Long-term bleeding events after mechanical aortic valve replacement in patients under the age of 60.

BACKGROUND: Although younger patients are supposed to be less susceptible to bleeding complications of mechanical aortic valve replacement (mAVR) than older patients, there is a relative paucity of data on this subject. Therefore, it remains uncertain whether younger patients are really at a lower risk of these complications than older patients. METHODS: Incidence rates of bleeding events during 15 years of follow-up after mAVR were compared between 163 patients under 60 (group I), 122 patients between 60 and 65 (group II), and 145 patients over 65 (group III) years of age at operation. The target international normalised ratio (INR) was 3.0-4.0. RESULTS: During 15 years of follow-up, the annual incidence rate of major bleeding events (excluding haemorrhagic stroke) was lower in the youngest as compared with the oldest group (3.0 versus 4.7 %, respectively; p = 0.030). However, the annual incidence rate of haemorrhagic stroke was as high in the youngest as in the two older groups (0.6 versus 0.7 % and 0.7 %, respectively; p = 0.928). CONCLUSIONS: With a target INR of 3.0-4.0, patients under 60 years of age are at equally high risk of haemorrhagic stroke after mAVR as older patients. This finding confirms the relevance of a lower target INR as used in international guidelines.

Ontogeny and organ-specific steroidal glycoside diversity is associated with differential expression of steroidal glycoside pathway genes in two Solanum dulcamara leaf chemotypes.

Solanaceous plants, such as Solanum dulcamara, produce steroidal glycosides (SGs). Leaf SG profiles vary among S. dulcamara individuals, leading to distinct phytochemical phenotypes ('chemotypes') and intraspecific phytochemical diversity ('chemodiversity'). However, if and how SG chemodiversity varies among organs and across ontogeny, and how this relates to SG metabolism gene expression is unknown. Among organs and across ontogeny, S. dulcamara plants with saturated (S) and unsaturated (U) SG leaf chemotypes were selected and clonally propagated. Roots, stems and leaves were harvested from vegetative and flowering plants. Extracts were analysed using untargeted LC-MS. Expression of candidate genes in SG metabolism (SdGAME9, SdGAME4, SdGAME25, SdS5αR2 and SdDPS) was analysed using RT-qPCRs. Our analyses showed that SG chemodiversity varies among organs and across ontogeny in S. dulcamara; SG richness (Dmg) was higher in flowering than vegetative plants. In vegetative plants, Dmg was higher for leaves than for roots. Lack of SdGAME25 expression in U-chemotype leaves, while readily expressed in roots and stems, suggests a pivotal role for SdGAME25 in differentiation of leaf chemotypes in vegetative and flowering plants. By acting as an ontogeny-dependent chemotypic switch, differential regulation of SdGAME25 enables adaptive allocation of SGs, thereby increasing SG chemodiversity in leaves. This indicates that differential expression and/or regulation of glycoalkaloid metabolism genes, rather than their presence or absence, explains observed chemotypic variation in SG chemodiversity among organs and across ontogeny.

Glycosome assembly in trypanosomes: variations in the acceptable degeneracy of a COOH-terminal microbody targeting signal.

Trypanosomes compartmentalize most of their glycolytic enzymes in a peroxisome-like microbody, the glycosome. The specificity of glycosomal targeting was examined by expression of chloramphenicol acetyltransferase fusion proteins in trypanosomes and monkey cells. Compartmentalization was assessed by cell fractionation, differential detergent permeabilization, and immunofluorescence. The targeting signal of trypanosome phosphoglycerate kinase resides in the COOH-terminal hexapeptide, NRWSSL; a basic amino acid is not required. The minimal targeting signal is, as for mammalian cells, a COOH-terminal tripeptide related to -SKL. However, the acceptable degeneracy of the signal for glycosomal targeting in trypanosomes is considerably greater than that for peroxisomal targeting in mammals, with particularly relaxed requirements in the penultimate position.

[Unexplained right-sided heart failure following open heart surgery: mind the pericardium]. / Onverklaarde rechtsdecompensatie na een openhartoperatie: denk aan het hartzakje.

Three men, aged 67 years, 80 years and 53 years, respectively, developed signs and symptoms of progressive right-sided heart failure following open heart surgery. They were diagnosed with constrictive pericarditis based on echocardiography, cardiac magnetic resonance and cardiac catheterisation. Following pericardiectomy, two of the patients fully recovered, while one, the 80-year-old man, died during convalescence. When signs and symptoms of progressive right-sided heart failure develop after open heart surgery, a diagnosis of constrictive pericarditis should be considered. Constrictive pericarditis after open heart surgery may be caused by inflammation of the pericardium; an old, fibrotic haemopericardium, which may be diffuse or loculated; pericardial adhesions; or a combination of these entities. Diagnosing constrictive pericarditis is difficult and may take a long time. However, it is important to recognise this disorder early before it has progressed to an advanced stage. Pericardiectomy is the only effective therapy. When performed too late, survival is significantly reduced.

Magnetic coupling to the advanced Virgo payloads and its impact on the low frequency sensitivity.

We study the electromagnetic coupling of the Advanced Virgo (AdV) input mirror payload in response to a slowly time-varying magnetic field. As the problem is not amenable to analytical solution, we employ and validate a finite element (FE) analysis approach. The FE model is built to represent as faithfully as possible the real object, and it has been validated by comparison with experimental measurements. The intent is to estimate the induced currents and the magnetic field in the neighbourhood of the payload. The procedure found 21 equivalent electrical configurations that are compatible with the measurements. These have been used to compute the magnetic noise contribution to the total AdV strain noise. At the current stage of development, AdV seems to be unaffected by magnetic noise, but we foresee a non-negligible coupling once AdV reaches the design sensitivity.

Isolated left ventricular noncompaction in a patient presenting with a subacute myocardial infarction.

Isolated left ventricular noncompaction is a rare cardiomyopathy that is often not recognised. So far, it is not well established how best to manage this abnormality. We describe a patient in whom the diagnosis of isolated left ventricular noncompaction was made after presentation with a subacute myocardial infarction. Because of nonsustained ventricular tachycardias during hospitalisation, which were inducible and deteriorated into ventricular fibrillation on electrophysiological examination after coronary artery bypass grafting, he received an implantable defibrillator. Whether the ventricular tachycardias were due to the myocardial infarction or to the noncompacted myocardium remains uncertain. (Neth Heart J 2007;15:109-11.).

Prevalence and clinical significance of an elevated cardiac troponin I in patients presenting to the Emergency Department without chest pain.

BACKGROUND: Cardiac troponins are currently measured in patients presenting with chest pain. Little is known about routinely measured cardiac troponins in patients presenting without chest pain. The aim of this study was to determine the prevalence and clinical significance of an elevated cardiac troponin I (cTnI) in patients presenting to the Emergency Department without chest pain. METHODS: During a 6-month period, we routinely measured cTnI in all patients presenting to the internist, neurologist, or lung specialist for reasons other than chest pain. We followed patients with an elevated cTnI for 1 year and determined mortality and incidence of non-fatal myocardial infarction, percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG). RESULTS: cTnI was elevated in 41 out of 1130 patients (3.6%). Patients with an elevated cTnI were older (78 vs. 62 years) and more often admitted to the hospital (95% vs. 78%) than those with a normal cTnI. Twenty-six patients (63%) with an elevated cTnI died within 1 year. Approximately 50% of these deaths were cardiac-related. Two patients (4.9%) suffered a non-fatal myocardial infarction, while no patient underwent PCI or CABG during follow-up. CONCLUSION: Routinely measured cTnI is seldom elevated in a general population of patients presenting to the Emergency Department without chest pain. Patients with an elevated cTnI are, on the average, 16 years older than those with a normal level. An elevated cTnI is clearly associated with an unfavorable outcome.

Post-transcriptional control of the differential expression of phosphoglycerate kinase genes in Trypanosoma brucei.

The genes for the cytosolic and glycosomal phosphoglycerate kinases (PGK) of Trypanosoma brucei are found in a compact tandem array together with a third PGK-related gene, expressed at low level. Expression of the two PGK genes is differentially regulated in the life cycle of T. brucei: the glycosomal PGK and its mRNA are abundant in the mammalian stage of the cycle but not in the insect stage, whereas the reverse is found for the cytosolic PGK and its mRNA. Nevertheless, our experiments indicate that the mRNAs for both isoenzymes are derived from a common precursor. Nuclease protection experiments using fragments cloned into single-stranded DNA vectors show the presence of low abundance RNA species running through one gene into the next. Indeed minor RNA species larger than the mature mRNAs are visible in overexposed RNA blots. Analysis of nascent RNA in a nuclear run-on assay indicates that the entire PGK gene array is transcribed at an equal rate throughout in both life cycle stages. We conclude that the PGK genes are part of one large multicistronic transcription unit, which is processed to yield the individual mRNAs with concomitant addition of the 5' 35-nucleotide mini-exon sequence, characteristic of all trypanosome mRNAs. It follows that the steady-state levels of the PGK mRNAs are controlled post-transcriptionally.

Evidence for gene conversion between the phosphoglycerate kinase genes of Trypanosoma brucei.

Trypanosoma brucei contains a tandem array of three genes for phosphoglycerate kinase (PGKase), genes A, B and C, each coding for a different protein. We have compared allelic variants of this gene array and find evidence for gene conversion between the three genes. Near the 3' end, the different alleles and gene B contain a variable sequence that is similar to the corresponding sequence in either gene A or gene C. This sequence is flanked by glycine triplets that are conserved in all PGKases from bacteria to mammals. The triplets are encoded by (GGT)n, resulting in sequences that resemble the recombination-promoting chi-sites of Escherichia coli. Upstream of the variable sequence, there is an area of 800 base-pairs in which genes A, B and C are highly homologous; in all three genes this region ends with a sharp boundary at which gene B again shows segmental homology with both genes A and C. These results suggest that repeated gene conversion events partially erase the differences between genes A, B and C that arise in evolution and suggest that chi-like sequences may act as recombinational hotspots in protozoa such as T. brucei.

Successful management of postinfarction ventricular septal rupture.

Ventricular septal rupture is a rare but devastating complication of acute myocardial infarction. Especially in patients with cardiogenic shock, right ventricular dysfunction or an inferior infarct mortality is very high. We present a case in which an 83-year-old patient survived rupture of the ventricular septum complicating an inferior myocardial infarction. Unlike most patients his haemodynamic status did not deteriorate and delayed elective surgical repair was carried out successfully.

Coronary artery dissection following blunt chest trauma: a case report.

Coronary artery dissection following blunt chest trauma is rare. We report the case of a 43-year-old woman who was admitted with a subacute inferior myocardial infarction due to dissection of the right coronary artery. Ten days earlier, she had sustained a minimal chest trauma. The literature is reviewed and management is discussed.

Targeting efficiencies of various permutations of the consensus C-terminal tripeptide peroxisomal targeting signal.

Two types of peptide signals are known to independently target proteins into the peroxisomal matrix. One of these is a consensus C-terminal tripeptide which is conserved in many microbody proteins derived from diverse species. The second signal is an N-terminal sequence found in a small subset of peroxisomal proteins. We have tested 18 possible variants of the consensus tripeptide targeting signal for their ability to facilitate the transport of a cytosolic passenger protein, chloramphenicol acetyltransferase, into peroxisomes of monkey kidney cells. Our results reveal the presence of a hierarchy of preferred amino acid substitutions at each position of the tripeptide.

A phosphoglycerate kinase-related gene conserved between Trypanosoma brucei and Crithidia fasciculata.

Trypanosoma brucei and Crithidia fasciculata both contain three different phosphoglycerate kinase (PGK) genes, A, B and C, in a tandem array. The genes B and C encode the major PGKs: the cytosolic and glycosomal PGKs, respectively. The PGK-A genes of both Trypanosomatid species encode open reading frames related to PGK, which have most active site residues conserved, but contain an insert of 80 amino acids at approximately position 80 of the 420 amino acids average PGK sequence. The deduced amino acid sequence of these inserts is conserved between T. brucei and C. fasciculata (48% positional identity), indicating its functional importance. Although we have not been able to demonstrate PGK activity in the PGK-A gene product, we consider it likely that this gene codes for a minor PGK with special function.

[Atrial fibrillations: daily occurrence possibly leading to embolism in an extremity]. / Boezemfibrilleren: alledaags, maar mogelijk leidend tot embolisatie naar een extremiteit.

A 64-year old woman had been tired and short of breath for the previous few months. During the past few days she had experienced disruptions in the movement and feeling of the right arm and both feet as well as a loss of strength and a heavy feeling in her right leg. Due to atrial fibrillation she had recently started using digoxin and due to possible arterial embolisms in the extremities she had recently started using acenocoumarol. Further investigations revealed one large thrombus in the left atrium, two large thrombi in the left auricle and a serious constriction in the right iliac artery. The thrombi were treated with heparin and oral anticoagulants; the ischaemia which probably occurred as a result of this was successfully treated with embolectomy. After the cardiac thrombi had disappeared, the patient was electrically converted to sinus rhythm. One month later, the patient was still in sinus rhythm and her clinical picture had improved. As she does not feel the atrial fibrillation, she will be permanently maintained on oral anticoagulants. In patients with atrial fibrillations, the possibility of an embolisation towards the extremities deserves serious consideration.

Clinical significance of reverse redistribution on technetium-99m tetrofosmin single-photon emission computed tomography: an 18-month follow-up study.

BACKGROUND: The clinical and prognostic significance of reverse redistribution on technetium-99m (99mTc) single-photon emission computed tomography (SPECT) is unclear. OBJECTIVES: To determine outcomes of chest pain patients showing reverse redistribution after 99mTc tetrofosmin SPECT versus SPECT showing no reverse redistribution. METHODS: Patient outcomes (death, nonfatal myocardial infarction, coronary artery bypass grafting and percutaneous transluminal coronary angioplasty) within 18 months after 99mTc tetrofosmin SPECT were determined in two populations of ambulatory patients, most of whom had been evaluated because of chest pain: a population of 57 patients whose SPECT images showed reverse redistribution without reversible or fixed defects, versus a control population of 98 patients whose SPECT images were normal (no reverse redistribution, no reversible defects, no fixed defects). RESULTS: Stepwise logistic regression analysis showed that the population of patients with reverse redistribution did not have a worse 18-month outcome in comparison with the control population of patients without reverse redistribution (3.5% versus 9.2%, respectively; p=0.15 corrected for age and gender). CONCLUSION: Reverse redistribution on 99mTc tetrofosmin SPECT does not appear to be an unfavourable prognostic factor in ambulatory chest pain patients.

Balloon aortic valvuloplasty as a bridge to aortic valve replacement in a patient with severe calcific aortic stenosis.

This case report describes a patient with severe calcific aortic stenosis who was initially considered inoperable because of a very poor left ventricular function and severe pulmonary hypertension. After balloon aortic valvuloplasty, the clinical and haemodynamic status of the patient improved to such an extent that subsequent aortic valve replacement was considered possible and eventually proved to be successful. Balloon aortic valvuloplasty has value as a potential bridge to aortic valve replacement when the risks for surgery are considered to be too high.

Predicting 30-day mortality of aortic valve replacement by the AVR score.

OBJECTIVES: The objective of this study is to develop a simple risk score to predict 30-day mortality of aortic valve replacement (AVR). METHODS: In a development set of 673 consecutive patients who underwent AVR between 1990 and 1993, four independent predictors for 30-day mortality were identified: body mass index (BMI) ≥30, BMI <20, previous coronary artery bypass grafting (CABG) and recent myocardial infarction. Based on these predictors, a 30-day mortality risk score-the AVR score-was developed. The AVR score was validated on a validation set of 673 consecutive patients who underwent AVR almost two decennia later in the same hospital. RESULTS: Thirty-day mortality in the development set was ≤2% in the absence of any predictor (class I, low risk), 2-5% in the solitary presence of BMI ≥30 (class II, mild risk), 5-15% in the solitary presence of previous CABG or recent myocardial infarction (class III, moderate risk), and >15% in the solitary presence of BMI <20, or any combination of BMI ≥30, previous CABG or recent myocardial infarction (class IV, high risk). The AVR score correctly predicted 30-day mortality in the validation set: observed 30-day mortality in the validation set was 2.3% in 487 class I patients, 4.4% in 137 class II patients, 13.3% in 30 class III patients and 15.8% in 19 class IV patients. CONCLUSIONS: The AVR score is a simple risk score validated to predict 30-day mortality of AVR.