Patient-physician discordance in goals of care for patients with advanced cancer.

Background: Shared decision-making at end of life (eol) requires discussions about goals of care and prioritization of length of life compared with quality of life. The purpose of the present study was to describe patient and oncologist discordance with respect to goals of care and to explore possible predictors of discordance. Methods: Patients with metastatic cancer and their oncologists completed an interview at study enrolment and every 3 months thereafter until the death of the patient or the end of the study period (15 months). All interviewees used a 100-point visual analog scale to represent their current goals of care, with quality of life (scored as 0) and survival (scored as 100) serving as anchors. Discordance was defined as an absolute difference between patient and oncologist goals of care of 40 points or more. Results: The study enrolled 378 patients and 11 oncologists. At baseline, 24% discordance was observed, and for patients who survived, discordance was 24% at their last interview. For patients who died, discordance was 28% at the last interview before death, with discordance having been 70% at enrolment. Dissatisfaction with eol care was reported by 23% of the caregivers for patients with discordance at baseline and by 8% of the caregivers for patients who had no discordance (p = 0.049; ϕ = 0.20). Conclusions: The data indicate the presence of significant ongoing oncologist-patient discordance with respect to goals of care. Early use of a simple visual analog scale to assess goals of care can inform the oncologist about the patient's goals and lead to delivery of care that is aligned with patient goals.

[Enhanced structural transformations in DNA macromolecules exposed to weak thermalized neutron field].

We examined now an ultraweak thermalized neutron field (UTNF) affects the structural transformation in DNA macromolecules at room temperature. IR-spectroscopy, electrophoresis, and filtration through nitrocellulose filter measurements revealed that UTNF irradiation with a fluence of F(n) - 1.0 - 3.7 x 10(7) n/cm2 (the absorbed dose as low as 10 - 50 microGy) can induce non negligible structural changes in DNA macromolecules in film as well as in an aqueous solution. These structural changes appear as a type of reversible conformational transition from the A-form to a disordered state, as well as through intermolecular cross-link formations and the generation of double-strand breaks.

Vascular endothelial growth factor improves functional outcome and decreases secondary degeneration in experimental spinal cord contusion injury.

Spinal cord injury leads to acute local ischemia, which may contribute to secondary degeneration. Hypoxia stimulates angiogenesis through a cascade of events, involving angiogenesis stimulatory substances, such as vascular endothelial growth factor (VEGF). To test the importance of angiogenesis for functional outcome and wound healing in spinal cord injury VEGF165 (proangiogenic), Ringer's (control) or angiostatin (antiangiogenic) were delivered locally immediately after a contusion injury produced using the NYU impactor and a 25 mm weight-drop. Rats treated with VEGF showed significantly improved behavior up to 6 weeks after injury compared with control animals, while angiostatin treatment lead to no statistically significant changes in behavior outcome. Furthermore, VEGF-treated animals had an increased amount of spared tissue in the lesion center and a higher blood vessel density in parts of the wound area compared with controls. These effects were unlikely to be due to increased cell proliferation as determined by bromo-deoxy-uridine-labeling. Moreover, VEGF treatment led to decreased levels of apoptosis, as revealed by TUNEL assays. In situ hybridization demonstrated presence of mRNA for VEGF receptors Flt-1, fetal liver kinase-1, neuropilin-1 and -2 in several important cellular compartments of the spinal cord. The different experiments indicate that beneficial effects seen by acute VEGF delivery was attributable to protection/repair of blood vessels, decreased apoptosis and possibly also by other additional effects on glial cells or certain neuron populations.

[Ultraweak thermalized neutron field as an underestimated factor of DNA structural transformation]. / Pole ul'traslabykh termalizovannykh neitronov kak faktor strukturnykh transcformatsii DNK.

It was shown that thermalized neutrons in superlow doses were capable of inducing detectable structural transformations in DNA films and DNA solutions.

Intraoperative magnetic resonance imaging: considerations for the operating room of the future.

Recent technological advances have made possible the introduction of the magnetic resonance imaging (MRI) system into the operating room to guide neurosurgical interventions. We review the possibilities and limitations associated with various open-configuration magnet designs, including systems from the Phillips, Siemens, General Electric, Odin and IMRIS designs. This technology has been shown to be a feasible adjunct to current neurosurgical management of intracranial brain tumors for both biopsy and resection procedures and shows significant potential applications for epilepsy surgery, spine surgery and for minimally invasive interventional techniques. Combined with other surgical planning modalities, intra-operative MRI scanners provide an evolutionary influence on the design of today's operating room.

Möbius' syndrome: features and etiology.

PURPOSE: To review the clinical features and possible aetiology of all cases of Möbius' syndrome presented at the Royal Alexandra Hospital for Children in Sydney, Australia, from 1963 through 1995. METHODS: All charts of patients suffering from Möbius' syndrome were reviewed, and each patient was thoroughly assessed by a geneticist and a pediatric ophthalmologist. RESULTS: Patterns of systemic and ocular clinical features became evident. Of 23 patients in the series, 10 (43%) had a history significant events in utero. CONCLUSIONS: All patients suffering from Möbius' syndrome require thorough assessment by a multidisciplinary team including a geneticist or pediatrician and a pediatric ophthalmologist. Significant vascular events of pregnancy may explain some cases of fetal vascular disruption to the brainstem.

Severe cervical dysplasia and nasal cartilage calcification following prenatal warfarin exposure.

We present an infant who was exposed to warfarin throughout pregnancy and has warfarin embryopathy. When the child was examined radiologically at 20 months areas of calcification were visible in the septal and alar cartilages of the small external part of the nose. The location of this ectopic calcification is consistent with that seen in an animal model of the warfarin embryopathy. It supports the hypothesis that warfarin interferes with the prenatal growth of the cartilaginous nasal septum by inhibiting the normal formation of a vitamin K-dependent protein that prevents calcification of cartilage. The child also had severe abnormalities of the cervical vertebrae and secondary damage to the spinal cord. Cervical vertebral anomalies are a relatively common finding in the warfarin embryopathy and in the related Binder syndrome.

Anal anomalies: an uncommon feature of velocardiofacial (Shprintzen) syndrome?

We report three cases of velocardiofacial syndrome (VCFS) with anal anomalies who have deletions of the 22q11 region and a further case where the proband has VCFS clinically and her father has an anal anomaly. It is important to consider VCFS in the differential diagnosis of children with anal anomalies and to look for other features of the syndrome, such as asymmetrical crying facies, submucous cleft of the palate, developmental delay, cardiac anomalies, and hypoparathyroidism.

Carbohydrate deficient glycoprotein syndrome type I: a cause of cerebellar vermis hypoplasia.

To report the first case of carbohydrate deficient glycoprotein syndrome Type I (CDG I) that has been identified in Australia and confirmed enzymatically to raise the awareness of paediatricians with regard to CDG I and its manifestations, implications and diagnostic investigations. Clinical and autopsy findings of an infant with CDG I are presented. The diagnosis of CDG I was suggested by the clinical findings and biochemical abnormalities and was confirmed by showing an abnormal transferrin isoform pattern. Subsequent studies showed a reduced level of phosphomannomutase in skin fibroblasts. Carbohydrate-deficient glycoprotein syndrome I is one of the many causes of cerebellar hypoplasia. It is an important disorder to identify because of the prognostic and genetic implications and may be underdiagnosed in Australia.

Velo-cardio-facial and partial DiGeorge phenotype in a child with interstitial deletion at 10p13--implications for cytogenetics and molecular biology.

We report on a female with a interstitial deletion of 10p13 and a phenotype similar to that seen with the 22q deletion syndromes (DiGeorge/velo-cardio-facial). She had a posterior cleft palate, perimembranous ventricular septal defect, dyscoordinate swallowing, T-cell subset abnormalities, small ears, maxillary and mandibular hypoplasia, broad nasal bridge, deficient alae nasi, contractures of fingers and developmental delay. This could indicate homology of some developmental genes at 22q and 10p so that patients with the velocardiofacial phenotype who do not prove to be deleted on 22q are candidates for a 10p deletion.

Two cases of maternal antenatal splenic rupture and hypotension associated with Moebius syndrome and cerebral palsy in offspring. Further evidence for a utero placental vascular aetiology for the Moebius syndrome and some cases of cerebral palsy.

UNLABELLED: We wish to report two cases of congenital abnormality after antenatal car accidents resulting in ruptured spleen and severe hypotension in the mothers at 8 and 14 weeks gestation. The first case had the classical Moebius syndrome with 6th and 7th cranial nerve palsy with abnormal brain stem evoked responses, presumably due to hypoxic/ischaemic brain stem damage and the second case had severe retardation and hypertonic cerebral palsy which at post mortem was found to be due to old hypoxic/ischaemic lesions to the caudate nucleus putamen and striatum. CONCLUSION: The cases described provide evidence that severe maternal hypotension during pregnancy can be associated with lesions to the midbrain and brain stem of offspring. The mechanism is probably utero-placental insufficiency, and extrapolation from these two unusual cases would support utero-placental insufficiency as a cause of Moebius syndrome and limb deficiency after chorionic villus sampling.

Prenatal exposure to phenytoin, facial development, and a possible role for vitamin K.

Ten patients with maxillonasal hypoplasia (Binder "syndrome"), who were prenatally exposed to phenytoin (usually in combination with other anticonvulsants), were identified retrospectively. In addition to their facial anomalies, 6 of the patients were radiographed neonatally and showed punctate calcification, characteristic of chondrodysplasia punctata. Evidence is presented that the facial abnormalities seen in these children are due to anticonvulsant-induced vitamin K deficiency, causing abnormal development of the cartilaginous nasal septum. We propose that early vitamin K supplementation of at-risk pregnancies may prevent the development of maxillonasal hypoplasia, which in some patients is severely disfiguring and causes great emotional distress. Correction of this facial defect requires surgical and dental treatment over a long period of time.

Amelia of the arms and femur/fibula deficiency with splenogonadal fusion in a child born to a consanguineous couple.

A male infant was born with symmetrical tetramelic limb deficiency consisting of bilateral upper limb amelia with severe symmetrical proximal focal femoral deficiency and fibula deficiency associated with left splenogonodal fusion of the discontinuous type, micrognathia, and a prominent capillary haemangioma of the face. The parents are first cousin Lebanese muslims. This observation suggests the possibility of recessive inheritance in some cases of the Amelia, Femur-Fibula dysostosis syndrome with or without splenogonadal fusion.