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Code for Record I (a) Kaposi sarcoma of lung C467 Code Kaposi sarcoma of lung to Kaposi’s avanafil 50 mg free shipping erectile dysfunction drugs boots, sarcoma discount 200 mg avanafil otc condom causes erectile dysfunction, specified site (C467) purchase 50 mg avanafil with amex erectile dysfunction natural remedy. C80 Malignant neoplasm without specification of site Cancer Carcinoma Malignancy Malignant tumor or neoplasm Any neoplasm cross-referenced as “See also Neoplasm 200mg avanafil fast delivery erectile dysfunction drugs insurance coverage, malignant” Code for Record I (a) Carcinoma of stomach C169 Code to carcinoma of stomach (C169) as indexed. Neoplasm stated to be secondary Categories C77-C79 include secondary neoplasms of specified sites regardless of the morphological type of the neoplasm. The Index contains a listing of secondary neoplasms of specified sites under “Neoplasm. Code for Record I (a) Secondary carcinoma of intestine C785 Code to secondary carcinoma of intestine (C785). Codes for Record I (a) Secondary melanoma of lung C439 C780 Code to melanoma of unspecified site (C439). If a morphological type implies a primary site, such as hepatoma, consider this as if the word “primary” had been included. Codes for Record I (a) Metastatic carcinoma C80 (b) Pseudomucinous adenocarcinoma C56 Code to malignant neoplasm of ovary (C56), since pseudomucinous adenocarcinoma of unspecified site is assigned to the ovary in the Alphabetical Index. If two or more primary sites or morphologies are indicated, these should be coded according to Sections D, E and G. Independent (primary) multiple sites (C97) the presence of more than one primary neoplasm could be indicated in one of the following ways: • mention of two different anatomical sites • two distinct morphological types (e. If two or more sites mentioned in Part I are in the same organ system, see Section E. If the sites are not in the same organ system and there is no indication that any is primary or secondary, code to malignant neoplasms of independent (primary) multiple sites (C97), unless all are classifiable to C81-C96, or one of the sites mentioned is a common site of metastases or the lung (see Section G). Codes for Record I (a) Cancer of stomach 3 months C169 (b) Cancer of breast 1 year C509 Code to malignant neoplasms of independent (primary) multiple sites (C97), since two different anatomical sites are mentioned and it is unlikely that one primary malignant neoplasm would be due to another. Codes for Record I (a) Hodgkin disease C819 (b) Carcinoma of bladder C679 Code to malignant neoplasms of independent (primary) multiple sites (C97), since two distinct morphological types are mentioned. Codes for Record I (a) Acute lymphocytic leukemia C910 (b) Non-Hodgkin lymphoma C859 Code to non-Hodgkin lymphoma (C859), since both are classifiable to C81-C96 and the sequence is acceptable. Codes for Record I (a) Leukemia C959 (b) Non-Hodgkin lymphoma C859 (c) Carcinoma of ovary C56 Code to malignant neoplasms of independent (primary) multiple sites (C97), since, although two of the neoplasms are classifiable to C81-C96, there is mention of another morphology. When dealing with multiple sites, only sites in Part I of the certificate should be considered (see Section E). If malignant neoplasms of more than one site are entered on the certificate, the site listed as primary should be selected. More than one neoplasm of lymphoid, hematopoietic or related tissue If two or more morphological types of malignant neoplasm occur in lymphoid, hematopoietic or related tissue (C81-C96), code according to the sequence given since these neoplasms sometimes terminate as another entity within C81-C96. Acute exacerbation of, or blastic crisis (acute) in, chronic leukemia should be coded to the chronic form. Codes for Record I (a) Acute lymphocytic leukemia C910 (b) Non-Hodgkin lymphoma C859 Code to non-Hodgkin lymphoma (C859). Codes for Record I (a) Acute and chronic lymphocytic leukemia C910, C911 Code to chronic lymphocytic leukemia (C911). Multiple sites in the same organ/organ system Malignant neoplasm categories providing for overlapping sites designated by. This applies when the certificate describes the sites as one site “and” another or if the sites are mentioned on separate lines. If one or more of the sites reported is a common site of metastases, see Section G. Codes for Record I (a) Carcinoma of descending colon and sigmoid C186 C187 Code to malignant neoplasm of colon (C189) since both sites are subsites of the same organ. Codes for Record I (a) Carcinoma of head of pancreas C250 (b) Carcinoma of tail of pancreas C252 Code to malignant neoplasm of pancreas, unspecified (C259) since both sites are subsites of the same organ. If two or more sites are mentioned and all are in the same organ system, code to the. Stomach and gallbladder are in the same organ system and reported together in the same part. Codes for Record I (a) Carcinoma of vagina and cervix C52 C539 Code to malignant neoplasm of female genital organs (C579). Vagina and cervix are in the same organ system and are reported together in the same part. Codes for Record I (a) Cardiac arrest I469 (b) Carcinoma of prostate and bladder C61 C679 Code to malignant neoplasms of independent (primary) multiple sites (C97), since there is no available. Although, generally only sites in Part I should be considered, the Classification provides linkages for certain sites when reported anywhere on the certificate. Combine other parts of esophagus, C152 or C155 and stomach, C169 to code C160 in the same manner. Other exceptions to the multiple sites concept the following examples are exceptions to the multiple sites concept. Also, in the same manner, combine C820 and C822 to code C821; combine C833 and C830 to code C832; and combine C830 and C833 to code C832. Codes for Record I (a) Brain metastasis C793 (b) Lung tumor C349 Code to malignant lung tumor (C349). Codes for Record I (a) Metastatic involvement of chest wall C798 (b) Carcinoma in situ of breast C509 Code to malignant carcinoma of breast (C509). Metastatic neoplasm When a malignant neoplasm spreads or metastasizes it generally retains the same morphology even though it may become less differentiated. Some metastases have such a characteristic microscopic appearance that the pathologist can infer the primary site with confidence,. The adjective “metastatic” is used in two ways - sometimes meaning a secondary from a primary elsewhere and sometimes denoting a primary that has given rise to metastases. Neoplasms qualified as metastatic are always malignant, either primary or secondary.

Effect of inorganic or organic selenium supplementation on reproductive performance and tissue trace mineral concentrations in gravid first-parity gilts avanafil 100 mg otc erectile dysfunction can cause pregnancy, fetuses best avanafil 100mg erectile dysfunction doctor in bhopal, and nursing piglets cheap 200 mg avanafil visa impotence medication. This stated that because of the wide variability in methods to measure B12 and folate local pathways should be clinically orientated and based on locally generated normal ranges 100 mg avanafil mastercard erectile dysfunction treatment phoenix, with standardised international units. These were then verified by comparison with a set of 300 normal volunteer samples from the local area. The effect of the proposed changes were then modelled on a set of >50,000 real results from our current method/system. The change in the ranges looks large but our new method gives results about 21% lower than the previous method and the change of units reduces the reported number by a further 26%. Normal Ranges in Hull and East Yorkshire the normal ranges for B12 and folate levels based on the above methodology are: B12 (115 to 1000 pmol/L) (B12 levels just within the normal range can lead to symptoms so results 115-150 should be assessed on an individual basis) Folate (>3µg/L) Diet assessment and advice is essential as dietary deficiency can be easily corrected. There are two pathways for investigation and management for B12 depending on the indication for it being tested and one for folate. Cobalamin Deficiency There are many pitfalls for the investigation of haematinic deficiency and routine testing should not be undertaken. Updated April 2018 Review: April 2021 Hull and East Riding Prescribing Committee tests are not sensitive or specific and assays for cobalamin (B12) and folate show wide variation within the same patients and between methods and are difficult to interpret. B12 and folate should always be assessed together due to the close relationship of metabolism. However, once a patient has commenced B12 replacement there is no further need for it to be measured again. Other tests may become available locally in the future to assist decision making for treatment in cases of borderline results. Some specialist tests sent to other labs are available for better understanding of B12 metabolism. The interpretation of B12 outside these indications is more complex and results should be interpreted with caution. Objective evidence of B12 deficiency – glossitis Many non specific symptoms may be caused by B12 deficiency including tiredness, fatigue and other neuropsychiatric symptoms and B12 assessment should only be assessed if no other cause is found. There are currently no indications for B12 supplementation without assessment of B12 levels. Investigation and management of B12 deficiency can be divided into two based on indications for assessment. Updated April 2018 Review: April 2021 Hull and East Riding Prescribing Committee 1. Management of B12 deficiency with strong suspicion with objective indications for testing. B12 checked with objective evidence of deficiency with B12 <150 Serum B12 <115 pmol/L Serum B12 115-150 pmol/L * Probable deficiency Commence B12 replacement Commence B12 replacement Check anti-intrinsic factor antibodies Check anti-intrinsic factor antibodies Consider referral to appropriate specialty based on symptoms/signs ** anti-intrinsic factor anti-intrinsic factor Definite Objective No Objective response antibodies +ve antibodies –ve response and/or Anti-intrinsic antibodies Lifelong treatment Lifelong treatment anti-intrinsic factor -ve as pernicious as pernicious antibodies +ve anaemia anaemia if clinical Lifelong treatment as No need for further response pernicious anaemia testing No need for further No need for further testing testing* Commence oral B12 replacement for 12 weeks Check anti-intrinsic factor antibodies anti-intrinsic factor anti-intrinsic factor * Results just above the lower limit of antibodies +ve antibodies –ve normal (115-150) in the face of strong Lifelong treatment as Repeat B12 after 12 clinical suspicion of B12 deficiency pernicious anaemia weeks should receive a trial of therapy with response assessment. Updated April 2018 Review: April 2021 Hull and East Riding Prescribing Committee 2. B12 checked without objective evidence of deficiency Serum B12 <85pmol/L Serum B12 86-114 pmol/L Commence B12 replacement Repeat B12 level Check anti-intrinsic factor antibodies after 8 weeks anti-intrinsic anti-intrinsic Repeat test normal Level remains factor antibodies factor antibodies No B12 deficiency low +ve –ve No need for further 86-114 pmol/L testing Lifelong Lifelong treatment as treatment as Commence oral B12 pernicious pernicious replacement for 12 weeks anaemia anaemia if Check anti-intrinsic factor No need for clinical response further testing antibodies No need for further testing anti-intrinsic factor anti-intrinsic factor antibodies +ve antibodies –ve Repeat B12 after 12 Lifelong treatment as weeks pernicious anaemia *Referral to appropriate Repeat test normal Repeat 86-114 specialty: Poor B12 pmol/L Neurology, haematology, intake/absorbtion care of Continue oral B12 Consider lifelong I. Updated April 2018 Review: April 2021 Hull and East Riding Prescribing Committee Referral for second line testing If there is strong objective evidence of B12 deficiency (macrocytic anaemia, neurological symptoms or failure to thrive) despite normal levels second line testing under specialist guidance is indicated. This guidance needs to be directed by a specialty appropriate to the patient: neurology, paediatrics, care of the elderly or haematology. Second line testing is complex with significant pitfalls and appropriate tests include: 1. Plasma total homocysteine This is raised in B12 deficiency but not specific becoming elevated in folate deficiency, B6 deficiency, renal disease and hypothyroidism. Plasma methylmalonic acid This is raised in B12 deficiency but again is not specific being raised in renal disease and by haemoconcentration and small bowel bacterial overgrowth. Results of second line testing by a specialist require correlation with patient symptoms and response to therapy. Once commenced B12 levels should only be assessed if clinical suspicion of B12 deficiency develops. Updated April 2018 Review: April 2021 Hull and East Riding Prescribing Committee Pitfalls of B12 measurement Drug use:  Metformin Metformin paradoxically reduces the serum cobalamin level but improves intracellular metabolism. Reduced B12 levels in those on metformin are rarely clinically significant and usually improve with dietary improvement of B12 intake. B12 should only be assessed in patients with diabetes if objective evidence of deficiency is present including peripheral neuropathy or macrocytic anaemia. Low levels should be investigated with anti-intrinsic factor antibodies and should be treated with a short course of B12 (50 micrograms orally for 4 weeks). This usually causes a subclinical deficiency but oral replacement (25-100 micrograms orally) may be appropriate if objective evidence of deficiency is found. In the absence of objective features of B12 deficiency there is no need for replacement. Levels should only be assessed if objective symptoms develop and this is the only indication for treatment. Gastrointestinal surgery  Both gastrectomy and bariatric surgery can lead to B12 deficiency and require regular monitoring and replacement if levels are falling despite good dietary intake. Pregnancy  Pregnancy causes a physiological lowering of plasma cobalamin levels by up to 30% by the third trimester. Empirical treatment of cobalamin deficiency should be given if paraesthesia, neuropathy or megaloblastic anaemia occurs. Vegetarian and vegan diets  Vegetarians and vegans are at increased risk of B12 deficiency especially during pregnancy and when breastfeeding.

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Sin embargo discount 50 mg avanafil fast delivery erectile dysfunction treatment algorithm, estas valoraciones pueden predecir el potencial de sensibilización discount avanafil 50mg without prescription erectile dysfunction drug types, pero no necesariamente el de auto- inmunogenicidad de los agentes y no representan una vía sistémica de exposición order avanafil 200mg without a prescription erectile dysfunction medication new. La carga para la salud y los costos elevados de las enferme- dades autoinmunitarias resaltan su importancia con respecto a una evaluación del riesgo discount avanafil 100mg with mastercard smoking and erectile dysfunction causes. En la evaluación del riesgo de autoinmunidad asociado con agentes químicos o físicos se deben considerar los datos epidemiológicos disponibles, la identificación del peligro y los datos de la relación dosis-respuesta derivados de estudios realizados en animales y personas, los datos relativos al mecanismo de acción y los factores de susceptibilidad. El proceso de evaluación del riesgo puede ayudar a calcular en último término el costo de las enferme- dades autoinmunitarias asociadas con la exposición a agentes quími- cos y físicos. En la actualidad, la evaluación del riesgo para agentes sospechosos de inducir o exacerbar la autoinmunidad o las enferme- dades autoinmunitarias tropieza con la dificultad de la ausencia de información apropiada, en particular modelos animales validados. Debido a la carga de las enfermedades autoinmunitarias a nivel individual y colectivo, la evaluación del riesgo con respecto a este grupo de enfermedades adquiere una importancia especial. These resources are available to help resolve any unusual cases involving autoimmune disease diagnosis. When this cannot be done, we will make partial shipments unless otherwise notifed at the time of order confrmation. Please provide the reason for the return (ordering error, shipping error, technical problem, etc. Nothing disclosed herein is to be construed as a recommendation to use our products in violation of any patents. However, said information and products are ofered without warranty or guarantee since the ultimate conditions of use and the variability of the materials tested are beyond our control. We cannot be responsible for patent infringements or other violations that may occur with the use of these products. This fully automated system has the potential to increase productivity while providing more consistent results. Fine to coarse weak, difuse staining of the nuclei and negative Multiple nuclear dots throughout the nuclei with speckling in approximately 30-60% of interphase mitotic cells. These resources are available to help resolve any unusual cases involving autoimmune disease diagnosis. When this cannot be done, we will make partial shipments unless otherwise notifed at the time of order confrmation. Please provide the reason for the return (ordering error, shipping error, technical problem, etc. Nothing disclosed herein is to be construed as a recommendation to use our products in violation of any patents. However, said information and products are ofered without warranty or guarantee since the ultimate conditions of use and the variability of the materials tested are beyond our control. We cannot be responsible for patent infringements or other violations that may occur with the use of these products. Box 12000, Jerusalem 91120, Israel 2Department of Pathology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel 3Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel 4Ministry of Health, Israel 5Institute of Gastroenterology, Assaf Harofeh Medical Center, Zerifin, Israel See Editorial, pages 444–446 Background/Aims:Nutritional supplements are frequently considered to be harmless but indiscriminate use of unlabelled ingredients may lead to significant adverse reactions. Twelve patients with acute idiopathic liver injury in association with con- Ò sumption of Herbalife products were investigated. Liver biopsies demonstrated active hepatitis, portal inflammation rich with eosinophils, ductular reaction and parenchymal inflammation with peri-central accentuation. One patient developed sub-fulminant and two fulminant episodes of hepatic failure. Hepatitis resolved in eleven patients, while one patient succumbed to complications following liver transplantation. We call Ò for prospective evaluation of Herbalife products for possible hepatotoxicity. Until then, caution should be exercised by consumers, especially among individuals suffering from underlying liver disease. Their use is prevalent world- q the authors who have taken part in this study declared that they do wide because they are considered to be ‘‘natural’’ and not have anything to disclose regarding conflict of interest with respect hence free of adverse reactions [1]. Serum acetaminophen levels and urinary toxic screening neither regulated nor controlled. A histopathology report from a liver explant titis is often caused by either the concomitant consump- removed from patient number 5 was obtained from a German trans- plant center in Essen. Anecdotal success and personal experience are frequently the driving force for Demographic and clinical descriptive data are presented as num- bers and percentages or as means and standard deviations. Role of the funding source dence-based proof regarding the relative risk associated with intake of such agents [1]. In 2004, four index cases were identified at the Had- No sponsor(s) were involved in study design; in the collection, analysis, and interpretation of data; in the writing of the report; and in the deci- assah Medical Center, Jerusalem, Israel, consisting of sion to submit the paper for publication. Results ical Center investigation, aimed to identify additional cases, and to assess the hepatotoxic potential of Herba- 3. Characteristics of the patients, background illness and medications are depicted in Table 1. Seven patients were Ashkenazi, four Sephardic, and one was of Israeli-Arab origin. In 2004, four index cases were identified at the Hadassah Medical Seven patients were employed in clerical jobs, two were Center, Jerusalem, Israel, consisting of patients suffering from acute Ò housewives, and three were employed as Herbalife dis- unexplained liver injury apparently associated with the recent con- sumption of HerbalifeÒ products. Following public notification, two additional cases (trea- Ò ted during 2002 and 2003) were recognized. Consumption of Herbalife products Ò Nine patients consumed Herbalife products for 2. Data collection weight reduction, and three for improvement of well- Ò Twelve patients (ten systematically-identified and two randomly- being. The three patients who were Herbalife distribu- identified) underwent an interview which included a detailed question- tors self-administered the products.

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J Surg Res betes on long-term prognosis in patients on mortality and costs in acute ischemic 105:181–188 100mg avanafil fast delivery erectile dysfunction medicine for heart patients, 2002 with unstable angina and non-Q-wave stroke buy 50 mg avanafil with mastercard impotence natural treatment. Diabetes 47:1412– tion 102:1014–1019 order avanafil 200 mg visa erectile dysfunction commercials, 2000 across clinical subtypes of acute stroke quality avanafil 100 mg ketoconazole impotence. Brady P, Terzic A: the sulfonylurea con- Smits P: Effects of sulfonylurea deriva- sion reduces the incidence of deep ster- troversy: more questions from the heart. Howes L, Sundaresan P, Lykos D: Car- J Pharmacol 419:85–92, 2001 Thorac Surg 67:352–362, 1999 diovascular effects of oral hypoglycemic 221. Meinert C, Knatterud G, Prout T, Klimt abolish myocardial protection afforded duces mortality in patients wth diabetes C, University Group Diabetes Program: by either ischemic preconditioning or undergoing coronary artery bypass A study of the effects of hypoglycemic diazoxide. Diabetes 19:789–830, 1970 Preda I, Koltai M: Influence of diabetic Bookin S, Kanhere V, Starr A: Glucose 210. Klepzig H, Kober G, Matter C, Luus H, Brancati F: Perioperative glycemic con- 211. Murry C, Jennings R, Reimer K: Precon- Schneider H, Boedeker K, Kiowski W, trol and the risk of infectious complica- ditioning with ischemia: a delay of lethal Amann F, Gruber D, Harris S, Burger W: tions in a cohort of adults with diabetes. Cir- Sulfonylureas and ischaemic precondi- Diabetes Care 22:1408–1414, 1999 culation 74:1124–1136, 1986 tioning; a double-blind, placebo-con- 200. Deutsch E, Berger M, Kussmaul W, Hir- trolled evaluation of glimepiride and R, Weekers F, Verwaest C, Schetz M, shfeld J, Herrmann H, Laskey W: Adap- glibenclamide. Eur Heart J 20:439–446, Vlasselaers D, Ferdinande P, Lauwers P: tation to ischemia during percutaneous 1999 Outcome benefit of intensive insulin transluminal coronary angioplasty: clinic, 224. Legtenberg R, Houston R, Smits P, Oese- therapy in the critically ill: insulin dose hemodynamic, and metabolic features. Crit Care Med Circulation 82:2044–2051, 1990 by glibenclamide in isolated, working, 31:359–366, 2003 213. Circulation 96: relaxation and intracellular Ca tran- plasminogen activator-related intracere- 29–32, 1997 sients in adult rat ventricular myocytes. Harrower A: Comparative tolerability of insulin analog lispro in variable combi- induced myocardial dysfunction in type sulphonylureas in diabetes mellitus. Diabetes 51:808–812, 2002 Drug Safety 22:313–320, 2000 Diabetes Care 22:468–477, 1999 229. O’Keefe J, Blackstone E, Sergeant P, Mc- J, Gubbi A, Alexander G: Lactic acidosis 255. N Engl J Med 338:265–266, use in medical inpatients with diabetes Heart J 19:1696–1703, 1998 1998 mellitus. Emslie-Smith A, Boyle D, Evans J, Sulli- 1997 coronary events in older persons with van F, Morris A: Contraindications to 256. Fam Pract Cardiol 88:556–557, 2001 Diabet Med 18:483–488, 2001 Res J 14:313–322, 1994 232. Eur Heart J indications to metformin therapy in pa- lin infusion in diabetic ketoacidosis. Calabrese A, Coley K, DaPos S, Swanson ment of severe diabetes mellitus by insu- betic patients after myocardial infarc- D, Rao R: Evaluation of prescribing prac- lin infusion. Halkin A, Roth A, Jonas M, Behar S: Sul- lidinedione use in Medicare patients 1974 fonylureas are not associated with in- with heart failure. Salpeter S, Greyber E, Pasternak G, Sal- small doses of insulin in treatment of di- infarction. J Thromb Thrombolysis 12: peter E: Metformin does not increase fa- abetic ketoacidosis. Br Med J 2:694– 177–184, 2001 tal or nonfatal lactic acidosis or blood 698, 1974 236. Lancet patients with acute myocardial infarc- 60:333–343, 2000 2:1221–1224, 1975 tion. Weih M, Amberger N, Wegener S, the treatment of type 2 diabetes mellitus: the efficacy of low-dose versus conven- Dirnagl U, Reuter T, Einhaupl K: Sulfo- a critical review. Clin Ther 22:1151– tional therapy of insulin for treatment of nylurea drugs do not influenced initial 1168, 2000 diabetic ketoacidosis. Idris I, Gray S, Donnelly R: Rosiglitazone 633–638, 1976 in stroke patients with diabetes. Arch in conventionally treated patients with Lim S, Nam M, Lee H, Cha B: Preventive Intern Med 137:1367–1376, 1977 diabetes mellitus and acute myocardial effects of rosiglitazone on restenoss after 266. Endocrin Metab Clin Intensive Care Med 7:11–14, 1980 141:713–715, 1981 North Am 21:457–475, 1992 301. J Gen Intern Med 1714–1719, 2001 Endocrinol Metab 6:1–22, 1992 10:154–161, 1995 302. In Inter- the maintenance of overnight euglyce- Metab Clin North Am 21:415–432, 1992 national Textbook of Diabetes Mellitus. In Therapy for Diabetes Melli- Cortez C, Melendez S, Ipp E: An over- Arch Intern Med 157:669–675, 1997 tus and Related Disorders. In Medical Management of Type in noninsulin-dependent diabetes melli- betic ketoacidosis: zero-mortality under 1 Diabetes. Hill A: Continuous intravenous insulin 1:385–389, 1995 crises in patients with diabetes. Mittra B: Potassium, glucose, and insulin infusion versus intermittent bolus appli- gery.

Thus order 200 mg avanafil free shipping depression and erectile dysfunction causes, we each have a minimum of 12 cheap 50mg avanafil amex other uses for erectile dysfunction drugs,000 purchase avanafil 100 mg on line erectile dysfunction medications online,000 discount avanafil 100 mg free shipping erectile dysfunction at the age of 18,000,000,000,000,000 nucleotides, the majority of them unneeded. Why should bone marrow cells spend energy and resources maintaining all those nucleotides for enzymes that produce skin pigment, fingernails, or hair? Clearly, any bioengineer who designed a protein synthesis system by placing introns into the blueprint would be fired very quickly. So would a chip designer who insisted that the manufacturer keep the nonfunctioning β hemoglobin pseudochip in the computer along with its perfectly functioning counterpart. Some mechanisms currently suspected as junk undoubtedly will turn out to be important as knowledge of genetics expands. It will tinker with and adopt any ad hoc solution with no consideration as to how elegant the solution is designed and no forethought about whether that solution will be beneficial or detrimental to the organism after the problem is solved. The only reason for evolution to be concerned about simplicity and efficiency is when the lack of them interferes with reproduction. If an inefficient and complex system impedes reproduction, evolution could actually make the organism more complicated with a series of string and bubble gum patches as long as those patches overcome the problems with reproduction. It is likely that many aspects of human behavior are not simple, logical, efficient, and parsimonious, or for that fact, even nice from a moral standpoint. Perhaps much of our behavior is illogical, inefficient, and complicated when viewed through the faculty of reason. C oliC ell F u e e o p e r o n n the r e n to s e s s e n t, th e e g u to r y o the i n n d s w i th th e n d e v e n ts th e tr n s c ti o n e n z ym e s o m tta n g th e m s e l e s n d tr n s c n g e n e s o w n s tr e a o f th e e g u to r y n d n g. In this chapter, we examine several Mendelian traits and disorders in order to illustrate the basic principles of how genes and gene products relate to behavior. They begin with the genetic disorder of phenylketonuria that illustrates basic principles of metabolic pathways and conclude with sickle cell anemia, a disorder that illustrates the relationship between genes, ecology, and ethnicity. Hence, it is the chromosome and not the gene that is truly the physical unit of inheritance. The term locus (plural = loci) is a synonym for gene; it carries with it the implication that a gene has a fixed location on a chromosome. An organism like this is called a homozygote (homo for "same" and zygote for "fertilized egg"). The strict definition of a homozygote is an organism that has the same two alleles at a gene. For example, someone who inherits an A allele from mom but a B allele from dad is a heterozygote. A genotype may refer to only one locus or it may refer in an abstract sense to many loci. Height, weight, extraversion, intelligence, interest in blood sports, memory, and shoe size are all phenotypes. There is not always a simple, one-to-one correspondence between a genotype and a phenotype. These phenotypes come about when a drop of blood is exposed to a chemical that reacts to the polypeptide chain produced from the A allele and then to another chemical that reacts specifically to the polypeptide chain produced from a B allele. If someone takes a drop of your blood, adds the A chemical to it, and observes a reaction, then it is clear that you must have at least one A allele—although, of course, you may actually have two A alleles. Finally, there are several terms used to describe allele action in terms of the phenotype that is observed in a heterozygote. When the phenotype of a heterozygote is the same as the phenotype of one of the two homozygotes, then the allele in the homozygote is said to be dominant and the allele that is "not observed" is termed recessive. Similarly, allele B is dominant to O, or in different words, allele O is recessive to B. When the phenotype of the heterozygote takes on a value somewhere between the two homozygotes, then allele action is said to be partially dominant, incompletely dominant, additive, or codominant, depending on exact value of the heterozygote. For example, the allele action of A depends entirely on the other allele—i t is dominant to O but codominant to B. Let us now examine three central terms that describe the relationship between a single gene and a phenotype. Penetrance is defined as the probability that a person exhibits a phenotype given that the person has the genotype for that phenotype. When applied to disease, penetrance refers to the probability that a person will develop the disorder given that the person has the genotype for the disorder. Penetrance is a conditional probability, so it is literally a number that can logically range from 0 to 1. Complete penetrance refers to disorders and traits where the probability is very close to 1. The second phenomenon relating genotype to phenotype is pleiotropism or pleiotropy. Pleiotropy refers to the phenomenon that a single gene can influence more than a single phenotype. Two phenotypes—intellect and movement—will be used here to demonstrate pleiotropism. As the disorder progresses, the person gradually develops involuntary motor movements in the head and limbs. The loss of voluntary motor control worsens and the person eventually loses the2 ability to walk and feed himself. Eventually dementia (the progressive and irreversible loss of cognitive functioning) occurs. Variable expressivity occurs when a single gene results in a range of phenotypic values for a single trait. A classic example is the relationship between intelligence and 1 You may have noted the cautionary phrases "close to 1.

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