Patient Satisfaction and Quality of Life Among Adult Women with Androgenetic Alopecia Using 5% Topical Minoxidil

BACKGROUND: Androgenetic alopecia (AGA) is a common, genetically predisposed condition that begins after puberty and whose frequency increases with age; although biologically benign, AGA can impact patients both psychologically and socially, contributing to an impairment on their quality of life. OBJECTIVE: We sought to evaluate the psychological, social, and quality of life impairments inherent in women with AGA using 5% minoxidil daily for at least six months. DESIGN: Thirty-one women with diffuse central hair thinning and shaft miniaturization who were using 5% minoxidil daily for at least six months responded to a clinical questionnaire and underwent trichoscopy. RESULTS: 83.9 percent (n=26) of the participants reported they were satisfied with the 5% minoxidil treatment and its convenience. Hair loss influenced social life in 54.8 percent (n=17) of the respondents and choice of hair cut/hairstyle in 87.1 percent (n=27) of respondents. For 51.6 percent (n=16) hair loss was slightly increased, although it did not increase after beginning treatment. A frontoparietal pattern (74.2%, n=23), very low capillary density (61.3%, n=19), trichodynia (32.3%, n=10), and negative traction test (100%, n=31) were also observed. Miniaturization occurred in 100 percent (n=31) of patients, frontal/occipital hair thickness was reduced in 83.9 percent (n=26), and more than 10 percent of velus hair in the frontal area was observed in 83.9 percent (n=26) of patients. The number of hair shafts per follicular unit was reduced in 67.7 percent (n=21), and a higher frontal to occipital ratio of follicular units with one hair shaft was seen in 74.2 percent (n=23) of patients. Empty follicles, large numbers of peripillar brownish halo, scalp pigmentation, mild Ludwig''s baldness degree, and quality of life scores of 4±3.5 points were observed. CONCLUSION: Our results indicate that patient satisfaction and quality of life of women with AGA on 5% topical minoxidil are high, although hair loss influences daily habits and social life.     

Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance

Upregulation of the inducible gene products MICA (human) and Rae-1 (mouse) may promote tumor surveillance and autoimmunity by engaging the activating receptor NKG2D on natural killer (NK) cells and T cells. Nevertheless, sustained expression of MICA by tumors can also elicit NKG2D downregulation, perhaps indicating 'immunoevasion'. Investigating this paradox, we report here that constitutive Rae-1epsilon transgene expression in normal epithelium elicited local and systemic NKG2D downregulation, generalized but reversible defects in NK cell-mediated cytotoxicity and mild CD8(+) T cell defects. The extent of NKG2D downregulation correlated well with the incidence and progression of cutaneous carcinogenesis, emphasizing the utility of NKG2D as a marker of tumor resistance. Thus, NKG2D engagement is a natural mediator of immunosurveillance, which can be compromised by locally sustained ligand expression but potentially restored by innate immune activation.     

Perceived social support and tumor estrogen/progesterone receptor status as predictors of natural killer cell activity in breast cancer patients

This report is concerned with the prediction of natural killer (NK) cell activity in 61 Stage I and II breast cancer patients, between the ages of 25 and 70, who were accrued to this project. All baseline interview and testing data were obtained either just before patients were discharged from the hospital, or at their first outpatient visit, within two weeks of discharge. A major interest of this project is the predictive value of perceived social support, as a potential "stress" buffer, related to NK activity. In the main model reported here, we found that a significant amount of NK activity variance could be explained by five variables. Higher NK activity could be predicted by the perception of high quality emotional support from a spouse or intimate other, perceived social support from the patient's physician, estrogen receptor-negative tumor status, having an excisional biopsy as surgical treatment, and actively seeking social support as a major coping strategy (R2 = 0.33, F(5,55) = 5.5, p less than 0.0004). Findings are discussed in terms of host interaction with tumor endocrine status, and the role that social support might play in modulating such activity.     

Melanoma

The incidence of melanoma in the US is rising at a rate second only to that of lung cancer in women. Early stage melanoma is curable, but once metastatic, it is almost uniformly fatal. The immunotherapy of melanoma is a new and exciting therapeutic modality that is being extensively investigated worldwide. Interferon-alpha has an approximately 16% response rate in metastatic melanoma. In the randomised trials to date, no combination of chemotherapeutic or hormonal agent with interferon-alpha has proven to be superior to dacarbazine, the reference agent for the treatment of metastatic melanoma. The role of interferon-alpha-2b in the adjuvant therapy of localised melanoma at high risk for relapse has recently been established, with the results of 2 large randomised trials conducted by the US Intergroup, one showing improvement in both relapse-free survival and overall survival, and the other in relapse-free survival only. Interferon-gamma has not been effective in the adjuvant setting or in metastatic disease, but is part of combination protocols used for regional therapy for extremity melanomas. Interleukin-2 has an overall response rate of 15 to 20% in metastatic melanoma and produces some complete and durable remissions. The US Food and Drug Administration has recently approved the use of high-dose bolus administration of recombinant interleukin-2 for the therapy of metastatic melanoma. Results of combination chemotherapy and immunotherapy regimens containing interleukin-2 (biochemotherapy) are promising, and ongoing research will determine whether a survival impact will be confirmed in randomised studies. Vaccine therapy is another exciting area of research, and clinical trials are ongoing in both metastatic melanoma and as adjuvant therapy. A bewildering array of vaccines (whole cell, carbohydrate and peptide) is available, and it remains to be seen which of these numerous preparations will be most effective. Adjuvant therapy trials with a ganglioside GM2 vaccine and others are ongoing. Numerous peptide vaccines are also being investigated for metastatic melanoma, singly and in combination with other immunotherapeutic agents.     

Effects of antidepressant drugs on the dopamine D2/D3 receptors in the rat brain differentiated by agonist and antagonist binding – an autoradiographic analysis

In the present study the effect of antidepressant drugs on the density of dopamine D₂/D₃ receptors in the rat forebrain was examined using autoradiography, since this technique provides the appropriate anatomical resolution. Male Wistar rats were treated with three various antidepressant drugs: imipramine, citalopram and mianserin in a dose of 10 mg/kg p.o., acutely (single dose) or repeatedly (twice a day for 14 days). To estimate the distribution of D₂/D₃ receptors, we chose following radioligands: [³H]raclopride, a non-selective antagonist of D₂/D₃ receptors, and [³H]quinpirole, a non-selective D₂/D₃ agonist. When [³H]raclopride was used as a radioligand, no significant differences in the density of D₂/D₃ receptors were observed after administration of the investigated drugs. However, following repeated administration of imipramine, citalopram and mianserin, a significant increase in the binding of [³H]quinpirole was observed, both in the nucleus caudatus and nucleus accumbens septi. In some cases the increase of [³H]quinpirole binding was also observed after acute treatment with antidepressant drugs. Thus, using an agonist as a radioligand, we were able to see upregulation of dopamine D₂/D₃ receptors in the rat forebrain following administration of antidepressant drugs, which might be interpreted as the biochemical correlative for the postsynaptic dopamine D₂/D₃ receptor supersensitivity observed in previous behavioral studies. Received: 13 February 1998 / Accepted: 13 November 1998     

NEOPLASTIC DISEASE AND DELETION 22q11.2: A MULTICENTRIC STUDY AND REPORT OF TWO CASES

Deletion 22q11.2 is a chromosomal abnormality detected in young patients with clinical manifestations of the DiGeorge/velocardiofacial syndrome. Conotruncal heart defects are also associated with del22q11.2. An association of these cardiac malformations with neoplasias has been observed. Our series includes two cases of malignancies, a hepatoblastoma and a renal-cell carcinoma, arising in children with complex cardiac malformations. The aim of the study was to determine if the deletion at 22q11.2 was present and could be responsible for both pathological processes. Del22q11.2 was identified in both cases. Comparative genomic hybridization revealed terminal gains on chromosomes 1q and Xq and terminal loss on 1p in the hepatoblastoma, and gains in 1p, 12q, 16p, 20q, 22q, and whole chromosome 19 and loss of Xq in the renal-cell carcinoma. Our results confirm a common genetic basis for cardiac malformations, and del22q11.2 presents a risk factor for the development of pediatric tumours.     

Development of fluridil,a topical suppressor of the androgen receptor in androgenetic alopecia

Nonsteroidal antiandrogens (AA) cannot be topically used for androgenetic alopecia (AGA) because of systemic resorption. A new class of androgen receptor (AR) suppressors designed for safe topical treatment of AGA was synthesized from (3‐amino‐2‐hydroxy‐2‐methyl‐N‐(4‐nitro‐3‐trifluoromethyl)phenyl) propanamide (BP‐34), to contain perfluoroalkyl moieties. The trifluoromethyl derivative (fluridil) at 10 μM decreased expression of the AR in LNCaP human cells by 95%, its serum half‐life was 6 h; it decomposes hydrolytically to BP‐34 and trifluoroacetic acid. Acute intraperitoneal maximum tolerated dose (MTD) of fluridil in mice is 270–300 mg/kg/d and the subacute MTD is 450 mg/kg/d. The oral LD₅₀ in mice was 2,872 mg/kg in males, 2,232 mg/kg in females, and >2,500 mg/kg in rats. Fluridil solution in isopropanol was not cutaneously absorbed in rabbits, did not sensitize or show any phototoxic or photoallergic effects on guinea pig skin, and demonstrated no skin irritation potential in rabbits and humans. Fluridil solid induced only slight and reversible eye irritancy in rabbits and displayed no cytotoxicity to rabbit corneal fibroblasts in vitro. Fluridil demonstrated no significant mutagenicity potential by Ames method. In a double‐blind study, 43 males with AGA, Norwood grade II to Va, used topical 2% fluridil in isopropanol or the vehicle daily for 12 months. Anagens (growing hairs) increased in the fluridil group from 76% to 89%. All hematological and biochemistry values remained within normal range, including testosterone, which varied but seasonally. No fluridil or its decomposition product (BP‐34) was detected in serum. No adverse side effects were reported. Drug Dev. Res. 59:292–306, 2003. © 2003 Wiley‐Liss, Inc.