Biomedical subjects

J Gielen

Publications and source records attributed to J Gielen.

At least 19 recordsLinked to original sources

PubMed2006

Prevalence, extension and characteristics of fluid-fluid levels in bone and soft tissue tumors.

The purpose of this study was to determine the prevalence, extension and signal characteristics of fluid-fluid levels in a large series of 700 bone and 700 soft tissue tumors. Out of a multi-institutional database, MRI of 700 consecutive patients with a bone tumor and MRI of 700 consecutive patients with a soft tissue neoplasm were retrospectively reviewed for the presence of fluid-fluid levels. Extension (single, multiple and proportion of the lesion occupied by fluid-fluid levels) and signal characteristics on magnetic resonance imaging of fluid-fluid levels were determined. In all patients, pathologic correlation was available. Of 700 patients with a bone tumor, 19 (10 male and 9 female; mean age, 29 years) presented with a fluid-fluid level (prevalence 2.7%). Multiple fluid-fluid levels occupying at least one half of the total volume of the lesion were found in the majority of patients. Diagnoses included aneurysmal bone cyst (ten cases), fibrous dysplasia (two cases), osteoblastoma (one case), simple bone cyst (one case), telangiectatic osteosarcoma (one case), "brown tumor" (one case), chondroblastoma (one case) and giant cell tumor (two cases). Of 700 patients with a soft tissue tumor, 20 (9 males and 11 females; mean age, 34 years) presented with a fluid-fluid level (prevalence 2.9%). Multiple fluid-fluid levels occupying at least one half of the total volume of the lesion were found in the majority of patients. Diagnoses included cavernous hemangioma (12 cases), synovial sarcoma (3 cases), angiosarcoma (1 case), aneurysmal bone cyst of soft tissue (1 case), myxofibrosarcoma (1 case) and high-grade sarcoma "not otherwise specified" (2 cases). In our series, the largest reported in the literature to the best of our knowledge, the presence of fluid-fluid levels is a rare finding with a prevalence of 2.7 and 2.9% in bone and soft tissue tumors, respectively. Fluid-fluid levels remain a non-specific finding and can occur in a wide range of bone and soft tissue tumors, both benign and malignant. Therefore, they cannot be considered diagnostic of any particular type of tumor, and the diagnosis should be made on the basis of other radiological and clinical findings.

Adolescent↗

PubMed2005

Prospective evaluation of emerging bacteria in cystic fibrosis.

BACKGROUND: Bacteria contribute considerably to the progression of lung disease in cystic fibrosis. In this prospective, multi-centre study, we aimed to evaluate the occurrence of emerging bacteria and the physicians' assessments of the clinical importance of these findings. METHODS: Twelve CF centres (total number of patients: 1419) reported the detection of any Stenotrophomonas maltophilia, Burkholderia cepacia complex, MRSA, Alcaligenes xylosoxidans, Klebsiella species and Mycobacteria during an observation period of 6 months. RESULTS: 213 specimens with emerging bacteria were reported from 145 different patients. The proportion of patients with emerging bacteria differed between centres (3-38%, mean: 12.6%) and increased with age. The predominant bacterium was S. maltophilia (n=106 positive specimens), followed by Klebsiellae (n=36), B. cepacia complex (n=31), A. xylosoxidans (n=16), Mycobacteria (n=11), MRSA (n=11), and others (n=2). In many instances the same microorganisms had already been reported earlier, indicating intermittent or chronic colonisation. The clinical status was reported to be stable in 70% of patients, and antibiotic treatment was anticipated for 46% of positive specimens. Comparison of clinical data to age matched controls did not reveal any significant differences with regard to pulmonary and nutritional status prior to detection of emerging bacteria. CONCLUSION: These data suggest a high variability between centres regarding the prevalence of emerging bacteria. Most patients maintained a stable clinical condition during the 6-month study period despite being colonised with emerging bacteria.

Adolescent↗

PubMed2004

Does the location of a vascular loop in the cerebellopontine angle explain pulsatile and non-pulsatile tinnitus?

The purpose was to investigate patients with unexplained pulsatile and non-pulsatile tinnitus by means of MR imaging of the cerebellopontine angle (CPA) and to correlate the clinical subtype of tinnitus with the location of a blood vessel (in the internal auditory canal or at the cisternal part of the VIIIth cranial nerve). Clinical presentation of tinnitus and perceptive hearing loss were correlated. In 47 patients with unexplained tinnitus, an MR examination of the CPA was performed. Virtual endoscopy reconstructions were obtained using a 3D axial thin-section high-resolution heavily T2-weighted gradient echo constructive interference in steady state (CISS) data-set. High-resolution T2-weighted CISS images showed a significantly higher number of vascular loops in the internal auditory canal in patients with arterial pulsatile tinnitus compared to patients with non-pulsatile tinnitus (P<0.00001). Virtual endoscopy images were used to investigate vascular contacts at the cisternal part of the VIIIth cranial nerve in patients with low pitch and high pitch non-pulsatile tinnitus. A significantly different distribution of the vascular contacts (P=0.0320) was found. Furthermore, a correlation between the clinical presentation of non-pulsatile tinnitus (high pitch and low pitch) and the perceptive hearing loss was found (P=0.0235). High-resolution heavily T2-weighted CISS images and virtual endoscopy of the CPA can be used to evaluate whether a vascular contact is present in the internal auditory canal or at the cisternal part of the VIIIth cranial nerve and whether the location of the vascular contact correlates with the clinical subtype of tinnitus. Our findings suggest that there is a tonotopical structure of the cisternal part of the VIIIth cranial nerve. A correlation between the clinical presentation of tinnitus and hearing loss was found.

Adolescent↗

PubMed2004

Abnormal response to metabolic stress in schizophrenia: marker of vulnerability or acquired sensitization?

BACKGROUND: Previous work suggests that individuals with schizophrenia display an altered homovanillic acid (HVA) response to metabolic stress. The present study replicated and extended this paradigm, including individuals with elevated genetic risk for schizophrenia. METHOD: Patients with psychosis (n = 50), non-psychotic first-degree relatives of patients with psychosis (n = 51) and controls without psychosis (n = 50) underwent, in randomized order, double-blind administration of placebo and the glucose analogue 2-deoxy-D-glucose (2DG), which induces a mild, transient clinical state of glucoprivation. Plasma HVA and cortisol were assessed twice before the start of the 2DG/placebo infusion (baseline values), as well as four times post infusion. Data were analysed using multi-level random regression techniques. RESULTS: During the stress condition, significant increases in plasma HVA and cortisol were found. The increase in plasma HVA level during the stress condition was significantly stronger in patients than in controls, whereas this was not the case in relatives v. controls. The increase in plasma cortisol during the stress condition was significantly less in patients than controls, but no significant difference in the increase of plasma cortisol during stress was found in the comparison between relatives and controls. CONCLUSIONS: Patients with psychosis, but not their non-psychotic first-degree relatives, show an altered neurobiological response to metabolic stress, suggesting that this dysregulation is not a genetically transmitted vulnerability, but an illness-related effect, possibly reflecting acquired sensitization of neuroendocrine systems by repeated environmental stressors or repeated stimulation with agonistic drugs.

Adolescent↗

PubMed2003

[Evaluation of glomerular filtration rate in clinical practice].

Glomerular filtration rate (GFR) is the most frequently used parameter to evaluate the renal function. GFR may be estimated with serum creatinine, creatinine clearance based on 24 hours urine collection or Cockcroft formula. All these methods have bias. Other approaches have thus been proposed. The limitations and advantages of isotopic methods and recent mathematical approaches (MDRD formula) are reviewed.

Chromium Radioisotopes↗

PubMed2003

[Cystatin C in the evaluation of renal function].

Glomerular filtration rate (GFR) is the best indicator of renal function. GFR is usually estimated by serum creatinine or the creatinine clearance calculated on urine collected over 24 hours or with the Cockcroft formula. These methods are however limited. Serum creatinine has a very poor sensitivity and urine collection is difficult. Cystatin C is a protease inhibitor produced in a constant manner by nucleated cells. This molecule is freely filtrated by the glomerule and quite completely catabolized in the proximal tubules. Its plasmatic concentration might thus be used to estimate GFR. Presently available data allow to conclude that plasmatic cystatin C is at least as good as serum creatinine to estimate GFR. It is less sensible to changes in body mass. Its determination appears more sensitive to detect early mild changes in GFR. Reference values are presently available for the different methods of determination. Cystatin C plasma level determination is more expensive than routine creatinine plasma determination. In the absence of very significant advantages, this might explain its limited use in daily clinical practice.

Biomarkers↗

PubMed2002

Lymphadenopathy at the medial epitrochlear region in cat-scratch disease.

Our objective was to describe the imaging features of lymphadenopathy at the medial epitrochlear region as frequently seen in cat-scratch disease (CSD) and to compare these features with those seen in non-CSD. Ten patients (four males and six females) presented with a subcutaneous soft tissue mass at the medial epitrochlear region. Three patients were younger than 15 years. Magnetic resonance imaging was performed in all patients. All lesions turned out to be regional lymphadenopathy instead of soft tissue neoplasm. They were caused by benign disorders in eight cases, including seven CSD and one other infection, and in two cases by metastatic disease. All lesions, except for three benign ones, were solitary. On MRI, high signal intensity (SI) strands in the surrounding soft tissue on T2-weighted images (WI) were present in all cases. Three cases of CSD showed homogeneous SI on both T1- and T2WI. After contrast administration, a moderate, homogeneous enhancement was seen. The other seven lesions, except for one metastasis, had both solid and liquid components. Liquid components showed high SI on T2WI without enhancement, whereas solid components had intermediate SI on T2WI and marked enhancement after contrast administration. Pathological findings in seven patients, including four with CSD, supported the tentative diagnosis made on MRI. One of two patients with CSD had positive serological test. Cat-scratch disease is a major cause of a soft tissue swelling at the medial epitrochlear region. Identification of lymphadenopathy and its presentation on MRI may be helpful in eliciting an animal-scratch history and achieving diagnostic and therapeutic aims in patients without primary cancer.

Adolescent↗

PubMed2002

Nodular fasciitis: correlation of MRI findings and histopathology.

OBJECTIVE: To compare the histopathology of nodular fasciitis (NF) with the magnetic resonance imaging (MRI) findings in order to evaluate the basis of the MR signal characteristics. DESIGN AND PATIENTS: Ten patients with NF, nine females and 1 male, with an age ranging from 13 to 58 years (mean 26.8 years) were studied. MRI findings, available in all 10 patients, were compared with the histopathology in nine patients, and an area-to-area comparative study of the whole specimen section histopathology and MRI was performed in two patients. RESULTS: On the basis of an excisional biopsy or resection specimen, the nine lesions were classified into myxoid ( n=4), cellular ( n=3) and fibrous ( n=2) subtypes. Four myxoid lesions with a subcutaneous location showed a homogeneous SI comparable with muscle on T1-weighted images, high SI on T2-weighted images, and had homogeneous enhancement. One cellular lesion presented with homogeneous, slightly higher SI than muscle on T1-weighted images and inhomogeneous, high SI on T2-weighted images. Alcian blue stain of the whole specimen section revealed the lesion had two parts corresponding to different enhancement patterns on MRI. The blue-stained myxoid part showed markedly diffuse enhancement, while the non-stained cystic space had only peripheral enhancement. Two other cellular lesions had the same appearance on both T1- and T2-weighted images and showed inhomogeneous, diffuse enhancement. One fibrous subtype lesion presented with inhomogeneous, overall slightly higher SI than muscle on T1-weighted images, lower SI at the periphery and high SI in the center on STIR images and only peripheral enhancement. Microscopy and CD-31 staining of the lesion showed more extracellular matrix, with poor vascularity in the center and more collagenous matrix with higher vascularity at the periphery. CONCLUSION: Although similar findings were found in some lesions, the large histologic variability of NF hampers the definition of a prototype of NF on MRI. However, the MRI appearance of the myxoid subtype is rather characteristic. Histologic findings reflect the different SI characteristics and enhancement pattern on MRI.

Adolescent↗

PubMed2002

[Analysis of results taken with "tweezers": some pitfalls in clinical biological interpretation].

Like other medical investigations, laboratory tests are not free from uncertainties or errors which limit their clinical value. Usually two levels of variations are identified: the analytical and biological levels. This paper presents some sources of variations and provides different examples. The concept of reference value is also discussed, as well as the clinician's viewpoint regarding the interpretation of laboratory results.

Diagnostic Techniques and Procedures↗

PubMed2001

Congenital skeletal abnormalities: an introduction to the radiological semiology.

Despite the recent advances in the molecular diagnosis of congenital abnormalities, the initial identification and the decision to refer a patient for further molecular analysis and expensive genetic tests still relies frequently on clinical and radiological criteria. The radiological identification of syndromes, dwarfs and dysplasias is a difficult task, because there are so many findings to consider and so many syndromes to remember that the problem is overwhelming. There is a definite need for an easy and systematic analysis system, in order to try to categorize a skeletal dysplasia in a certain group. In this brief review, we suggest an approach to the evaluation of skeletal syndromes, based on the analysis of cardinal criteria, from which the most useful information is derived, and additional criteria, making further differentiation possible. Generally, cardinal information is derived from analysis of the long bones, hands, pelvis and the spine, whereas the analysis of other skeletal elements, like the skull, feet, and other flat bones is of additional value.

Bone Diseases, Developmental↗

PubMed2001

Rat gap junction connexin-30 inhibits proliferation of glioma cell lines.

Connexins, the structural components of gap junctions, control cell growth and differentiation and are believed to belong to a family of tumour suppressor genes. Studies on connexin localization in brain showed that several of these proteins were expressed in distinct compartments of the brain in a cell-type specific manner, indicating that different gap junctions play specific roles in the physiology of the mammalian brain. In this report, we first cloned rat connexin-30 cDNA from brain and showed that it was expressed in long-term primary culture of rat astrocytes. In order to examine the potential role of connexin-30 in tumour cell proliferation, we transfected the connexin-30 cDNA into two rat glioma cell lines (9L and C6) which have lost its expression. Transfected clones adequately expressed membrane-bound connexin-30 protein. Connexin-30-expressing clones showed slower growth, lower DNA synthesis and reduced proliferation in soft agar as compared with the parental and control cells. We concluded that connexin-30 may also probably be considered as a tumour suppressor in rat gliomas.

Amino Acid Sequence↗

PubMed2000

Additive effect between NF-kappaB subunits and p53 protein for transcriptional activation of human p53 promoter.

The tumor suppressor p53 plays a pivotal role in the cellular response to DNA damage as it controls DNA repair, cell cycle arrest and apoptosis. We studied the autoregulation of human p53 gene transcription in colon cancer cell lines. Wild-type p53 has been shown to autoregulate its own transcription either positively or negatively and probably in a cell-type-specific manner. Indeed, a p53 binding site has been described in the human and murine p53 promoters, but a direct binding of wild-type p53 protein to this site has never been reported. In this study, we demonstrated a transactivation of human p53 promoter by wild-type p53 in human colon cancer cells. We identified in the human p53 promoter a novel potential p53-responsive element that binds wild-type p53. Moreover, wild-type p53 protein transactivated a reporter plasmid containing a luciferase gene driven by a minimal promoter harboring this p53 binding site. Finally, as the p53 promoter contains an NF-kappaB binding site, we demonstrated an additive effect when NF-kappaB subunits and p53 protein combined to transactivate the human p53 promoter.

Adenocarcinoma↗

PubMed2000

Pharmacological modulation of the bystander effect in the herpes simplex virus thymidine kinase/ganciclovir gene therapy system: effects of dibutyryl adenosine 3',5'-cyclic monophosphate, alpha-glycyrrhetinic acid, and cytosine arabinoside.

The herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene/ganciclovir system was first applied to the treatment of glioblastoma tumors, but was hampered by the low gene transfection yield. Fortunately, the gap junction-dependent diffusion of phosphorylated ganciclovir metabolites from transfected cells to their neighbors proved to enhance the overall benefit of this strategy. However, as tumor cells are often gap junction-deficient, we sought to restore this property pharmacologically and hence to improve the efficacy of the treatment. We demonstrated that this approach was feasible in glioblastoma cells using dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) (100 microM) as a pharmacological inducer of gap junctions. alpha-Glycyrrhetinic acid (25 microM), on the other hand, strongly inhibited both gap junction-mediated intercellular communication and the bystander effect, thus confirming the role of gap junctions in HSV-tk-mediated bystander killing. Using cytosine arabinoside as a growth inhibitor, we underlined the role of tumor cell proliferation in the sensitivity of HSV-tk-transfected cells to ganciclovir and demonstrated its correlation with the importance of the bystander effect.

Animals↗

PubMed2000

Early stage results after oesophageal resection for malignancy - colon interposition vs. gastric pull-up.

OBJECTIVE: The aims of our study were to determine if using the colon as a digestive transplant after oesophagectomy for cancer was associated with increased postoperative complications, and to assess the impact of preoperative radiochemotherapy on postoperative hospital outcome. METHODS: From January 1990 to December 1998, 130 patients underwent oesophageal resection for malignancy. There were 103 males and 27 females (age: 61.3+/-11.5 years). Indications were squamous cell carcinoma in 69 patients and adenocarcinoma in 61. Preoperatively 30 patients (eight in stage IIB, 18 in stage III, and four in stage IV) received radiochemotherapy. There were 84 subtotal oesophagectomies, with anastomosis in the neck in 44 patients and at the thoracic inlet in 40, and 46 distal oesophageal resections. Digestive continuity was restored with the stomach in 92 patients (age: 63.4+/-10.2 years) and the colon in 38 (age: 52.3+/-12.8 years). With the exception of age (P<0.0001), there was no significant preoperative difference between gastric and colonic groups. RESULTS: Hospital mortality was 8.5% (11 patients), decreasing from 18.5% (before 1993) to 3.8% (since 1993). One patient (2.5%) died in the colonic graft group and ten (11%) in the gastric pull-up group (P=0.17). Postoperative complications occurred in 40 patients (31%), respectively, in ten (26%) and 30 (33%) patients after colonic and gastric transplants (P=0.48), and were pulmonary insufficiency or infection in 29 patients, anastomotic fistula in six, myocardial infarction in five, recurrent nerve palsy in four, renal insufficiency in three, and cerebrovascular accident in one. All fistulas occurred in the gastric pull-up group. The incidence of postoperative pulmonary complications was 70% (21/30 patients) in the subgroup who received preoperative radiochemotherapy, as compared to 11% (5/44 patients) in the subgroup of comparable staging, but without preoperative treatment (P<0.001). CONCLUSIONS: Colonic grafts are not associated with increased postoperative mortality or complications. Our results suggest that preoperative neoadjuvant treatment significantly increases postoperative pulmonary complications.

Adenocarcinoma↗

PubMed2000

Cytosine deaminase suicide gene therapy for peritoneal carcinomatosis.

Gene therapy is a novel therapeutic approach that might soon improve the prognosis of some cancers. We investigated the feasibility of cytosine deaminase (CD) suicide gene therapy in a model of peritoneal carcinomatosis. DHD/K12 colorectal adenocarcinoma cells transfected in vitro with the CD gene were highly sensitive to 5-fluorocytosine (5-FC), and a bystander effect could also be observed. Treating CD+ cells with 5-FC resulted in apoptosis as detected by terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick-end labeling. In vitro, several human cell lines derived from ovarian or colorectal carcinomas, as well as the rat glioblastoma 9 L cell line, responded to CD/5-FC and showed a very strong bystander effect. 5-FC treatment of peritoneal carcinomatosis generated in syngeneic BDIX rats by CD-expressing DHD/K12 cells led to a complete and prolonged response and to prolonged survival. Our study thus demonstrated the efficacy of CD suicide gene therapy for the treatment of peritoneal carcinomatosis.

Animals↗

PubMed2000

Antitumoral vaccination with granulocyte-macrophage colony-stimulating factor or interleukin-12-expressing DHD/K12 colon adenocarcinoma cells.

Immunomodulating gene therapy for the treatment of malignant diseases is under extensive investigation. In this study, we induced an antitumoral immune response with murine interleukin-12 (mIL-12) and murine granulocyte-macrophage colony-stimulating factor (GM-CSF)-secreting tumor cells in a model of peritoneal carcinomatosis. Intraperitoneal injection of DHD/K12 tumoral cells engineered to produce IL-12 or GM-CSF did not generate any tumors, whereas untransduced DHD/K12 cells gave rise to peritoneal carcinomatosis. IL-12-expressing DHD/K12 cells also protected against tumors derived from coinjected parental cells. To test whether cytokine-producing cells could elicit a memory antitumoral immune response, animals received a challenge with parental DHD/K12 cells 35 days after the injection of proliferating or irradiated DHD/K12 engineered cells. Under our experimental conditions, irradiated tumor cells did not generate any antitumoral immunity. In contrast, tumor development was delayed and survival increased in the animals vaccinated with cytokine-secreting proliferating cells. A specific cytotoxic T-lymphocyte response against DHD/K12 parental cells was observed after vaccination with GM-CSF-expressing cells. Our results demonstrated that intraperitoneal vaccination with IL-12- or GM-CSF-expressing adenocarcinoma cells induced a systemic immune antitumoral response that may be useful as an adjuvant therapy after surgical resection of colorectal cancer.

Adenocarcinoma↗

PubMed2000

Combined suicide and cytokine gene therapy for peritoneal carcinomatosis.

BACKGROUND: Gene therapy is a novel approach for the treatment of cancers, and tumours disseminated in the peritoneal cavity are suitable for in situ delivery of a therapeutic gene. AIMS: The efficacy of a therapy combining a suicide gene (herpes simplex virus type I thymidine kinase (HSV-TK)) and cytokine genes was investigated in a model of peritoneal carcinomatosis induced by colon carcinoma cells in syngeneic rats. MATERIAL AND METHODS: Pre-established macroscopic tumours in BDIX rats were treated by intraperitoneal injections of retrovirus producing cells (FLYA13 TK, FLYA13 granulocyte macrophage-colony stimulating factor (GM-CSF), FLYA13 interleukin 12 (IL-12)) and ganciclovir (GCV). RESULTS: TK/GCV treated animals showed a slight increase in survival time (72 days) compared with the control group (63 days) while the association of cytokine and TK/GCV gene therapy resulted in significantly improved survival, with a large proportion of animals remaining tumour free on day 480 (60% and 40% for TK/GCV/GM-CSF and TK/GCV/IL-12 treated animals, respectively). Histological analysis of treated animals showed that the remaining tumour nodes were infiltrated by mononuclear cells but no major differences were observed between the various treatments. Immunohistochemical analysis revealed that lymphoid CD4(+) and CD8(+) T cells as well as macrophages accumulated outside untreated tumour nodes while CD8(+) and CD25(+) activated T cells and macrophages heavily infiltrated the tumours after the different treatments. CONCLUSIONS: Our data indicate that combined suicide and cytokine gene therapy is a powerful approach for the treatment of macroscopic peritoneal carcinomatosis.

Animals↗

PubMed2000

Similar efficiency of DNA-liposome complexes and retrovirus-producing cells for HSV-tk suicide gene therapy of peritoneal carcinomatosis.

Several experimental approaches have been tested for suicide gene delivery into tumor cells, including viral and non-viral vectors. In this study, we compared the efficiency of Herpes Simplex Virus type 1 thymidine kinase gene (HSV-tk) delivery by retrovirus-producing cells and DNA/liposome complexes for the treatment of peritoneal carcinomatosis induced in syngeneic rats by DHD/K12 colorectal adenocarcinoma cells. After in vitro determination of the best transduction conditions, rats were treated with multiple intraperitoneal injections of plasmid DNA containing one or two copies of CMV-driven HSV-tk gene (pCMV-TK and p(CMV-TK)2, respectively) associated with LipofectAMINE, each injection being followed by a Ganciclovir (GCV) course. Animals treated by DNA/liposome complexes and GCV or with retrovirus-producing cells and GCV showed a similar increase of survival as compared to the control group. After DNA/ liposome injections, expression of the tk transgene was detected in tumor nodes (epiploon) and also in liver, lung, spleen, bowels and brain. The expression was not homogeneous throughout the different organs and most likely reflected the transfection of only a limited number of cells.

Adenocarcinoma↗