Disturbed nuclear orientation and cellular migration in A-type lamin deficient cells.

The nuclear lamina and the cytoskeleton form an integrated structure that warrants proper mechanical functioning of cells. We have studied the correlation between structural alterations and migrational behaviour in fibroblasts with and without A-type lamins. We show that loss of A-type lamins causes loss of emerin and nesprin-3 from the nuclear envelope, concurring with a disturbance in the connection between the nucleus and the cytoskeleton in A-type lamin-deficient (lmna -/-) cells. In these cells functional migration assays during in vitro wound healing revealed a delayed reorientation of the nucleus and the microtubule-organizing center during migration, as well as a loss of nuclear oscillatory rotation. These observations in fibroblasts isolated from lmna knockout mice were confirmed in a 3T3 cell line with stable reduction of lmna expression due to RNAi approach. Our results indicate that A-type lamins play a key role in maintaining directional movement governed by the cytoskeleton, and that the loss of these karyoskeletal proteins has important consequences for functioning of the cell as a mechanical entity.

Repeat sudden unexpected and unexplained infant deaths: natural or unnatural?

BACKGROUND: There have been suggestions that when two or three unexpected unexplained infant deaths occur within a family they are more likely to be unnatural than natural. We aimed to estimate the probability that a second infant death is natural versus unnatural. METHODS: The Care of Next Infant programme (CONI) supports parents who have previously had an unexpected and apparently unexplained infant death and is currently available in over 90% of health districts in England, Wales, and Northern Ireland. We studied all deaths in 6373 infants who had completed the CONI programme by December, 1999. After a CONI death, we made detailed enquiries into the previous death and the CONI death, including a family interview, a review of autopsies, and case discussion. FINDINGS: 57 (8.9 per 1000) CONI infants died. Nine deaths were inevitable, and 48 were unexpected. 44 families lost one child, and two families lost two children. Of the 46 first CONI deaths, 40 were natural; the other six were probable homicides, five committed by one or both parents (two criminally convicted). The ratio of 40 natural to six unnatural deaths is 6.7 (95% CI 2.8-19.4). Enquiries identified 18 families with two SIDS(sudden infant death syndrome) deaths and two families with probable covert double homicides (ratio 9.0 [2.2 to 80.0]). There were no convictions in 13 incomplete cases. Families with three deaths are reported. INTERPRETATION: Repeat unexpected infant deaths are most probably natural.

Associations between ambient ozone, hydrocarbons, and childhood wheezy episodes: a prospective observational study in south east London.

OBJECTIVES: To explore the hypothesis that hydrocarbon species and other air pollutants which accumulate at low and high concentrations of ozone are more directly associated with childhood wheezy episodes than ozone. METHODS: Prospective observational study over 1 year set in the Lewisham district of south east London. The daily attendance rate of children with acute wheeze at the accident and emergency department of Lewisham Hospital was related to local measurements of ozone, hydrocarbon species, nitrogen dioxide (NO2), sulphur dioxide (SO2) and small particulate matter with diameter < 10 microns (PM10). RESULTS: An inverse relation was found between the air pollutants and ozone. After seasonal and meteorological adjustment a non-linear U shaped trend was found between incidence of wheeze and ozone. The trend was significant in children < 2 years of age but not in older children. In the younger age group, after adjustment for season, temperature, wind speed, and respiratory infection, the incidence relative to that at the mean daily ozone concentration of 32.7 micrograms/m3, was estimated to increase by 65% (95% confidence interval (95% CI) 22% to 122%) at an ozone concentration of 5 micrograms/m3 (1.5 SDs below the mean) and by 63% (95% CI -6% to 184%) at 80 micrograms/m3 (2.5 SDs above the mean). For several hydrocarbons there were significant positive linear relations found, again in children < 2 years of age but not older children. For benzene, the incidence increased by 8% (95% CI 2 to 13%) per SD (SD 2.8 micrograms/m3) increase in benzene concentration. A same day association between incidence and ozone was found to be the most significant but for other pollutants a lag of 2 days gave the most significant associations. No significant association was found for the non-hydrocarbon pollutants including SO2, NO2, and PM10. CONCLUSIONS: A U shaped relation was found between ozone and the incidence of wheezy episodes in young children. Certain hydrocarbon pollutants accumulate in the atmosphere when ozone concentrations are low, and are associated with childhood wheezy episodes. However, the U shaped association of ozone on incidence cannot be explained by these other pollutants. The finding supports an earlier finding that incidences of wheeze are at a minimum when ozone concentrations are 30-40 micrograms/m3.

Autoimmune haemolytic anaemia in infancy with anti-Kpb specificity.

Autoimmune haemolytic anaemia (AIHA) in infancy is rare. We report a case of AIHA in a male infant whose serum contained an antibody with apparent anti-Kpb specificity. Autoantibody with anti-Kpb specificity has been described in adults; to our knowledge, this is the first case of this kind described in infancy with AIHA. Clinical course and response to red cell transfusion are described.

Concepts of GTDs: an oncology workstation.

In Germany, computer systems have been used in hospital cancer registries for more than 10 years. Primarily, they have been used for retrospective documentation of malignant tumors, and these resources have rarely been tapped for the support of follow up care and statistical evaluation. In response to the increasing availability of PC-systems and growing interest in computer networks, we have decided to design and develop a new oncology information system which covers two important aspects of oncology care: (1) the documentation of all relevant data items for the cancer registries, and (2) the routine support of the physician in the clinical treatment process. In this paper we discuss the design and concept of this oncology information system as well as experiences gained during the development process are discussed. Future plans to further extend the system to a comprehensive oncology workstation are presented.

Temporary inhibition of growth and adrenal suppression associated with the use of steroid nose drops.

Inhibition of growth and adrenal suppression are reported following the use of intranasal beta-methasone (0.1%) in a 9-year-old boy with cystic fibrosis and nasal polyps and in a 3-year-old girl with allergic rhinitis. On stopping treatment catch-up growth occurred and adrenal function returned to normal.

Pulmonary uptake of sestamibi on early post-stress images: angiographic relationships, incidence and kinetics.

Early post-stress imaging with 99Tcm-sestamibi has the potential to reveal ancillary markers of severe coronary artery disease. Lung/myocardial ratios of sestamibi were assessed after pharmacologic, exercise or combined stress, and these were compared with historical controls who were stressed similarly, but imaged with 201Tl. Forty initial patients had planar imaging and correlating angiograms; pulmonary uptake for sestamibi related to severe coronary artery stenoses when measured on immediate images, started at 4 min post-stress (P = 0.04), but had a poor relationship to angiographic findings when measured on delayed clinical images. Of 180 subsequent studies, increased pulmonary uptake of sestamibi was seen more frequently (incidence = 34%) in those with abnormal tomograms compared to those with normal tomograms (incidence = 13%, P < 0.01), but appeared less frequently than on abnormal 201Tl studies (incidence = 60%). With sequential imaging for 5 min after injection, pulmonary uptake showed a greater fall with time on sestamibi studies than on matched 201Tl studies. No consistent differences were seen among the stress modalities. As an ancillary sign of haemodynamically severe disease, increased pulmonary uptake can be seen after various stress modalities, but may be more difficult to apply with sestamibi than with thallium imaging.

Pseudo-Bartter's syndrome in cystic fibrosis.

Seven cases of cystic fibrosis complicated by chronic salt depletion and failure to thrive were studied. After replacement of the salt deficit, the metabolic abnormalities resolved, and weight gain was rapid. This should be considered as a differential diagnosis in children who have been diagnosed as having cystic fibrosis, but who fail to thrive despite standard treatment.

A comparative study on the effects of propofol in emulsion and Intralipid on fat metabolism.

The present study compared the effects on lipid metabolism of propofol in emulsion (Diprivan) and a fat emulsion (Intralipid) in doses containing the same amount of soya bean oil. Twenty patients received epidural anesthesia for gonarthroscopy and were randomly divided in two groups. Before the start of surgery the patients of group P received a bolus of 2 mg/kg of propofol followed by a one hour infusion of 6 mg/kg/h. In group I, a bolus of 0.2 mg/kg of Intralipid 10% was followed by an infusion of 0.6 ml/kg/h for one hour. These figures represent equivalent amounts of soya bean oil administered. Blood samples were obtained for analysis of serum triglycerides, cholesterol, phospholipids, free fatty acids, aproproteins, and the separated lipoprotein fractions. There were few significant differences between propofol in emulsion and Intralipid in the effects on lipid metabolism. The changes in the measured serum lipid components were mild and rarely lasted longer than 2 h after the end of infusion.

The captopril test: an aid to investigation of hypertension.

Twenty three children aged from 5 to 16 with mild to moderate hypertension were investigated using the orally active angiotensin converting enzyme inhibitor captopril. Falls in both systolic and diastolic blood pressure after a single dose of captopril were significantly correlated with initial plasma renin activity. In addition, some information about the aetiology of hypertension was deduced from the renin response to captopril. The blood pressure response to captopril is a useful screening test for renin dependent hypertension in childhood.

Sodium transport in erythrocytes: differences between normal children and children with primary and secondary hypertension.

The following measurements were made in normal children, children with primary hypertension, and children with secondary hypertension: erythrocyte intracellular sodium concentration, total sodium efflux rate constant, and maximum binding of ouabain to erythrocytes reflecting the number of sodium/potassium adenosine triphosphatase pump sites. Children with primary hypertension had a significantly higher mean erythrocyte intracellular sodium concentration (8.2 compared with 6.6 and 6.7 mmol/l cells), and significantly lower total sodium efflux rate constant (0.5071 compared with 0.6983 and 0.6197) and maximum binding of ouabain to erythrocytes (9.1 compared with 11.7 and 11.0 nmol/l cells) than normal children and children with secondary hypertension, respectively.

Erythrocyte sodium transport in Bartter's syndrome.

Erythrocyte sodium transport was evaluated by measurement of intracellular Na concentration (ICNa), 22Na efflux rate constant (NaERC) and 3H-ouabain binding (BMax) (reflecting the number of Na/K ATPase pump sites) in 9 children with Bartter's syndrome compared to controls (children and adults) and children with various forms of salt wasting disease. There were no differences between control children and adults. In untreated Bartter's syndrome ICNa was significantly increased with NaERC and BMax significantly decreased compared to findings in controls and patients with other salt wasting disease. On prostaglandin synthetase inhibitor (Indomethacin) therapy, ICNa decreased but remained higher than in controls, NaERC increased to normal values but BMax remained low. These data support the view that there is a widespread defect in membrane electrolyte transport in Bartter's syndrome but suggest that the benefit of indomethacin therapy is not manifest via an effect on Na/K ATPase.

Brain revascularisation in hypertension.

Neurological symptoms in hypertensive subjects may be a reflection of intracranial vascular disease and not just a consequence of hypertension. Two hypertensive children with renovascular disease, neurological symptoms, and severe cerebral arterial disease were treated by extracranial-intracranial arterial bypass surgery with improvement of symptoms and easier control of blood pressure. Where revascularisation surgery is appropriate, this should be undertaken before neurological complications arise.