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Peruvian Hair Loss Treatment Summary


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Structure and function of the hair follicle

The main functions of mammalian hair are insulation and camouflage. These are no longer necessary for the naked ape, although vestiges of this remain in the seasonal patterns of our hair growth (Randall and Ebling 1991) and the erection of our body hairs when shivering with cold. Mammals often have specialised hairs as neuroreceptors e.g. whiskers and this remains slightly in human body hair with its good nerve supply. However, the main functions of human hair are protection and communication. Eyelashes and eyebrow hairs prevent substances entering the eyes and scalp hair may protect the scalp and back of the neck from sun damage during our upright posture. During puberty the development of axillary and pubic hair signals the beginning of sexual maturity in both sexes (Marshall and Tanner 1969 1970 Winter and Faiman 1972 1973) while the male beard, like the mane of the lion, readily distinguishes the sexes. 6.2.2 Structure of the hair follicle Each hair is produced by a hair follicle....

The mechanism of androgen action in the hair follicle

Papilla Whisker

The form of testosterone or its more potent metabolite, 5a-dihydrotestosterone. The hormone-receptor complex, generally in combination with transcriptional regulators then activates the appropriate gene transcription for that cell type. Androgen insufficiency patients without functional androgen receptors demonstrate the essential requirement for androgen receptors within hair follicles for the development of the hair growth ascribed in 6.3.2 to androgens (Hiort, this volume Chapter 3). These individuals produce no body hair at puberty, even with high circulating androgen levels, nor do they go bald (Fig. 6.3). Men with 5a-reductase deficiency also contribute to our understanding because they exhibit axillary and female pattern pubic hair, but very little beard growth they are not reported to have male pattern baldness either (Griffin and Wilson 1989) (Fig. 6.3). A role for 5a-reductase in male pattern baldness is also supported by the ability of oral finasteride, a 5a-reductase type...

The paradoxical effects of androgens on human hair growth

Vellus Hair

6.3.1 Human hair growth before and after puberty In utero the humanbodyiscoveredwith quite long, colourless lanugo hairs. These are shed before birth and at birth, or shortly after, babies normally exhibit pigmented, quite thick protective hairs on the eyebrows and eyelashes and variable amounts on the scalp by the age of three or four the scalp hair is usually quite well developed, though it will not yet have reached its maximum length. These readily visible pigmented hairs are known as terminal hairs and are formed by large deep terminal follicles (Fig. 6.2). This emphasises that terminal hair growth on the scalp, eyelashes and eyebrows is not androgen-dependent. The rest of the body is often considered hairless but, except for the glabrous skin of the lips, palms and sole of the feet, is normally covered with fine, short almost colourless vellus hairs produced by small short vellus follicles (Fig. 6.2). The molecular mechanisms involved in the distribution and formation of the...

Clinical studies with finasteride in men with androgenetic alopecia

As in the development program in men with BPH, initial clinical studies with finasteride in men with male pattern hair loss (androgenetic alopecia, AGA) were directed toward demonstration ofbiochemical efficacy (Kaufman 1996). Androgen receptor number, DHT content and 5aR activity were all reported to be higher in balding than non-balding scalp from subjects with AGA, lending further support to the hypothesis that lowering DHT content in the scalp would be useful in the treatment of patients with AGA (Dallob et al. 1994 Price 1975 Randall et al. 1991 Sawaya 1991). Subsequent immunolocalization and enzyme inhibitor studies demonstrated that type 2 5aR protein was expressed in structures within the hair follicle (Bayne et al. 1999 Hoffmann and Happle 1999). The early studies with finasteride in men with AGA demonstrated that daily oral administration reduced the DHT content ofthe affected scalp in a dose-dependent manner, based on analysis of scalp biopsies, and suggested that the dose...

The treatment of androgenpotentiated hair disorders

6.5.1 Androgenetic alopecia Currently, the most effective treatment for male pattern baldness is the transplant of follicles from non-balding sites into the balding region, capitalising on the retention ofthe different intrinsic responses to androgen discussed earlier. This has significant disadvantages not only is it very invasive and heavily reliant on the skill of the operator for a good cosmetic result, but the alopecia continues to progress behind the transplanted area so that further transplants are often required. Antiandrogen therapy is not a practical option for men due to the side-effects, but cyproterone acetate, in combination with estrogen to ensure contraception, has been used in women. It increased the percentage of hair follicles in anagen and may cause some regrowth, but is probably most effective in preventing further progression (Dawber and Van Neste 1995 Peereboom-Wynia et al. 1989). Since cyproterone acetate is unavailable in the USA, spirolactone and high-dose...

Alopecia Clinical Summary

It can be classified into scarring (absence of follicles) and nonscarring (presence of follicles) alopecia. Scarring alopecia is commonly caused by discoid lupus erythematosus (erythematous mottled pigmentation and atrophic scalp scarring) and folliculitis decalvans (multiple crops of pustules on the scalp). Occasionally, prolonged bacterial and inflammatory fungal infections (kerion) can induce scarring on the scalp. Nonscarring alopecia results from alopecia areata (annular areas of alopecia on the scalp or beard area), telogen effluvium (diffuse scalp shedding of hair 2 to 3 months after a stressful event, illness, or new medication), anagen effluvium (diffuse scalp shedding after chemotherapy), trichotillomania (constant pulling of the hair), traction alopecia (chronic tension of braided hair causing alopecia), and tinea capitis. Syphilis can cause a patchy, moth-eaten alopecia.

Serum dihydrotestosterone DHT

Determination of dihydrotestosterone (DHT) does not play a role in routine monitoring oftestosterone replacement therapy, but maybe of importance in experimental use of testosterone preparations and monitoring biological effects of androgens. Due to the high 5a-reductase activity in skin, transdermal testosterone application is associated with increased serum DHT-levels this applies especially to scrotal application. The DHT adds to the overall androgenicity of the preparation and a patient receiving transdermal treatment maybe well substituted clinically although his serum testosterone does not reflect this. In these cases occasional measurement of serum DHT maybe indicated (see Chapter 21).

Transplanted Hairs

Are you over 55, and has the hair loss taken place slowly over many years possible cause Male-pattern baldness (which can also affect women) typically causes this type of hair loss. In this condition, which often runs in families, hair follicles are oversensitive to the male hormone testosterone. In women, the levels of these hormones in the body often rise after the menopause. action Hair loss cannot be prevented. Recent treatments, such as the drug minoxidil applied to the scalp or finasteride taken as tablets, will produce hair regrowth in some people, but this growth will be lost again when the treatment is discontinued. Surgical transplantation of hairs is another option (see Hair transplant, above). action Treat your hair gently, avoiding the excessive use of chemicals (perms and dyes) or heat on your hair. If your hair loss is extensive, or if you are concerned, consult your doctor. possible causes Patchy hair loss may be the result of ringworm (especially if the scalp is...

Hair Loss

Hair loss, known as alopecia, is a fairly common side effect of chemotherapy or radiation to the scalp. Severity may range from hair thinning to complete loss of hair. Strangely, when hair grows back, it may be softer, thicker, or of a different texture than before. Sometimes gray hair that falls out is replaced with hair of the patient's original color. Occasionally, patients may also lose hair in other area of the body, such as from the eyebrows, arms, groin, and so on. Although much less disturbing to the body's functioning than nausea or other side effects, patients are often devastated psychologically by hair loss because hair is frequently an integral part of the patient's body image. To minimize hair loss and protect new hair that's growing in Though unproven, some patients wear an ice turban or keep cold compresses on the head during chemotherapy treatments to inhibit the drugs from reaching the hair follicles. If hair loss is expected, choose a wig before treatment. Synthetic...

Cytotoxic Chemotherapeutic Agents

Cytotoxic chemotherapeutic agents can be defined as those that inhibit tumor growth by killing tumor cells directly. These agents rely on tumor cells' dividing more rapidly than normal cells to achieve an acceptable therapeutic index. Still, their actions are necessarily nonspecific and many common cyto-toxic chemotherapy side effects (e.g., myelosuppression, alopecia) reflect effects on normal dividing cells. General indications for cytotoxic chemotherapy include curing certain tumors, palliating symptoms, or prolonging progression-free survival. Most patients with a CNS tumor receive chemotherapy for this last reason. Relative contraindications include active infections, limited probability of prolonged survival even if tumor regression occurs, and severe debilitation.

Keeping Track Of Your Side Effects

* Examples dry mouth, urinating frequently, rash, acne, stomachaches, insomnia, headaches, fatigue, hair loss, problems with concentration, hand tremor, If you're not sure which medication causes which side effect, simply list each side effect you experience and put a * next to each one.

Sex Hormones and OPLL

Estrogen and androgen play an important role in bone metabolism, and deficiency of these sex hormones causes bone loss. Motegi et al. reported that serum total estrogen levels are elevated in male OPLL patients, whereas serum levels of 5a-dihydrotestosterone are low 13 . They also studied estrogen receptors in surgical specimens of OPLL tissues using a receptor-binding assay and found that estrogen receptors in cells from the posterior longitudinal ligaments of OPLL patients had higher affinities than those from non-OPLL patients. Because estrogen is shown to stimulate the synthesis of growth factors such as IGF-I 19 and transforming growth factor-P (TGFP) 20 in osteoblastic cells, the observed changes in serum estrogen and tissue estrogen receptors may be associated with increased production of these growth factors in OPLL tissues. However, these results cannot explain why there are many more male than female patients with OPLL.

Influence of testosterone on sexual behaviour in men

Indeed, in several studies a significant relationship between physiological androgen levels and male sexual behaviour was observed. In a Swedish epidemiological investigation of 500 men aged 51 years low levels of non SHBG-bound testosterone were associated with low sexual interest (Nilsson et al. 1995). In young soldiers aged 18 to 22 years serum concentrations of 5a-dihydrotestosterone were a significant hormonal determinant of orgasmic frequency (Mantzoros et al. 1995). In young healthy volunteers Knussmann et al. (1986) could ascertain significantly positive correlations of salivary and total serum testosterone with the frequency of orgasms during the 48 hours following blood sampling. In their study, the majority of intraindividual correlation coefficients (from 6 samples per subject) were also positive but some negative and insignificant ones were found as well. This finding points to the great interindividual variability of behavioural responses to

Endogenous testosterone levels

In contrast to Shute etal. (1983) and Gouchie and Kimura (1991), several studies have shown a significant linear testosterone-cognitive relationship. Gordon and Lee (1986) investigated 32 men with four visual-spatial and four verbal tests and determined testosterone levels of their subjects. Testosterone concentrations correlated significantly positively with one spatial orientation task, but not with any of the other spatial or verbal tests. The study by Christiansen and Knussmann (1987b) attempted a broader investigation of the effects of androgens on spatial and non-spatial cognitive abilities in a larger sample of 117 men in their twenties. They collected blood and saliva samples to determine serum concentrations of testosterone, non SHBG-bound saliva testosterone, and 5a-dihydrotestosterone (DHT). Cognitive functioning was ascertained by 11 spatial and verbal ipsative test scores, reflecting intraindividual variance in the performance of these tasks, independent of the person's...

What happens if I develop bone pain

When multiple painful bone metastases are present, hemibody radiation may be used. Because this therapy affects a larger area of the body, there are more side effects, including lowering of the blood pressure (hypotension), nausea, vomiting, diarrhea, lung irritation, hair loss, and lowering of the blood count. Hemibody radiation is also given over several treatment sessions. It can lead to pain control that lasts up to one year in as many as 70 of individuals.

Regulation Of Hifa Molecules

Lectin perfusion demonstrated an increase in the number of small-caliber vessels and capillaries immediately beneath the epidermis and surrounding each hair follicle. The latter observation is consistent with keratin-14 expression in the hair outer root sheath cells. Lectin perfusion additionally demonstrated that the architecture in the skin microvessels of K14-HIF-1aAODD transgenic mice was normal, but computer analysis of microvascular density revealed a 60 increase in the number of microves-sels per unit length area in the transgenic compared to the nontransgenic mice (Elson et al. 2001). Figure 4. Transgenic mice expressing a constitutively active HIF-1a mutant lacking the ODD display increased vascularity. Expression of the HIF-1aAODD cDNA was targeted to the basal keratinocytes of skin using a keratin-14 promoter. Compared to nontransgenic littermate controls (A), the transgenic mice evidence a pinker color of unfurred skin, prominent vascularity of the ears, and a slight coat...

Radiation Therapy

Complications associated with radiation therapy can be divided into two time frames acute effects occurring during or shortly after treatment, and late effects occurring months to years after completion of treatment. Acute side effects in adults are usually more pronounced than in children and consist of nausea, vomiting, fatigue, alopecia, skin erythema, significant

Bone density in men with disorders of androgen action

A clinical model of androgen effects on bone tissue is represented by the cohort of men undergoing therapeutic orchiectomy for the treatment of prostate cancer or sexual delinquency. In 12 men of the latter group, bone mineral density of the lumbar spine decreased after bilateral orchiectomy (Stepan etal. 1989). Corresponding effects were seen in men treated with surgical or chemical castration for prostate cancer as a consequence, osteoporotic fractures were significantly increased in comparison to controls (14 vs. 1 ) (Daniell 1997 2000). This has been recently confirmed by a study involving 429 men who underwent bilateral orchiectomy for treatment of prostate cancer. Fractures were ascertained from medical records and compared with expected numbers based on local incidence rates this demonstrated a three-fold increase of fractures accounted for by moderate trauma of the hip, spine and distal forearm, locations traditionally linked with osteoporosis (Melton etal. 2003). The...

The role of 5areduction and aromatization of testosterone in the muscle

Although the enzyme 5a-reductase is expressed at low concentrations within the muscle (Bartsch etal. 1983), we do not knowwhether conversion of testosterone to dihydrotestosterone (DHT) is required for mediating androgen effects on the muscle. Men with benign prostatic hypertrophy who are treated with a 5a-reductase inhibitor do not experience muscle loss. Similarly, individuals with congenital 5a-reductase deficiency have normal muscle development at puberty. These data suggest that 5a-reduction of testosterone is not obligatory for mediating its effects on the muscle. Sattler etal. (1998) have reported that serum dihydrotestosterone levels are lower and testosterone to dihydrotestosterone ratios higher in HIV-infected men than in healthy men. These investigators have proposed that a defect in testosterone to dihydrotestosterone conversion may contribute to wasting in a subset of HIV-infected men. If this hypothesis is true, then it would be rational to treat such patients with...

Testosterone metabolism in the prostate

Quantitatively, the major circulating androgen in the blood is testosterone. Within the prostate, however, testosterone is enzymatically converted to 5a-dihydrotestosterone (DHT) (Wilson 1984). The class of enzymes responsible for the irreversible conversion of testosterone to DHT are the membrane-bound NADPH-dependent A4-3-ketosteroid 5a-oxidoreductases (i.e., 5a-reductases) (Bruchovsky and Wilson 1968). Biochemical studies have demonstrated that the irreversible conversion of testosterone to DHT by 5a-reductase (Fig. 12.1), involves a sequential series of steps (Levy et al. 1990). Initially, reduced nicotinamide-adenine din-ucleotide phosphate (NADPH) cofactor binds to the 5a-reductase enzyme to form a 5a-reductase-NADPH complex. Once formed, testosterone binds to this 5a-reductase-NADPH complex. Electrons are stereospecifically transferred from NADPH to reduce the A4 double bond of testosterone, producing a 5a-reductase-oxidized NADP+-5a-DHT complex. After 5a-DHT is produced, it...

Paracrine androgen axis in the normal prostate

In contrast to the regulation of transcription of the prostate differentiation marker proteins, AR in the nuclei of the secretory luminal cells does not directly regulate the survival of these cells nor does it positively regulate the proliferation and survival of the prostatic epithelial stem and transit amplifying cells. Instead, survival of the secretory luminal cells and the proliferation of the transit amplifying cells requires the androgen-dependent production of peptide growth factors by the prostatic stromal cells (Cunha etal. 1987 Hayward etal. 1992 Kurita etal. 2001). These processes are initiated by testosterone diffusing from the capillary bed in the stromal compartment of the normal prostate across the basement membrane (BM) to enter the basal epithelial cells. These basal cells express 5a-reductase type I and II proteins which enzymatically convert testosterone to 5a-dihydrotestosterone (Bonkhoff etal. 1996). Once formed, DHT diffuses both into the secretory luminal...

Acute Physical Effects of Malignancy and Treatment

Many childhood cancers are initially invisible to the child and family. They become evident through common and seemingly benign symptoms, such as bruising, fatigue, loss of appetite, or weight loss. Other types of cancers cause more severe or dramatic symptoms, such as seizures, diplopia, confusion, paralysis, weakness, or fractured bones. For many children, however, the physical difficulties of dealing with cancer are associated primarily with the treatment rather than the disease. Pain, nausea, amputation, infections, and ulcerations are all acute side effects of cancer treatment. Radiation and antitumor chemotherapy target rapidly dividing cells, a characteristic of most malignancies. However, mucosa, hair, skin, and bone marrow are also made up of rapidly dividing cells, so these are also destroyed by chemotherapy and radiation, resulting in the characteristic problems of nausea, hair loss, bleeding, anemia, and immunosuppression seen in cancer patients during active treatment...

Adjuvant Systemic Therapy

Therefore, the recommendation for adjuvant therapy is determined by the patient's risk, which depends on the lymph node status, tumor diameter, and tumor histologic grade. Other factors that contribute to prognosis in a less quantifiable way include S-phase fraction and HER-2 neu overexpres-sion.21,27,89,106,110,114 Estrogen receptor status is an independent predictor of both overall survival and of positive response to treatment with tamoxifen. It indicates that relapses are likely to be delayed, as compared with relapses in patients who are estrogen-receptor negative with otherwise identical prognostic features.92 Overall, patient risk assessment as well as patient medical comorbidities and hormone-receptor status determine the recommended treatment options. At present, a shared decision-making process, with the patient taking an active role, is the most common approach. Some patients may elect a less efficacious therapy, such as tamoxifen alone, to avoid toxicity such as alopecia...

Effects on Academic Functioning

In addition to the medical obstacles to school attendance, children may feel uncomfortable at school. Changes in their appearance, such as hair loss, may make them self-conscious. They may feel unable to explain to their peers or teachers why they missed an activity or did not complete an assignment. Teachers may also feel ill prepared to explain the situation to their other students or may be fearful of having the child reenter the classroom while on active treatment. To address these issues, pedi-atric cancer programs have information they can send to schools, or they can have someone communicate directly with the teacher and or school nurse. School reintegration can also be facilitated with a visit to the classroom by a trained person, allowing children to ask questions (Labay et al. 2004).

Emergency Department Treatment and Disposition

Evaluation of alopecia in the emergency department should focus on the history and infectious etiologies. Treatment for tinea capitis and kerions requires systemic antifungals, long-term treatment, and periodic laboratory monitoring. Referral to a dermatologist or primary care physician is recommended. In an at-risk patient, screening for syphilis should be considered. Bacterial infections should be treated with antibiotics after bacterial cultures are obtained. Other forms of alopecia can be referred to a dermatologist. Alopecia. Alopecia totalis is loss of all scalp hair and eyebrows. (Photo contributor Lawrence B. Stack, MD.)

Classification and symptoms of hypogonadism

Voice mutation will not occur. The frontal hairline will remain straight without lateral recession, beard growth is absent or scanty, the pubic hairline remains straight. Hemoglobin and erythrocytes will be in the lower normal to subnormal range. Early development of fine perioral and periorbital wrinkles are characteristic. Muscles remain underdeveloped. The skin is dry due to lack of sebum production and free of acne. The penis remains small, the prostate is underdeveloped. Spermatogenesis will not be initiated and the testes remain small. If an ejaculate can be produced it will have a very small volume. Libido and potency will not develop. A lack of testosterone occurring in adulthood cannot change body proportions, but will result in decreased bone mass and osteoporosis. Early-on lower backache and, at an advanced stage, vertebral fractures may occur. Once mutation has occurred the voice will not change again. Lateral hair recession and baldness...

Impact of Breast Disease on the Patient

Most commonly, women with invasive breast cancer and axillary lymph node involvement require chemotherapy for periods up to 6 or 7 months after mastectomy. Many of the agents used to treat the patient have significant side effects, including nausea, vomiting, and alopecia. There are medicines available to help control the nausea and vomiting, but the alopecia presents another special problem. Although the woman recognizes that she will lose her hair and knows that it will grow back, she suffers further from low self-esteem. In our society, hair is a

Past Clinical Studies

A further study included trials with no replicates, and contained six studies. It showed that in five out of six cases the main outcomes were positive however, these were limited to very specific criteria, such as small airways resistance for common colds (Cohen and Dressler, 1982), prophylaxis of bronchi for bronchitis (Ferley et al., 1989), lessening smoking withdrawal symptoms (Rose and Behm, 1993, 1994), relief of anxiety (Morris et al., 1995), and treatment of alopecia areata (Hay et al., 1998). The alleviation of perineal discomfort (Dale and Cornwell, 1994) was not significant.

Phase I And Phase Ii Studies

Or the use of minoxidil in androgenetic alopecia. It is widely accepted that a phase I study is one that examines the initial introduction of a drug in human beings with the treatment tested either in normal volunteers or in patients. The main issues are the pharmacokinetics, pharmaco-dynamics and tolerability of the drug being tested with a focus on assessing inter-patient variability. While problems with systemic drugs in dermatology do not differ from those usually encountered in other speciality areas, some peculiarities exist with the assessment of topical drugs. Penetration within the deep epidermal layers and dermis is a parameter of particular interest since it clearly affects the local activity of the drug itself. On the other hand, pharmacokinetic parameters describing such a penetration are less stringent as compared with systemic drugs. The assessment can be performed on normal or diseased skin. Relevant methods are those which allow measurements of the concentration of...

Tumour typeRecommended margin

The technique is most commonly used for oral and nasal tumours that are not amenable to surgical resection. The prognosis is, however, still guarded and many tumours recur 6-9 months after treatment. Side effects, such as erythema of exposed skin and mucous membranes, alopecia, skin thickening and abnormal hair coloration, may also occur. Owners must therefore be given careful advice before embarking on a treatment programme so that they are fully aware of the possible outcomes.

What It Can Do for You

It is what light therapy cannot do for you that must be carefully examined. There is no acceptable evidence that light therapy in any of its manifestations will cure cancer, arthritis, menstrual difficulties, tooth decay, hair loss, Alzheimer's disease, or any of the other diseases and conditions it promises to treat.

Laboratory Evaluation

Where the 2 g 24 hr accounts for nitrogen losses from GI epithelium, skin, hair loss, and sweat. The total urine nitrogen can be determined by dividing the 24-hour urinary urea nitrogen by 0.85. In patients with extensive diarrhea or other losses of nitrogen (e.g., through pancreatic fistula), other methods must be used to calculate nitrogen losses, such as by the use of pyrochemiluminescence.

Dermatological disease

The frequency and cosmetic impact of male pattern balding has, over millennia, led to innumerable attempted cures . Prompted by a paradoxical claim that topical testosterone could cause hair regrowth, a double-blind, randomised study of 51 balding men showed that topical application of 1 testosterone propionate cream daily to one side of the scalp for a median of 4-5 months was no more effective than placebo applied to the other half of the scalp (Savin 1968). Given the dependence of male pattern balding on masculine levels of androgen exposure after puberty, acceleration of hair loss might have been expected but the study endpoints (investigator and patient subjective global grading of regrowth) were not designed to detect this. More recently controlled studies of a topical 5a-reductase inhibitor have added a selective anti-androgen to the already vast list of baldness cures (Rittmaster 1994).

Sheehans Syndrome 1977 1995

In 1995, Natalie Lomeo was delivered by elective Cesarean section at her local Community Medical Center (CMC) in Pennsylvania. She had an extensive blood loss during the operation, and a postpartum hemorrhage followed. Although she exhibited signs of hemorrhagic shock, blood was not transfused until much later in the day. Over the next 3 years, she complained of fatigue, weakness, dizziness, hair loss, amenorrhea, dyspareunia, and vasomotor symptomatology. In 1998, the diagnosis of Sheehan's syndrome was made. She then took legal action against her obstetrician and the CMC. However, the defendants filed for summary judgment, asserting that her claim was time-barred under Pennsylvania law, as it had been filed more than 2 years after the allegedly negligent conduct. The Common Pleas Court denied the motion for dismissal, saying that the litigation clock only started to run when Sheehan's syndrome was diagnosed27. What happened next was not reported, so the case was probably settled.

Rationale for and development of 5areductase inhibitors

The findings in subjects with genetic 5aR deficiency established essential roles for DHT in both male external genital development in utero and the pathogenesis of common, androgen-dependent disorders of adult men. Subsequently, several laboratories attempted to synthesize inhibitors of the human 5aR enzyme intended for clinical investigation to test for utility in the treatment of patients afflicted with these disorders, which include BPH, prostate cancer and male pattern hair loss (androgenetic alopecia, AGA).

Acute submandibular staphylococcal lymphadenitis

Infection of the skin hair follicles and which passes down the lymphatics to settle in submandibular lymph node. The child may not have been previously exposed to a staphylococcal infection and, the immune reaction being insufficient to deal with this challenge, the node is overwhelmed and becomes an abscess itself. This is similar to any acute inflammatory swelling at the lower border of the mandible. There may be surface reddening and it will be tender to palpation the temperature may be elevated. Dental examination shows no carious focus and this generally will raise suspicions of a staphylococcal infection. There may be evidence of infection of a hair follicle on the face on that side or a history of recent nasal congestion such as a head cold.

Topoisomerase Inhibitors

Side effects include mucositis, myelosuppression, alopecia, phlebitis, hypersensitivity reactions, and secondary leukemias. Irinotecan, a camptothecin analog, inhibits topoisomerase I to interfere with DNA synthesis through the active metabolite SN38, which is 100-fold more potent in vitro. The pharmacokinetics of irinotecan are best described by a three-compartment model, with an a-half-life of 0.07 hours, a P-half-life of 2.2 hours, and a terminal half-life of about 18 hours.19 Irinotecan has shown activity in the treatment of cancers of the colon, rectum, cervix, and lung. Irinotecan induced diarrhea may be life-threatening. IV atropine should be used to treat diarrhea that occurs during the first 24 hours of administration. Loperamide, 2 mg every 2 hours or 4 mg every 4 hours until diarrhea has stopped for 12 hours, should be used for diarrhea occurring for more than 24 hours after administration. Other side effects include myelosuppression, fatigue, and...

The ideal tissueselective androgen

Is implemented in vitro by recruitment of comodulators from which are known, they are expressed in the desired target tissues. For example FHL2 may coactivate androgen mediated action in the heart specifically and may be useful for heart muscle specific androgen benefits. In addition, recruitment of corepressors to the AR in prostate cells is beneficial to inhibit the androgen-dependent transactivation of target genes. For reasons to avoid undesired side effects, also androgens which are not 5a-reducible and therefore have no increased activity in organs with 5a-reductase (e.g. prostate, skin and hair follicle) are preferably used (see 20.2.1). Some beneficial androgen action especially in bone, brain and cardiovascular are not mediated by the androgen itself, but the aromatised product (see 20.2.1). The ideal tissue-selective androgen for hormone replacement should have the liability for aromatisation. The requirements for female androgen substitution differ from males. Anabolic...

Clinical Use and Adverse Effects of Specific Antiepileptic Drugs

Valproic acid is a branched-chain fatty acid that was approved for use in the United States in 1978. The enteric-coated preparation, divalproex sodium, became available in 1983. Multiple mechanisms likely contribute to its broad spectrum of action, including inhibition of sustained repetitive firing through blockade of voltage-gated Na+ channels. Valproic acid is effective against generalized and partial seizures including absence, myoclonic, and tonic-clonic seizures. High protein binding and hepatic enzyme inhibition contribute to the high incidence of drug interactions. Adverse reactions include tremor, weight gain, alopecia, hyperammonemia, carnitine deficiency, and thrombocytopenia. Fulminant hepatic failure and fatal pancreatitis have been reported. Valproate is available in 250-mg tablets and syrup (250 mg 5 ml), and divalproex sodium in 125-, 250-, and 500-mg tablets and 125-mg sprinkles for mixture with food. Rectal and parenteral formulations are being developed.

Musculoskeletal Diseases

Myotonic dystrophy is the most common of the muscular dystrophies. This autosomal dominant disease shows characteristic facial features (a thin narrow face with drooping eyelids, frontal baldness) and muscle weakness of the neck, hands, and extremities. The patient has a high steppage gait and difficulty in grasp relaxation (myotonia). Fifty percent ofsuch patients have a cardiomyopathy (137) and occasionally complete heart block (138).

Progressive Diseases of Infancy and Childhood

Figure 31-3 Glutaricaciduria, biotinidase deficiency and biopterin-dependent phenylketonuria. Clockwise from left upper corner. Infant with glutaricaciduria type I (GAT I) showing dystonic posture and rigidity in flexion. MRI of the brain showing open operculum sign and frontotemporal atrophy in infant with GAT I. Alopecia in a biotinidase-deficient 9-month-old infant with frequent myoclonic seizures from age 3 months. Infant with biopterin-dependent phenylketonuria due to 6-pyruvoyl tetrahydropterin synthase (6-PTS) deficiency showing dystonic grimacing and fisting of hands and hypotonic pithed frog posture of legs. The reason for selective targeting of the auditory center is unknown. Alopecia (see Fig 31-3 ) and dermatitis in these patients are possible owing to depletion of fatty Biotin-responsive mild forms of HCS deficiency and milder forms of propionicacidemia must be ruled out by clinical and laboratory observations. Alopecia and rash can be encountered in deficiency of zinc or...

Table 34 Causes and associations of trachyonychia


Idiopathic (twenty-nail dystrophy) (Figure 3.34) Alopecia areata (Figure 3.32) Lichen planus (Figures 3.37, 3.38) Eczematous histology Chemicals and alopecia areata makes it common to observe trachyonychia in other conditions frequently associated with alopecia areata, such as atopic dermatitis, ichthyosis or Down's syndrome. Table 3.4 lists the known causes and associations of trachyonychia. alopecia areata a clinical and pathological study, J Am Acad Dermatol 25 266-270. Tosti A, Bardazzi F, Piraccini BM, Fanti PA (1994) Trachyonychia (twenty nail dystrophy) clinical and pathological study of 23 patients, Br J Dermatol 131 866-872.

Intracranial Lipoma Embryologic Origin

Intracranial Lipoma Sites

(intracerebral and bony) Mandibular hypoplasia, macrostomia, upper vertebral anomalies, and epibulbar dermoids Soft scalp masses with overlying alopecia, papular skin lesions over face and eyes, and progressive intracranial calcifications Midline craniofacial anomalies, hypertelorism, cranium bifidum, cleft lip or nose, and mental retardation Caf -au-lait lesions, neurofibromas, Lisch nodules, plexiform neuromas

Table 43 Causes and associations of onychogryphosis Dermatological

What Causes Pincer Nails

Positive, homogeneous, rounded or oval, amorphous masses surrounded by normal squamous cells which are usually separated from each other by empty spaces caused by the fixation process. These clumps, which coalesce and enlarge, have been described in psoriasis of the nail, onychomycosis, eczema and alopecia areata, and also in some hyperkeratotic processes such as subungual warts and pincer nails. The horny excrescences of the nail bed are not very obvious, but the ridged structure may become apparent if the nail plate is cut and shortened.

Mecanism Of Centripetal Lipid Accumulation Supraclavicular Fat And Face

Hypothyroidism is considered primary when increased TSH levels accompany low T3 and T4 levels, suggesting thyroid pathology. In secondary or central hypothyroidism, low T3 and T4 are associated with low TSH and suggest pituitary insufficiency. Thyroid hormone deficiency causes mental retardation in infants, growth delay in children, and myxedema in adults. Symptoms of thyroid hormone insufficiency include cold intolerance, weight gain, memory loss, dry skin, hair loss, brittle nails, constipation, increased sleep demand, and fatigue. Severe, untreated hypothyroidism can lead to coma and even death. Hypothyroidism from TSH or TRH deficiency can result from hypothalamic or pituitary destruction (neoplastic, inflammatory, granulomatous, vascular, traumatic, autoimmune, or from radiation necrosis). In the presence of an expanding pituitary mass (i.e., pituitary adenoma), loss of TSH secretion is typically associated with other hormonal abnormalities because there is a step-wise loss of...

Androgen dynamics in women

Testosterone, the most clinically relevant circulating androgen, has both an adrenal contribution (about 25 ) and an ovarian contribution (about 25 ), but is mostly produced by peripheral bioconversion from circulating A4A (Burger 2002). By virtue of its relatively large ovarian contribution, serum testosterone is probably the best measure of ovarian androgen production. Dihydrotestosterone (DHT) is produced almost exclusively in target tissues by 5a-reductase action on circulating testosterone circulating levels are negligible and felt to be largely a reflection of spillover from the primarily intracrine action of this hormone. The circulatory androgen dynamics in premenopausal women are illustrated in Fig. 17.1.

Adult testosterone levels

In a group of traditionally living Kung San hunter-gatherers (so-called bushmen) from the Kalahari desert in Namibia, Christiansen and Winkler (1992) found that within a subgroup of physically aggressive San men violent behaviour correlated significantly and positively with free testosterone and 5a-dihydrotestosterone (DHT) levels. As the physically aggressive men also exhibited higher mean values in body measurements of robustness of the face and trunk, this finding may point to a possible pathway of indirect androgen action on human aggression, in addition to the widely accepted influence of testosterone on aggressive behaviour via its action on specific sites in the central nervous system.

Masculine secondary sexual adornments a comparative perspective

Nasalis Larvatus Skica

The relatively conspicuous visual traits of adult human males include facial hair, male pattern baldness, and body hair all these traits vary considerably in their expression both within and between human populations. A score of 10 was allocated for these sexually dimorphic characters in men (Dix-son et al. 2005), which is high, given the relatively modest sex differences in human body weights. Among the monkeys and apes which have polygy-nous mating systems, scores for male-biased sexual dimorphism in visual adornments are significantly correlated with the degree of sexual dimorphism in body size the largest males have the most striking secondary sexual adornments (Figure 17.19). It is probable that the human male would justify even higher scores using this rating scale, if sex differences in facial morphology were to be taken into consideration. Very little is known about the origins of the human beard, or of male pattern baldness, and the marked reduction of human body hair. One...

Pharmacologic Therapy Chemotherapy

Traditional chemotherapeutic agents interfere with processes during cell division or affect DNA replication in nondividing cells, resulting in cell death. Unfortunately, these agents are not specific for cancer cells, and other tissues in the body often are affected. Rapidly cycling cells, both tumor and normal tissue such as bone marrow, epithelial cells of the GI tract, and hair follicles, are most susceptible to chemotherapy toxicity. Because the dose of traditional chemotherapy agents is determined in phase I studies where the maximum tolerated dose is considered the best dose, toxicity is seen neuropathy, aopecia. and cardiovascular Fatigue, nausea vomiting, skin toxicity, neuropathy, anemia, hypersensitivity, and Mild alopecia

A 9substituted camptothecins

Reversible, noncumulative, and dose-related neutropenia was the DLT in all five schedules (309-313). With a 24-h continuous infusion every 3 weeks, thrombocytopenia was an added DLT in heavily pretreated patients (310). Neutrophil and platelet count nadirs occurred between days 10 and 15, with recovery by day 22. Nonhematological toxicities included mild to moderate gastrointestinal toxicity (nausea, vomiting, stomatitis, diarrhea), fatigue, asthenia, and alopecia (309-313). Transient and reversible liver dysfunction was also observed, and in a Japanese study this event was dose limiting at the dose of 6.65 mg m2 (309,312). Diflomotecan, one of the fluorinated homocamptothecin derivatives, has entered Phase I clinical testing. Oral diflomotecan administered once daily for 5 days every 3 weeks was limited by dose-dependent myelosuppression (317). Other toxicities observed were gastrointestinal (i.e., mild nausea and vomiting), alopecia, and fatigue. The recommended dose for Phase II...

Benign Neoplasia Benign Prostatic Hyperplasia

Prostate tissue is androgen responsive throughout life. 5a-Reductase inhibitors inhibit the conversion of testosterone to dihydrotestosterone, leading to glandular atrophy and reduced prostate volume (20 -30 ) (Thorpe and Neal, 2003). It takes many months for these medicines to become effective. Sexual side effects are the most prominent. These drugs also reduce PSA by up to 50 . Based on the Prostate Cancer Prevention Trial, family physicians should discuss potential benefits and harms of 5a-reductase inhibitors (see Prostate Cancer) when using these medications for BPH and LUTS (Kramer et al., 2009). Prostate enlargement can progress

Hormonal Regulation Prostate

Hormone Found The Prostate Gland

Hormonal regulation of the prostate gland. ACTH, adrenocorticotropic hormone DHT, dihydrotestosterone FSH, follicle-stimulating hormone GH, growth hormone LH, luteinizing hormone LHRH, luteinizing hormone-releasing hormone PROL, prolactin R, receptor. (From DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy A Pathophysiologic Approach, 6th ed. New York McGraw-Hill, 2005 1856.) FIGURE 92-2. Hormonal regulation of the prostate gland. ACTH, adrenocorticotropic hormone DHT, dihydrotestosterone FSH, follicle-stimulating hormone GH, growth hormone LH, luteinizing hormone LHRH, luteinizing hormone-releasing hormone PROL, prolactin R, receptor. (From DiPiro JT, Talbert RL, Yee GC, et al, eds. Pharmacotherapy A Pathophysiologic Approach, 6th ed. New York McGraw-Hill, 2005 1856.)

Psychosomatic aspects of atopic dermatitis

Significance Neurosecratory

The prevalence of anxiety and depression was mostly investigated. Depression scores and suicidal reflections were mostly found in the cases of disfiguring skin diseases Gupta et al14 found suicidal thoughts in 7.2 of the inpatient psoriatic patients, in 5.6 of the patients with (non-cystic) acne, in 2.1 of AD and outpatient psoriatic patients, while alopecia areata patients reported no suicidal thoughts at all. In an investigation in German departments of dermatology, 23.2 of the heads of the departments found psychotherapeutic therapy to be a necessary requirement in addition to dermatological treatment.15 14. Gupta MA, Gupta AK. Depression and suicidal ideation in dermatology patients with acne, alopecia areata, atopic dermatitis and psoriasis. Br J Dermatol 1998 139 846-50.

Directed Neurological Examination

The examiner may recognize sudomotor failure by noting a dryness of the skin and a lack of resistance to gentle stroking with the fingerpads or to a tuning fork run over the skin. Sudomotor failure may take the form of an isolated generalized anhidrosis or a diffuse autonomic failure with other associated findings. A search should be made for localized increases in or absence of sweating and for asymmetrical patterns of skin temperature or color. In patients with disturbances of autonomic innervation of the face, the physician may note gustatory sweating, flushing, and facial anhidrosis. Acral vasomotor changes that may be observed include acrocyanosis, pallor, mottling, livedo reticularis, or erythema. y Skin temperature changes can be assessed by palpation. Other findings to be noted include atrophic skin changes, alopecia, hypertrichosis, nail thickening, skin decoloration or deformation, and Charcot's joints. Allodynia and hyperalgesia are components of a complex regional pain...

Use Of Essential Oils Mainly As Chemical Agents And Not For Their Odor

Alopecia areata was treated in a randomized trial using aromatherapy carried out over 7 months. The test group massaged a mixture of 2 drops of Thymus vulgaris, 3 drops Lavandula angustifolia, 3 drops of Rosmarinus officinalis, and 2 drops of Cedrus atlantica in 3 mL of jojoba and 20 mL grapeseed oil into the scalp for 2 min minimum every night. The control group massaged the carrier oils alone (Hay et al., 1998). There was a significant improvement in the test group (44 ) compared with the control group (15 ). The smell of the essential oils (psychological physiological) and or their chemical nature on the scalp may have achieved these long-term results. On the other hand, the scalp may have healed naturally anyway after 7 months.

Structure and Physiology

Senile Loss Elasticity

There is atrophy of the epidermis, hair follicles, and sweat glands, which results in thinning skin. The skin becomes fragile and discolored. Wrinkling and dryness result from reduced skin turgor. In addition, the nails become thin and brittle, with marked ridging. There is decreased vascularity of the dermis, which contributes to prolonged healing time. There are common pigmentary changes, such as the development of senile lentigines, or ''liver spots.'' These brown macules are commonly found on the backs of the hands, forearms, and face. They are caused by localized mild epidermal hyperplasia, in association with increased numbers of melanocytes and increased melanin production. Figure 25-1 shows senile lentigines on the hand of an 87-year-old woman. Hair loses its pigment, which commonly results in ''graying'' of the hair. With the reduction in the number of hair follicles, there is hair loss all over the body head, axilla, pubic area, and extremities. With the reduction in...

Direct effects of testosterone on erection

Numerous studies in animal models have demonstrated a direct testosterone-dependency of erection. In castrated rats, the intracavernosal blood pressure of the penis was insufficient in response to induced erection by electrical field stimulation of the cavernosal nerve. Testosterone replacement restored the normal erectile response (Mills etal. 1994). In the rat, the primary mode of action of testosterone for erectile function seems to be the stimulation of neurogenic and endothelial nitric oxide synthesis (e.g. Baba et al. 2000a 2000b Chamness et al. 1995 Garban et al. 1995 Marin etal. 1999 Park etal. 1999 Penson etal. 1996 Reilly etal. 1997 Schirar etal. 1997 Seftel 1997 Zvara etal. 1995). This effect is mediated by testosterone or dihydrotestosterone, but not by estradiol (Lugg etal. 1995). In addition, castration induces programmed smooth muscle cell death in the rat penis, indicating that androgens may have an important role in maintaining smooth muscle growth and functional...

Incision and Drainage of Cutaneous Abscess

A cutaneous abscess is identified by a fluctuance or compressible softness in skin surrounded by induration, inflammation, warmth, and tenderness. Furuncles are superficial and result from abscess formation in a sweat gland or hair follicle. Carbuncles are deeper and extend into the subcutaneous tissue. Offending bacteria include Staphylococcus aureus, streptococci, and occasionally gram-negative rods. These infections can be severe in patients with diabetes or vascular disease. Primary treatment of an abscess is surgical drainage. An area of induration alone with no fluctuance indicates isolated cel-lulitis and is treated with antibiotics and warm compresses.

Effects of exogenous testosterone on cardiovascular risk factors

Taken as one argument to explain the unexpected neutral or even adverse effect of postmenopausal hormone replacement on coronary artery disease. In two studies of healthy eugonadal men treatment with either increasing dosages of testosterone enanthate or dihydrotestosterone or recombinant chorionic gonadotropin as well as suppression of endogenous testosterone with a gonadotropin releasing hormone agonist had no effect on CRP levels. Neither had dihydrotestosterone any effect on serum levels of soluble adhesion molecules (Ng etal. 2002 Singh etal. 2002).

Toxicities and Management of Preparative Regimens

Myelosuppression is a frequent dose-limiting toxicity for antineoplastics when administered in the conventional doses used to treat cancer. However, because myelosuppression is circumvented with hematopoietic rescue in the case of patients receiving HSCT, the dose-limiting toxicities of these myeloablative preparative regimens are nonhematologic and vary with the preparative regimen used. Most patients undergoing HSCT experience toxicities commonly associated with chemotherapy (e.g., alopecia, mucositis, nausea and vomiting, and infertility), albeit these toxicities are magnified in the HSCT population.

What are the 5alpha reductase inhibitors

The 5-alpha reductase inhibitors are a class of medications that inhibit the enzyme 5-alpha reductase. The enzymes 5-alpha reductase are present in two isoforms type 1 and type 2. Type 1 is found predominantly in extrapr-ostatic tissues such as the skin and liver, although it is also found in the prostate. Type 2 is found predominantly in the prostate. The type 2 5-alpha reductase enzyme in the prostate is responsible for converting testosterone to its active form in the prostate, dihydrotestosterone. Dihydrotestosterone mediates secondary sexual characteristics, including prostate growth (Figure 22). Testosterone (T) Dihydrotestosterone (DHT)

Electromagnetic Therapies

By the eleventh and twelfth centuries, lodestones were thought to have curative powers and were used to treat gout, arthritis, baldness and other ailments, as described by medieval writers. Scholars of the time also believed that magnets could cause and cure melancholy. Aphrodisiac powers were attributed to lodestones probably because of their magnetic ability to attract.

Apoptosis Oxidative Stress and BPH

Claus et al. 67 studied the apoptotic and proliferative rates in the epithelium and the stroma of BPH. They also demonstrated the apoptotic and proliferative rate in the epithelium of normal prostatic tissue. Interestingly, the results of this study indicate a decrease in the apoptotic rate in the stroma of BPH which may explain the enlargement of the prostatic tissue 68 . Apoptosis, also known as programmed cell death, plays an important role in all stages of an organism's development. While there are controversies in the literature regarding the role of apoptosis in aging, age-associated increases in apoptosis have been observed in several physiological systems, including the human immune system, human hair follicle, and rat skeletal muscle 69 Apoptotic cell death is executed via two major signaling pathways, the intrinsic and extrinsic pathways, in either caspase-dependent or caspase-independent manners 70 . The intrinsic pathway involves the induction...

Role of 5areductase in androgen physiology and pathophysiology

During the last century, the identification and characterization of the major sex steroids, which include androgens, estrogens, and progestins, helped define their biologic functions. Androgens were demonstrated to be essential for normal male sexual differentiation in utero and for development and maintenance of male secondary sexual characteristics, including terminal body hair growth, muscle mass, sexual behavior and fertility. Androgens are steroid hormones and, as such, produce effects by binding to an intracellular receptor, forming a hormone-receptor com-plexthat interacts with DNAto modulate protein transcription (Mainwaring 1977). Testosterone, the major circulating androgen in adult men, was logically suspected to be the hormone responsible for these effects. Observations in 46XY subjects with inborn androgen insensitivity (syndrome of testicular feminization) confirm that the sexual phenotype in humans is predominantly female in the absence of androgen effects (Morris et...

Parrot Beak Nails Raynauds

Raynaud Syndrome And Toe Nails

Renal dialysis transplant thyroid disease Dermatoses alopecia areata Darier's disease lichen planus psoriasis Club-shaped terminal phalanges mandibular hypoplasia, delayed cranial closure dysplastic clavicles atrophy of skin over hands and feet alopecia AR or XR Unusual facies with large nose

Clinical studies with finasteride in women

Finasteride is not indicated for use in women. Due to its mechanism of action (type 2 5aR inhibition), finasteride use is contraindicated in women when they are or may be pregnant because of the risk of undervirilization of a developing male fetus. However, several studies have been published testing finasteride in women with a variety of disorders, including female pattern hair loss and hirsutism. 18.7.1 Study in postmenopausal women with androgenetic alopecia To determine whether finasteride has utility in the treatment of women with AGA (female pattern hair loss), a randomized, placebo-controlled, one-year study of 137 postmenopausal women with AGA was conducted (Price etal. 2000). Women were eligible if they were assessed by the investigator as being Ludwig class I to II (Ludwig 1977) and Savin scale hair density and pattern classification 3 to 5 (Savin 1994). At the end of one year, no benefit of finasteride treatment compared to placebo was demonstrated in any predefined...

Seals of Excavated Tombs

In places where there is too much light (chhing, clear) water, disease of the scalp (thu alopecia, ringworm, psoriasis, etc.) and goitre (ying) are commonly found. In places where there is too much heavy (chung, turbid) water, people suffering from swellings and oedematous ulcers of the lower leg (thung1) are commonly found and there are many seriously affected who are unable to walk at all (pi). Where sweet (kan) water abounds, men and women will be health y and handsome. Where acrid (hsin) water abounds there will be many skin lesions, such as abscesses (chii) and smaller boils (iso) where bitter (khu) water abounds there will be many people with bent bones (wang yii).

B dosefinding trials

Numerous Phase I clinical trials with topotecan in different schedules of drug administration have been performed (183). Based on the in vitro data on long-term exposure and the fact that efficacy of the drug has been demonstrated to be dependent on the schedules of administration, two schedules were selected for Phase II studies. Firstly, there is a 30-min i.v. infusion daily for 5 consecutive days every 3 weeks, at a dose of 1.5 mg m2 day. In this schedule, the DLT is short lasting, noncumulative myelosuppression (184-186). Nonhematological toxicities are usually mild and reversible and include nausea, vomiting, fatigue, alopecia, and sometimes diarrhea. Phase II studies with the drug administered in this schedule revealed response rates ranging from 9.5 to 25 in pretreated patients with ovarian cancer, and response rates of 10-39 in patients with SCLC (187-190). In addition, a comparative randomized, multicenter trial in which patients with recurrent ovarian cancer were treated,...

Clinical Features

Although any body part or aspect of physical appearance may be a source of concern and several body parts may be involved simultaneously, concerns generally focus on the patient's face or head (e.g., size or shape of the nose, eyes, lips, teeth, or other facial features thinning hair excessive facial hair acne wrinkles scars). Individuals may spend hours per day checking their appearance, engage in excessive grooming or exercising to minimize or erase the defect, and or become housebound.

Category C Severely Symptomatic

Anemia, neutropenia, nausea, anorexia, fatigue, insomnia, headache, myalgia, myopathy Pancreatitis, peripheral neuropathy, hyperamylasemia, hyperuricemia, transaminase elevations Peripheral neuropathy (dose-dependent), pancreatitis, rash, stomatitis, gastrointestinal disturbances Peripheral neuropathy, arthralgia, myalgia, anemia, asthenia, gastrointestinal complaints, headache, insomnia Pancreatitis, paresthesias, peripheral neuropathy, rash, cough, headache, dizziness, fatigue, hair loss, insomnia

Associated Neurological Findings

Assessment of vital signs, preferably performed prior to administration of medications, is very important. Fever should always be construed as a sign of organic disease and should trigger consideration of a spinal tap. In a patient taking a neuroleptic, fever may accompany the neuroleptic malignant syndrome and may warrant consideration of this diagnosis. Once the vital signs are known, the general physical examination should be performed with the aim of identifying contributory factors to a behavior disorder. The general appearance may reveal obesity or cachexia. Central obesity and hirsutism suggest endocrine derangements, whereas hair loss may indicate lupus, thyroid disease, or simply an unrelated skin condition. Weight loss may be evident by excessive skin folds or a cachectic appearance and may accompany depressive syndromes. Changes in skin color may suggest endocrine disorders or a neurocutaneous syndrome. Evaluation of the head may reveal evidence of trauma or gingival...

Metabolism of testosterone

Testosterone Metabolism

There are several possibilities for the metabolism of testosterone (see Figure 1.7). Aromatization or reduction of the A4bond of testosterone give rise to 17 -estradiol and 5a-dihydrotestosterone, respectively. These steroids have completely different biological activities since they interact with discrete receptors in the cell. Actions of testosterone on target tissues are therefore significantly modulated by metabolic reactions. When a target cell is estrogen-dependent, the aromatase activity in target cells and the supply of androgen substrate are of major importance for determining the rate of synthesis of estrogens. In humans the aromatase cytochrome P450 enzyme (p450arom or CYP19) is encoded by a single gene. This gene is expressed in many tissues including the placenta, ovary, testis, fat tissue, liver, brain, hair, follicles and the brain. A very few cases of complete aromatase deficiency due to a gene defect have been noted (Morishima et al. 1995 Bulun 1996). The activity of...

Transport of androgens in the body

Sex hormone binding globulin (SHBG), and albumin (see Figure 1.6). Binding proteins in body fluids can act as a storage form for steroids that have a high rate of metabolism during passage of blood through the liver (Mendel 1989). In this way, extensive metabolism of active steroids can be inhibited. However, the presence of SHBG and albumin in body fluids is not essential for steroid homeostasis. This can be inferred from analbuminemic rats that possess neither SHBG nor albumin. In these rats, which are fertile, the total plasma concentration of testosterone is much closer to the free concentration in normal rats (Mendel et al. 1989). The free testosterone concentration is within the range of the affinity constant of the androgen receptor Kd 10-9-10-10M. Changes in the peripheral free testosterone concentration can therefore be directly sensed by the androgen receptor if there is equilibration between the exterior and interior of androgen target cells. It is not easy to envisage how...

Trafficking between the testicular compartments

Steroids such as pregnenolone, progesterone and testosterone not only rapidly pass the Leydig cell membranes but they can also equilibrate rapidly between different testicular compartments (van Doorn etal. 1974). The secretion pattern in the testis is thus most likely determined by amounts that are produced inside the tissue, the permeability characteristics of the membranes and the binding proteins in various testicular fluids. The Leydig cells in the testis are surrounded by an interstitial fluid that is rich in plasma proteins and the cells are also in close contact with blood vessels. The preferential direction of secretion in the testis is mainly determined by the concentration gradient and flow rates ofthe various fluids. Since theblood flow is much higher than the flow ofthe interstitial fluid, most ofthe unconjugated steroids diffuse from the interstitial space to the blood and leave the testis via the venous blood (Maddocksand Sharpe 1989). The porcine testis is an exception...

Steroids other than testosterone

Some specific intermediates of the steroidogenic cascade are worth mentioning when testosterone substitution is practised. In the human, as well as in the pig, testicular pregnenolone and progesterone can also be oxidized to steroids other than testosterone, such as 16-androgens which can be further metabolised to androstenone (5a-androst-16-en-3-one) and androstenol (5a-androst-16-en-3p-or 3a-ol) in sweat glands (Weusten et al. 1987a). Although these steroids are not recognized as biologically active steroids in a classical sense, they clearly act as pheromones in pigs. Humans can also perceive these pheromones but there are less convincing data about the ultimate responses (Comfort 1971 Cowley and Brooksbank 1991). Another specific testicular metabolite derived from progesterone is 3a-hydroxy-4-pregnen-20-one, produced by immature Sertoli cells from rats. This steroid is reported to specifically suppress FSH secretion by the pituitary cells (Wiebe 1997). The biological effects of...

Rapid nontranscriptional action of the androgen receptor

The most extensively analysed mechanism of the rapid action mediated by the AR occurs through the activation of c-Src. Rapid activation of ERK-1 and ERK-2 by the androgen dihydrotestosterone was blocked by the Src family tyrosine kinase inhibitor PP1 (Migliaccio etal. 2000). Furthermore embryonic fibroblasts derived from Src- - mice when transfected with the AR failed to show a rapid activation of ERK-1 and ERK-2 in response to androgen, confirming the role of Src in the AR. At the mechanistic level, the AR is thought to activate Src by binding to the SH3 domain of this protein. This activation process is also aided by the a or -isoforms of the estrogen receptor (ERa of ER ). These receptors are thought to bind to the SH2 domain of c-Src to activate this kinase together with the AR. In cells expressing both the AR and ER, activation of ERK-1 and ERK-2 by DHT can be inhibited by antiestrogen and the rapid effect of estrogen can be inhibited by antiandrogen (Migliaccio etal. 2000). This...

Pluripotent stem cells as the target of androgen action

Because testosterone administration has reciprocal effects on muscle mass and fat mass, and increases satellite cell number, we considered the possibility that the target of androgen action might be a precursor cell from which muscle and fat cells are derived. We hypothesized that testosterone regulates body composition by promoting the commitment of mesenchymal pluripotent cells into myogenic lineage and inhibiting their differentiation into adipogenic lineage. To test this hypothesis, we treated pluripotent, mesenchymal C3H 10T1 2 cells with testosterone (0-300 nM) or dihydrotestosterone (0-30 nM) for 0-14 days (Singh et al. 2003). We evaluated myogenic conversion by immunochemical staining for early (MyoD) and late (myosin heavy chain II MHC) myogenic markers, and measurements of MyoD and MHC mRNA and protein (Fig. 8.4). Adipogenic differentiation was assessed by adipocyte counting, and by measurements of PPAR7 2 mRNA, and PPAR7 2 and C EBPa proteins. The number of MyoD+ myogenic...

Nongenomic effects of androgens

Recently, effects of testosterone on calcium mobility through cell membranes of T cells were reported (Benten etal. 1997). Since T cells do not possess the classical androgen receptors, this biological response also indicates the involvement of unconventional plasma membrane receptors for the expression of these androgen effects. Another example of the involvement of alternative androgen receptors can be found in eels. In eels nanomolar concentrations of 11-ketotestosterone, for which no nuclear receptor has been found, are essential for maintaining sper-matogenesis in vitro. Under these conditions high concentrations of testosterone or dihydrotestosterone were inactive (Miura etal. 1991).

Metabolism of androgens in different tissues

Testosterone is metabolised to the more active androgen dihydrotestosterone (DHT) by 5a-reductase, which has much greater affinity to the AR than T and enhances AR-mediated transcription of target genes amplifying therefore the action of testosterone. The reductase is expressed especially in organs like skin, hair follicle and prostate and thereby contribute to undesired side-effects of androgens on baldness, acne, hirsutism (in women) and on the prostate.

Lessons from genetic studies on the role of testosterone in atherosclerosis

In the absence of controlled intervention studies and in view of the conflicting data presented above, it is difficult to predict the net effects of testosterone on cardiovascular disease. Further difficulties arise from the fact that associations found in observational studies do not prove causal relationships and that in theory several effects of testosterone on intermediate phenotypes can be exerted via either non-genomic or genomic mechanisms, the latter being mediated either directly via testosterone and dihydrotestosterone or indirectly via estradiol. Genetic studies on the associations or effects of genetic variation in the androgen receptor and estrogen

In foetal sexual differentiation

By testosterone which reaches its target tissues, e.g. the external male genitalia, via the blood stream. Depending on the anatomical region, testosterone can be further converted to dihydrotestosterone. Both testosterone and dihydrotestosterone enter the target cells and bind to the cytoplasmic AR. The AR belongs to the nuclear receptor superfamily and is a ligand activated transcription factor of androgen regulated genes (Hiort and Holterhus 2000). Binding of the ligand induces an activation cascade involving dissociation of the receptor from heat shock proteins, receptor phosphorylation, dimerization, translocation of the receptor into the nucleus, interaction with specific hormone responsive elements within the promoter region of androgen regulated genes and assembly of the basal transcription machinery finally resulting in specific gene transcription. Binding of the androgenic ligand to the AR is a highly specific event (Poujol etal. 2000). While earlier studies stressed the...

Frequency of steroid hormone misuse

Since 1999 prohormones of testosterone (Fig. 24.2), dihydrotestosterone (Fig. 24.3), steroids with 5a-androst-1-ene structure (Fig. 24.3), and prohormones of nortes-tosterone (Fig. 24.4) have been marketed in the United States as nutritional supplements. Prohormones are advertised as having effects similar to testosterone, dihydrodestosterone and nortestosterone because of a high conversion rate of prohormones to the physiologically effective steroids in the human body after oral,

Effects of testosterone on macrophage functions

Monocytes which have immigrated into the vascular wall differentiate to macrophages and bind lipoproteins which have permeated the endothelium and become modified within the arterial wall, for example by oxidation. Unregulated uptake of oxidatively modified lipoproteins via type A scavenger receptors leads to the intracellular accumulation of cholesteryl esters in macrophages and thereby to foam cell formation. Foam cells together with T-lymphocytes, release inflammatory mediators which stimulate the proliferation and migration of smooth muscle cells (Glass and Witztum 2001 Li and Glass 2002 Ross 1999). Estradiol inhibits oxidation of LDL both in the presence and absence of cells including macrophages. By contrast, testosterone increases the oxidation of LDL by placental macrophages in vitro (Zhu etal. 1997). Moreover, dihydrotestosterone dose-dependently stimulates the uptake of acetylated LDL by scavenger receptor type A and, hence, the intracellular cholesteryl ester accumulation...

Contamination of nutritional supplements with prohormones

In relation to the total number of products purchased per country most of the positive supplements (84 ) originate from companies located in the United States. The positive supplements showed anabolic androgenic steroid concentrations of 0.01 xg g up to 190 jxg g. Excretion studies with application of supplements containing nortestosterone prohormones corresponding to a total uptake of more than 1 xg resulted in urinary concentrations of the nortestosterone metabolite norandrosterone above the cut-off limit (2 ng ml urine for male) for several hours (positive doping result). Positive doping tests caused by contaminated supplements with prohormones of only testosterone or dihydrotestosterone have not been proved which is explainable by the low amounts of contamination and the applied tests which have to differentiate between endogenous and exogenous origin of testosterone and which will not be influenced by ingestion of low amounts of prohormones or testosterone itself.

Androgeninduced liver disorders

A consistent adverse feature of pharmacological androgen therapy, regardless of indication, is the risk of androgen-induced liver disorders (Ishak and Zimmerman 1987). These involve biochemical effects on hepatic function, hepatotoxicity (hepatitic or cholestatic) and liver tumor development (benign or malignant) and peliosis hepatis. These risks are a class-specific adverse effect of 17a-alkylated androgens, especially when used orally but no reliable estimates of the incidence or prevalence are available. The East German national sports doping programme involving oral 17a-alkylated androgens resulted in deaths from liver failure and chronic liver disease (Franke and Berendonk 1997). Every marketed 17a-alkylated androgen is associated with hepatotoxicity, whereas other androgens (1-methyl androgens, nandrolone, testosterone, dihydrotestosterone) are not hepatotoxic. Cholestasis and functional impairment of liver function (BSP retention, antipyrine clearance) are consistently impaired...

Statureforage and Weightforage percentiles

Thoracic Cutaneous Hemangioma

Is there evidence of traumatic alopecia from pulling out of the hair The damaged hair is broken at various lengths. Are small, circular, punched-out lesions of uniform size present These may represent cigarette burns. A large circular-type burn on the buttocks and thighs may result from the infant's immersion in scalding water. Inflicted tap water scalds are the most common type of nonaccidental burn injury. The most common sites include the perineum or extremities. The child pictured in Figure 24-32 has first- and second-degree burns on the penis, thighs, and inguinal and suprapubic areas. The buttocks and sacrum were spared. These burns were caused by holding the child under hot water from the faucet. Burns by a hot object are the second most common type of inflicted burns. A well-circumscribed affected area with the outline of the hot object used is commonly seen. Figure 24-33 shows the typical appearance of specific types of burns. The diagnosis of physical child abuse is...

Secondary Syphilis Clinical Summary

The rash of secondary syphilis occurs 2 to 10 weeks after resolution of the primary lesions. It begins as a nonpruritic macular rash that evolves into a papulosquamous rash involving primarily the trunk, palms, and soles. The rash is often annular in shape. Diffuse, painless lymphadenopathy is also seen at this stage. Mucous patches represent mucous membrane involvement of the tongue and buccal mucosa. Condyloma lata can be seen during this stage, as can patchy alopecia. The manifestations of this stage resolve without treatment in several months.

Pathways involved in the spreading of the mechanical signal to neighboring cells

Estradiol and dihydrotestosterone both amplify the response of bone to mechanical stimulation via a mechanism which is independent of prostanoid formation 16 . The mitogenic effects of estrogen and EGF involve the estrogen receptor, whereas those of FGF and the IGFs do not 17 . Thus, antiestrogens like tamoxifen and ICI 182780 prevent osteoblastic proliferative responses to strain, while estradiol enhances strain-induced mitogenesis. The reduced ability to maintain the structural strength of bone after the menopause could be explained by less effective strain-related remodeling when estrogen is absent and or the estrogen receptor could be down-regulated. Recent studies indicate that strain may di

Effects of testosterone on cardiovascular risk factors

Clinical studies indicating that therapeutically-induced changes in HDL-C may not necessarily be accompanied by changes in cardiovascular risk (Hersberger and von Eckardstein 2003). Fifth, testosterone can exert its metabolic effects directly or by its metabolites estradiol and dihydrotestosterone. The effects of testosterone and estradiol, in particular, can be either additive (for example on Lp(a)) or counteractive (for example on HDL-C). Sixth, polymorphisms in the genes of the androgen and estrogen receptors, sex hormone binding globulin (SHBG), 5a-reductase and aromatase, regulate genomic effects and the bioavailability of testosterone, dihy-drotestosterone and estradiol, respectively. Thus, at a given serum concentration the bioactivity and metabolic effects of testosterone can be diverse.

Erythropoiesis and marrow stimulation

Androgen therapy has long been used clinically to stimulate erythropoiesis since the original observational study of 68 women with breast cancer which demonstrated significant, sometimes dramatic, increases in hemoglobin levels after the administration of 100 mg testosterone or dihydrotestosterone propionate injections three times weekly (Kennedy and Gilbertsen 1957). In addition, androgen therapy has smaller and less consistent effects on other bone marrow cell lineages that produce neutrophils and platelets. Androgen therapy increases hemoglobin in healthy men (Palacios etal. 1983 Wu etal. 1996) as well as augmenting the hemoglobin responses to recombinant human erythropoietin (EPO) in renal anemia (Ballal etal. 1991) and

Lesch Nyhan Disease Hypoxanthine Guanine Phosphoribosyltransferase Deficiency

The main clinical sign is self-injurious behavior resulting in tissue loss. Enzyme activity of HPRT can be assayed by radiochemical methods from dried blood spots, cultured skin fibroblasts, and hair follicle cells in probands and suspected female carriers. Biochemical analysis must be confirmed by molecular genetic analysis, particularly for female carriers. The entire HPRT locus has been sequenced, and the mutations in Lesch-Nyhan disease are extremely heterogeneous. The majority are detected by polymerase chain reaction-based techniques, usually amplification of genomic DNA and direct sequencing. In a small percentage, Southern blot analysis using HPRT complementary DNA as a probe is necessary to detect translocations or duplications.

Associated Medical Findings

Skeletal abnormalities like kyphoscoliosis and pes cavus, as well as diabetes and cardiac symptoms, are associated with Friedreich's ataxia. Cold intolerance, dry skin, and hair loss indicate hypothyroidism. Pulmonary and gynecological examination might show signs of bronchial or ovarian carcinoma, respectively. Cervical adenopathy might reveal Hodgkin's disease. Subacute, reversible ataxia associated with pyrexia suggests viral cerebellitis. Repeated bronchopulmonary infections suggest ataxia-telangiectasia. Examination of the cardiovascular system might disclose a structural cardiac lesion or rhythm disturbances, which indicate a possible

Steroid Hormones Oxidative Stress and Prostate

Prostate development, maturation, and normal function depends on the activity of the androgens testosterone and its derivative dihydrotestosterone (DHT). DHT, synthesized from testosterone in the prostate by 5a-reductase, has a more potent effect due to its higher affinity to the androgen receptor (AR) 81 . The AR in turn binds to androgen receptor elements (ARE) present in the promoter regions of many genes involved in cellular proliferation 82 . Traditionally, the initial stages of prostate cancer are controlled by androgen deprivation therapy however, aberrant AR activity in prostate tumors finally leads to the development of a highly malignant state of disease unresponsive to androgen control 83 .

Coloured lines

Multiple Normal increase with age after early adulthood (Figures 3.1, 3.3, 3.4) With all causes of thin nail plates Lichen planus (Figure 3.5) Rheumatoid arthritis Graft-versus-host disease Psoriasis Darier's disease Poor circulation Collagen vascular diseases Radiation Frostbite Alopecia areata Nail-patella syndrome _Systemic amyloidosis_

Figure 328

It has been shown that regular pitting may convert to rippling or ridging, and these two conditions appear, at times, to be variants of uniform pitting (Figures 3.26-3.28). Nails showing diffuse pitting grow faster than the apparently normal nails in psoriasis. Occasional pits occur on normal nails. Deep pits can be attributed to psoriasis, and profuse pitting is most often due to this condition (Figures 3.29, 3.30). In alopecia areata (Figure 3.31) shallow pits are usually seen and they are often numerous, leading to trachyonychia (rough nail) and twenty-nail dystrophy however, curiously, one nail often remains unaffected for a long time, Pits may also occur in eczema or occupational trauma. In some cases a genetic basis is thought likely. In secondary syphilis and pityriasis rosea pitting occurs rarely. One case of the latter has been observed with the pits distributed on all the finger nails at corresponding levels, analogous to Beau's lines.


This describes the phase in which the wound is covered with epithelial cells. Macrophages release epidermal growth factor (EGF) which stimulates both the proliferation and migration of epithelial cells. Keratinocytes at the wound margins and around hair follicle remnants synthesise fibronectin which forms a temporary matrix along which the cells migrate. The cells move over the wound surface in a leap-frog fashion, the first cell remaining on the wound surface and forming a new basement membrane. When cells meet, either in the centre of the wound, forming islets of cells, or at the margin, they stop. This is known as contact inhibition. Epithelial cells only move over viable tissue and require a moist environment (Winter, 1962). In sutured wounds, epithelial cells also migrate along the suture tracks. They are either pulled out with the sutures, or gradually disappear.


Left to right double-edged thinning scissors - for thinning hair and blending in the coat carbon steel straight-cutting scissors Filipino heavy-duty scissors - used on 'feathers' for straight cuts two pairs of different-sized curved scissors for cutting hair around the feet Fig 9.4 Grooming scissors. Left to right double-edged thinning scissors - for thinning hair and blending in the coat carbon steel straight-cutting scissors Filipino heavy-duty scissors - used on 'feathers' for straight cuts two pairs of different-sized curved scissors for cutting hair around the feet


Sodium and chloride are the major electrolytes in the body water. They are needed for acid-base balance and for the regulation of the concentration of the body fluids. Chloride is a component of bile and hydrochloric acid. Fish, eggs, whey and poultry meal are rich in both sodium and chloride. A deficiency of these minerals can arise from excessive fluid loss, such as occurs in vomiting and diarrhoea. Signs include exhaustion, inability to control water balance, dry skin and hair loss. An excess will cause a greater than normal fluid intake and may predispose animals to hypertension and therefore heart and kidney problems.


Two minor side effects of beam therapy are pubic hair loss and fatigue. The hair loss may be temporary or permanent, but the radiation does not affect hair on the head. Fatigue, which may be marked, usually begins three to four weeks after the treatment course begins. Exercise can help one study reported that men who walked for thirty minutes each day during the treatment period experienced less radiation fatigue.6

Fat Soluble Vitamins

Although your body controls the creation of vitamin A from beta-carotene, it has no control when you ingest straight vitamin A, which can be found in vitamin tablets. Over-supplementation can be extremely toxic, resulting in general fatigue and weakness, severe headaches, blurred vision, insomnia, hair loss, menstrual irregularities, skin rashes, and joint pain. In extreme cases, there can be liver and brain damage. Huge doses taken in the prenatal period can cause birth defects.

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