The influence of growth temperature on the ability to ferment D-sorbitol was investigated in Escherichia coli O157:H7. It was found that O157:H7 strains have a temperature-sensitive sorbitol ...phenotype. D-Sorbitol transport and sorbitol-6-phosphate dehydrogenase activities were expressed in sorbitol-fermenting cells grown at 30 degrees C but only at a low level at 40 degrees C. Sorbitol-positive variants able to transport D-sorbitol were easily selected at 30 degrees C from culture of Sor(-) E. coli O157:H7 strains.
To evaluate surgical complications, patterns of lymph node metastases, and calcitonin response to compartment-oriented lymphadenectomy in patients with primary or recurrent medullary thyroid ...carcinoma (MTC).
The majority of patients with invasive MTC have metastasis to regional lymph nodes at the time of diagnosis, as evidenced by the frequent finding of persistently elevated calcitonin levels after thyroidectomy and the high rates of recurrence in the cervical lymph nodes reported in retrospective studies. These data have provided the rationale for surgeons to perform a more extensive lymphadenectomy at the time of initial thyroidectomy and to consider reoperative cervical lymphadenectomy in patients with persistently elevated calcitonin levels after thyroidectomy.
Forty patients underwent surgery for MTC from 1991 to 1997 (23 sporadic cases, 17 familial cases). Patients were divided into three groups based on whether they had undergone previous thyroidectomy and on the results of standardized staging studies performed after referral to the authors' institution. Group 1 (11 patients) had received no previous surgery; group 2 (13) underwent thyroidectomy before referral and had an elevated calcitonin level without radiologic evidence of local regional or distant metastases; and group 3 (16) underwent thyroidectomy before referral and had an elevated calcitonin level with radiologic evidence of local-regional recurrence. The central neck compartment was dissected in all patients; preoperative staging and the extent of previous surgery dictated the need for lateral (modified radical) neck dissection. After primary or reoperative surgery, calcitonin levels were assessed.
All patients had major reductions in postoperative calcitonin levels. Seven (29%) of 24 patients in groups 1 and 2 achieved normal calcitonin values compared with only 1 (6%) of 16 in group 3. Postoperative complications included seven cases (17%) of permanent hypoparathyroidism; five (71%) of these occurred in group 3. There were no iatrogenic recurrent laryngeal nerve injuries; one patient required recurrent nerve resection to achieve complete tumor extirpation. At a median follow up of 35 months, local recurrence was documented in 5 (13%) of 40 patients.
Compartment-oriented lymphadenectomy performed early in the course of MTC is safe and may return calcitonin levels to normal in up to 25% of carefully selected patients. However, reoperation for bulky cervical disease (group 3) rarely results in normal calcitonin levels and is associated with a high incidence of permanent hypoparathyroidism.
Undescended parathyroid adenoma Kanack, Melissa D; Maawy, Ali A; Oh, Deborah K ...
BMJ case reports,
03/2015, Letnik:
2015
Journal Article
Recenzirano
Odprti dostop
Undescended parathyroid adenomas are rare, representing 0.08% of all parathyroid adenomas; however, they make up 7% of the underlying cause of failed cervical exploration in patients with persistent ...primary hyperparathyroidism. A 43-year-old woman with no significant medical or family history presented with fatigue and was diagnosed with primary hyperparathyroidism; however, preoperative imaging including sestamibi scan and ultrasound was unable to identify the hyperfunctioning gland. She underwent a neck exploration and hemithyroidectomy and partial parathyroidectomy with failure of resolution of her disease. Subsequent work up including a CT of the neck demonstrated a 1.9 cm mass adjacent to the left submandibular gland. This was removed with postoperative normalisation of the patient's serum calcium and parathyroid hormone levels.
Pendant plusieurs décennies, la problématique du programme politique monarchique a monopolisé l’historiographie contemporaine des frontières naturelles de la France. En effet, des années 1815/1830 ...jusqu’à celles de l’entre-deux guerres, deux thèses se sont imposées tour à tour. La première, soutenue par une large partie des historiens du XIXe siècle, a défendu l’idée selon laquelle la monarchie de l’Ancien Régime se serait donnée pour but de rendre à la France les limites de l’ancienne Gaule. La seconde, soutenue essentiellement par Gaston Zeller, cherche à démontrer que tous ces historiens ont eu une lecture trop « téléologique » de l’histoire de France. Si la question de ce prétendu programme politique monarchique a occupé une place importante de l’historiographie contemporaine, elle n’est pourtant pas centrale et de nouvelles perspectives de recherche s’offrent aujourd’hui à l’historien, comme celle de la définition de la « frontière naturelle ». Bien que l’expression ne soit pas inconnue des documents de l’époque moderne, les occurrences restent rares, les contemporains de l’Ancien Régime usant de diverses formules synonymes renvoyant toutes à un concept métaphysique, religieux et philosophique centré sur l’ordre naturel : à ce titre, les frontières naturelles sont des limites physiques imposées aux peuples et aux États par Dieu dès la Création pour que chacun d’eux puisse vivre en parfaite harmonie et en paix perpétuelle. Les frontières naturelles de la France proviennent d’un univers mental et mythique. Mental, puisque la redécouverte des textes antiques achève de graver dans la mémoire collective la notion d’une Gaule-France. Mythique, en raison du fait que la France succède à la Gaule par le processus de réappropriation de l’espace antique romain par Clovis. Tout un mythe de construction territoriale de l’espace de l’État français se met en place, soutenu et encouragé par la monarchie, non seulement par le biais de l’éducation mais aussi par la diffusion de nombreux ouvrages imprimés avec le privilège du roi. Mais par le traité de Verdun de 843, le « mythe de la France éternelle » s’effondre, le partage de l’empire de Charlemagne amputant la France d’une partie de ses frontières originelles. Aussi le Grand Siècle, qui coïncide avec le réveil de la conscience nationale, voit-il l’émergence de grandes figures mythiques : à ce titre, certains rois et certains ministres deviennent, à l’époque moderne, des symboles de la restauration de l’ordre naturel qui se fonde sur les lois fondamentales du royaume de France. Cependant, si la monarchie ne s’est pas donné pour but de rendre à la France les limites de l’ancienne Gaule, les frontières naturelles ont parfois orienté la politique extérieure pour défendre les impératifs stratégiques en matière de sécurité du territoire : tel est le cas du traité des Pyrénées de 1659 et de celui d’Utrecht de 1713. Bien que ces traités posent un problème d’application par la suite, l’article 42 de la paix des Pyrénées, qui fixe la frontière entre la France et l’Espagne au niveau du Roussillon et de la Catalogne, va faire l’objet, tout au long du XVIIIe siècle, de revendications politiques de la part des communautés françaises résidant dans les parties centrale et occidentale de la chaîne montagneuse. Dès lors, les frontières naturelles deviennent un enjeu de lutte majeure entre le pouvoir monarchique et ses sujets frontaliers.
Metastatic colorectal cancer (mCRC) most frequently occurs in elderly patients (pts), but these are less frequently treated with chemotherapy (CT) than younger ones. We report the final results of ...the first phase III study in elderly pts with mCRC receiving a 5FU-based CT with or without irinotecan.
Elderly pts (75+) with previously untreated mCRC were randomly assigned to receive a 5FU-based CT, either alone or in combination with irinotecan (FU arms: LV5FU2 or simplified LV5FU2, IRI arms: LV5FU2-CPT11 or FOLFIRI, reduced dosage for cycles 1 and 2). Stratification criteria were: center, Charlson index, Karnofsky index, previous adjuvant CT, sex, age, alkaline phosphatases. Primary endpoint was progression free survival (PFS). 240 events (282 pts) were required to demonstrate an improvement of median PFS from 5.5 to 7.9 months (m) in the IRI arm (bilateral α = 5%, β = 80%). Secondary endpoints were overall survival (OS), safety, objective response rate (ORR), QOL and geriatric evaluation. Kaplan-Meier estimation, log-rank tests and Cox model (HR with 95%CI) were used.
Between 06/2003-05/2010, 142 pts were randomly assigned to FU and 140 to IRI. Median age was similar in both arms 80 years (range 74-92). Main characteristics were well-balanced. Median duration of treatment was 3.5 m in FU and 4.5 m in IRI. At least one CT dose reduction was observed for 30.9% pts in FU and 52.6% pts in IRI. No significant difference was observed for the median PFS: FU 5.2 m vs IRI 7.3 m, HR = 0.84 (0.66-1.07), p = 0.15. ORR was superior in IRI arm (p = 0.002): FU 27.4% (95% CI: 20.1-35.8) vs IRI 46.3% (95% CI: 37.6-55.1). Median OS was 14.2 m in FU vs 13.3 m in IRI, HR = 0.96 (0.75-1.24). More patients presented grade 3-4 toxicities in IRI arm (76.3% vs 52.2%), mainly neutropenia (38.5% vs 5.2% of pts), diarrhea (22.2% vs 5.2% of pts) and febrile neutropenia (6.7% vs 0.7% of pts). Toxic deaths occurred in 2 pts in each arm.
In this elderly population, adding irinotecan to an infusional 5FU-based CT seems to increase PFS but does not improve survival and was associated with an increased toxicity.
E. Mitry: Aventis, Pfizer: sponsor of the trial.
All other authors have declared no conflicts of interest.
Anti-CA125 antibodies have been used in immunoassays to quantify levels of shed antigen in the serum of patients who are under surveillance for epithelial ovarian cancer (EOC). However, there is ...currently no molecular imaging probe in the clinic for the assessment of CA125 expression
in vivo
. The present study describes the development of an
18
F-labeled single-chain variable fragment (scFv) for PET imaging of CA125 in preclinical EOC models. Anti-CA125 scFv was derived from MAb-B43.13 by recombinant expression of the fragment in
E.coli
. Fragment scFv-B43.13 was purified via immobilized metal affinity chromatography and characterized for antigen binding via immuno-staining and flow cytometry. Prosthetic group
N
-succinimidyl 4-
18
Ffluorobenzoate (
18
FSFB) was used for radiolabeling of scFv-B43.13. Preclinical ovarian cancer models were developed based on ovarian cancer cell lines OVCAR3 (CA125-positive) and SKOV3 (CA125-negative) in NIH-III mice. The radiopharmacological profile of
18
F-labeled scFv-B43.13 (
18
FFBz-scFv-B43.13) was studied with PET.
18
FFBz-scFv-B43.13 was prepared in radiochemical yields of 3.7 ± 1.8% (n = 5) at an effective specific activity of 3.88 ± 0.76 GBq/µmol (n = 5). The radiotracer demonstrated selective uptake in CA125-positive OVCAR3 cells and virtually no uptake in CA125-negative SKOV3 cells. Standardized uptake values (SUV) of radioactivity uptake in OVCAR3 tumors was 0.5 (n = 3) and 0.3 (n = 2) in SKOV3 tumors after 60 min post injection (p.i.).
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