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Query: UMLS:C0011849 (diabetes)
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Melioidosis is endemic in South East Asia, Asia and northern Australia. Infection usually follows percutaneous inoculation or inhalation of the causative bacterium, Burkholderia pseudomallei, which is present in soil and surface water in the endemic region. While 20-36% of melioidosis cases have no evident predisposing risk factor, the vast majority of fatal cases have an identified risk factor, the most important of which are diabetes, alcoholism and chronic renal disease. Half of all cases present with pneumonia, but there is great clinical diversity, from localised skin ulcers or abscesses without systemic illness to fulminant septic shock with multiple abscesses in the lungs, liver, spleen and kidneys. At least 10% of cases present with a chronic respiratory illness (sick > 2 months) mimicking tuberculosis and often with upper lobe infiltrates and/or cavities on chest radiography. As with tuberculosis, latency with reactivation decades after infection can also occur, although this is rare. Confirmation of diagnosis is by culture of B. pseudomallei from blood, sputum, throat swab or other samples. Microbiology laboratories need to be informed of the possibility of melioidosis, as those not familiar with it can misidentify the organism. Antibiotic therapy is initial intensive therapy with i.v. ceftazidime or meropenem or imipenem +/- cotrimoxazole for > or = 10 days, followed by eradication therapy with cotrimoxazole +/- doxycycline +/- chloramphenicol (first 4 weeks only) for > or = 3 months. Melioidosis has been increasingly recognised in returning travellers in Europe and recently melioidosis and colonisation with B. pseudomallei have been documented in cystic fibrosis patients visiting or resident in endemic areas.
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PMID:Melioidosis: an important cause of pneumonia in residents of and travellers returned from endemic regions. 1451 49

Burkholderia pseudomallei (melioidosis) is usually found in endemic areas of Southeast Asia and Northern Australia. However, a few cases of confirmed melioidosis indigenous to Puerto Rico and the Americas have been reported previously. We describe the occurrence of a B. pseudomallei infection in a female with insulin-dependent diabetes mellitus exposed to flood waters in Puerto Rico. We conclude that B. pseudomallei should be considered a potential pathogen in high-risk patients with severe community-acquired pneumonia and sepsis in Puerto Rico especially in individuals exposed to flood waters during rainy seasons. A more thorough epidemiologic and microbiologic surveillance with environmental sampling may be warranted in the island.
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PMID:Severe community-acquired pneumonia and sepsis caused by Burkholderia pseudomallei associated with flooding in Puerto Rico. 1544 87

Between 1996 and 2002, 162 cases of pulmonary melioidosis were reported from Srinagarind Hospital, Khon Kaen, northeast Thailand, 90 acute vs 72 subacute/chronic. Patients averaged 50 years of age and half worked as farmers. The male to female ratio was between 2 and 3 to 1 depending on the subgrouping. Burkholderia pseudomallei was confirmed by a culture or a four-fold rise in titer in the majority of cases, while the others were presumptive diagnoses based on response to treatment. Pulmonary melioidosis presented as either acute fulminant pneumonia or as an indolent disease. The common concurrent medical illness was diabetes mellitus. Mean incubation of the acute vs the sub-acute/chronic form was 8.7 vs 54.4 days, respectively. Leukocytosis was detected in 70% of cases. Sputum Gram's stain was not sensitive for diagnosis. Sputum culture and blood culture were diagnostic for 31.1 vs 22.2 and 40 vs 37.5% of the acute vs subacute/chronic forms, respectively. The common radiographic patterns for acute pneumonia were localized patchy alveolar infiltrate or hematogenous pattern. A bilateral diffuse patchy alveolar infiltration or multiple nodular lesions characterized the latter. Upper-lobe involvement with early cavitation and rapid progression were common. In the subacute/chronic forms, the radiographic pattern sometimes mimicked tuberculosis, with upper lobe involvement, patchy alveolar infiltrate with cavities or fibroreticular lesions. In approximately 30% of cases, liver and/or splenic abscess were common sites of extrapulmonary infection. Respiratory failure and septic shock from acute pulmonary melioidosis was 20% fatal. Early empirical antibiotic therapy should be given for severe pneumonia.
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PMID:Clinical manifestation of pulmonary melioidosis in adults. 1568 84

A rare case of pulmonary melioidosis is reported. The patient was a 62-year-old man presenting with subacute fever, dry cough, and significant weight loss. A chest x-ray revealed a right paratracheal mass. The findings from fiberoptic bronchoscopy were a blunt carina and normal tracheobronchial tree. The patient had an underlying disease of poorly controlled diabetes mellitus, heavy smoking, and heavy alcoholic drinking. One of the two cultured blood specimens grew B. pseudomallei. The pathological finding of transbronchial biopsy at the apical segment of the right upper lung showed lymphocytic infiltrates. He was treated with two weeks of intravenous ceftazidime plus cotrimoxazole followed by 5 months of oral doxycycline plus cotrimoxazole. Clinical symptoms significantly improved and the right paratracheal mass disappeared.
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PMID:Pulmonary melioidosis presenting with right paratracheal mass. 1569 Nov 41

Melioidosis, caused by the gram-negative saprophyte Burkholderia pseudomallei, is a disease of public health importance in southeast Asia and northern Australia that is associated with high case-fatality rates in animals and humans. It has the potential for epidemic spread to areas where it is not endemic, and sporadic case reports elsewhere in the world suggest that as-yet-unrecognized foci of infection may exist. Environmental determinants of this infection, apart from a close association with rainfall, are yet to be elucidated. The sequencing of the genome of a strain of B. pseudomallei has recently been completed and will help in the further identification of virulence factors. The presence of specific risk factors for infection, such as diabetes, suggests that functional neutrophil defects are important in the pathogenesis of melioidosis; other studies have defined virulence factors (including a type III secretion system) that allow evasion of killing mechanisms by phagocytes. There is a possible role for cell-mediated immunity, but repeated environmental exposure does not elicit protective humoral or cellular immunity. A vaccine is under development, but economic constraints may make vaccination an unrealistic option for many regions of endemicity. Disease manifestations are protean, and no inexpensive, practical, and accurate rapid diagnostic tests are commercially available; diagnosis relies on culture of the organism. Despite the introduction of ceftazidime- and carbapenem-based intravenous treatments, melioidosis is still associated with a significant mortality attributable to severe sepsis and its complications. A long course of oral eradication therapy is required to prevent relapse. Studies exploring the role of preventative measures, earlier clinical identification, and better management of severe sepsis are required to reduce the burden of this disease.
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PMID:Melioidosis: epidemiology, pathophysiology, and management. 1583 29

A patient with musculoskeletal melioidosis masquerading as diabetic amyotrophy is described. A 43-year-old man presented with left thigh pain, fever, malaise and loss of weight. He had diabetes mellitus for six years. He was initially diagnosed with diabetic amyotrophy and was treated conservatively. Recurrence of symptoms prompted further investigations which revealed melioidosis of the left femur. Magnetic resonance imaging showed an enhancing subperiosteal collection. The diagnosis was confirmed by open biopsy and tissue culture. Acute treatment consisted of intravenous ceftazidime for 24 days and oral cotrimoxazole. The patient showed marked improvement clinically and biochemically. He was discharged with oral doxycycline and cotrimoxazole for three months. This disease is eminently treatable, but can be a diagnostic challenge when it presents in an uncommon site.
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PMID:Musculoskeletal melioidosis masquerading as diabetic amyotrophy. 1585 93

Melioidosis is associated with significant mortality in countries in which it is endemic. Previous studies have demonstrated that quantitative Burkholderia pseudomallei counts in blood are predictive of mortality. Here we examine the relationship between outcomes and quantitative B. pseudomallei counts in urine. A total of 755 patients presenting to Sappasithiprasong Hospital, Ubon Ratchathani, northeast Thailand (in the northeast part of the country), with melioidosis between July 1993 and October 2003 had quantitative urine cultures performed within 72 h of admission. Urine culture results were divided into the following groups: (i) no growth of B. pseudomallei from a neat sample or pellet, (ii) positive result from a centrifuged pellet only (< 10(3) CFU/ml), (iii) detection of between 10(3) CFU/ml and 10(5) CFU/ml from a neat sample, or (iv) detection of > or = 10(5) CFU/ml from a neat sample. The overall in-hospital mortality rate was 45%. Patients with negative urine cultures had the lowest death rate (39%). Mortality rates rose with increasing B. pseudomallei counts in urine, from 58% for those with positive spun pellets only to 61% for those with between 10(3) CFU/ml and 10(5) CFU/ml and 71% for those with > or = 10(5) CFU/ml. This was independent of age, presence of bacteremia, known risk factors for melioidosis such as diabetes, and the prior administration of antibiotics. The presence of B. pseudomallei in urine during systemic infection is associated with a poor prognosis.
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PMID:Role and significance of quantitative urine cultures in diagnosis of melioidosis. 1587 55

The incidence of diabetic nephropathy has been increasing. Studies have shown that oxidative stress (due to increased oxidant production and/or decreased antioxidant activity) is a critical underlying mechanism. The principal intracellular reductant is NADPH whose production is mainly dependent on glucose-6-phosphate dehydrogenase (G6PD) activity. Our work in cultured cells previously showed that high glucose caused activation of protein kinase A (PKA) and subsequent phosphorylation and inhibition of G6PD activity and hence decreased NADPH (Zhang Z, Apse K, Pang J, and Stanton RC. J Biol Chem 275:40042-40047, 2000). The purpose of this study was to determine whether these findings occur in diabetic rats (induced by streptozotocin) compared with control. G6PD activity and accordingly NADPH levels and glutathione levels were significantly decreased in diabetic kidneys compared with control kidneys. Lipid peroxidation was significantly increased, which correlated with decreased G6PD activity (r = 0.48). G6PD expression was significantly reduced, which correlated with decreased G6PD activity (r = 0.72). PKA activity and serine phosphorylation of G6PD were significantly increased and were closely correlated with decreased G6PD activity (r = 0.51 for PKA activity; r = 0.93 for serine phosphorylation of G6PD). Insulin treatment and/or correction of hyperglycemia ameliorated the changes caused by diabetes. In conclusion, chronic hyperglycemia caused inhibition of G6PD activity via decreased expression and increased phosphorylation of G6PD, which therefore led to increased oxidative stress.
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PMID:Diabetes causes inhibition of glucose-6-phosphate dehydrogenase via activation of PKA, which contributes to oxidative stress in rat kidney cortex. 1595 80

A retrospective study was performed on culture-positive patients (n = 57) with melioidosis presenting to the Townsville Hospital to define the epidemiology of the disease in Queensland, Australia. Mortality was 25% (n = 14) with a 9% (n = 5) relapse rate. At presentation, primary organs involved included the lungs (58%; n = 33), genitourinary system (11%; n = 6), skin and soft tissue (9%; n = 5), bone and joints (4%; n = 2), central nervous system (4%; n = 2), mycotic aneurysm (2%; n = 1) and peritonitis (2%; n = 1). No focus of infection could be identified in 12% of cases (n = 7). There was no significant difference in the clinical presentation of melioidosis in Queensland compared with the Northern Territory. Regional trends in the clinical presentation of melioidosis in Australia compared with Southeast Asia were confirmed. Risk factors for disease included diabetes (42%), excess alcohol consumption (42%), chronic lung disease (26%), immunosuppressive drug use (12%), renal disease (11%), malignancy (7%) and autoimmune disease (5%). No risk factors were identifiable in 18% of cases. The presence of multiple risk factors for melioidosis was not significantly associated with increased mortality (P > 0.05).
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PMID:Clinical presentation of melioidosis in Queensland, Australia. 1611 29

Diabetes mellitus is a major predisposing factor for Burkholderia pseudomallei infection. This study surveyed serum samples from 356 Taiwanese patients with diabetes mellitus for anti-flagellin antibodies against B. pseudomallei. Antibody titer to B. pseudomallei was positive in 3.0% (11/365) of diabetes mellitus patients. All seropositive individuals were aged > or =60, indicating that elderly and diabetic adults are at high risk of B. pseudomallei infection. In this study, diabetic females, who were usually housewives, had a seropositive rate of 81.1%. However, the incidence of melioidosis in males (usually working outdoors) was 93.7% based on clinical cases. We suggest that exposure of males and females to B. pseudomallei in this study was via different routes of infection.
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PMID:Seroprevalence of melioidosis in diabetic patients in Taiwan. 1611 74


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