Occupational egg allergy in an embryological research facility.

BACKGROUND: Hen and quail eggs are commonly used in embryological research. While immunoglobin E (IgE)-associated allergy to hens' egg proteins is recognized in employees in the food industry, there are no previous reports from workers in embryological research. Two newly identified cases prompted us to examine the extent of this problem in a university laboratory. AIMS: To determine the prevalence and determinants of sensitization to egg among a group of workers in an embryological research laboratory. METHODS: Following the identification of egg sensitization in two research workers, we surveyed 116 employees from a single embryology research laboratory in 2005. Sensitization to egg was assessed by skin prick tests and/or specific IgE measurement and examined in relation to a number of potential determinants, including the extent of appropriate control measures. RESULTS: Four employees were sensitized to egg, each with digestive symptoms of egg allergy. All had worked directly with eggs, giving a prevalence of specific sensitization in that group of 6.1% (95% confidence interval (CI) [1.7%, 14.8%]). There was a statistically significant trend for those sensitized to report a shorter duration of exposure to eggs and less frequent use of hygiene control measures to reduce exposure. CONCLUSIONS: Sensitization to eggs among those occupationally exposed to egg protein in research work occurs more commonly than in the general population. The presence of digestive symptoms after eating eggs may be indicative of sensitization to egg and should be incorporated into health evaluation of exposed workers.

Right ventricular dilatation in the fetus: a study of associated features and outcome.

Right ventricular dilatation is an infrequent finding at fetal echocardiography. Previous studies have documented an association with aortic coarctation. However, there are associations with other congenital abnormalities. We reviewed our experience of fetal right heart dilatation in order to recognize concurrent anomalies and to assess the outcome of the affected fetuses. We studied all fetuses with right ventricular dilatation over a 5-year period. We documented associated cardiac and noncardiac lesions, and outcome data were assessed in terms of the number of fetuses that were born live and the number surviving to 2 months of age. Forty-three fetuses with right heart dilatation were seen. Fifteen had associated cardiac abnormalities: most commonly coarctation (n = 4) and VSD (n = 4). Seven had associated noncardiac abnormalities. There were seven fetuses who also had chromosomal abnormalities. In total, there were three terminations of pregnancy, four intrauterine deaths, one stillbirth and 35 live-births. Twenty-eight were alive at 2 months of age (70% of the nonterminated pregnancies). Fetal right heart dilatation is frequently associated with both cardiac and noncardiac congenital abnormalities. Our outcome figures suggest a guarded prognosis be given during counseling of parents of fetuses with right heart dilatation.

Cross-sectional echocardiographic demonstration of duct-related intimal tissue plaques within the pulmonary artery.

The cross-sectional and colour flow mapping echocardiographic appearances of extension of ductal tissue within the pulmonary artery in three infants referred for echocardiographic assessment of a cardiac murmur are reported. The ductal plaques described may be common but are not necessarily of clinical significance.

Recurrence risks in offspring of adults with major heart defects: results from first cohort of British collaborative study.

BACKGROUND: Congenital heart defects are generally assumed to have a multifactorial aetiology. We have tested this hypothesis by studying adults with heart defects and their families. METHODS: We identified 1094 patients who survived surgery for major cardiac defects before 1970. We chose individuals with disturbance of situs or segmental connection, with atrioventricular septal defect or with tetralogy of Fallot. After exclusion and non-participation, 727 individuals were traced. Each was visited by an investigator and completed a detailed questionnaire. If possible, all "normal" offspring were examined by a paediatric cardiologist. FINDINGS: The 727 individuals had 393 live offspring. There were 71 miscarriages and five terminated pregnancies. Overall, we found recurrent heart defects in 16 liveborn offspring--a recurrence risk of 4.1%. This result differed significantly from sibling risk (2.1%; p=0.021). More congenital heart defects occurred in the offspring of affected women than in those of affected men (p=0.047); when all malformations (cardiac and non-cardiac) in the offspring were taken into account the excess was more significant (p=0.032). We found an excess of miscarriages in the offspring of affected women (p=0.001). In tetralogy of Fallot, heart defects occurred in seven (3.1%) of 223 offspring, 12 (2.2%) of 539 siblings, five (0.3%) of 1575 second-degree relatives, and eight (0.3%) of 2728 third-degree relatives. INTERPRETATION: Our findings do not support a polygenic basis for all heart defects. Atrioventricular septal defect seems to be a single-gene defect and tetralogy of Fallot a polygenic disorder with a small number of interacting genes. Our data suggest that isolated transposition of the great arteries is a sporadic defect.

Differences in the synaptic complement of thoracic motoneurons of adult and ageing cats after permanent or reversible axotomy.

We have compared the effects of intercostal nerve crush (reversible axotomy) or nerve transection with proximal ligation (permanent axotomy) on the somatic synaptic terminals of thoracic motoneurons of adult (1-2 years) and ageing (10-15 years) cats. Retrograde axonal transport of horseradish peroxidase (HRP) was used to identify axotomised motoneurons; control motoneurons were labelled by the intramuscular injection of HRP. Synaptic frequency and cover of control motoneurons in adult and ageing cats was similar. In adults, 8-16 days following both types of axotomy, synaptic cover was halved without any significant change in synaptic frequency. By 32-64 days following reversible axotomy, synaptic frequency and cover were not significantly different from controls. By contrast, 32-64 days following permanent axotomy synaptic frequency and cover were reduced to 30-50% of adult control values. In ageing cats 2 months following reversible axotomy, synaptic frequency and cover were reduced to 40% and 33% of ageing control values, respectively, while no significant change from controls was found 2 months following permanent axotomy. The long-term synaptic response of axotomised motoneurons in ageing cats is therefore opposite to that of adults.

Axon-glial relations during regeneration of axons in the adult rat anterior medullary velum.

The anterior medullary velum (AMV) of adult Wistar rats was lesioned in the midsagittal plane, transecting all decussating axons including those of the central projection of the IVth nerve. At selected times up to 200 days after transection, the degenerative and regenerative responses of axons and glia were analyzed using transmission and scanning electron microscopy and immunohistochemistry. In particular, both the capacity of oligodendrocytes to remyelinate regenerated fibers and the stability of the CNS/PNS junctional zone of the IVth nerve rootlet were documented. Transected central AMV axons exhibited four patterns of fiber regeneration in which fibers grew: rostrocaudally in the reactive paralesion neuropil (Group 1); randomly within the AMV (Group 2); into the ipsilateral IVth nerve rootlet, after turning at the lesion edge and growing recurrently through the old degenerated contralateral central trochlear nerve trajectory (Group 3); and ectopically through paralesion tears in the ependyma onto the surface of the IVth ventricle (Group 4). Group 1-3 axons regenerated unperturbed through degenerating central myelin, reactive astrocytes, oligodendrocytes, microglia, and large accumulations of hematogenous macrophages. Only Group 3 axons survived long term in significant numbers, and all became myelinated by oligodendrocytes, ultimately establishing thin sheaths with relatively normal nodal gaps and intersegmental myelin sheath lengths. Schwann cells at the CNS/PNS junction of the IVth nerve rootlet did not invade the CNS, but astrocyte processes grew across the junction into the PNS portion of the IVth nerve. The basal lamina of the junctional glia limitans remained stable throughout the experimental period.

General practice on a new housing estate. 1956.

An analysis has been carried out of the records kept for the year 1953 by six doctors practising on a new housing estate near London. The population of the estate is described in terms of age, sex, and social class. 76 per cent. of the registered patients consulted a doctor at some time during the year, the consultation rate per person being 4.1 based on the average registered population; females had more consultations than males; 80 per cent. of all consultations were made by people under the age of 45. One-sixth of the patients accounted for about half of the consultations, and 30 per cent. of the consultations were made by the 7 per cent. of registered patients who consulted twelve or more times in the year. The consultation rates showed a slight, but statistically significant, social gradient, with more consultations among patients in the lower social classes. The illness rate was 26 per person, and was higher among males in infancy and old age, and among females between the ages of 5 and 64. A method of estimating the duration of sickness in terms of the period under medical care was employed. This showed that 70 per cent. of all illnesses were dealt with in single consultations, and that only 3 per cent. of illnesses were under care for more than 90 days. Over half of the practice population were under care for less than 5 days, and only 8 per cent. for more than 90 days. The proportion of patients having more than 30 days sickness generally increased with age, but there was a slight fall among the women aged 65 and over. Certificates were issued at the rate of about one for every five consultations, two-thirds of these being necessitated by the requirements of the National Insurance regulations. Prescriptions were issued at the rate of about one per consultation, the prescription rate being 41 per person. Only 5 per cent. of the practice population consulted the doctor but did not obtain a prescription. About 30 per cent. of the patients who consulted a doctor were referred outside the practices, 80 per cent. of all referrals being to hospitals, either as inpatients or as out-patients. The person-hospital referral rate was 20 per 100, and there were 31 referrals for every 100 registered patients. Males over 65 had the highest rates for consultations, illnesses, prescriptions, and referrals. The reason for this is discussed. The value of record-keeping by general practitioners is stressed, together with the need for a generally accepted method of expressing rates in studies of this kind.

Location of a folding protein and shape changes in GroEL-GroES complexes imaged by cryo-electron microscopy.

Protein folding mediated by the molecular chaperone GroEL occurs by its binding to non-native polypeptide substrates and is driven by ATP hydrolysis. Both of these processes are influenced by the reversible association of the co-protein, GroES (refs 2-4). GroEL and other chaperonin 60 molecules are large, cylindrical oligomers consisting of two stacked heptameric rings of subunits; each ring forms a cage-like structure thought to bind polypeptides in a central cavity. Chaperonins play a passive role in folding by binding or sequestering folding proteins to prevent their aggregation, but they may also actively unfold substrate proteins trapped in misfolded forms, enabling them to assume productive folding conformations. Biochemical studies show that GroES improves the efficiency of GroEL function, but the structural basis for this is unknown. Here we report the first direct visualization, by cryo-electron microscopy, of a non-native protein substrate (malate dehydrogenase) bound to the mobile, outer domains at one end of GroEL. Addition of GroES to GroEL in the presence of ATP causes a dramatic hinge opening of about 60 degrees. GroES binds to the equivalent surface of the GroEL outer domains, but on the opposite end of the GroEL oligomer to the protein substrate.

ATP induces large quaternary rearrangements in a cage-like chaperonin structure.

BACKGROUND: The chaperonins, a family of molecular chaperones, are large oligomeric proteins that bind nonnative intermediates of protein folding. They couple the release and correct folding of their ligands to the binding and hydrolysis of ATP. Chaperonin 60 (cpn60) is a decatetramer (14-mer) of 60 kD subunits. Folding of some ligands also requires the cooperation of cpn10, a heptamer of 10 kD subunits. RESULTS: We have determined the three-dimensional arrangements of subunits in Rhodobacter sphaeroides cpn60 in the nucleotide-free and ATP-bound forms. Negative stain electron microscopy and tilt reconstruction show the cylindrical structure of the decatetramer comprising two rings of seven subunits. The decatetramer consists of two cages joined base-to-base without a continuous central channel. These cages appear to contain bound polypeptide with an asymmetric distribution between the two rings. The two major domains of each subunit are connected on the exterior of the cylinder by a narrower bridge of density that could be a hinge region. Binding of ATP to cpn60 causes a major rearrangement of the protein density, which is reversed upon the hydrolysis of the ATP. Cpn10 binds to only one end of the cpn60 structure and is visible as an additional layer of density forming a cap on one end of the cpn60 cylinder. CONCLUSIONS: The observed rearrangement is consistent with an inward 5-10 degrees rotation of subunits, pivoting about the subunit contacts between the two heptamers, and thus bringing cpn60 domains towards the position occupied by the bound polypeptide. This change could explain the stimulation of ATPase activity by ligands, and the effects of ATP on lowering the affinity of cpn60 for ligands and on triggering the release of folding polypeptides.

DiGeorge syndrome with isolated aortic coarctation and isolated ventricular septal defect in three sibs with a 22q11 deletion of maternal origin.

DiGeorge syndrome was diagnosed in an infant who had an interrupted aortic arch, hypoparathyroidism, and low T lymphocyte numbers. Two siblings had heart defects that are not commonly described in DiGeorge syndrome (a membranous ventricular septal defect and coarctation of the aorta respectively). These siblings did not have evidence of thymic dysfunction or hypoparathyroidism. Chromosome analysis showed that the mother, whose cardiovascular examination was normal, and her three offspring with heart defects had a 22q11 interstitial deletion, which was confirmed by molecular analysis. This family suggests that 22q11 deletions can cause apparently isolated heart defects and that the range of these defects may be wider than previously recognised. Once the genes that are deleted in this family are characterised they will be useful candidate genes in the investigation of isolated cardiac malformations.

Retrograde response to axotomy of motoneurons in the thoracic spinal cord of the aging cat.

The retrograde response of HRP-labelled intercostal motoneurons was compared in adult (1-2 years) and aging (10-15 years) cats, 64-68 days following crush of intercostal nerves or following nerve transection with proximal ligation. A comparison of the neuroglial response to these two lesions was also made. In both adult and aging cats, 64-68 days following nerve crush, most labelled motoneurons had a normal appearance. In contrast, 64-68 days following nerve transection and ligation the Nissl bodies of labelled motoneurons lacked the highly ordered ultrastructure characteristic of normal and control motoneurons. No axotomy-induced neuronal loss was found in aging cats. A three-fold increase in numbers of microglial cells was quantified in the ipsilateral ventral horn of aging cats following nerve transection and ligation. This increase was not seen following nerve crush in aging cats, nor following either type of nerve injury in adult cats. Numbers of astroglia and oligodendroglia were unaffected by axotomy in adult and aging animals.

Primary malignant cardiac tumors in children.

A child with a primary malignant cardiac tumor prompted a review of all 13 cases reported in Great Britain from 1962-1983. Only 4 definitely malignant tumors were identified, giving an incidence of between 1 in 38 and 1 in 90 x 10(6). All 4 patients died without evidence of metastases. Cardiac transplantation should be considered.

Continuous ECG monitoring of children with cancer receiving domperidone.

Domperidone is an effective antiemetic for children receiving cytotoxic therapy. There have been reports of cardiac arrest in older patients associated with domperidone. We carried out continuous ECG monitoring of 18 children receiving domperidone intravenously in a dose of 1 mg/kg body weight. No serious dysrhythmias were noted during 379 h of recording. Single premature beats, transient sinus pauses, and nodal block were occasionally associated with vomiting and were no more common than would be expected in a population of normal children.

Determinants of cardiac performance in severe aortic stenosis.

Left ventricular (LV) myocardial function and the influence on LV pump performance of associated coronary arterial disease, of outflow obstruction and its consequences, and of altered ventricular pressure-volume characteristics were examined in a representative group of 28 adult patients with symptomatic severe aortic stenosis (valvular orifice area less than 0.50 sq cm/sq m). Eighteen patients (64%) exhibited depressed LV pump performance with levels of ejection fraction less than 0.50. In seven patients, coronary arterial disease documented by either arteriographic studies or postmortem analyses was associated with a segmental (i.e., nonhomogeneous) LV contractile disorder consistent with previous myocardial infarction. In the remaining 11 patients a homogeneous LV contractile disorder was the result of chronic outflow obstruction and its consequences. The possibility that reduced ventricular performance might be accounted for by increased afterload could not be supported by significant correlation between LV contractile characteristics (estimated from the ejection fraction and the mean circumferential fiber shortening rate) and indices of afterload (including LV systolic pressure, aortic valvular orifice area, and mean systolic wall tension). This observation suggested that myocardial hypertrophy and other consequences of longstanding obstruction to outflow played a primary role in depression of LV performance in these patients. Left ventricular end-diastolic volume was abnormal in all but three patients with depressed LV function; this increase was accompanied by a disproportionately greater increment in end-diastolic pressure, suggesting that reduced distensibility limited the ability of the ventricle to compensate for reduced contractile performance by means of the Starling mechanism.

Congenital absence of the left circumflex coronary artery in the systolic click syndrome.

The anatomy of the coronary artery circulation was examined by means of selective coronary arteriography in 19 patients, evaluated because of disabling chest pain and ECG abnormalities, with typical clinical findings of the systolic click syndrome (SCS). In 17 (89.5%), the elft circumflex coronary artery (LCCA) was absent; a single marginal branch arose from the left main vessel, but no vessel was present in or near the atrioventricular (A-V) groove. In contrast, the LCCA was identified in 74 of 78 control patients (94.9%) considered to have representative normal distribution of coronary artery branches, All but two patients with SCS exhibited reduced contraction of the segment of left ventricular (LV) myocardium surrounding the mitral valve ring (extent of systolic diameter decrease 1.4 +/- 3.1% vs normal 31.8 +/- 3.4%, P lwss than 0.001), as well as of the LV inflow tract (diameter decreasce 16.2 +/- 2.5% vs normal 38.6 +/- 1.8% P less than 0.001); both of these regions of the left ventricle derive their vascular supply from the LCCA, An identical segmental LV contraction disorder was observed in seven patients with functionally single vessel occlusive coronary artery disease involving the LCCA, An identical finding in this study was a relatively high incidence of absent LCCA (42%) in 19 patients with atypical angina and normal coronary arteriograms. It is concluded that a congenital anomaly of the coronary circulation, with absent LCCA, may be responsible for segmental myocardial dysfunction in some patients with SCS. In turn, this segmental contraction disorder may determine functional abnormality of the mitral valve apparatus.

Localized left ventricular myocardial defect leading to fatal cerebral embolism.

The case of a previously health 17-year-old youth who presented a fatal cerebral infarct is described. A localized defect in the anterior left ventricular myocardium with overlying thrombus, and left ventricular hypertrophy were found at necropsy. An old infarct was found in the left kidney. There were no signs of ischaemic or inflammatory heart disease. The possible origins of the lesion are discussed.