Monitoring CD8a+ T Cell Responses to Radiotherapy and CTLA-4 Blockade Using [64Cu]NOTA-CD8a PET Imaging

Molecular Imaging and Biology - Current response assessment systems for cancer patients receiving immunotherapy are limited. This is due to the associated inflammatory response that may confound...     

Cancer in offspring of parents engaged in agricultural activities in Norway: Incidence and risk factors in the farm environment

In this study of cancer in offspring we demonstrate that factors linked to horticulture and use of pesticides are associated with cancer at an early age, whereas factors in animal husbandry, in particular poultry farming, are associated with cancers in later childhood and young adulthood. Incident cancer was investigated in offspring born in 1952–1991, to parents identified as farm holders in agricultural censuses in Norway in 1969–1989. In the follow-up of 323,292 offspring for 5.7 million person-years, 1,275 incident cancers were identified in the Cancer Registry for 1965–1991. The standardized incidence for all cancers was equal to the total rural population of Norway, but cohort subjects had an excess incidence of nervous-system tumours and testicular cancers in certain regions and strata of time that could imply that specific risk factors were of importance. Classification of exposure indicators was based on information given at the agricultural censuses. Risk factors were found for brain tumours, in particular non-astrocytic neuroepithelial tumours: for all ages, pig farming tripled the risk [rate ratio (RR), 3.11; 95% confidence interval (CI), 1.89–5.13]; indicators of pesticide use had an independent effect of the same magnitude in a dose-response fashion, strongest in children aged 0 to 14 years (RR, 3.37; 95% CI, 1.63–6.94). Horticulture and pesticide indicators were associated with all cancers at ages 0 to 4 years, Wilms' tumour, non-Hodgkin's lymphoma, eye cancer and neuroblastoma. Chicken farming was associated with some common cancers of adolescence, and was strongest for osteosarcoma and mixed cellular type of Hodgkin's disease. The main problem in this large cohort study is the crude exposure indicators available; the resulting misclassification is likely to bias any true association towards unity. © 1996 Wiley-Liss, Inc.     

One-stage repair of cardiac and arch anomalies without circumlatory arrest

Indian Journal of Thoracic and Cardiovascular Surgery -     

Evaluation of endothelial cell culture as a model system of vascular ageing

The purpose of this study was to evaluate the relevance of long-term endothelial cell culture as a model system of vascular ageing. Micro- and macrovascular endothelial cells were serially passaged until replicative senescence and their ability to form tube-like structures when cultured on Matrigel was assessed throughout their lifespan. For both cell types low passage cultures adopted a homogeneous cobblestone morphology, while senescent cultures were extremely heterogeneous. Furthermore, both cell types showed a reduction in tube formation ability with in vitro ageing, which is in accordance with the reduction in angiogenic potential observed with ageing in vivo. Examination of senescence associated β-galactosidase activity revealed an increased activity in cells forming tubes as compared to cells cultured on plastic, which could be attributed to an increased lysosomal content of cells undergoing tube formation. As this increased senescence associated β-galactosidase activity was unrelated to the replicative age of the cells, senescence associated β-galactosidase activity may not be a relevant senescence marker for differentiating endothelial cells. The age-related reduction in tube formation ability suggested that long-term culture of endothelial cells may be a valid model system of vascular ageing, which makes it an ideal platform for high throughput screening of compounds influencing angiogenesis.     

Use of the flexible bronchoscope and Infrared Red Intubation System in a known difficult airway in the intensive care unit

This case report describes a patient in the ICU in need of urgent intubation, for whom video laryngoscope‐guided intubation had previously failed. The Infrared Red Intubation System (IRRIS) may enhance the chance of successful flexible bronchoscope intubation, especially when performed by non‐expert anesthesiologists.     

Heterogeneity of neocortical cerebral blood flow deficits in dementia of the Alzheimer type: a [99mTc]-d,l-HMPAO SPECT study.

Regional cerebral blood flow (rCBF) was measured with high resolution brain dedicated single photon emission computer tomography (SPECT) and [99mTc]-d,l-hexamethyl-propylene-amine-oxime (HMPAO) in 25 patients with probable Alzheimer's disease and in 25 control subjects, selected according to rigorous inclusion and exclusion criteria. The aim was to analyse the topography of rCBF deficits in individual patients. In the group of patients with Alzheimer's disease as a whole, global CBF was reduced, but a factorial analysis of variance did not show disproportionate reduction of rCBF in any brain region. A parametric analysis of the rCBF data in individual patients was carried out with reference to normal values for internal rCBF ratios and to 13 different abnormal rCBF patterns. These theoretical patterns were predefined by showing significant hypoperfusion in at least one, or in any relevant combination of two, three, or four, of four major brain regions (a left and right frontal and a left and right posterior region). All patients with Alzheimer's disease and none of the control subjects had an abnormal rCBF pattern. Eleven of the 13 different patterns were seen in the patients. Frontal changes were seen in 19 (76%) of the patients, more often than previously reported. No single Alzheimer's disease pattern could be derived from our data. The number of regions with hypoperfusion, but not the presence of frontal changes, correlated significantly with the duration of disease. It is concluded that a clinical diagnosis of probable Alzheimer's disease is associated with heterogeneous patterns of rCBF deficits as measured with SPECT and [99mTc]-d,l-HMPAO. This heterogeneity may reflect different stages of the disease or cognitive subtypes and help explain published discrepancies concerning the topography of hypoperfusion in Alzheimer's disease. An analysis of individual rCBF data may add important information in the investigation of diseases with heterogeneous effects on the brain.     

Interobserver variation in the evaluation of neurological signs: observer dependent factors.

Introduction - Interobserver variation among four observers in evaluation of eight selected neurological signs was investigated. Material & methods - Two hundred and two consecutive unselected inpatients were examined by two senior neurologists and two trainees, all without knowledge of the neurological case history. The signs examined were: anisocoria, jerky eye movements, facial palsy, elbow extension force, finger-nose test, Barré sign, knee jerk, and extensor plantar reflex. Observed agreement rates and kappa coefficients were calculated in order to compare the interobserver variability among neurologists and trainees, and to evaluate differences in the interobserver variability between signs. Results - Observed agreement rates varied from 0.80 to 0.95 for neurologists and from 0.65 to 0.98 for trainees. For neurologists kappa coefficients ranged from 0.40 to 0.67 and for trainees from 0.22 to 0.81. The neurologists had higher kappa values than the trainees in 5 signs, but this difference was only statistically significant for jerky eye movements. For the individual signs the observed agreement rates were between 0.50 and 0.93 for all four examiners combined, and overall kappa values varied from 0.32 to 0.71 with highest agreement for facial palsy and lowest for knee jerk. Conclusion - The magnitude of the interobserver and intersign variation indicates that the interpretation of the neurological signs tested, without knowledge of the case history, should be done with some caution.     

INTERACTION BETWEEN CARBAMAZEPINE AND PROPOXYPHENE IN MAN

This investigation was carried out because of a clinical suspicion of drug interaction between Propoxyphene (PRX) hydrochloride and Carbamazepine (CBZ). Seven out-patients, six suffering from epilepsy and one from trigeminal neuralgia, treated with CBZ alone or in combination with phenobarbitone, received PRX hydrochloride capsules, 65 mg three times a day. Two patients stopped the PRX intake after 2 days due to severe side effects. Three of the remaining patients had symptoms and signs of drug intoxication. Blood samples were examined by thin-layer chromatography. A marked increase (45-77 per cent) in CBZ plasma level was found in all patients on combined treatment of CBZ and PRX. There were no significant changes in CBZ-10,11-epoxide level. The results suggest an inhibition of CBZ metabolism when CBZ and PRX are administered simultaneously.