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Talk:Rhetoric and Composition/Grammar and Mechanics

A few notes here. First, we don't want to spend too much time working on this section. We don't want to make grammarians out of people. Instead, they need to know just enough to stop from doing things that will detract from their ethos as writers. They don't really need to know all the terms for things; just how to write sentences that are free of errors. Many of us love grammar for its own sake, but it tends to scare students. Most students will try to use these pages to figure out problems their teachers have identified in their writing. We should write clear explanations and plenty of examples--all the while avoiding jargon. --Mattbarton.exe 01:34, 6 December 2005 (UTC)

I changed some terms and some capitalization in the headers for the errors list because of inconsistency and logic problems: if we're going to call them errors, "subject-verb agreement" isn't an error, it's a topic area. "When subjects and verbs don't agree" is an error. I agree to a certain extent about the jargon, but some terms are unavoidable and are helpful for clarity and brevity, both in presenting and learning; a few select terms and brief definitions are helpful tools to arm writers. -- Parrhesia

Sounds good to me. BTW, if you look at the toolbar that pops up when you edit the page, one button looks like a signature. It's a useful tool for leaving your name and time. --Mattbarton.exe 17:14, 6 December 2005 (UTC)

Links
I think the links at the bottom could use some brief annotations. --Mattbarton.exe 19:17, 27 September 2007 (UTC)

Other stuff
I was wondering about the possibility of adding sections such as: who/whom, "to lay versus to lie", "affect" versus "effect" -- just some common errors writer's tend to make. Comments? Are they located somewhere else in the book? --Kyoung 03:31, 14 November 2007 (UTC)

They may be in the editing section, but seems like a "usage" or "common mistakes" section would be a good addition. --Mattbarton.exe 20:26, 29 November 2007 (UTC)

My name is Lisa, and as a self-professed grammar nerd, I'd love to look this page over to see if I can offer any examples or clarification as well as address some of the needs mentioned in above comments.--Ljbertrand09 (discuss • contribs) 01:02, 4 February 2017 (UTC)-

I created the linked "Commonly Confused Words" and will proofread this page soon, in addition to annotating the links at the bottom of the page.--Ljbertrand09 (discuss • contribs) 02:59, 16 February 2017 (UTC)

I proofread this page and annotated the links at the bottom. I noticed that the "Commonly Confused Words" section I created somewhat repeats some of the homonyms listed in the "Words that sound the same" section earlier, but I left the page as is because it offers additional examples. --Ljbertrand09 (discuss • contribs) 20:31, 18 February 2017 (UTC)


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Handbook of Genetic Counseling/Hemoglobinopathy Screening and Hemoglobin D-Punjab

Hemoglobinopathy Screening and Hemoglobin D-Punjab

Family History

 * Some of the things I'm looking for in your family history include:
 * Birth defects
 * History of pregnancy losses
 * learning difficulties or MR
 * chronic health problems
 * anemia or blood problems
 * anyone that has difficulty breathing or fatigues easily
 * anyone who has had pregnancy losses
 * anyone who died at a young age or unexpectedly
 * Anything else that you think might be running in your family
 * Ask details about country where relatives are from because Hemoglobin D trait is more common in some ethnicities
 * In Punjab region of India and Pakistan it is much more common (up to 3% of the population is has hemoglobin D trait)
 * Also more common in people of English, Irish, or Scottish descent than other ethnic groups
 * Estimated prevalence among American blacks is .1-.4% (Zago MA and Costa FF (1988))
 * Ask about consanguinity

Overview of Hemoglobin and genes

 * Hemoglobin is the protein in blood that carries oxygen and gives blood its red color
 * There are hundreds of different hemoglobin variants
 * Hemoglobin A is the usual type of hemoglobin that is made in children and adults
 * Hemoglobin D is one of the many hemoglobin variants
 * The kind of hemoglobin our body makes depends on the genes we inherit
 * Genes are the units of inheritance that tell our bodies how to grow and develop
 * Some genes tell our bodies how to make protein chains that are essential components of hemoglobin
 * One pair of genes tells the body how to make a component of hemoglobin are called beta globin genes
 * Changes in these beta globin genes can alter the instructions for the cell and can result in different hemoglobinopathies
 * We usually get one copy of the beta globin gene from our mother and one from our father
 * We know that ____ inherited one gene that was altered and results in the variant hemoglobin D being made and one gene that is unchanged and results in the usual hemoglobin, hemoglobin A.
 * The presence of one of the normal genes is enough to keep an individual form having any symptoms we call these people carriers

Potential Risks for future offspring

 * If a person has two genes that are variants then they may have some health problems, but whether they do and the extent of problems depends on the variants they have
 * One of the more common variants of the beta globin gene is one that causes sickle cell trait and sickle cell anemia due to a specific change
 * Are you familiar with sickle cell disease
 * Sickle cell disease only occurs if a person has two beta globin genes with the specific change present
 * A person has sickle cell trait if they have one of the normal genes and one of the variant genes called S (and like those with hemoglobin D trait they do not have symptoms)
 * Sickle cell trait is more common than hemoglobin D trait
 * Sickle cell trait occurs in about 8% of African Americans
 * Prevalence among Hispanics whose families originated from the Caribbean, Central America, or South America is approximately 4%
 * Carrier rate among 2 million screened over 4 years in California showed 6,921 nonblack infants had sickle cell trait ( .35%)
 * 58 out of 2 million non black children had sickle cell disease from Calif. Newborn screen
 * When one partner has hemoglobin D trait and the other has sickle cell trait there is a 1 in 4 or 25% chance with each pregnancy that the child will have what is called sickle/D disease or (SD disease). (draw punnett square)
 * SD disease is similar to Sickle cell Disease
 * They can have severe hemolytic anemia (when they are asymptomatic the Hb D is usually a different variant)
 * May have enlarged spleen, periods of severe pain called crisis, and often require blood transfusions
 * They can have some of the serious life-threatening complications seen in individuals with sickle cell anemia such as increased risk of infections that will require prompt medical treatment
 * (Perea F J et al. 1999) reported 4 people with SD had chronic hemolytic anemia and similar course to those with severe sickle cell anemia
 * Child reported in 1984 had severe life threatening complications
 * Early diagnosis and education to recognize problems and treat promptly can decrease mortality rates

Also possible to have Hb D-Punjab with other variants

 * Hb D (homozygous)
 * Most reports show that Hb D homozygous individuals do not have symptoms (Adekile, A D et al. (1996) and Zago, MA & Costa FF (1988).)
 * Hematology is essentially normal in these individuals (Adekile AD et al. (1996)).
 * Hb D and beta thalassemia trait reportedly to be even more rare than Hb D homozygotes
 * Showed to not cause problems in at least 13 individuals reported worldwide as of 1999
 * (Perea FJ et al. 1999) reported 3 patients with Beta thal / HbD with similar values to beta thal/ beta A heterozygote and showed microcytic and hypochromic anemia, but no harmful consequences

Testing

 * Discuss ability to do simple blood test for parents to determine if they are carriers for the variants so we can clarify risks for future children (hemoglobin electrophoresis with an A2 quanitiation to identify possible beta thal)
 * Covered by most insurance companies
 * Some may require preauthorization so you may want to find out if this is necessary before ordering testing
 * Also possible to perform this testing on future partner of _____ to determine if her children are at risk for any of the hemoglobinopathies and she may want genetic counseling when she reaches a point in her life where she is considering having a family.
 * Direct mutation analysis by PCR possible (see below)

Beta Globin Variants

 * Gene: ß globin
 * Test: Direct mutation analysis by PCR for Hb C, E, O-Arab, D-Punjab, or other KNOWN variants as specified by the referrer.
 * CPT Codes:
 * (For descriptive purposes only) 83891 x1
 * 83894 x2
 * 83898 x1
 * 83904 x2
 * 83912 x1
 * Sensitivity: Should be high
 * Turnaround Time: Up to 3 weeks
 * Cost: $200 per individual
 * $600 per fetus
 * Special Considerations: We require hemoglobin electrophoresis & other relevant clinical confirmation with each sample.
 * This test is for molecular confirmation of a known beta globin variant. If the beta globin variant is unknown, please order the beta globin complete gene sequencing test.
 * http://www.hopkinsmedicine.org/dnadiagnostic/betavariants.htm

How does the screening test determine which category a baby fits?

 * Newborn screening test done in Utah since Sep 2001 measures the percentage of different types of hemoglobins using hemoglobin electrophoresis

Psychosocial concerns

 * may be nervous and think there is something serious
 * may be a lot of information to understand at once so talk about letter
 * guilt about passing on something
 * May be concerned about risks for future pregnancies

Facts about Hb D

 * Hb D most common form is called Hb D-Punjab after the area in India and Pakistan where it is most frequent
 * Hb D-Punjab is also referred to as Hb D-Los Angeles and by other names
 * Hemoglobin D co-migrates with hemoglobin S at alkaline pH
 * Hb D does not sickle
 * Hb D is fourth most frequently occurring Hb variant
 * Hb D results from a GAA ->CAA mutation at codon 121 glutamic acid changed to glutamine
 * Quantity in heterozygote is ~40% and has been found in combination with Hb S, Hb C, Hb E, beta-thal, alpha-thal, and homozygous state

Web resources

 * www.urmc.rochester.edu/genetics -- great patient literature
 * www.sicklecelldisease.org -- Sickle Cell Disease Association of America
 * http://sickle.bwh.harvard.edu/menu_sickle.html -- basic information about hemoglobin etc.

license: Creative Commons - Attribution Share-Alike - https://creativecommons.org/licenses/by-sa/4.0/


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Handbook of Genetic Counseling/Hemophilia and Von Willebrand Disease

Hemophilia and Von Willebrand Disease

Hemophilia (- term to include hemophilia A (factor 8), hemophilia B (factor 9) and von Willebrand's Disease)

Von Willebrand Disease (Vascular Hemophilia or pseudohemophilia)

 * Caused by lack of von Willebrand factor
 * Usually helps in the clotting process by binding to the surface of the wall and then making platelets bind to the surface of the blood vessel wall. Once they bind, it brings other platelets to clump on the surface=blood stops flowing and a clot is formed.
 * It is the thing that locates the platelets to the correct spot = affects platelet adhesion process.
 * People may have a smaller amount of protein produced or they have a change in function.
 * von Willebrand protein is also a carrier protein for Factor 8 = if it is not working properly you have decreased factor 8 as well.
 * Prevalence = up to 1/100 (1%) of the population
 * Characteristics - VARY even in families
 * Easy bruising is the major problem
 * Recurrent nosebleeds
 * Heavy menstrual cycles
 * Bleeding after surgery
 * Bleeding at delivery of a baby (during pregnancy you get increased vWf )
 * Diagnosis
 * Best done by clinical diagnosis and family history
 * Also done by homeostasis screening tests (but they can be normal in mild cases)
 * Bleeding time - a test that gets messed up by taking aspirin
 * Antigenic levels of vWf - an immunoassay
 * mild = 25-35% normal amount
 * severe = <5%
 * affected by blood type = A, B, AB have higher levels 48-240 u/dl and O have 36-160 u/dl.
 * Platelet aggregation studies - only aggregation with ristocetin would be informative
 * Von Willebrand factor activity = looks at ristocetin co-factor. Usually low if above is low.
 * Von Willebrand multimers = look to see if the reason it is not functioning is because the larger multimers are not present.
 * Direct DNA testing for Type IIA or IIB
 * Problems with pregnancy, newborn period, times of stress or agitation
 * Inheritance
 * AR (severe or Type III)
 * AD (mild, Type IIA and IIB)
 * You can be a symptomatic or asymptomatic carrier depending on other factors.
 * Chromosome 12
 * Treatment
 * Either drug or blood products - intravenously
 * Type I = DDAVP (Stimate) - synthetic agent that releases vWf from storage sites. Only works if there is some vWf present.
 * Type IIA = DDAVP
 * Type IIB = Humate-P or cryoprecipitate
 * Severe = Humate-P or cryoprecipitate
 * Platelet type = platelet concentrates
 * Factor 8 concentrates Do NOT work because they don't have enough vWf.
 * Lifestyle
 * Mild = treatment only before surgery
 * Severe = avoid taking aspirin and avoid activities with high risk of injury. Take Tylenol instead.

Hemophilia A and B

 * Caused by decrease of lack of Factor 8 or 9
 * Coagnulation is a process of activation of a variety of factors in sequence (I-XIII)
 * Deficiency in the factors can be Type I (reduced concentration) or Type II (defect in function)
 * Factor 8 is called the Antihaemophilic globulin
 * Factor 9 is the Christmas factor
 * Characteristics
 * Muscle or joint bleeding
 * <5% the normal value have spontaneous bleeding (esp. <2%)
 * >5% have bleeding after sugeries
 * Inheritance
 * X-linked recessive
 * Diagnosis
 * The two in indistinguishable clinically = they have to determined by specific factor assays.
 * Clotting factor assays

Hemophilia A

 * Incidence 1/10,000
 * Genetics/inheritance
 * X linked recessive
 * In 1/3 cases it is a new mutation
 * The gene is close to the tip Xq.
 * Heterogenetic
 * Values
 * plasma levels of factor 8: normal = 0.5-1.5 iu/ml
 * Carriers = 50% normal value typically (can be affected by lionization)
 * <.02 iu/ml = severe
 * 0.02-0.05 iu/ml = moderate
 * >0.05 iu/ml = mild
 * Characteristics
 * spontaneous recurrent bleeding in the knees, elbows, ankles, shoulders (large joints and muscles!!!)
 * bleeding occurs 2-4 times per month
 * Starts around 6 months (mobility)
 * Can lead to lots of pain and loss of cartilage and osteoartrithis
 * There can be intracranial bleeding = death in adults
 * Diagnosis
 * Reduced factor 8
 * Normal vWf, Rcofactor, and bleeding time
 * Treatment
 * Provide Factor 8 concentrates to arrest bleeding immediately
 * Prenatal testing
 * Traditionally a two step process: sexing (by amnio at16 weeks) and then blood drawing(19-20 weeks)
 * CVS can be done with gene probes that have been determined by the mother and family prior to testing.

Hemophilia B

 * Prevalence
 * 1/5 that of Hemophilia A
 * Cause
 * Deficiency of Factor 9 which is Vitamin K dependent
 * Genetics/Inheritance
 * X-linked recessive
 * Characteristics
 * same as above
 * Treatment
 * Give frozen plasma
 * Give factor 9 concentrate
 * Values
 * Vary greatly but generally use above values for A


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User:Bluelip~enwikibooks

I hang around at http://bluelip.blips.net most often.

title: User:Bluelip~enwikibooks


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Handbook of Genetic Counseling/Hereditary Breast Cancer - BRCA1 and BRCA2

Hereditary Breast Cancer - BRCA1 and BRCA2

Introduction and Contracting

 * Introduce myself as a GC student
 * Elicit any questions or concerns
 * Find out about how she first found out that she had cancer
 * Assess what she knows about hereditary breast cancer
 * Find out how she feels about testing
 * Address any immediate concerns
 * Outline what will be done during visit
 * Other concerns will be answered in more detail
 * Review medical and family history
 * Hereditary vs. nonhereditary cancer
 * Genes associated with breast/ovarian cancer
 * General risks and risk for you and your family

Family and Medical History

 * Review their medical history
 * Explain the pedigree (looking for anything that might have a genetic component, but focusing in detail on cancers in the family)
 * Obtain information on the family
 * Affected members
 * Current age
 * Age of onset
 * Type and location of primary cancer (unilateral/bilateral)
 * Stage of cancer
 * Stage 0 is a noninvasive tumor
 * Stage I is a small locally invasive tumor w/out lymph node involvement
 * Stage II is a medium-sized tumor with or without lymph node involvement
 * Stage III is a locally advanced cancer, usually with axillary node matastases
 * Stage IV has already metastasized to distant sites
 * Other cancers
 * Environmental exposures
 * Any other health concerns
 * Unaffected members
 * Current age
 * Health history
 * If deceased -age and cause

Hereditary vs. Sporadic Cancer

 * Everybody is at risk for developing cancer and there are both non-genetic and genetic risk factors that may increase a person's risk for breast cancer (* are the main ones to mention)
 * Gender (99% of breast cancer occurs in women)
 * Age (77% occur after age 50)
 * Menarche before age 9 (RR 1.2)
 * Menopause after age 50-52 (RR 2.0)
 * Nulliparity (RR 2.0) except for BRCA mutation carriers, it makes them more likely to develop breast cancer by age 40 than nulliparous carriers
 * Previous history of breast biopsies
 * Atypical hyperplasia diagnosed by breast biopsy
 * Obesity
 * Hormone replacement therapy increase risk of breast cancer if used for more than 5-10 years. However HRT seems to decrease risk of ovarian cancer
 * Oral contraceptives may slightly increase risk, but it is dependent on dosage of progestin and estrogen. (Those using lower doses of estrogens and progestins did not seem to have an increased risk while those using the early contraceptives that were higher dosage did have some slight increase.)
 * Major cancer susceptibility genes may account for 5-10% of breast cancer
 * Less than 1 % associated with genetic syndromes such as Cowden, Bloom, Peutz-Jeghers, and Werner's syndromes.
 * Lifetime risk of breast cancer in women is 11-12%
 * Usually when a person gets breast cancer it is sporadic meaning the individual did not inherit a genetic predisposition for breast cancer
 * A small percentage get cancer that is inherited (hereditary cancer)
 * 5-10% of breast cancer is inherited (2/3 (66%) of these are associated with BRCA1/2)
 * 5-10% of ovarian cancer is inherited (90% are BRCA1/2)
 * Clues we look for in determining whether cancer is hereditary
 * Cancer in 2 close relatives on same side of family
 * More than one affected generation
 * Early age at diagnosis (under age 45-50 for breast cancer)
 * Bilateral/ multiple primary tumors
 * Rare/ unusual cancers (i.e. male breast cancer)
 * Combination of tumors consistent with specific cancer syndrome (i.e. individual with both breast and ovarian cancer)
 * 15-20% of individuals with breast cancer are not likely to have a single gene predisposition to breast and ovarian cancer, but have more family members with breast cancer than we would expect simply by chance. These individuals have familial cancer. The reason for the higher prevalence of cancer in these families is unknown, but it may be the combination of a few predisposing genes as well as environmental factors.
 * Explain the reasons we think their family is or is not at risk of having hereditary cancer

Genes Associated with Cancer

 * Hereditary cancers are caused by a change in a specific gene
 * Explain genes and chromosomes
 * Explain location of the known genes that predispose a person to breast and ovarian cancer
 * BRCA1: chromosome 17q (women with it carry a 56-87% lifetime risk of breast cancer 5-8 X's the risk of general population)
 * BRCA2: chromosome 13q (37-85% lifetime risk of breast cancer, 10-20% risk of ovarian cancer compared to 1.5% for other women, 6% lifetime risk for male breast cancer which is over 100 fold increase compared to general pop risk in males)
 * These are both tumor suppressor genes that control whether our cells are allowed to divide
 * When there is a change in the gene it is turned off or doesn't function properly
 * Changes in our genes are happening all the time due to environmental factors and to mistakes that can be made when a cell divides
 * When both copies of the gene are inactivated, the cell doesn't know when it is allowed to divide and it will therefore divide uncontrollably.
 * This can lead to cancer
 * In the case of sporadic cancer both copies of the gene in the same cell have to be altered
 * In heritable cancer, if you inherit an altered nonfunctional gene you only need one change to occur in the other copy of the gene in one cell to get cancer. So you are essentially one step closer to cancer and this may explain why we see earlier onset of hereditary cancer and a higher risk.

Risk Assessment

 * Background risks:
 * Ashkenazi Jewish - 1/40 risk of carrying one of the 3 specific BRCA1 or BRCA2 mutations
 * Non-Ashkenazi: 1/400 risk of carrying any mutation in BRCA1 or BRCA2
 * Risks can be estimated based on the family history
 * Various models used to estimate risks of having one of these genes in the family
 * When this was done for your family it was found that your risk of having BRCA1 or BRCA2 was _______________
 * Just because someone has a mutation in one of these genes doesn't mean they will develop cancer but their risks of developing certain types of cancer increase
 * Some individuals with a cancer predisposing gene will survive to an elderly age without developing cancer
 * Among those that do develop cancer the age of onset varies
 * It is uncertain why some individuals will have multiple primary cancers before age 50 while others with the same predisposing gene may not develop cancer until age 70
 * The lifetime chance of getting breast cancer in the general population of women is about 11-12%.
 * The risk is significantly increased in women with a mutation (50-85% for both BRCA1/2)
 * The chance of having a second breast cancer that is not a recurrence is also very high in mutation carriers (40-60% BRCA1).
 * The chance of having ovarian cancer is also significantly increased from about 1-2% in the general population up to about 15-45% in BRCA1 carriers and 10-20% in BRCA 2 carriers
 * Males can be mutation carriers also and develop breast cancer (males that carry BRCA2 mutations have about 6% chance, a 100 fold increase)
 * Other cancers possibly increased risk with BRCA1 mutation (prostate RR=3.3 and colon RR=4.0)
 * BRCA2 mutation associated with increased prostate, laryngeal and pancreatic cancer risks (unknown magnitude of increased risk)

Testing Options

 * BRCA1/BRCA2 testing is offered if the risk is calculated to be 10% or higher
 * Testing usually begins with an affected family member because if they are found not to have a mutation then it tells us more information than if an unaffected member did not have a mutation in one of these genes
 * If a mutation is found in that family member than it is less expensive to test unaffected family members because they look for that same mutation
 * Types of testing
 * Comprehensive BRACAnalysis
 * sequencing of both BRCA1 and BRCA2
 * Myriad cost is $3100
 * Rapid BRACAnalysis
 * same as BRACAnalysis, but results in 7-10 days
 * Myriad cost is $3680
 * Single site BRACAnalysis
 * Single mutation analysis for individuals with known BRCA1 or BRCA2 mutations in the family
 * Myriad cost is $440
 * Multisite 3 BRACAnalysis (detects about 83% of mutations in this population 17% are carriers of other mutations)
 * Three mutation analysis for Ashkenazi individuals
 * Myriad cost is $535
 * If a negative result can do full sequencing

Test Results

 * 3 possible results
 * NEGATIVE --Neither of the two genes have changes in them. If this were the case it wouldn't rule out the suspicion that the family has a hereditary form of breast cancer. However, if there is no history of ovarian cancer it might ease their mind because then it could be assumed that their risk of ovarian cancer is probably not likely to be increased above the population risk
 * VARIANT OF UNCERTAIN SIGNIFICANCE --There is a change but we are unsure of what it means and whether it would lead to an increased cancer risk (estimated to occur about 10% of time)
 * POSITIVE --A change is found in the gene that would cause it not to make a functional protein and would therefore lead to an increased cancer risk
 * Test results back in about 4-6 weeks
 * The lab will call when they are about to send the results and we will make a follow-up appointment to go over what the results mean and what the options are

Testing Pros

 * Know your risk more definitively
 * Know risk to your children of carrying the gene
 * Reduce anxiety often associated with not knowing
 * Choose prevention options based upon results

Testing Cons

 * Cost of the procedure
 * Insurance issues ( i.e. whether or not they want their insurance company to pay for the test, but this is probably more of an issue for those that don't already have cancer)
 * Fear of genetic discrimination, although there is no evidence that this is a problem (Should not be a problem if on a group health insurance plan due to HIPAA.)
 * Adverse psychological effects
 * Transmitter guilt
 * Survivor guilt
 * Depression
 * Anxiety
 * Other family members may not want to know
 * Result may not be informative if a variant is found of uncertain significance and this may provoke even more anxiety and uncertainty

Screening Options

 * More aggressive screening may be considered when there is an increased risk for developing breast or ovarian cancer
 * Breast screening
 * Mammography every year beginning at age 25-35 for mutation carriers
 * Clinical breast exam every 6 months beginning by age 20
 * Monthly self-breast exam beginning by age 18
 * Ovarian screening
 * Not shown to be effective in large-scale clinical trials
 * Transvaginal U/S w/ color doplar imaging, CA-125, and pelvic exam every 6-12 months starting age 25-35

Possible Prevention Options

 * Prophylactic surgeries
 * prophylactic mastectomy
 * reduces breast cancer risk by 90% and death by 81% (Mayo Clinic retrospective study between 1960-1993 that did not include mutation status, but many were probably mutation carriers)
 * reconstruction (TRAM transverse rectus abdominal muscle, silicone or saline implants)
 * most women satisfied with mastectomy but may cause body image and self-esteem problems and they lose nipple sensitivity
 * in individuals with mutations risk of second cancer if breast tissue remains is estimated to be 60% by age 70
 * prophylactic oophorectomy
 * reduces risk of ovarian cancer (BUT no guarantee because ovarian cancer can arise in the peritoneum so risk is reduced to about 2-5%)
 * reduces breast cancer risk by up to 70% if removed before age 40 and 40% if removed between 40-49, not really significant change if removed after 50
 * recommended after child bearing is complete
 * Chemoprevention
 * tamoxifen reduces breast cancer risk by 45% in high-risk women (but unknown if BRCA carriers have the same benefit) data suggest that in mutation carriers it is effective at reducing risk of second primary cancer in long term survivors and reduces contralateral breast cancer by 50-75%
 * raloxifene may reduce breast cancer risk
 * birth control pills used for a total of 6 years or more reduces ovarian cancer by 60% in BRCA mutation carriers and after 3 years reduces it by 40-50%, but may slightly increase breast cancer risk

Psychosocial Assessment

 * Are there any other questions or concerns?
 * Determine interest in options?
 * Why does the person want or not want testing?
 * What will the client do with the result (both positive and negative result)?
 * Will she change medical management?
 * Who will she share the result with?
 * If testing is decided on determine if they would want to bring someone back with them when they receive their results.


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Handbook of Genetic Counseling/Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) and Lobular Carcinoma In Situ (LCIS)

Hereditary Neuropathy with Liability to Pressure Palsies (HNPP) and Lobular Carcinoma In Situ (LCIS)

Introduction and Contracting

 * Thank you for filling out the forms that we sent you
 * I reviewed the information and understand that you have some questions and concerns about breast cancer, HNPP specifically genetic testing, heart disease and allergies.
 * Do you have other questions or concerns?
 * Do you (B) have any questions or concerns?

Pedigree
(already put together from intake, but ask some more questions)
 * Anyone else with a diagnosis of HNPP?
 * Anyone in the family have muscle weakness
 * Anyone with sensory loss (i.e. insensitive to heat or cold or touch)
 * Anyone with toes or feet that are mishappen or look unusual
 * Anyone with difficulty walking or moving
 * Anyone else with cancer in the family
 * Anyone with birth defects (spina bifida, heart defects, cleft lip)
 * Anyone with MR or LD
 * Consanguinity and ethnicity
 * Review who has allergies and heart disease (anyone else?)
 * Anything that you didn't already mention in the form you filled out that you are concerned might be hereditary?

Medical and Psychosocial History

 * Could you explain how you were diagnosed with HNPP?
 * When did you first notice symptoms?
 * What symptoms do you have?
 * Does it interfere with your daily activities?
 * What have you done to help deal with the symptoms?
 * What is the most difficult part of having HNPP?
 * Do you have any concerns about the diagnosis?
 * Has anyone explained the inheritance of HNPP?
 * Do you have any other health problems?
 * Assess if he works or attends school
 * How is his support network
 * Do friends know about diagnosis

Lobular Carcinoma In Situ (LCIS)

 * Tumor that is confined to the lobule (milk producing glands) of the breast
 * Noninvasive tumor that is not believed to progress to cancer
 * Behaves differently from the more common invasive cancers
 * Risk is increased for breast cancer though, in women with LCIS
 * Study of 211 patients followed for 30 years and only 36 developed invasive cancer (13%)
 * These cancers occurred in either breast and were not confined to original LCIS location
 * Some experts therefore believe that LCIS is not a true precancer
 * Only 6 of the 36 died of cancer and none of those six came back for regular exams
 * Other studies since show range of invasive breast cancer risk after LCIS between 16-27% over 30 years.
 * Relative risk for breast cancer if diagnosed with LCIS is 7.2 (chart from Dr. Susan Love's Breast Book and calculated using the study of 211 patients)
 * Prevention options include:
 * Bilateral mastectomy-some choose because they want to know they have done everything they can to prevent cancer
 * Follow-up exams every 6 mos and yearly mammograms.
 * Take tamoxifen for less than 5 years (shown to decrease chance of breast cancer 56% in women with LCIS)
 * There is no need to make an immediate decision
 * Radiation and chemo are not necessary
 * No reason to obtain clean margins since it doesn't become cancer itself

Hereditary Breast Cancer

 * All cancers are due to changes in the genetic material of cells
 * However, most cancer is sporadic (meaning that a person does not usually inherit a genetic predisposition that makes them more susceptible to cancer)
 * In about 5-10% of breast cancers, the woman has inherited a single predisposing gene for breast cancer and we call this hereditary breast cancer.
 * Although LCIS increases risk for breast cancer in an individual, it is not related to hereditary breast cancer and does not increase your risk of having inherited a mutation in one of the predisposing genes
 * The two known genes that account for most hereditary breast cancer are BRCA1 and BRCA2
 * These genes act like brakes on a car and help tell the cell when to stop dividing
 * If there are changes in these genes it is like the brakes of a car went out and the cell can continue to divide and may lead to cancer
 * In families that have a mutation in one of these genes we see a number of characteristics that are clues that there is a hereditary cancer
 * These include-(show visual aid)
 * Based on family history we can calculate the chance of having a BRCA mutation, but we don't use LCIS in the calculation because it is not associated with an increased risk for these mutations. (We only use individuals with invasive cancer in the risk assessment)
 * Even in families that have a couple of these clues their chance of having a mutation in BRCA1 or BRCA2 can still be quite low
 * For instance, I saw a patient last week with breast cancer dx in her 40's and her mother and maternal grandmother had breast cancer in their 60's, but their chance of having a mutation was only around 10%
 * These families, if they do not have a mutation found, are more likely to fall into a category called familial breast cancer (where we see more breast cancer than expected by chance which is probably due to a number of factors, but these factors are unknown at this time)

Overview

 * Disorder of peripheral nerves (nerves traveling to the limbs)
 * Predisposes individuals to repeated pressure neuropathies (i.e. carpal tunnel syndrome and peroneal palsy with foot drop)
 * Slowly progressive, hereditary, neuromuscular disorder which makes an individual susceptible to nerve injury from pressure, stretch or repetitive use.
 * When injured, the nerves demyelinate or lose their insulating covering
 * Pressure palsies are episodes of numbness and weakness in the injured area
 * Recovery is often complete (if not the resulting disability is usually mild)
 * Some have signs of mild to mod peripheral neuropathy

Prevalence

 * Uncertain, but estimated to be 2-5 cases per 100,000 (may be higher due to undiagnosed cases)

Description

 * Recurrent sensory and motor neuropathy in a single nerve beginning in adolescence or young adulthood
 * Most common symptom is acute onset of non-painful mononeuropathy
 * History of physical compression of nerve may or may not be present
 * Usually starts in 20's to 30's but range is 10-70's
 * Some asymptomatic and some may have just one episode
 * Most common sites
 * Peroneal nerve causing foot drop
 * Ulnar nerve causing weakness, atrophy and sensory loss over hand
 * Median nerve at wrist causing carpal tunnel syndrome and sensory loss over thumb and index finger
 * Full recovery in days to months occurs in ½ of episodes
 * Remaining symptoms rarely severe
 * Some develop diffuse polyneuropathy (% unknown)
 * Absent ankle reflexes (50-80%)
 * Diffusely reduced tendon reflexes (15-30%)
 * Mild to moderate pes cavus foot deformity (20% of symptomatic individuals)
 * One case reported with severe respiratory insufficiency (gene deletion and proximal muscle atrophy)

Diagnosis

 * Established in adults who have recurrent focal compression neuropathies and a family history consistent with AD inheritance
 * Presence of underlying neuropathy further supports dx
 * Other phenotypes besides typical presentation
 * Recurrent positional short-term sensory symptoms
 * Progressive mononeuropathy
 * CMT-like polyneuropathy
 * Chronic sensory polyneuropathy
 * Chronic inflammatory demyelinating polyneuropathy-like
 * Some patients can be asymptomatic
 * Delayed nerve conduction may be present
 * Prolongation of distal nerve conduction latencies (found in virtually all patients even if no symptoms)
 * General nerve speed is normal, but some have diffuse polyneuropathy
 * Key diagnostic features (Mouton 1999)
 * Bilateral slowing of sensory and motor nerve conduction at carpal tunnel with at least one abnormal finding for motor conduction in one peroneal nerve
 * Sural nerve biopsy often shows demyelination and focal enlargement of nerve (tomaculous change) but this is not specific for HNPP

Genetics

 * Due to changes or deletion of PMP22 gene (peripheral myelin protein 22) located at 17p11.2
 * Gene is similar to growth arrest specific gene in mouse and rat
 * There are flanking repeat sequences at the locus which may be mechanism for deletion
 * Likely that there is gene dosage effect because mutations are not gain of function
 * Normal gene product present in compact myelin and this PMP22 protein decreased in peripheral nerve of those affected

Inheritance and Risks

 * Autosomal Dominant (AD) inheritance with most individuals inheriting it
 * Parents may serve as carriers without showing signs or symptoms
 * Child has a sporadic mutation
 * Parent is asymptomatic or mildly affected and was not diagnosed
 * 50% risk to sibling if parent affected
 * No instances of germline mosaicism, but theoretically possible
 * 50% risk to children of affected

Genetic testing

 * DNA testing for deletion that includes PMP22 gene
 * Detects 80% of patients and available clinically
 * Remaining 20% have a point mutation producing frameshifts, premature termination or other abnormalities of protein (a number of which can be tested for clinically)
 * There are some geneotype phenotype correlations for frameshift and point mutations
 * Can test at risk adults who are asymptomatic
 * Should discuss motivation for testing (Why would it be helpful to them to be tested)
 * Discuss life, health, disability insurance coverage and employment discrimination
 * Do not test asymptomatic children due to it being adult onset
 * Removes their choice to not know
 * Possibility of stigmatization

Prenatal testing
not offered because not clinically available

Related disorders and Differential Diagnosis

 * (Charcot Marie Tooth) CMT1A and some patients with CMT4 also have mutations in the gene PMP22
 * pressure palsies most commonly result of environmentally acquired compression
 * those with underlying neuropathy (i.e. if have diabetes mellitus), increased risk of compression neuropathies
 * acquired type of pressure palsies same as those in HNPP
 * Charcot Marie Tooth
 * Sometimes HNPP involves brachial plexus and can overlap symptoms of hereditary neuralgic amyotrophy (distinct disorder maps to 17q)

Management

 * No treatment for biochemical defect or special diet or vitamins alter HNPP
 * Risk factors for PP's
 * Sitting with legs crossed
 * Occupations with repetitive wrist motions
 * Leaning on elbows prolonged period
 * Rapid weight loss
 * Bracing may be useful (wrist splint or ankle-foot-orthosis (AFO) for foot drop)
 * Controversial whether surgical decompression of nerve is beneficial

Web references

 * Geneclinics (www.geneclinics.com) HNPP
 * http://www.hnpp.org/welcome.htm
 * http://www.charcot-marie-tooth.org
 * What is Neuropathy

Patient resources and references

 * http://www.hnpp.org/welcome.htm (website to learn about HNPP)
 * Charcot-Marie-Tooth Association
 * 2700 Chestnut street
 * Chester, PA 19013-4867
 * Phone: 1-800-606-CMTA
 * Fax: 610-499-9267
 * Email: CMTAssoc@aol.com
 * http://www.charcot-marie-tooth.org


text:
Handbook of Genetic Counseling/Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

Hereditary Nonpolyposis Colorectal Cancer (HNPCC)

Contracting

 * Introductions
 * What are your main concerns? What do you hope to learn today?
 * What do you know about colon cancer?

Review Family and Medical History

 * Medical History
 * How have you gotten to this point?
 * Screening practices?
 * Other significant illnesses, hospitalizations?
 * Family History
 * Other individuals with any type of cancer?
 * If affected:
 * Age and date at diagnosis, death
 * Current age
 * Type, location, stage of primary cancer
 * Secondary cancer - metastasis or new primary
 * Environmental exposures
 * If unaffected:
 * Current age
 * Health and history of illness
 * If deceased, cause and age at death
 * Screening practices
 * Family thoughts on cause of cancer?

Colon Cancer

 * Third leading cause of cancer in men and women
 * 9% of new cancer diagnoses, 11% of all cancer deaths
 * Incidence is over 130,000 new cases per year
 * About 5-10% of all colorectal cancers are hereditary
 * 3-5% due to HNPCC
 * 1% due to FAP
 * About 10-30% of colorectal cancers are familial
 * Caused by uncontrolled proliferation of cells in colon or rectum
 * Symptoms may include blood in stool, diarrhea, constipation, stomach cramps, frequent bloating, weight loss, or unusual and continuing lack of energy
 * Cancer cells may enter blood or lymphatic system and metastasize to form secondary tumors in other parts of body
 * Multifactorial disorder involving both genetic and non-genetic factors
 * Non-genetic factors
 * Diet: high fat, low fiber, high red meat intake
 * Colorectal polyps (adenomatous polyps)
 * Alcohol, cigarettes
 * Chronic disease of bowel (Crohn's disease, inflammatory bowel disease, ulcerative colitis)
 * Obesity
 * Genetic factors
 * Hereditary colorectal cancer syndromes
 * HNPCC and FAP
 * Rare colorectal syndromes: Peutz-Jeghers Syndrome, Juvenile Polyposis Coli
 * All cancers have genetic component but not all are hereditary

Genetic Etiology of Hereditary Colon Cancer

 * Autosomal dominant inheritance
 * Each child of mutation carrier has 50% chance of inheriting mutation
 * Mutations in DNA mismatch repair genes
 * MSH2 at 2p22
 * MLH1 at 3p21
 * PMS1 at 2q31
 * PMS2 at 7p22
 * MSH6 at 2p16
 * 60% of HNPCC due to mutations in MSH2 or MLH1
 * Carcinogenesis due to loss of heterozygosity of one of genes above
 * Causes defective mismatch repair
 * Mutations accumulate throughout the genome
 * Microsatellite instability (MSI)
 * Provides indirect evidence for presence or absence of germline mutation
 * Due to genome wide instability of replication and repair of repeat sequences
 * 10-15% of sporadic tumors show MSI, >95% of HNPCC tumors show MSI
 * Penetrance variable - use lifetime cancer risks for mutation carriers
 * Mutation also increases risk for other types of cancer besides colorectal cancer
 * 30% risk of second primary 10 years after original diagnosis
 * 50% risk of second primary 15 years after original diagnosis

Cancer Risk Assessment

 * Features of hereditary colorectal cancer
 * More than one generation affected
 * Early age at diagnosis
 * Bilateral or multiple primary cancers
 * Combination of tumors consistent with specific cancer syndrome
 * Strengths and limitations of cancer risk assessment
 * Knowledge of family history may be limited
 * Cancer occurs with or without hereditary cancer syndrome
 * Can't diagnose on the basis of family history information alone
 * Features associated with HNPCC
 * Polyps present in small numbers or not at all
 * Proximal (right-sided) colon cancer
 * Mean age at diagnosis is 45 years
 * Individual risk based on personal/family history: ________
 * Muir-Torre Syndrome
 * Variant of HNPCC
 * Associated with MSH2 or MLH1 mutations
 * Typical features of HNPCC
 * Also includes sebaceous gland tumors and keratoacanthomas
 * Turcot Syndrome
 * Rare hereditary syndrome of multiple colorectal adenomas and brain tumors
 * Two subtypes
 * APC mutations associated with medulloblastomas
 * MMR mutations associated with glioblastomas

Genetic Testing

 * Diagnostic/Testing Criteria for HNPCC
 * Amsterdam Criteria
 * Family must meet ALL of the following
 * Three cases of colorectal cancer
 * One affected person is first-degree relative of other two
 * Two successive generations affected
 * One diagnosis < 40 years
 * FAP excluded in cases of colon cancer
 * Tumors verified by pathology
 * Failure to meet these criteria DOES NOT exclude HNPCC
 * Modified Amsterdam Criteria
 * Family must meet ALL of the following
 * Three relatives with HNPCC-related cancer
 * One person is first-degree relative of other two
 * Two successive generations affected
 * One diagnosis < 50 years
 * FAP excluded in cases of colon cancer
 * Tumors verified by pathology
 * HNPCC-related cancers include colorectal, endometrial, small bowel, ureter, renal pelvis)
 * Bethesda Guidelines for eligibility for MSI testing
 * Family or proband meets at least one criteria
 * Family fits either Amsterdam criteria
 * Proband has two HNPCC-related cancers
 * Proband has CRC plus 1st degree relative with HNPCC-related cancer or CRC adenoma <45 years
 * Colorectal or endometrial cancer diagnosed before 45 years
 * Right-sided colon cancer if undifferentiated diagnosed before 45 years
 * Signet-ring cell type colorectal diagnosed before 45 years
 * Colon adenomas diagnosed before 45 years
 * If high MSI, proceed to germline mutation testing
 * Common adult cancers may be due to one of several genes or genetic and environmental interactions
 * Negative result difficult to interpret since it can be more than one gene
 * Preferable to identify mutation in relative with cancer before testing other at-risk relatives
 * General population screening not appropriate for this reason
 * DNA banking is option to defer testing until sometime in future
 * Testing procedures
 * Process
 * Blood drawn here and sent to outside lab (Myriad)
 * Results usually take about 4 weeks
 * Payment methods
 * Patient pay with check, money order, credit card
 * Insurance claims
 * Submit patient insurance authorization with sample
 * Requires 20% copay or insurance verified patient portion
 * Medicare claims - Medicare Waiver of Liability required
 * Institutional pay - Myriad bills institution directly
 * Current prices
 * Comprehensive COLARIS (MLH1 and MSH2 sequencing) $1950
 * Single Site COLARIS (known family mutation) $315
 * Micorsatellite Instability $600
 * Used to screen before DNA testing
 * Must be done on tumor tissue
 * Cannot be billed to insurance
 * Practice guidelines for testing
 * If positive for Bethesda criteria, start with MSI
 * If MSI high, consider genetic testing
 * If MSI low or negative, consider testing if Amsterdam positive
 * If Bethesda and Amsterdam negative, manage based on family history
 * Mutation identified
 * Increased risk for cancer
 * Gene could be passed on to children
 * Other at-risk relatives should be informed and offered counseling
 * Important to establish management plan
 * Insurance issues
 * Mutation not identified
 * Inherited cancer can't be ruled out since mutation may have been missed or exist in another gene
 * May be no genetic explanation for cancer in family
 * Person with cancer who does not have mutation may be sporadic case
 * Relatives may still be at risk and should discuss family history with their doctor
 * Limitations of testing
 * Can't predict when a person with a mutation will develop cancer
 * Not all persons with mutation will develop cancer
 * Some mutations may be missed or can't be interpreted
 * Efficacy of screening for some related cancers (e.g. ovarian) is unknown
 * Benefits of testing
 * May provide information
 * Explanation for cancer in family
 * Increased surveillance or plan for future
 * Clarify risks to children and other family members
 * Reassurance
 * Colon surveillance in at risk persons proven to reduce mortality
 * Risks of testing
 * Insurability
 * Employment issues
 * Confidentiality
 * May alter family relationships
 * Adverse psychological effects
 * Survivor guilt
 * Transmitter guilt
 * Depression
 * Anxiety
 * Not appropriate to offer testing for adult onset disorders for prenatal diagnosis or to anyone under age 18

Screening and Management Options

 * Screening guidelines
 * Colonoscopy
 * Starting at age 25 or 5-10 years before age of first colorectal cancer diagnosis
 * Repeat every 1-2 years
 * Surveillance decreases mortality by 65%, decreases CRC by 62%
 * Promotes early detection, improved survival
 * Endometrial and ovarian cancer
 * Transvaginal ultrasound, CA-125 levels starting 30-35 every 1-2 years
 * Endometiral biopsy annually starting at age 25
 * Stomach
 * If previous family member affected
 * Upper GI endoscopy every 1-2 years starting at age 30
 * Urinary tract
 * If previous family member affected
 * Ultrasound and urine cytology every 1-2 years starting at age 30
 * Prophylactic surgery
 * Effectiveness unknown so no recommendations for or against surgery
 * Does not eliminate cancer risk
 * Subtotal colectomy
 * Hyterectomy with or without oophorectomy
 * Chemoprevention
 * Current multicenter trial recruiting patients with known mutation or high MSI tumors and Amsterdam positive family history
 * No chemopreventive therapies for HNPCC.
 * NSAIDs can reduce number of adenomas in FAP and may work for HNPCC too

Psychosocial Issues

 * Motivation for undergoing testing
 * Decision-making about testing, surveillance, and prevention
 * Stress level, previous experiences with cancer
 * Reactions to positive, negative, and uninformative results
 * Changes in medical management
 * Who else will be told about results
 * Family, social support system

Resources

 * IMPACC (Intestinal Multiple Polyposis and Colorectal Cancer
 * PO Box 11
 * Conyngham, PA 18219
 * (717) 788-1818

 * American Cancer Society
 * National Headquarters
 * 1599 Clifton Road, N.E.
 * Atlanta, GA 30329
 * (800) ACS-2345

 * Hereditary Colorectal Cancer Registry
 * The Johns Hopkins Hospital
 * 550 North Broadway, Suite 108
 * Baltimore, MD 21205-2011
 * (410) 955-3875


text:
Handbook of Genetic Counseling/Holoprosencephaly

Holoprosencephaly

Contracting

 * Introduce myself
 * Elicit concerns of the family- what questions do they have?

Interim Medical History

 * Who are the doctors that Lil' Jane is currently seeing? Dr. Doktour- pediatrician?
 * Has she had any illnesses since we saw her last? Does it take her longer to recover from colds than you would expect?
 * Surgeries/hospitalizations?
 * Recent test/procedures?
 * Hearing (ABER) and vision test results? Did Lil' Jane see endocrinology? Results? Any pituitary involvement? Recommendation for hormone replacement therapy?
 * When is she seeing cardiology again?
 * Is she taking any medications?
 * Is Lil' Jane still receiving EI services? PT and OT? How often?
 * Address Dr. H's concern about hypertonia of the hip. Did increased PT help?
 * Has she had any seizures?
 * Trouble breathing? Turning blue?
 * Diarrhea or constipation?
 * What is she eating? How often?
 * Developmental assessment- minimal: tell me what kinds of things Lil' Jane is doing? Is she babbling at all? Rolling over, smiling etc…

Interim Family History

 * Have there been any new births, deaths, or diagnoses on either side of the family?

Psychosocial Issues

 * Who is living in your home?
 * How is the family coping?
 * Support network?
 * Who is helping with Lil' Jane's needs?
 * Does a home health care nurse still help out during the week? How often?
 * Do mom and dad work outside of the home? Occupation?
 * Any plans of becoming pregnant?
 * Are you happy with the care that Lil' Jane is receiving?
 * How does the family feel? Anxious? Worried?
 * Insurance? Any financial concerns?

Recurrence Risks

 * The risk for recurrence in this family is very low, 1-2 %, given that both parents have normal karyotypes.

Definition

 * Holoprosencephaly (HPE) is a structural anomaly of the brain (occurs during the 3rd week of gestation) in which the developing forebrain fails to divide into two separate hemispheres and ventricles. There is incomplete cleavage of the forebrain (prosencephalon) into right and left hemispheres, into the telecephalon and diencephalon, and into the olfactory and optic bulbs and tracts.

Genetic Etiology

 * An extremely variable phenotypic expression occurs both in sporadic HPE and among members of the same family with an inherited form of HPE
 * Environmental
 * Teratogen: Maternal diabetes; 1% risk of fetus having HPE
 * Alcohol
 * TORCH
 * Genetic mechanism
 * Chromosomal: 25-50% of HPE cases are caused by a chromosome abnormality
 * Numerical: Trisomies 13, 18 and Triploidy
 * Structural: Reported in virtually all chromosomes
 * Most common include duplications or deletions at (13q), del (18p), del (7)(q36),
 * Can occur due to a de novo rearrangement or from an inherited from a normal parent with a balanced rearrangement.
 * Monogenic (gene penetrance ~ 30%): syndromic
 * Autosomal dominant, autosomal recessive, and multifactorial inheritance can be seen.
 * At least 25 different conditions have been described in which HPE is an occasional finding; the majority of these disorders are rare.
 * Monogenic: nonsyndromic
 * The nonsyndromic forms of HPE that are best understood at a molecular genetic level are inherited in an autosomal dominant manner.
 * Genes associated:
 * SHH (7q36), ZIC2 (13q32), SIX3 (2p21), TGIF (18p11.3)

Prevalence

 * HPE is the most common forebrain defect in humans, with a prevalence of 1:250 in embryos and 1:10,000-1:12,000 at birth.

Categories

 * HPE encompasses a variety of brain malformations, with different degrees of severity.
 * Alobar HPE, the most severe, in which there is a single ventricle and no separation of the cerebral hemispheres.
 * Semilobar HPE, the left and right frontal parietal lobes are fused and the interhemispheric fissure is only present posteriorly.
 * Lobar HPE, the mildest form, in which the left and right central hemispheres and the lateral ventricles are separated, but the most rostral aspect of the telencephalon, frontal lobes, are fused ventrally.
 * Middle interhemispheric fusion variant (MIHF or syntelencephaly), in which there is failure of separation of the posterior frontal and parietal lobes, with varying lack of cleavage of the basal ganglia and thalami, and absence of the body of the corpus callosum but presence of the genu and splenium of the corpus callosum. It is debated whether MIHF is part of the HPE spectrum or a separate entity.

Clinical Features

 * HPE is accompanied by a spectrum of characteristic craniofacial anomalies in about 80% of patients.
 * In the majority of patients with HPE, a correlation exists between the facial anomalies and the subtype of HPE. (Of note, patients with all subtypes can have a relatively normal facial appearance).
 * The spectrum of facial anomalies begins with cyclopia and extends in an unbroken sequence to the normal face as seen in nonpenetrant carriers of autosomal dominant HPE.
 * Malformations of the nose:
 * complete absence
 * agenesis of the nasal cartridge, and
 * proboscis (flat nose with a single central nostril without nasal bones)
 * Palatal anomalies:
 * midline and lateral clefts
 * midline palatal ridge,
 * bifid uvula
 * absence of the superior labial frenulum
 * A single central incisor may be present. Although a single central incisor is a non-specific finding, it is a distinctive microform in autosomal dominant HPE.

 * Developmental delay is present in virtually all individuals with the HPE spectrum of CNS anomalies. The degree of delay is variable, correlating with the severity of the brain malformation.
 * Seizures are common.
 * Hydrocephalus can occur.
 * Hypothalamic and brainstem dysfunction may lead to instability of temperature, heart rate, respiration, and swallowing difficulties.
 * Pituitary dysgenesis is manifested by partial or complete panhypopituitarism with abnormal function of any or all of the anterior and/or posterior pituitary hormones.
 * Feeding problems sometimes require gastrostomy tube. Excessive intestinal gas/colic, irritability, and constipation frequently occur.
 * Aspiration pneumonia can be a complication of poor coordination of swallowing.
 * Erratic sleep patterns can occur.

Natural History

 * Age of onset: newborn period, when facial features warrant further investigation
 * A significant proportion of more mildly affected children survive past 12 months.
 * Among patients with a normal karyotype, an inverse relationship exists between the severity of the facial phenotype and survival length.
 * Individuals with cyclopia generally do not survive beyond one week of age
 * Approximately one half of children with alobar HPE die before the age of 4-5 months and 20% live past the first year of life.
 * Among individuals with isolated semilobar or lobar HPE, without significant malformations of other organs, more than 50% are alive at the age of 12 months.
 * Almost all survivors have apparently normal vision and hearing; they smile and demonstrate memory.

Testing

 * Imaging of the brain by CT scan or MRI confirms the diagnosis of HPE, defines the subtype, and identifies associated CNS anomalies such as hydrocephalus and pituitary involvement.
 * Chromosome analysis of blood
 * Molecular genetic testing of the genes known to cause HPE is currently available on a research only basis.

Management

 * Most children benefit from a multidisciplinary team approach.
 * A major aspect of treatment is support and counseling of the parents.
 * Hormone replacement therapy has been successful in some children with pituitary dysfunction.
 * Anticonvulsive therapies can help decrease the frequency and intensity of seizures.
 * Feeding difficulties and failure to thrive may be managed with gastrostomy tube placement.
 * Placement of a shunt may be necessary in children with HPE and hydrocephalus.
 * In older children, surgical repair of cleft of the lip and /or palate may be indicated

Risk of Recurrence

 * Dependent upon the mode of inheritance
 * AD nonsyndromic HPE = 50% recurrence risk
 * Numerical Chromosomal HPE = 1% or less (depends on the abnormality and the maternal age)
 * Structural chromosomal HPE = depend on the type of structural rearrangement
 * Sporadic: low - 50% (if gonadal mosaicism)


text:
.NET Development Foundation/Value types

Value Types
Data types, such as integers and floating-point numbers that are copied when they are passed as arguments (that is, they are passed by value). In the .NET Framework, these are called value types. The runtime supports two kinds of value types: Built-in value types and User-defined value types.

Value types are stored as efficiently as primitive types, yet you can call methods on them. You can create instances of value types, pass them as parameters, store them as local variables, or store them in a field of another value type or object. Value types do not have the overhead associated with storing an instance of a class and they do not require constructors.

For each value type, the runtime supplies a corresponding boxed type, which is a class that has the same state and behavior as the value type. When you define a value type, you are defining both the boxed and the unboxed type.

Value types can have fields, properties, and events. They can also have methods.

 * reference: http://msdn.microsoft.com/library/default.asp?url=/library/en-us/cpguide/html/cpconvaluetypes.asp

title: .NET Development Foundation/Value types


text:
Handbook of Genetic Counseling/Huntington Disease

Huntington Disease

Contracting

 * What have you been told already about HD and the reason you were referred to see us?
 * Wondering what questions or concerns you might like to discuss with us today?
 * How has your diagnosis of a neurodegenerative disorder changed your life the most?
 * Since HD is usually passed on by a parent I like to begin by taking a family medical history to see if any other family members may have had symptoms of HD. Sometimes HD can be misdiagnosed as something else like Parkinson's or Alzheimer's disease because they share some of the same symptoms and other times family members have passed away before symptoms of HD develop
 * We can then discuss the cause of HD and details about the genetic testing we have to offer you.
 * Dr. ____ will also be in later to perform a short physical examination and further discuss HD

HD overview

 * An inherited progressive brain disease
 * It often causes uncontrolled movements (chorea), problems with coordination, difficulty with memory and mental processing, and emotional or personality changes.

Incidence

 * A rare disease, occurring in 3-7 people per 100,000 people in populations of western European descent
 * About 1 in 10,000 in N. America
 * HD is less common in Japan, China, Finland, and African Americans

Disease Manifestations

 * Presently no effective therapy to halt progression of disease
 * Most often symptoms develop between age 30-50
 * Approximately 25% of patients with HD exhibit the first symptoms after age 50
 * About 10% have juvenile Huntington disease with onset before age 20
 * Epileptic seizures are common in early onset cases with 30-50% of juvenile patients being affected
 * Chorea is not common in children with juvenile HD
 * Early symptoms
 * subtle changes in coordination
 * involuntary movements (chorea)
 * non-repetitive, non-periodic, jerking of limbs, face or torso
 * present in over 90% of patients with HD
 * continuously present during the waking hours, cannot be suppressed voluntarily and are worsened by stress
 * difficulty in mental planning
 * depressed or irritable mood
 * memory impairments
 * As HD progresses there is increased difficulty with voluntary movement
 * May have outbursts of aggressive behaviors and social disinhibition
 * A global decline in cognitive capabilities occurs in all HD patients
 * Personality changes may develop; some develop affective psychosis or schizophrenic psychosis
 * Suicide occurs in up to 12% of patients
 * Behavioral disturbances such as intermittent explosiveness, apathy, aggression, alcohol abuse, sexual dysfunction and deviations, are frequent
 * Delusions, often paranoid, are also common
 * Hallucinations are less common
 * In the late stages of HD, behavior problems are gradually lessened, but motor disability becomes severe and the patient is often totally dependent, can't speak, and can't control bladder function, weight loss often becomes a concern
 * Disease usually progresses slowly over a 15-20 year period after which death occurs

What Causes Huntington Disease?

 * In order to understand what causes HD and to understand the testing for HD it is helpful to review some genetics
 * Review chromosomes, genes, DNA, nucleotides
 * Gene IT-15 (discovered in 1993)
 * located on chromosome 4
 * area in the gene where there are tri-nucleotide repeats
 * Most individuals have between 9 and 26 repeats
 * Alleles of 27-35 CAG repeats are considered intermediate alleles. A person with an allele in the intermediate range do not develop HD, but they may have children with HD if the number of repeats increases when the gene is passed on
 * An allele in the range of 36-41 is associated with reduced penetrance for symptomatic HD (they may or may not develop symptoms of HD)
 * The HD gene produces a protein (Huntingtin)
 * widely expressed
 * function unknown
 * CAG expansion causes altered structural and biochemical properties
 * The protein has been shown to accumulate in neurons within the brain
 * Uncertain if this accumulation is what causes symptoms
 * Inverse correlation between CAG repeat length and the age of onset
 * Patients with adult onset of symptoms usually have an expansion that ranges from 40-55 CAG repeats
 * Patients with juvenile onset of symptoms usually have expansions about 60 repeats
 * Repeat length does not correlate with any other clinical feature, exact age of onset, or rate of progression

Inheritance

 * AD inheritance
 * Homozygotes are no more severely affected clinically than heterozygotes
 * Offspring of an individual with a mutant allele have a 50% chance of inheriting the disease-causing mutation
 * Approximately 3% of individuals with HD have no family history of condition
 * Reasons family history may be negative
 * Alternate paternity
 * Adoption
 * Early death of a parent
 * Failure to recognize symptoms or misdiagnosis
 * Late age of onset in a parent
 * Presence of intermediate allele or reduced penetrance allele in a parent
 * New mutations are rare
 * Genetic anticipation
 * Disease severity or decreasing age of onset can occur in successive generations
 * Anticipation occurs more commonly in paternal transmission of the mutated allele
 * The risk of expansion of intermediate allele into the disease range is about 2.5% when transmitted by the father
 * This phenomenon arises from instability of the CAG repeat during spermatogenesis
 * Large expansions in CAG repeat size occur almost exclusively through paternal transmission

Diagnostic Testing

 * Diagnosis of HD rests on a positive family history, characteristic clinical findings, and molecular DNA testing the reveals an expansion of the CAG repeat in the HD gene
 * Imaging studies including MRI, CT, SPECT, and PET may provide additional support for the clinical diagnosis. (used mainly to determine whether other conditions are contributing to the neurologic dysfunction)

Direct DNA testing

 * Blood test
 * Measures number of CAG repeats
 * 98.8% sensitive, 100% specificity
 * Sometimes results are uninformative, but if CAG repeat is within the normal range likely that your symptoms are due to a different neurodegenerative disorder
 * Cost of testing is approximately $270
 * Insurance - already symptomatic

Psychosocial Considerations

 * Probably beyond initial reaction to diagnosis of progressive neurodegenerative disorder
 * Encourage to carry on normally as long as possible
 * Others with HD have said it helps to try and live in the moment
 * Families should expect to deal with a variety of emotions
 * Realizing that this may be genetic and if children will inherit it
 * Watching things you used to do slowly slip away
 * Family members having to watch as loved one slowly looses their motor and cognitive skills
 * Moodiness, aggressiveness, emotional outbursts can be difficult for caregiver
 * Plans and potential concerns for the future
 * How are you coping with the likelihood that you will have to eventually give up work
 * Legal, financial, health insurance
 * Being dependent on others
 * Caregivers having time for themselves (not being selfish)
 * What have you told other family members?
 * How is the rest of the family reacting?
 * Do they know it could be genetic?
 * Different family members react differently based on their personalities, fears, and types of coping strategies
 * If testing were to come back showing you have HD how do you think you will react?
 * Would this be different if it came back showing you don't have HD
 * If positive for HD there is a support group
 * Don't be too reassuring, but provide hope that a lot of research is ongoing to try and understand the disease better
 * HD can provide challenges to family relationships
 * Roles and family dynamics may change
 * Have you come across any of these challenges
 * How have you dealt with problems in the past
 * Changes in sexual activity

Differential Diagnosis

 * Differential diagnosis include other conditions that involve chorea, dementia, and psychiatric disturbances
 * Many non-inherited conditions are associated with chorea
 * These include tardive dyskinesia, thyrotoxicosis, cerebrovascular disease, cerebral lupus, and polycythemia
 * Usually be excluded by other clinical features in a patient with suspected HD
 * Neuroancanthocytosis -- considered if muscle wasting, absent lower limb tendon reflexes, and signs of neuropathy are present
 * Benign hereditary chorea usually presents with nonprogressive chorea without dementia
 * Creutzfeld-Jakob disease progresses more rapidly then HD and has myoclonus as a prominent involuntary movement
 * For children, Hallervorden-Spatz syndrome, Lesch-Nyhan syndrome, and other metabolic diseases must be excluded when there is no known family history of HD
 * SCA

Management

 * Limited to symptomatic treatment
 * Choreic movements can be partially suppressed by neuroleptics
 * Anti-Parkinsonian agents may ameliorate hypokinesia and rigidity
 * Psychiatric disturbances such as depression, psychotic symptom, and outbursts of aggression may respond well to psychotropic drugs
 * Cognitive impairment is not amenable to treatment
 * There is no effective therapy to slow down disease progression

Reproductive Options

 * There are alternative reproductive options for those not wishing to risk transmitting the disorder to offspring
 * Prenatal testing is possible using DNA that has been extracted via amniocentesis or chorionic villus sampling (CVS).
 * Preimplantation genetic diagnosis (PGD) is also available. This technology uses in vitro fertilization (IVF) to produce embryos, which are tested for the HD mutation. Only embryos without the CAG expansion are implanted into the uterus.
 * You can have this procedure done without knowing if you actually carry the mutation
 * Consider cost per IVF cycle and success rates

Resources

 * Huntington's Disease Society of America
 * 158 West 29th Street, 7th Floor
 * New York, NY 10001-5300
 * Phone: 212-242-196; 800-345-HDSA
 * Fax: 212-239-3430
 * Email: hdsainfo@hdsa.org
 * www.hdsa.org

 * Huntington Society of Canada
 * 151 Frederick Street, Suite 400
 * Kitchener, Ontario N2H 2M2
 * Phone: 519-749-7063 or 1-800-998-7398
 * Fax: 519-749-8965
 * Email: info@hsc-ca.org
 * www.hsc-ca.org


text:
Handbook of Genetic Counseling/Hyper-extensibility

Hyper-extensibility

Contracting

 * Review a few things about medical history
 * Review a few things about family history
 * Physical exam
 * Make any testing recommendations
 * Answer any questions

Psychosocial Issues

 * Issue of nothing being wrong…may have to deal with the possibility of something else being wrong than the original thought (glaucoma/nearsightedness/Stickler's)
 * Mom not recognizing the hyper-extensibility of herself/children/family.

Other possible counseling issues

 * Dominant inheritance (Stickler's syndrome, inheritance)
 * Recessive inheritance
 * Multifactorial inheritance


text:
Handbook of Genetic Counseling/Hypoplasia - Agenesis of the Corpus Callosum

Hypoplasia - Agenesis of the Corpus Callosum

Definition

 * underdevelopment (hypoplasia) complete absence (agenesis) of the CC

Corpus collosum

 * The area of the brain (large fiber tract) which permits the exchange of information between the left and right cerebral hemispheres.
 * "the seat of the soul". Used to be that the thickness of its body was related to the level of intelligence.
 * Function is uncertain because there is no consistent pattern when it is malformed or absent.
 * Embryology: forms between 9-16 weeks of development. anterior to posterior.

Incidence
rare; no specific numbers

Diagnosis

 * ACC is usually diagnosed between 0-2 years (by MRI or CT scan) but may never be dx.
 * May occur as severe syndrome, a milder condition, or an asymptomatic finding
 * Signs and Symptoms:
 * Seizures (infantile spasms)
 * Feeding problems
 * Delays in holding head erect, sitting, standing and walking
 * microcephaly

Possible clinical impairments

 * Deficit or delay in mental and physical development, hand-eye coordination and/or visual and auditory memory
 * Could also include: hydrocephaly, seizures, dyskinesia, repetitive speech, headaches

Etiology

 * Most are isolated/sporadic
 * Males and females equally affected
 * May be caused by a genetic syndrome such as:
 * Aicardi's syndrome: ACC, infantile spasms, severe mental retardation and chorioretinal lacunae
 * Grubben syndrome
 * Wolf-Hirschhorn syndrome: chromosome abnormality
 * Opitz-Frias syndrome
 * Joubert syndrome
 * X-linked syndromes: Bertini, Opitz-Kaveggia, Orofaciodigital, Proud, Pyruvatedehydrogenase
 * May be associated with other cerebral anomalies such as Arnold-Chiari malformation, Dandy-Walker syndrome, Andermann syndrome, schizencephaly, holoprosencephaly and migrational anomalies
 * Sometimes associated with complex multi-system anomalies and chromosomal abnormalities (trisomy 13 and 18).

Management

 * No specific treatment. May involve managing treatment of other conditions such as hydrocephaly and seizures if they occur

Prognosis

 * Excellent in most isolated cases
 * Does not cause death in vast majority
 * Many will lead normal lives and have average intelligence
 * Children w/ ACC and DD and/ or seizures should be screened for metabolic disorders.
 * Mental retardation is not progressive

Resources

 * NINDS Agenesis of the Corpus Callosum Information Page www.ninds.nih.gov/health_and _medical/disorders/agenesis_doc.htm
 * Agenesis of the Corpus Collosum. Mental Retardation and Congenital Malformations of the Central Nervous System. Warkany, J, Lemire, R, Cohen, M.
 * Human Embryology. Larsen, WJ.


text:
Handbook of Genetic Counseling/Hypotonia - Developmental Delay

Hypotonia - Developmental Delay

Contracting

 * Introductions, acknowledge prior contact
 * Assess main concerns of patient
 * Why are they visiting Genetics today?
 * What do they hope to gain from the session?
 * explore desire to have a diagnosis
 * mother previously mentioned that they had come to terms with not having a diagnosis
 * Overview of today's session
 * Restate patient's concerns
 * Medical history, family history, physical exam, genetics, recurrence risk, testing options and limitations

Pediatric Intake

 * Family History
 * any relatives with hypotonia? developmental delay or learning disabilities? MR? -- no to all
 * history of infant deaths or miscarriages? birth defects? -- no
 * diabetes? cancer? thyroid prolems? heart problems? respiratory problems? genetic conditions? -- no to all
 * consanguinity? -- no

Differential Diagnosis

 * Canavan disease
 * autosomal recessive
 * characterized by developmental delays by age 3-5 months, severe hypotonia involving "head lag", and inability to sit, walk, or speak
 * hypotonia eventually changes to spasticity and help with feeding is necessary
 * macrocephaly
 * Testing
 * urine analysis for concentration of N-acetylaspartic acid (NAA)
 * increased in affected patients
 * blood analysis for levels of aspartoacylase enzymatic activity
 * often unmeasurable in affected patients

Myotonic Dystrophy

 * autosomal dominant
 * incidence of 1/20,000
 * suspected in infants with hypotonia, facial muscle weakness, generalized weakness, club foot, and respiratory insufficiency or failure
 * Mild -- characterized by cataract and mild myotonia
 * Classic -- characterized by muscle weakness and wasting, cataracts, myotonia, cardiac conduction abnormalities
 * Congenital -- hypotonia, severe generalized weakness at birth, often have respiratory problems and early death, MR common
 * Testing
 * DNA analysis is 100% sensitive
 * detects an expansion of the CTG trinucleotide repeat in the DMPK gene (19q13)
 * > 37 repeats is abnormal
 * > 50 repeats are symptomatic
 * > 1000 repeats often seen in congenital type
 * Cerebellar Ataxia
 * most types have onset in adulthood
 * Spinocerebellar Ataxia 7 -- failure to thrive and loss of motor milestones, loss of vision
 * Spinocerebellar Ataxia 8 -- common initial symptoms are scanning dysarthria with a characteristic drawn-out slowness of speech and gait instability, hyperactive tendon reflexes
 * onset can be as early as one year old
 * Testing -- CTA/CTG expansion in the SCA8 gene (13q21) can be detected via DNA analysis
 * Aicardi syndrome
 * X-linked dominant inheritance
 * characterized by the partial or complete absence of the corpus callosum (the structure that links the 2 hemispheres of the brain), infantile spasms, mental retardation, and an ocular abnormality called lacunae (lesions) of the retina of the eyes
 * may be associated with other brain defects such as microcephaly or porencephalic cysts (cerebrospinal fluid-filled cavities or gaps in the brain)
 * onset generally begins between the ages of 3 and 5 months
 * Myasthenia gravis (familial infantile)
 * autosomal recessive
 * characterized by respiratory and feeding difficulties in an infant
 * absence or weakness of the ocular muscles is also characteristic
 * Familial Dysautonomia
 * characteristics include lack of tearing, emotional lability, paroxysmal hypertension, increased sweating, cold hands and feet, corneal anesthesia, erythematous blotching of the skin, and drooling
 * the absence of the fungiform papillae of the tongue is also characteristic
 * scoliosis is often severe and neuropathic joints of the Charcot type may develop
 * Ashkenazi-Jewish heritage is common

Previous Testing

 * chromosomal testing done previously -- results normal

Psychosocial Issues

 * How important is a diagnosis to you?
 * If the visit to Genetics does not result in a diagnosis, what will this mean to you?
 * Are you worried about your child having a "label"?
 * Financial concerns
 * Support Network
 * do attend meeting of "Mother of Special Children" each month
 * support from family? friends? church?
 * Educational concerns

Support Groups and Resources

 * Mothers of Special Children
 * www.mothersofspecialchildren.com
 * meet the second Monday of each month at 7:30
 * Hyde Park Bethlehem United Church
 * Hyde Park and Madison Road

 * Ohio Coalition for the Education of Children with Disabilities
 * www.ocecd.org
 * Director: Margaret Burley
 * Co-Director: Lee Ann Derugen
 * Executive Office
 * 165 West Center Street, Suite 302
 * Marion, OH 43302-3741
 * Phone (740) 382-5452 or (800) 374-2806 (in Ohio)
 * Fax (740) 383-6421
 * E-mail: ocecd@gte.net

 * March of Dimes Birth Defects Foundation
 * 1275 Mamaroneck Avenue
 * White Plains, NY 10605
 * email: resourcecenter@modimes.org
 * internet: http://www.modimes.org
 * Tel: 914-428-7100 888-MODIMES (663-4637)
 * Fax: 914-428-8203


text:
Rhetoric and Composition/Parentheses

What Do Parentheses Do?
Parentheses can be used to enclose an interjected, explanatory, or qualifying remark, mathematical quantities, etc. The words placed inside the brackets are not necessary for the interrupted sentence to be complete.

 * Setting off incidental/accompanying information
 * Examples:
 * Be sure to call me (extension 2104) when you get this message.
 * Copyright affects how much regulation is enforced (Lessig 2004).

 * Enclose numbers and letters that label items listed in a sentence

title: Rhetoric and Composition/Parentheses


text:
User talk:Admrboltz

Talk:Cingular Wireless FAQ
Answered you there. --John Navas 07:47, 6 December 2005 (UTC)

ISPDA@CINGULARGPRS.COM
Belated answer to you in Talk:Cingular Wireless FAQ. --John Navas 23:03, 24 December 2005 (UTC)
 * I would be happy to email you the authoritative Cingular documentation. (My Home Page has email contact information.) --John Navas 08:57, 27 December 2005 (UTC)
 * Done as requested. --John Navas 01:17, 28 December 2005 (UTC)

title: User talk:Admrboltz


text:
AT&T Mobility FAQ/Data Connect Configuration

This is a setup guide for AT&T Mobility Data Connect (as distinct from MEdia Net). Important Notes:
 * This information is provided as a public service without warranty of any kind. Use at your own risk.
 * Items not covered here should be left at default values unless you really know what you are doing.

Differences between Data Connect and MEdia Net

 * Data Connect uses AT&T Data Connect profiles (settings) to provide standard Internet connections with AT&T as the ISP (Internet Service Provider). Connections can be configured with or without Data Acceleration (which significantly boosts throughput by means of image compression [which reduces image quality], caching, and transport optimization). Data Connect is more expensive than MEdia (as of this writing).
 * MEdia Net uses the AT&T WAP profile (settings) to support most types of Internet access (e.g., HTTP [Web browsing], SMTP/POP3/IMAP Email, FTP, Telnet, SSH, SSL). However, not all protocols seem to be fully supported, so problems may be seen with such things as VPN, and Data Acceleration is not available. Note that MEdia will not work with AT&T Data Connect profiles. MEdia is less expensive than Data Connect (as of this writing).

Handset (Phone) Configuration
If WAP isn't already working on the handset, the handset and SIM must first be configured for AT&T WAP:

 * This is best accomplished by asking AT&T Support (dial 611) to "push" WAP settings to the handset (normally done automatically by SMS when a WAP package [e.g., MEdia] is added to the account).
 * Alternative: Cingular On-line Phone & Device Support Select your Network, and handset Manufacturer and Model (or a similar device) to access Device Setup.
 * Another alternative (untested), for Sony Ericsson devices, is to use the Configurator on the Sony Ericsson website. Select Configurators, Phone model, WAP Read more, and then follow the prompts. (Email and MMS can also be configured this way.)

This configuration is sufficient for WAP and/or Web browsing with the handset alone. It's also sufficient for Email given an Email client in the handset that has been properly configured (including selection of the WAP profile for connections).

Using Windows XP Dial-Up Networking

 * Create a handset modem entry. If your handset connection (serial cable, USB cable, IrDA, Bluetooth) created a modem entry for your handset (e.g., Standard Modem over Bluetooth link), then you can skip to next major step (Create DUN connection); otherwise:
 * Obtain the latest handset modem driver.
 * Make sure your handset connection (serial cable, USB cable, IrDA, Bluetooth) is installed properly, and note the COM port assigned. Make sure the handset is connected and powered on.
 * Use Control Panel → Modem to Add the handset modem. Windows should detect the modem, and then search for the best driver. When it does, give Windows the location of the modem driver, and complete the installation. (If auto-detection fails, try to Add the modem manually using the appropriate COM port with the driver.)
 * Create a new Windows Dial-Up Networking (DUN) Connection:
 * Control Panel → Network Connections → Create a new connection

 * Network Connection Type : Connect to the Internet

 * Getting Ready : Set up my connection manually

 * Internet Connection : Connect using a dial-up modem

 * Select a Device : (Select just your serial, USB, IrDA, or Bluetooth connection)

 * Connection Name : AT&T Data Connect (or whatever you want)

 * Phone Number to Dial : *99# (uses default GPRS profile)

 * User name : WAP@CINGULARGPRS.COM (must be all uppercase)
 * Password : CINGULAR1 (must be all uppercase)
 * Confirm password : CINGULAR1 (must be all uppercase)
 * Make this the default Internet connection : (probably not)

 * Completing : Click Finish

 * Set the port speed. (Especially important for EGPRS/EDGE!)
 * See How To Set the Port Speed in Windows XP?

Use this Dial-Up Connection to connect your computer to the Internet with AT&T GPRS/EGPRS(EDGE).

Using AT&T Communication Manager (Handset)
AT&T Communication Manager is a software package that makes it easier to connect your computer to the Internet over AT&T. Available for free download (inc. help files on same download page). Includes drivers for mobile devices sold by AT&T.

Do not connect your mobile device before starting this procedure:
 * Install and launch the software : Select Configure a phone as a tethered modem.
 * Select the method of connection : This example is Bluetooth.
 * Connect your mobile device when instructed to do so : Give Windows time to recognize it before proceeding.
 * Device recognized and configured : With your mobile device showing in the box, click Finish.
 * Edit Connection Profile : You're not really ready to go yet because the port speed needs to be configured! Select Connections Edit → Connection Profiles
 * Profiles → Add : Profiles for Data Connect are pre-configured, but you'll have to add a profile for MEdia, so click Add.
 * GSM : Select AT&T Internet
 * Create Custom Profile
 * IP Settings : Leave both on automatic
 * General : Change the Profile name to whatever you want (e.g., AT&T MEdia), set any other options as desired, and click Finish.
 * Launch your new Profile : Select (verify settings) and click Connect.
 * Connected! : You should now be connected to AT&T MEdia.

Using BVRP/Motorola mobile PhoneTools

 * BVRP mobile PhoneTools works with a wide range of devices.
 * Motorola mobile PhoneTools (branded version of BVRP mobile PhoneTools) works only with Motorola devices. (Low-cost sources include Shopoem.)

Illustrated with Motorola V551:
 * Create Internet Connection : After starting mobile PhoneTools, click the Internet Connection icon.
 * Launch it : A new Internet connection should be created automatically. Launch it to test it.
 * Connection opening: Here's how it should look while launching the new Internet connection.
 * Completed
 * This process should create a standard Windows Dial-Up Networking (DUN) connection that can be managed and used in Windows (Control Panel → Network Connections) without having to launch mobile PhoneTools. Be sure to set the port speed...

 * Set the port speed. (Especially important for EGPRS/EDGE!)
 * See How To Set the Port Speed in Windows XP?

Using AT&T Communication Manager (PC Card)
Use the procedure in Using AT&T Communication Manager (Handset), selecting PC Card as the method of connection

Using Sony Ericsson Wireless Manager
Works only with Sony Ericsson [PC Card devices:
 * 1) Install the Sony Ericsson Wireless Manager:
 * 2) * This is best accomplished by downloading the latest version from the Global support area of the Sony Ericsson website. Select Location, Enter product name and click on the appropriate Matching products link, Software, Applications, Wireless Manager, Download here, and Download.
 * 3) * Or use the CD that comes with the PC Card.
 * 4) When the Wireless Manager is run for the first time, the Connection Wizard will start automatically. Enter the following settings:
 * Create a new connection : AT&T MEdia (or whatever name you prefer)

 * Type of Connection : GPRS (selects the default GPRS profile)
 * Choose network : Other

 * Primary APN : wap.cingular (must be all lowercase)

 * User ID : WAP@CINGULARGPRS.COM (must be all uppercase)
 * Password : CINGULAR1 (must be all uppercase)
 * Save password : Check

 * Finish

Use the Wireless Manager to connect your computer to the Internet.

Email

 * The usual problem when sending email from a handset with SMTP capability is the outgoing SMTP server. Thanks to spammers, outgoing SMTP servers now generally require some form of authentication when you're off the provider's network. You should be able to find out what kind(s) of authentication are supported by contacting the email provider (e.g., your ISP). Finding out what your handset supports may be a bigger challenge—documentation is often woefully inadequate in this area.
 * If the email provider supports POP3 before SMTP authentication, then you need to find a way to have the handset do a POP3 check or download before sending mail.
 * Some handsets (e.g., Sony Ericsson Z600) now have support for SMTP-AUTH (Authenticated SMTP, different from POP3 before SMTP). For this to work, you usually need to configure the handset with a valid mailbox id and password for the email provider.
 * On the AT&T network you can use cwmx.com (preferred, no footer added) or photo.mycingular.com (adds a photo messaging footer) as an outgoing SMTP server. Since you're authenticated by being on the AT&T network, no further authentication is required.

Speed

 * Handsets and PC Cards do not all have the same data performance—maximum speeds are limited by GPRS/EGPRS/EDGE Multislot Class (and the carrier). In general, all reasonably recent GPRS/EGPRS/EDGE-capable devices from Ericsson and Sony Ericsson support Class 8 (4+1) and Class 10 (4+2, max of 5), whereas most Nokia devices (as of this writing) are limited to slower Class 4 (3+1) and Class 6 (3+2, max 4). Motorola has both Class 4 and Class 8 devices. (The first number is the maximum number of downlink slots, and the number after the "+" is the maximum number of uplink slots.) This can translate into a substantial difference in throughput—if supported by the carrier, Class 8 is 33% faster on downlink than Class 4.
 * Connections between handsets and "tethered" devices (e.g., notebook computer, PDA) are typically implemented as a serial port, either real or virtual, and port speed usually defaults to 115 Kbps. (Bluetooth is typically implemented on a computer as a virtual serial port that will go as fast as 921.6 Kbps, but which runs at only 115.2 Kbps by default.) While 115 Kbps is generally fast enough for GPRS, it can be a bottleneck for EGPRS(EDGE) (as well as UMTS/HSDPA). In general, port speed should be at least 230 Kbps for GPRS and 460 Kbps for EGPRS(EDGE) (920 Kbps for UMTS/HSDPA).

WAP

 * WAP as built into many handsets is much more limited than standard HTTP—much of the Internet (World Wide Web) cannot be accessed through WAP.


text:
Operations Strategy/JIT

JIT (Just in Time) production concepts originated with the Japanese. JIT is a philosophy focusing on the elimination of waste in and management or production system. This waste can be in any form, waste materials, wasted effort, lost time though inefficient processes, etc.. One area where waste is eliminated is in the movement of work in process in a manufacturing system where material is pulled through by demand from the next step in the process, thus production is limited to the needs of the next step or internal customer in the system. The technique called KANBAN is run by using a series of signals which tell production when to reorder inventory. This historically can be as simple as a product missing from the shelf or an empty container or can be signalled by use of a card or indicator.

JIT was first developed by Toyota, but is now in used in most manufacturing industry.

title: Operations Strategy/JIT


text:
User talk:Leonard G.

For my background, interests, and some of my contributions to Wikipedia, please see [http://en.wikipedia.org/wiki/User:Leonard_G. my user page there]. For comments concerning the Wikibook Electric Vehicle Conversion please add to my talk page here at Wikibooks and notify me on [http://en.wikipedia.org/wiki/User talk:Leonard_G. my talk page at Wikipedia]. Leonard G. 02:52, 21 October 2007 (UTC)

Image licenses
I found an image of yours still without license: Image:WPEVShutdownAlarms.png. Please, check if you have any more that need fixed. Thank you. --Derbeth talk 09:09, 6 December 2005 (UTC)

title: User talk:Leonard G.


text:
User talk:71.109.220.143

Please stop. If you continue to blank pages, you will be blocked from editing.

title: User talk:71.109.220.143


text: User talk:61.17.42.96

title: User talk:61.17.42.96


text:
User talk:68.123.205.150

Please stop adding nonsense to Wikibooks. It is considered vandalism. If you would like to experiment, use the sandbox. Thank you.

title: User talk:68.123.205.150


text:
User talk:68.32.180.208

Please stop. If you continue to vandalize pages, you will be blocked from editing Wikibooks.

title: User talk:68.32.180.208


text:
User talk:68.45.68.156

Please stop. If you continue to vandalize pages, you will be blocked from editing Wikibooks.

title: User talk:68.45.68.156


text: User talk:68.203.234.246

title: User talk:68.203.234.246


text:
User talk:203.145.179.2

Please stop adding nonsense to Wikibooks. It is considered vandalism. If you would like to experiment, use the sandbox. Thank you.

title: User talk:203.145.179.2


text:
User talk:212.138.47.15

Please stop adding nonsense to Wikibooks. It is considered vandalism. If you would like to experiment, use the sandbox. Thank you.

title: User talk:212.138.47.15


text:
User talk:212.138.47.21

Please stop. If you continue to blank pages, you will be blocked from editing.

title: User talk:212.138.47.21


text:
User talk:69.193.162.57

The Wealthy Barber
You (or at least someone with your IP address) previously contributed to The Wealthy Barber. This book has been suggested for deletion. You might want to see the discussion at Votes for deletion. --JMRyan 10:30, 6 December 2005 (UTC)

title: User talk:69.193.162.57


text:
Vietnamese/D vs. gi

In standard Vietnamese (aka the textbook version), "gi" sounds like the "z" in the English word "zero" while "d" sounds like "y" in "you". However, as dialects play a very important role in spoken Vietnamese, these are pronounced differently in different regions. In the Northern dialect (relatively close to the standard textbook language), both "d" and "gi" (and also "r") are pronounced like "z" in "zero". In the Southern dialect, both "d" and "gi" are pronounced like "y" in "you". Central Vietnam has many local dialects (Thanh Hoa, Nghe An, Hue, Quang Nam, etc.), where the pronunciations more or less range between the Northern and Southern versions.

title: Vietnamese/D vs. gi