Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In chronic granulomatous disease (CGD) enzyme-deficient neutrophils and mononuclear cells lack the respiratory burst required for biocidal activity. Recurrent infections lead to granulomas in various organs but brain lesions are rare. In the present case, a 23-year-old male with numerous infections since early childhood died of overwhelming pulmonary aspergillosis. He first began to experience neurological deficits at the age of 17. Computerized tomography and magnetic resonance imaging revealed fleeting white matter lesions that were interpreted as multiple sclerosis (MS). At post mortem, three types of brain lesions were found: (1) Pigmented macrophages in perivascular spaces and the leptomeninges similar to those reported previously. They contained fine, golden-brown, lipofuscin-like material whose chemical composition included a sulfur peak by X-ray analysis. (2) Focal, well-demarcated, "burnt out" white matter lesions with loss of both myelin and axons and intense sclerosis. (3) Diffuse areas of mild pallor in the centrum ovale which spared the U fibers. The pigmented macrophages are characteristic of those seen in the periphery in CGD. The origin of the discrete, destructive white matter lesions is unclear. They may have resulted from: (i) earlier activity by CGD macrophages; (ii) previous infections due to sepsis or embolism; or (iii) possibly post-infectious encephalomyelitis. The more diffuse, mild, white matter lesions are attributed to edema. Evidence for MS, progressive multifocal leukoencephalopathy, or human immunodeficiency virus encephalitis was lacking. This case is presented to alert us to look more carefully for brain lesions in CGD, characterize them and to help determine their cause.
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PMID:Brain lesions in chronic granulomatous disease. 202 50

To determine whether immunosuppression by total lymphoid irradiation (TLI) slowed deterioration of chronic progressive multiple sclerosis (MS), functional impairment score and blood lymphocyte counts were compared at 6-month intervals through 4 years following treatment of MS patients by either TLI (n = 27) or sham irradiation (n = 21). At each interval, 20 to 30% fewer TLI-treated patients had deteriorated (p less than 0.05 at 6, 12, and 18 months), and the difference in mean functional impairment score between groups became progressively greater (p less than 0.01 at 42 and 48 months). Benefit accrued principally to the 17 TLI-treated patients with absolute blood lymphocyte counts less than 900/mm3 3 months after treatment, whose mean functional impairment score remained within 0.6 units of baseline (p = NS), whereas the ten TLI patients with higher post-treatment lymphocyte counts had progressive deterioration (p less than 0.05 to p less than 0.001 versus TLI-treated patients with lower lymphocyte counts at all intervals except 30 months) and had deteriorated by more than 5 functional scale units by 42 and 48 months. Side effects were minor and complications rare in TLI-treated patients, but one TLI-treated patient developed staphylococcal sepsis. Thus, TLI slows deterioration of chronic progressive MS, with what appears to be enduring benefit through 4 years compartmented to patients with greater induced lymphopenia. Modification of lymphoid irradiation regimens to increase the proportion of MS patients who achieve a favorable degree of lymphopenia and to avert functional hyposplenism may further improve the benefit/risk ratio.
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PMID:Effect of total lymphoid irradiation on functional status in chronic multiple sclerosis: importance of lymphopenia early after treatment--the pros. 329 Jul 13

This study explored the prevalence of comorbid conditions in hospitalized patients with multiple sclerosis (MS) who were 65 years of age or older. Using 1989 data from the Quality of Care Medicare Provider Analysis and Review (MEDPAR) file, hospitalized MS patients were compared with respect to discharge diagnoses to an age- and sex-matched group of hospitalized patients without MS. As expected, the following discharge diagnoses were more common (P < 0.05) for MS patients: urinary tract infection, pneumonia, septicemia and cellulitus. In contrast, MS patients were less likely (P < 0.05) to have discharge diagnoses of acute myocardial infarction, heart failure, hypertension, angina pectoris, cerebrovascular disease, diabetes mellitus and chronic obstructive pulmonary disease. Possible explanations include under-reporting of certain comorbid conditions on discharge records of MS patients, a protective effect of MS or its treatment, reduced prevalence of risk factors, disproportionate mortality in younger MS patients with comorbidity and the benefits of medical surveillance.
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PMID:Patterns of comorbidity in elderly patients with multiple sclerosis. 772 46

Topics include treatment of multiple sclerosis (MS) with T cell receptor (TCR) peptides, rheumatoid arthritis (RA) with IL-1ra, IL-2 toxin conjugate, or antibodies to TNF, to CD4, or to ICAM-1, sepsis and five other diseases with IL-1ra, and treatment of experimental animal diseases with soluble receptors, IL-12, TGF-beta2, or small molecule antagonists of cytokines.
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PMID:Clinical and preclinical studies presented at the Keystone Symposium on Arthritis, Related Diseases, and Cytokines. 821 99

The pathophysiology of organ system failure in sepsis, in particular the effects of septic shock on the central nervous system, are still incompletely understood. Lipopolysaccharide (LPS) from Gram-negative bacteria affects the permeability of the blood-brain barrier and causes the activation of brain microglia. A growing body of research supports involvement of activated brain microglia in brain pathologies caused by infectious diseases, trauma, tumors, ischemia, Alzheimer's disease, Parkinson's disease, Down's syndrome, multiple sclerosis and AIDS. Those seminal studies that have contributed to the characterization of the in vivo and in vitro effects of LPS on microglia function, mediator generation and receptor expression are presented within a historical perspective. In particular, all those in vitro studies on O2-, H2O2 and NO. generation by either unprimed or primed microglia have been extensively reviewed. The apparent controversial effect of LPS on microglia O2- is discussed. Because treatment modalities for septic shock have not significantly affected the current high mortality, alternative strategies with antioxidants are currently being investigated. Reduction of microglia O2- generation is proposed as a possible complementary strategy to antioxidative therapy for septic shock and CNS pathologies that involve activated microglia.
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PMID:Therapeutic implications of microglia activation by lipopolysaccharide and reactive oxygen species generation in septic shock and central nervous system pathologies: a review. 981

Tyrosine kinase blockers from the AG 126/AG-556 tyrphostin family are shown to inhibit the lipopolysaccharide (LPS)-induced production of tumor necrosis factor alpha (TNFalpha), nitric oxide (NO), and prostaglandin E2 (PGE2) in primary rat astrocytes cultures. The tyrphostin AG-556 which was previously shown to be effective against sepsis in mice and dogs also show excellent efficacy in inhibiting experimental autoimmune encephalomyelitis (EAE) in mice. AG-556 does not block the activation of JNK/SAPK and of p38/HOG and therefore seems to act at a target down stream to these kinases which is activated in stress or at a target on an obligatory parallel pathway. These findings together with previous results showing inhibition of sepsis in mice and dogs suggest that protein tyrosine kinase (PTK) blockers of the AG-556 family may be considered in the management of human autoimmune disorders such as multiple sclerosis (MS).
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PMID:Suppression of experimental autoimmune encephalomyelitis by tyrphostin AG-556. 987 84

A 60-year-old woman with multiple sclerosis and recurrent urinary tract infections (UTI) was evaluated for the recent onset of a dry cough, dyspnea on exertion, and jaundice. Investigation demonstrated interstitial lung disease with bilateral infiltrates and unilateral effusion, as well as a severe chronic active hepatitis with marked fibrosis. Other notable features were positive antinuclear antibodies and anti-smooth-muscle antibodies and the absence of any possible cause except for nitrofurantoin treatment (Macrodantin, 100 mg/day), which the patient had been taking for the previous 3 years as a prophylactic measure against UTI. The patient died of pneumococcal septicemia less than 30 days after presentation. Pulmonary or hepatic injury caused by nitrofurantoin treatment is rare; their combined occurrence is hardly ever described. Combined drug-induced pulmonary and hepatic toxicity is reviewed and should be considered early in the differential diagnosis to allow reversibility and avoid serious outcomes.
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PMID:Nitrofurantoin-induced immune-mediated lung and liver disease. 1033 21

Multiple sclerosis (MS) is an immune-mediated disease that may be amenable to high-dose immunosuppression with peripheral blood stem cell transplantation (SCT) in selected patients. Five MS patients (all women, ages 39-47 years) received granulocyte colony-stimulating factor (G-CSF) for stem cell mobilization, CD34 cell selection for T-cell depletion, a preparatory regimen of busulfan (1 mg/kg x 16 doses) and cyclophosphamide (120 mg/kg), and antithymocyte globulin (10 mg/kg x 3 doses) at the time of stem cell infusion. Days required to recover absolute neutrophil count >500 were 12 to 14 and platelet count >20,000 were 17 to 58. Posttransplantation infectious complications in the first year after SCT occurred in 3 of 5 patients, and 1 patient died at day 22 after SCT from influenza A pneumonia. Neuropathologic study in this patient showed demyelinating plaques with surrounding macrophages but only rare T cells. In 2 patients, MS flared transiently with G-CSF. Magnetic resonance imaging gadolinium enhancement was present in 3 of 5 patients before transplantation and 0 of 4 after SCT. There were cerebrospinal fluid oligoclonal bands at 1 year after SCT, similar to the pretransplantation assays. Sustained suppression of peripheral blood mononuclear cell proliferative responses to myelin antigens occurred after SCT, but new responses to some myelin peptide fragments also developed after SCT. In 1 patient, enzyme-linked immunospot (ELISPOT) assays done 9 months after SCT showed a predominant T helper 2 (Th2) cytokine pattern. Neurological progression of 1 point on the extended disability status scale was seen in 1 patient 17 months after SCT. Another patient who was neurologically stable died abruptly 19 months after SCT from overwhelming S. pneumoniae sepsis. The remaining patients have had stable MS (follow-up, 18 and 30 months). In summary, our experience confirms the high-risk nature of this approach. Further studies and longer follow-up would be needed to determine the significance of new lymphocyte proliferative responses after SCT and the overall effect of this treatment on the natural history of MS.
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PMID:Peripheral blood stem cell transplantation in multiple sclerosis with busulfan and cyclophosphamide conditioning: report of toxicity and immunological monitoring. 1107 Dec 62

Misoprostol, a prostaglandin E1 analog, is a racemate of four stereoisomers. On administration it rapidly de-esterifies to its active form, misoprostolic acid. Misoprostolic acid is 85% albumin bound and has a half-life of approximately 30 minutes. It is excreted in urine as inactive metabolites. No significant drug interactions have been reported. Besides its gastrointestinal protective and uterotonic activities, misoprostol regulates various immunologic cascades. It inhibits platelet-activating factor and leukocyte adherence, and modulates adhesion molecule expression. It protects against gut irradiation injury, experimental gastric cancer, enteropathy, and constipation. It improves nutrient absorption in cystic fibrosis. Misoprostol has utility in acetaminophen and ethanol hepatotoxicity, hepatitis, and fibrosis. It is effective in asthmatics and aspirin-sensitive asthmatic and allergic patients. It lowers cholesterol and severity of peripheral vascular diseases, prolongs survival of cardiac and kidney transplantation, synergizes cyclosporine, and protects against cyclosporine-induced renal damage. It works against drug-induced renal damage, interstitial cystitis, lupus nephritis, and hepatorenal syndrome. It is useful in periodontal disease and dental repair. Misoprostol enhances glycosoaminoglycan synthesis in cartilage after injury. It prevents ultraviolet-induced cataracts and reduces intraocular pressure in glaucoma and ocular hypertension. It synergizes antiinflammatory and analgesic effects of diclofenac or colchicine and has been administered to treat trigeminal neuralgic pain. It reduces chemotherapy-induced hair loss and recovery time from burn injury, and is effective in treating sepsis, multiple sclerosis, and pancreatitis.
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PMID:Misoprostol therapeutics revisited. 1119 38

Ciguatera poisoning, a toxinological syndrome comprising an enigmatic mixture of gastrointestinal, neurocutaneous and constitutional symptoms, is a common food-borne illness related to contaminated fish consumption. As many as 50000 cases worldwide are reported annually, and the condition is endemic in tropical and subtropical regions of the Pacific Basin, Indian Ocean and Caribbean. Isolated outbreaks occur sporadically but with increasing frequency in temperate areas such as Europe and North America. Increase in travel between temperate countries and endemic areas and importation of susceptible fish has led to its encroachment into regions of the world where ciguatera has previously been rarely encountered. In the developed world, ciguatera poses a public health threat due to delayed or missed diagnosis. Ciguatera is frequently encountered in Australia. Sporadic cases are often misdiagnosed or not medically attended to, leading to persistent or recurrent debilitating symptoms lasting months to years. Without treatment, distinctive neurologic symptoms persist, occasionally being mistaken for multiple sclerosis. Constitutional symptoms may be misdiagnosed as chronic fatigue syndrome. A common source outbreak is easier to recognize and therefore notify to public health organizations. We present a case series of four adult tourists who developed ciguatera poisoning after consuming contaminated fish in Vanuatu. All responded well to intravenous mannitol. This is in contrast to a fifth patient who developed symptoms suggestive of ciguatoxicity in the same week as the index cases but actually had staphylococcal endocarditis with bacteraemia. In addition to a lack of response to mannitol, clinical and laboratory indices of sepsis were present in this patient. Apart from ciguatera, acute gastroenteritis followed by neurological symptoms may be due to paralytic or neurotoxic shellfish poisoning, scombroid and pufferfish toxicity, botulism, enterovirus 71, toxidromes and bacteraemia. Clinical aspects of ciguatera toxicity, its pathophysiology, diagnostic difficulties and epidemiology are discussed.
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PMID:Ciguatera poisoning: a global issue with common management problems. 1178 97


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