What are the Effects of Sleeping Pills on My Body
You have spent countless nights tossing and turning in bed, trying to find a way to fall asleep. Then, we you do finally fall asleep hours later, the slightest noise or movement jars you awake once again. It is a frustrating scenario, and unfortunately, it plays over and over again each night without fail. You want to visit your doctor and find a remedy to this problem, but you are scared of what the effects of sleeping pills will be on your body.
You are no doubt scared because of the horrible stories publicized on the news of the side effects of sleeping pills on patients. Who hasn’t heard of people sleep walking, driving, eating or even going to work while technically still sleeping? These scenarios are no doubt the worst nightmares of people and will keep them from seeking treatments that really can help the problems.
So, before visiting your doctor, it’s wise to research what the effects of sleeping pills can be so you will be aware before the doctor prescribes something to you. Any sleeping pill that your doctor will prescribe is either a sedative or tranquilizer, meant to relax your body and muscles.The effects of sleeping pills on your body are generally the same no matter what type of sleeping pill you take, because they all have similar actions. The effects of sleeping pills vary from person to person, but can range from mental to physical effects and can be mild or severe.
Examples of physical effects of sleeping pills are difficulty eating, nausea, upset stomach, dizziness, drowsiness or dry mouth. These usually occur because of the chemical reactions that take place in your body when on the medication. The medication is strong and can upset the sensitive lining of your stomach.
Examples of mental effects of sleeping pills are irritability, confusion, tremors, nervousness and hallucinations. Ironically, some types of sleeping pills can even make people have difficulty sleeping! The effects are different on each patient, all the more reason why to visit your doctor to find out what will work for you.
If you are pregnant, you will not be able to take sleeping pills because of the medicine’s ability to cross over the placenta and to the baby.
If this scares you and you don’t want to take sleeping pills because of the potential for side effects, visit with your doctor. He may be able to recommend other treatments to help cure your insomnia and get a good night’s rest. These treatments can include hypnosis, lifestyle changes or changes to your diet and exercise regimen.
Do not spend another night tossing and turning until you see the morning sun. Research your options and then visit with you doctor to determine the best course of action for you. Working together, you will find the best treatment for your body. At the end of the day, you won’t regret it. You will be sleeping instead!
Do you want to learn more about the effects of sleeping pills on your body? If so, you can find that information along with general information on ambien cr zolpidem and the latest research on ambien and sleep disorders at our web site! We are the Sleep Experts and want to help you get a better night's sleep. Stop by today!
Article Source: EzineArticles
Tuesday, August 14, 2007
Monday, August 13, 2007
Agammaglobulinemia
Agammaglobulinemia
Background:
Agammaglobulinemia or hypogammaglobulinemia is the most common of the primary immunodeficiencies, accounting for approximately 50% of cases. Three major types can be described: X-linked, early-onset, and late-onset. After more than 50 years since the clinical entity was first described by Bruton in 1952, the molecular defect in X-linked agammaglobulinemia (XLA) has been elucidated. In Bruton's honor, the gene responsible has been named Btk, which stands for Bruton tyrosine kinase.
An estimated 90% of patients with early-onset agammaglobulinemia and absence of B cells have abnormalities in the Btk gene (ie, Bruton agammaglobulinemia or XLA). XLA is further discussed in detail in the article Bruton Agammaglobulinemia. Late-onset disease is usually referred to as Common Variable Immunodeficiency (CVID), also described separately. However, reports are increasing of adults who are diagnosed with XLA.
The remaining type is early-onset non–Bruton agammaglobulinemia, with low or absent serum immunoglobulin (Ig). Most cases are autosomal agammaglobulinemia and represent a very heterogeneous group, including Ig deficiency with increased immunoglobulin M (hyper-IgM syndrome), which is also discussed separately (see X-linked Immunodeficiency With Hyper IgM). In addition, some infants have an initially low Ig level that eventually increases to normal levels. This is known as Transient Hypogammaglobulinemia of Infancy and is discussed in detail in a separate article.
Recently, defective antibody production and low circulating numbers of B cells were described in some female infants and in males in whom no Btk abnormalities were detected. These observations imply the involvement of other genes. This article describes the cases of agammaglobulinemia caused by defects other than Btk. However, since the clinical manifestations and treatments are similar, information from Btk-deficient patients is included because of the lack of sufficient patients. Finally, some secondary immunodeficiency situations are also described because these need to be recognized in addition to the primary diseases. For other B-cell defects, such as specific Ig deficiencies (eg, immunoglobulin A [IgA] or immunoglobulin G [IgG] subclass deficiencies), refer to the article B-Cell Disorders.
Pathophysiology:
Although defects may occur in many steps in B-cell development and maturation, resulting in the lack of Ig production, the most common and well-described defect is the maturation of the pro–B cell to pre–B cell (see Image 1). In the fetal bone marrow, the first committed cell in B-cell development is the early pro-B cell identified by its ability to proliferate in the presence of interleukin-7 (IL-7). These cells develop into late pro–B cells in which rearrangement of the heavy chain occurs. This rearrangement process requires the recombination activating genes RAG1 and RAG2, which are controlled by IL-7 and perhaps other factors.
When the heavy chain is produced, it is transported to the cell surface by the Ig-a (CD79a) and Ig-b (CD82) heterodimers or by the surrogate light chain. Progression from this late pro–B-cell to the pre–B-cell stage involves the rearrangement and joining of the various segments of the heavy chain. The completion of rearrangement of the light and heavy chains and the presence of surface IgM results in the immature B cell, which then leaves the bone marrow. Increasing levels of immunoglobulin D (IgD) in the transitional cells finally results in the mature B cell with IgM and IgD both expressed. The mature B cells circulate between secondary lymphoid organs and migrate into lymphoid follicles of the spleen and lymph nodes in response to further stimuli and various chemokines. T cells stimulate B cells to undergo further proliferation and Ig class switching, leading to the expression of the various isotypes IgG, IgA, or immunoglobulin E (IgE).
The m heavy-chain gene on chromosome 14 is the most frequent abnormality in a patient with agammaglobulinemia and decreased B cells who does not have a defect in Btk. Ig- a and Ig-b are encoded by the mb-1 and B29 genes, respectively. A case involving a female patient with a mutation in the Ig-a gene has been described. A case involving a male patient with hypogammaglobulinemia caused by mutation at the l5/14/1 gene, resulting in a defect in the surrogate light chain, has also been described. Other mutations in the components of the pre–B-cell and B-cell antigen receptor complex (eg, defects in the B-cell linker protein, BLNK) account for 5-7% of patients with defects in early B-cell development. These patients have normal numbers of pro–B cells but no pre–B or mature B cells. Clinically, they are not different from patients with XLA.
Activation of B-cell receptor (BCR) induces the recruitment of Syk, which phosphorylates BLNK, a contributor to the activation of Btk that affects other intracellular signaling events.
These findings indicate that a defect in any of the steps in B-cell development may be clinically important. Approximately 85% of patients with defects in early B-cell development have XLA. However, when a female has an absence of serum Ig and peripheral blood B cells, the patient clearly does not have Bruton agammaglobulinemia or mutations in the Btk gene. The elucidation of her specific gene defects may shed additional information on B-cell development.
The exact defects have not yet been determined in other patients in whom agammaglobulinemia has been associated with a mosaic of ring chromosome 18 (Litzman, 1998) or hypogammaglobulinemia in a male with ring chromosome 21 (Ohga, 1997). Patients with B-cell deficiency associated with intrauterine growth retardation have been described (Revy, 2000), and patients with agammaglobulinemia with spondyloepiphyseal dysplasia and retinal dystrophy have also been described (Roifman, 1999). The syndrome of X-linked hypogammaglobulinemia with growth hormone deficiency also exists. This has been mapped to the same region that encompasses the Btk gene and may involve a gene controlling growth hormone production, implying a small contiguous gene deletion that includes both the gene for XLA and another closely linked gene involved in growth hormone production. Note that the structural gene for growth hormone is located on the long arm of chromosome 17.
In addition to the genetic defects described above, other pathophysiology mechanisms may result in hypogammaglobulinemia or agammaglobulinemia, such as viral infections, malignancy, or drug effects. These are described in more detail in Causes.
Frequency:
- In the US: Agammaglobulinemia occurs in approximately 1 in 250,000 males in the United States.
- Internationally: In a study of serum Ig levels in 2000 consecutive patients in Saudi Arabia, agammaglobulinemia was diagnosed at a rate of 250 per 100,000 individuals. These patients accounted for 16% of the primary humoral immunodeficiency groups (with selective IgA 45%, CVID 29%, and selective IgG 10%). Spain's Registry for Primary Immunodeficiency Diseases reported 1079 cases registered between January 1980 and December 1995. Of these, 49 were reported as XLA. In Brazil, of 166 cases of primary immunodeficiencies diagnosed over 15 years, 60.8% (101) were primary humoral deficiencies. Of these, XLA was the least frequent (9), compared with IgA deficiency (60) and transient hypogammaglobulinemia (14). In South Africa, antibody deficiencies predominate, accounting for 56% (52 of 93) of diagnoses, compared to Australia, where antibody deficiencies comprised 71% of 500 cases enrolled in a national registry. In Hong Kong, humoral defects were identified in 50 of 117 patients diagnosed with primary immunodeficiency.
Mortality/Morbidity: Patients with agammaglobulinemia are at risk of frequent and recurrent infections. Severe bacterial infections resulting in pneumonias or meningitis and subsequent bacteremia could be fatal; however, the major causes of morbidity are chronic upper pulmonary disease (eg, sinusitis) or lower pulmonary disease (eg, bronchiectasis).
- In patients with agammaglobulinemia, one study indicated that, although the incidence of bacterial infections resulting in hospitalization decreased from 0.40-0.06 per patient per year during intravenous Ig replacement, chronic sinusitis and bronchiectasis continue to occur.
- Central nervous enteroviral infections can be especially disabling, resulting in a long-term CNS debilitating state.
- Autoimmune and allergic manifestations are another source of morbidity in these patients.
Sex: Agammaglobulinemia can be either X-linked (XLA) or autosomal recessive. XLA is more often recognized as Bruton agammaglobulinemia.
Age: Because of passive, transplacental acquisition of maternal IgG, newborns have normal levels of serum IgG and do not have problems until the IgG is catabolized. Because newborns cannot produce their own Ig, increased susceptibility to infections develops in infants older than 6 months. Patients with non-Btk mutations tend to be younger at the time of diagnosis, and they are more likely to have severe complications.
History: History is similar to that for Bruton agammaglobulinemia because the patient is unable to produce functional humoral immunity. Patients may have problems with recurrent upper and/or lower respiratory tract infections or with chronic diarrhea. However, patients with mutations in the m heavy chain and non-Btk mutations tend to develop symptoms earlier and are more likely to have severe symptoms.
- Encapsulated bacteria with Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and pseudomonal species (in that order) cause most infections. Other bacteria, such as Salmonella and Giardia species, may also cause problems. Two cases of Campylobacter coli infection (one with bacteremia and cellulitis; another with pericarditis) have also been described.
- Almost three fourths of patients with agammaglobulinemia have infections occurring in the upper respiratory tract with otitis and sinusitis. Lower respiratory tract infections (eg, pneumonia, bronchiolitis), gastrointestinal tract infections (eg, gastroenteritis), or both occur in more than two thirds of patients.
- Other bacterial infections, such as pyoderma, sepsis, meningitis, osteomyelitis, and septic arthritis occur less frequently. Lower-grade pathogens, such as Pneumocystis carinii pneumonia, have also been reported. Additionally, sites of infection may be unusual with the encapsulated pyogenic bacteria, such as H influenzae lymphadenopathy or pneumococcal meningitis.
- Although patients with agammaglobulinemia are usually able to handle viral infections, they are susceptible to certain viruses that replicate in the gastrointestinal tract and then spread to the CNS. This indicates the importance of antibody production in limiting the spread of infections by enteroviruses such as poliovirus, echovirus, and coxsackievirus.
- Patients may present with vaccine-related poliomyelitis after immunization with the live poliovirus vaccine (see Hidalgo's report). Although prolonged secretions of a virus have been described (up to 637 days after vaccination), poliovirus carriers among people with primary immune deficiency appears to be rare, based on 3 separate studies, and may not manifest with disease.
- Alternately, echovirus infection of the CNS may cause chronic encephalomyelitis or meningoencephalitis. In 13 patients with primary hypogammaglobulinemia, Rudge et al (1996) described 3 clinical pictures: (1) progressive myelopathy in 1 patient, (2) myelopathy progressing to an encephalopathy in 4 patients, and (3) pure encephalopathy in 8 patients. Enteroviral infection was found in 7 patients by either culture or polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF). However, Katamura et al (2002) described a nonprogressive viral myelitis in a patient and suggested that the prognosis of CNS infections in agammaglobulinemia is not determined by the Ig level alone and that they are not always progressive or fatal.
- The use of interventricular infusion of Ig has been well-documented in these patients.
- Virus-induced autoimmune diseases such as a dermatomyositislike syndromes and chronic arthritis may also occur. These diseases suggest an element of antibody production dysregulation in their pathogenesis, although in some cases, enteroviruses have been isolated from skin or joints.
- Mycoplasma or Ureaplasma organisms may play a role in other cases of chronic arthritis. In a survey of 358 patients with primary antibody deficiency, mycoplasmal infection was the most common cause of severe chronic erosive arthritis. Patients with mild cases rapidly respond to antimicrobial therapy, such as tetracycline. In more severe cases, arthritis improved following treatment with Ig. Overall, 7-22% of agammaglobulinemia patients develop joint manifestations.
- A case of juvenile onset psoriatic arthritis has been described in a patient with agammaglobulinemia.
- The constellation of symptoms in a family of brothers with leukoencephalopathy, arthritis, colitis, and hypogammaglobulinemia prompted some to label this the LACH syndrome (Bonkowsky, 2004).
- Other associated autoimmune disorders most commonly include hematological manifestations (eg, thrombocytopenia, hemolytic anemia, neutropenia) and also alopecia totalis, glomerulonephritis, protein-losing enteropathy, malabsorption with disaccharidase deficiency, and amyloidosis.
- Other patients in whom measurements of Ig may be helpful include those with renal dialysis and patients in pediatric ICUs. In the former, IgG and IgG subclass deficiency were found in 8 out of 12 children undergoing continuous ambulatory peritoneal dialysis (Akman, 2002). Similarly, total IgG was below the normal for age in 14 of 20 patients admitted to a pediatric ICU (Rehman, 2003). However, a small number of patients was studied.
Physical: Patients with agammaglobulinemia appear to be healthy between bouts of infections. Patients usually do not fail to thrive, although chronic diarrhea, if present, could cause some dehydration and malabsorption. Any abnormal physical findings indicate presence of various infections for which patients have increased susceptibility. Concomitant short stature in a male suggests X-linked hypogammaglobulinemia with growth hormone deficiency syndrome.
- Most patients with agammaglobulinemia were recognized to have immunodeficiency during or shortly after their first hospitalization for infection. Most of the patients had a history of recurrent otitis or upper respiratory tract infection at the time of diagnosis, which when combined with the physical finding of markedly small or absent tonsils and cervical lymph nodes, should alert physicians to the diagnosis of agammaglobulinemia.
- Some patients have cutaneous manifestations representing several unique syndromes. One of these is known as WHIM syndrome, consisting of warts, hypogammaglobulinemia, infections, and myelokathexis. The gene responsible for this syndrome has been identified as a chemokine receptor CXCR4 (Gulino, 2003). The presence of warts may be unique since another individual has been described as having intestinal lymphangiectasis with hypogammaglobulinemia and lymphopenia as well as unrelenting cutaneous warts but without a history of infections (Lynn, 2004).
Causes: Genetic factors have included mutations of Btk only (accounting for 85-90% of patients with early onset agammaglobulinemia and an absence of B cells). The remaining cases in males and females are clinically similar to XLA and represent mutations affecting the IGHM, CD79AA, and IGLL1 genes involved in the composition of the pre-BCR or the BLNK gene involved in pre-BCR signal transduction. Non-XLA patients may have other defects that result in an arrest of B-cell differentiation at a pro–B-cell level (before the onset of Ig gene rearrangements) or defects in an adjacent gene to the Btk gene responsible for growth hormone production (XLA with growth hormone deficiency).
Also, certain infections and drugs may result in low or absent Ig levels.
- Genetic factors are described in the following examples:
- A female has been described with a translocation involving a new gene in chromosome 9 (LRRC8) that resulted in a block in B-cell differentiation at pro–,B- to pre–B-cell transition (Sawada, 2003). She had minor facial anomalies and congenital agammaglobulinemia and absent B cells in peripheral blood.
- Patients with mutations in the m heavy chain usually present initially when aged 4 months with pneumonia, otitis, gastroenteritis, chronic enterovirus encephalitis, and Pseudomonas aeruginosa septic shock. One 15-month-old child presented with fever, weakness, rash, and neutropenia 2 weeks after an oral poliovirus vaccine.
- One newborn girl with mutation in the Ig-a gene developed recurrent diarrhea and failure to thrive in the first month of life. By age 1 year, she had chronic bronchitis.
- One infant boy with mutation in the l light chain had recurrent otitis media at age 2 months. At age 3 years, he had H influenzae meningitis with arthritis.
- One boy with a BLNK defect presented with overwhelming sepsis during childhood. With IVIG treatment, he has survived to adulthood without any growth or developmental delay.
- Other patients have been described with reduced pro-B cells but no identifiable molecular defect. One was a 4-month-old infant girl with failure to thrive, recurrent otitis, candidiasis, H influenzae arthritis, and herpes simplex stomatitis. Another girl had microcephaly, persistent diarrhea, failure to thrive, and recurrent respiratory and gastrointestinal infections. This patient eventually developed pancytopenia with progressive bone marrow failure.
- Certain viral infectious have been shown to cause transient or permanent immune deficiency.
- Congenital rubella can cause hypogammaglobulinemia. Although infection with human immunodeficiency virus (HIV) usually causes hypergammaglobulinemia, in some reported pediatric cases, patients had hypogammaglobulinemia.
- Patients with X-linked lymphoproliferative syndrome (ie, Duncan disease, Purtilo syndrome) may develop overwhelming disease with infection by Epstein-Barr virus with subsequent agammaglobulinemia and a decrease in B cells. Therefore, any male with persistent hypogammaglobulinemia following mononucleosis should be closely monitored for X-linked lymphoproliferative disease.
- Drug-induced hypogammaglobulinemia has been described with immunosuppressive agents (eg, corticosteroids, rituximab), epilepsy medications (eg, phenytoin, carbamazepine), and antipsychotic medications (eg, chlorpromazine). Recurrent infections and reduced serum Ig levels resolved when treatment with the medication was stopped.
- Oral prednisone at a dose of at least 12.5 mg/d for patients with asthma has been shown to be able to result in hypogammaglobulinemia (Kawano, 2002). Hypogammaglobulinemia is also frequently seen in steroid-sensitive nephrotic syndrome. Therefore, in patients with autoimmune diseases such as systemic lupus erythematosus who are being treated with prednisone and other immunosuppressive medications, the hypogammaglobulinemia could be due to either medication use or could reflect the underlying autoimmune process.
- Some have speculated on the association between anticonvulsant hypersensitivity syndrome (a life-threatening, drug-induced, multiorgan system reaction) with herpesvirus reactivation and hypogammaglobulinemia.
- Speculation that phenytoin-induced suppressor T-cell activity and subsequent antibody deficiency has found some support with in vitro experiments.
- Malignancies such as leukemias, multiple myeloma, and neuroblastoma may have an associated hypogammaglobulinemia.
- Excessive protein loss from the gastrointestinal tract may result in hypogammaglobulinemia; however, primary antibody deficiency may also cause chronic diarrhea. Therefore, any protein-losing enteropathy should be considered in patients presenting with hypogammaglobulinemia. In these situations, specific antibody responses are intact, and circulating B cells are normal. On the other hand, gastrointestinal protein loss may also occur from lymphatic obstruction in diseases such as intestinal lymphangiectasia. Concomitant loss of lymphocytes into the intestinal tract may result in lymphopenia.
- Similarly, patients with chylothorax will also have hypogammaglobulinemia (IgG=179+/-35 mg/dL) and lymphopenia (985+/-636 cells/mL) (Orange, 2003).
Article from: eMedicine
Background:
Agammaglobulinemia or hypogammaglobulinemia is the most common of the primary immunodeficiencies, accounting for approximately 50% of cases. Three major types can be described: X-linked, early-onset, and late-onset. After more than 50 years since the clinical entity was first described by Bruton in 1952, the molecular defect in X-linked agammaglobulinemia (XLA) has been elucidated. In Bruton's honor, the gene responsible has been named Btk, which stands for Bruton tyrosine kinase.
An estimated 90% of patients with early-onset agammaglobulinemia and absence of B cells have abnormalities in the Btk gene (ie, Bruton agammaglobulinemia or XLA). XLA is further discussed in detail in the article Bruton Agammaglobulinemia. Late-onset disease is usually referred to as Common Variable Immunodeficiency (CVID), also described separately. However, reports are increasing of adults who are diagnosed with XLA.
The remaining type is early-onset non–Bruton agammaglobulinemia, with low or absent serum immunoglobulin (Ig). Most cases are autosomal agammaglobulinemia and represent a very heterogeneous group, including Ig deficiency with increased immunoglobulin M (hyper-IgM syndrome), which is also discussed separately (see X-linked Immunodeficiency With Hyper IgM). In addition, some infants have an initially low Ig level that eventually increases to normal levels. This is known as Transient Hypogammaglobulinemia of Infancy and is discussed in detail in a separate article.
Recently, defective antibody production and low circulating numbers of B cells were described in some female infants and in males in whom no Btk abnormalities were detected. These observations imply the involvement of other genes. This article describes the cases of agammaglobulinemia caused by defects other than Btk. However, since the clinical manifestations and treatments are similar, information from Btk-deficient patients is included because of the lack of sufficient patients. Finally, some secondary immunodeficiency situations are also described because these need to be recognized in addition to the primary diseases. For other B-cell defects, such as specific Ig deficiencies (eg, immunoglobulin A [IgA] or immunoglobulin G [IgG] subclass deficiencies), refer to the article B-Cell Disorders.
Pathophysiology:
Although defects may occur in many steps in B-cell development and maturation, resulting in the lack of Ig production, the most common and well-described defect is the maturation of the pro–B cell to pre–B cell (see Image 1). In the fetal bone marrow, the first committed cell in B-cell development is the early pro-B cell identified by its ability to proliferate in the presence of interleukin-7 (IL-7). These cells develop into late pro–B cells in which rearrangement of the heavy chain occurs. This rearrangement process requires the recombination activating genes RAG1 and RAG2, which are controlled by IL-7 and perhaps other factors.
When the heavy chain is produced, it is transported to the cell surface by the Ig-a (CD79a) and Ig-b (CD82) heterodimers or by the surrogate light chain. Progression from this late pro–B-cell to the pre–B-cell stage involves the rearrangement and joining of the various segments of the heavy chain. The completion of rearrangement of the light and heavy chains and the presence of surface IgM results in the immature B cell, which then leaves the bone marrow. Increasing levels of immunoglobulin D (IgD) in the transitional cells finally results in the mature B cell with IgM and IgD both expressed. The mature B cells circulate between secondary lymphoid organs and migrate into lymphoid follicles of the spleen and lymph nodes in response to further stimuli and various chemokines. T cells stimulate B cells to undergo further proliferation and Ig class switching, leading to the expression of the various isotypes IgG, IgA, or immunoglobulin E (IgE).
The m heavy-chain gene on chromosome 14 is the most frequent abnormality in a patient with agammaglobulinemia and decreased B cells who does not have a defect in Btk. Ig- a and Ig-b are encoded by the mb-1 and B29 genes, respectively. A case involving a female patient with a mutation in the Ig-a gene has been described. A case involving a male patient with hypogammaglobulinemia caused by mutation at the l5/14/1 gene, resulting in a defect in the surrogate light chain, has also been described. Other mutations in the components of the pre–B-cell and B-cell antigen receptor complex (eg, defects in the B-cell linker protein, BLNK) account for 5-7% of patients with defects in early B-cell development. These patients have normal numbers of pro–B cells but no pre–B or mature B cells. Clinically, they are not different from patients with XLA.
Activation of B-cell receptor (BCR) induces the recruitment of Syk, which phosphorylates BLNK, a contributor to the activation of Btk that affects other intracellular signaling events.
These findings indicate that a defect in any of the steps in B-cell development may be clinically important. Approximately 85% of patients with defects in early B-cell development have XLA. However, when a female has an absence of serum Ig and peripheral blood B cells, the patient clearly does not have Bruton agammaglobulinemia or mutations in the Btk gene. The elucidation of her specific gene defects may shed additional information on B-cell development.
The exact defects have not yet been determined in other patients in whom agammaglobulinemia has been associated with a mosaic of ring chromosome 18 (Litzman, 1998) or hypogammaglobulinemia in a male with ring chromosome 21 (Ohga, 1997). Patients with B-cell deficiency associated with intrauterine growth retardation have been described (Revy, 2000), and patients with agammaglobulinemia with spondyloepiphyseal dysplasia and retinal dystrophy have also been described (Roifman, 1999). The syndrome of X-linked hypogammaglobulinemia with growth hormone deficiency also exists. This has been mapped to the same region that encompasses the Btk gene and may involve a gene controlling growth hormone production, implying a small contiguous gene deletion that includes both the gene for XLA and another closely linked gene involved in growth hormone production. Note that the structural gene for growth hormone is located on the long arm of chromosome 17.
In addition to the genetic defects described above, other pathophysiology mechanisms may result in hypogammaglobulinemia or agammaglobulinemia, such as viral infections, malignancy, or drug effects. These are described in more detail in Causes.
Frequency:
- In the US: Agammaglobulinemia occurs in approximately 1 in 250,000 males in the United States.
- Internationally: In a study of serum Ig levels in 2000 consecutive patients in Saudi Arabia, agammaglobulinemia was diagnosed at a rate of 250 per 100,000 individuals. These patients accounted for 16% of the primary humoral immunodeficiency groups (with selective IgA 45%, CVID 29%, and selective IgG 10%). Spain's Registry for Primary Immunodeficiency Diseases reported 1079 cases registered between January 1980 and December 1995. Of these, 49 were reported as XLA. In Brazil, of 166 cases of primary immunodeficiencies diagnosed over 15 years, 60.8% (101) were primary humoral deficiencies. Of these, XLA was the least frequent (9), compared with IgA deficiency (60) and transient hypogammaglobulinemia (14). In South Africa, antibody deficiencies predominate, accounting for 56% (52 of 93) of diagnoses, compared to Australia, where antibody deficiencies comprised 71% of 500 cases enrolled in a national registry. In Hong Kong, humoral defects were identified in 50 of 117 patients diagnosed with primary immunodeficiency.
Mortality/Morbidity: Patients with agammaglobulinemia are at risk of frequent and recurrent infections. Severe bacterial infections resulting in pneumonias or meningitis and subsequent bacteremia could be fatal; however, the major causes of morbidity are chronic upper pulmonary disease (eg, sinusitis) or lower pulmonary disease (eg, bronchiectasis).
- In patients with agammaglobulinemia, one study indicated that, although the incidence of bacterial infections resulting in hospitalization decreased from 0.40-0.06 per patient per year during intravenous Ig replacement, chronic sinusitis and bronchiectasis continue to occur.
- Central nervous enteroviral infections can be especially disabling, resulting in a long-term CNS debilitating state.
- Autoimmune and allergic manifestations are another source of morbidity in these patients.
Sex: Agammaglobulinemia can be either X-linked (XLA) or autosomal recessive. XLA is more often recognized as Bruton agammaglobulinemia.
Age: Because of passive, transplacental acquisition of maternal IgG, newborns have normal levels of serum IgG and do not have problems until the IgG is catabolized. Because newborns cannot produce their own Ig, increased susceptibility to infections develops in infants older than 6 months. Patients with non-Btk mutations tend to be younger at the time of diagnosis, and they are more likely to have severe complications.
History: History is similar to that for Bruton agammaglobulinemia because the patient is unable to produce functional humoral immunity. Patients may have problems with recurrent upper and/or lower respiratory tract infections or with chronic diarrhea. However, patients with mutations in the m heavy chain and non-Btk mutations tend to develop symptoms earlier and are more likely to have severe symptoms.
- Encapsulated bacteria with Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus, and pseudomonal species (in that order) cause most infections. Other bacteria, such as Salmonella and Giardia species, may also cause problems. Two cases of Campylobacter coli infection (one with bacteremia and cellulitis; another with pericarditis) have also been described.
- Almost three fourths of patients with agammaglobulinemia have infections occurring in the upper respiratory tract with otitis and sinusitis. Lower respiratory tract infections (eg, pneumonia, bronchiolitis), gastrointestinal tract infections (eg, gastroenteritis), or both occur in more than two thirds of patients.
- Other bacterial infections, such as pyoderma, sepsis, meningitis, osteomyelitis, and septic arthritis occur less frequently. Lower-grade pathogens, such as Pneumocystis carinii pneumonia, have also been reported. Additionally, sites of infection may be unusual with the encapsulated pyogenic bacteria, such as H influenzae lymphadenopathy or pneumococcal meningitis.
- Although patients with agammaglobulinemia are usually able to handle viral infections, they are susceptible to certain viruses that replicate in the gastrointestinal tract and then spread to the CNS. This indicates the importance of antibody production in limiting the spread of infections by enteroviruses such as poliovirus, echovirus, and coxsackievirus.
- Patients may present with vaccine-related poliomyelitis after immunization with the live poliovirus vaccine (see Hidalgo's report). Although prolonged secretions of a virus have been described (up to 637 days after vaccination), poliovirus carriers among people with primary immune deficiency appears to be rare, based on 3 separate studies, and may not manifest with disease.
- Alternately, echovirus infection of the CNS may cause chronic encephalomyelitis or meningoencephalitis. In 13 patients with primary hypogammaglobulinemia, Rudge et al (1996) described 3 clinical pictures: (1) progressive myelopathy in 1 patient, (2) myelopathy progressing to an encephalopathy in 4 patients, and (3) pure encephalopathy in 8 patients. Enteroviral infection was found in 7 patients by either culture or polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF). However, Katamura et al (2002) described a nonprogressive viral myelitis in a patient and suggested that the prognosis of CNS infections in agammaglobulinemia is not determined by the Ig level alone and that they are not always progressive or fatal.
- The use of interventricular infusion of Ig has been well-documented in these patients.
- Virus-induced autoimmune diseases such as a dermatomyositislike syndromes and chronic arthritis may also occur. These diseases suggest an element of antibody production dysregulation in their pathogenesis, although in some cases, enteroviruses have been isolated from skin or joints.
- Mycoplasma or Ureaplasma organisms may play a role in other cases of chronic arthritis. In a survey of 358 patients with primary antibody deficiency, mycoplasmal infection was the most common cause of severe chronic erosive arthritis. Patients with mild cases rapidly respond to antimicrobial therapy, such as tetracycline. In more severe cases, arthritis improved following treatment with Ig. Overall, 7-22% of agammaglobulinemia patients develop joint manifestations.
- A case of juvenile onset psoriatic arthritis has been described in a patient with agammaglobulinemia.
- The constellation of symptoms in a family of brothers with leukoencephalopathy, arthritis, colitis, and hypogammaglobulinemia prompted some to label this the LACH syndrome (Bonkowsky, 2004).
- Other associated autoimmune disorders most commonly include hematological manifestations (eg, thrombocytopenia, hemolytic anemia, neutropenia) and also alopecia totalis, glomerulonephritis, protein-losing enteropathy, malabsorption with disaccharidase deficiency, and amyloidosis.
- Other patients in whom measurements of Ig may be helpful include those with renal dialysis and patients in pediatric ICUs. In the former, IgG and IgG subclass deficiency were found in 8 out of 12 children undergoing continuous ambulatory peritoneal dialysis (Akman, 2002). Similarly, total IgG was below the normal for age in 14 of 20 patients admitted to a pediatric ICU (Rehman, 2003). However, a small number of patients was studied.
Physical: Patients with agammaglobulinemia appear to be healthy between bouts of infections. Patients usually do not fail to thrive, although chronic diarrhea, if present, could cause some dehydration and malabsorption. Any abnormal physical findings indicate presence of various infections for which patients have increased susceptibility. Concomitant short stature in a male suggests X-linked hypogammaglobulinemia with growth hormone deficiency syndrome.
- Most patients with agammaglobulinemia were recognized to have immunodeficiency during or shortly after their first hospitalization for infection. Most of the patients had a history of recurrent otitis or upper respiratory tract infection at the time of diagnosis, which when combined with the physical finding of markedly small or absent tonsils and cervical lymph nodes, should alert physicians to the diagnosis of agammaglobulinemia.
- Some patients have cutaneous manifestations representing several unique syndromes. One of these is known as WHIM syndrome, consisting of warts, hypogammaglobulinemia, infections, and myelokathexis. The gene responsible for this syndrome has been identified as a chemokine receptor CXCR4 (Gulino, 2003). The presence of warts may be unique since another individual has been described as having intestinal lymphangiectasis with hypogammaglobulinemia and lymphopenia as well as unrelenting cutaneous warts but without a history of infections (Lynn, 2004).
Causes: Genetic factors have included mutations of Btk only (accounting for 85-90% of patients with early onset agammaglobulinemia and an absence of B cells). The remaining cases in males and females are clinically similar to XLA and represent mutations affecting the IGHM, CD79AA, and IGLL1 genes involved in the composition of the pre-BCR or the BLNK gene involved in pre-BCR signal transduction. Non-XLA patients may have other defects that result in an arrest of B-cell differentiation at a pro–B-cell level (before the onset of Ig gene rearrangements) or defects in an adjacent gene to the Btk gene responsible for growth hormone production (XLA with growth hormone deficiency).
Also, certain infections and drugs may result in low or absent Ig levels.
- Genetic factors are described in the following examples:
- A female has been described with a translocation involving a new gene in chromosome 9 (LRRC8) that resulted in a block in B-cell differentiation at pro–,B- to pre–B-cell transition (Sawada, 2003). She had minor facial anomalies and congenital agammaglobulinemia and absent B cells in peripheral blood.
- Patients with mutations in the m heavy chain usually present initially when aged 4 months with pneumonia, otitis, gastroenteritis, chronic enterovirus encephalitis, and Pseudomonas aeruginosa septic shock. One 15-month-old child presented with fever, weakness, rash, and neutropenia 2 weeks after an oral poliovirus vaccine.
- One newborn girl with mutation in the Ig-a gene developed recurrent diarrhea and failure to thrive in the first month of life. By age 1 year, she had chronic bronchitis.
- One infant boy with mutation in the l light chain had recurrent otitis media at age 2 months. At age 3 years, he had H influenzae meningitis with arthritis.
- One boy with a BLNK defect presented with overwhelming sepsis during childhood. With IVIG treatment, he has survived to adulthood without any growth or developmental delay.
- Other patients have been described with reduced pro-B cells but no identifiable molecular defect. One was a 4-month-old infant girl with failure to thrive, recurrent otitis, candidiasis, H influenzae arthritis, and herpes simplex stomatitis. Another girl had microcephaly, persistent diarrhea, failure to thrive, and recurrent respiratory and gastrointestinal infections. This patient eventually developed pancytopenia with progressive bone marrow failure.
- Certain viral infectious have been shown to cause transient or permanent immune deficiency.
- Congenital rubella can cause hypogammaglobulinemia. Although infection with human immunodeficiency virus (HIV) usually causes hypergammaglobulinemia, in some reported pediatric cases, patients had hypogammaglobulinemia.
- Patients with X-linked lymphoproliferative syndrome (ie, Duncan disease, Purtilo syndrome) may develop overwhelming disease with infection by Epstein-Barr virus with subsequent agammaglobulinemia and a decrease in B cells. Therefore, any male with persistent hypogammaglobulinemia following mononucleosis should be closely monitored for X-linked lymphoproliferative disease.
- Drug-induced hypogammaglobulinemia has been described with immunosuppressive agents (eg, corticosteroids, rituximab), epilepsy medications (eg, phenytoin, carbamazepine), and antipsychotic medications (eg, chlorpromazine). Recurrent infections and reduced serum Ig levels resolved when treatment with the medication was stopped.
- Oral prednisone at a dose of at least 12.5 mg/d for patients with asthma has been shown to be able to result in hypogammaglobulinemia (Kawano, 2002). Hypogammaglobulinemia is also frequently seen in steroid-sensitive nephrotic syndrome. Therefore, in patients with autoimmune diseases such as systemic lupus erythematosus who are being treated with prednisone and other immunosuppressive medications, the hypogammaglobulinemia could be due to either medication use or could reflect the underlying autoimmune process.
- Some have speculated on the association between anticonvulsant hypersensitivity syndrome (a life-threatening, drug-induced, multiorgan system reaction) with herpesvirus reactivation and hypogammaglobulinemia.
- Speculation that phenytoin-induced suppressor T-cell activity and subsequent antibody deficiency has found some support with in vitro experiments.
- Malignancies such as leukemias, multiple myeloma, and neuroblastoma may have an associated hypogammaglobulinemia.
- Excessive protein loss from the gastrointestinal tract may result in hypogammaglobulinemia; however, primary antibody deficiency may also cause chronic diarrhea. Therefore, any protein-losing enteropathy should be considered in patients presenting with hypogammaglobulinemia. In these situations, specific antibody responses are intact, and circulating B cells are normal. On the other hand, gastrointestinal protein loss may also occur from lymphatic obstruction in diseases such as intestinal lymphangiectasia. Concomitant loss of lymphocytes into the intestinal tract may result in lymphopenia.
- Similarly, patients with chylothorax will also have hypogammaglobulinemia (IgG=179+/-35 mg/dL) and lymphopenia (985+/-636 cells/mL) (Orange, 2003).
Article from: eMedicine
Saturday, August 11, 2007
What Can You Do? Be Involved in Your Health Care
What Can You Do? Be Involved in Your Health Care
1. The single most important way you can help to prevent errors is to be an active member of your health care team.
That means taking part in every decision about your health care. Research shows that patients who are more involved with their care tend to get better results. Some specific tips, based on the latest scientific evidence about what works best, follow.
Medicines
2. Make sure that all of your doctors know about everything you are taking. This includes prescription and over-the-counter medicines, and dietary supplements such as vitamins and herbs.
At least once a year, bring all of your medicines and supplements with you to your doctor. "Brown bagging" your medicines can help you and your doctor talk about them and find out if there are any problems. It can also help your doctor keep your records up to date, which can help you get better quality care.
3. Make sure your doctor knows about any allergies and adverse reactions you have had to medicines.
This can help you avoid getting a medicine that can harm you.
4. When your doctor writes you a prescription, make sure you can read it.
If you can't read your doctor's handwriting, your pharmacist might not be able to either.
5. Ask for information about your medicines in terms you can understand—both when your medicines are prescribed and when you receive them.
- What is the medicine for?
- How am I supposed to take it, and for how long?
- What side effects are likely? What do I do if they occur?
- Is this medicine safe to take with other medicines or dietary supplements I am taking?
- What food, drink, or activities should I avoid while taking this medicine?
6. When you pick up your medicine from the pharmacy, ask: Is this the medicine that my doctor prescribed?
A study by the Massachusetts College of Pharmacy and Allied Health Sciences found that 88 percent of medicine errors involved the wrong drug or the wrong dose.
7. If you have any questions about the directions on your medicine labels, ask.
Medicine labels can be hard to understand. For example, ask if "four doses daily" means taking a dose every 6 hours around the clock or just during regular waking hours.
8. Ask your pharmacist for the best device to measure your liquid medicine. Also, ask questions if you're not sure how to use it.
Research shows that many people do not understand the right way to measure liquid medicines. For example, many use household teaspoons, which often do not hold a true teaspoon of liquid. Special devices, like marked syringes, help people to measure the right dose. Being told how to use the devices helps even more.
9. Ask for written information about the side effects your medicine could cause.
If you know what might happen, you will be better prepared if it does—or, if something unexpected happens instead. That way, you can report the problem right away and get help before it gets worse. A study found that written information about medicines can help patients recognize problem side effects and then give that information to their doctor or pharmacist.
1. The single most important way you can help to prevent errors is to be an active member of your health care team.
That means taking part in every decision about your health care. Research shows that patients who are more involved with their care tend to get better results. Some specific tips, based on the latest scientific evidence about what works best, follow.
Medicines
2. Make sure that all of your doctors know about everything you are taking. This includes prescription and over-the-counter medicines, and dietary supplements such as vitamins and herbs.
At least once a year, bring all of your medicines and supplements with you to your doctor. "Brown bagging" your medicines can help you and your doctor talk about them and find out if there are any problems. It can also help your doctor keep your records up to date, which can help you get better quality care.
3. Make sure your doctor knows about any allergies and adverse reactions you have had to medicines.
This can help you avoid getting a medicine that can harm you.
4. When your doctor writes you a prescription, make sure you can read it.
If you can't read your doctor's handwriting, your pharmacist might not be able to either.
5. Ask for information about your medicines in terms you can understand—both when your medicines are prescribed and when you receive them.
- What is the medicine for?
- How am I supposed to take it, and for how long?
- What side effects are likely? What do I do if they occur?
- Is this medicine safe to take with other medicines or dietary supplements I am taking?
- What food, drink, or activities should I avoid while taking this medicine?
6. When you pick up your medicine from the pharmacy, ask: Is this the medicine that my doctor prescribed?
A study by the Massachusetts College of Pharmacy and Allied Health Sciences found that 88 percent of medicine errors involved the wrong drug or the wrong dose.
7. If you have any questions about the directions on your medicine labels, ask.
Medicine labels can be hard to understand. For example, ask if "four doses daily" means taking a dose every 6 hours around the clock or just during regular waking hours.
8. Ask your pharmacist for the best device to measure your liquid medicine. Also, ask questions if you're not sure how to use it.
Research shows that many people do not understand the right way to measure liquid medicines. For example, many use household teaspoons, which often do not hold a true teaspoon of liquid. Special devices, like marked syringes, help people to measure the right dose. Being told how to use the devices helps even more.
9. Ask for written information about the side effects your medicine could cause.
If you know what might happen, you will be better prepared if it does—or, if something unexpected happens instead. That way, you can report the problem right away and get help before it gets worse. A study found that written information about medicines can help patients recognize problem side effects and then give that information to their doctor or pharmacist.
Hospital Stays
10. If you have a choice, choose a hospital at which many patients have the procedure or surgery you need.
Research shows that patients tend to have better results when they are treated in hospitals that have a great deal of experience with their condition.
11. If you are in a hospital, consider asking all health care workers who have direct contact with you whether they have washed their hands.
Handwashing is an important way to prevent the spread of infections in hospitals. Yet, it is not done regularly or thoroughly enough. A recent study found that when patients checked whether health care workers washed their hands, the workers washed their hands more often and used more soap.
12. When you are being discharged from the hospital, ask your doctor to explain the treatment plan you will use at home.
This includes learning about your medicines and finding out when you can get back to your regular activities. Research shows that at discharge time, doctors think their patients understand more than they really do about what they should or should not do when they return home.
Surgery
13. If you are having surgery, make sure that you, your doctor, and your surgeon all agree and are clear on exactly what will be done.
Doing surgery at the wrong site (for example, operating on the left knee instead of the right) is rare. But even once is too often. The good news is that wrong-site surgery is 100 percent preventable. The American Academy of Orthopaedic Surgeons urges its members to sign their initials directly on the site to be operated on before the surgery.
Other Steps You Can Take
14. Speak up if you have questions or concerns.
You have a right to question anyone who is involved with your care.
15. Make sure that someone, such as your personal doctor, is in charge of your care.
This is especially important if you have many health problems or are in a hospital.
16. Make sure that all health professionals involved in your care have important health information about you.
Do not assume that everyone knows everything they need to.
17. Ask a family member or friend to be there with you and to be your advocate (someone who can help get things done and speak up for you if you can't).
Even if you think you don't need help now, you might need it later.
18. Know that "more" is not always better.
It is a good idea to find out why a test or treatment is needed and how it can help you. You could be better off without it.
19. If you have a test, don't assume that no news is good news.
Ask about the results.
20. Learn about your condition and treatments by asking your doctor and nurse and by using other reliable sources.
20 Tips to Help Prevent Medical Errors
20 Tips to Help Prevent Medical Errors
Patient Fact Sheet
Medical errors are one of the Nation's leading causes of death and injury. A recent report by the Institute of Medicine estimates that as many as 44,000 to 98,000 people die in U.S. hospitals each year as the result of medical errors. This means that more people die from medical errors than from motor vehicle accidents, breast cancer, or AID.
Government agencies, purchasers of group health care, and health care providers are working together to make the U.S. health care system safer for patients and the public. This fact sheet tells what you can do.
What are Medical Errors?
Medical errors happen when something that was planned as a part of medical care doesn't work out, or when the wrong plan was used in the first place. Medical errors can occur anywhere in the health care system:
- Hospitals.
- Clinics.
- Outpatient Surgery Centers.
- Doctors' Offices.
- Nursing Homes.
- Pharmacies.
- Patients' Homes.
Errors can involve:
- Medicines.
- Surgery.
- Diagnosis.
- Equipment.
- Lab reports.
They can happen during even the most routine tasks, such as when a hospital patient on a salt-free diet is given a high-salt meal.
Most errors result from problems created by today's complex health care system. But errors also happen when doctors and their patients have problems communicating. For example, a recent study supported by the Agency for Healthcare Research and Quality (AHRQ) found that doctors often do not do enough to help their patients make informed decisions. Uninvolved and uninformed patients are less likely to accept the doctor's choice of treatment and less likely to do what they need to do to make the treatment work.
Article from: ahrq.gov
Friday, August 10, 2007
Premature Ventricular Contraction, PVC (article3)
Premature Ventricular Contraction
Prehospital Care
- Perform telemetry.
- Secure intravenous (IV) access.
- Administer oxygen.
- Complex ectopy in the setting of myocardial ischemia or causing hemodynamic instability should be suppressed. Use lidocaine for patients with myocardial ischemia.
Emergency Department Care
- The decision to treat PVCs in the emergency or outpatient settings depends on the clinical scenario. In the absence of cardiac disease, isolated, asymptomatic ventricular ectopy, regardless of configuration or frequency, requires no treatment. With cardiac disease, certain toxic effects, and electrolyte imbalances, treatment may be required. Establish telemetry and IV access, initiate oxygen, and obtain a 12-lead ECG.
- Hypoxia: Treat the underlying cause; secure the ABCs and provide oxygen.
- Drug toxicity: Specific therapy is indicated for certain toxic effects. Examples include digoxin (Fab antibodies), tricyclics (bicarbonate), and aminophylline (GI decontamination and possibly hemodialysis).
- Correct electrolyte imbalances, particularly those of magnesium, calcium, and potassium.
- Acute ischemia and/or infarction
- Early diagnosis and treatment of acute infarction/ischemia are the cornerstones of therapy.
- The routine use of lidocaine and other type I antiarrhythmic agents in the setting of acute MI is no longer recommended because of their toxic effects.
- Acute ischemia or infarction includes patients with ectopy in the period immediately after receiving thrombolytic agents, during which complex ectopy frequently is seen.
- Only in the setting of symptomatic, complex ectopy is lidocaine likely to benefit a patient having an MI.
- Beta-blockers have proven efficacy in the setting of acute MI and are safe to use.
Consultations
Involvement of a cardiologist may be indicated if the patient's condition is refractory to standard therapy.
Therapy for complex ventricular ectopy depends on the setting and the underlying cause. In drug toxicity, specific therapies are available. With electrolyte imbalances, correction of abnormalities is therapeutic. Lidocaine is the drug of choice (DOC) in the setting of complex ectopy in the peri-MI period if the patient is symptomatic, yet no firm evidence supports this practice.
Article from: eMedicine
Prehospital Care
- Perform telemetry.
- Secure intravenous (IV) access.
- Administer oxygen.
- Complex ectopy in the setting of myocardial ischemia or causing hemodynamic instability should be suppressed. Use lidocaine for patients with myocardial ischemia.
Emergency Department Care
- The decision to treat PVCs in the emergency or outpatient settings depends on the clinical scenario. In the absence of cardiac disease, isolated, asymptomatic ventricular ectopy, regardless of configuration or frequency, requires no treatment. With cardiac disease, certain toxic effects, and electrolyte imbalances, treatment may be required. Establish telemetry and IV access, initiate oxygen, and obtain a 12-lead ECG.
- Hypoxia: Treat the underlying cause; secure the ABCs and provide oxygen.
- Drug toxicity: Specific therapy is indicated for certain toxic effects. Examples include digoxin (Fab antibodies), tricyclics (bicarbonate), and aminophylline (GI decontamination and possibly hemodialysis).
- Correct electrolyte imbalances, particularly those of magnesium, calcium, and potassium.
- Acute ischemia and/or infarction
- Early diagnosis and treatment of acute infarction/ischemia are the cornerstones of therapy.
- The routine use of lidocaine and other type I antiarrhythmic agents in the setting of acute MI is no longer recommended because of their toxic effects.
- Acute ischemia or infarction includes patients with ectopy in the period immediately after receiving thrombolytic agents, during which complex ectopy frequently is seen.
- Only in the setting of symptomatic, complex ectopy is lidocaine likely to benefit a patient having an MI.
- Beta-blockers have proven efficacy in the setting of acute MI and are safe to use.
Consultations
Involvement of a cardiologist may be indicated if the patient's condition is refractory to standard therapy.
Therapy for complex ventricular ectopy depends on the setting and the underlying cause. In drug toxicity, specific therapies are available. With electrolyte imbalances, correction of abnormalities is therapeutic. Lidocaine is the drug of choice (DOC) in the setting of complex ectopy in the peri-MI period if the patient is symptomatic, yet no firm evidence supports this practice.
Article from: eMedicine
Wednesday, August 8, 2007
Premature Ventricular Contraction, PVC (article2)
Premature Ventricular Contraction, PVC
Lab Studies
- Obtain serum electrolyte levels, in particular potassium levels. Consider checking the magnesium level, especially in patients with low potassium levels.
- In selected patients, a drug screen may be helpful.
- For patients taking medication with known proarrhythmic effects (eg, digoxin, theophylline), drug levels may be useful.
Other Tests
- ECG allows the physician to characterize the ventricular ectopy and determine its cause. In addition to the standard 12-lead ECG, a 2-minute rhythm strip may help in determining frequency of the ectopy and capture infrequent PVCs. Findings may include the following:
- Left ventricular hypertrophy
- Active cardiac ischemia (ST-segment depression or elevation and or T-wave inversion)
- In patients with previous MI - Q waves or loss of R waves, bundle branch block
- Electrolyte abnormalities (hyperacute T waves, QT prolongation)
- Drug effects (QRS widening, QT prolongation)
- On ECG, PVCs may be premature in relation to the next expected beat of the basic rhythm. The pause after the premature beat is usually a fully compensatory pause. The R-R interval surrounding the premature beat is equal to double the basic R-R interval, showing that the ectopic beat did not reset the sinus node.
- PVCs may appear in a pattern of bigeminy, trigeminy, or quadrigeminy, which describe a pattern of PVCs occurring every other, every third, or every fourth beat, respectively.
- PVCs with identical morphologies on a tracing are called monomorphic or unifocal. If the PVCs demonstrate 2 or more different morphologies, they are referred to as multiform, pleomorphic, or polymorphic.
- PVCs usually are described in terms of the Lown grading system for premature beats. The higher the grade, the more serious the ectopy.
- Grade 0 = No premature beats
- Grade 1 = Occasional ( <30/h)>
- Grade 2 = Frequent (>30/h)
- Grade 3 = Multiform
- Grade 4 = Repetitive (A = Couplets, B = Salvos of = or > 3) Grade 5 = R-on-T pattern
- Holter 24-hour monitors are useful in quantifying and characterizing ventricular ectopy.
- Holters also have been used to determine treatment efficacy in patents with frequent or complex PVCs.
- Suppression of ectopy on Holter monitoring is not always predictive of survival.
- The most important role for Holter monitoring is risk stratification of patients with a recent MI or known left ventricular dysfunction.
- More than 60% of healthy, middle-aged men have ventricular ectopy on Holter monitoring.
-Signal-averaged ECG
- Signal-averaged ECGs (SAECGs) may have a future role in identifying patients at risk for complex ventricular ectopy and nonsustained ventricular tachycardia (NSVT).
- SAECGs may have a role in identifying patients with complex ectopy who may benefit from electrophysiologic studies (EPS).
- Echocardiography is useful not only in evaluating the ejection fraction, which is important in determining the prognosis and also in identifying valvular disease or ventricular hypertrophy.
Procedures
- Exercise stress testing (EST) is best used complementary to Holter monitoring. In patients with complex ectopy, EST can unmask NSVT triggered by increased catecholamines or myocardial ischemia.
- The role of EPS in complex ventricular ectopy is an area of both intense research and debate. A joint American Heart Association (AHA)/American College of Cardiology (ACC) statement suggested the following:
- Routine EPS are not indicated in low-risk patients after MI. Low risk refers to simple ectopy, good left ventricular function, and low congestive heart failure (CHF) class.
- EPS are indicated in high-risk patients with complex ectopy.
- EPS are though to be beneficial in patients with sustained ventricular tachycardia more than 24 hours after MI.
Article sorce: eMedicine
Lab Studies
- Obtain serum electrolyte levels, in particular potassium levels. Consider checking the magnesium level, especially in patients with low potassium levels.
- In selected patients, a drug screen may be helpful.
- For patients taking medication with known proarrhythmic effects (eg, digoxin, theophylline), drug levels may be useful.
Other Tests
- ECG allows the physician to characterize the ventricular ectopy and determine its cause. In addition to the standard 12-lead ECG, a 2-minute rhythm strip may help in determining frequency of the ectopy and capture infrequent PVCs. Findings may include the following:
- Left ventricular hypertrophy
- Active cardiac ischemia (ST-segment depression or elevation and or T-wave inversion)
- In patients with previous MI - Q waves or loss of R waves, bundle branch block
- Electrolyte abnormalities (hyperacute T waves, QT prolongation)
- Drug effects (QRS widening, QT prolongation)
- On ECG, PVCs may be premature in relation to the next expected beat of the basic rhythm. The pause after the premature beat is usually a fully compensatory pause. The R-R interval surrounding the premature beat is equal to double the basic R-R interval, showing that the ectopic beat did not reset the sinus node.
- PVCs may appear in a pattern of bigeminy, trigeminy, or quadrigeminy, which describe a pattern of PVCs occurring every other, every third, or every fourth beat, respectively.
- PVCs with identical morphologies on a tracing are called monomorphic or unifocal. If the PVCs demonstrate 2 or more different morphologies, they are referred to as multiform, pleomorphic, or polymorphic.
- PVCs usually are described in terms of the Lown grading system for premature beats. The higher the grade, the more serious the ectopy.
- Grade 0 = No premature beats
- Grade 1 = Occasional ( <30/h)>
- Grade 2 = Frequent (>30/h)
- Grade 3 = Multiform
- Grade 4 = Repetitive (A = Couplets, B = Salvos of = or > 3) Grade 5 = R-on-T pattern
- Holter 24-hour monitors are useful in quantifying and characterizing ventricular ectopy.
- Holters also have been used to determine treatment efficacy in patents with frequent or complex PVCs.
- Suppression of ectopy on Holter monitoring is not always predictive of survival.
- The most important role for Holter monitoring is risk stratification of patients with a recent MI or known left ventricular dysfunction.
- More than 60% of healthy, middle-aged men have ventricular ectopy on Holter monitoring.
-Signal-averaged ECG
- Signal-averaged ECGs (SAECGs) may have a future role in identifying patients at risk for complex ventricular ectopy and nonsustained ventricular tachycardia (NSVT).
- SAECGs may have a role in identifying patients with complex ectopy who may benefit from electrophysiologic studies (EPS).
- Echocardiography is useful not only in evaluating the ejection fraction, which is important in determining the prognosis and also in identifying valvular disease or ventricular hypertrophy.
Procedures
- Exercise stress testing (EST) is best used complementary to Holter monitoring. In patients with complex ectopy, EST can unmask NSVT triggered by increased catecholamines or myocardial ischemia.
- The role of EPS in complex ventricular ectopy is an area of both intense research and debate. A joint American Heart Association (AHA)/American College of Cardiology (ACC) statement suggested the following:
- Routine EPS are not indicated in low-risk patients after MI. Low risk refers to simple ectopy, good left ventricular function, and low congestive heart failure (CHF) class.
- EPS are indicated in high-risk patients with complex ectopy.
- EPS are though to be beneficial in patients with sustained ventricular tachycardia more than 24 hours after MI.
Article sorce: eMedicine
Premature Ventricular Contraction, PVC
Premature Ventricular Contraction (PVC)
Background:
Premature ventricular contraction (PVC) is caused by an ectopic cardiac pacemaker located in the ventricle. PVCs are characterized by premature and bizarrely shaped QRS complexes usually wider than 120 msec on with the width of the ECG. These complexes are not preceded by a P wave, and the T wave is usually large, and its direction is opposite the major deflection of the QRS.
The clinical significance of PVCs depends on their frequency, complexity, and hemodynamic response.
Pathophysiology:
PVCs reflect activation of the ventricles from a site below the atrioventricular node (AVN). Suggested mechanisms for PVCs are reentry, triggered activity, and enhanced automaticity.
Reentry occurs when an area of 1-way block in the Purkinje fibers and a second area of slow conduction are present. This condition is frequently seen in patients with underlying heart disease that creates areas of differential conduction and recovery due to myocardial scarring or ischemia. During ventricular activation, the area of slow conduction activates the blocked part of the system after the rest of the ventricle has recovered, resulting in an extra beat. Reentry can produce single ectopic beats or can trigger paroxysmal tachycardia.
Triggered beats are considered to be due to after-depolarizations triggered by the preceding action potential. These are often seen in patients with ventricular arrhythmias due to digoxin toxicity and reperfusion therapy after myocardial infarction (MI).
Enhanced automaticity suggests an ectopic focus of pacemaker cells in the ventricle that has a subthreshold potential for firing. The basic rhythm of the heart raises these cells to threshold, which precipitates an ectopic beat. This process is the underlying mechanism for arrhythmias due to excess catecholamines and some electrolyte deficiencies, particularly hyperkalemia.
Factors that increase the risk of PVCs include male sex, advanced age, African American race, hypertension and underlying ischemic heart disease, a bundle branch block on 12-lead ECG, hypomagnesemia, and hypokalemia.
Frequency:
United States
PVCs are one of the most common arrhythmias and can occur in patients with or without heart disease. The prevalence of PVCs varies greatly, with estimates of less than 3% to more than 60% in asymptomatic individuals.
Data from large, population-based studies indicate that the prevalence ranges from less than 3% for young white women without heart disease to almost 20% for older African American individuals with hypertension.
Mortality/Morbidity
The clinical significance of PVCs depends on the clinical context in which they occur.
- PVCs in young, healthy patients without underlying structural heart disease are usually not associated with any increased rate of mortality.
- PVCs in older patients, in particular those with underlying heart disease, are associated with an increased risk of adverse cardiac events, particularly sustained ventricular dysrhythmias and sudden death.
- In patients who have had a MI, the risk of malignant ventricular arrhythmias and sudden death is related to the complexity and frequency of the PVCs. Patients with PVCs in Lown classes 3-5 are at greatest risk (see Lown grading criteria below).
Race
African American race is associated with an increased frequency of PVCs on routine monitoring. In a large population-based study of PVC prevalence, African American race alone increased the risk of PVCs by 30% compared with the risk in white individuals.
Sex
Ventricular ectopy is more prevalent in men than in women of the same age. Male sex alone increases the risk of identifying PVCs on routine screening, with an odds ratio for male sex of 1.39 compared with women.
Age
PVC frequency increases with age, reflecting the increased prevalence of hypertension and cardiac disease in aging populations.
History
The important elements in obtaining a history from patients with ventricular ectopy are a history of cardiac disease or structural heart disease. Current medications that may be proarrhythmic or that may increase the risk of abnormal potassium or magnesium levels and use of drugs or medications that are sympathomimetic (eg, ephedrine-containing products, cocaine), may also provide important clues to the source of the PVCs.
Symptoms pertinent to the management of the PVC's are those that suggest underlying ischemic cardiac disease, such as chest pain or its anginal equivalent, or those suggesting hemodynamic compromise, such as lightheadedness or syncope.
- Patients are usually asymptomatic.
- Cannon A waves or the increased force of contraction due to postextrasystolic potentiation of contractility can cause palpitations and neck and/or chest discomfort.
- The patient may report feeling that his or her heart "stops" after a PVC.
- Patients with frequent PVCs or bigeminy may report syncope. This symptom is due to either inadequate stroke volume or decreased cardiac output caused by the condition effectively halving the heart rate.
- Long runs of PVCs can result in hypotension.
- Exercise can increase or decrease the PVC rate.
Physical
Important findings on the physical examination are those that provide clues to the underlying cause of the ventricular ectopy.
- Blood pressure: Frequent PVCs may result in hemodynamic compromise. Frank hypotension is rare, but relative hypotension is not uncommon, particularly in patients with underlying cardiac disease.
- Pulse: The ectopic beat may produce a diminished or absent pulse depending on the force of the ventricular contraction.
- Pulse oximetry: Hypoxia may precipitate PVCs.
- Cardiac findings: Cannon A waves may be observed in the jugular venous pulse if the timing of the PVC causes an atrial contraction against a closed tricuspid valve.
- Cardiopulmonary findings: Findings in conjunction with longstanding hypertension (elevated BP and an S4) or CHF (S3 and rales) are important clues to the cause and clinical significance of PVCs.
- Neurologic findings: Agitation and findings of sympathetic activation (eg, dilated pupils, warm and dry skin, tremor, tachycardia, hypertension) suggest that catecholamines may be the cause of the ectopy.
Causes
- Cardiac
- Acute MI or ischemia
- Myocarditis
- Cardiomyopathy, dilated or hypertrophic
- Myocardial contusion
- Mitral valve prolapse
- Hypoxia and/or hypercapnia
- Medications (eg, digoxin, sympathomimetics, tricyclic antidepressants, aminophylline, caffeine)
- Illicit substances (eg, cocaine, amphetamines, alcohol, tobacco)
- Hypomagnesemia, hypokalemia, hypercalcemia
Article source: eMedicine
Background:
Premature ventricular contraction (PVC) is caused by an ectopic cardiac pacemaker located in the ventricle. PVCs are characterized by premature and bizarrely shaped QRS complexes usually wider than 120 msec on with the width of the ECG. These complexes are not preceded by a P wave, and the T wave is usually large, and its direction is opposite the major deflection of the QRS.
The clinical significance of PVCs depends on their frequency, complexity, and hemodynamic response.
Pathophysiology:
PVCs reflect activation of the ventricles from a site below the atrioventricular node (AVN). Suggested mechanisms for PVCs are reentry, triggered activity, and enhanced automaticity.
Reentry occurs when an area of 1-way block in the Purkinje fibers and a second area of slow conduction are present. This condition is frequently seen in patients with underlying heart disease that creates areas of differential conduction and recovery due to myocardial scarring or ischemia. During ventricular activation, the area of slow conduction activates the blocked part of the system after the rest of the ventricle has recovered, resulting in an extra beat. Reentry can produce single ectopic beats or can trigger paroxysmal tachycardia.
Triggered beats are considered to be due to after-depolarizations triggered by the preceding action potential. These are often seen in patients with ventricular arrhythmias due to digoxin toxicity and reperfusion therapy after myocardial infarction (MI).
Enhanced automaticity suggests an ectopic focus of pacemaker cells in the ventricle that has a subthreshold potential for firing. The basic rhythm of the heart raises these cells to threshold, which precipitates an ectopic beat. This process is the underlying mechanism for arrhythmias due to excess catecholamines and some electrolyte deficiencies, particularly hyperkalemia.
Factors that increase the risk of PVCs include male sex, advanced age, African American race, hypertension and underlying ischemic heart disease, a bundle branch block on 12-lead ECG, hypomagnesemia, and hypokalemia.
Frequency:
United States
PVCs are one of the most common arrhythmias and can occur in patients with or without heart disease. The prevalence of PVCs varies greatly, with estimates of less than 3% to more than 60% in asymptomatic individuals.
Data from large, population-based studies indicate that the prevalence ranges from less than 3% for young white women without heart disease to almost 20% for older African American individuals with hypertension.
Mortality/Morbidity
The clinical significance of PVCs depends on the clinical context in which they occur.
- PVCs in young, healthy patients without underlying structural heart disease are usually not associated with any increased rate of mortality.
- PVCs in older patients, in particular those with underlying heart disease, are associated with an increased risk of adverse cardiac events, particularly sustained ventricular dysrhythmias and sudden death.
- In patients who have had a MI, the risk of malignant ventricular arrhythmias and sudden death is related to the complexity and frequency of the PVCs. Patients with PVCs in Lown classes 3-5 are at greatest risk (see Lown grading criteria below).
Race
African American race is associated with an increased frequency of PVCs on routine monitoring. In a large population-based study of PVC prevalence, African American race alone increased the risk of PVCs by 30% compared with the risk in white individuals.
Sex
Ventricular ectopy is more prevalent in men than in women of the same age. Male sex alone increases the risk of identifying PVCs on routine screening, with an odds ratio for male sex of 1.39 compared with women.
Age
PVC frequency increases with age, reflecting the increased prevalence of hypertension and cardiac disease in aging populations.
History
The important elements in obtaining a history from patients with ventricular ectopy are a history of cardiac disease or structural heart disease. Current medications that may be proarrhythmic or that may increase the risk of abnormal potassium or magnesium levels and use of drugs or medications that are sympathomimetic (eg, ephedrine-containing products, cocaine), may also provide important clues to the source of the PVCs.
Symptoms pertinent to the management of the PVC's are those that suggest underlying ischemic cardiac disease, such as chest pain or its anginal equivalent, or those suggesting hemodynamic compromise, such as lightheadedness or syncope.
- Patients are usually asymptomatic.
- Cannon A waves or the increased force of contraction due to postextrasystolic potentiation of contractility can cause palpitations and neck and/or chest discomfort.
- The patient may report feeling that his or her heart "stops" after a PVC.
- Patients with frequent PVCs or bigeminy may report syncope. This symptom is due to either inadequate stroke volume or decreased cardiac output caused by the condition effectively halving the heart rate.
- Long runs of PVCs can result in hypotension.
- Exercise can increase or decrease the PVC rate.
Physical
Important findings on the physical examination are those that provide clues to the underlying cause of the ventricular ectopy.
- Blood pressure: Frequent PVCs may result in hemodynamic compromise. Frank hypotension is rare, but relative hypotension is not uncommon, particularly in patients with underlying cardiac disease.
- Pulse: The ectopic beat may produce a diminished or absent pulse depending on the force of the ventricular contraction.
- Pulse oximetry: Hypoxia may precipitate PVCs.
- Cardiac findings: Cannon A waves may be observed in the jugular venous pulse if the timing of the PVC causes an atrial contraction against a closed tricuspid valve.
- Cardiopulmonary findings: Findings in conjunction with longstanding hypertension (elevated BP and an S4) or CHF (S3 and rales) are important clues to the cause and clinical significance of PVCs.
- Neurologic findings: Agitation and findings of sympathetic activation (eg, dilated pupils, warm and dry skin, tremor, tachycardia, hypertension) suggest that catecholamines may be the cause of the ectopy.
Causes
- Cardiac
- Acute MI or ischemia
- Myocarditis
- Cardiomyopathy, dilated or hypertrophic
- Myocardial contusion
- Mitral valve prolapse
- Hypoxia and/or hypercapnia
- Medications (eg, digoxin, sympathomimetics, tricyclic antidepressants, aminophylline, caffeine)
- Illicit substances (eg, cocaine, amphetamines, alcohol, tobacco)
- Hypomagnesemia, hypokalemia, hypercalcemia
Article source: eMedicine
Subscribe to:
Posts (Atom)