By J. Rufus. Fayetteville State University.
Critical Thinking Scenario John buy himcolin 30gm cheap, 11 years of age himcolin 30 gm free shipping, is brought to the pediatric nurse practitioner for his annual sports physical buy 30gm himcolin overnight delivery. You note that John is in the 25th percentile for height and the 50th percentile for weight himcolin 30 gm visa. Factors that might inﬂuence their desire for increased height and the use of growth hormone to accomplish this. If John uses growth hormone, outline some of the disadvantages and side effects. OVERVIEW Corticotropin-releasing hormone or factor (CRH or CRF) causes release of corticotropin (also called adrenocor- The hypothalamus and pituitary gland (Fig. They are anatomically connected by the hy- and its secretion is inﬂuenced by several neurotransmitters. The hypothalamus controls secretions of the Acetylcholine and serotonin stimulate secretion; gamma- pituitary gland. The pituitary gland, in turn, regulates secre- aminobutyric acid (GABA) and norepinephrine inhibit secre- tions or functions of other body tissues, called target tissues. The ability of CRH to stimulate corticotropin secretion The pituitary gland is actually two glands, each with different is increased by vasopressin and decreased or prevented by structures and functions. The anterior pituitary is composed of somatostatin and elevated levels of glucocorticoids. The posterior pituitary is anatomically an characterized by excess cortisol. It does not manufacture any hormones itself but release of growth hormone in response to low blood levels stores and releases hormones synthesized in the hypothalamus. Found in the pancreas as well as the hypo- thalamus, GHRH structurally resembles a group of hor- mones that includes glucagon, secretin, vasoactive intestinal Hypothalamic Hormones peptide, and gastric inhibitory peptide. Secretion of hypo- thalamic GHRH is stimulated by dopamine, norepineph- The hypothalamus produces a releasing hormone or an inhibit- rine, epinephrine, GABA, acetylcholine, and serotonin. The ing hormone that corresponds to each of the major hormones of stimulatory effect of GHRH on secretion of growth hor- the anterior pituitary gland. GHRH may be used to 325 326 SECTION 4 DRUGS AFFECTING THE ENDOCRINE SYSTEM Hypothalamus Hypothalamic-releasing hormones Posterior pituitary ADH Kidneys Anterior pituitary Oxytocin Uterus Breasts Growth ACTH TSH FSH LH Female LH Prolactin hormone Male Adrenal Thyroid Testis Breast cortex Ovary Most body Glucocorticoids, Thyroxine Estrogen Progesterone Testosterone tissues mineralocorticoids, and androgens Figure 23–1 Hypothalamic and pituitary hormones and their target organs. The hypothalamus produces hormones that act on the anterior pituitary or are stored in the posterior pituitary. The anterior pituitary produces hormones that act on various body tissues and stimulate production of other hormones. A long-acting somatostatin analog, octreotide (Sando- Growth hormone release-inhibiting hormone (so- statin), may be used to treat acromegaly and TSH-secreting matostatin) inhibits release of growth hormone. It is distributed throughout the brain and of thyroid-stimulating hormone (TSH or thyrotropin) in re- spinal cord, where it functions as a neurotransmitter. TRH may be used is also found in the intestines and the pancreas (where it in diagnostic tests of pituitary function and hyperthyroidism. Somatostatin Gonadotropin-releasing hormone (GnRH) causes re- secretion is increased by several neurotransmitters, includ- lease of follicle-stimulating hormone (FSH) and luteinizing ing acetylcholine, dopamine, epinephrine, GABA, and nor- hormone (LH). In addition to inhibiting growth hormone, somatostatin also Prolactin-releasing factor is active during lactation after inhibits other functions, including secretion of corticotropin, childbirth. Hypothalamic somatostatin blocks the action of GHRH Anterior Pituitary Hormones and decreases thyrotropin-releasing hormone (TRH)-induced release of TSH. Growth hormone stimulates secretion of so- The anterior pituitary gland produces seven hormones. Lack of progesterone Corticotropin, also called ACTH, stimulates the adrenal causes slough and discharge of the endometrial lining as cortex to produce corticosteroids. Growth hormone, also called somatotropin, stimulates Prolactin plays a part in milk production by nursing growth of body tissues.
Teach the client to avoid • Learn self-care activities use of hot water bottles or electric heating pads buy himcolin 30 gm lowest price, cutting • Manage drug therapy to prevent or minimize hypo- toenails if vision is impaired buy himcolin 30 gm with amex, use of strong antiseptics on glycemia and other adverse effects the feet buy himcolin 30gm free shipping, and cutting corns or calluses buy discount himcolin 30 gm. Also teach the • Develop a consistent pattern of diet and exercise client to report any lesions on the feet to the physician. Interventions Evaluation Use nondrug measures to improve control of diabetes and • Check blood sugar reports regularly for normal or ab- to help prevent complications. Self- monitoring of blood glucose levels allows the client to see Goals of Therapy the effects of diet, exercise, and hypoglycemic medications on blood glucose levels and may promote compliance. For most clients, the goals of treatment are to maintain blood Several products are available for home glucose mon- glucose at normal or near-normal levels; promote normal me- itoring. All involve obtaining a drop of capillary blood tabolism of carbohydrate, fat, and protein; prevent acute and from a ﬁnger with a sterile lancet. The blood is placed on long-term complications; and prevent hypoglycemic episodes. The There is strong evidence that strict control of blood sugar amount of blood glucose can be read with various ma- delays the onset and slows progression of complications of di- chines (eg, glucometers). In addition to glycemic control, other measures can be • Test urine for ketones when the client is sick, when blood used to help prevent end-stage renal disease. Administration glucose levels are above 200 mg/dL, and when episodes of angiotensin-converting enzyme (ACE) inhibitors (eg, cap- of nocturnal hypoglycemia are suspected. Also teach topril) has protective effects on the kidneys in both type 1 and clients and family members to test urine when indicated. Although ACE inhibitors are also used in the treat- by observing for signs and symptoms of urinary tract ment of hypertension, their ability to delay nephropathy seems infection, peripheral vascular disease, vision changes, to be independent of antihypertensive effects. Teach clients sures to preserve renal function include effective treatment of CHAPTER 27 ANTIDIABETIC DRUGS 395 CLIENT TEACHING GUIDELINES Antidiabetic Drugs General Considerations If you take acarbose (Precose) or miglitol (Glyset) along ✔ Wear or carry diabetic identiﬁcation (eg, a Medic-Alert neck- with insulin, glimepiride (Amaryl), glipizide (Glucotrol), lace or bracelet) at all times, to aid treatment if needed. Few other diseases require as much adap- glucose (or glucagon) for treatment. Sucrose (table sugar) tation in activities of daily living, and you must be well and other oral carbohydrates do not relieve hypoglycemia informed to control the disease, minimize complications, because the presence of acarbose or miglitol prevents and achieve an optimal quality of life. Although much in- their digestion and absorption from the gastrointestinal formation is available from health care providers (physi- (GI) tract. If American Diabetes Association you take insulin, glucagon should be available in the 1660 Duke St. Alexandria, VA 22314 ✔ The best way to prevent, delay, or decrease the severity 1-800-ADA-DISC of diabetes complications is to maintain blood sugar at Other measures include ✔ In general, a consistent schedule of diet, exercise, and regular visits to health care providers, preferably a team medication produces the best control of blood sugar lev- of specialists in diabetes care; regular vision and glau- els and the least risk of complications. In addition, if you ✔ Diet, weight control, and exercise are extremely impor- have hypertension, treatment can help prevent heart tant in managing diabetes. Exercise helps body tissues use insulin better, counter drugs unless these are discussed with the physi- which means that glucose moves out of the bloodstream cian treating the diabetes because adverse reactions and and into muscles and other body tissues. For example, nasal decongestants more normal blood glucose levels and decreases long- (alone or in cold remedies) and asthma medications may term complications of diabetes. In addition, liquid cold remedies to take a medication, notify a health care provider. To and cough syrups may contain sugar and raise blood glu- control blood sugar most effectively, medications are bal- cose levels. If you take insulin, you need ✔ If you wish to take any kind of herbal or dietary supple- to know what type(s) you are taking, how to obtain more, ment, you should discuss this with the health care and how to store it. Regular and NPH insulins and mix- provider who is managing your diabetes. There has been tures (eg, Humulin) are available over-the-counter; Hu- little study of these preparations in relation to diabetes; malog, NovoLog, and Lantus require a prescription.
Advances have been all high-grade purchase 30gm himcolin with mastercard, diffuse malignancies discount 30gm himcolin amex, differing achieved by many single institutions and coopera- markedly from the distribution of histologic types tive groups treating childhood leukaemias buy himcolin 30 gm with mastercard, includ- typically seen among older adults buy 30gm himcolin otc. Patients tant genetic markers can now be identiﬁed by with high risk or metastatic disease at diagnosis probes, using FISH (ﬂuorescence in situ hybridi- or those who recur after front-line therapies sation) or PCR (polymerase chain reaction) in continue to pose challenges and should properly virtually all patients. Translocations, such as the beneﬁt from pilot trials and Phase I or II studies t(4;11),11–13 t(9;22)14–16 and t(1;19),17,18 confer of new treatments. On the other hand, patients with the cryptic t(12;21) genetic PROGNOSTIC FACTORS, TRANSLATIONAL 19–21 lesion encoding the TEL-AML1 transcript, RESEARCH AND THERAPEUTICALLY with hyperdiploid leukaemia identiﬁed by ﬂow RELEVANT RISK GROUPS cytometric measurement of DNA index (typically 53+ chromosomes in their primary clone),22,23 or Successful childhood cancer research is in large with speciﬁc trisomies detected by FISH, such as 4, 10 and 17,23,24 have a more favourable out- part dependent upon its translational research programme. Over the past three decades, initial come and can be targeted for less intensive treat- diagnosis and classiﬁcation of childhood cancer ment. As an example of the latter, POG investi- has become far more sophisticated, as laboratory gators designed a trial (#9201) with less intense scientists have collaborated closely with clinical chemotherapy for ALL patients with lesser risk of investigators. In addition, special biological and relapse, deﬁned by initial white blood cell counts pharmacological studies, conducted during and <50 000, age between 1 and 10 years, absence of after treatment, offer tools to clinical investigators CNS disease, and presence of one or both of the that were never previously available. Slow early response to parameningeal head/neck and genitourinary non- induction treatment is predictive of an adverse bladder/prostate regions; (3) grossly complete outcome and can be deﬁned in several ways: surgical removal of localised tumour at diagno- slow clearance of circulating blast cells to one sis; (4) embryonal/botryoid histology; (5) tumour week of prednisone or multiagent induction, or size ≤5 cm; and (6) age younger than 10 years greater than 25% marrow blasts on day 7 (or at diagnosis. Quantitation of MRD by low, intermediate and high risk are predicted to immunologic methods or PCR assay of rear- have an estimated three-year EFS rate of 88%, 55–76% and <30%, respectively. Such laborato- ual variability in response to cancer treatment is ries help the research programme in terms of sci- surely related to genetic polymorphisms in drug- entiﬁc expertise, quality control and correlative metabolising enzymes, transporters, receptors and science. Few institutions can afford to maintain other drug targets, and suggests that these genetic such laboratories solely for their own paediatric differences may form a solid scientiﬁc basis for cancer patients, and web-based informatics appli- optimising therapies within the context of clinical cations afford access to the most sophisticated trials. Treatment is then tailored to risk status, commonly consider- Because childhood cancer is rare and the response ing variables such as patient age, extent of dis- to conventional treatment good, most children ease and tumour biology. For example, the risk never experience recurrent disease and are thus CHILDHOOD CANCER 107 108 TEXTBOOK OF CLINICAL TRIALS Table 7. International Neuroblastoma Staging System (INSS) Stage 1: Localized tumour continued to the area of origin; complete gross resection, with or without microscopic residual disease; identiﬁable ipsilateral and contralateral lymph node negative for tumour. Stage 2A: Unilateral with incomplete gross resection; identiﬁable ipsilateral and contralateral lymph node negative for tumour. Stage 2B: Unilateral with complete or incomplete gross resection; with ipsilateral lymph node positive for tumour; identiﬁable contralateral lymph node negative for tumour. Stage 3: Tumour inﬁltrating across midline with or without regional lymph node involvement; or unilateral tumour with contralateral lymph node involvement; or midline tumour with bilateral lymph node involvement. Stage 4: Dissemination of tumour to distant lymph nodes, bone marrow, liver or other organs except as deﬁned in stage 4S. Stage 4S: Localized primary tumour as deﬁned in stage 1 or 2, with dissemination limited to liver, skin or bone marrow Risk group and protocol assignment schema: POG and CCG INSS N-myc Shimada DNA Risk stage Age (y) status histology ploidy group/study 1 0–21 Any Any Any Low 2A and 2B <1 Any Any Any Low ≥1–21 Nonampliﬁeda Any NA Low ≥1–21 Ampliﬁedb Favourable NA Low ≥1–21 Ampliﬁed Unfavourable NA High 3 <1 Nonampliﬁed Any Any Intermediate <1 Ampliﬁed Any Any High ≥1–21 Nonampliﬁed Favourable NA Intermediate ≥1–21 Nonampliﬁed Unfavourable NA High ≥1–21 Ampliﬁed Any NA High 4 <1 Nonampliﬁed Any Any Intermediate <1 Ampliﬁed Any Any High ≥1–21 Any Any NA High 4S <1 Nonampliﬁed Favourable > o w <1 Nonampliﬁed Any 1 Intermediate <1 Nonampliﬁed Unfavourable Any Intermediate <1 Ampliﬁed Any Any High aN-myc copy number ≤10. Phase I are accomplished as multi-institutional collab- trials are designed to estimate the maximal tol- orations. Paediatric drug development requires erated dose of a drug, to determine the nature separate Phase I studies (i. While eligibility varies, diatric patients may tolerate either higher or patients have typically failed front-line therapy lower levels of drugs and may exhibit toxici- and usually they will also have failed second-line ties unique to children. Because of the small number of pae- emphasis may also reﬂect unique agents active diatric patients eligible for Phase I trials, most in paediatric tumours, differing from agents that CHILDHOOD CANCER 109 are of the highest priority for cancers common paediatric Phase I trials have been established. A problem recently identiﬁed is the determination The basic design is to begin at about 80% of MTDs in paediatric trials that are lower of the adult maximal tolerated dose. Patients are than those deﬁned in adult patients, which may entered in cohorts and treated at increasing doses. There is a well- three patients, the dose is raised to the next established association between prior therapy level (usually a 20–30% escalation), in succes- and reduced tolerance to myelotoxic drugs. If two or all three of these initially pretreated patients deﬁne MTDs that tend to be accrued patients experience dose-limiting toxic- lower than those determined in adult patients ity (DLT), the maximum tolerated dose (MTD) with minimal prior therapy, then application of will have been deemed exceeded. Finally, if one the paediatric MTD to less heavily pretreated patient amongst the initial three patients experi- paediatric patients, e. If six patients are needed, a dose escalation will occur if a total of one in PHASE II STUDY DESIGN six (i. Typically, the dependent variable can vary from study to study, but it generally is an objective all or none response variable falls into two categories: (a) Grade 3, 4 or 5 such as achievement of a complete or partial non-haematologic toxicity other than (1) Grade (>50%) response. Interim results are masked 3 nausea/vomiting; (2) Grade 3 transaminase from the participants until the study closes to elevation; and (3) Grade 3 fever/infection and accrual and response information for all patients (b) Grade 4 myelosupression, that lasts more has been established.