Hair loss and alopecia research abstracts II

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Br J Dermatol. 2003 Jun;148(6):1205-11.

Female alopecia: the mediating effect of attachment patterns on changes in subjective health indicators.

Schmidt S.

Department of Medical Psychology, Pav. S 35, University Hospital of Hamburg Eppendorf, Martinistr. 52, 20246 Hamburg, Germany.

Background The interrelationship between female alopecia and psychological disorders is complex, with a range of psychosocial consequences, but also antecedents. Psychosocial antecedents are to a large extent interpersonal and can be assumed to have a mediating effect on health care utilization and subjective health. Objectives To analyse whether changes in health-related quality of life (QoL) are mediated by relational or attachment styles and whether these styles are associated with a particular, dysmorphophobic type of alopecia. Methods Seventy-four women with androgenetic and diffuse alopecia underwent psychological assessment at the first consultation at a university clinic and at 2 months' follow-up. Attachment styles were evaluated by an observer rating scale. As a primary endpoint a disease-specific QoL instrument was employed. Results Findings indicated an association between patients with nonvisible hair loss and the ambivalent attachment style. Global clinical impressions and attachment indicators, e.g. attachment security and coping strategies, showed significant contributions in predicting changes in the QoL scales 'self-esteem' and 'emotions'. Conclusions These findings suggest that attachment security may be one of the underlying mechanisms mediating subjective health and that a specific attachment vulnerability can be identified in a subgroup of patients with female alopecia. Future studies will have to focus on the relevance of attachment patterns in the doctor-patient relationship and on psychotherapeutic interventions.

Gan To Kagaku Ryoho. 2003 May;30(5):653-9.

Weekly paclitaxel administration in the adjuvant therapy of primary breast cancer

[Article in Japanese]

Takahashi H, Takahashi M, Taguchi K, Sasaki F, Todo S.

Dept. of Pediatric Surgery, Hokkaido University School of Medicine.

PURPOSE: To investigate feasibility and toxicity of weekly paclitaxel administration in the adjuvant therapy of primary breast cancer. PATIENTS AND METHODS: Thirty-one patients with primary breast cancer received sustained weekly infusion of paclitaxel at a dose of 90 mg/body for 6 weeks followed by a 2-week interval. This weekly schedule was repeated twice. Leukocytes were checked immediately before every infusion and the dose was reduced to 80 mg/body when grade 1 neutropenia occurred. All patients were assessable for feasibility and toxicity. RESULTS: A total 349 weekly paclitaxel infusions were administrated to 31 patients (median, 12 infusions/patient). The median delivered dose-intensity was 88.0 mg/body/week (range 80 to 90). Therapy was well tolerated and completed in 27 patients. Four patients refused to continue the therapy because of nausea, fatigue, dizziness and weight gain. Grade 2 neutropenia occurred in 10 patients (32.3%), but grade 3 neutropenia did not occur. Grade 1 peripheral neuropathy occurred in 3 patients (9.7%). Grade 1 nausea occurred in 3 patients (9.7%). CONCLUSION: Weekly paclitaxel administration is well tolerated with a favorable toxicity profile in patients with primary breast cancer in the adjuvant setting. Weekly paclitaxel therapy can be performed safely in the outpatient setting.

Eur J Cancer Care (Engl). 2003 Jun;12(2):154-61.

The effectiveness of scalp cooling in preventing alopecia for patients receiving epirubicin and docetaxel.

Macduff C, Mackenzie T, Hutcheon A, Melville L, Archibald H.

Centre for Nurse Practice Research and Development, The Robert Gordon University, Aberdeen, UK.

The aim of this study was to establish the effectiveness of scalp cooling in preventing alopecia for patients with breast cancer who received the trial combination chemotherapy of Epirubicin and Docetaxel. Doubt remains about the general effectiveness of scalp cooling in preventing hair loss for patients receiving chemotherapy. There is very little information available about its specific effectiveness with combinations of Taxanes and Anthracycline drugs. Of the 40 patients who received this drug combination, 10 were included in a pilot study whereas the remaining 30 constituted the main study sample. A randomized controlled study was undertaken whereby the intervention group received scalp cooling via gel cool caps and the control group received no specific preventative intervention. Nurses assessed participants' hair loss using a modified version of the WHO scale at seven time points and also recorded hair loss photographically. Two independent experts rated the photographs using the same scale. Patients self-reported in relation to overall hair loss, hair condition, levels of emotional upset, negativity about appearance, hair re-growth and wig use. Significantly greater hair loss was apparent in the control group during most of the treatment period. However, the level of protection afforded by the cool caps was relatively poor with this chemotherapy combination. The marginal benefits of scalp cooling in this context must be clearly explained to patients.

J Cardiovasc Risk. 2003 Jun;10(3):227-31.

Hair loss, insulin resistance, and heredity in middle-aged women. A population-based study.

Matilainen V, Laakso M, Hirsso P, Koskela P, Rajala U, Keinanen-Kiukaanniemi S.

aDepartment of Public Health Science and General Practice, University of Oulu bUnit of General Practice, Central University Hospital of Oulu.

CONTEXTThe association of androgenic alopecia (AGA) with insulin resistance, coronary artery disease and hypercholesterolemia has been previously reported in men, but no such association has been reported in women with female androgenic alopecia (AGA). Female AGA has usually been linked with hyper-androgenism and hirsutism and, most recently, also with polycystic ovarian syndrome (PCOS), even though epidemiological documentation of the latter association is scanty. Polycystic ovarian syndrome is quite common among Caucasian women, and its association with insulin resistance is well documented.OBJECTIVES AND DESIGNThe aim of this study was to obtain a more precise estimation of the prevalence on female AGA and to describe its possible connections with insulin resistance linked parameters and with paternal and maternal family history of alopecia. A cross-sectional population based cohort survey was carried out in the City of Oulu, Finland in 1998.SETTING AND PARTICIPANTSAs a part of a population based cohort study the hair status of 324 women aged 63 years was assessed by a modification of Ludwig's scale. The background data consisting of anthropometric measures (weight, height, body mass index, waist, hip and neck circumferences), smoking status, chronic diseases and their medication as well as the family history of AGA were collected by questionnaires and interviews made by study nurses and in clinical examination. Blood samples for laboratory tests were taken on the same occasion.RESULTSThe prevalence of extensive loss of hair (at least grade II or III on Ludwig's scale) was quite high (31.2%). The insulin resistance associated parameters, such as waist and neck circumferences, abdominal obesity measured by waist-to-hip ratio, mean insulin concentration (11.3 mU/l versus 9.95 mU/l, p=0.02) or urinary albumin-to-creatinine ratio (1.80 versus 1.58, p=0.01), were significantly higher in women with extensive hair loss compared to those with normal hair or only minimal hair loss (grade I on Ludwig's scale). The women belonging to the highest quintiles of neck or waist circumferences had significantly increased risk for extensive hair loss compared to those with normal hair or minimal hair loss, the unadjusted ORs being 2.25 (95% CI, 1.26-4.03) and 1.75 (95% CI, 1.00-3.07), respectively. Similarly in women with hyperinsulinemia (fs-insulin >10 mU/l), microalbuminuria (urinary albumin-to-creatinine ratio exceeding the highest microalbuminuria decile (>2.5 mg/mmol) and paternal history of AGA the ORs for alopecia were increased being 1.65 (95% CI, 1.02-2.67), 2.39 (95% CI, 1.21-4.73) and 2.08 (95% CI, 1.26-3.44). All of these ORs, except those for highest quintiles of waist and neck circumferences remained significant in multiple adjusted models.CONCLUSIONSAccording to the results of this study, female AGA (grade II or III on Ludwig's scale) was quite common among Finnish women aged 63 years. Our results support the hypothesis that women with some markers of insulin resistance have significantly increased risk for female AGA. Paternal history of alopecia seemed to be more common in female AGA compared to women with normal or minimal loss of hair.

Support Care Cancer. 2003 Jun;11(6):371-7. Epub 2003 Mar 21.

Scalp hypothermia to prevent chemotherapy-induced alopecia is effective and safe: A pilot study of a new digitized scalp-cooling system used in 74 patients.

Ridderheim M, Bjurberg M, Gustavsson A.

Department of Oncology, University Hospital, 221 85, Lund, Sweden

GOALS. The aim of this study was to examine the efficacy and safety of a new digitized, controlled, scalp-cooling system to prevent chemotherapy-induced alopecia. METHOD. Seventy-four female cancer patients who received 13 varying chemotherapy regimens were included in a nonrandomized pilot study. The Digni 2-3 with Dignicap system consists of a refrigerator unit and a control unit integrated into a mobile cabinet and connected to a tight-fitting cooling cap. This system maintains a constant scalp temperature of +5 degrees C for many hours. In this study, 60 patients were treated for ovarian cancer with either taxane or epirubicin combination chemotherapy. Eight patients with Hodgkin's lymphoma, three with breast cancer, two with endometrial cancer, and one with sarcoma were also included. Photo documentation and patient assessment of hair loss and discomfort were performed. RESULTS. In anthracycline-treated patients, total prevention of hair loss was observed, whereas hair loss in paclitaxel/docetaxel-treated patients was minimal to none. The combination of anthracycline and taxane resulted in more hair loss, but only three of six patients used a wig. Scalp cooling was generally very well tolerated; only two of 74 patients discontinued use of the cold cap due to discomfort. No scalp metastases occurred over a median follow-up period of 15 months. CONCLUSIONS. The digitized, controlled, scalp-cooling system represents an effective and safe device that should be clinically evaluated in a randomized trial and in studies using other chemotherapy regimens to determine optimal temperatures and durations of cooling for maximal efficacy.

Australas J Dermatol. 2003 May;44(2):106-9.

PUVA treatment of alopecia areata totalis and universalis: a retrospective study.

Whitmont KJ, Cooper AJ.

Royal North Shore Hospital, Pacific Highway, St Leonards, New South Wales, Australia.

The results of PUVA treatment of alopecia areata (AA) totalis and universalis were reviewed in 26 adult patients. Eight of 15 patients with AA totalis and six of 11 patients with AA universalis achieved a complete response (>90% hair regrowth). Patients with AA totalis had a greater incidence of treatment failure (<25% hair regrowth) than those with AA universalis. Patients with a family history of AA were significantly less likely to have a positive response to PUVA than those with no family history. Sex, age at diagnosis and treatment, interval between diagnosis and treatment, and background of atopy were not significant determinants of outcome. Although unable to show significance for clinical response to treatment, this study demonstrates complete hair regrowth in patients with both AA totalis (53%) and universalis (55%) while reporting a low relapse rate among these patients (21%) within a long period of follow up (mean 5.2 years).

Ann Dermatol Venereol. 2003 Mar;130(3):326-30.

Intravenous pulse methylprednisolone therapy for severe alopecia areata: an open study of 66 patients

[Article in French]

Assouly P, Reygagne P, Jouanique C, Matard B, Marechal E, Reynert P, Bachelez H, Dubertret L.

Centre de Sante Sabouraud, Paris.

INTRODUCTION: Treatment of alopecia areata is a difficult challenge. Some European publications have shown encouraging results with high dose pulse corticosteroid therapy in extensive plurifocal alopecia areata. We undertook a prospective open study between January 2000 and December 2001 using repeated pulse each month, with the aim of identifying the effects of this repetition and underlining the best indications. PATIENTS AND METHODS: Sixty-six patients aged 9 to 60 years old presenting an extensive alopecia areata exceeding 30% of the scalp surface (n=47), alopecia totalis (n=8), alopecia universalis (n=8), ophiasic alopecia (n=3), for less than 12 months entered this study. The administered treatment was methylprednisolone 500 mg/d during 3 days or 5 mg/kg twice per day during 3 days in children. These pulses were repeated after 4 and 8 weeks, then a second series was carried out or not according to cases. The main evaluation criterion was the percentage of new terminal hair appearing on the bald areas, appreciated by clinical and photographic evaluation at 3 and 6 months. RESULTS: Ophiasic alopecia areata did not respond to treatment. A quarter of patients presenting universal alopecia had a good response (higher than 80 p. 100) followed by a relapse in half the cases. Half of the patients presenting alopecia totalis had a good response, which was maintained three times out of four. Multifocal alopecia areata seems the best indication since the patients under study presented a good response in 63.8 p. 100 of cases (78 p. 100 when it was a first episode and 90.5 p. 100 if the treatment had been started in less than 3 months before). The repetition of the pulses did not appear to increase the number of responders. CONCLUSION: This study provides the best indication of pulse methylprednisolone therapy: first recent episode of extensive plurifocal alopecia areata. These results are less convincing in long term history or other forms of alopecia areata.

Br J Nurs. 2003 May 8-21;12(9):550-8.

Case study of alopecia universalis and web-based news groups.

Fox J.

Nursing and Midwifery Department, University College Worcester.

This article presents findings from an 18-month case study of a web-based news group used by individuals with alopecia universalis. Content analysis of 228 episodes of web-based communication that occurred in relation to themes of discussion was undertaken, supported by the use of concept mapping (Northcott, 1996). Analysis identified a core concept relating to that of a community of shared experience together with four supportive themes. The themes were the search for understanding and meaning, carrying on, seeking balance between past, present and future, and relating to new self, others, and the world. The article discusses the increased growth in the use of the web as a vehicle for exploring health concerns and the specific ethical and methodological issues raised by research in this area.

J Am Acad Dermatol. 2003 May;48(5):752-9.

Transplants from balding and hairy androgenetic alopecia scalp regrow hair comparably well on immunodeficient mice.

Krajcik RA, Vogelman JH, Malloy VL, Orentreich N.

Orentreich Foundation for the Advancement of Science Inc, Cold Spring-on-Hudson, New York 10516, USA.

Human hair follicles were grafted onto 2 strains of immunodeficient mice to compare the regeneration potential of vellus (miniaturized, balding) and terminal (hairy, nonbalding) follicles from males and a female exhibiting pattern baldness. Each mouse had transplants of both types of follicles from a single donor for direct comparison. Grafted follicles from 2 male donors resulted in nonsignificant differences in mean length (52 mm vs 54 mm) and mean diameter (99 microm vs 93 microm) at 22 weeks for hairs originating from balding and hairy scalp, respectively, corresponding to 400% versus 62% of the mean pretransplantation diameters. Follicles from the female donor transplanted to several mice also resulted in nonsignificant differences in length (43 mm vs 37 mm) for hairs from balding and hairy scalp, respectively, during a period of 22 weeks. The mean diameter of the originally vellus hairs increased 3-fold, whereas the terminal hairs plateaued at approximately 50% of pretransplantation diameter, resulting in a final balding hair volume double that of the nonbalding hairs. This report shows that miniaturized hair follicles of pattern alopecia can quickly regenerate once removed from the human scalp and can grow as well as or better than terminal follicles from the same individual.

J Invest Dermatol. 2003 May;120(5):771-5.

Major locus on mouse chromosome 17 and minor locus on chromosome 9 are linked with alopecia areata in C3H/HeJ mice.

Sundberg JP, Boggess D, Silva KA, McElwee KJ, King LE, Li R, Churchill G, Cox GA.

The Jackson Laboratory, Bar Harbor, Maine 04609-1500, USA.

Alopecia areata is an autoimmune disease that targets actively growing (anagen) hair follicles in humans, mice, rats, dogs, horses, and cattle. C3H/HeJ mice spontaneously develop alopecia areata from 5 mo of age and older in females and later in males. Frequency of disease approached 20% in a colony by 18 mo of age. C57BL/6J mice do not develop alopecia areata. A segregating F2 population of female mice (n=1096) was generated from crossing these two strains. Alopecia areata (n=138) and clinically normal (n=214) mice were genotyped at 12 mo of age using 211 microsatellite probes. The peak logarithm of odds ratio score on mouse chromosome 17 (10.9) was around marker D17Mit134 at 16.9 cM from the centromere. The mouse histocompatibility locus, H2, the mouse equivalent of human leukocyte antigen in humans, was a likely candidate. Twelve-month-old C3H.SW-H2b/SnJ mice (C3H/HeJ congenic mice in which the H2k purported susceptibility locus was replaced with the H2b purported resistance locus) did not develop alopecia areata, supporting this locus as being important in alopecia areata. A suggestive linkage was also found on mouse Chromosome 9 (logarithm of odds ratio score 2.0) around D9Mit206, 20 cM from the centromere. The interval on mouse Chromosome 17 contains several orthologous genes potentially associated with human alopecia areata.

Clin Immunol. 2003 Mar;106(3):181-7.

Transfer of alopecia areata in the human scalp graft/Prkdc(scid) (SCID) mouse system is characterized by a TH1 response.

Gilhar A, Landau M, Assy B, Ullmann Y, Shalaginov R, Serafimovich S, Kalish RS.

Skin Research Laboratories, Flieman Medical Center, Haifa, Israel.

Alopecia areata is an autoimmune condition directed at hair follicles, which results in loss of hair. We have previously demonstrated that it is possible to transfer hair loss, along with the immunohistologic findings of alopecia areata, to human scalp grafts on Prkdc(scid) (SCID) mice by injection of autologous activated lesional T-cells. This study examines the cytokine profile of T-cells and follicular epithelium following transfer of hair loss. Two consistent findings significantly (P < 0.01) associated with hair loss were production of interferon-gamma-inducible protein-10 kDa (IP-10) by follicular epithelium (13/13), and production of INF-gamma by infiltrating T-cells (10/12). Noninjected control grafts regrew hair, and were generally negative for IP-10 (positive 2/9), and INF-gamma (positive 2/9), but expressed of IL-10 on the follicular epithelium (7/9). These data support an INF-gamma TH1 pathogenesis for hair loss in alopecia areata.

Dermatology. 2003;206(3):189-91.

Association between Smoking and Hair Loss: Another Opportunity for Health Education against Smoking?

Trueb RM.

Department of Dermatology, University Hospital of Zurich, Switzerland.

Besides being the single most preventable cause of significant morbidity and an important cause of death in the general population, tobacco smoking has been associated with adverse effects on the skin. Smoke-induced premature skin ageing has attracted the attention of the medical community, while only recently an observational study has indicated a significant relationship between smoking and baldness. The mechanisms by which smoking causes hair loss are multifactorial and are probably related to effects of cigarette smoke on the microvasculature of the dermal hair papilla, smoke genotoxicants causing damage to DNA of the hair follicle, smoke-induced imbalance in the follicular protease/antiprotease systems controlling tissue remodeling during the hair growth cycle, pro-oxidant effects of smoking leading to the release of pro-inflammatory cytokines resulting in follicular micro-inflammation and fibrosis and finally increased hydroxylation of oestradiol as well as inhibition of the enzyme aromatase creating a relative hypo-oestrogenic state. In view of the psychological impact of androgenetic alopecia on affected men and women, increasing public awareness of the association between smoking and hair loss offers an opportunity for health education against smoking that may be more effective than the link between smoking and facial wrinkles or grey hair, since the latter can be effectively counteracted by current aesthetic dermatologic procedures, while treatment options for androgenetic alopecia are limited.

J Dermatol Sci. 2003 Apr;31(2):91-8.

The extract of Thujae occidentalis semen inhibited 5alpha-reductase and androchronogenetic alopecia of B6CBAF1/j hybrid mouse.

Park WS, Lee CH, Lee BG, Chang IS.

Skin Research Team, Skin Research Institute, Amore Pacific Corporation R&D Center 314-1 Bora-ri, Kiheung-eup, Yongin-si, Kyounggi-do, South Korea.

BACKGROUND: The conversion of testosterone to dihydrotestosterone; 5alpha-androstan-17beta-ol-3-one by 5alpha-reductase plays a crucial role in hair baldness and prostatomegaly. Recent approach showed specific inhibitors for 5alpha-reductase type 2 such as finasteride promoted hair growth in male pattern alopecia. OBJECTIVE: In order to search for effective medicinal plant extracts applied topically for androgenetic alopecia, we screened natural plant extracts having inhibitory activities of 5alpha-reductase type 2 and demonstrated its biological function in androgen-related animal models. METHODS: We evaluated the inhibition activities of numerous plant extracts by contact cell based metabolic method using a stable HEK 293 cell line expressing human 5alpha-reductase (type 2). To elucidate the biological activity in vivo, the Thujae occidentalis semen (TOS) extract was topically applied to fuzzy rat and androchronogenetic alopecia (AGA) mouse, respectively. The secreted sebum and the size of sebaceous glands of fuzzy rat were measured after 6 weeks. Also, after the topical treatment with TOS extract and androgen receptor antagonist (cyproterone acetate) simultaneously with subcutaneous injection of testosterone (1 mg/mice/day), hair loss patterns of female B6CBAF1/j hybrid mouse were observed. RESULTS: TOS extract showed higher inhibition activity of 5alpha-reductase type 2(IC(50) value=2.6 microg/ml) than that of gamma-linolenic acid, but lower than that of finasteride. When applied to fuzzy rat, the amount of sebum and sebaceous gland size decreased remarkably. In AGA model, alopecia degrees of two groups, treated with TOS extract (P<0.015) or cyproterone acetate (P<0.01), were lower than that of vehicle (propylene glycol:ethanol=7:3) and there was no difference between above two groups. CONCLUSION: We have demonstrated the inhibitory activity of TOS extract for 5alpha-reductase type 2 and its biological action in two animal models, suggesting that TOS extract would be used as an effective agent for male pattern baldness by modifying androgen conversion.

Vet Dermatol. 2003 Apr;14(2):91-7.

Retrospective evaluation of sex hormones and steroid hormone intermediates in dogs with alopecia.

Frank LA, Hnilica KA, Rohrbach BW, Oliver JW.

Department of Small Animal Clinical Sciences, University of Tennessee, Knoxville, TN 37996-4544, USA.

The purpose of this study was to determine if there are specific steroid hormone aberrations associated with suspect endocrine alopecias in dogs in whom hypothyroidism and hyperadrenocorticism have been excluded. Steroid hormone panels submitted to the UTCVM endocrinology laboratory over a 7.5-year period (783 samples) from dogs with alopecia were reviewed. During this period, 276 dogs met the criteria for inclusion and were comprised of 54 different breeds. Approximately 73% of dogs had at least one baseline or post-ACTH stimulation steroid hormone intermediate greater than the normal range. The most frequent hormone elevation noted was for progesterone (57.6% of samples). When compared with normal dogs, oestradiol was significantly greater in Keeshond dogs and progesterone was significantly greater in Pomeranian and Siberian Husky dogs. Not all individual dogs had hormone abnormalities. Chow Chow, Samoyed and Malamute dogs had the greatest percentage of normal steroid hormone intermediates of the dogs in this study. Baseline cortisol concentrations were significantly correlated with progesterone, 17-hydroxyprogesterone (17-OHP) and androstenedione. Results of this study suggest that the pathomechanism of the alopecia, at least for some breeds, may not relate to steroid hormone intermediates and emphasizes the need for breed specific normals.

Cell Struct Funct. 2003 Feb;28(1):97-104.

Autoimmune hair loss induced by alloantigen in C57BL/6 mice.

Zong ZP, Matsui S, Li AL, Katsuda S, Yamaguchi N.

Department of Serology.

Exponentially growing Meth-A cells expressing H-2K(d).D (d) antigen were found to induce alopecia when injected intraperitoneally into normal C57BL/6 mice, which express the H-2K(b).D (b) antigen. However, the capacity to induce alopecia disappeared when Meth-A cells were treated with K252a, which inhibits protein kinases. Histologically, skin in affected areas showed dense mononuclear cell infiltration and a focal foreign-body giant-cell reaction in hair follicles. The subtyping of lymphocytes in peripheral blood demonstrated a significant difference between normal mice and Meth-A cell-injected mice. To further examine the mechanism by which the alloantigen induces alopecia, lymphocytes isolated from the peripheral blood of normal C57BL/6 mice were cultured in medium containing Meth-A cell homogenate, phytohemagglutinin (PHA) and recombinant mouse interleukin-2 (rm IL-2), and intravenously injected into normal C57BL/6 mice. The adoptive transfer of the lymphocytes induced alopecia in a similar way. These findings suggest that the protein kinase-modulated alloantigen induces alopecia by disturbing the immunological homeostasis, and that lymphokine-activated killer cells play an important role in induction of alopecia by cross-reacting with hair follicles.

Br J Dermatol. 2003 Mar;148(3):553-7.

Compound heterozygosity for mutations in the hairless gene causes atrichia with papular lesions.

Indelman M, Bergman R, Lestringant GG, Peer G, Sprecher E.

Department of Dermatology and Laboratory of Molecular Dermatology, Rambam Medical Center, Haifa, Israel.

BACKGROUND: Congenital atrichias represent a complex and heterogeneous group of genodermatoses, which have been shown in several consanguineous families to result from homozygous mutations in the hairless gene (HR). OBJECTIVES: To identify the molecular basis of congenital atrichia in a non-consanguineous family. METHODS: Genetic analysis was carried out in a two-generation family with two children with congenital atrichia and one healthy child. RESULTS: We established a diagnosis of atrichia with papular lesions based on clinical and histopathological data. We identified a heterozygous 11-bp deletion (189-199del) in the two affected children and their mother. In addition, the two affected children and their father were shown to carry a non sense mutation (Q478X), which has previously been described in a Pakistani family. Haplotype analysis revealed that mutation Q478X occurred independently in the two families. CONCLUSIONS: We have identified the first case of compound heterozygosity for mutations in HR as well as the first instance of a recurrent mutation in this gene. These data further expand our understanding of the molecular pathomechanisms underlying congenital atrichias.

Am Fam Physician. 2003 Mar 1;67(5):1007-14.

Alopecia in women.

Thiedke CC.

Department of Family Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.

Alopecia can be divided into disorders in which the hair follicle is normal but the cycling of hair growth is abnormal and disorders in which the hair follicle is damaged. Androgenetic alopecia is the most common cause of hair loss in women. Other disorders include alopecia areata, telogen effluvium, cicatricial alopecia, and traumatic alopecias. The diagnosis is usually based on a thorough history and a focused physical examination. In some patients, selected laboratory tests or punch biopsy may be necessary. Topically administered minoxidil is labeled for the treatment of androgenetic alopecia in women. Corticosteroids and other agents are typically used in women with alopecia areata. Telogen effluvium is often a self-limited disorder. Because alopecia can be devastating to women, management should include an assessment for psychologic effects.

Dermatol Online J. 2003 Feb;9(1):4.

Pilot study of a novel treatment for androgenetic alopecia using enriched cell culture medium: clinical trials.

Lindenbaum ES, Feitelberg AL, Tendler M, Beach D, Gamliel-Lazarovich A, Har-Shai Y, Hirshowitz B.

Androgenetic Alopecia (AA) afflicts a large part of the population and of the many treatments available today none is completely satisfactory. Testing the efficacy and safety of a novel topical treatment for AA which is based on cell culture medium supplemented with insulin, thyroxin and growth hormone (CCM). The 48 participants classified as androgenetic alopecia Type II, III or IV on the Hamilton scale, concluded a randomized, vehicle-controlled, double-blind trial of 6 months duration. Under occlusive cover the gel was self applied for at least 3 hours daily. Evaluation was based on hair counts, investigator global assessment and participants self-administered questionnaire. Cessation of hair loss was reported by most participants within 28 weeks, and further confirmed by the hair count (HC) in ~80% of participants. Moreover, as early as 4 months after the start of the treatment, a time dependent increase of up to 50% in HC was observed. The average change in HC between the two groups differed significantly (p=0.007), with values of 4.1% for control and 13.8% for CCM. Following 4 months of treatment, a time dependent increase in HC (>10%) above minimal was observed in 55% of the CCM and 25% of the control and this trend continued. At 6 months 63% of the CCM and 33% of the control group exhibited increase of HC higher than 10%. The average increase in HC in the CCM and the control groups was 17.1% and 8.9% respectively (p=0.035). Self evaluation questionnaires revealed a time dependent increase in satisfaction in the CCMusers compared to the control. While the average score at T2 was similar in CCM and control (2.7 and 2.6 respectively), the score at T6 in the CCM increased to 5.9 and decreased to -0.4 in the control (p=0.007). Global-clinical evaluation following six months treatment revealed significantly (p=0.02) more hair loss in the control group (40%) compared to the CCM (7%) treated group. CCM was found effective in treating androgenetic alopecia in men. It induced cessation of hair loss, increased rate of hair growth and appearance of new hair. No side effects were reported or observed.

Dermatol Surg. 2003 Mar;29(3):230-4; discussion 234.

Corrective hair restoration techniques for the aesthetic problems of temperoparietal flaps.

Brandy DA.

Department of Dermatology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.

BACKGROUND: Temperoparieto-occipital flaps (Juri flap) and temperoparietal flaps (Elliott) were commonly performed in the previous decades but have fallen out of favor for the most part with the development of follicular unit hair transplantation. Besides high complication rates, these procedures created straight abrupt hairlines in many cases, posterior hair direction, hair density that was disproportionately thick, and blunt temperofrontal angles. OBJECTIVE: Because there are many patients who live with cosmetic deformities created by previous flap procedures, the objective of this article is to present a series of techniques that will restore these patients to normal cosmesis. METHODS: The techniques for amelioration of poor cosmesis secondary to flap procedures are (1) undulating follicular unit grafting anterior to the hairline, (2) removal of 2- to 3-mm cylinders of hair-bearing scalp at the anterior hairline, (3) removal of 2- to 3-mm cylinders of hair-bearing scalp from within the flap itself, and (4) appropriate fusiform excision techniques to create a normal temperofrontal angle. RESULTS: The combination of the aforementioned techniques has restored a very natural cosmesis in patients who have poor aesthetics after flap surgery. CONCLUSION: Many patients exist who have had Juri and Elliott flaps. Although the cosmetic deformities that are created from these flaps are difficult to improve, they can be ameliorated effectively through a series of maneuvers that are described in this article.

Hum Genet. 2003 Apr;112(4):400-3. Epub 2003 Feb 14.

Notch4, a non-HLA gene in the MHC is strongly associated with the most severe form of alopecia areata.

Tazi-Ahnini R, Cork MJ, Wengraf D, Wilson AG, Gawkrodger DJ, Birch MP, Messenger AG, McDonagh AJ.

Dermato-Immunogenetics Group, Biomedical Genetics Project, Division of Genomic Medicine, D Floor Medical School, Royal Hallamshire Hospital, University of Sheffield, Sheffield, S10 2RX, UK.

Alopecia areata (AA) is a disorder primarily affecting the hair and nails in which associated autoimmune or atopic disease is common. Genetically, it is a complex trait with evidence of a role for genes of the major histocompatibility complex (MHC), the interleukin-1 cluster and chromosome 21 in the pathogenesis. The strongest association is with HLA class II alleles, although whether this indicates a direct contribution to the pathogenesis or results merely from linkage disequilibrium with nearby disease genes is unknown. Notch4 is a recently defined gene in the HLA class III region. Notch signalling is a direct determinant of keratinocyte growth arrest and entry into differentiation. A possible role for Notch in hair growth has been indicated by transgenic mouse findings that activation of the Notch pathway in the hair cortex leads to aberrant differentiation of adjacent hair-shaft layers. Notch4 is therefore a plausible candidate gene for AA. We have examined two polymorphisms in the coding sequence of the Notch4 gene at positions +1297 and +3063 in a case-control study of 116 AA patients and 142 ethnically matched, healthy control subjects. The initial analysis showed a significant association of AA in the overall data set with the Notch4(T+1297C) polymorphism (P<0.001) but not with Notch4(A+3063G). To confirm this association, we genotyped an additional 62 patients and found that the risk for disease was higher in Notch4(+1297C) homozygotes [odds ratio (OR) 3.43 (1.63, 7.19)] than in heterozygotes [OR 2.58 (1.57, 4.24)]. On classifying the patients by severity of disease, the association appeared to be confined to the severest form (alopecia universalis) [OR 4.02 (1.64, 9.88), P=0.0014]. These results support previous findings showing that different HLA susceptibility alleles are associated with mild and severe AA.

Australas J Dermatol. 2003 Feb;44(1):62-6.

Androgenetic alopecia in a postmenopausal woman as a result of ovarian hyperthecosis.

Kim Y, Marjoniemi VM, Diamond T, Lim A, Davis G, Murrell D.

Clinical School and Department of Anatomical Pathology, University of New South Wales, New South Wales, Australia.

A 65-year-old woman presented with an 8-year history of progressive frontotemporal alopecia and hirsutism. She had elevated serum levels of testosterone, androstenedione and estradiol. Ultrasound and computed tomography imaging suggested a right ovarian mass, while bilateral ovarian venous sampling demonstrated increased testosterone levels originating from both ovarian veins. Histology obtained following bilateral oophorectomy demonstrated bilateral ovarian hyperthecosis. Six months after surgery, the patient remains well with no progression of the alopecia. Ovarian hyperthecosis is a rare cause of androgenetic alopecia in postmenopausal women. The role of hyperthecosis and its relationship to androgenetic alopecia is reviewed.

Australas J Dermatol. 2003 Feb;44(1):10-8.

Methods of evaluating hair growth.

Chamberlain AJ, Dawber RP.

Department of Dermatology, Churchill Hospital, Headington, Oxford, United Kingdom.

For decades, scientists and clinicians have examined methods of measuring scalp hair growth. With the development of drugs that stem or even reverse the miniaturization of androgenetic alopecia, there has been a greater need for reliable, economical and minimally invasive means of measuring hair growth and, specifically, response to therapy. We review the various methods of measurement described to date, their limitations and value to the clinician. In our opinion, the potential of computer-assisted technology in this field is yet to be maximized and the currently available tools are less than ideal. The most valuable means of measurement at the present time are global photography and phototrichogram-based techniques (with digital image analysis) such as the 'TrichoScan'. Subjective scoring systems are also of value in the overall assessment of response to therapy and these are under-utilized and merit further refinement.

Cancer Res. 2003 Jun 15;63(12):3037-42.

Inhibition of the Development of Metastatic Squamous Cell Carcinoma in Protein Kinase C epsilon Transgenic Mice by alpha-Difluoromethylornithine Accompanied by Marked Hair Follicle Degeneration and Hair Loss.

Wheeler DL, Ness KJ, Oberley TD, Verma AK.

Departments of Human Oncology [D. L. W., K. J. N., A. K. V.] and Pathology and Laboratory Medicine [T. D. O.], Medical School, University of Wisconsin, Madison, Wisconsin 53762, and Veterans Administration Hospital, Madison, Wisconsin 53705 [T. D. O.].

The role of 12-O-tetradecanoylphorbol-13-acetate (TPA)-stimulated polyamine biosynthesis in the development of metastatic squamous cell carcinoma (mSCC) in protein kinase C epsilon (PKCepsilon) transgenic mice was determined. TPA treatment induced epidermal ornithine decarboxylase (ODC) activity and putrescine levels approximately 3-4-fold more in PKCepsilon transgenic mice than their wild-type littermates. Development of mSCC by the 7,12-dimethylbenz(a)anthracene (100 nmol)-TPA (5 nmol) protocol in PKCepsilon transgenic mice was completely prevented by administration of the suicide inhibitor of ODC alpha-difluoromethylornithine (DFMO, 0.5% w/v) in the drinking water during TPA promotion. However, DFMO treatment led to marked hair loss in PKCepsilon transgenic mice. DFMO treatment-associated hair loss in PKCepsilon transgenic mice was accompanied by a decrease in the number of intact hair follicles. These results indicate that TPA-induced ODC activity and the resultant accumulation of putrescine in PKCepsilon transgenic mice are linked to growth and maintenance of hair follicles, and the development of mSCC. Severe hair loss observed in PKCepsilon transgenic mice on DFMO during skin tumor promotion has not been reported before in the prevention of cancer in other animal models or in human cancer prevention trials.

Eur J Dermatol. 2003 Mar-Apr;13(2):150-60.

Efficacy and tolerability of finasteride 1 mg in men aged 41 to 60 years with male pattern hair loss.

Whiting DA, Olsen EA, Savin R, Halper L, Rodgers A, Wang L, Hustad C, Palmisano J.

Dallas Associated Dermatologists, 3600 Gaston Avenue, #1051 LB76, Dallas, TX 75246, USA.

A 24-month double-blind, randomized, placebo-controlled, parallel-group, multicenter study of 424 men was conducted to determine the efficacy and tolerability of finasteride 1 mg on hair growth/loss in men aged 41 to 60 years with mild-to-moderate, predominantly vertex male pattern hair loss. Efficacy was evaluated by review of global photographs of the vertex scalp taken at baseline and at Months 6, 12, 18, and 24 and by patient self-assessments and investigator clinical assessments of change from baseline in hair growth/loss collected at Months 6, 12, 18, and 24. Safety analyses included assessment of clinical and laboratory adverse experiences, including sexual adverse experiences. Analysis of global photographic assessment data showed significant improvement in hair growth for men in the finasteride group compared with those taking placebo beginning at Month 6 (p < 0.001) and maintained through Month 24 (p < 0.001). Results of the patient self-assessment and investigator assessments were consistent with those from the global photographic assessment. Finasteride 1 mg improved scalp hair growth in men aged 41 to 60 years with predominantly vertex male pattern hair loss compared with results seen with placebo. Improvement was evident by 6 months of treatment and continued through 24 months. Treatment with finasteride 1 mg was generally well tolerated.

Pediatrics. 2003 Mar;111(3):685-7.

Toe tourniquet syndrome in association with maternal hair loss.

Strahlman RS.

Department of Pediatrics, Patuxent Medical Group, Columbia, MD 21045, USA.

Increased hair loss a few months after delivering an infant is a common postpartum condition known as telogen effluvium. A much less common condition involving young infants is the hair-thread tourniquet syndrome, or toe tourniquet syndrome, which involves hair or thread becoming so tightly wrapped around an appendage that pain, injury, and sometimes loss of the appendage result. This case report is the first known description of the hair-thread tourniquet syndrome in association with maternal telogen effluvium. A literature review shows that accidental cases involving human hair almost always involve the toes, and usually occur at the age when mothers are experiencing excessive hair loss. This association is significant in that anticipatory guidance of new parents experiencing rapid hair loss may prevent cases of the toe tourniquet syndrome and its associated morbidity.

J Liposome Res. 2002 Feb-May;12(1-2):143-8.

Follicular liposomal delivery systems.

Ciotti SN, Weiner N.

Johnson & Johnson Consumer Products, Skillman, NJ 08558, USA.

Traditionally, the prime pathway for the topical delivery of active agents across the skin was thought to be through intercellular routes and transcellular routes of the stratum corneum. However, alternative means such as via appenageal transport, i.e., follicular transport, is gaining more acceptances in the scientific community. Targeting specific sites of the hair follicle may represent a feasible therapeutic approach to skin diseases such as hair loss. It is therefore an object of this research to develop novel liposomal formulations for enabling the topical delivery of difficult-to-absorb agents for localized action, specifically to the hair follicles and sebaceous glands. We examined small and large molecules. The small molecule chosen was minoxidil, a known hair growth stimulator. The large molecular weight molecule was plasmid DNA encoded with interleukin-1 receptor antagonist protein (IL-1ra).

Am J Pathol. 2003 Mar;162(3):803-14.

Stress inhibits hair growth in mice by induction of premature catagen development and deleterious perifollicular inflammatory events via neuropeptide substance P-dependent pathways.

Arck PC, Handjiski B, Peters EM, Peter AS, Hagen E, Fischer A, Klapp BF, Paus R.

Department of Internal Medicine, Charite School of Medicine, Humboldt University, Berlin, Germany.

It has been much disputed whether or not stress can cause hair loss (telogen effluvium) in a clinically relevant manner. Despite the paramount psychosocial importance of hair in human society, this central, yet enigmatic and controversial problem of clinically applied stress research has not been systematically studied in appropriate animal models. We now show that psychoemotional stress indeed alters actual hair follicle (HF) cycling in vivo, ie, prematurely terminates the normal duration of active hair growth (anagen) in mice. Further, inflammatory events deleterious to the HF are present in the HF environment of stressed mice (perifollicular macrophage cluster, excessive mast cell activation). This provides the first solid pathophysiological mechanism for how stress may actually cause telogen effluvium, ie, by hair cycle manipulation and neuroimmunological events that combine to terminate anagen. Furthermore, we show that most of these hair growth-inhibitory effects of stress can be reproduced by the proteotypic stress-related neuropeptide substance P in nonstressed mice, and can be counteracted effectively by co-administration of a specific substance P receptor antagonist in stressed mice. This offers the first convincing rationale how stress-induced hair loss in men may be pharmacologically managed effectively.

Am J Clin Dermatol. 2003;4(6):371-8.

Skin aging and menopause : implications for treatment.

Raine-Fenning NJ, Brincat MP, Muscat-Baron Y.

Academic Division of Reproductive Medicine, University of Nottingham, Nottingham, UK.

The skin is one of the largest organs of the body, which is significantly affected by the aging process and menopause. The significant changes sustained by the skin during the menopause are due to the effect sustained on the skin's individual components.The estrogen receptor has been detected on the cellular components of the skin. Accordingly, dermal cellular metabolism is influenced by the hypoestrogenoemic state of menopause leading to changes in the collagen content, alterations in the concentration of glycoaminoglycans and most importantly the water content. Consequently changes in these basic components leads to an alteration in function compatible with skin aging.Changes in the skin collagen leads to diminished elasticity and skin strength. Collagen content may be measured by various methods such as direct skin biopsy, skin blister assessment for collagen markers and skin thickness measurement. All these variables indicate a reduction in collagen content following menopause. This may be reversed with the administration of estrogen given both topically and systemically.A reduction in hydrophilic glycoaminglycans leads to a direct reduction in water content, which influences the skin turgor. These effects on glycoaminoglycans, due to the hypoestrogenia, have been clearly shown in animal studies and appeared to be rapidly reversed with the application of estrogens. The sum total of these basic effects on the skin leads to wrinkles, the skin condition typifying skin aging.Structures resident in the skin are likewise influenced by menopause. Changes to the cutaneous vascular reactivity are noted following menopause. Capillary blood flow velocity decreases significantly in postmenopausal women. Postmenopausal flushing is due to profound vasodilatation in the dermal papillae. Hair growth is also influenced by the hormonal milieu and consequently hair loss has been associated with the beginning of menopause.Treatments administered for menopause, in particular hormone replacement therapy, appear to alter its effects on the basic components of the skin as well as the more complex structures residing in the skin, consequently retarding the skin aging process.

What is hair?

Curly Hair

Biology of hair growth and development.

The phenomenon of hair loss.

Methods and treatments for hair loss and baldness.

Drugs and hair transplantation surgery for hair loss and baldness.

Hair loss linked to other health problems

Baldness by choice and fashion

Alopecia info.

Alopecia treatment info.

Hair care info.

Hair loss and alopecia research articles: abstracts and source links.

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