Global assessment of the knowledge and confidence in managing allergic disorders among primary care pediatricians across Europe: An EAACI task force report.

BACKGROUND: Pediatricians are often the first point of contact for children in Primary Care (PC), but still perceive gaps in their allergy knowledge. We investigated self-perceived knowledge gaps and educational needs in pediatricians across healthcare systems in Europe so that future educational initiatives may better support the delivery of allergy services in PC. METHOD: A multinational survey was circulated to pediatricians who care for children and adolescents with allergy problems in PC by the EAACI Allergy Educational Needs in Primary Care Pediatricians Task Force from February to March 2023. A 5-point Likert scale was used to assess the level of agreement with questionnaire statements. Thirty surveys per country were the cut-off for inclusion and statistical analysis. RESULTS: In this study, 1991 respondents were obtained from 56 countries across Europe and 210 responses were from countries with a cut-off below 30 participants per country. Primary care pediatricians (PCPs) comprised 74.4% of the respondents. The majority (65.3%) were contracted to state or district health services. 61.7% had awareness of guidelines for onward allergy referral in their countries but only 22.3% were aware of the EAACI competencies document for allied health professionals for allergy. Total sample respondents versus PCPs showed 52% and 47% of them have access to allergy investigations in their PC facility (mainly specific IgE and skin prick tests); 67.6% and 58.9% have access to immunotherapy, respectively. The main barrier to referral to a specialist was a consideration that the patient's condition could be diagnosed and treated in this PC facility, (57.8% and 63.6% respectively). The main reasons for referral were the need for hospital assessment, and partial response to first-line treatment (55.4% and 59.2%, 47% and 50.7%, respectively). Learning and assessment methods preference was fairly equally divided between Traditional methods (45.7% and 50.1% respectively) and e-learning 45.5% and 44.9%, respectively. Generalist physicians (GPs) have the poorest access to allergy investigations (32.7%, p = .000). The majority of the total sample (91.9%) assess patients with allergic pathology. 868 (43.6%) and 1117 (46.1%), received allergy training as undergraduates and postgraduates respectively [these proportions in PCPs were higher (45% and 59%), respectively]. PCPs with a special interest in allergology experienced greater exposure to allergy teaching as postgraduates. GPs received the largest amount of allergy teaching as undergraduates. Identifying allergic disease based on clinical presentation, respondents felt most confident in the management of eczema/atopic dermatitis (87.4%) and rhinitis/asthma (86.2%), and least confident in allergen immunotherapy (36.9%) and latex allergy (30.8%). CONCLUSION: This study exploring the confidence of PCPs to diagnose, manage, and refer patients with allergies, demonstrated knowledge gaps and educational needs for allergy clinical practice. It detects areas in need of urgent improvement especially in latex and allergen immunotherapy. It is important to ensure the dissemination of allergy guidelines and supporting EAACI documents since the majority of PCPs lack awareness of them. This survey has enabled us to identify what the educational priorities of PCPs are and how they would like to have them met.

Indications and practice of diverting ileostomy after colorectal resection and anastomosis in ovarian cancer cytoreduction.

OBJECTIVE: To determine the factors related with diverting ileostomy performance after colorectal resection and anastomosis, in advanced ovarian cancer cytoreductive surgery. METHODS: We have previously demonstrated the risk factors associated with anastomotic leak after colorectal anastomosis: Advanced age at surgery, low serum albumin level, additional bowel resections, manual anastomosis and distance of the anastomosis from the anal verge. However, use of diverting ileostomy is strongly variable and depends on individual surgeon preferences and training. Eight hospitals participated in this retrospective study. Data of 695 patients operated for ovarian cancer with primary colorectal anastomosis were included (January 2010-June 2018). Fourteen pre-/intraoperatively defined variables were identified and analysed as justification factors for use of diverting ileostomy. RESULTS: The rate of diverting ileostomy in the entire cohort was 19.13% (133/695; range within individual centers 4.6-24.32%). Previous treatment with bevacizumab [OR 2.8 (1.3-6.1); p=0.01]; additional bowel resections [OR 3.0 (1.8-5.1); p<0.001]; extended operating time [OR 1.005 (1.003-1.006); p<0.001] and intra-operative red blood transfusion [OR 2.7 (1.4-5.3); p<0.001] were found to be independently associated with diverting ileostomy performance. Assuming a 7% AL rate cut-off, up to 51.8% of DI presented an AL risk below 7% and might have been spared. CONCLUSIONS: The risk factors that drive the gynecologic oncology surgeons to perform a diverting ileostomy, seem to differ from the actual risk factors that we have identified to be associated with postoperative anastomotic leak. Broader awareness of the risk factors that contribute to a higher perioperative risk profile, will facilitate a better risk stratification process and possibly avoid unnecessary stoma formation in ovarian cancer patients.

Evaluation of an Online Educational Program for Parents and Caregivers of Children With Food Allergies.

BACKGROUND AND OBJECTIVE: The increasing prevalence of food allergy affects both patients and their families. Objective: The aim of this study was to evaluate the impact of an online educational program designed for parents and caregivers of children with food allergies. The program was developed by a multidisciplinary group comprising health care professionals, researchers, and expert patients under the participatory medicine model. MATERIAL AND METHODS: Participants took a 2-week online educational program covering major topics in food allergy management. General knowledge about the disease, symptoms, treatment, and topics relevant to families' daily lives were evaluated. The contents included educational videos, online forums, and live video chats. A pretest/posttest questionnaire survey was used to evaluate the impact of the program. RESULTS: A total of 207 participants enrolled in the educational program, which was completed by 130 (62.8%). Knowledge acquisition improved significantly following participation in the program in 15 out of 30 items (50%), reaching P<.001 for 8 items (26.7%). Of the 207 participants who started the program, 139 (67.1%) visited online forums, and 27.5% attended video chats. Average overall satisfaction with the educational program was 8.78 (on a scale of 0 to 10). CONCLUSIONS: The results obtained show that parents improved their knowledge in all areas of food allergy. The high level of satisfaction among participants suggests that digital learning tools are effective and motivational, enabling patients to acquire appropriate knowledge and thus increasing their quality of life.

[Analysis of the positive predictive value of the subcategories of BI-RADS(®) 4 lesions: preliminary results in 880 lesions]. / Análisis del valor predictivo positivo de las subcategorías BI-RADS(®)4: resultados preliminares en 880 lesiones.

OBJECTIVES: The positive predictive values (PPV) of the subcategories of BI-RADS(®) 4 lesions (A/B/C) vary widely, and their correlation with specific descriptors has yet to be defined. We aimed to analyze the PPV of the subcategories and of the mammographic and ultrasonographic descriptors assigned to each. MATERIAL AND METHODS: We analyzed 880 histologically confirmed lesions prospectively classified as BI-RADS(®) 4 A/B/C between 2003 and 2010. The statistical analysis included significance tests, contingency tables, and relative risk (RR) ratios, calculated for 545 mammographic lesions and 627 ultrasonographic lesions. RESULTS: The PPV was 8.8% for subcategory 4A, 18.9% for subcategory 4B, and 58.3% for subcategory 4C. The correlation between PPV and lesions was what we expected, with three exceptions: a) the PPV of 4A was greater than that of 4B in nodules that were irregular or had uncircumscribed margins on ultrasonography and in microcalcifications with segmental distribution on mammography, b) BI-RADS(®) 3 lesions classified as BI-RADS(®) 4, and c) identical lesions classified in distinct subcategories. In the contingency table analysis, the mammographic lesions were 4B/C and the ultrasonographic lesions were 4B. On mammography, the RR was significant for nodules with irregular shape (RR=3.205) and for those with spiculated margins (RR=2.469), as well as for microcalcifications that were pleomorphic (RR=2.531) or amorphous (RR=0.334), and for those with segmental (RR=1.895). On ultrasonography, the RR were significant for all the descriptors, with values greater than 1 for irregular shape (RR=1.977) and uncircumscribed margins (RR=2.277). CONCLUSIONS: Our results corroborate previous reports. The exceptions can be explained by aspects related to variability and nonradiological factors that might influence the classification and PPV. Mathematical models should be developed to enable the objective classification and these should include factors not related to imaging.

Dosage of anti-PD-1 monoclonal antibodies: a cardinal open question.

Discovery and clinical development of monoclonal antibodies with the ability to interfere in the regulation of the immune response have significantly changed the landscape of oncology in recent years. Among the active agents licensed by the regulatory agencies, nivolumab and pembrolizumab are paradigmatic as the most relevant ones according to the magnitude of available data derived from the extensive preclinical and clinical experience. Although in both cases the respective data sheets indicate well-defined dosage regimens, a review of the literature permits to verify the existence of many issues still unresolved about dosing the two agents, so it must be considered an open question of potentially important consequences, in which to work to improve the effectiveness and efficiency of use.

A prospective observational study of the clinical and pathological impact of stereotactic body radiotherapy (SBRT) as a neoadjuvant strategy of chemoradiation in pancreatic cancer.

PURPOSE/OBJECTIVE(S): To improve the curative resection rates and prognoses, a variety of neoadjuvant (NA) strategies have been explored in PDAC. In our institution, non-metastatic PDACs have been treated with a NA intent with induction multiagent chemotherapy and SBRT. The primary endpoint was to increase R0 resection rate. The secondary endpoints were the analysis of the clinical tolerance, the pathological response, the local control (LC) and the OS. MATERIALS/METHODS: All consecutive patients with non-metastatic PDAC underwent SBRT as part of the NA strategy were included. A total dose of 40-62 Gy were delivered in 5-10 fractions. Surgery was performed after SBRT and restaging. RESULTS: Since February 2014 to December 2018, 45 patients were enrolled. Thirty-two patients underwent surgery (71.1%), 10 out of 15 were initially unresectable disease patients (66.75%). R0 resection rate was 93% (30 patients) and pN0 status was achieved in 20 patients (60.6%). Tumour regression grade (TRG): 12 patients with complete response or marked response (TRG 0-1: 37.5%), 16 patients with moderate response (TRG 2: 50%) and four patients with poor response (TRG 3: 12.5%). The median follow-up was 16.2 m (range 6.6-59.6 m) since diagnosis. The LC rate achieved was very high (95.5%). Actuarial 12 and 24 m OS was 67.4% and 35.9% respectively. No grade 3 or higher toxicity related to SBRT was observed. CONCLUSION: The results are encouraging, suggesting that SBRT has a significant role in the management of these patients and further studies will be necessary to prove these findings.

Determining personalized treatment by gene expression profiling in metastatic breast carcinoma patients: a pilot study.

PURPOSE: The present study evaluates the massive study of gene expression in metastatic breast carcinoma (MBC) patients using microarray gene expression profiling (MAGE) complemented with conventional sequencing, immunohistochemistry (IHC) and fluorescent "in situ" hybridization (FISH), seeking to optimize the treatment in a subset of heavily pretreated patients and with limited life expectancy. PATIENTS, MATERIAL AND METHODS: MBC patients in hormone therapy progression with survival expectancy of at least 3 months (m) have been included. The MAGE contains gene probes representing genes known to potentially interact with available drugs as cited in the literature. RESULTS: Thirty-nine procedures were performed from October 2010 to April 2016. Within the 30 evaluable procedures, considering all hormonal manipulations as a single line, the patients had received a median of 4 treatment lines prior to MAGE (range 1-7). Progression was observed in 6 cases, stable disease (SD) in 7 cases and partial response (PR) in 16 cases, which implies a clinical benefit rate (SD + PR) of 76%. Actuarial median progression-free survival (PFS) was 6 m (95% CI 2.5-9.5) in patients with clinical benefit. The median overall survival (OS) for the entire series was 11 m (95% CI 2.2-19.8). CONCLUSION: Data presented here indicate that the use of MAGE provides relevant information to establish personalized treatment in frail patients with limited life expectancy in which therapeutic futility is a particularly difficult burden to assume.

Pathology findings and clinical outcomes after risk reduction salpingo-oophorectomy in BRCA mutation carriers: a multicenter Spanish study.

OBJECTIVE: To determine the incidence of serous tubal intraepithelial carcinoma (STIC) after risk reduction salpingo-oophorectomy(RRSO), and to describe oncological outcomes after RRSO. MATERIALS AND METHODS: BRCA pathogenic mutation carriers who had undergone an RRSO were evaluated in this retrospective multicenter observational study. Patients were only included when fallopian tubes were analyzed following the protocol for Sectioning and Extensively Examining the FIMbria (SEE-FIM). Surgeries were performed between June 2010 and April 2017 at eight Spanish hospitals. RESULTS: A total of 359 patients met the inclusion criteria. STIC was diagnosed in 3 (0.8%) patients; one of them underwent surgical staging due to positive peritoneal washing, with absence of disease at the final pathology report. None of the three patients received adjuvant chemotherapy and were free of disease at last follow-up. Fallopian tube and ovarian carcinoma were diagnosed in 5 (1.4%) and 1 (0.3%), respectively. At a median (range) follow-up time of 29 (3-92) months, five patients had a newly diagnosed breast cancer. Other types of cancer, which were diagnosed during the follow-up time, included: serous primary peritoneal carcinoma (n = 1), serous endometrial carcinoma (n = 1), colon (n = 1), pancreas (n = 1), jaw (n = 1), and lymphoma (n = 1). Seven patients died due to different types of cancer: breast (n = 4), pancreas (n = 1), jaw (n = 1), and colon (n = 1). CONCLUSION: The incidence of STIC after RRSO in BRCA mutation carriers is low (0.8%) and it presents an excellent oncological outcome. Patients after RRSO, however, run the risk to develop other types of cancer during follow-up and should be properly advised before the prophylactic surgery.

Analysis of fiducial markers used for on-line verification in the external-beam radiotherapy of patients with cranial tumours.

PURPOSE: Evaluate the fiducial marker-based position verification in the external-beam radiotherapy of patients with cranial tumour. METHODS: Thirteen patients with intracranial tumours were treated with external- beam radiotherapy using 3 gold markers implanted in the skull. Before each fraction the patient was positioned on the treatment table and 2 orthogonal portal images were performed to localise the 3 gold seeds and the target position was calculated using a commercialised computer program (ISOLOC software, MEDTEC). This program provides the couch movements required to move the target to the isocentre. RESULTS: When the set-up error was corrected using the coordinates of the 3 markers, the final movements were less than 2 mm in all cases: lateral, mean v., 1.21 mm; longitudinal, 1.23 mm; and anteroposterior, 1.18 mm. No serious complications related to the gold marker insertion were noted. CONCLUSION: The use of 3 implanted fiducial seeds is an optimal technique for precise set-up in patients with brain tumours treated with external radiotherapy. This commercial system is highly suitable for fractionated stereotactic irradiation.

[Risk factors for transfusion in primary knee arthroplasty]. / Factores predictivos de transfusión en la artroplastia primaria de rodilla.

OBJECTIVE: Transfusion is becoming safer but is not free of risk. It is important to establish a good approach to transfusion management and calculate real losses. Risk factors for transfusion should be identified. MATERIAL AND METHODS: This was a prospective study of 102 patients who did not receive intraoperative autotransfusion of shed blood, selected from a group of 127 who were undergoing primary knee arthroplasty. We initially calculated the amount of blood shed. Then, by multivariate logistic regression analysis we identified the model that best predicted that a patient would require transfusion. Receiver operating characteristic curves were constructed and the area under the curves calculated. RESULTS: Mean (SD) blood loss was calculated to be 1786 (710) mL. The best model considered initial hemoglobin (Hb), weight, height, and sex as predictive factors: Probability = 1/ (1+e(-Z)), where Z = 11.542 - 1.074 x initial Hb (g/dL) - 0.039 x Weight (kg) + 0.031 x Height (cm) + 0.267 x (sex: male=1 or female=0). The area under the ROC curve was 0.805 (0.44). CONCLUSION: Initial Hb, which can be modified before surgery, is one of the factors that most affects whether or not the patient will need a transfusion. Therefore, one of our first objectives in the process of managing transfusion is to improve preoperative Hb values.

Feasibility of robotic radical hysterectomy after neoadjuvant chemotherapy in women with locally advanced cervical cancer.

OBJECTIVE: To evaluate the safety and feasibility of robotic radical hysterectomy (RRH) in women with locally advanced cervical cancer (LACC) after neoadjuvant chemotherapy (NACT). MATERIAL AND METHODS: A retrospective comparative longitudinal observational study was performed in 30 patients with LACC FIGO stage IB2-IIB who underwent RRH after NACT between February 2008 and September 2014. This group was compared with a cohort of 176 patients underwent RRH with cervical cancer FIGO stage IA2-IB1 in the same period of time. RESULTS: Patients' age, BMI, ASA score, comorbidity, and previous abdominal surgery, was similar between groups. FIGO stage significantly differed between groups; 29 (96.6%) of patients had FIGO stage IB2 in NACT group and 163 (92.6%) were FIGO stag IB1 in women without NACT, p < 0.001. Type of RRH was also significantly different between groups. Type C1 RRH was significantly more common in NACT group, p = 0.015. Mean (SD) tumor size was significantly bigger in NACT, 27.0 (13.7) mm versus 20.9 (9.0) mm in early stage versus LACC, respectively. p = 0.023. Mean (SD) surgical time was significantly longer in NACT group (307.8 (40.2) min versus 277.4 (45.4) min, p = 0.001). Estimated blood loss and length of the hospital stay were similar between groups. There were no significant differences in terms of intraoperative and postoperative complications. CONCLUSIONS: RRH after NACT in women with LACC seems to be safe and feasible. These results need to be confirmed in studies with a larger patients sample.

Lack of efficacy of atenolol for the prevention of neurally mediated syncope in a highly symptomatic population: a prospective, double-blind, randomized and placebo-controlled study.

OBJECTIVES: This study was designed to evaluate the efficacy of atenolol for the long-term management of patients with vasovagal syncope. The primary hypothesis was that atenolol is not superior to placebo for the treatment of vasovagal syncope. BACKGROUND: There is no definitive well-controlled analysis of the efficacy of beta-adrenergic blocking agents in patients with recurrent vasovagal syncope. METHODS: This is a prospective, randomized, double-blind, placebo-controlled study. Fifty patients with recurrent vasovagal syncope were included (at least two episodes in the last year). A baseline tilt test was performed. Twenty patients (40%) had a positive tilt test. Intravenous atenolol prevented a second positive tilt in five patients. The patients were randomized to receive either atenolol or a placebo (26 patients atenolol 50 mg/day, 24 patients placebo). The follow-up procedure lasted one year. The primary end point of the study was the time to first recurrence of syncope. RESULTS: In the intention-to-treat analysis, the group treated with atenolol had a similar number of patients with recurrent syncopal episodes as the placebo group. The Kaplan-Meier actuarial estimates of time to first syncopal recurrence showed that the probability of remaining free of syncope drops similarly in both groups and that there was no statistical difference between both curves (patients treated with atenolol vs. the placebo) with a log-rank test p value of 0.4517. CONCLUSIONS: The recurrence of neurocardiogenic syncope in highly symptomatic patients treated with atenolol is similar to that of patients treated with placebo.

Localized remodeling of the Escherichia coli chromosome: the patchwork of segments refractory and tolerant to inversion near the replication terminus.

The behavior of chromosomal inversions in Escherichia coli depends upon the region they affect. Regions flanking the replication terminus have been termed nondivisible zones (NDZ) because inversions ending in the region were either deleterious or not feasible. This regional phenomenon is further analyzed here. Thirty segments distributed between 23 and 29 min on the chromosome map have been submitted to an inversion test. Twenty-five segments either became deleterious when inverted or were noninvertible, but five segments tolerated inversion. The involvement of polar replication pause sites in this distribution was investigated. The results suggest that the Tus/pause site system may forbid some inversion events, but that other constraints to inversion, unrelated to this system, exist. Our current model for deleterious inversions is that the segments involved carry polar sequences acting in concert with other polar sequences located outside the segments. The observed patchwork of refractory and tolerant segments supports the existence of several NDZs in the 23- to 29-min region. Microscopic observations revealed that deleterious inversions are associated with high frequencies of abnormal nucleoid structure and distribution. Combined with other information, the data suggest that NDZs participate in the organization of the terminal domain of the nucleoid.

Polarization of the Escherichia coli chromosome. A view from the terminus.

The E. coli chromosome replication arms are polarized by motifs such as RRNAGGGS oligomers, found preferentially on leading strands. Their skew increases regularly from the origin to dif (the site in the center of the terminus where chromosome dimer resolution occurs), to reach a value of 90% near dif. Convergent information indicates that polarization in opposite directions from the dif region controls tightly the activity of dif, probably by orienting mobilization of the terminus at cell division. Another example of polarization is the presence, in the region peripheral to the terminus, of small non-divisible zones whose inversion interferes with spatial separation of sister nucleoids. The two phenomena may contribute to the organization of the Ter macrodomain.

ARDS associated with boutonneuse fever.

The adult respiratory disease syndrome is associated with multiple disorders. At least one of the rickettsial diseases, RMSF, has been reported to be associated with noncardiogenic pulmonary edema. We report herein another rickettsial disease, boutonneuse fever, which is produced by Rickettsia conorii and is usually a mild disease, that in our patient was associated with ARDS.

Multiple cycles of dose-intensive chemotherapy with repeated stem cell support as induction treatment in metastatic breast cancer: a feasibility study.

The purpose of this trial was to study feasibility and tolerance of a dose-intensive multicyclic alternating induction chemotherapy with repeated stem cell support in a series of 43 metastatic breast cancer patients. Anthracycline-naive patients (n = 21) received cyclophosphamide 2.5 g/m(2) plus doxorubicin 80 mg/m(2) alternating every 14 days with paclitaxel 200-350 mg/m(2) plus cisplatin 120 mg/m(2). Patients who had previously received anthracyclines (n = 22) received cisplatin 120 mg/m(2) plus etoposide 600 mg/m(2) alternating with paclitaxel 200-350 mg/m(2) plus ifosfamide 8 g/m(2). Peripheral blood stem cells were infused after every course except the first, with a median CD34(+) dose of 2.1 x 10(6)/kg per cycle. Positive selection of CD34(+) cells was performed in good mobilizers. The median number of cycles administered was six (4-8), and the time interval between them was 17 days. Median summation dose intensities (SDI) actually administered for the CA-TP and PE-TI protocol were 4.95 and 4.69, respectively (87% of scheduled SDI). There were 15 complete (35%) and 21 partial responses (49%), for an overall response rate of 84% (95% CI, 73%-95%). Infection or neutropenic fever occurred in 50% of the cycles. There was one treatment-related death. After a median follow-up of 26 months, the median event-free-survival was 12 months (95% CI: 10-14) and overall survival was 31 months. These high dose-intensity induction treatments seem to be feasible with sequential stem cell support.

High-dose BCNU and autologous progenitor cell transplantation given with intra-arterial cisplatinum and simultaneous radiotherapy in the treatment of high-grade gliomas: benefit for selected patients.

A phase II study of postoperative high-dose carmustine (HDBCNU), intracarotid cisplatin (CDDP), and radical radiotherapy in patients with high-grade glioma was performed. Patients underwent 4-6 consecutive days of blood hematopoietic progenitor cell (HPC) apheresis without prior mobilization. Chemotherapy included intracarotid CDDP, 60 mg/m2, and BCNU, 900 mg/m2. HPC were infused 48 h after HDBCNU. Whole brain irradiation, up to 50 Gy, was started on the 8th day after HPC infusion. With a median follow-up time of 44 months, median overall survival was 15.5 months. Eight patients (23.5%) are alive free of disease 2-6 years after treatment (seven out of 25 patients with glioblastoma multiforme and one out of nine patients with anaplastic astrocytoma). Survival was influenced by young age, good performance and complete surgical resection. Two patients (5.8%) died of therapy-related complications. Acute hematological toxicity of HDBCNU was moderate, with a full recovery on day 26. No acute pulmonary or hepatic toxicity was found. Late severe neurological toxicity was observed in one third of patients surviving beyond 2 years. We conclude that HDBCNU, 900 mg/m2, intracarotid CDDP and radical radiotherapy appear to benefit some patients with high-grade gliomas, and phase III studies should preferentially select young patients with resectable tumors.

Salmonella dublin infection: a rare cause of spontaneous bacterial peritonitis and chronic colitis in alcoholic liver cirrhosis.

Salmonella dublin is a veterinary pathogen which rarely causes human illness, although reported human isolates have increased over the past two decades. This serovar of salmonella is unusually invasive and life-threatening, although the clinical pattern of human infection is not well known. We describe a 51-year-old cirrhotic patient who presented with severe liver failure, chronic diarrhoea and left-sided segmental colitis. Radiological and endoscopic findings suggested Crohn's colitis. During the hospital stay he developed a spontaneous bacterial peritonitis (SBP) and S. dublin was isolated in the ascitic fluid. Our report supports the view that this salmonella serovar should be kept in mind as a rare cause of SBP in cirrhotic patients, especially in those cases with chronic colitis resembling Crohn's disease.

Plasmid pKM101-dependent repair and mutagenesis in Escherichia coli cells with mutations lexB30 tif and zab-53 in the recA gene.

Bacterial survival after UV irradiation was increased in E. coli K12 lexB30 and tif zab-53 mutants harboring plasmid pKM101. Mutagenesis in response to UV was observed in these bacteria which, in absence of pKM101, are not UV-mutable. The mutator effect observed in unirradiated wild-type cells containing pKM101 was higher than incubation at 30 degrees C with adenine than at 37 degrees C. This effect was still enhanced by tif mutation, even in the tif zab-53 strain, but it was abolished by lexB30 mutation. In the tif zab-53 (pKM101) strain, repair and mutagenesis of UV-irradiated phage lambda was observed, but not in the lexB30 mutant carrying pKM101. The pKM101 mutant, pGW1, was unable to protect tif zab-53 bacteria against killing by UV, whereas the protection of lexB30 was intermediate; moreover, it did not promote the mutator effect at 30 degrees C or enhance phage repair and mutagenesis in tif zab-53 cells. All UV-induced bacterial mutations in lexB30 (pKM101) strain were suppressors; in contrast, true revertants were found after UV irradiation of the tif zab-53 (pKM101) cells. We suggest that the constitutive activity of RecA protein is enough for the production of UV-promoted suppressor mutations, whereas true reversions require a more active form of this protein which could exert its effects directly or by acting at a regulatory level on other cellular functions.

Intra-arterial hepatic treatment with carboplatin (CBDCA) and 5-fluorouracil (5-FU) in metastases from colorectal carcinoma.

Thirty-one patients with hepatic metastases from colorectal carcinoma were treated with carboplatin (CBDCA), 55 mg/m2, given in a 4-hour intra-arterial infusion daily for 5 days, and 5-fluorouracil, 900 mg/m2, given in a 20-hour intra-arterial infusion daily for 5 days. Cycles were administered every 5 weeks. Objective responses were observed in 16 (51.6%) patients (5 complete and 11 partial responses). Another 13 patients maintained stable disease, and 2 patients rapidly progressed. The overall median survival was 23.5 months. The 16 patients with objective response had a median survival of 26.5 months. In this series, no evidence of biliary sclerosis, cholecystitis, chemical hepatitis, or myelosuppression was observed. Complications of drug delivery system were observed in 14 (45.16%) patients. In conclusion, intra-arterial hepatic chemotherapy with CBDCA-5FU was associated with a modest benefit, expressed in good quality responses and extended survival of approximately 2 years in about half of the treated patients.