Urban and rural differences in out-of-hospital cardiac arrest in Ireland.

BACKGROUND: More than a third of Ireland's population lives in a rural area, defined as the population residing in all areas outside clusters of 1500 or more inhabitants. This presents a challenge for the provision of effective pre-hospital resuscitation services. In 2012, Ireland became one of three European countries with nationwide Out-of-Hospital Cardiac Arrest (OHCA) register coverage. An OHCA register provides an ability to monitor quality and equity of access to life-saving services in Irish communities. AIM: To use the first year of national OHCAR data to assess differences in the occurrence, incidence and outcomes of OHCA where resuscitation is attempted and the incident is attended by statutory Emergency Medical Services between rural and urban settings. METHODS: The geographical coordinates of incident locations were identified and co-ordinates were then classified as 'urban' or 'rural' according to the Irish Central Statistics Office (CSO) definition. RESULTS: 1798 OHCA incidents were recorded which were attended by statutory Emergency Medical Services (EMS) and where resuscitation was attempted. There was a higher percentage of male patients in rural settings (71% vs. 65%; p = 0.009) but the incidence of male patients did not differ significantly between urban and rural settings (26 vs. 25 males/100,000 population/year p = 0.353). A higher proportion of rural patients received bystander cardiopulmonary resuscitation (B-CPR) 70% vs. 55% (p ≤ 0.001), and had defibrillation attempted before statutory EMS arrival (7% vs. 4% (p = 0.019), respectively). Urban patients were more likely to receive a statutory EMS response in 8 min or less (33% vs. 9%; p ≤ 0.001). Urban patients were also more likely to be discharged alive from hospital (6% vs. 3%; p = 0.006) (incidence 2.5 vs. 1.1/100,000 population/year; p ≤ 0.001). Multivariable analysis of survival showed that the main variable of interest i.e. urban vs. rural setting was also independently associated with discharge from hospital alive (OR 3.23 (95% CI 1.43-7.31)). CONCLUSION: There are significant disparities in the incidence of resuscitation attempts in urban and rural areas. There are challenges in the provision of services and subsequent outcomes from OHCA that occur outside of urban areas requiring novel and innovative solutions. An integrated community response system is necessary to improve metrics around OHCA response and outcomes in rural areas.

Light echoes reveal an unexpectedly cool η Carinae during its nineteenth-century Great Eruption.

η Carinae is one of the most massive binary stars in the Milky Way. It became the second-brightest star in our sky during its mid-nineteenth-century 'Great Eruption', but then faded from view (with only naked-eye estimates of brightness). Its eruption is unique in that it exceeded the Eddington luminosity limit for ten years. Because it is only 2.3 kiloparsecs away, spatially resolved studies of the nebula have constrained the ejected mass and velocity, indicating that during its nineteenth-century eruption, η Car ejected more than ten solar masses in an event that released ten per cent of the energy of a typical core-collapse supernova, without destroying the star. Here we report observations of light echoes of η Carinae from the 1838-1858 Great Eruption. Spectra of these light echoes show only absorption lines, which are blueshifted by -210 km s(-1), in good agreement with predicted expansion speeds. The light-echo spectra correlate best with those of G2-to-G5 supergiants, which have effective temperatures of around 5,000 kelvin. In contrast to the class of extragalactic outbursts assumed to be analogues of the Great Eruption of η Carinae, the effective temperature of its outburst is significantly lower than that allowed by standard opaque wind models. This indicates that other physical mechanisms such as an energetic blast wave may have triggered and influenced the eruption.

Primary hyperparathyroidism in pregnancy-a rare cause of life-threatening hypercalcemia: case report and literature review.

Objective. To report a case of primary hyperparathyroidism in a pregnant patient, report the obstetric and neonatal outcomes, and review the relevant literature. Results. A 29-year-old primigravida was successfully treated for PHP with minimally invasive resection of a parathyroid adenoma in the second trimester of pregnancy. A healthy baby girl was delivered at 37-week gestation with an unremarkable neonatal course. To the best of our knowledge, this is the second case report in the literature utilizing intraoperative PTH during a parathyroidectomy in a pregnant woman. Conclusions. Primary hyperparathyroidism is a rare life-threatening condition that can present during pregnancy. The diagnosis can be difficult to establish during pregnancy, given the nonspecific symptoms related to hypercalcemia. However, a better understanding of the condition, improved diagnostic studies, and well-organized multidisciplinary management decisions can significantly reduce the morbidity and mortality associated with the disease during pregnancy. This case report is presented to highlight the value of early diagnosis and appropriate management of PHP during pregnancy.

Effects of vitamin D insufficiency on bone mineral density in African American men.

UNLABELLED: In African American men serum, 25-hydroxyvitamin D (25-OHD) was below 30 ng/ml in 89% of subjects. In overall group, there was no correlation between 25-OHD and bone mineral density (BMD). A subgroup analysis of subjects with 25-OHD

Intrasellar plasmacytoma presenting as a non-functional invasive pituitary macro-adenoma: case report & literature review.

We report an uncommon case of an intrasellar plasmacytoma presenting as a non-functional invasive pituitary macro-adenoma as the first manifestation of multiple myeloma. A 57 year old woman was referred to our department with a presumed diagnosis of a non-functioning pituitary macro-adenoma. She reported a 3 month history of headaches and a 2 week history of sudden onset of right facial numbness. Preoperative endocrine evaluation was remarkable only for a modestly elevated serum prolactin. A magnetic resonance imaging (MRI) scan revealed 3.6 x 5 x 4 cm enhancing homogeneous intrasellar mass with extension into the sphenoid and cavernous sinuses bilaterally; the optic chiasm was not displaced. She underwent transphenoidal surgery of the sellar lesion. The surgical specimen was heavily infiltrated with abnormal plasma cells, which stained almost exclusively for Kappa light chain immunoglobulins. An extensive investigation was undertaken to look for occult myelomatous disease. A diagnosis of multiple myeloma was made 1 month later based on a combination of clinical, pathological and radiologic features. She underwent radiation therapy directed towards the residual sellar tumor, followed by chemotherapy and autologous stem cell transplantation. Review of the world literature revealed only 22 previous reports of patients in whom a solitary plasmacytoma or multiple myeloma first presented as a sellar mass; in all cases mimicking clinically and radiologically a non-functioning invasive pituitary adenoma however with additional cranial nerve involvement. Intrasellar plasma cell tumors are rare tumors which may mimic non-functioning invasive pituitary tumors. The diagnosis should be suspected in patients with well preserved anterior pituitary function and cranial nerve neuropathies in the presence of significant sellar destruction.

Coronary calcification and osteoporosis in men and postmenopausal women are independent processes associated with aging.

The objective of this study was to investigate whether low bone mass is directly associated with the severity of coronary atherosclerosis in men and postmenopausal women self-referred for evaluation of coronary atherosclerosis and osteoporosis. Low bone mass was evaluated by measurement of bone mineral density (BMD) using quantitative computerized tomography (QCT). Coronary atherosclerosis was evaluated by measurement of coronary calcium (CC) burden using electron beam computerized tomography (EBCT). Using a cross-sectional design, we tested the hypothesis that osteoporosis and coronary atherosclerosis are correlated, age-dependent processes. Study variables were BMD, CC scores, and other known risk factors for osteoporosis and atherosclerosis. Qualifying for the study were 313 postmenopausal women and 167 men. Men had higher baseline CC scores and higher body mass indexes compared to women. In females, those patients with coronary calcification were older and had significantly lower BMD compared to those without calcification. In males, those patients with coronary calcification were older. By univariate correlation analysis, the degree of coronary calcification was inversely associated with BMD in postmenopausal women (P < 0.0001) but not in men. However, after controlling for age, this association was absent for both men and postmenopausal women. Using multivariate logistic regression analysis in women and men separately, age was the only significant predictor of positive CC status and low BMD. Our study suggests that in postmenopausal women and in men, after controlling for age, osteoporosis and coronary atherosclerosis are independent processes.

Utility of screening tools for the prediction of low bone mass in African American men.

INTRODUCTION: Osteoporosis remains under-diagnosed, particularly in African American men, despite the availability of reliable diagnostic tests. In women, several screening tools, including heel ultrasound and clinical assessment tools, reliably predict low bone mass, however the usefulness of these screening tools in African American men is unknown. The aim of this study was to determine the utility of screening tools, namely heel ultrasound, the osteoporosis self-assessment tool (OST), weight-based criterion (WBC) and body mass index (BMI), in screening for low bone mass in African American men. MATERIALS AND METHODS: African American men 35 years of age and older were invited to participate. The OST risk index is a score based on age and weight [(weight in kilograms--age in years)x0.2]. Bone mineral density (BMD) of the heel was measured by heel ultrasound, and BMD of both the lumbar spine and hip were determined by dual energy X-ray absorptometry (DXA). One hundred and twenty-eight men fulfilled the inclusion criteria for our study. RESULTS: The population prevalence of osteopenia and osteoporosis were 39% and 7%, respectively. Using a heel ultrasound T-score cut-off value of -1 or less, we predicted low bone mass (T-score of -2 or less at the hip) with a sensitivity of 83%, a specificity of 71% and an area under the curve (AUC) of 0.80. Using an OST cut-off value of 4, we predicted low bone mass with a sensitivity of 83%, a specificity of 57% and an AUC of 0.83. The OST risk index ranged from 18.1 to -6.1, based on which we categorized risk as: low, 5 or greater; moderate, 0-4; high, -1 or less. Of the men with a high-risk OST score, 87% had either osteopenia or osteoporosis based on World Health Organization (WHO) criteria. Using the WBC alone with a cut-off value of 85 kg, we predicted low bone mass with a sensitivity of 74%, a specificity of 50% and an AUC of 0.70. A BMI cut-off value of 30 or greater yielded a sensitivity of 83%, a specificity of 43% and an AUC of 0.70 for the diagnosis of low bone mass. DISCUSSION: The prevalence of osteopenia and osteoporosis were unexpectedly high in outpatient African American male veterans, who are considered to be at low risk for low bone mass. Heel ultrasound was able to predict low bone mass with sufficiently high sensitivity and specificity for use as a screening tool. Surprisingly, WBC and BMI proved ineffective in predicting low bone mass with adequate sensitivity and specificity. The OST, a clinical formula based on weight and age, appeared to be an easy and reliable screening tool for identifying men at high risk for low bone mass.

Effects of changes in pH and CO2 on pulmonary arterial wall tension are not endothelium dependent.

We examined the changes in isolated pulmonary artery (PA) wall tension on switching from control conditions (pH 7.38 +/- 0.01, PCO2 32.9 +/- 0.4 Torr) to isohydric hypercapnia (pH change 0.00 +/- 0.01, PCO2 change 24.9 +/- 1.1 Torr) or normocapnic acidosis (pH change -0.28 +/- 0.01, PCO2 change -0.3 +/- 0.04 Torr) and the role of the endothelium in these responses. In rat PA, submaximally contracted with phenylephrine, isohydric hypercapnia did not cause a significant change in mean (+/- SE) tension [3.0 +/- 1.8% maximal phenylephrine-induced tension (Po)]. Endothelial removal did not alter this response. In aortic preparations, isohydric hypercapnia caused significant (P < 0.01) relaxation (-27.4 +/- 3.2% Po), which was largely endothelium dependent. Normocapnic acidosis caused relaxation of PA (-20.2 +/- 2.6% Po), which was less (P < 0.01) than that observed in aortic preparations (-35.7 +/- 3.4% Po). Endothelial removal left the pulmonary response unchanged while increasing (P < 0.01) the aortic relaxation (-53.1 +/- 4.4% Po). These data show that isohydric hypercapnia does not alter PA tone. Reduction of PA tone in normocapnic acidosis is endothelium independent and substantially less than that of systemic vessels.

Molecular recognition of a Salmonella trisaccharide epitope by monoclonal antibody Se155-4.

The binding site of monoclonal antibody Se155-4, which has been the object of successful crystallographic and antibody-engineering studies, is shown by solid-phase immunoassays to be complementary to a branched trisaccharide, alpha-D-Galp(1-->2) [alpha-D-Abep(1-->3)]-alpha-D-Manp(1, rather than to the tetrasaccharide repeating unit alpha-D-Galp(1-->2) [alpha-D-Abep(1-->3)]-alpha-D-Manp(1-->4) alpha-L-Rhap(1- of the bacterial antigen. Specificity for the 3,6-dideoxy-D-xylo-hexose (3,6-dideoxy-D-galactose) epitope present in Salmonella paratyphi B O-antigens was ensured by screening hybridoma experiments with glycoconjugates derived from synthetic oligosaccharides. Detailed epitope mapping of the molecular recognition by modified and monodeoxy oligosaccharide derivatives showed that complementary surfaces and three antibody-saccharide hydrogen bonds are essential for full binding activity. Both hydroxyl groups of the 3,6-dideoxy-D-galactose residue were obligatory for binding and consistent with the directional nature of their involvement in carbohydrate-protein hydrogen bonds; related tetrasaccharides built from the isomeric 3,6-dideoxyhexoses, 3,6-dideoxy-D-glucose, paratose, and 3,6-dideoxy-D-mannose, tyvelose were not bound by the antibody. Titration microcalorimetry measurements were consistent with the hydrogen-bonding map inferred from the crystal structure and suggest that the displacement of water molecules from the binding site accounts for the favorable entropy that accompanies binding of the native trisaccharide determinant. The protein sequences determined for the antibody VL and VH domains reveal somatic mutation of the VL germ line gene, implying that this antibody-binding site results from a mature antibody response.

Preliminary crystallographic analysis of a Fab specific for the O-antigen of Shigella flexneri cell surface lipopolysaccharide with and without bound saccharides.

The Fab of a monoclonal anti-carbohydrate antibody, SYA/J6 (IgG3, kappa, murine), raised against the O-polysaccharide antigen of the cell surface lipopolysaccharide of variant Y Shigella flexneri, a Gram negative bacterium, has been crystallized in the unliganded form and in complex with tri- and pentasaccharide antigens. The three crystal forms belong to the tetragonal space group P4(3)2(1)2, or P4(1)2(1)2, with very similar unit cell dimensions and an asymmetric unit that contains one molecule of about 50,000 Daltons, and a fourth crystal form belongs to monoclinic space group P2(1) that contains four molecules of Fab in an asymmetric unit. Whereas diffractions of these crystals on an area detector-rotating anode system extend to only about 3.5 A resolution, those measured using an imaging plate and synchrotron radiation at the Photon Factory facility extend to 2.5 A.

Probing the combining site of an anti-carbohydrate antibody by saturation-mutagenesis: role of the heavy-chain CDR3 residues.

The carbohydrate-binding site in Fab fragments of an antibody specific for Salmonella serogroup B O-polysaccharide has been probed by site-directed mutagenesis using an Escherichia coli expression system. Of the six hypervariable loops, the CDR3 of the heavy chain was selected for exhaustive study because of its significant contribution to binding-site topography. A total of 90 mutants were produced and screened by an affinity electrophoresis/Western blotting method. Those of particular interest were further characterized by enzyme immunoassay, and on this basis seven of the mutant Fabs were selected for thermodynamic characterization by titration microcalorimetry. With regard to residues that hydrogen bond to ligand through backbone interactions, Gly102H could not be substituted, while several side chains could be introduced at Gly100H and Tyr103H with relatively little effect on antigen binding. There was, however, a preference for nonpolar side chains at position 103H. Substitution of His101H with carboxylate and amide side chains gave mutants with binding affinities approaching that of the wild type; complete side-chain removal by mutation to Gly was tolerated with a 10-fold reduction in binding constant. Analysis of binding by titration microcalorimetry revealed some dramatic thermodynamic changes hidden by the similarity of the binding constants. Similar effects were observed with residue changes in an Arg-Asp salt-bridge at the base of the loop. These results indicate that alterations to higher affinity anti-carbohydrate antibodies are characterized by an enthalpy-entropy compensation factor which allows for fundamental changes in the nature of the binding interactions but impedes engineering for increases in affinity.

Preliminary crystal structure analysis of an Fab specific for a Salmonella O-polysaccharide antigen.

The Fab from an IgG1, lambda murine monoclonal antibody with specificity for the O-polysaccharide antigen of Salmonella typhimurium has been crystallized in the absence and presence of hapten. The conditions for crystal growth were vapor diffusion equilibration with 16 to 23% polyethylene glycol 8000 solutions. Data have been collected from crystals of the complex in space group P212121, a = 60.6 A, b = 111.3 A, c = 61.1 A, and refinement of a molecular replacement solution is underway.

Synthesis and expression in Escherichia coli of DNA encoding the murine lambda 1 chain of a monoclonal antibody specific for Salmonella serotype B O-antigen.

A 658 bp DNA sequence corresponding to the murine lambda 1 chain of a monoclonal antibody, Se155-4, specific for the Salmonella serotype B O-antigen, was designed using Escherichia coli preferred codons and chemically synthesized by ligation of synthetic fragments into a linearized plasmid followed by transformation into E. coli. A synthetic signal peptide (ompA) was fused to express the L chain as a free polypeptide into the periplasm of E. coli cells. After isolation and purification, heterologous recombination of the E. coli L chain with mouse H chain gave an active antigen-binding protein. The activity was 15-20% when compared to protein created by an equivalent association of isolated natural mouse L and H chains as measured by a direct EIA assay. In inhibition experiments with the polysaccharide antigen, the two proteins showed identical titration curves and 50% inhibition points, indicating comparable KA values.