Biomedical subjects

P Sfikakis

Publications and source records attributed to P Sfikakis.

At least 19 recordsLinked to original sources

PubMed2002

A placebo and active comparator-controlled trial of rofecoxib for the treatment of rheumatoid arthritis.

OBJECTIVE: To evaluate the efficacy and tolerability of rofecoxib 25 mg and 50 mg once daily versus placebo and naproxen 500 mg twice daily in patients with RA. METHODS: Eligible patients were randomized (double-blind) to placebo (n = 289), rofecoxib 25 mg (n = 306), 50 mg (n = 286) once daily, or naproxen (n = 142) for 12 weeks. Efficacy assessments included the ACR core set, with prespecified primary endpoints: patient and investigator global assessments of disease activity, tender and swollen joint counts. Investigator-reported adverse experiences, routine laboratory and vital sign measurements were monitored. RESULTS: Rofecoxib 25 mg, 50 mg, and naproxen provided similar treatment effects, significantly different from placebo, consistent with improvement, for all primary endpoints. Effects were evident at the earliest assessment (week 2) and sustained for 12 weeks. All treatments were generally well-tolerated. CONCLUSIONS: Rofecoxib 25 mg once daily had similar efficacy to naproxen 500 mg twice daily (a standard dose). No additional benefit was seen with 50 mg rofecoxib.

Adult↗

PubMed2000

Waldenström's macroglobulinemia: clinical features, complications, and management.

PURPOSE: To review the clinical features, complications, and treatment of Waldenström's macroglobulinemia, a low-grade lymphoproliferative disorder that produces monoclonal immunoglobulin (Ig) M. METHODS: A review of published reports was facilitated by the use of a MEDLINE computer search and by manual search of the Index Medicus. RESULTS: The clinical manifestations associated with Waldenström's macroglobulinemia can be classified according to those related to direct tumor infiltration, to the amount and specific properties of circulating IgM, and to the deposition of IgM in various tissues. Asymptomatic patients should be followed without treatment. For symptomatic patients, standard treatment consists primarily of oral chlorambucil; nucleoside analogs, such as fludarabine and cladribine, are effective in one third of previously treated patients and in up to 80% of previously untreated patients. Preliminary evidence suggests that anti-CD20 monoclonal antibody may be active in about 30% of previously treated patients and that high-dose therapy with autologous stem-cell rescue is effective in most patients, including some with resistance to nucleoside analogs. CONCLUSION: Waldenström's macroglobulinemia has a wide clinical spectrum that practicing physicians need to recognize early to reach the correct diagnosis. When therapy is indicated, oral chlorambucil is the standard primary treatment, but cladribine or fludarabine can be used when a rapid cytoreduction is desirable. Prospective randomized trials are required to elucidate the impact of nucleoside analogs on patients' survival. A nucleoside analog is the treatment of choice for patients who have been previously treated with an alkylating agent.

Aged↗

PubMed1995

CD28 expression on T cell subsets in vivo and CD28-mediated T cell response in vitro in patients with rheumatoid arthritis.

OBJECTIVE: In view of the critical importance of the CD28-CD80 (B7/BB1) costimulatory pathway in antigen-specific T cell activation and clonal expansion, we examined CD28 surface molecule expression in vivo, and T cell receptor/CD3-mediated and B7/BB1-costimulated T cell proliferation in vitro, in rheumatoid arthritis (RA). METHODS: Two-color immunofluorescence analyses of peripheral blood and synovial fluid-derived T cells, as well as 3H-thymidine incorporation assays, were performed. RESULTS: In the peripheral blood of 31 patients with active, untreated RA, a mean of 91% (range 48-100%) of CD4+ and 46% (range 13-82%) of CD8+ T cell subsets were CD28+, which was not significantly lower than normal. Although an overall decrease in the number of T cells was not observed, the numbers of CD28+CD8+ T cells were significantly lower in RA patients (mean 233/microliters, versus 292/microliters in controls), and this decrease was more pronounced in patients with severe disease (mean 172/microliters). CD28 expression on peripheral CD8+ T cells in RA patients, but not in healthy individuals, correlated inversely with T cell activation as assessed by HLA-DR antigen expression. In contrast to the peripheral blood, RA synovial fluid T cells were almost exclusively CD28+, suggesting that migration of CD28+CD8+ T cells to active sites of inflammation may occur. In vitro proliferative responses of peripheral blood T cells to B7/BB1 costimulation in the presence of mitogenic doses of anti-CD3 monoclonal antibody were identical in patients with RA and healthy individuals. CONCLUSION: Functionally intact CD28+ T cells may contribute to the abnormal immunoregulation and joint inflammation in RA.

Adult↗

PubMed1995

Molecular and immunohistochemical study of class I growth factor receptors in squamous cell lung carcinomas.

The class I growth factor receptor family includes epidermal growth factor receptor, i.e. c-erbB-1, c-erbB-2 and c-erbB-3 molecules. These receptors have a significant sequence homology and play an important role in cell growth and differentiation. To further investigate their implication in squamous cell lung carcinomas (SqCLCs), we studied the protein expression by immunohistochemistry and examined for possible gene amplification by a novel semi-quantitative differential polymerase chain reaction (DPCR) technique. Expression of c-erbB-1, c-erbB-2 and c-erbB-3 was present in 65%, 28% and 10% respectively, of 40 SqCLCs cases. Seven of the 11 cases that expressed c-erbB-2, as well as all 4 c-erbB-3 expressing cases, also stained with the anti-c-erbB-1 mAb. Expression of c-erbB-1, but not of c-erbB-2 or c-erbB-3, correlated with the grade of tumor differentiation (100%, 64% and 36% positive cases of well, moderately and poorly differentiated cases respectively, p < 0.003). In addition, c-erbB-1 expression correlated with the presence of regional lymph node metastases within the moderately differentiated group. The c-erbB-1 gene was amplified in 11/40 (28%) cases, all of which overexpressed c-erbB-1 protein, while c-erbB-2 gene amplification was detected in only one case. There was no c-erbB-3 gene amplification in any of the 40 SqCLCs cases. These findings suggest that c-erbB-1, c-erbB-2 and c-erbB-3 receptors do not have a common role and are of different physiological importance, at least at the stage of clinically overt tumor in human SqCLCs.

Base Sequence↗

PubMed1994

Serum concentrations of soluble intercellular adhesion molecule-1 and progress towards disease in patients infected with HIV.

Intercellular adhesion molecule-1 (ICAM-1) is a membrane-bound molecule that is primarily involved in cell to cell adhesive interactions of the immune system. Concentrations of soluble ICAM-1 (s-ICAM-1) shed into the circulation were measured by a quantitative ELISA in HIV-infected persons without AIDS, patients with AIDS with or without evidence of acute opportunistic infection at the time of sampling, and HIV-seronegative patients with toxoplasmosis, community-acquired pneumonia, leishmaniasis and rickettsial infections. Patients were classified on the basis of clinical condition and CD4+ T-cell counts according to the 1993 revised HIV classification of the USA Centers for Disease Control. Concentrations of s-ICAM-1 in the serum of HIV-infected persons without AIDS-indicator conditions (categories A1, A2, B1 and B2) as well as in the serum of patients with AIDS (categories A3, B3, C1, C2 and C3) were significantly higher than normal (mean +/- S.E.M. 469 +/- 23, n = 60 and 780 +/- 73, n = 56, respectively, versus 329 +/- 15 ng/ml, P < 0.0001 and < 0.0001 respectively) and differed also significantly from each other (P < 0.0001). Raised concentrations of s-ICAM-1 in the serum of afebrile patients with AIDS but without acute opportunistic infection at the time of sampling (mean +/- S.E.M. 672 +/- 76, n = 29) did not differ from those of the remaining patients with AIDS or from those of HIV-seronegative patients with the infections studied. A steady and significant increase of serum concentrations of s-ICAM-1 with progress of disease according to clinical category (categories A-->B-->C, p = 0.0007) as well as with the loss of circulating CD4+ T-cells (categories 1-->2-->3, p = 0.009) was observed. Individual serum concentrations of s-ICAM-1 showed negative correlations with individual total lymphocyte (P = 0.004), CD4+ T-cell (P = 0.05), CD8+ T-cell counts (P = 0.03) as well as positive correlation with serum concentrations of soluble interleukin-2 receptors (P < 0.0001), an indirect marker of progress of HIV-related disease. Serum concentrations of s-ICAM-1 did not differ between patients with AIDS who were receiving or not receiving zidovudine at the time of sampling. A longitudinal survey is needed in order to determine whether measuring serum concentrations of s-ICAM-1, although not specific, has any predictive or prognostic value in these patients as well as whether this bioactive molecule has any pathogenetic role in the progress of disease in HIV infection.

Acquired Immunodeficiency Syndrome↗

PubMed1994

B7/BB1 provides an important costimulatory signal for CD3-mediated T lymphocyte proliferation in patients with systemic lupus erythematosus (SLE).

Successful T cell activation via the T cell receptor (TCR)/CD3 complex requires at least one contact-dependent second signal delivered by costimulatory molecules, including the B7/BB1 molecule, that are present on antigen-presenting cells (APC). SLE is characterized by multiple complex lymphocyte abnormalities of undefined molecular origin. It is currently unclear whether an intrinsic defect of T cell or an underlying APC dysfunction is responsible for defective in vitro proliferation of T cells from patients with SLE. We planned the present experiments to ask whether the TCR/CD3-mediated and B7/BB1-costimulated T cell proliferation is normal in these patients. We used enriched T cell populations that were stimulated with an anti-CD3 MoAb in the presence of controlled quantities of functional B7/BB1 antigen. Freshly isolated T cells from 17 SLE patients (10 and seven patients with either active or inactive disease, respectively) and 11 normal individuals were cocultured with irradiated B7/BB1-transfected P815 cells or parental P815 cells in the presence of OKT3 MoAb at optimal and suboptimal concentrations for 2.5-7 days. Normal or SLE T cells responded similarly to stimulation via anti-CD3, in the absence of B7/BB1 antigen. A several-fold increase in T cell proliferation in the presence of B7/BB1 antigen was observed. Proliferation was inhibited in the presence of anti-B7/BB1 MoAb, but not with control MoAbs. Interestingly, dose-response curves and time kinetics of B7/BB1 costimulation were similar in T cells from patients with either active or inactive SLE at the time of study, and normal individuals. In addition, no differences in the IL-2 receptor release by T cells cultured under these conditions were observed between SLE patients and normal individuals. These results demonstrate that CD28 signalling is not intrinsically impaired in patients with SLE; further studies to investigate whether abnormal B7/BB1 expression is involved in the autoimmune process are needed.

Adult↗

PubMed1993

Meropenem versus imipenem/cilastatin in the treatment of intraabdominal infections requiring surgery.

In a prospective randomized study meropenem was compared with imipenem/cilastatin in the treatment of 62 patients with intraabdominal infections requiring surgery. The patients were suffering from diffuse or local peritonitis of moderate severity complicating in most cases gangrenous appendicitis, stomach perforation or gallbladder disease. There were 30 patients in the meropenem group and 32 patients in the imipenem/cilastatin group. Both antibiotic regimens were given intravenously at a dosage of 1 g every 8 h for a mean duration of 7.7 days in the meropenem group versus 8.6 days in the imipenem/cilastatin group. Fifty-nine aerobic strains and 15 anaerobic strains were isolated from cultures of pus taken intraoperatively, the meropenem MICs ranging from < or = 0.25 to 2 micrograms/ml. At follow-up at least one month after treatment the outcome was considered successful in all of 27 evaluable patients given meropenem and in all of 29 evaluable patients given imipenem/cilastatin. Both antibiotic regimens were well tolerated.

Adult↗

PubMed1993

Pattern of treatment among diabetic patients in a sample of urban Greek population.

It is well known that therapeutic habits and diabetic patient's compliance differ substantially between different populations. It is also accepted that if patients are recruited in specialized diabetes centers some important bias is likely to occur, e.g. an excess of insulin-treated subjects. Therefore, population studies are very helpful in order to establish treatment patterns in different populations. A descriptive study was performed during an epidemiological survey conducted on 12,842 randomly selected inhabitants of a suburb of Athens (both sexes, all ages). 509 persons were recorded as known diabetics. Information concerning the type of treatment was collected. Reliable data were available on 490 diabetic individuals. 145 (29.6%) of them were following diet alone, while 270 (55.1%) were receiving antidiabetic tablets and only 75 (15.1%) injected insulin. In patients 40 years old or more (n = 471), the corresponding numbers were 30.1, 56.5 and 13.4% respectively. Thus, it is obvious that insulin-treated patients represent a small percentage of the total diabetic population. It seems that these differences are caused by genetic as well as other factors.

Adolescent↗

PubMed1992

Correlation of reciprocal ST-segment depression after acute myocardial infarction with coronary angiographic findings.

We studied 266 consecutive patients with acute myocardial infarction to assess the significance of electrocardiographic "mirror images". Ninety-four (group A) had anterior wall and 132 (group B) had inferior wall infarction. Thirty-one group A patients had stenosis of the right coronary artery greater than 85% in diameter (subgroup A1), and 63 either had a normal right coronary artery or less than 85% stenosis (subgroup A2). Of group B patients 62 had greater than 85% stenosis of the left anterior descending (subgroup B1) and 70 had a left anterior descending or less than 85% stenosis (subgroup B2). ST-segment depression was significantly greater in depth and duration in subgroup A1 than A2 (p = 0.02) and in subgroup B1 than B2 (p = 0.02, p = 0.01, respectively). Left ventricular ejection fraction was lower in subgroup A1 than A2 (p less than 0.001) and in B1 than B2 (p less than 0.001). There was a strongly positive correlation between depth and duration of ST-segment depression and the Gensini index (r = 0.78, 0.84) for anterior and inferior infarction, respectively. In conclusion, increased depth and duration of ST-segment depression opposite the infarct are indicative of ischemia, and are related to the extent of coronary artery disease, the degree of stenosis of the vessels supplying the opposite wall and of left ventricular dysfunction.

Aged↗

PubMed1991

Skull, patella and thigh cryptococcosis after a crashing injury of the temporal bone.

An unusual case of triple location (skull, patella and thigh) Cryptococcus neoformans is described. The peculiarity of the case is based on the probability of direct post-traumatic bone inoculation, subsequent seeding from skull to patella, thigh and cerebral spinal fluid (CSF), patella involvement, lack of evidence of lung involvement and lack of predisposing underlying disease. The response to surgery and a combination of amphotericin B and 5-flucytosine administration was favorable without relapse at follow-up after 7-year discontinuation of therapy.

Bone Diseases↗

PubMed1991

Comparative kinetics and efficacy of amikacin administered once or twice daily in the treatment of systemic gram-negative infections.

In an open randomized study the safety, efficacy and kinetics of a twice-daily amikacin (7.5 mg/kg bd) regimen (group A) was compared with a once-daily dosage (15 mg/kg) schedule (group B). Thirty patients were enrolled in each group. They were suffering from urinary tract infections (37), respiratory tract infections (17), soft-tissue infections (3), exacerbation of chronic prostatitis (1), acute cholangitis (1) and abdominal abscess (1). Aggravating factors were present in 77% and 60% of the groups respectively. The pathogens isolated included strains of various Enterobacteriaceae (53) and Pseudomonas aeruginosa (10) In 76.7 vs 97% (P less than 0.05) the clinical result was satisfactory with pathogen eradication in 80 vs 86.7%. However, there were proportionately more patients in the 7.5 mg/kg bd regimen with respiratory tract infection (40 vs 13%) and fewer patients with urinary tract infections (40 vs 80%). Mild and transient nephrotoxicity and ototoxicity was observed in five and three patients respectively. More patients in group B had amikacin trough concentrations less than or equal to 5 mg/l and peak levels greater than 40 mg/l (P less than 0.001) as well as serum bactericidal titres greater than or equal to 1:16 (P less than 0.05) without significant serum amikacin accumulation over time. It is concluded that amikacin administered once daily is well tolerated and provides better serum bactericidal activity than the twice-daily regimen.

Adult↗

PubMed1991

Kinetics and comparative efficacy of ofloxacin versus co-trimoxazole in the asymptomatic bacteriuria of elderly subjects.

In a prospective randomized study ofloxacin (400 mg orally once daily) versus co-trimoxazole (320/1,600 mg orally once daily) were given for 3 weeks in 30 and 22 elderly semimobile patients respectively, suffering from asymptomatic bacteriuria. From the obtained results it was evident that: (a) ofloxacin was superior to co-trimoxazole regarding eradication of bacteriuria (p less than 0.05) particularly in patients with a positive antibody-coated bacteria test; (b) a high rate of superinfections and reinfections with strains resistant to co-trimoxazole was observed in both groups indicative of hidden underlying conditions predisposing to urinary tract infections and (c) ofloxacin did not accumulate in serum during prolonged therapy but the half-life ranged between 8.3 and 10.2 h.

Aged↗

PubMed1990

Diffusing capacity of the lung and nifedipine in systemic sclerosis.

Lung involvement in systemic sclerosis may be due in part to a functional abnormality of the pulmonary vasculature. To investigate the possible role of a pulmonary vasospastic process in this disorder, 21 non-smoking patients who had no evidence of cardiac disease or pulmonary hypertension were evaluated with pulmonary function tests prior to administration of nifedipine, 30 minutes after a single oral dose of nifedipine (20 mg), and after 4 weeks of treatment with nifedipine (10 mg 3 times daily). Treatment with nifedipine did not significantly change any of the pulmonary function values, except for the carbon monoxide diffusing capacity (DLCO). The linear trend between the individual DLCO values at baseline and their changes immediately following the initial 20-mg dose of nifedipine (r = -0.603, P = 0.02) and after 4 weeks of treatment (r = -0.636, P = 0.01) showed that the lower the DLCO value at baseline, the greater the improvement caused by nifedipine. These findings support the hypothesis of a potentially reversible pulmonary vasospasm in systemic sclerosis and suggest that nifedipine may be useful in the treatment of lung disease in these patients; however, further studies are needed.

Adult↗

PubMed1990

A prospective angiographic study of the coronary collateral circulation in coronary arterial disease.

A prospective angiographic study of the coronary collateral circulation was performed in 600 consecutive patients found to have significant coronary arterial disease at cardiac catheterization. As the number of diseased coronary vessels increased the evidence of collaterals rose significantly (P = 0.00002) and the intensity of the collateral circulation increased (P = 0.05). For totally occluded lesions the collateral incidence was 70.4%, independent of the particular vessel involved. For stenoses greater than 90% collateral frequency and intensity were significantly greater for lesions of the right coronary artery than of the left anterior descending and the left circumflex arteries. The distribution of the coronary collateral circulation is described quantitatively according to the site of the lesion. Finally, a coronary collateral circulation occurred more frequently (P less than 0.000 001) and excepting Grade I, the intensity of the coronary collateral circulation was significantly greater in patients with a history of acute myocardial infarction.

Analysis of Variance↗

PubMed1990

Pefloxacin versus imipenem in the therapy of nosocomial lung infections of intensive care unit patients.

In a prospective open randomized trial pefloxacin (400 mg, iv, 8-hourly) and imipenem (1 g, iv, 8-hourly) were given for 5-30 days to 35 and 36 ICU patients, respectively, suffering from bronchopneumonia (54) or purulent bronchitis (17). All were spiking high fevers (greater than or equal to 39 degrees C) while 25 and 26 patients in the two groups were under mechanical ventilation. Underlying predisposing disorders, mainly chronic obstructive pulmonary disease, ischaemic heart disease, neurological diseases and traumatic lung injuries, were encountered in almost all. In appropriate bronchial secretion cultures, multiresistant Acinetobacter anitratus (40), Pseudomonas aeruginosa (25), various Enterobacteriaceae (17) and Staphylococcus aureus (6) were isolated. A successful clinical response, as proved by elimination of abnormal lung x-ray findings, temperature normalization and decreases in oxygen requirements, permitting weaning from mechanical ventilation and/or removal of nasotracheal intubation, was observed in 23 patients given pefloxacin (65.7%) and 19 patients given imipenem (52.8%). The differences in clinical outcome did not reach statistical significance. During therapy pathogens persisted in 9 (25.7%) patients given pefloxacin versus 18 (50%) given imipenem (P less than 0.05), while persisters developed resistance to pefloxacin and imipenem in seven and 12 patients, respectively (P less than 0.05). Tolerance was excellent for both antimicrobials. In the therapy of lung infections in ICU patients, pefloxacin when compared to imipenem was associated with more promising results, lower numbers of persisting pathogens and a lower incidence of resistance development.

Acinetobacter Infections↗

PubMed1990

Recovery from insulin-induced hypoglycemia after saccharose or glucose administration.

This study compared the effects of saccharose and glucose on the recovery from insulin hypoglycemia. 17 normal volunteers (12 men, 5 women, 25-40 years old) received the same dose (0.1 IU i.v.) of semisynthetic rapid-acting human insulin on two different days after an overnight fast. Blood glucose and C peptide were measured in venous blood samples before as well as at regular time intervals after insulin administration. 30 min after the injection, 20 g saccharose or 20 g glucose p.o. (diluted in water) were given. The mean glucose values were at most time intervals higher after glucose than after saccharose administration. In addition, glucose ingestion resulted in an earlier and steeper blood glucose rise (mean recovery rates during the first 5 min 3.10 and 1.38 mg/dl/min for glucose and saccharose, respectively). The C peptide values decreased progressively and did not achieve baseline levels even at 120 min in spite of blood sugar normalization. It is concluded that glucose acts faster than saccharose in insulin-induced hypoglycemia. Exogenous insulin results in a prolonged depression of C peptide which lasts longer than the hypoglycemic effect.

Adult↗

PubMed1989

Pharmacokinetics of three newer quinolones in pregnant and lactating women.

Sixty pregnant women with fetuses affected by beta-thalassemia major underwent termination of gestation induced by amniocentesis and intrauterine instillation of prostaglandin F2 alpha between 19 and 25 weeks. Pharmacokinetics of ciprofloxacin in maternal blood and amniotic fluid were studied after two doses of ciprofloxacin (200 mg intravenously every 12 hours), after two doses of pefloxacin (400 mg intravenously every 12 hours), and after two doses of ofloxacin (400 mg intravenously every 12 hours). Twenty patients were studied in each group. The ranges of mean maternal serum and amniotic fluid levels were as follows: ciprofloxacin in maternal serum 0.01 to 0.28 micrograms/ml, in amniotic fluid 0.1 to 0.13 micrograms/ml; pefloxacin in maternal serum 2.65 to 4.31 micrograms/ml, in amniotic fluid 1.97 to 2.74 micrograms/ml; and ofloxacin in maternal serum 0.07 to 0.68 micrograms/ml, in amniotic fluid 0.13 to 0.25 micrograms/ml. Three groups of lactating women (10 women in each), were given three doses of 750 mg ciprofloxacin orally, 400 mg pefloxacin orally, and 400 mg ofloxacin orally. Serum and milk samples were obtained simultaneously at two, four, six, nine, 12, and 24 hours after dosage administration. The mean breast milk levels of ciprofloxacin at the corresponding time intervals were 3.79, 2.26, 0.86, 0.51, 0.20, and 0.02 micrograms/ml. The mean breast milk levels of pefloxacin were 3.54, 3.43, 2.93, 2.24, 1.79, and 0.88 micrograms/ml, and of ofloxacin, 2.41, 1.91, 1.25, 0.64, 0.29, and 0.05 micrograms/ml. It is concluded that all studied quinolones penetrate the placenta and are found in amniotic fluid at low concentrations and at much higher levels in breast milk. Because of the potential for quinolones to cause arthropathy in juvenile animals, their use should be avoided in pregnant and lactating women.

Adult↗

PubMed1989

Comparison of haemodynamic effects of nifedipine and molsidomine in patients with coronary artery disease.

The haemodynamic effects of oral nifedipine 20 mg and molsidomine 4 mg were compared in 24 patients with coronary artery disease. Molsidomine unlike nifedipine caused a significant fall in mean pulmonary artery pressure and left ventricular end-diastolic pressure. Both drugs caused a significant and comparable reduction in systolic and diastolic blood pressure. Although only nifedipine significantly reduced systemic vascular resistance the difference between the drugs was not significant. The heart rate was significantly increased by nifedipine but not by molsidomine. The ejection phase indices were all increased by molsidomine and the increment in the mean normalized systolic ejection rate was significantly greater than that due to nifedipine. The left ventricular end-systolic volume index decreased significantly after molsidomine but not nifedipine. Neither drug significantly affected left ventricular end diastolic volume index, stroke volume index, maximal rate of rise of left ventricular pressure or left ventricular stroke work index.

Adult↗