Life-history strategies of the rock hind grouper Epinephelus adscensionis at Ascension Island.

Epinephelus adscensionis sampled from Ascension Island, South Atlantic Ocean, exhibits distinct life-history traits, including larger maximum size and size at sexual maturity than previous studies have demonstrated for this species in other locations. Otolith analysis yielded a maximum estimated age of 25 years, with calculated von Bertalanffy growth parameters of: L∞ = 55·14, K = 0·19, t0 = -0·88. Monthly gonad staging and analysis of gonad-somatic index (IG ) provide evidence for spawning from July to November with an IG peak in August (austral winter), during which time somatic growth is also suppressed. Observed patterns of sexual development were supportive of protogyny, although further work is needed to confirm this. Mean size at sexual maturity for females was 28·9 cm total length (LT ; 95% C.I. 27·1-30·7 cm) and no females were found >12 years and 48·0 cm LT , whereas all confirmed males sampled were mature, >35·1 cm LT with an age range from 3 to 18 years. The modelled size at which 50% of individuals were male was 41·8 cm (95% C.I. 40·4-43·2 cm). As far as is known, this study represents the first comprehensive investigation into the growth and reproduction of E. adscensionis at its type locality of Ascension Island and suggests that the population may be affected less by fisheries than elsewhere in its range. Nevertheless, improved regulation of the recreational fishery and sustained monitoring of abundance, length frequencies and life-history parameters are needed to inform long-term management measures, which could include the creation of marine reserves, size or temporal catch limits and stricter export controls.

Cardiac manifestations of subarachnoid hemorrhage.

INTRODUCTION: Cardiac manifestations of intracranial subarachnoid hemorrhage patients include mild electrocardiogram variability, reversible left ventricular dysfunction (Takotsubo), non-ST elevation myocardial infarction, ST-elevation myocardial infarction and cardiac arrest, but their clinical relevance is unclear. The aim of the present study was to categorize the relative frequency of different cardiac abnormalities in patients with subarachnoid hemorrhage and determine the influence of each abnormality on outcome.  METHODS: A retrospective review of 617 consecutive patients who presented with non-traumatic aneurysmal subarachnoid hemorrhage at our institution was performed. A cohort of 87 (14.1%) patients who required concomitantly cardiological evaluation was selected for subgroup univariate and multi-variable analysis of radiographic, clinical and cardiac data.  RESULTS: Cardiac complications included myocardial infarction arrhythmia and congestive heart failure in 47%, 63% and 31% of the patients respectively. The overall mortality of our cohort (23%) was similar to that of national inpatient databases. In our cohort a high World Federation of Neurosurgical Surgeons grading scale and a troponin level >1.0 mcg/L were associated with a 33 times and 10 times higher risk of death respectively. CONCLUSIONS: Among patients suffering from cardiac events at the time of aneurysmal subarachnoid hemorrhage, those with myocardial infarction and in particular those with a troponin level greater than 1.0 mcg/L had a 10 times increased risk of death. 

Outcomes of adult orthotopic heart transplantation with extended allograft ischemic time.

BACKGROUND: Heart procurement for orthotopic heart transplant (OHT) is limited by the conventional 4 hours of ischemic time (IT). Based on a recent report from our center showing that extended IT from a young donor group is safe, we widened our geographical reach, resulting in almost 40% of our transplants having an IT > 4 hours. METHODS: We retrospectively reviewed records of adult patients who underwent OHT from January 2006 to December 2011. The primary outcome was survival, and secondary outcomes included resource utilization, end-organ dysfunction, and acute cellular rejection. Overall survival was analyzed using Kaplan-Meier curves and log-rank tests. Secondary outcomes were compared with a combination of parametric and nonparametric statistics. RESULTS: A total of 323 patients underwent OHT. There was a significant difference in overall survival between the standard and extended IT groups (85.7% vs 76.4%, P = .03). There were no significant differences between the groups for secondary outcomes except a higher incidence of liver dysfunction in the extended IT group (84.9% vs 73%, P = .01). Further analysis revealed that mortality remains similar if IT is below 4 hours and between 4 and 5 hours, but begins to climb after 5 hours, driving the difference between our standard and extended IT. CONCLUSIONS: Limited donor availability for OHT dictates alternative strategies to enlarge the donor pool. Although there is an overall increasing risk with extended IT beyond 4 hours, it may be possible to safely increase the threshold to at least 5 hours without compromising the outcomes.

Physicians' intentions to change pap smear frequency following human papillomavirus vaccination.

STUDY OBJECTIVE: We evaluated factors associated with physicians' intentions to perform Pap smears in human papillomavirus-vaccinated women. DESIGN: Physicians were mailed a survey asking about intentions to change cervical cancer screening based on patients' human papillomavirus vaccination status. PARTICIPANTS: A national sample of 1,738 Family Physicians, Internal Medicine Physicians, Pediatricians, and Obstetricians and Gynecologists was selected from the American Medical Association Physician Masterfile. Completed surveys were received from 1,118 physicians, of which 791 were included in the analyses. MAIN OUTCOME MEASURES: Bivariate analyses compared physician, practice, and patient characteristics by intention change screening frequency. Significant variables were included in a multivariable logistic regression model. RESULTS: Overall, 81.8% (n = 647) of physicians reported not planning to change Pap smear frequency for vaccinated women. Internal Medicine physicians were significantly more likely than Obstetrician/Gynecologists to report intentions to change frequency for vaccinated patients. Other factors significantly associated with the intention to change frequency were self-identification as a late adopter of new vaccines, a solo practice, and practicing primarily in a clinic or hospital-based setting. CONCLUSIONS: Although it appears most clinicians understand that human papillomavirus vaccination should not alter current screening practices, there is a need to develop and evaluate interventions for physicians who are likely to change their screening pattern based on human papillomavirus vaccination receipt.

The lost art of intubation: assessing opportunities for residents to perform neonatal intubation.

OBJECTIVE: The objective of this study is to assess the opportunities afforded to and competence of pediatric residents in performing neonatal endotracheal intubations. STUDY DESIGN: The records of all intubations performed on neonates over a 3-year period at a university-based birthing hospital were reviewed to assess the relationships between outcomes, types of providers and the setting of intubations. RESULT: A total of 785 attempts were made during 362 intubations. Pediatric residents were given the opportunity to intubate 38% of the cohort (n=137) and were successful on 21% of the attempts. Residents were more likely to perform intubation in the neonatal intensive care unit (vs delivery room; P<0.001), in non-emergency situations (P<0.001), and on older (P<0.001) and larger (P=0.07) infants. CONCLUSION: Opportunities for residents to intubate neonates were few and their success rate was low. In the current care paradigm, it is doubtful if trainees can be sufficiently skilled in endotracheal intubation during residency. Residents that plan to pursue procedure-intensive subspecialties may benefit from other models for training.

Follow-up of 1715 SNPs from the Wellcome Trust Case Control Consortium genome-wide association study in type I diabetes families.

The advent of genome-wide association (GWA) studies has revolutionized the detection of disease loci and provided abundant evidence for previously undetected disease loci that can be pooled together in meta-analysis studies or used to design follow-up studies. A total of 1715 SNPs from the Wellcome Trust Case Control Consortium GWA study of type I diabetes (T1D) were selected and a follow-up study was conducted in 1410 affected sib-pair families assembled by the Type I Diabetes Genetics Consortium. In addition to the support for previously identified loci (PTPN22/1p13; ERBB3/12q13; SH2B3/12q24; CLEC16A/16p13; UBASH3A/21q22), evidence supporting two new and distinct chromosome locations associated with T1D was observed: FHOD3/18q12 (rs2644261, P=5.9 x 10(-4)) and Xp22 (rs5979785, P=6.8 x 10(-3); http://www.T1DBase.org). There was independent support for both SNPs in a GWA meta-analysis of 7514 cases and 9045 controls (P values=5.0 x 10(-3) and 6.7 x 10(-6), respectively). The chromosome 18q12 region contains four genes, none of which are obvious functional candidate genes. In contrast, the Xp22 SNP is located 30 kb centromeric of the functional candidate genes TLR8 and TLR7 genes. Both TLR8 and TLR7 are functional candidate genes owing to their key roles as pathogen recognition receptors and, in the case of TLR7, overexpression has been associated directly with murine autoimmune disease.

Analysis of 55 autoimmune disease and type II diabetes loci: further confirmation of chromosomes 4q27, 12q13.2 and 12q24.13 as type I diabetes loci, and support for a new locus, 12q13.3-q14.1.

A candidate gene study was conducted on 10 established type II diabetes genes and 45 genes associated with autoimmune diseases, including type I diabetes (T1D), in a maximum of 1410 affected sib-pair families assembled by the Type I Diabetes Genetics Consortium. Associations at P values <10(-3) were found for three known T1D regions at chromosomes 4q27, 12q13.2 and 12q24.13 (http://www.T1DBase.org). Support was obtained for a newly identified T1D candidate locus on chromosome 12q13.3-12q14.1 (rs1678536/KIF5A: P=8.1 x 10(-3); relative risk (RR) for minor allele=0.89, 95% CI=0.82-0.97), which has a separate association from the previously reported T1D candidate locus ERBB3/12q13.2-q13.3. Our new evidence adds to that previously published for the same gene region in a T1D case-control study (rs1678542; P=3.0 x 10(-4); odds ratio (OR)=0.92, 95% CI=0.88-0.96). This region, which contains many genes, has also been associated with rheumatoid arthritis.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis presenting with diffusion MR imaging changes.

Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) presents with focal or diffuse nonenhancing MR imaging abnormalities in 50% of patients with SREAT during subacute exacerbation. Vasculitic changes in biopsy studies as well as the elevation of antithyroid antibodies and CSF protein suggests an inflammatory cause. We report the case of a patient with SREAT with changes on diffusion-weighted MR imaging, which improved with corticosteroid therapy and plasmapheresis, supporting the theory of inflammatory changes in exacerbation of presumptive SREAT.

Lack of isohemagglutinin production following minor ABO incompatible unrelated HLA mismatched umbilical cord blood transplantation.

While immune hemolysis due to donor isohemagglutinin (IH) production often complicates minor ABO incompatible peripheral blood hematopoietic stem cell transplantation (PBSCT), it is not known if this occurs with umbilical cord blood transplantation (UCBT). We compared IH production and hemolysis following minor ABO allogeneic PBSCT and UCBT. We reviewed 24 ABO minor incompatible allogeneic PBSCTs and 14 ABO minor incompatible UCBTs. Patients were evaluated for donor-derived IH by reverse ABO grouping. Evaluation of hemolysis was based on clinical and laboratory findings of anemia associated with increased RBC transfusion need, concomitant with the appearance of donor-derived IH. Of the 24 ABO minor incompatible allogeneic PBSCTs, 15 produced donor-derived IH from 6 to 88 days following transplantation, with seven of 15 patients exhibiting clinically evident hemolysis. There was no significant difference in days to leukocyte engraftment or infused CD34 cells in patients with or without donor-derived IH. None of the 14 patients receiving ABO incompatible UCBTs showed evidence of donor-derived IH following transplantation with a median follow-up of 60 days. We conclude that donor IHs are not produced in patients undergoing minor ABO incompatible UCBTs suggesting fundamental immunologic differences between allogeneic PBSCT and UCBT.

Common VKORC1 and GGCX polymorphisms associated with warfarin dose.

We report a novel combination of factors that explains almost 60% of variable response to warfarin. Warfarin is a widely used anticoagulant, which acts through interference with vitamin K epoxide reductase that is encoded by VKORC1. In the next step of the vitamin K cycle, gamma-glutamyl carboxylase encoded by GGCX uses reduced vitamin K to activate clotting factors. We genotyped 201 warfarin-treated patients for common polymorphisms in VKORC1 and GGCX. All the five VKORC1 single-nucleotide polymorphisms covary significantly with warfarin dose, and explain 29-30% of variance in dose. Thus, VKORC1 has a larger impact than cytochrome P450 2C9, which explains 12% of variance in dose. In addition, one GGCX SNP showed a small but significant effect on warfarin dose. Incorrect dosage, especially during the initial phase of treatment, carries a high risk of either severe bleeding or failure to prevent thromboembolism. Genotype-based dose predictions may in future enable personalised drug treatment from the start of warfarin therapy.

Consanguineous hemolytic uremic syndrome secondary to Escherichia coli O157:H7 infection treated with aggressive therapeutic plasma exchange.

We describe the successful management of an elderly husband and wife with Escherichia coli O157:H7 associated hemolytic uremic syndrome (HUS) treated with aggressive therapeutic plasma exchange (TPE) with replacement with fresh frozen plasma. Following twelve TPEs (three 1.5 volume; nine 1 volume), the husband's platelet count increased from 45 x 10(9)/L to 183 x 10(9)/L. Following ten 1.5 volume TPEs, the wife's platelet count increased from 30 x 10(9)/L to 193 x 10(9)/L. This is the first known occurrence of E. coli O157:H7 associated HUS in an elderly husband and wife successfully treated with aggressive TPE. We conclude that early, aggressive TPE should be considered and may be life-saving for E coli O157:H7 associated HUS in the elderly.

Pretransfusion compatibility testing for red blood cell administration.

The purpose of pretransfusion compatibility testing is to prevent incompatible red blood cell transfusions that could lead to immune mediated hemolytic transfusion reactions. Some hemolytic transfusion reactions may have serious sequelae including hemoglobinemia, disseminated intravascular coagulation, renal failure, and death. This article reviews the most comprehensive recent analyses of the laboratory methods used during pretransfusion compatibility testing in the United States. Most of the laboratory practice data have been published in the College of American Pathologists Transfusion Medicine Survey Sets and in a national survey called the Pre-Transfusion Testing Survey. This article couples and trends the data of these comprehensive surveys with an assessment of the literature to present the current practice of pretransfusion compatibility testing.

Massive blood transfusion.

Pediatricians in the hospital setting must frequently treat children who require massive transfusion (MT) in a variety of clinical situations ranging from major trauma to neonatal hyperbilirubinemia. After identifying the need for massive transfusion, the pediatrician must select the appropriate blood components. Different blood components have specific temperature, preservative, and time requirements for their storage. Changes, termed storage lesions, occur over time in blood components during storage; biochemical changes include decreased levels of 2,3-DPG, a decrease in pH, and an increase in supernatant potassium (K+) with a concurrent decrease in intracellular K+. These changes may affect the function and the viability of components. Additionally, physical changes such as deformation of the red cell membrane occur during storage. Knowledge of these storage lesions is necessary for the pediatrician to make the most appropriate decisions regarding the preparation and selection of components during MT. Serious complications of MT include hemostatic abnormalities, biochemical/metabolic abnormalities, hypothermia, mechanical injury and the effect of Rh incompatibility, each of which has a specific management response. Pediatricians need to be aware of the potential complications associated with massive transfusion, to take measures to prevent them when possible, to anticipate additional transfusion requirements, and to know how to manage them in the pediatric patient.

Pleomorphic liposarcoma: a clinicopathologic analysis of 19 cases.

Pleomorphic liposarcoma is a variant of liposarcoma defined morphologically by the presence of pleomorphic lipoblasts. Because of its rarity, there are limited studies with long-term follow-up information. Nineteen pleomorphic liposarcomas were studied. Unequivocal pleomorphic lipoblasts were required for inclusion. In each case, the following features were noted: tumor site; tumor size; tumor depth; predominant histologic pattern (epithelioid or malignant fibrous histiocytoma [MFH]-like); extent of necrosis (absent, less than 15%, or at least 15%); mitotic counts; treatment and clinical follow-up. Patients were 11 females and 8 males, aged 33-87 years (mean, 64.5 y; median, 70 y). Tumors involved the extremities (13 patients: intramuscular in 10, subcutaneous in 2, depth unknown in 1), retroperitoneum (4 patients), mediastinum (1 patient), and paratesticular region (1 patient). Size ranged from 4.5--31 cm (mean, 11.9 cm; median, 12.0 cm). Predominant pattern was epithelioid in 7 and MFH-like in 12. Necrosis was present in 15 (79%) and was extensive (36 15%) in 14 patients. Mitotic counts ranged from 0.2--3.4/10 high-power fields (mean, 1.4; median, 1.4) by the average-count method and from 1--6/10 high power fields by the highest count method (mean, 2.9; median, 3.0). All patients were treated surgically; 10 patients received adjuvant chemotherapy and/or radiation therapy. On follow-up of 18 patients (range, 2--129 mo; mean, 35.4 mo; median, 23 mo) nine (50%) were dead of disease (range, 2--48 mo; mean, 20.1 mo; median, 12 mo), one died of other causes 2 months after diagnosis, two were alive with disease, five were disease free, and one was alive at 129 months (tumor status unknown). Five had recurrences (range, 3--28 mo; mean, 14.4 mo; median, 8 mo), and four of five (80%) with recurrences were dead of disease. Metastases developed in eight patients (range, 4--48 mo; mean, 19.5 mo; median, 11.5 mo), most commonly to the lungs. In conclusion, pleomorphic liposarcoma is a rare tumor of adulthood that occurs most commonly in the deep, soft tissues of the extremities. It behaves as a high-grade sarcoma that frequently metastasizes, most commonly to the lungs. Although this tumor has a wide range of histologic appearances, no clinical or pathologic feature is predictive of a more aggressive clinical course.

Genetic control of pathogenic mechanisms in autoimmune demyelinating disease.

Multiple sclerosis is a disease of discrete phenotypes in different individuals. Animal models have been useful in identifying self-antigens that become the focus of autoimmune attack and genetic loci that control susceptibility to disease. We have previously demonstrated a role for Fas-dependent pathogenesis in the induction of EAE in B10.PL mice immunized with MBP. Others have indicated a Fas-independent mechanism predominates in SJL mice immunized with PLP. Here we compare the response of (B10.PLxSJL)F1 and parental mice under similar conditions for induction of EAE. The results indicate that immunodominance and dominant pathogenic mechanisms are both under genetic control, but can be inherited independently. The data also indicate that the dominant pathogenic mechanism can change during the course of disease in an individual. Elucidation of the genetic elements controlling pathogenesis during the course of disease would provide important information in designing therapeutic strategies for individuals in a heterogeneous patient population.

The role of fas ligand in vivo as a cause and regulator of pathogenesis.

Recent studies have significantly advanced our understanding of the physiological and pathogenic functions of Fas and Fas ligand (FasL) in vivo. In particular, roles for Fas-FasL interactions both in the induction and regulation of organ-specific autoimmune diseases have been defined and in some cases the specific targets and effectors of these interactions have been identified. Understanding the dynamic role of the Fas-FasL pathway in autoimmunity will provide insight into how best to modulate this interaction to achieve therapeutic benefits.

Dual role for Fas ligand in the initiation of and recovery from experimental allergic encephalomyelitis.

We have previously demonstrated a role for Fas and Fas ligand (FasL) in the pathogenesis of experimental allergic encephalomyelitis (EAE). However, using an active induction paradigm we could not distinguish between FasL expressed on activated CD4(+) T cells from that expressed on other inflammatory or resident central nervous system (CNS) cells. To address this issue, we have conducted reciprocal adoptive transfer experiments of nontransgenic or myelin basic protein-specific T cell receptor transgenic wild-type, lpr, or gld lymphocytes into congenic wild-type, lpr, and gld hosts. We found that FasL expressed on donor cells is important for the development of EAE, as FasL-deficient lymphocytes transfer attenuated disease. Furthermore, Fas expressed in the recipient animals is important for the progression of EAE, as clinical signs of disease in lpr recipients were dramatically attenuated after transfer of either wild-type or lpr T cells. Surprisingly, these experiments also identified CNS cells as a source of functional FasL. Host-derived FasL appears to be especially important in the recovery from EAE, as many gld recipients of wild-type lymphocytes develop prolonged clinical signs of disease. Thus it appears that FasL plays distinct roles in EAE during the initiation of and recovery from disease.