Perfusion Pressure Is a Critical Determinant of the Intratumoral Extravasation of Oncolytic Viruses.

Antitumor efficacy of oncolytic virotherapy is determined by the density and distribution of infectious centers within the tumor, which may be heavily influenced by the permeability and blood flow in tumor microvessels. Here, we investigated whether systemic perfusion pressure, a key driver of tumor blood flow, could influence the intratumoral extravasation of systemically administered oncolytic vesicular stomatitis virus (VSV) in myeloma tumor-bearing mice. Exercise was used to increase mean arterial pressure, and general anesthesia to decrease it. A recombinant VSV expressing the sodium iodide symporter (NIS), which concentrates radiotracers at sites of infection, was administered intravenously to exercising or anesthetized mice, and nuclear NIS reporter gene imaging was used to noninvasively track the density and spatial distribution of intratumoral infectious centers. Anesthesia resulted in decreased intratumoral infection density, while exercise increased the density and uniformity of infectious centers. Perfusion state also had a significant impact on the antitumor efficacy of the VSV therapy. In conclusion, quantitative dynamic radiohistologic imaging was used to noninvasively interrogate delivery of oncolytic virotherapy, highlighting the critical importance of perfusion pressure as a driver of intratumoral delivery and efficacy of oncolytic viruses.

Early postoperative obstruction after Roux-en-Y gastric bypass.

We report a case of early postoperative intestinal obstruction after gastric bypass. The most frequent radiologic presentation is one of gastric dilatation on the CT scan. It is a true surgical emergency.

Maternal perinatal undernutrition has long-term consequences on morphology, function and gene expression of the adrenal medulla in the adult male rat.

Epidemiological studies suggest that maternal undernutrition sensitises to the development of chronic adult diseases, such as type 2 diabetes, hypertension and obesity. Although the physiological mechanisms involved in this 'perinatal programming' remain largely unknown, alterations of stress neuroendocrine systems such as the hypothalamic-pituitary-adrenal (HPA) and sympathoadrenal axes might play a crucial role. Despite recent reports showing that maternal perinatal undernutrition disturbs chromaffin cells organisation and activity in male rats at weaning, its long-term effects on adrenal medulla in adult animals are unknown. Using a rat model of maternal perinatal 50% food restriction (FR50) from the second week of gestation until weaning, histochemistry approaches revealed alterations in noradrenergic chromaffin cells aggregation and in cholinergic innervation in the adrenal medulla of 8-month-old FR50 rats. Electron microscopy showed that chromaffin cell granules exhibited ultrastructural changes in FR50 rats. These morphological changes were associated with reduced circulating levels and excretion of catecholamines. By contrast, catecholamine plasma levels were significantly increased after a 16 or 72 h of fasting, indicating that the responsiveness of the sympathoadrenal system to food deprivation was accentuated in FR50 adult rats. Among 384 pituitary adenylate cyclase-activating polypeptide-sensitive genes, we identified 129 genes (33.6%) that were under expressed (ratio < 0.7) in FR50 animals. A large number of these genes are involved in cytoskeleton remodelling and vesicle trafficking. Taken together, our results show that maternal perinatal undernutrition programmes adrenomedullary function and gene expression in adult male rats. Because catecholamines contribute to metabolic homeostasis, as well as arterial blood pressure regulation, the alterations observed in the adrenal medulla of adult male FR50 rats may participate in the programming of chronic adult diseases.

[Imaging features of neurologic and orthopedic complications from severe trauma]. / Imagerie des complications neuro-orthopédiques des traumatismes graves.

Cranial and spinal trauma are a frequent cause of disability in the general population. Post-traumatic paraplegia or quadriplegia or hemiplegia from vascular injury (CVA) can lead to early complications (respiratory, cardiovascular, urinary, cutaneous, infectious...) that may have an impact on the immediate prognosis. Neurologic and orthopedic complications occur later and further impair the quality of life of patients. Orthopedic complications include: neurogenic paraosteoarthropathy (NPOA) or neurogenic osteoma or myositis ossificans (NMO). The nomenclature currently in use is NMO; Osseous complications: osteoporosis and secondary insufficiency fractures; Joint complications: degenerative arthropathy and stiffness; Overuse mechanical complications; Muscular complications; Infectious complications: arthritis and myositis complicating skin ulcers and bed sores. The purpose of this paper is to describe these neuro-orthopedic complications and review their imaging features.

Tissue-specific programming expression of glucocorticoid receptors and 11 beta-HSDs by maternal perinatal undernutrition in the HPA axis of adult male rats.

Maternal undernutrition leads to intrauterine growth retardation and predisposes to the development of pathologies in adulthood. The hypothalamo-pituitary-adrenal axis is a major target of early-life programming. We showed previously that perinatal maternal 50% food restriction leads to hypothalamo-pituitary-adrenal axis hyperactivity and disturbs glucocorticoid feedback in adult male rats. To try to better understand these alterations, we studied several factors involved in corticosterone sensitivity. We showed that unlike the restricted expression of 11 beta-HSD2 mRNA, the 11 beta-HSD1, glucocorticoid, and mineralocorticoid receptor genes are widely distributed in rat. In contrast to the hypothalamus, we confirmed that maternal undernutrition modulates hippocampal corticosterone receptor balance and leads to increased 11 beta-HSD1 gene expression. In the pituitary, rats exhibited a huge increase in both mRNA and mineralocorticoid receptor binding capacities as well as decreased 11 beta-HSD1/11 beta-HSD2 gene expression. Using IN SITU hybridization, we showed that the mineralocorticoid receptor gene was expressed in rat corticotroph cells and by other adenopituitary cells. In the adrenal gland, maternal food restriction decreased 11beta-HSD2 mRNA. This study demonstrated that maternal food restriction has both long-term and tissue-specific effects on gene expression of factors involved in glucocorticoid sensitivity and that it could contribute, via glucocorticoid excess, to the development of adult diseases.

Drosophila deoxyribonucleoside kinase mutants with enhanced ability to phosphorylate purine analogs.

Transduced deoxyribonucleoside kinases (dNK) can be used to kill recipient cells in combination with nucleoside prodrugs. The Drosophila melanogaster multisubstrate dNK (Dm-dNK) displays a superior turnover rate and has a great plasticity regarding its substrates. We used directed evolution to create Dm-dNK mutants with increased specificity for several nucleoside analogs (NAs) used as anticancer or antiviral drugs. Four mutants were characterized for the ability to sensitize Escherichia coli toward analogs and for their substrate specificity and kinetic parameters. The mutants had a reduced ability to phosphorylate pyrimidines, while the ability to phosphorylate purine analogs was relatively similar to the wild-type enzyme. We selected two mutants, for expression in the osteosarcoma 143B, the glioblastoma U-87M-G and the breast cancer MCF7 cell lines. The sensitivities of the transduced cell lines in the presence of the NAs fludarabine (F-AraA), cladribine (CdA), vidarabine and cytarabine were compared to the parental cell lines. The sensitivity of 143B cells was increased by 470-fold in the presence of CdA and of U-87M-G cells by 435-fold in the presence of F-AraA. We also show that a choice of the selection and screening system plays a crucial role when optimizing suicide genes by directed evolution.

Leishmaniosis due to Leishmania infantum in a FIV and FelV positive cat with a squamous cell carcinoma diagnosed with histological, serological and isoenzymatic methods.

Leishmaniosis caused by Leishmania infantum is an endemic zoonosis present in the Mediterranean area. Canidae (dog and fox) constitute the main reservoir hosts for the parasite, whilst wild rodents or the cat can be carriers of the protozoan and are considered as secondary potential reservoirs. This paper describes a case of disseminated feline leishmaniosis with cutaneous (ulcerative), visceral (spleen and lymph nodes) and blood involvement in a FIV-FelV positive cat. The microscopic identification of the Leishmania infection was initially made on a skin biopsy of the temporal area, where a squamous cell carcinoma was diagnosed. The diagnosis of the disease was achieved by several serological techniques (ELISA, IFAT and Western-blot). The strain was obtained by blood culture, characterized by electrophoresis of isoenzymes and identified as Leishmania infantum zymodeme MON-1. Since the infection due to L. infantum is a zoonosis, the potential feline reservoir should be more investigated. Serological analysis by Western blot on domestic cats provides a useful tool. In veterinary practice, feline leishmaniosis should be systematically included in the differential diagnosis when compatible cutaneous lesions are present, especially in the endemic areas of canine leishmaniosis.

Imaging findings in three cases of the nodular type of muscular sarcoidosis.

OBJECTIVE: Sarcoidosis is a granulomatous multisystem disorder that may uncommonly involve muscle. We report the sonographic and MRI findings in three cases of the nodular type of muscular sarcoidosis. CONCLUSION: Intramuscular hypoechoic well-defined nodules in young patients or patients with a history of sarcoidosis suggest the diagnosis of intramuscular sarcoid. MRI is useful in detecting muscle sarcoid, evaluating the extent and distribution of muscle involvement, and monitoring the patient during follow-up after steroid therapy. MRI showed nodules that were iso- or hyperintense relative to muscle on T1-weighted sequences. On T2-weighted images and STIR sequences, we observed numerous intramuscular nodules of homogeneous high signal intensity. All nodules enhanced homogeneously on contrast-enhanced T1-weighted sequences. Disappearance of all nodules was seen on follow-up sonograms and MR images after patients had received steroid therapy.

Neurohypophysial receptor gene expression by thymic T cell subsets and thymic T cell lymphoma cell lines.

Neurohypophysial oxytocin (OT) and vasopressin (VP) genes are transcribed in thymic epithelium, while immature T lymphocytes express functional neurohypophysial receptors. Neurohypophysial receptors belong to the G protein-linked seven-transmembrane receptor superfamily and are encoded by four distinct genes, OTR, V1R, V2R and V3R. The objective of this study was to identify the nature of neurohypophysial receptor in thymic T cell subsets purified by immunomagnetic selection, as well as in murine thymic lymphoma cell lines RL12-NP and BW5147. OTR is transcribed in all thymic T cell subsets and T cell lines, while V3R transcription is restricted to CD4+CD8+ and CD8+ thymic cells. Neither V1R nor V2R transcripts are detected in any kind of T cells. The OTR protein was identified by immunocytochemistry on thymocytes freshly isolated from C57BL/6 mice. In murine fetal thymic organ cultures, a specific OTR antagonist does not modify the percentage of T cell subsets, but increases late T cell apoptosis further evidencing the involvement of OT/OTR signaling in the control of T cell proliferation and survival. According to these data, OTR and V3R are differentially expressed during T cell ontogeny. Moreover, the restriction of OTR transcription to T cell lines derived from thymic lymphomas may be important in the context of T cell leukemia pathogenesis and treatment.

Proliferative myositis in a patient with AIDS.

We report a case of proliferative myositis in the right biceps of a 56-year-old man with acquired immune deficiency syndrome (AIDS). Imaging methods included sonography, computed tomography and magnetic resonance imaging. The diagnosis was made by a core-cut biopsy and fine needle aspiration biopsy with immunohistochemical analysis. The lesion disappeared after 2 months without treatment. It is particularly important to determine whether intramuscular masses arising in patients with AIDS are due to an infectious or malignant process.

[Value of MRI to evaluate extra-abdominal desmoid fibromatosis]. / Apport de l'IRM dans l'étude des fibromatoses desmoïdes extra-abdominales.

PURPOSE: To describe the MR appearance of extra-abdominal desmoid fibromatosis, especially using sequences such as MR angiography, STIR and FAT SAT. Materials and methods. We reviewed retrospectively the MRI studies of 8 patients (4 men and 4 women) with histologically proved desmoid fibromatosis. In five patients the lesion corresponded to recurrent disease. Eleven MRI examinations were available (Siemens, Vision, 1.5T) including the following sequences: pre- and postcontrast T1 weighted (11 cases), STIR (9 cases), and MRA (3 cases). All lesions were imaged in at least two orthogonal planes. CT was available for 5 patients. RESULTS: The lesions were localized to the girdles in 8 cases and to the upper extremity in 3 cases. Most lesions (10/11) were isointense to muscle on noncontrast T1W images and showed intense enhancement on postcontrast T1W images. All lesions (9/9) were hyperintense on STIR images. CONCLUSION: A STIR sequence is useful as a first sequence to identify smaller lesions (usually recurrences) and to better adapt the FOV of following sequences, especially before administration of intravenous contrast. MR angiography may be valuable for surgical planning.

Laparoscopic repair of incisional hernia: a retrospective study of 159 patients.

BACKGROUND: In this long-term retrospective study, a laparoscopic technique was used for incisional hernia repair. METHODS: Over a 6-year period, we performed laparoscopic repairs with prosthetic mesh in 159 patients suffering from incisional hernia. Morbidity factors were noted and operative data were collected. In addition, early and long-term complications and recurrences were analyzed. RESULTS: There were no deaths as a result of the procedure. In 21 patients (13.8%), the operation was converted to an open procedure. Small bowel perforation occurred in three patients (1.9%). Mean hospital stay was 3.5 days. Early complications occurred in 61 patients (44%). The mean follow-up time was 49 months. There were no infections of the prosthetic mesh. Residual abdominal pain was reported in 31 patients (26%). Bowel obstructions requiring resection were found in two patients (1%), and hernia recurrence was observed in 19 patients (15.7%). CONCLUSIONS: Laparoscopic herniorraphy is a promising technique with all the advantages of minimal-invasive surgery. Nevertheless, close attention needs to be paid to the choice of the hernia and mesh size and to the fixing of the mesh.

[Bacterial cellulitis. Forms borderline between medical and surgical (3 cases)]. / Dermohypodermites bactériennes.

BACKGROUND: An acute infectious cellulitis may be managed medically (erysipelas or non-necrotizing infectious cellulitis) or surgically (necrotizing infectious cellulitis, necrotizing fasciitis). We report 3 cases of non-necrotizing infectious cellulitis borderline between medical and surgical forms, complicated by compartment syndrome, the surgical decompression of which permitted patients' cure. CASE REPORTS: Three patients, 27, 52 and 84 years old, were admitted for an acute infectious cellulitis of the leg. At admission, the leg area involved was erythematous, painful, indurated, with one or several bullae, purpura, pustules, hypoesthesia or limited skin necrosis, and no immediate need for surgical exploration. The clinical evolution was characterized by the slow appearance or extension of signs of severity, despite the modification in antibiotic treatment. Magnetic resonance imaging findings were indicative of a non-necrotizing infectious cellulitis in 2 patients. In one patient, necrotizing fasciitis could not be excluded. In all patients, surgical exploration showed an important quantity of non-purulent fluid between muscles and hypodermis, with no evidence of abscess or necrosis. A large incision rapidly cured all patients. DISCUSSION: These three observations were characterized by the initial signs of moderate severity and no response to an appropriate medical treatment, which led to surgical exploration. Surgery showed no abscess or necrosis but an important quantity of sterile fluid; it also permitted rapid cure of patients. These cases present a borderline form of infectious cellulitis, with severe local inflammation caused by a compartment syndrome. Surgical decompression was needed for cure. The potential value of magnetic resonance imaging in this situation should also be stressed.

[Calcific retropharyngeal tendinitis: unusual diagnosis]. / Tendinite calcifiante rétropharyngée: une lésion rare à évoquer.

Acute calcific retropharyngeal tendinitis is a rare entity that often is initially misdiagnosed a retropharyngeal abscess and treated with IV administration of antibiotics. In our 2 cases, imaging enabled a correct diagnosis to be made. Two patients were admitted to the hospital with dysphagia, severe neck discomfort and fever. Lateral radiographs of the cervical spine and CT were obtained in both cases, while MRI was obtained in one case. Calcification of the prevertebral muscles was demonstrated by CT in both cases, and detected on lateral radiographs in only one case. Soft tissue swelling was noted at CT and MRI. A clinical diagnosis of calcific retropharyngeal tendinitis may be difficult to achieve and a definitive diagnosis can be confirmed at imaging studies.

Oxytocin receptor gene expression in rat mammary gland: structural characterization and regulation.

The differential, tissue-specific regulation of oxytocin (OT) binding sites allows the neurohypophysial nonapeptide OT to fulfill a dual role: to induce uterine contractions at parturition and to mediate milk ejection during lactation. Whereas uterine OT binding sites are up-regulated prior to parturition and are rapidly down-regulated thereafter, mammary gland OT binding sites gradually increase throughout gestation and remain up-regulated during the ensuing lactation period. Here, we structurally characterized OT receptor (OTR) mRNA in mammary gland and analyzed its expression during gestation and lactation and in response to steroid treatment. In mammary gland tissues, we found a 6.7 and a 5.4 kb OTR mRNA species, and both species were further analyzed by RACE (rapid amplification of cDNA ends). The 6.7 kb mRNA was found to be common to mammary gland and uterus and to extend 618 nucleotides beyond the published sequence of the rat OTR gene. The 5.4 kb mRNA species is unique to the mammary gland and terminates at a mammary gland-specific polyadenylation site that is not preceded by a classical polyadenylation signal. RT-PCR analysis did not provide any evidence for differences in the coding regions, suggesting that both uterine and mammary gland OTR mRNAs encode the same receptor protein. Furthermore, primer extension experiments showed that no differences exist in the specific transcriptional initiation sites of the OTR gene in the two tissues. During pregnancy, OTR mRNA per mammary gland increased approximately 150-fold and remained high during lactation, consistent with the previously identified regulation of OT binding sites and the role of OT during lactation. Whereas estrogen administration strongly induced the uterine OTR mRNA levels (>5-fold), mammary gland remained unaffected by steroid treatment. Moreover, tamoxifen had no effect on the mammary gland OTR mRNA level. In summary, our data demonstrate a differential control of OTR expression in uterus versus mammary gland and a mammary gland-specific OTR mRNA polyadenylation site. However, this differential control apparently does not involve the expression of different receptor genes nor the utilization of tissue-specific transcriptional initiation sites.