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Biomedical subjects

C Roque

Publications and source records attributed to C Roque.

18 recordsLinked to original sources
PubMed2005

[Giant thymolipoma].

Thymolipoma is an uncommon benign tumor (accounting for 2% to 9% of thymus tumors). We present the case of a 26-year-old man who sought medical attention for left-sided pleural pain of 3 months duration. Computed tomography showed a mass in the left side of the chest occupying both the anterior mediastinum and the left pleural cavity. This mass caused lung collapse and mediastinal shift. Magnetic resonance imaging revealed a large fatty tumor and transthoracic biopsy with radiological guidance confirmed the diagnosis. The tumor was resected through a left thoracotomy. No postsurgical complications occurred and the histopathological diagnosis was thymolipoma.

Adult↗
PubMed2003

Cognitive performance and MR markers of cerebral injury in cognitively impaired MS patients.

OBJECTIVE: To relate neuropsychological performance to measures of cerebral injury in persons with MS selected for cognitive impairment. METHODS: Participants were 37 individuals with relapsing-remitting (59.5%) and secondary progressive (40.5%) MS. They were tested at baseline as part of a clinical trial to enhance cognition with an acetylcholinesterase inhibitor. Eligibility criteria included at least mild cognitive impairment on a verbal learning and memory task. A modified Brief Repeatable Battery of Neuropsychological Tests formed the core of the behavioral protocol. Neuroimaging measures were central (ventricular) cerebral atrophy, lesion volume, and ratios of N-acetyl aspartate (NAA) to both creatine and choline. RESULTS: A clear, consistent relation was found between cognitive and MR measures. Among neuroimaging measures, central atrophy displayed the highest correlations with cognition, accounting for approximately half the variance in overall cognitive performance. NAA ratios in right hemisphere sites displayed larger correlations than those on the left. Multiple regression models combining the MR measures accounted for well over half the variance in overall cognitive performance. The Symbol Digit Modalities Test was the neuropsychological task most strongly associated with the neuroimaging variables. CONCLUSIONS: If a strong and stable association can be firmly established between cognitive and MR variables in appropriate subsets of MS patients, it might aid in the investigation of interventions to enhance cognition and modify the course of the disease.

Adult↗
PubMed2001

Dose-escalation, phase I/II study of azithromycin and pyrimethamine for the treatment of toxoplasmic encephalitis in AIDS.

OBJECTIVE: To assess the safety, tolerance and activity of increasing doses of azithromycin in combination with pyrimethamine for the treatment of toxoplasmic encephalitis (TE) in patients with AIDS. DESIGN: A phase I/II dose-escalation study of oral azithromycin in combination with pyrimethamine. SETTING: Eight clinical sites in the United States. PATIENTS: Forty-two adult HIV-infected patients with confirmed or presumed acute TE. METHODS: Patients were enrolled into three successive cohorts receiving azithromycin 900, 1200 and 1500 mg a day with pyrimethamine as induction therapy. The induction period was 6 weeks followed by 24 weeks of maintenance therapy. MAIN OUTCOME MEASURES: Patient response was evaluated clinically and radiologically. RESULTS: Of the 30 evaluable patients, 20 (67%) responded to therapy during the induction period. Ten experienced disease progression. Of the 15 patients who received maintenance therapy, seven (47%) relapsed. Six patients discontinued treatment during the induction period as a result of reversible toxicities. Treatment-terminating adverse events occurred most frequently among the patients receiving the 1500 mg dose. CONCLUSION: The combination of azithromycin (900-1200 mg a day) and pyrimethamine may be useful as an alternative therapy for TE among patients intolerant of sulfonamides and clindamycin, but maintenance therapy with this combination was associated with a high relapse rate. The combination was safe, but low-grade adverse events were common.

AIDS-Related Opportunistic Infections↗
PubMed2000

Therapy for patients with high grade astrocytoma using intraarterial chemotherapy and radiation therapy.

BACKGROUND: High grade astrocytomas account for approximately 40% of all primary brain tumors. The median survival is approximately 8-10 months for patients with glioblastoma multiforme and 36 months for patients with anaplastic astrocytoma. The results of systemic chemotherapy in the treatment of brain tumors have been reported to be less than satisfactory, mainly because of the blood-brain barrier impermeability for chemotherapeutic drugs. Intraarterial chemotherapy has been an attractive alternative with which to overcome this problem. METHODS: Eighty-three patients with high grade astrocytoma (glioblastoma multiforme [63 patients] and anaplastic astrocytoma--[20 patients]) were treated with intraarterial (intracarotid and/or intravertebral) chemotherapy and radiation therapy between 1987 and 1997. Patients received cisplatin, 60 mg/m2, and etoposide, 40 mg/m2. Radiation therapy was delivered either after completion of the chemotherapy or concomitantly with the chemotherapy. RESULTS: Thirty-four of 71 evaluable patients with high grade astrocytoma (48%) responded to the chemotherapy. The median survival for patients with glioblastoma multiforme who received chemotherapy prior to radiation therapy was 20 months versus 7 months for those patients who underwent concomitant chemotherapy/radiation therapy. Patients with anaplastic astrocytoma who received chemotherapy prior to radiation therapy had a median survival of 45 months compared with 12 months for patients who received concomitant chemotherapy/ radiation therapy. The toxicity profile has been reported to be mild and well tolerated. CONCLUSIONS: Intraarterial chemotherapy for patients with glioblastoma multiforme, delivered prior to radiation therapy, appears to result in a median survival three times longer than that achieved with concomitant chemotherapy/radiation therapy. In addition, patients appear to survive substantially longer than they do after radiation therapy with the addition of systemic chemotherapy. Side effects are reported to be acceptable.

Adult↗
PubMed2000

Effect of aspirin on platelet desaggregation induced by SR121566, a potent GP-IIb/IIIa antagonist.

Since results of recent clinical trial, performed in patients suffering from acute coronary syndromes, suggested that aspirin improved the efficacy of an anti-GP-IIb/IIIa therapy, this work was set to study the mechanism underlying such a mechanism of aspirin. SR121566 (3 mg/kg, i.v.), a new selective antagonist of the GP-IIb/IIIa complex inhibited thrombus formation which occurred following electrical stimulation of the carotid artery of rabbits. On rabbits pre-treated with aspirin (10 mg/kg, i.v.), a bolus injection of SR121566 produced a strong reversal of thrombosis compared with the effect obtained on rabbits treated with SR121566 alone. In vitro, the addition of SR121566 to human platelets during the ADP-induced aggregation process resulted in a reversal of the aggregation which was nearly complete when it was added 30 s after the induction of aggregation, but progressively decreased when SR121566 was added at later times. ADP-induced platelet aggregation in the presence of aspirin (1 mM) was comparable to that obtained in control platelet-rich plasma, but the addition of SR121566 at all time points of the aggregation process was followed by a complete reversal of the aggregation even at later time points (> 120 s). Histological examination of the platelet aggregates showed a clear-cut difference in the platelet content between control and aspirin-treated platelets which contained much more dense granules. Inhibition of the release of thrombospondin by aspirin may account for a significant part of its pro-desaggregating activity as demonstrated by the effect of the tetrapeptide VTCG, an inhibitor of the binding of thrombospondin to its receptor, which strongly potentiated the activity of SR121566 as a desaggregating agent. Therefore, our study shows that aspirin pretreatment promotes a 'thrombolytic' activity of GP-IIb/IIIa inhibitors and, in particular, of SR121566, a potent and selective member of this new class of compounds. This effect is mainly due to an inhibition of the release of the platelet granule content and in particular to thrombospondin. This observation may contribute to a greater efficacy of GP-IIb/IIIa inhibitors for the treatment of thrombosis in atherosclerotic patients.

Adenosine Diphosphate↗
PubMed1999

Toxicities related to intraarterial infusion of cisplatin and etoposide in patients with brain tumors.

Chemotherapy for malignant brain tumors has a limited efficacy largely due to restricted blood-brain barrier permeability for chemotherapeutic drugs. Intraarterial chemotherapy (IAC) has the advantage of increased uptake during the first passage of the drugs through tumor capillaries. Initial IAC trials had less than satisfactory results due to unacceptable toxicities. Between 1987 and 1996, 173 patients with primary and metastatic brain tumors were treated with intraarterial (intracarotid and/or intravertebral) cisplatin and etoposide (VP-16). Out of these, 168 patients, who received a total of 438 cycles, were evaluated for the incidence of toxicities. Patients received either cisplatin at 40 mg/m2 and VP-16 at 20 mg/m2 or cisplatin at 60 mg/m2 and VP-16 at 40 mg/m2. Nausea and vomiting were the most common toxicities (42 patients, 14% of cycles). Arterial puncture was associated with a 1.6% incidence of groin hematomas (6 patients), and a 0.7% incidence of failure to canulate the carotid or vertebral arteries (3 patients). Neurologic toxicities included headache (1.4% of cycles, 5 patients), focal seizures (1.4% of cycles, 5 patients), transient confusion and urinary retention/incontinence (1.9% of cycles, 8 patients), and blurred vision (0.9% of cycles, 4 patients). We have not seen visual loss, strokes, major vessel dissection or thrombosis, or myelosuppression. Toxicity incidence was higher in patients with metastatic brain tumors than in those with primary brain tumors (34% versus 17%, p < 0.001). It was also higher in patients who had brain radiation therapy (RT) prior to IAC than in those who had RT concomitant with IAC (31% versus 19%, p = 0.05). No significant difference in toxicity incidence was noticed between patients who received RT concomitant with IAC and those who received RT after IAC (19% and 23% respectively, p = 0.08). Intracarotid chemotherapy given prior to RT resulted in 23 months of median survival for patients with glioblastoma multiforme. Intraarterial chemotherapy with cisplatin and VP-16 is a relatively safe treatment modality, especially in patients with primary brain tumors who have not received brain radiotherapy.

Adolescent↗
PubMed1999

Colocalization of sterol isomerase and sigma(1) receptor at endoplasmic reticulum and nuclear envelope level.

SR31747A is a sigma ligand previously described as having original immunosuppressive properties. Two SR31747A targets were recently identified and termed sigma(1) or SR-BP-1 (SR31747A-binding protein-1) and hSI (human sterol isomerase). In order to characterize these proteins further, we examined their expression and localization at the subcellular level. Based on the amino acid sequence deduced from the cloned hSI, anti-hSI polyclonal antibody was raised against the N-terminal fragment of the protein. Using this antibody, we performed Western-blot experiments to demonstrate the presence of hSI in various B and T cell lines, and hSI expression was quantified in these cell lines by flow cytometry and estimated at 15 000-30 000 sites per cell. Subcellular localization studies by both confocal and electron microscopy, performed on THP1 cells with anti-hSI antibody and with the previously described anti-(SR-BP-1) monoclonal antibody, demonstrated that: (a) hSI was colocalized with SR-BP-1; (b) hSI and SR-BP-1 were associated with the endoplasmic reticulum and with the outer and inner membranes of the nuclear envelope; (c) both proteins were delocalized during the cell cycle at the mitosis step when the nuclear membranes disappeared. Taken together our results suggest that both SR31747A-binding proteins not only play a role in sterol metabolism but indirectly affect lipoprotein functions.

Antibodies, Monoclonal↗
PubMed1997

Vasculitis owing to infection.

Infections are a recognized cause of secondary vasculitis. A variety of pathogens have a propensity to involve blood vessels. Vasculitis, non-vasculitic vasculopathy, and mycotic aneurysms lead to infarction and hemorrhage of nervous system tissue. Treatment of infection-related vasculitis should include appropriate antimicrobial therapy directed against the offending pathogen, and appropriate management of cerebrovascular complications.

Bacterial Infections↗
PubMed1996

Entry and distribution of fluorescent antiproliferative heparin derivatives into rat vascular smooth muscle cells: comparison between heparin-sensitive and heparin-resistant cultures.

We studied the binding and entry of fluorescein (FITC)-labeled heparin derivatives into rat aortic smooth muscle cells (SMC) by confocal microscopy. FITC-labeled heparin fractions or FITC-labeled SR 80037A, a potent antiproliferative heparin derivative (Bârzu et al., Eur. J. Pharmacol., 219:225-233 1992), were prepared and their antiproliferative activity was confirmed. By incubating SMC with FITC-labeled heparins, a specific cell-associated fluorescence was found. Cellular fluorescence was mostly located around the nucleus and at the level of cell contacts or cell adhesion. The fluorescence was displaced neither by chasing with excess of unlabeled heparins nor by washing with 1 M NaCl, which proved that labeled heparins had been internalized by SMC. Kinetics of internalization of FITC-heparins suggested receptor-mediated endocytosis of heparins by SMC. Double labeling of SMC with biotinylated Concanavalin A and FITC-SR 80037A also indicated that heparin derivative enters the endocytic pathway. The process was accelerated when serum was present in the incubation medium. Treatment of cells with chloroquine (50 microM) induced accumulation of FITC-SR 80037A in the late endosomes, around the nucleus. No fluorescence labeling could be evidenced inside the nucleus. Neither electron microscopy nor cell fractionation experiments performed with SMC previously incubated with [3H]-heparin were able to ascertain nuclear uptake of heparin, as proposed by other workers (Busch et al., Cell Biol., 116:31-42; 1992; Sing et al., Drug Dev. Res., 29:129-136 1993). The cell-associated fluorescence was very weak in SMC resistant to the antiproliferative activity of heparin, selected by long-term heparin treatment (HT-SMC) as previously shown [Bârzu et al., J. Cell. Physiol., 160:239-248, 1994]. The HT-SMC differed from control SMC with regard to expression of extracellular matrix proteins. These cells exhibited very low expression of fibronectin and prevalent expression of laminin and synthesized less cell-associated glycosaminoglycans. From our results, the following conclusions can be drawn: (1) the antiproliferative heparins are bound and internalized by SMC without being taken up into the nucleus; (2) there is a correlation between the binding and/or the internalization process and the sensitivity of SMC to the antiproliferative activity of heparins; and (3) selection of heparin-resistant SMC by long treatment with heparin results in particular growth pattern of SMC (absence of focal overgrowth), associated with changes in the expression of the extracellular matrix components (fibronectin, laminin, and cell-bound glycosaminoglycans).

Animals↗
PubMed1994

Subcellular localization of peripheral benzodiazepine receptors on human leukocytes.

BACKGROUND: The peripheral-type benzodiazepine receptor (PBR) was initially identified in many peripheral tissues and in some blood cells. Drugs that bind with high affinity to PBRs have previously been described as having immunomodulating properties. The number of PBRs varies according to the cell population considered. The aim of this study was to study the localization of PBRs in two human leukocyte populations, T4-lymphocytes, and monocytes. EXPERIMENTAL DESIGN: Both cell populations were purified by negative immunoselection in order to keep only the physiologically accessible sites on the viable cells. Mitochondria were quantified by electron microscopy and flow cytometric analysis. Subcellular localization was then studied after PBR photoaffinity labeling using electron microscopic ultrastructural autoradiography. RESULTS: We have shown that monocytes contain twice as many mitochondria as lymphocytes. We have also shown that the global labeling of monocytes by ultrastructural autoradiography is actually higher than that of lymphocytes and the labeling of monocyte mitochondria is higher than that of lymphocyte mitochondria. In addition, the distribution of subcellular labeling indicates that there are different populations of mitochondria in one cell, i.e., labeled and unlabeled, and that the percentage of labeled mitochondria is greater in monocytes. These results are consistent with those obtained in previous binding studies. Finally, over 50% of receptors are localized in cell compartments devoid of visible mitochondria. CONCLUSIONS: The subcellular distribution of the PBR shows that this receptor could have other physiologic functions towards immune cells than a function associated with mitochondria.

Autoradiography↗
PubMed1993

Distribution profile and properties of peripheral-type benzodiazepine receptors on human hemopoietic cells.

The cellular localization of peripheral-type benzodiazepine receptors (PBRs) was characterized in several human blood cell subpopulations including erythrocytes, platelets, monocytes and polymorphonuclear neutrophils (PMN), B, NK, T8 and T4-cells. Pharmacological properties of the PBR were established by binding studies and PBR mRNA expression was measured by quantitative polymerase chain reaction based method. These data clearly indicate 1) the PBR is pharmacologically homogeneous in the various types of blood cells, 2) the rank order of PBR cell density is monocytes = PMN > lymphocytes >> platelets > erythrocytes, 3) the PBR appears to be transcriptionally regulated since mRNA levels are roughly correlated with PBR density.

Antibodies, Monoclonal↗
PubMed1992

Regulation of cytochrome P450IA1 gene expression in a human intestinal cell line, Caco-2.

The expression and inducibility of cytochrome P450IA1 isozyme was investigated in the human carcinoma cell line Caco-2 cultured between days 7 and 35 in the absence or the presence of various enzyme inducers such as 3-methylcholanthrene, beta-naphthoflavone (beta NF), dioxin, isosafrole, rifampycin, dexamethasone or phenobarbital. 7-Ethoxyresorufin O-deethylase activity (EROD) was maximal at day 25 when the differentiation of Caco-2 cells, characterized by the level of the brush border associated enzymes such as sucrase isomaltase and alkaline phosphatase, was higher. The inducibility of this enzyme activity was found to be maximal when cells were treated between days 7 and 10. After a 3-day treatment of Caco-2 cells with 50 microM beta NF, EROD achieved 36.6 +/- 14.6 pmol/min/mg compared to 2.5 +/- 1.1 pmol/min/mg in untreated cells. This enzyme activity appeared to be supported only by P450IA1 isozyme because: 1) EROD was quantitatively inhibited by alpha-naphthoflavone, a P450IA1-specific inhibitor; otherwise, phenacetin O-deethylation was completely abolished in the presence of alpha-naphthoflavone and not by furafylline, a P450IA2-specific inhibitor; 2) EROD was induced after treatment with 3-methylcholanthrene, beta NF and dioxin, which are P450IA1 inducers, but not by isosafrole, a P450IA2-specific inducer; 3) cytochrome P450IA1 apoprotein could be immunodetected by antibodies directed against rabbit cytochrome P450-LM6, orthologous to P450IA1, in polycyclic hydrocarbon-treated cells; 4) under the latter conditions, P450IA1 mRNA accumulation was specifically detected, but not P450IA2 mRNA.(ABSTRACT TRUNCATED AT 250 WORDS)

Benzoflavones↗
PubMed1991

Intracarotid chemotherapy with etoposide and cisplatin for malignant brain tumors.

Chemotherapy for tumors of the central nervous system has a limited efficacy presumably because of restricted blood-brain barrier permeability. The advantage of regional intra-arterial administration of anticancer drugs is an increased uptake during the first passage of the drugs through tumor capillaries. Twenty patients with high-grade astrocytomas (HGA) and 28 patients with metastatic brain tumors (MBT) received intracarotid/intravertebral infusion of etoposide and cisplatin. Eight patients with HGA who underwent incomplete resection responded to chemotherapy alone. Four additional patients had complete resection of the tumor. Median survival time of the group (responders and nonresponders) has been 14 months. Twelve patients with MBT responded to chemotherapy alone (six had complete response [CR], and six had partial response [PR]) with a median survival time of 7 months. Intra-arterial chemotherapy (IAC) appears to be effective with acceptable toxicities. Accrual of additional patients is required before a final conclusion can be reached.

Adult↗
PubMedDate not supplied

MRI findings in children infected by Borrelia burgdorferi.

Cranial magnetic resonance imaging abnormalities were observed in 8 children (5 boys, 3 girls; ages 4-14 years) with neurologic problems following infection by Borrelia burgdorferi, the etiologic agent of Lyme disease. Neurologic features included headache (6), behavioral changes (5), facial palsy (2), papilledema (2), papilledema with diplopia (1), disturbance of sleep pattern (2), and carpal tunnel syndrome (1). Two MRI studies demonstrated multiple focal areas of increased signal intensity in white matter on long TR (both proton-density and T2-weighted) images.

Adolescent↗
PubMedDate not supplied

Interactive computerized microscopy as a tool for quantifying vascular remodelling effects of diabetes and V1a receptor antagonist SR 49059 on rat mesenteric arterial bed.

A methodology using interactive computerized microscopy (ICM) was developed to quantify in the mesenteric arterial bed the morphometric changes associated with diabetes and the influence of treatment with SR 49059, an antagonist of vasopressin V1a receptors. Four groups of rats were studied: untreated normal (N) or streptozotocin- (60 mg/kg i.v.) induced diabetic (D), and treated (0.4 mg/g SR 49059 included in food) normal (NT) or diabetic (DT) animals. Treatment was initiated 4 days after diabetes induction and continued for 3 weeks. Nested (hierarchical) analysis of variance of ICM data was performed on raw diameter or after logarithmic normalization of area and nuclei values. Diabetes was associated with an increase in arterial diameters, and in total vessel, wall, media, adventitia, and lumen areas. The same parameters, with the exception of the lumen, were also increased in DT as compared to D. The number of nuclei in the media or adventitia was increased in D as compared to N, and in DT as compared to D. In summary, ICM is allowed to further characterize the vascular mesenteric changes and describe for the first time the enlargement of adventitia associated with diabetes. Our study also suggested that the blockade of Via receptors is unable to prevent diabetes-related vascular changes, although the slight increase in food intake associated with SR 49059 treatment may have had an indirect influence on angiopathy development.

Animals↗
PubMedDate not supplied

Low doses of endotoxin potentiate venous thrombosis in the rabbit.

Procoagulant activity of the endothelium and of monocytes was induced by an intravenous administration of a low dose of endotoxin in the rabbit. Venous thrombosis induced by a 45-min stasis of the jugular vein was dramatically increased after the administration of endotoxin. Endotoxin enhanced venous thrombosis in a dose-dependent manner which was the highest after the administration of 1 microgram/kg. This effect increased with time but was optimal when endotoxin was injected 4 h before stasis induction. Leukocytes appear to play a key role in this process since mechlorethamine-induced leukopenia totally inhibited thrombus formation. Hirudin and heparin, administered intravenously 5 min before stasis, were both potent inhibitors of endotoxin-induced venous thrombosis exhibiting ED50 values of 3.8 +/- 1.0 and 2.3 +/- 1.1 microgram/kg, respectively.

Animals↗
PubMedDate not supplied

Brain imaging of an alcoholic with MRI, SPECT, and PET.

A medically healthy chronic alcoholic without evidence of neurological and neuropsychological impairment was studied with magnetic resonance imaging (MRI), single photon emission computerized tomography (SPECT), and positron emission tomography (PET). An age-matched normal volunteer was evaluated with the same scans for comparison. The MRI of the alcoholic revealed prominent ventricles and mild cortical atrophy. SPECT and PET revealed predominant involvement of the frontal cortex as shown by decreased frontal blood flow and metabolism. This case illustrates the sensitivity of brain imaging techniques in detecting cerebral abnormalities even in the absence of neurologic and/or neuropsychological impairments.

Alcoholism↗