Burkhardt Seifert

Hybridization and speciation

Hybridization has many and varied impacts on the process of speciation. Hybridization may slow or reverse differentiation by allowing gene flow and recombination. It may accelerate speciation via adaptive introgression or cause near‐instantaneous speciation by allopolyploidization. It may have multiple effects at different stages and in different spatial contexts within a single speciation event. We offer a perspective on the context and evolutionary significance of hybridization during speciation, highlighting issues of current interest and debate. In secondary contact zones, it is uncertain if barriers to gene flow will be strengthened or broken down due to recombination and gene flow. Theory and empirical evidence suggest the latter is more likely, except within and around strongly selected genomic regions. Hybridization may contribute to speciation through the formation of new hybrid taxa, whereas introgression of a few loci may promote adaptive divergence and so facilitate speciation. Gene regulatory networks, epigenetic effects and the evolution of selfish genetic material in the genome suggest that the Dobzhansky–Muller model of hybrid incompatibilities requires a broader interpretation. Finally, although the incidence of reinforcement remains uncertain, this and other interactions in areas of sympatry may have knock‐on effects on speciation both within and outside regions of hybridization.

Clinical Features and Outcomes of Takotsubo (Stress) Cardiomyopathy

BACKGROUND The natural history, management, and outcome of takotsubo (stress) cardiomyopathy are incompletely understood. METHODS The International Takotsubo Registry, a consortium of 26 centers in Europe and the United States, was established to investigate clinical features, prognostic predictors, and outcome of takotsubo cardiomyopathy. Patients were compared with age- and sex-matched patients who had an acute coronary syndrome. RESULTS Of 1750 patients with takotsubo cardiomyopathy, 89.8% were women (mean age, 66.8 years). Emotional triggers were not as common as physical triggers (27.7% vs. 36.0%), and 28.5% of patients had no evident trigger. Among patients with takotsubo cardiomyopathy, as compared with an acute coronary syndrome, rates of neurologic or psychiatric disorders were higher (55.8% vs. 25.7%) and the mean left ventricular ejection fraction was markedly lower (40.7±11.2% vs. 51.5±12.3%) (P<0.001 for both comparisons). Rates of severe in-hospital complications including shock and death were similar in the two groups (P=0.93). Physical triggers, acute neurologic or psychiatric diseases, high troponin levels, and a low ejection fraction on admission were independent predictors for in-hospital complications. During long-term follow-up, the rate of major adverse cardiac and cerebrovascular events was 9.9% per patient-year, and the rate of death was 5.6% per patient-year. CONCLUSIONS Patients with takotsubo cardiomyopathy had a higher prevalence of neurologic or psychiatric disorders than did those with an acute coronary syndrome. This condition represents an acute heart failure syndrome with substantial morbidity and mortality. (Funded by the Mach-Gaensslen Foundation and others; ClinicalTrials.gov number, NCT01947621.).

Outcome of pulmonary vascular disease in pregnancy: a systematic overview from 1978 through 1996

OBJECTIVES Published reports were reviewed to evaluate the characteristics of peripartal management and the late pregnancy outcome in women with pulmonary vascular disease (PVD). BACKGROUND Pulmonary hypertension poses one of the highest risks for maternal mortality, but actual data on the maternal and neonatal prognosis in this group are lacking. METHODS Reports published from 1978 through 1996 of Eisenmengers syndrome (n = 73), primary pulmonary hypertension (PPH) (n = 27) and secondary vascular pulmonary hypertension (SVPH) (n = 25) complicating late pregnancy were included and analyzed using logistic regression analysis. RESULTS Maternal mortality was 36% in Eisenmengers syndrome, 30% in PPH and 56% (p < 0.08 vs. other two groups) in SVPH. Except for three prepartal deaths due to Eisenmengers syndrome, all fatalities occurred within 35 days after delivery. Neonatal survival ranging from 87% to 89% was similar in the three groups. Previous pregnancies, timing of the diagnosis and hospital admission, operative delivery and diastolic pulmonary artery pressure were significant univariate (p < 0.05) maternal risk factors. Late diagnosis (p = 0.002, odds ratio 5.4) and late hospital admission (p = 0.01, odds ratio 1.1 per week of pregnancy) were independent predictive risk factors of maternal mortality. CONCLUSIONS In the last two decades maternal mortality was comparable in patients with Eisenmengers syndrome and PPH; however, it was relevantly higher in SVPH. Maternal prognosis depends on the early diagnosis of PVD, early hospital admission, individually tailored treatment during pregnancy and medical therapy and care focused on the postpartal period.

Outcome of cardiovascular surgery and pregnancy: A systematic review of the period 1984-1996 ☆ ☆☆

The outcomes of cardiovascular operations during pregnancy, at delivery, and post partum were reviewed from published material in the period 1984-1996. Surgery during pregnancy resulted in fetal-neonatal morbidity and mortality of 9% and 30%, respectively, and in maternal morbidity and mortality of 24% and 6%, respectively. Duration of pregnancy at surgery and duration and temperature of cardiopulmonary bypass did not influence fetal-neonatal outcome. Maternal complications and mortality of surgery immediately after delivery were 29% and 12%, respectively, and for surgery performed with a postpartum interval the respective rates were 38% and 14%. Hospitalization after week 27 of gestation and extreme emergency contributed significantly to poor maternal outcome. Maternal deaths were reported in 9% of valvular procedures and in 22% of aortic or arterial dissection repairs and pulmonary embolectomies. Fetal-neonatal risks of maternal surgery during pregnancy are high and unpredictable. Maternal risks of cardiovascular procedures during pregnancy are moderate, significantly increase if an operation is performed at or after delivery, and, overall, should be considered as higher than those in nonpregnant cardiovascular surgical patients.

Human CD271-Positive Melanoma Stem Cells Associated with Metastasis Establish Tumor Heterogeneity and Long-term Growth

Human melanoma is composed of distinct cell types reminiscent of neural crest derivatives and contains multipotent cells that express the neural crest stem cell markers CD271(p75(NTR)) and Sox10. When isolated from solid tumors by using a method that leaves intact cell surface epitopes, CD271-positive, but not CD271-negative, cells formed tumors on transplantation into nude or nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. These tumors fully mirrored the heterogeneity of the parental melanoma and could be passaged more than 5 times. In contrast, in more immunocompromised NOD/SCID/IL2rγ(null) mice, or in natural killer cell-depleted nude or NOD/SCID mice, both CD271-positive and CD271-negative tumor cell fractions established tumors. However, tumors resulting from either fraction did not phenocopy the parental tumors, and tumors derived from the CD271-negative cell fraction could not be passaged multiple times. Together, our findings identify CD271-positive cells as melanoma stem cells. Our observation that a relatively high frequency of CD271/Sox10-positive cells correlates with higher metastatic potential and worse prognosis further supports that CD271-positive cells within human melanoma represent genuine cancer stem cells.

Paravalvular leakage after mitral valve replacement: improved long-term survival with aggressive surgery?

BACKGROUND Following mitral valve replacement, surgical closure of paravalvular leaks is usually advised in severely symptomatic patients and in those requiring blood transfusions for persisting haemolysis. However, the long-term prognosis of less symptomatic patients or those not needing blood transfusions is unknown. METHODS Between 1987 and 1997, we observed 96 patients with mitral paravalvular leakage. A paraprosthetic leak was diagnosed after a median time of 119 days (range: 1 day-23 years) after primary mitral valve replacement. During an average follow-up of 5 years (range: 1-23 years), 50/96 patients were referred for surgical closure. RESULTS Compared with patients who received conservative treatment, those referred for surgery had a significantly lower mean preoperative haematocrit (P = 0.002) with a higher proportion of patients being in the NYHA class III/IV (P = 0.03). Age, gender, left ventricular function and number and size of leaks did not differ between the groups. The 30-day postoperative mortality for valve reoperation was 6% (3/50); during follow-up three further patients died, resulting in an overall mortality rate of 12%. In the group treated conservatively there was a mortality rate of 26% (12/46). Thus, the actuarial survival for patients referred for surgery was 98, 90 and 88% after 1, 5 and 10 years, compared with 90, 75 and 68% for patients treated conservatively (long-rank P = 0.03). In addition, there was a significant increase in mean haematocrit levels (P = 0.0001) and an improvement in NYHA class III/IV symptoms (P = 0.002), vertigo (P = 0.001) and fatigue (P = 0.001) after surgery. CONCLUSIONS Following mitral valve replacement, a more aggressive surgical treatment is recommended for patients with paraprosthetic leaks. Surgery should be offered to less symptomatic patients, as well as those not requiring blood transfusion.

Value of (18F)-FDG positron emission tomography, computed tomography, and magnetic resonance imaging in diagnosing primary and recurrent ovarian carcinoma

Abstract. The aim of this study was to compare prospectively the accuracy of whole-body positron emission tomography (PET), CT and MRI in diagnosing primary and recurrent ovarian cancer. Nineteen patients (age range 23–76 years) were recruited with suspicious ovarian lesions at presentation (n = 8) or follow-up for recurrence (n = 11). All patients were scheduled for laparotomy and histological confirmation. Whole-body PET with FDG, contrast-enhanced spiral CT of the abdomen, including the pelvis, and MRI of the entire abdomen were performed. Each imaging study was evaluated separately. Imaging findings were correlated with histopathological diagnosis. The sensitivity, specificity and accuracy for lesion characterization in patients with suspicious ovarian lesions (n = 7) were, respectively: 100, 67 and 86 % for PET; 100, 67 and 86 % for CT; and 100, 100 and 100 % for MRI. For the diagnosis of recurrent disease (n = 10), PET had a sensitivity of 100 %, specificity of 50 % and accuracy of 90 %. The PET technique was the only technique which correctly identified a single transverse colon metastasis. Results for CT were 40, 50 and 43 %, and for MRI 86, 100 and 89 %, respectively. No statistically significant difference was seen. Neither FDG PET nor CT nor MRI can replace surgery in the detection of microscopic peritoneal disease. No statistically significant difference was observed for the investigated imaging modalities with regard to lesion characterization or detection of recurrent disease; thus, the methods are permissible alternatives. The PET technique, however, has the drawback of less accurate spatial assignment of small lesions compared with CT and MRI.

HIV-Specific Differences in Outcome of Squamous Cell Carcinoma of the Anal Canal: A Multicentric Cohort Study of HIV-Positive Patients Receiving Highly Active Antiretroviral Therapy

PURPOSE To define clinical outcome after definitive chemoradiotherapy (CRT) of anal carcinoma in HIV-infected patients treated with highly active antiretroviral therapy (HAART). PATIENTS AND METHODS A multicentric cohort comparison of 40 HIV-positive patients with HAART and 81 HIV-negative patients treated with radiotherapy (RT) or CRT was retrospectively performed. Local disease control (LC), relapse-free survival (RFS), overall survival (OS), cancer-specific survival (CSS), toxicity, and prognostic factors were investigated. RESULTS HIV-positive patients were younger (mean age, 48 v 62 years; P < .0005), predominantly male (93% v 25%; P < .0005), and with early-stage (P = .06) and large-cell histology (90% v 67%; P = .005) disease. RT or CRT resulted in complete response in 92% (HIV positive) and 96% (HIV negative) of cases. Five-year OS was 61% (95% CI, 44% to 78%) in HIV-positive and 65% (95% CI, 53% to 77%) in HIV-negative patients (median follow-up, 36 months). Five-year LC was 38% (95% CI, 5% to 71%) in HIV-positive and 87% (95% CI, 79% to 95%) in HIV-negative patients (P = .008) compromising CSS and sphincter preservation. Grade 3/4 acute skin (35% v 17% [HIV negative]; P = .04) and hematologic (33% v 12% [HIV negative]; P = .08) toxicity together approximated 50% in HIV-positive patients. RFS in HIV-positive patients was associated with RT dose (P = .08) and severe acute skin toxicity (P = .04). CONCLUSION Long-term LC and acute toxicity represent major clinical challenges in HIV-positive patients with anal carcinoma. Even if fluoropyrimidine-based CRT is feasible and may result in similar response rates and OS as in HIV-negative patients, improved treatment strategies with better long-term outcome are warranted.

Hemodilution tolerance in patients with coronary artery disease who are receiving chronic beta-adrenergic blocker therapy

Hemodilution tolerance is not well defined in patients with coronary artery disease receiving beta-adrenergic blockers chronically. Ninety patients scheduled for coronary artery bypass graft (CABG) surgery were randomized to a hemodilution (n = 60) and a control group (n = 30). During midazolam-fentanyl anesthesia, hemodynamic variables, ST segment deviation, and O2 consumption were determined prior to and after 6 and 12 mL/kg isovolemic exchange of blood for 6% hydroxyethyl starch. Hemoglobin decreased from 12.6 +/- 0.2 to 9.9 +/- 0.2 g/dL (mean +/- SEM, P < 0.05). With stable filling pressures, cardiac index increased from 2.05 +/- 0.05 to 2.27 +/- 0.05 L centered dot min-1 centered dot m-2 (P < 0.05) and O2 extraction from 27.4% +/- 0.6% to 31.2% +/- 0.7% (P < 0.05), resulting in stable O2 consumption. No alterations in ST segments were observed in leads II and V5 during hemodilution. Individual increases in cardiac index and O2 extraction were not linearly related to age and left ventricular (LV) ejection fraction (P = 0.841, P = 0.799). We conclude that isovolemic hemodilution to a hemoglobin value of 9.9 +/- 0.2 g/dL is well tolerated and fully compensated in patients with coronary artery disease receiving beta-adrenergic blockers chronically. Within the investigated ranges, the compensatory mechanisms during hemodilution are largely independent of age (35-81 yr) and LV ejection fraction (26%-83%). (Anesth Analg 1996;82:687-94)

Citrate storage affects Thrombelastograph® analysis

Background Thrombelastograph® analysis (TEG®) is used to evaluate blood coagulation. Ideally, whole blood is immediately processed. If impossible, blood may be citrated and assessed after recalcification. No data describe the effect of such treatment and storage on TEG® parameters. Methods Three studies were performed in 90 surgical patients. In 30 patients, blood was citrated (1:10, 0.129 M) and recalcified (20 &mgr;l 2 M CaCl2 to 340 &mgr;l citrated blood), and TEG® was performed with native blood and after recalcification after 0, 15, and 30 min of citrate storage. In another 30 patients, TEG® was performed with citrated blood recalcified immediately and after 1–72 h storage. In a third study, thrombin–antithrombin complex, prothrombin fragment 1+2, and &bgr;-thromboglobulin were measured (using enzyme-linked immunoabsorbant assay tests) at corresponding time points. Data were compared using repeated-measures analysis of variance and post hoc paired t tests. Results TEG® parameters were different in recalcified citrated blood compared with native blood (P < 0.05) and changed significantly during 30-min (P < 0.025) and 72-h (P < 0.001) citrate storage. TEG® parameters measured between 1 and 8 h of citrate storage were stable. Thrombin–antithrombin complex and prothrombin fragment 1+2 values were not elevated in native blood. After 30 min of citrate storage a gradual thrombin activation was observed, as evidenced by increasing thrombin–antithrombin complex and prothrombin fragment 1+2 values (P < 0.05). &bgr;-Thromboglobulin level was increased after 2 and 8 h of citrate storage (P < 0.01). Conclusions Analysis of native blood yields the most reliable TEG® results. Should immediate TEG® processing not be possible, citrated blood may be used if recalcified after 1–8 h.