Identification of High-Risk Groups among Node-Positive Patients with Stage IB and IIA Cervical Carcinoma

The purpose of the present study was to identify a subset of high-risk patients among surgically treated node-positive patients with stage IB and IIA cervical carcinoma. From 1982 through 1991, 334 patients underwent radical hysterectomy for FIGO stage IB and IIA cervical carcinoma. In 68 patients pathological analysis of the surgical specimen revealed positive pelvic nodes. In this group, a Cox proportional hazard analysis was performed to examine the prognostic significance of clinicopathological variables. Only for adenocarcinoma (P= 0.002) and parametrium infiltration (P= 0.003) was evidence of an association with prognosis found. Based on these two factors, patients with positive pelvic nodes were categorized into a low-risk group (squamous cell carcinoma without parametrium infiltration,N= 33) and a high-risk group (squamous cell carcinoma with parametrium infiltration or adenocarcinoma,N= 34). The 5-year disease-specific survival in the low-risk group was 94% compared with 60% in the high-risk group (P= 0.003). For patients in the high-risk group, there is an urgent need for alternative adjuvant treatment to improve outcome.     

Response of sensitive and resistant IgM immunocytomas to cis-diamminedichloroplatinum(II) does not correlate with the platination level or with the formation or removal of DNA adducts

 An IgM immunocytoma cell line sensitive to cis-diamminedichloroplatinum(II) (CDDP) and a subline with acquired resistance were grown in LOU/M rats. In a previous study with such rats that had been treated with a high dose of CDDP (10 mg/kg) the tumors did not show differences in cellular platinum content or DNA-adduct levels, either immediately after treatment or 24 h later. Recently, this high dose was found to overcome resistance. Therefore, the study was repeated with a 10-fold lower dose (1 mg/kg, i.v.). At 1 and 24 h after treatment, tumor and kidney tissue were assayed for cellular platinum (atomic absorption spectroscopy, AAS) and DNA platination (immunochemical detection of the four CDDP-DNA adducts). The results were compared with previous data. All tissues showed a linear response to dose with regard to platinum uptake as well as adduct formation, with no quantitative difference being seen between the tumors. Also the relative occurrence of the four adducts was very similar. Between 1 and 24 h, in tumors a substantial decrease occurred in both platinum content and adduct level; the kidneys showed little reduction, if any. At the lower CDDP dose a somewhat larger loss of platinum and removal of DNA adducts was observed for the resistant tumor, but these differences could be explained by “dilution”, as this tumor continues to grow after low-dose treatment (about 20% within 24 h). Since the strong difference observed between the tumors in sensitivity to CDDP cannot be attributed to differences in CDDP uptake, efficiency of adduct formation, or repair capability, other mechanisms are held responsible. Received 10 August 1995 / Accepted: 14 August 1996     

NMR Studies of Retinoid-Protein Interactions: The Conformation of [13C]-β-Ionones Bound to β-Lactoglobulin B

Purpose. Vitamin A (retinol) and its metabolites comprise the natural retinoids. While the biological action of these molecules are thought to be primarily mediated by ca. 55 kDa nuclear retinoic acid receptors, a number of structurally similar 15-20 kDa proteins are involved in the transport, and possibly metabolism, of these compounds. The milk protein -lactoglobulin B (-LG) is an 18 kDa protein which binds retinol and may be involved in oral delivery of retinol to neonates. -LG also binds drugs and other natural products and is of potential interest as a protective delivery vehicle. Methods. To examine the conformation of the model retinoid -ionone both in solution and when bound to -LG, NMR and computational methods have been employed. Results. Taken together, NMR studies of -ionone in solution measuring scalar and dipolar coupling, as well as CHARMm calculations, suggest -ionone prefers a slightly twisted 6-s-cis conformation. Isotope-edited NMR studies of ^l3C-labeled -ionones bound to -LG, primarily employing the HMQC-NOE experiment, suggest -ionone also binds to -LG in its 6-s-cis conformation. Conclusions. The methods employed here allow estimates of protein-bound ligand conformation. However, additional sites of ligand labeling will be necessary to aid in binding site localization.     

Prenatal and early postnatal fatty acid status and neurodevelopmental outcome

The present review addresses the effect of pre- and postnatal supplementation of nutrition with long-chain polyunsaturated fatty acids (LCPUFA) on neurodevelopmental outcome. The few studies which addressed the effect of prenatal LCPUFA status or prenatal LCPUFA supplementation suggest that a better prenatal arachidonic acid (AA) and doxosahexaenoic acid (DHA) status might be related to a better neurodevelopmental outcome until at least 18 months of age. A review of the few randomized controlled trials on formula supplementation with LCPUFA in preterm infants did not provide evidence for a significant beneficial effect of LCPUFA on developmental outcome. A review of the trials on formula supplementation with LCPUFA in term infants revealed that supplementation with LCPUFA, in particularly supplementation with >or=0.30% DHA, has a beneficial effect on neurodevelopmental outcome until 4 months. The studies could not demonstrate a consistent positive effect beyond that age. It was concluded that the relatively subtle effects of LCPUFA supplementation on neurodevelopmental outcome do not only depend on dosage but also on the gestational period during which the nutritional components are supplied: supplementation prior to term seems to have more effect than that after term.     

Reimagining care for young adults living with type 1 diabetes

Young adults living with type 1 diabetes often struggle to achieve what clinicians consider to be optimal levels of metabolic control. Despite the impact that this can have on a young person''s future risk of complications, there are relatively few studies reporting new ways of organizing or delivering care to this cohort. In this article, we explore some of the reasons why young adult diabetes care is challenging, and describe approaches to “re‐imagining” how care might be improved. The work is informed by the ‘Making Care Fit’ collaborative and by a program of research, entitled D1 Now, involving co‐design of a complex person‐centered intervention with young adults.     

Influence of aneurysm wall stiffness and the presence of intraluminal thrombus on the wall movement of an aneurysm - an in vitro study

The purpose of this in vitro study was to investigate the influence of aneurysm wall stiffness and of the presence of intraluminal thrombus (ILT) on aneurysm wall movement. Three latex aneurysms were used with different wall stiffness. The aneurysms, equipped with 20 tantalum markers, were attached to an in vitro circulation model. Fluoroscopic roentgenographic stereo photogrammetric analysis was used to measure marker movement during six cardiac cycles at three different systemic pressures. To investigate the influence of ILT on wall movement, we repeated the same experiment with one of the aneurysms. The aneurysm sac was then filled with one of two E-moduli differing thrombus analogues (Novalyse 8 and 20) or with perfusate as a control. It was noted that the amplitude of the wall movement (mm) increased significantly (P < 0.05) as the compliance of the wall increased. The mean amplitude of the wall movement decreased (P < 0.05) as the stiffness (E-modulus) of the ILT increased. In conclusion, ILT has a 'cushioning effect'. Wall movement (and theoretically wall stress) diminishes when the stiffness of the ILT increases. Compliance of the aneurysm wall influences wall movement. When the stiffness of the wall increases, the wall movement diminishes.     

Evaluating the accuracy of resection planes in mandibular surgery using a preoperative,intraoperative, and postoperative approach

In mandibular surgery, three-dimensionally printed patient-specific cutting guides are used to translate the preoperative virtually planned resection planes to the operating room. This study was performed to determine whether cutting guides are positioned according to the virtual plan and to compare the intraoperative position of the cutting guide with the resection performed. Nine patients were included. The exact positions of the resection planes were planned virtually and a patient-specific cutting guide was designed and printed. After surgical placement of the cutting guide, intraoperative cone beam computed tomography (CBCT) was performed. Postoperative CT was used to obtain the final resection planes. Distances and yaw and pitch angles between the preoperative, intraoperative, and postoperative resection planes were calculated. Cutting guides were positioned on the mandible with millimetre accuracy. Anterior osteotomies were performed more accurately than posterior osteotomies (intraoperatively positioned and final resection planes differed by 1.2 ± 1.0 mm, 4.9 ± 6.6°, and 1.8 ± 1.5°, respectively, and by 2.2 ± 0.9 mm, 9.3 ± 9°, and 8.3 ± 6.5° respectively). Differences between intraoperatively planned and final resection planes imply a directional freedom of the saw through the saw slots. Since cutting guides are positioned with millimetre accuracy compared to the virtual plan, the design of the saw slots in the cutting guides needs improvement to allow more accurate resections.