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Biomedical subjects

K Georgilis

Publications and source records attributed to K Georgilis.

16 recordsLinked to original sources

Pneumonia due to Candida krusei.

A case of post-transplantation pneumonia due to Candida krusei is reported. A 42-year-old man was admitted 28 days after heart transplantation with cough, pleuritic pain and fever. A chest computed tomograph showed multiple alveolar infiltrates bilaterally. He received broad-spectrum antibiotics, fluconazole for oral candidiasis, and cotrimoxazole for possible Pneumocystis carinii. A short-lived period of improvement was followed by respiratory failure. Cultures of bronchial washings grew C. krusei and C. albicans. The infection was documented by histology and culture obtained by transthoracic aspiration. Treatment with amphotericin B was initiated, but the patient died. Histology and culture of a pulmonary specimen, obtained immediately post mortem, further documented the infection with C. krusei.

Adult↗

Conservative management of PID.

The goals in the management of pelvic inflammatory disease (PID) are not only treatment of the infection and prevention of immediate complications, but also prevention of its long-term consequences. There are criteria for hospitalization, but patients who do not meet them can be safely treated as outpatients. A variety of sexually transmitted and other microorganisms can cause this infection, but the most important are Chlamydia trachomatis and Neisseria gonorrhoeae. Regimens with activity against gonococci, chlamydiae, streptococci, gram-negative bacteria, and anaerobes should be administered. Several such antimicrobial regimens have shown very good clinical and microbiologic efficacy. However, their efficacy in preventing long-term complications, such as infertility, has not been established. Close follow-up is an important part of management. Evaluation of male sexual partners is imperative to prevent reinfection. Better diagnostic techniques and treatment modalities for PID must be developed to prevent its long-term consequences.

Anti-Bacterial Agents↗

Aetiology of fever in patients with acute stroke.

OBJECTIVE: Fever in patients with acute stroke is usually related to infectious complications. In some cases, a focus of infection cannot be identified, fever does not respond to empirical antibiotic treatment and is thought to be due to the central nervous system lesion. The aim of this study was to determine the frequency and origin of fever in patients with acute stroke and the characteristics associated with the presence of fever. DESIGN: A retrospective study of 36 months' duration. SETTING: The study was carried out at 'Alexandra' Hospital, a tertiary care teaching centre in Athens, Greece. SUBJECTS: A total of 330 patients hospitalized for acute stroke from June 1992 until July 1994. RESULTS: In 37.6% of 330 patients, fever was noted; 22.7% had a documented infection and 14.8% had fever without a documented infection. In univariate analysis, older age was associated with the presence of fever (P = 0.001). The development of fever was associated with intracerebral haemorrhage versus ischaemic infarct (P < 0.001) and with the presence of mass effect (P < 0.001), transtentorial herniation (P < 0.001), intraventricular blood (P < 0. 001), and larger size of ischaemic infarct (P = 0.0001) and of haemorrhage (P = 0.0002). Patients with fever had lower scores on admission on the Glasgow Coma Scale (P = 0.0001) and the Scandinavian Stroke Scale (P = 0.0001). The development of fever was associated with prior use of an invasive technique (P < 0.001) and more specifically with urinary catheterization (P < 0.001), but not with the presence of risk factors for infection. Patients with fever had a worse outcome assessed by the Modified Rankin Scale (P = 0. 0001) and the Barthel Index (P = 0.0001). In multivariate analysis, age, Scandinavian Stroke Scale score and mass effect were found to be significantly associated with fever (P = 0.035, P = 0.0001 and P = 0.0004, respectively). Patients with fever without documented infection had an earlier onset of fever than those with infection (P = 0.0061). In a logistic regression analysis, the only factor predictive of fever without documented infection versus infection was earlier onset of fever (P = 0.029). CONCLUSION: Patients with acute stroke who develop fever are older, suffer severe stroke, their fever is associated with the use of invasive techniques, and they have a poor outcome. In patients with fever without a focus of infection, the only characteristic that is different from patients with known infection is earlier onset of fever.

Acute Disease↗

Microfilaremia from a Dirofilaria-like parasite in Greece. Case report.

In Europe, zoonotic filarial infections in humans are caused by two species, Dirofilaria immitis and Dirofilaria repens. These parasites are associated mainly with embolic infarcts of the pulmonary artery and subcutaneous nodules, respectively. An unusual dirofilarial infection in a Greek patient who showed marked eosinophilia and microfilaremia is presented. Although the identification of Dirofilaria species is not conclusive, this report is the first on a case of microfilaremia from a Dirofilaria infection in an immunocompetent patient.

Aged↗

Fibroblasts protect the Lyme disease spirochete, Borrelia burgdorferi, from ceftriaxone in vitro.

The Lyme disease spirochete, Borrelia burgdorferi, can be recovered long after initial infection, even from antibiotic-treated patients, indicating that it resists eradication by host defense mechanisms and antibiotics. Since B. burgdorferi first infects skin, the possible protective effect of skin fibroblasts from an antibiotic commonly used to treat Lyme disease, ceftriaxone, was examined. Human foreskin fibroblasts protected B. burgdorferi from the lethal action of a 2-day exposure to ceftriaxone at 1 microgram/mL, 10-20 x MBC. In the absence of fibroblasts, organisms did not survive. Spirochetes were not protected from ceftriaxone by glutaraldehyde-fixed fibroblasts or fibroblast lysate, suggesting that a living cell was required. The ability of the organism to survive in the presence of fibroblasts was not related to its infectivity. Fibroblasts protected B. burgdorferi for at least 14 days of exposure to ceftriaxone. Mouse keratinocytes, HEp-2 cells, and Vero cells but not Caco-2 cells showed the same protective effect. Thus, several eukaryotic cell types provide the Lyme disease spirochete with a protective environment contributing to its long-term survival.

Adenocarcinoma↗

Live Borrelia burgdorferi preferentially activate interleukin-1 beta gene expression and protein synthesis over the interleukin-1 receptor antagonist.

Lyme arthritis is one of the few forms of chronic arthritis in which the cause is known with certainty. Because cytokines are thought to contribute to the pathogenesis of chronic arthritis, we investigated the effect of the Lyme disease spirochete, Borrelia burgdorferi, on the gene expression and synthesis of IL-1 beta and the IL-1 receptor antagonist (IL-1ra) in human peripheral blood mononuclear cells. Live B. burgdorferi induced fivefold more IL-1 beta than IL-1 alpha and sevenfold more IL-1 beta than IL-1ra; LPS or sonicated B. burgdorferi induced similar amounts of all three cytokines. This preferential induction of IL-1 beta was most dramatic in response to a low passage, virulent preparation of B. burgdorferi vs. three high passage avirulent strains. No difference in induction of IL-1ra was seen between these strains. The marked induction of IL-1 beta was partially diminished by heat-treatment and abrogated by sonication; IL-1ra was not affected. This suggested that a membrane component(s) accounted for the preferential induction of IL-1 beta. However, recombinant outer surface protein beta induced little IL-1 beta. By 4 h after stimulation, B. burgdorferi induced sixfold more IL-1 beta protein than LPS. In contrast to LPS-induced IL-1 beta mRNA which reached maximal accumulation after 3 h, B. burgdorferi-induced IL-1 beta mRNA showed biphasic elevations at 3 and 18 h. B. burgdorferi-induced IL-1ra mRNA peaked at 12 h, whereas LPS-induced IL-1ra mRNA peaked at 9 h. IL-1 beta synthesis increased in response to increasing numbers of spirochetes, whereas IL-1ra synthesis did not. The preferential induction by B. burgdorferi of IL-1 beta over IL-1ra is an example of excess agonist over antagonist synthesis induced by a microbial pathogen, and may contribute to the destructive lesion of Lyme arthritis.

Adult↗

Neutrophil chemotactic factors in synovial fluids of patients with Lyme disease.

We examined synovial fluid samples from 14 patients with Lyme arthritis for the presence of neutrophil chemotactic factors. Thirteen of the synovial fluids stimulated chemotaxis of normal human neutrophils. The chemotactic activity was heat-sensitive and was not inhibited by antibody to C5a or antibody to interleukin-8, or by a competitive inhibitor of the chemotactic peptide f-Met-Leu-Phe. A culture supernatant of Borrelia burgdorferi also contained neutrophil chemoattractants. Chromatography demonstrated that the chemoattractants in the synovial fluid samples were different from those in the B burgdorferi culture supernatant. One of the major chemotactic factors in Lyme disease synovial fluid had a calculated molecular weight of 13,900. We conclude that a novel, host-derived chemoattractant is present in the synovial fluid of patients with Lyme disease.

Chemotactic Factors↗

Infectivity of Borrelia burgdorferi correlates with resistance to elimination by phagocytic cells.

The Lyme disease spirochete, Borrelia burgdorferi, causes a disseminated infection in vivo, implying resistance to clearance by phagocytic cells. Because B. burgdorferi loses its infectivity after in vitro cultivation, the relationships between serial passaging of the organism in vitro, its susceptibility to elimination by phagocytes, and its infectivity were examined. When three different high-passage strains were incubated for 4 h at 37 degrees C with peripheral blood mononuclear cells, macrophages, or polymorphonuclear neutrophils, 45%-67% of the organisms were eliminated. In contrast, two low-passage strains were resistant to elimination by phagocytes, and only 5%-6% of the organisms were removed after 4 h. All five strains equally stimulated the neutrophil oxidative burst, indicating that evasion of phagocytes was not a result of avoidance of recognition by these cells. The two low-passage strains were infective when injected into mice, whereas the three high-passage ones were not. These observations indicate that infectivity of the Lyme disease spirochete correlates with resistance to elimination by phagocytic cells.

Animals↗

The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells.

We examined whether the synthesis of interleukin-1 or tumor necrosis factor, two cytokines with potent inflammatory activities, is influenced by dietary supplementation with n-3 fatty acids. Nine healthy volunteers added 18 g of fish-oil concentrate per day to their normal Western diet for six weeks. We used a radioimmunoassay to measure interleukin-1 (IL-1 beta and IL-1 alpha) and tumor necrosis factor produced in vitro by stimulated peripheral-blood mononuclear cells. With endotoxin as a stimulus, the synthesis of IL-1 beta was suppressed from 7.4 +/- 0.9 ng per milliliter at base line to 4.2 +/- 0.5 ng per milliliter after six weeks of supplementation (43 percent decrease; P = 0.048). Ten weeks after the end of n-3 supplementation, we observed a further decrease to 2.9 +/- 0.5 ng per milliliter (61 percent decrease; P = 0.005). The production of IL-1 alpha and tumor necrosis factor responded in a similar manner. Twenty weeks after the end of supplementation, the production of IL-1 beta, IL-1 alpha, and tumor necrosis factor had returned to the presupplement level. The decreased production of interleukin-1 and tumor necrosis factor was accompanied by a decreased ratio of arachidonic acid to eicosapentaenoic acid in the membrane phospholipids of mononuclear cells. We conclude that the synthesis of IL-1 beta, IL-1 alpha, and tumor necrosis factor can be suppressed by dietary supplementation with long-chain n-3 fatty acids. The reported antiinflammatory effect of these n-3 fatty acids may be mediated in part by their inhibitory effect on the production of interleukin-1 and tumor necrosis factor.

Adult↗

In vitro effects of omega-3 fatty acids on neutrophil intracellular calcium homeostasis and receptor expression for FMLP and LTB4.

Diets enriched in omega-3 fatty acids exert antiinflammatory properties by suppressing some neutrophil (PMN) functions. Changes in cytosolic Ca2+ concentration, [Ca2+]i, are important for PMN activation and are in part regulated by membrane Ca2+ ATPases. Since membrane proteins are influenced by their lipid environment, we investigated the in vitro effects of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on the [Ca2+]i of PMNs in response to f-Met-Leu-Phe (FMLP), leukotriene B4 (LTB4), and ionomycin. The resting [Ca2+]i of PMNs (in high Ca2+ environment) was increased after pretreatment (37 degrees C, 2 h) with DHA, but not with EPA, or the other fatty acids, oleic acid (OA), or linolenic acid (LA). The stimulated [Ca2+]i by either FMLP or LTB4 was suppressed in a high Ca2+ environment after pretreatment with either EPA or DHA but not with OA or LA. The stimulated [Ca2+]i rise by ionomycin was augmented after pretreatment with DHA but not with EPA, OA, or LA. Pretreatment of PMNs with either EPA or DHA reduced the receptor expression for both FMLP and LTB4. Since omega-3 fatty acids inhibit the expression of receptors for two activators of PMNs, FMLP and LTB4, as well as the [Ca2+]i rise in response to those two stimuli, we propose that the antiinflammatory properties of EPA and DHA may be attributed, at least in part, to alteration in membrane activation of phagocytes.

Adult↗

Human recombinant interleukin 1 beta has no effect on intracellular calcium or on functional responses of human neutrophils.

The effect of human recombinant interleukin 1 beta (rIL 1 beta) on human neutrophils was examined. rIL 1 beta, even at concentrations of 100 ng/ml (100 half-maximal T cell stimulating U/ml) did not change significantly the intracellular free calcium concentration, [Ca++]i, whereas the control stimulus, fmet-leu-phe, significantly elevated [Ca++]i. rIL 1 beta also failed to stimulate production of superoxide, degranulation of lysosomal enzymes, phagocytosis of bacterial particles, chemotaxis, or chemokinesis of human neutrophils. This is substantial evidence that superphysiologic concentrations of interleukin 1 have no direct effect on [Ca++]i, as well as on functional responses of neutrophils.

Adult↗

The Athens stroke registry: results of a five-year hospital-based study.

The advent and wide application of new technology, especially noninvasive techniques, has enabled physicians to more completely investigate and clarify the etiopathogenic mechanisms of stroke. Such data have not been available until recently for Southeastern Europe. In addition, during the last decades, strategies for the modification of risk factors and primary prevention may have changed the prevalence of each subgroup of stroke as well. We investigated 1, 042 consecutive patients who had first strokes, during a period of 5 years (from June 1992 to May 1997) and classified them prospectively based on etiopathogenic mechanisms. Patients with transient ischemic attacks and subarachnoid hemorrhage were excluded. There were 613 male and 429 female patients, with a mean age of 70.2 +/- 11.9 years. Forty-six percent of the patients arrived within 3 h from stroke onset. The probable mechanisms were: large-artery atherosclerosis, 156 (15%); lacunes, 177 (17%); cardioembolic, 335 (32.1%); infarct of unknown cause, 182 (17.5%); miscellaneous causes, 35 (3.3%), and intracerebral hemorrhage (ICH), 157 (15.1%). In the cardioembolic group, nonvalvular atrial fibrillation (NVAF) was the probable cause in 225 patients, especially in patients older than 75 years (65%). The overall hospital mortality was 15.2% (from 0.6% for lacunar stroke to 34% for ICH). In our population, cardioembolism is the most frequent subtype of stroke. NVAF is the most likely source, especially in older patients.

Adult↗