in treatment of infections, neoplastic and autoimmune diseases. This chapter will critically review the past and current data concerning the components of transfer factor and their effects on immunologic and inflammatory reactions. Some of the recently developed animal models will be described and evaluated, and the clinical studies that have provided conclusive data regarding efficacy will be reviewed.

Animals↗
PubMed1980

Disorders of phagocyte chemotaxis.

Recent advances in understanding the physiologic and biochemical bases for recruitment of phagocytes to inflammatory sites has led to the recognition of patients who have recurrent infections because of abnormalities of phagocyte chemotaxis. In some of these patients there is abnormal chemoattractant mediator production or regulation, whereas in others there are defects in phagocytic cell function. The cellular defects in chemotaxis can be characterized as either intrinsic defects of the cellular motility apparatus or acquired defects from mediators influencing cell function or from shifts in circulating phagocyte subpopulations. Systematic study of these defects has resulted in functional, biochemical, and ultrastructural characterization of abnormal phagocyte chemotaxis in certain patients, and in some patients study has led to rational approaches for treatment. Clinical trials assessing the efficacy of such pharmacologic agents are underway.

Adolescent↗
PubMed1980

Treatment of chronic mucocutaneous candidiasis with ketoconazole: a controlled clinical trial.

Twelve patients with chronic mucocutaneous candidiasis were assigned by random allocation to a 6-month course of treatment with ketoconazole or placebo in a double-blind trial. All six recipients of ketoconazole had remission of symptoms and virtually complete regression of mucosal, skin, and nail lesions, whereas only two of the six receiving placebo had even temporary mucosal clearing, and none had improvement of skin or nail disease. The clinical outcome in the ketoconazole-treated group was significantly more favorable (p = 0.001) than in the placebo-treated group. The six patients receiving placebo in the controlled trial were then treated with ketoconazole in an open trial, and all responded favorably. Hepatitis, probably drug induced, developed in one patient after 6 months of treatment but proved to be mild and reversible. Oral ketoconazole is an effective treatment for chronic mucocutaneous candidiasis.

Adolescent↗