Original Article Goldberg, Y P; MacFarlane, J; MacDonald, M L ...
Clinical genetics,
04/2007, Letnik:
71, Številka:
4
Journal Article
Recenzirano
Congenital indifference to pain (CIP) is a rare condition in which patients have severely impaired pain perception, but are otherwise essentially normal. We identified and collected DNA from ...individuals from nine families of seven different nationalities in which the affected individuals meet the diagnostic criteria for CIP. Using homozygosity mapping and haplotype sharing methods, we narrowed the CIP locus to chromosome 2q24-q31, a region known to contain a cluster of voltage-gated sodium channel genes. From these prioritized candidate sodium channels, we identified 10 mutations in the SCN9A gene encoding the sodium channel protein Nav1.7. The mutations completely co-segregated with the disease phenotype, and nine of these SCN9A mutations resulted in truncation and loss-of-function of the Nav1.7 channel. These genetic data further support the evidence that Nav1.7 plays an essential role in mediating pain in humans, and that SCN9A mutations identified in multiple different populations underlie CIP. PUBLICATION ABSTRACT
Congenital indifference to pain (CIP) is a rare condition in which patients have severely impaired pain perception, but are otherwise essentially normal. We identified and collected DNA from ...individuals from nine families of seven different nationalities in which the affected individuals meet the diagnostic criteria for CIP. Using homozygosity mapping and haplotype sharing methods, we narrowed the CIP locus to chromosome 2q24–q31, a region known to contain a cluster of voltage‐gated sodium channel genes. From these prioritized candidate sodium channels, we identified 10 mutations in the
SCN9A
gene encoding the sodium channel protein Na
v
1.7. The mutations completely co‐segregated with the disease phenotype, and nine of these
SCN9A
mutations resulted in truncation and loss‐of‐function of the Na
v
1.7 channel. These genetic data further support the evidence that Na
v
1.7 plays an essential role in mediating pain in humans, and that
SCN9A
mutations identified in multiple different populations underlie CIP.
Congenital indifference to pain (CIP) is a rare condition in which patients have severely impaired pain perception, but are otherwise essentially normal. We identified and collected DNA from ...individuals from nine families of seven different nationalities in which the affected individuals meet the diagnostic criteria for CIP. Using homozygosity mapping and haplotype sharing methods, we narrowed the CIP locus to chromosome 2q24-q31, a region known to contain a cluster of voltage-gated sodium channel genes. From these prioritized candidate sodium channels, we identified 10 mutations in the SCN9A gene encoding the sodium channel protein Na sub(v)1.7. The mutations completely co-segregated with the disease phenotype, and nine of these SCN9A mutations resulted in truncation and loss-of-function of the Na sub(v)1.7 channel. These genetic data further support the evidence that Na sub(v)1.7 plays an essential role in mediating pain in humans, and that SCN9A mutations identified in multiple different populations underlie CIP.
In a previous pilot study, we demonstrated that adjunctive treatment with hyperbaric oxygen (HBO) appears to be feasible and safe in patients with acute myocardial infarction (AMI) and may result in ...an attenuated rise in creatine phosphokinase (CPK), more rapid resolution of pain and ST changes. This randomized multicenter trial was organized to further assess the safety and feasibility of this treatment in human subjects. Patients with an AMI treated with recombinant tissue plasminogen activator (rTPA) or streptokinase (STK), were randomized to treatment with HBO combined with either rTPA or STK, or rTPA or STK alone. An analysis included 112 patients, 66 of whom had inferior AMIs (p = NS). The remainder of the patients had anterior AMIs. The mean CPK at 12 and 24 h was reduced in the HBO patients by approximately 7.5% (p = NS). Time to pain relief was shorter in the HBO group. There were 2 deaths in the control and 1 in those treated with HBO. The left ventricle ejection fraction (LVEF) on discharge was 51.7% in the HBO group as compared to 48.4% in the controls (p = NS). The LVEF of the controls was 43.4 as compared to 47.6 for those treated, approximately 10% better (no significant difference). Treatment with HBO in combination with thrombolysis appears to be feasible and safe for patients with AMI and may result in an attenuated CPK rise, more rapid resolution of pain and improved ejection fractions. More studies are needed to assess the benefits of this treatment.
In Pakistan, recent and dramatic shifts in the economic, political, and social contexts of teachers' lives have significantly affected their personal and professional horizons. These teachers, in ...turn, are now in a position to extend and expand these horizons. My research, entitled, I Am, Therefore, We Are: A Narrative inquiry into the Stories of Experience of Three Women Teachers of Balochistan and Northern Pakistan, deals with the stories of experience of three remarkable Pakistani women teachers: Dr. Naghmana Ansari, Shahida Sultan Shah, and Shama Ali. What they have in common is their heroic struggle to acquire an education and to earn higher degrees, which they achieved only through great personal sacrifice and despite improbable odds. Narrating their unique stories; showing how their lives have been shaped by Pakistan's geographical, historical, economic, political, and social legacy; describing the significance that Karachi, Balochistan, and the Northern Areas (the three research sites) have held for the women; and, finally, interpreting their stories within the frameworks of narrative inquiry, on the one hand, and feminist theory and praxis, on the other (the ‘interpenetration’ of which has resulted in the formulation of a new concept, “narrative feminism”), constitute the four major aims of this thesis.
A computer-aided engineering (CAE) environment for the design and analysis of computer-controlled multibody systems is defined, and a prototype environment is demonstrated in this paper. The overall ...integrated environment includes systems for three-dimensional geometric modeling and animation, multibody system dynamics, finite element analysis, and control system design. In this paper, the integration of a multibody system dynamics program IMP with the control system design program MATRIXx is demonstrated. Transfer functions from the multibody system model, together with mathematical models of any electrical, pneumatic and hydraulic components, are used in MATRIXx for control system synthesis. The controller architecture and parameters are specified in block diagram form and converted to a real-time program through an automatic code generator in MATRIXx. This program is downloaded to a microprocessor for controlling the actual, physical plant. In the CAE environment of this paper, the controller program, with any non-mechanical component models included, is combined with the original IMP non-linear mechanical system model. The dynamic response of this complete system is studied to verify the controller design for this non-linear, more realistic mechanical model.
A cohort of breech presentation cases from one certified nurse-midwife's practice was analyzed retrospectively to determine the effectiveness of a postural technique to promote version to a cephalic ...presentation. Forty-six (7.5%) fetuses out of 608 were diagnosed using Leopold maneuvers to be presenting breech at 30 weeks gestation. Mothers were instructed to lie supine and inverted on an ironing board placed at a 45-degree angle for a set time daily until version occurred or 37 weeks gestation. Those remaining breech were referred to an obstetrician for an external cephalic version (ECV). A binomial distribution was used to compare results to the 3–4% national average for term breech presentations. Significantly fewer breech presentations occurred following postural management. Thus, the combination of early intervention at 30–32 weeks gestation with a postural technique followed by ECV near term was effective in achieving version of a breech presentation to a cephalic.
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