Hair Transplantation for Men with Advanced Degrees of Hair Loss

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Plastic and Reconstructive Surgery 2003; 111(1):414-421
Hair Transplantation for Men with Advanced Degrees of Hair Loss

In the field of surgical hair restoration, there is probably no greater challenge than treating the individual with advanced male pattern hair loss. Recent developments in follicular unit grafting and recognition of the natural appearance of the transplanted frontal forelock have now made it possible to obtain excellent, undetectable results in these patients. Over a 22-month period, the onset correlating with the time when the author began to use the technique of follicular unit grafting, 61 of 322 hair transplant procedures (approximately 20 percent) performed for male pattern hair loss were on men with, or at high risk of developing, advanced male pattern hair loss. Uniformly, the creation of some type of frontal forelock provided excellent results and high patient satisfaction. The concept of the frontal forelock is not new. Developments in aesthetic principles, enhanced understanding of its applicability, and the applied advantages of follicular unit grafting allow for the first time, truly undetectable results.

J Invest Dermatol 2002 Aug;119(2):392-402

Gene array profiling and immunomodulation studies define a cell-mediated immune response underlying the pathogenesis of alopecia areata in a mouse model and humans.

Alopecia areata is a suspected autoimmune hair loss disease. In a rodent model, alopecia areata can be induced in normal haired C3H/HeJ mice by transfer of skin grafts from mice with spontaneous alopecia areata. At weeks 2, 4, 6, and 10 after surgery, grafted mice were euthanized, skin collected and processed for histology, and RNA extracted. Age-matched sham-grafted mice, and mice with and without spontaneous alopecia areata, were similarly processed. For comparison, skin biopsies from alopecia areata and androgenetic alopecia affected humans were also collected. Skin mRNA processed to cDNA was analyzed using Affymetrix mouse 11K and human 6800 gene chip(R) array technology. Microarray results indicated 42 known genes upregulated or downregulated during onset of mouse alopecia areata consistent with an inflammatory cell-mediated disease pathogenesis involving antigen presentation, costimulation, and a T helper 1 lymphocyte response. In contrast, 114 genes, many regulating immunoglobulin response, were altered late in disease development. In alopecia areata affected humans, 95 genes were significantly modulated. As confirmation of microarray analysis results, lymph node and spleen cells from alopecia areata affected mice injected into normal haired littermates transferred the alopecia areata phenotype. Alopecia areata onset could be inhibited in skin-grafted mice by modulation with B7.1- and B7.2-specific monoclonal antibodies. In addition, depletion of CD4+ CD8+ expressing cells in chronic alopecia areata affected mice using monoclonal antibodies permitted hair regrowth. The results consistently demonstrated the importance of an immune cell-mediated disease mechanism in alopecia areata pathogenesis and suggested targeting antigen-presenting cells and reactive lymphocytes may be effective in alopecia areata treatment.

J Clin Endocrinol Metab 2001 Dec;86(12):5762-4

Production rates of dihydrotestosterone in healthy men and women and in men with male pattern baldness: determination by stable isotope/dilution and mass spectrometry.

Production rates of dihydrotestosterone (DHT) were determined in healthy men (n = 8), in healthy women during the follicular phase of their menstrual cycle (n = 7), and in young men with male pattern baldness (n = 8) using the stable isotope dilution technique and mass spectrometry. [2,3,4-(13)C]DHT was infused for 10 h at doses of 15 microg/h (men) and 2 microg/h (women), and blood samples were obtained at 20-min intervals during the last 4 h of the observation period. Production rates estimated between April and June were 2.9 +/- 1.1 microg/h (women) and 17.8 +/- 6.2 microg/h (men). In men production rates of DHT were similar (16.2 +/- 7.7 microg/h) when the investigation was repeated between October and December. Mean production rates of DHT in young men with male pattern baldness (60 +/- 50 microg/h) were higher than those in healthy men (P < 0.005). Although this group included two individuals with normal production rates of DHT, the production rate of DHT was markedly elevated (range, 32.0-161.0 microg/h) in the remaining patients. Stable isotope-labeled infusions of DHT are suitable for clinical use in a routine setting to obtain analytically correct estimates of DHT production in vivo. In the majority of men with male pattern baldness endogenous production of DHT is markedly increased, providing a rationale for therapeutic 5 alpha-reductase inhibition in this disorder.

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.

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.

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