Cytomegalovirus colitis in children with inflammatory bowel disease.
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Biomedical subjects
Publications and source records attributed to J Viala.
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ATP-dependent proteases of the ClpP type are widespread in eubacteria. These proteolytic complexes are composed of a proteolytic subunit and an ATPase subunit. They are involved in the degradation of denatured proteins, but also play a role in specific regulatory pathways. In Streptomyces lividans strains which lack the proteolytic subunit ClpP1, cell cycle progression has been shown to be blocked at early stages of growth. In this study, we examined the role of the ATPase subunit ClpX, a possible partner of the products of the clpP1 operon. A clpX mutant was obtained and it was shown that its growth was impaired only on acidic medium. Thus, the clpX phenotype differs from the clpP1 phenotype, indicating that these two components have only partially overlapping roles. We also analyzed the expression of clpX. Although clpX expression is increased under heat-shock conditions in many bacteria, we found that this is not the case in S. lividans.
PURPOSE: The aim of this open-label phase II study was to evaluate the activity of raltitrexed (Tomudex; AstraZeneca, Cergy, France) and oxaliplatin combination therapy in patients with diffuse malignant pleural mesothelioma. PATIENT AND METHODSs: Fifteen pretreated and 55 chemotherapy-naive patients (median age, 60 years; World Health Organization performance status of < or = 2) were enrolled. Most patients (66%) had advanced disease. Patients received raltitrexed 3 mg/m2 followed by oxaliplatin 130 mg/m2 every 3 weeks. RESULTS: Twenty-four patients (34%) were classified as having a poor prognosis. In the overall study population, 14 patients (20%) had a partial response, and 32 patients (46%) had stable disease. The symptomatic response rates were as follows: shortness of breath, 36%; pain, 30%; activity, 23%; appetite, 21%; and asthenia, 20%. Median time to disease progression was 18 weeks (95% confidence interval [CI], 13 to 22 weeks). In chemotherapy-naive patients, median survival was 31 weeks (95% CI, 23 to 40 weeks) from the start of treatment and 49 weeks (95% CI, 40 to 52 weeks) from diagnosis of mesothelioma. In pretreated patients, median survival was 44 weeks (95% CI, 24 to 40 weeks) from the start of treatment and 226 weeks (95% CI, 63 to 292 weeks) from the diagnosis of mesothelioma. Overall 1-year survival was 26% (95% CI, 15.5% to 36.4%), survival was 22% (95% CI, 10.9% to 33.2%) in chemotherapy-naive patients and 40% (95% CI, 15.2% to 64.8%) in pretreated patients. Hematologic toxicity was mild, and there was no alopecia. The most common adverse events were asthenia, nausea/vomiting, and paraesthesia, and no treatment-related deaths were reported. CONCLUSION: The raltitrexed and oxaliplatin combination is an active outpatient regimen in malignant mesothelioma and has an acceptable tolerability profile.
CASES: Two patients with histologically proven port-site metastasis following laparoscopic procedures for ovarian cancer underwent a CT scan. These two patients were initially treated for a stage IA and III ovarian cancer. Port-site recurrence occurred six and 19 weeks following the laparoscopic procedure. In one patient, the abdominal wall recurrence was associated with peritoneal carcinosis. In both patients, CT scan revealed the presence of an heterogeneous nodular lesion inside the left oblique muscle. Histologic analysis confirmed the diagnosis of port-site recurrence. CONCLUSIONS: Port-site metastases could be observed in the treated patients with a laparoscopic approach for ovarian cancer. When this diagnosis is clinically suspected, a CT scan should be performed in order to precise the diagnosis of port-site metastasis and to evaluate potential intra-abdominal recurrent disease. However, only histologic examination can confirm a diagnosis of port-site recurrence.
PURPOSE: To describe and correlate with radiation therapy the occurrence of cerebral radiation necrosis in patients irradiated for nasopharyngeal or ethmoidal tumor. Materials and Methods. From 1986 to 1998, 1 201 patients, 981 with nasopharyngeal tumors, and 220 with ethmoidal tumors were treated by radiotherapy. Twenty eight developed cerebral necrosis. MRI were performed in all patients and CT in 18 patients. Diagnosis was considered at imaging, and confirmed by follow-up. RESULTS: The incidence of cerebral radionecrosis was 2.33%. The time interval between treatment and necrosis ranged from 2 months to 9 years. CT showed edema and/or focal enhancement in all cases except for 4 patients with normal CT examinations. MRI showed edema and/or abnormal focal punctate or gyriform enhancement in all patients. Lesions were localized in the temporal lobe (n=18), frontal lobe (n=9), pons (n=3) and optic nerve (n=2). The doses related to the areas of necrosis ranged from 13 to 135Gy. In 2 cases necrosis was situated at the boundaries of the radiation field. Imaging follow-up showed complete (n=3) or incomplete remission (n=1), lesion progression (n=11), cerebral atrophy (n=5) and stability (n=7). CONCLUSION: MRI is useful to diagnose cerebral necrosis. New technologies may reduce the incidence of this complication.
The aim of this study was to compare the clinical usefulness of ultrasmall superparamagnetic iron oxide (USPIO) MR contrast media (Sinerem, Guerbet Laboratories, Aulnay-sous-Bois, France) with precontrast MRI in the diagnosis of metastatic lymph nodes in patients with head and neck squamous cell carcinoma, using histology as gold standard. Eighty-one previously untreated patients were enrolled in a multicenter phase-III clinical trial. All patients had a noncontrast MR, a Sinerem MR, and surgery within a period of 15 days. The MR exams were analyzed both on site and by two independent radiologists (centralized readers). Correlation between histology and imaging was done per lymph node groups, and per individual lymph nodes when the short axis was > or = 10 mm. For individual lymph nodes, Sinerem MR showed a high sensitivity (> or = 88%) and specificity (> or = 77%). For lymph node groups, the sensitivity was > or = 59% and specificity > or = 81%. False-positive results were partially due to inflammatory nodes; false-negative results from the presence of undetected micrometastases. Errors of interpretation were also related to motion and/or susceptibility artifacts and problems of zone assignment. Sinerem MR had a negative predictive value (NPV) > or = 90% and a positive predictive value (PPV) > or = 51%. The specificity and PPV of Sinerem MR were better than those of precontrast MR. Precontrast MR showed an unexpectedly high sensitivity and NPV which were not increased with Sinerem MR. The potential contribution of Sinerem MR still remains limited by technical problems regarding motion and susceptibility artifacts and spatial resolution. It is also noteworthy that logistical problems, which could reduce the practical value of Sinerem MR, will be minimized in the future since Sinerem MR alone performed as good as the combination of precontrast and Sinerem MR.
BACKGROUND AND PURPOSE: Synovial sarcomas are soft-tissue tumors that rarely occur in the head and neck. The purpose of this study was to evaluate their CT and MR imaging appearance and to show that they may have a surprisingly benign imaging appearance. METHODS: Eight patients with histologically proved synovial sarcoma underwent CT; additionally, MR imaging examinations were performed in five of the eight cases. Attenuation and signal intensity on CT scans and MR images, respectively, were studied by two radiologists. They analyzed the location, size, margins, homogeneity, presence of adenopathies and infiltrative signs, and enhancement after injection of contrast medium. RESULTS: Four tumors were located in the hypopharynx, two arose from the infratemporal fossa, one arose from the maxillary sinus, and one arose from the faucial tonsil. Tumor sizes ranged from 27 to 70 mm. On CT scans and MR images, six lesions were homogeneous and well defined, with smooth margins. The remaining tumors were heterogeneous. In two cases, adjacent tissues were invaded. Calcifications were observed in one case and adenopathy in two cases. In three cases, the lesions were isointense on T1-weighted MR images and hypointense on T2-weighted MR images, and in the other two cases in which MR imaging was performed, the lesions were both isointense and hypointense on both T1- and T2-weighted images. Only the two local recurrent lesions were multilocular. CONCLUSION: Synovial sarcomas are aggressive sarcomas that may appear "benign" in some cases. In a young man, a synovial sarcoma may be suspected when a well-demarcated, homogeneous lesion is found in the head and neck.
The aim of this study was to review the experience of the Institut Gustave Roussy in 163 patients with malignant mesothelioma over a 9-year period. Data from seven consecutive prospective trials, four of chemo-immunotherapy and three of chemotherapy were reviewed. The rationale, methods and results of these trials are summarised and discussed. 98 patients were included in four phase II trials of chemo-immunotherapy whose common denominator was a combination of cisplatin and alpha-interferon. The response rate ranged from 15% to 40%. High-dose weekly cisplatin combined with alpha-interferon yielded the highest response rate but the toxicity of this regimen was considered unacceptable. Neither higher doses of alpha-interferon or the addition of mitomycin C or interleukin-2 to the regimen were able to enhance the activity of this combination. 18 patients were included in a paclitaxel-cisplatin phase II trial. The response rate was only 6% (95% confidence interval (CI): 0-24) and toxicity was also significant. This regimen was, therefore, considered ineffective. Of 17 patients with mesothelioma included in a phase I trial that combined raltitrexed and oxaliplatin, 6 (35%) obtained a partial response. Responses were seen even in cisplatin-refractory mesothelioma. Preliminary results of a subsequent ongoing phase II trial using raltitrexed (3 mg/m(2)) and oxaliplatin (130 mg/m(2)) have confirmed this promising activity with a 30% (9/30) response rate (95% CI: 15-49). The tolerance of this outpatient regimen is acceptable (no significant haematological toxicity and no alopecia) and compares favourably with that of our previous regimens. The final results concerning response and survival are required to confirm the efficacy of this combination. The preliminary results of two studies suggest promising activity with the combination of raltitrexed-oxaliplatin in malignant mesothelioma. The efficacy/toxicity ratio of this combination compares favourably with that of our previous chemotherapy and chemo-immunotherapy regimens.
The clpP genes are widespread among living organisms and encode the proteolytic subunit of the Clp ATP-dependent protease. These genes are present in a single copy in most eubacteria. However, five clpP genes were identified in Streptomyces coelicolor. The clpP1 clpP2 operon was studied: mutations affected the growth cycle in various Streptomyces. Here, we report studies of the expression of the clpP3 clpP4 operon in Streptomyces lividans. The clpP3 operon was induced in a clpP1 mutant strain, and the regulation of expression was investigated in detail. The product of the putative regulator gene, downstream from clpP4, was purified. Gel migration shift assays and DNase I footprinting showed that this protein binds to the clpP3 promoter and recognizes a tandem 6 bp palindromic repeat (TCTGCC-3N-GGCAGA). In vivo, this DNA-binding protein, named PopR, acts as an activator of the clpP3 operon. Studies of popR expression indicate that the regulator is probably controlled at the post-transcriptional level.
BACKGROUND: Port-site metastasis after laparoscopic surgery for gynecologic cancer is a recognized entity. CASES: Five patients underwent laparoscopic peritoneal biopsies for a stage III (n = 4) or IV (n = 1) ovarian cancer with moderate or poor differentiation. The sixth patient underwent a laparoscopic lymphadenectomy for vaginal carcinoma with bulky metastatic pelvic lymph nodes. CONCLUSION: In order to avoid port-site metastasis, patients with an obviously malignant ovarian tumor and ascites should not be treated with laparoscopy using pneumoperitoneum. If a malignant ovarian tumor is discovered during laparoscopy, the interval between initial surgery and complete cytoreductive surgery (with resection of laparoscopic ports) followed by chemotherapy should be as short as possible. For patients with uterine cancer and bulky nodes, laparoscopic lymphadenectomy should be avoided to avoid trocar implantation metastasis.
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The genes of Streptomyces coelicolor A3(2) encoding catalytic subunits (ClpP) and regulatory subunits (ClpX and ClpC) of the ATP-dependent protease family Clp were cloned, mapped and characterized. S. coelicolor contains at least two clpP genes, clpP1 and clpP2, located in tandem upstream from the clpX gene, and at least two unlinked clpC genes. Disruption of the clpP1 gene in S. lividans and S. coelicolor blocks differentiation at the substrate mycelium step. Overexpression of clpP1 and clpP2 accelerates aerial mycelium formation in S. lividans, S. albus and S. coelicolor. Overproduction of ClpX accelerates actinorhodin production in S. coelicolor and activates its production in S. lividans.
PURPOSE: To evaluate magnetic resonance (MR) imaging results after administration of gadolinium texaphyrin, a tumor-selective radiation sensitizer that is detectable at MR imaging, and to determine an appropriate intravenous dose of gadolinium texaphyrin for repeated injections during radiation therapy, the dose-limiting toxicity of reiterated doses of gadolinium texaphyrin, the maximal tolerated dose, the biolocalization of gadolinium texaphyrin (as assessed at MR examinations), and the response to treatment. MATERIALS AND METHODS: Ten daily intravenous injections of gadolinium texaphyrin, each followed by whole-brain radiation therapy (total of 10 fractions, 30 Gy), were administered to patients with brain metastases in a multicenter study. At the study institution, 11 patients underwent MR imaging before and after the first injection, after the 10th injection, and 8 weeks after entry into the study. RESULTS: MR imaging revealed selective drug uptake in metastases, without enhancement of normal brain tissue. In 10 patients, tumor uptake was higher after the 10th injection than after the first injection, which indicated accumulation of gadolinium texaphyrin in metastases. One lesion was visible only after the 10th injection and not at the pretherapeutic MR examination with injection of conventional gadolinium-based contrast material. Response to treatment was defined as a reduction in the size of the metastases between the preinjection MR study and the last MR study; seven patients achieved partial remission with tumor regression exceeding 50% of the initial size, and four achieved a minor response with less than 50% tumor regression. CONCLUSION: These preliminary results indicate that gadolinium texaphyrin is tumor selective and that brain metastases can be depicted at MR imaging long after the administration of gadolinium texaphyrin.
OBJECTIVE: To quantitate initial mammographic signs and to describe post-therapeutic patterns of inflammatory breast cancer. MATERIAL AND METHODS: Two radiologists retrospectively analyzed the initial clinical and mammographic findings of 92 patients with inflammatory breast carcinoma. The post-therapeutic mammogram (n = 75) was considered abnormal when focal opacity and or malignant-type microcalcifications were still visible. RESULTS: Redness of the skin, "peau d'orange' and increased temperature were the most common findings. A palpable mass was noted in 97% with axillary lymph node involvement in 83% of cases. All initial mammograms were abnormal. Isolated inflammatory signs were observed in 14% and malignant signs in 86% of patients (opacity = 77% and/or malignant-type microcalcifications = 47%). Skin thickening was seen in 93.5%, nipple inversion in 56.5%, increased breast density in 93.5%, stromal coarsening in 85% and hypervascularisation in 32.5% of mammograms. On post-therapeutic mammograms, 35 patients (46.5%) were suspected of having residual disease. During follow-up, 19 patients (25.3%) relapsed locally: 75% had abnormal post-therapeutic mammograms. CONCLUSION: The presence of isolated inflammatory signs on the mammogram is sufficient to suspect inflammatory breast carcinoma and biopsy must be performed in doubtful cases. Radical surgery is indicated when persistent malignant signs are still visible on mammogram after conservative treatment.
BACKGROUND: A granulocytosis associated with the use of silver sulfadiazine has been described in burn patients. This agranulocytosis may be due to either an allergic reaction or a bone marrow toxicity by silver sulfadiazine. CASE REPORT: A 1-month old baby was hospitalized in pediatric intensive care unit after a stage one repair of a tracheoesophegeal fistula. Gastroesophageal reflux and tracheomalacia appeared in the post operative period. When she was 2-months old, she developed a perineal erythema. A topical therapy was begun, with daily applications of silver sulfadiazine and ketoconazole. Five days later, agranulocytosis (granulocytes = 0.21 x 10(9).L-1) occurred. Silver sulfadiazine therapy was immediately stopped. Granulocyte count returned to normal over a few days. No other etiology than silver sulfadiazine could be found to explain agranulocytosis. The small surface of administration, the chronology of the events and the rapid correction of the disorders after silver sulfadiazine interruption argued for an immuno-allergic reaction to this drug. Medical problems were easily controlled and the patient recovered well. CONCLUSION: This event occurred when sulfadiazine was applied in a small cutaneous area in a young baby. This may be an argument for an allergic reaction; alternatively, it could be explained by an increased cutaneous absorption of a cytotoxic drug in younger people.
BACKGROUND: Telephone calls for advice are common in pediatric emergency departments. This study was conducted to determine the nature of these calls and the answers provided. METHODS: From 24 April through 24 July 1994, all telephone calls requesting pediatric advice in the emergency department of the Poissy Hospital were independently analysed by two pediatricians from forms prospectively filled in for each call by the resident or the attending people who answered the call. RESULTS: Of the 239 registered calls, 186 could be analysed. They represented, in number, 15.25% of the children seen at the same emergency department during the study period. Weekend and holiday calls accounted for 35.5% of calls. 7.8% of calls were received from 0.01 am to 8.00 am, 28.7% from 8.01 am to 4.00 pm, and 63.5% from 4.01 pm to 12.00 pm. Thirty-seven percent concerned children under one year of age. The caller was one of the parents in 93% of cases. The four most frequent complaints were fever (26.5%), requests for information (17.2%), rash (12.3%), and vomiting (10.2%). The review of calls by two pediatricians determined that 67% of children did not need to be seen by a physician within six hours; 28% needed to be seen within 6 hours, and 5% needed to be seen within one hour. The advice given was followed in 88% of cases; 96% of callers were satisfied with their calls management. CONCLUSIONS: Telephone advice constitutes an important part of the activity in the pediatric emergency department. Instructional programs in telephone management are necessary for physicians. These programs should include communication skills and familiarization with protocols concerning the most frequent complaints, especially those regarding children under one year of age.
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