The Finnish Interprofessional Medication Assessment (FIMA): baseline findings from home care setting.

PURPOSE: Medication-related problems and declined functional capacity are closely associated factors among older people. The purpose of this study is to describe the procedure of interprofessional medication assessment in home care context and the baseline characteristics of the study population. METHODS: The FIMA study was a randomized, controlled intervention study comparing general practitioner-led interprofessional medication assessment and usual care. Patients' chronic diagnoses and medication use as well as physical and cognitive functions were investigated. Performance in daily activities, use of care services and help from family and relatives, self-rated health and health-related quality of life, and adverse effects commonly related to medication were assessed. RESULTS: The home care patients (n = 512) had significant disease burden and functional limitations. The mean number of all medicines was 15 and that of regularly taken medicines 10. The majority of patients (87%) had excessive polypharmacy. The most commonly used (97%) ATC medicine class was nervous system medicines. Clinically relevant (class C or D SFINX record) drug-drug interactions were seen in 74% of the patients. The most frequent risks of adverse effects were risk of bleeding (66%), constipation (58%) and orthostatism (54%) occurring in over half of the patients. Medicines affecting renal function were used by 85% of the patients. CONCLUSIONS: There is an evident need and justification for medication assessments in home care. In most cases, home care patients fulfill the criteria for regular medication assessments.

An EGFR wild type-EGFRvIII-HB-EGF feed-forward loop regulates the activation of EGFRvIII.

EGFRvIII is a key oncogene in glioblastoma (GBM). EGFRvIII results from an in-frame deletion in the extracellular domain of EGFR, does not bind ligand and is thought to be constitutively active. Although EGFRvIII dimerization is known to activate EGFRvIII, the factors that drive EGFRvIII dimerization and activation are not well understood. Here we present a new model of EGFRvIII activation and propose that oncogenic activation of EGFRvIII in glioma cells is driven by co-expressed activated EGFR wild type (EGFRwt). Increasing EGFRwt leads to a striking increase in EGFRvIII tyrosine phosphorylation and activation while silencing EGFRwt inhibits EGFRvIII activation. Both the dimerization arm and the kinase activity of EGFRwt are required for EGFRvIII activation. EGFRwt activates EGFRvIII by facilitating EGFRvIII dimerization. We have previously identified HB-EGF, a ligand for EGFRwt, as a gene induced specifically by EGFRvIII. In this study, we show that HB-EGF is induced by EGFRvIII only when EGFRwt is present. Remarkably, altering HB-EGF recapitulates the effect of EGFRwt on EGFRvIII activation. Thus, increasing HB-EGF leads to a striking increase in EGFRvIII tyrosine phosphorylation while silencing HB-EGF attenuates EGFRvIII phosphorylation, suggesting that an EGFRvIII-HB-EGF-EGFRwt feed-forward loop regulates EGFRvIII activation. Silencing EGFRwt or HB-EGF leads to a striking inhibition of EGFRvIII-induced tumorigenicity, while increasing EGFRwt or HB-EGF levels resulted in accelerated EGFRvIII-mediated oncogenicity in an orthotopic mouse model. Furthermore, we demonstrate the existence of this loop in human GBM. Thus, our data demonstrate that oncogenic activation of EGFRvIII in GBM is likely maintained by a continuous EGFRwt-EGFRvIII-HB-EGF loop, potentially an attractive target for therapeutic intervention.

Non-pituitary origin sellar tumours mimicking pituitary macroadenomas.

Although the large majority of sellar tumours are pituitary adenomas, several other pituitary and non-pituitary origin tumours arise in the sellar and parasellar regions. Given their location, non-adenomatous lesions frequently mimic pituitary macroadenomas and can pose a diagnostic challenge for the radiologist. Distinguishing rare sellar lesions from the common macroadenoma helps to direct the correct surgical approach and reduce the risk of incomplete resection and/or complications such as cerebrospinal fluid leak with the potential for meningitis. The purpose of this article is to review the imaging features of non-pituitary-origin sellar tumours, focusing on characteristics that may distinguish them from pituitary macroadenomas. Lesions include meningioma, metastatic disease, epidermoid cyst, germinoma, chondrosarcoma, giant cell tumour, and giant aneurysm.

Instrumentation for the in situ control of carrier recombination characteristics during irradiation by protons.

Instrument and methods for the remote and in situ control of carrier recombination parameters during irradiation by protons of energy in the range of 3-8 MeV are presented. Direct techniques for measurements and separation of carrier recombination and trapping/generation characteristics based on the analysis of microwave probed photoconductivity transients during exposure on protons of different energies and irradiations at different temperatures are described. Simultaneously, a spectroscopy of activation energy of dominant traps has been performed before and just after irradiation by temperature scans of variation in the recombination parameters.

Ion beam processing of Au nanowires.

In nanoelectronics a nanowire forms an elemental building block enabling a charge transfer in complex nanostructures. Ion beam etching has been applied for downsizing of prefabricated Au nanowires in the sub-50 nm linewidth regime, aiming at achieving effective cross sections of less than 10 nm. Low energy Ar+ and Ga+ ions were employed for dry ion beam etching of Au nanowires. Nanometer-precise gradual downsizing to an effective diameter as small as 9 nm has been achieved when using Ar+ ions. In contrast, the chemical nature of Ga and its surface condensation into a nanosized phase turned out to act destructively on the nanowires' morphology, hampering the process of downsizing. In the surface nanocondensate Ga was found to coexist in both solid and liquid states, exhibiting polymorphism and peculiar dynamics under ion irradiation.

Self-diffusion of (31)Si and (71)Ge in relaxed Si(0.20)Ge(0.80) layers.

Self-diffusion of implanted (31)Si and (71)Ge in relaxed Si(0.20)Ge(0.80) layers has been studied in the temperature range 730-950 degrees C by means of a modified radiotracer technique. The temperature dependences of the diffusion coefficients were found to be Arrhenius-type with activation enthalpies of 3.6 eV and 3.5 eV and preexponential factors of 7.5 x 10(-3) m(2) s(-1) and 8.1 x 10(-3) m(2) s(-1) for (31)Si and (71)Ge , respectively. These results suggest that, as in Ge, in Si(0.20)Ge(0.80) both (31)Si and (71)Ge diffuse via a vacancy mechanism. Since in Si(0.20)Ge(0.80) (71)Ge diffuses only slightly faster than (31)Si , in self-diffusion studies on Si-Ge (71)Ge radioisotopes may be used as substitutes for the "uncomfortably" short-lived (31)Si radiotracer atoms.

Quantifying the risk of extreme seasonal precipitation events in a changing climate.

Increasing concentrations of atmospheric carbon dioxide will almost certainly lead to changes in global mean climate. But because--by definition--extreme events are rare, it is significantly more difficult to quantify the risk of extremes. Ensemble-based probabilistic predictions, as used in short- and medium-term forecasts of weather and climate, are more useful than deterministic forecasts using a 'best guess' scenario to address this sort of problem. Here we present a probabilistic analysis of 19 global climate model simulations with a generic binary decision model. We estimate that the probability of total boreal winter precipitation exceeding two standard deviations above normal will increase by a factor of five over parts of the UK over the next 100 years. We find similar increases in probability for the Asian monsoon region in boreal summer, with implications for flooding in Bangladesh. Further practical applications of our techniques would be helped by the use of larger ensembles (for a more complete sampling of model uncertainty) and a wider range of scenarios at a resolution adequate to analyse average-size river basins.

Characterization and control of terpene emissions in Finnish sawmills.

This article describes an experimental study of terpene emission rates during fresh pine and spruce sawing and processing. Total terpene emission was determined by summing the product of the exhaust airflow rate and the mean concentration in the exhaust. Terpene concentrations were measured at fixed sampling points between the sawing lines. Terpene emission during pine sawing was found to be around 10 times greater than that during spruce sawing. The emission rates given here can be used to predict emission rates for various production rates. The predicted emission rates can be used in mass balance models to predict concentrations or required airflow rates to achieve the target concentration level.

Tetrachloroethylene emissions and exposure in dry cleaning.

Tetrachloroethylene (PCE) emissions and the exposure of workers in six commercial and three industrial dry-cleaning establishments that use dry-to-dry machines were determined. The personal samples and area samples [8-hr time-weighted average (TWA) and short-term exposure] were collected with charcoal tubes and passive monitors. The temporal variation of PCE concentration in the workplace air was monitored using a Fourier transform infrared analyzer (FTIR). The PCE emission rates were determined by multiplying the average PCE concentration in the room and the total airflow rate in the room. The PCE emissions were related to the cleaning rate in units of kg/hr. The operators' mean TWA exposure in commercial shops and industrial establishments was 28 (4.1 ppm) and 32 mg/m3 (4.6 ppm), and the pressers' exposure was 3.4 (0.5 ppm) and 7.7 mg/m3 (1.1 ppm), respectively. The customer service personnel had the lowest TWA exposure with a mean value of 0.8 mg/m3 (0.1 ppm). The highest peak concentration (2300 mg/m3; 334 ppm) was observed during cleaning of the lint and button trap, during which operation respirators were used. The PCE emission rates ranged from 4 to 118 g/hr corresponding to emission factors (mass of solvent evaporated per mass of cleaned cloths) of 0.3-3.6 g/kg. The workers' exposure to PCE was below the occupational limit values in the United States [according to the American Conference of Governmental Industrial Hygienists (ACGIH)] and in Finland. The outdoor PCE emissions were clearly below the limit values given in the European Union volatile organic compound (VOC) directive requirements.

Contaminant dispersion in the vicinity of a worker in a uniform velocity field.

The transportation of gaseous contaminant from a low and moderate low impulse (momentum<1 m s(-1)) source to the breathing zone was studied in a uniform air stream flow. Results of the effects of the direction and the velocity of principal air flow, convection due to a human body, arm movement of a human being and the type of source on the concentration profiles are presented. Three important results were obtained. Firstly, for a given low and moderate impulse low impulse contaminant source in the near field of a worker, his/her orientation relative to the principal air flow direction is the most important factor in reducing occupational exposure, with an air velocity of about 0.3 m s(-1). Secondly, the effect of convection resulting from body heat on air flow was lower than expected. Thirdly, arm movements influence contaminant dispersion, and should be included when models assessing exposure are developed. The present data can also be used to validate existing computational fluid dynamic (CFD) models.

Diffuse axonal injury in a rugby player.

Sections of the cerebrum, cerebellum, and brain stem of a rugby player who died 15 hours after being tackled were stained using an immunoperoxidase technique to detect beta-amyloid protein. The sections of the pons showed axonal spheroids in the base, and those of the cerebellum showed axonal spheroids in deep white matter. The findings demonstrated axonal injury following a fall from the victim's height in a team sporting event.

Vertebral artery compression resulting from head movement: a possible cause of the sudden infant death syndrome.

OBJECTIVE: Vertebral artery compression causing brainstem ischemia has been suggested to underlie the sudden infant death syndrome. Vertebral artery distortion from neck movements has been demonstrated by angiography in infants, but direct evidence for arterial compression is lacking. In an attempt to demonstrate vertebral artery compression from head movement, we examined at postmortem the vertebral arteries of infants after neck extension or rotation. METHODS: The C1-C7 spinal column, together with a 2-cm rim of skull base, was removed from 20 infants dying from sudden infant death syndrome or other causes. In 5 cases the neck was extended, in 9 cases it was rotated 90 degrees to the right, and in 6 cases the neck was held in the neutral position. The neck was maintained in these positions during formalin fixation, and serial sections of selected blocks were examined microscopically. RESULTS: In 3 of 5 extended cases, bilateral vertebral artery compression was seen between the occipital bone and C1. In 3 of 9 rotated cases, the left vertebral artery was compressed adjacent to C1 before the artery entered the transverse foramen. No vertebral artery compression was seen in the necks held in the neutral position. CONCLUSIONS: The vertebral arteries of some infants can be compressed by neck movement. This could induce lethal brainstem ischemia in infants with inadequate collateral blood flow or with poor compensatory arterial dilatation, and may underlie some cases of sudden infant death syndrome.

The evaluation of a low resolution fourier transform infrared (FTIR) gas analyser for monitoring of solvent emission rates under field conditions.

The applicability of a low resolution (8 cm-1) Fourier transform infrared (FTIR) gas analyser with an absorption path length of 3 m was evaluated for the on-line monitoring of organic solvent mixture emissions in a flexographic ink manufacturing plant. The on-line monitoring revealed that the highest variations of solvent concentrations, up to three decades, occurred in the exhaust air. The FTIR analyser with a dynamic range of four decades covers well the concentration ranges typically found in the exhaust air and in the workroom air of ink manufacturing plants. The average emission rate of solvent mixture based on a sampling period of two days was 1.8 kg h-1 consisting of mainly ethanol (70%), ethyl acetate (15%) and propan-2-ol (11%). The detection limits of the analyser for the solvent compounds ranged from 0.3 to 4.3 mg m-3 and the measurement uncertainty was less than 10% in the concentration range of 8-15,000 mg m-3. These characteristics make the apparatus appropriate for most industrial hygiene applications. An FTIR spectrophotometer, equipped with an multipoint sampling unit, facilitates rapid identification of solvent components, real-time display of concentration data relevant to workroom air and environment monitoring as well as process control. Furthermore, the on-line concentration information enabled a rapid selection of representative sampling locations. The spectrophotometer is transportable, rugged and relatively simple to calibrate even in a hostile industrial environment.

Role of cytology in the intraoperative diagnosis of central demyelinating disease.

OBJECTIVE: To determine the usefulness of cytology in the intraoperative diagnosis of central demyelinating disorders. STUDY DESIGN: Smears of three multiple sclerosis (MS) plaques and two progressive multifocal leukoencephalopathy (PML) lesions prepared intraoperatively were examined and compared. The cytologic features were contrasted with those of infiltrating astrocytomas. RESULTS: The preparations of demyelinating lesions revealed normal or reactive astrocytes and large numbers of foamy macrophages, the key diagnostic finding. The preparations of the lesions of PML contained virally infected oligodendrocytes. The specific cell types were identified easily because cytoplasmic margins could be distinguished. CONCLUSION: Cytologic preparations of lesions of PML and MS permitted rapid identification of the diagnostic features and distinguished them from infiltrating astrocytomas, the most important lesion in the differential diagnosis. The findings demonstrated the utility of cytology in the diagnosis of central demyelinating diseases.

Prevalence of Wernicke-Korsakoff syndrome in Australia: has thiamine fortification made a difference?

OBJECTIVE: To determine the prevalence of the Wernicke-Korsakoff syndrome (WKS) in Australia and compare this with previous studies. DESIGN AND SETTING: Prospective autopsy study at the New South Wales Institute of Forensic Medicine, 1996-1997. METHODS: Brains of deceased people (aged over 15 years) derived from 2212 sequential autopsies performed between 1 January 1996 and 31 December 1997 were studied macroscopically and microscopically to identify cases of WKS. MAIN OUTCOME MEASURES: Standard histological criteria for WKS and any available clinical data. RESULTS: Twenty-five cases of WKS were identified (prevalence, 1.1%), mostly among the 5.9% of the 2212 people who had a history suggestive of alcohol abuse. Only four cases (16%) had been diagnosed during life. CONCLUSIONS: There has been a significant reduction in the prevalence of WKS in Australia since the introduction of thiamine enrichment of bread flour. While the prevalence is still higher than in most other Western countries, further research is needed before adding thiamine to alcoholic beverages can be recommended.

Cytomegalovirus retinitis and optic neuritis in a child with severe combined immunodeficiency syndrome.

BACKGROUND: Although cytomegalovirus (CMV) infection of the retina and brain is common in patients with acquired immunodeficiency syndrome (AIDS), it is exceedingly rare in patients with immunodeficiencies due to other causes. This is the first report on ocular and cerebral histopathology of disseminated CMV in a child with severe combined immunodeficiency syndrome (SCID). METHODS: The authors examined by routine histopathologic methods the eyes of a 2-year-old white boy with SCID and bilateral CMV retinitis who died after failure of a third attempt at allogeneic bone marrow transplantation (BMT). RESULTS: Cytomegalovirus inclusions were found in the necrotic retinal remnants, in the hyperplastic and scarred retinal pigment epithelium, and bilaterally in the optic nerves. There were infiltrates of macrophages in response to the infection or the infused silicon, but no lymphoid infiltrates. Cytomegalovirus inclusions also were found in brain tissue. CONCLUSION: The histologic features resembled those of CMV retinitis and optic neuritis in AIDS.

Analysis of 10B by PIGE with factor analytical gamma-ray peak identification.

Studying the biodistribution of boronated compounds for B neutron capture therapy (BNCT) requires the accurate detection of low levels of boron (10B) in biological samples. Proton induced gamma-ray emission analysis (PIGE) of 10B was found to be viable in a study of low density lipoprotein (LDL), in tissue and blood samples. However, the method is sensitive to Na present in the samples and can therefore not be used for accurate measurements of 10B concentrations below 5 ppm in samples containing Na. PIGE can be considered to be an appropriate reference method for chemical B analysis. The factor analytical method presented here is the most objective way to separate Na and B peaks from each other, and the factorizing method can be applied in different forms of spectral analysis.

The incidence and spectrum of neurological injury after open fetal surgery.

A preterm infant's immature brain is susceptible to both anoxic and hemorrhagic injury during periods of physiological stress. The advent of in utero surgery has created a new population of premature patients at risk for central nervous system (CNS) injury. The aim of this study was to evaluate the frequency and nature of CNS injuries in fetal surgical patients. Of 33 fetuses with known neurological outcome after fetal surgery, CNS injuries were identified in seven (21%). Of the seven, four had significant episodes of fetal bradycardia (3) or neonatal hypotension (1), which suggests that asphyxia contributed to the neurological injury. The CNS injuries in the other three patients occurred unexpectedly and without associated signs of fetal distress. The authors speculate that these injuries may have been caused by sudden fluxes in cerebral blood flow, induced by maternal hypoxia (1) or by maternally administered tocolytic drugs (2) used to treat postoperative preterm labor.

Pituitary adenoma as an unsuspected clival tumor.

Pituitary adenomas are common tumors that account for about 10% of intracranial neoplasms. Most arise from the adenohypophysis and are confined to the region of the sella turcica. Other sites may be involved as a result of extension, infiltration, or ectopic location. However, posterior extension or ectopic involvement of the clivus of the sphenoid and occipital bones is rare. Seven patients with destructive clival masses were referred to our institution with presumptive diagnoses of chordomas. In all cases, histologic workup revealed pituitary adenomas. Because they represent a subset of adenomas, the histologic features of the tumors were studied, and the clinical histories of the patients were reviewed. Five of the patients were men, aged 31 to 67 years, and two were women, aged 55 and 67 years. Four patients had extremely high plasma concentrations of prolactin (8,132-22,424 ng/ml, nl < 15). Four tumors resembled usual sellar adenomas; however, three exhibited nuclear pleomorphism, mitotic figures, and other morphologic features, suggesting alternate diagnoses. Three required immunoperoxidase stains in addition to those for pituitary hormones, and three required electron microscopy for diagnosis. Destructive invasion of the clivus by pituitary adenomas is rare, and anaplastic features of some of the tumors may lead to difficult diagnoses.