Lifetime Measurements of Excited States in

Lifetimes of the first excited 2^{+} and 4^{+} states in the extremely neutron-deficient nuclide ^{172}Pt have been measured for the first time using the recoil-distance Doppler shift and recoil-decay tagging techniques. An unusually low value of the ratio B(E2:4_{1}^{+}→2_{1}^{+})/B(E2:2_{1}^{+}→0_{gs}^{+})=0.55(19) was found, similar to a handful of other such anomalous cases observed in the entire Segré chart. The observation adds to a cluster of a few extremely neutron-deficient nuclides of the heavy transition metals with neutron numbers N≈90-94 featuring the effect. No theoretical model calculations reported to date have been able to explain the anomalously low B(E2:4_{1}^{+}→2_{1}^{+})/B(E2:2_{1}^{+}→0_{gs}^{+}) ratios observed in these cases. Such low values cannot, e.g., be explained within the framework of the geometrical collective model or by algebraic approaches within the interacting boson model framework. It is proposed that the group of B(E2:4_{1}^{+}→2_{1}^{+})/B(E2:2_{1}^{+}→0_{gs}^{+}) ratios in the extremely neutron-deficient even-even W, Os, and Pt nuclei around neutron numbers N≈90-94 reveal a quantum phase transition from a seniority-conserving structure to a collective regime as a function of neutron number. Although a system governed by seniority symmetry is the only theoretical framework for which such an effect may naturally occur, the phenomenon is highly unexpected for these nuclei that are not situated near closed shells.

Cancer effect on periprocedural thromboembolism and bleeding in anticoagulated patients.

BACKGROUND: Patients with active cancer are often on chronic anticoagulation and frequently require interruption of this treatment for invasive procedures. The impact of cancer on periprocedural thromboembolism (TE) and major bleeding is not known. PATIENTS AND METHODS: Two thousand one hundred and eighty-two consecutive patients referred for periprocedural anticoagulation (2484 procedures) using a standardized protocol were followed forward in time to estimate the 3-month incidence of TE, major bleeding and survival stratified by anticoagulation indication. For each indication, we tested active cancer and bridging heparin therapy as potential predictors of TE and major bleeding. RESULTS: Compared with patients without cancer, active cancer patients (n=493) had more venous thromboembolism (VTE) complications (1.2% versus 0.2%; P=0.001), major bleeding (3.4% versus 1.7%; P=0.02) and reduced survival (95% versus 99%; P<0.001). Among active cancer patients, only those chronically anticoagulated for VTE had higher rates of periprocedural VTE (2% versus 0.16%; P=0.002) and major bleeding (3.7% versus 0.6%; P<0.001). Bridging with heparin increased the rate of major bleeding in cancer patients (5% versus 1%; P=0.03) without impacting the VTE rate (0.7% versus 1.4%, P=0.50). CONCLUSIONS: Cancer patients anticoagulated for VTE experience higher rates of periprocedural VTE and major bleeding. Periprocedural anticoagulation for these patients requires particular attention to reduce these complications.

Predictors of major bleeding in peri-procedural anticoagulation management.

BACKGROUND: Appropriate periprocedural management for chronically anticoagulated patients requires assessment of patient-specific thrombosis and bleeding risks. However, predictors of post-procedure bleeding are unknown. OBJECTIVES: To determine the 3-month cumulative incidence and independent predictors of peri-procedural bleeding in chronically anticoagulated patients requiring temporary warfarin interruption for an invasive procedure. METHODS: In a protocol driven, cohort study design, all patients referred to the Mayo Clinic Thrombophilia Center for peri-procedural anticoagulation management (1997-2007; n = 2182), were followed forward in time to determine the 3-month cumulative incidence of peri-procedural bleeding (Kaplan-Meier product limit) and potential predictors of bleeding (Cox proportional hazards). Decisions to 'bridge' with low-molecular-weight heparin were based on estimated thromboembolism and bleeding risk. RESULTS: Indications for chronic anticoagulation included venous thromboembolism (38%), atrial fibrillation (30%) and mechanical heart valves (27%). Of these, 1496 (69%) patients received bridging therapy. The 3-month cumulative incidence rates of major and overall bleeding were 2.1% and 5.1%, respectively. Major bleeding occurred more frequently in patients receiving bridging therapy (3% vs. 1%; P = 0.017). Independent predictors (hazard ratio; 95% confidence interval) of major bleeding included mitral mechanical heart valve (2.2; 1.1-4.3), active cancer (1.8; 1.0-3.1), prior bleeding history (2.6; 1.5-4.5) and re-initiation of heparin therapy within 24 h after the procedure (1.9; 1.1-3.4). CONCLUSION: Factors predisposing to peri-procedural bleeding are primarily patient-specific. Premature heparin re-initiation is an avoidable provider-specific variable to consider.

Immediate intraocular pressure changes following intravitreal injections of triamcinolone, pegaptanib, and bevacizumab.

PURPOSE: To assess the intraocular pressure (IOP) changes, within the first 30 min after intravitreal injection of 0.1 ml (4 mg) triamcinolone, 0.09 ml (0.3 mg) pegaptanib, and 0.05 ml (1.25 mg) bevacizumab. METHODS: Records of patients who received intravitreal triamcinolone, pegaptanib, and bevacizumab and who had their IOP measured post-injection were reviewed. RESULTS: A total of 212 injections were performed (76 bevacizumab in 63 patients, 42 triamcinolone in 41 patients, 94 pegaptanib in 74 patients). At 10 min, over 87% of eyes receiving each drug had an IOP of less than 35 mmHg. Three of the 42 eyes receiving intravitreal triamcinolone were treated with IOP-lowering drops for pressures of 44, 46, and 60 mmHg. No patients treated with intravitreal bevacizumab or pegaptanib received IOP-lowering drops. The number of eyes in each injection group that had an IOP rise >10 mmHg within 30 min after injection was 27.6% of eyes receiving bevacizumab, 33.3% of eyes receiving triamcinolone, and 36.2% of eyes receiving pegaptanib. At 10 min, eyes with glaucoma were less likely to have an IOP<35 mmHg, but this difference became less marked with time. CONCLUSION: In our series, most patients receiving intravitreal injections did not require IOP-lowering drops after injection, and none required a paracentesis.

Body fat distribution, serum glucose, lipid and insulin response to meals in Alström syndrome.

BACKGROUND: Alström syndrome is an autosomal recessive condition characterized by obesity, insulin resistance and hypertriglyceridaemia. Responses to fat and carbohydrate ingestion are important in planning dietetic advice and may help to explain the mechanism of metabolic disorder in the syndrome. METHODS: After a 12-h fast, five Alström subjects received a 3.1 MJ (742 kcal), 75.8% fat breakfast on day 1, and a 3.3 MJ (794 kcal), 77.5% carbohydrate breakfast on day 2. Serum glucose, triglyceride and insulin levels were measured at baseline, and 2 and 3.5 h post-meal. Abdominal computerized tomography in three subjects and magnetic resonance imaging in one demonstrated distribution of abdominal fat. RESULTS: Body fat was distributed subcutaneously, as well as viscerally. There were no changes in serum glucose, insulin or triglycerides after the high fat meal. Triglycerides remained stable after the high carbohydrate meal but glucose and log insulin levels increased [8.4 +/- 4.1 to 13.4 +/- 6.9 mmol L(-1) (P < 0.05) and 2.6 +/- 0.27 to 3.15 +/- 0.42 pmol L(-1) (P < 0.05), respectively]. CONCLUSIONS: Dietetic advice in Alström syndrome must include calorie restriction to reduce obesity, which is predominantly subcutaneous. This study has shown that low carbohydrate advice may prove more effective than fat restriction in control of hyperglycaemia and hyperinsulinism. A single high energy meal does not exacerbate hypertriglyceridaemia.

Syndromic obesity and diabetes: changes in body composition with age and mutation analysis of ALMS1 in 12 United Kingdom kindreds with Alstrom syndrome.

CONTEXT: Alström syndrome (AS) is a monogenic form of infancy-onset obesity and insulin resistance, caused by ALMS1 mutations. The natural history of the insulin resistance is unknown, in particular how this relates to changes in body composition. It is also unclear how ALMS1 mutations relate to the characteristic phenotype. OBJECTIVES: Our objectives were to characterize body composition and metabolic parameters, to establish ALMS1 mutation spectrum of United Kingdom AS patients, and to determine whether a genotype-phenotype correlation exists. DESIGN AND PATIENTS: We conducted a cross-sectional cohort study of 12 unrelated subjects with AS. Age-standardized body composition was assessed by anthropometry and dual-energy x-ray absorptiometry and insulin sensitivity by homeostasis model assessment. The exons and intron-exon boundaries of ALMS1 were directly sequenced. SETTING: The study was performed during the annual Alström Syndrome UK multidisciplinary screening clinic. RESULTS: AS patients have early-onset obesity, but body mass index, waist circumference, and body fat from dual-energy x-ray absorptiometry were negatively correlated with age (r = -0.37, P = 0.2; r = -0.84, P = 0.002; and r = -0.6, P = 0.05). Despite this, insulin resistance increased, demonstrated by raised fasting insulin and fall in homeostasis model assessment insulin sensitivity with age (r = -0.64, P = 0.02). ALMS1 mutations were identified in 10 of 12 patients, with a potential founder mutation in exon 16 present in five [np 10775del (C); Del3592fs/ter3597]. No genotype-phenotype correlation was observed. CONCLUSIONS: We identified mutations in ALMS1 in more than 80% of patients with no genotype-phenotype correlation. In AS, severe childhood obesity, waist circumference, and body fat decrease with age, whereas insulin resistance increases. The abdominal obesity, insulin resistance, diabetes, hypertriglyceridemia, and hypertension suggest that AS could represent a monogenic model for the metabolic syndrome.

Cutaneous lymphosarcoma in a stallion.

Multiple cutaneous lymphosarcomas were diagnosed in an 8-year-old Thoroughbred stallion presented for evaluation of lumps on its scrotum. Histological examination of skin biopsy samples showed a homogenous pattern of lymphoid tissue suggestive of a T-cell lymphosarcoma. Immuno-histochemical tests showed a positive reaction to Rabbit/Anti-Human T-Cell, CD3 antibodies confirming T-cell lymphosarcoma. The animal was not treated and was subsequently euthanased.

Lack of involvement of known DNA methyltransferases in familial hydatidiform mole implies the involvement of other factors in establishment of imprinting in the human female germline.

BACKGROUND: Differential methylation of the two alleles is a hallmark of imprinted genes. Correspondingly, loss of DNA methyltransferase function results in aberrant imprinting and abnormal post-fertilization development. In the mouse, mutations of the oocyte-specific isoform of the DNA methyltransferase Dnmt1 (Dnmt1o) and of the methyltransferase-like Dnmt3L gene result in specific failures of imprint establishment or maintenance, at multiple loci. We have previously shown in humans that an analogous inherited failure to establish imprinting at multiple loci in the female germline underlies a rare phenotype of recurrent hydatidiform mole. RESULTS: We have identified a human homologue of the murine Dnmt1o and assessed its pattern of expression. Human DNMT1o mRNA is detectable in mature oocytes and early fertilized embryos but not in any somatic tissues analysed. The somatic isoform of DNMT1 mRNA, in contrast, is not detectable in human oocytes. In the previously-described family with multi-locus imprinting failure, mutation of DNMT1o and of the other known members of this gene family has been excluded. CONCLUSIONS: Mutation of the known DNMT genes does not underlie familial hydatidiform mole, at least in the family under study. This suggests that trans-acting factors other than the known methyltransferases are required for imprint establishment in humans, a concept that has indirect support from recent biochemical studies of DNMT3L.

Perceptions of mission-critical organizational resources: a survey of substance prevention and treatment agencies in the southwest.

This article explores administrator and staff perceptions of mission-critical agency capacity in a predominantly Hispanic region that has a high degree of acculturation and elevated use of alcohol, tobacco, and other drugs. The domains explored are financial resources, proposal development, agency policies, organizational structure, communication, leadership, planning, and networking capabilities. Although significant differences were found among all eight domains, both staff and administrators concurred regarding the two areas of least capacity--financial resources and proposal development--and the two areas of greatest capacity--planning and networking capabilities. The authors suggest that agreement about the ranking of the domains is the most important finding rather than the differences between administrators and staff. A discussion of the practice and educational implications concludes the article.

Comparison of Chen Medium and Optisol-GS for human corneal preservation at 4 degrees C: results of transplantation.

PURPOSE: To compare results after transplantation of donor corneas stored in Chen Medium (containing beta-hydroxybutyrate without sodium bicarbonate or chondroitin sulfate) to corneas stored in Optisol-GS medium (containing sodium bicarbonate and 2.5% chondroitin sulfate). METHODS: We performed 32 consecutive penetrating keratoplasties with donor corneas stored at 4 degrees C in either Chen Medium or Optisol-GS by random assignment. Corneal thickness measurements were made at 1 day, 1 week, 3 weeks, 2 months, and 1 year postkeratoplasty. Specular microscopic images of the donor endothelium were obtained at the beginning of storage and 2 months and 1 year postkeratoplasty. The percentage of intact epithelium 1 day after keratoplasty and the graft epithelialization time were estimated by the surgeons. Donor rim cultures were performed. RESULTS: No statistically significant differences in corneal thickness or endothelial cell loss between the corneas stored in the two media were found at any time, although differences of less than 12% cell loss or 0.09-mm thickness at 2 months or less than 25% cell loss or 0.10-mm thickness at 1 year could not be excluded with 90% certainty in this small series. The mean percentages of intact graft epithelium on day 1, 64% for Chen Medium and 65% for Optisol-GS, were not significantly different. Endothelial cell density 2 months postkeratoplasty was significantly decreased for corneas stored in both media. Endothelial cell loss at 2 months was directly correlated with storage time in both media. CONCLUSIONS: After keratoplasty, no statistically significant differences in corneal thickness, epithelial survival, and endothelial cell loss were found between corneas stored in Chen Medium and Optisol-GS. Endothelial cell loss at 2 months was significantly correlated with storage time in both media.

Interleukin-6 regulation of the human DNA methyltransferase (HDNMT) gene in human erythroleukemia cells.

Methylation of mammalian DNA by the DNA methyltransferase enzyme (dnmt-1) at CpG dinucleotide sequences has been recognized as an important epigenetic control mechanism in regulating the expression of cellular genes (Yen, R. W., Vertino, P. M., Nelkin, B. D., Yu, J. J., el-Deiry, W., Cumaraswamy, A., Lennon, G. G., Trask, B. J., Celano, P., and Baylin, S. B. (1992) Nucleic Acids Res. 20, 2287-2291; Ramchandani, S., Bigey, P., and Szyf, M. (1998) Biol. Chem. 379, 535-5401). Here we show that interleukin (IL)-6 regulates the methyltransferase promoter and resulting enzyme activity, which requires transcriptional activation by the Fli-1 transcription factor (Spyropoulos, D. D., Pharr, P. N., Lavenburg, K. R., Jackers, P., Papas, T. S., Ogawa, M., and Watson, D. K. (1998) Mol. Cell. Biol. 15, 5643-5652). The data suggest that inflammatory cytokines such as IL-6 may exert many epigenetic changes in cells via the regulation of the methyltransferase gene. Furthermore, IL-6 regulation of transcription factors like Fli-1, which can help to direct cells along opposing differentiation pathways, may in fact be reflected in part by their ability to regulate the methylation of cellular genes.

Keratometric results during the first year after keratoplasty: adjustable single running suture technique versus double running suture technique.

BACKGROUND AND OBJECTIVE: To compare the 3-month and 1-year postoperative keratometric results in a retrospective sequential series of corneal grafts performed with either a double running suture technique or an adjustable single running suture technique. MATERIALS AND METHODS: Keratometry values obtained 3 months and 1 year after penetrating keratoplasty, when sutures were still present, were compared between 31 grafts with double running sutures and 27 grafts with single running sutures, 15 of which had been adjusted postoperatively. RESULTS: No significant difference in mean keratometry between the 2 groups was found either 3 months or 12 months after keratoplasty. Mean keratometric astigmatism was significantly less in the single running group at both 3 months (2.2 +/- 1.9 vs 4.5 +/- 2.8, mean +/- SD, P <0.001) and 12 months (3.0 +/- 2.2 vs 4.2 +/- 2.1, P = 0.03). Within groups, there was no significant change from 3 months to 12 months in either mean keratometry or keratometric astigmatism. CONCLUSION: The single running suture technique, with postoperative adjustments, produced less keratometric astigmatism during the first postoperative year, when sutures were still in place.

Gender differences and temporal trends in clinical characteristics, stress test results and use of invasive procedures in patients undergoing evaluation for coronary artery disease.

OBJECTIVES: This study examined gender differences and temporal changes in the clinical characteristics of patients referred for nuclear stress imaging, their imaging results and subsequent utilization of coronary angiography and revascularization. BACKGROUND: Gender bias may influence resource utilization in patients with coronary artery disease (CAD). No study has analyzed gender differences and time trends in patients referred for noninvasive testing and subsequent use of invasive procedures. METHODS: Between January 1986 and December 1995, 14,499 patients (5,910 women and 8,589 men) without established CAD underwent stress myocardial perfusion imaging. The clinical characteristics, imaging results, coronary angiograms and revascularization outcomes were compared in women and men over time. RESULTS: The mean pretest probability of CAD was lower in women (45%) than in men (70%) (p < 0.001). More women (69%) than men (42%) had normal nuclear images (p < 0.001). Men (17%) were more likely than women (8%) to undergo coronary angiography (p < 0.001). Male gender was independently associated with referral for coronary angiography (multivariate model: chi-square = 16, p < 0.001) but was considerably weaker than the imaging variables (summed reversibility score: chi-square = 273, p < 0.001). Revascularization was performed in more men (46% of the population undergoing angiography) than women (39%) (p = 0.01), but gender was not independently associated with referral to revascularization. There were no significant differences in clinical, imaging or invasive variables between the genders over time. CONCLUSIONS: There was little evidence for a bias against women in this study. Women were somewhat less likely to undergo coronary angiography but were referred for stress perfusion imaging more liberally. Practice patterns remained constant over this 10-year period.

Spiritual assessment: a review of major qualitative methods and a new framework for assessing spirituality.

This article introduces a new qualitative spiritual assessment instrument. It reviews existing qualitative assessment tools and presents a new multidimensional spiritual assessment framework. The instrument consists of two components: a spiritual history in which consumers relate their spiritual life story in a manner analogous to a family history and an interpretive framework to assist practitioners in eliciting and synthesizing the full potentiality of strengths extant in clients' spiritual lives. Common spiritual strengths the framework is designed to evoke are discussed, and a number of interventions based on prevalent spiritual strengths are suggested.

Prediction of severe coronary artery disease and long-term outcome in patients undergoing vasodilator SPECT.

BACKGROUND: Vasodilator perfusion imaging has not been extensively evaluated for predicting severe coronary artery disease (CAD) or long-term prognosis. METHODS AND RESULTS: The goals of this study were to develop a model to predict left main/3-vessel CAD in patients undergoing vasodilator thallium 201 imaging and coronary angiography (angiographic population) and to test the long-term prognostic value of this model in a separate cohort of patients who were not referred for angiography (prognostic population). In the angiographic population (n = 653) the chi2 value of the clinical model (containing the variables age, sex, and prior myocardial infarction) in the prediction of severe CAD was 32. The addition of 3 vasodilator Tl-201 variables (magnitude of ST-segment depression, summed reversibility score, and increased lung uptake) increased the model chi2 value to 114 (P <.001). Only 9% of predicted low-risk patients versus 57% of predicted high-risk patients had severe CAD. In the prognostic population (n = 521) survival rates free of cardiac death or myocardial infarction at 7 years were 91%, 73%, and 51%, respectively, for patient groups predicted to be at low, intermediate, and high risk of severe CAD (P <.001). CONCLUSIONS: Clinical and vasodilator Tl-201 variables can accurately predict the risk of severe CAD. Stress Tl-201 variables add incremental information to clinical variables. The same model also predicts patient outcome.

Degradation of albumin in meningococcal sepsis.

We postulate that the proteolytic degradation of albumin into fragments could link the rapidity of the shock, rash, and hypocalcaemia associated with meningococcal sepsis. We examined urine of children with meningococcal disease and urine from control children with no sepsis and found albumin fragments of about 45 kDa, 25 kDa, and less than 20 kDa only in the urine of children with meningococcal sepsis and associated purpura. Exogenous or endogenous proteases, or both, may be released in severe meningococcal sepsis and, in association with an inadequate antiprotease response, result in albumin degradation. This may be a contributory factor to the rapid shock, hypocalcaemia, and rash seen in meningococcal sepsis.

Predictors of macrovascular disease in patients with type 2 diabetes mellitus.

OBJECTIVE: To assess the importance of classic and nonclassic risk factors in the development of coronary artery disease (CAD) or cerebrovascular disease (CVD) in patients with type 2 diabetes mellitus (DM). PATIENTS AND METHODS: In this community-based, prospective cohort study, quantitative measurements for cholesterol, triglycerides (TGs), glucose, and lipoprotein(a) detected as a sinking pre-beta-lipoprotein band on electrophoresis were obtained from 1968 through 1982 from 449 patients who were free of CAD and CVD but had type 2 DM. Demographic data and covariables obtained were age, body mass index, duration of diabetes, sex, smoking, and hypertension. The relationship of individual continuous factors to the development of CAD and CVD as well as multivariate models were evaluated with use of the Cox proportional hazards model. The primary outcome was to determine which risk factors are associated with development of CAD or CVD in patients with type 2 DM. RESULTS: After a mean follow-up of 13 years, 216 CAD and 115 CVD events had developed. The hazard ratio estimates with 95% confidence intervals (CIs) for CAD after multivariate analysis were significant for age, 1.45 (95% CI, 1.27-1.67); fasting glucose levels at enrollment, 1.63 (95% CI, 1.17-2.25); smoking, 1.45 (95% CI, 1.10-1.91); and TGs, 1.49 (95% CI, 1.15-1.92). The hazard ratio estimates for CVD were significant for age, 1.95 (95% CI, 1.59-2.38); hypertension, 1.89 (95% CI, 1.30-2.74); fasting glucose levels at enrollment, 1.69 (95% CI, 1.06-2.70); and smoking, 1.57 (95% CI, 1.07-2.30). CONCLUSION: In diabetic patients, age, fasting glucose levels, smoking, and TG levels are independent risk factors for development of CAD events. Age, hypertension, glucose, and smoking predicted development of CVD events.

The long-term outcome of glaucoma filtration surgery.

PURPOSE: To determine the long-term outcome of glaucoma filtration surgery in preserving vision. Visual loss from progressive glaucomatous damage and from complications of surgery, both short and long term, were included. METHODS: A retrospective, community-based, longitudinal study of residents of Olmsted County, Minnesota, who were newly diagnosed with open-angle glaucoma between 1965 and 1980 and underwent filtration surgery in these or subsequent years through 1998. Intraocular pressure (IOP), visual acuity, visual fields, and progression to legal blindness were monitored. Kaplan-Meier analysis was used to determine the cumulative probabilities of changes in these parameters. RESULTS: 73 eyes of 49 patients underwent conventional filtration surgery. Analysis of the first eye having surgery revealed a mean preoperative IOP of 27.6 +/- 8.5 mm dropping to 16.7 +/- 5.6 mm at year one, and remaining in this range throughout follow-up (14.7 +/- 3.0 mm at 10 years; with or without use of medications). The probability of progression to blindness was 46% at 10 years after surgery, as calculated by Kaplan-Meier analysis. Eyes going blind had a postoperative IOP equal to or lower than those not becoming blind (14.0 +/- 4.4 vs. 15.4 +/- 3.0 at postoperative year 10). Eyes going blind had more advanced field loss at the time of surgery, with scotomas above and below the horizontal axis, than eyes not going blind, which had scotomas in only one hemifield. Three patients developed late bleb leaks; two patients developed endophthalmitis. The probability of undergoing cataract surgery was 37% by 10 years postoperatively, which did not differ significantly from the cohort of patients not undergoing surgery at a comparable time point. CONCLUSIONS: Filtration surgery was associated with a 54% probability of preservation of vision from progression to legal blindness at 10 years after surgery. Patients becoming blind had more advanced field loss at the time of surgery; IOP was similar between those going blind and those retaining vision.