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Biomedical subjects

D P Lookingbill

Publications and source records attributed to D P Lookingbill.

At least 19 recordsLinked to original sources

Inocoterone and acne. The effect of a topical antiandrogen: results of a multicenter clinical trial.

BACKGROUND AND METHODS: Because acne is androgen dependent, antiandrogen therapy might improve the condition. Inocoterone acetate (RU 882) is a nonsteroidal antiandrogen that binds to the androgen receptor and has antiandrogenic activity in animal models. To test its topical effect on acne, 126 male subjects with facial acne completed a 16-week, multi-center, double-blind study in which the twice-daily application of a 10% solution of inocoterone was compared with vehicle solution. Baseline and monthly examinations included acne lesion counts and general and endocrine laboratory tests. RESULTS: Inflammatory papules and pustules showed greater reduction in the inocoterone-treated subjects than in the subjects treated with vehicle. This difference achieved statistical significance by week 12 (24% reduction vs 10%) and week 16 (26% reduction vs 13%) and, with longitudinal analysis, throughout the course of the study. Global assessments and changes in comedo counts and sebum excretion rates were not significantly different between the groups. No serious adverse reactions were encountered. CONCLUSIONS: In this double-blind study of 126 male subjects with acne, a topical solution of the antiandrogen inocoterone, compared with vehicle, produced a modest but statistically significant reduction in the number of inflammatory acne lesions.

Acne Vulgaris

Clinical and biochemical parameters of androgen action in normal healthy Caucasian versus Chinese subjects.

Stimulation of androgen-sensitive hair follicles is mediated by dihydrotestosterone (DHT), which is formed in these tissues by 5 alpha-reduction of testosterone. A possible mechanism for increased body hair in some human populations might, therefore, be an increase in 5 alpha-reductase activity, resulting in elevated tissue levels of DHT. If present, this finding could have other important clinical implications, since the 5 alpha-reductase enzyme is pivotal in the pathophysiology of prostatic disease. To explore differences in clinical and biochemical parameters of androgen action, we conducted a study of 184 caucasian and Chinese subjects in whom we evaluated chest hair density and serum levels of androgen precursors and 5 alpha-reduced androgen metabolites. Differences in chest hair density were most notable in the men, in whom comparative mean chest hair scores (using a scale of 0-4) were 3.0 vs. 0.8 (P less than 0.0001), caucasian vs. Chinese. Levels of 5 alpha-reduced androgen products were also strikingly higher in the caucasian vs. Chinese subjects. Serum 3 alpha-androstanediol glucuronide levels (nanomoles per L) were 34.7 +/- 2.4 vs. 19.7 +/- 0.9 (P less than 0.001) for the men and 21.5 +/- 3.2 vs. 9.4 +/- 0.6 (P less than 0.001) for the women, and serum levels of androsterone glucuronide (nanomoles per L) were 179 +/- 26 vs. 107 +/- 7 (P less than 0.01) for the caucasian vs. Chinese men and 173 +/- 23 vs. 81 +/- 9 (P less than 0.001) for the women. Serum levels of total and bioavailable testosterone did not differ between the racial groups, but serum levels of the precursor androgens, dehydroepiandrosterone sulfate and androstenedione, were significantly higher in the caucasian vs. Chinese men, but not in the women. We conclude that increased serum levels of 5 alpha-reduced androgen metabolites in caucasians vs. Chinese subjects provide circumstantial evidence for a racial difference in 5 alpha-reductase activity and suggest a mechanism for the increased body hair observed in the caucasian men. Increased levels of precursor androgens may also play a role.

Adolescent

Cutaneous manifestations of multiple myeloma.

We report the cutaneous manifestations of multiple myeloma, using a retrospective review of 115 patients' records obtained from tumor registry files. Five patients were found to have biopsy-proved extramedullary plasmacytomas without extension from an underlying bony focus. Twelve patients had ecchymoses without thrombocytopenia; two of them had biopsy-proved amyloidosis. One patient presented with pyoderma gangrenosum and was subsequently diagnosed with multiple myeloma. The last patient initially presented with what clinically appeared to be leukocytoclastic vasculitis, and, in the course of a standard workup, he was diagnosed with multiple myeloma. These findings are discussed with regard to the current literature on the cutaneous manifestations of multiple myeloma.

Adult

Skin involvement as the presenting sign of internal carcinoma. A retrospective study of 7316 cancer patients.

From tumor registry data of 7316 cancer patients, we found 367 cases (5.0%) with skin involvement. Skin involvement was present at the time of presentation in 92 patients (1.3%), only 26 of whom had remote metastases. Skin involvement was the first sign of cancer in 59 patients (0.8%); 22 had direct extension of their tumor into the skin, 20 had local metastases, and 17 had distal metastases. Direct invasion was most common with breast cancer and second most common with oral cavity cancer. Local metastases were also most frequently caused by breast cancer but occurred in surgical scars in three women with pelvic cancer and in perianal abscesses in one patient with rectal carcinoma as well. Except for metastases from unknown primary sites, distant metastases were rare as presenting signs, and their origins were widely distributed. Our data show that internal cancer uncommonly presents with skin involvement. Nevertheless, an index of suspicion should be maintained and biopsy performed, particularly for nonhealing ulcers, persistent indurated erythema, and unexplained skin nodules.

Breast Neoplasms

A novel X-linked combined immunodeficiency disease.

A novel X-linked combined immunodeficiency disease was found in five living males in an extended family in the United States. The age of the affected males ranged from 2.5 to 34 yr. The most prominent clinical abnormalities were a paucity of lymphoid tissue; recurrent sinusitis, otitis media, bronchitis, and pneumonia; severe varicella; and chronic papillomavirus infections. The principal immunologic features of the disorder were normal concentrations of serum immunoglobulins but restricted formation of IgG antibodies to immunogens; normal numbers of B cells and NK cells but decreased numbers of CD4+ and CD8+ T lymphocytes, particularly the CD45RA+ subpopulations; diminished proliferative responses of blood T cells to allogeneic cells, mitogens and antigens; and decreased production of IL-2 by mitogen stimulated blood lymphocytes. Thus, affected males in this family carry an abnormal gene on their X chromosome that results in a combined immunodeficiency that is distinct from previously reported disorders.

Adolescent

Immunosuppression in men with bowenoid papulosis.

The immune status of four men with bowenoid papulosis was evaluated. Each case had been refractory to multiple methods of treatment. Three of the men had other infections and demonstrated a depletion of T4-helper cells. Two of these patients were anergic on skin testing, and the third showed weak reactivity. The fourth patient, who had no evidence of additional infections, had a normal T4 value and T4/T8 ratio, but was anergic on skin testing. All the men were serologically negative for human immunodeficiency virus antibodies. One of the immunosuppressed patients developed squamous cell carcinoma of the tongue, which, along with his bowenoid papulosis, contained human papillomavirus 16 DNA. We suggest that patients with persistent bowenoid papulosis be investigated for altered immune status and followed up as potential candidates for the development of epithelial malignant neoplasms.

Adult

Yield from a complete skin examination. Findings in 1157 new dermatology patients.

A complete skin examination has been recommended by many dermatologists. The purpose of this study was to determine the yield of this examination. Of 1157 consecutively treated new dermatology patients, 1106 (96%) agreed to a total skin examination. Important incidental lesions were found in 162 (15%) of these patients. The types of incidental findings included (1) rashes helpful in establishing the primary diagnosis--20 patients (1.8%); (2) important rashes unrelated to the primary diagnosis--37 patients (3.3%); (3) malignant tumors--22 patients (2.0%); (4) clinically dysplastic nevi--25 patients (2.3%); and (5) congenital nevi--31 patients (2.8%). One patient had an incidental melanoma and another was found to have Kaposi's sarcoma, which led to the diagnosis of acquired immunodeficiency syndrome (AIDS). It is concluded that a complete skin examination is productive and it is recommended for all new dermatology patients.

Adolescent

Correlation of serum 3 alpha-androstanediol glucuronide with acne and chest hair density in men.

Serum 3 alpha-androstanediol glucuronide (3 alpha-Adiol-G) is considered to be an indicator of peripheral tissue androgen metabolism. Precursor circulating androgens are converted in peripheral tissue to dihydrotestosterone (DHT), which is ultimately metabolized to 3 alpha-Adiol-G and secreted from the cell. Elevated serum 3 alpha-Adiol-G concentrations have been reported in women in hyperandrogenic states. We studied 44 consecutive male medical students for chest hair density, acne, and serum dehydroepiandrosterone sulfate (DHEA-S), total testosterone (total T), free and albumin-bound (bioavailable) T (bio T), and 3 alpha-Adiol-G concentrations. Although there was considerable overlap of serum 3 alpha-Adiol-G values among the groups defined by hair density or acne scores, we found statistically significant correlations between serum 3 alpha-Adiol-G and chest hairiness (P = 0.0034), acne (P = 0.0005), and a combined chest hairiness and acne score (P = 0.0018). There was no significant correlation between these clinical parameters and the levels of precursor androgens. There was, however, a strong correlation between serum 3 alpha-Adiol-G and bio T (P = 0.0005), suggesting that in men serum 3 alpha-Adiol-G levels may be dependent upon available free and albumin-bound T. The correlations in men of serum 3 alpha-Adiol-G with chest hair density, acne, and the hairiness and acne index supports the hypothesis that the serum levels of 3 alpha-Adiol-G reflect the extent of androgen action in peripheral tissues.

Acne Vulgaris

Effect of isotretinoin on serum levels of precursor and peripherally derived androgens in patients with acne.

Sebaceous glands are stimulated by androgens and can convert them to more active forms. Isotretinoin, however, has a profound inhibitory effect on sebaceous gland size and function. This study evaluated the effect of isotretinoin on serum levels of precursor and tissue-derived androgens. Twenty-four subjects (15 men and nine women) were treated for 20 weeks with 1 mg/kg/d of isotretinoin. Serum samples were obtained at baseline, 8, 16, and 24 weeks, and assayed for precursor androgens--total testosterone (TT), free testosterone (free T), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEA-S); and tissue androgens--dihydrotestosterone (DHT), and its metabolite, 3 alpha-androstanediol glucuronide (3 alpha-diol G). Isotretinoin had no meaningful effects on precursor androgens, except for producing an elevation of free T in women. In contrast, isotretinoin produced depressions in the serum levels of DHT and 3 alpha-diol G in women and in 3 alpha-diol G in men. These decreases are believed to be the result, rather than the cause, of a reduction in the size of the sebaceous glands: The magnitude of the observed decreases may represent the amount of tissue-derived androgens that sebaceous glands normally contribute to the circulating pool.

Acne Vulgaris

Human papillomavirus type 16 in bowenoid papulosis, intraoral papillomas, and squamous cell carcinoma of the tongue.

A 33-year-old immunosuppressed man developed bowenoid papulosis on his genitalia, velvety papules and plaques in his mouth, and invasive squamous cell carcinoma of his tongue. All three lesions were positive for human papillomavirus type 16 (HPV-16). The case provides further circumstantial evidence for a role of HPV-16 in epithelial neoplasia. The possible roles of a second HPV infection and of immunosuppression are also discussed.

Adult

Plasmapheresis in a patient with scleromyxedema.

We describe a patient with progressive scleromyxedema who failed to respond to previously described treatment modalities. A trial of plasmapheresis was initiated, but after an initial promising response, his disease continued to progress. The skin involvement appeared to progress even more rapidly after the plasmapheresis was discontinued.

Adult

Effects of relaxation therapy and hypnotizability in chronic urticaria.

The therapeutic results of hypnosis with relaxation therapy were evaluated in 15 patients with chronic urticaria of 7.8 years' average duration. Compared with baseline and control session values, the hypnosis session provided relief of pruritus as measured by three self-report parameters. There was no change in the number of hives. All subjects were given a standard test for hypnotizability. Assuming that the results were not biased by their preceding relaxation sessions, we determined that six subjects were hypnotizable and nine were nonhypnotizable. Subjects in both groups improved symptomatically, but hypnotizable subjects had fewer hives and became more symptomatic during the control (testing and history taking) session. Hypnotizable subjects also more frequently related stress as a causative factor. At a follow-up examination five to 14 months after the completion of the experimental sessions, six patients were free of hives and an additional seven reported improvement.

Adult

Histologically proven leukemia cutis carries a poor prognosis in acute nonlymphocytic leukemia.

A retrospective study of fifty-eight patients with acute nonlymphocytic leukemia was undertaken to determine the incidence of leukemia cutis and whether skin involvement serves as a prognostic indicator. A clinical diagnosis of leukemia cutis was made in eleven patients (19 percent), and five patients (8.6 percent) had biopsy-confirmed skin involvement. Patients with biopsy-proven leukemia cutis had a median postdiagnosis survival of only 12.5 weeks compared with fifty weeks for the group without skin involvement. We conclude that leukemia cutis is a biopsy diagnosis that occurs in a minimum of 8.6 percent of patients with acute nonlymphocytic leukemia in whom survival appears to be shortened.

Actuarial Analysis

A direct gravimetric technique for measuring sebum excretion rate.

The standard gravimetric method for measuring sebum excretion rates involves ether extraction of the collected sebum. We have evaluated a more direct method in which the collecting papers were pre- and post-weighed in glass beakers under conditions of stable temperature and humidity. Weights were adjusted allowing for control weight gain or loss, due mainly to day to day changes in weight room humidity. The direct method compared favourably with the ether extraction method in determining: (1) sebum collected from 43 subjects (r = 0.991, P less than 0.001), (2) left versus right forehead comparisons in 19 subjects (direct method: r = 0.966, P less than 0.001; ether extraction method: (r = 0.963, P less than 0.001), and (3) recovery of sebum from 32 premeasured standards (r = 0.997, P less than 0.001). The findings demonstrate the accuracy of the direct gravimetric procedure which is also simpler, safer and less expensive than methods currently in use.

Forehead

Tissue production of androgens in women with acne.

Precursor and target tissue-produced androgens were measured in the plasma of eighteen women with mild to moderate acne. Mean plasma levels of the precursor androgens (total testosterone, free testosterone, androstenedione, and dehydroepiandrosterone sulfate) wer similar to levels in a group of carefully selected acne-free and hirsute-free, age-matched female controls. In contrast, plasma 3 alpha-androstanediol glucuronide (3 alpha-diol G) values were elevated in 13 of the patients, with a mean value for the entire group nearly threefold that of the normal controls (117 vs 43 ng/dl; p less than 0.001). These results support the concept that target tissue androgen production plays an important hormonal role in the pathogenesis of acne in women and that plasma 3 alpha-diol G may be the most sensitive marker of this process.

Acne Vulgaris

Herpes zoster and occult malignancy.

Herpes zoster and malignancy have both been associated with conditions of immune suppression. It has been well documented that herpes zoster occurs more frequently in patients with a previously diagnosed malignancy, especially lymphoma. To determine whether there is an increased frequency of malignancy subsequent to the diagnosis of herpes zoster, we studied fifty outpatients with herpes zoster and compared them with fifty control patients with psoriasis. In a follow-up period ranging from 24 to 68 months, one individual in the herpes zoster group developed a subsequent malignancy, in comparison to none in the control population and to 1.5 cancer cases expected in the general population. These results support the view that herpes zoster is not a marker for an occult malignancy.

Adenocarcinoma