The effect of feeding adequate or deficient vitamin B6 or folic acid to breeders on methionine metabolism in 18-day-old chick embryos.

Three isotopic tracers ([2,3,3-2H3]-L-serine, [2H11]-L-betaine, and [1-13C]-L-methionine) were administered by amnion injection into 18-day-old chick embryos to investigate the kinetics of methionine metabolism. The embryos utilized were from eggs collected from 34-week-old Cobb 500 broiler breeders that were fed either a control diet containing folic acid (1.25 mg/kg diet) and pyridoxine HCl (5 mg/kg diet) or diets devoid of supplemental pyridoxine or folic acid. Intermediate metabolites of methionine metabolism and polyamines were analyzed in 18-day-old chick embryos. There were no differences in hepatic [2H2] methionine or [2H3] cysteine enrichments or in physiological concentrations of sulfur amino acids for chick embryos from breeders fed the control diet and embryos from breeders fed diets containing no pyridoxine or folic acid. Supplementation of B6 or folic acid did not affect the production of methionine and cysteine in chick embryos. However, breeders fed the control diet with both folic acid and pyridoxine supplementation produced embryos with a two-fold reduction of hepatic homocysteine and increased spermine compared with embryos from breeders fed diets containing no supplemental pyridoxine or folic acid (P < 0.05). Hepatic S-adenosylmethionine for embryos from breeders fed no supplemental B6 was half the concentration compared with embryos from breeders fed the control diet. Embryos from breeders fed the control diet were utilized to determine the proportion of homocysteine going through remethylation and transsulfuration and also to determine the pathway of remethylation. Sixty-five percent of the methyl groups used for homocysteine remethylation from control embryos was via the MFMT pathway. Alternatively, 61% of homocysteine from control embryos was remethylated via the MFMT and the BHMT reactions and 39% of homocysteine was catabolized to cysteine via the transsulfuration pathway. These data show that in embryos, intermediate metabolites of methionine and polyamines increase in concentration when pyridoxine levels are provided in deficient concentrations to the breeder hen. In addition, this research demonstrates that folic acid deficient embryos conserve methionine, rather than catabolize it to cysteine.

[Finger pain and personality changes after chemotherapy initiation via a central venous port system in a 67-year-old female patient]. / Fingerschmerz und Wesensveränderungen nach Chemotherapieeinleitung über einen Portkatheter bei einer 67-jährigen Patientin.

Central venous port systems are an integral part of chemotherapy. Early recognition and management of arterial malposition are crucial to prevent further complications. A 67-year-old female with breast cancer underwent central venous port implantation for adjuvant chemotherapy. After administration of the first chemotherapy the patient developed acute bihemispheric cerebral infarction and myocardial ischemia due to arterio-arterial emboli with a toxic encephalopathic component. After systemic lysis and surgical removal of the central venous port system, the patient showed a complete recovery.

Skills, expertise and role of Australian emergency clinicians in caring for people with advanced cancer.

OBJECTIVES: To explore the views of Australian emergency department (ED) clinicians about their skills, role and expertise in caring for people with advanced cancer. METHODS: A cross-sectional electronic survey of doctors and nurses working in Australian EDs was undertaken. Comparisons were made by demographics and whether respondents had received palliative care education. RESULTS: The sample comprised 444 doctors (response rate 13.5%), the majority Fellows (emergency medicine specialists) of the Australasian College for Emergency Medicine, and 237 nurses, from all states, territories and regions (metropolitan and regional). A minority (n=123, 20.6%) felt that the ED was not an appropriate place for patients with advanced cancer to present for acute care, while almost two-thirds (n=397, 64.8%) found caring for such patients rewarding, particularly nurses and those who had received palliative care education; very few (n=40, 6.5%) reported feeling uncomfortable talking to the families of dying patients. A minority (n=129, 21.0%) felt that it was not appropriate for junior medical staff to assess these patients, nurses much more than doctors (42.9% vs 8.5%, p<0.001). Over half (n=338, 55.1%) felt sufficiently skilled in managing pain for people with advanced cancer, with Fellows, more experienced doctors, and those who had received palliative care education more likely to feel skilled. CONCLUSIONS: ED clinicians in Australia, particularly those who have received palliative care education, feel comfortable and adequately skilled in managing people with advanced cancer presenting to EDs, and most find it rewarding. The importance of palliative care education to emergency clinicians' training should be recognised.

Care of the dying cancer patient in the emergency department: findings from a National survey of Australian emergency department clinicians.

BACKGROUND: Patients with cancer are presenting to emergency departments (ED) for end-of-life care with increasing frequency. Little is known about this experience for patients and ED clinicians in Australia. AIMS: To assess the barriers and enablers regarding end-of-life care for cancer patients as perceived by Australian ED clinicians. METHODS: There were 4501 Australian ED clinicians invited through their professional colleges to complete an online survey, using multiple-choice and free-text responses. RESULTS: A total of 681 ED clinicians responded, most (84.2%) felt comfortable providing care to the dying and found it to be rewarding (70.9%). Although 83.8% found caring for the dying a reasonable demand on their role as clinician, 83.8% also agreed that the ED is not the right place to die. Respondents demonstrated a wide range of views regarding caring for this patient group in ED through free-text responses. In addition, 64.5% reported that futile treatment is frequently provided in the ED; the main reasons reported were that limitations of care were not clearly documented, or discussed with the patient or their family. Almost all (94.6%) agreed that advance care plans assist in caring for dying patients in the ED. CONCLUSIONS: Our findings provide important new insights into a growing area of care for ED. Barriers and enablers to optimal care of the dying patient in ED were identified, and especially the reported high occurrence of futile care, likely a result of these barriers, is detrimental to both optimal patient care and allocation of valuable healthcare resources.

[Differentiated antiplatelet therapy for acute coronary syndromes]. / Differenzierte antithrombozytäre Therapie bei akutem Koronarsyndrom.

Dual antiplatelet therapy is the cornerstone of maintenance medication following invasive treatment of patients with acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). Over the last decade, P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. The debate was enriched by the results of the large phase III clinical trials for prasugrel (TRITON) and ticagrelor (PLATO) compared to clopidogrel in patients with acute coronary syndromes. This article summarizes the critical details und subanalyses of both study programmes and highlights on clinical decision making when using the three P2Y12 blockers in acute coronary syndromes. A special focus is on higher risk patients such as those with ST elevation myocardial infarction and those with coexisting diabetes, but also on minimizing relevant bleedings, which are common during more intense platelet inhibition.

Ideal care and the realities of practice: interdisciplinary relationships in the management of advanced cancer patients in Australian emergency departments.

PURPOSE: Over the course of their illness, a person with cancer is likely to see a number of different healthcare professionals, including those in the emergency department (ED). There is limited research examining the interaction and communication between the involved healthcare professionals when such a patient presents to the ED. This study aimed to explore the views and experiences of interdisciplinary interactions of healthcare professionals caring for patients with advanced cancer who present to the ED. METHODS: Focus groups and semistructured interviews were conducted with clinical staff working in ED, oncology and community and hospital-based palliative care services. Interviews and focus groups were recorded and transcribed verbatim. Thematic analysis was undertaken by three researchers independently. These themes were then discussed by the wider team and consensus reached on themes and subthemes. RESULTS: Eighty-three healthcare professionals participated in focus groups, and 11 were interviewed. The over-arching theme to emerge was one of a conflict between ideal care and the realities of practice, particularly arising where clinicians from different services were required to work together to provide care. This idea was further understood through a series of subthemes including communication, decision-making and understanding of other services. CONCLUSIONS: Participants articulated agreed upon ideals of optimal care for advanced cancer patients across all three services, however there was frequently discord between these ideals and the actual care provided. Service demands and the day-to-day stressors of practice appeared to influence people's actions and engender conflict.

Australian resident doctors want more palliative medicine education: a survey of attitudes and perceived needs.

Most expected deaths occur in acute hospitals, and medical staff providing end-of-life care are generally not palliative medicine specialists. Through a voluntary self-administered survey, this study explored resident doctors' attitudes to palliative medicine and their perceived educational needs. Fifty-two resident doctors participated (response rate 39%), mostly acknowledging the importance of palliative medicine to their practice and emphasising that further postgraduate education is necessary.

Aortic arch repair: let it beat!

Objective aortic arch repair (AAR) on the beating heart may reduce cross-clamping times and offer improved postoperative cardiac function.Methods A single-center review of all patients (n = 24) who underwent surgical AAR during biventricular repair between 01/2006 and 01/2008 was done. All patients were operated on under cardiopulmonary bypass (CPB) with antegrade cerebral perfusion (ACP). During AAR, 13 patients (group 1) received cardioplegic arrest, and were compared to 11 patients (group 2) who underwent a beating-heart modification with selective myocardial perfusion. Seventeen patients had additional intracardiac lesions and underwent simultaneous correction during the procedure.Results Durations of CPB, AAR and ACP did not differ statistically between groups. Cardioplegic arrest time was significantly lower in group 1 (34 ± 13 vs. 76 ± 11 min, p = 0.02) and resulted in a subsequent reduction of myocardial ischemic damage as borne out by lower postoperative levels of troponin T and CK-MB (2.5 ± 0.7 vs. 7.1 ± 1.4 ng/mL, p = 0.02; 68.7 ± 11.5 vs. 149.1 ± 27.2 U/l, p = 0.03). We observed an enhanced patient recovery with shorter inotropic and ventilatory support times (p < 0.05).Conclusion Pediatric aortic arch correction on a CPB beating heart with selective myocardial perfusion is technically feasible and safe. The reduction of the myocardial ischemic time is effective and results in less myocardial damage.

[Risk factor "smoking" : smoking cessation in patients with cardiovascular diseases]. / Risikofaktor "Rauchen" : Wege aus der Nikotinsucht bei Patienten mit kardiovaskulären Erkrankungen.

Smoking is the most frequent cause of avoidable premature death. Annually, almost 6 million people die due to nicotine consumption. Comparing modifiable cardiovascular risk factors, smoking has the strongest impact on cardiovascular mortality. More than 50% of all premature myocardial infarctions are related to nicotine consumption. Even in patients with known coronary disease receiving optimal medical therapy, there is a remarkable additional preventive effect of smoking cessation detectable. Therefore, smoking cessation is an essential component of primary and secondary prevention strategies. Smoking cessation programs applying a combination of behavior therapy and supporting medical treatment have been demonstrated to be the most effective.

[Limitation of operability. What does the internist need to know?]. / Einschränkung der Operationsfähigkeit. Was muss der Internist wissen?

The number of elderly people that are critically ill and are send for surgery is rising rapidly. As co-morbidities such as heart disease have huge impact on the perioperative risk, identification of specific risk factors should guide the pre- and perioperative management. Several risk scores and the guidelines published by the European Society of Cardiology recently are currently available and are reviewed in the current manuscript. Evaluation of the medical history of the individual patient and functional tests are the basis for further decisions. Patients that are suffering from co-morbidities or reduced physical fitness are identified as risk patients. Patients without risk factors can be sent for surgery without additional evaluation. In moderate risk patients medication should be optimized prior to surgery. Except emergency surgery cases critical illness should be identified and treated before surgery is initiated. Depending on the number of potential risk factors non-invasive cardiac stress tests are recommended. Depending on the results also coronary angiography/-angioplasty should be performed. Acute coronary syndromes or unstable angina should preferentially be treated prior to surgery.

Expression of carcinoembryonic antigen-related cell adhesion molecule 1 in acute rejection of human renal allografts.

BACKGROUND: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is expressed on various cell types and mediates homophilic cell adhesion. CEACAM1 plays an important role in cell morphogenesis and angiogenesis. Furthermore, CEACAM1 regulates adhesive activity of immune-competent cells, suggesting an additional role in inflammatory processes. METHODS: Therefore, in the present study the expression of CEACAM1 was analysed retrospectively in renal biopsies from kidney transplant recipients (stable graft [Ctr; n = 18], acute vascular rejection [AVR; n = 14], acute tubulointerstitial rejection [AIR; n = 9], and combined vascular and interstitial rejection [AVIR; n = 7]). Expression patterns of CEACAM1 were determined using immunohistochemistry and quantitative morphometry. RESULTS: All biopsy specimens from patients with stable grafts showed low CEACAM1 levels, suggesting a constitutive expression in renal transplants. In patients with acute rejection, CEACAM1 was markedly up-regulated. AVR revealed the highest tubular CEACAM1 levels (4.9 +/- 0.5% [AVR] vs 2.2 +/- 0.3% [Ctr] of tubular area; P < .05), whereas interstitial rejections showed the highest glomerular expressions (4.5 +/- 0.5% [AIR] vs 0.9 +/- 0.1% [Ctr] of glomerular area; P < .05). CONCLUSIONS: An up-regulated expression of CEACAM1 in tubular and/or glomerular cells is an indicator of acute inflammatory processes in biopsy specimens from patients with acute renal allograft rejections and, therefore, might be used as a new clinical marker.

Double discordance in the hypoplastic left heart.

A neonate was transferred for an intracardiac mass. Initially, the mass was mistaken for a hypoplastic right ventricle, a thrombus, or a tumor. Only a thorough segmental and sequential analysis showed double discordance with a hypoplastic left ventricle. No such entity has yet been described.

Utility of N-terminal brain natriuretic peptide plasma concentrations in comparison to lactate and troponin in children with congenital heart disease following open-heart surgery.

We conducted a prospective study in a pediatric cardiac intensive care unit in order to determine the diagnostic value of N-terminal brain natriuretic peptide (N-BNP) plasma concentration in the perioperative care of children with congenital heart disease (CHD). N-BNP plasma concentrations were determined by using a validated enzyme immunoassay. We measured N-BNP the day before surgery and up to 15 days postoperatively in 23 children (age range, 0.25-11 years) undergoing cardiac surgery due to various CHDs. Supply and duration of catecholamines, vasodilators, and respiratory therapy were determined and correlated to N-BNP. In addition, troponin T (TnT) and arterial Lactat (aL) concentrations were measured simultaneously. We found a significant correlation between preoperative and maximal N-BNP levels and dosage of vasodilators (r = 0.41, p < 0.02 and r = 0.83, p < 0.01, respectively). Maximal TnT and aL levels were not correlated to dosage of vasodilators. The dosage and duration of catecholamines, the duration of respiratory therapy, and the plasma concentration of TnT and aL were not correlated to pre- or perioperative N-BNP. Maximal TnT and aL levels were correlated to duration (r = 0.53, p < 0.01 and r = 0.48, p < 0.02) and dosage (r = 0.52, p < 0.02 and r = 0.60, p < 0.01) of catecholamines and duration of respiratory therapy (r = 0.57, p < 0.01 and r = 0.50, p < 0.02). As recent studies show, N-BNP appears to be a powerful neurohumoral indicator of ventricular function and prognosis for guiding therapy in the outpatient department or for discriminating cardiac from noncardiac symptoms. In contrast, the value of N-BNP for guiding perioperative therapy in pediatric cardiac intensive care units is limited.

In vitro evaluation of Haemonetics MCS+ apheresis platelet concentrates treated with photochemical pathogen inactivation following plasma volume reduction using the INTERCEPT Preparation Set.

Pathogen inactivation using the INTERCEPT Blood System requires platelet resuspension in InterSol and reduced plasma. Platelets in plasma collected on the Haemonetics MCS+ were processed on the INTERCEPT Preparation Set for plasma volume reduction and addition of InterSol. The use of the Preparation Set resulted in a mean platelet loss of 5.6 +/- 3.4%. Subsequent photochemical treatment (PCT) with amotosalen and ultraviolet A light, and 7 days of storage, resulted in acceptable changes for platelet swirling, lactate, lactate dehydrogenase (LDH), platelet factor-4 (PF4), p-selectin, glycoprotein V (GpV), pO2, pCO2, tumour necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8). All platelet units processed with the Preparation Set and PCT met European requirements for leucoreduction and pH values.

Ross and Ross-Konno procedure in children and adolescents: mid-term results.

OBJECTIVES: The aim of the study was to analyze mid-term results of aortic root replacement with pulmonary autograft in children and adolescents in two centers. METHODS: From December 1997 through August 2003, a total of 66 patients underwent the Ross procedure in two centers. Indication for Ross procedure was predominantly aortic stenosis in 24 patients and predominantly aortic regurgitation (AR) in 22 patients. Twenty patients with severe left ventricular outflow tract obstruction (LVOTO) underwent Ross-Konno procedure. No patient had a geometric mismatch of more than 5 mm in favor of the aortic annulus. RESULTS: There was no early death. One patient died 3 months after surgery due to bacterial endocarditis. Survival on median follow-up period of 2.4 years was 98.5%. Neo-aortic regurgitation was none in 29 (44%) patients, trivial in 35 (53%) patients and mild in 2 (3%) patients. One patient (1.5%) needed aortic valve replacement because of autograft failure. Actuarial freedom from more than trivial neo-aortic regurgitation, or aortic valve replacement was 95% at 5 years follow-up. There was no patient either with recurrent LVOTO or significant aortic root dilatation. Freedom from redo was 93% at 5 years of follow-up. There had been a significant reduction (P = 0.001) and normalization in the left ventricle diastolic diameter index and left ventricle mass index, respectively, within 3-12 months after operation. Sixty-three percent of all operated patients are without medication; no one is on anticoagulation therapy. CONCLUSIONS: Our 7 years experience with the Ross and Ross-Konno operation has shown excellent mid-term results, with mortality rate approaching zero in both simple and complex left heart lesions, even in the neonates and infants. It is a procedure of choice in children with severe anomaly of the aortic valve and/or left ventricular outflow tract obstruction. The main concern is dilatation of the neo-aortic root leading to progression of AR, especially in the settings of geometric mismatch of aortic and pulmonary roots and bicuspid, regurgitant aortic valve. The risk of autograft failure in these specific subsets of patients remains to be determined.

[MRI of congenital heart disease in childhood]. / MR-Tomographie kongenitaler Herzvitien im Kindesalter.

MRI provides a non-invasive diagnostic tool complementing echocardiography on one hand, and showing advantages over echocardiography, on the other hand, especially after corrective procedures. The multiple different MRI sequences need to be adapted to examinations of children and patients with congenital heart disease (CHD), and can be used to detect morphologic changes, blood-flow in the heart and thoracic vessels and diastolic or systolic function of myocardium. Several factors determine the success of the examination of a complex congenital heart disease or a postoperative situs. Pediatric radiologists and radiologists experienced in congenital heart diseases have to work in close cooperation. Echocardiography should be performed before MRI. The results of prior examinations and the clinical history of the patients, including possible palliative or reconstructive operations, must be available before MRI to guide the planning of the examination. With a systematic segmental approach to the situs, to the atrial and ventricular morphology, and to the visceroatrial, atrioventricular and ventriculoarterial connections, most CHDs can be diagnosed correctly. With appropriate knowledge, MRI can also be performed quite accurately after complex operations and may avoid or delay invasive diagnostic procedures. The aim of this article is to impart knowledge, to mention problems and to provide guidance in the performance of cardiac MRI in patients with CHD.

Biventricular repair of double outlet right ventricle with non-committed ventricular septal defect (VSD) by VSD rerouting to the pulmonary artery and arterial switch.

OBJECTIVES: Biventricular repair of double outlet right ventricle non-committed ventricular septal defect (DORVncVSD) is usually achieved by a VSD rerouting to the aorta. This technique can be limited by the presence of tricuspid chordae and by the pulmonary artery to tricuspid valve distance. Furthermore, there is an important risk of late subaortic obstruction related to the long patch required that creates a potential akinetic septal area. Presented here is another technique; by VSD rerouting to the pulmonary infundibulum and arterial switch. METHODS: Ten patients, with DORVncVSD, underwent a VSD rerouting to the pulmonary infundibulum followed by arterial switch. Seven had a previous pulmonary artery banding and one a moderate infundibular stenosis. The median age at surgery was 16 months (range 3 weeks to 4.5 years). All patients had a bilateral infundibulum, with a large persistent subaortic conus, D malposition of the aorta, side-by-side vessels and double loop coronary patterns. The VSD was perimembranous with inlet or trabecular extension. Subaortic obstruction was constant. The VSD was severely distant from both the aortic and the pulmonary annulus. The operation was conducted through a combined approach. The VSD was constantly enlarged superiorly. The almost permanent subaortic obstruction was released. The VSD was always found quite close to the pulmonary infundibular ostium. The arterial switch technique was adapted to the complex coronary anatomy. RESULTS: There was one non-cardiac death. At a mean follow-up of 20 months, all nine survivors are in NYHA class I, in sinus rhythm, and have no subaortic gradient greater than 15 mm. CONCLUSION: This technique of VSD rerouting to the pulmonary artery and arterial switch limits greatly the size of the rerouting patch, respects the tricuspid chordae and is independent of the pulmonary artery-tricuspid valve distance. In this early series of biventricular repair of DORVncVSD, the VSDs were always found close to the pulmonary artery, allowing this new type of repair.

Role of editing in plant mitochondrial transfer RNAs.

Editing in plant mitochondria consists in C to U changes and mainly affects messenger RNAs, thus providing the correct genetic information for the biosynthesis of mitochondrial (mt) proteins. But editing can also affect some of the plant mt tRNAs encoded by the mt genome. In dicots, a C to U editing event corrects a C:A mismatch into a U:A base pair in the acceptor stem of mt tRNA(Phe) (GAA). In larch mitochondria, three C to U editing events restore U:A base pairs in the acceptor stem, D stem and anticodon stem, respectively, of mt tRNA(His) (GUG). For both these mt RNA(Phe) and tRNA(His), editing of the precursors is a prerequisite for their processing into mature tRNAs. In potato mt tRNA(Cys) (GCA), editing converts a C28:U42 mismatch in the anticodon stem into a U28:U42 non-canonical base pair, and reverse transcriptase minisequencing has shown that the mature mt tRNA(Cys) is fully edited. In the bryophyte Marchantia polymorpha this U residue is encoded in the mt genome and evolutionary studies suggest that restoration of a U28 residue is necessary when it is not encoded in the gene. However, in vitro studies have shown that neither processing of the precursor, nor aminoacylation of tRNA(Cys), requires C to U editing at this position. But sequencing of the purified mt tRNA(Cys) has shown that Psi is present at position 28, indicating that C to U editing is a prerequisite for the subsequent isomerization of U into Psi at position 28.