Interleukin-12 suppresses filaria-induced pulmonary eosinophilia, deposition of major basic protein and airway hyperresponsiveness

Tropical Pulmonary Eosinophilia (TPE) is a severe form of allergic asthma caused by the host inflammatory response to filarial helminths in the lung microvasculature, and is characterized by pulmonary eosinophilia, increased filarial-specific IgG and IgE antibodies, and airway hyperresponsiveness. The current study examined the effect of IL-12 on pulmonary eosinophilia, deposition of eosinophil major basic protein and airway hyperresponsiveness in mice inoculated i.v. with Brugia malayi microfilariae. Injection of recombinant murine IL-12 modulated the T helper (Th) response in the lungs from Th2- to Th1-like, with elevated IFN-γ, and decreased IL-4 and IL-5 production. Consistent with this shift in cytokine response, antigen-specific IgG2a was elevated, and IgG1 and total serum IgE were decreased. In addition, eosinophils in BAL fluid from IL-12 treated mice were reduced from 56% to 11%, and there was no detectable MBP on respiratory epithelial cells. Importantly, IL-12 suppressed airway hyperresponsiveness compared with saline-injected control animals. Taken together, these data clearly demonstrate that by modulating Th associated cytokine production, IL-12 down-regulates filaria-induced lung immunopathology .     

ATP1A3 mutations in infants: a new rapid‐onset dystonia–Parkinsonism phenotype characterized by motor delay and ataxia

We report new clinical features of delayed motor development, hypotonia, and ataxia in two young children with mutations (R756H and D923N) in the ATP1A3 gene. In adults, mutations in ATP1A3 cause rapid‐onset dystonia–Parkinsonism (RDP, DYT12) with abrupt onset of fixed dystonia. The parents and children were examined and videotaped, and samples were collected for mutation analysis. Case 1 presented with fluctuating spells of hypotonia, dysphagia, mutism, dystonia, and ataxia at 9 months. After three episodes of hypotonia, she developed ataxia, inability to speak or swallow, and eventual seizures. Case 2 presented with hypotonia at 14 months and pre‐existing motor delay. At age 4 years, he had episodic slurred speech, followed by ataxia, drooling, and dysarthria. He remains mute. Both children had ATP1A3 gene mutations. To our knowledge, these are the earliest presentations of RDP, both with fluctuating features. Both children were initially misdiagnosed. RDP should be considered in children with discoordinated gait, and speech and swallowing difficulties.     

Factors influencing nurses’ attitudes towards healthcare information technology

Huryk l.a. (2010) Journal of Nursing Management 18, 606–612
Factors influencing nurses’ attitudes towards healthcare information technology Aim(s) This literature review examines the current trend in nurses’ attitudes toward healthcare information technology (HIT). Background HIT implementation and expansion are at the core of global efforts to improve healthcare quality and patient safety. As a large portion of the healthcare workforce, nurses’ attitudes towards HIT are likely to have a major impact on the electronic health record (EHR) implementation process. Evaluation A search of PubMed, CINAHL and Medline databases produced 1930 combined hits. Returned articles were scanned for relevancy and applicability. Thirteen articles met all criteria and were subsequently reviewed in their entirety. Key Issue(s) In accordance with two change theories, if HIT implementation projects are to be successful, nurses must recognize that incorporating EHRs into their daily practice is beneficial to patient outcomes. Conclusion(s) Overall, the attitudes of nurses toward HIT are positive. Increased computer experience is the main demographic indicator for positive attitudes. The most common detractors are poor system design, system slowdown and system downtime. Nurses are also fearful that the use of technology will dehumanize patient care. Implications for nursing management Involving nurses in system design is likely to improve post-implementation satisfaction. Creating a positive, supportive atmosphere appears to be instrumental to sustainability.     

Magnetocardiographic Pacemapping for Nonfluoroscopic Localization of Intracardiac Electrophysiology Catheters

The purpose of the study was to validate, in patients, the accuracy of magnetocardiography (MCG) for three-dimensional localization of an amagnetic catheter (AC) for multiple monophasic action potential (MAP) with a spatial resolution of 4 mm2. The AC was inserted in five patients after routine electrophysiological study. Four MAPs were simultaneously recorded to monitor the stability of endocardial contact of the AC during the MCG localization. MAP signals were band-pass filtered DC-500 Hz and digitized at 2 KHz. The position of the AC was also imaged by biplane fluoroscopy (XR), along with lead markers. MCG studies were performed with a multichannel SQUID system in the Helsinki BioMag shielded room. Current dipoles (5mm; 10mA), activated at the tip of the AC, were localized using the equivalent current dipole (ECD) model in patient-specific boundary element torso. The accuracy of the MCG localizations was evaluated by: (1) anatomic location of ECD in the MRI, (2) mismatch with XR. The AC was correctly localized in the right ventricle of all patients using MRI. The mean three-dimensional mismatch between XR and MCG localizations was 6 ± 2 mm (beat-to-beat analysis). The coefficient of variation of three-dimensional localization of the AC was 1.37% and the coefficient of reproducibility was 2.6 mm. In patients, in the absence of arrhythmias, average local variation coefficients of right ventricular MAP duration at 50% and 90% ofrepolarization, were 7.4% and 3.1%, respectively. This study demonstrates that with adequate signal-to-noise ratio, MCG three-dimensional localizations are accurate and reproducible enough to provide nonfluoroscopy dependant multimodal imaging for high resolution endocardial mapping of monophasic action potentials.     

Monitoring Dietary Change in a Low-Fat Diet Intervention Study: Advantages of Using 24-Hour Dietary Recalls vs Food Records

Objective The purpose of the study was to evaluate two methods of dietary assessment for monitoring change in fat intake in a low-fat diet intervention study.Design The two dietary assessment methods were a 4-day food record (4DFR) and an unannounced 24-hour dietary recall conducted by telephone interview (referred to as a telephone recall [TR]). Subjects were assigned randomly to either a low-fat diet intervention group or a control group that received no counseling about fat intake. Dietary data were collected at baseline, 6 months, and 12 months.Subjects Two hundred ninety postmenopausal women with localized breast cancer were recruited at seven clinical centers in the United States.Statistical analysis Analysis of variance was used to test for significant differences in mean fat and energy intakes.Results Three sources of error were identified: (a) an instrument effect, suggesting underreporting at baseline of approximately 8% in mean energy intake and 11% in mean fat intake in the TR group compared with the 4DFR group (P=.0001); (b) a repeated measures effect observed for the 4DFR, suggesting underreporting of approximately 7% for energy intake and 14% for fat intake in the control group at 6 and 12 months compared with baseline values (P<.001); and (c) an adherence effect (or compliance bias), suggesting greater compliance to the low-fat intervention diet when subjects were keeping food records than when estimates were based on the unannounced TR. Compared with the TR, the 4DFR overestimated the extent of fat reduction in the low-fat diet intervention group by 41% (P=.08) and 25% (P=.62) at 6 and 12 months, respectively.Application Multiple days of unannounced 24-hour recalls may be preferable to multiple-day food records for monitoring dietary change in diet intervention studies. J Am Diet Assoc. 1996; 96:574-579.     

The molecular aetiology of haemophilia A in a New Zealand patient group

The genetic basis of haemophilia A (HA) is well-established, and many haematology services are supported by molecular biology laboratories that offer factor VIII genetic testing for HA patients. This report describes the results from factor VIII gene (F8) analysis of a New Zealand cohort of 45 proband HA patients. We screened all proband HA patients attending local clinics to determine the molecular basis of disease in each case. We also aimed to evaluate the significance of founder effect in this population and to explain an unusual case of HA in a female patient. HA patients were screened for the common F8 gene inversion mutations using previously described PCR-based techniques, and for single base substitution mutations using denaturing high performance liquid chromatography and DNA sequencing. Analysis of microsatellite markers located within or near F8 was used to determine identity by descent and trace inheritance patterns of disease alleles. X-chromosome inactivation (XCI) patterns were detected using methylation specific PCR. Pathogenic F8 gene mutations were detected in all 45 HA patients in this cohort and non-random XCI was confirmed in a female haemophiliac. We report nine novel F8 mutations, including two splicing mutations, a five nucleotide deletion and a large deletion at the 5' end of the gene. The molecular aetiology of HA was similar to that described in other studies but the distribution of mutations was unusual due to founder effects, with almost a quarter of all probands being descended from just three individuals.     

The location of the major bands on chromosome 1 at diakinesis in the human male and the relationship between banding pattern and chiasma localization

Q-banded chromosome 1 bivalents from six human males were measured in order to determine the locations of the major band borders. Chiasma position was also recorded in these bivalents in order to determine whether chiasmata preferentially occurred in Q-bright regions, Q-dark regions or in the interfaces between. The results indicated that the locations of the major bands of chromosome 1 were very similar at diakinesis and at mitotic prometaphase and that chiasma distribution was not governed by the banding pattern of the chromosome.