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Biomedical subjects

J Papadimitriou

Publications and source records attributed to J Papadimitriou.

At least 19 recordsLinked to original sources

Virus spread, tissue inflammation and antiviral response in brains of flavivirus susceptible and resistant mice acutely infected with Murray Valley encephalitis virus.

Inborn resistance to flaviviruses, conferred by a single chromosome 5 locus Flv, is a genetic trait operative in wild mice and a few strains of laboratory mice. In this study we have used in situ hybridisation to trace the spread of flavivirus genomic RNA within the brains of flavivirus susceptible C3H/HeJARC and congenic resistant C3H.PRI- Flv(r) mice following infection with Murray Valley encephalitis virus (MVE) in parallel to studying a brain histopathology and induction of cellular genes involved in antiviral response. We find that in contrast to a high viral RNA content in brains of susceptible mice, viral RNA was markedly reduced in the cortex, olfactory bulb, thalamus and hypothalamus of resistant mice. Trace amounts of viral RNA were detected in the medulla oblongata while it was completely absent from the hippocampus, pons and cerebellum of resistant mice at different time points post infection. The low virus titres within brains of resistant mice coincided with a very mild inflammation, low counts of infiltrating inflammatory cells, and lower IFN I/II and TNFalpha gene induction than in susceptible mice. Furthermore, transcripts of several genes belonging to a 2',5'-oligoadenylate synthetase ( OAS) family, implicated in IFN I-inducible OAS/RNase L antiviral pathway, showed similar brain tissue induction in both strains of mice suggesting only minor contribution of this pathway to the resistance phenotype.

2',5'-Oligoadenylate Synthetase↗

Surgical adjuvant therapy of rectal carcinoma: a controlled evaluation of leucovorin, 5-fluorouracil and radiation therapy with or without interferon-alpha2b.

BACKGROUND: The aim of this study was to determine whether the efficacy of the combination of 5-fluorouracil (5-FU), leucovorin (LV) and radiation therapy (RT) could be improved by the addition of interferon-alpha2b (IFN-alpha) in patients who have had a 'curative' resection, for rectal adenocarcinoma (Dukes' B2/C; T3 N0, T4 N0, N1-3). PATIENTS AND METHODS: A total of 207 eligible patients with a performance status of 0 or 1 were randomized postoperatively between days 21 and 70 to one of the two treatment groups: group A, LV 20 mg/m2 i.v. bolus and 5-FU 425 mg/m2 i.v. days 1-5 and 29-33, LV 20 mg/m2 and 5-FU 400 mg/m2 days 57-60 and 85-88, LV 20 mg/m2 and 5-FU 380 mg/m2 days 1-5 and 29-33 with the second day 1 occurring 28 days after the completion of RT (45 Gy); group B, LV, 5-FU and RT as in group A, and IFN-alpha 5 x 10(6) IU s.c. three times during each week chemotherapy is given. RESULTS: 104 patients were randomized into group A and 103 into group B. There was no statistically significant difference in either disease-free survival or overall survival between the two groups. Toxicity was also the same, except for the flu-like syndrome associated with the IFN-alpha administration. CONCLUSIONS: There was no difference in efficacy between the two combinations. Toxicity was greater with the LV + 5-FU + IFN-alpha regimen because of the flu-like syndrome.

Adenocarcinoma↗

Haemodynamic changes in ischaemic vs. anhepatic pig experimental model of acute liver failure.

BACKGROUND AND OBJECTIVE: The removal of the non-functioning liver in cases of fulminant liver failure has been advocated by some authors as a means of improving haemodynamic instability and acid-base disturbances associated with acute liver failure. METHODS: The aim of the present experimental study was to investigate whether maintaining a non-functioning liver is preferable over removing it in terms of haemodynamic variables, after acute hepatic failure has been surgically induced. Twenty Landrace pigs were used in the study. All of them underwent portocaval anastomosis and ligation of the hepatic artery. After an 18-h period and with biochemical indices of fulminant hepatic failure clearly demonstrated, the animals were randomly assigned to one of two groups: in 10 pigs (Group A) the ischaemic liver was left in situ and no further surgical intervention was undertaken. The other 10 (Group B) underwent total hepatectomy. Haemodynamic monitoring was the same in both groups. No inotropes were administered throughout the whole period of observation. RESULTS: Haemodynamic deterioration was observed in the hepatectomized pigs (Group B) whereas the group with the ischaemic liver in situ (Group A) remained stable in terms of the haemodynamic variables evaluated until the end of the experiment. (Cardiac index in Group A 7.59 +/- 1.25 L min(-1) m(-2) vs. 2.92 +/- 0.68 L min(-1) m(-2) in Group B, P < 0.05.) CONCLUSIONS: The concept of salvage hepatectomy in cases of acute liver failure should be redefined since there seems to be some experimental evidence that it may not be as beneficial as originally thought.

Analysis of Variance↗

Retinal projections throughout optic nerve regeneration in the ornate dragon lizard, Ctenophorus ornatus.

In goldfish and frog, optic nerve regeneration is successful, with restoration of retinotopic projections in visual brain centres and the return of functional vision within 1-2 months. By contrast, at 1 year after unilateral optic nerve crush in the ornate dragon lizard (Ctenophorus ornatus), the regenerated retinotectal projections lack topographic order, presumably explaining why the lizards are blind via the experimental eye (Beazley et al. [1997] J. Comp. Neurol. 377:105-120). To determine whether other abnormalities are associated with the inability to restore topographic projections in the lizard, we charted anatomically the time course, accuracy, and stability of optic nerve regeneration by examining visual projections with the lipophillic dye 1,1'-dioctadecyl-3,3,3', 3'-tetramethylindocarbocyanine perchlorate (DiI) applied to the optic disk at intervals up to 1 year after optic nerve crush; in addition, DiI tracing of small groups of axons was used to examine the topicity of axons projecting to the tectum. Axons re-innervated visual centres from between 1 and 2 months, a time frame comparable with that in goldfish and frog. However, the projections in lizard were found to differ from those in goldfish and frog in three major ways. First, there was considerable variability within the projection patterns both between individual lizards at any one stage and with time. Second, the projections were inaccurate. As in normal lizards, the major projection was to the contralateral optic tectum, although it lacked detectable retinotopic axon order throughout. Furthermore, misrouting occurred such that regenerating axons formed a persistent projection to the ipsilateral side of the brain that was considerably stronger and more widespread than normal. Minor visual centres also became re-innervated but, in addition, regenerating axons formed persistent projections into the opposite optic nerve and to non-retino-recipient regions such as the nucleus rotundus, hypothalamus, and olfactory nerve, as well as the posterior and tectal commissures. Third, the projections appeared unstable. Projections to both tecta were strongest between 3 and 5 months, but they diminished thereafter. The results suggest that, compared with goldfish and frog, in lizards both pathway and target cues are degraded and/or cannot be read adequately; as a consequence, regenerating axons are unable to navigate exclusively to visual centres and cannot re-form stable connections.

Animals↗

Controlled production of active cathepsin D in retinal pigment epithelial cells following adenovirus-mediated gene delivery.

The transduction of a low cathepsin D-producing retinal pigment epithelial cell line with a recombinant adenovirus, Ad.proCatD, carrying a viral promoter and the precursor form of the lysosomal enzyme cathepsin D, procathepsin D, led to the upregulation of proCatD expression. However, the resultant aspartic protease activity did not exceed that observed in normal primary human retinal pigment epithelial cells. Following the injection of Ad. proCatD into rat eyes, immunohistochemistry and Western blot analysis localized the expression of procathepsin D to the retinal pigment epithelial cell layer and to the sclera/choroid/retinal epithelial cell layers, respectively. This upregulation of procathepsin D expression was accompanied by a limited increase in aspartic protease activity. The injected eyes did not demonstrate any of the retinal changes that have been associated with the overproduction and secretion of active cathepsin D. Immunoelectronmicroscopy of Ad.proCatD-transduced retinal pigment epithelial cells demonstrated the presence of cathepsin D not only in cytoplasmic vesicles and lysosomes but also in the nucleoli and, less strongly, elsewhere in euchromatic regions of some 10% of cells. In spite of the upregulated expression of procathepsin D, the production of active cathepsin D in Ad.proCatD-transduced retinal pigment epithelial cells was strictly controlled. It is proposed that active cathepsin D production is controlled at the point of posttranslational modification by an intranuclear feedback mechanism initiated by the relative excess of procathepsin D in Ad. proCatD-transduced retinal pigment epithelial cells.

Adenoviridae↗

Morphological features of Murray Valley encephalitis virus infection in the central nervous system of Swiss mice.

We have examined the histological and ultrastructural features of CNS infection with Murray Valley encephalitis (MVE) virus in mice inoculated with a virulent parental strain (BH3479). Light microscopic examination revealed neuronal necrosis in the olfactory bulb and hippocampus of MVE-infected brains by 5 days post-infection (pi). Electron microscopy of these regions showed endoplasmic reticulum membrane proliferation, and tubular and spherical structures in the cisternae of the endoplasmic reticulum, Golgi complex and nuclear envelope. At seven to eight days pi, infected neurones exhibited chromatin condensation and extrusion, nuclear fragmentation, loss of segments of the nuclear envelope, reduced surface contact with adjacent cells and loss of cytoplasmic organelles. This cell injury was particularly noticeable in the proximal CA3 and distal CA1 regions of the hippocampus. The inflammatory cell profile consisted of macrophages, lymphocytes and especially neutrophils, and many of these inflammatory cells were apoptotic. High mortality rates in the BH3479-infected population of mice correlated with the intense polymorphonuclear and mononuclear leucocyte inflammatory infiltrate in the CNS.

Animals↗

Splenic abscess. An old disease with new interest.

BACKGROUND/AIMS: To study the demographics, signs and symptoms, causes, risk factors, imaging findings, bacteriologic profile, treatment and outcome of patients with splenic abscess. METHOD: The medical records of 17 patients with splenic abscess at two tertiary-care hospitals between 1989 and 1997 were retrospectively reviewed. The demographic data, physical and radiological findings, treatment, bacteriology reports and outcome of treatment were reviewed. RESULTS: The mean age of patients was 43 years (range 7-79 years). Fever and abdominal pain were the most prominent signs. Seven patients were immunocompromised, three had abscessed hydatic cysts, two were drug users and three suffered from splenic trauma, infarction, and endocarditis, respectively. No predisposing factor was identified in 2 patients. In all cases, CT demonstrated the splenic lesion(s). Staphylococcus species and Bacteriodes were the most common microbes, identified in the blood and abscess cultures. Thirteen patients underwent splenectomy, two medical therapy and two no therapy with respective survival rates of 92, 100 and 0%. CONCLUSION: Splenic abscess is a rare surgical entity encountered mostly in immunocompromised patients. CT scan is the gold standard for the definite diagnosis. Splenectomy is the treatment of choice, while medical therapy should be reserved for unusual pathogens provided that an effective antimicrobial agent is available.

Abdominal Abscess↗

Incidence of vein thrombosis in peripheral intravenous nutrition: effect of fat emulsions.

The relative risk of thrombophlebitis induced by either Long-chain Triglycerides (LCTs) or Medium-chain Triglycerides (MCTs) during peripheral i.v. nutrition (PIN) was evaluated. A total of 76 patients were randomly assigned into group A (n=40) and group B (n=36). The nutritional requirements in both groups were covered by a standardized regime of osmolality 1130 mOsm and pH 5.2, which provided 14 kg/day(-1) nitrogen, 600 kcal/day(-1) of carbohydrates and 1000 kcal/day(-1) of lipids. Group A received the lipids as pure LCTs while group B received a mixture of LCTs/MCTs at a ratio 1:1. The infused nutritional volume was 2000 ml and was delivered via a suitable vein in a proximal forearm, using a fine bore polyurethane 22G catheter. The two standardized regimes were evaluated over a 10 day period regarding the incidence of thrombophlebitis. The cumulative risk of thrombophlebitis was documented to be significantly lower in group A compared to group B (17.5% versus 44.4%, P < 0.05). LCTs appear to prolong peripheral vein feeding by lessening the reaction of venous endothelium to the irritating nutritional infusate.

Double-Blind Method↗

The murine cytomegalovirus chemokine homolog, m131/129, is a determinant of viral pathogenicity.

Chemokines are important mediators of the early inflammatory response to infection and modify a wide range of host immune responses. Functional homologs of cellular chemokines have been identified in a number of herpesviruses, suggesting that the subversion of the host chemokine response contributes to the pathogenesis of these viruses. Transcriptional and reverse transcription-PCR analyses demonstrated that the murine cytomegalovirus (MCMV) chemokine homolog, m131, was spliced at the 3' end to the adjacent downstream open reading frame, m129, resulting in a predicted product of 31 kDa, which is significantly larger than most known chemokines. The in vivo impact of m131/129 was investigated by comparing the replication of MCMV mutants having m131/129 deleted (Deltam131/129) with that of wild-type (wt) MCMV. Our studies demonstrate that both wt and Deltam131/129 viruses replicated to equivalent levels during the first 2 to 3 days following in vivo infection. However, histological studies demonstrated that the early inflammatory response elicited by Deltam131/129 was reduced compared with that of wt MCMV. Furthermore, the Deltam131/129 mutants failed to establish a high-titer infection in the salivary glands. These results suggest that m131/129 possesses proinflammatory properties in vivo and is important for the dissemination of MCMV to or infection of the salivary gland. Notably, the Deltam131/129 mutants were cleared more rapidly from the spleen and liver during acute infection compared with wt MCMV. The accelerated clearance of the mutants was dependent on NK cells and cells of the CD4(+) CD8(+) phenotype. These data suggest that m131/129 may also contribute to virus mechanisms of immune system evasion during early infection, possibly through the interference of NK cells and T cells.

Amino Acid Sequence↗

The real incidence of extracapsular (satellite) cysts of liver echinococcus.

BACKGROUND: The presence of extracapsular (Satellite) cysts in liver echinococcus granulosus is known for many years. In one of our previous studies of radiological (CT) material they were found to be present in 16% of cases. METHODS: In the present study the operative findings, in cases of total capsectomy (cystopericystectomy) or partial lobectomy are presented. RESULTS: The real incidence of these cysts in operative specimens was as high as 29,5%. They were present in 15 out of 51 totally excised cysts. CONCLUSIONS: We conclude that satellite cysts are present more often than they are radiologically detected. As they can be incriminated as a cause of recurrence of the disease they must be excised en block with the main parasitic cysts, by means of more radical procedures such as cystopericystectomy or partial hepatectomy, whenever it is feasible.

Adolescent↗

What do Greek physicians know about managing cancer pain?

BACKGROUND: Pain is prevalent in cancer patients. Although the World Health Organization has issued guidelines for treating pain in cancer patients, pain is often not treated optimally. Numerous barriers have been identified that prevent health care professionals from providing effective treatment for pain. The knowledge and attitudes of health care professionals with regard to pain and its impact on the patient are among them. The purpose of the present study was to evaluate knowledge about and attitudes toward cancer pain and its management among Greek oncologists, surgeons, anesthesiologists, and general practitioners. METHOD: Knowledge of the principles and methods of cancer pain treatment was assessed by a questionnaire distributed to a representative sample of 1,200 Greek physicians. RESULTS: The study results highlight very substantial knowledge deficits in the treatment of cancer pain by the evaluated physicians. CONCLUSIONS: Cancer pain management in Greece is still developing, and the latest knowledge is spreading slowly but steadily.

Adult↗