Mass spectrometric analysis of unknown haemoglobin fractions identified by high-performance liquid chromatography in an antenatal screening programme.

AIMS: The majority of haematology laboratories use automated high-performance liquid chromatography (HPLC) as a primary method in the screening of samples for haemoglobin variants and thalassaemia. HPLC detects adducted fractions, such as HbA1C and other peaks of unknown significance. The National Health Service (NHS) Sickle and Thalassaemia Screening Programme does not mandate further assessment of these unknown peaks, but their presence may cause concern or precipitate detailed investigations. Mass spectrometry (MS) is being increasingly used in NHS Laboratories and is an effective method of characterising variant haemoglobins. METHOD: Antenatal blood samples accepted for NHS Sickle and Thalassaemia Screening Programme from 2005 to 2013 were assessed. Those samples with unidentified peaks on HPLC were further analysed by Liquid chromatography tandem MS (LCMSMS). RESULTS: 58,493 samples were processed. 966 (1.6%) significant haemoglobinopathies were identified. 68 patients (0.11%) were found to have unidentified peaks on HPLC. α chain variants: two were hyperunstable α variants, Hb Adana and Hb H/Constant Spring. The patient with HbH/Constant Spring required transfusion during pregnancy. Other abnormalities include 24 unstable α chain variants of minimal clinical significance and 17 α chain variants of no clinical significance. The frequency of ß chain abnormalities was lower, with 10 patients having an insignificant ß chain variant, 4 mildly unstable ß chain variants (2 of whom had increased oxygen affinity) and 4 with variants associated with increased oxygen affinity. CONCLUSIONS: The prevalence of unidentified variants on automated HPLC within our population is 0.1%. LCMSMS is an effective technique to assist in the characterisation of unknown haemoglobin variants. α chain variants of limited clinical significance were the most commonly detected abnormality.

Proprioceptive cues modulate further processing of spatially congruent auditory information. a high-density EEG study.

Multisensory integration and interaction occur when bimodal stimuli are presented as either spatially congruent or incongruent, but temporally coincident. We investigated whether proprioceptive cues interact with auditory attention to one of two sound sources in free-field. The participant's task was to attend to either the left or right speaker and to respond to occasional increased-bandwidth targets via a footswitch. We recorded high-density EEG in three experimental conditions: the participants either held the speakers in their hands (Hold), reached out close to them (Reach), or had their hands in their lap (Lap). In the last two conditions, the auditory event-related potentials (ERPs) revealed a prominent negativity around 200 ms post-stimulus (N2 wave) over fronto-central areas, which is a reliable index of further processing of spatial stimulus features in free-field. The N2 wave was markedly attenuated in the 'Hold' condition, which suggests that proprioceptive cues apparently solidify spatial information computed by the auditory system, in so doing alleviating the need for further processing of spatial coordinates solely based on auditory information.

The activity of yeast ADH I and ADH II with long-chain alcohols and diols.

The activities of yeast ADH I and ADH II towards long chain alcohols and diols were studied using rather unusual conditions (1.0 M Tris pH 8.75, approximately 0.3 mg/ml enzyme and [S]<<

Strain-dependent variation in the NADH-dependent diacetyl reductase activities of larger- and alebrewing yeasts.

Significant differences were observed in the zymogram patterns of NAD(+)-dependent ethanol dehydrogenase and acetoin dehydrogenase activity in seven strains of brewer's yeast examined by non-denaturing PAGE. Bottom-fermenting (lager) strains contained quite different activity bands of acetoin dehydrogenase activity compared with top-fermenting (ale) strains. These differences were confirmed when cell-free extracts of ale yeasts were heated at 55 degrees C. This destroyed most of the diacetyl reductase activity, while leaving acetaldehyde reductase and other reductase activities unaffected. In contrast, heating cell-free extracts of lager yeasts at 55 degrees C inactivated diacetyl reductase activity and the other reductase activities at the same rate, and more slowly than with ale strains. Similar distinctions between the two types of yeast could be made by examining the effect of heat on the ratio (activity of the various substrates with NADH as electron donor)/(activity with reduced acetylpyridine-adenine dinucleotide as electron donor). The data show that the acetoin dehydrogenase/diacetyl reductase enzyme present in ale-yeast strains differs in mobility and heat-stability from that of larger strains, and that both can be distinguished from the major alcohol dehydrogenase activity bands.

Morphological aspects of the development of hydrocephalus in a mouse mutant (SUMS/NP).

The SUMS/NP is a mouse mutant with a recessive gene for congenital hydrocephalus. The condition is detectable outwardly at 3 days after birth and affected animals die soon after weaning. The heads of fetuses from 14 to 20 days gestation and at 1, 4, 5, 12 and 18 days after birth have been sectioned for light microscopy and the volume of the lateral ventricles measured in all but the three oldest ages. At 16 days gestation and earlier all fetuses had a relatively large lateral ventricle volume. Hydrocephalus was first detected from volume measurements at 18 days gestation and generally became progressively more severe with age. Hydrocephalic animals, in addition to lateral and third ventricle dilatation, always showed a reduction in the cross-sectional area of the cerebral aqueduct or a total absence of the aqueduct. All hydrocephalics, with the exception of two fetuses, also had cystic cavitation of the forebrain around the lateral ventricles. Electron microscopy of animals with a reduced aqueduct showed the ventral part to be absent in hydrocephalics.

Coronary artery dissection - a complication of cardiac catheterization without sequelae: case report and review of the literature.

This report describes an acute right coronary artery dissection occurring during diagnostic cardiac catheterization. Following catheter manipulation in the vicinity of the aortic valve, the patient complained of mild chest discomfort and had transient electrocardiographic evidence of acute inferior wall myocardial infarction with runs of 2:1 atrioventricular block. Within 5 min, the EKG reverted to precatheterization appearance, and the patient was asymptomatic. Coronary angiography revealed a dissection of the proximal vessel without obstruction. The patient had no clinical sequelae while monitored in the intensive care unit. The patient underwent elective aortic and mitral valve replacement. The area of the dissection was directly visualized, and no abnormality was noted. We review the literature of spontaneous and iatrogenic coronary artery dissections with regard to pathology, diagnosis, and prognosis, and make recommendations for therapy.

Value of Holter monitoring in assessing cardiac arrhythmias in symptomatic patients.

Holter electrocardiographic monitoring in 55 symptomatic patients with syncope, palpitations or dizziness uncovered significant arrhythmias in 30 patients (55 percent). By providing an observation period of at least 24 hours including a period of sleep, the procedure aided detection and diagnosis in both symptomatic and asymptomatic patients of transient arrhythmias or conduction abnormalities not documented by routine electrocardiograms. Bradyarrhythmias accounted for the majority of arrhythmias recorded in 21 or 30 symptomatic patients (70 percent); 15 had sinus bradycardia (35 to 55 beats/min) alone and 6 also had long episodes of sinus arrest of up to 5 seconds. Two had sinus bradycardia with periods of atrioventricular block with Wenckebach phenomenon. Five patients had a tachycardia-bradycardia syndrome; three had other episodic arrhythmias and one had pacemaker failure. In 15 (60 percent) of the 25 patients without arrhythmias, monitoring did not document the cause of symptoms. Holter monitoring is of considerable value in assessing the efficacy and adequacy of drug treatment, especially in patients with known heart disease, and in detecting pacemaker malfunction. However, very long periods of monitoring may be needed to make a diagnosis in those with only sporadic symptoms.

Disappearance of abnormal Q waves after aortocoronary bypass surgery.

Sixty-one patients were selected from 100 consecutive patients under-going aortocoronary artery bypass. The number of vessels diseased as defined by coronary arteriography and the number of bypass grafts were recorded. Review of the preoperative electrocardiograms showed an infarct pattern in 26 of the 61 patients and analysis of the postoperative electrocardiograms revealed loss of abnormal Q waves in 3 of the 26. The pre- and postoperative clinical course of these three patients is analyzed and the extent of their coronary artery disease and number of bypass grafts compared with those of the 23 patients who had persistence of the infarction pattern and the 17 patients who manifested new Q waves. Possible explanations for the disappearance of abnormal Q waves are discussed.

Bacterial endocarditis with ruptured sinus of Valsalva and aorticocardiac fistula.

A case is presented of bacterial endocarditis with a ruptured sinus of Valsalva and formation of an aorticocardiac fistula from the right coronary sinus into the right atrium and right ventricle. The pathologic, clinical and surgical aspects of bacterial endocarditis complicated by a ruptured sinus of Valsalva and an aorticocardiac fistula are analyzed. This complication of bacterial endocarditis is still uncommon, but alertness to its diagnosis makes possible early and successful surgical treatment.