Joao A C Lima, M.B.A., M.D.
https://www.hopkinsmedicine.org/profiles/results/directory/profile/0001032/joao-lima
R E F E R E N C E S References to studies included in this review Habayeb 2010 Habayeb O advanced pain treatment center union sc order cheap elavil on line, Goodburn S quadriceps pain treatment purchase elavil pills in toronto, Chudleigh T southern california pain treatment center order genuine elavil, Brockelsby J jaw pain tmj treatment order elavil 50mg without prescription, Aagaard-Tillery 2009 Missfelder-Lobos H pacific pain treatment center generic elavil 50 mg otc, Hackett G pain treatment guidelines 2012 order elavil 50mg with visa, et al. Herman A, Dreazen E, Tovbin J, Weinraub Z, Bukovsky Audibert 2001 Y, Maymon R. Comparison between disclosure and non Audibert F, Dommergues M, Benattar C, Taieb J, Thalabard disclosure approaches for trisomy 21 screening tests. Comparison and integration of rst trimester fetal nuchal translucency and second trimester maternal serum Babbur 2005 screening for fetal Down syndrome. Prospective audit of a one-centre combined nuchal translucency and triple test programme for the Malone 2005 detection of trisomy 21. Prospective experience with integrated prenatal screening and rst trimester combined screening Benattar 1999 for trisomy 21 in a large Canadian urban center. Journal of Medical Screening 2010;17(1):8-12 (Erratum in Rodrigues 2009 Journal of Medical Screening 2010;17(2):106). Guanciali-Franchi 2010 Sequential screening for trisomy 21 by nuchal translucency Guanciali-Franchi P, Iezzi I, Matarrelli B, Morizio E, measurement in the rst trimester and maternal serum Calabrese G, Palka G. Effectiveness of crosstrimester test in biochemistry in the second trimester in a low-risk selecting high-risk pregnant women to undergo invasive population. Alexioy 2009 Abbas 1995 Alexioy E, Alexioy E, Trakakis E, Kassanos D, Farmakidis Abbas A, Chard T, Nicolaides K. Maternal serum S100 protein in normal and Down American College 2009 syndrome pregnancies. Pruebas prenatales para detectar el sindrome de in pregnancies with abnormal triple-screen results. Risk of Down syndrome and any clinically Inhibin A and pro-alphaC Inhibin A in Down syndrome signicantchromosome defect in pregnancies with abnormal and normal pregnancies. Prenatal Diagnosis 1998;18(11): triple-screen and normal targeted ultrasonographic results. Antsaklis A, Papantoniou N, Mesogitis S, Michalas S, Bahado-Singh 1999 Aravantinos D. Specicity of fetal tricuspid regurgitation in prediction of Bahado-Singh 2002 Down syndrome in Thai fetuses at 17-23 weeks of gestation. Screening for Down syndrome using rst Bar-Hava 2001 trimester ultrasound and second-trimester maternal serum Bar-Hava I, Yitzhak M, Krissi H, Shohat M, Shalev J, markers in a low-risk population: a prospective longitudinal Czitron B, et al. Axt-Fleidner 2006 Barkai 1996 Axt-Fliedner R, Schwarze A, Kreiselmaier P, Krapp M, Barkai G, Goldman B, Ries L, Chaki R, Dor J, Cuckle H. Combined second-trimester biochemical and ultrasound Bas-Budecka 2007 screening for Down syndrome. Baviera 2004 Incorporation of inhibin-A in second-trimester screening Baviera G, Carbone C, Corrado F, Mastrantonio P. Fetal gender impact on multiple-marker Benn 2005 screening results. Risk of chromosome abnormalities in the presence of Benn 2005a bilateral or unilateral choroid plexus cysts. Preliminary evidence for associations between specic 1-glycoprotein in fetal trisomies. Maternal and after in vitro fertilization pregnancies for fetal trisomy serum alpha-fetoprotein prenatal screening for Down screening. Comparison of modes of ascertainment proteins after in vitro fertilisation and their implications for for mosaic vs complete trisomy 21. An outcomes Borrell 2007 analysis of ve prenatal screening strategies for trisomy Borrell A, Mercade I, Casals E, Borobio V, Seres A, Soler A, 21 in women younger than 35 years. Screening for Borruto 2002 chromosomal defects by fetal nuchal translucency at 11 to Borruto F, Comparetto C, Acanfora L, Bertini G, Rubaltelli 14 weeks. Second-trimester genetic sonogram for detection gonadotrophin concentrations in singleton pregnancies. Second-trimester levels of maternal Braithwaite 1996 urinary gonadotropin peptide in down syndrome pregnancy. Population screening for aneuploidy using maternal age Brambati B, Tului L, Alberti E. Nuchal translucency screening: how do women Brizzi L, Cariati E, Periti E, Nannini R, Torricelli F, Cappelli actually utilize the results. First-trimester maternal serum biochemical Chelli 2008 indicators in Down syndrome. Ultrasound in Obstetrics & Gynecology 2008;31(2): serum marker in screening for Down syndrome. Elevated maternal midtrimester serum free human Down syndrome screening: think twice. Cole L, Isozaki T, Palomaki G, Canick J, Iles R, Kellner Chitayat 2002 L, et al. Combining Inhibin A with existing second-trimester Journal of Obstetrics and Gynecology. Maternal serum activin A and follistatin levels in pregnancies with Down Cowans 2011 syndrome. Early rst-trimester maternal serum placental growth factor Cuckle 1999c in trisomy 21 pregnancies. Diagnosis and signicance of cystic Crossley 1993 hygroma in the rst trimester. Maternal smoking: age distribution, levels of alpha fetoprotein and human chorionic gonadotrophin, and effect Dancoine 2001 on detection of Down syndrome pregnancies in second Dancoine F, Couplet G, Mainardi A, Sukno F, Jaumain P, trimester screening.
Current approaches in the treatment of relapsed and refractory acute myeloid leukemia running knee pain treatment 25mg elavil. Clonal hematopoiesis of indeterminate potential and its distinction from myelodysplastic syndromes pain treatment center bismarck nd purchase 50 mg elavil amex. Low-dose azacitidine after allogeneic stem cell transplantation for acute leukemia long island pain treatment center order 25mg elavil mastercard. Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia pain tmj treatment order elavil on line. See Full Prescribing Information for recommended dosage pain pain treatment hemorrhoids generic 75mg elavil with amex, anemia pain diagnostic treatment center sacramento ca purchase elavil 25 mg with amex, epistaxis, diarrhea, hypoesthesia and alopecia. The recommended starting dosage in patients with Congenital Neutropenia is 6 mcg/kg as a twice daily subcutaneous injection and the recommended starting dosage in patients with Idiopathic or Cyclic Neutropenia is 5 mcg/kg as a single daily subcutaneous injection. Dosage Adjustments in Patients with Severe Chronic Neutropenia Chronic daily administration is required to maintain clinical benefit. Thereafter, if the patient is clinically stable, less frequent routine monitoring is recommended. Discard any vial or prefilled syringe left at room temperature for greater than 24 hours. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit (the solution is clear and colorless). This 24-hour time period includes the time during room temperature storage of the infusion solution and the duration of the infusion. Evaluate patients who report left upper abdominal or shoulder pain for an enlarged spleen or splenic rupture. The diagnoses were based upon azotemia, hematuria (microscopic and macroscopic), proteinuria, and renal biopsy. Episodes vary in frequency, severity and may be life-threatening if treatment is delayed. Patients who develop symptoms of capillary leak syndrome should be closely monitored and receive standard symptomatic treatment, which may include a need for intensive care. The possibility that filgrastim acts as a growth factor for any tumor type cannot be excluded. Manifestations may include generalized signs and symptoms such as fever, abdominal pain, malaise, back pain, and increased inflammatory markers. Consider aortitis in patients who develop these signs and symptoms without known etiology. The patients in these studies were median age 61 (range 29 to 78) years and 64% were male. Patients receiving autologous bone marrow transplantation only were included in the analysis. Adverse Reactions in Patients with Cancer Undergoing Autologous Peripheral Blood Progenitor Cell Collection the adverse reaction data in Table 3 are from a series of 7 trials in patients with cancer undergoing mobilization of autologous peripheral blood progenitor cells for collection by leukapheresis. The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay, and the observed incidence of antibody (including neutralizing antibody) positivity in an assay may be influenced by several factors, including assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of the incidence of antibodies to filgrastim in the studies described below with the incidence of antibodies in other studies or to other products may be misleading. While available data suggest that a small proportion of patients developed binding antibodies to filgrastim, the nature and specificity of these antibodies has not been adequately studied. In these 11 patients, no evidence of a neutralizing response was observed using a cell based bioassay. Cytopenias resulting from an antibody response to exogenous growth factors have been reported on rare occasions in patients treated with other recombinant growth factors. In animal reproduction studies, effects of filgrastim on prenatal development have been studied in rats and rabbits. No maternal or fetal effects were observed in pregnant rats at doses up to 58 times the human doses. Filgrastim has been shown to have adverse effects in pregnant rabbits at doses 2 to 10 times higher than the human doses (see Data). All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. No major differences were seen between treated and untreated women with respect to pregnancy outcome (including miscarriage and preterm labor), newborn complications (including birth weight), and infections. Methodological limitations of these studies include small sample size and lack of generalizability due to the underlying maternal condition. Animal Data Effects of filgrastim on prenatal development have been studied in rats and rabbits. Filgrastim has been shown to have adverse effects in pregnant rabbits at doses 2 to 10 times higher than the human doses. In pregnant rabbits showing signs of maternal toxicity, reduced embryo-fetal survival (at 20 and 80 mcg/kg/day) and increased abortions (at 80 mcg/kg/day) were observed. In pregnant rats, no maternal or fetal effects were observed at doses up to 575 mcg/kg/day, which is approximately 58 times higher than the human dose of 10 mcg/kg/day. Offspring of rats administered filgrastim during the peri-natal and lactation periods exhibited a delay in external differentiation and growth retardation ( 20 mcg/kg/day) and slightly reduced survival rate (100 mcg/kg/day). There are a few case reports describing the use of filgrastim in breastfeeding mothers with no adverse effects noted in the infants. Other filgrastim products are secreted poorly into breast milk, and filgrastim products are not absorbed orally by neonates. Of the 123 patients, 12 were infants (7 months to 2 years of age), 49 were children (2 to 12 years of age), and 9 were adolescents (12 to 16 years of age). Of the 13 731 patients in the surveillance study, 429 were pediatric patients < 18 years of age (range 0. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Filgrastim is produced by Escherichia coli (E coli) bacteria into which has been inserted the human granulocyte colony-stimulating factor gene. See table below for product composition of each single-dose vial or prefilled syringe. Such changes were transient and were not associated with clinical sequelae, nor were they necessarily associated with infection. After intravenous administration, the volume of distribution averaged 150 mL/kg and the elimination half-life was approximately 3. Continuous 24-hour intravenous infusions of 20 mcg/kg over an 11 to 20-day period produced steady-state serum concentrations of filgrastim with no evidence of drug accumulation over the time period investigated. The absolute bioavailability of filgrastim after subcutaneous administration is 60% to 70%. Specific Populations Patients Acutely Exposed to Myelosuppressive Doses of Radiation the pharmacokinetics of filgrastim is not available in patients acutely exposed to myelosuppressive doses of radiation. Pediatric Patients the pharmacokinetics of filgrastim in pediatric patients after chemotherapy are similar to those in adult patients receiving the same weight-normalized doses, suggesting no age-related differences in the pharmacokinetics of filgrastim [see Use in Specific Populations (8. Renal Impairment In a study with healthy volunteers, subjects with moderate renal impairment, and subjects with end-stage renal disease (n = 4 per group), higher serum concentrations were observed in subjects with end-stage renal disease. Hepatic Impairment Pharmacokinetics and pharmacodynamics of filgrastim are similar between subjects with hepatic impairment and healthy subjects (n = 12/group). The study included 10 subjects with mild hepatic impairment (Child-Pugh Class A) and 2 subjects with moderate hepatic impairment (Child-Pugh Class B). Therefore, filgrastim dose adjustment for patients with hepatic impairment is not necessary. Filgrastim failed to induce bacterial gene mutations in either the presence or absence of a drug metabolizing enzyme system. Filgrastim had no observed effect on the fertility of male or female rats at doses up to 500 mcg/kg. Histopathologic examination of the liver and spleen revealed evidence of ongoing extramedullary granulopoiesis, and dose-related increases in spleen weight were seen in all species. In Study 1, patients received up to 6 cycles of intravenous chemotherapy including intravenous cyclophosphamide and doxorubicin on day 1; and etoposide on days 1, 2, and 3 of 21 day cycles. Study drug was administered subcutaneously daily beginning on day 4, for a maximum of 14 days. A total of 210 patients were evaluable for efficacy and 207 were evaluable for safety. The demographic and disease characteristics were balanced between arms with a median age of 62 (range 31 to 80) years; 64% males; 89% Caucasian; 72% extensive disease and 28% limited disease. In Study 4 the initial induction therapy consisted of intravenous daunorubicin days 1, 2, and 3; cytosine arabinoside days 1 to 7; and etoposide days 1 to 5. The demographic and disease characteristics were balanced between arms with a median age of 54 (range 16 to 89) years; 54% males; initial white blood cell count (65% < 25,000/mm3 and 27% > 100,000/mm3); 29% unfavorable cytogenetics. The main efficacy endpoint was median duration of severe neutropenia defined as neutrophil count < 500/mm3. The number of days of febrile neutropenia was also reduced significantly in this study (13. The underlying disease was: 67% hematologic malignancy, 24% aplastic anemia, 9% other. In addition, patients must have experienced a clinically significant infection during the previous 12 months. The median age was 12 years (range 7 months to 76 years); 46% males; 34% idiopathic, 17% cyclic and 49% congenital neutropenia. The 10 mcg/kg daily dose is selected for humans exposed to myelosuppressive doses of radiation because the exposure associated with such a dose is expected to exceed the exposure associated with a 10 mcg/kg dose in non-human primates [see Pharmacokinetics (12. The planned sample size was 62 animals, but the study was stopped at the interim analysis with 46 animals because efficacy was established. Starting on day 1 after irradiation, animals received daily subcutaneous injections of placebo (5% dextrose in water) or filgrastim (10 mcg/kg/day). Animals received medical management consisting of intravenous fluids, antibiotics, blood transfusions, and other support as required. Prefilled Syringes (SingleJect) Single-dose, prefilled syringe with 27 gauge, inch needle with an UltraSafe Needle Guard, containing 300 mcg/0. Single-dose, prefilled syringe with 27 gauge, inch needle with an UltraSafe Needle Guard, containing 480 mcg/0. The needle cap of the prefilled syringe contains dry natural rubber (a derivative of latex) [see Dosage and Administration (2. Advise patients to report pain in these areas to their physician immediately [see Warnings and Precautions (5. Advise patients to report dyspnea to their physician immediately [see Warnings and Precautions (5. Advise patients to seek immediate medical attention if signs or symptoms of hypersensitivity reaction occur [see Warnings and Precautions (5. Discuss potential risks and benefits for patients with sickle cell disease prior to the administration of human granulocyte colony-stimulating factors [see Warnings and Precautions (5. Symptoms include swelling of the face or ankles, dark colored urine or blood in the urine, or a decrease in urine production. Advise patients to report signs or symptoms of glomerulonephritis to their physician immediately [see Warnings and Precautions (5. Advise patients to report signs or symptoms of vasculitis to their physician immediately [see Warnings and Precautions (5. Symptoms may include fever, abdominal pain, malaise, back pain, and increased inflammatory markers. Advise patients to report signs and symptoms of aortitis to their physician immediately [see Warnings and Precautions (5. The needle cap on the prefilled syringe contains dry natural rubber (derived from latex). Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Your healthcare provider may decide subcutaneous injections can be given at home by you or your caregiver. Call your healthcare provider right away if you have pain in the left upper stomach (abdomen) area or your left shoulder.
Although the majority of breast cancer cases are sporadic davis pain treatment center statesville nc discount elavil 25 mg free shipping, approximately 5% have an inherited component chronic back pain treatment guidelines elavil 75 mg with amex. The remaining exons premature termination of translation using the protein truncation test groin pain treatment exercises buy 10mg elavil fast delivery. Screening for the common mutation is therefore undertaken as the first step in investigating families from these population groups pain treatment herniated disc purchase elavil 75 mg visa. Genetic disorders may pain medication for dogs natural order elavil 25 mg fast delivery, however alpha pain treatment center berwyn il generic 75 mg elavil with amex, be amenable to treatment, either symptomatic or potentially curative. Treatment may range from conventional drug or dietary Gene product management and surgery to the future possibility of gene therapy. The level at which therapeutic intervention can be applied is influenced by the state of knowledge about the Metabolic Functional Structural primary genetic defect, its effect, its interaction with effect effect effect environmental factors, and the way in which these may be Figure 19. Conventional treatment Increasing knowledge of the molecular and biochemical basis of genetic disorders will lead to better prospects for therapeutic intervention and even the possibility of prenatal treatment in some disorders. In the future, treatment of common multifactorial disorders may be improved if genotype analysis of affected individuals identifies those who are likely to respond to particular drugs. In most single gene disorders, the primary defect is not yet amenable to specific treatment. Conventional treatment aimed at relieving the symptoms and preventing complications remains important and may require a multidisciplinary approach. Management of Duchenne muscular dystrophy, for example, includes neurological and Figure 19. Lay organisations often provide additional support for the patients and their families. The Muscular Dystrophy Organisation, for example, provides information leaflets, supports research, and employs family care officers who work closely with families and the medical services. Environmental modification the effects of some genetic disorders may be minimised by avoiding or reducing exposure to adverse environmental factors. These environmental effects are well recognised in common disorders such as coronary heart disease, and individuals known to be at increased genetic risk should be encouraged to make appropriate lifestyle changes. Attacks of acute intermittent porphyria can be precipitated by drugs such as anticonvulsants, oestrogens, barbiturates and sulphonamides, and these should be avoided in affected individuals. In individuals with glucose-6-phosphate dehydrogenase deficiency, drugs such as primaquine and dapsone, as well as ingesting fava beans, cause haemolysis. Myotonic dystrophy is associated with increased anaesthetic risk and suxamethonium must not be given to people with pseudocholinesterase deficiency. This enables them to ensure that they are not exposed M A to the triggering agents in any future anaesthetic. It is recommended that susceptible individuals wear a MedicAlert or E L similar medical talisman containing written information at all D E times. Exposure to sunlight precipitates skin fragility and blistering I R in all the porphyrias except the acute intermittent form. The MedicAlert foundation registered charity website address is Surgical management. Many primary congenital malformations are amenable to successful surgical correction. The presence of structural abnormalities is often identified by prenatal ultrasound scanning, and this allows arrangements to be made for delivery to take place in a unit with the necessary neonatal surgical facilities when this is likely to be required. In a few instances, birth defects such as posterior urethral valves, may be amenable to prenatal surgical intervention. In some disorders surgery may be required for abnormalities that are secondary to an underlying metabolic disorder. In girls with congenital adrenal hyperplasia, virilisation of the external genitalia is secondary to excess production of androgenic steroids in utero and requires reconstructive surgery. In other disorders, structural complications may occur later, such as the aortic dilatation that may develop in Marfan syndrome. Surgery may also be needed in genetic disorders that predispose to neoplasia, such as the multiple endocrine neoplasia syndromes, where screening family members at risk permits early intervention and improves prognosis. Methionine Metabolic manipulation Some inborn errors of metabolism due to enzyme deficiencies Homocysteine can be treated effectively. Although direct replacement of the missing enzyme is not generally possible, enzyme activity can Homocystine be enhanced in some disorders. Vitamins act as cofactors in certain enzymatic reactions and can be effective if given in doses above the usual physiological requirements. For example, Cystathionine -synthase homocystinuria may respond to treatment with vitamin B6, certain types of methylmalonic aciduria to vitamin B12, and multiple carboxylase deficiency to biotin. For example, thiamine may permit a switch to pyruvate metabolism by means of pyruvate dehydrogenase in pyruvate carboxylase deficiency. Cystathionine the clinical features of an inborn error of metabolism may be due to accumulation of a substrate that cannot be metabolised. The classical example is phenylketonuria, in which the absence of phenylalanine hydroxylase results in high concentrations of phenylalanine, causing mental retardation, Homoserine Cysteine Cystine seizures and eczema. In requires vitamin B6 cofactor 100 Treatment of genetic disorders other disorders the harmful substrate may have to be removed by alternative means, such as the chelation of copper with penicillamine in Wilson disease and peritoneal dialysis or haemodialysis in certain disorders of organic acid metabolism. In hyperuricaemia, urate excretion may be enhanced by probenecid or its production inhibited by allopurinol, an inhibitor of xanthine oxidase. In another group of inborn errors of the metabolism the signs and symptoms are due to deficiency of the end product of a metabolic reaction, and treatment depends on replacing this end product. Defects occurring at different stages in biosynthesis of adrenocortical steroids in the various forms of congenital adrenal hyperplasia are treated by replacing cortisol, alone or together with aldosterone in the salt losing form. Gene product replacement Gene product replacement therapy is an effective strategy when the deficient gene product is a circulatory peptide or protein. In some cases transgenic animals have been created that produce human gene products as an alternative to cloning in microbial systems. A potential problem associated with gene product replacement is the initiation of an immunological reaction to Table 19. An alternative method of replacement is that of organ or cellular transplantation, which aims at providing a permanent functioning source of the missing gene product. This approach has been applied to some inborn errors of metabolism, such as mucopolysaccharidoses, using bone marrow transplantation Box 19. No such Introduction of toxic gene Direct cell death in treatments are currently available, but many gene therapy trials neoplastic or infective are underway. Most of these have gene cytotoxic drugs in involved genetic manipulation in the therapy of cancer, some neoplastic or infective have involved infectious diseases or immune system disorders diseases Introduction of antigen or Stimulation of immune and a few have involved inherited disorders, notably cystic cytokine gene response to kill cells in fibrosis. Human trials are all aimed at altering the genetic neoplastic or infective material and function of somatic cells. Although gene therapy diseases involving germline cells has been successful in animal studies (for example curing thalassaemia in mice) manipulation of Introduction of normally human germline cells is not sanctioned because of ethical and functioning gene safety concerns. So far, results of human gene therapy trials have been disappointing in terms of any long-term therapeutic Disease phenotype benefit and many technical obstacles remain to be overcome. The classical gene therapy approach is to introduce a Phenotype correction functioning gene into cells in order to produce a protein product that is missing or defective, or to supply a gene that has a novel function. This type of gene augmentation approach Introduction of toxic gene could be appropriate for conditions that are due to deficiency of a particular gene product where the disease process may be reversed without very high levels of gene expression being required. Autosomal recessive and X linked recessive disorders are likely to be the best candidates for this approach since most are due to loss of function mutations leading to deficient or defective gene products. Augmentation gene therapy is not Introduction of prodrug gene likely to be successful in autosomal dominant disorders, since affected heterozygotes already produce 50% levels of normal gene product from their normal allele. In these cases, gene therapy is not likely to restore gene product production to levels that will have a therapeutic effect. In neoplastic disorders the classical gene therapy approach aims to introduce genes whose products help to kill malignant cells. The genes Cytotoxic agent introduced may produce products that are toxic, act as prodrugs to aid killing of cells by conventionally administered Introduction of antigen or cytokine gene cytotoxic agents, or provoke immune responses against the neoplastic cells. In ex vivo experiments and trials, cells are removed and cultured before being manipulated and replaced. This approach is feasible for therapies involving cells such as haemopoetic cells and skin cells that can be easily cultured and transplanted. In Host response in vivo methods, the modifying agents are introduced directly into the individual. The production of adequate stem cells Remove bone amounts of gene products in appropriate cells and tissues is marrow needed with appropriate control of gene expression and cells reliable methods of monitoring therapeutic effects. Before Gene transfer application of gene therapy to humans, in vitro studies are needed together with proof of efficiency and safety in animal Incorporate required gene models. The possibility of insertional mutagenesis and the into viral vector dangers of expressing genes in inappropriate tissues need to be considered. There may also be immunological reactions Select for cells expressing mounted against viral vector material or the gene product itself Inject inserted gene if this represents a protein that is novel to the individual being recombinant treated. This applies to autosomal dominant disorders where the mutation has a dominant negative effect, producing a protein with a new and detrimental function, as in Huntington disease. For this reason it is Information on specific genes important to use online information that comes from a GeneCards (bighost. The following section attempts to genes, their products and their involvement in disease. It offers provide a short guide to websites that may be of relevance to concise information about the functions of all human genes clinical genetics and associated specialties. The human map database can be searched by cytogenetic location, gene or Search engines marker name, accession number or the disease name. Entries on each sites are given below (all are preceded by ): gene are referenced with links provided to the PubMed tm database. The Bioinformatics division gives registered users A useful starting point for general information about human access to a large range of databases and computer programs to genetics can be found at the British Society for Human aid genomic and proteomic research. The strength of information on specific inherited disorders and the role of 104 the internet and human genetics genetic testing in the diagnosis, management and genetic organise conferences for families and professionals as well as counselling of patients with inherited conditions. Autosome Any chromosome other than the Consanguinity Marriage or partnership between sex chromosomes. Autozygosity Homozygosity for alleles identical Consultand the person through whom a family by descent in the offspring of with a genetic disorder is referred consanguineous couples. Bayesian analysis Mathematical method for Contiguous Syndrome caused by deletion of a calculating probability of carrier gene syndrome group of neighbouring genes, state in mendelian disorders by some or all of which contribute combining several independent to the phenotype. Cytogenetics the study of normal and abnormal Candidate gene A gene identified as being a chromosomes. Discordance Presence of a trait in only one Centromere the portion of a chromosome member of a pair of twins. Interphase the stage of the nucleus between Fluorescence in situ Use of fluorescent nucleic acid cell divisions. Meiosis Cell division during gametogenesis Haploid Normal state of gametes, containing resulting in haploid gametes. Mendelian disorder Inherited disorder due to a defect Haplotype Particular set of alleles at linked in a single gene. Heterozygote Person possessing different alleles at Mismatch repair Natural enzymatic process that a particular locus on homologous corrects mis-paired nucleotides chromosomes. Proband Index case through whom a family Mitosis Cell division occurring in somatic is identified. Monozygotic twins Twins derived from a single Purine Nitrogenous base: adenine or fertilised egg. Mosaicism Presence in a person of two Pyrimidine Nitrogenous base: cytosine, different cell lines derived from thymine or uracil. Recessive Trait expressed in people who are Multifactorial disorder Disorder caused by interaction of homozygous or hemizygous for a more than one gene plus the particular gene, but not in those effect of environment. Recombination Crossing over between homologous Mutation Alteration to the normal sequence chromosomes at meiosis which of nucleotides in a gene. Segregation Separation of alleles during meiosis Phenotype Physical or biochemical so that each gamete contains only characteristics of a person one member of each pair of reflecting genetic constitution alleles. Syndrome A combination of clinical features Uniparental disomy the inheritance of both copies of a forming a recognisable entity. Teratogen An agent that may damage a Uniparental Inheritance of both chromosomes developing embryo. Trinucleotide repeat A repeated sequence of three nucleotides that becomes expanded and unstable in a group of genetic disorders. The molecular genetics of haemostasis Edinburgh: Churchill Livingstone, 1998 and its inherited disorders. Stretch to your pain-free end point, then breathe deeply through your belly and relax as you exhale. It is best to stretch with a warmed-up body, about the temperature that causes a light sweat. For pain reduction, it is best to stretch tight muscles at night just before going to bed. When tight muscles are no longer tight, you may decrease frequency to 2-3 times per week.
If the symptoms take a few determine the aims of treatment and any advice minutes to ease pain relief treatment for sciatica order elavil 50mg visa, the symptoms are irritable and that may be required pain treatment for pinched nerve buy 75mg elavil with visa. Twenty-four hour behaviour of symptoms Stage of the condition the clinician determines the 24-hour behaviour of the symptoms by asking questions about In order to determine the stage of the condition pain management treatment options purchase elavil amex, night pain treatment kolkata buy cheap elavil 50mg on-line, morning and evening symptoms ayurvedic treatment for shingles pain buy generic elavil 75mg on-line. Has the patient (or a member of his/her family) been diagnosed as having rheumatoid arthritis Has the patient ever been prescribed long-term (6 months or more) med For each symptomatic area the clinician should ication or steroid therapy Has the patient been discover how long the symptom has been pre taking anticoagulants recently Has the patient been and whether there was a known cause that pro X-rayed or had any other medical tests recently If the patient Routine spinal X-rays are no longer considered complains of headaches pain treatment algorithm generic elavil 75 mg without a prescription, the clinician should nd necessary prior to conservative treatment as they out whether there have been any factors that only identify the normal age-related degenerative precipitated the onset, such as trauma, stress, changes, which do not necessarily correlate surgery or occupation. To enced symptoms of spinal cord compression, conrm the relationship between the symptoms, which are bilateral tingling in the hands or feet the clinician asks what happened to other symp and/or disturbance of gait Often it is not from the patient and/or the medical notes: possible to examine fully at the rst attendance q the details of any relevant medical history and so examination of the structures must be involving the cervical spine and related areas. Past treatment examination may require caution in certain records may be obtained for further conditions such as vertebrobasilar information. Examples of relevant informa A physical examination planning form can be tion might include the age of the patient, employ useful for clinicians to help guide them through ment, the home situation, any dependants and the clinical reasoning process (Figs 2. Factors from this information may indicate direct and/or indirect mechanical inuences on the cervical spine. Each of these posi tive tests is highlighted by an asterisk (*) and used Plan of the physical examination to determine the value of treatment intervention When all this information has been collected, the within and between treatment sessions. It is useful at and detail of the physical tests described below this stage to highlight with asterisks (*), for ease need to be appropriate to the patient being exam of reference, important ndings and particularly ined. Some tests will be irrelevant, others will only one or more functional restrictions. These can need to be carried out briey, while others will then be re-examined at subsequent treatment need to be fully investigated. In order to plan the physical examination, the Observation following hypotheses need to be developed from the subjective examination: Informal observation q Structures that must be examined as a possible the clinician should observe the patient in cause of the symptoms. Informal observation Joint tests include integrity tests and active and will have begun from the moment the clinician passive physiological movements of the upper begins the subjective examination and will con cervical spine and other relevant joints. The clinician examines spinal posture in sitting and standing, noting the Joint integrity tests (Pettman 1994) posture of head and neck, thoracic spine and upper limbs. The tests described below are consid upper cervical spine is the shoulder crossed syn ered positive if the patient experiences one or drome (Janda 1994), which was described in more of the following symptoms: a loss of bal Chapter 3. Patients who experience headaches ance in relation to head movement, unilateral may have a forward head posture (Watson 1994). The patient may in isolation and it may be necessary to observe the require further diagnostic investigations of the patient more fully for a full postural examination. It must be neutral position, the clinician gently distracts the remembered that handedness and level and fre head. If this is symptom-free then the test is quency of physical activity may well produce repeated with the head exed on the neck. Some Reproduction of symptoms suggests upper cer muscles are thought to shorten under stress, vical ligamentous instability, particularly impli while other muscles weaken, producing muscle cating the tectorial membrane (Pettman 1994). The forces applied to test ance are thought to be the cause of the shoulder the stability of the spine are directed in the sagit crossed syndrome mentioned above, as well as tal plane and are therefore known as sagittal other abnormal postures outlined in Table 6. The age, gender and ethnicity of patients anterior force bilaterally to the atlas and axis on and their cultural, occupational and social back the occiput (Fig. With towards themselves, their condition and the clin the patient supine, the clinician applies a posteri ician. The clinician needs to be aware of and sen or force bilaterally to the anterolateral aspect of sitive to these attitudes, and to empathize and the transverse processes of the atlas and axis on communicate appropriately so as to develop a the occiput (Fig. The force applied to test the stability of the spine is directed in the coronal plane and is therefore known as a coronal stress test. With the patient supine, the clinician supports the occiput and the left side of the arch of the atlas, for example, with the other hand resting over the right side of the arch of the axis. No movement of the head is possible if the contralateral alar liga ment is intact. The test is repeated with the upper cervical spine in exion, neutral and extension. This test is carried out if the previous lateral exion stress test is positive, to determine whether the instabil ity is due to laxity of the alar ligament or due to Figure 5. In sitting, the clini cian xes C2 by gripping the lamina and then rotates the head. When the excessive rotational motion limit contralateral lateral exion and rotation is in the same direction as the excessive lateral movement of the occiput on the cervical spine. Active and passive physiological joint movement For both active and passive physiological joint movement, the clinician should note the following: q the quality of movement (includes clicking or joint noises through the range) q the range of movement q the behaviour of pain through the range of movement q the resistance through the range of movement and at the end of the range of movement q Any provocation of muscle spasm. The left hand cups around the anterior aspect of the mandible while the right hand grips over the occiput. Both hands then apply a force to cause the head to rotate forwards on the upper cervical spine. The right hand holds underneath the mandible while the left hand and forearm lie over the head. The head and neck are displaced forwards and then both hands apply a force to cause the head to rotate backwards on the upper cervical spine. The hands grasp around the head at the level of the ears and apply a force to tilt the head laterally on the upper cervical spine. The head is moved into upper cervical extension and then moved into left rotation and then left lateral exion. For the upper cervical spine, the following q Left upper cervical quadrant should be tested: q Right upper cervical quadrant. For further information q Cervical extension about the active range of movement the follow q Upper cervical extension ing can be carried out: q Left lateral exion q Right lateral exion q the movement can be repeated several times q Left rotation q the speed of the movement can be altered q Right rotation q Movements can be combined (Edwards 1994, q Compression 1999). The hands are placed so that the index and middle nger lie directly underneath the occiput and between the transverse process of C1 and the mastoid process. Slump sitting or mandibular joint, lower cervical spine and tho knee extension will increase symptoms from racic spine. These joints can be tested fully (see abnormal neurodynamics, but will produce no relevant chapter) or, if they are not suspected to change if the headaches are caused by the joints be a source of symptoms, the relevant clearing or soft tissues of the cervical spine. For details of these general tests, the reader is directed to Daniels & Worthingham (1986), Cole et al (1988) Figure 5. Greater detail may be required to test the strength of individual muscles, in particular 1994). These muscles are tested by the clinician those muscles prone to become weak (Janda observing the pattern of movement which occurs 1994), which include serratus anterior, middle when the patient exes the head from a supine and lower bres of trapezius and the deep neck position. Testing the strength of these muscles is the sternocleidomastoid initiates the movement, described in Chapter 3. Relative strength is function of the deep neck exors more objective assessed indirectly by observing posture as ly (Jull 1994). The patient lies supine with a towel already mentioned, by the quality of active under the head to position the cervical spine in movement, noting any changes in muscle neutral, ensuring that the head is parallel to the recruitment patterns, and by palpating muscle ceiling. The patient is then asked with the muscles of the shoulder girdle are the to carry out a gentle nod of the head, which important muscles that support and control the should increase the pressure in the normal by joints of the neck. Normal function of the lowing muscles may be necessary: longus colli, deep neck exors is considered to be the ability longus capitis, upper, middle and lower bres of to hold this contraction for 10 seconds and repeat trapezius and serratus anterior. These muscles the contraction 10 times (Jull, personal com stabilize the neck by supporting the weight of the munication, 1999). The emphasis is on low load head against gravity and allowing efcient func endurance and the patient should be able to sus tional activity of the upper limbs. Inability Weak deep neck exors have been found to be to hold an even pressure may indicate poor associated with cervicogenic headaches (Watson endurance of the deep neck exors. The clinician may the cutaneous nerve distribution and der be able to palpate sternocleidomastoid to feel for matome areas are shown in Figure 3. Testing the length of these nerves enables the clinician to distinguish the muscles is described in Chapter 3. The facial nerve (7th cra nial) supplies the muscles of facial expression, Isometric muscle testing while the mandibular nerve (5th cranial) sup Test the cervical spine exors, extensors, lateral plies the muscles of mastication. This is usually carried out with the patient in sit ting but may be done in supine. Neurological examination involves examining the these tests are described in detail in Chapter 3. Other neural diagnostic tests Plantar response to test for an upper motor neu Integrity of the nervous system rone lesion (Walton 1989). Light touch and ward fanning of the other toes occurs with an pain sensation of the face, head and neck are test upper motor neurone lesion. A knowledge of the Special tests cutaneous distribution of nerve roots (derma tomes) and peripheral nerves enables the clini In the case of the upper cervical spine, the special cian to distinguish the sensory loss due to a root tests are vascular tests. There are two symptoms are not caused by a disturbance of the sets of tests, one for patients who do not com vestibular system. The movement is then released for 10 seconds before the next movement is carried out. Some functional ability has already been tested If dizziness, nausea or any other symptom asso by the general observation of the patient during ciated with vertebrobasilar insufciency (distur the subjective and physical examinations. Any further functional and hemiplegia) (Bogduk 1994) is provoked dur testing can be carried out at this point in the ing any part of the test, it is considered positive examination and may include sitting postures or and testing should be stopped immediately. Clues the test is positive, this contraindicates manipu for appropriate tests can be obtained from the lation of the cervical spine. In standing, the clinician main head, face, thoracic spine and upper limbs, as tains head position while the patient moves the appropriate. The accessory movements for C1 are shown in the clinician should note the following: Figure 5. The head is rotated to the right and thumb pressure is applied to the transverse process of C1.
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