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Biomedical subjects

C Popa

Publications and source records attributed to C Popa.

At least 19 recordsLinked to original sources
PubMed2006

Repeated B lymphocyte depletion with rituximab in rheumatoid arthritis over 7 yrs.

OBJECTIVE: To assess safety and efficacy of repeated B-cell depletion with rituximab in patients with rheumatoid arthritis (RA). METHODS: Thirty-seven patients with refractory RA entered into a programme of repeated B-lymphocyte depletion (up to 5 cycles, 89 cycles in total) with protocols based on the anti-CD20 monoclonal antibody, rituximab, have been observed over periods of >5 yrs (n = 22) or 3-5 yrs (n = 14). RESULTS: Twenty two subjects have been followed up for >5 yrs. Average duration of benefit per cycle was 15 months (maximum 43 months), and time to re-treatment 20 months. Nineteen patients remain on the programme. Patients were withdrawn for lack of efficacy (n = 5), hypersensitivity infusion reaction (n = 1), brevity of response (n = 8), or occurrence of adverse respiratory events (n = 1). Sixteen major lower respiratory events occurred during the 180 patient-yrs of follow-up. Of these only one had low IgG. In patients receiving rituximab +/- cyclophosphamide (cy) carcinomata have developed as follows: breast (3, +cy), ovary (1, +cy), transitional cell (1, +cy), and renal cell (1, -cy). Falls in total immunoglobulin levels to below the normal range occurred in 12 patients for IgM (undetectable levels in three after repeated cycles), seven for IgG and one for IgA, not taking into account patients who started off with low immunoglobulin levels before the first cycle. CONCLUSION: Repeated B-lymphocyte depletion over a 5-yr period appears to be an acceptable and relatively well-tolerated therapy in RA with a relatively high rate of continuation. Long-term effects on immunoglobulin levels require surveillance.

Adult↗
PubMed2005

Markers of inflammation are negatively correlated with serum leptin in rheumatoid arthritis.

BACKGROUND: Leptin regulates food intake and modulates immunity and inflammation. A positive feedback mechanism has been described between tumour necrosis factor (TNF) and leptin, and it has been suggested that leptin potentiates inflammation in patients with rheumatoid arthritis (RA). OBJECTIVE: To assess whether inflammation correlates with leptin concentrations in patients with RA, and whether anti-TNF treatment modulates leptin concentrations in these patients. METHODS: Leptin, IL6 and CRP were measured (at baseline and after 2 weeks of treatment) in the blood of 31 patients with RA starting either anti-TNF treatment or placebo, and in 18 healthy controls. RESULTS: In patients with RA, plasma leptin concentrations at baseline correlated inversely with the degree of inflammation as assessed by C reactive protein (CRP; r(s)(2) = 0.21, p<0.01) or interleukin (IL) 6 concentrations (r(s)(2) = 0.22, p<0.008). Mean (SD) leptin concentrations did not differ between patients with RA and controls (6.0 (4.6) v 4.2 (2.8) ng/ml in men; 15.1 (7.9) v 13.4 (5.2) ng/ml in women). Short course anti-TNF treatment for 2 weeks did not modify leptin concentrations, despite significant reduction of CRP and IL6. CONCLUSION: A significant inverse correlation between inflammation and leptin concentrations was found in patients with active RA, although plasma leptin concentrations did not significantly differ from those in healthy controls. This suggests that active chronic inflammation may lower plasma leptin concentrations. Two weeks' treatment with anti-TNF did not change plasma leptin concentrations and longer treatment may be needed to see an effect on leptin.

Adalimumab↗
PubMed2005

Titanium--hydroxyapatite porous structures for endosseous applications.

Materials for uncemented endosseous implants have to assure an as short as possible osseointegration time. Thus, a material with both surface bioactivity and a porous outer structure can become a preferred choice for this type of applications. This paper presents a class of titanium-base PM composites, reinforced with particulate hydroxyapatite. Raw materials were titanium powder, obtained through hydriding--milling--dehydriding, with the grain size of 63-100 microm, and sol-gel hydroxyapatite (HA) powder, produced by the reaction between Ca(NO3)2 x 4H2O and (NH4)2HPO4. Blends with 5 to 50% HA were prepared and pressed in a rigid die, producing single composition or gradual composition samples. The applied pressure was of 400, 500 or 600 MPa. Sintering was performed in vacuum, at 1160 ( composite function)C. All samples, although well sintered, displayed swelling during sintering, due to diffusion into the matrix. The increase in volume is more severe for higher amounts of HA in the green compacts and for higher applied compaction pressure. Compacts with a gradual increase of the HA content are recommended from the functional and mechanical point of view, but the increase should be slow, not to produce interlayer cracks. The outer surface shows interconnected pores, suitable for the ingrowth of vital new bone.

Bone and Bones↗
PubMed2005

Side effects of anticytokine strategies.

Anticytokine strategies probably represent the most important breakthrough in the treatment of inflammatory diseases in the last decade. However, blocking the bioactivity of proinflammatory cytokines, crucial activators of host defence, has proved to be accompanied by an increased susceptibility to infections, especially with Mycobacteria, Salmonellae and fungal pathogens. Multiple mechanisms for these side effects have been proposed, such as inhibition of gamma-interferon production, decreased expression of pattern-recognition receptors, and leucocyte apoptosis. Caution is therefore warranted when these treatments are given to patients with an increased risk for infections. A range of side effects other than infection have been reported.

Adalimumab↗
PubMed2005

Cryptic fibromuscular dysplasia in the meningeal vessels. An autopsy study.

We retrospectively evaluate the presence of cryptic fibromuscular dysplasia (FMD) (i.e. not macroscopically visible and not associated to FMD in larger arteries) in the small meningeal vessels in a comprehensive series of patients. Such a study has not been performed before to our knowledge. The meningeal tissue has been systematically examined in a series of 100 consecutive autopsies. The immunohistochemical study was performed in one case with leptomeningeal FMD. In the whole series only one case had FMD in the small leptomeningeal arteries. The histological variant was intimal fibroplasia, a rare variant of FMD. Immunohistochemistry was necessary to confirm this peculiar change of the vascular wall. Cryptic fibromuscular dysplasia in the meninges is a very rare finding in our series of autopsied patients--1% of cases, in concordance with the literature data. The clinical associations of this lesion are difficult to be related to this lesion. A cryptic presence of FMD must be suspected in some cases with stroke.

Autopsy↗
PubMed2004

Influence of anti-tumour necrosis factor therapy on cardiovascular risk factors in patients with active rheumatoid arthritis.

BACKGROUND: Tumour necrosis factor (TNF) is known to increase the concentrations of interleukin (IL) 6 and C reactive protein (CRP) and to induce proatherogenic changes in the lipid profile and may increase the cardiovascular risk of patients with rheumatoid arthritis (RA) and other inflammatory disorders. OBJECTIVE: To assess whether anti-TNF therapy modifies the cardiovascular risk profile in patients with RA. METHODS: The lipoprotein spectrum and the inflammation markers CRP and IL6 were investigated in 33 patients with RA treated with human anti-TNF monoclonal antibodies (D2E7, adalimumab, Humira) and 13 patients with RA given placebo, before and after 2 weeks' treatment. RESULTS: In the anti-TNF treated group, the mean (SD) concentrations of HDL-cholesterol were significantly higher after 2 weeks' treatment (0.86 (0.30) mmol/l v 0.98 (0.33) mmol/l, p<0.01), whereas LDL and triglyceride levels were not significantly changed. Additionally, a significant decrease in CRP (86.1 (54.4) mg/l v 35.4 (35.0) mg/l, p<0.0001), and IL6 (88.3 (60.5) pg/ml v 42.3 (40.7) pg/ml, p<0.001) concentrations was seen in this group. No changes in lipid profile, IL6, or CRP levels were seen in the placebo group. CONCLUSIONS: TNF neutralisation with monoclonal anti-TNF antibodies increased HDL-cholesterol levels and decreased CRP and IL6 levels after 2 weeks. Therefore this treatment may improve the cardiovascular risk profile of patients with RA.

Adalimumab↗
PubMed2001

[Quality assurance of drug prescription in primary health care. A new database software makes the drug therapy surveillance easier].

Quality assurance of drug prescription is a pre-requisite for rational drug use. From 22 health-care centres in the south-western area of the Stockholm County Council region, drug-prescription data were obtained from the patients' computerised medical recordings. This could be done with the aid of a specially designed database program. The drug-prescription data from the 22 health-care centres were collected and compiled in a central unit. Thereafter the results were brought back to the health-care centres, in which the quality assurance of drug prescription could be started.

Community Health Centers↗
PubMed2001

Histone hyperacetylation induced by histone deacetylase inhibitors is not sufficient to cause growth inhibition in human dermal fibroblasts.

Use of specific histone deacetylase inhibitors has revealed critical roles for the histone deacetylases (HDAC) in controlling proliferation. Although many studies have correlated the function of HDAC inhibitors with the hyperacetylation of histones, few studies have specifically addressed whether the accumulation of acetylated histones, caused by HDAC inhibitor treatment, is responsible for growth inhibition. In the present study we show that HDAC inhibitors cause growth inhibition in normal and transformed keratinocytes but not in normal dermal fibroblasts. This was despite the observation that the HDAC inhibitor, suberic bishydroxamate (SBHA), caused a kinetically similar accumulation of hyperacetylated histones. This cell type-specific response to SBHA was not due to the inactivation of SBHA by fibroblasts, nor was it due to differences in the expression of specific HDAC family members. Remarkably, overexpression of HDACs 1, 4, and 6 in normal human fibroblasts resulted in cells that could be growth-inhibited by SBHA. These data suggest that, although histone acetylation is a major target for HDAC inhibitors, the accumulation of hyperacetylated histones is not sufficient to cause growth inhibition in all cell types. This suggests that growth inhibition, caused by HDAC inhibitors, may be the culmination of histone hyperacetylation acting in concert with other growth regulatory pathways.

Acetylation↗
PubMed2001

Chemical control of perennial and annual weeds in herbicide resistant soybean crops.

In Romania, the first tests with Roundup Ready on soybean crops were performed in 1998, on 2 soil types: a) at Teleorman Station on chernozem containing 3.5% humus, 4.5% clay b) at Brăila Station placed in Danube Meadow on alluvial soil containing 3.90% humus and 46% clay. In every locality cultivated soybean cultivar S.2254 was resistant to glyphosate. During the three years of experiments (1998-2000) the crop of soybean was infested with various species of weeds (both annual and perennial) of which the most important are: Sorghum halepense (60-80%), Echinochloa crus-galli, Setaria glauca, Amaranthus retroflexus, Solarium nigrum, Yanthium italicum, Abutilon theoprasthi, Sinapis arvensis, Datum stramonium, Polygonum persicaria, Calystegia sepium, Cirsium arvense. In 3 years of experience the best weed control and the highest soybean production were obtained in the variants treated 2 times postemergent with Roundup Ready at a dose of 3 + 3 l/ha. Similar results were also obtained in the farms of the Academy of Agricultural Forestry Sciences, where GMO soybean was cultivated on 1500 hectares.

Dose-Response Relationship, Drug↗
PubMed2000

E2F-1 induces proliferation-specific genes and suppresses squamous differentiation-specific genes in human epidermal keratinocytes.

Squamous differentiation of keratinocytes is associated with decreases in E2F-1 mRNA expression and E2F activity, and these processes are disrupted in squamous cell carcinoma cell lines. We now show that E2F-1 mRNA expression is increased in primary squamous cell carcinomas of the skin relative to normal epidermis. To explore the relationship between E2F-1 and squamous differentiation further, we examined the effect of altering E2F activity in primary human keratinocytes induced to differentiate. Promoter activity for the proliferation-associated genes, cdc2 and keratin 14, are inhibited during squamous differentiation. This inhibition can be inhibited by overexpression of E2F-1 in keratinocytes. Overexpression of E2F-1 also suppressed the expression of differentiation markers (transglutaminase type 1 and keratin 10) in differentiated keratinocytes. Blocking E2F activity by transfecting proliferating keratinocytes with dominant negative E2F-1 constructs inhibited the expression of cdc2 and E2F-1, but did not induce differentiation. Furthermore, expression of the dominant negative construct in epithelial carcinoma cell lines and normal keratinocytes decreased expression from the cdc2 promoter. These data indicate that E2F-1 promotes keratinocyte proliferation-specific marker genes and suppresses squamous differentiation-specific marker genes. Moreover, these data indicate that targeted disruption of E2F-1 activity may have therapeutic potential for the treatment of squamous carcinomas. Oncogene (2000).

Base Sequence↗
PubMed2000

A randomized clinical trial of combinations of artesunate and azithromycin for treatment of uncomplicated Plasmodium falciparum malaria in Thailand.

Recently, a combination of artesunate and mefloquine has proved effective, although is contraindicated in early pregnancy and young children. Azithromycin, a widely used antibiotic and has antimalarial effects, replace mefloquine as a new alternative antimalarial regimen. Two hundred and two uncomplicated falciparum malaria patients were randomly assigned to 1 of 3 regimens. Patients in group I (n = 68) received artesunate 200 mg once daily for 3 days, group II (n = 67) received artesunate 200 mg together with mefloquine 10 mg/kg on the first 2 days and artesunate 200 mg together with mefloquine 5 mg/kg on the third day, and group III (n = 67) received artesunate 200 mg together with azithromycin 50 mg once daily for 3 days. The 28 day cure rates were 44, 98 and 56%, respectively. The median time to recrudescence was significantly longer in group III. In conclusion, a combination of artesunate and azithromycin might be useful in treating children in whom bacterial and malarial infections may be concomitant. However, further work is required in order to enhance its clinical efficacy.

Adolescent↗
PubMed1999

Histone deacetylase inhibitors as potential anti-skin cancer agents.

The regulation of squamous differentiation is a tightly regulated process involving transcriptional repression and activation. Previous studies have established that squamous carcinoma cell lines inappropriately regulate the transcription of genes important to the control of squamous differentiation. Histone deactylase inhibitors such as trichostatin A (TSA) and butyrate disrupt normal chromatin structure and cause alterations in gene expression/regulation. For these reasons, we examined the effects of both butyrate and TSA on the growth and differentiation of human keratinocytes or squamous carcinoma cells in tissue culture. We found that treatment of keratinocytes or squamous carcinoma cells with butyrate induced a reversible growth arrest. TSA, on the other hand, induced an irreversible growth arrest in both keratinocytes and squamous carcinoma cells. The growth arrest of keratinocytes induced by TSA or butyrate was accompanied by a reduction in the mRNA levels for proliferation gene cdk1 and an induction of the mRNA for the differentiation-specific transglutaminase type I gene (TG1). In contrast, the squamous carcinoma cells had decreased cdk1 and TG1 mRNA in response to TSA or butyrate. Both of these agents produced transient increases in the acetylation of histone H4 in keratinocytes and squamous carcinoma cells. These data indicated that TSA may have potential as a topical treatment for epidermal malignancies.

Antineoplastic Agents↗
PubMed1999

Cytochrome P450, CYP26AI, is expressed at low levels in human epidermal keratinocytes and is not retinoic acid-inducible.

Retinoids, and their synthetic analogues, are well-established regulators of the squamous differentiation programme both in vivo and in vitro. Despite this, very few studies have focused on the mechanism by which retinoid action is terminated, e.g. metabolism. Recently, a new cytochrome P450 family member (CYP26AI) was cloned. CYP26AI was reported to have substrate specificity for retinoids and to be retinoid-inducible. In this study, we have examined the expression and retinoic acid (RA) inducibility of CYP26AI in human epidermis and cultured keratinocytes. We found very low levels of CYP26AI mRNA expression in both epidermis and keratinocytes. Furthermore, we found no evidence for RA inducibility of CYP26 mRNA expression. This lack of RA inducibility was not due to inactivity of the retinoids, as we show that transglutaminase was still repressed by RA in the same cultures. Despite the low levels of CYP26AI expression in the keratinocytes, the keratinocytes were still capable of significant RA metabolism. In conclusion, our study reports, for the first time, that CYP26AI is unlikely to contribute to RA metabolism in keratinocytes. These studies also indicate that as yet unknown isoforms of cytochrome P450 may be involved in RA metabolism in keratinocytes.

Cell Line↗
PubMed1999

Histone deacetylase inhibitors: novel anticancer agents.

Previous studies have established that the regulation of gene expression is dependent upon the nucleosomal integrity of nuclear DNA. To a large extent, this integrity is dictated by the acetylation status of the core histone particles. The acetylation of histones is, in turn, controlled by the combined activity of specific acetylases and deacetylases. Moreover, disruption of histone acetylases and deacetylases has been linked to a wide variety of human cancers. For this reason, the recent availability of potent and specific histone deacetylase inhibitors has provoked a great deal of interest amongst cancer biologists, oncologists and pharmacologists. Within the past 2- 3 years, several novel histone deacetylase inhibitors have been reported, many of which have already been tested in vivo in mouse models of cancer. In this review we focus on the rationale behind the use of histone deacetylase inhibitors as anticancer agents. Moreover, we review some of the recent findings pertaining to the use of these compounds as anticancer agents.

Journal Article↗
PubMed1998

Drug utilization 90%--a simple method for assessing the quality of drug prescribing.

OBJECTIVES: To describe a simple method for assessing the quality of drug prescribing. METHODS: We tested the idea that the number of drugs accounting for 90% of drug use--drug utilization 90% (DU90%)--may serve as an indicator of the quality of drug prescribing. We ranked the drugs by volume of defined daily doses (DDD) and determined how many drugs accounted for the DU90% segment. We also compared this segment with the pharmacotherapeutic guidelines issued by the Regional (local) Drug Committee to determine the adherence to its recommendations (index of adherence). The cost per DDD within the DU90% segment and for the remaining 10% was also calculated. The utilization of drugs based on prescriptions purchased during April 1995 was determined for 24 primary health care (PHC) centres in southwestern Stockholm. RESULTS: The number of different products, defined as all products marketed under a single brand name within an ATC (anatomic therapeutic chemical) category, in the DU90% segment varied twofold (81-164) between the 24 PHC centres. Differences in the number of GPs per PHC centre accounted for a third of this variation. The compliance with the Drug Committee recommendations varied between 54% and 78%. There was no relationship between the number of products accounting for the DU90% segment and the adherence to local prescription guidelines, i.e. prescribing more products did not increase the adherence. The costs for the DU90% drugs varied from 2.26 SEK/DDD in one PHC centre to 3.75 in another one, with an average cost of 2.87 SEK/DDD, while for the remaining 10% it was the double (6:54 SEK/DDD). In all, the DU90% drugs made up 80.8% of the total cost as compared with 19.2% for the remaining 10%. In the DU90% segment, there was no clear relationship between adherence to the guidelines and the cost/DDD, i.e. following the evidence-based guidelines appeared to provide a higher quality of prescribing rather than cheaper prescribing. CONCLUSIONS: The DU90% is an inexpensive, flexible, and simple method for assessing the quality of drug prescribing in routine health care. The number of products in the DU90% segment and adherence to prescription guidelines may serve as general quality indicators. The method may be adapted to provide comparative data between PHC centres, hospitals, regions etc. that may be cross-sectional and longitudinal. Other quality criteria, specific for each class of drugs, should complement these general indicators.

Catchment Area, Health↗
PubMed1998

Modelling human depth perception in binocular vision: obtaining the horizontal disparity map.

The paper presents a computer application developed as a tool for implementing, developing, and testing computational models for stereopsis. Two models for solving the correspondence problem and computing the stereo disparity map have been implemented. One of them is biologically inspired (it models the behaviour of simple and complex cells from the striate cortex) and the paper details the results obtained on random-dot stereograms and on pairs of real images.

Algorithms↗
PubMed1995

[Primary solid tumors of the mesentery].

The interest for the primary solid tumors of the mesentery (TSPM) is justified by the difficulties of preoperative diagnosis and surgical treatment of these unusual lesions. We analyzed 68 TSPM operated in the Department of General Surgery of Fundeni Hospital between 1960-1993. In the study were included only the lymphoma presented as mesenteric masses (n = 17); the enlarged mesenteric lymph nodes were excluded. The most common malignant tumor was the fibroma (n = 8) and lipoma (n = 10). In the resection of mesenteric tumors exposure of the superior mesenteric vessels is important. The relation between tumoral and superior mesenteric vessels is the necessary criterion of resectability: in 41 cases from 43 unresectable lesions the reason of unresectability was the invasion of the superior mesenteric vein and artery; in only two cases the reason was the presence of liver metastases. The resectability was not influenced by the multiplicity of the lesions: in all cases with multiple mesenteric tumors (6 patients) the resection was performed. The distant metastases of TSPM are rare; on the contrary, the local invasion is common.

Adult↗