Concurrent LOH at multiple loci in human malignant mesothelioma with preferential loss of NF2 gene region

Human malignant mesothelioma (MM) is a highly aggressive neoplasm related to occupational asbestos exposure and characterised by a long latency period between the exposure and onset of disease. Previous studies indicate that losses at different genomic regions are present in MM. We examined allele loss at three known tumour suppressor gene regions (22q/NF2 gene, 9p/p16 gene, and 3p/FHIT gene) and at two other frequently deleted areas (14q and 6q) in MM. Loss of heterozygosity (LOH) was investigated in cell cultures and primary tumours with several highly polymorphic markers for each site. To study if LOH of the NF2 gene is a consistent feature in MM, we performed a more detailed analysis of chromosome 22q that included a NF2 marker (NF2CA3). We observed a high frequency of LOH occurring simultaneously at multiple loci. In particular, 100% of the cultured MM cells exhibited LOH at the NF2 gene region. From the other chromosomal sites analysed, recurrent allele loss was detected at 9p (5/7; 71%), 3p (4/7; 57%), 14q (3/7; 43%), and 6q (3/7; 43%). Of the 32 tumours, even those trimmed to exclude normal tissue, few showed LOH, suggesting consielment by normal cells within MM tumours, whereas tumour cells in primary cultures showed LOH already in passages 1-2. In conclusion, our present LOH data indicate that MM cells exhibit allele losses at multiple tumour suppressor gene sites concurrently, involving NF2 gene preferentially. This supports the view that the accumulation of multiple genetic hits is characteristic to malignant transformation of MM cells.     

Critical role for GALR1 galanin receptor in galanin regulation of neuroendocrine function and seizure activity

The GALR1 galanin receptor is expressed at high levels within the central nervous system. To determine which specific actions of galanin are mediated by GALR1, we have developed mice with an insertional inactivating mutation within the gene encoding GALR1 (Galr1). Homozygous Galr1-/- mice are viable and capable of breeding. They exhibit no significant difference in growth rate relative to Galr1+/+ controls but have reduced circulating levels of insulin-like growth factor-I (IGF-I) and exhibit spontaneous tonic-clonic seizures. The phenotype of these mice identifies a critical role for GALR1 in neuroendocrine regulation and in mediating the anti-seizure activity of galanin.     

Conducting case study research in occupational therapy

Background:  Case study research has been used increasingly in psychology and sociology in recent years. It provides researchers with an opportunity to explore a situation involving one individual or several individuals over time from multiple points of view.
Methods:  This literature review explains case study research as a method and summerises its scientific merit, also providing an example of its use.
Results:  Case study research offers occupational therapists a scientific methodology that can be used to understand and develop occupational therapy practice.
Conclusion:  This paper argues that case study research should be used more extensively by occupational therapists as the method respects the basic principles of occupational therapy.     

Perinatal indomethacin treatment and neonatal complications in preterm infants

To evaluate the incidence of neonatal complications among infants exposed to indomethacin antenatally, postnatally or both ante-and postnatally (combined), the records of 240 infants of gestational ages between 23 to 32 weeks were analysed retrospectively. Antenatal indomethacin treatment for longer than 2 days with a daily or cumulative dosage ≥150 mg correlated with a significantly higher incidence of grade I-II intraventricular haemorrhage. Combined exposure, cumulative antenatal exposure ≥150 mg and duration of antenatal exposure of more than 2 days was associated with necrotising enterocolitis and a cumulative exposure with sepsis. There was no independent association between indomethacin exposure and pneumothorax, bronchopulmonary dysplasia or respiratory distress syndrome. Conclusion Preterm infants with exposure to antenatal indomethacin might be at increased risk of grade I and II intraventricular haemorrhage and those with both ante- and postnatal exposure at an increased risk of necrotising enterocolitis and sepsis. Received: 18 January 1999 / Accepted: 8 July 1999     

Wheezing due to rhinovirus infection in infancy: Bronchial hyperresponsiveness at school age

Background: Characteristics related to decreased lung function and increased bronchial responsiveness after early childhood wheezing requiring hospitalization are not fully established.
Methods: Seventy-nine children with wheezing requiring hospitalization at age <2 years were prospectively followed up and re-investigated at age 5.6–8.8 years when the measurements of baseline lung function and bronchial responsiveness to exercise were performed.
Results: At early school age, 23% of children had decreased lung function, and 13% had increased bronchial responsiveness to exercise. Predictors of decreased lung function were maternal history of smoking during pregnancy (odds ratio [OR], 12.8; 95% confidence interval [CI]: 1.2–139.6), parental history of asthma (OR, 4.3; 95%CI: 1.1–17.1), and female gender (OR, 4.0; 95%CI: 1.2–13.7). Increased bronchial responsiveness was associated with rhinovirus infection-induced wheezing in infancy (OR, 6.5; 95%CI: 1.2–36.3), and early cat or dog exposure leading to sensitization (OR, 26.6; 95%CI: 1.3–525.2). Inhaled anti-inflammatory therapy was common in children with rhinovirus infection-induced wheezing in infancy ( n  = 13/19; P  = 0.001 vs children with other/no confirmed virus infection etiology for wheezing in infancy, n  = 16/60), which may have improved lung function and attenuated bronchial responsiveness in them.
Conclusions: After early childhood wheezing requiring hospitalization, one-fourth of children will have decreased lung function and one-eighth of children will show increased bronchial responsiveness at school age. Gender, heredity of asthma, and antenatal exposure to tobacco smoke are predictors of decreased lung function, whereas rhinovirus infection etiology of wheeze and early animal exposure leading to sensitization are associated with increased bronchial responsiveness later in childhood.     

Laboratory and field evaluation of a new personal sampling system for assessing the protection provided by the N95 filtering facepiece respirators against particles

OBJECTIVES: We have recently developed a new personal sampling system for the real-time measurement of the protection provided by respirators against airborne dust and micro-organisms. The objective of this study was to evaluate the performance characteristics of the new sampling system in both laboratory and field conditions. METHODS: The measurements were conducted using the N95 filtering facepiece respirators and the newly developed personal sampling system put on a manikin (laboratory study) or donned by a human subject (laboratory and field studies). Two inhalation flow rates (0 and 40 l min(-1)) in conjunction with the sampling flow rate (10 l min(-1)) were tested in the manikin-based experiments to investigate the effects of the leak location (nose, cheek and chin) and the depth of the sampling probe (0, 5, 10 and 15 mm) within the respirator. The effect of human activity on the protection factor was evaluated using a variety of head movements and breathing patterns when a human subject wore the respirator in a room-size laboratory test chamber. The field study was conducted during corn harvesting with a respirator worn by a human subject on a combine. RESULTS: There was no significant difference in the protection factors for different leak locations, or for sampling probe depths, when the inhalation rate was 0 l min(-1). For the inhalation rate of 40 l min(-1), the protection factors for nose leaks were higher than those for chin and cheek leaks. Furthermore, the protection factor was the lowest and showed the least variation when the sampling probe depth was equal to 0 mm (imbedded on the respirator surface). Human subject testing showed that the grimace maneuver decreased the protection factor and changed the original respirator fit. The protection factor during breath holding was lower than that found during inhalation and exhalation. Field results showed greater variation than laboratory results. CONCLUSIONS: The newly designed personal sampling system efficiently detected the changes in protection factors in real time. The sampling flow was least affected by the inhalation flow when the sampling probe was imbedded on the respirator surface. Leak location, breathing patterns and exercises did affect the measurement of the protection factors obtained using an N95 filtering facepiece respirator. This can be attributed to the differences in the in-mask airflow dynamics contributed by the leak, filter material, sampling probe and inhalation. In future studies, it would be beneficial if the laboratory data could be integrated with the field database.     

The importance of alveolar bone loss, width of periodontal space, visibility of lamina dura and divergence of roots on the rocking moments in extraction of teeth in the lower jaw

The purpose of this study was to investigate the effect of the alveolar bone loss, with width of the periodontal space, the visibility of the lamina dura and the divergence of the roots on the rocking moments that were measured by means of strain gauges and on their acting times. Of the factors studied, alveolar bone loss had the greatest effect on the moments. The extraction time shortened when alveolar bone loss increased. When the periodontal space widened, the moments used decreased. The extraction time was significantly lengthened when the roots were diverged.     

Children with Functional Motor Limitations: The Effects on Family Strengths

Sixty children with functional motor limitations (age range from 15months to 7years 3months) and their parents participated in the study. The objective was to explore the relationship of the severity of their restrictions on family strengths. Functional motor abilities of the children were assessed using Autti-Ramos Scale. Cognitive functions were assessed using the Swedish standardized version of the Griffiths Scales of Mental Development. Family strengths were indexed using the Family Functioning Style Scale. The social-economical status, childrens age and caretakers age were taken into account. Overall, the results indicated that family strengths were rather strong. Only families rearing a child with severe participation limitations (functional motor limitations and cognitive difficulties) showed less strengths concerning family identity and internal coping relative to families with a child with milder participation limitations.This research has been made possible by the grants of theTampere University Foundation and Medical Research Fund of Tampere University Hospital, Finland. We thank Matti Koivikko, MD, PhD, and Markku Ojanen, PhD, for their critical comments.