Oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX6). GERCOR

For patients resistant to leucovorin (LV) and 5-fluorouracil (5-FU), the addition of oxaliplatin (85 or 100 mg/m2) to bimonthly LV-5-FU has given a response rate of 20-46%. The highest response rate has been observed with oxaliplatin 100 mg/m2 (FOLFOX2). The present phase II study (FOLFOX6) infused oxaliplatin (100 mg/m2) with LV (400 mg/m2) as a 2-h infusion on day 1, followed by bolus 400 mg/m2 and a 46-h infusion (2.4-3 g/m2) of 5-FU, every 2 weeks. Among the 60 patients treated, 16 (27%) had partial responses (95% confidence interval: 15-38), 27 (45%) had stable disease, 15 (25%) experienced disease progression and 2 (3%) had non-measurable disease. From the start of FOLFOX6, median progression-free survival was 5.3 months and median survival 10.8 months. From the 448 cycles analysed, NCI-CTC grade 3-4 toxicities per patient were: peripheral neuropathy 16%, nausea 7%, diarrhoea 7%, mucositis 5%, neutropenia 24%, thrombocytopenia 2%. Overall 26 (46%) patients experienced grade 3-4 toxicities. Because of toxicity, only 36% of the patients received > or = 90% of the scheduled oxaliplatin dose intensity. FOLFOX6 was active in pretreated patients resistant to LV-5-FU and is being investigated as first-line therapy. We are now investigating FOLFOX7, a regimen with a higher oxaliplatin dose intensity and a lower 5-FU dose.     

Biomechanical comparison of three fixation techniques for unstable thoracolumbar burst fractures. Laboratory investigation

OBJECT: Increased structural stability is considered sufficient justification for higher-risk surgical procedures, such as circumferential fixation after severe spinal destabilization. However, there is little biomechanical evidence to support such claims, particularly after traumatic lumbar burst fracture. The authors sought out to compare the biomechanical performance of the following 3 fixation strategies for spinal reconstruction after decompression for an unstable thoracolumbar burst fracture: 1) short-segment anterolateral fixation; 2) circumferential fixation; and 3) extended anterolateral fixation. METHODS: Thoracolumbar spines (T10-L4) from 7 donors (mean age at death 64+/-6 years; 1 female and 6 males) were tested in pure moment loading in flexion-extension, lateral bending, and axial rotation. Thoracolumbar burst fractures were surgically induced at L-1, and testing was repeated sequentially for each of the following fixation techniques: short-segment anterolateral, circumferential, and extended anterolateral. Primary and coupled 3D motions were measured across the instrumented site (T12-L2) and compared across treatment groups. RESULTS: Circumferential and extended anterolateral fixations were statistically equivalent for primary and off-axis range-of-motions in all loading directions, and short-segment anterolateral fixation offered significantly less rigidity than the other 2 methods. CONCLUSIONS: The results of this study strongly suggest that extended anterolateral fixation is biomechanically comparable to circumferential fusion in the treatment of unstable thoracolumbar burst fractures with posterior column and posterior ligamentous injury. In cases in which an anterior procedure may be favored for load sharing or canal decompression, extension of the anterior instrumentation and fusion one level above and below the unstable segment can result in near equivalent stability to a 2-stage circumferential procedure.     

Ultrasound‐guided percutaneous tenotomy for the treatment of iliopsoas impingement: A description of technique and case study

Iliopsoas impingement is a commonly recognised source of groin pain following total hip replacement. When conservative measures fail, open or arthroscopic iliopsoas tendon release can reliably alleviate pain and improve function. This article describes an alternative ultrasound‐guided percutaneous technique, achieving iliopsoas tenotomy utilising a modified 18G coaxial needle and thus minimising the morbidity and cost associated with an open or arthroscopic procedure. This method proved successful with resultant complete resolution of patient symptoms. To the knowledge of the authors, this is the first case of ultrasound‐guided percutaneous iliopsoas tenotomy for iliopsoas impingement post total hip replacement.     

Claudin 1 differentiates endometrioid and serous papillary endometrial adenocarcinoma

OBJECTIVE: The expression of claudins, the main tight junction proteins involved in cell adhesion and carcinogenesis, was studied in endometrioid (type I) and seropapillary (type II) endometrial adenocarcinoma. The characteristics and possible diagnostic potential of claudin expression pattern were investigated in the two cancer types having different prognosis. METHODS: Protein and mRNA expression of claudins was evaluated in 17 endometrioid carcinomas and 15 seropapillary adenocarcinomas by immunohistochemistry and real-time PCR in comparison with 38 cases of hyperplasia, normal proliferative and secretory endometrium samples. Further, protein expressions used in diagnostics (estrogen and progesterone receptors, p53, PCNA and beta-catenin) were also studied. RESULTS: In endometrioid carcinoma and hyperplasia low claudin 1 and high claudin 2 protein contents, whereas in seropapillary adenocarcinoma high claudin 1 and low claudin 2 levels were detected. Intense protein expression was noted for claudins 3, 4, 5, and 7, without significantly different patterns in carcinoma, hyperplasia, secretory, and proliferative endometrium. Real-time PCR results confirmed differences in claudin 1 but not claudin 2 mRNA expression, whereas some minor discrepancies were observed in comparison with immunohistochemistry patterns. CONCLUSION: The two types of endometrial adenocarcinomas were well distinguished by claudins 1 and 2 by immunohistochemistry, claudins 3, 4, and 7, however, did not prove useful in distinguishing the two entities. The similar claudin pattern seen in hyperplasia and endometrioid carcinoma and the differences regarding seropapillary adenocarcinoma support the dualistic model of endometrial carcinogenesis. The claudin pattern of the two tumor types might reflect a different cellular or pathogenetic pathway as well as a different cell adhesion behavior explaining the invasive properties.     

Speech-controlled generation of radiology reports

Voice entry has been successfully employed to generate radiology reports with a word recognizer with a 1,000-word lexicon capacity. About 50% of reports were able to be dictated with a single 900-word lexicon. This was split into five sections by anatomic or subspecialty application. Each was augmented to 900 words. By switching from one lexicon to another, it was possible to dictate more than 70% of reports. With exclusive use of three lexicons in subspecialty areas (gastrointestinal radiology, neuroradiology, and mammography), and with further modification of the respective vocabulary, it has been possible to employ the system 88% of the time. Twelve percent of cases included wording that was beyond the scope of the lexicon. Computer subsets that allow different translations of some words when used in different contexts have been used. Some of these are used as triggers that will print whole lines, sentences, or even complete reports. Dictation times with voice entry take about 20% longer. Recognition reliability has been greater than 95%.     

Cytotoxic and genotoxic effects of matrices for cartilage tissue engineering

Customizing auricles with biodegradable polyurethane colonized with autologous chondrocytes as an approach for tissue engineering cartilage transplants has been suggested for the reconstruction of the external ear to repair auricular deformities. Dextrose, triethanolamine and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (PEG-PPG-PEG) are matrices of an open-pored polyurethane three-dimensional scaffold. After release from the polymer, these compounds can be absorbed into the human organism. Therefore, cytotoxic effects on human chondrocytes and lymphocytes and genotoxic effects on human lymphocytes were determined. Propidium iodide and fluoresceine diacetate staining as well as quantitative proliferations testing with EZ4U served to detect cytotoxic effects on chondrocytes. In lymphocytes cytotoxicity was checked by trypan blue staining and the alkaline single cell microgel electrophoresis (Comet) assay was used to study genotoxic effects. Dose-dependent cytotoxicity and genotoxicity of the matrices could be shown. Concentrations up to 4.25 mg/ml for dextrose, 0.15 mg/ml for PEG-PPG-PEG and 0.9 mg/ml for triethanolamine did not show cytotoxic effects in chondrocytes or genotoxic effects in lymphocytes. These data suggest that dextrose, triethanolamine and PEG-PPG-PEG could be safely used if scaffolds made of open-pored polyurethane do not release these compounds at a rate giving higher concentrations at the site of implantation or in body fluids, respectively.     

Risk factors for development of dehydration in young children with acute watery diarrhoea: a case-control study

In a case-control study to understand the risk factors for development of life-threatening dehydration, a total of 379 children comprising 243 cases (moderate or severe dehydration) and 136 controls (non or mild dehydration) up to 2 years of age suffering from acute watery diarrhoea were studied. By univariate analysis, the presence of vibrios in stool, withdrawal of breast feeding during diarrhoea, not giving fluids, including oral rehydration solution (ORS), during diarrhoea, frequent purging (> 8/ day), vomiting (> 2/day) and undernutrition were identified as risk factors. However, by multivariate analysis after controlling for confounders, withdrawal of breast feeding during diarrhoea (odds ratio (OR) = 6.8, p < 0.00001) and not giving ORS during diarrhoea (OR = 2.1, p < 0.006) were identified as significant risk factors. The confounding variables which also contributed significantly to increasing the risk were age (≤ 12 months; OR = 2.7, p = 0.001), frequent purging (> 8/day; OR = 4.1, p < 0.00001), vomiting (> 2/day; OR = 2.4, p = 0.001) and severe undernutrition (%median <60 weight-for-age of Indian Academy of Paediatrics classification; OR = 3.1, p = 0.001). We feel that these findings will be useful for Global and National Diarrhoeal Diseases Control Programmes for formulating intervention strategies for preventing death due to diarrhoeal dehydration.