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IFN has been associated with an autoimmune alopecia areata (30), but, more commonly, mild nonspecific hair loss occurs, which can be particularly disturbing to some patients, but will almost always resolve after cessation of IFN. Alopecia is no more common with rebetron combination therapy, and is seen to some degree in up to 32 of patients treated for 1 yr. The authors have seen one patient who lost all body hair, secondary to IFN, with normal return of hair after stopping IFN. Several hints for reducing the impact and degree of alopecia include placing a silk scarf on the pillow, or using satin pillowcases low-pressure showers during hairwashing trim longer, heavier hair, which will fall out more rapidly avoid perms, gels, and mousses and use wide-toothed combs or natural bristle brushes. The authors have not used agents such as minoxidil during IFN therapy, but this may be a reasonable approach in patients in whom hair loss is causing major emotional stress.

Niche for Normal and Cancer Stem Cells

Hair pigmentation is mediated by the melanocyte (MC) stem cell (SC) system residing in each individual hair follicle (HF). The melanocyte stem cell (MSC) system represents a regenerative type SC system that undergoes a regeneration cycle repeating quiescent and activated states. Concerning the MSC system, the regeneration cycle is regulated coordi-nately with that of follicular keratinocytes (hair cycle). We have shown previously that MSCs are distinguished from other compartments of MCs by a number of features (Fig. 1) (Nishimura et al. 2002). First, MSCs localize in the vicinity of the bulge region of the HF, whereas other compartments are located in the hair matrix at the lower part of the HF. Second, MSCs are quiescent until being reactivated when the new hair regeneration cycle is initiated. Third, MSCs are resistant to block of the c-kit signal, whereas the c-kit signal is essential for survival of other MC compartments. In fact, when an antagonistic mAb to c-kit is injected in...

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.

Side Effect Management

Musculoskeletal pain Psychiatric disorders Insomnia Irritability Depression Emotional lability Concentration impairment Nervousness Respiratory system disorders Dyspnea Sinusitis Skin and appendages disorders Alopecia Rash Pruritus Special senses, other disorders Taste perversion

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.

Signs and Symptoms of the Arteritic Form of AION j Note

Giant Cell Arteritis

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 (...

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...

Cytotoxic Antibiotics

Cytotoxic antibiotics depress the bone marrow, cause gastrointestinal upsets and stomatitis, alopecia, cardiomyopathy (daunorubicin and doxorubicin) and pulmonary fibrosis and skin rashes (bleomycin). Some of these effects are dose-dependent, for example, doxorubicin-induced cardiomyopathy. Others may be potentiated by concomitant use of radiotherapy.

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....

Comprehension Questions

59.4 A 24-year-old woman complains of bothersome hirsutism and skipping periods. She does not have evidence of voice changes, hair loss, or clitoromegaly. Pelvic examination does not reveal adnexal masses. Serum DHEA-S. testosterone, and 17-hydroxyprogesterone levels are normal. LH FSH ratio is 2 1. Which of the following is the most likely diagnosis

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.

Experimental Control Of Oxidative Stress Pathways

Several groups have been developing animal models with mitochondria deficiencies 91-93 . These models include the adenine nucleotide translocator (ANT-1), mitochondria superoxide dismutase- (SOD2-) deficient mice, Tfam-deficient mice, and the PolgA. ANT-1- deficient mice are a model for chronic ATP deficiency. These mice have increased production of ROS and hydrogen peroxide and a parallel increase in mtDNA mutations consistent with levels seen in much older mice 94 . SOD2-deficient mice die in the neonatal period from dilated cardiomyopathy or neonatal degeneration in the brain stem 92, 93 . The Tfam-deficient mice exhibit cytochrome c oxidase deficiency and die at around 3 weeks of age 95 . PolgA is a more recent mouse model, independently developed by two groups 29, 96 , that expresses a deficient version of the nucleus-encoded catalytic subunit of mtDNA polymerase. These mice develop a mtDNA mutator phenotype with a three- to fivefold increase in levels of mtDNA point mutations,...

Approach To Hirsutism

The pattern of hair growth is genetically predetermined. Differences in hair growth between ethnic groups are secondary to variations in hair follicle concentration and 5-a-reductase activity. Hair growth can be divided into three phases anagen (growing phase), catagen (involution phase), and telogen (quiescent phase). Hair length is determined by the length of the anagen phase, and the stability of hair is determined by the length of the telogen phase. Hair found on the face, axilla, chest, breast, pubic area, and anterior thighs are termed sex hair because they respond to sex hormones. Androgens (especially testosterone) initiate growth of, and increase the diameter and pigmentation of, sex hair. Androgens may be produced by the ovary or adrenal gland or by peripheral conversion. Dehydroepiandrosterone sulfate (DHEA-S) is derived almost exclusively from the adrenal gland. Dihydrotestosterone (DHT) is metabolized from testosterone by 5-a-reductase increased activity of 5-a-reductase...

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.

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...

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).

Balancing Benefits and Risks

To estimate the risks that might be associated with the clinical trial, consideration must be paid to the nature and potential severity of specific side effects from drugs being tested and the possibility of less favorable outcomes in women in control groups receiving standard therapy. In this trial, the side effects include nausea, vomiting, hair loss, neurological deficits, fluid retention, and reduced blood cell counts. In addition, there could be asthenia that commonly occurs with chemotherapy, the time spent in receiving treatment, the costs of the treatment, and the side effects, time, and costs associated with administration of growth factors given to counteract the decrease in blood cell counts.

Marbps And Disease Manifestation

Diet Cure Lipomas

Likewise, the SAR binding domain of SAF-A loses its DNA binding potential upon proteolytic cleavage during apoptosis (Gohring and Fackelmayer, 1997). There are reports that nuclear matrix proteins associate with granular nuclear bodies and undergo modifications in cells that undergo apoptosis (Zweyer et al., 1997). In most of the cases, the loss of DNA binding ability of MARBPs becomes central to the altered function. For example, Ku deficiency leads to extreme radiation sensitivity and high levels of chromosomal aberrations (Gu et al., 1997). This is due to the fact that the Ku heterodimer (Ku 70 80) binds to DNA double strand breaks and facilitate repair by non-homologus end joining pathway (Walker et al., 2001). In case of invasive breast cancer, a specific nuclear matrix binding protein called NMP has been identified, that recognizes a unconventional MAR in the promoter, stimulates the levels of NFkB, that in turn increases the DNA binding activity of NFkB observed in c-erb2 and...

Designing a Treatment Plan

Goaldevelopment In the context of this approach, long-term goals can be global descriptions of positive outcomes. For example, Jongsma and Peterson (1995) list the problem (e.g., impulse control disorder), a problem definition ( Pattern of impulsively pulling out hair leading to significant hair loss p. 72), and then a long-term goal ( Establish the ability to effectively channel impulses p. 73). Objective construction Objectives are short-term goals, cast in behaviorally measurable language. From the preceding example, objectives could include Decrease the overall frequency of impulsive actions or Increase the ability for self-observation (Jongsma & Peterson, 1995, p. 73). For managed care or insurance

CMyc and Activated Ras During Skin Tumorigenesis Cooperation at the Cancer Stem Cell Level

A number of transgenic mouse models have been used to study the in vivo effects of c-Myc ectopic or overexpression in murine skin. For example, human c-Myc (Waikel et al. 1999) or 4-OH tamoxifen-inducible, human c-MycER (Pelengaris et al. 1999 Flores et al. 2004) were targeted to the postmitotic (endogenously c-Mycneg) suprabasal compartment of the skin with the loricrin or involucrin promoters, respectively. In both cases, the mice developed epidermal hyperplasia and papillo-mas as a result of differentiated keratinocytes re-entering the cell cycle while subsequent terminal differentiation was inhibited. Interestingly, Loricrin-Myc mice exhibit reduced sensitivity to UV-B-induced apoptosis, suggesting that Myc may possess unexpected antiapoptotic functions, at least in some cell types (Waikel et al. 1999). Similar tumors were obtained by overexpressing mouse c-Myc within the basal layer of the epidermis, hair follicle outer root sheath, sebaceous glands, and hair follicle bulge...

Approach To Diseases Of The Breast Palpable Breast Mass

Laboratory testing is usually unnecessary in the evaluation of mastalgia, although a pregnancy test should be performed in reproductive-age women. Hormonal contraceptives or hormone replacement therapy may be causes of breast pain and consideration should be given to discontinuation or reduction of estrogen dosages. An appropriately fitted supportive bra and lifestyle changes, such as tobacco cessation, caffeine elimination, and stress reduction techniques, are often successful in alleviating symptoms. Evening primrose oil is available over the counter, is well tolerated, and often provides relief. For women with unrelenting pain in spite of the above modifications, danazol, an antigonadotropin, is Food and Drug Administration (FDA) approved for the treatment of breast pain, but is relatively expensive and has numerous side effects (hair loss, acne, weight gain, irregular menses).

Clinical Approach

If untreated, syphilis progresses to a second stage, in which the disease disseminates widely, and the patient may present with a pruritic, maculopapu-lar diffuse rash that classically involves the palms and soles. Patients also may have these lesions orally, called mucous patches, and they may suffer constitutional symptoms such as fever, myalgias, and headache. Other typical skin findings include condyloma lata, a gray papillomatous lesion found in intertriginous areas, and patchy hair loss.

Hyaluronan Synthase Gene Expression

Hyaluronic Acid Skin Cancer

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...

Neuropsychology Of Aged Rodents

Bimonte-Nelson and colleagues 51 also reported on the importance of hormone-related cognitive enhancements in aged male rats by demonstrating that testosterone, which is aromatized to estrogen, improved working memory. In contrast, administration of dihydrotestosterone, which is not aromatized to estrogen, did not attenuate age-related deficits in working memory. Thus, hormone therapy in aged males and females may have beneficial effects on some aspects of cognition when the age of the subjects is taken into consideration.

Vincristine Oncovin Vincasar PFS Side Effects and Contraindications. Vincristine causes severe tissue necrosis upon extravasation (123).Neurotoxicity is a significant potential problem with vincristine and is often treated in part by reducing the dose of the drug (347). Myelosuppression also occurs but to a lesser extent and this effect should be monitored to prevent significant toxicity to the patient. Gout can occur with vincristine administration and can be controlled by use of allopuri-nol. The other side effects of vinblastine are common to antitumor agents (alopecia, ulceration, nausea, diarrhea, etc.). Side Effects and Contraindications. Vinorelbine causes severe tissue necrosis upon extravasation as well as phlebitis (355). Prior i.v. administration of cimetidine partially avoids this. Mild neurotoxicity and myelosuppression occur and these effects should be monitored to prevent significant toxicity to the patient. Its most notable toxic side effect appears to be granulocytopenia. The other...

Ergogenic Aids Anabolic Steroids

Reverse Anabolic

It is clear that the use of anabolic steroids produces adverse effects on the liver and reproductive and cardiovascular systems. Effects on the liver include peliosis hepatitis (blood-filled cysts), impaired excretory function (jaundice), and liver tumors ACSM, 1984 . Cardiovascular effects include an increase in blood pressure, abnormal alterations in cardiac tissue, and abnormal lipoprotein-lipid profiles Hurley et al., 1984b . Males can experience a significant reduction in sperm production, testicular size, and testosterone and gonadotrophin production, and females often experience a deepening of voice, male pattern baldness, enlargement of the clitoris, a reduction in breast size, a disruption in their menstrual cycle, and an increase in facial hair. Most of these effects are irreversible even after the drugs are discontinued. There are also many psychological effects including an increase in aggressive behavior, an increase in anger and hostility, large deviations in mood, and...

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...

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...

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...

Clinical Studies In Patients With Metastatic Breast Cancer Phase 2 Study

None of the women in this study experienced severe hypersensitivity reactions. The observed toxicity profile was similar to that which is typical for solvent-taxanes grade 4 neutropenia occurred in 15 patients (24 ) primarily during the first treatment cycle, grade 3 sensory neuropathy occurred in seven patients (11 ), and grade 2 sensory neuropathy occurred in 12 patients (19 ). Severe (grade 3 and 4) neutropenia and sensory neuropathy in this study were less frequent than reported for solvent-based paclitaxel at a lesser dose (250 mg m2 vs. 300 mg m2) infused over three hours (73 and 22 , respectively) or 24 hours (81 and 13 , respectively) (12). Nausea, vomiting, fatigue, arthralgia, myalgia, and alopecia were reported to be easily managed, and are well recognized as taxane-associated toxicities (11).

Dermatologic Complications

Patients with underlying psoriasis or lichen planus may have an exacerbation of their skin condition, when they are treated with IFN. In addition, IFN may cause the de novo development of both psoriasis and lichen planus. autoimmune alopecia may also be associated with IFN therapy This is discussed in the next subheadings.

Pretreatment Evaluation And Education

Dry, itchy skin Alopecia fatigue and headache, depression and irritability, alopecia, nausea and vomiting, loss of appetite, insomnia, and the potential for disturbances in bone marrow and thyroid function. Ribavirin side effects, such as hemo-lysis and risk of teratogenicity, are discussed in detail. The patient is advised on the need for adequate contraception, and, if the patient is a female of childbearing potential, she is informed that monthly pregnancy tests will be performed while she is on therapy, and for 6 mo after stopping therapy. A detailed discussion of the authors' approach to these other side effects is found later in this chapter.

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

Is Fimbrin Involved in Cancer

Interestingly, fimbrin expression was also reported to be rapidly up-regulated in LNCaP cells by dihydrotestosterone and oestradiol (J.P. Zheng et al. 1997). This observation does not per se contribute much to the argument that fimbrin is involved in the transformation of normal epithelium to carcinoma. Testicular hormones are the major factors that regulate the growth and development of the prostate. It is

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...

Prostate Cancer Stem Cells A Target for New Therapies

Despite intensive study, we still know little about the aetiology of prostate cancer. The patient risk group is well defined, namely elderly men, and as a result most therapies and aetiological studies have centred on male sex hormones. Initially, as a result of the pioneering work of Charles Huggins almost 70 years ago (1941), removal of androgen supply by either orchiectomy or the chemical blockade of adrenal androgen and subsequent direct inhibition of androgen receptor binding to the activated (dihydrotestosterone) form of androgen (since the 1980s) provided almost instant relief from symptoms and longer-term tumour regression (Furr 1996). While these treatments remain palliative, prostate cancer eventually derives resistance to androgen-based therapies and returns in a frequently more aggressive, androgen independent form, which is fatal within 2 years of recurrence on average.

Contraindications and Side Effects

Dactinomycin is contraindicated in the presence of chicken pox or herpes zoster, wherein administration may result in severe exacerbation, occasionally including death. The drug is extremely corrosive in soft tissues, so extravasation can lead to severe tissue damage (14). To avoid this the drug is usually injected into infusion tubing rather than being injected directly into veins. When combined with radiation therapy, exaggerated skin reactions can occur as can an increase in GI toxicity and bone marrow problems. Secondary tumors can be observed in some cases that can be attributed to the drug. Dactinomycin is carcinogenic and mutagenic in animal studies and malformations in animal fetuses have also been observed. Nausea and vomiting are common along with renal, hepatic, and bone marrow function abnormalities. The usual alopecia, skin eruptions, GI ulcerations, proctitis, anemia, and other blood dyscrasias, esophagitis, anorexia, malaise, fatigue, and fever, for example, are also...

Therapeutic Uses Daunorubicin is

Alopecia, rash, contact dermatitis, urticaria, nausea, vomiting, mucositis, diarrhea, abdominal pain, fever, chills, and (occasionally) anaphylaxis are observable. When given along with cyclophosphamide, its cardiotoxicity is enhanced and enhanced toxicity is seen when given concurrently with methotrexate.

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...


Patients with hypothyroidism can present with a wide range of symptoms, including lethargy, weight gain, hair loss, dry skin, slowed mentation or for-getfulness, constipation, intolerance to cold, and a depressed affect. In older patients, hypothyroidism can be confused with Alzheimer disease and other conditions that cause dementia. In women, it is often confused with depression. Physical findings that can present in hypothyroid patients include low blood pressure, bradycardia, nonpitting edema, hair thinning or loss, dry skin, and a diminished relaxation phase of reflexes.

Stem Cell Therapy

The patient receives the stem cells through a venous catheter placed in a large vein in the neck or chest area. The cells travel to the bone marrow, where they produce new white blood cells, red blood cells, and platelets in a process called engraftment. Reconstitution of the bone marrow takes several weeks, although full recovery of the immune system can take a year or more. The most severe side effect associated with this therapy is the risk of serious infections developing during the period of bone marrow reconstitution. Other side effects such as nausea, vomiting, and hair loss are due to the radiotherapy.


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).

Cancer Therapy

Genomic developments are also enabling physicians to treat many cancers with alternatives to the traditional chemotherapy and its associated nausea, muscle wasting, and hair loss. For example, Figure 3.7 lists several of the prominent monoclonal antibody drugs that have been cleared for use by the FDA. Monoclonal antibody therapies, which are based on clones of a particular type of white blood cell that attack specific diseased cells, are available to treat a variety of cancers and other disorders.

Lung Cancer

In the current study, which ran from March 2001 to February 2002 at Indiana University in Indianapolis, 571 patients with recurrent NSCLC were given docetaxel or pemetrexed in a phase III clinical trial (see chapter 8). As of May 2003 the survival rate of the patients was about the same whether they were treated with pemetrexed (8.3 months) or docetaxel (7.9 months). Patients in both treatment groups had about a 30 percent chance of surviving for one year. Survival was no different between the two groups of patients, but those treated with pemetrexed were less likely to suffer from fever and infections caused by low levels of white blood cells. They were also less likely to be hospitalized for fever or other side effects or to need treatment to stimulate production of white blood cells. In addition, patients treated with pemetrexed suffered less hair loss and less numbness in the arms and legs.

Blood Cell

Fatty acids required in the diet for normal growth. In mammals, include linoleic and gamma-linolenic acids, obtained from plant sources, without which poor growth, scaly skin, hair loss and eventually death occur. Precursors of arachidonic acid and prostaglandins.

Case Scenario 122

The special chemistry section received laboratory requests for the following hormones total testosterone, free testosterone, FSH, midfollicular LH, mid-follicular prolactin, androstenedione, DHEAS, dihydrotestosterone, andro-standiol glucuronide, and sex hormone-binding globulin. Many of these laboratory tests were to be sent to a reference laboratory. The referral database was consulted so that the correct type of specimen was collected and proper storage and handling conditions were met prior to performing the tests at the reference laboratory. The patient was a 23-year-old African-American female with a preliminary diagnosis of hirsutism and infertility. Previous laboratory results showed a slightly elevated 8 00 a.m. plasma cortisol level but a low-dose dexamethasone test showed normal cortisol suppression. The following laboratory results were obtained initially from the special chemistry section


Drugs used in chemotherapy are designed to target cancer cells, but they often damage or kill normal cells as well. Death of normal cells leads to a variety of side effects, some of them quite severe. Cancer drugs target actively dividing cells consequently, any normal tissue consisting of proliferating cells will also be affected, most notably the bone marrow, digestive tract, testes, ovaries, and hair follicles. Some drugs may also affect postmitotic cells in the heart, kidney, bladder, lungs, and nervous system. In some cases, these tissues may be permanently damaged. Given the range of tissues affected, it is not surprising that chemotherapy involving the first three categories described above is associated with a large number of side effects fatigue, nausea and vomiting, pain, hair loss, anemia, secondary infections, and poor blood clotting. HAIR LOSS Hair follicles, like intestinal epithelium, are actively dividing cells that are killed by chemotherapy. The death of these cells...

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


Multiple drug resistance (MDR) was early recognized as a barrier to cancer therapy (Biedler et al. 1970). The common mechanism responsible for cross-resistance to multiple structurally unrelated agents was determined to be reduced cellular permeability (Ling and Thompson 1974), mediated by a family of highly conserved proteins known as ATP-binding cassette (ABC) transporters (Leslie et al. 2005). Although ABC transporter expression is recognized as a significant cause of chemotherapy resistance, the prevalent paradigm understands MDR in cancer to result from drug-mediated selection of cells with ABC transporter gene amplification (Chen et al. 2002) or regional gene activation (Wang et al. 2006). More recently, it has become apparent that normal adult tissue stem cells, including hematopoietic (Udomsakdi et al. 1991 Chaudhary and Roninson 1991 Goodell et al. 1996), airway (Giangreco et al. 2004), pituitary (Chen et al. 2005), small intestine (He et al. 2005), and testes (Riou et al....

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...

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).

The PTCH Receptors

Ptch2 expression and function in mouse mammary gland development have not been investigated systematically. Homozygous Ptch2 mutants display few phenotypic abnormalities, but they do show hair loss (alopecia) and skin hyperplasias (Lee et al. 2006b Nieuwenhuis et al. 2006). However, homozygous dams are able to support litters, indicating that mammary function is not altered dramatically. As with the ligands, the possibility exists of functional redundancy among the two Ptch genes (Lee et al. 2006b). Mice homozygous for Ptch2 disruption as a single-gene mutation do not show increased incidence of tumor formation, but loss of Ptch2 shows functional synergy with Ptchl het-erozygosity and led to an increased frequency of tumor types normally observed in Ptchl heterozygotes, as well as to a broader range of tumors observed (Lee et al. 2006b).


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,...

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...

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,...

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