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Follicular Diseases Causing Scarring Alopecia

Follicular destruction results in scarring alopecia that can be classified as primary or secondary. In primary scarring alopecias, the follicle is the target of inflammation. In secondary scarring alopecias, the follicle is an innocent bystander that, nevertheless, is destroyed. Examples of secondary scarring alopecias include morphea and tumors (alopecia neoplastica). In this chapter, we will consider only the primary scarring alopecias. In this group of diseases, the inflammation can be primarily lymphocytic or neutrophilic. Although all parts of the follicle can be involved, the disease is felt to destroy the bulge area of the follicle, where the arrector pili muscles insert. This area contains the follicular stem cells necessary for regeneration of the lower follicle during normal follicular cycling. When this part of the follicle is destroyed, the follicle is doomed. The sebaceous glands are also destroyed in primary scarring alopecias. The destruction of these structures and the...

Alopecia Areata

Many diseases of hair follicles result in alopecia, which is simply defined as any type of hair loss. The alopecias are conventionally grouped into nonscarring and scarring categories. Nonscarring alopecias may be localized or diffuse. Since the follicles are not destroyed in the nonscarring alopecias, there is potential for regrowth or return to normal hair density in these conditions. Follicular diseases that result in follicular destruction and permanent hair loss are termed scarring alopecias. There is some confusion in this categorization scheme because some of the nonscarring alopecias can eventuate over many years into areas of permanent alopecia through follicular drop-out.

Rationale for the Use of 5aReductase Inhibitors in Cancer Treatment

Steroid 5a-reductase is a membrane bound, NADPH-dependent enzyme that is responsible for the selective, irreversible conversion (reduction) of 4-ene-3-oxosteroids into the corresponding 5a-3-oxosteroids (Fig. 10). Two genes code for 5a-reductase activity, the 5a-reductase type 1 and type 2 (5aR-1 and 5aR-2), and they are only 50 homologous on the protein level 114 . 5aR-1 is mainly expressed in the sebaceous glands of the skin and in the liver, whereas 5aR-2 is expressed in androgen-sensitive tissues, i.e. prostate, epididymis and other reproductive tissues 115 . The 5a-reductases are important regulators of endocrine action in androgen-sensitive cells. The 5aR-2 isoenzyme has a high affinity for the most important substrate testosterone (Km 4-50 nM) while the affinity of the 5aR-1 for testosterone is considerably lower (Km 1-5 M). The physiological roles of testosterone and dihy-drotestosterone (DHT) are quite different. In males, testosterone determines the modification of external...

Alphahydr0xylase Deficiency

Labs Markedly reduced dihydrotestosterone with normal testosterone level. Decreased 5-a-reductase activity. Discussion An autosomal-recessive disorder of virilization affecting genetic males. 5-a-reductase converts testosterone to dihydrotestos-terone. Lack of type 2 isozyme of 5-alpha-reductase produces a decrease in dihydrotestosterone, which is responsible for virilization of the external genitalia.

The Concept of The Champion in Drug Discovery Benign Prostatic Hypertrophy and the Inhibition of 5aReductase

From time to time, a person in a non-managerial position will have a marked impact on the research organization by single handedly becoming the champion for a specific research project. To those who were privileged to interact with him, Dr Glen Arth served as a splendid example of a champion. Dr Arth, an outstanding experimentalist, had been one of the important players in Dr Sarett's total synthesis of cortisone, which was the only practical rather than 'formal' synthesis of this hormone. Later, Dr Arth championed the search for a treatment of a disease that burdens many elderly men, known as benign prostatic hypertrophy (BPH). In the 1950s, Merck started to take an interest in investigating the role of androgens in several disorders linked to male sex hormones such as prostate disease, acne, and 'male pattern baldness.' Critical to the eventual success of the program was the recognition in the late 1960s that the enzyme 5a-reductase converts the male hormone testosterone into the...

Steroids and Lipoproteins in the CNS

Estrogenic control of apoE mRNA is directly shown in vitro. In mixed glial cultures (65-75 astrocytes, 15-20 microglia, 10-15 oligodendrocytes originated from cerebral cortex from 1-5 day old rat pups), the levels of apoE mRNA are increased 2-fold by the addition of 17p-estradiol at a concentration of 0.1nM (approximately blood levels at late proestrus or pregnancy). This apoE induction occurs in both astrocytes and microglia. However, no induction is caused by corticosterone or dihydrotestosterone (Fig. 3.3). This upregulation is dependent upon cell-cell interactions, as neither astrocytes or microglia respond to estrogen with increased apoE mRNA when grown in monotypic culture.26 Cell-cell contact is also necessary for this increase,29 as separation of astrocytes and microglia with a 0.45 im pore-size filter removed the estrogen effect.

Signs and Symptoms of the Arteritic Form of AION j Note

The average age at the onset of anterior ischemic optic neuropathy in patients with temporal arteritis (AAION) is about 75 years. Arteritis can also present with branch retinal vessel occlusions, choroidal infarctions, or retinal ischemia, as indicated by the presence of numerous cottonwool spots. Ischemic pareses of the extraocular muscles may be present, and ischemia of the scalp, sufficient to cause patchy areas of hair loss, have been known to appear. Even myocardial infarctions, hemispheric strokes, and cranial nerve palsies can be caused by severe forms of arteritic disease. Temporal arteritis (also called giant cell arteritis, cranial arteritis, or Horton's cephalgia a now-obsolete term ) has the following typical signs and symptoms headache, jaw claudication, scalp pain when combing or brushing the hair, malaise, fatigue, low-grade fever, anorexia, migratory myalgias, weight loss, and thickened, cord-like enlargements of the superficial, subcutaneous arteries of the scalp (...

Therapeutic Cancer Vaccines Vs Traditional Cancer Treatment

Traditional cancer drugs are cytotoxic agents, meaning that they kill cells. Although most chemotherapeutics preferentially affect rapidly dividing cells (i.e., cancer cells), they cannot differentiate between malignant and normal cells. The unavoidable toxicity to normal cells often results in treatment-related toxicities such as increased susceptibility to bleeding and infection, mucositis, nausea and vomiting, hair loss, etc. This nonspecific approach to cancer treatment makes it more suitable for use in disease settings in which the tumor burden is high, such as advanced or metastatic disease.

Historical Context

For long outside the body and enters through mucous membranes or skin, typically sexually transmitted (venereal) passed from mother to child (congenital) or spread through blood transfusions. Its four recognizable stages are primary, secondary, latent, and tertiary. Treatment should begin at first indication, usually when, in the sexually transmitted kind, a chancre or lesion appears on the genitals within four to six weeks of infection. If untreated, the secondary stage from six to 12 weeks after infection includes headache, fever, nausea, swollen lymph nodes, rashes, sore throat, and fatigue. Lesions may persist, and grayish patches with red areolae may occur on the mucous membranes of the mouth and genital region. Hair patches often fall out (alopecia areata). After three months symptoms may come and go but the whole body is now infected as bacteria invade vital organs, bone marrow, and the central nervous system. During a period of latency, from a few years to the end of life, the...

Toxicities of radioimmunotherapy

The major complications of radioimmunotherapy are infusional reactions during the administration of the cold antibody, especially the rituximab, and myelo-suppression that occurs around 7-9 weeks after therapy. Febrile neutropenia or infections that require hospitalization are uncommon events. There is little in the way of alopecia, nausea, vomiting, or mucositis. Because of the radioactive iodine, I-131 tositumomab therapy is associated with hypothyroidism in fewer than 10 of patients.

Essential Fatty Acids

Ample intake of the EFAs (see pp.89) is vital during infancy. Because infants absorb fat poorly and have low fat stores, they are particularly sensitive to EFA deficiency and quickly develop signs of deficiency if fat intake is low. Infants fed formulas deficient in li-noleic acid for just a few days may develop a dry, eczema-like, flaky skin rash, diarrhea, hair loss, and impaired wound healing. Deficiency also impairs platelet function and lowers resistance to infection. Regular intake of EFAs is therefore critical during infancy, and although breast milk is rich in EFAs, not all infant formulas have adequate amounts.

Suppression of Autoimmune Disease by Regulatory Cells from Donors with or Without the Relevant SelfAg

In murine autoimmune prostatitis, in which prostate Ags are expressed at the age of 2 weeks, it was found that total male spleen cells suppressed better than female cells (Taguchi and Nishizuka 1987). The male supremacy was lost when the cell donors were neonatally orchiectomized to prevent prostate development, but it was restored when prostate development was subsequently induced by dihydrotestosterone. We have confirmed this interesting finding by showing that CD4+CD25+ T cells from male donors also suppressed more efficiently than cells from female donors (Setiady et al., unpublished data). Importantly, exposure of cell donors to endogenous Ag for only 10 days was sufficient to enhance the regulatory capacity of CD4+CD25+ T cells of Ag-negative donors to that of Ag-positive donors. This finding is relevant to AOD suppression. For example, for the inexperienced male cells to rapidly gain regulatory capacity through encounter with the ovarian Ag in the d3tx recipients, it may need...

Hyaluronan in Epidermal Appendices and Other Derivatives of Ectodermal Epithelium

The stratified epithelia in the hair follicle, including outer and inner root sheaths, show hyaluronan in the same pattern as epidermis, abundant around the non-differentiated cells but absent in the differentiated cell layers (23). The fat-laden sebocytes in the sebaceous glands show an interesting pattern, with a cell surface hyaluronan staining shifting into the cells upon maturation (Fig. 1c). This feature may be associated with the fact that maturating sebocytes were one of the few cases in which CD44 was missing from hyaluronan-positive cells (23).

Synopsis Of The Play

Professor Vivian Bearing, literary researcher, is now herself the subject of cancer research. Two dissimilar fields of study form the foundation of a moving play looking at the boundaries of the intellect and the expanses of the heart. Primarily set in a University Hospital Comprehensive Cancer Center room, there are no action breaks between scenes and no intermission in the 90-minute play. Therefore, lighting changes signify important transitions. Dr. Bearing enters an empty stage pushing an IV pole, giving immediacy to her dire situation. She wears two overlapping hospital gowns for modesty and a hospital ID bracelet, and covers her baldness with a baseball cap. Out of a cast of nine, Bearing carries the play, intermittently breaking the fourth wall by directly addressing the audience. Setting the tone for the play, in her professorial voice she asks the audience, Hi. How are you feeling today Then in a witty academic response slightly mocking, she analyzes the question's ironic...

Microanatomical And Embryological Considerations

Although we often think of hair follicles, sebaceous glands, and apocrine glands as distinct elements, all three components actually stem from the same structure, which has been termed the folliculosebaceous-apocrine unit. For practical purposes, the terms follicle, hair follicle, folliculosebaceous unit, and folliculosebaceous-apocrine unit are used interchangeably. The folliculosebaceous-apocrine unit is a structure that provides insulatory, cosmetic, and pheromonic functions to the mammalian organism. The eccrine unit is a completely independent structure that serves as a thermoregulatory device via secretion of sweat.

Effects of Selenium Antagonistic Elements

The cancer-protecting effects of selenium are counteracted by selenium-antagonistic elements that may be found in foods, the drinking water, or the environment (17-23). Some of these elements, arsenic (As), lead, mercury, and cadmium, for example, are known to inhibit selenium-dependent enzymes, impede selenium uptake, or to form unreactive selenides accumulating in organs and tissues, while others counteract the cancer-protective effects of selenium indirectly by stimulating oxygen radical production. Accordingly, the selenium requirement increases in the presence of such elements. These findings are relevant to occupational medicine A Swedish study (24) revealed that lung tissues from foundry workers who had died from lung and other types of cancer exhibit much higher arsenic selenium ratios than those from foundry workers who had died from heart disease or accidents. Higher arsenic selenium ratios were observed in the scalp hair of miners of a tin mine in China who developed lung...

Mpact of Symptom control on Therapeutic Decisions

Palliative care addresses issues specifically related to morbidity, rather than mortality. Morbidity encompasses existential concerns (fear, anxiety, concerns about body image, sexual attractiveness, competence, depression, isolation, and abandonment), symptoms that are caused by the disease itself (pain, weight loss, dyspnea, gastrointestinal symptoms, lack of mobility), and therapy-related symptoms (hair loss, weight gain, nausea, vomiting, and mutilating surgical procedures, including amputation, evisceration, and venous access devices). Adequate attention to relief of symptoms can transform a devastating experience into one that is manageable, and which may even enhance personal growth and intimacy 8, 9 .

Carp X Carp Xi Ca

Basal cells of epidermis and squamous mucosa of uterine cervix negative high level in the basal cells in and near the infundibulum and medulla of hair follicle sweats glands negative Focal expression in the basal cells of the epidermis squamous mucosa of uterine cervix negative basal cells of hair follicle negative diffuse reactivity of sweat and salivary glands

The DiGeorge Syndrome and Other Forms of SCID due to Defective Thymic Epithelial Development

These mice have an inherited defect of certain types of epithelial cells in the skin, leading to hairlessness, and in the lining of the third and fourth pharyngeal pouches, causing thymic hypoplasia. The disorder is due to a mutation in the FoxN1 gene encoding a Forkhead family transcription factor that is required for the normal development of certain ectoderm-derived cell types. Affected mice have rudimentary thymuses in which T cell maturation cannot occur normally. As a result, few or no mature T cells are present in peripheral lymphoid tissues, and cell-mediated immune reactions cannot occur. Autosomal recessive FOXN1 mutations have been described in a small number of patients who present with SCID, alopecia (hair loss), and nail dystrophy. An even rarer defect in the thymus has been described involving a mutation in CORONIN-1A, which encodes a protein that regulates the actin cytoskeleton. The absence of functional CORONIN-1A results in defective egress of...

Hyaluronan Synthase Gene Expression

Numerous studies have indicated that Has2 is the key gene with respect to the bulk of the HA biosynthesis that occurs in mammals (13-17). Has2 is expressed broadly during mouse embryogenesis, correlating with all previously described spatial and temporal localizations for HA ((18) and Tien and Spicer, manuscript in preparation). These include the endocardial cushions of the developing heart, craniofacial mesenchyme, precartilage areas, hypertrophic chondrocytes, neural crest cells and their derivatives (Fig. 1A). In contrast, Has1 is expressed only during gastrulation (E7.5-E8.5) in a more general pattern (data not shown), and Has3 is expressed only by the mesenchymal component of developing teeth and hair (Fig. 1B-F). Both teeth and hair develop through strong interactions between epithelial cells and mesenchymal cells (20). Within each developing hair follicle, Has3 expression is transient, correlating with the timing of condensation. In contrast, Has3 expression is detectable as...

Summary and conclusion

HA has been previously thought of as 'a goo', quite simply a large, hydrated, slippery molecule. The results obtained from the molecular dissection of HA function in the mouse demonstrate that this simple polysaccharide has diverse functions during morphogenesis. HA can indeed act as a space filling, or perhaps more accurately, a space-creating molecule, acting as the nucleus around which an organized, hydrated HA-dependent ECM is assembled. This function is important in the outgrowth of the nasal processes (49), in the expansion of the cardiac jelly of the heart and in the formation of a large hydrated matrix around the neural tube prior to neural crest cell exit. A large organized HA-dependent extracellular matrix may effectively inhibit cell-cell adhesion. Accordingly, if such a matrix is endocytosed or degraded, cell-cell contact may be achieved. This is essentially the process underlying condensation, which occurs for instance during chondrogenesis and hair follicle development....

Demonstration of a Structure Toxicity Relationship A Strategy for Lead Progression

The drug-sparing 30-day toxicology protocol designed by Piper required that my laboratory need only prepare 8-12 g of each test compound. The use of such limited drug quantities was feasible, as the protocol would involve the dosing of only three rats per sex. As the rationale of the study was to enable the expeditious identification of oxazolidinones having at least a 10-fold therapeutic index in the rat, the test compounds were dosed orally, twice daily (b.i.d.), at a dosage level 10-fold the ED50 (the effective dose (mgkg_ 1) that protected 50 of the mice from death after an injection of a lethal dose of S. aureus). As the comparative study progressed, the toxicologists reported several distinct toxicological findings that were readily apparent by clinical observation in the group of rats dosed orally with ( + )-DuP-721 at 100mgkg_ 1 day_ 1. Those findings included alopecia, severe anorexia, ataxia, and the death of one of the six animals another two animals observed in a moribund...

Development Of Ectodermderived Organs

The epidermal appendages, including the hair, nails, and sebaceous glands, are also derived from the basal layer stem cells at designated sites. The formation of epidermal appendages is regulated by epidermal and dermal factors. For hair formation, it is necessary to establish a hair follicle primordium, the early form of the hair follicle. The follicle primordium is derived from the basal layer. At a specific site where dermal fibroblasts are activated by autocrine regulatory factors, the basal layer cells form cell clusters, undergo shape changes, and invade the dermal layer, forming scattered cell nodes. The dermal fibroblasts release growth factors, which stimulate the node cells to divide and differentiate into hair follicle cells and keratin hair shaft. The hair shaft grows out of the dermal layer and forms hair. There are follicle stem cells that can self-renew and differentiate into hair cells and regenerate the hair shaft when hair is damaged, removed, or shed. When the basal...

Ancient Roman Cosmetic Unearthed

Biotechnology has contributed to the development of cosmetics that not only beautify but that also have a medicinal action. Known as cosmeceuticals, sunscreens, baldness treatments, and anti-dandruff shampoos are three examples. Although the term cosmeceut-ical is gaining popularity, the FDA does not recognize it and requires any product with the properties of a drug to be approved as a drug.

Radiation as a Cancer Therapy

It was soon noted that roentgen rays could burn the skin or irreparably damage internal organs or structures. In 1896, Dr. D.W. Gage of McCook, New Brunswick, writing in New York's Medical Record, noted cases of hair loss, reddened skin, skin sloughing, and strange growths or lesions. I wish to suggest, he wrote mildly, that more be understood regarding the action of the roentgen rays before the general practitioner adopts them in his daily work (81).

Literary Analysis

The mind helped mask awareness of the disease's vague physical symptoms. Now in stage 4 with metastatic spread to distant organs, late detection means little possibility of significant recovery. The play begins in medias res with Bearing, a researcher herself, signed up for an eight-month research protocol involving chemotherapy and high-dose experimental drugs given fictional names. To shrink her grapefruit-size tumor healthy cells will die along with the cancer. By consenting to the study she contributes to knowledge but suffers harsh side effects, including hair loss, nausea and vomiting, compromised immunity, fatigue, and pain. Cancer in a no-nonsense university professor, now a research subject detached from the outside world, causes her to become vulnerable.

Acne Keloidalis Nuchae Also Known As Folliculitis Keloidalis

Figure 1 (A) Well-circumscribed areas of nonscarring hair loss in typical alopecia areata. (B) Marginal hair loss in ophiasis pattern alopecia areata. (C) Diffuse hair loss in diffuse alopecia areata. (D) Exclamation point hairs (arrows) in an active patch of alopecia areata. Figure 1 (A) Well-circumscribed areas of nonscarring hair loss in typical alopecia areata. (B) Marginal hair loss in ophiasis pattern alopecia areata. (C) Diffuse hair loss in diffuse alopecia areata. (D) Exclamation point hairs (arrows) in an active patch of alopecia areata. Figure 2 (A) Low power view demonstrating normal follicular density, numerous telogen follicles ( 90 ), and follicular miniaturization in alopecia areata (T V 1 3). (B) Four telogen germinal units (thin arrows) and several pigment casts (thick arrows) in a biopsy of alopecia areata. (C) Peribulbar lymphocytic infiltrates around vellus hair follicles in alopecia areata. (D) Peribulbar lymphocytic infiltrate around a terminal hair follicle in...

Hormonal regulation of bone remodeling

Sex hormones are major regulators of bone turnover and remodeling in both genders. Estrogens reduce bone loss by inhibiting the generation of new osteoclasts, reducing the activation frequency of the BMU and promoting apoptosis of mature osteoclasts via mechanisms that are not well understood. Some of the effects of estrogen seem to be mediated via the modulation of growth factors and cytokines, while others are associated with binding to at least two different estrogen receptors (ERa, ERb). A reduction in circulating endogenous estrogen levels, as occurs during and after menopause, has been shown to prolong osteoclast survival and stimulate the recruitment and hence generation of osteoclasts. The result is an increase in the activation frequency of the BMU, reflected in a high bone turnover state.14 While there is no doubt that androgens (i.e., testosterone, dihydrotestosterone) play a dominant role in male bone health, it also appears that circulating estradiol levels are important...

Psychosocial and Supportive Care

Honing social and interpersonal skills is an important developmental milestone during adolescence. Cancer treatment for these patients must accommodate this important developmental process. We have discharged a patient from the intensive care unit to allow her to attend her senior prom, and readmitted her when the party was over. Yet boundaries must be set, so that treatment effectiveness is not compromised to keep a social calendar. Certainly, cancer therapy causes practical problems in social arenas. Adolescent and young adult patients, who are developmentally dependent on peer-group approval, often feel isolated from peers by their experience the cancer patient's issues are illness and death, while their peers are consumed by lipstick and homework. All adolescents agonize over their personal appearance and hate to be singled out or to appear different. In adolescents with cancer, having to be isolated from peers and society by having a disease that makes them different and having...

Dna Repair Mechanisms

The RAD2 gene product has been shown to have the ability to act as a single-stranded DNA endonuclease, directly implicating the RAD2 gene and its XPG human homologue as an important component in the incision of a damaged DNA strand during excision repair.131 Two other human DNA repair defect diseases, Cockayne's syndrome (CS) and PIBIDS, which is a photosensitive form of the brittle-hair disease trichothiodystrophy (TTD), also have genetic defects that may correlate to genes in yeast. It is peculiar, however, that patients with PIBIDS have all of the symptoms of CS as well as some of those of TTD, and patients with CS and PIBIDS do not appear to have a higher than expected incidence of cancer. This is one of the curious examples of a remarkable clinical heterogeneity among patients with the same apparent genetic defects, that is, the same mutation in different individuals giving rise to different clinical syndromes. Such heterogeneity has been...

Dehydroepiandrosterone DHEA

DHEA has multiple possible adverse effects. It may cause liver injury. Other side effects include acne, hair loss, voice deepening, fatigue, altered menstruation, abdominal pain, hypertension, and increased risk of some hormone-sensitive cancers, including breast, endometrial, and prostate cancer. The safety of long-term DHEA use has not been established.

Studies in MS and Other Conditions

Aromatherapy has been studied in a few other unrelated conditions. Small studies on older people with dementia have produced mixed results. Inhalation of black pepper extract may decrease the craving for cigarettes. People with a form of baldness called alopecia areata may benefit from scalp massage using a mixture of thyme, rosemary, lavender, and cedar-wood oils.

Mycosis Fungoidessezary Syndrome

Pathology The skin lesions of MF are histologically characterized by an epidermal infiltrate of small- to intermediate-sized cells with irregular, cerebriform nuclei. The presence of such cells in small clusters, known as Pautrier's microabscesses, is very characteristic of the disease, but in most cases the epidermal infiltrate is present predominantly as scattered, single atypical cells.114 The dermal component may be variable, ranging from a sparse, often band-like, infiltrate in earlier lesions to an extensive collection of malignant cells filling the dermis in advanced stages (Figures 52.19 and 52.20). In a variant form of MF, known as pagetoid reticulosis, the dermal component is characteristically absent. Some cases of MF are associated with follicular mucinosis, a condition of mucinous changes within a hair follicle accompanied by an infiltrate of malignant cells within the follicular epithelium. The variant known as granulomatous slack skin typically shows a granulomatous...

Treatment of Advanced CLL

Pression and in particular granulocytopenia. CAP-treated patients had a higher frequency and severity of nausea and vomiting (25 vs 5 ,p 0.001) and alopecia (65 vs 2 ,p 0.001). These results indicate that FDB compared favorably with CAP in terms of response, although this difference did not induce a survival improvement. On the basis of these results (observed in a previous interim analysis held in September 1996), it was decided to discontinue accrual in this group. As expected, median survival was better for stage B (81 mo) than for stage C patients (60 mo). Causes of death were related to CLL in 75 of cases, and overall survival did not differ among the three arms (67, 70, and 69 mo in the ChOP, CAP, and FDB groups, respectively). Incidences of infections ( 5 ) and autoimmune hemolytic anemia ( 2 ) during the six courses were similar in the randomized groups, whereas FDB, compared with ChOP and CAP, induced more frequent protracted thrombocytopenia (p 0.003) and less frequent...

Endocrine Disorders Associated with Myofascial Pain

The most common complaints found in hyperthyroidism include muscle weakness and pain, TrPs, heat intolerance, increased sweating, thinning hair, increased appetite, emotional mental difficulties, and sexual dysfunction. The physical findings may reveal a goiter, proptosis, loss of convergence, lid lag, increased deep tendon reflexes, tachycardia, cardiac arrhythmias, and a fine, fast tremor of the hands fingers. Laboratory findings include high levels of T3 (triiodo-thyronine), T4, and free thyroxine index. The TSH is typically low. Muscle weakness, wasting, spasm, and pain are frequently associated with Cushing's disease secondary to an adrenocorticotropic hormone (ACTH)-secreting tumor of the pituitary, with associated adrenal hyperplasia and Cushing's syndrome (secondary to a primary adrenal tumor or ectopic production of ACTH). Other signs and symptoms include female facial hirsutism, round, red facies, purple abdominal striae, thin skin with easy bruising, thinning scalp hair,...

Quality of Survival

The quality of survival, both during and after therapy, is a critical issue for adolescents and young adults. Quality of life is poor during the months and years when most adolescents and young adults with cancer are treated, and the acute and delayed toxicities of cancer therapy are undeniably among the worst associated with the treatment of any chronic disease. The acute toxicities of nausea, vomiting, mucositis, alopecia, weight gain (or excessive loss), acne, bleeding, and infection are generally harder for adolescents to cope with than for either younger or older persons. Delayed complications may be of low concern to patients in this age group during treatment, but after therapy has been completed these complications can be frightening and real. Cardiomyopathies, growth disturbances, and neu-ropsychological side effects are examples of adverse late effects that are hard to describe in a meaningful way before initiating therapy to an adolescent or young adult. A particularly...

Diagnosis

The earliest signs that are suggestive of a diagnosis include failure to thrive, alopecia, and subcutaneous skin changes suggesting scleroderma. Variable degrees of insulin resistance and inconsistent abnormalities of serum cholesterol and other lipids are found, but there are no demonstrable abnormalities of thyroid, parathyroid, pituitary, or adrenal function. We studied five cases of progeria and found 24-hr growth hormone levels to be normal, but reduced levels of insulinlike growth factor I and markedly increased basal metabolic rates were found, suggesting a profile of bioinactive growth hormone (35).

Toxicity

There is a strong temptation to perform significance tests for each toxicity. However, it is usually inappropriate to do this because standard advice for significance tests is not usually followed. In particular, as described with reference to Table 9.6, null and alternative hypotheses are not clearly stated, a lack of significant difference between arms is treated as a 'proof' of equivalence and adjustment is not always made for multiple testing. Further, it should be noted that the trial alone is unlikely to be the only source of toxicity data for the treatments being compared. For example, in the above ICON2 trial it would not be informative to perform a significance test of whether the rate of alopecia Alopecia is different in the two treatments, before other issues are addressed. Issues are how important is the side effect of alopecia to patients and what sort of differences between alopecia are important Thus, if the relative toxicity of the treatments are likely to be critical...

Antimitotics

Tumor, chronic leukemia, thyroid cancer, brain tumors, and trophoblastic neoplasia. Adverse reactions are broad, including typical side effects of cytotoxic chemothera-peutics, such as myelosuppression, mucosi-tis, fever, anemia, and alopecia. Vincristine also causes additional side effects, such as hypertension, neuropathy, depression, Raynaud's phenomenon, myocardial infarction, and pulmonary edema. Resistance mechanisms include gp170-mediated MDR and mutations in tubulin subunit proteins that decrease drug binding. Vinorelbine is a semisynthetic derivative of vinblastine that also inhibits tubulin polymerization and disrupts spindle assembly in the M phase. This compound has a higher specificity for mitotic microtubules and a lower affinity for axonal microtu-bules, reducing neuropathy. Vinorelbine is indicated in the treatment of lung cancer, breast cancer, and ovarian cancer. Adverse reactions are similar to those produced by vinblastine include myelosuppression, nausea,...

Mouse Phenotype

Although embryonic development of the r r mice appeared to be normal, as early as approximately 4 weeks of age they began to develop thick skin and patchy hair loss accounted for by dermal fibrosis. In older mice ( 5-6 months) skin abnormalities consisting of thickening and roughening, associated with patchy hair loss and small ulcerations were regularly observed.33 Indeed, in our initial report, we had not yet systematically examined the younger mice. Examination of skin sections revealed that the dermis from the r r mutant mice was significantly thicker than that from control (r r) mice and was filled with dense collagen fibers (Fig.10.4). The collagen fibers were irregular in form and penetrated deeply into the hypodermis. The overall increased thickness of the skin in the homozygous r r mice, extending from the epidermis to the muscular layer, was accounted for by the increase in thickness in the dermis. The hair follicles appeared to be buried within the dense collagenous...

As In The Skin

In striking contrast to the expression of CAs I and II and according to Ivanov et al. (2001), CA IX is not expressed in normal human skin. All epithelial cells of the normal skin and all endothelial cells of capillaries and sweat glands remain totally unstained for CA IX. The same authors through immunohistochemical studies recently demonstrated the presence of CA IX in basal cells, in and around the infudibulum and medulla of the hair follicle (Ivanov et al. 2001). In line with these observations, more recent investigations demonstrate a faint but always present staining for CAs I, II and IX in the cells surrounding the hair shaft. However, whereas

Clinical efficacy

This drug has clinical activity in a number of malignancies including pancreatic, lung, ovarian, bladder, and breast cancer (13). In fact, it was initially approved for the treatment of metastatic pancreatic cancer based on studies showing that it improved overall quality of life (14,15). Overall gemcitabine is well tolerated with its major dose limiting toxicity being myelosuppression as it is with the other antimetabolites. Nausea and vomiting are not uncommon however, they are only severe in fewer than 15 of patients. Transient rashes that tend to be macular, erythematous, and puritic, flu-like symptoms, and alopecia may occur. Optimal systemic dosing of this drug is not necessarily defined and certainly the optimal dosing for combined therapy with radiation is undefined at this stage. Most regimens using the drug for its systemic effect administer between 800 and 1250 mg m2 iv once a week for 3 out of a 4-wk cycle (13).

The Taxanes

Taxane to show antineoplastic activity in vitro. Paclitaxel was originally isolated from the bark of the western yew tree, Taxus brevifolia (50). Phase I studies defined its toxicity profile, which included neutropenia, neuropathy, mucositis, arthralgias, hypersensitivity reactions, nausea, and alopecia (51,52).

Anabolic Steroids

General effects of anabolic steroids (86) include baldness, acne (typically affecting the shoulders and upper back), raised blood pressure and heart rate, fluid retention, and a reduction in high-density lipoprotein cholesterol. Long-term effects include an increased risk of thrombosis. Gynecomastia may occur, and the prostate gland may swell, resulting in impaired micturition. Most of these effects are dose dependent and more likely with prolonged administration. In women, menstrual irregularities are reported, with permanent enlargement of the clitoris. There may also be growth of facial and body hair, male pattern baldness, and decreased breast size. Abuse of sex steroids by recreational body builders may be an unrecognized cause of subfertility (88).

Vinca Alkaloids

Toxicity Although vincas are structurally similar, their spectra of activity and adverse effects differ significantly. The dose-limiting toxicity of vincristine is neurotoxicity, likely due to inhibition of microtubule effects related to neuronal transmission.65 This can manifest as sensory and or motor neuropathy and is characterized by paresthesias, palsies, and pain. Autonomic complications, such as abdominal pain, orthostatic hypotension, constipation, and paralytic ileus, may also occur. For this reason, vincristine doses have traditionally been limited to 2 mg, although recent protocols are challenging this maximum dose. Other adverse effects associated with vincristine include SIADH and alopecia. Fatal cases of intrathecal administration have been reported.66 While the potential for myelosuppression exists with vincristine, it is uncommon at standard doses. Conversely, the dose-limiting toxicity for vinblastine and vinorelbine is myelosuppression. Anemia and thrombocytopenia...

Acute toxicity

The major acute toxicity of 2-CdA is myelosuppression. In their long-term follow-up study, investigators at Scripps Clinic noted a 16 incidence of Grade 3 and a 71 incidence of Grade 4 neutropenia in the first 135 consecutive treated patients.5 Ten percent had Grade 3 and 10 had Grade 4 thrombocytopenia. Grade 3 anemia occurred in 20 and Grade 4 in 2 . Forty-two percent developed neutropenic fever, though in only 13 , was an infection documented. Of these, the most common infecting organism was Staphylococcus, usually associated with the indwelling intravenous catheter. Although there were several oral herpetic infections and acute dermatomal herpes reactivations, no fungal infections were found. This high rate of neutropenia with culture negative neutropenic fever was also noted at similar rates in other single-institution series with 2-CdA. Despite the frequency of myelosuppression, additional acute toxicities were uncommon. There were no significant rates of nausea, vomiting,...

Pharmacology

These drugs produce other notable toxicities including a peripheral neuropathy characterized by numbness, paresthesia, and a symmetric distal loss of sensation including proprioception, vibration, pinprick, and temperature effects in a glove and stocking distribution (1). Myalgias and malaise are also common peritreatment complaints. Paclitaxel has also been associated with cardiac rhythm disturbances, myocardial ischemia, and reversible alopecia. Docetaxel has been associated with skin toxicity in the form of a puritic maculopapular rash on the forearms and hands as well as alopecia, nail changes, and stomatitis that is seen more frequently than with paclitaxel. Docetaxel has also been found to cause a unique fluid retention syndrome characterized by edema and third spacing of fluids including pleural effusions and ascites. The use of prophylactic steroid therapy and lower single doses appears to have decreased the incidence and severity of this side-effect (1).

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