An evaluation of the mini-Wright peak flow meter.

The mini-Wright peak flow meter (MPFM) has been evaluated, and the results obtained from it show a strong positive correlation (r=0.970) with the Wright's peak flow meter (PFM). MPFM measurements, however, were biased to be about 38 1/min higher than PFM measurements (95% confidence limits 31.01/min to 45.01/min). Between instrument variation was found (F--ratio 3.67 with 9 and 81 degrees of freedom: P less than 0.001). In practice this did not appreciably affect individual measurements greatly as 95% confidence limits on any individual measurements were increased from +/-24 1/min to +/-27 1/min. There was no significant day-to-day variability in measurements obtained with individual instruments. The MPFM is a pocket-sized, simple, cheap, and robust instrument for following changes in ventilatory function. In clinical trails and surveys, however, both the bias in favour of the MPFM compared to the PFM and inter-machine variation must be taken into account. As the manufacturers have altered the scale to remove the bias since this study was performed, it will be important to know whether the original or the modified meter is being used in future studies.     

A review of boron neutron capture therapy (BNCT) and the design and dosimetry of a high-intensity, 24 keV, neutron beam for BNCT research

This paper reviews the development of boron neutron capture therapy (BNCT) and describes the design and dosimetry of an intermediate energy neutron beam, developed at the Harwell Laboratory, principally for BNCT research. Boron neutron capture therapy is a technique for the treatment of gliomas (a fatal form of brain tumour). The technique involves preferentially attaching 10B atoms to tumour cells and irradiating them with thermal neutrons. The thermal neutron capture products of 10B are short range and highly damaging, so they kill the tumour cells, but healthy tissue is relatively undamaged. Early trials required extensive neurosurgery to exposure the tumour to the thermal neutrons used and were unsuccessful. It is thought that intermediate-energy neutrons will overcome many of the problems encountered in the early trials, because they have greater penetration prior to thermalization, so that surgery will not be required. An intermediate-energy neutron beam has been developed at the Harwell Laboratory for research into BNCT. Neutrons from the core of a high-flux nuclear reactor are filtered with a combination of iron, aluminium and sulphur. Dosimetry measurements have been made to determine the neutron and gamma-ray characteristics of this beam, and to monitor them throughout the four cycles used for BNCT research. The beam is of high intensity (approximately 2 x 10(7) neutrons cm-2 s-1, equivalent to a neutron kerma rate in water of 205 mGy h-1) and nearly monoenergetic (93% of the neutrons have energies approximately 24 keV, corresponding to 79% of the neutron kerma rate).     

Sleep apnoea in Scheie''s syndrome

An 18-year-old student presented with a two-year history of daytime sleepiness and noisy breathing during sleep. Both he and his brother, aged 25 years, had Scheie's syndrome, a mucopolysaccharidosis characterised by small stature, micrognathia, corneal clouding, hepatosplenomegaly, raised urinary mucopolysaccharides, and undetectable levels of alpha-L-iduronidase assayed in cultured fibroblasts. Both brothers had sleep apnoea (apnoea index, 59 and 35 respectively) during which there was a significant fall in heart rate and arterial oxygen saturation. One brother had EEG changes suggestive of cerebral hypoxia and the other had ventricular extrasystoles at the end of several episodes. Tracheostomy in the younger brother produced a dramatic symptomatic improvement and reduced the number and severity of apnoeic episodes (post-tracheostomy apnoea index 2.4).     

Activated Akt expression in breast cancer: correlation with p53, Hdm2 and patient outcome

Activation of protein kinase-B/Akt (pAkt) is mediated by oestrogen and involves HER-2 in vitro, to phosphorylate Hdm2 and influence p53 cytoplasmic localisation and degradation. Expression of all active Akt isoforms (pAkt) were examined, together with p53/Hdm2 subcellular expression in invasive ductal breast cancers (IDCs), to evaluate whether in vitro findings were related to clinical data and determine the effect on outcome. Immunohistochemical expression of serine 473 specific phosphorylated Akt (pAkt) isoforms (Akt-1,2,3) was evaluated in 97 patients, together with subcellular expression of p53/Hdm2. The results show that pAkt was evaluable in 95 patients with cytoplasmic expression in 81% and more likely to be associated with larger tumours (P=0.007), with no correlation with HER-2 expression. pAkt correlated with increasing levels of cytoplasmic p53 (P=0.025) and was associated with a reduced disease-free survival (P=0.04; univariate). In conclusion, pAkt has implications in breast cancer growth through mechanisms inactivating p53 with an association with immunohistochemical p53 expression, which is preferentially cytoplasmic. Despite in vitro associations, pAkt appears to be a variable marker of HER-2 expression.     

Restraint stress is associated with changes in glucocorticoid immunoregulation

Psychological stress has been associated with activation of the hypothalamic-pituitary-adrenal (HPA) axis and impaired cell-mediated immune (CMI) responses. There is also evidence suggesting that intermittent chronic stress differentially alters CMI across different immune compartments, but the mechanisms underlying this phenomenon have not been explored in detail. In the present study, we investigated (i) acute and chronic restraint stress effects in Sprague-Dawley rats on both peripheral blood lymphocyte (PBL) and splenocyte mitogen-induced proliferation and (ii) also determined whether differential stress effects within these immune compartments might reflect alterations in lymphocyte sensitivity to glucocorticoids. It was found that while acute stress exposure significantly raised plasma corticosterone levels (1048% vs. controls, P<.001), this response was attenuated in the animals previously exposed to chronic intermittent stress (-79.66% vs. acute; P<.001). Acute stress increased phytohemagglutinin (PHA)-induced lymphocyte proliferation in the spleen (69.04%, P=.01) and suppressed PBL proliferation (-45.52%, P<.001). Neither of these changes were observed following chronic stress. We also demonstrated that reexposure to the stressor rapidly increased splenocyte sensitivity to in vitro dexamethasone (P<.05) and corticosterone (P<.05) in chronically stressed rats. Our data (1) confirm that acute stress is associated with compartment-specific changes in CMI function, (2) indicate that chronic stress is associated with habituated endocrine and immune responses and (3) that stressor exposure rapidly alters splenocyte sensitivity to glucocorticoids and we suggest that the latter may contribute to differential stress effects across immune compartments.     

Glass rod detectors for small field, stereotactic radiosurgery dosimetric audit

This paper demonstrates the feasibility of using glass rod detectors for quality assurance audit of radiosurgery units. Five radiosurgery units (3 Gamma Knife model C, 1 Gamma Knife model U and 1 Cyberknife) located in California participated in the study. At each center glass rod detectors were used to measure a number of dosimetric parameters including relative collimator output factor and absolute dose rate. The Gamma Knife data obtained is in excellent agreement with the commissioning data generated by the manufacturer for each unit and the Cyberknife data is in general agreement with the data published by other centers. In particular the output factor of the 4 mm Gamma Knife helmet factor, a subject of abundant debate, was measured in the range 0.863-0.872 with an accuracy of better than 1% across the four participating centers. It is hoped that this pilot study will facilitate a nationwide postal audit of stereotactic radiosurgery units.     

The effects of witnessing domestic violence on behavioural problems and depressive symptomatology. A community sample of pupils from St Lucia

Behavioural problems and depressive symptomatology were evaluated in a sample of 60 St Lucian pupils who came from homes where parents were either in violent or non-violent marital relationships. Teachers rated pupils using the Revised Behaviour Problem Checklist (RBPC) while self rating scores were obtained from pupils using either the Reynolds Child Depression Scale (RCDS) or the Reynolds Adolescent Depression Scale (RADS), depending on the age of the pupil. The results indicated that those pupils whose parents were experiencing violent marital discord showed significantly higher levels of both depression and behavioural problems than those pupils not exposed to domestic violence. In addition, exposed children exhibited more behavioural problems but less depressive symptomatology than adolescents. The results from this study are consistent with those of more developed countries. The theoretical implications of these findings are discussed and methodological refinements are suggested for further research.     

Insulin‐like growth factor‐II is produced by,signals to and is an important survival factor for the mature podocyte in man and mouse

Podocytes are crucial for preventing the passage of albumin into the urine and, when lost, are associated with the development of albuminuria, renal failure and cardiovascular disease. Podocytes have limited capacity to regenerate, therefore pro‐survival mechanisms are critically important. Insulin‐like growth factor‐II (IGF‐II) is a potent survival and growth factor; however, its major function is thought to be in prenatal development, when circulating levels are high. IGF‐II has only previously been reported to continue to be expressed in discrete regions of the brain into adulthood in rodents, with systemic levels being undetectable. Using conditionally immortalized human and ex vivo adult mouse cells of the glomerulus, we demonstrated the podocyte to be the major glomerular source and target of IGF‐II; it signals to this cell via the IGF‐I receptor via the PI3 kinase and MAPK pathways. Functionally, a reduction in IGF signalling causes podocyte cell death in vitro and glomerular disease in vivo in an aged IGF‐II transgenic mouse that produces approximately 60% of IGF‐II due to a lack of the P2 promoter of this gene. Collectively, this work reveals the fundamental importance of IGF‐II in the mature podocyte for glomerular health across mammalian species. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.