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1.
R Soc Open Sci ; 10(5): 230056, 2023 May.
Article in English | MEDLINE | ID: mdl-37153363

ABSTRACT

Recently, Cooke et al. (Cooke et al. 2022 R. Soc. Open Sci. 9, 211165. (doi:10.1098/rsos.211165)) used a three-dimensional coupled chemistry-climate model (WACCM6) to calculate ozone column depths at varied atmospheric O2 levels. They argued that previous one-dimensional (1-D) photochemical model studies, e.g. Segura et al. (Segura et al. 2003 Astrobiology 3, 689-708. (doi:10.1089/153110703322736024)), may have overestimated the ozone column depth at low pO2, and hence also overestimated the lifetime of methane. We have compared new simulations from an updated version of the Segura et al. model with those from WACCM6, together with some results from a second three-dimensional model. The discrepancy in ozone column depths is probably due to multiple interacting parameters, including H2O in the upper troposphere, lower boundary conditions, vertical and meridional transport rates, and different chemical mechanisms, especially the treatment of O2 photolysis in the Schumann-Runge (SR) bands (175-205 nm). The discrepancy in tropospheric OH concentrations and methane lifetime between WACCM6 and the 1-D model at low pO2 is reduced when absorption from CO2 and H2O in this wavelength region is included in WACCM6. Including scattering in the SR bands may further reduce this difference. Resolving these issues can be accomplished by developing an accurate parametrization for O2 photolysis in the SR bands and then repeating these calculations in the various models.

2.
R Soc Open Sci ; 9(1): 211165, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35070343

ABSTRACT

The history of molecular oxygen (O2) in Earth's atmosphere is still debated; however, geological evidence supports at least two major episodes where O2 increased by an order of magnitude or more: the Great Oxidation Event (GOE) and the Neoproterozoic Oxidation Event. O2 concentrations have likely fluctuated (between 10-3 and 1.5 times the present atmospheric level) since the GOE ∼2.4 Gyr ago, resulting in a time-varying ozone (O3) layer. Using a three-dimensional chemistry-climate model, we simulate changes in O3 in Earth's atmosphere since the GOE and consider the implications for surface habitability, and glaciation during the Mesoproterozoic. We find lower O3 columns (reduced by up to 4.68 times for a given O2 level) compared to previous work; hence, higher fluxes of biologically harmful UV radiation would have reached the surface. Reduced O3 leads to enhanced tropospheric production of the hydroxyl radical (OH) which then substantially reduces the lifetime of methane (CH4). We show that a CH4 supported greenhouse effect during the Mesoproterozoic is highly unlikely. The reduced O3 columns we simulate have important implications for astrobiological and terrestrial habitability, demonstrating the relevance of three-dimensional chemistry-climate simulations when assessing paleoclimates and the habitability of faraway worlds.

3.
J Clim ; 32(22): 7629-7642, 2019 Nov 15.
Article in English | MEDLINE | ID: mdl-33132515

ABSTRACT

An accurate quantification of the stratospheric ozone feedback in climate change simulations requires knowledge of the ozone response to increased greenhouse gases. Here, we present an analysis of the ozone layer response to an abrupt quadrupling of CO2 concentrations in four chemistry-climate models. We show that increased CO2 levels lead to a decrease in ozone concentrations in the tropical lower stratosphere, and an increase over the high latitudes and throughout the upper stratosphere. This pattern is robust across all models examined here, although important inter-model differences in the magnitude of the response are found. As a result of the cancellation between upper and lower stratospheric ozone, the total column ozone response in the tropics is small, and appears to be model dependent. A substantial portion of the spread in the tropical column ozone is tied to inter-model spread in upwelling. The high latitude ozone response is strongly seasonally dependent, and shows increases peaking in late-winter and spring of each hemisphere, with prominent longitudinal asymmetries. The range of ozone responses to CO2 reported in this paper has the potential to induce significant radiative and dynamical effects on the simulated climate. Hence, these results highlight the need of using an ozone dataset consistent with CO2 forcing in models involved in climate sensitivity studies.

4.
J Geophys Res Space Phys ; 121(7): 7153-7165, 2016 Jul.
Article in English | MEDLINE | ID: mdl-31404353

ABSTRACT

The meteoric metal layers (Na, Fe, and K)-which form as a result of the ablation of incoming meteors-act as unique tracers for chemical and dynamical processes that occur within the upper mesosphere/lower thermosphere region. In this work, we examine whether these metal layers are sensitive indicators of decadal long-term changes within the upper atmosphere. Output from a whole-atmosphere climate model is used to assess the response of the Na, K, and Fe layers across a 50 year period (1955-2005). At short timescales, the K layer has previously been shown to exhibit a very different seasonal behavior compared to the other metals. Here we show that this unusual behavior is also exhibited at longer timescales (both the ~11 year solar cycle and 50 year periods), where K displays a much more pronounced response to atmospheric temperature changes than either Na or Fe. The contrasting solar cycle behavior of the K and Na layers predicted by the model is confirmed using satellite and lidar observations for the period 2004-2013.

5.
Geophys Res Lett ; 42(9): 3619-3626, 2015 05 16.
Article in English | MEDLINE | ID: mdl-27478284

ABSTRACT

Measurements of the diurnal cycle of potassium (K) atoms between 80 and 110 km have been made during October (for the years 2004-2011) using a Doppler lidar at Kühlungsborn, Germany (54.1°N, 11.7°E). A pronounced diurnal variation is observed in the K number density, which is explored by using a detailed description of the neutral and ionized chemistry of K in a three-dimensional chemistry climate model. The model captures both the amplitude and phase of the diurnal and semidiurnal variability of the layer, although the peak diurnal amplitude around 90 km is overestimated. The model shows that the total potassium density (≈ K + K+ + KHCO3) exhibits little diurnal variation at each altitude, and the diurnal variations are largely driven by photochemical conversion between these reservoir species. In contrast, tidally driven vertical transport has a small effect at this midlatitude location, and diurnal fluctuations in temperature are of little significance because they are small and the chemistry of K is relatively temperature independent.

6.
Spinal Cord ; 49(3): 337-44, 2011 Mar.
Article in English | MEDLINE | ID: mdl-20877331

ABSTRACT

STUDY DESIGN: Female Wistar rats (225 g) underwent spinal cord injury (SCI) at the T4 segment and were assigned to one of the three groups treated with: (1) saline; (2) 7.5 mg kg(-1) Reparixin; or (3) 15 mg kg(-1) Reparixin. Reparixin is a small molecule, allosteric noncompetitive inhibitor of CXCR1 and CXCR2 chemokine receptors involved in inflammation. METHODS: Spinal cord homogenates at 12 and 72 h post-SCI were assayed for tumor necrosis factor α (TNF-α) and cytokine-induced neutrophil chemoattractant (CINC)-1 using enzyme-linked immunosorbant assay (ELISA). Myeloperoxidase activity and western blots for CD68, Fas and p75 content were used to assess inflammation and death receptor ligands, respectively. Histopathology and neurological outcomes were assessed by immunohistochemistry, locomotion scoring and cardiovascular measurement of autonomic dysreflexia 4 weeks post-SCI. RESULTS: Both 7.5 and 15 mg kg(-1) doses of Reparixin reduced levels of TNF-α and CINC-1 72 h post-SCI and decreased macrophage (CD68) content in the spinal cord lesion. Only 15 mg kg(-1) Reparixin reduced both Fas and p75 levels in the spinal cord compared with untreated SCI. We observed a reduced lesion area and increased neuron number in the gray matter of Reparixin-treated rats. Hindlimb motor scores at 7 and 28 days post-SCI were improved by 15 mg kg(-1) Reparixin treatment. Both 7.5 and 15 mg kg(-1) Reparixin reduced development of autonomic dysreflexia 4 weeks post-SCI. The change in mean arterial pressure, induced by cutaneous or visceral stimulation, was reduced by 40-50%. CONCLUSION: Acute treatment with 15 mg kg(-1) Reparixin reduces acute inflammation and is associated with minor improvements in motor function and a significant reduction in the severity of autonomic dysreflexia.


Subject(s)
Autonomic Dysreflexia/drug therapy , Autonomic Dysreflexia/metabolism , Inflammation Mediators/antagonists & inhibitors , Receptors, Interleukin-8A/antagonists & inhibitors , Receptors, Interleukin-8B/antagonists & inhibitors , Spinal Cord Injuries/drug therapy , Spinal Cord Injuries/metabolism , Acute Disease , Animals , Autonomic Dysreflexia/pathology , Disease Models, Animal , Female , Inflammation Mediators/physiology , Nerve Degeneration/drug therapy , Nerve Degeneration/metabolism , Nerve Degeneration/pathology , Rats , Rats, Wistar , Receptors, Interleukin-8A/physiology , Receptors, Interleukin-8B/physiology , Spinal Cord Injuries/pathology , Sulfonamides/pharmacology
7.
J Health Popul Nutr ; 28(5): 501-8, 2010 Oct.
Article in English | MEDLINE | ID: mdl-20941902

ABSTRACT

Afghans comprise one of the largest groups of refugees in the world, with the majority living in Pakistan. The objective of this study was to identify commonly-occurring reproductive tract infections (RTIs), describe knowledge of women about RTIs, and assess physical and behavioural factors contributing to the development of RTIs. Afghan women presenting at Basic Health Units in refugee camps in Haripur, Pakistan, with reproductive health-related complaints, were included in the study (n=634). Data collection included implementation of an interviewer-administered questionnaire, along with a physical examination and laboratory tests. A descriptive analysis was conducted first. Qualitative data were coded and analyzed using predetermined themes. Chi-square test was used for determining the possible relationships between a binary outcome and categorical risk factors. Over three-fourths (76.7%) of those who reported to the health clinics with reproductive complaints had an RTI. Nearly half (49.5%) of these women were diagnosed with some form of vaginitis, and 14.7% were diagnosed with clinical suspicion of pelvic inflammatory disease (PID). Women with cervical prolapse (p = 0.033) or who cleansed after intercourse (p = 0.002) were more likely to have vaginitis. There was a significant difference (p = 0.017) in the prevalence of suspected PID among women who used mud only (11.1%), any water (18.8%), and an old cloth or toilet paper (9.8%) for cleansing after defaecation. Specific physical and behavioural contributors to the high prevalence of RTIs in this population were identified, and recommendations to ameliorate these factors are offered.


Subject(s)
Ambulatory Care Facilities/statistics & numerical data , Genital Diseases, Female/epidemiology , Refugees , Adolescent , Adult , Afghanistan/ethnology , Aged , Child , Female , Genital Diseases, Female/microbiology , Humans , Middle Aged , Pakistan/epidemiology , Young Adult
8.
Ann R Coll Surg Engl ; 92(2): 101-5, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20353638

ABSTRACT

Ilizarov frames provide a versatile fixation system for the management of bony deformities, fractures and their complications. The frames give stability, soft tissue preservation, adjustability and functionality allowing bone to realise its full osteogenic potential. It is important that we have a clear and concise understanding of the Ilizarov principles of deformity correction to best make use of this fixation system. In this review article, the history of Ilizarov frame, the basic sciences behind it, the mechanical principles governing its use and the clinical use of the fixation system are discussed.


Subject(s)
Bone Malalignment/surgery , Ilizarov Technique/instrumentation , Equipment Design , External Fixators , Humans , Ilizarov Technique/adverse effects , Osteogenesis, Distraction/instrumentation , Osteogenesis, Distraction/methods , Stress, Mechanical
9.
Injury ; 41(2): 147-50, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19647820

ABSTRACT

Although there is much in the literature regarding pin site infections, there is no accepted, validated method for documenting their state. We present a system for reliably labelling pin sites on any ring fixator construct and an easy-to-remember grading system to document the state of each pin site. Each site is graded in terms of erythema, pain and discharge to give a 3-point scale, named "Good", "Bad" and "Ugly" for ease of recall. This system was tested for intra- and inter-observer reproducibility. 15 patients undergoing elective limb reconstruction were recruited. A total of 218 pin sites were independently scored by 2 examiners. 82 were then re-examined later by the same examiners. 514 pin sites were felt to be "Good", 80 "Bad" and 6 "Ugly". The reproducibility of the system was found to be excellent. We feel our system gives a quick, reliable and reproducible method to monitor individual pin sites and their response to treatment.


Subject(s)
Bone Nails/adverse effects , Ilizarov Technique/instrumentation , Prosthesis-Related Infections/diagnosis , Clinical Protocols , Femoral Fractures/surgery , Humans , Observer Variation , Prosthesis-Related Infections/etiology , Reproducibility of Results , Tibial Fractures/surgery , Treatment Outcome
10.
J Perinatol ; 28(3): 182-7, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18059464

ABSTRACT

OBJECTIVE: To learn about household maternal and newborn health knowledge and practices to aid the design of newborn programming within Save the Children's Haripur Program. STUDY DESIGN: In April, we conducted 43 semi-structured interviews (SSIs) and 34 focus group discussions among men, women of reproductive age and health service providers; in September, we added 21 SSIs among new mothers, new fathers and dais. Two investigators analyzed the findings according to themes within six care types: antenatal, delivery, immediate newborn, routine postpartum, special maternal and special newborn. RESULT: Findings indicated poor maternal diet and antenatal care-seeking. Home delivery with an untrained dai was the norm. Respondents knew about benefits of clean delivery, but rarely put knowledge into practice. Knowledge and practices for maintaining the newborn's warmth were good. Delayed initiation of breastfeeding, avoidance of colostrum and prelacteal feeding were almost universal. Unhygienic cord care, including an unclean cut and application of ghee on the cord-stump, was the norm. After delivery, mothers often maintained low fluid intake but otherwise reported healthy nutritional practices. Knowledge of some danger signs in newborns was common, but timely action upon recognition was not. CONCLUSION: Although the findings illustrate some beneficial practices, many reported practices are harmful to the newborn. These findings, consistent with the sparse existing data in Pakistan, inform program interventions for household-level behavioral change.


Subject(s)
Breast Feeding/psychology , Health Knowledge, Attitudes, Practice , Infant Care , Maternal Welfare/ethnology , Postnatal Care , Adult , Breast Feeding/ethnology , Fathers , Female , Focus Groups , Humans , Infant, Newborn , Interviews as Topic , Male , Midwifery , Mothers , Pakistan , Pregnancy , Prenatal Care
11.
J Mater Sci Mater Med ; 18(12): 2283-90, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17562143

ABSTRACT

The Advanced JAX Bone Void Filler System (AJBVFS) is a novel bone graft material manufactured by Smith and Nephew Orthopaedics Ltd. and comprises beta tri-calcium phosphate granules with carboxymethylcellulose (CMC) gel as a handling agent. This study investigated the potential, in vitro, of the AJBVFS to function as a delivery system for cell therapy to enhance healing of bone defects. The attachment of rabbit bone marrow stromal cells (rbBMSCs), human BMSCs (hBMSCs) and human bone-derived cells (hBDCs) to JAX granules and the effect of CMC gel on cell proliferation and differentiation were investigated. There were slight species differences in the number and morphology of cells attached on the JAX granules with less rbBMSC attachment than human. All cells tolerated the presence of CMC gel and a reduction in cell number was only seen after longer exposure to higher gel concentrations. Low concentrations of CMC gel enhanced proliferation, alkaline phosphatase (ALP) expression and ALP activity in human cells but had no effect on rbBMSC. This study suggests that AJBVFS is an appropriate scaffold for the delivery of osteogenic cells and the addition of CMC gel as a handling agent promotes osteogenic proliferation and differentiation and is therefore likely to encourage bone healing.


Subject(s)
Bone Marrow Cells/drug effects , Bone Substitutes/pharmacology , Calcium Phosphates/pharmacology , Carboxymethylcellulose Sodium/pharmacology , Cell- and Tissue-Based Therapy/methods , Stromal Cells/drug effects , Adult , Aged , Animals , Bone Marrow Cells/physiology , Bone Substitutes/chemistry , Calcium Phosphates/chemistry , Carboxymethylcellulose Sodium/chemistry , Cell Adhesion/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Female , Gels/pharmacology , Humans , Male , Materials Testing , Middle Aged , Rabbits , Species Specificity , Stromal Cells/physiology , Tissue Scaffolds
12.
Bone ; 40(4): 939-47, 2007 Apr.
Article in English | MEDLINE | ID: mdl-17175212

ABSTRACT

Currently, available synthetic bone substitutes have adequate osteoconductive properties but have little or no osteoinductivity. Recent research has focused on using osteogenic growth factors or cells to provide this. JAX is a beta tricalcium phosphate bone graft substitute that has a novel shape and interlocking design. This study investigated delivery methods and the use of autologous cell therapy to enhance healing of a bone defect using JAX as a scaffold. Bone marrow was harvested from 24 New Zealand White rabbits. The mononuclear cell fraction was isolated and culture expanded. Bilateral 1.5 cm defects in the ulna were filled with: Group 1: JAX alone, Group 2: JAX plus 1x10(7) autologous BMSCs injected at the time of surgery, Group 3: JAX plus 8x10(6) autologous BMSCs cultured on granules for 14 days prior to surgery, Group 4: JAX plus fresh bone marrow (BMA), Group 5: cortical autograft, Group 6: JAX plus 2.5 microg VEGF. Radiographs demonstrated that there was more new bone in the BMA and VEGF groups compared to JAX alone. Groups containing autologous BMSCs were only slightly better than JAX alone in the amount of bone in the defect but did improve bridging of the osteotomy. Histomorphometry identified a significant increase in bone volume in the BMA group compared to JAX alone. BMA and VEGF enhanced healing of bone defects whereas expanded BMSCs provided little advantage over scaffold alone. There was no difference between delivery methods of autologous BMSCs. These observations suggest that the provision of osteogenic cells alone is insufficient to enhance bone healing and that additional factors are required to initiate this process in vivo.


Subject(s)
Bone Substitutes/therapeutic use , Calcium Phosphates/therapeutic use , Ulna Fractures/therapy , Animals , Bone Marrow Transplantation , Fracture Healing/drug effects , Male , Microscopy, Electron, Scanning , Osteogenesis , Rabbits , Radiography , Stromal Cells/transplantation , Transplantation, Autologous , Ulna Fractures/diagnostic imaging , Ulna Fractures/pathology , Vascular Endothelial Growth Factor A/therapeutic use
13.
Ulster Med J ; 75(3): 200-6, 2006 Sep.
Article in English | MEDLINE | ID: mdl-16964812

ABSTRACT

OBJECTIVE: To study the outcome following treatment for proximal femoral fracture in elderly people. METHODS: All consecutive males and females admitted to the acute fracture service at the Royal Victoria Hospital and the Belfast City Hospital for the 3 years from 1999 to 2001 were studied. The data was collected by trained research nurses. Variables gathered included age, sex, marital status, mental state, pre-injury Barthel score and the American Society of Anaesthesiology (ASA) physical status grading. The information was gathered on admission to hospital and at four, six and 12 months after the injury. RESULTS: The total number of patients studied between January 1999 to December 2001 was 2834 of whom 77% were female and 23% were male. The mean (median) length of stay in the acute fracture service was 10.7 (9 days). The mean (median) length of stay in the rehabilitation ward was 35.3 (24 days). The 30-day mortality was 6.9%, the four-month mortality 15.6 % and one year mortality 22.3 %. Of those subjects living at home at the time of fracture 68% remained at home at one year. Factors predicting successful return home were higher mental test score, younger age, female sex, higher Barthel score, better pre-injury mobility and better ASA score. Of those able to walk independently outdoors before injury 40% regained this ability by 12 months. Factors predicting return of pre-injury mobility were poorer pre-injury mobility, younger age, higher mental test score, better ASA category, higher Barthel score, and previous residence at home. The proportion admitted from their own home and discharged by 56 days was 56%. CONCLUSION: The standardised measurement of outcome in hip fracture subjects enables comparison between units and facilitates improvement in standards of care available to the increasing number of elderly patients presenting with proximal femoral fracture.


Subject(s)
Femoral Neck Fractures/mortality , Femoral Neck Fractures/rehabilitation , Hospitals, Public/statistics & numerical data , Outcome Assessment, Health Care , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Female , Femoral Neck Fractures/surgery , Hip Fractures/mortality , Hip Fractures/rehabilitation , Hip Fractures/surgery , Humans , Length of Stay/statistics & numerical data , Male , Middle Aged , Northern Ireland/epidemiology , Patient Discharge/statistics & numerical data , Prospective Studies , Quality Indicators, Health Care , Survival Analysis
14.
Heart ; 90(4): 394-9, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15020513

ABSTRACT

OBJECTIVES: To determine the community based prevalence of rheumatic heart disease (RHD) in the rural population of the district of Rahim Yaar Khan in Pakistan. SUBJECTS AND METHODS: A representative sample of the rural population of Rahim Yaar Khan district was selected. RHD was screened for by physical examination and the diagnosis was confirmed with echocardiographic Doppler studies. Sociodemographic data on each screened person were collected. RESULTS: 54 cases of RHD were found among the 9430 people screened (prevalence of 5.7 in 1000, 95% confidence interval 4.2 to 7.2). Females were significantly more likely to be affected. There was no significant relation with other factors studied (education, crowding, and socioeconomic status). Less than 20% of those found to have RHD were aware of their diagnosis before participation in this study and only three affected people (8%) were taking rheumatic prophylaxis. CONCLUSIONS: There is a high prevalence of RHD among the rural population of Pakistan. The prevalence has not declined over the past three decades. Nearly all people with RHD, including most of those who know their diagnosis, do not receive the benefit of potentially life saving secondary prevention measures.


Subject(s)
Rheumatic Heart Disease/epidemiology , Rural Health/statistics & numerical data , Adolescent , Adult , Age Distribution , Aged , Child , Child, Preschool , Female , Heart Valve Diseases/epidemiology , Humans , Male , Marital Status , Middle Aged , Pakistan/epidemiology , Prevalence , Risk Factors , Sex Distribution
16.
Food Nutr Bull ; 23(4 Suppl): 48-52, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12503231

ABSTRACT

Children who are weighed for growth monitoring are frequently clothed, especially in the cold weather. Health workers commonly estimate and subtract the weight of these clothes, but the accuracy of these estimates is unknown. We assessed the accuracy of child weights adjusted for estimated clothing typical of hot, cold, and extremely cold ambient temperatures. Trained field workers weighed a sample of 212 children 6 to 42 months old from the ViSION project, adjusted the weights using a job aid describing the weights of common clothing by season and age, and then weighed the clothing to calculate the actual clothing and child weights. Fieldworker estimates of the weight of the clothing that children wore during weighing were remarkably good. In nearly all cases (207 of 212; 97.7%), the difference between the estimated and actual clothing weight was less than the precision of the child scales (+/- 50 g), and most (181 of 212; 84.5%) were within 25 g. Thus, the calculated child weights were, in fact, equivalent to the actual child weights. Using simulations, we found that improperly accounting for clothing weight can overestimate weight-for-age by 0.1 to 0.4 Z score. Accurate weights are possible, even under adverse conditions. Our training methods, clothing album, and job aid might benefit nutrition research and programming in Viet Nam as well as settings with colder climates.


Subject(s)
Body Weight , Child, Preschool , Clothing , Female , Humans , Infant , Male , Observer Variation , Reproducibility of Results , Seasons , Vietnam
17.
J Neurochem ; 81(6): 1152-65, 2002 Jun.
Article in English | MEDLINE | ID: mdl-12068064

ABSTRACT

The N -methyl-D-aspartate receptor (NMDAR) is a multimeric transmembrane protein composed of at least two subunits. One subunit, NR1, is derived from a single gene and can be subdivided into three regions: the N-terminal extracellular domain, the transmembrane regions, and the C-terminal intracellular domain. The N-terminal domain is responsible for Mg2+ metal ion binding and channel activity, while the transmembrane domains are important for ion channel formation. The intracellular C-terminal domain is involved in regulating receptor activity and subcellular localization. Our recent experiments indicated that the intracellular C-terminal domain, when expressed independently, localizes almost exclusively in the nucleus. An examination of the amino acid sequence reveals the presence of a putative nuclear localization sequence (NLS) in the C1 cassette of the NR1 intracellular C-terminus. Using an expression vector designed to test whether a putative NLS sequence is a valid, functional NLS, we have demonstrated that a bi-partite NLS does in fact exist within the NR1-1 C-terminus. Computer algorithms identified a putative helix-loop-helix motif that spanned the C0C1 cassettes of the C-terminus. These data suggest that the NR1 subunit may represent another member of a family of transmembrane proteins that undergo intramembrane proteolysis, releasing a cytosolic peptide that is actively translocated to the nucleus leading to alterations in gene regulation.


Subject(s)
Nuclear Localization Signals , Receptors, N-Methyl-D-Aspartate/genetics , Receptors, N-Methyl-D-Aspartate/metabolism , Amino Acid Sequence/genetics , Animals , Cell Extracts/chemistry , Cell Line/chemistry , Cell Nucleus/metabolism , Clone Cells , Molecular Sequence Data , Nuclear Localization Signals/genetics , PC12 Cells/chemistry , Protein Structure, Secondary , Protein Structure, Tertiary/genetics , Rats , Receptors, N-Methyl-D-Aspartate/chemistry , Receptors, N-Methyl-D-Aspartate/physiology , Recombinant Proteins/metabolism
18.
J Orthop Trauma ; 16(4): 245-9, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11927805

ABSTRACT

OBJECTIVES: To measure the late morbidity of nailed isolated tibial fractures, using both a generic health score and disease-specific scores. To determine the correlation between the two types of outcome measure. DESIGN: Retrospective study, using a combination of case notes and radiographic review plus current clinical assessment. SETTING: Fracture Outcomes Research Unit in a U.K. teaching hospital. PATIENTS: Eighty-three patients with isolated fractures of the tibial diaphysis. Follow-up time was a minimum of three years from injury (mean fifty-seven months). INTERVENTION: All patients were treated primarily by closed, reamed intramedullary nailing. OUTCOME MEASUREMENTS: Iowa Knee and Ankle Scores, visual analogue pain scores for fracture site and knee and ankle joints, and the Short Form 36 health status questionnaire. RESULTS: Sixty-four (77.1%) fractures united after the first procedure. Twenty-nine (34.9%) patients had pain around the knee at rest, fifty-nine (71.1%) had difficulty in kneeling, and thirteen (15.7%) were still experiencing some pain at their fracture site; 69% of patients had excellent results based on the Iowa scores as well as the SF-36 scores. Pain at the knee correlated with low Physical Component Summary and Mental Component Summary scores, and fracture site pain correlated with only low Physical Component Summary score. There was a significant correlation between the disease-specific scores and the SF-36 scores, and only patients with an excellent Iowa grade had "normal" SF-36 scores. CONCLUSION: After tibial nailing, mild deficits registered by Iowa scores are associated with a significant disability and unhappiness as registered by the SF-36. According to the patient-oriented outcomes tool, 31% of late results are "unsatisfactory."


Subject(s)
Fracture Fixation, Intramedullary , Health Status Indicators , Outcome Assessment, Health Care , Tibial Fractures/surgery , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pain Measurement , Patient Satisfaction , Recovery of Function/physiology , Retrospective Studies , Tibial Fractures/physiopathology , Time Factors
19.
J Neurotrauma ; 18(10): 1107-19, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11686496

ABSTRACT

Spinal cord injury leads to many forms of autonomic dysfunction including autonomic dysreflexia, a condition involving recurrent episodes of paroxysmal hypertension and associated bradycardia. This hypertension may reach intensities that are life-threatening. We investigated autonomic dysreflexia and the sprouting of central processes of primary afferent neurons (a potential mechanism for autonomic dysreflexia) in a clinically-relevant calibrated clip-compression model of spinal cord injury in the rat. Autonomic dysreflexia was induced by colon distension in the conscious rats 2 weeks after severe (50-g) clip compression injury of the spinal cord at the 4th thoracic segment. The central arbor of small-diameter primary afferent fibers in laminae III-VII of the spinal cord dorsal horn was also assessed at 2 weeks after cord injury by quantitative morphometry, using calcitonin gene-related peptide as a marker. In response to colon distension, arterial pressure increased by 41 +/- 3 mmHg from a resting value of 109 +/- 4 mmHg, and heart rate decreased by 124 +/- 13 beats/min from a value of 515 +/- 16 beats/min (n = 7). Minimal locomotor function was recovered by these rats: by 2 weeks after injury they attained scores of only 3.1 +/- 1.3 on the Basso, Beattie and Bresnahan scale. Histopathology of the clip-compression lesion site in the cord consisted of extensive central necrosis extending several segments rostral and caudal to the lesion. Quantitative measures of the small-diameter afferent arbors revealed significant increases in area ranging from 20-27% in thoracolumbar segments caudal to the injury (n = 5) in comparison to sham-injured rats (n = 6). A second study was done to assess the impact of severity of injury on the relationship between the size of the primary afferent arbors and autonomic dysreflexia. At 2 weeks after milder (20-g) clip injury at T4, rats exhibited responses to colon distension that were not those associated with autonomic dysreflexia (n = 5). Arterial pressure increased by only 16 +/- 3 mmHg and heart rate tended to increase (+19 +/- 12 beats/min). These rats attained a locomotor score of 7.1 +/- 0.4 by 2 weeks. The lesions at the injury site also contained necrosis and mild cavitation within the gray matter. No change in the small-diameter afferent arbor was detected at 2 weeks after the 20-g clip injury at T4 (n = 6 rats). These findings suggest that after severe but not mild clip compression injury of the spinal cord, sprouting of the afferent component of the spinal reflex are contributes to the development of autonomic dysreflexia. Neither dysreflexia, nor changes in the afferent arbor size occurred after mild cord injury. This clinically relevant clip compression cord injury model, studied more frequently for locomotor function, is excellent for investigating mechanisms for the development of autonomic dysreflexia and strategies for its prevention.


Subject(s)
Autonomic Dysreflexia/physiopathology , Neurons, Afferent/pathology , Spinal Cord Injuries/pathology , Spinal Cord Injuries/physiopathology , Animals , Autonomic Dysreflexia/etiology , Blood Pressure/physiology , Calcitonin Gene-Related Peptide/metabolism , Coloring Agents , Estrous Cycle/physiology , Female , Heart Rate/physiology , Immunohistochemistry , Male , Motor Activity/physiology , Nerve Fibers/pathology , Nerve Fibers, Myelinated/pathology , Posterior Horn Cells/pathology , Rats , Spinal Cord/pathology , Spinal Cord Injuries/complications
20.
Health Policy Plan ; 16(3): 248-55, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11527865

ABSTRACT

BACKGROUND: Between 1987 and 1998 Save the Children conducted a child survival programme in Mali with the goal of reducing maternal and child morbidity and mortality. An integral part of this programme was a computerized demographic surveillance and health information system (HIS) that gathered data on individuals on an on-going basis. OBJECTIVE: To assess the overall coverage and quality of the data in the HIS, to identify specific health districts that needed improvements in data collection methods, and to determine particular areas of weakness in data collection. METHODS: Random samples of 20 mothers with children <5 years were selected in each of 14 health districts. Mothers were interviewed about pregnancies, live births, deaths of children <5, and children's growth monitoring and immunization status. The Lot Quality Assurance Method (LQAS) was used to identify districts in which records and interview results did not meet predetermined levels of acceptability. Data collected in the interviews were combined to estimate overall coverage and quality. RESULTS: When all variables were analyzed, all 14 lots were rejected, and it was estimated that 52% of all events occurring in the community were registered in ProMIS. Much of this poor performance was due to immunization and growth monitoring data, which were not updated due to printer problems. Coverage of events increased (92%) when immunizations and growth monitoring were excluded, and no lots were rejected. When all variables were analyzed for quality of data recorded, six lots were rejected and the overall estimation was 83%. With immunizations and growth monitoring excluded, overall quality was 86% and no lots were rejected. CONCLUSIONS: The comprehensive computerized HIS did not meet expectations. This may be due, in part, to the ambitious objective of complete and intensive monitoring of a large population without adequate staff and equipment. Future efforts should consider employing a more targeted and streamlined HIS so that data can be more complete and useful.


Subject(s)
Database Management Systems/organization & administration , Health Surveys , Quality Assurance, Health Care/methods , Voluntary Health Agencies , Adolescent , Adult , Censuses , Child , Child, Preschool , Data Collection , Female , Humans , Infant , Infant Mortality , Mali/epidemiology , Maternal Mortality , Middle Aged , Pregnancy , Sampling Studies , Surveys and Questionnaires
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