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By G. Kadok. North Carolina School of the Arts.

Vaccination in this patient rules out influenza as an etiologic agent D order hydrochlorothiazide 25 mg free shipping blood pressure chart dr oz. Chemoprophylaxis is effective for one type of this infectious agent Key Concept/Objective: To know and understand influenza virus infections Two major types of antigenic change can occur: drift and shift purchase 12.5mg hydrochlorothiazide with amex heart attack burger. Antigenic drift refers to relatively minor changes in hemagglutinin and less often with neuraminidase that occur frequently (usually every few years) and sequentially in the setting of selective immunologic pressure in the population. Drift results from point mutations of the cor- responding RNA segment. The surface glycoproteins induce host humoral and cellular immune responses and are responsible for the changing antigenicity of influenza virus- es. Antigenic shift occurs only in influenza A viruses and results from acquisition of a new gene segment for hemagglutinin with or without one for neuraminidase. Several rapid assays are commercially available in the United States to detect influenza A and B occurring together; one of these assays is able to rapidly differentiate between influen- za A and influenza B. Making a definitive diagnosis can have a significant impact on medical management. The efficacy of the influenza vaccine is 70% to 90% in young adults, especially when the vaccine antigen and the circulating strain are closely matched. Although vaccination is less effective in elderly and immunocompromised patients, vaccination provides partial protection against pneumonia and death. Amantadine and rimantadine are active against influenza A only. A new class of com- pounds, the neuraminidase inhibitors, is active against influenza A and B viruses. The neuraminidase inhibitors are also effective for prophylaxis of influenza A and B infec- tions. A 22-year-old female college student presents to your office as a new walk-in patient. She has no med- ical history and takes no medications. She states that she had unprotected sex with a new partner about 1 week ago. Four days ago, she developed fever and chills, severe fatigue, painful groin swellings, and "blisters" on her labia. She states that she has had a total of five sexual partners. On physical examination, the patient is afebrile, has tender superficial inguinal lymphadenopathy measuring 2 cm bilaterally, and has several clustered vesicular lesions on her labia majora. Which of the following statements regarding herpes simplex virus (HSV) infections is false? Direct contact with infected secretions is the principal mode of transmission of HSV B. Herpes simplex virus type 2 (HSV-2) is transmitted more efficiently from males to females than from females to males C. HSV-2 is a local infection that is confined to the genitourinary system D. Among the general public, herpetic whitlow is typically caused by HSV-2 Key Concept/Objective: To understand the important clinical features of HSV-2 infection Direct contact with infected secretions is the principal mode of HSV transmission. HSV- 1 is usually transmitted by an oral route and HSV-2 by a genital route. Transmission of HSV occurs frequently, even in the absence of lesions. HSV-2 is transmitted more effi- ciently from males to females than from females to males. Autoinoculation to other skin sites also occurs, more often with HSV-2 than with HSV-1. Extragenital lesions 7 INFECTIOUS DISEASE 85 develop during the course of primary infection in 10% to 18% of patients. Aseptic meningitis is not uncommon with primary genital herpes, particularly in women; in rare instances, herpetic sacral radiculomyelitis occurs.

Which cluster of highly polymorphic genes encodes these cell surface markers? The chemokine histocompatibility cluster Key Concept/Objective: To understand that MHC encodes HLA The MHC—so called because of its prominent role in rejection of allogeneic tissue—is a pri- mary barrier to transplantation of solid organ purchase hydrochlorothiazide 25 mg otc blood pressure 40 over 30, tissue 25mg hydrochlorothiazide with visa arrhythmia from alcohol, and hematopoietic stem cells. This closely linked cluster of highly polymorphic genes, grouped on the short arm of chromo- some 6, encodes cell surface molecules (e. The normal role of the MHC is presen- tation of endogenous and exogenous peptide antigen fragments to T lymphocytes, there- by initiating an immune response against the molecule (or pathogenic organism) from which the peptide was derived. The extreme variability of molecular structure in the MHC antigens permits a wide range of different peptides to be presented by autologous human 6 BOARD REVIEW antigen-presenting cells, although individual subjects may have a specific repertoire of MHC antigens that do not present certain antigens effectively. The focused immunogenic- ity of MHC molecules and the variability of these molecules among individuals render them prominent targets for the immune response in the context of solid organ and bone marrow transplantation. In cases in which live allogeneic cells are the target of the immune response, the apparent target is the nonself MHC molecule itself. Freedom from rejection and, in the case of bone marrow transplantation, graft-versus-host disease is improved with HLA matching of donor and recipient. A 72-year-old woman with emphysema presents for evaluation for possible lung transplantation. Laboratory evaluation for cytokine polymorphism of the transforming growth factor (TGF) gene, con- sidered as homozygosity for TGF-α, is associated with graft fibrosis in 93% of lung transplant recipients. TGF-α has two well-studied dimorphic positions within the leader sequence of the gene whose variants are found in concert with one another. What designation is given to variants at polymorphic positions that display this relationship? Allelic disequilibrium Key Concept/Objective: To understand the relationships between polymorphic nucleotide posi- tions in or near an expressed gene on the same chromosome with regards to whether they occur in populations independently of one another There can be multiple polymorphic nucleotide positions in or near an expressed gene on the same chromosome. In such cases, it is desirable to know whether specific variants at each of the polymorphic positions are independent of the variants at the other positions. If examination of a population shows that the variants at the different positions occur independently of one another, the system is said to be in Hardy-Weinberg equilibrium. If certain variants at one of the positions are statistically associated with specific variants at another of the linked positions, the system is said to exhibit linkage disequilibrium. Hardy-Weinberg equilibrium can be reestablished over many generations through recom- bination events. The closer the polymorphic loci are to each other on the chromosome, the less likelihood there is of a recombination, and the specific alleles at the two linked loci are more likely to be inherited en bloc as a haplotype. A clinical investigator studying the genetic predisposition of individuals with a family history of diabetes mellitus to develop clinical diabetes discovers a novel genetic polymorphism in a cohort of such patients. Which of the following describes a mutation whose frequency becomes established at more than 1% to 2% of the population? A single nucleotide polymorphism Key Concept/Objective: To understand that genetic polymorphisms with a frequency of more than 1% to 2% are alleles The fundamental basis of genetic polymorphism in a population is variation of the nucleotide sequence of DNA at homologous locations in the genome. These differences in sequence can result from mutations involving a single nucleotide or deletions or insertions of variable numbers of contiguous nucleotides. Each of these variants presumably occurred in a single ancestor in the distant past. Most new mutations are extinguished through ran- dom genetic drift and never become established in the population at any significant fre- 6 IMMUNOLOGY/ALLERGY 7 quency. When the gene frequency of a mutation becomes established at more than 1% to 2%, it is often given the appellation of allele. If there are two polymorphic positions with- in a gene, each of which has two alleles, a given individual will have up to four definable alleles. These are inherited as two parental haplotypes, each of which carries one allele from each of the two loci. Extensive population studies permit sophisticated maximum- likelihood estimates of haplotype frequencies within the population. The ability to deduce haplotypes provides a much higher degree of specificity to the analysis of genetic poly- morphism, because the haplotype more accurately defines a larger inherited region of DNA.

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Fever purchase hydrochlorothiazide 25 mg otc blood pressure log excel, pain discount hydrochlorothiazide 25 mg without a prescription arteria innominada, erythema, edema, and purulent drainage often occur when early infections are caused by pyogenic organisms such as S. When early infections are caused by less pathogenic organisms, such as S. Chronic contiguous 52 BOARD REVIEW infections are usually diagnosed 6 to 24 months after surgery. Most infections are prob- ably introduced during surgery but remain quiescent for a long time. A 13-year-old girl is brought to your office by her mother for evaluation of left leg pain. Two weeks ago, the patient began to experience anterior left leg pain, which caused a slight limp. Over the past 2 weeks, the pain has become more severe, and the patient has experienced temperatures of up to 101° F (38. The patient reports that approximately 4 weeks ago, she sustained an injury to her left leg during a soccer game. At that time, x-rays were negative for a fracture, and the swelling and bruising resolved with rest and the use of ice packs. Laboratory studies reveal leukocytosis with a left shift. X-rays at this time show deep soft tissue swelling and periosteal elevation. Which of the following statements regarding osteomyelitis in children is true? In over 50% of cases of osteomyelitis in children, blood cultures are positive B. In most cases of osteomyelitis in children, the infection has a single focus in the small bones of the feet and hands C. Most cases of osteomyelitis in children are polymicrobial D. Most cases of osteomyelitis in children are associated with marked drainage from the site of osteomyelitis Key Concept/Objective: To know the key features of osteomyelitis in children Hematogenous osteomyelitis is usually seen in children between 1 and 15 years of age, in adults older than 50 years, or in persons who abuse I. In children, infection usually occurs as a single focus in the metaphyseal area of long bones (particularly the tibia and femur). Children may be predisposed to infection associated with minor trau- ma that causes a small hematoma, vessel obstruction, and bone necrosis. Blood cultures are positive in more than half of patients. Although in most children, symptoms are present for 3 weeks or less, some children may present with vague symptoms of 1 to 3 months’ duration. Most cases of hematogenous osteo- myelitis are monomicrobial. In newborns, group B streptococci and gram-negative bacilli are common. In children, streptococci and Haemophilus influenzae are often seen. However, evidence from a retrospective study in Canada showed that vaccination of infants and children succeeded in eliminating H. Polymicrobial hematogenous osteomyelitis is usually caused by S. A 27-year-old man presents to the emergency department for evaluation of fever and rash. He was well until 4 days ago, when he developed fever, a rash on his left wrist and both ankles, and diffuse body aches. He states that he just returned from a trip to the mountains of northern Georgia, where he spent a week mountain biking. This is an annual trip that he and friends take in April. He denies having cough, shortness of breath, sore throat, or dysuria, but he has developed some moderate, constant abdominal pain. He states that his rash has now spread to involve most of his trunk.

There may be facial hydrochlorothiazide 25mg line arteria yugular, pharyngeal order 25 mg hydrochlorothiazide fast delivery blood pressure chart and pulse rate, and respiratory weakness involved. Sensory systems are spared, as are the extraocular muscles. Pathogenesis The cause of AMAN is not known, although one theory suggests it may result from Campylobacter jejuni infection. Cases almost always occur in the summer months, and are preceded by a gastrointestinal illness. As with AMSAN, axons may be the specific target of autoimmune attack. Diagnosis Laboratory: Protein is increased in the CSF. Sometimes, IgG anti-GMI or anti-GalNac-GD1a ganglioside antibodies are present. Electrophysiology: CMAPS are initially low with relative preservation of conduction velocities; amplitudes are then absent. Therapy IVIG and plasma exchange (as outlined for AIDP) and supportive care are the only treatments available. References Hiraga A, Mori M, Ogawara K, et al (2003) Differences in patterns of progression in demyelinating and axonal Guillain-Barre syndromes. Neurology 61: 471–474 Kuwabara S, Ogawara K, Mizobuchi K, et al (2001) Mechanisms of early and late recovery in acute motor axonal neuropathy. Muscle Nerve 24: 288–291 Tekgul H, Serdaroglu G, Tutuncuoglu S (2003) Outcome of axonal and demyelinating forms of Guillain-Barre syndrome in children. Pediatr Neurol 28: 295–299 289 Acute motor and sensory axonal neuropathy (AMSAN) Genetic testing NCV/EMG Laboratory Imaging Biopsy ++ ++ Degeneration occurs in motor and sensory axons. Anatomy/distribution Both weakness and sensory loss are found, sometimes with respiratory paral- Symptoms ysis. AMSAN is clinically indistinguishable from very acute AIDP. The only major Clinical syndrome/ difference is that axons are the specific target of the immune reaction. Most signs patients become quadriplegic and unable to breathe in a matter of days. Immune reactions are believed to be directed against axons. Another model Pathogenesis suggests that axonal degeneration is secondary to nerve root demyelination. Campylobacter jejuni infection is implicated (see AMAN). Laboratory: Diagnosis Protein is increased in the CSF. Sometimes, IgG anti-GMI or anti-GalNac-GD1a ganglioside antibodies are present. Electrophysiology: EMG and nerve conductions are abnormal, with reduced SNAPs and CMAPs with relative sparing of conduction velocities. IVIG and plasma exchange (as outlined for AIDP) and supportive care are the Therapy only treatments available. Residual weakness usually remains, and some Prognosis require ventilation for long periods of time. Donofrio P (2003) Immunotherapy of idiopathic inflammatory neuropathies. Muscle Nerve References 28: 273–292 Lindenbaum Y, Kissel JT, Mendell JR (2001) Treatment approaches for Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. Neurol Clin 19: 187–204 290 Acute inflammatory demyelinating polyneuropathy (AIDP, Guillain-Barre syndrome) Genetic testing NCV/EMG Laboratory Imaging Biopsy +++ +- + + Fig.

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