Chronic bacterial infections

Cystic fibrosis (CF) is a recessive genetic disorder prevalent among whites in North America and certain parts of northern Europe. It is characterized by chronic bacterial infections of the airways and sinuses, fat maldigestion due to pancreatic exocrine insufficiency, infertility in males due to abnormal development of the vas deferens, and elevated levels of chloride in sweat (> 60 mmol/L). 

Numerous FTS analogs that exhibit biological effects in the differentiation of T-lymphocytes have now been synthesized 140). Information is already available about the possibility of using the peptide derivatives thymosin at and FTS therapeutically in the treatment of disorders of the immune system (e.g. in patients with congenital T-cell deficiency or chronic bacterial infections). 

Polyclonal increases in serum immunoglobulins are the normal response to infections. IgG response predominates in autoimmune responses IgA in skin, gut, respiratory, and renal infections and IgM in primary viral infections and bloodstream parasites, such as malaria. Chronic bacterial infections may cause an increase in serum levels of all immunoglobulins. In such cases, estimations of the individual immunoglobulins seldom provide more information than protein electrophoresis. They are of value, however, in the differential diagnosis of liver disease and of intrauterine infections. In primary biliary cirrhosis, the IgM level is greatly increased in chronic active hepatitis, IgG and sometimes IgM are increased and in portal cirrhosis, IgA and sometimes IgG are increased. In intrauterine infections, production of IgM by the fetus increases, and the IgM level in umbilical cord blood is increased. Estimations of IgE are used in the management of asthma and other allergic conditions, especially in children. 

Cystic fibrosis is a hereditary disorder caused by mutation in the cystic fibrosis transmembrane conductance regulator gene that encodes a cyclic adenosine monophosphate-regulated chloride channel. Defects in chloride ion transport in the airway epithelia lead to abnormal airway secretions, impaired mucociliary clearance, chronic bacterial infection, bronchiectasis, and premature death. Delivery of the cystic fibrosis transmembrane conductance regulator cDNA by adenovirus vectors or the plasmid-liposome complex resulted in transient correction of the defects in patients with cystic fibrosis. Formulations of cationic lipid-DNA complexes for aerosol delivery are being explored to improve on the gene therapy approach. 

Many patients with infection have a reduced serum level of folate, particularly those with chronic bacterial infections. However, the development of a megaloblastic anemia is uncommon and when it does occur is perhaps more often associated with the treatment. It is probable that the folate deficiency is the result of a combination of fiictors including poor dietary intake, low reserves, an increased demand due to an increased cell turnover, impaired absorption, vomiting, and impaired metabolism due to the toxic state of the patient (C17, M16, W25). Pyrexia may also inhibit the reduction of folate. Panders and Rupert (P13) found that if folic acid was incubated with a chicken liver enzyme preparation at an elevated temperature the reduction of folic acid to tetrahydrofolic acid was inhibited. 

The chloride channel is vital for proper absorption of salt (NaCl) and water across the plasma membranes of the epithelial cells that line ducts and tubes in tissues such as lungs, liver, small intestine, and sweat glands. Chloride transport occurs when signal molecules open CFTR Cl channels in the apical (top) membrane surface of epithelial cells. In CF the failure of CFTR channels results in the retention of Cl within the cells. A thick mucus or other secretion forms because osmotic pressure causes the excessive uptake of water. The most obvious features of CF are lung disease (obstructed air flow and chronic bacterial infections), and pancreatic insufficiency (impaired production of digestive enzymes that can result in severe nutritional deficits). In the majority of CF patients, CFTR is defective because of a deletion mutation at Phe508, which causes... 

Tuberculosis (TB) is a disease that has been known from the earliest of recorded history. It is characterized as a chronic bacterial infection caused by Mycobacterium... 

Biological Applications Calcium indicators treating cancer, chronic bacterial infection, glaucoma, ocular hypertension, HTV-associated conditions, " infectious diseases, neurodegenerative disorders, neurological conditions, psychiatric conditions Industrial Applications Not reported... 

Azenabor, A. A. Treatment of chronic bacterial infection and related pathologies. PCT Int. Appl. WO 2005007082, 2005 Chem. Abstr. 2005, 142, 127559. 

Streptomycin, being imabsorbable from the bowel, is injected intramuscularly. It leapt to fame as the first drug that could cure tuberculosis, but its toxic effect on the eighth cranial nerve often led to permanent deafness. It is now used mainly as an auxiliary to other drugs, notably isoniazid, to prevent the emergence of resistant strains in tuberculosis. Another current use of streptomycin is with either penicillin or tetracycline for treating chronic bacterial infections. 

The Center for Disease Control and Prevention conducted a randomized epidemiological study on patients who had received morphine nerve paste post-operatively for pain management purposes. Ninety-four percent of the patients used in the cohort presented themselves with surgical-site comphcations such as edema and inflammation 24 days (median) post-operation. Upon culturing of the wounds, 64% tested positive for bacterial infection. It is important to note that aU of the patients were found to have residual morphine paste on board indicative of a chronic morphine state (Sacerdote et al. 2000). 

Staphylococcus, Moraxella, or other opportunistic bacteria typically cause chronic conjunctivitis.10 Moraxella infections may cluster in groups of women who share makeup.12 Both acute and chronic bacterial conjunctivitis are self-limiting except if caused by staphylococci.13 Because of this, the pathogens are rarely cultured unless the case is unresponsive to treatment. While infection typically begins in one eye, it will often spread to both within 48 hours.11... 

Sinusitis, or inflammation of the paranasal sinuses, is better described as rhinosinusitis that also involves inflammation of contiguous nasal mucosa, which occurs in virtually all cases of viral respiratory infections. Acute rhinosinusitis is characterized by symptoms that resolve completely in less than 4 weeks, whereas chronic rhinosinusitis typically persists as cough, rhi-norrhea, or nasal obstruction for more than 90 days. Acute bacterial rhinosinusitis (ABRS) refers to an acute bacterial infection of the sinuses that can occur independently or be superimposed on chronic sinusitis. The focus of this section will be on ABRS and appropriate treatment. 

Onychomycosis is a chronic infection that rarely remits spontaneously. Adequate treatment is essential to prevent spread to other sites, secondary bacterial infections, cellulitis, or gangrene. Due to the chronic nature and impenetrability of nails, topical agents have low efficacy rates for treating onychomycosis. Oral agents that can penetrate the nail matrix and nail base, such as itraconazole and terbinafine, are more effective than ciclopirox lacquer. Itraconazole and terbinafine demonstrate mycological cure rates of 62%37 and 76%,38 respectively, while ciclopirox has a cure rate of 29% to 36%.39... 

Chronic lymphocytic leukemia in patients who have had a serious bacterial infection... 

Since cellular immunity results in the release of chemotactic lymphocytes that in turn enhance phagocytosis, a deficiency in cellular immunity may also result in chronic infections. Cellular immunity is mediated by T cells, macrophages, and NK cells involved in complex compensatory networks and secondary changes. Immunosuppressive agents may act directly by lethality to T cells, or indirectly by blocking mitosis, lymphokine synthesis, lymphokine release, or membrane receptors to lymphokines. In addition, cellular immunity is involved in the production and release of interferon, a lymphokine that ultimately results in blockage of viral replication (Table 15.4). Viruses are particularly susceptible to cytolysis by T cells since they often attach to the surface of infected cells. Thus, immunosuppression of any of the components of cellular immunity may result in an increase in protozoan, fungal, and viral infections as well as opportunistic bacterial infections. 

The O2 formed by NADPH oxidase activity can rapidly be converted into H2O2 and other toxic species that destroy microorganisms and impart injury to surrounding host tissue. The most direct evidence for the role of NADPH oxidase in host defense has come from studies of patients who have genetic defects in NADPH oxidase activity (chronic granulomatous disease). Chronic granulomatous disease patients suffer from recurrent, severe bacterial infections, which are often fatal in early childhood. 

What has been achieved until now In the year 2001, several liposome and antibody based strategies have been or will soon be approved for clinical application, some for the treatment of cancer, some for the treatment of bacterial infections, some for chronic inflammatory diseases. Furthermore many monoclonal antibodies without a drug or pharmacologically active molecule attached are in the clinic. Their intrinsic targeting and effector function is obviously sufficient for the pharmacological effect. 

Dust particles inhaled in tobacco smoke, together with bronchial mucus, must be removed from the airways by the ciliated epithelium. Ciliary activity, however, is depressed by tobacco smoke mucociliary transport is impaired. This depression favors bacterial infection and contributes to the chronic bronchitis associated with regular smoking. Chronic injury to the bronchial mucosa could be an important causative factor in increasing the risk in smokers of death from bronchial carcinoma. 

Secondary bacterial infection of acute bronchitis and acute bacterial exacerbation of chronic bronchitis 500q12 h 10... 

Acute Bacterial exacerbation of chronic Bronchitis, secondary Bacterial infection of acute Bronchitis PO 500 mg ql2h for 10 days. 

Chronic lymphocytic leukemia (CLL) Immune globulin (IV)2 400 mg/kg IV every 3-4 weeks. Dosage should be adjusted upward if bacterial infections occur. CLL patients with hypogammaglobulinemia and a history of at least one serious bacterial infection. 

The evidence that O is a product of the burst has already been summarized. Another direct consequence of the formation of O is the reduction of nitroblue tetrazolium to form an insoluble deposit of blue formazan. The reduction of nitro blue tetrazolium had been observed to occur in PMNs in patients with bacterial infections. In intact cells this appears to be a consequence of the formation of O it fails to occur in PMNs from patients with chronic granulomatous disease which cannot undergo the respiratory burst it is diminished by anaerobiosis and it is inhibitable by superoxide dismutase... 

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