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)

The Wiskott-Aldrich syndrome is an uncommon X-linked recessive disease characterized by eczema, thrombocytopenia, and immunodeficiency. The clinical features begin early in life and include recurrent infections, bleeding, and severe eczema. Unless the condition is treated by bone marrow transplantation, the prognosis of Wiskott-Aldrich syndrome is grave, and premature death caused by sepsis, hemorrhage, or lymphoreticular malignancy is common. Although the biochemical defect responsible for the syndrome is not known, recent investigations with restriction fragment length polymorphisms have mapped the Wiskott-Aldrich syndrome locus to the proximal portion of the short arm of the human X chromosome (Xp11). The isolation of these DNA markers makes feasible both carrier detection and prenatal diagnosis of Wiskott-Aldrich syndrome and provides an important adjunct to the management of Wiskott-Aldrich syndrome for patients and their families. These genetic data, in conjunction with the recent identification of a specific O-glycosylation defect in lymphocytes from patients with Wiskott-Aldrich syndrome, present an opportunity for the eventual isolation of the Wiskott-Aldrich syndrome gene and identification of the underlying cellular defect. We review the clinical and laboratory features of this syndrome and summarize the new molecular and biochemical approaches that can be used in diagnosis, genetic counseling, and treatment.
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PMID:Wiskott-Aldrich syndrome: new molecular and biochemical insights. 140 1

Septicemia is a rare complication of platelet transfusion. A case is reported of transfusion-associated septicemia in a 66-year-old man who received a 10-unit pool of platelets. During transfusion, he experienced rigors, wheezing, dyspnea, and fever. A total of four blood cultures drawn 10 and 36 hours after discontinuation of the transfusion grew Staphylococcus epidermidis. Culture of the residual platelet pool yielded S. epidermidis with a colony count of 10(5) organisms per mL. Strain identity of all four blood isolates and the platelet pool isolate was confirmed by gel electrophoresis of EcoRI and HindIII restriction digests of whole-cell DNA. There have been 31 prior reported cases of platelet transfusion-associated septicemia, of which 9 have been caused by coagulase-negative staphylococci. Systemic reactions to platelet transfusions should prompt consideration of transfusion-associated bacteremia as the cause.
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PMID:Staphylococcus epidermidis bacteremia from transfusion of contaminated platelets: application of bacterial DNA analysis. 141 88

Pearson's syndrome is a disease of refractory sideroblastic anemia and exocrine pancreatic dysfunction due to abnormal mitochondrial DNA (mtDNA). A male infant with Pearson's syndrome developed necrosis of both thalami and basal ganglia when he suffered from gastroenteritis at 1 year and 11 months of age. He died of sepsis at the age of 2 years and 4 months. Analysis of mtDNA from various organs revealed abnormal mtDNA with deletion by 5 kbp, confirming the diagnosis. At autopsy, the brain had symmetrical cavities in putamen, caudate nuclei and medial nuclei of the thalami. Ferruginous granules in nerve cells in medial thalamic nuclei, and scattered round bodies with neuronophagia in lateral nuclei were found at light microscopic observation. Electron microscopy showed that these granules were composed of radiating spicules and a dense layer containing packed cytoplasmic organelles, respectively. The macroscopic distribution of brain lesions was very similar to and characteristic of Leigh's disease. This similarity leads to the supposition that defective intracellular energy utilization common to Leigh's disease could be responsible for brain lesions in this case. Although the histological appearance was somewhat atypical for Leigh's disease, very acute formation of brain lesions in this case was thought to have caused the histological difference.
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PMID:Brain lesions of the Leigh-type distribution associated with a mitochondriopathy of Pearson's syndrome: light and electron microscopic study. 141 84

Thirty-four women with metastatic breast cancer were treated at the National Cancer Institute of the National Institutes of Health, with a regimen of leucovorin (L), 500 mg/m2 i.v. over 30 min, followed in 1 h by 5-fluorouracil (5-FU), 375 mg/m2 i.v. bolus on days 1-5, and carboplatin (CBDCA), 50-100 mg/m2 i.v. bolus on days 2-4, every 28 days. All patients had received previous combination chemotherapy with at least one regimen (29 patients with 5-FU-containing regimens). CBDCA, 100 mg/m2 on days 2-4, resulted in grade 4 neutropenia in 10 out of 11 patients associated with sepsis in all 10 patients. CBDCA, 75 mg/m2 (seven patients) and 50 mg/m2 (15 patients), resulted in grade 4 neutropenia in six and eight patients, and neutropenic sepsis in five and two cases, respectively. Grade 4 thrombocytopenia occurred in 10, five and two patients receiving 100, 75 and 50 mg/m2 of CBDCA, respectively. Other toxicities included grade 3/4 mucositis in 18 patients and grade 3/4 diarrhea in 10 patients. Twenty nine patients were evaluable for response, with one pathologic complete response (3%), two partial responses (6%), 18 stable disease (53%) and eight (24%) progressive disease. Sites of response included bone, viscera and soft tissue. The median time from entry on study to progression, for responders, was 15 months. When platinum-DNA adduct formation in peripheral white blood cells was analyzed in 27 patients at 24 h after drug administration, a significant correlation between adduct level and CBDCA cumulative dose was found.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Therapy of patients with metastatic breast cancer with 5-fluorouracil, leucovorin and carboplatin. 145 Apr 39

Group B streptococci (GBS) are the most common cause of pneumonia and sepsis during the neonatal period; however, the pathogenesis of this infection is poorly understood. We investigated the ability of GBS to enter epithelial cells in culture. Two strains of GBS were capable of invading immortalized respiratory epithelial cell lines in vitro at different levels, suggesting strain differences in invasiveness. Intracellular replication was not observed. Invasion required actin microfilaments but not microtubular cytoskeletal elements. Active bacterial protein, DNA, and RNA syntheses were required for invasion. These findings are consistent with our previous observation of intracellular GBS in the lungs of infected primates. We hypothesize that this organism may access the bloodstream by direct invasion of the epithelial cell barrier.
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PMID:Respiratory epithelial cell invasion by group B streptococci. 145 49

Pseudomonas aeruginosa remains a cause of serious wound infection and mortality in burn patients. By means of restriction fragment length polymorphism analysis and a DNA probe for the pilin gene of Pseudomonas, a lethal strain of nosocomial P. aeruginosa was identified as the cause of an outbreak of wound infections among burn patients. Environmental surveys suggested an association of the outbreak with hydrotherapy provided to many patients in a common facility. In a trial of burn wound care without hydrotherapy, overall mortality was reduced significantly, mortality associated with pseudomonas sepsis was eliminated, and the strain of P. aeruginosa associated with earlier mortality was eradicated. Moreover, fewer nosocomial pseudomonas infections, lower levels of pseudomonas resistance to aminoglycoside antibiotics, significantly fewer pseudomonas infections of skin graft donor sites, and later appearance of Pseodomonas species in burn patients were found during the period when hydrotherapy was not used.
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PMID:Epidemiology of infections with Pseudomonas aeruginosa in burn patients: the role of hydrotherapy. 145 65

Since the development of recombinant DNA technology, there has been a rapid expansion of research concerning the use of recombinant DNA synthesized human growth hormone (rhGH) for the treatment of clinical disorders. rhGH has been used to treat patients with acute catabolic stress caused by surgery, trauma and sepsis, children with chronic renal insufficiency and impaired growth, patients undergoing maintenance hemodialysis who are malnourished, and individuals on weight reduction diets. These studies indicate that rhGH enhances protein balance in acutely stressed patients and in malnourished maintenance hemodialysis patients, promotes catch-up growth in children with chronic renal failure, and may reduce protein wasting and enhance lipolysis in obese individuals on weight reduction diets. Experimental studies suggest that in addition to enhancing anabolism, rhGH may increase both immune function and the rate of wound healing. Many, but not all, of the effects of rhGH are mediated through insulin-like growth factor I (IGF-I). For example, the hyperglycemic and lipolytic effects of rhGH do not seem to be caused by IGF-I. Animal or human studies suggest that with severe malnutrition or severe sepsis, rhGH treatment may neither increase serum IGF-I levels nor promote anabolism. These observations provide a rationale for administering IGF-I as an anabolic hormone for severely malnourished or septic patients with renal failure. Further studies will be necessary to examine both the short-term and long-term potential benefits and adverse effects of rhGH or rhIGF-I treatment in these conditions.
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PMID:The rationale for the use of growth hormone or insulin-like growth factor I in adult patients with renal failure. 146 73

To assess the role of enterovirulent Escherichia coli at home and abroad, faeces samples of patients with diarrhoea and of healthy controls in Tunisia, Seville (southern Spain) and the Netherlands were investigated. Enterovirulent E. coli were identified by hybridization with five different non-radioactively labelled DNA probes specific for enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC) and verocytotoxin producing E. coli (VTEC). ETEC was the main causative agent of travellers' diarrhoea in Tunisia. The isolation of ETEC in the Netherlands was shown to be related to travel in endemic areas. EPEC probe positive strains were isolated in children and in adults, but were not in all cases associated with intestinal disease. During this study no VTEC were detected. From an immunocompromised kidney transplantation patient with sepsis and diarrhoea ETEC were isolated from blood.
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PMID:[Detection of diarrhea-causing Escherichia coli using DNA-probes]. 148 Feb 42

A steroid binding capacity assay and a radioimmunoassay were both used to measure corticosteroid binding globulin (CBG) in serum samples from 22 patients with sepsis. An approximately 50% discordancy between the two values in one patient suggested the presence of a CBG variant with reduced affinity for cortisol, and this was confirmed by Scatchard analysis. We therefore used the polymerase chain reaction to amplify exons that encode for human CBG from the genomic DNA of this patient. This revealed two mutations within the coding sequences: one of which results in a Leu----His substitution at residue 93 and another which encodes a Ser----Ala substitution at residue 224 of the human CBG polypeptide. To assess the impact of each substitution on the steroid binding affinity of CBG, each mutation was introduced separately into a normal human CBG cDNA, and the normal and mutated cDNAs were expressed in Chinese hamster ovary cells. Scatchard analysis of the CBG produced in culture indicated that the His93 mutation (Kd = 2.24 +/- 1.75 nM) reduced the cortisol binding affinity of CBG (mean +/- SD) significantly (P less than 0.024) when compared to normal CBG (Kd = 0.64 +/- 0.31 nM), while the Ala224 mutation (Kd = 0.63 +/- 0.33 nM) did not influence cortisol binding affinity. We therefore conclude that residue 93 may play an important role in determining the structure of the CBG steroid binding site.
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PMID:A Leu----His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol. 150 7

Freedom from infection is the result of many tiers of immune defenses that harmoniously interact to rid the body of microorganisms and their products, which are perceived as foreign. The ability to distinguish self from nonself is embodied in lymphocytes, which serve both effector and regulatory functions. Through the elaboration of cytokines and immunoglobulins, lymphocytes recruit nonspecific immune effectors, focus their activity, and modulate the intensity of the immune response. The phylogenetically more primitive complement system serves a similar function. Although congenital defects in immune function occur, by far the most common causes of immunodeficiency are acquired and occur in patients treated for cancer with myelosuppressive, cytolytic drugs and in transplant recipients treated with immunosuppressants. HIV infection and malnutrition are responsible for even larger numbers of immunocompromised patients worldwide. The nature and severity of infections that occur as a result of immunodeficiency vary as a function of the immune effector targeted and the degree to which it is dysfunctional. Granulocytopenia is well tolerated unless the absolute number of circulating cells falls below 500/mm3. Profound granulocytopenia and deficits of neutrophil function are often manifest as bacterial or fungal infections. Complement deficiency predisposes to infection with encapsulated bacteria such as pneumococci, meningococci, and Haemophilus influenzae. T cells play such a central role in the immune response that their derangement is associated with susceptibility to almost any potential pathogen. These patients often succumb to mortal opportunistic infections. Recent advances in hybridoma and recombinant DNA technology have provided us with immunologic reagents that enable us to manipulate the immune response. Anti-CD3 monoclonal antibody has permitted salvage of solid organ transplants in well-defined clinical settings. Monoclonal antibodies against TNF-alpha and lipopolysaccharide may alter the consequences of gram-negative sepsis. Alternatively, recombinant cytokines have been associated with clinically significant tumor regression in selected patients, presumably by enhancing the nascent antitumor immune response. The development of immunologic reagents such as these in concert with our growing understanding of the immune system may translate to improved care for immunocompromised patients.
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PMID:Immune function and dysfunction. A primer for the radiologist. 157 Mar 93


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